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  1. Plasma Aldosterone Concentration Is Positively Associated With Pulse Pressure in Patients With Primary Hypertension

    PubMed Central

    Yao, Xiaoguang; Li, Nanfang; Zhang, Yujie; Zhang, Juhong; Abulikm, Suofeiya; Zhang, Delian; Chang, Guijuan; Zhou, Keming; Kong, Jianqiong

    2015-01-01

    Abstract Increasing evidence showed a link between arterial elasticity and stiffness and pulse pressure (PP), in which plasma aldosterone may play a role. The observational study aimed to explore the potential relations between plasma aldosterone concentration (PAC) and PP in patients with hypertension. We evaluated the relation between PP and PAC in supine, seated, and upright positions in 195 patients with primary hypertension who underwent postural stimulation test. They were divided into 3 groups by tertiles of PP: PP ≤ 44 mm Hg (n = 70), 44 mm Hg < PP ≤ 51 mm Hg (n = 63), and PP ≥ 51 mm Hg (n = 62). The PAC in different postures was compared, respectively. The results showed the following. First, segregated by tertiles of PP, serum K+, 24-hour systolic blood pressure, 24-hour diastolic blood pressure, sex, upright PAC, and seated PAC showed statistically significant differences in groups. Second, the PAC were significantly different in 3 levels of PP regardless of postures, the individuals with PP ≥ 51 mm Hg had the highest PAC. On contrast, the patients with PAC > 12 ng/dL showed greater PP than those with PAC ≤ 12 ng/dL. Third, weak associations between PP and upright (r = 0.288, P < 0.001), seated (r = 0.265, P < 0.001), and supine postures (r = 0.191, P = 0.008) were detected by simple correlation analysis. After corrected serum K+, age, and sex, the partial correlation coefficients did not change greatly. Fourth, the logistic regression model was constructed with PP ≥ 40 mm Hg or PP < 40 mm Hg as the dependent variable; the serum K+[OR = 0.043, 95% CI: 1.09(1.00–1.12)] and PAC [OR = 0.025, 95%CI: 0.35(0.13–0.88)] were included as significant contributing factors. The results showed that higher PAC was weakly, but significantly, correlated to greater PP regardless of different postures, suggesting that higher PAC may be a risk factor of reduced arterial

  2. Aldosterone response to angiotensin II during hypoxemia

    SciTech Connect

    Colice, G.L.; Ramirez, G.

    1986-07-01

    Exercise stimulates the renin-angiotensin-aldosterone system (RAAS). However, increases in plasma aldosterone concentrations (PAC) are suppressed when exercise is performed at high altitude or under hypoxemic conditions. As the angiotensin-II response to high-altitude exercise is normal, it is speculated that an inhibitor, discharged during hypoxemia, acted to suppress angiotensin-II-mediated aldosterone release. A study was conducted to test this hypothesis, taking into account the measurement of the aldosterone response to exogenous angiotensin II during normoxemia and hypoxemia. It was found that the dose-response curve of PAC to angiotensin II was not significantly inhibited by the considered model of hypoxemia. The hypoxemia-mediated release of an angiotensin II inhibitor does, therefore, not explain the previous observations of PAC suppression during hypoxemic exercise. 28 references.

  3. Plasma aldosterone and sweat sodium concentrations after exercise and heat acclimation

    NASA Technical Reports Server (NTRS)

    Kirby, C. R.; Convertino, V. A.

    1986-01-01

    The relationship between plasma aldosterone levels and sweat sodium excretion after chronic exercise and heat acclimation was investigated, using subjects exercised, at 40 C and 45 percent humidity, for 2 h/day on ten consecutive days at 45 percent of their maximal oxygen uptake. The data indicate that, following heat acclimation, plasma aldosterone concentrations decrease, and that the eccrine gland responsiveness to aldosterone, as represented by sweat sodium reabsorption, may be augmented through exercise and heat acclimation.

  4. Role of ACTH and Other Hormones in the Regulation of Aldosterone Production in Primary Aldosteronism

    PubMed Central

    El Ghorayeb, Nada; Bourdeau, Isabelle; Lacroix, André

    2016-01-01

    The major physiological regulators of aldosterone production from the adrenal zona glomerulosa are potassium and angiotensin II; other acute regulators include adrenocorticotropic hormone (ACTH) and serotonin. Their interactions with G-protein coupled hormone receptors activate cAMP/PKA pathway thereby regulating intracellular calcium flux and CYP11B2 transcription, which is the specific steroidogenic enzyme of aldosterone synthesis. In primary aldosteronism (PA), the increased production of aldosterone and resultant relative hypervolemia inhibits the renin and angiotensin system; aldosterone secretion is mostly independent from the suppressed renin–angiotensin system, but is not autonomous, as it is regulated by a diversity of other ligands of various eutopic or ectopic receptors, in addition to activation of calcium flux resulting from mutations of various ion channels. Among the abnormalities in various hormone receptors, an overexpression of the melanocortin type 2 receptor (MC2R) could be responsible for aldosterone hypersecretion in aldosteronomas. An exaggerated increase in plasma aldosterone concentration (PAC) is found in patients with PA secondary either to unilateral aldosteronomas or bilateral adrenal hyperplasia (BAH) following acute ACTH administration compared to normal individuals. A diurnal increase in PAC in early morning and its suppression by dexamethasone confirms the increased role of endogenous ACTH as an important aldosterone secretagogue in PA. Screening using a combination of dexamethasone and fludrocortisone test reveals a higher prevalence of PA in hypertensive populations compared to the aldosterone to renin ratio. The variable level of MC2R overexpression in each aldosteronomas or in the adjacent zona glomerulosa hyperplasia may explain the inconsistent results of adrenal vein sampling between basal levels and post ACTH administration in the determination of source of aldosterone excess. In the rare cases of glucocorticoid remediable

  5. The Potential of ACTH in the Genesis of Primary Aldosteronism.

    PubMed

    Funder, John W

    2016-01-01

    Aldosterone is a homeostatic hormone, rising in volume depletion, sodium deficiency, and potassium loading, in response to angiotensin11 and elevation of plasma potassium. Pathophysiologically, in primary aldosteronism (PA) aldosterone levels are inappropriate for the patient's sodium and potassium status, and thus outside the normal feedback loop. ACTH is equivalent with A11 and [K(+)] in elevating aldosterone: its effects differ from those of the other secretagogues in four ways. First, it is not sustained; second, it raises aldosterone and cortisol secretion with equal potency; third, it is outside the normal feedback loops, reflecting the epithelial action of aldosterone; and finally its possible role in driving inappropriate aldosterone secretion (aka PA) is not widely recognized. Thirty years ago, it was shown that on a fixed sodium intake of 175 meq/day 36 of 100 unselected hypertensives, in whom PA has been excluded on contemporary criteria, had 24 h urinary aldosterone levels above the upper limit of normotensive controls. More recently, the dexamethasone enhanced fludrocortisone suppression test (FDST) showed 29% of unselected hypertensives to have plasma aldosterone concentrations above the upper limit of normotensive controls. In subjects negative for PA on the FDST, 27% were extremely hyper-responsive to ultra-low dose ACTH infusion; the remaining 73% showed minimal aldosterone elevation, as did normotensive controls: all three groups had negligible cortisol responses. On treadmill testing, no differences were found between groups in (minimally altered) ACTH and cortisol levels: hyper-responders to ultra-low ACTH, however, showed a major elevation in PAC. The implications of these studies, when validated, are substantial for PA, in that approximately half of hypertensive patients appear to show inappropriate aldosterone levels for their sodium status. The physiological role(s) of ACTH as an acute aldosterone secretagogue, and the mechanisms whereby

  6. The Potential of ACTH in the Genesis of Primary Aldosteronism

    PubMed Central

    Funder, John W.

    2016-01-01

    Aldosterone is a homeostatic hormone, rising in volume depletion, sodium deficiency, and potassium loading, in response to angiotensin11 and elevation of plasma potassium. Pathophysiologically, in primary aldosteronism (PA) aldosterone levels are inappropriate for the patient’s sodium and potassium status, and thus outside the normal feedback loop. ACTH is equivalent with A11 and [K+] in elevating aldosterone: its effects differ from those of the other secretagogues in four ways. First, it is not sustained; second, it raises aldosterone and cortisol secretion with equal potency; third, it is outside the normal feedback loops, reflecting the epithelial action of aldosterone; and finally its possible role in driving inappropriate aldosterone secretion (aka PA) is not widely recognized. Thirty years ago, it was shown that on a fixed sodium intake of 175 meq/day 36 of 100 unselected hypertensives, in whom PA has been excluded on contemporary criteria, had 24 h urinary aldosterone levels above the upper limit of normotensive controls. More recently, the dexamethasone enhanced fludrocortisone suppression test (FDST) showed 29% of unselected hypertensives to have plasma aldosterone concentrations above the upper limit of normotensive controls. In subjects negative for PA on the FDST, 27% were extremely hyper-responsive to ultra-low dose ACTH infusion; the remaining 73% showed minimal aldosterone elevation, as did normotensive controls: all three groups had negligible cortisol responses. On treadmill testing, no differences were found between groups in (minimally altered) ACTH and cortisol levels: hyper-responders to ultra-low ACTH, however, showed a major elevation in PAC. The implications of these studies, when validated, are substantial for PA, in that approximately half of hypertensive patients appear to show inappropriate aldosterone levels for their sodium status. The physiological role(s) of ACTH as an acute aldosterone secretagogue, and the mechanisms whereby

  7. Epicardial Fat Thickness and Primary Aldosteronism.

    PubMed

    Iacobellis, G; Petramala, L; Marinelli, C; Calvieri, C; Zinnamosca, L; Concistrè, A; Iannucci, G; De Toma, G; Letizia, C

    2016-04-01

    Primary aldosteronism (PA) is associated with increased cardiovascular risk and left ventricle (LV) changes. Given its peculiar biomolecular and anatomic properties, excessive epicardial fat, the heart-specific visceral fat depot, can affect LV morphology. Whether epicardial fat can be associated with aldosterone and LV mass (LVM) in patients with PA is unknown. We performed ultrasound measurement of the epicardial fat thickness (EAT) in 79 consecutive newly diagnosed patients with PA, 59 affected by bilateral adrenal hyperplasia (IHA), 20 aldosterone-producing adenoma (APA), and 30 patients with essential hypertension (low renin hypertension) (EH). The 3 groups did not differ by age, sex distribution, body mass index (BMI), waist circumference (WC), or blood pressure values. EAT showed a trend of increase in both APA and IHA groups when compared to patients with EH (8.3±1.8 vs. 7.9±1.3 vs. 7.8±2 mm, respectively). EAT was significantly correlated with indexed LVM in the IHA group (r=0.35, p<005), better than BMI or WC were. Interestingly, EAT was highly associated with plasma aldosterone concentrations (PAC) and PAC/plasma renin activity (PRA) (PAC/PRA) in the APA group (p=0.58, p=0.37, p<0.01, for both), whereas BMI and WC were not. EAT was also correlated with PRA in the IHA group (p=-0.28, p<0.05). Our study indicates a novel and interesting interaction of EAT with PA, independent of obesity, abdominal fat and blood pressure control. EAT can locally affect LVM, at least in patients with IHA. Further studies in larger population will be required to confirm these findings. PMID:26983926

  8. Effect of heat stress and drinking water salt supplements on plasma electrolytes and aldosterone concentration in broiler chickens

    NASA Astrophysics Data System (ADS)

    Deyhim, F.; Teeter, R. G.

    1995-12-01

    An experiment was conducted to evaluate the effects of supplementing drinking water with isomolar (0.067 mol/l) KCl or NaCl on mass gain, food and water consumption, rectal temperature, and plasma concentrations of aldosterone, Na+, and K+ in broiler chickens reared in thermoneutral and cycling heat stressing environments. Heat stress decreased ( P≤0.05) mass gain, food consumption, and plasma concentrations of Na+ and K+, while increases ( P≤0.05) in plasma concentrations of aldosterone, rectal temperature, and water consumption were observed. Drinking water supplemented with either KCl or NaCl increased ( P≤0.05) broiler mass gain and water consumption, but had no effect ( P>0.1) on the other variables evaluated. The results of this study indicate that broiler chickens in a heat stress environment are under osmotic stress and supplementing drinking water with 0.067 mol/1 KCl or NaCl does not lessen this stress.

  9. Reverse osmosis concentrate treatment via a PAC-MF accumulative countercurrent adsorption process.

    PubMed

    Zhao, Chunxia; Gu, Ping; Cui, Hangyu; Zhang, Guanghui

    2012-01-01

    Organic pollutants in reverse osmosis (RO) concentrates from wastewater reclamation are mainly comprised of low molecular weight biorefractory compounds. Generally, advanced oxidation methods for oxidizing these organics require a relatively high level of energy consumption. In addition, conventional adsorption removal methods require a large dose of activated carbon. However, the dose can be reduced if its full adsorption capacity can be used. Therefore, the combined technology of powdered activated carbon (PAC) adsorption and microfiltration (MF) membrane filtration was studied to develop a countercurrent two-stage adsorption process. A PAC accumulative adsorption prediction method was proposed based on the verification of a PAC multi-stage adsorption capacity equation. Moreover, the prediction method was amended for a more accurate prediction of the effluent quality because adsorption isotherm constants were affected by the initial adsorbate concentration. The required PAC dose for the accumulative countercurrent two-stage adsorption system was 0.6 g/L, whereas that of the conventional adsorption process was 1.05 g/L when the dilution factor(F) was 0.1 and the COD and DOC removal rates were set to 70% and 68.1%, respectively. Organic pollutants were satisfactorily removed with less consumption of PAC. Effluent from this combined technology can be further reclaimed by an RO process to improve the overall recovery rate to between 91.0% and 93.8% with both economic and environmental benefits. PMID:22082527

  10. [The renin-angiotensin-aldosterone system during the extraction, concentration and reinfusion of ascitic fluid in cirrhotic patients].

    PubMed

    Giorcelli, V; Fossale, P G

    1983-01-01

    The course of hepatic cirrhosis involves alterations to the sodium-water balance, the aetiopathogenetic causes of which are still not entirely known. At first major importance was assigned to the role of secondary hyperaldosteronism which develops during the ascitic phase. This was subsequently recognised to have only a permissive rather than determinant function. Changes in the renin-angiotensin-aldosterone (RAA) system and variations in hydrosaline balance as the extracellular volume (ECV) expands during the reinfusion of concentrated ascitic fluid have been studied. The data reported show that ECV expansion causes increased diuresis, natriuresis and osmolar clearance. The RAA system is suppressed and at the same time kaliuresis increases. The latter factor points up the role played by increased solute flow to the distal tube in the diuretico-metabolic response, where aldosterone plays a purely permissive part. PMID:6675585

  11. Role of Nox2 and p22phox in Persistent Postoperative Hypertension in Aldosterone-Producing Adenoma Patients after Adrenalectomy

    PubMed Central

    Geng, Xiaojing; Yan, Li; Dong, Jun; Liang, Ying; Deng, Yajuan; Li, Ting; Luo, Tongfeng; Lin, Hailun; Zhang, Shaoling

    2016-01-01

    Adrenal aldosterone-producing adenoma (APA), producing the salt-retaining hormone aldosterone, commonly causes secondary hypertension, which often persists after unilateral adrenalectomy. Although persistent hypertension was correlated with residual hormone aldosterone, the in vivo mechanism remains unclear. NADPH oxidase is the critical cause of aldosterone synthesis in vitro. Nox2 and p22phox comprise the NADPH oxidase catalytic core, serving to initiate a reactive oxygen species (ROS) cascade that may participate in the pathology. mRNAs of seven NADPH oxidase isoforms in APA were evaluated by RT-PCR and Q-PCR and their proteins by immunohistochemistry and Western blotting. NADPH oxidase activity was also detected. Nox2 and p22phox were especially abundant in APA. Particularly higher Nox2 and p22phox gene and protein levels were seen in APA than controls. Significant correlations between Nox2 mRNA and aldosterone synthase (CYP11B2) mRNA (R = 0.66, P < 0.01) and Nox2 protein and baseline plasma aldosterone concentration (PAC) (R = 0.503, P < 0.01) were detected in APA; however, none were found between p22phox mRNA, CYP11B2 mRNA, p22phox protein, and baseline PAC. Importantly, we found that Nox2 localized specifically in hyperplastic zona glomerulosa cells. In conclusion, our results highlight that Nox2 and p22phox may be directly involved in pathological aldosterone production and zona glomerulosa cell proliferation after APA resection. PMID:27057164

  12. High concentration powdered activated carbon-membrane bioreactor (PAC-MBR) for slightly polluted surface water treatment at low temperature.

    PubMed

    Ma, Cong; Yu, Shuili; Shi, Wenxin; Tian, Wende; Heijman, S G J; Rietveld, L C

    2012-06-01

    In this study, different concentrations of PAC combined with MBR were carried out to treat slightly polluted surface water (SPSW) at low temperature (10°C). Effects of PAC on the efficiencies of operation, treatment, and the performance of the process were investigated. It was found that the effluent quality, performance efficiency, resistance of shock load were all enhanced and chemical irreversible membrane fouling was reduced with increasing dosage of PAC in MBR. Only when the concentration of PAC which acted as biological carriers was high enough (i.g., 50 g/L), nitrification without initial inoculation in the filtration tank could start within 19 days and be completed within 35 days at 10°C. Fifty grams per liter PAC was the optimal dosage in MBR for stable and extended operation. Under this condition, mean removal efficiencies of ammonia nitrogen (NH(3)-N), dissolved organic carbon (DOC) and UV(254) were 93%, 75%, and 85%, respectively. PMID:22386626

  13. Platelet Activation Test in Unprocessed Blood (Pac-t-UB) to Monitor Platelet Concentrates and Whole Blood of Thrombocytopenic Patients

    PubMed Central

    Roest, Mark; van Holten, Thijs C.; Fleurke, Ger-Jan; Remijn, Jasper A.

    2013-01-01

    Summary Background Platelet concentrate transfusion is the standard treatment for hemato-oncology patients to compensate for thrombocytopenia. We have developed a novel platelet activation test in anticoagulated unprocessed blood (pac-t-UB) to determine platelet function in platelet concentrates and in blood of thrombocytopenic patients. Methods We have measured platelet activity in a platelet concentrate and in anticoagulated unprocessed blood of a post-transfusion thrombocytopenic patient. Results Our data show time-dependent platelet activation by GPVI agonist (collagen related peptide; CRP), PAR-1 agonist (SFLLRN), P2Y12 agonist (ADP), and thromboxane receptor agonist (U46619) in a platelet concentrate. Furthermore, pac-t-UB showed time-dependent platelet activation in unprocessed blood of a post-transfusion patient with thrombocytopenia. Testing platelet function by different agonists in relation to storage show that 3-day-old platelet concentrates are still reactive to the studied agonists. This reactivity rapidly drops for each agonists during longer storage. Discussion Pac-t-UB is a novel tool to estimate platelet function by different agonists in platelet concentrates and in unprocessed blood of thrombocytopenic patients. In the near future, we will validate whether pac-t-UB is an adequate test to monitor the quality of platelet concentrates and whether pac-t-UB predicts the bleeding risk of transfused thrombocytopenic patients. PMID:23652405

  14. Diagnostic Role of Captopril Challenge Test in Korean Subjects with High Aldosterone-to-Renin Ratios

    PubMed Central

    Kim, Jung Hee; Park, Kyeong Seon; Hong, A Ram; Shin, Chan Soo; Kim, Seong Yeon

    2016-01-01

    Background Diagnosis of primary aldosteronism (PA) begins with aldosterone-to-renin ratio (ARR) measurement followed by confirmative tests. However, the ARR has high false positive rates which led to unnecessary confirmatory tests. Captopril challenge test (CCT) has been used as one of confirmatory tests, but the accuracy of it in the diagnosis of PA is still controversial. We aimed to examine the clinical efficacy of CCT as a post-screening test in PA. Methods In a prospective study, we enrolled subjects with suspected PA who had hypertension and ARR >20 (ng/dL)/(ng/mL/hr). Sixty-four patients who underwent both the saline infusion test and the CCT were included. Results The diagnostic performance of plasma aldosterone concentration (PAC) post-CCT was greater than that of ARR post-CCT and ARR pre-CCT in PA (area under the curve=0.956, 0.797, and 0.748, respectively; P=0.001). A cut-off value of 13 ng/dL showed the highest diagnostic odds ratio considering PAC post-CCT at 60 and 90 minutes. A PAC post-CCT of 19 ng/dL had a specificity of 100%, which can be used as a cut-off value for the confirmative test. Determining the diagnostic performance of PAC post-CCT at 90 minutes was sufficient for PA diagnosis. Subjects with PAC post-CCT at 90 minutes <13 ng/dL are less likely to have PA, and those with PAC post-CCT at 90 minutes ≥13 but <19 ng/dL should undergo secondary confirmatory tests. Conclusion The CCT test may be a reliable post-screening test to avoid the hospitalization in the setting of falsely elevated ARR screening tests. PMID:27184013

  15. Endothelial dysfunction in patients with primary aldosteronism: a biomarker of target organ damage.

    PubMed

    Liu, G; Yin, G-S; Tang, J-y; Ma, D-J; Ru, J; Huang, X-H

    2014-12-01

    Primary aldosteronism (PA) has been associated with increased target organ damage (TOD), most likely through mineralocorticoid receptor-dependent endothelial dysfunction, in comparison with essential hypertension (EH). The aim of this study was to evaluate the level of biomarkers of endothelial dysfunction in PA and the relationship with left ventricular hypertrophy (LVH) and microalbuminuria (MAU). A total of 50 PA patients and 51 patients with EH individually matched for age, sex, blood pressure and duration of hypertension participated in this study. Biomarkers of endothelial dysfunction, including von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1) and oxidized low-density lipoprotein (ox-LDL), were measured. Plasma aldosterone concentration (PAC), MAU and echocardiography were also evaluated. In PA patients, vWF, ICAM-1, ox-LDL, LVH and MAU were all significantly higher than in EH patients (all P<0.05). Furthermore, LVH was positively correlated with PAC (P=0.002), vWF (P=0.013) and ox-LDL (P=0.020). MAU was positively correlated with PAC (P<0.001), vWF (P=0.013) and ICAM-1 (P=0.001). Multiple regression analysis indicated that vWF, ICAM-1 and PAC independently predicted MAU (all P<0.05). Likewise, PAC, vWF and ox-LDL were significant predictors of LVH (all P<0.05). Taken together, our results suggest that endothelial dysfunction may contribute to TOD in PA patients. PMID:24553636

  16. Primary aldosteronism caused by unilateral adrenal hyperplasia: rethinking the accuracy of imaging studies.

    PubMed

    Chen, Su-Yu; Shen, Sjen-Jung; Chou, Chien-Wen; Yang, Chwen-Yi; Cheng, Hon-Mei

    2006-03-01

    A rare type of aldosteronism, known as unilateral adrenal hyperplasia (UAH), is difficult to diagnose, not only because it fails to conform to the typical common subtypes, but also because imaging results are unreliable. We report 2 Taiwanese patients with UAH. Case 1 was a 44-year-old man with 2 episodes of hypokalemic paralysis. Hypertension and suppressed plasma renin activity (PRA) with elevated plasma aldosterone concentration (PAC) were observed. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a right adrenal mass, but adrenal scintigraphy revealed no definite laterality. The patient underwent a laparoscopic right adrenalectomy. Adrenal cortical hyperplasia was discovered from results of the histologic analysis. Case 2 was a 33-year-old woman referred for hypokalemia, hypertension, and a left adrenal mass found on a CT scan. However, MRI revealed normal adrenal glands. The adrenal vein sampling for PAC showed overproduction of PAC from the left adrenal gland. A laparoscopic left adrenalectomy was done. Pathology results revealed micronodular cortical hyperplasia with central hemorrhage. Blood pressure, plasma potassium, aldosterone, and renin activity levels returned to normal after operation in both cases. Both patients have been well for 3 years and 16 months, respectively, after surgery. We review the literature and discuss the limitations of imaging studies. PMID:16599018

  17. Aldosterone blood test

    MedlinePlus

    ... hypotension) Aldosterone is a hormone released by the adrenal glands . It helps the body regulate blood pressure. Aldosterone ... may be due to Bartter syndrome (extremely rare) Adrenal glands release too much aldosterone hormone ( primary hyperaldosteronism - usually ...

  18. Acutely elevated vasopressin increases circulating concentrations of cortisol and aldosterone in fasting northern elephant seal (Mirounga angustirostris) pups

    NASA Technical Reports Server (NTRS)

    Ortiz, Rudy M.; Wade, Charles E.; Ortiz, C. Leo; Talamantes, Frank

    2003-01-01

    The physiological actions of vasopressin (VP) in marine mammals are not well defined. To help elucidate its hormonal and renal effects in this group of mammals, northern elephant seal (Mirounga angustirostris) pups (N=7; 99+/-4 kg) were first infused with 0.9% saline (control; 220 ml), followed 24 h later with VP (as a 20 ng kg(-1) bolus, then 2 ng kg(-1) min(-1) for approximately 35 min in 225+/-16 ml saline). During both control and VP periods, blood samples were collected prior to infusion, and 15, 30, 60, 120 min and 24 h after infusion to examine the hormonal responses of the pups to VP. Renal responses were quantified from 24 h urine samples obtained prior to infusion (control) and 24 h post-infusion. Compared to the control period, infusion of VP increased plasma concentrations of cortisol over a 120 min period and aldosterone over 30 min, while plasma renin activity (PRA) was decreased for a 120 min period. The plasma urea:creatinine ratio was elevated following infusion of VP. Urine output and osmotic clearance were increased by 69+/-18% (mean +/- S.E.M.) and 36+/-10%, respectively, but free water clearance and glomerular filtration rate were not significantly altered 24 h post-infusion of VP. Solute (osmolality, Na(+), K(+) and Cl(-)) excretion and fractional excretion of electrolytes were also increased when compared to control values. The increase in cortisol concentration suggests that VP may possess corticotropin releasing hormone-like activity in elephant seals. If osmotic diuresis and natriuresis are typical consequences of elevated [VP] in fasting pups, then not increasing VP normally during the fast may serve as a protective mechanism to avoid the potential loss of Na(+) induced by elevated [VP]. Therefore, under natural fasting conditions, pups may be highly sensitive to small changes in [VP], resulting in the maintenance of water and electrolyte balance.

  19. Suppression of Aldosterone Secretion After Recumbent Saline Infusion Does Not Exclude Lateralized Primary Aldosteronism.

    PubMed

    Cornu, Erika; Steichen, Olivier; Nogueira-Silva, Luis; Küpers, Elselien; Pagny, Jean-Yves; Grataloup, Christine; Baron, Stéphanie; Zinzindohoue, Franck; Plouin, Pierre-François; Amar, Laurence

    2016-10-01

    Guidelines recommend suppression tests such as the saline infusion test (SIT) to ascertain the diagnosis of primary aldosteronism (PA) in patients with a high aldosterone:renin ratio. However, suppression tests have only been evaluated in small retrospective series, and some experts consider that they are not helpful for the diagnosis of PA. In this study, we evaluated whether low post-SIT aldosterone concentrations do exclude lateralized PA. Between February 2009 and December 2013, 199 patients diagnosed with PA on the basis of 2 elevated aldosterone:renin ratio results and a high basal plasma or urinary aldosterone level or high post-SIT aldosterone level had a selective adrenal venous sampling. We used a selectivity index of 2 and a lateralization index of 4 to interpret the adrenal venous sampling results. Baseline characteristics of the patients were the following (percent or median): men 63%, 48 years old, office blood pressure 142/88 mm Hg, serum potassium 3.4 mmol/L, aldosterone:renin ratio 113 pmol/mU, plasma aldosterone concentration 588 pmol/L. The proportion of patients with lateralized adrenal venous sampling was 12 of 41 (29%) among those with post-SIT aldosterone <139 pmol/L (5 ng/dL) and 38 of 104 (37%) among those with post-SIT aldosterone <277 pmol/L (10 ng/dL). Post-SIT aldosterone levels were not associated with the blood pressure outcome of adrenalectomy. A low post-SIT aldosterone level cannot rule out lateralized PA, even with a low threshold (139 pmol/L). Adrenal venous sampling should be considered for patients who are eligible for surgery with elevated basal aldosterone levels even if they have low aldosterone concentrations after recumbent saline suppression testing. PMID:27600182

  20. Aldosterone and Renin Test

    MedlinePlus

    ... renin tests are used to evaluate whether the adrenal glands are producing appropriate amounts of aldosterone and to ... caused by the overproduction of aldosterone by the adrenal glands , usually by a benign tumor of one of ...

  1. A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery

    PubMed Central

    Morimoto, R; Satani, N; Iwakura, Y; Ono, Y; Kudo, M; Nezu, M; Omata, K; Tezuka, Y; Seiji, K; Ota, H; Kawasaki, Y; Ishidoya, S; Nakamura, Y; Arai, Y; Takase, K; Sasano, H; Ito, S; Satoh, F

    2016-01-01

    Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl−1 and aldosterone renin activity ratio of 90.2 (ng dl−1 per ng ml−1 h−1), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl−1 confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production. PMID:26538381

  2. A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

    PubMed

    Morimoto, R; Satani, N; Iwakura, Y; Ono, Y; Kudo, M; Nezu, M; Omata, K; Tezuka, Y; Seiji, K; Ota, H; Kawasaki, Y; Ishidoya, S; Nakamura, Y; Arai, Y; Takase, K; Sasano, H; Ito, S; Satoh, F

    2016-06-01

    Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production. PMID:26538381

  3. Stimulation and suppression of aldosterone in plasma of normal man and in primary aldosteronism

    PubMed Central

    Horton, R.

    1969-01-01

    The effect of stimulating and suppressive influences on plasma aldosterone in normal man and in patients with primary aldosteronism were studied using a sensitive double-isotope derivative assay for aldosterone. In normal sitting subjects, values were 9.2±0.9 (SE) mμg/100 ml and in subjects supine for 1 hr plasma aldosterone was 5.2±0.4 (SE) mμg/100 ml. Adrenocorticotropic hormone (ACTH), 0.5 U/hr, produced a rise of 46.8±22 (SE) mμg which was similar to the 1-hr effect of an infusion of a synthetic ACTH (β1-24, Cortrosyn). Angiotensin II in pressor amounts also increased plasma aldosterone 21.5±2.9 (SE) without change in plasma cortisol, whereas a subpressor dose ([unk]) had minimal effect. Fludrocortisone, 1.2 mg/day for 3 days, suppressed plasma aldosterone levels to 1.8±0.7 (SE) mμg/100 ml in five normal sitting subjects (P < 0.01); however, dexamethasone, 2 mg/day for 1-2 days, did not lower aldosterone concentration in plasma. In six patients with primary aldosteronism, plasma aldosterone on a normal sodium diet was 39.1±4.4 (SE) which differed significantly from normal sitting or supine subjects (P < 0.001). In contrast to the normal subjects, neither a pressor infusion of angiotensin II for 1 hr, nor fludrocortisone, 1.2 mg/day for 3 days, impressively altered plasma aldosterone levels. This approach appears to be useful for the study of the acute physiology and control mechanisms of aldosterone production in normal and hypertensive man. PMID:4307457

  4. Aldosterone sensitizes connecting tubule glomerular feedback via the aldosterone receptor GPR30

    PubMed Central

    Ren, YiLin; D'Ambrosio, Martin A.; Garvin, Jeffrey L.; Leung, Pablo; Kutskill, Kristopher; Wang, Hong; Peterson, Edward L.

    2014-01-01

    Increasing Na delivery to epithelial Na channels (ENaC) in the connecting tubule (CNT) dilates the afferent arteriole (Af-Art), a process we call connecting tubule glomerular feedback (CTGF). We hypothesize that aldosterone sensitizes CTGF via a nongenomic mechanism that stimulates CNT ENaC via the aldosterone receptor GPR30. Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing luminal NaCl in the CNT. During the control period, the concentration of NaCl that elicited a half-maximal response (EC50) was 37.0 ± 2.0 mmol/l; addition of aldosterone 10−8 mol/l to the CNT lumen caused a left-shift (decrease) in EC50 to 19.3 ± 1.3 mmol/l (P = 0.001 vs. control; n = 6). Neither the transcription inhibitor actinomycin D nor the translation inhibitor cycloheximide prevented the effect of aldosterone (control EC50 = 34.7 ± 1.9 mmol/l; aldosterone+actinomycin D EC50 = 22.6 ± 1.6 mmol/l; P < 0.001 and control EC50 = 32.4 ± 4.3 mmol/l; aldosterone+cycloheximide EC50 = 17.4 ± 3.3 mmol/l; P < 0.001). The aldosterone antagonist eplerenone prevented the sensitization of CTGF by aldosterone (control EC50 = 33.2 ± 1.7 mmol/l; aldosterone+eplerenone EC50 = 33.5 ± 1.3 mmol/l; n = 7). The GPR30 receptor blocker G-36 blocked the sensitization of CTGF by aldosterone (aldosterone EC50 = 16.5 ± 1.9 mmol/l; aldosterone+G-36 EC50 = 29.0 ± 2.1 mmol/l; n = 7; P < 0.001). Finally, we found that the sensitization of CTGF by aldosterone was mediated, at least in part, by the sodium/hydrogen exchanger (NHE). We conclude that aldosterone in the CNT lumen sensitizes CTGF via a nongenomic effect involving GPR30 receptors and NHE. Sensitized CTGF induced by aldosterone may contribute to renal damage by increasing Af-Art dilation and glomerular capillary pressure (glomerular barotrauma). PMID:24966088

  5. Effects of Vitamin D Supplementation on Plasma Aldosterone and Renin-A Randomized Placebo-Controlled Trial.

    PubMed

    Grübler, Martin R; Gaksch, Martin; Kienreich, Katharina; Verheyen, Nicolas; Schmid, Johannes; Ó Hartaigh, Bríain W J; Richtig, Georg; Scharnagl, Hubert; Meinitzer, Andreas; Pieske, Burkert; Fahrleitner-Pammer, Astrid; März, Winfried; Tomaschitz, Andreas; Pilz, Stefan

    2016-07-01

    Increasing evidence describes a possible interplay between vitamin D insufficiency with increased aldosterone. The authors sought to evaluate the effect of vitamin D supplementation on plasma aldosterone concentration (PAC) in patients with hypertension and 25-hydroxyvitamin D[25(OH)D] insufficiency. The Styrian Vitamin D Hypertension Trial was a single-center, double-blind, placebo-controlled randomized clinical trial conducted from 2011 to 2014. Two hundred patients with arterial hypertension and 25(OH)D levels <30 ng/mL were enrolled. Study participants were randomized to receive either 2800 IU of vitamin D3 or placebo. The present investigation is a post hoc analysis using analysis of covariance adjusting for baseline differences. A total of 188 participants (mean±standard deviation age, 60.1±11.3 years; 47% women; 25(OH)D, 21.2±5.6 ng/mL) completed the trial. Mean differences between baseline and follow-up PAC in the control and intervention arm were +3.3 ng/dL and +0.9 ng/dL, respectively (P=.04). The findings indicate that vitamin D3 supplementation significantly decreases PAC in patients with arterial hypertension and 25(OH)D insufficiency. PMID:27098193

  6. Comparison of eplerenone and spironolactone for the treatment of primary aldosteronism.

    PubMed

    Karashima, Shigehiro; Yoneda, Takashi; Kometani, Mitsuhiro; Ohe, Masashi; Mori, Shunsuke; Sawamura, Toshitaka; Furukawa, Kenji; Seta, Takashi; Yamagishi, Masakazu; Takeda, Yoshiyu

    2016-03-01

    The mineralocorticoid receptor (MR) is expressed in the kidneys and in adipose tissue, and primary aldosteronism (PA) is associated with metabolic syndrome. This study assessed the effects of MR blockade by eplerenone (EPL) and spironolactone (SPL) on blood pressure (BP) and metabolic factors in patients with PA. Fifty-four patients with PA were treated with one of two MRAs, EPL (25-100 mg daily, n=27) or SPL (12.5-100 mg daily, n=27) for 12 months. Visceral (VAT) and subcutaneous adipose tissue were quantified using CT and FatScan imaging analysis software. Body mass index, homeostasis model assessment-insulin resistance (HOMA-IR), serum creatinine, potassium and lipids, urinary albumin excretion (UAE) and plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were measured before and after treatment. EPL and SPL decreased BP and increased serum potassium levels to similar degrees. PAC and PRA did not differ between the two groups. Although treatment with the MRAs did not change HOMA-IR or serum lipids, they significantly decreased UAE and VAT (P<0.05). These results suggest that EPL and SPL are effective and safe for the treatment of PA. The long-term metabolic and renal effects of these MRAs should be further investigated. PMID:26606875

  7. Diurnal variability of polycyclic aromatic compound (PAC) concentrations: Relationship with meteorological conditions and inferred sources

    NASA Astrophysics Data System (ADS)

    Alam, Mohammed S.; Keyte, Ian J.; Yin, Jianxin; Stark, Christopher; Jones, Alan M.; Harrison, Roy M.

    2015-12-01

    Polycyclic aromatic hydrocarbons (PAH) and their nitro and oxy derivatives have been sampled every three hours over one week in winter at two sites in Birmingham UK. One site is heavily influenced by road traffic and is close to residential dwellings, while the other site is a background urban location at some distance from both sources of emission. The time series of concentrations has been examined along with the ratio of concentrations between the two sampling sites. A comparison of averaged diurnal profiles has shown different patterns of behaviour which has been investigated through calculating ratios of concentration at 18:00-21:00 h relative to that at 06:00-09:00 h. This allows identification of those compounds with a strong contribution to a traffic-related maximum at 06:00-09:00 h which are predominantly the low molecular weight PAHs, together with a substantial group of quinones and nitro-PAHs. Changes in partitioning between vapour and particulate forms are unlikely to influence the ratio as the mean temperature at both times was almost identical. Most compounds show an appreciable increase in concentrations in the evening which is attributed to residential heating emissions. Compounds dominated by this source show high ratios of 18:00-21:00 concentrations relative to 06:00-09:00 concentrations and include higher molecular weight PAH and a substantial group of both quinones and nitro-PAH. The behaviour of retene, normally taken as an indicator of biomass burning, is suggestive of wood smoke only being one contributor to the evening peak in PAH and their derivatives, with coal combustion presumably being the other main contributor. Variations of PAH concentrations with wind speed show a dilution behaviour consistent with other primary pollutants, and high concentrations of a range of air pollutants were observed in an episode of low temperatures and low wind speeds towards the end of the overall sampling period consistent with poor local dispersion

  8. Changes in plasma angiotensin II, aldosterone, arginine vasotocin, corticosterone, and electrolyte concentrations during acclimation to dry condition and seawater in the crab-eating frog.

    PubMed

    Uchiyama, Minoru; Maejima, Sho; Wong, Marty K S; Preyavichyapugdee, Narin; Wanichanon, Chaitip; Hyodo, Susumu; Takei, Yoshio; Matuda, Kouhei

    2014-01-01

    The crab-eating frog Fejervarya cancrivora inhabits mangrove swamps and marshes in Southeast Asia. In the present study, circulating angiotensin II (Ang II), aldosterone (Aldo), arginine vasotocin (AVT), and corticosterone (Cort) concentrations as well as various blood parameters were studied under osmotically stressful conditions. Following acclimation to hyperosmotic seawater and dry condition for 5days, body weight was significantly decreased. Under both conditions, plasma Na(+), Cl(-), and urea concentrations, hematocrit values (Ht; blood volume indicator), and osmolality were significantly increased. Dehydration associated with hypovolemic and hyperosmotic states of body fluids was induced during acclimation to hyperosmotic seawater and dry condition in the crab-eating frogs. Ang II, Aldo, AVT, and Cort were maintained within relatively narrow concentration ranges in the control frogs; however, in frogs under dry and hyperosmotic seawater conditions, large variations were observed among individuals in each group. Mean plasma Ang II and Aldo concentrations significantly increased in hyperosmotic seawater-acclimated and desiccated frogs. Although mean plasma AVT concentrations in dehydrated frogs of both the groups were approximately 2.0-3.5 times higher than those in the control frogs, the differences were not significant because of the variation. There was a significant correlation between plasma osmolality and AVT as well as Ang II but not Aldo. A significant correlation was also observed between Ht and AVT as well as Ang II. Plasma Ang II was significantly correlated with plasma Aldo. These results indicate that the crab-eating frogs may exhibit similar physiological responses to both seawater-acclimated and dry conditions. It appears that under dehydrated conditions, osmoregulatory mechanisms participate in stabilization of the situation. The renin-angiotensin system may have pivotal roles in body fluid regulation under volemic and osmotic stress in the

  9. Effect and mechanism of poly (ADP-ribose) polymerase-1 in aldosterone-induced apoptosis

    PubMed Central

    QIAO, WEIWEI; ZHANG, WEILI; SHAO, SHUHONG; GAI, YUSHENG; ZHANG, MINGXIANG

    2015-01-01

    The present study aimed to investigate the effects of aldosterone on vascular endothelial cells and the viability of poly (ADP-ribose) polymerase 1 (PARP1) in cells, and to examine the molecular mechanisms underlying the effects of aldosterone on vascular endothelial cell injury. Cultured endothelial cells were treated either with different concentrations of aldosterone for the same duration or with the same concentrations of aldosterone for different durations, and the levels of apoptosis and activity of PARP1 in the cells were detected, respectively. Aldosterone receptor antagonists or PARP1 inhibitors were added to cells during treatment with aldosterone and the levels of apoptosis and activity of PARP1 were detected. As the concentration of aldosterone increased or the treatment time increased, the number of apoptotic cells and the activity of PARP1 increased. The aldosterone receptor antagonists and PARP1 inhibitors inhibited the increase of apoptosis and PARP1 activity caused by aldosterone treatment. Aldosterone activated the activity of PARP1 via the aldosterone receptor, inhibiting cell proliferation and inducing apoptosis. Treatment with PARP1 may be used as a target for vascular diseases caused by aldosterone at high concentrations. PMID:25872931

  10. Aldosterone and the conquest of land.

    PubMed

    Colombo, L; Dalla Valle, L; Fiore, C; Armanini, D; Belvedere, P

    2006-04-01

    The sequence of the phylogenetic events that preceded the appearance of aldosterone in vertebrates is described, starting from the ancestral conversion of cytochrome P450s from oxygen detoxification to xenobiotic detoxification and synthesis of oxygenated endobiotics with useful functions in intercellular signalling, such as steroid hormones. At the end of the Silurian period [438-408 million yr ago, (Mya)], a complete set of cytochrome P450s for corticoid synthesis was presumably already available, except for mitochondrial cytochrome P450c18 or aldosterone synthase encoded by CYP11B2. This gene arose by duplication of the CYP11B gene in the sarcopterygian or lobe-finned fish/tetrapod line after its divergence from the actinopterygian or ray-finned fish line 420 Mya, but before the beginning of the colonization of land by tetrapods in the late Devonian period, around 370 Mya. The fact that aldosterone is already present in Dipnoi, which occupy an evolutionary transition between water- and air-breathing but are fully aquatic, suggests that the role of this steroid was to potentiate the corticoid response to hypoxia, rather than to prevent dehydration out of the water. In terrestrial amphibians, there is no differentiation between the secretion rates and gluco- and mineralocorticoid effects of aldosterone and corticosterone. In sauropsids, plasma aldosterone concentrations are much lower than in amphibians, but regulation of salt/water balance is dependent upon both aldosterone and corticosterone, though sometimes with opposed actions. In terrestrial mammals, aldosterone acquires a specific mineralocorticoid function, because its interaction with the mineralocorticoid receptor is protected by the coexpression of the enzyme 11beta-hydroxysteroid dehydrogenase type 2, which inactivates both cortisol and corticosterone. There is evidence that aldosterone can be also synthesized extra-adrenally in brain neurons and cardiac myocytes, which lack this protection and where

  11. Use of piretanide, a new loop diuretic, in cirrhosis with ascites: relationship between the diuretic response and the plasma aldosterone level.

    PubMed Central

    Arroyo, V; Bosch, J; Casamitjana, R; Cabrera, J; Rivera, F; Rodés, J

    1980-01-01

    Twenty patients with cirrhosis and ascites but no renal failure were given piretanide, a new loop diuretic, in order to investigate its efficacy and to relate the diuretic response with the pretreatment plasma aldosterone concentration. Eleven patients responded to piretanide 12 mg/day (equivalent in potency to 80 mg furosemide); there was no response in nine patients. Both groups were similar with regard to liver function, plasma urea, serum creatinine, plasma electrolytes, urine volume, and urine potassium concentration. The basal urinary sodium excretion was significantly higher in those patients who responded (23.6 +/- 5.7 mmol/day vs. 4.3 +/- 1.42 mmol/day; P < 0.01) (M +/- SE). Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were normal or only slightly increased in patients who responded to piretanide (PRA = 1.22 +/- 0.20 ng/ml/h; PAC = 12.25 +/- 2.20 ng/100 ml) and very high in patients who did not respond (PRA = 8.71 +/- 1.18 ng/ml/h; PAC = 84.6 +/- 16.2 ng/100 ml) (P < 0.001). Patients unresponsive to piretanide 12 mg/day also failed to respond when the dose was increased to 24 mg/day. However, the addition of spironolactone, 150 mg/day, to piretanide was followed in these patients by a marked increase in diuresis and natriuresis. These results strongly suggest that the pre-treatment level of aldosterone is an important factor influencing the response to loop diuretics in patients with non-azotaemic cirrhosis and ascites. PMID:7439805

  12. Response Prediction and Influence of Tolvaptan in Chronic Heart Failure Patients Considering the Interaction of the Renin-Angiotensin-Aldosterone System and Arginine Vasopressin.

    PubMed

    Kadota, Muneyuki; Ise, Takayuki; Yagi, Shusuke; Iwase, Takashi; Akaike, Masashi; Ueno, Rie; Kawabata, Yutaka; Hara, Tomoya; Ogasawara, Kozue; Bando, Mika; Bando, Sachiko; Matsuura, Tomomi; Yamaguchi, Koji; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka

    2016-07-27

    The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response. PMID:27357439

  13. Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension.

    PubMed

    Giles, Thomas D; Bakris, George; Oparil, Suzanne; Weber, Michael A; Li, Huiling; Mallick, Madhuja; Bharucha, David B; Chen, ChunLin; Ferguson, William G

    2015-11-01

    After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further. PMID:26362831

  14. Aldosterone, Parathyroid Hormone, and the Use of Renin-Angiotensin-Aldosterone System Inhibitors: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Brown, Jenifer; de Boer, Ian H.; Robinson-Cohen, Cassianne; Siscovick, David S.; Kestenbaum, Bryan; Allison, Matthew

    2015-01-01

    Context: Aldosterone and PTH are implicated in the pathogenesis of cardiovascular and skeletal diseases. An expanding body of evidence supports a bidirectional and positive physiologic relationship between aldosterone and PTH. Large population-based studies confirming this relationship, and whether it may be targeted as a potential method to mitigate the clinical consequences associated with excess aldosterone and PTH, are needed. Objective: We hypothesized that higher aldosterone levels would associate with higher PTH, and that the use of renin-angiotensin-aldosterone system (RAAS) inhibitors would predict lower PTH in a large, multi-ethnic, community-based cohort. Design, Setting, Participants: We conducted cross-sectional analyses of participants in the Multi-Ethnic Study of Atherosclerosis without apparent primary hyperparathyroidism or chronic kidney disease (n = 5668). We evaluated associations of RAAS inhibitor use with PTH concentration among 1888 treated hypertensive participants. We also tested associations of serum aldosterone concentration with PTH concentration among 1547 participants with these measurements. Outcome: Serum PTH concentration. Results: Higher aldosterone associated with higher PTH (β = 0.19 pg/ml per 1 ng/dl of aldosterone, P < .0001), and this finding was most pronounced among those with a primary hyperaldosteronism-like phenotype. There was a stepwise increment in PTH when comparing untreated normotensives, hypertensives using RAAS inhibitors, untreated hypertensives, and treated hypertensives using non-RAAS inhibitors (40.8, 45.0, 46.2, 47.1 pg/ml, respectively). The use of any RAAS inhibitor independently associated with lower PTH (β = −2.327 pg/ml per use of RAAS inhibitor, P = .006), when compared with the use of any non-RAAS inhibitor medication. Conclusions: Higher serum aldosterone concentration is associated with higher serum PTH concentration, and the use of RAAS inhibitors is associated with lower PTH concentration

  15. Metoclopramide inhibits aldosterone biosynthesis in vitro.

    PubMed

    Lauer, C G; Braley, L M; Menachery, A I; Williams, G H

    1982-07-01

    Metoclopramide, a dopaminergic antagonist, has consistently elevated plasma aldosterone levels in vivo. To determine whether this was a direct action of metoclopramide on adrenal steroidogenesis, we examined the response of collagenase-dispersed rat adrenal glomerulosa cells to metoclopramide in vitro. The effect of increasing concentrations of metoclopramide (3 X 10(-10) to 3 X 10(-4) M) on basal as well as angiotensin II (2.4 X 10(-10) to 2.4 X 10(-8) M)-, ACTH (3.5 X 10(-11) M)- and potassium (5.9 meq/liter)-stimulated aldosterone production was evaluated. Metoclopramide caused a dose-related decrease in basal and stimulated aldosterone production (P less than 0.01). In addition, metoclopramide also blocked basal and stimulated corticosterone production (P less than 0.01). This was not due to an irreversible toxic effect, since glomerulosa cells preincubated with 3 X 10(-4) M metoclopramide excluded trypan blue dye and responded to ACTH stimulation. Sodium metabisulfite, an antioxidant present in the metoclopramide preparation, did not contribute to the metoclopramide effect. These results indicate that metoclopramide is an aldosterone antagonist in vitro, contrary to reported data obtained in vivo. Thus, metoclopramide may be a partial dopaminergic agonist: in vitro where dopamine levels are negligible, it is an agonist, whereas in vivo where dopamine concentrations are greater, it is an antagonist. PMID:6282568

  16. Adrenal Venous Sampling: Where Is the Aldosterone Disappearing to?

    SciTech Connect

    Solar, Miroslav; Ceral, Jiri; Krajina, Antonin; Ballon, Marek; Malirova, Eva; Brodak, Milos; Cap, Jan

    2010-08-15

    Adrenal venous sampling (AVS) is generally considered to be the gold standard in distinguishing unilateral and bilateral aldosterone hypersecretion in primary hyperaldosteronism. However, during AVS, we noticed a considerable variability in aldosterone concentrations among samples thought to have come from the right adrenal glands. Some aldosterone concentrations in these samples were even lower than in samples from the inferior vena cava. We hypothesized that the samples with low aldosterone levels were unintentionally taken not from the right adrenal gland, but from hepatic veins. Therefore, we sought to analyze the impact of unintentional cannulation of hepatic veins on AVS. Thirty consecutive patients referred for AVS were enrolled. Hepatic vein sampling was implemented in our standardized AVS protocol. The data were collected and analyzed prospectively. AVS was successful in 27 patients (90%), and hepatic vein cannulation was successful in all procedures performed. Cortisol concentrations were not significantly different between the hepatic vein and inferior vena cava samples, but aldosterone concentrations from hepatic venous blood (median, 17 pmol/l; range, 40-860 pmol/l) were markedly lower than in samples from the inferior vena cava (median, 860 pmol/l; range, 460-4510 pmol/l). The observed difference was statistically significant (P < 0.001). Aldosterone concentrations in the hepatic veins are significantly lower than in venous blood taken from the inferior vena cava. This finding is important for AVS because hepatic veins can easily be mistaken for adrenal veins as a result of their close anatomic proximity.

  17. PACS industry in Korea

    NASA Astrophysics Data System (ADS)

    Kim, Hee-Joung

    2002-05-01

    PACS industry in Korea has been rapidly growing, since government had supported collaborative PACS project between industry and university hospital. In the beginning, PACS industry had focused on developing peripheral PACS solutions, while the Korea PACS society was being formed. A few companies had started developing and installing domestic large-scale full-PACS system for teaching hospitals. Several years later, many hospitals have installed full-PACS system with national policy of reimbursement for PACS exams in November 1999. Both experiences of full-PACS installation and national policy generated tremendous intellectual and technological expertise about PACS at all levels, clinical, hospital management, education, and industrial sectors. There are now more than 20 domestic PACS companies. They have enough experiences which are capable of installing a truly full-PACS system for large-scale teaching hospitals. As an example, a domestic company had installed more than 40 full-PACS systems within 2-3 years. Enough experiences of full-PACS installation in Korea lead PACS industry to start exporting their full-PACS solutions. However, further understanding and timely implementation of continuously evolving international standard and integrated healthcare enterprise concepts may be necessary for international leading of PACS technologies for the future.

  18. The metabolism and secretion of aldosterone in elderly subjects.

    PubMed

    Flood, C; Gherondache, C; Pincus, G; Tait, J F; Tait, S A; Willoughby, S

    1967-06-01

    The secretion rates [34 +/- 6 (SE) mug per day, 9 subjects] and metabolic clearance rates (MCR) [1,288 +/- 120 (SE) L of plasma per day, 9 subjects] of aldosterone in elderly subjects are significantly lower than those of young subjects [77 +/- 7 (SE) mug per day and 1,631 +/- 106 (SE) L per day, respectively]. There is a correlation of the MCR and secretion rate values (p = 0.02), but the calculated plasma concentrations (secretion rate/MCR) are also significantly low in the elderly subjects [2.6 +/- 0.3 (SE) compared with concentrations in the plasma from young subjects of 4.7 +/- 0.6 (SE) mug per 100 ml plasma]. The urinary excretion of radioactivity from oral and intravenously administered labeled aldosterone as aldosterone in the neutral extract, as aldosterone released by acid hydrolysis, and as tetrahydroaldosterone released by incubation with beta-glucuronidase is generally similar for young and elderly subjects except that a larger portion of the oral compared with the intravenous dose is excreted as free aldosterone in the elderly subjects, indicating that the splanchnic extraction is reduced. The calculated splanchnic blood flow (assuming no alteration in extrasplanchnic metabolism) is also slightly lowered. Therefore, as in patients with mild cardiac dysfunction, the lowered MCR of subjects is due to both reduced splanchnic extraction and blood flow. However, unlike the heart failure patients, in the elderly subjects the plasma concentration of aldosterone is also reduced. PMID:6026101

  19. Intracellular mediators of potassium-induced aldosterone secretion

    SciTech Connect

    Ganguly, A.; Chiou, S.; Davis, J.S. )

    1990-01-01

    We have investigated the intracellular messengers of potassium in eliciting aldosterone secretion in calf adrenal glomerulosa cells since there were unresolved issues relating to the role of phosphoinositides, cAMP and protein kinases. We observed no evidence of hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}) in {sup 3}H-inositol labeled alf adrenal cells or increase of cAMP in response to potassium. Addition of calcium channel blocker, nitrendipine after stimulating adrenal glomerulosa cells with potassium, markedly inhibited aldosterone secretion. A calmodulin inhibitor (W-7) produced greater reduction of aldosterone secretion than an inhibitor of protein kinase C (H-7). These results suggest that a rise in cytosolic free calcium concentration through voltage-dependent calcium channel and calmodulin are the critical determinants of aldosterone secretion stimulated by potassium.

  20. Global and Renal-Specific Sympathoinhibition in Aldosterone Hypertension

    PubMed Central

    Lohmeier, Thomas E.; Liu, Boshen; Hildebrandt, Drew A.; Cates, Adam W.; Georgakopoulos, Dimitrios; Irwin, Eric D.

    2015-01-01

    Recent technology for chronic electrical activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12µg/kg/day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ~ 40% and arterial pressure by 16±2 mmHg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mmHg) was diminished (~ 55%) during aldosterone hypertension as compared to control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy. PMID:25895584

  1. Global- and renal-specific sympathoinhibition in aldosterone hypertension.

    PubMed

    Lohmeier, Thomas E; Liu, Boshen; Hildebrandt, Drew A; Cates, Adam W; Georgakopoulos, Dimitrios; Irwin, Eric D

    2015-06-01

    Recent technology for chronic electric activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12 μg/kg per day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ≈40% and arterial pressure by 16±2 mm Hg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mm Hg) was diminished (≈55%) during aldosterone hypertension when compared with control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy. PMID:25895584

  2. Cortisol and aldosterone comparisons of cottontail rabbits collected by shooting, trapping, and falconry.

    PubMed

    Hamilton, G D; Weeks, H P

    1985-01-01

    Cortisol and aldosterone levels were measured in plasma of eastern cottontail rabbits (Sylvilagus floridanus) collected by three different methods, i.e., shooting, live-trapping and falconry. Cortisol levels ranged from near 0 to 27.5 micrograms/100 ml and aldosterone from near 0 to 220 ng/100 ml. Shot animals had significantly lower cortisol concentrations than those taken by either of the other methods. Trapped cottontails also had significantly lower aldosterone levels. PMID:3981742

  3. Effects of aldosterone on transient outward K+ current density in rat ventricular myocytes

    PubMed Central

    Bénitah, Jean-Pierre; Perrier, Emeline; Gómez, Ana María; Vassort, Guy

    2001-01-01

    Aldosterone, a major ionic homeostasis regulator, might also regulate cardiac ion currents. Using the whole-cell patch-clamp technique, we investigated whether aldosterone affects the 4-aminopyridine-sensitive transient outward K+ current (Ito1). Exposure to 100 nm aldosterone for 48 h at 37 °C produced a 1.6-fold decrease in the Ito1 density compared to control myocytes incubated without aldosterone. Neither the time- nor voltage-dependent properties of the current were significantly altered after aldosterone treatment. RU28318 (1 μm), a specific mineralocorticoid receptor antagonist, prevented the aldosterone-induced decrease in Ito1 density. When myocytes were incubated for 24 h with aldosterone, concentrations up to 1 μm did not change Ito1 density, whereas L-type Ca2+ current (ICa,L) density increased. After 48 h, aldosterone caused a further increase in ICa,L. The delay in the Ito1 response to aldosterone might indicate that it occurs secondary to an increase in ICa,L. After 24 h of aldosterone pretreatment, further co-incubation for 24 h either with an ICa,L antagonist (100 nm nifedipine) or with a permeant Ca2+ chelator (10 μm BAPTA-AM) prevented a decrease in Ito1 density. After 48 h of aldosterone treatment, we observed a 2.5-fold increase in the occurrence of spontaneous Ca2+ sparks, which was blunted by co-treatment with nifedipine. We conclude that aldosterone decreases Ito1 density. We suggest that this decrease is secondary to the modulation of intracellular Ca2+ signalling, which probably arises from the aldosterone-induced increase in ICa,L. These results provide new insights into how cardiac ionic currents are modulated by hormones. PMID:11711569

  4. Impact of Aldosterone-Producing Adenoma on Endothelial Function and Rho-Associated Kinase Activity in Patients With Primary Aldosteronism

    PubMed Central

    Matsumoto, Takeshi; Oki, Kenji; Kajikawa, Masato; Nakashima, Ayumu; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Kohno, Nobuoki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Noma, Kensuke; Liao, James K.; Higashi, Yukihito

    2016-01-01

    The purpose of this study was to evaluate vascular function and activity of Rho-associated kinases in patients with primary aldosteronism. Vascular function, including flow-mediated vasodilation and nitroglycerine-induced vasodilation, and Rho-associated kinase activity in peripheral leukocytes were evaluated in 21 patients with aldosterone-producing adenoma, 23 patients with idiopathic hyperaldosteronism, and 40 age-, gender-, and blood pressure-matched patients with essential hypertension. Flow-mediated vasodilation was significantly lower in the aldosterone-producing adenoma group than in the idiopathic hyperaldosteronism and essential hypertension groups (3.2±2.0% vs. 4.6±2.3% and 4.4±2.2%, P<0.05, respectively), whereas there was no significant difference in flow-mediated vasodilation between the idiopathic hyperaldosteronism and essential hypertension groups. There was no significant difference in nitroglycerine-induced vasodilation in the three groups. Rho-associated kinase activity was higher in the aldosterone-producing adenoma group than in the idiopathic hyperaldosteronism and essential hypertension groups (1.29±0.57 vs. 1.00±0.46 and 0.81±0.36, P<0.05, respectively), whereas there was no significant difference in Rho-associated kinase activity between the idiopathic hyperaldosteronism and essential hypertension groups. Flow-mediated vasodilation correlated with age (r=−0.31, P<0.01), plasma aldosterone concentration (r=−0.35, P<0.01) and aldosterone to renin ratio (r=−0.34, P<0.01). Rho-associated kinase activity correlated with age (r=−0.24, P=0.04), plasma aldosterone concentration (r=0.33, P<0.01) and aldosterone to renin ratio (r=0.46, P<0.01). After adrenalectomy, flow-mediated vasodilation and Rho-associated kinase activity were restored in aldosterone-producing adenoma patients. Aldosterone-producing adenoma was associated with both endothelial dysfunction and increased Rho-associated kinase activity compared with those in

  5. Zero gravity and cardiovascular homeostasis. The relationship between endogenous hyperprolactinemia and plasma aldosterone

    NASA Technical Reports Server (NTRS)

    Haber, E.; Re, R. N.; Kourides, I. A.; Weihl, A. C.; Maloof, F.

    1978-01-01

    Prolactin, thyrotropin and aldosterone were measured by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in normal women before and after the intravenous injection of 200 micrograms of thyrotropin releasing hormone. Prolactin increased at 15 minutes following thyrotropin releasing hormone. Plasma renin activity was not different from control levels during the first hour following the administration of thyrotropin releasing hormone, nor did the plasma aldosterone concentration differ significantly from the control levels during this period. However, with upright posture, an increase in aldosterone and in plasma renin activity was noted, demonstrating a normal capacity to secrete aldosterone. Similarly, no change in aldosterone was seen in 9 patients with primary hypothyroidism given thyrotropin releasing hormone, despite the fact that the increase in prolactin was greater than normal. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

  6. Effects of aldosterone on insulin sensitivity and secretion

    PubMed Central

    Luther, James M.

    2014-01-01

    Dr. Conn originally reported an increased risk of diabetes in patients with hyperaldosteronism in the 1950’s, although the mechanism remains unclear. Aldosterone-induced hypokalemia was initially described to impair glucose tolerance by impairing insulin secretion. Correction of hypokalemia by potassium supplementation only partially restored insulin secretion and glucose tolerance, however. Aldosterone also impairs glucose-stimulated insulin secretion in isolated pancreatic islets via reactive oxygen species in a mineralocorticoid receptor-independent manner. Aldosterone-induced mineralocorticoid receptor activation also impairs insulin sensitivity in adipocytes and skeletal muscle. Aldosterone may produce insulin resistance secondarily by altering potassium, increasing inflammatory cytokines, and reducing beneficial adipokines such as adiponectin. Renin-angiotensin system antagonists reduce circulating aldosterone concentrations and also the risk of type 2 diabetes in clinical trials. These data suggest that primary and secondary hyperaldosteronism may contribute to worsening glucose tolerance by impairing insulin sensitivity or insulin secretion in humans. Future studies should define the effects of MR antagonists and aldosterone on insulin secretion and sensitivity in humans. PMID:25194457

  7. Evaluation of aldosterone excretion in very low birth weight infants.

    PubMed

    Abdel Mohsen, Abdel Hakeem; Taha, Gamal; Kamel, Bothina A; Maksood, Mohamed Abdel

    2016-01-01

    Data about aldosterone production and excretion in the neonatal period are still few and controversial. Our objectives are to assess urinary aldosterone excretion (UAE) in very low birth weight (VLBW) infants and to identify clinical and biochemical variables that may influence this excretion. Thirty VLBW infants (14 males and 16 females), their gestational age <32 weeks and body weight <1500 g, were included in the study. Demographic and clinical data were recorded, within the first 72 h of life and urine and blood samples were collected for the measurement of urinary aldosterone and serum potassium, sodium, and chloride. The mean UAE value was 0.176 ± 0.05 μg/24 h and the mean absolute UAE was 1906 ± 271 pg/mL. There was a statistically significant positive correlation between UAE and gestational age and birth weight; also, infants with respiratory distress syndrome had higher urinary aldosterone levels than infants without respiratory distress. Only plasma sodium was a significant independent factor that negatively influenced UAE on linear regression analysis. The renin-angiotensin-aldosterone system of VLBW infants seems to be able, even immediately after birth, to respond to variations of plasma sodium concentrations; measurement of UAE constitutes an interesting method to determine aldosterone production in VLBW infants. PMID:27424689

  8. The predictability of renin-angiotensin-aldosterone system factors for clinical outcome in patients with acute decompensated heart failure.

    PubMed

    Nakada, Yasuki; Takahama, Hiroyuki; Kanzaki, Hideaki; Sugano, Yasuo; Hasegawa, Takuya; Ohara, Takahiro; Amaki, Makoto; Funada, Akira; Yoshida, Akemi; Yasuda, Satoshi; Ogawa, Hisao; Anzai, Toshihisa

    2016-06-01

    Although counter-regulation between B-type natriuretic peptide (BNP) levels and renin-angiotensin-aldosterone system (RAAS) activation in heart failure (HF) has been suggested, whether the regulation is preserved in acute decompensated heart failure (ADHF) patients remains unclear. This study aimed to determine: (1) the relationship between RAAS activation and clinical outcomes in ADHF patients, and (2) the relationships between plasma BNP levels and degrees of activation in RAAS factors. This study included ADHF patients (n = 103, NYHA3-4, plasma BNP > 200 pg/ml). We studied the predictability of RAAS factors for cardiovascular events and the relationships between plasma BNP levels and the degrees of activation in RAAS factors, which were evaluated by plasma renin activity (PRA) and aldosterone concentration (PAC). PRA was a strong predictor of cardiovascular (CV) events over 1 year, even after accounting for plasma BNP levels (hazard ratio (HR): 1.04, CI [1.02-1.06], p < 0.01) and medication such as RAAS blockers (HR: 1.03, CI [1.01-1.05], p < 0.01), whereas PAC was borderline-significant (univariate analysis, p = 0.06). Cut-off value of PRA (5.3 ng/ml/h) was determined by AUC curve. Of the enrolled patients, higher PRA was found in 40 % of them. Although no correlation between the plasma BNP levels and PRA was found (p = 0.36), after adjusting for hemodynamic parameters, eGFR and medication, a correlation was found between them (p = 0.01). Elevated RAAS factors were found in a substantial number of ADHF patients with high plasma BNP levels in the association with hemodynamic state, which predicts poor clinical outcomes. The measurements of RAAS factors help to stratify ADHF patients at risk for further CV events. PMID:25964073

  9. Laboratory investigation of primary aldosteronism.

    PubMed

    Stowasser, Michael; Taylor, Paul J; Pimenta, Eduardo; Ahmed, Ashraf H Al-Asaly; Gordon, Richard D

    2010-05-01

    Availability and wider application of the plasma aldosterone/renin ratio (ARR) as a screening test for primary aldosteronism (PA) has led to the recognition that PA is the most common potentially curable and specifically treatable form of hypertension, possibly accounting for as many as 5-13% of patients. Aldosterone excess also has adverse cardiovascular consequences that go above and beyond hypertension development. These findings support the concept that PA plays an important role in cardiovascular disease states and should be systematically sought and specifically treated, and have led to the development of a US Endocrine Society clinical guideline for the detection, diagnosis and management of this condition. Reliable detection requires that interfering factors (including medications known to alter the ratio) are controlled before ARR measurement (or their effects taken into account), and reliable methods such as fludrocortisone suppression testing are used to confirm PA. Because computed tomography frequently misses aldosterone-producing adenomas yet demonstrates non-functioning nodules, adrenal venous sampling is the only dependable way to differentiate unilateral (surgically correctable) from bilateral (usually treated with aldosterone antagonist medications) forms of PA. For the glucocorticoid-remediable form of PA (familial hyperaldosteronism type I), genetic testing for the causative 'hybrid' 11beta-hydroxylase/aldosterone synthase gene has greatly facilitated detection. Laboratory assessment (including suppression testing post-operatively, and renin measurement during treatment with aldosterone antagonist medications) can assist in assessing therapeutic responses and in guiding ongoing management. Development of new, highly reliable high-throughput mass spectrometric methods for measuring aldosterone and renin should further enhance detection and reliability of diagnostic workup for PA. PMID:20498828

  10. Within-patient reproducibility of the aldosterone: renin ratio in primary aldosteronism.

    PubMed

    Rossi, Gian Paolo; Seccia, Teresa Maria; Palumbo, Gaetana; Belfiore, Anna; Bernini, Giampaolo; Caridi, Graziella; Desideri, Giovambattista; Fabris, Bruno; Ferri, Claudio; Giacchetti, Gilberta; Letizia, Claudio; Maccario, Mauro; Mallamaci, Francesca; Mannelli, Massimo; Patalano, Anna; Rizzoni, Damiano; Rossi, Ermanno; Pessina, Achille Cesare; Mantero, Franco

    2010-01-01

    The plasma aldosterone concentration:renin ratio (ARR) is widely used for the screening of primary aldosteronism, but its reproducibility is unknown. We, therefore, investigated the within-patient reproducibility of the ARR in a prospective multicenter study of consecutive hypertensive patients referred to specialized centers for hypertension in Italy. After the patients were carefully prepared from the pharmacological standpoint, the ARR was determined at baseline in 1136 patients and repeated after, on average, 4 weeks in the patients who had initially an ARR > or =40 and in 1 of every 4 of those with an ARR <40. The reproducibility of the ARR was assessed with Passing and Bablok and Deming regression, coefficient of reproducibility, and Bland-Altman and Mountain plots. Within-patient ARR comparison was available in 268 patients, of whom 49 had an aldosterone-producing adenoma, on the basis of the "4-corner criteria." The ARR showed a highly significant within-patient correlation (r=0.69; P<0.0001) and reproducibility. Bland-Altman plot showed no proportional, magnitude-related, or absolute systematic error between the ARR; moreover, only 7% of the values, for example, slightly more than what could be expected by chance, fell out of the 95% CI for the between-test difference. The accuracy of each ARR for pinpointing aldosterone-producing adenoma patients was approximately 80%. Thus, although it was performed under different conditions in a multicenter study, the ARR showed a good within-patient reproducibility. Hence, contrary to previously claimed poor reproducibility of the ARR, these data support its use for the screening of primary aldosteronism. PMID:19933925

  11. Up-regulation of FGF23 release by aldosterone.

    PubMed

    Zhang, Bingbing; Umbach, Anja T; Chen, Hong; Yan, Jing; Fakhri, Hajar; Fajol, Abul; Salker, Madhuri S; Spichtig, Daniela; Daryadel, Arezoo; Wagner, Carsten A; Föller, Michael; Lang, Florian

    2016-02-01

    The fibroblast growth factor (FGF23) plasma level is high in cardiac and renal failure and is associated with poor clinical prognosis of these disorders. Both diseases are paralleled by hyperaldosteronism. Excessive FGF23 levels and hyperaldosteronism are further observed in Klotho-deficient mice. The present study explored a putative aldosterone sensitivity of Fgf23 transcription and secretion the putative involvement of the aldosterone sensitive serum & glucocorticoid inducible kinase SGK1, SGK1 sensitive transcription factor NFκB and store operated Ca(2+) entry (SOCE). Serum FGF23 levels were determined by ELISA in mice following sham treatment or exposure to deoxycorticosterone acetate (DOCA) or salt depletion. In osteoblastic UMR106 cells transcript levels were quantified by qRT-PCR, cytosolic Ca(2+) concentration utilizing Fura-2-fluorescence, and SOCE from Ca(2+) entry following store depletion by thapsigargin. As a result, DOCA treatment and salt depletion of mice elevated the serum C-terminal FGF23 concentration. In UMR106 cells aldosterone enhanced and spironolactone decreased SOCE. Aldosterone further increased Fgf23 transcript levels in UMR106 cells, an effect reversed by mineralocorticoid receptor blockers spironolactone and eplerenone, SGK1 inhibitor EMD638683, NFκB-inhibitor withaferin A, and Ca(2+) channel blocker YM58483. In conclusion, Fgf23 expression is up-regulated by aldosterone, an effect sensitive to SGK1, NFκB and store-operated Ca(2+) entry. PMID:26773502

  12. Primary aldosteronism and pregnancy.

    PubMed

    Landau, Ester; Amar, Laurence

    2016-06-01

    Hypertension (HT) is a complication of 8% of all pregnancies and 10% of HT cases are due to primary aldosteronism (PA). There is very little data on PA and pregnancy. Given the changes in the renin angiotensin system during pregnancy, the diagnosis of PA is difficult to establish during gestation. It may be suspected in hypertensive patients with hypokalemia. A comprehensive literature review identified reports covering 40 pregnancies in patients suffering from PA. Analysis of these cases shows them to be high-risk pregnancies leading to maternal and fetal complications. Pregnancy must be programmed, and if the patient has a unilateral form of PA, adrenalectomy should be performed prior to conception. It is customary to stop spironolactone prior to conception and introduce antihypertensive drugs that present no risk of teratogenicity. When conventional antihypertensive drugs used during pregnancy fail to control high blood pressure, diuretics, including potassium-sparing diuretics may be prescribed. Adrenalectomy can be considered during the second trimester of pregnancy exclusively in cases of refractory hypertension. A European retrospective study is currently underway to collect a larger number of cases. PMID:27156905

  13. Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism.

    PubMed

    Umakoshi, Hironobu; Naruse, Mitsuhide; Wada, Norio; Ichijo, Takamasa; Kamemura, Kohei; Matsuda, Yuichi; Fujii, Yuichi; Kai, Tatsuya; Fukuoka, Tomikazu; Sakamoto, Ryuichi; Ogo, Atsushi; Suzuki, Tomoko; Nanba, Kazutaka; Tsuiki, Mika

    2016-05-01

    Adrenal venous sampling is considered to be the most reliable diagnostic procedure to lateralize aldosterone excess in primary aldosteronism (PA). However, normative criteria have not been established partially because of a lack of data in non-PA hypertensive patients. The aim of the study was to investigate aldosterone concentration and its gradient in the adrenal vein of non-PA hypertensive patients. We retrospectively studied the results of cosyntropin-stimulated adrenal venous sampling in 40 hypertensive patients who showed positive screening testing but negative results in 2 confirmatory tests/captopril challenge test and saline infusion test. Plasma aldosterone concentration, aldosterone/cortisol ratio, its higher/lower ratio (lateralization index) in the adrenal vein with cosyntropin stimulation were measured. Median plasma aldosterone concentration in the adrenal vein was 25 819 pg/mL (range, 5154-69 920) in the higher side and 12 953 (range, 1866-36 190) pg/mL in the lower side (P<0.001). There was a significant gradient in aldosterone/cortisol ratio between the higher and the lower sides (27.2 [5.4-66.0] versus 17.3 [4.0-59.0] pg/mL per μg/dL;P<0.001) with lateralization index ranging from 1.01 to 3.87. The aldosterone lateralization gradient was between 1 to 2 in 32 patients and 2 to 4 in 8 patients. None of the patients showed lateralization index ≥4. The present study demonstrated that plasma aldosterone concentration in the adrenal veins showed significant variation and lateralization gradient even in non-PA hypertensive patients. Adrenal venous sampling aldosterone lateralization gradients between 2 and 4 should be interpreted with caution in patients with PA because these gradients can be found even in patients with negative confirmatory testing for PA. PMID:26975712

  14. The Metabolism and Secretion of Aldosterone in Elderly Subjects*

    PubMed Central

    Flood, C.; Gherondache, C.; Pincus, G.; Tait, J. F.; Tait, S. A. S.; Willoughby, S.

    1967-01-01

    The secretion rates [34 ± 6 (SE) μg per day, 9 subjects] and metabolic clearance rates (MCR) [1,288 ± 120 (SE) L of plasma per day, 9 subjects] of aldosterone in elderly subjects are significantly lower than those of young subjects [77 ± 7 (SE) μg per day and 1,631 ± 106 (SE) L per day, respectively]. There is a correlation of the MCR and secretion rate values (p = 0.02), but the calculated plasma concentrations (secretion rate/MCR) are also significantly low in the elderly subjects [2.6 ± 0.3 (SE) compared with concentrations in the plasma from young subjects of 4.7 ± 0.6 (SE) μg per 100 ml plasma]. The urinary excretion of radioactivity from oral and intravenously administered labeled aldosterone as aldosterone in the neutral extract, as aldosterone released by acid hydrolysis, and as tetrahydroaldosterone released by incubation with β-glucuronidase is generally similar for young and elderly subjects except that a larger portion of the oral compared with the intravenous dose is excreted as free aldosterone in the elderly subjects, indicating that the splanchnic extraction is reduced. The calculated splanchnic blood flow (assuming no alteration in extrasplanchnic metabolism) is also slightly lowered. Therefore, as in patients with mild cardiac dysfunction, the lowered MCR of subjects is due to both reduced splanchnic extraction and blood flow. However, unlike the heart failure patients, in the elderly subjects the plasma concentration of aldosterone is also reduced. PMID:6026101

  15. Endocrine effects of lithium. III. Hypermagnesaemia and activation of the renin-aldosterone system.

    PubMed

    Transbøl, I; Christiansen, C; Baastrup, P C; Nielsen, M D; Giese, J

    1978-07-01

    Hypermagnesaemia is a well-known but as yet unexplained concomitant of lithium treatment. Prior suggestions implicating a role for aldosterone in magnesium homoeostasis prompted this study of plasma renin, plasma aldosterone and serum magnesium in 17 maniodepressive patients on long-term lithium treatment. In addition to hypermagnesaemia (P less than 0.001), this group of patients had raised plasma levels of aldosterone (P less than 0.001) and increased plasma renin concentration (P less than 0.05). Serum magnesium was positively correlated to plasma aldosterone (r = 0.58, P less than 0.02). The relation between activation of the renin-aldosterone system and the presence of hypermagnesaemia during chronic lithium treatment could conceivably be mediated through a lithium-induced hypovolaemic state. PMID:581026

  16. Rapid Induction of Aldosterone Synthesis in Cultured Neonatal Rat Cardiomyocytes under High Glucose Conditions

    PubMed Central

    Nagoshi, Tomohisa; Nishikawa, Tetsuo; Date, Taro; Yoshimura, Michihiro

    2013-01-01

    In addition to classical adrenal cortical biosynthetic pathway, there is increasing evidence that aldosterone is produced in extra-adrenal tissues. Although we previously reported aldosterone production in the heart, the concept of cardiac aldosterone synthesis remains controversial. This is partly due to lack of established experimental models representing aldosterone synthase (CYP11B2) expression in robustly reproducible fashion. We herein investigated suitable conditions in neonatal rat cardiomyocytes (NRCMs) culture system producing CYP11B2 with considerable efficacy. NRCMs were cultured with various glucose doses for 2–24 hours. CYP11B2 mRNA expression and aldosterone concentrations secreted from NRCMs were determined using real-time PCR and enzyme immunoassay, respectively. We found that suitable conditions for CYP11B2 induction included four-hour incubation with high glucose conditions. Under these particular conditions, CYP11B2 expression, in accordance with aldosterone secretion, was significantly increased compared to those observed in the cells cultured under standard-glucose condition. Angiotensin II receptor blocker partially inhibited this CYP11B2 induction, suggesting that there is local renin-angiotensin-aldosterone system activation under high glucose conditions. The suitable conditions for CYP11B2 induction in NRCMs culture system are now clarified: high-glucose conditions with relatively brief period of culture promote CYP11B2 expression in cardiomyocytes. The current system will help to accelerate further progress in research on cardiac tissue aldosterone synthesis. PMID:24288663

  17. Effect of aldosterone-producing adenoma on endothelial function and Rho-associated kinase activity in patients with primary aldosteronism.

    PubMed

    Matsumoto, Takeshi; Oki, Kenji; Kajikawa, Masato; Nakashima, Ayumu; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Kohno, Nobuoki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Noma, Kensuke; Liao, James K; Higashi, Yukihito

    2015-04-01

    The purpose of this study was to evaluate vascular function and activity of Rho-associated kinases (ROCKs) in patients with primary aldosteronism. Vascular function, including flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation, and ROCK activity in peripheral leukocytes were evaluated in 21 patients with aldosterone-producing adenoma (APA), 23 patients with idiopathic hyperaldosteronism (IHA), and 40 age-, sex-, and blood pressure-matched patients with essential hypertension (EHT). FMD was significantly lower in the APA group than in the IHA and EHT groups (3.2±2.0% versus 4.6±2.3% and 4.4±2.2%; P<0.05, respectively), whereas there was no significant difference in FMD between the IHA and EHT groups. There was no significant difference in nitroglycerine-induced vasodilation in the 3 groups. ROCK activity was higher in the APA group than in the IHA and EHT groups (1.29±0.57 versus 1.00±0.46 and 0.81±0.36l; P<0.05, respectively), whereas there was no significant difference in ROCK activity between the IHA and EHT groups. FMD correlated with age (r=-0.31; P<0.01), plasma aldosterone concentration (r=-0.35; P<0.01), and aldosterone:renin ratio (r=-0.34; P<0.01). ROCK activity correlated with age (r=-0.24; P=0.04), plasma aldosterone concentration (r=0.33; P<0.01), and aldosterone:renin ratio (r=0.46; P<0.01). After adrenalectomy, FMD and ROCK activity were restored in patients with APA. APA was associated with both endothelial dysfunction and increased ROCK activity compared with those in IHA and EHT. APA may have a higher risk of future cardiovascular events. PMID:25624340

  18. Adipocytes, aldosterone and obesity-related hypertension.

    PubMed

    Dinh Cat, Aurelie Nguyen; Friederich-Persson, Malou; White, Anna; Touyz, Rhian M

    2016-07-01

    Understanding the mechanisms linking obesity with hypertension is important in the current obesity epidemic as it may improve therapeutic interventions. Plasma aldosterone levels are positively correlated with body mass index and weight loss in obese patients is reported to be accompanied by decreased aldosterone levels. This suggests a relationship between adipose tissue and the production/secretion of aldosterone. Aldosterone is synthesized principally by the adrenal glands, but its production may be regulated by many factors, including factors secreted by adipocytes. In addition, studies have reported local synthesis of aldosterone in extra-adrenal tissues, including adipose tissue. Experimental studies have highlighted a role for adipocyte-secreted aldosterone in the pathogenesis of obesity-related cardiovascular complications via the mineralocorticoid receptor. This review focuses on how aldosterone secretion may be influenced by adipose tissue and the importance of these mechanisms in the context of obesity-related hypertension. PMID:27357931

  19. Recent Developments in Primary Aldosteronism.

    PubMed

    Asbach, E; Williams, T A; Reincke, M

    2016-06-01

    Primary aldosteronism (PA) is the most frequent endocrine cause of secondary arterial hypertension. Sporadic forms of PA caused mainly by an aldosterone producing adenoma (APA) or idiopathic adrenal hyperplasia (IAH) predominate; in contrast, familial forms (familial hyperaldosteronism types I, II and III) affect only a minor proportion of PA patients. Patient based registries and biobanks, international networks and next generation sequencing technologies have emerged over recent years. Somatic hot-spot mutations in the potassium channel GIRK4 (encoded by KCNJ5), in ATPases and a L-type voltage-gated calcium-channel correlate with the autonomous aldosterone production in approximately half of all APAs. The recently discovered form FH III is caused by different germline KCNJ5 mutations with variable clinical presentations and severity. Autoantibodies to the angiotensin II Type 1 receptor have been identified in patients with PA and possibly play a pathophysiological role in the development of PA. Adrenal vein sampling (AVS) represents the gold standard in differentiating unilateral and bilateral forms of PA. Recent consensus papers have tried to implement current guidelines in order to standardise the technique of AVS. New techniques like segmental AVS might allow a finer mapping of the aldosterone production within the adrenal gland. The measurement of the steroids 18-hydroxycortisol and 18-oxocortisol by liquid chromatography tandem mass spectrometry has been shown to be useful to distinguish between unilateral and bilateral forms of PA. PMID:27219889

  20. PACS on mobile devices

    NASA Astrophysics Data System (ADS)

    Parikh, Ashesh; Mehta, Nihal

    2015-03-01

    Recent advances in internet browser technologies makes it possible to incorporate advanced functionality of a traditional PACS for viewing DICOM medical images on standard web browsers without the need to pre-install any plug-ins, apps or software. We demonstrate some of the capabilities of standard web browsers setting the stage for a cloud-based PACS.

  1. PACS for GU radiology

    NASA Astrophysics Data System (ADS)

    Hayrapetian, Alek S.; Barbaric, Zoran L.; Weinberg, Wolfram S.; Chan, Kelby K.; Loloyan, Mansur; Taira, Ricky K.; Huang, H. K.

    1991-07-01

    The authors have developed a PACS module for genito-urinary radiology. This module is based on image acquisition subsystem, database and storage server/cluster controllers, communication networks, display workstation and local database, and dedicated digitizer and printer. The design guideline for this system is generality and flexibility. As such this module serves as a prototype for future PACS module designs.

  2. Secretory function of the renin-aldosterone system in patients with anorexia nervosa.

    PubMed

    Fujita, M; Tamai, H; Mizuno, O; Nakagawa, T

    1991-01-20

    Patients with anorexia nervosa frequently demonstrate dehydration, electrolyte imbalance and low blood pressure that are secondary to starvation. Hyperactivity of the Renin-Aldosterone system and insensitivity to the pressor effects of exogenous angiotensin II are observed in Pseudo-Bartter syndrome caused by the abuse of diuretics or laxatives and self-induced vomiting, however, little information about the Renin-Aldosterone system has been reported in patients with anorexia nervosa. This study was designed to investigate the secretory function of the Renin-Aldosterone system in anorexia nervosa. The subjects were 13 patients with anorexia nervosa and 6 normal controls. Experiment 1: Angiotensin II infusion test was performed. Blood pressure was measured every 5 minutes, and the samples for plasma renin and serum aldosterone analysis were taken every 15 minutes during infusion test. Experiment 2: Plasma renin activity and serum aldosterone concentration were measured before and after one-hour walking. The results were as follows; (1) Basal plasma renin activity and serum aldosterone concentration in patients were not significantly higher than those in normal subjects. (2) Hypertensive response with elevation of the diastolic pressure during angiotensin II infusion in patients similar to that of normal subjects was observed. (3) Responses of plasma renin activity and serum aldosterone concentration after one-hour walking were significantly greater in patients than in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2013346

  3. Does Aldosterone Play a Significant Role for Regulation of Vascular Tone?

    PubMed

    Lyngsø, Kristina S; Assersen, Kasper; Dalgaard, Emil G; Skott, Ole; Jensen, Boye L; Hansen, Pernille B L

    2016-07-01

    Besides the well-known renal effects of aldosterone, the hormone is now known to have direct vascular effects. Clinical observations underline substantial adverse effects of aldosterone on cardiovascular function. The source of systemic circulating aldosterone is the adrenal gland zona glomerulosa cells through stimulus-secretion coupling involving depolarization, opening of L- and T-type calcium channels and aldosterone synthase activation. Local formation and release in peripheral tissues such as perivascular fat is recognized. Where does aldosterone affect the vasculature? Mineralocorticoid receptors (MRs) are present in endothelial and vascular smooth muscle cells, and MR-independent pathways are also involved. The vascular effects of aldosterone are complex, both concentration and temporal and spatial aspects are relevant. The acute response includes vasodilation through endothelial nitric oxide formation and vasoconstrictor effects through endothelial-contracting cyclooxygenase-derived factors and a changed calcium handling. The response to aldosterone can change within the same blood vessels depending on the exposure time and status of the endothelium. Chronic responses involve changed levels of reactive oxygen radicals, endothelial Na-influx and smooth muscle calcium channel expression. Furthermore, perivascular cells for example mast cells have also been suggested to participate in the chronic response. Moreover, the vascular effect of aldosterone depends on the status of the endothelium which is likely the cause of the very different responses to aldosterone and MR treatment observed in human studies going from increased to decreased flow depending on whether the patient had prior cardiovascular disease with endothelial dysfunction or not. A preponderance of constrictor versus dilator responses to aldosterone could therefore be involved in the detrimental vascular actions of the hormone in the setting of endothelial dysfunction and contribute to explain

  4. [Aldosterone/renin ratio in the diagnosis of primary aldosteronism].

    PubMed

    Ríos, María Carolina; Izquierdo, Anahí; Sotelo, Mercedes; Honnorat, Egle; Rodríguez Cuimbra, Silvia; Catay, Erika; Popescu, Bogdan M

    2011-01-01

    Primary aldosteronism (PA) is a possible cause of endocrine hypertension. Recent studies have suggested a prevalence ranging between 5% and 15% of all hypertensive patients, and 20% in patients with refractory hypertension.The objective of this transversal study was to establish the prevalence of PA in a hypertensive population using the aldosterone / plasma renin ratio (ARR) as a screening method, considering that the prevalence rates for PA among hypertensive people present a wide range and that there are only few reports in Argentina. This ratio was then related with the degree of hypertension and with the presence or absence of hypokalemia. Serum aldosterone and plasma renin activity levels were measured in 123 hypertensive patients after discontinuing all medications that could interfere with the hormonal tests. Patients with an aldosterone/plasma renin activity ratio > 25 were submitted to the saline suppression test (SST) to confirm the diagnosis of PA, followed by computed tomography (CT) of the abdomen. Twenty patients presented an ARR > 25 (16.4%). Eighteen were submitted to the SST, eight had a diagnosis of PA confirmed with positive SST (6.5%). Of 8 patients who underwent an abdominal CT, two showed adenoma, and six normal adrenal anatomy. All the eight patients with a PA diagnosis belonged to group II and III of hypertension according to Joint National Committee VI (JNC VI), and only 4 (50%) were normokalemic. We found a 6.5% prevalence of PA, associated with grade II and III hypertension, and normal potassium values in half of the patients with PA. PMID:22167725

  5. The future of PACS.

    PubMed

    Nagy, Paul G

    2007-07-01

    How will the future of picture archiving and communication systems (PACS) look, and how will this future affect the practice of radiology? We are currently experiencing disruptive innovations that will force an architectural redesign, making the majority of today's commercial PACS obsolete as the field matures and expands to include imaging throughout the medical enterprise. The common architecture used for PACS cannot handle the massive amounts of data being generated by even current versions of computed tomography and magnetic resonance scanners. If a PACS cannot handle today's technology, what will happen as the field expands to encompass pathology imaging, cone-beam reconstruction, and multispectral imaging? The ability of these new technologies to enhance research and clinical care will be impaired if PACS architectures are not prepared to support them. In attempting a structured approach to predictions about the future of PACS, we offer projections about the technologies underlying PACS as well as the evolution of standards development and the changing needs of a broad range of medical imaging. Simplified models of the history of the PACS industry are mined for the assumptions they provide about future innovations and trends. The physicist frequently participates in or directs technical assessments for medical equipment, and many physicists have extended these activities to include imaging informatics. It is hoped that by applying these speculative but experienced-based predictions, the interested medical physicist will be better able to take the lead in setting information technology strategies that will help facilities not only prepare for the future but continue to enjoy the benefits of technological innovations without disruptive, expensive, and unexpected changes in architecture. A good PACS strategy can help accelerate the time required for innovations to go from the drawing board to clinical implementation. PMID:17821975

  6. Ginsenoside Rg1 reduces aldosterone-induced autophagy via the AMPK/mTOR pathway in NRK-52E cells.

    PubMed

    Wang, Li; Mao, Nan; Tan, Rui-Zhi; Wang, Hong-Lian; Wen, Ji; Liu, Yu-Hang; Furhad, Md; Fan, Jun-Ming

    2015-08-01

    Aldosterone is a steroid hormone secreted from the adrenal cortex, which regulates blood pressure. Higher concentrations of aldosterone can cause several diseases, including hypertension, diabetic nephropathy and chronic kidney disease. Previous reports have demonstrated that aldosterone has a pathogenic role in renal injury via reactive oxygen species (ROS), which involves the regulation of autophagy. However, whether aldosterone can induce autophagy in renal tubular cells remains to be elucidated. In the present study, elevated autophagy was observed in rat renal tubular NRK-52E cells exposed to aldosterone, which was demonstrated by the increased number of autophagosomes, conversion of LC3-I to LC3-II and the expression of Beclin-1. The enhanced autophagy was accompanied by increased production of intracellular ROS, which was reversed by N-acetylcysteine, a specific inhibitor of ROS signaling. Furthermore, treatment with ginsenoside Rg1 reduced the aldosterone-induced autophagy and production of ROS, possibly through reducing the phosphorylation of AMPK and preserving mTOR activity. These findings demonstrated that aldosterone promoted ROS generation and increased autophagy in the NRK-52E cells. Ginsenoside Rg1 effectively relieved aldosterone-induced oxidative stress and abnormal autophagy, suggesting that Rg1 may be used as a potential therapeutic drug to inhibit the renal injury, which is induced by aldosterone. PMID:26063203

  7. The role of urinary aldosterone for the diagnosis of primary aldosteronism.

    PubMed

    Ceral, J; Malirova, E; Ballon, M; Solar, M

    2014-08-01

    When diagnosing primary aldosteronism, the measurement of urinary aldosterone after oral sodium loading is one of the currently recommended confirmatory tests. The aim of the study was to assess the repeatability and interpretation of urinary aldosterone in patients examined for suspected primary aldosteronism. Sixty-four hypertensive patients with suspected primary aldosteronism were prospectively enrolled and examined according to the study protocol. After antihypertensive medications interfering with renin-angiotensin-aldosterone system were withdrawn for at least 2 weeks, the confirmatory testing was performed: oral sodium loading preceded the collection of 24-h urine sample and subsequent saline infusion test. The identical procedures were repeated after 2 weeks. The concordant results of both saline infusion tests served for confirmation/exclusion of primary aldosteronism. Forty-nine patients were included in data analysis. Primary aldosteronism was excluded in 16, and confirmed in 33 individuals. The repeatability of urinary aldosterone was evaluated in 44 patients: the difference of urinary aldosterone levels ranged between 1 and 88% (median 31%). Ninety-three urine samples from 49 patients were used to validate the interpretation of urinary aldosterone in respect to the diagnosis of primary aldosteronism made by saline infusion testing; 96% sensitivity was characterized by urinary aldosterone ≥19 nmol/day, and 96% specificity was associated with urinary aldosterone ≥92 nmol/day. In 22 (45%) patients, urinary aldosterone remained in the "gray" zone between 19 and 92 nmol/day in all provided samples. The estimation of urinary aldosterone excretion after oral sodium loading is associated with marked intraindividual variability, and significant number of inconclusive results. PMID:24810470

  8. Comparison of two radioimmunoassay kits for aldosterone determination.

    PubMed

    Sampson, E J; Derck, D D; Demers, L M

    1976-08-01

    Two commercially available radioimmunoassay kits for aldosterone determination not requiring preliminary chromatographic purification were examined. Aldosterone standard curve solutions prepared from the CIS kit, Nuclear International Corp., (x-axis) and Diagnostic Products kit (y-axis) were assayed with both kits and the results yielded a regression equation of y = 0.834x + 0.08 nmol/liter. Analytical recovery experiments with aldosterone added to urine and serum showed 120% and 101% recovery with the CIS kit, respectively, and 92% and 92% recovery with the Diagnostic Products kit, respectively. Both kits demonstrated good parallelism with urine and serum. Antibody specificity was tested with six structurally related steroids and each kit showed virtually no cross-reactivity at clinically normal serum concentrations. Serum aldosterone values were compared before (y-axis) and after (x-axis) column chromatography on Sephadex LH-20, with the following regression equations: y = 1.070x + 0.092 nmol/liter for the CIS kit and y = 1.023x + 0.093 nmol/liter for the Diagnostic Products kit. Regression equations comparing patient samples between kits, CIS (x-axis) and Diagnostic Products (y-axis), were: y = 0.832x + 0.007 mumol/24 h with urine and y = 0.850x + 0.097 nmol/liter with serum. PMID:954186

  9. Aldosterone Antagonists in Monotherapy Are Protective against Streptozotocin-Induced Diabetic Nephropathy in Rats

    PubMed Central

    Banki, Nora F.; Ver, Agota; Wagner, Laszlo J.; Vannay, Adam; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya-Nagy; Kenesei, Eva; Rosta, Klara; Reusz, Gyorgy; Szabo, Attila J.; Tulassay, Tivadar; Baylis, Chris; Fekete, Andrea

    2012-01-01

    Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. PMID:22761931

  10. Aldosterone antagonists in monotherapy are protective against streptozotocin-induced diabetic nephropathy in rats.

    PubMed

    Banki, Nora F; Ver, Agota; Wagner, Laszlo J; Vannay, Adam; Degrell, Peter; Prokai, Agnes; Gellai, Renata; Lenart, Lilla; Szakal, Dorottya-Nagy; Kenesei, Eva; Rosta, Klara; Reusz, Gyorgy; Szabo, Attila J; Tulassay, Tivadar; Baylis, Chris; Fekete, Andrea

    2012-01-01

    Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers. PMID:22761931

  11. Aldosterone perturbs adiponectin and PAI-1 expression and secretion in 3T3-L1 adipocytes.

    PubMed

    Li, P; Zhang, X-N; Pan, C-M; Sun, F; Zhu, D-L; Song, H-D; Chen, M-D

    2011-06-01

    Aldosterone is considered as a new cardiovascular risk factor that plays an important role in metabolic syndrome; however, the underlying mechanism of these effects is not clear. Hypoadiponectinemia and elevated circulating concentration of plasminogen activator inhibitor-1 (PAI-1) are causally associated with obesity-related insulin resistance and cardiovascular disease. The aim of the present study is to investigate the effect of aldosterone on the production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Northern and Western blot analyses revealed that aldosterone treatment inhibited adiponectin mRNA expression and secretion and simultaneously enhanced PAI-1 mRNA expression and secretion in a time- and dose-dependent manner. Rosiglitazone did not prevent aldosterone's effect on adiponectin or PAI-1 expression. In contrast, tumor necrosis factor (TNF)-α produced dramatic synergistic effects on adiponectin and PAI-1 expression when added together with aldosterone. Furthermore, the effects of aldosterone on adiponectin and PAI-1 expression appear to be mediated through glucocorticoid receptor (GR) but not mineralocorticoid receptor (MR). These results suggest that the effects of aldosterone on adiponectin and PAI-1 production are one of the underlying mechanisms linking it to insulin resistance, metabolic syndrome and cardiovascular disease. PMID:21667402

  12. PACS image security server

    NASA Astrophysics Data System (ADS)

    Cao, Fei; Huang, H. K.

    2004-04-01

    Medical image security in a PACS environment has become a pressing issue as communications of images increasingly extends over open networks, and hospitals are currently hard-pushed by Health Insurance Portability and Accountability Act (HIPAA) to be HIPPA complaint for ensuring health data security. Other security-related guidelines and technical standards continue bringing to the public attention in healthcare. However, there is not an infrastructure or systematic method to implement and deploy these standards in a PACS. In this paper, we first review DICOM Part15 standard for secure communications of medical images and the HIPAA impacts on PACS security, as well as our previous works on image security. Then we outline a security infrastructure in a HIPAA mandated PACS environment using a dedicated PACS image security server. The server manages its own database of all image security information. It acts as an image Authority for checking and certificating the image origin and integrity upon request by a user, as a secure DICOM gateway to the outside connections and meanwhile also as a PACS operation monitor for HIPAA supporting information.

  13. Interleukin-18 deficiency protects against renal interstitial fibrosis in aldosterone/salt-treated mice.

    PubMed

    Tanino, Akiko; Okura, Takafumi; Nagao, Tomoaki; Kukida, Masayoshi; Pei, Zuowei; Enomoto, Daijiro; Miyoshi, Ken-Ichi; Okamura, Haruki; Higaki, Jitsuo

    2016-10-01

    Interleukin (IL)-18 is a member of the IL-1 family of cytokines and was described originally as an interferon γ-inducing factor. Aldosterone plays a central role in the regulation of sodium and potassium homoeostasis by binding to the mineralocorticoid receptor and contributes to kidney and cardiovascular damage. Aldosterone has been reported to induce IL-18, resulting in cardiac fibrosis with induced IL-18-mediated osteopontin (OPN). We therefore hypothesized that aldosterone-induced renal fibrosis via OPN may be mediated by IL-18. To verify this hypothesis, we compared mice deficient in IL-18 and wild-type (WT) mice in a model of aldosterone/salt-induced hypertension. IL-18(-/-) and C57BL/6 WT mice were used for the uninephrectomized aldosterone/salt hypertensive model, whereas NRK-52E cells (rat kidney epithelial cells) were used in an in vitro model. In the present in vivo study, IL-18 protein expression was localized in medullary tubules in the WT mice, whereas in aldosterone-infused WT mice this expression was up-regulated markedly in the proximal tubules, especially in injured and dilated tubules. This renal damage caused by aldosterone was attenuated significantly by IL-18 knockout with down-regulation of OPN expression. In the present in vitro study, aldosterone directly induced IL-18 gene expression in renal tubular epithelial cells in a concentration- and time-dependent manner. These effects were inhibited completely by spironolactone. IL-18 may be a key mediator of aldosterone-induced renal fibrosis by inducing OPN, thereby exacerbating renal interstitial fibrosis. Inhibition of IL-18 may therefore provide a potential target for therapeutic intervention aimed at preventing the progression of renal injury. PMID:27413021

  14. Evaluation of the effects of occupational noise exposure on serum aldosterone and potassium among industrial workers.

    PubMed

    Zare, Sajad; Nassiri, Parvin; Monazzam, Mohammad Reza; Pourbakht, Akram; Azam, Kamal; Golmohammadi, Taghi

    2016-01-01

    The existing literature indicates that occupational exposure to noise may have adverse effects on workers' health. The aim of this study was to evaluate the possible effects of exposure to different sound pressure levels (SPLs) on serum aldosterone and potassium concentration among Iranian blue collar workers in Golgohar Mining and Industrial Company in Sirjan, Kerman Province, Iran. This case-control study was performed on 45 workers of Golgohar Mining and Industrial Company. The subjects consisted of 30 workers from manufacturing departments and 15 office employees of the mining company. The controls, mainly with administrative jobs were exposed to 72 dBA SPL. Cases, in two separate groups, were exposed to noise levels of 88 dBA and 103 dBA, respectively. Noise intensity was measured at the desired locations. Noise measurements were performed according to the International Organization for Standardization (ISO) 9612. To measure the serum aldosterone and potassium concentrations, a 5 mL blood sample was taken from each worker at the specified time intervals and aldosterone concentration was determined using enzyme-linked immunosorbent assay (ELISA) test in the laboratory. Repeated measurement and Spearman's correlation coefficient analysis were used with α = 0.05. Exposure to the different levels of sound pressure resulted in different aldosterone concentrations and meanwhile an increase in the SPL did not affect the concentration of potassium. From 10:00 AM to 10:30 AM, as SPL increased, aldosterone concentrations did not increase significantly but from 13:30 PM to 14:00 PM, raised SPL led to a significant increase in aldosterone concentration. However, there was no correlation between the concentration of potassium and different factors. This study indicated that increases in SPLs affect aldosterone concentration but at the same time do not have significant effects on serum potassium level. PMID:26780955

  15. Evaluation of the effects of occupational noise exposure on serum aldosterone and potassium among industrial workers

    PubMed Central

    Zare, Sajad; Nassiri, Parvin; Monazzam, Mohammad Reza; Pourbakht, Akram; Azam, Kamal; Golmohammadi, Taghi

    2016-01-01

    The existing literature indicates that occupational exposure to noise may have adverse effects on workers’ health. The aim of this study was to evaluate the possible effects of exposure to different sound pressure levels (SPLs) on serum aldosterone and potassium concentration among Iranian blue collar workers in Golgohar Mining and Industrial Company in Sirjan, Kerman Province, Iran. This case-control study was performed on 45 workers of Golgohar Mining and Industrial Company. The subjects consisted of 30 workers from manufacturing departments and 15 office employees of the mining company. The controls, mainly with administrative jobs were exposed to 72 dBA SPL. Cases, in two separate groups, were exposed to noise levels of 88 dBA and 103 dBA, respectively. Noise intensity was measured at the desired locations. Noise measurements were performed according to the International Organization for Standardization (ISO) 9612. To measure the serum aldosterone and potassium concentrations, a 5 mL blood sample was taken from each worker at the specified time intervals and aldosterone concentration was determined using enzyme-linked immunosorbent assay (ELISA) test in the laboratory. Repeated measurement and Spearman's correlation coefficient analysis were used with α = 0.05. Exposure to the different levels of sound pressure resulted in different aldosterone concentrations and meanwhile an increase in the SPL did not affect the concentration of potassium. From 10:00 AM to 10:30 AM, as SPL increased, aldosterone concentrations did not increase significantly but from 13:30 PM to 14:00 PM, raised SPL led to a significant increase in aldosterone concentration. However, there was no correlation between the concentration of potassium and different factors. This study indicated that increases in SPLs affect aldosterone concentration but at the same time do not have significant effects on serum potassium level. PMID:26780955

  16. Modulation of aldosterone levels by -344 C/T CYP11B2 polymorphism and spironolactone use in resistant hypertension.

    PubMed

    Fontana, Vanessa; de Faria, Ana Paula Cabral; Barbaro, Natália Ruggeri; Sabbatini, Andréa Rodrigues; Modolo, Rodrigo; Lacchini, Riccardo; Moreno, Heitor

    2014-03-01

    Interindividual variability in plasma aldosterone levels comprises environmental and genetic sources. Increased aldosterone levels have been associated with higher risk of hypertension and target-organ damage related to hypertension. Aldosterone excess and intravascular volume expansion are implicated in pathophysiology of resistant hypertension (RH). We sought to investigate whether -344 C/T polymorphism (rs1799998) in aldosterone synthase gene (CYP11B2) is associated with plasma aldosterone levels in patients with resistant hypertension. Sixty-two patients with resistant hypertension were enrolled in this cross-sectional study. Genotypes were obtained by allelic discrimination assay using real time polymerase chain reaction. Multivariable linear regression was used to identify whether TT genotype was a predictor of aldosterone levels. No differences in clinical and laboratorial parameters were found among genotype groups. We found an additive effect of the T allele on plasma aldosterone concentration in RH. Also, there was higher aldosterone levels in TT homozygous under use of spironolactone compared with C carriers and compared with TT subjects who was not under use of spironolactone. TT genotype and the use of spironolactone were significant predictors of aldosterone levels in RH subjects. Plasma aldosterone concentration is significantly associated with -344 C/T CYP11B2 polymorphism and with the treatment with spironolactone in resistant hypertensive subjects. PMID:24388430

  17. Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families.

    PubMed

    Kuipers, Allison L; Kammerer, Candace M; Pratt, J Howard; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Zmuda, Joseph M

    2016-05-01

    Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (bothP<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension. PMID:26975710

  18. Endocrine and Hypertensive Disorders of Potassium Regulation: Primary Aldosteronism

    PubMed Central

    Weiner, I. David

    2013-01-01

    The identification that primary aldosteronism is a common cause of resistant hypertension is a significant advance in our ability to care for patients with hypertension. Primary aldosteronism is common, and when unrecognized is associated with increased incidence of adverse cardiovascular outcomes. Identification of primary aldosteronism is based upon use of the plasma aldosterone level, plasma renin activity and the aldosterone:renin ratio (ARR). Differentiation between unilateral and bilateral autonomous adrenal aldosterone production then guides further therapy, with use of mineralocorticoid receptor blockers for those with bilateral autonomous adrenal aldosterone production and laparoscopic adrenalectomy for those with unilateral autonomous aldosterone production. In this review, we discuss in detail the pathogenesis of primary aldosteronism-induced hypertension and potassium disorders, the evaluation of the patient with suspected primary aldosteronism and the management of primary aldosteronism, both through medications and through surgery. PMID:23953804

  19. Reversed association between aldosterone and mortality in hemodialysis patients: Role of volume overload.

    PubMed

    Hung, Szu-Chun; Tarng, Der-Cherng

    2016-07-01

    The role of aldosterone has expanded from its genomic effects that involve renal sodium transport to nongenomic effects such as cardiac and renal fibrosis. Elevated aldosterone levels are associated with increased mortality in the general population. However, the association is reversed in patients with end-stage renal disease on maintenance hemodialysis. We have shown that the inverse association between aldosterone and mortality in hemodialysis patients is due to the confounding effect of volume overload. Volume overload, which is prevalent in patients with chronic kidney disease, is associated with both lower aldosterone concentrations and higher mortality. Our findings support salt and water restriction and treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control. PMID:26826322

  20. Acute and Chronic Regulation of Aldosterone Production

    PubMed Central

    Hattangady, Namita; Olala, Lawrence; Bollag, Wendy B.; Rainey, William E.

    2011-01-01

    Aldosterone is the major mineralocorticoid synthesized by the adrenal. Secretion of aldosterone is regulated tightly by the adrenocortical glomerulosa cells due to the selective expression of CYP11B2 in the outermost zone, the zona glomerulosa. Aldosterone is largely responsible for regulation of systemic blood pressure through the absorption of electrolytes and water under the regulation of certain specific agonists. Angiotensin II (Ang II), potassium (K+) and adrenocorticotropin (ACTH) are the main physiological agonists which regulate aldosterone secretion. The mechanisms involved in this process may be regulated minutes after a stimulus (acutely) through increased expression and phosphorylation of the steroidogenic acute regulatory (StAR) protein, over hours to days (chronically) by increased expression of the enzymes involved in the synthesis of aldosterone, particularly aldosterone synthase (CYP11B2). Imbalance in any of these processes may lead to several aldosterone excess disorders. In this review we attempt to summarize the key molecular events involved in and specifically attributed to the acute and chronic phases of aldosterone secretion. PMID:21839803

  1. Familial varieties of primary aldosteronism.

    PubMed

    Stowasser, M; Gunasekera, T G; Gordon, R D

    2001-12-01

    1. Improved approaches to screening and diagnosis have revealed primary aldosteronism (PAL) to be much more common than previously thought, with most patients normokalaemic. The spectrum of this disorder has been further broadened by the study of familial varieties. 2. Familial hyperaldosteronism type I (FH-I) is a glucocorticoid-remediable form of PAL caused by the inheritance of an adrenocorticotrophic hormone (ACTH)- regulated, hybrid CYP11B1/CYP11B2 gene. Diagnosis has been greatly facilitated by the advent of genetic testing. The severity of hypertension varies widely in FH-I, even among members of the same family, and has demonstrated relationships with gender, degree of biochemical disturbance and hybrid gene crossover point position. Hormone "day curve" studies show that the hybrid gene dominates over wild-type CYP11B2 in terms of aldosterone regulation. This may be due, in part, to a defect in wild-type CYP11B2-induced aldosterone production. Control of hypertension in FH-I requires only partial suppression of ACTH and much smaller glucocorticoid doses than previously recommended. 3. Familial hyperaldosteronism type II (FH-II) is not glucocorticoid remediable and is not associated with the hybrid gene mutation. Familial hyperaldosteronism type II is clinically, biochemically and morphologically indistinguishable from apparently non-familial PAL. Linkage studies in one informative family did not show segregation of FH-II with the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL. PMID:11903322

  2. Aldosterone Production and Signaling Dysregulation in Obesity.

    PubMed

    Vecchiola, Andrea; Lagos, Carlos F; Carvajal, Cristian A; Baudrand, Rene; Fardella, Carlos E

    2016-03-01

    In the past decades, we have extended the view of aldosterone effects beyond epithelial tissues. New evidence regarding the aldosterone/mineralocorticoid receptor (MR) pathway in active metabolic tissues, including adipose tissue, has confirmed its pathogenic role in systemic inflammation, endothelial dysfunction, insulin resistance, and dyslipidemia. Obesity, a current epidemic worldwide, increases aldosterone production by several adipocyte factors such as leptin but is also associated with local aldosterone production. In addition, obesity can modulate MR activation leading to signaling dysregulation and a pro-inflammatory profile of adipocytes. Current knowledge have deciphered that this phenotypical differences of obesity may be explained, at least in part, by novel non-genomic activation of MR, new inducers of aldosterone synthesis, and probably by several epigenetic modifications. In addition, with the understanding of the complex interplay of obesity, hormones, and receptors, targeted pharmacological therapy is expected and is currently under active research. PMID:26838033

  3. Influence of aldosterone on collagen synthesis and proliferation of rat cardiac fibroblasts

    PubMed Central

    Rombouts, Krista; Wielant, Annemie; Hellemans, Karine; Schuppan, Detlef; Geerts, Albert

    2001-01-01

    Previous in vivo studies in men and experimental animal models have shown that hyperaldosteronemia is correlated with cardiac fibrosis due to increased total collagen synthesis. As yet, it is unclear whether aldosterone has direct pro-fibrogenic effect on cardiac fibroblasts, the fibrogenic effector cell in the myocardium, and if so which procollagens specifically are synthesized at higher rates. The present study aims at establishing whether de novo collagen synthesis by cardiac fibroblasts is enhanced following exposure for 2×24 h to pharmacological (10−7 – 10−8 M), near-physiological (10−9 M) or physiological (10−10 – 10−11 M) aldosterone concentrations. During the last 24 h, cells were metabolically labelled with [35S]-methionine/[35S]-cysteine. Labelled procollagens were immunoprecipitated quantitatively using antibodies against specific procollagens. Contrary to expectations, 10−7 M aldosterone inhibited significantly de novo synthesis of procollagens type I and IV (−35% and −42%, respectively). For procollagen type III, only a tendency towards inhibition was observed. At lower concentrations of aldosterone (10−8 – 10−10 M), synthesis of procollagens type I, III or IV was unaffected. Cellular DNA synthesis under influence of aldosterone was evaluated by measuring BrdU incorporation. Cells were treated with aldosterone, while BrdU was added during the last 16 h of treatment. Aldosterone had no demonstrable effect on cellular proliferation. Reverse transcription-polymerase chain reaction (RT – PCR) clearly demonstrated the presence of mineralocorticoid receptor mRNA in cardiac fibroblasts. In spite of the expression of the mineralocorticoid receptor by cultured cardiac fibroblasts, the pro-fibrogenic effect of aldosterone as observed in vivo, is not likely to be due to a direct effect of this hormone in cardiac fibroblasts. PMID:11522615

  4. Aldosterone: from biosynthesis to non-genomic action onto the proteome.

    PubMed

    Zöllner, Susanne; Hwang, Kyung Hoon; Wilzewski, Britta; Carapito, Christine; Leize-Wagner, Emmanuelle; Van Dorsselaer, Alain; Bernhardt, Rita

    2008-10-01

    An increased aldosterone concentration can lead to a progression of heart diseases and to myocardial fibrosis. These fatal processes can be prevented by e.g. inhibiting the mineralocorticoid receptor (MR), which is nowadays part of a commonly applied standard therapy. Moreover, selective inhibition of aldosterone synthase (CYP11B2) is a straightforward goal whereby CYP11B1, a key enzyme in glucocorticoid biosynthesis exhibiting a high structure identity with CYP11B2 should not be inhibited. Therefore, effective test systems have been developed and rather potent and selective CYP11B2 compounds like SIAS-1 have been identified by our group. In addition to finding new inhibitors, we investigated which proteins are directly influenced by aldosterone focussing on non-genomic effects. Schizosaccharomyces pombe was chosen as a model organism, since this yeast does not contain nuclear steroid receptors, but many genes and regulatory mechanisms that are close to those of mammals. Besides creating a reference map for this organism, protein spots affected by aldosterone as well as deoxycorticosterone (DOC) and corticosterone have been identified. In case of aldosterone, a regulatory effect of proteins that are connected with structural proteins, signal cascades, osmoregulation and calcium pathway as well as to general metabolism have been discovered. DOC causes overlapping but also different effects compared with aldosterone. As shown exemplarily for GAPDH, the aldosterone-mediated effects in S. pombe can also be verified in mammalian cells. These and further investigations contribute to a deeper understanding of so-called non-genomic aldosterone effects. PMID:18280527

  5. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    SciTech Connect

    Chartier, L.; Schiffrin, E.L.

    1987-04-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC/sub 50/) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC/sub 50/. In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated /sup 45/Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry.

  6. VLDL-activated cell signaling pathways that stimulate adrenal cell aldosterone production.

    PubMed

    Tsai, Ying-Ying; Rainey, William E; Johnson, Maribeth H; Bollag, Wendy B

    2016-09-15

    Aldosterone plays an important role in regulating ion and fluid homeostasis and thus blood pressure, and hyperaldosteronism results in hypertension. Hypertension is also observed with obesity, which is associated with additional health risks, including cardiovascular disease. Obese individuals have high serum levels of very low-density lipoprotein (VLDL), which has been shown to stimulate aldosterone production; however, the mechanisms underlying VLDL-induced aldosterone production are still unclear. Here we demonstrate in human adrenocortical carcinoma (HAC15) cells that submaximal concentrations of angiotensin II and VLDL stimulate aldosterone production in an additive fashion, suggesting the possibility of common mechanisms of action. We show using inhibitors that VLDL-induced aldosterone production is mediated by the PLC/IP3/PKC signaling pathway. Our results suggest that PKC is upstream of the extracellular signal-regulated kinase (ERK) activation previously observed with VLDL. An understanding of the mechanisms mediating VLDL-induced aldosterone production may provide insights into therapies to treat obesity-associated hypertension. PMID:27222295

  7. Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass.

    PubMed Central

    Schunkert, H.; Hense, H. W.; Muscholl, M.; Luchner, A.; Kürzinger, S.; Danser, A. H.; Riegger, G. A.

    1997-01-01

    OBJECTIVE: Cardiac growth may be modulated in part by the trophic effects of neurohormones. The aim of the present study was to investigate the relation between the basal activity of the renin-angiotensin-aldosterone system and left ventricular mass. DESIGN: A population based sample of 615 middle-age subjects was studied by standardised echocardiography; anthropometric measurements; and biochemical quantification of renin, pro-renin, angiotensinogen, angiotensin converting enzyme (ACE), and aldosterone. RESULTS: Echocardiographic left ventricular mass index correlated significantly with arterial blood pressure, age, and body mass index. In addition, in men ACE activity was significantly related to left ventricular mass index in univariate (P = 0.0007) and multivariate analyses (P = 0.008). Men with left ventricular hypertrophy presented with significantly higher serum ACE concentrations than those with normal left ventricular mass index (P = 0.002). In both men and women serum aldosterone was strongly related to septal and posterior wall thickness. Furthermore, in women serum aldosterone was positively and independently associated with left ventricular mass index (P = 0.0001). This effect was most prominent in hypertensive women. Finally, women with left ventricular hypertrophy presented with significantly higher serum aldosterone (P = 0.01). No significant associations with left ventricular mass index were observed for angiotensinogen, renin, or pro-renin. CONCLUSIONS: The data suggest that the variability of serum ACE or aldosterone, as occurred in this large population based sample, may contribute to the modulation of left ventricular mass. Images PMID:9038690

  8. Estimation of urinary aldosterone using thin-layer chromatography and fluorimetry.

    PubMed Central

    Mattingly, D; Martin, H; Tyler, C M

    1993-01-01

    AIMS--To develop a fluorimetric method for the estimation of urinary aldosterone; to establish a normal range in 24 hour and overnight urine samples; and to investigate the use of overnight urines for detecting hyperaldosteronism. METHODS--Essential steps include hydrolysis of the 18 conjugate to release aldosterone and its oxidation with Benedict's solution, followed by thin-layer chromatography on silica gel and development of fluorescence on the plate with sulphuric acid. RESULTS--There was a linear correlation between the amount of aldosterone and the area under the peak on the chromatogram. The mean intra-assay and interassay coefficients of variation were 4.4% and 6.8%, respectively. The mean aldosterone excretion in 67 adults was 15.7 (SD 8.1) nmol/24 hours. The mean overnight excretion in 65 adults was 2.6 (1.4) nmol/8 hours. The method detected raised concentrations in patients with primary and secondary aldosteronism. CONCLUSIONS--This technique provides an accurate means of assaying urinary aldosterone. Overnight estimations seem to be as effective as 24 hour assays for identifying patients with hyperaldosteronism. PMID:8282834

  9. SFE/SFHTA/AFCE primary aldosteronism consensus: Introduction and handbook.

    PubMed

    Amar, Laurence; Baguet, Jean Philippe; Bardet, Stéphane; Chaffanjon, Philippe; Chamontin, Bernard; Douillard, Claire; Durieux, Pierre; Girerd, Xaxier; Gosse, Philippe; Hernigou, Anne; Herpin, Daniel; Houillier, Pascal; Jeunemaitre, Xavier; Joffre, Francis; Kraimps, Jean-Louis; Lefebvre, Hervé; Ménégaux, Fabrice; Mounier-Véhier, Claire; Nussberger, Juerg; Pagny, Jean-Yves; Pechère, Antoinette; Plouin, Pierre-François; Reznik, Yves; Steichen, Olivier; Tabarin, Antoine; Zennaro, Maria-Christina; Zinzindohoue, Franck; Chabre, Olivier

    2016-07-01

    The French Endocrinology Society (SFE) French Hypertension Society (SFHTA) and Francophone Endocrine Surgery Association (AFCE) have drawn up recommendations for the management of primary aldosteronism (PA), based on an analysis of the literature by 27 experts in 7 work-groups. PA is suspected in case of hypertension associated with one of the following characteristics: severity, resistance, associated hypokalemia, disproportionate target organ lesions, or adrenal incidentaloma with hypertension or hypokalemia. Diagnosis is founded on aldosterone/renin ratio (ARR) measured under standardized conditions. Diagnostic thresholds are expressed according to the measurement units employed. Diagnosis is established for suprathreshold ARR associated with aldosterone concentrations >550pmol/L (200pg/mL) on 2 measurements, and rejected for aldosterone concentration<240pmol/L (90pg/mL) and/or subthreshold ARR. The diagnostic threshold applied is different if certain medication cannot be interrupted. In intermediate situations, dynamic testing is performed. Genetic forms of PA are screened for in young subjects and/or in case of familial history. The patient should be informed of the results expected from medical and surgical treatment of PA before exploration for lateralization is proposed. Lateralization is explored by adrenal vein sampling (AVS), except in patients under 35 years of age with unilateral adenoma on imaging. If PA proves to be lateralized, unilateral adrenalectomy may be performed, with adaptation of medical treatment pre- and postoperatively. If PA is non-lateralized or the patient refuses surgery, spironolactone is administered as first-line treatment, replaced by amiloride, eplerenone or calcium-channel blockers if insufficiently effective or poorly tolerated. PMID:27315757

  10. PACS pitfalls and bottlenecks

    NASA Astrophysics Data System (ADS)

    Huang, H. K.; Lou, Shyhliang A.; Wong, Albert W. K.

    1997-05-01

    PACS pitfalls are mostly created from human error, whereas bottlenecks are due to imperfect design in either the PACS or image acquisition devices. These drawbacks can only be realized through accumulated clinical experience. Pitfalls due to human error are often initiated at imaging acquisition devices and at workstations. Three major errors at the acquisition devices are entering wrong input parameters, stopping an image transmission process improperly, and incorrect patient positioning. The error occurring most often at the workstation happens when the user enters too many key strokes or clicks the mouse too often before the workstation can respond. Other pitfalls at the workstation unrelated to human error are missing location markers in a CT or MR scout view, images displayed with unsuitable look-up-tables, and white boarders in CR images due to x-ray collimation. Pitfalls created due to human intervention can be minimized by a better quality assurance program and periodic in-service training, and by interfacing image acquisition devices to the HIS/RIS. Bottlenecks affecting the PACS operation include network contention; CR, CT, and MR images stacked up at acquisition devices; slow response from workstations; and long delays for image retrieval from the long term archive. Bottlenecks can be alleviated by improving the system architecture, re- configuring the networks, and streamlining operational procedures through a gradual understanding of the clinical environment. We have identified most of the pitfalls and bottlenecks discussed above in our hospital-integrated PACS based on the past two years of clinical experience. This paper categorizes some of these problems, illustrates their effect on PACS operations, and suggests methods for circumventing them.

  11. Aldosterone and type 2 diabetes mellitus.

    PubMed

    Zavatta, Guido; Casadio, Elena; Rinaldi, Eleonora; Pagotto, Uberto; Pasquali, Renato; Vicennati, Valentina

    2016-04-01

    Primary hyperaldosteronism (PA) has recently been demonstrated to be strictly associated to metabolic syndrome as compared with essential hypertension (EH). Besides, the characteristics of metabolic syndrome are different in PA compared to EH, as high fasting glucose is more frequent in the former condition. The adverse effect of excess aldosterone on insulin metabolic signaling has generated increasing interest in the role of hyperaldosteronism in the pathogenesis of insulin resistance and resistant hypertension. Moreover, aldosterone receptor antagonist therapy in diabetic and cardiopathic patients improved coronary flow. The aim of this review is to present recent knowledge about the relationship between aldosterone, insulin resistance and diabetes. PMID:26876814

  12. Inflammatory markers in primary aldosteronism.

    PubMed

    Šomlóová, Z; Petrák, O; Rosa, J; Štrauch, B; Indra, T; Zelinka, T; Haluzík, M; Zikán, V; Holaj, R; Widimský, J

    2016-06-20

    Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-alpha and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-alpha (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71-1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35+/-1.42 vs. 5.97+/-1.29 10(9) l); APA vs. IHA: TNF-alpha (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63-1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37+/-1.41 vs. 5.71+/-1.21 10(9) l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] microg/l, p

  13. Serum aldosterone and death, end-stage renal disease, and cardiovascular events in blacks and whites: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

    PubMed

    Deo, Rajat; Yang, Wei; Khan, Abigail M; Bansal, Nisha; Zhang, Xiaoming; Leonard, Mary B; Keane, Martin G; Soliman, Elsayed Z; Steigerwalt, Susan; Townsend, Raymond R; Shlipak, Michael G; Feldman, Harold I

    2014-07-01

    Prior studies have demonstrated that elevated aldosterone concentrations are an independent risk factor for death in patients with cardiovascular disease. Limited studies, however, have evaluated systematically the association between serum aldosterone and adverse events in the setting of chronic kidney disease. We investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort. We also evaluated the association between aldosterone and incident congestive heart failure and atherosclerotic events in participants without baseline cardiovascular disease. Cox proportional hazards models were used to evaluate independent associations between elevated aldosterone concentrations and each outcome. Interactions were hypothesized and explored between aldosterone and sex, race, and the use of loop diuretics and renin-angiotensin-aldosterone system inhibitors. During a median follow-up period of 5.4 years, 587 participants died, 743 developed end-stage renal disease, 187 developed congestive heart failure, and 177 experienced an atherosclerotic event. Aldosterone concentrations (per SD of the log-transformed aldosterone) were not an independent risk factor for death (adjusted hazard ratio, 1.00; 95% confidence interval, 0.93-1.12), end-stage renal disease (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.17), or atherosclerotic events (adjusted hazard ratio, 1.04; 95% confidence interval, 0.85-1.18). Aldosterone was associated with congestive heart failure (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02-1.35). Among participants with chronic kidney disease, higher aldosterone concentrations were independently associated with the development of congestive heart failure but not for death, end-stage renal disease, or atherosclerotic events. Further studies should evaluate whether mineralocorticoid receptor antagonists may reduce adverse events in individuals with

  14. Regulation of aldosterone secretion by Cav1.3.

    PubMed

    Xie, Catherine B; Haris Shaikh, Lalarukh; Garg, Sumedha; Tanriver, Gizem; Teo, Ada E D; Zhou, Junhua; Maniero, Carmela; Zhao, Wanfeng; Kang, Soosung; Silverman, Richard B; Azizan, Elena A B; Brown, Morris J

    2016-01-01

    Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, CaV1.2, over CaV1.3. In H295R cells transfected with wild-type or mutant CaV1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 μM of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 μM). Selective CaV1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of CaV1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of CaV1.3. PMID:27098837

  15. Regulation of aldosterone secretion by Cav1.3

    PubMed Central

    Xie, Catherine B.; Haris Shaikh, Lalarukh; Garg, Sumedha; Tanriver, Gizem; Teo, Ada E. D.; Zhou, Junhua; Maniero, Carmela; Zhao, Wanfeng; Kang, Soosung; Silverman, Richard B.; Azizan, Elena A. B.; Brown, Morris J.

    2016-01-01

    Aldosterone-producing adenomas (APAs) vary in phenotype and genotype. Zona glomerulosa (ZG)-like APAs frequently have mutations of an L-type calcium channel (LTCC) CaV1.3. Using a novel antagonist of CaV1.3, compound 8, we investigated the role of CaV1.3 on steroidogenesis in the human adrenocortical cell line, H295R, and in primary human adrenal cells. This investigational drug was compared with the common antihypertensive drug nifedipine, which has 4.5-fold selectivity for the vascular LTCC, CaV1.2, over CaV1.3. In H295R cells transfected with wild-type or mutant CaV1.3 channels, the latter produced more aldosterone than wild-type, which was ameliorated by 100 μM of compound 8. In primary adrenal and non-transfected H295R cells, compound 8 decreased aldosterone production similar to high concentration of nifedipine (100 μM). Selective CaV1.3 blockade may offer a novel way of treating primary hyperaldosteronism, which avoids the vascular side effects of CaV1.2-blockade, and provides targeted treatment for ZG-like APAs with mutations of CaV1.3. PMID:27098837

  16. Detection, Diagnosis, and Treatment of Primary Aldosteronism

    MedlinePlus

    ... that results when one or both of your adrenal glands (small glands about the size of a prune ... aldosterone is a benign (noncancerous) tumor in one adrenal gland or if both adrenal glands are overactive. A ...

  17. A decreased metabolic clearance rate of aldosterone in benign essential hypertension

    PubMed Central

    Nowaczynski, W.; Kuchel, O.; Genest, J.

    1971-01-01

    Aldosterone secretion rate, metabolic clearance rate, and/or plasma concentration were determined in 16 patients with benign, uncomplicated essential hypertension and compared with those of control subjects. The mean metabolic clearance rate of aldosterone in 10 patients was significantly (P < 0.001) lower (mean 867 liters of plasma/day per m2 ±270 SD) than in a group of 7 healthy subjects (mean 1480 liters/day per m2 ±265 SD). Secretion rates in 13 patients (including the 10 already mentioned) tended to be low (83 ±43 vs. 109 ±54 μg/day) and plasma concentrations tended to be high (13.6 ±4.6 vs. 7.5 ±4.8 ng/100 ml), but neither of these differences was statistically significant. The lower metabolic clearance rate could account for elevated plasma concentrations of aldosterone even when the secretion rate is normal or low. Measurement of secretion rate or urinary excretion only is therefore insufficient to establish the presence and/or mode of evolution of hyperaldosteronism. Failure of the aldosterone secretion to adapt fully to a decreased aldosterone metabolic clearance rate (MCR) could explain the state of relative hyperaldosteronism in patients with benign essential hypertension, even when the secretion rate and the urinary excretion rate are in the normal range. PMID:5116208

  18. Urinary Aldosterone/Creatinine Ratio After Fludrocortisone Suppression Consistent with PHA in a Cat.

    PubMed

    Koutinas, Christos K; Soubasis, Nektarios C; Djajadiningrat-Laanen, Sylvia C; Kolia, Elissavet; Theodorou, Konstantina

    2015-01-01

    A 9 yr old cat was presented with clinical signs and laboratory abnormalities attributed to arterial hypertension (mean systolic arterial pressure, 290 mm Hg). Plasma aldosterone concentration was increased at the time of admission (651 pmol/L), but serum creatinine and potassium concentrations were within the reference range. A second increased aldosterone (879 pmol/L) and normal plasma renin activity (1.85 ng/mL/hr) resulted in an increased aldosterone/renin ratio, which was suggestive of primary hyperaldosteronism (PHA). To further support the diagnosis of PHA, the urinary aldosterone/creatinine ratio was calculated both before and after oral administration of fludrocortisone acetate (0.05 mg/kg q 12 hr for 4 consecutive days). The urinary aldosterone/creatinine ratio was 92.6 × 10(-9) before fludrocortisone administration and 155.8 × 10(-9) 4 days later. Absence of suppression was typical of PHA. The cat had a limited response to antihypertensive medication and died before treatment for PHA could be instituted. A necropsy was not permitted by the owner. PMID:26355586

  19. Aldosterone and aldosterone receptor antagonists in patients with chronic heart failure

    PubMed Central

    Nappi, Jean M; Sieg, Adam

    2011-01-01

    Aldosterone is a mineralocorticoid hormone synthesized by the adrenal glands that has several regulatory functions to help the body maintain normal volume status and electrolyte balance. Studies have shown significantly higher levels of aldosterone secretion in patients with congestive heart failure compared with normal patients. Elevated levels of aldosterone have been shown to elevate blood pressure, cause left ventricular hypertrophy, and promote cardiac fibrosis. An appreciation of the true role of aldosterone in patients with chronic heart failure did not become apparent until the publication of the Randomized Aldactone Evaluation Study. Until recently, the use of aldosterone receptor antagonists has been limited to patients with severe heart failure and patients with heart failure following myocardial infarction. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) study added additional evidence to support the expanded use of aldosterone receptor antagonists in heart failure patients. The results of the EMPHASIS-HF trial showed that patients with mild-to-moderate (New York Heart Association Class II) heart failure had reductions in mortality and hospitalizations from the addition of eplerenone to optimal medical therapy. Evidence remains elusive about the exact mechanism by which aldosterone receptor antagonists improve heart failure morbidity and mortality. The benefits of aldosterone receptor antagonist use in heart failure must be weighed against the potential risk of complications, ie, hyperkalemia and, in the case of spironolactone, possible endocrine abnormalities, in particular gynecomastia. With appropriate monitoring, these risks can be minimized. We now have evidence that patients with mild-to-severe symptoms associated with systolic heart failure will benefit from the addition of an aldosterone receptor antagonist to the standard therapies of angiotensin-converting enzyme inhibitors and beta

  20. Effect of powdered activated carbon (PAC) and cationic polymer on biofouling mitigation in hybrid MBRs.

    PubMed

    Jamal Khan, S; Visvanathan, C; Jegatheesan, V

    2012-06-01

    In this study, the influence of powdered activated carbon (PAC) and cationic polymer (MPE50) was investigated on the fouling propensity in hybrid MBRs. Three laboratory scale MBRs were operated simultaneously including MBR(Control), MBR(PAC), and MBR(Polymer). Optimum dosages of PAC and polymer to the MBR(PAC) and MBR(Polymer), respectively were determined using jar tests. It was found that the MBR(PAC) exhibited low fouling tendency and prolonged filtration as compared to the other MBRs. Improved filtration in MBR(PAC) was attributed to the flocculation and adsorption phenomena. The effective stability of the biomass by PAC in the form of biological activated carbon (BAC) was verified by the increase in mean particle size. The BAC aided sludge layer exhibited porous cake structure resulting in the prolong filtration. However, both the membrane hybrid systems revealed effective adsorption of organic matter by 40% reduction in the soluble EPS concentration. PMID:22264429

  1. PAC spectroscopy of electronic ceramics

    SciTech Connect

    Gardner, J.A.; Wang, Ruiping; Schwenker, R.; Evenson, W.E.; Rasera, R.L.; Sommers, J.A.

    1991-12-31

    Dilute indium dopants in cerium oxides and YBa{sub 2}Cu{sub 3}O{sub x} have been studied by{sup 111}In/Cd Perturbed Angular Correlation (PAC) spectroscopy. By controlling oxygen vacancy concentration in the cerium oxides through doping or high-temperature vacuum annealing, we have found that indium always forms a defect complex unless the sample is doped to reduce greatly the oxygen vacancy concentration. Three different vacancy-associated complexes are found with concentrations that depend on doping and oxygen stoichiometry. Another defect complex occurs in samples having negligible vacancy concentration. At low temperatures, evidence is found of interaction with an electronic hole trapped by {sup 111}Cd after the radioactive decay of the {sup 111}In parent. In YBa{sub 2}Cu{sub 3}O{sub x} the indium substitutes preferentially at the Y site but has measurable probability of substitution in at least one of the two copper sites. A symmetry change near 650 {degree}C is consistent with the well-documented orthorhombic/tetragonal transition for samples in air or oxygen.

  2. PAC spectroscopy of electronic ceramics

    SciTech Connect

    Gardner, J.A.; Wang, Ruiping; Schwenker, R. . Dept. of Physics); Evenson, W.E. . Dept. of Physics and Astronomy); Rasera, R.L. . Dept. of Physics); Sommers, J.A. )

    1991-01-01

    Dilute indium dopants in cerium oxides and YBa{sub 2}Cu{sub 3}O{sub x} have been studied by{sup 111}In/Cd Perturbed Angular Correlation (PAC) spectroscopy. By controlling oxygen vacancy concentration in the cerium oxides through doping or high-temperature vacuum annealing, we have found that indium always forms a defect complex unless the sample is doped to reduce greatly the oxygen vacancy concentration. Three different vacancy-associated complexes are found with concentrations that depend on doping and oxygen stoichiometry. Another defect complex occurs in samples having negligible vacancy concentration. At low temperatures, evidence is found of interaction with an electronic hole trapped by {sup 111}Cd after the radioactive decay of the {sup 111}In parent. In YBa{sub 2}Cu{sub 3}O{sub x} the indium substitutes preferentially at the Y site but has measurable probability of substitution in at least one of the two copper sites. A symmetry change near 650 {degree}C is consistent with the well-documented orthorhombic/tetragonal transition for samples in air or oxygen.

  3. Fault-tolerant PACS server

    NASA Astrophysics Data System (ADS)

    Cao, Fei; Liu, Brent J.; Huang, H. K.; Zhou, Michael Z.; Zhang, Jianguo; Zhang, X. C.; Mogel, Greg T.

    2002-05-01

    Failure of a PACS archive server could cripple an entire PACS operation. Last year we demonstrated that it was possible to design a fault-tolerant (FT) server with 99.999% uptime. The FT design was based on a triple modular redundancy with a simple majority vote to automatically detect and mask a faulty module. The purpose of this presentation is to report on its continuous developments in integrating with external mass storage devices, and to delineate laboratory failover experiments. An FT PACS Simulator with generic PACS software has been used in the experiment. To simulate a PACS clinical operation, image examinations are transmitted continuously from the modality simulator to the DICOM gateway and then to the FT PACS server and workstations. The hardware failures in network, FT server module, disk, RAID, and DLT are manually induced to observe the failover recovery of the FT PACS to resume its normal data flow. We then test and evaluate the FT PACS server in its reliability, functionality, and performance.

  4. Some considerations about evolution of idiopathic primary aldosteronism.

    PubMed

    Armanini, D; Fiore, C

    2009-07-01

    The prevalence of primary aldosteronism has increased since many patients who were previously considered as being affected by low renin essential hypertension are actually satisfying the new diagnostic criteria using plasma aldosterone/ plasma renin activity (PRA) ratio. Many of these cases could be classified as subclinical hyperaldosteronism, having normal aldosterone and low PRA, or in alternative the normal range of aldosterone should be revised. Idiopathic hyperaldosteronism can, in many cases, be considered as an evolutive disease: it can be hypothesized that the biochemical picture can be preceded by essential hypertension and that, after several years, primary aldosteronism can evolve back to essential hypertension due to age-related reduced vascular and adrenal sensitivity to angiotensin II. This effect is also evident after longterm treatment with aldosterone receptors blockers and therefore it possible that aldosterone-receptors blockers are able to normalize the sensitivity of glomerulosa to angiotensin II even after long-term withdrawal. The use of aldosterone receptors blockers prevents cardiovascular complications due to local aldosterone effect at the level of endothelium and mononuclear leukocytes; therefore, these drugs should be also considered for therapy of patients with hypertension. It is not excluded that aldosterone receptor blockers could prevent the onset of idiopathic hyperaldosteronism and its complications in patients with hypertension without primary hyperaldosteronism. From all these considerations it follows that the concept of normal range of aldosterone should be revised and the use of aldosterone receptor blockers should be revisited. PMID:19893360

  5. Recent advances in diagnosis and treatment of primary aldosteronism.

    PubMed

    Veglio, F; Morello, F; Rabbia, F; Leotta, G; Mulatero, P

    2003-08-01

    Primary aldosteronism is the most common form of secondary hypertension. The use of aldosterone/plasma renin activity ratio (ARR) as a screening test has elevated its prevalence up to 10% of hypertensive patients. Idiopathic bilateral adrenal hyperplasia and aldosterone-producing adrenal adenoma are the leading causes of primary aldosteronism. Most patients with this conditions are normokalemic and clinically undistinguishable from essential hypertensives. However, they suffer from anticipated and more severe target organ damage than other hypertensives. Thus, being primary aldosteronism a common, specifically treatable and sometimes surgically cured form of hypertension, a prompt diagnosis is necessary and cannot be overlooked. The measurement of ambulatory ARR represents the screening test and should be performed in the majority of hypertensive patients. ARR higher than a set cutoff suggests the need of a confirmatory test for primary aldosteronism, such as intravenous saline load or fludrocortisone suppression test. If inability to suppress aldosterone is demonstrated, the disease is confirmed. The subtype evaluation is based on adrenal imaging (CT scan) and selective adrenal venous sampling. The latter is the gold standard for the diagnosis of a lateralized aldosterone secretion, as typically observed in aldosterone-producing adenomas. Microadenomas are frequently overlooked by adrenal image. If lateralization is confirmed, unilateral adrenalectomy is the reasonable therapeutic option, leading to a significant reduction of blood pressure, if not normotension. If bilateral aldosterone excess is demonstrated, an aldosterone receptor antagonist should be administered. This article reviews and discusses the new data about prevalence, diagnosis and treatment of primary aldosteronism. PMID:14605590

  6. Cardiovascular and hormonal (aldosterone) responses in a rat model which mimics responses to weightlessness

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Steffen, J. M.

    1984-01-01

    Cardiovascular responses and fluid/electrolyte shifts seen during spaceflight have been attributed to cephalad redistribution of vascular fluid. The antiorthostatic (AO) rat (suspended, head-down tilt of 15-20 deg) is used to model these responses. This study documents that elevated blood pressures in AO rats are sustained for periods of up to seven days, compared with presuspension values. Increased blood pressures in AO rats suggests a specific response to AO positioning, potentially relatable to a cephalad fluid shift. To assess a role for hormonal regulation of sodium excretion, serum aldosterone levels were measured. Circulating aldosterone concentrations were seen to increase approximately 100 percent during seven days of AO suspension, concurrently with a pronounced natriuresis. These results suggest that aldosterone may not be involved in the long term regulation of increased Na(+) excretion in AO animals. These studies continue to show the usefulness of models for the development of animal protocols for space flight.

  7. 'PACS at Penn'

    NASA Astrophysics Data System (ADS)

    Arenson, Ronald L.; Seshadri, Sridhar B.; Kundel, Harold L.; DeSimone, Debra

    1989-05-01

    History: Our experience with Medical Image Management Systems (MIMS, also called PACS) began in 1982 with the creation of a digital subtraction angiography (DSA) unit. This DSA system was built utilizing a DeAnza image array processor with boards fabricated by our staff to interface with a Siemens angiography room. Because of the need to transmit and eventually store very large image files on a remote computer, we designed and fabricated a point-to-point fiber-optic link [82-ARENA. This device was later marketed by Canoga Systems and was an important contribution to the design of commercial fiber-optic networks. Recognizing the importance of a versatile Radiology Information System (RIS) and its critical inter-relationship to a MIMS, some very early work on RIS design was carried out [79-ARENA, [79.B-AREN ], [84-AREN ].

  8. Enhanced Soluble Serum CD40L and Serum P-Selectin Levels in Primary Aldosteronism.

    PubMed

    Petramala, L; Iacobellis, G; Carnevale, R; Marinelli, C; Zinnamosca, L; Concistrè, A; Galassi, M; Iannucci, G; Lucia, P; Pignatelli, P; Ciardi, A; Violi, F; De Toma, G; Letizia, C

    2016-07-01

    Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients [subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA)], matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients. PMID:27101095

  9. MITOCHONDRIA-TARGETED CARDIOPROTECTION IN ALDOSTERONISM

    PubMed Central

    Shahbaz, Atta U.; Kamalov, German; Zhao, Wenyuan; Zhao, Tieqiang; Johnson, Patti L.; Sun, Yao; Bhattacharya, Syamal K.; Ahokas, Robert A.; Gerling, Ivan C.; Weber, Karl T.

    2010-01-01

    Chronic aldosterone/salt treatment (ALDOST) is accompanied by an adverse structural remodeling of myocardium that includes multiple foci of microscopic scarring representing morphologic footprints of cardiomyocyte necrosis. Our previous studies suggested that signal-transducer-effector pathway leading to necrotic cell death during ALDOST includes intramitochondrial Ca2+ overloading, together with an induction of oxidative stress and opening of the mitochondrial permeability transition pore (mPTP). To further validate this concept, we hypothesized mitochondria-targeted interventions will prove cardioprotective. Accordingly, 8-wk-old male Sprague-Dawley rats receiving 4 wks ALDOST were cotreated with either quercetin (Q), a flavonoid with mitochondrial antioxidant properties, or cyclosporine A (CsA), an mPTP inhibitor, and compared to ALDOST alone or untreated, age-/sex-matched controls. We monitored: mitochondrial free Ca2+ and biomarkers of oxidative stress, including 8-isoprostane and H2O2 production; mPTP opening; total Ca2+ in cardiac tissue; collagen volume fraction (CVF) to quantify replacement fibrosis, a biomarker of cardiomyocyte necrosis; and employed TUNEL assay to address apoptosis in coronal sections of ventricular myocardium. Compared to controls, at 4 wks ALDOST we found: a marked increase in mitochondrial H2O2 production and 8-isoprostane levels, an increased propensity for mPTP opening, and greater concentrations of mitochondrial free [Ca2+]m and total tissue Ca2+, coupled with a 5-fold rise in CVF without any TUNEL-based evidence of cardiomyocyte apoptosis. Each of these pathophysiologic responses to ALDOST were prevented by Q or CsA cotreatment. Thus, mitochondria play a central role in initiating the cellular-molecular pathway that leads to necrotic cell death and myocardial scarring. This destructive cycle can be interrupted and myocardium salvaged with its structure preserved by mitochondria-targeted cardioprotective strategies. PMID:20966765

  10. The Aldosterone Renin Ratio (ARR) APP as Tool to Enhance the Detection Rate of Primary Aldosteronism.

    PubMed

    Rossi, Gian Paolo; Bisogni, Valeria

    2016-06-01

    Primary aldosteronism is one of the most common forms of secondary hypertension, but it is often under diagnosed, which leads to the development of cardiovascular damage, and excess costs for long-term drug treatment and management of complications. The aldosterone to renin ratio (ARR) is a key step for early detection of primary aldosteronism, but unfortunately is not easily estimated. This is because plasma aldosterone and renin are measured with different assays, which provide results in different units of measure, with ensuing difficulty of obtaining the calculation of the ARR in the proper units and impossibility of interpreting results with reference to established cut off values. Therefore, doctors are often unable to draw unambiguous conclusions to be used for the clinical decision-making. To the aim of making the diagnostic work-up easier, we have developed an Application that provide a swift calculation of the ARR regardless of the units of measure used for plasma aldosterone and renin values. If the concomitant serum potassium level is available the App also provides the patient's probability of having an aldosterone-producing adenoma based on a validated logistic discriminant analysis. PMID:26883242

  11. Aldosterone blockade in CKD: emphasis on pharmacology.

    PubMed

    Schwenk, Michael H; Hirsch, Jamie S; Bomback, Andrew S

    2015-03-01

    Besides its epithelial effect on sodium retention and potassium excretion in the distal tubule, aldosterone promotes inflammation and fibrosis in the heart, kidneys, and blood vessels. As glomerular filtration rate falls, aldosterone is inappropriately elevated relative to extracellular fluid expansion. In addition, studies in CKD patients on angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and/or direct renin inhibitors have shown that aldosterone levels paradoxically rise in approximately 30% to 40% of patients on these renin-angiotensin system-blocking drugs. Hence, there is interest in using mineralocorticoid receptor blockers that directly target the inflammatory and fibrotic effects of aldosterone in CKD patients. This interest, however, is tempered by a number of unresolved issues, including the safety of using such drugs in advanced CKD and ESRD populations, and the potential for differences in drug efficacy according to race and ethnicity of patient populations. A better understanding of mineralocorticoid receptor blocker pharmacology should help inform future research directions and clinical practice decisions as to how best to use these agents in CKD. PMID:25704349

  12. Effect of spironolactone on the renin-aldosterone system in rats.

    PubMed

    Jiménez, W; Martínez-Pardo, A; Arroyo, V; Gaya, J; Rivera, F

    1988-09-01

    PRA, PRC and the plasma concentration of aldosterone (Aldo) were measured in rats (Sp-rats) receiving a daily sc injection of Spironolactone, (Sp, 20 mg in olive oil) and in control rats (C-rats) receiving olive oil only. Animals were studied one day after starting treatment, 5 days on treatment or after 5 weeks on the study. PRA, PRC and Aldo were significantly increased in Sp-rats as compared to C-rats throughout all the study. In additional Sp-rats and C-rats, the urine volume, serum Na+ and K+ concentration, Na+ and K+ intake and the urinary excretion of Na+, K+ and aldosterone-18-glucuronide (UAldV) were serially measured during 5 weeks. The total radioactivity plasma clearance after an i.v. bolus injection of 3H-aldosterone was subsequently measured in (5 Sp-rats and 5 C-rats). No significant differences in serum Na+ and K+ concentration and in Na+ and K+ balance were observed between Sp-rats and C-rats. UAldV was significantly higher in Sp-rats than in C-rats during all the study. After 5 weeks on treatment the total radioactivity plasma clearance was significantly higher in Sp-rats than in C-rats. These results indicate that Sp, at high dosage, stimulates renin release and aldosterone secretion by a mechanism unrelated to alterations in Na+ and K+ balance. PMID:3068736

  13. Fitting PAC spectra with stochastic models: PolyPacFit

    NASA Astrophysics Data System (ADS)

    Zacate, M. O.; Evenson, W. E.; Newhouse, R.; Collins, G. S.

    2010-04-01

    PolyPacFit is an advanced fitting program for time-differential perturbed angular correlation (PAC) spectroscopy. It incorporates stochastic models and provides robust options for customization of fits. Notable features of the program include platform independence and support for (1) fits to stochastic models of hyperfine interactions, (2) user-defined constraints among model parameters, (3) fits to multiple spectra simultaneously, and (4) any spin nuclear probe.

  14. Treatment of coal gasification wastewater by membrane bioreactor hybrid powdered activated carbon (MBR–PAC) system.

    PubMed

    Jia, Shengyong; Han, Hongjun; Hou, Baolin; Zhuang, Haifeng; Fang, Fang; Zhao, Qian

    2014-12-01

    A laboratory-scale membrane bioreactor hybrid powdered activated carbon (MBR–PAC) system was developed to treat coal gasification wastewater to enhance the COD, total phenols (TPh), NH4+ removals and migrate the membrane fouling. Since the MBR–PAC system operated with PAC dosage of 4 g L−1, the maximum removal efficiencies of COD, TPh and NH4+ reached 93%, 99% and 63%, respectively with the corresponding influent concentrations of 2.27 g L−1, 497 mg L−1 and 164 mg N L−1; the PAC extraction efficiencies of COD, TPh and NH4+ were 6%, 3% and 13%, respectively; the transmembrane pressure decreased 34% with PAC after 50 d operation. The results demonstrate that PAC played a key role in the enhancement of biodegradability and mitigation of membrane fouling. PMID:25461944

  15. Primary aldosteronism associated with severe rhabdomyolysis due to profound hypokalemia.

    PubMed

    Goto, Atsushi; Takahashi, Yoshihiko; Kishimoto, Miyako; Minowada, Shigeru; Aibe, Hitoshi; Hasuo, Kanehiro; Kajio, Hiroshi; Noda, Mitsuhiko

    2009-01-01

    A 55-year-old Japanese man was admitted to our hospital with severe weakness. Without measurement of serum electrolyte concentrations, diuretic therapy for hypertension was started 2 weeks prior to admission. Laboratory findings showed profound hypokalemia (1.4 mEq/L), and extreme elevation of the serum creatinine phosphokinase levels (15,760 IU/L), suggesting that the patient had hypokalemic paralysis and hypokalemia-induced rhabdomyolysis. Further evaluations, including adrenal venous sampling strongly suggested that he had primary aldosteronism. He was treated successfully by laparoscopic adrenalectomy. This case provides an important lesson that serum electrolyte concentrations should be measured in hypertensive patients before the administration of antihypertensive agents. PMID:19218772

  16. Genotype-Specific Steroid Profiles Associated With Aldosterone-Producing Adenomas.

    PubMed

    Williams, Tracy Ann; Peitzsch, Mirko; Dietz, Anna S; Dekkers, Tanja; Bidlingmaier, Martin; Riester, Anna; Treitl, Marcus; Rhayem, Yara; Beuschlein, Felix; Lenders, Jacques W M; Deinum, Jaap; Eisenhofer, Graeme; Reincke, Martin

    2016-01-01

    Primary aldosteronism comprises 2 main subtypes: unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia. Somatic KCNJ5 mutations are found in APA at a prevalence of around 40% that drive and sustain aldosterone excess. Somatic APA mutations have been described in other genes (CACNA1D, ATP1A1, and ATP2B3) albeit at a lower frequency. Our objective was to identify genotype-specific steroid profiles in adrenal venous (AV) and peripheral venous (PV) plasma in patients with APAs. We measured the concentrations of 15 steroids in AV and PV plasma samples by liquid chromatography-tandem mass spectrometry from 79 patients with confirmed unilateral primary aldosteronism. AV sampling lateralization ratios of steroids normalized either to cortisol or to DHEA+androstenedione were also calculated. The hybrid steroid 18-oxocortisol exhibited 18- and 16-fold higher concentrations in lateralized AV and PV plasma, respectively, from APA with KCNJ5 mutations compared with all other APA combined together (P<0.001). Lateralization ratios for the KCNJ5 group were also generally higher. Strikingly, we demonstrate that a distinct steroid signature can differentiate APA genotype in AV and PV plasma. Notably, a 7-steroid fingerprint in PV plasma correctly classified 92% of the APA according to genotype. Prospective studies are necessary to translate these findings into clinical practice and determine if steroid fingerprinting could be of value to select patients with primary aldosteronism who are particularly suitable candidates for adrenal venous sampling because of a high probability of having an APA. PMID:26573708

  17. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism.

    PubMed

    Mulatero, Paolo; Rabbia, Franco; Milan, Alberto; Paglieri, Cristina; Morello, Fulvio; Chiandussi, Livio; Veglio, Franco

    2002-12-01

    Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. Antihypertensive therapy can interfere with the interpretation of this parameter, but a correct washout period can be potentially harmful. We have investigated the effects of therapy with atenolol, amlodipine, doxazosin, fosinopril, and irbesartan on the ARR in a group of 230 patients with suspected primary aldosteronism. The percent change from control of ARR in patients taking amlodipine was -17%+/-32; atenolol, 62%+/-82; doxazosin, -5%+/-26; fosinopril, -30%+/-24; and irbesartan, -43%+/-27. The ARR change induced by atenolol was significantly higher compared with that induced by all other drugs (P<0.0001), and the ARR change induced by irbesartan was significantly lower than that induced by doxazosin (P<0.0001). One of 55 patients from the group taking amlodipine (1.8%) and 4/17 of the patients taking irbesartan (23.5%) gave a false-negative ARR (<50). None of the patients of the groups taking fosinopril, doxazosin, and atenolol displayed a false-negative ARR. Doxazosin and fosinopril can be used in hypertensive patients who need to undergo aldosterone and PRA measurement for the diagnosis of primary aldosteronism; amlodipine gave a very small percentage of false-negative diagnoses. beta-Blockers also do not interfere with the diagnosis of primary aldosteronism, but they can be responsible for an increased rate of false-positive ARRs. The high rate of false-negative diagnoses in patients undergoing irbesartan treatment requires confirmation in a higher number of patients. PMID:12468576

  18. Studies on the subcommissural organ area in the rat: the effects aldosterone infused into the central nervous system

    SciTech Connect

    Dundore, R.L.

    1985-01-01

    D-aldosterone (5 ng/..mu..l/hr) was infused for six days into the area of the subcommissural organ (SCO) of conscious rats to test the hypothesis that the SCO and the adrenal zona glomerulosa are related functionally in a negative feedback manner. Aldosterone increased urinary sodium loss and the sodium/potassium ratio. These effects still occurred when cannulae were displaced caudally up to 1 mm from the targeted SCO area. Aldosterone decreased the cross-sectional area of the adrenal medulla without affecting chromaffin cell density. Adrenal content of corticosterone was increased. These effects were highly dependent upon proper cannula placement and were not observed when the tip of the cannula was not in contact with the cerebrospinal fluid of the pineal recess over the rostral two-thirds of the SCO. Aldosterone infused intracerebroventricularly (ivt) into a lateral ventricle had no effect on sodium excretion, adrenal corticosterone concentration or adrenal morphology. After the infusion of radiolabelled aldosterone into the SCO area, the majority of the radioactivity was restricted to an area about 1-2 mm in diameter from the SCO. Iron-dextran injected intraperiotoneally did not accumulate in the SCO; therefore, the blood-brain barrier is intact. It is concluded that the effects of aldosterone were dependent upon the area of the brain in which it was infused. Aldosterone increased sodium excretion by an action in the SCO and/or adjacent structures. A relationship between mineralocorticoids and the adrenal modulla mediated by the SCO is also postulated. With regard to the blood-brain and brain-CSF barriers, the SCO more closely resembles general brain tissue than other circumventricular organs.

  19. PCaPAC 2006 Proceedings

    SciTech Connect

    Pavel Chevtsov; Matthew Bickley

    2007-03-30

    The 6-th international PCaPAC (Personal Computers and Particle Accelerator Controls) workshop was held at Jefferson Lab, Newport News, Virginia, from October 24-27, 2006. The main objectives of the conference were to discuss the most important issues of the use of PCs and modern IT technologies for controls of accelerators and to give scientists, engineers, and technicians a forum to exchange the ideas on control problems and their solutions. The workshop consisted of plenary sessions and poster sessions. No parallel sessions were held.Totally, more than seventy oral and poster presentations as well as tutorials were made during the conference, on the basis of which about fifty papers were submitted by the authors and included in this publication. This printed version of the PCaPAC 2006 Proceedings is published at Jefferson Lab according to the decision of the PCaPAC International Program Committee of October 26, 2006.

  20. The renin-angiotensin-aldosterone system and its blockade in diabetic nephropathy: main focus on the role of aldosterone.

    PubMed

    Schjoedt, Katrine Jordan

    2011-04-01

    Diabetic nephropathy is the most common cause of end-stage renal disease in the western world. Despite major improvements in both prevention and treatment of diabetic nephropathy, there is a continuous need to improve identification and treatment of "non-responders". In recent years, several experimental studies have shown that aldosterone plays a role in the development and progression of diabetic nephropathy, independent of angiotensin II and blood pressure levels. Blocking the renin-angiotensin-aldosterone system with an ACE-inhibitor (ACEI) and/or ambulatory blood pressure should theoretically inhibit the secretion of aldosterone. However, an increase in aldosterone during long-term treatment with ACEIs, so-called aldosterone escape or aldosterone breakthrough, has been described. In the present thesis, our studies evaluating the incidence and clinical impact (i.e. a faster rate of decline in kidney function) of aldosterone escape in type 1 diabetic patients with diabetic nephropathy, possible mechanisms of aldosterone escape, and finally the beneficial effect of blocking aldosterone on albuminuria, blood pressure and renal autoregulation is being reviewed, together with some aspects of the existing treatment recommendations. PMID:21466768

  1. Preparation of PAC libraries. Final technical report

    SciTech Connect

    Pieter J. de Jong

    1997-12-31

    The goals of this project were to create P1 Artificial Chromosome (PAC) cloning vectors and use these vectors to generate, characterize, and distribute both human and mouse genomic PAC libraries to the scientific community.

  2. Control of aldosterone secretion during sodium restriction: Adrenal receptor regulation and increased adrenal sensitivity to angiotensin II

    PubMed Central

    Aguilera, G.; Hauger, R. L.; Catt, K. J.

    1978-01-01

    The mechanism of increased adrenal sensitivity to angiotensin II during the aldosterone response to sodium restriction was investigated in the rat. Sodium restriction for 36 hr markedly increased the aldosterone-stimulating effect of low-dose (1 ng/min) infusion of angiotensin II and caused enhanced binding of 125I-labeled angiotensin II to the zona glomerulosa in vivo. Conversely, in vivo binding of 125I-labeled angiotensin II was significantly decreased after 36 hr of high-sodium intake. In isolated glomerulosa cells, the increased binding of angiotensin II after sodium restriction was shown to result from a significant increase in receptor affinity (+80%) and a smaller increase in receptor concentration (+25%). The corresponding aldosterone responses in dispersed cells showed an increase in sensitivity to angiotensin II, commensurate with the increased receptor affinity. More prolonged sodium restriction (4 days) caused a further increase in angiotensin receptor concentration (+70%) and maximal aldosterone response (+50%), whereas the binding affinity of adrenal receptors and the sensitivity of the in vitro aldosterone response had returned to normal. During sodium loading for 36 hr and 4 days, the converse effects on adrenal angiotensin II receptors and aldosterone production were observed. Also, in contrast to the consistent increase in angiotensin II receptors in the adrenal glands of sodium-restricted animals, the angiotensin II binding capacity of uterine smooth muscle was decreased by 40% after 7 days of sodium restriction. The rapid regulation of receptor affinity and concentration during changes in sodium intake provides a basis for the dynamic modulation of aldosterone responses by dietary sodium content. During sodium restriction, the sequential changes in receptor affinity and concentration account for the enhanced binding and steroidogenic actions of angiotensin II in vivo and in vitro. These receptor changes, and the converse effects of sodium

  3. PACS and electronic health records

    NASA Astrophysics Data System (ADS)

    Cohen, Simona; Gilboa, Flora; Shani, Uri

    2002-05-01

    Electronic Health Record (EHR) is a major component of the health informatics domain. An important part of the EHR is the medical images obtained over a patient's lifetime and stored in diverse PACS. The vision presented in this paper is that future medical information systems will convert data from various medical sources -- including diverse modalities, PACS, HIS, CIS, RIS, and proprietary systems -- to HL7 standard XML documents. Then, the various documents are indexed and compiled to EHRs, upon which complex queries can be posed. We describe the conversion of data retrieved from PACS systems through DICOM to HL7 standard XML documents. This enables the EHR system to answer queries such as 'Get all chest images of patients at the age of 20-30, that have blood type 'A' and are allergic to pine trees', which a single PACS cannot answer. The integration of data from multiple sources makes our approach capable of delivering such answers. It enables the correlation of medical, demographic, clinical, and even genetic information. In addition, by fully indexing all the tagged data in DICOM objects, it becomes possible to offer access to huge amounts of valuable data, which can be better exploited in the specific radiology domain.

  4. RIS minus PACS equals film.

    PubMed

    Tellis, Wyatt M; Andriole, Katherine P; Jovais, Christopher S; Avrin, David E

    2002-01-01

    Web-based integration methods can be used to resolve a fundamental issue in the transition from film to a picture archiving and communication system (PACS): the identification of relevant prior studies only available on film. Even in the most ambitious conversions from a film-based environment to PACS, there are issues regarding prior studies not on PACS. Failure to compare with prior exams is one of the known risk factors for malpractice in radiology. While most commercial PACS systems today have some degree of RIS integration, knowledge of prior studies is usually limited to an awareness of studies in the PACS. On the other hand, most RIS systems today do not or cannot distinguish between studies on film and those in PACS. We made the observation, from a set theory perspective, that in general: Therefore we sought to create a system that would query both the RIS and PACS and reconcile the results using the above set operation. The query is initiated from a display station via the invocation of a Web browser installed on that station. The process of starting the browser is implemented using a scripting language provided by the workstation vendor, though the use of other mechanisms, such as the CCOW (Clinical Context Object Workgroup) or IHE (RSNA Integrated Healthcare Enterprise) interfaces, can be supported by this architecture. The medical record number, which identifies the current patient and is the primary parameter of the query, is passed as part of the URL (Universal Resource Locator) used to launch the browser. Once running, the browser connects to a Web server that hosts a JSP (Java Server Page) page that performs a DICOM query of the PACS and an HL7 query of the RIS, and then collates the results using the set operation described above. Both the DICOM and HL7 functionality are provided by Java-based toolkits developed in house. The results are returned to the client's browser as a standard HTML page with a tabular format detailing which studies are on

  5. Urological diagnosis using clinical PACS

    NASA Astrophysics Data System (ADS)

    Mills, Stephen F.; Spetz, Kevin S.; Dwyer, Samuel J., III

    1995-05-01

    Urological diagnosis using fluoroscopy images has traditionally been performed using radiographic films. Images are generally acquired in conjunction with the application of a contrast agent, processed to create analog films, and inspected to ensure satisfactory image quality prior to being provided to a radiologist for reading. In the case of errors the entire process must be repeated. In addition, the radiologist must then often go to a particular reading room, possibly in a remote part of the healthcare facility, to read the images. The integration of digital fluoroscopy modalities with clinical PACS has the potential to significantly improve the urological diagnosis process by providing high-speed access to images at a variety of locations within a healthcare facility without costly film processing. The PACS additionally provides a cost-effective and reliable means of long-term storage and allows several medical users to simultaneously view the same images at different locations. The installation of a digital data interface between the existing clinically operational PACS at the University of Virginia Health Sciences Center and a digital urology fluoroscope is described. Preliminary user interviews that have been conducted to determine the clinical effectiveness of PACS workstations for urological diagnosis are discussed. The specific suitability of the workstation medium is discussed, as are overall advantages and disadvantages of the hardcopy and softcopy media in terms of efficiency, timeliness and cost. Throughput metrics and some specific parameters of gray-scale viewing stations and the expected system impacts resulting from the integration of a urology fluoroscope with PACS are also discussed.

  6. Technical aspects of PACS in Korea

    NASA Astrophysics Data System (ADS)

    Kim, JongHyo

    2002-05-01

    Korea is one of the fastest growing countries in the number of filmless hospitals. More than 70 hospitals have converted to filmless environments by adopting full PAC systems during the last two years. The patient care environment in Korean hospitals was not favorable to PACS implementation. In many out patient clinics, doctors had to see more than hundred patients a day. It was not rare for a radiologist to read several hundred of exams a day. Also, the PACS teams were mandated to acquire full scale PACS capable of incorporating not only radiological images but also color images produced in other imaging departments. In order to take root in Korean environment, the PACS in Korea had to pass through some technical modifications that included introduction of recent hardware technologies and development of new software features. This paper describes various technical aspects of PAC systems in Korea that have met difficult requirements and enabled wide spread of PAC systems to real clinical practice.

  7. A useful tool to improve the case detection rate of primary aldosteronism: the aldosterone-renin ratio (ARR)-App.

    PubMed

    Rossi, Gian Paolo; Bisogni, Valeria

    2016-05-01

    The aldosterone-renin ratio is the most popular test for the case detection of primary aldosteronism, which entails the most common, albeit overlooked, form of endocrine secondary hypertension. A major hindrance to the clinical use of the aldosterone-renin ratio depends on the difficulty of achieving the calculation of this ratio, given that laboratories provide plasma aldosterone in different units of measurement, and renin is measured as plasma renin activity or direct active renin. We have therefore developed an App, which can be downloaded from the ESH website and the Apple store, to assist practising physicians in performing this calculation. Our hope is that this simple tool will help in increasing the detection rate of primary aldosteronism and ultimately the long-term cure of many hypertensive patients. PMID:26870884

  8. Renin-angiotensin-aldosterone system and electrolyte metabolism in rat blood after flight aboard Cosmos-1129 biosatellite

    SciTech Connect

    Kvetnansky, R.; Tigranyan, R.A.; Jindra, A.; Viting, T.A.

    1982-08-01

    Blood plasma aldosterone concentration and renin activity were studied in rats flow in space on the Cosmos 1129 satellite using radioimmunoassay techniques. Immediately after the flight, the animals presented significant decreases in plasma renin activity, as compared to rats in the vivarium control and animals in the synchronous experiment. R. J.

  9. PACS strategy for imaging centers.

    PubMed

    Bedel, Victoria; Zdanowicz, Mark

    2004-01-01

    Picture archiving and communications systems (PACS) have been available in imaging centers for many years, but they often were less functional, were not well integrated into patient information systems, and lacked the network backbone to implement a system. As modalities are replaced and technology improves, the ability and time for an imaging center to acquire, integrate, and utilize PACS has arrived. However, each imaging center must determine why it should invest in PACS. A business plan is the fundamental need. Each imaging center must understand its target market, growth rate, and staffing plans. Additional considerations lie in current and future modality availability, the need for offsite delivery of images and reports, and the potential need for remote transmission of images. These issues must be identified and prioritized. A multidisciplinary team is essential. The most successful PACS implementation begins with complete involvement from all levels. The team should be comprised of people with complementary skills who are committed to a common purpose, set of performance goals, and approach for which they hold themselves mutually accountable. The team must jointly decide on the project's objectives. These objectives fall under 4 categories: clinical, service, financial, and performance. PACS must be considered a tool to help accomplish each objective. The imaging center must determine its top priorities, then translate them into a technology "wish list." The center can then list those pieces of technology that are most important and prioritize them. There are even more considerations for connecting multiple imaging centers. The team must create a comprehensive request for proposal (RFP) and determine the vendors that will receive the document. Once the RFP responses have been received and the vendor has been selected, an effective training plan must be executed. Training plans should be competency-based, ensuring comfort and competency among all staff. Upon

  10. Integrating organic micropollutant removal into tertiary filtration: Combining PAC adsorption with advanced phosphorus removal.

    PubMed

    Altmann, Johannes; Sperlich, Alexander; Jekel, Martin

    2015-11-01

    Direct addition of powdered activated carbon (PAC) to a deep-bed filter was investigated at pilot-scale as a single advanced treatment stage for simultaneous removal of organic micropollutants (OMPs) and phosphorus from secondary effluent. PAC doses of 10-50 mg/L were assessed with regard to their impacts on filter performance and removal of 15 selected OMPs over a period of 18 months. The PAC was effectively retained by the filter and had no negative effect on filter head loss. Filter runtime until particle breakthrough depended mainly on coagulant dose and did not decrease significantly due to the additional PAC load. Removal of suspended solids and phosphorus by coagulation was effective independent of the PAC dose. A PAC dose of 35 mg/L PAC was suitable to remove well-adsorbing OMPs (e.g. carbamazepine, diclofenac) by >80% and medium adsorbing OMPs (e.g. primidone, sulfamethoxazole) by 50-80%. Median removals were 50-80% for well-adsorbing and 30-50% for medium adsorbing OMPs with 20 mg/L PAC. Abatement of all OMPs was low (<50%) with 10 mg/L PAC, possibly because of the high effluent organic matter content (median dissolved organic carbon (DOC) concentrations of 11.2 mg/L). In addition to adsorptive removal, relevant concentration decreases of certain OMPs (e.g. 4-formylaminoantipyrine) were attributed to biological transformation in the filter. Adsorption onto accumulating PAC in the top layer of the filter bed led to improved OMP adsorption with increasing filter runtime. The comparison of OMP removal in the pilot filter with laboratory adsorption tests demonstrates that batch test results can be applied to estimate adsorptive OMP removal in real applications. PMID:26210030

  11. Renin and aldosterone at high altitude in man.

    PubMed

    Keynes, R J; Smith, G W; Slater, J D; Brown, M M; Brown, S E; Payne, N N; Jowett, T P; Monge, C C

    1982-01-01

    Measurements have been made of hormonal changes relevant to salt and water balance during prolonged exposure to hypoxia to improve our understanding of the syndrome of acute mountain sickness. We have attempted to delineate the detailed inter-relationships between the renin-aldosterone and the vasopressin systems by a metabolically controlled study, involving an orthostatic stress (45 degrees head-up tilt) and an injection of a standard dose of ACTH to test adrenal responsiveness. Three Caucasian medical students underwent a 7-day equilibration at 150 m (Lima, Peru), followed by a 6-day sojourn at 4350 m (Cerro de Pasco, Peru) and a final 7 days at 150 m. Measurements were made of sodium and potassium balance, body weight and the 24-h renal excretion of vasopressin, cortisol and aldosterone 18-glucuronide. These variables showed little change, except for that of aldosterone 18-glucuronide, which fell sharply at altitude and rebounded even more sharply on return to sea level. At altitude, basal plasma levels of renin activity and aldosterone fell, and the response to orthostasis was attenuated, but the fall of plasma renin activity, as compared to plasma aldosterone, was delayed; on return to sea level this dissociation was exacerbated with the return of normal renin responsiveness lagging behind that of aldosterone. We suggest that unknown factors which dissociate the orthodox renin-aldosterone relationship, other than the activity of the angiotensin I-converting enzyme, are operative on exposure to hypoxia. PMID:7057120

  12. A particular phenotype in a girl with aldosterone synthase deficiency.

    PubMed

    Williams, Tracy A; Mulatero, Paolo; Bosio, Maurizio; Lewicka, Sabina; Palermo, Mario; Veglio, Franco; Armanini, Decio

    2004-07-01

    Aldosterone synthase deficiency (ASD) usually presents in infancy as a life-threatening electrolyte imbalance. A 4-wk-old child of unrelated parents was examined for failure to thrive and salt-wasting. Notable laboratory findings were hyperkalemia, high plasma renin, and low-normal aldosterone levels. Urinary metabolite ratios of corticosterone/18-hydroxycorticosterone and 18-hydroxycorticosterone/aldosterone were intermediate between ASD type I and type II. Sequence analysis of CYP11B2, the gene encoding aldosterone synthase (P450c11AS), revealed that the patient was a compound heterozygote carrying a previously described mutation located in exon 4 causing a premature stop codon (E255X) and a further, novel mutation in exon 5 that also causes a premature stop codon (Q272X). The patient's unaffected father was a heterozygous carrier of the E255X mutation, whereas the unaffected mother was a heterozygous carrier of the Q272X mutation. Therefore, the patient's CYP11B2 encodes two truncated forms of aldosterone synthase predicted to be inactive because they lack critical active site residues as well as the heme-binding site. This case of ASD is of particular interest because despite the apparent lack of aldosterone synthase activity, the patient displays low-normal aldosterone levels, thus raising the question of its source. PMID:15240589

  13. Aldosterone Increases Oxidant Stress to Impair Guanylyl Cyclase Activity by Cysteinyl Thiol Oxidation in Vascular Smooth Muscle Cells*S⃞

    PubMed Central

    Maron, Bradley A.; Zhang, Ying-Yi; Handy, Diane E.; Beuve, Annie; Tang, Shiow-Shih; Loscalzo, Joseph; Leopold, Jane A.

    2009-01-01

    Hyperaldosteronism is associated with impaired endothelium-dependent vascular reactivity owing to increased reactive oxygen species and decreased bioavailable nitric oxide (NO·); however, the effects of aldosterone on vasodilatory signaling pathways in vascular smooth muscle cells (VSMC) remain unknown. Soluble guanylyl cyclase (GC) is a heterodimer that is activated by NO· to convert cytosolic GTP to cGMP, a second messenger required for normal VSMC relaxation. Here, we show that aldosterone (10-9-10-7 mol/liter) diminishes GC activity by activating NADPH oxidase in bovine aortic VSMC to increase reactive oxygen species levels and induce oxidative posttranslational modification(s) of Cys-122, a β1-subunit cysteinyl residue demonstrated previously to modulate NO· sensing by GC. In VSMC treated with aldosterone, Western immunoblotting detected evidence of GC β1-subunit disulfide bonding, whereas mass spectrometry analysis of a homologous peptide containing the Cys-122-bearing sequence exposed to conditions of increased oxidant stress confirmed cysteinyl sulfinic acid (m/z 435), sulfonic acid (m/z 443), and disulfide (m/z 836) bond formation. The functional effect of these modifications was examined by transfecting COS-7 cells with wild-type GC or mutant GC containing an alanine substitution at Cys-122 (C122A). Exposure to aldosterone or hydrogen peroxide (H2O2) significantly decreased cGMP levels in cells expressing wild-type GC. In contrast, aldosterone or H2O2 did not influence cGMP levels in cells expressing the mutant C122A GC, confirming that oxidative modification of Cys-122 specifically impairs GC activity. These findings demonstrate that pathophysiologically relevant concentrations of aldosterone increase oxidant stress to convert GC to an NO·-insensitive state, resulting in disruption of normal vasodilatory signaling pathways in VSMC. PMID:19141618

  14. Obesity, hypertension and aldosterone: is leptin the link?

    PubMed

    Xie, Ding; Bollag, Wendy B

    2016-07-01

    Obesity is a serious health hazard with rapidly increasing prevalence in the United States. In 2014, the World Health Organization estimated that nearly 2 billion people worldwide were overweight with an estimated 600 million of these obese. Obesity is associated with many chronic diseases, including cardiovascular disease and hypertension. Data from the Framingham Heart study suggest that approximately 78% of the risk for hypertension in men and 65% in women is related to excess body weight, a relationship that is further supported by studies showing increases in blood pressure with weight gain and decreases with weight loss. However, the exact mechanism by which excess body fat induces hypertension remains poorly understood. Several clinical studies have demonstrated elevated plasma aldosterone levels in obese individuals, especially those with visceral adiposity, with decreased aldosterone levels measured in concert with reduced blood pressure following weight loss. Since aldosterone is a mineralocorticoid hormone that regulates blood volume and pressure, serum aldosterone levels may link obesity and hypertension. Nevertheless, the mechanism by which obesity induces aldosterone production is unclear. A recent study by Belin de Chantemele and coworkers suggests that one adipose-released factor, leptin, is a direct agonist for aldosterone secretion; other adipose-related factors may also contribute to elevated aldosterone levels in obesity, such as very low-density lipoprotein (VLDL), the levels of which are elevated in obesity and which also directly stimulates aldosterone biosynthesis. This focused review explores the possible roles of leptin and VLDL in modulating aldosterone secretion to underlie obesity-associated hypertension. PMID:27252389

  15. Aldosterone Activates NF-κB in the Collecting Duct

    PubMed Central

    Leroy, Valérie; De Seigneux, Sophie; Agassiz, Victor; Hasler, Udo; Rafestin-Oblin, Marie-Edith; Vinciguerra, Manlio; Martin, Pierre-Yves; Féraille, Eric

    2009-01-01

    Besides its classical effects on salt homeostasis in renal epithelial cells, aldosterone promotes inflammation and fibrosis and modulates cell proliferation. The proinflammatory transcription factor NF-κB has been implicated in cell proliferation, apoptosis, and regulation of transepithelial sodium transport. The effect of aldosterone on the NF-κB pathway in principal cells of the cortical collecting duct, a major physiologic target of aldosterone, is unknown. Here, in both cultured cells and freshly isolated rat cortical collecting duct, aldosterone activated the canonical NF-κB signaling pathway, leading to increased expression of several NF-κB–targeted genes (IκBα, plasminogen activator inhibitor 1, monocyte chemoattractant protein 1, IL-1β, and IL-6). Small interfering RNA–mediated knockdown of the serum and glucocorticoid-inducible kinase SGK1, a gene induced early in the response to aldosterone, but not pharmacologic inhibition of extracellular signal–regulated kinase and p38 kinase, attenuated aldosterone-induced NF-κB activation. Pharmacologic antagonism or knockdown of the mineralocorticoid receptor prevented aldosterone-induced NF-κB activity. In addition, activation of the glucocorticoid receptor inhibited the transactivation of NF-κB by aldosterone. In agreement with these in vitro findings, spironolactone prevented NF-κB–induced transcriptional activation observed in cortical collecting ducts of salt-restricted rats. In summary, aldosterone activates the canonical NF-κB pathway in principal cells of the cortical collecting duct by activating the mineralocorticoid receptor and by inducing SGK1. PMID:18987305

  16. The suitability of 160Tb as a PAC probe for studies of biomolecules.

    PubMed

    Sidhu, N P; Sahota, H S; Cheema, T S

    1988-01-01

    The gamma-ray perturbed angular correlation (PAC) studies were made with 160Tb as a probe in MES (2[N-morpholino]-ethane sulphonic acid) solutions of various concentrations. The measurements indicate no influence of concentration of the environment on its interaction with Tb3+ ion and as such reveal the fact that 160Tb is not a good probe for PAC studies. PMID:2840419

  17. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma

    PubMed Central

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E.; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-01-01

    Abstract We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (β = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05). We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  18. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 5: Genetic diagnosis of primary aldosteronism.

    PubMed

    Zennaro, Maria-Christina; Jeunemaitre, Xavier

    2016-07-01

    While the majority of cases of primary aldosteronism (PA) are sporadic, four forms of autosomal-dominant inheritance have been described: familial hyperaldosteronism (FH) types I to IV. FH-I, also called glucocorticoid-remediable aldosteronism, is characterized by early and severe hypertension, usually before the age of 20 years. It is due to the formation of a chimeric gene between the adjacent CYP11B2 and CYP11B1 genes (coding for aldosterone synthase and 11β-hydroxylase, respectively). FH-I is often associated with family history of stroke before 40years of age. FH-II is clinically and biochemically indistinguishable from sporadic forms of PA and is only diagnosed on the basis of two or more affected family members. No causal genes have been identified so far and no genetic test is available. FH-III is characterized by severe and early-onset hypertension in children and young adults, resistant to treatment and associated with severe hypokalemia. Mild forms, resembling FH-II, have been described. FH-III is due to gain-of-function mutations in the KCNJ5 gene. Recently, a new autosomal-dominant form of familial PA, FH-IV, associated with mutations in the CACNA1H gene, was described in patients with hypertension and PA before the age of 10years. In rare cases, PA may be associated with complex neurologic disorder involving epileptic seizures and cerebral palsy (Primary Aldosteronism, Seizures, and Neurologic Abnormalities [PASNA]) due to de novo germline CACNA1D mutations. PMID:27315758

  19. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.

    PubMed

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-05-01

    We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production.Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production.The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (β = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05).We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  20. Compaction and multiple chain assembly of DNA with the cationic polymer poly(aluminum chloride) (PAC).

    PubMed

    Matsuzawa, Yukiko; Kanbe, Toshio; Yoshikawa, Kenichi

    2004-07-20

    Assembly of DNA molecules by the addition of poly(aluminum chloride) (PAC) was studied. In the absence of PAC, electron microscopy indicated the formation of elongated coiled DNA molecules. In the presence of PAC, multiple doughnut-like structures, 8-15 nm thick, formed and fused together. When salt was added, the doughnut-like structures tended to be thinner and the morphology of the fused doughnuts became irregular. We obtained a view of a single DNA structure by fluorescent microscopy, which revealed that individual DNA molecules undergo a discrete transition from an elongated to compacted state with an increase in PAC concentration. Electron microscopic observation showed that a regular doughnut is the typical structure seen under low salt conditions. At high salt concentrations, the doughnut shape deformed, yielding results similar to those produced by the salt effect on DNA assembly at high DNA concentrations. PMID:15248734

  1. Sphere-Pac Evaluation for Transmutation

    SciTech Connect

    Icenhour, A.S.

    2005-05-19

    The U.S. Department of Energy Advanced Fuel Cycle Initiative (AFCI) is sponsoring a project at Oak Ridge National Laboratory with the objective of conducting the research and development necessary to evaluate the use of sphere-pac transmutation fuel. Sphere-pac fuels were studied extensively in the 1960s and 1970s. More recently, this fuel form is being studied internationally as a potential plutonium-burning fuel. For transmutation fuel, sphere-pac fuels have potential advantages over traditional pellet-type fuels. This report provides a review of development efforts related to the preparation of sphere-pac fuels and their irradiation tests. Based on the results of these tests, comparisons with pellet-type fuels are summarized, the advantages and disadvantages of using sphere-pac fuels are highlighted, and sphere-pac options for the AFCI are recommended. The Oak Ridge National Laboratory development activities are also outlined.

  2. History of aldosterone on its 50th birthday.

    PubMed

    Fiore, Cristina; Calò, Lorenzo A; Colombo, Lorenzo; Grimm, Clarence E; Armanini, Decio

    2006-01-01

    The paper describes the impact of mineralocorticoid substances on water regulation from Theophrastus (IV century B.C.) to Thomas Addison (1849). It also opens to the missed discovery of aldosterone of I.A. Macchi. PMID:16874725

  3. Tracking PACS usage with open source tools.

    PubMed

    French, Todd L; Langer, Steve G

    2011-08-01

    A typical choice faced by Picture Archiving and Communication System (PACS) administrators is deciding how many PACS workstations are needed and where they should be sited. Oftentimes, the social consequences of having too few are severe enough to encourage oversupply and underutilization. This is costly, at best in terms of hardware and electricity, and at worst (depending on the PACS licensing and support model) in capital costs and maintenance fees. The PACS administrator needs tools to asses accurately the use to which her fleet is being subjected, and thus make informed choices before buying more workstations. Lacking a vended solution for this challenge, we developed our own. PMID:20830501

  4. Population Association of China (PAC).

    PubMed

    Xiong, Y

    1983-12-01

    In the past 3 years, the Population Association of China, an independent, academic, and nongovernment organization established in February 1981, organized demographers throughout China to tackle the population problems that emerged in the course of the nation's socioeconomic development. Thus, by organizing and promoting exchanges, the Association did help to push forward the vigorous development of population science. Now PAC has over 500 individuals and organized units as members. It has 90 council members and 19 permanent council members. Its annual tasks and research priorities are discussed and decided by the permanent council, and then implemented in various departments and localities by its council or association members. The Population Association has organized various academic activities among demographers to study the characteristics of different periods. 1983 is an important year for the reform of social and economic systems in China. The new situation and problems brought about by the reform are bound to affect the control of population growth. Consequently, the Association decided to emphasize the control of population growth in rural areas. At the same time, the Association advocated a style of study which required people to delve into the realities of life and to investigate and study these realities thoroughly. For this purpose, 3 discussions were either financed or authorized by the Association in a single year. At the symposiums, demographers and field workers, proceeding from their country's reality and by applying the Marxist point of view, tried to find effective solutions to the demographic problems. As a result, they produced a number of valuable academic reports. In the last few years, PAC played an important role in international academic activities and exchanges. Reviewing the past and looking ahead to the future, PAC will further unite China's demographers to make new contributions to the development of the country's population science

  5. Protein prenylation is required for aldosterone-stimulated Na+ transport.

    PubMed

    Blazer-Yost, B L; Hughes, C L; Nolan, P L

    1997-06-01

    Aldosterone stimulation of transcellular Na+ flux in polarized epithelial cells is dependent on at least one transmethylation reaction, but the substrate of this signaling step is unknown. Because it is clear that the majority of cellular protein methylation occurs in conjunction with protein prenylation, we examined the importance of prenylation to aldosterone-stimulated Na+ transport in the A6 cell line. Lovastatin, an inhibitor of the first committed step of the mevalonate pathway, inhibits the natriferic effect of aldosterone but does not inhibit insulin-stimulated Na+ flux. The addition of a farnesyl group does not appear to be involved in aldosterone's action. Neither alpha-hydroxyfarne-sylphosphonic acid, an inhibitor of farnesyl:protein transferase, nor N-acetyl-S-farnesyl-L-cysteine, an inhibitor of farnesylated protein methylation, inhibits the hormone-induced increase in Na+ transport. In contrast, N-acetyl-S-geranyl-geranyl-L-cysteine, an inhibitor of geranylgeranyl protein methylation, completely abolishes the aldosterone-induced increase in Na+ flux with no effect on insulin-mediated Na+ transport or cellular protein content. These data indicate that methylation of a geranylgeranylated protein is involved in aldosterone's natriferic action. PMID:9227422

  6. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism

    PubMed Central

    Scholl, Ute I.; Goh, Gerald; Stölting, Gabriel; de Oliveira, Regina Campos; Choi, Murim; Overton, John D.; Fonseca, Annabelle L.; Korah, Reju; Starker, Lee F.; Kunstman, John W.; Prasad, Manju L.; Hartung, Erum A.; Mauras, Nelly; Benson, Matthew R.; Brady, Tammy; Shapiro, Jay R.; Loring, Erin; Nelson-Williams, Carol; Libutti, Steven K.; Mane, Shrikant; Hellman, Per; Westin, Gunnar; Åkerström, Göran; Björklund, Peyman; Carling, Tobias; Fahlke, Christoph; Hidalgo, Patricia; Lifton, Richard P.

    2013-01-01

    Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations in the potassium channel KCNJ5 that result in cell depolarization and Ca2+ influx cause ~40% of these tumors1. We found five somatic mutations (four altering glycine 403, one altering isoleucine 770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 non-KCNJ5-mutant APAs. These mutations lie in S6 segments that line the channel pore. Both result in channel activation at less depolarized potentials, and glycine 403 mutations also impair channel inactivation. These effects are inferred to cause increased Ca2+ influx, the sufficient stimulus for aldosterone production and cell proliferation in adrenal glomerulosa2. Remarkably, we identified de novo mutations at the identical positions in two children with a previously undescribed syndrome featuring primary aldosteronism and neuromuscular abnormalities. These findings implicate gain of function Ca2+ channel mutations in aldosterone-producing adenomas and primary aldosteronism. PMID:23913001

  7. Archival storage solutions for PACS

    NASA Astrophysics Data System (ADS)

    Chunn, Timothy

    1997-05-01

    While they are many, one of the inhibitors to the wide spread diffusion of PACS systems has been robust, cost effective digital archive storage solutions. Moreover, an automated Nearline solution is key to a central, sharable data repository, enabling many applications such as PACS, telemedicine and teleradiology, and information warehousing and data mining for research such as patient outcome analysis. Selecting the right solution depends on a number of factors: capacity requirements, write and retrieval performance requirements, scaleability in capacity and performance, configuration architecture and flexibility, subsystem availability and reliability, security requirements, system cost, achievable benefits and cost savings, investment protection, strategic fit and more.This paper addresses many of these issues. It compares and positions optical disk and magnetic tape technologies, which are the predominant archive mediums today. Price and performance comparisons will be made at different archive capacities, plus the effect of file size on storage system throughput will be analyzed. The concept of automated migration of images from high performance, high cost storage devices to high capacity, low cost storage devices will be introduced as a viable way to minimize overall storage costs for an archive. The concept of access density will also be introduced and applied to the selection of the most cost effective archive solution.

  8. Web-based PACS and EHR system

    NASA Astrophysics Data System (ADS)

    Parikh, Ashesh; Mehta, Nihal

    2015-03-01

    We demonstrate how a cloud-based PACS can exchange information with other medical systems, including other cloud-based PACS, to provide a comprehensive and integrated view of a patient's health record. Such a consolidated report will lead to improved patient care.

  9. Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs.

    PubMed

    Armanini, Decio; Sabbadin, Chiara; Donà, Gabriella; Clari, Giulio; Bordin, Luciana

    2014-05-01

    Canrenone is a derivative of spironolactone with lower antiandrogen activity. The drug is used only in few countries and can block all the side effects of aldosterone (ALDO). The drug is effective even in the presence of normal concentrations of ALDO. Mineralcorticoid receptor antagonists block the inflammatory activity of ALDO at the level of target tissues as heart, vessels and mononuclear leukocytes. Canrenone reduces the progression of insulin resistance and of microalbuminuria in type 2 diabetes and other related diseases. Both canrenone and hydrochlorothiazide can enhance the effect of treatment with ACE inhibitors and angiotensin II receptor blockers on microalbuminuria, but ALDO receptor blockers are more active. This different action is due to the fact that only canrenone blocks mineralocorticoid receptors. Serum potassium and renal function should be monitored before and during the treatment. ALDO receptor blockers are recommended in addition to polytherapy for resistant hypertension, but there are no studies on the effect of the drug as first-choice therapy. PMID:24617854

  10. Picture archiving and communications systems (PACS).

    PubMed

    Honeyman, J C; Frost, M M; Huda, W; Loeffler, W; Ott, M; Staab, E V

    1994-01-01

    Although there has been a recent increase in interest in picture archiving and communications systems (PACS) topics, little has been published to assist the non-technical person in understanding the complexities of the technologies required for a PACS implementation. This issue of Current Problems in Radiology defines each PACS component and explains why each is important in a system design. PACS installations at the University of Florida are used as examples to tie the concepts together. The infrastructure required for PACS consists of the information system interfaces, networks, and databases. Information system interfaces guarantee consistent patient data across all platforms and reduce labor requirements by eliminating duplicate data entry. Data networks move information from the originating location to users around the hospital, clinic, campus, city, or world. In the PACS environment, the data consist of patient and study information as well as images and information about these images. Databases organize the data from multiple sources into a coherent package that can be queried for many different purposes, such as retrieving images, reviewing patient and study information, studying practice statistics, and performing outcomes analysis. PACS components consist of acquisition nodes, archives, and output devices. Acquisition nodes may include "digital modalities" such as CT, MRI, nuclear medicine, and computed radiography (CR), along with devices to convert from analog to digital, such as digitizers and frame grabbers. Options for archives are discussed along with configuration schemes. Output devices include both hard copy (film and paper prints) and soft copy (workstations for display and diagnosis). Finally, a description of the PACS installations at the University of Florida is presented, with comments on some of the difficulties and complexities encountered. A discussion of the cost and benefits of PACS is included, along with a forecast of the future of

  11. Aldosterone Contributes to Elevated Left Ventricular Mass in Black Boys

    PubMed Central

    Murro, Diana G; Beavers, Melinda; Harshfield, Gregory A; Kapuku, Gaston K

    2012-01-01

    Background Left Ventricular Hypertrophy (LVH) poses a great risk of cardiovascular morbidity and mortality in adults and may pose a serious risk in children. Adult studies have shown Renin Angiotensin Aldosterone System (RAAS) levels are directly correlated with left ventricular mass index (LVMI). This purpose of this study is to explore race and sex-related effects of the RAAS on LVMI in adolescents. Methods Data was collected from a sample of 89 blacks (44 girls, 45 boys) and 102 whites (40 girls, 62 boys) ages 15–19. Data collected included, sex, age, body mass index (BMI), LVMI, baseline blood pressure, and levels of aldosterone and angiotensin II. Results In black males, increased aldosterone levels were correlated with decreased sodium excretion (r=−0.336, p=0.024), increased blood pressure (r=0.358, p=0.016), and increased LVMI (r=0.342, p=0.022). In black females, increased aldosterone levels correlated with increased baseline blood pressure (r=0.356, p=0.018). In white males, increased aldosterone was correlated decreased sodium excretion (r=−0.391, p=0.002). In white females, aldosterone levels correlated with increased baseline blood pressure (r=0.323, p=0.042) and decreased sodium excretion (r=−0.342, p=0.031). Conclusions The results suggest the following model in black males: increased aldosterone leads to increased sodium retention, causing a volume-mediated increase in blood pressure; increased blood pressure results in increased left ventricular mass and eventually LVH. PMID:23179199

  12. Molecular and Cellular Mechanisms of Aldosterone Producing Adenoma Development

    PubMed Central

    Boulkroun, Sheerazed; Fernandes-Rosa, Fabio Luiz; Zennaro, Maria-Christina

    2015-01-01

    Primary aldosteronism (PA) is the most common form of secondary hypertension with an estimated prevalence of ~10% in referred patients. PA occurs as a result of a dysregulation of the normal mechanisms controlling adrenal aldosterone production. It is characterized by hypertension with low plasma renin and elevated aldosterone and often associated with hypokalemia. The two major causes of PA are unilateral aldosterone producing adenoma (APA) and bilateral adrenal hyperplasia, accounting together for ~95% of cases. In addition to the well-characterized effect of excess mineralocorticoids on blood pressure, high levels of aldosterone also have cardiovascular, renal, and metabolic consequences. Hence, long-term consequences of PA include increased risk of coronary artery disease, myocardial infarction, heart failure, and atrial fibrillation. Despite recent progress in the management of patients with PA, critical issues related to diagnosis, subtype differentiation, and treatment of non-surgically correctable forms still persist. A better understanding of the pathogenic mechanisms of the disease should lead to the identification of more reliable diagnostic and prognostic biomarkers for a more sensitive and specific screening and new therapeutic options. In this review, we will summarize our current knowledge on the molecular and cellular mechanisms of APA development. On one hand, we will discuss how various animal models have improved our understanding of the pathophysiology of excess aldosterone production. On the other hand, we will summarize the major advances made during the last few years in the genetics of APA due to transcriptomic studies and whole exome sequencing. The identification of recurrent and somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D) and ATPases (ATP1A1 and ATP2B3) allowed highlighting the central role of calcium signaling in autonomous aldosterone production by the adrenal. PMID:26124749

  13. Small-Conductance Ca2+-Activated Potassium Channels Negatively Regulate Aldosterone Secretion in Human Adrenocortical Cells.

    PubMed

    Yang, Tingting; Zhang, Hai-Liang; Liang, Qingnan; Shi, Yingtang; Mei, Yan-Ai; Barrett, Paula Q; Hu, Changlong

    2016-09-01

    Aldosterone, which plays a key role in maintaining water and electrolyte balance, is produced by zona glomerulosa cells of the adrenal cortex. Autonomous overproduction of aldosterone from zona glomerulosa cells causes primary hyperaldosteronism. Recent clinical studies have highlighted the pathological role of the KCNJ5 potassium channel in primary hyperaldosteronism. Our objective was to determine whether small-conductance Ca(2+)-activated potassium (SK) channels may also regulate aldosterone secretion in human adrenocortical cells. We found that apamin, the prototypic inhibitor of SK channels, decreased membrane voltage, raised intracellular Ca(2+) and dose dependently increased aldosterone secretion from human adrenocortical H295R cells. By contrast, 1-Ethyl-2-benzimidazolinone, an agonist of SK channels, antagonized apamin's action and decreased aldosterone secretion. Commensurate with an increase in aldosterone production, apamin increased mRNA expression of steroidogenic acute regulatory protein and aldosterone synthase that control the early and late rate-limiting steps in aldosterone biosynthesis, respectively. In addition, apamin increased angiotensin II-stimulated aldosterone secretion, whereas 1-Ethyl-2-benzimidazolinone suppressed both angiotensin II- and high K(+)-stimulated production of aldosterone in H295R cells. These findings were supported by apamin-modulation of basal and angiotensin II-stimulated aldosterone secretion from acutely prepared slices of human adrenals. We conclude that SK channel activity negatively regulates aldosterone secretion in human adrenocortical cells. Genetic association studies are necessary to determine whether mutations in SK channel subtype 2 genes may also drive aldosterone excess in primary hyperaldosteronism. PMID:27432863

  14. The Role of Aldosterone in Obesity-Related Hypertension.

    PubMed

    Kawarazaki, Wakako; Fujita, Toshiro

    2016-04-01

    Obese subjects often have hypertension and related cardiovascular and renal diseases, and this has become a serious worldwide health problem. In obese subjects, impaired renal-pressure natriuresis causes sodium retention, leading to the development of salt-sensitive hypertension. Physical compression of the kidneys by visceral fat and activation of the sympathetic nervous system, renin-angiotensin systems (RAS), and aldosterone/mineralocorticoid receptor (MR) system are involved in this mechanism. Obese subjects often exhibit hyperaldosteronism, with increased salt sensitivity of blood pressure (BP). Adipose tissue excretes aldosterone-releasing factors, thereby stimulating aldosterone secretion independently of the systemic RAS, and aldosterone/MR activation plays a key role in the development of hypertension and organ damage in obesity. In obese subjects, both salt sensitivity of BP, enhanced by obesity-related metabolic disorders including aldosterone excess, and increased dietary sodium intake are closely related to the incidence of hypertension. Some salt sensitivity-related gene variants affect the risk of obesity, and together with salt intake, its combination is possibly associated with the development of hypertension in obese subjects. With high salt levels common in modern diets, salt restriction and weight control are undoubtedly important. However, not only MR blockade but also new diagnostic modalities and therapies targeting and modifying genes that are related to salt sensitivity, obesity, or RAS regulation are expected to prevent obesity and obesity-related hypertension. PMID:26927805

  15. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently

    PubMed Central

    Lee, Seung-Eun; Lee, You-Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung-Han; Oh, Young Lyun

    2015-01-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  16. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently.

    PubMed

    Lee, Seung Eun; Kim, Jae Hyeon; Lee, You Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung Han; Oh, Young Lyun

    2015-12-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  17. PacBio Sequencing and Its Applications

    PubMed Central

    Rhoads, Anthony; Au, Kin Fai

    2015-01-01

    Single-molecule, real-time sequencing developed by Pacific BioSciences offers longer read lengths than the second-generation sequencing (SGS) technologies, making it well-suited for unsolved problems in genome, transcriptome, and epigenetics research. The highly-contiguous de novo assemblies using PacBio sequencing can close gaps in current reference assemblies and characterize structural variation (SV) in personal genomes. With longer reads, we can sequence through extended repetitive regions and detect mutations, many of which are associated with diseases. Moreover, PacBio transcriptome sequencing is advantageous for the identification of gene isoforms and facilitates reliable discoveries of novel genes and novel isoforms of annotated genes, due to its ability to sequence full-length transcripts or fragments with significant lengths. Additionally, PacBio’s sequencing technique provides information that is useful for the direct detection of base modifications, such as methylation. In addition to using PacBio sequencing alone, many hybrid sequencing strategies have been developed to make use of more accurate short reads in conjunction with PacBio long reads. In general, hybrid sequencing strategies are more affordable and scalable especially for small-size laboratories than using PacBio Sequencing alone. The advent of PacBio sequencing has made available much information that could not be obtained via SGS alone. PMID:26542840

  18. Strategy of DIN-PACS benchmark testing

    NASA Astrophysics Data System (ADS)

    Norton, Gary S.; Lyche, David K.; Richardson, Nancy E.; Thomas, Jerry A.; Romlein, John R.; Cawthon, Michael A.; Lawrence, David P.; Shelton, Philip D.; Parr, Laurence F.; Richardson, Ronald R., Jr.; Johnson, Steven L.

    1998-07-01

    The Digital Imaging Network -- Picture Archive and Communication System (DIN-PACS) procurement is the Department of Defense's (DoD) effort to bring military medical treatment facilities into the twenty-first century with nearly filmless digital radiology departments. The DIN-PACS procurement is unique from most of the previous PACS acquisitions in that the Request for Proposals (RFP) required extensive benchmark testing prior to contract award. The strategy for benchmark testing was a reflection of the DoD's previous PACS and teleradiology experiences. The DIN-PACS Technical Evaluation Panel (TEP) consisted of DoD and civilian radiology professionals with unique clinical and technical PACS expertise. The TEP considered nine items, key functional requirements to the DIN-PACS acquisition: (1) DICOM Conformance, (2) System Storage and Archive, (3) Workstation Performance, (4) Network Performance, (5) Radiology Information System (RIS) functionality, (6) Hospital Information System (HIS)/RIS Interface, (7) Teleradiology, (8) Quality Control, and (9) System Reliability. The development of a benchmark test to properly evaluate these key requirements would require the TEP to make technical, operational, and functional decisions that had not been part of a previous PACS acquisition. Developing test procedures and scenarios that simulated inputs from radiology modalities and outputs to soft copy workstations, film processors, and film printers would be a major undertaking. The goals of the TEP were to fairly assess each vendor's proposed system and to provide an accurate evaluation of each system's capabilities to the source selection authority, so the DoD could purchase a PACS that met the requirements in the RFP.

  19. Performance Evaluation of a Clinical PACS Module

    NASA Astrophysics Data System (ADS)

    Taira, Ricky K.; Cho, Paul S.; Huang, H. K.; Mankovich, Nicholas J.; Boechat, Maria I.

    1989-05-01

    Picture archiving and communication systems (PACS) are now clinically available in limited radiologic applications. The benefits, acceptability, and reliablity of these systems have thus far been mainly speculative and anecdotal. This paper discusses the evaluation of a PACS module implemented in the pediatric radiology section of a 700-bed teaching hospital. The PACS manages all pediatric inpatient images including conventional x-rays and contrast studies (obtained with a computed radiography system), magnetic resonance images, and relevant ultrasound images. A six-monitor workstation is available for image review.

  20. Aldosterone, Renin, and Diabetes Mellitus in African Americans: The Jackson Heart Study.

    PubMed

    Joseph, Joshua J; Echouffo-Tcheugui, Justin B; Kalyani, Rita R; Yeh, Hsin-Chieh; Bertoni, Alain G; Effoe, Valery S; Casanova, Ramon; Sims, Mario; Correa, Adolfo; Wu, Wen-Chih; Wand, Gary S; Golden, Sherita H

    2016-04-01

    We examined the association of both aldosterone and renin, with insulin resistance, β-cell function, and incident diabetes in a large African American cohort. Renin-angiotensin-aldosterone system with higher levels of aldosterone and renin is associated with insulin resistance, compensatory increased β-cell function and incident diabetes in African Americans. PMID:26908112

  1. A Case of Glucocorticoid Remediable Aldosteronism and Thoracoabdominal Aneurysms

    PubMed Central

    Shahrrava, Anahita; Moinuddin, Sunnan; Boddu, Prajwal; Shah, Rohan

    2016-01-01

    Glucocorticoid remediable aldosteronism (GRA) is rare familial form of primary aldosteronism characterized by a normalization of hypertension with the administration of glucocorticoids. We present a case of GRA and thoracoabdominal aneurysm complicated by multiple aortic dissections requiring complex surgical and endovascular repairs. Registry studies have shown a high rate of intracranial aneurysms in GRA patients with high case fatality rates. The association of thoracoabdominal aneurysms with GRA has not been described, thus far, in literature. Studies have shown that high tissue aldosterone levels concomitant with salt intake have a significant role in the pathogenesis of aneurysms and this may explain the formation of aneurysms in the intracranial vasculature and aorta. The association of GRA with thoracic aortic aneurysms needs to be further studied to develop screening recommendations for early identification and optimal treatment. Also, the early use of mineralocorticoid antagonists may have a significant preventive and attenuating effect in aneurysm formation, an association which needs to be confirmed in future studies. PMID:27366333

  2. Effect of swimming on the production of aldosterone in rats.

    PubMed

    Lieu, Fu-Kong; Lin, Chih-Yung; Wang, Paulus S; Jian, Cai-Yun; Yeh, Yung-Hsing; Chen, Yi-An; Wang, Kai-Lee; Lin, Yi-Chun; Chang, Ling-Ling; Wang, Guei-Jane; Wang, Shyi-Wu

    2014-01-01

    It has been demonstrated that exercise is one of the stresses known to increase the aldosterone secretion. Both potassium and angiotensin II (Ang II) levels are shown to be correlated with aldosterone production during exercise, but the mechanism is still unclear. In an in vivo study, male rats were catheterized via right jugular vein (RJV), and divided into four groups namely water immersion, swimming, lactate infusion (13 mg/kg/min) and pyruvate infusion (13 mg/kg/min) groups. Each group was treated for 10 min. Blood samples were collected at 0, 10, 15, 30, 60 and 120 min from RJV after administration. In an in vitro study, rat zona glomerulosa (ZG) cells were challenged by lactate (1-10 mM) in the presence or absence of Ang II (10(-8) M) for 60 min. The levels of aldosterone in plasma and medium were measured by radioimmunoassay. Cell lysates were analyzed by immunoblotting assay. After exercise and lactate infusion, plasma levels of aldosterone and lactate were significantly higher than those in the control group. Swimming for 10 min significantly increased the plasma Ang II levels in male rats. Administration of lactate plus Ang II significantly increased aldosterone production and enhanced protein expression of steroidogenic acute regulatory protein (StAR) in ZG cells. These results demonstrated that acute exercise led to the increase of both aldosterone and Ang II secretion, which is associated with lactate action on ZG cells and might be dependent on the activity of renin-angiotensin system. PMID:25289701

  3. Effect of Swimming on the Production of Aldosterone in Rats

    PubMed Central

    Wang, Paulus S.; Jian, Cai-Yun; Yeh, Yung-Hsing; Chen, Yi-An; Wang, Kai-Lee; Lin, Yi-Chun; Chang, Ling-Ling; Wang, Guei-Jane; Wang, Shyi-Wu

    2014-01-01

    It has been demonstrated that exercise is one of the stresses known to increase the aldosterone secretion. Both potassium and angiotensin II (Ang II) levels are shown to be correlated with aldosterone production during exercise, but the mechanism is still unclear. In an in vivo study, male rats were catheterized via right jugular vein (RJV), and divided into four groups namely water immersion, swimming, lactate infusion (13 mg/kg/min) and pyruvate infusion (13 mg/kg/min) groups. Each group was treated for 10 min. Blood samples were collected at 0, 10, 15, 30, 60 and 120 min from RJV after administration. In an in vitro study, rat zona glomerulosa (ZG) cells were challenged by lactate (1–10 mM) in the presence or absence of Ang II (10−8 M) for 60 min. The levels of aldosterone in plasma and medium were measured by radioimmunoassay. Cell lysates were analyzed by immunoblotting assay. After exercise and lactate infusion, plasma levels of aldosterone and lactate were significantly higher than those in the control group. Swimming for 10 min significantly increased the plasma Ang II levels in male rats. Administration of lactate plus Ang II significantly increased aldosterone production and enhanced protein expression of steroidogenic acute regulatory protein (StAR) in ZG cells. These results demonstrated that acute exercise led to the increase of both aldosterone and Ang II secretion, which is associated with lactate action on ZG cells and might be dependent on the activity of renin-angiotensin system. PMID:25289701

  4. [The effect of aldosterone A on renal potassium excretion].

    PubMed

    Winther, Signe Abitz; Egfjord, Martin

    2011-01-10

    Recent studies have shown expression of the following regulatory WNK kinases in the kidney: the full-length WNK1 (L-WNK1), the shorter kidney specific WNK1 transcript (KS-WNK1), formed by alternative splicing, and WNK4. Aldosterone activates expression of KS-WNK1 and inhibits WNK4 via SGK1 - both leading to stimulation of ENaC and activation of ROMK, and increased potassium excretion. Thus, further characterization of the WNK system may lead to elucidation of the dual anti-natriuretic and kaliuretic effects of aldosterone, in situations where only activation of one of these effects is needed. PMID:21219845

  5. Severe hypertension in primary aldosteronism and good response to surgery.

    PubMed

    Clarke, D; Wilkinson, R; Johnston, I D; Hacking, P M; Haggith, J W

    1979-03-01

    11 patients with primary aldosteronism have been encountered over 11 years and submitted to surgery in a provincial teaching hospital serving a population of 3 million. Contrary to classical teaching, the hypertension has usually been very severe. Precise identification of the site of the lesion preoperatively has been possible by the measurement of adrenal-vein aldosterone levels, and results of surgery have been excellent. The iodocholesterol adrenal scan also correctly identified the site of the adenoma in 5 out of 7 patients in which it was used. Adrenal venography was of little value except in siting catheters. PMID:85065

  6. BIOLOGICAL TREATMENT OF HIGH STRENGTH PHARMACEUTICAL WASTEWATER--A CASE HISTORY USING PAC (POWDERED ACTIVATED CARBON) TECHNOLOGY

    EPA Science Inventory

    From September to December 1984 pharmaceutical wastewater containing high concentrations of total chemical oxygen demand (TCOD) was treated in trailer mounted, activated sludge pilot plants. Three systems were operated in parallel. Powdered activated carbon (PAC) was added to two...

  7. Current developments in departmental PACS for ultrasound.

    PubMed

    Grenier, L E; Eng, P

    1995-01-01

    1. INTRODUCTION TO DEPARTMENTAL PACS. Full or partial Departmental PACS is generally taken to mean an image management system focused on serving the needs of a specific modality or modality application. It will provide a modality specific means of image acquisition, specialized redisplay of images, distribution, and local long term storage of images. A Departmental PACS can be considered in isolation or as a component in a distributed Radiology PACS which consists of one or more departmental work groups on a back bone, potentially with shared resources. 2. DEPARTMENTAL PACS Issues Implementation of a Departmental PACS requires an in-depth knowledge of departmental clinical practice and work flow in all affected areas in the department, including patient intake, image collection, data routing, retrieval of previous image data, reporting, and long term data management and storage. Optimization of modality specific image display systems requires significant involvement from representative physician users. System architectures and user interfaces must be flexible enough to support the span of variation in clinical practice encountered in the site. A departmental PACS should offer a variety of "open" communications interfaces, both local and wide area, recognizing that outreach efforts are often driven by specific imaging departments. Interfaces to other departmental PAC systems and other information systems must be considered in order to facilitate institutions developing "Best of Breed" PACS systems. As hospitals move toward the integrated electronic medical record, means need to exist for a client process launched from a physician desktop to acquire images and/or reports from a departmental system. At minimum, HIS/RIS interfaces need to be considered to minimize re-keying of data and reduce data entry errors. 3. DESIGN OBJECTIVES FOR ALI ULTRAPACS. The key objectives were to design a product which could function either as a free standing PACS or as a departmental

  8. Preliminary results of a PACS implementation

    NASA Astrophysics Data System (ADS)

    Kishore, Sheel; Khalsa, Satjeet S.; Seshadri, Sridhar B.; Arenson, Ronald L.

    1991-07-01

    The Radiology Department at the University of Pennsylvania is in the process of clinically testing the first phase of its PACS implementation. The first phase has been designed to support two Intensive Care Units, two GE SIGNA MR units and a Du Pont FD 2000 Film Digitizer. The entire system has been running clinically for about three months. Any PACS effort involves integrating software and hardware from different manufactures. Some of the equipment on a PACS network are often 'closed' and provide limited access. In addition, the entire PACS system is expected to provide uninterrupted service, have adequate throughput and ensure data integrity. By and large, these goals have been met. Clinical testing has provided valuable insights about system integration and highlighted areas of improvement in the system design. A detailed discussion of these results is presented.

  9. Three-component competitive adsorption model for flow-through PAC systems. 1. Model development and verification with a PAC/membrane system.

    PubMed

    Li, Qilin; Mariñas, Benito J; Snoeyink, Vernon L; Campos, Carlos

    2003-07-01

    Natural organic matter (NOM) interferes with the adsorption of trace organic compounds on porous adsorbents such as powdered activated carbon (PAC) by pore blockage and direct competition for adsorption sites. The competitive effect of NOM in flow-through systems in which the retention time of the PAC is greater than the hydraulic retention time of the system can be magnified because NOM from the influent water can continue to adsorb on the PAC retained in the system. As a result, the adsorption capacity and the diffusion coefficient of trace compounds can decrease as NOM from the influent water accumulates. In this study, a dynamic three-component adsorption model was developed to quantitatively describe the removal of a trace compound from water in flow-through PAC processes. The system was simplified by using p-dichlorobenzene (p-DCB) to represent the NOM fraction that competes directly with the target trace organic atrazine for adsorption sites and by using poly(styrene sulfonate) (PSS-1.8k) to represent large, pore-blocking NOM. The model was based on the homogeneous surface diffusion assumption with the adsorption capacity of atrazine being gradually adjusted using a simplified version of the ideal adsorbed solution theory model developed in this study. The surface diffusion coefficients of atrazine and p-DCB were modeled as a function of the surface concentration of the pore-blocking compound, PSS-1.8k. The model was verified experimentally with a PAC/microfiltration (MF) system. The use of single-solute adsorption parameters obtained from batch isotherm and kinetic tests resulted in good model predictions for the adsorption of atrazine and the two model compounds under operating conditions typical of PAC/MF systems. The model will be applied to study various operating conditions and other system parameters of PAC/membrane systems in part 2 of this study. PMID:12875406

  10. Overview of Polycyclic Aromatic Compounds (PAC)

    PubMed Central

    Achten, Christine; Andersson, Jan T.

    2015-01-01

    The chemical group of polycyclic aromatic compounds (PAC), including the better-known subgroup of polycyclic aromatic hydrocarbons (PAH) and the heterocyclic aromatic compounds (NSO-PAC, heterocycles), comprise several thousand individual compounds. It is hard to find a comprehensive overview in the literature of these PACs that includes a substantial amount of relevant properties. Here an attempt is made to summarize the most studied but also some less well-known PACs. In addition to basic data such as recommended names, abbreviations, CAS numbers, molecular formulas, chemical structures, and exact mono-isotopic molecular weights, physico-chemical properties taken from the literature like boiling points, vapor pressures, water solubilities, Henry's Law constants, n-octanol-water partition coefficients (log KOW), and pKa are summarized. Selected toxicological data are listed indicating carcinogenic and mutagenic activity or effects on different organisms. PAC nomenclature is a complex topic, so suggestions for practical use are made. Regarding available data, estimated (instead of measured) values should be used with caution because considerable deviations from experimentally determined values can occur. For an enhanced understanding of the behavior of single PACs in comparison with each other, some of the properties mentioned above are plotted vs. the number of rings or the degree of alkylation. Also, some physico-chemical data are correlated with different functional groups as substituents of the PAHs. This article reveals that rather little is known about the less common PACs, e.g., higher molecular weight compounds, alkylated or otherwise substituted aromatics, for instance, keto-, oxo-, amino-, nitro-, cyano-PAHs, or some heterocyclic aromatic compounds, including their derivatives. It mirrors the limited state of knowledge about the variety of PACs that do not belong to the 16 EPA PAHs. PMID:26823644

  11. Effect of PAC addition on sludge properties in an MBR treating high strength wastewater.

    PubMed

    Satyawali, Yamini; Balakrishnan, Malini

    2009-04-01

    This paper examines the sludge characteristics in a submerged membrane bioreactor (MBR) operated on a high strength wastewater from an alcohol distillery. Two membrane bioreactors, each with a 30 microm mesh filter, were investigated with and without addition of powdered activated carbon (PAC). Experiments were conducted with varying organic loading rates ranging from 3.4 to 6.9 kgCOD m(-3) day(-1) and the specific oxygen uptake rate (SOUR), sludge volume index (SVI), mixed liquor suspended solids (MLSS), particle size and extracellular polymeric substances (EPS) were monitored over a 180 day period. Respirometric experiments did not show enhancement in microbial activity with PAC supplementation. Addition of PAC decreased the SVI thereby perceptibly improving sludge dewaterability. The sludge particle size, which increased with time, appeared to be independent of PAC addition but was influenced by the aeration intensity. PAC also did not affect the sludge EPS concentration; however, the EPS composition, in terms of protein/carbohydrate (polysaccharide) ratio was altered resulting in a high P/C ratio. FTIR analysis of the sludge samples indicated that the functional groups associated with the sludge polysaccharides appear to be involved in its interaction with PAC. PMID:19201006

  12. Short history of PACS (Part II: Europe).

    PubMed

    Lemke, Heinz U

    2011-05-01

    Although the concept of picture archiving and communications systems (PACS) was developed in Europe during the latter part of the 1970s, no working system was completed at that time. The first PACS implementations took place in the United States in the early 1980s, e.g. at Pennsylvania University, UCLA, and Kansas City University. Some more or less successful PACS developments also took place in Europe in the 1980s, particularly in the Netherlands, Belgium, Austria, the United Kingdom, France, Italy, Scandinavia, and Germany. Most systems could be characterized by their focus on a single department, such as radiology or nuclear medicine. European hospital-wide PACS with high visibility evolved in the early 1990s in London (Hammersmith Hospital) and Vienna (SMZO). These were followed during the latter part of the 1990s by approximately 10-20 PACS installations in each of the major industrialized countries of Europe. Wide-area PACS covering several health care institutions in a region are now in the process of being implemented in a number of European countries. Because of limitations of space some countries, for example, Denmark, Finland, Spain, Greece, as well as Eastern European countries, etc. could not be appropriately represented in this paper. PMID:21466932

  13. Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability.

    PubMed

    Miró, Lluïsa; Pérez-Bosque, Anna; Maijó, Mònica; Amat, Concepció; Naftalin, Richard J; Moretó, Miquel

    2013-05-01

    In vivo studies show that raised aldosterone (Aldo) during low-Na adaptation regulates the growth of pericryptal myofibroblasts and reduces the permeability of the colonic epithelium. The aim of this study was to reproduce in vitro the in vivo condition of increased Aldo using human CCD-18Co myofibroblasts and T84 colonic epithelial cells to measure myofibroblast and epithelial proliferation and the expression of intercellular junction proteins. Proliferation was quantified by measuring 5-bromo-2'-deoxyuridine incorporation. The myofibroblast expression of EGF, VEGFa, and transforming growth factor-β1 (TGF-β1) was measured by real-time PCR and the expression of junctional complex proteins by Western blot. Aldo stimulated the proliferation of myofibroblasts by 70% (P < 0.05) and increased EGF mRNA expression by 30% (P < 0.05) without affecting VEGFa and TGF-β1. EGF concentration in the incubation medium increased by 30% (P < 0.05) 24 h after Aldo addition, and these effects were prevented by the addition of spironolactone. Myofibroblast proliferation in response to Aldo was mediated by EGF receptor (EGFR) and involved both MAPKK and phosphatidylinositol 3-kinase pathways. When T84 cells were incubated with medium from myofibroblasts stimulated with Aldo (conditioned medium), the expression of β-catenin and claudin IV was increased by 30% (P < 0.05) and proliferation by 40% (P < 0.05). T84 proliferation decreased when α-EGF, or the EGFR antagonist AG1478, was present. Results in vivo indicate that rats fed a low-salt diet showed an increased expression of EGF and EGFR in the colonic mucosa. These results support the view that changes in colonic permeability during low-Na adaptation are mediated by the EGF secreted by myofibroblasts in response to raised Aldo. PMID:23467299

  14. TISSUE 65ZINC TRANSLOCATION IN A RAT MODEL OF CHRONIC ALDOSTERONISM

    PubMed Central

    Selektor, Yelena; Parker, Robert B.; Sun, Yao; Zhao, Wenyuan; Bhattacharya, Syamal K.; Weber, Karl T.

    2009-01-01

    Zinc, an essential micronutrient, is involved in wound healing. The hypozincemia seen with chronic aldosteronism is associated with enhanced fecal and urinary excretory Zn losses while its tissue distribution is less certain. Herein, we monitored tissue 65Zn distribution in uninephrectomized rats at wks 1 and 4 of aldosterone/salt treatment (ALDOST). Plasma and tissue total radionucleotide uptake was determined by calculating its mean radioactivity at 1, 4, 8, 24, and 48 h after intravenous 65Zn administration and where respective area under the concentration-time curves (AUC) were determined by the linear trapezoidal rule and expressed as a tissue:plasma AUC ratio. Tissues examined included: injured heart and kidney in response to ALDOST and incised skin; noninjured liver, skeletal muscle, and spleen, sites of stress-linked Zn uptake; and bone, a major storage and release site when Zn homeostasis is threatened. Compared to age-/gender-matched controls, with wk 1 and 4 ALDOST we found: reduced plasma 65Zn; an accumulation of 65Zn in heart and kidneys, where a well-known vasculopathy involves intramural vessels, and in incised skin at wk 1; an organ-specific increase in tissue 65Zn in liver, in keeping with upregulated metallothionein expression, skeletal muscle, and spleen; and a fall in bone and skin 65Zn at wk 4. Thus a wide-ranging disturbance in Zn homeostasis appears during ALDOST to include its translocation from plasma to injured heart, kidneys and skin and noninjured liver, skeletal muscle and spleen, together with a resorption of stored Zn in bone at wk 4. Zinc dyshomeostasis is an integral feature of chronic aldosteronism. PMID:18427278

  15. Role of the Renin-Angiotensin System and Aldosterone on Cardiometabolic Syndrome

    PubMed Central

    Stiefel, P.; Vallejo-Vaz, A. J.; García Morillo, S.; Villar, J.

    2011-01-01

    Aldosterone facilitates cardiovascular damage by increasing blood pressure and through different mechanisms that are independent of its effects on blood pressure. In this respect, recent evidence involves aldosterone in the pathogenesis of metabolic syndrome. Although this relationship is complex, there is some evidence suggesting that different factors may play an important role, such as insulin resistance, renin-angiotensin-aldosterone system, oxidative stress, sodium retention, increased sympathetic activity, levels of free fatty acids, or inflammatory cytokines and adipokines. In addition to the classical pathway by which aldosterone acts through the mineralocorticoid receptors leading to sodium retention, aldosterone also has other mechanisms that influence cardiovascular tissue remodelling. Finally, overweight and obesity promote the adrenal secretion of aldosterone, increasing the predisposition to type 2 diabetes mellitus. Further studies are needed to better establish therapeutic strategies that act on the blockade of mineralocorticoid receptor in the treatment and prevention of cardiovascular diseases related to the excess of aldosterone and the metabolic syndrome. PMID:21785705

  16. Activating mutations in CTNNB1 in aldosterone producing adenomas.

    PubMed

    Åkerström, Tobias; Maharjan, Rajani; Sven Willenberg, Holger; Cupisti, Kenko; Ip, Julian; Moser, Ana; Stålberg, Peter; Robinson, Bruce; Alexander Iwen, K; Dralle, Henning; Walz, Martin K; Lehnert, Hendrik; Sidhu, Stan; Gomez-Sanchez, Celso; Hellman, Per; Björklund, Peyman

    2016-01-01

    Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5-10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3. The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation. PMID:26815163

  17. 21 CFR 862.1045 - Aldosterone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Aldosterone test system. 862.1045 Section 862.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  18. 21 CFR 862.1045 - Aldosterone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Aldosterone test system. 862.1045 Section 862.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  19. 21 CFR 862.1045 - Aldosterone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Aldosterone test system. 862.1045 Section 862.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  20. 21 CFR 862.1045 - Aldosterone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Aldosterone test system. 862.1045 Section 862.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  1. 21 CFR 862.1045 - Aldosterone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Aldosterone test system. 862.1045 Section 862.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  2. Reversible heart rhythm complexity impairment in patients with primary aldosteronism

    NASA Astrophysics Data System (ADS)

    Lin, Yen-Hung; Wu, Vin-Cent; Lo, Men-Tzung; Wu, Xue-Ming; Hung, Chi-Sheng; Wu, Kwan-Dun; Lin, Chen; Ho, Yi-Lwun; Stowasser, Michael; Peng, Chung-Kang

    2015-08-01

    Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1-5, area 6-15, and area 6-20 on MSE analysis (all p < 0.05). Area 1-5, area 6-15, area 6-20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy.

  3. Activating mutations in CTNNB1 in aldosterone producing adenomas

    PubMed Central

    Åkerström, Tobias; Maharjan, Rajani; Sven Willenberg, Holger; Cupisti, Kenko; Ip, Julian; Moser, Ana; Stålberg, Peter; Robinson, Bruce; Alexander Iwen, K.; Dralle, Henning; Walz, Martin K.; Lehnert, Hendrik; Sidhu, Stan; Gomez-Sanchez, Celso; Hellman, Per; Björklund, Peyman

    2016-01-01

    Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3. The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation. PMID:26815163

  4. High strength distillery wastewater treatment by a PAC-MBR with low PAC dosage.

    PubMed

    Basu, Subhankar; Kaushik, Ankita; Saranya, P; Batra, Vidya S; Balakrishnan, Malini

    2016-01-01

    Augmentation of membrane bioreactors (MBRs) with activated carbon is established to offer several operational advantages. This work investigates the influence of low dosing (2 g/L) of powdered activated carbons (PACs) with different characteristics on the performance of MBR treating high strength molasses distillery wastewater containing difficult-to-biodegrade recalcitrant components. Two MBRs, augmented with different PACs, were operated in parallel over a period of 240 days and their performance monitored in terms of biomass growth, reduction in chemical oxygen demand (COD), sludge properties like extracellular polymeric substances content, filterability, and morphology. Removal of organics and coloring matter by adsorption, biodegradation and membrane filtration was estimated. Although adsorptive removal of color and COD is influenced by the properties of the PAC used, the performance of the PAC-MBRs was independent of PAC properties. Both PACs preferentially adsorbed the low molecular weight components in distillery wastewater. Retention by the membrane filter with the secondary cake layer contributed to reduction in color and COD of treated effluent. The findings indicate that low dosing with PAC adsorbing low molecular weight organics has a limited role in PAC-MBR treating distillery wastewater. PMID:26942533

  5. Experience with high-performance PACS

    NASA Astrophysics Data System (ADS)

    Wilson, Dennis L.; Goldburgh, Mitchell M.; Head, Calvin

    1997-05-01

    Lockheed Martin (Loral) has installed PACS with associated teleradiology in several tens of hospitals. The PACS that have been installed have been the basis for a shift to filmless radiology in many of the hospitals. the basic structure for the PACS and the teleradiology that is being used is outlined. The way that the PACS are being used in the hospitals is instructive. The three most used areas for radiology in the hospital are the wards including the ICU wards, the emergency room, and the orthopedics clinic. The examinations are mostly CR images with 20 percent to 30 percent of the examinations being CT, MR, and ultrasound exams. The PACS are being used to realize improved productivity for radiology and for the clinicians. For radiology the same staff is being used for 30 to 50 percent more workload. For the clinicians 10 to 20 percent of their time is being saved in dealing with radiology images. The improved productivity stems from the high performance of the PACS that has been designed and installed. Images are available on any workstation in the hospital within less than two seconds, even during the busiest hour of the day. The examination management functions to restrict the attention of any one user to the examinations that are of interest. The examination management organizes the workflow through the radiology department and the hospital, improving the service of the radiology department by reducing the time until the information from a radiology examination is available. The remaining weak link in the PACS system is transcription. The examination can be acquired, read, an the report dictated in much less than ten minutes. The transcription of the dictated reports can take from a few hours to a few days. The addition of automatic transcription services will remove this weak link.

  6. Defining the PACS profession: an initial survey of skills, training, and capabilities for PACS administrators.

    PubMed

    Nagy, Paul; Bowers, George; Reiner, Bruce I; Siegel, Eliot L

    2005-12-01

    The need for specialized individuals to manage picture archiving and communications systems (PACS) has been recognized with the creation of a new professional title: PACS administrator. This position requires skill sets that bridge the current domains of radiology technologists (RTs), information systems analysts, and radiology administrators. Health care organizations, however, have reported difficulty in defining the functions that a PACS administrator should perform-a challenge compounded when the tries to combine this complex set of capabilities into one individual. As part of a larger effort to define the PACS professional, we developed an extensive but not exclusive consensus list of business, technical, and behavioral competencies desirable in the dedicated PACS professional. Through an on-line survey, radiologists, RTs, information technology specialists, corporate information officers, and radiology administrators rated the importance of these competencies. The results of this survey are presented, and the implications for implementation in training and certification efforts are discussed. PMID:16249838

  7. Aldosterone-induced glycoproteins: electrophysiological-biochemical correlation.

    PubMed

    Szerlip, H M; Weisberg, L; Geering, K; Rossier, B C; Cox, M

    1988-05-01

    Aldosterone induces the synthesis of a group of glycoproteins (GP65,70) in toad urinary bladders which are potential effectors of the natriferic action of this hormone. In the present study we have confirmed that aldosterone produces a two-phase electrophysiological response. During the early phase (less than 3 h) short-circuit current and transepithelial conductance increase in parallel, while during the late phase (greater than 3 h) short-circuit current continues to increase without any further change in conductance. By biosynthetically labeling aldosterone-treated toad bladders with [35S]methionine either during the early (h 0-2 or 1-3) or the late (h 4-6 or 7-9) phases of the natriferic response, we have demonstrated that GP65,70 is synthesized as a late effect of aldosterone. Since synthesis of GP65,70 occurs at a time when the electromotive force of the Na+ pump is increasing, and since GP65,70 biochemically resembles the beta subunit of Na+/K+-ATPase, studies were undertaken to examine whether GP65,70 is the beta subunit. Purified amphibian renal beta subunit was analyzed by two-dimensional polyacrylamide gel electrophoresis and was found to have an isoelectric point and Mr value similar to those of GP65,70. However, when nitrocellulose blots containing wheat germ agglutinin-purified proteins from aldosterone-treated bladders were stained with monospecific polyclonal antibodies developed against the beta subunit, GP65,70 was not recognized, whereas a group of slightly more acidic proteins of similar Mr were recognized. Thus, GP65,70 is not the beta subunit of Na+/Ka+-ATPase. Further studies are needed to determine the cellular function of GP65,70. PMID:2835098

  8. Reengineering the picture archiving and communication system (PACS) process for digital imaging networks PACS.

    PubMed

    Horton, M C; Lewis, T E; Kinsey, T V

    1999-05-01

    Prior to June 1997, military picture archiving and communications systems (PACS) were planned, procured, and installed with key decisions on the system, equipment, and even funding sources made through a research and development office called Medical Diagnostic Imaging Systems (MDIS). Beginning in June 1997, the Joint Imaging Technology Project Office (JITPO) initiated a collaborative and consultative process for planning and implementing PACS into military treatment facilities through a new Department of Defense (DoD) contract vehicle called digital imaging networks (DIN)-PACS. The JITPO reengineered this process incorporating multiple organizations and politics. The reengineered PACS process administered through the JITPO transformed the decision process and accountability from a single office to a consultative method that increased end-user knowledge, responsibility, and ownership in PACS. The JITPO continues to provide information and services that assist multiple groups and users in rendering PACS planning and implementation decisions. Local site project managers are involved from the outset and this end-user collaboration has made the sometimes difficult transition to PACS an easier and more acceptable process for all involved. Corporately, this process saved DoD sites millions by having PACS plans developed within the government and proposed to vendors second, and then having vendors respond specifically to those plans. The integrity and efficiency of the process have reduced the opportunity for implementing nonstandard systems while sharing resources and reducing wasted government dollars. This presentation will describe the chronology of changes, encountered obstacles, and lessons learned within the reengineering of the PACS process for DIN-PACS. PMID:10342167

  9. The HERSCHEL/PACS early Data Products

    NASA Astrophysics Data System (ADS)

    Wieprecht, E.; Wetzstein, M.; Huygen, R.; Vandenbussche, B.; De Meester, W.

    2006-07-01

    ESA's Herschel Space Observatory to be launched in 2007, is the first space observatory covering the full far-infrared and submillimeter wavelength range (60 - 670 microns). The Photodetector Array Camera & Spectrometer (PACS) is one of the three science instruments. It contains two Ge:Ga photoconductor arrays and two bolometer arrays to perform imaging line spectroscopy and imaging photometry in the 60 - 210 micron wavelength band. The HERSCHEL ground segment (Herschel Common Science System - HCSS) is implemented using JAVA technology and written in a common effort by the HERSCHEL Science Center and the three instrument teams. The PACS Common Software System (PCSS) is based on the HCSS and used for the online and offline analysis of PACS data. For telemetry bandwidth reasons PACS science data are partially processed on board, compressed, cut into telemetry packets and transmitted to the ground. These steps are instrument mode dependent. We will present the software model which allows to reverse the discrete on board processing steps and evaluate the data. After decompression and reconstruction the detector data and instrument status information are organized in two main PACS Products. The design of these JAVA classes considers the individual sampling rates, data formats, memory and performance optimization aspects and comfortable user interfaces.

  10. Digital neuroangiography: an innovative application of PACS

    NASA Astrophysics Data System (ADS)

    Hademenos, George J.; Valentino, Daniel J.; Close, Robert A.; Duckwiler, Gary R.; Vinuela, Fernando

    1994-05-01

    An important aspect of interventional neuroradiological procedures is the ability to access and interact with digital angiographic images to select and clinically evaluate intravascular therapeutic treatment. These issues can be adequately addressed and successfully accomplished using PACS. PACS provides the key technologies needed to access, display, and analyze sequential angiographic images. A dedicated neuroradiology PACS network consisting of workstations for the review of diagnostic data, quantitative analysis of arterial blood flow, and therapeutic assessment has been established at UCLA. The PACS provides not only a reliable and efficient infrastructure for on-line image retrieval and delivery of all digitally acquired angiographic images, but could also serve as a network supercomputing resource for computationally intensive calculations of hemodynamic parameters in the cerebral vasculature. In summary we have developed an innovative application of PACS in neuroangiography. It offers: (1) automatic optimized image display upon acquisition; (2) automatic retrieval of archived cases for a current patient; and, (3) a rapid, streamlined user interface for the quantitation of hemodynamic flow phenomena in normal and diseased cerebral vessels.

  11. Effect of PAC addition on immersed ultrafiltration for the treatment of algal-rich water.

    PubMed

    Zhang, Yan; Tian, Jiayu; Nan, Jun; Gao, ShanShan; Liang, Heng; Wang, Meilian; Li, Guibai

    2011-02-28

    The aim of this study was to evaluate the effect of powdered activated carbon (PAC) addition on the treatment of algal-rich water by immersed ultrafiltration (UF), in terms of permeate quality and membrane fouling. Experiments were performed with a hollow-fiber polyvinyl chloride ultrafiltration membrane at a laboratory scale, 20-25°C and 10 L/(m(2) h) constant permeate flux. UF could achieve an absolute removal of Microcystis aeruginosa cells, but a poor removal of algogenic organic matter (AOM) released into water, contaminants responsible for severe membrane fouling. The addition of 4 g/L PAC to the immersed UF reactor significantly alleviated the development of trans-membrane pressure and enhanced the removal of dissovled organic carbon (by 10.9±1.7%), UV(254) (by 27.1±1.7%), and microcystins (expressed as MC-LR(eq), by 40.8±4.2%). However, PAC had little effect on the rejection of hydrophilic high molecular weight AOM such as carbohydrates and proteins. It was also identified that PAC reduced the concentrations of carbohydrates and proteins in the reactor due to decreased light intensity, as well as the MC-LR(eq) concentration by PAC adsorption. PMID:21216530

  12. Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups

    NASA Technical Reports Server (NTRS)

    Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.

    2000-01-01

    The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period. Copyright 2000 Academic Press.

  13. Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors.

    PubMed

    Briet, Marie; Barhoumi, Tlili; Mian, Muhammad Oneeb Rehman; Coelho, Suellen C; Ouerd, Sofiane; Rautureau, Yohann; Coffman, Thomas M; Paradis, Pierre; Schiffrin, Ernesto L

    2016-05-01

    We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors in Agtr1a(-/-) and wild-type (WT) mice infused with aldosterone for 14 days while receiving 1% NaCl in drinking water. Aldosterone increased systolic blood pressure (BP) by ≈30 mm Hg in WT mice and ≈50 mm Hg in Agtr1a(-/-) mice. Aldosterone induced aortic and small artery remodeling, impaired endothelium-dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition and vascular inflammation. None of these vascular effects were observed in Agtr1a(-/-) mice. Aldosterone effects were prevented by the AGTR1 antagonist losartan in WT mice. In contrast to aldosterone, norepinephrine caused similar BP increase and mesenteric artery remodeling in WT and Agtr1a(-/-) mice. Agtr1a(-/-) mice infused with aldosterone did not increase sodium excretion in response to a sodium chloride challenge, suggesting that sodium retention could contribute to the exaggerated BP rise induced by aldosterone. Agtr1a(-/-) mice had decreased mesenteric artery expression of the calcium-activated potassium channel Kcnmb1, which may enhance myogenic tone and together with sodium retention, exacerbate BP responses to aldosterone/salt in Agtr1a(-/-) mice. We conclude that although aldosterone activation of mineralocorticoid receptors raises BP more in Agtr1a(-/-) mice, AGTR1a is required for mineralocorticoid receptor stimulation to induce vascular remodeling and inflammation and endothelial dysfunction. PMID:27045029

  14. Type I receptors in parotid, colon, and pituitary are aldosterone selective in vivo

    SciTech Connect

    Sheppard, K.; Funder, J.W. )

    1987-10-01

    Previous in vivo studies have demonstrated that type I receptors in the rat kidney are aldosterone selective, whereas those in the hippocampus do not appear to discriminate between aldosterone and corticosterone. The authors have injected mature rats with ({sup 3}H)aldosterone or ({sup 3}H)corticosterone plus 100-fold excess of RU 28362, with or without unlabeled aldosterone or corticosterone, and compared type I receptor occupancy in two classic mineralocorticoid target tissues (parotid and colon) and in the pituitary. Mature rats were killed 10-180 min after tracer administration; ({sup 3}H)aldosterone was well taken up and retained in all tissues, whereas ({sup 3}H)corticosterone was significantly retained only in the pituitary 10 min after tracer administration. To assess a possible role for corticosterone-binding globulin (CBG) in conferring aldosterone specificity on type I receptors, 10-day-old rats (with very low levels of CBG) were similarly injected. In the colon and parotid, ({sup 3}H)aldosterone binding was at least an order of magnitude higher than that of corticosterone; in the pituitary aldosterone binding was approximately three times that of corticosterone. They interpret these data as evidence that in the parotid and colon type I receptors are aldosterone selective by a non-CBG-requiring mechanism, whereas in the pituitary there appear to be both aldosterone-selective and nonselective type I sites.

  15. A Rare Presentation of Primary Hyperparathyroidism with Concurrent Aldosterone-Producing Adrenal Carcinoma

    PubMed Central

    Molina-Ayala, Mario; Ramírez-Rentería, Claudia; Manguilar-León, Analleli; Paúl-Gaytán, Pedro; Ferreira-Hermosillo, Aldo

    2015-01-01

    Aldosterone-producing adrenocortical carcinomas are an extremely rare cause of hyperaldosteronism (<1%). Coexistence of different endocrine tumors warrants additional screening for multiple endocrine neoplasia syndromes, especially in young patients with large or malignant masses. We present the case of a 40-year-old man with a history of hypertension that presented with an incidental left adrenal tumor during an ultrasound performed for nephrolithiasis. Biochemical assessment showed a mildly elevated calcium (11.1 mg/dL), high parathyroid hormone, and a plasma aldosterone concentration/plasma renin activity ratio of 124.5 (normal < 30), compatible with primary hyperparathyroidism with a concomitant primary hyperaldosteronism. A Tc99m-MIBI scintigraphy showed an abnormally increased tracer uptake in the right superior parathyroid and abdominal computed tomography confirmed a left adrenal tumor of 20 cm. The patient underwent parathyroidectomy and adrenalectomy with final pathology reports of parathyroid hyperplasia and adrenal carcinoma with biochemical remission of both endocrinopathies. He was started on chemotherapy, but the patient developed a frontal cortex and an arm metastasis and finally died less than one year later. PMID:26161274

  16. Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.

    PubMed

    Rossier, Bernard C; Baker, Michael E; Studer, Romain A

    2015-01-01

    Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases. PMID:25540145

  17. Mineralocorticoid receptor is involved in the aldosterone pathway in human red blood cells

    PubMed Central

    Bordin, Luciana; Saccardi, Carlo; Donà, Gabriella; Sabbadin, Chiara; Andrisani, Alessandra; Ambrosini, Guido; Plebani, Mario; Brunati, Anna Maria; Ragazzi, Eugenio; Gizzo, Salvatore; Armanini, Decio

    2016-01-01

    We have recently demonstrated that excessive aldosterone (Aldo) secretion in primary aldosteronism (PA) is associated with red blood cells (RBC) senescence. These alterations were prevented/inhibited by cortisol (Cort) or canrenone (Can) raising the hypothesis that Aldo effects in RBC may be mediated by mineralocorticoid receptor (MR), though to date MR has never been demonstrated in human RBC. The aim of this multicenter comparative study was to investigate whether Aldo effects were mediated by MR in these a-nucleated cells. We included 12 healthy controls (HC) and 22 patients with PA. MR presence and activation were evaluated in RBC cytosol by glycerol gradient sedimentation, Western blotting, immuno-precipitation and radioimmunoassay. We demonstrated that RBC contained cytosolic MR, aggregated with HSP90 and other proteins to form multiprotein complex. Aldo induced MR to release from the complex and to form MR dimers which were quickly proteolyzed. Cort induced MR release but not dimers formation while Can was not able to induce MR release. In addition, RBC cytosol from PA patients contained significantly higher amounts of both MR fragments (p<0.0001) and Aldo (p<0.0001) concentrations. In conclusion, in RBC a genomic-like Aldo pathway is proposed involving MR activation, dimerization and proteolysis, but lacking nuclear transcription. In addition, dimers proteolysis may ensure a sort of Aldo scavenging from circulation by entrapping Aldo in MR fragments. PMID:27158328

  18. Mineralocorticoid receptor is involved in the aldosterone pathway in human red blood cells.

    PubMed

    Bordin, Luciana; Saccardi, Carlo; Donà, Gabriella; Sabbadin, Chiara; Andrisani, Alessandra; Ambrosini, Guido; Plebani, Mario; Brunati, Anna Maria; Ragazzi, Eugenio; Gizzo, Salvatore; Armanini, Decio

    2016-01-01

    We have recently demonstrated that excessive aldosterone (Aldo) secretion in primary aldosteronism (PA) is associated with red blood cells (RBC) senescence. These alterations were prevented/inhibited by cortisol (Cort) or canrenone (Can) raising the hypothesis that Aldo effects in RBC may be mediated by mineralocorticoid receptor (MR), though to date MR has never been demonstrated in human RBC. The aim of this multicenter comparative study was to investigate whether Aldo effects were mediated by MR in these a-nucleated cells. We included 12 healthy controls (HC) and 22 patients with PA. MR presence and activation were evaluated in RBC cytosol by glycerol gradient sedimentation, Western blotting, immuno-precipitation and radioimmunoassay. We demonstrated that RBC contained cytosolic MR, aggregated with HSP90 and other proteins to form multiprotein complex. Aldo induced MR to release from the complex and to form MR dimers which were quickly proteolyzed. Cort induced MR release but not dimers formation while Can was not able to induce MR release. In addition, RBC cytosol from PA patients contained significantly higher amounts of both MR fragments (p<0.0001) and Aldo (p<0.0001) concentrations. In conclusion, in RBC a genomic-like Aldo pathway is proposed involving MR activation, dimerization and proteolysis, but lacking nuclear transcription. In addition, dimers proteolysis may ensure a sort of Aldo scavenging from circulation by entrapping Aldo in MR fragments. PMID:27158328

  19. The future of PACS in healthcare enterprises.

    PubMed

    Faggioni, Lorenzo; Neri, Emanuele; Castellana, Carlo; Caramella, Davide; Bartolozzi, Carlo

    2011-05-01

    Picture Archiving and Communication System (PACS), which was originally designed as a tool for facilitating radiologists in interpreting images more efficiently, is evolving into a hospital-integrated system storing diagnostic imaging information that often reaches far beyond Radiology. The continuous evolution of PACS technology has led to a gradual broadening of its applications, ranging from teleradiology to CAD (Computer-Assisted Diagnosis) and multidimensional imaging, and is moving into the direction of providing access to image data outside the Radiology department, so to reach all the branches of the healthcare enterprise. New perspectives have been created thanks to new technologies (such as holographic media and GRID computing) that are likely due to expand PACS-based applications even further, improving patient care and enhancing overall productivity. PMID:20634012

  20. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 7: Medical treatment of primary aldosteronism.

    PubMed

    Pechère-Bertschi, Antoinette; Herpin, Daniel; Lefebvre, Hervé

    2016-07-01

    Spironolactone, which is a potent mineralocorticoid receptor antagonist, represents the first line medical treatment of primary aldosteronism (PA). As spironolactone is also an antagonist of the androgen and progesterone receptor, it may present side effects, especially in male patients. In case of intolerance to spironolactone, amiloride may be used to control hypokaliemia and we suggest that eplerenone, which is a more selective but less powerful antagonist of the mineralocorticoid receptor, be used in case of intolerance to spironolactone and insufficient control of hypertension by amiloride. Specific calcic inhibitors and thiazide diuretics may be used as second or third line therapy. Medical treatment of bilateral forms of PA seem to be as efficient as surgical treatment of lateralized PA for the control of hypertension and the prevention of cardiovascular and renal morbidities. This allows to propose medical treatment of PA to patients with lateralized forms of PA who refuse surgery or to patients with PA who do not want to be explored by adrenal venous sampling to determine whether they have a bilateral or lateralized form. PMID:27315759

  1. A Layered Approach To Pacs Network Architecture

    NASA Astrophysics Data System (ADS)

    Hegde, Shankar S.; Prewitt, Judith M.

    1984-08-01

    Although the functions performed by the different nodes on the PACS network are many, it is possible to formulate a minimum set of service primitives such that the application software residing at the nodes can utilize those primitives to perform the functions. These primitives define the framework for the communication interface. The question of how these primitives fit into the concept of a layered network architecture is explored in this paper. The OSI model as applicable to the PACS network is described, the areas that need standardization are briefly mentioned, and the ongoing standardization efforts are addressed from the OSI perspective.

  2. PACS clinical experience at Georgetown University.

    PubMed

    Horii, S C; Mun, S K; Levine, B; Lo, B; Garra, B S; Zeman, R K; Freedman, M; Leftridge, C; Schellinger, D; Keyes, J

    1991-01-01

    Georgetown University Hospital has been operating an image management and communications system (IMACS or PACS) for three-and-a-half years. This work was initially funded under the Army Medical Research and Development Command Digital Imaging Network Systems (DINS) project. The system was taken from a research system supporting only radiology tasks to one extended to clinical use, and has been used in clinical work for two-and-a-half years. This paper will summarize our PACS clinical experience and will describe the operational features implemented and those still necessary. PMID:1913567

  3. High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism.

    PubMed

    Armanini, Decio; Nacamulli, Davide; Scaroni, Carla; Lumachi, Franco; Selice, Riccardo; Fiore, Cristina; Favia, Gennaro; Mantero, Franco

    2003-11-01

    The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p < 0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension. PMID:14665720

  4. Microalbuminuria and hypertension in pregnancy: role of aldosterone and inflammation.

    PubMed

    Armanini, Decio; Ambrosini, Guido; Sabbadin, Chiara; Donà, Gabriella; Clari, Giulio; Bordin, Luciana

    2013-09-01

    Women with a history of hypertension in pregnancy are at increased risk of microalbuminuria later in life. Microalbuminuria is a marker of kidney dysfunction frequently related to an inflammatory event. Pregnancy is a dynamic process characterized by immune tolerance, angiogenesis, and hormonal regulation. Menstruation and pregnancy are associated with a physiological inflammation, which is altered in preeclampsia and probably in other hypertensive situations of pregnancy. An imbalance between pro-oxidant factors and the ability to scavenge these factors produces oxidative stress, which has been evaluated in many cells, but leukocytes are the main source of inflammatory cytokines and experimental and clinical evidence support a possible role of aldosterone as a mediator of placental and renal damage mediated by growth factors, reactive oxygen species, and cytokines. Angiotensin-converting enzyme inhibitors and aldosterone receptor blockers are frequently effective in reducing the risk of progression of cardiovascular and renal disease. PMID:24034651

  5. Roles of aldosterone in vascular calcification: An update.

    PubMed

    Gao, Jingwei; Zhang, Kun; Chen, Jie; Wang, Mong-Heng; Wang, Jingfeng; Liu, Pinming; Huang, Hui

    2016-09-01

    Both clinical and experimental studies have demonstrated that vascular calcification (VC) is a common pathology shared in many chronic diseases such as chronic kidney disease (CKD) and diabetes. It's an independent risk factor for cardiovascular events. Since the pathogenesis of VC is complicated, current therapies have limited effects on the regression of VC. Therefore, it is urgent to investigate the potential mechanisms and find new targets for the treatment of VC. Aldosterone (Aldo), a mineralocorticoid hormone, is the metabolite of renin-angiotensin-aldosterone system (RAAS) activation, which can exert genomic and non-genomic effects on the cardiovascular system. Recent data suggests that Aldo can promote VC. Here, we summarized the roles of Aldo in the process of VC and a series of findings indicated that Aldo could act as a potentially therapeutic target for treating VC. PMID:27238972

  6. Renin and aldosterone measurements in the management of arterial hypertension.

    PubMed

    Viola, A; Monticone, S; Burrello, J; Buffolo, F; Lucchiari, M; Rabbia, F; Williams, T A; Veglio, F; Mengozzi, G; Mulatero, P

    2015-06-01

    Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy. PMID:25993253

  7. Cost justification of filmless PACS and national policy

    NASA Astrophysics Data System (ADS)

    Lim, Jae H.

    2002-05-01

    The expense of installing PACS is high so most Korean hospitals cannot afford to purchase the system easily. We can justify the cost of PACS by considering the visible and invisible benefits. As a visible benefit we can save the cost of films and equipments for film processing. Invisible benefits of PACS is the cost of film handling. Generally, doctors spend some 25 minutes in handling X-ray films everyday and they spend 10 days (84 hours) throughout a year. Radiology technicians, nurses, orderlies and clerks also handle films and the total salary for handling films by doctors and paramedics will be considerable. Considering the visible and invisible benefits, cost of PACS is justified and PACS can be installed in every hospital, whatever their size. The Korean Society of PACS tried to make reimbursement of the cost of PACS and persuaded the government officers and eventually the Ministry of Health and Welfare decided to reimburse the use of PACS in hospitals. Based on the money reimbursed, general hospitals or university hospitals will earn enough money to purchase a PACS in 3 - 5 years. After the Korean government started to reimburse the cost of PACS, many hospitals wanted to install PACS and the number of hospitals installing PACS is soaring.

  8. 24 CFR 891.735 - Notice upon PAC expiration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Notice upon PAC expiration. 891.735... and Individuals-Section 162 Assistance § 891.735 Notice upon PAC expiration. The PAC will provide that... will be required to pay as rent as a result of the expiration. The notice of expiration will...

  9. Overview of the genetic determinants of primary aldosteronism

    PubMed Central

    Al-Salameh, Abdallah; Cohen, Régis; Desailloud, Rachel

    2014-01-01

    Primary aldosteronism is the most common cause of secondary hypertension. The syndrome accounts for 10% of all cases of hypertension and is primarily caused by bilateral adrenal hyperplasia or aldosterone-producing adenoma. Over the last few years, the use of exome sequencing has significantly improved our understanding of this syndrome. Somatic mutations in the KCNJ5, ATP1A1, ATP2B3 or CACNA1D genes are present in more than half of all cases of aldosterone-producing adenoma (~40%, ~6%, ~1% and ~8%, respectively). Germline gain-of-function mutations in KCNJ5 are now known to cause familial hyperaldosteronism type III, and an additional form of genetic hyperaldosteronism has been reported in patients with germline mutations in CACNA1D. These genes code for channels that control ion homeostasis across the plasma membrane of zona glomerulosa cells. Moreover, all these mutations modulate the same pathway, in which elevated intracellular calcium levels lead to aldosterone hyperproduction and (in some cases) adrenal cell proliferation. From a clinical standpoint, the discovery of these mutations has potential implications for patient management. The mutated channels could be targeted by drugs, in order to control hormonal and overgrowth-related manifestations. Furthermore, some of these mutations are associated with high cell turnover and may be amenable to diagnosis via the sequencing of cell-free (circulating) DNA. However, genotype-phenotype correlations in patients harboring these mutations have yet to be characterized. Despite this recent progress, much remains to be done to elucidate the yet unknown mechanisms underlying sporadic bilateral adrenal hyperplasia. PMID:24817817

  10. Time-dependent aldosterone metabolism in toad urinary bladder

    SciTech Connect

    Brem, A.S.; Pacholski, M.; Morris, D.J.

    1988-04-01

    Aldosterone (Aldo) metabolism was examined in the toad bladder. Bladders were incubated with (/sup 3/H)aldosterone (10(-7) M) for 5 h, 1 h, or 10 min. Tissues were analyzed for metabolites using high-pressure liquid chromatography (HPLC). In separate experiments, Na+ transport was assessed by the short-circuit current (SCC) technique. Following a 5-h tissue incubation, about 25% of the (/sup 3/H)-aldosterone was converted into metabolites including a polar monosulfate metabolite, 20 beta-dihydroaldo (20 beta-DHAldo), small quantities of 5 beta-reduced products, and a variety of 5 alpha-reduced Aldo products including 5 alpha-DHAldo, 3 alpha,5 alpha-tetrahydroaldo (3 alpha,5 alpha-THAldo), and 3 beta,5 alpha-THAldo. Tissues metabolized approximately 10% of the labeled hormone into the same compounds by 1 h. Measurable quantities of these metabolites were also synthesized by bladders exposed to Aldo for only 10 min and then incubated in buffer for an additional 50 min without Aldo. Bladders pretreated with the spironolactone, K+-canrenoate (3.5 X 10(-4) M), and stimulated with Aldo (10(-7) M) generated a peak SCC 44 +/- 6% of that observed in matched pairs stimulated with Aldo (P less than 0.001; n = 6). K+-canrenoate also markedly diminished (/sup 3/H)aldosterone metabolism at both 5 and 1 h. Thus, metabolic transformation of Aldo begins prior to hormone-induced increases in Na+ transport. Both the generation of certain metabolites (e.g., 5 alpha-reductase pathway products) and the increase in Na+ transport can be selectively inhibited by K+-canrenoate.

  11. Physiological techniques in the study of rapid aldosterone effects.

    PubMed

    Yusef, Yamil R; Thomas, Warren; Harvey, Brian J

    2014-01-01

    Molecular imaging and electrophysiological techniques are powerful tools to analyze the responses stimulated by aldosterone and other hormones in target tissues. Studies with Ussing-type chambers can be used to measure and characterize changes in transepithelial currents resulting from hormone treatment. Confocal imaging techniques can be used in real time or in fixed preparations to evaluate the localization of receptors, signalling intermediates, and transporters. PMID:25182774

  12. Bartter Syndrome with Normal Aldosterone Level: An Unusual Presentation.

    PubMed

    Huque, S S; Rahman, M H; Khatun, S

    2016-04-01

    Bartter syndrome (BS) is a hereditary disease, with an autosomal recessive or autosomal dominant mode of transmission. It is characterized by salt wasting hypochloraemic, hypokalaemic metabolic alkalosis and hyperreninaemia with normal blood pressure. The primary defect is in the thick ascending limb of loop of Henle (TAL). Herein, we report a case that had typical features of BS like severe dehydration, severe hypokalaemia, metabolic alkalosis and failure to thrive but had normal aldosterone level which is very uncommon. PMID:27277374

  13. Morphological adaptations to induced changes in transepithelial sodium transport in chicken lower intestine (coprodeum): a study of resalination, aldosterone stimulation, and epithelial turnover.

    PubMed

    Elbrønd, V S; Skadhauge, E; Thomsen, L; Dantzer, V

    1998-06-01

    Transepithelial sodium transport and epithelial morphology during short-term adaptation to resalination or aldosterone stimulation were studied in the chicken coprodeum. Coprodeum was sampled for light and electron microscopy after 0-3 days of resalination in hens on a low-NaCl diet and after 0-6 days of aldosterone stimulation in hens on a high-NaCl diet. Sodium transport was measured in vitro with Ussing chambers. Plasma osmolality and electrolyte concentrations were measured in aldosterone-stimulated hens. Epithelial proliferation and migration between 1 h and 16 days were investigated in chickens on high-NaCl and low-NaCl diets using a bromodeoxyuridine technique. Resalination abolished the otherwise high sodium transport within 1 day, while the height and number of microvilli, as well as the number of brush cells, decreased over 3 days. Aldosterone stimulation increased sodium transport, the height and number of microvilli, and the brush-cell number. Bromodeoxyuridine studies indicated an epithelial cell turnover of more than 16 days. The results thus demonstrate that epithelial cells have an unusual capacity to adjust rap- idly to variations in sodium intake. A strong correlation between structure and function was apparent. PMID:9582411

  14. Biological determinants of aldosterone-induced cardiac fibrosis in rats.

    PubMed

    Robert, V; Silvestre, J S; Charlemagne, D; Sabri, A; Trouvé, P; Wassef, M; Swynghedauw, B; Delcayre, C

    1995-12-01

    To determine the events leading to cardiac fibrosis in aldosterone-salt hypertensive rats, we studied protein and mRNA accumulation of procollagens I and III for 60 days. After 3 and 7 days of treatment systolic pressure was normal, and no histological or biochemical changes were seen in rat hearts. At day 15 arterial pressure was raised (+40%) and left ventricular hypertrophy was +15%. Cardiac examination after hemalun-eosin staining and immunolabeling with anticollagen I and III antibodies showed no structural alterations, but an 83% increase in right ventricular type III procollagen mRNA levels was found. At 30 and 60 days we found progressive cardiac fibrosis, with inflammatory cells, myocyte necrosis, and elevation of both types I and III procollagen mRNA levels in both ventricles. To determine whether aldosterone had effects on Na,K-ATPase that might lead to ionic disturbances and induce myocyte necrosis, we studied the major cardiac Na,K-ATPase isoform genes. Although Na,K-ATPase alpha 1- and beta 1-subunit mRNA levels were elevated in kidney at day 1, neither of these cardiac transcripts nor the specific alpha 2 isoform was altered between 1 and 15 days. These results show that accumulation of procollagen mRNAs occurs before collagen deposition. Cardiac alterations are late and not preceded by changes in Na,K-ATPase cardiac gene expression, precluding a direct modulation of cardiac collagen synthesis and Na,K-ATPase by aldosterone. PMID:7490157

  15. Anatomy of an Extensible Open Source PACS.

    PubMed

    Valente, Frederico; Silva, Luís A Bastião; Godinho, Tiago Marques; Costa, Carlos

    2016-06-01

    The conception and deployment of cost effective Picture Archiving and Communication Systems (PACS) is a concern for small to medium medical imaging facilities, research environments, and developing countries' healthcare institutions. Financial constraints and the specificity of these scenarios contribute to a low adoption rate of PACS in those environments. Furthermore, with the advent of ubiquitous computing and new initiatives to improve healthcare information technologies and data sharing, such as IHE and XDS-i, a PACS must adapt quickly to changes. This paper describes Dicoogle, a software framework that enables developers and researchers to quickly prototype and deploy new functionality taking advantage of the embedded Digital Imaging and Communications in Medicine (DICOM) services. This full-fledged implementation of a PACS archive is very amenable to extension due to its plugin-based architecture and out-of-the-box functionality, which enables the exploration of large DICOM datasets and associated metadata. These characteristics make the proposed solution very interesting for prototyping, experimentation, and bridging functionality with deployed applications. Besides being an advanced mechanism for data discovery and retrieval based on DICOM object indexing, it enables the detection of inconsistencies in an institution's data and processes. Several use cases have benefited from this approach such as radiation dosage monitoring, Content-Based Image Retrieval (CBIR), and the use of the framework as support for classes targeting software engineering for clinical contexts. PMID:26497879

  16. PACS infrastructure supporting e-learning.

    PubMed

    Mildenberger, Peter; Brüggemann, Kerstin; Rösner, Freya; Koch, Katja; Ahlers, Christopher

    2011-05-01

    Digital imaging is becoming predominant in radiology. This has implications for teaching support, because conventional film-based concepts are now obsolete. The IHE Teaching File and Clinical Study Export (TCE) profile provides an excellent platform to enhance PACS infrastructure with educational functionality. This can be supplemented with dedicated e-learning tools. PMID:20619986

  17. Small PACS implementation using publicly available software

    NASA Astrophysics Data System (ADS)

    Passadore, Diego J.; Isoardi, Roberto A.; Gonzalez Nicolini, Federico J.; Ariza, P. P.; Novas, C. V.; Omati, S. A.

    1998-07-01

    Building cost effective PACS solutions is a main concern in developing countries. Hardware and software components are generally much more expensive than in developed countries and also more tightened financial constraints are the main reasons contributing to a slow rate of implementation of PACS. The extensive use of Internet for sharing resources and information has brought a broad number of freely available software packages to an ever-increasing number of users. In the field of medical imaging is possible to find image format conversion packages, DICOM compliant servers for all kinds of service classes, databases, web servers, image visualization, manipulation and analysis tools, etc. This paper describes a PACS implementation for review and storage built on freely available software. It currently integrates four diagnostic modalities (PET, CT, MR and NM), a Radiotherapy Treatment Planning workstation and several computers in a local area network, for image storage, database management and image review, processing and analysis. It also includes a web-based application that allows remote users to query the archive for studies from any workstation and to view the corresponding images and reports. We conclude that the advantage of using this approach is twofold. It allows a full understanding of all the issues involved in the implementation of a PACS and also contributes to keep costs down while enabling the development of a functional system for storage, distribution and review that can prove to be helpful for radiologists and referring physicians.

  18. [Designing and implementation of a PACS].

    PubMed

    Zhou, Hai-yan; Yao, Xing; Zhu, Yue-ming; Duan, Hui-long; Lu, Xu-dong; Zhao, Chen-hui

    2006-11-01

    PACS (Picture Archiving and Communication System) is successfully applied in Huzhou Central Hospital, and is well integrated with its HIS system by WEBSERVICE middleware. The system supports DICOM 3.0 Standard, and DICOM gateways are installed for modalities that do not support DICOM so as to have implemented the digitalization of all the image departments in the hospital. PMID:17300012

  19. Aldosterone acutely stimulates NCC activity via a SPAK-mediated pathway

    PubMed Central

    Mistry, Abinash C.; Hanson, Lauren; Mallick, Rickta; Wynne, Brandi M.; Thai, Tiffany L.; Bailey, James L.; Klein, Janet D.; Hoover, Robert S.

    2013-01-01

    Hypertension is a leading cause of morbidity and mortality worldwide, and disordered sodium balance has long been implicated in its pathogenesis. Aldosterone is perhaps the key regulator of sodium balance and thus blood pressure. The sodium chloride cotransporter (NCC) in the distal convoluted tubule of the kidney is a major site of sodium reabsorption and plays a key role in blood pressure regulation. Chronic exposure to aldosterone increases NCC protein expression and function. However, more acute effects of aldosterone on NCC are unknown. In our salt-abundant modern society where chronic salt deprivation is rare, understanding the acute effects of aldosterone is critical. Here, we examined the acute effects (12–36 h) of aldosterone on NCC in the rodent kidney and in a mouse distal convoluted tubule cell line. Studies demonstrated that aldosterone acutely stimulated NCC activity and phosphorylation without affecting total NCC abundance or surface expression. This effect was dependent upon the presence of the mineralocorticoid receptor and serum- and glucocorticoid-regulated kinase 1 (SGK1). Furthermore, STE20/SPS-1-related proline/alanine-rich kinase (SPAK) phosphorylation also increased, and gene silencing of SPAK eliminated the effect of aldosterone on NCC activity. Aldosterone administration via a minipump in adrenalectomized rodents confirmed an increase in NCC phosphorylation without a change in NCC total protein. These data indicate that acute aldosterone-induced SPAK-dependent phosphorylation of NCC increases individual transporter activity. PMID:23739593

  20. Postural plasma aldosterone response in "upright hyperkalemia" associated with selective hypoaldosteronism.

    PubMed

    Rado, J P; Simatupang, T; Boer, P; Dorhout Mees, E J

    1977-07-01

    Upright posture induced a consistent increase in serum K with a blunted plasma aldosterone response in four male renal patients with selective hypoaldosteronism. Dietary Na restriction induced a dramatic increase in the suppressed plasma aldosterone without returning the elevated serum K levels to normal and abolishing the postural serum K change. Therefore it is concluded that "upright hyperkalemia" may not be caused exclusively by suppression or/and inadequate postural response of aldosterone. Cellular disturbance in the regulation of K distribution might be an additional explantation for the aldosterone unresponsive postural K change. PMID:907798

  1. RIS requirements to support a PACS infrastructure

    NASA Astrophysics Data System (ADS)

    Honeyman-Buck, Janice C.; Frost, Meryll M.; Moser, Robert; Huda, Walter; Staab, Edward V.

    1996-05-01

    The purpose of this research and development effort was to solve several image management problems in Picture Archiving and Communications Systems (PACS). First, the patient and study information associated with images was not always correct and only rarely complete. This was due to human error in entering information on a console, and from incomplete data entry forms on image producing equipment. Second, in at least one area, Computed Radiography, the task of data entry was so time consuming that throughput suffered. The third problem was image routing, both within the Department of Radiology and throughout the hospital. The last identified problem was the lack of a common key between the PACS database the Radiology Information System (RIS) database so reports and images could be associated with each other. An RIS/PACS interface was developed in which RIS packets were sent to a PACS process at the time request forms were printed. These packets were parsed to various acquisition computers based on the modality type where they were stored in a MSQL Database for use in validating studies as they were completed prior to being transferred to PACS. DICOM header information from incoming studies were `matched' to a database entry based on the medical record number and modality. Whenever possible, an additional match was made on an accession number stored in the header. A match could result in the DICOM header being completed with detailed information about the patient, patient location, requesting service, and the procedure or study. In the case of the Kodak CR unit, patient and study information were sent directly to the CR workstation where they were accessible using a bar code interface at the time plates were ready to be processed. Routing within the radiology department was determined by comparing the RIS procedure code with an MSQL table to locate the workstation(s) used for viewing this type of study. The data of birth was used to determine whether the study

  2. Medical imaging, PACS, and imaging informatics: retrospective.

    PubMed

    Huang, H K

    2014-01-01

    Historical reviews of PACS (picture archiving and communication system) and imaging informatics development from different points of view have been published in the past (Huang in Euro J Radiol 78:163-176, 2011; Lemke in Euro J Radiol 78:177-183, 2011; Inamura and Jong in Euro J Radiol 78:184-189, 2011). This retrospective attempts to look at the topic from a different angle by identifying certain basic medical imaging inventions in the 1960s and 1970s which had conceptually defined basic components of PACS guiding its course of development in the 1980s and 1990s, as well as subsequent imaging informatics research in the 2000s. In medical imaging, the emphasis was on the innovations at Georgetown University in Washington, DC, in the 1960s and 1970s. During the 1980s and 1990s, research and training support from US government agencies and public and private medical imaging manufacturers became available for training of young talents in biomedical physics and for developing the key components required for PACS development. In the 2000s, computer hardware and software as well as communication networks advanced by leaps and bounds, opening the door for medical imaging informatics to flourish. Because many key components required for the PACS operation were developed by the UCLA PACS Team and its collaborative partners in the 1980s, this presentation is centered on that aspect. During this period, substantial collaborative research efforts by many individual teams in the US and in Japan were highlighted. Credits are due particularly to the Pattern Recognition Laboratory at Georgetown University, and the computed radiography (CR) development at the Fuji Electric Corp. in collaboration with Stanford University in the 1970s; the Image Processing Laboratory at UCLA in the 1980s-1990s; as well as the early PACS development at the Hokkaido University, Sapporo, Japan, in the late 1970s, and film scanner and digital radiography developed by Konishiroku Photo Ind. Co. Ltd

  3. Cost-effective ultrasound PACS solution

    NASA Astrophysics Data System (ADS)

    Honeyman-Buck, Janice C.; Frost, Meryll M.; Staab, Edward V.

    1995-05-01

    Picture archiving and communication systems (PACS) have been quite successful at the University of Florida in the areas of CT, MR, and nuclear medicine. In each case, although we have not always been able to provide the optimal level of performance, we have been able to solve a problem and the systems are used extensively. Ultrasound images are required in a number of locations and the multiformat camera print capability was no longer adequate for the growing volume in the ultrasound section. Although we were certain we could successfully implement PACS for ultrasound, new forces in health care dictate that we justify our system in terms of cost. We analyzed the feasibility of a PACS solution for ultrasound and designed a system that meets our needs and is cost effective. We evaluated the ultrasound operation in terms of image acquisition patterns and throughput requirements. An inventory of existing and PACS equipment was made to determine the feasibility of interfacing the two systems. Commercial systems were evaluated for functionality and cost and a system was designed to meet our needs. The only way to achieve our goal of installing a cost effective ultrasound PACS was to eliminate film and use the cost savings to offset the cost of new equipment and development. We designed a system that could be produced using inexpensive components and existing hardware and software to meet our needs. A commercial vendor was chosen to provide the ultrasound acquisition. The Radiology Information System interface used at the University provides the necessary data to build a DICOM header, and an existing DICOM server routes the images to the appropriate workstations, archives, and printers. Additional storage is added to an existing archive to accommodate the ultrasound images and two existing workstations are evaluated for use in ultrasound.

  4. PACS experience at the University of Hokkaido Medical School

    NASA Astrophysics Data System (ADS)

    Irie, Goro; Miyasaka, Kazuo; Miyamoto, Kenji; Kojima, Tetsuhumi; Yamamoto, Isao; Kudo, Toshihiko

    1990-08-01

    Seven months experiences of a filmless PACS (named HU-PACS) which covers Radiology, Orthopedic, Internal medicine and General Surgery departments are reported. The PACS has only 20 Image terminals but handles more than 50% of images produced which is about 1000 images per working day. Physicians of the departments have many criticisms and opinions on the PACS but generally speaking it is well accepted and inspiring the physicians to improve the PACS in its image quality and other functions instead of being discarded. Preliminary clinical assessment are performed and reported also.

  5. Aldosterone-to-Renin Ratio Is Associated With Reduced 24-Hour Heart Rate Variability and QTc Prolongation in Hypertensive Patients

    PubMed Central

    Grübler, Martin R.; Kienreich, Katharina; Gaksch, Martin; Verheyen, Nicolas; Hartaigh, Bríain Ó.; Fahrleitner-Pammer, Astrid; März, Winfried; Schmid, Johannes; Oberreither, Eva-Maria; Wetzel, Julia; Catena, Cristiana; Sechi, Leonardo A.; Pieske, Burkert; Tomaschitz, Andreas; Pilz, Stefan

    2016-01-01

    Abstract Aldosterone is considered to exert direct effects on the myocardium and the sympathetic nervous system. Both QT time and heart rate (HR) variability (HRV) are considered to be markers of arrhythmic risk and autonomous dysregulation. In this study, we investigated the associations between aldosterone, QT time, and HRV in patients with arterial hypertension. We recruited 477 hypertensive patients (age: 60.2 ± 10.2 years; 52.3% females) with a mean systolic/diastolic 24-hour ambulatory blood pressure monitoring (ABPM) value of 128 ± 12.8/77.1 ± 9.2 mmHg and with a median of 2 (IQR: 1–3) antihypertensive agents. Patients were recruited from the outpatient clinic at the Department of Internal Medicine of the Medical University of Graz, Austria. Blood samples, 24-hour HRV derived from 24-hour blood pressure monitoring (ABPM) and ECG's were obtained. Plasma aldosterone and plasma renin concentrations were measured by means of a radioimmunoassay. Twenty-four-hour urine specimens were collected in parallel with ABPM. Mean QTc was 423.3 ± 42.0 milliseconds for males and 434.7 ± 38.3 milliseconds for females. Mean 24H-HR and 24H-HRV was 71.9 ± 9.8 and 10.0 ± 3.6 bpm, respectively. In linear regression analyses adjusted for age, sex, body mass index, ABPM, and current medication, aldosterone to active renin ratio (AARR) was significantly associated with the QTc interval, a marker for cardiac repolarization abnormalities (mean = 426 ± 42.4 milliseconds; β-coefficient = 0.121; P = 0.03) as well as with the 24-hour heart rate variability a surrogate for autonomic dysfunction (median = 9.67 [IQR = 7.38–12.22 bpm]; β-coefficient = −0.133; P = 0.01). In hypertensive patients, AARR is significantly related to QTc prolongation as well as HRV. Further studies investigating the effects of mineralocorticoid receptor blocker and aldosterone synthase inhibitors on QTc and HRV are warranted

  6. Future trends in picture archiving and communication system (PACS)

    NASA Astrophysics Data System (ADS)

    Al-Hajeri, Mona; Clarke, Malcolm

    2015-03-01

    Objective: This research investigates the needs and opinions of radiologists on the use of enhanced information technologies and approaches to improve the functionality of Picture Archiving and Communication Systems (PACS). Method: Six interviews were conducted in the main governmental hospital in Kuwait (AL-Sabah Hospital) with radiologists, including two senior radiologists, two junior radiologists, and two trainee radiologists undertaking the Irish radiology board. Results: The radiologists identified a number of limitations that exist in current PACS and requirements to enhance usability and functionality. However, it was the case that some of the radiologists had little knowledge about the advanced trends in PACS. Four themes emerged from the thematic analysis of the data: (1) limitations of traditional PACS; (2) Features and requirements that can increase PACS functionality; (3) web based solutions of PACS; (4) PACS in mobile phones. Conclusion: It is widely recognized that PACS has limitations. This research has identified themes that, when incorporated, will enhance the functionality of PACS and provide better quality clinical practice. This research has determined the important future trends of PACS. Primarily web based solutions and use in mobile phones. The findings from this research can be used as recommendations to vendors, for product development and medical institutes to consider when undertaking implementation of PACS and training future radiologists.

  7. PACS administrators' and radiologists' perspective on the importance of features for PACS selection.

    PubMed

    Joshi, Vivek; Narra, Vamsi R; Joshi, Kailash; Lee, Kyootai; Melson, David

    2014-08-01

    Picture archiving and communication systems (PACS) play a critical role in radiology. This paper presents the criteria important to PACS administrators for selecting a PACS. A set of criteria are identified and organized into an integrative hierarchical framework. Survey responses from 48 administrators are used to identify the relative weights of these criteria through an analytical hierarchy process. The five main dimensions for PACS selection in order of importance are system continuity and functionality, system performance and architecture, user interface for workflow management, user interface for image manipulation, and display quality. Among the subdimensions, the highest weights were assessed for security, backup, and continuity; tools for continuous performance monitoring; support for multispecialty images; and voice recognition/transcription. PACS administrators' preferences were generally in line with that of previously reported results for radiologists. Both groups assigned the highest priority to ensuring business continuity and preventing loss of data through features such as security, backup, downtime prevention, and tools for continuous PACS performance monitoring. PACS administrators' next high priorities were support for multispecialty images, image retrieval speeds from short-term and long-term storage, real-time monitoring, and architectural issues of compatibility and integration with other products. Thus, next to ensuring business continuity, administrators' focus was on issues that impact their ability to deliver services and support. On the other hand, radiologists gave high priorities to voice recognition, transcription, and reporting; structured reporting; and convenience and responsiveness in manipulation of images. Thus, radiologists' focus appears to be on issues that may impact their productivity, effort, and accuracy. PMID:24744278

  8. Aldosterone Induces Tissue Inhibitor of Metalloproteinases-1 Expression and Further Contributes to Collagen Accumulation: From Clinical to Bench Studies.

    PubMed

    Hung, Chi-Sheng; Chou, Chia-Hung; Liao, Che-Wei; Lin, Yen-Tin; Wu, Xue-Ming; Chang, Yi-Yao; Chen, Ying-Hsien; Wu, Vin-Cent; Su, Ming-Jai; Ho, Yi-Lwun; Chen, Ming-Fong; Wu, Kwan-Dun; Lin, Yen-Hung

    2016-06-01

    Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity. PMID:27113051

  9. Comparison of two PAC/UF processes for the removal of micropollutants from wastewater treatment plant effluent: process performance and removal efficiency.

    PubMed

    Löwenberg, Jonas; Zenker, Armin; Baggenstos, Martin; Koch, Gerhard; Kazner, Christian; Wintgens, Thomas

    2014-06-01

    Two hybrid membrane processes combining powdered activated carbon (PAC) adsorption with ultrafiltration (UF) were investigated regarding operational performance and efficiency to remove organic micropollutants from municipal wastewater treatment plant effluent. A pressurized PAC/UF (pPAC/UF) and a submerged PAC/UF (sPAK/UF) system were operated continuously over a period of six months. Both UF membrane systems showed good compatibility with the application of PAC showing no abrasion or other negative impacts. The pPAC/UF system reached permeability values up to 290 L/(m² h bar) at high fluxes of 80 L/(m² h) compared to the sPAC/UF with a permeability of up to 200 L/(m² h bar) at fluxes of up to 23 L/(m² h). Surface analysis of both membranes with scanning electron microscopy revealed no membrane deterioration after the six-month period of operation. On the surface of the pressurized membrane the formation of a PAC layer was observed, which may have contributed to the high permeability by forming a protective coating. Five micropollutants, i.e. sulfamethoxazole, carbamazepine, mecoprop, diclofenac and benzotriazole in ambient effluent concentrations were investigated. Both PAC/UF systems removed 60-95% of the selected micropollutants at a dosage of 20 mg PAC/L and 4 mg Fe(3+)/L. However, extreme peak loads of sulfamethoxazole with concentrations of up to 30 μg/L caused a considerable performance decrease for more than a week. PMID:24631942

  10. Simulation And Communication Aspects Of PACS

    NASA Astrophysics Data System (ADS)

    Reijns, G. L.; Bakker, A. R.; de Valk, J. P. J.

    1988-06-01

    The storage of large amounts of digital image data and the communication of the images within a hospital are major problems in the development of a Picture Archiving and Communications System (PACS). Image compression reduces both the problems of storage capacity and of the image transmission rate by approximately a factor 12. It is shown that the use of memory buffers at different hierarchical system levels provides for an additional reduction in the required transmission rate. In order to determine the communication rates and number and size of the buffers, the PACS has been modelled by a system of queues and servers. Queueing models can be analysed by means of computer simulation but also mathematically. Examples of mathematical analysis are given and a simplified model of the department of radiology is evaluated.

  11. Pacs: Part Of An Integrated Communications System

    NASA Astrophysics Data System (ADS)

    Thompson, B. G.; Brenton, Bradley C.; Staab, Edward V.; Perry, J. Randolph; Parrish, Denise; Johnston, R. Eugene; Creasy, Jeffrey L.

    1985-09-01

    The Department of Radiology at the University of North Carolina-Chapel Hill (UNC) has developed the concept for an integrated picture archiving and communications system. A communications network has been installed, and computer facilities are being interfaced within radiology areas. Other projects include the establishment of a computer simulation model of departmental operations and assembly of a limited picture archival and communication system (PACS) beginning with the CT and NMR Modalities. While this approach may provide immediate clinical benefits, the initial thrust has been towards evaluation of prototype systems with flexibility for modifications. PACS operational parameters are being studied for their acceptability in support of radiology clinical services. The goal is to provide objective operational data as a basis for planning system improvements.

  12. Evaluation of PACS in a multihospital environment

    NASA Astrophysics Data System (ADS)

    Siegel, Eliot L.; Reiner, Bruce I.; Protopapas, Zenon

    1998-07-01

    Although a number of authors have described the challenges and benefits of filmless operation using a hospital-wide Picture Archival and Communication System (PACS), there have been few descriptions of a multi-hospital wide area PACS. The purpose of this paper is to describe our two and a half year experience with PACS in an integrated multi-facility health care environment, the Veterans Affairs Maryland Health Care System (VAMHCS). On June 17, 1995 the Radiology and Nuclear Medicine services became integrated for four medical centers forming the VA Maryland Health Care System creating a single multi-facility imaging department. The facilities consisted of the Baltimore VA (acute and outpatient care, tertiary referral center), Ft. Howard (primarily long term care), Perry Point (primarily psychiatric care), and the Baltimore Rehabilitation and extended care facility (nursing home). The combined number of studies at all four sites is slightly more than 80,000 examinations per year. In addition to residents and fellows, the number of radiologists at Baltimore was approximately seven, with two at Perry Point, one at Ft. Howard, and no radiologists at the Rehabilitation and Extended Care facility. A single HIS/RIS, which is located physically at the Baltimore VAMC is utilized for all four medical centers. The multi- facility image management and communication system utilizes two separate PAC Systems that are physically located at the Baltimore VA Medical Center (BVAMC). The commercial system (GE Medical Systems) has been in place in Baltimore for more than 41/2 years and is utilized primarily in the acquisition, storage, distribution and display of radiology and nuclear medicine studies. The second PACS is the VISTA Imaging System, which has been developed as a module of the VA's HIS/RIS by and for the Department of Veterans Affairs. All of the radiology images obtained on the commercial PACS are requested by the VISTA Imaging System using DICOM query/retrieve commands

  13. The Medical Community's View On PACS

    NASA Astrophysics Data System (ADS)

    Glenn, William; Darlak, Joseph; Enzmann, Dieter R.; Gayler, Robert; James, A. Everette; Lehr, James L.; Newton, Carol; Partain, C. Leon; Zielonka, Jason S.; Marion, Joseph L.; Kouwenberg, Jef; Wake, Robert H.; Hindel, Robert; White, James M.

    1982-01-01

    Andre Duerinckx, PACS '82 Chairman. I think we can start with the second panel discussion, which will be the last activity of this conference. The Chairman of this Panel is Dr. Bill Glenn from Multi-Planar Diagnostic Imaging Inc. I want to say that what you are about to hear or say will be recorded, so please do use the microphones; don't say anything without using microphones. The same goes, of course, for the panel members.

  14. Impact Of Manual And Computer-Assisted PACS For Automated PACS

    NASA Astrophysics Data System (ADS)

    Lehr, James L.

    1983-05-01

    Considerations of totally electronic picture archiving system (PACS) often neglect the fact that every radiology practice currently has some system for storing and retrieving images and related alphanumeric data. Although these systems are usually manual, many departments now use on-line computers to help manage film flow. In either event, the creation of electronic PACS can be viewed as a classic data processing problem of automating an existing system, and the conversion should proceed through the usual steps of documenting the existing system in detail, and conducting feasibility studies and cost-benefit analyses. Documenting current systems should be facilitated by computer-assisted PACS - particularly documenting transaction volumes which can be provided as a by-product of radiology information management systems. Similarly cost-benefit analysis should be facilitated, although the cost/benefit ratio may be less favorable when comparing automated to computer-assisted PACS. Finally, information management features such as those provided by current on-line radiology systems provide a framework necessary to realize the full benefits of automated PACS.

  15. On-line performance characteristics of a radiology PACS

    NASA Astrophysics Data System (ADS)

    Wong, Albert W. K.; Loloyan, Mansur; Lou, Shyhliang A.; Huang, H. K.

    1992-07-01

    We have experienced that system reliability and performance become primary concerns when we moved our PACS from a research and development laboratory to a clinical environment. Providing consistent uptime builds user confidence and fast service accelerates system acceptance. The fault-tolerant mechanism implemented in our PACS has minimized system downtime. This paper considers the performance issues of an on-line multimodal PACS. The intent of conducting performance measurements on individual PACS components such as the radiological imaging devices, archive devices, host computers, and communication networks is to compare the throughput rates of these components in a real-time clinical environment as a basis of evaluating the overall throughput of a PACS system. Our primary goal is to identify the major factors that degrade the performance of a PACS, and to establish new strategies so that fast service with minimal delay is provided to the clinic. Approximately 200-Gbyte data transactions including CT, MR and CR images from our PACS were analyzed. Results showed that PACS throughput was limited by two major factors: (1) low-speed data interface used in the radiological imaging devices and archive devices; (2) network degradation due to heavy network traffic. We concluded that PACS throughput could be improved by well- designed network architecture and image-routing strategy. However, device-dependent low- speed data interface limited PACS performance.

  16. Reverse remodeling and recovery from cachexia in rats with aldosteronism.

    PubMed

    Cheema, Yaser; Zhao, Wenyuan; Zhao, Tieqiang; Khan, M Usman; Green, Kelly D; Ahokas, Robert A; Gerling, Ivan C; Bhattacharya, Syamal K; Weber, Karl T

    2012-08-15

    The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca(2+), coupled to oxidative stress with increased H(2)O(2) production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal. PMID:22730385

  17. Reverse remodeling and recovery from cachexia in rats with aldosteronism

    PubMed Central

    Cheema, Yaser; Zhao, Wenyuan; Zhao, Tieqiang; Khan, M. Usman; Green, Kelly D.; Ahokas, Robert A.; Gerling, Ivan C.; Bhattacharya, Syamal K.

    2012-01-01

    The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca2+, coupled to oxidative stress with increased H2O2 production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal. PMID:22730385

  18. Deep Herschel PACS point spread functions

    NASA Astrophysics Data System (ADS)

    Bocchio, M.; Bianchi, S.; Abergel, A.

    2016-06-01

    The knowledge of the point spread function (PSF) of imaging instruments represents a fundamental requirement for astronomical observations. The Herschel PACS PSFs delivered by the instrument control centre are obtained from observations of the Vesta asteroid, which provides a characterisation of the central part and, therefore, excludes fainter features. In many cases, however, information on both the core and wings of the PSFs is needed. With this aim, we combine Vesta and Mars dedicated observations and obtain PACS PSFs with an unprecedented dynamic range (~106) at slow and fast scan speeds for the three photometric bands. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.FITS files of our PACS PSFs (Fig. 2) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/591/A117

  19. Data protection and security issues of PACS

    NASA Astrophysics Data System (ADS)

    Bakker, Albert R.

    1992-07-01

    It is observed that the dataprotection aspects of PACS have hardly been explored, while for Hospital Information Systems (HIS) considerable attention has been paid to these aspects. In the dataprotection domain around HIS we distinguish the aspects data integrity (safety), usage integrity (confidentiality, privacy) and availability. A wide range of measures (dealing with hardware, software or organization/procedures) has been suggested to achieve adequate protection. For each system a selection of the suggested measures has to be made, where risk is balanced against costs. It seems that it is taken for granted that the usual measures as implemented for HIS will also be adequate for PACS. In this paper dataprotection aspects for PACS are discussed. Apart from similarities with the HIS situation also differences will be identified. In particular safeguarding the image databank requires special measured. Dataprotection should not be an add-on of the system, it should be taken into account in the design phase. As an illustration two alternatives for the organization of the image databank will be considered from the point of view of dataprotection. The one being consecutive historical storage of images, the other the clustering of images of the same patient on the same volume in the storage system.

  20. The HERSCHEL/PACS Spectrometer Pipeline

    NASA Astrophysics Data System (ADS)

    Schreiber, J.; Wieprecht, E.; de Jong, J.; Wetzstein, M.; Jacobson, J.; Huygen, R.; Appleton, P.; Bouwman, J.; Contursi, A.; Fadda, D.; Jean, C.; Klaas, U.; Royer, P.; Vandenbussche, B.

    2009-09-01

    ESA's Herschel Space Observatory, to be launched in 2009, is the first space observatory covering the full far-infrared and sub-millimeter wavelength range (60 - 670 micron). The Photodetector Array Camera & Spectrometer (PACS) is one of the three science instruments. It employs two Ge:Ga photoconductor arrays and two bolometer arrays to perform integral field spectroscopy and imaging photometry in the 60 - 210 micron wavelength band. The interactive PACS Spectrometer and Photometer \\citep{wieprecht09} Data Reduction Pipeline is integrated in the Herschel Data Processing System. The DP is implemented using Java technology and written in a common effort by the HERSCHEL Science Center (HSC) and the three instrument teams. We overview the concept and status of the PACS Spectrometer Data Reduction Pipeline. Additionally, we address the instrument mode-dependent data processing and the definition of the products of the different processing levels. Finally, we show first results by applying the pipeline on flight model instrument level test data.

  1. Design of a PACS cluster controller

    NASA Astrophysics Data System (ADS)

    Taira, Ricky K.; Wong, Albert W. K.; Stewart, Brent K.; Huang, H. K.

    1992-07-01

    Our PACS design consists of clusters of computerized devices. At the center of each cluster is an intelligent machine termed a cluster controller. A cluster controller performs the following tasks: (1) receives images from capture computers, (2) extracts descriptive text information describing the received studies, (3) updates a network-accessible database management system, (4) determines the destination workstations to forward the newly generated studies, (5) automatically retrieves necessary comparison images from a distributed optical archive, (6) automatically corrects the orientation of computed radiography images, (7) archives new studies onto optical disk, (8) deletes images stored on remote capture computers upon successful image archival, and (9) services archive retrieval requests from remote workstations and other cluster controllers. The cluster controller is the only class of PACS computers that must communicate with all other types of PACS nodes (acquisition, other cluster controllers, radiologist''s workstation, referring physician''s workstation, printing stations, and database servers). This paper presents details of the logical partitioning of computers into clusters and the central role of the cluster controller machines in image acquisition, image routing, optical archive management, and system reliability.

  2. Multiple communication networks for a radiological PACS

    NASA Astrophysics Data System (ADS)

    Wong, Albert W. K.; Stewart, Brent K.; Lou, Shyhliang A.; Chan, Kelby K.; Huang, H. K.

    1991-07-01

    The authors have implemented a communication network connecting multiple buildings for their picture archiving and communication system (PACS) in the Radiology Department at UCLA. The network consists of three types of local area networks (LANs) and a 1.0-km fiber-optic link connecting the outpatient and inpatient facilities. Images from radiologic imaging devices (4 CT scanners, 5 MR scanners, 4 CR units and 5 film digitizers) are transmitted to the acquisition computers via the Ethernet LAN. The fiber distributed data interface (FDDI) LAN then provides data communication among the cluster controllers, the acquisition computers, and the database servers. A 1-gigabit UltraNet LAN is used to route images from the cluster controllers to remote display workstations. All inter-building connections are through fiber-optic cables. Among these multiple networks, Ethernet offers multi-access to the multimodal PACS in image acquisition, FDDI controls a fast data flow so that all acquired images have a shorter residence time on local disks, and UltraNet provides high-speed transfer of images from the cluster controllers to the display workstations. The three-tiered functionality of Ethernet, FDDI, and UltraNet eliminates network traffic bottlenecks and hence provides high performance in image communication. The delay time of a 2K X 2K X 8-bit CR image (4 MBytes) from acquisition to display is less than 5 minutes. In addition, the standard Ethernet serves as a backup to guarantee network connectivity of the entire PACS.

  3. Methodology for the economic assessment of PACS

    NASA Astrophysics Data System (ADS)

    Langlotz, Curtis P.; Even-Shoshan, Orit; Seshadri, Sridhar B.; Brikman, Inna; Kishore, Sheel; Kundel, Harold L.; Schwartz, J. Sanford

    1994-05-01

    Most economic studies of Picture Archiving and Communications Systems (PACS) to date, including our own, have focused on the perspective of the radiology department and its direct costs. However, many researchers have suggested additional cost savings that may accrue to the medical center as a whole through increased operational capacity, fewer lost images, rapid simultaneous access to images, and other decreases in resource utilization. We describe here a new economic analysis framework we have developed to estimate these potential additional savings. Our framework is comprised of two parallel measurement methods. The first method estimates the cost of care actually delivered through online capture of charge entries from the hospital's billing computer and from the clinical practices' billing database. Multiple regression analyses will be used to model cost of care, length of stay, and other estimates of resource utilization. The second method is the measurement of actual resource utilization, such as technologist time, frequency and duration of film searches, and equipment utilization rates. The costs associated with changes in resource use will be estimated using wage rates and other standard economic methods. Our working hypothesis is that, after controlling for the underlying clinical and demographic differences among patients, patients imaged using a PACS will have shorter lengths of stay, shorter exam performance times, and decreased costs of care. We expect our analysis framework to explain and resolve some of the conflicting views of the cost-effectiveness of PACS.

  4. Extraordinarily high aldosterone, 901.0 ng/dL, in a patient with primary aldosteronism: an insight into the underlying mechanism.

    PubMed

    Okubo, Yosuke; Sato, Yuka; Nakasone, Yasuto; Shirotori, Katsuko; Oguchi, Kazuhiro; Matsushita, Tsuyoshi; Nishikawa, Tetsuo; Yamazaki, Yuto; Sasano, Hironobu; Komatsu, Mitsuhisa; Yamauchi, Keishi; Aizawa, Toru

    2016-02-29

    A 43-yr-old hypertensive male was admitted due to hypokalemia (1.8 mEq/L) and renal dysfunction (eGFR, 20.0 mL/min/1.73 m(2)). His plasma aldosterone was 901.0 ng/dL, plasma renin activity 5.7 ng/mL/hr, and aldosterone/renin activity ratio 158. Angiotensin II (AII) was 0.7 pg/mL, ACTH <1.0 pg/mL, and cortisol 21.6 μg/dL. Liquid chromatography-tandem mass spectrometry analysis showed that aldosterone (104 times the control) as well as its precursors were significantly elevated in the patient's plasma. A left adrenal (4-cm-diameter) tumor with (131)I-Adosterol® uptake was found and removed. Four days later, plasma aldosterone and renin activity had dropped to 7.73 ng/dL and 1.6 ng/mL/hr, respectively. However, they rose to 24.0 ng/dL and 10.9 ng/mL/hr, respectively, by Day 102. Nevertheless, magnetic resonance angiography found no evidence of a renovascular lesion. The tumor was a benign adrenocortical adenoma composed predominantly of clear cells positive for 17α-hydroxylase, [hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerases], and aldosterone synthase. A quantitative real-time polymerase chain reaction analysis of the tumor cells revealed that expression of the gene encoding aldosterone synthase was 85 times the control level. In addition, the tumor cells harbored G151R mutation of the inward rectifying potassium channel subfamily j, member 5 gene. The striking overexpression of aldosterone synthase by the tumor cells was considered the primary mechanism for the extravagant overproduction of aldosterone in this case. This overexpression may have resulted from integration of signals from AII and forced membrane depolarization due to the potassium channel mutation. PMID:26549209

  5. Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production.

    PubMed

    Hattangady, Namita G; Karashima, Shigehiro; Yuan, Lucy; Ponce-Balbuena, Daniela; Jalife, José; Gomez-Sanchez, Celso E; Auchus, Richard J; Rainey, William E; Else, Tobias

    2016-07-01

    Somatic and germline mutations in the inward-rectifying K(+) channel (KCNJ5) are a common cause of primary aldosteronism (PA) in aldosterone-producing adenoma and familial hyperaldosteronism type III, respectively. Dysregulation of adrenal cell calcium signaling represents one mechanism for mutated KCNJ5 stimulation of aldosterone synthase (CYP11B2) expression and aldosterone production. However, the mechanisms stimulating acute and chronic production of aldosterone by mutant KCNJ5 have not been fully characterized. Herein, we defined the effects of the T158A KCNJ5 mutation (KCNJ5(T158A)) on acute and chronic regulation of aldosterone production using an adrenal cell line with a doxycycline-inducible KCNJ5(T158A) gene (HAC15-TRE-KCNJ5(T158A)). Doxycycline incubation caused a time-dependent increase in KCNJ5(T158A) and CYP11B2 mRNA and protein levels. Electrophysiological analyses confirm the loss of inward rectification and increased Na(+) permeability in KCNJ5(T158A)-expressing cells. KCNJ5(T158A) expression also led to the activation of CYP11B2 transcriptional regulators, NURR1 and ATF2. Acutely, KCNJ5(T158A) stimulated the expression of total and phosphorylated steroidogenic acute regulatory protein (StAR). KCNJ5(T158A) expression increased the synthesis of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol, measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). All of these stimulatory effects of KCNJ5(T158A) were inhibited by the L-type Ca(2+) channel blocker, verapamil. Overall, KCNJ5(T158A)increases CYP11B2 expression and production of aldosterone, corticosterone and hybrid steroids by upregulating both acute and chronic regulatory events in aldosterone production, and verapamil blocks KCNJ5(T158A)-mediated pathways leading to aldosterone production. PMID:27099398

  6. Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands

    PubMed Central

    Nishimoto, Koshiro; Tomlins, Scott A.; Kuick, Rork; Cani, Andi K.; Giordano, Thomas J.; Hovelson, Daniel H.; Liu, Chia-Jen; Sanjanwala, Aalok R.; Edwards, Michael A.; Gomez-Sanchez, Celso E.; Nanba, Kazutaka; Rainey, William E.

    2015-01-01

    Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosterone-producing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APA-related aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na+/K+ transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosterone-driving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA. PMID:26240369

  7. Aldosterone and thyroid hormone interaction on the sodium and potassium transport pathways of rat colonic epithelium.

    PubMed

    Edmonds, C J; Willis, C L

    1990-01-01

    The effect of hypothyroidism on potassium adaptation (shown by increased potassium secretion in response to potassium loading) and on the action of aldosterone on potassium secretion and sodium fluxes was examined in the rat distal colon. Potassium adaptation, particularly the response to an acute potassium load, was impaired by hypothyroidism which also considerably reduced the rise of transepithelial electrical potential difference (p.d.) of total and transcellular (active) lumen-to-plasma sodium fluxes and of potassium secretion normally produced by aldosterone. These changes were, in part, corrected by a short period (3 days) of tri-iodothyronine replacement. Moreover in aldosterone-treated hypothyroid rats, amiloride in the lumen was considerably less effective in reducing the p.d. and sodium fluxes than in aldosterone-treated normal rats. The intracellular sodium transport pool was greater in the hypothyroid than in the normal rats (5.0 +/- 1.1 (S.E.M.) nmol/mg dry weight compared with 2.9 +/- 0.2 nmol/mg dry weight; P less than 0.02). Aldosterone increased the pool in the normal but not in the hypothyroid rats while amiloride had little effect on the pool in the aldosterone-treated hypothyroid rats but almost abolished it in aldosterone-treated normal rats. Aldosterone plays a major part in the adaptation of colonic sodium and potassium transport to sodium depletion or potassium excess; these adaptations were much impaired in hypothyroid animals. The present results are consistent with a deficiency in aldosterone induction of potassium- and amiloride-sensitive sodium pathways in the apical membrane of colonic epithelial cells in hypothyroid rats, a deficiency which limits the stimulant effect of aldosterone on sodium and potassium transport. PMID:2299278

  8. Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands.

    PubMed

    Nishimoto, Koshiro; Tomlins, Scott A; Kuick, Rork; Cani, Andi K; Giordano, Thomas J; Hovelson, Daniel H; Liu, Chia-Jen; Sanjanwala, Aalok R; Edwards, Michael A; Gomez-Sanchez, Celso E; Nanba, Kazutaka; Rainey, William E

    2015-08-18

    Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosterone-producing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APA-related aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na(+)/(K+) transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosterone-driving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA. PMID:26240369

  9. The role of potassium and other ions in the control of aldosterone synthesis

    SciTech Connect

    Kenyon, C.J.; Shepherd, R.M.; Fraser, R.; Pediani, J.D.; Elder, H.Y. )

    1991-01-01

    Fast and slow K+ efflux components, independently regulated by angiotensin II (AII), have been identified in bovine adrenocortical cells. The authors have further investigated the role of potassium in the control of aldosterone synthesis in two ways. Firstly, isotopic tracers, in conjunction with channel modulators, have been used to study the interrelationship of K+ and Ca2+ in the control of AII-stimulated aldosterone synthesis. Secondly, electron probe X-ray microanalysis (EPXMA) was used to quantify potassium, sodium, chlorine and phosphorous in control and AII-stimulated cells. The effects of verapamil on 43K efflux were measured at two stages during AII stimulation. During the first ten minutes of treatment, when efflux via the fast component predominates, AII and verapamil both slowed efflux and their effects were additive. If verapamil was added later, at the time when efflux by the fast component appeared exhausted and the stimulatory effect of AII on the slow efflux component was apparent, it again slowed efflux. These data suggest that verapamil prevents calcium-gated K+ channels from opening by blocking Ca2+ channels. However, verapamil had no effect on AII-stimulated calcium efflux. In addition to blocking Ca2+ channels, verapamil may directly inhibit potassium efflux. EPXMA showed a bimodal distribution of potassium concentrations in control cells. However, in cells stimulated with AII for five minutes, the mean potassium content was less than in controls and was not bimodally distributed. Sodium content was increased by AII-treatment, chlorine was lowered and phosphorus remained unchanged. The data confirm previous observations that AII inhibits Na+/K+ ATPase activity.

  10. Relationship of Ocular Microcirculation, Measured by Laser Speckle Flowgraphy, and Silent Brain Infarction in Primary Aldosteronism

    PubMed Central

    Kunikata, Hiroshi; Aizawa, Naoko; Kudo, Masataka; Mugikura, Shunji; Nitta, Fumihiko; Morimoto, Ryo; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Satoh, Fumitoshi; Takahashi, Hidetoshi; Ito, Sadayoshi; Takahashi, Shoki; Nakazawa, Toru

    2015-01-01

    Purpose Recent studies have shown that the risk of cerebro- and cardiovascular events (CVEs) is higher in patients with primary aldosteronism (PA) than in those with essential hypertension (EH), and that silent brain infarction (SBI) is a risk factor and predictor of CVEs. Here, we evaluated the relationship between findings from laser speckle flowgraphy (LSFG), a recently introduced non-invasive means of measuring mean blur rate (MBR), an important biomarker of ocular blood flow, and the occurrence of SBI in patients with PA. Methods 87 PA patients without symptomatic cerebral events (mean 55.1 ± 11.2 years old, 48 male and 39 female) were enrolled in this study. We measured MBR in the optic nerve head (ONH) with LSFG and checked the occurrence of SBI with magnetic resonance imaging. We examined three MBR waveform variables: skew, blowout score (BOS) and blowout time (BOT). We also recorded clinical findings, including age, blood pressure, and plasma aldosterone concentration. Results PA patients with SBI (15 of 87 patients; 17%) were significantly older and had significantly lower BOT in the capillary area of the ONH than the patients without SBI (P = 0.02 and P = 0.03, respectively). Multiple logistic regression analysis revealed that age and BOT were independent factors for the presence of SBI in PA patients (OR, 1.15, 95% CI 1.01–1.38; P = .03 and OR, 0.73, 95% CI 0.45–0.99; P = .04, respectively). Conclusion PA patients with SBI were older and had lower MBR BOT than those without SBI. Our analysis showed that age was a risk factor for SBI, and that BOT was a protective factor, in patients with PA. This suggests that BOT, a non-invasive and objective biomarker, may be a useful predictor of SBI and form part of future PA evaluations and clinical decision-making. PMID:25675373

  11. Cortisol-induced inhibition of ovine renin and aldosterone responses to hypotension

    SciTech Connect

    Wood, C.E.; Silbiger, J.

    1987-03-01

    Previous studies from this laboratory have demonstrated that in preterm fetal sheep increases in plasma cortisol (F) concentration equal in amplitude to fetal F stress responses suppress plasma renin activity (PRA). The purpose of this study was to investigate the possibility that this negative interaction exists in adult sheep. Cortisol was measured by radioimmunoassay. Five conscious ewes with chronically prepared carotid arterial loops were infused intravenously with F or vehicle for 5 h. One hour after the end of F or vehicle infusion, renin secretion was stimulated by hypotension produced by infusion of sodium nitroprusside. F infusion increased plasma F; during vehicle infusion plasma F did not change. F infusion decreased hematocrit from 29 +/- 2 to 26 +/- 1%. Basal PRA in vehicle- and F-infused groups were 0.4 +/- 0 and 0.2 +/- 0.1 ng angiotensin I-ml/sup -1/-h/sup -1/ and did not change. In vehicle-infused ewes, PRA increased from 0.4 +/- 0 to 4.6 +/- 0.4 and plasma aldosterone from 26.0 +/- 1.0 to 173.1 +/- 21.8 pg/ml, while in F-infused ewes, PRA increased from 0.2 +/- 1 to 3.3 +/- 0.4 ng angiotensin I-ml/sup -1/-h/sup -1/ and aldosterone from 25.0 +/- 0 to 48.2 +/- 23.2 pg/ml, significantly smaller responses. These results suggest that repeated stress may modulate the responses of the renin-angiotensin system in this species.

  12. Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after one month withdrawal of long-term therapy with aldosterone-receptor antagonist potassium canrenoate.

    PubMed

    Armanini, D; Scaroni, C; Mattarello, M J; Fiore, C; Albiger, N; Sartorato, P

    2005-03-01

    We have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110 mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125-160/80-100 mmHg). One month after withdrawal, the ratio aldosterone (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased only in 3 cases (median 18, range 6.1-125). We found a significant inverse correlation between the upright aldosterone/plasma renin activity (aldo/PRA) ratio, 1 month after withdrawal, and the number of years of therapy with potassium canrenoate. We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug. These data are consistent with possible regression of idiopathic primary hyperaldosteronism after long-term therapy with potassium canrenoate, or in alternative to a persistent effect of potassium canrenoate, on aldosterone synthesis. PMID:15952408

  13. Secure vendor environment (SVE) for PACS

    NASA Astrophysics Data System (ADS)

    Honeyman-Buck, Janice; Frost, Meryll

    2005-04-01

    A Secure Vendor Environment (SVE) was created to protect radiology modalities from network intrusion, worms, viruses, and other forms of damaging attacks. Many vendors do not attempt any form of network security and if an institution demands a non-standard and secure installation, a future system upgrade could and frequently does eliminate any security measures installed during the initial installation. The SVE isolates the vendor equipment behind a virtual firewall on a private network that is invisible to the outside world. All interactions must go though a device containing two network interface cards called an Application Processor that acts as a store-and forward router, performs DICOM repair, proxies modality worklist, and isolates the vendor modalities. A small VPN appliance can open the device temporarily for remote access by vendor engineers. Prior to the routine installation of the SVE, vendor equipment was often attacked by hostile network intruders and viruses or worms, sometimes rendering the equipment unusable until the vendor could reload the system. The resulted in considerable clinical downtime and loss of revenue. Since the relatively low cost SVE solution has routinely been installed with all new equipment, no intrusions have occurred, although our network sniffers and intrusion detectors indicate that we are constantly being scanned for vulnerability. Purpose: To provide a secure network for vendor equipment in a PACS environment while allowing vendor access for upgrades and system repairs. Method: The network administrators at our university believe that network security should be implemented at the machine level rather than relying on a firewall. A firewall solution could conceivably block unwanted intrusion from outside the university network, but would still allow literally thousands of potential network users to get through to the PACS network. All the PACS archive, display and routing systems are individually protected from intrusion, but

  14. Modeling The Economics Of PACS: What Is Important?

    NASA Astrophysics Data System (ADS)

    Saarinen, Allan O.; Haynor, David R.; Loop, John W.; Johnson, Linda; Russell, John; Mitchell, Kate; Nemerever, Marilyn

    1989-05-01

    Picture Archive and Communications Systems (PACS) represent a significant long term capital investment for radiology departments and hospitals. Many radiology departments want to acquire this new imaging technology, but they are still concerned about the cost of these systems. While a few studies have tried to quantify the costs and benefits of PACS, these studies have been limited in scope. The University of Washington is evaluating a Digital Imaging Network System (DINS) and PACS for the U.S. Army Medical Research and Development Command. Part of this evaluation includes developing a comprehensive cost model of PACS for one of the military's large health care facilities (a 400 bed hospital). The paper summarizes the methodology and multi-layered spreadsheet model developed at the University to forecast the costs and potential cost savings this health care facility might accrue if a hospital wide PACS is installed and film is eliminated. It also discusses the many important assumptions made in the model. A sensitivity analysis of the model is also presented. The model indicates that keeping PACS maintenance costs down is particularly critical to the cost effectiveness of PACS. That is, the film cost savings attributed to PACS can be largely offset by PACS equipment maintenance cost. The cost effectiveness of PACS will also hinge upon whether a number of intangible benefits, such as referring physician and support staff productivity gains can be attributed to PACS. This model also suggests that the pay back period for a hospital wide PACS will vary significantly dependent upon the mix of tangible versus intangible cost savings incorporated into the modeling process.

  15. Current status of the UCSF second-generation PACS

    NASA Astrophysics Data System (ADS)

    Huang, H. K.; Arenson, Ronald L.; Wong, Albert W. K.; Bazzill, Todd M.; Lou, Shyhliang A.; Andriole, Katherine P.; Wang, Jun; Zhang, Jianguo; Wong, Stephen T. C.

    1996-05-01

    This paper describes the current status of the second generation PACS at UCSF commenced in October 1992. The UCSF PACS is designed in-house as a hospital-integrated PACS based on an open architecture concept using industrial standards including UNIX operating system, C programming language, X-Window user interface, TCP/IP communication protocol, DICOM 3.0 image standard and HL7 health data format. Other manufacturer's PACS components which conform with these standards can be easily integrated into the system. Relevant data from HIS and RIS is automatically incorporated into the PACS using HL7 data format and TCP/IP communication protocol. The UCSF system also takes advantage of state-of-the-art communication, storage, and software technologies in ATM, multiple storage media, automatic programming, multilevel processes for a better cost-performance system. The primary PACS network is the 155 Mbits/sec OC3 ATM with the Ethernet as the back-up. The UCSF PACS also connects Mt. Zion Hospital and San Francisco VA Medical Center in the San Francisco Bay area via an ATM wide area network with a T1 line as the back-up. Currently, five MR and five CT scanners from multiple sites, two computed radiography systems, two film digitizers, one US PACS module, the hospital HIS and the department RIS have been connected to the PACS network. The image data is managed by a mirrored database (Sybase). The PACS controller, with its 1.3 terabyte optical disk library, acquires 2.5 gigabytes digital data daily. Four 2K, five, 1,600-line multiple monitor display workstations are on line in neuroradiology, pediatric radiology and intensive care units for clinical use. In addition, the PACS supports over 100 Macintosh users in the department and selected hospital sites for both images and textual retrieval through a client/server mechanism. We are also developing a computation and visualization node in the PACS network for advancing radiology research.

  16. Long term outcome of Aldosteronism after target treatments.

    PubMed

    Wu, Vin-Cent; Wang, Shuo-Meng; Chang, Chia-Hui; Hu, Ya-Hui; Lin, Lian-Yu; Lin, Yen-Hung; Chueh, Shih-Chieh Jeff; Chen, Likwang; Wu, Kwan-Dun

    2016-01-01

    There exists a great knowledge gap in terms of long-term effects of various surgical and pharmacological treatments on outcomes among primary aldosteronism (PA) patients. Using a validated algorithm, we extracted longitudinal data for all PA patients diagnosed in 1997-2010 and treated in the Taiwan National Health Insurance. We identified 3362 PA patients for whom the mean length of follow-up was 5.75 years. PA has higher major cardiovascular events (MACE) than essential hypertension (23.3% vs 19.3%, p = 0.015). Results from the Cox model suggest a strong effect of adrenalectomy on lowering mortality (HR = 0.23 with residual hypertension and 0.21 with resolved hypertension). While need for receptor antagonist (MRA) MRA after diagnosis suggests that a defined daily dose (DDD) of MRA between 12.5 and 50 mg may alleviate risk of death in a U-shape pattern. A specificity test identified patients who has aldosterone producing adenoma (HR = 0.50, p = 0.005) also confirmed adrenalectomy attenuated all-cause mortality. Adrenalectomy decreases long-term all-cause mortality independently from PA cure from hypertension. Prescription corresponding to a DDD between 12.5 and 50 mg may decrease mortality for patients needing MRA. It calls for more attention on early diagnosis, early treatment and prescription of appropriate dosage of MRA for PA patients. PMID:27586402

  17. Long term outcome of Aldosteronism after target treatments

    PubMed Central

    Wu, Vin-Cent; Wang, Shuo-Meng; Chang, Chia-Hui; Hu, Ya-Hui; Lin, Lian-Yu; Lin, Yen-Hung; Chueh, Shih-Chieh Jeff; Chen, Likwang; Wu, Kwan-Dun

    2016-01-01

    There exists a great knowledge gap in terms of long-term effects of various surgical and pharmacological treatments on outcomes among primary aldosteronism (PA) patients. Using a validated algorithm, we extracted longitudinal data for all PA patients diagnosed in 1997–2010 and treated in the Taiwan National Health Insurance. We identified 3362 PA patients for whom the mean length of follow-up was 5.75 years. PA has higher major cardiovascular events (MACE) than essential hypertension (23.3% vs 19.3%, p = 0.015). Results from the Cox model suggest a strong effect of adrenalectomy on lowering mortality (HR = 0.23 with residual hypertension and 0.21 with resolved hypertension). While need for receptor antagonist (MRA) MRA after diagnosis suggests that a defined daily dose (DDD) of MRA between 12.5 and 50 mg may alleviate risk of death in a U-shape pattern. A specificity test identified patients who has aldosterone producing adenoma (HR = 0.50, p = 0.005) also confirmed adrenalectomy attenuated all-cause mortality. Adrenalectomy decreases long-term all-cause mortality independently from PA cure from hypertension. Prescription corresponding to a DDD between 12.5 and 50 mg may decrease mortality for patients needing MRA. It calls for more attention on early diagnosis, early treatment and prescription of appropriate dosage of MRA for PA patients. PMID:27586402

  18. Why do cost-benefit studies of PACS disagree?

    NASA Astrophysics Data System (ADS)

    van Gennip, Elisabeth M.; Ottes, Fenno P.; van Poppel, Bas M.; Andriessen, J. H. T. H.

    1990-08-01

    Once the technical difficulties of PACS have been solved, the main obstacle for its introductionwill be its costs. Even though PACS is still under development, it is clear that the equipment for PACS will be much more expensive than the equipment used in the conventional situation. PACS may, however, pay itself back by allowing savings of film, space and personnel. The conclusions of some recent cost-benefit studies disagree on the costs and benefits of PACS. Some conclude that PACS would pay for itself, whereas according to others PACS would be (much) more expensive. We analyzed the latest cost-benefit studies, to find out why their outcomes diverge. The comparison of the results revealed striking differences. The calculations of the annual costs of a hospital wide PACS varied between 2 and 4 million dollars. These differences could not be explained by differences in the size of the hospitals, as indicated by the number of examinations. They were, in part, caused by the fact that the costs per piece of equipment, material or space varied per study. For instance the costs of 1 square foot of (archive) space varied from 10 to 140 per year. The variation in the given costs of the film based system, depended on the fact whether the time spent by medical personnel on film management was taken into account. The differences among these studies demonstrate clearly the need for uniform, well-defined criteria for the calculation of the costs and savings of PACS.

  19. Managed PACS operation with an automatic monitoring tool

    NASA Astrophysics Data System (ADS)

    Zhang, Jianguo; Han, Ruolin; Wu, Dongqing; Zhang, Xiaoyan; Zhuang, Jun; Feng, Jie; Wang, Mingpeng; Zhang, Guozhen; Wang, Cuanfu

    2002-05-01

    Huadong hospital in Shanghai with 800 beds provides health care services for inpatients and outpatients, as well as special senior and VIP patients. In order to move to digital imaging based radiology practice, and also provide better intra-hospital consultation services for senior and VIP patients, we started to implement PACS for hospital wide services from 1999, and also designed and developed an automatic monitoring system (AMS) to monitor and control PACS operation and dataflow to decrease the total cost of ownership for PACS operation. We installed the AMS on top of the Huadong Hospital PACS in the May of 2001. The installation was painless, did not interrupt the normal PACS operation, and took only one month. The PACS administrators with the AMS can now monitor and control the entire PACS operation in real time, and also track patient and image data flow automatically. These features make administrators take proper action even before user's complaint if any failure happened in any PACS component or process, they reduce the size of the management team, and decrease total cost of PACS ownership.

  20. Effect of powdered activated carbon (PAC) on MBR performance and effluent trihalomethane formation: At the initial stage of PAC addition.

    PubMed

    Gao, Yue; Ma, Defang; Yue, Qinyan; Gao, Baoyu; Huang, Xia

    2016-09-01

    In this study, the MBR was used to treat municipal wastewater for reuse. Effects of powdered activated carbon (PAC) addition on MBR system in terms of effluent water quality, trihalomethane (THM) formation and membrane organic fouling tendency of MBR sludge supernatant at the initial stage of PAC addition were investigated. Effects of chlorine dose and contact time on THM formation and speciation were also studied. PAC addition enhanced the removal of organic matters, especially aromatic components, which improved the UV254 removal rate from 34% to 83%. PAC addition greatly reduced the membrane organic fouling tendency of MBR sludge supernatant. PAC addition reduced the MBR effluent trihalomethane formation potential (THMFP) from 351.29 to 241.95μg/L, while increased THM formation reactivity by 42%. PAC addition enhanced the formation of higher toxic bromine-containing THMs. High chlorine dose and contact time resulted in higher THM formation but lower proportion of bromine-containing THMs. PMID:27318162

  1. Quinidine-sensitive K+ channels in the basolateral membrane of embryonic coprodeum epithelium: regulation by aldosterone and thyroxine.

    PubMed

    Illek, B; Fischer, H; Clauss, W

    1993-01-01

    Basolateral K+ channels and their regulation during aldosterone- and thyroxine-stimulated Na+ transport were studied in the lower intestinal epithelium (coprodeum) of embryonic chicken in vitro. Isolated tissues of the coprodeum were mounted in Ussing chambers and investigated under voltage-clamped conditions. Simultaneous stimulation with aldosterone (1 mumol.l-1) and thyroxine (1 mumol.l-1) raised short-circuit current after a 1- to 2-h latent period. Maximal values were reached after 6-7 h of hormonal treatment, at which time transepithelial Na+ absorption was more than tripled (77 +/- 11 microA.cm-2) compared to control (24 +/- 8 microA.cm-2). K+ currents across the basolateral membrane were investigated after permeabilizing the apical membrane with the pore-forming antibiotic amphotericin B and application of a mucosal-to-serosal K+ gradient. This K+ current could be dose dependently depressed by the K+ channel blocker quinidine. Fluctuation analysis of the short-circuit current revealed a spontaneous and a blocker-induced Lorentzian noise component in the power density spectra. The Lorentzian corner frequencies increased linearly with the applied blocker concentration. This enabled the calculation of single K+ channel current and K+ channel density. Single K+ channel current was not affected by stimulation, whereas the number of quinidine-sensitive K+ channels in the basolateral membrane increased from 11 to 26.10(6).cm-2 in parallel to the hormonal stimulation transepithelial Na+ transport. This suggests that the basolateral membrane is a physiological target during synergistic aldosterone and thyroxine regulation of transepithelial Na+ transport for maintaining intracellular K+ homeostasis. PMID:8151014

  2. Pharmacokinetics of aldosterone in patients with Addison's disease: effect of rifampicin treatment on glucocorticoid and mineralocorticoid metabolism.

    PubMed

    Schulte, H M; Mönig, H; Benker, G; Pagel, H; Reinwein, D; Ohnhaus, E E

    1987-12-01

    Treatment of tuberculosis with rifampicin in patients with pre-existing adrenal failure has been reported to induce adrenal crisis due to alteration of cortisol metabolism by induction of hepatic mixed liver oxygenase enzymes. To determine whether mineralocorticoid metabolism is altered by rifampicin treatment, we established the pharmacokinetics of immunoreactive aldosterone. The metabolic clearance rate (MCR) and plasma half-life of this material were measured before and after 6 days of rifampicin treatment (600 mg/day) in seven patients with Addison's disease due to tuberculosis. Antipyrine clearance and urinary 6-beta-hydroxycortisol excretion was determined to demonstrate induction of the cytochrome P450 dependent enzymes. Infusion of aldosterone at a constant rate of 0.17 mg/h over 4.5 h produced steady state concentrations after 2 h, with no difference before and after rifampicin treatment (mean +/- SD, 1649 +/- 144 vs 1586 +/- 80 pg/ml, respectively). The disappearance curve of IR-aldosterone from plasma was biexponential. No change could be observed in the plasma half-lives (alpha-phase 29 +/- 1.9 min vs 30 +/- 1.5 min, beta-phase 129 +/- 3.2 min vs 126 +/- 4.3 min), the MCR (1.47 +/- 0.1 l/h/kg vs 1.46 +/- 0.1 l/h/kg), and the volume of distribution (9.9 +/- 1.9 vs 10.2 +/- 0.3 l). The antipyrine half-life decreased significantly from 12.2 +/- 2.6 h to 7.6 +/- 0.9 h (P less than 0.05) with a rise in antipyrine clearance from 0.38 +/- 0.07 to 0.80 +/- 0.23 ml/min/kg (P less than 0.05) and no change in the volume of distribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3455371

  3. PAC91 - PROPERTIES AND COEFFICIENTS 1991

    NASA Technical Reports Server (NTRS)

    Mcbride, B. J.

    1994-01-01

    The two principal functions of PAC91 are to provide a means of generating theoretical thermodynamic functions from molecular constant data and to supply a means of fitting these functions to empirical equations by using a least-squares fit. The coefficients obtained from the fit may then be used to generate a library of thermodynamic data in a uniform and easy-to-use format for use in other computer codes. Several large compilations of selected or calculated thermodynamic data currently exist. Nevertheless, there is a continuing need for additional calculations due to the discovery of new species, the revision of existing molecular constant data and structural parameters, the need for data at temperatures other than those already published, the availability of new or revised heats of formation, dissociation or transition, and the revision of fundamental constants or atomic weights. Calculations may also be needed to compare the results of assuming various possible forms of the partition function. In addition, there is often a preference for thermodynamic data in functional rather than tabular form. In order to satisfy these needs, the PAC91 program can perform any combination of the following: (1) calculate thermodynamic functions (heat capacity, enthalpy, entropy, and Gibbs energy) for any set of 1 to 202 temperatures, (2) obtain a least-squares fit of the first three of these functions (either individually, two at a time, or all three simultaneously) for up to eight temperature intervals, and (3) calculate, as a function of temperature, heats of formation and equilibrium constants from assigned reference elements. The thermodynamic functions for ideal gases may be calculated from molecular constant data using one of several partition function variations provided by the program. For monatomic gases, one of three partition function cutoff techniques may be selected by the user, and unobserved but predicted electronic energy levels may be included by the program

  4. TRAF3IP2 mediates aldosterone/salt-induced cardiac hypertrophy and fibrosis.

    PubMed

    Sakamuri, Siva S V P; Valente, Anthony J; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Gardner, Jason D; Bysani, Chandrasekar

    2016-07-01

    Aberrant activation of the renin-angiotensin-aldosterone system (RAAS) contributes to adverse cardiac remodeling and eventual failure. Here we investigated whether TRAF3 Interacting Protein 2 (TRAF3IP2), a redox-sensitive cytoplasmic adaptor molecule and an upstream regulator of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), mediates aldosterone-induced cardiac hypertrophy and fibrosis. Wild type (WT) and TRAF3IP2-null mice were infused with aldosterone (0.2 mg/kg/day) for 4 weeks along with 1%NaCl in drinking water. Aldosterone/salt, but not salt alone, upregulated TRAF3IP2 expression in WT mouse hearts. Further, aldosterone elevated blood pressure to a similar extent in both WT and TRAF3IP2-null groups. However, TRAF3IP2 gene deletion attenuated aldosterone/salt-induced (i) p65 and c-Jun activation, (ii) extracellular matrix (collagen Iα1 and collagen IIIα1), matrix metalloproteinase (MMP2), lysyl oxidase (LOX), inflammatory cytokine (IL-6 and IL-18), chemokine (CXCL1 and CXCL2), and adhesion molecule (ICAM1) mRNA expression in hearts, (iii) IL-6, IL-18, and MMP2 protein levels, (iv) systemic IL-6 and IL-18 levels, and (iv) cardiac hypertrophy and fibrosis. These results indicate that TRAF3IP2 is a critical signaling intermediate in aldosterone/salt-induced myocardial hypertrophy and fibrosis, and thus a potential therapeutic target in hypertensive heart disease. PMID:27040306

  5. Aldosterone Induces Renal Fibrosis and Inflammatory M1-Macrophage Subtype via Mineralocorticoid Receptor in Rats

    PubMed Central

    Martín-Fernández, Beatriz; Rubio-Navarro, Alfonso; Cortegano, Isabel; Ballesteros, Sandra; Alía, Mario; Cannata-Ortiz, Pablo; Olivares-Álvaro, Elena; Egido, Jesús; de Andrés, Belén; Gaspar, María Luisa; de las Heras, Natalia; Lahera, Vicente; Moreno, Juan Antonio

    2016-01-01

    We aimed to evaluate macrophages heterogeneity and structural, functional and inflammatory alterations in rat kidney by aldosterone + salt administration. The effects of treatment with spironolactone on above parameters were also analyzed. Male Wistar rats received aldosterone (1 mgkg-1d-1) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg kg-1d-1). Systolic and diastolic blood pressures were elevated (p<0.05) in aldosterone + salt–treated rats. Relative kidney weight, collagen content, fibronectin, macrophage infiltrate, CTGF, Col I, MMP2, TNF-α, CD68, Arg2, and SGK-1 were increased (p<0.05) in aldosterone + salt–treated rats, being reduced by spironolactone (p<0.05). Increased iNOS and IFN-γ mRNA gene expression (M1 macrophage markers) was observed in aldosterone + salt rats, whereas no significant differences were observed in IL-10 and gene ArgI mRNA expression or ED2 protein content (M2 macrophage markers). All the observed changes were blocked with spironolactone treatment. Macrophage depletion with liposomal clodronate reduced macrophage influx and inflammatory M1 markers (INF-γ or iNOS), whereas interstitial fibrosis was only partially reduced after this intervention, in aldosterone plus salt-treated rats. In conclusion, aldosterone + salt administration mediates inflammatory M1 macrophage phenotype and increased fibrosis throughout mineralocorticoid receptors activation. PMID:26730742

  6. Polycystic ovary syndrome: Implications of measurement of plasma aldosterone, renin activity and progesterone.

    PubMed

    Armanini, Decio; Bordin, Luciana; Donà, Gabriella; Sabbadin, Chiara; Bakdounes, Leila; Ragazzi, Eugenio; Giorgino, Francesco L; Fiore, Cristina

    2012-05-01

    A positive correlation between aldosterone, inflammatory parameters, blood pressure and metabolic abnormalities in polycystic ovary syndrome (PCOS) has been reported in the early estrogenic phase. The aim of the study was to measure plasma aldosterone, plasma renin activity (PRA) and progesterone on the 21st day of the cycle, in women with PCOS and to consider the interrelationships between these hormones. Sixty-six consecutive normal BMI women with PCOS (median age 24 years, range 21-28 years) and 53 age- and body mass index-matched healthy controls were enrolled in the study. Aldosterone, aldosterone/PRA ratio (ARR) and Homeostasis Model Assessment (HOMA) index were significantly higher (p<0.0001) in PCOS women than controls. Positive correlations were found in PCOS but not in controls between (i) progesterone and aldosterone, (ii) aldosterone and PRA, (iii) PRA and progesterone. Mean blood pressures were within the normal range but significantly higher in PCOS than controls. The increase of plasma aldosterone, ARR and blood pressure in PCOS compared with controls is consistent with an increased mineralocorticoid effector mechanism in PCOS; prolonged therapy with spironolactone could counteract both the hyperandrogenism and reduce future cardiovascular risk. PMID:22387621

  7. Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney.

    PubMed

    Sheng, Lili; Yang, Min; Ding, Wei; Zhang, Minmin; Niu, Jianying; Qiao, Zhongdong; Gu, Yong

    2016-08-01

    Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. PMID:27317889

  8. ALDOSTERONE DYSREGULATION WITH AGING PREDICTS RENAL-VASCULAR FUNCTION AND CARDIO-VASCULAR RISK

    PubMed Central

    Brown, Jenifer M.; Underwood, Patricia C.; Ferri, Claudio; Hopkins, Paul N.; Williams, Gordon H.; Adler, Gail K.; Vaidya, Anand

    2014-01-01

    Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal- and cardio-vascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1,124 visits) in a Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression-to-stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics, and the renal-vascular responses to dietary sodium manipulation and angiotensin II (AngII) infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β= -4.60, p<0.0001) and higher SASSI (β= -58.63, p=0.001) predicted lower RPF and a blunted RPF response to sodium loading and AngII infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (p<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (p<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal-vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal-vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease. PMID:24664291

  9. Aldosterone and cortisol affect the risk of sudden cardiac death in haemodialysis patients

    PubMed Central

    Drechsler, Christiane; Ritz, Eberhard; Tomaschitz, Andreas; Pilz, Stefan; Schönfeld, Stephan; Blouin, Katja; Bidlingmaier, Martin; Hammer, Fabian; Krane, Vera; März, Winfried; Allolio, Bruno; Fassnacht, Martin; Wanner, Christoph

    2013-01-01

    Background Sudden cardiac death is common and accounts largely for the excess mortality of patients on maintenance dialysis. It is unknown whether aldosterone and cortisol increase the incidence of sudden cardiac death in dialysis patients. Methods and results We analysed data from 1255 diabetic haemodialysis patients participating in the German Diabetes and Dialysis Study (4D Study). Categories of aldosterone and cortisol were determined at baseline and patients were followed for a median of 4 years. By Cox regression analyses, hazard ratios (HRs) were determined for the effect of aldosterone, cortisol, and their combination on sudden death and other adjudicated cardiovascular outcomes. The mean age of the patients was 66 ± 8 years (54% male). Median aldosterone was <15 pg/mL (detection limit) and cortisol 16.8 µg/dL. Patients with aldosterone levels >200 pg/mL had a significantly higher risk of sudden death (HR: 1.69; 95% CI: 1.06–2.69) compared with those with an aldosterone <15 pg/mL. The combined presence of high aldosterone (>200 pg/mL) and high cortisol (>21.1 µg/dL) levels increased the risk of sudden death in striking contrast to patients with low aldosterone (<15 pg/mL) and low cortisol (<13.2 µg/dL) levels (HR: 2.86, 95% CI: 1.32–6.21). Furthermore, all-cause mortality was significantly increased in the patients with high levels of both hormones (HR: 1.62, 95% CI: 1.01–2.62). Conclusions The joint presence of high aldosterone and high cortisol levels is strongly associated with sudden cardiac death as well as all-cause mortality in haemodialysed type 2 diabetic patients. Whether a blockade of the mineralocorticoid receptor decreases the risk of sudden death in these patients must be examined in future trials. PMID:23211232

  10. Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells Both In Vitro and In Vivo

    PubMed Central

    Oteiza, Patricia I.; Link, Samuel; Hey, Valentin; Stopper, Helga; Schupp, Nicole

    2014-01-01

    Abstract Aims: An increased kidney cancer risk was found in hypertensive patients, who frequently exhibit hyperaldosteronism, known to contribute to kidney injury, with oxidative stress playing an important role. The capacity of kidney cells to up-regulate transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2), a key regulator of the cellular antioxidative defense, as a prevention of aldosterone-induced oxidative damage was investigated both in vitro and in vivo. Results: Aldosterone activated Nrf2 and increased the expression of enzymes involved in glutathione (GSH) synthesis and detoxification. This activation depended on the mineralocorticoid receptor (MR) and oxidative stress. In vitro, Nrf2 activation, GSH amounts, and target gene levels decreased after 24 h, while oxidant levels remained high. Nrf2 activation could not protect cells against oxidative DNA damage, as aldosterone-induced double-strand breaks and 7,8-dihydro-8-oxo-guanine (8-oxodG) lesions steadily rose. The Nrf2 activator sulforaphane enhanced the Nrf2 response both in vitro and in vivo, thereby preventing aldosterone-induced DNA damage. In vivo, Nrf2 activation further had beneficial effects on the aldosterone-caused blood pressure increase and loss of kidney function. Innovation: This is the first study showing the activation of Nrf2 by aldosterone. Moreover, the results identify sulforaphane as a substance that is capable of preventing aldosterone-induced damage both in vivo and in vitro. Conclusion: Aldosterone-induced Nrf2 adaptive response cannot neutralize oxidative actions of chronically increased aldosterone, which, therefore could be causally involved in the increased cancer incidence of hypertensive individuals. Enhancing the cellular antioxidative defense with sulforaphane might exhibit beneficial effects. Antioxid. Redox Signal. 21, 2126–2142. PMID:24512358

  11. PACS: implementation in the U.S. Department of Defense

    NASA Astrophysics Data System (ADS)

    Chacko, Anna K.; Wider, Ronald; Romlein, John R.; Cawthon, Michael A.; Richardson, Ronald R., Jr.; Lollar, H. William; Cook, Jay F.; Timboe, Harold L.; Johnson, Thomas G.; Fellows, Douglas W.

    2000-05-01

    The Department of Defense has been a leader in Radiology re- engineering for the past decade. Efforts have included the development of two landmark PACS specifications (MDIS and DIN- PACS), respective vendor selection and implementation programs. A Tri-Service (Army, Navy and Air Force) Radiology re-engineering program was initiated which identified transitioning to digital imaging, PACS and teleradiology as key enabling technologies in a changing business scenario. Subsequently, the systematic adjustment of procurement process for radiological imaging equipment included a focus on specifying PACS-capable-digital imaging modalities and mini- PACS as stepping stones to make the hospitals and health clinics PACS-ready. The success of the PACS and teleradiology program in the DOD is evidenced by the near filmless operation of most Army and Air Force Medical Centers, several community hospitals and several operational teleradiology constellations. Additionally, the MDIS PACSystem has become the commercial PACS product for General Electric Medical Systems. The DOD continues to forge ahead in the PACS arena by implementing advanced configurations and operational concepts such as the VRE (Virtual Radiology Environment), the negotiation of Regional Archiving and Regional PACS Maintenance Programs. Newer regulations (HIPAA, the FDA approval of digital mammography) have been promulgated impacting the culture and conduct of our business. Incorporating their requirements at the very outset will enable us to streamline the delivery of radiology. The DOD community has embraced the information age at multiple levels. The Healthcare portion of this community with these initiatives is integrating itself into DOD's future. The future holds great possibilities, promises and challenges for the DOD PACS programs.

  12. Rationale for a large facility PACS implementation

    NASA Astrophysics Data System (ADS)

    Donnelly, Joseph J.; Hindel, Peter P.; Anderson, John A.

    1992-07-01

    The Wright-Patterson USAF Medical Center (WPMC) is one of three DOD medical centers currently engaged in the installation of the ''Medical Diagnostic Imaging Support'' (MDIS) system. MDIS is a comprehensive hospital wide ''Picture Archiving and Communications System'' (PACS). In defining the requirements for the MDIS system it quickly became apparent that detailed operational information was necessary to adequately define the system requirements. This information included an understanding of the needs of our customers, workload data, current and expected future imaging capabilities, current problems encountered in meeting the needs of our customers, and the resources available to respond to these problems. Armed with this information the MDIS technical development team was able to define a detailed functional description for the MDIS system. This functional description was presented to industry in the form of a competitive solicitation with the subsequent submission of proposals by interested vendors. Following an extensive review of these proposals and the results of live benchmark evaluations, a contract was awarded to Loral Western Development Laboratory on September 27, 1991. This paper presents an operational overview of WPMC, a description of the deficiencies in our current image management system, and a discussion of the PACS to be installed this summer.

  13. Integration Of An MR Image Network Into A Clinical PACS

    NASA Astrophysics Data System (ADS)

    Ratib, Osman M.; Mankovich, Nicholas J.; Taira, Ricky K.; Cho, Paul S.; Huang, H. K.

    1988-06-01

    A direct link between a clinical pediatric PACS module and a FONAR MRI image network was implemented. The original MR network combines together the MR scanner, a remote viewing station and a central archiving station. The pediatric PACS directly connects to the archiving unit through an Ethernet TCP-IP network adhering to FONAR's protocol. The PACS communication software developed supports the transfer of patient studies and the patient information directly from the MR archive database to the pediatric PACS. In the first phase of our project we developed a package to transfer data between a VAX-111750 and the IBM PC I AT-based MR archive database through the Ethernet network. This system served as a model for PACS-to-modality network communication. Once testing was complete on this research network, the software and network hardware was moved to the clinical pediatric VAX for full PACS integration. In parallel to the direct transmission of digital images to the Pediatric PACS, a broadband communication system in video format was developed for real-time broadcasting of images originating from the MR console to 8 remote viewing stations distributed in the radiology department. These analog viewing stations allow the radiologists to directly monitor patient positioning and to select the scan levels during a patient examination from remote locations in the radiology department. This paper reports (1) the technical details of this implementation, (2) the merits of this network development scheme, and (3) the performance statistics of the network-to-PACS interface.

  14. P.A.C. Training Guide = Guia de Entrenamiento.

    ERIC Educational Resources Information Center

    Colorado Migrant Education Resource Center (CoMerc), Longmont.

    Intended to give Parent Advisory Council (PAC) members exposure to their roles and responsibilities, the guide, written in Spanish and English, provides information on how to train PAC members on parliamentary procedures (Roberts Rules) and the importance of agendas and agenda construction. The guide's eight sections cover the rules/regulations,…

  15. Design and Implementation of PACS at Georgetown University Hospital

    NASA Astrophysics Data System (ADS)

    Mun, S. K.; Benson, H.. R.; Choyke, P.; Fahey, F. H.; Wang, P. C.; Zeman, R. K...; Elliott, L. P.

    1985-09-01

    During the preparation and planning phase of the PACS project at Georgetown University Hospital it was realized that PACS requires truly the state of the art technology in data communication, image processing and man machine interfacing. It was also realized that un-like many other technology intensive devices used in radiology, PACS cannot be seen as an independent system that will provide well defined services. PACS will be the backbone of the department operation in clinical, educational and managerial functions. It will indeed be the nerve center of the radiologic services affecting every aspect of the department. PACS will have to be designed to perform in a cost-effective manner to widely varying needs within the radiology departments. The integration of ever changing complex technology that will impact every aspect of a radiology service is not a trivial matter. This transition period going from current manual film based PACS to Digital PACS can be long, expansive and disruptive unless careful planning preceeds the implementation. PACS is still an emerging technology at its infancy. Performance monitoring and evaluation of diversified functions have to be also established so that improvement to the system can be efficiently implemented. Thus the evaluation criteria should be also established as early as possible.

  16. Genetics of Aldosterone-Producing Adenoma in Korean Patients

    PubMed Central

    Song, Young Shin; Lee, Kyu Eun; Seo, Soo Hyun; Seong, Moon-Woo; Shin, Chan Soo; Kim, Sang Wan; Kim, Seong Yeon

    2016-01-01

    Objectives Recently, somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes were found to be associated with the pathogenesis of aldosterone-producing adenoma (APA). This study aimed to investigate the prevalence of somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D and examine the correlations between these mutations and the clinical and biochemical characteristics in Korean patients with APA. Methods We performed targeted gene sequencing in 66 patients with APA to detect somatic mutations in these genes. Results Somatic KCNJ5 mutations were found in 47 (71.2%) of the 66 patients with APA (31 cases of p.G151R and 16 cases of p.L168R); these two mutations were mutually exclusive. Somatic mutations in the ATP1A1, ATP2B3, and CACNA1D genes were not observed. Somatic KCNJ5 mutations were more prevalent in female patients (66% versus 36.8%, respectively; P = 0.030). Moreover, patients with KCNJ5 mutations comprised a significantly higher proportion of patients younger than 35 years of age (19.1% versus 0%, respectively; P = 0.040). There were no significant differences in pre-operative blood pressure, plasma aldosterone, serum potassium, lateralization index, and adenoma size according to mutational status. Patients with KCNJ5 mutations were less likely to need antihypertensive medications after adrenalectomy compared with those without mutation (36.2% versus 63.2%; P = 0.045). Conclusions The present study demonstrated the high prevalence of somatic KCNJ5 mutations in Korean patients with APA. Carriers of somatic KCNJ5 mutations were more likely to be female. Early diagnosis and better therapeutic outcomes were associated with somatic KCNJ5 mutations in APA. PMID:26807823

  17. Detailed description of the Mayo/IBM PACS

    NASA Astrophysics Data System (ADS)

    Gehring, Dale G.; Persons, Kenneth R.; Rothman, Melvyn L.; Salutz, James R.; Morin, Richard L.

    1991-07-01

    The Mayo Clinic and IBM/Rochester have jointly developed a picture archiving system (PACS) for use with Mayo's MRI and Neuro-CT imaging modalities. The system was developed to replace the imaging system's vendor-supplied magnetic tape archiving capability. The system consists of seven MR imagers and nine CT scanners, each interfaced to the PACS via IBM Personal System/2(tm) (PS/2) computers, which act as gateways from the imaging modality to the PACS network. The PAC system operates on the token-ring component of Mayo's city-wide local area network. Also on the PACS network are four optical storage subsystems used for image archival, three optical subsystems used for image retrieval, an IBM Application System/400(tm) (AS/400) computer used for database management and multiple PS/2-based image display systems and their image servers.

  18. PC reporting system for radiologists: practical use under PACS environment.

    PubMed

    Nakata, N; Yoshihiro, S; Miida, K; Tashima, M; Sunakawa, Y; Harada, J; Tada, S; Fukuda, K

    2001-07-01

    To evaluate the practical usefulness of several types of the reporting system especially for radiologists, we have developed and employed several reporting systems. We categorized those reporting systems as follows (1) stand alone PC reporting system; (2) linked reporting system with PACS environment; (3) integrated three-dimensional (3D) imaging workstation (WS) with the intranet. We have evaluated the advantages and disadvantages of those three systems, and compared between the reporting system without PACS and network reporting system with PACS. Using linked reporting system with PACS, radiologists could easily reference both previous reports and archived diagnostic images, and also make their teaching files quickly. In conclusion, the reporting system under PACS environment is found to be practical and helpful for Japanese radiologists. PMID:11378217

  19. Left ventricular hypertrophy in asymptomatic essential hypertension: its relationship with aldosterone and the increase in sodium-proton exchanger activity.

    PubMed

    Navarro-Lopez, F; Coca, A; Pare, J C; De La Sierra, A; Bosch, X; Urbano Marquez, A

    1993-11-01

    In order to analyse the hormonal and erythrocyte ion transport systems in relation to left ventricular hypertrophy (LV) in essential hypertension, a prospective study of 50 consecutive hypertensive patients under 55 years of age and without prior antihypertensive therapy was performed. Twenty-seven normal subjects with no family history of hypertension served as controls. LV hypertrophy, as assessed by echocardiography, was present in 64% of the hypertensive patients. This showed an increase (P < 0.001) in intra-erythrocyte Na+ concentration (8.1 +/- 1.2 vs 6.9 +/- 1 mmol.l-1.cells-1) and Na+:H+ exchange activity (8.8 +/- 4 vs 5.5 +/- 1.3 mmol.[l.cells.h-1]). There was a significant association between plasma aldosterone levels (19.1 +/- 12 ng.dl-1) with intra-erythrocyte Na+ content (r = 0.370, P < 0.05) and Na+:H+ exchange activity (r = 0.385, P < 0.01) as well as with echocardiographic LV mass index (138 +/- 40 g.m-2, r = 0.393, P < 0.01). The results are consistent with the concept that increased entry of Na+ into cells via Na+:H+ exchange could be a determining factor in left ventricular hypertrophy, which might be influenced by aldosterone. PMID:8281961

  20. Rapid effects of aldosterone in primary cultures of cardiomyocytes - do they suggest the existence of a membrane-bound receptor?

    PubMed

    Araujo, Carolina Morais; Hermidorff, Milla Marques; Amancio, Gabriela de Cassia Sousa; Lemos, Denise da Silveira; Silva, Marcelo Estáquio; de Assis, Leonardo Vinícius Monteiro; Isoldi, Mauro César

    2016-10-01

    Aldosterone acts on its target tissue through a classical mechanism or through the rapid pathway through a putative membrane-bound receptor. Our goal here was to better understand the molecular and biochemical rapid mechanisms responsible for aldosterone-induced cardiomyocyte hypertrophy. We have evaluated the hypertrophic process through the levels of ANP, which was confirmed by the analysis of the superficial area of cardiomyocytes. Aldosterone increased the levels of ANP and the cellular area of the cardiomyocytes; spironolactone reduced the aldosterone-increased ANP level and cellular area of cardiomyocytes. Aldosterone or spironolactone alone did not increase the level of cyclic 3',5'-adenosine monophosphate (cAMP), but aldosterone plus spironolactone led to increased cAMP level; the treatment with aldosterone + spironolactone + BAPTA-AM reduced the levels of cAMP. These data suggest that aldosterone-induced cAMP increase is independent of mineralocorticoid receptor (MR) and dependent on Ca(2+). Next, we have evaluated the role of A-kinase anchor proteins (AKAP) in the aldosterone-induced hypertrophic response. We have found that St-Ht31 (AKAP inhibitor) reduced the increased level of ANP which was induced by aldosterone; in addition, we have found an increase on protein kinase C (PKC) and extracellular signal-regulated kinase 5 (ERK5) activity when cells were treated with aldosterone alone, spironolactone alone and with a combination of both. Our data suggest that PKC could be responsible for ERK5 aldosterone-induced phosphorylation. Our study suggests that the aldosterone through its rapid effects promotes a hypertrophic response in cardiomyocytes that is controlled by an AKAP, being dependent on ERK5 and PKC, but not on cAMP/cAMP-dependent protein kinase signaling pathways. Lastly, we provide evidence that the targeting of AKAPs could be relevant in patients with aldosterone-induced cardiac hypertrophy and heart failure. PMID:27305962

  1. A case of primary aldosteronism combined with acquired nephrogenic diabetes insipidus

    PubMed Central

    Kim, Kitae; Lee, Jae Hyoung; Kim, Sun Chul; Cha, Dae Ryong; Kang, Young Sun

    2014-01-01

    Aldosterone-producing adrenal adenoma can induce various clinical manifestations as a result of chronic exposure to aldosterone. We report a rare case of a 37-year-old man who complained of general weakness and polyuria. He was diagnosed with aldosterone-producing adrenal adenoma and nephrogenic diabetes insipidus. Aldosterone enhances the secretion of potassium in the collecting duct, which can lead to hypokalemia. By contrast, nephrogenic diabetes insipidus, which manifests as polyuria and polydipsia, can occur in several clinical conditions such as acquired tubular disease and those attributed to toxins and congenital causes. Among them, hypokalemia can also damage tubular structures in response to vasopressin. The patient’s urine output was >3 L/d and was diluted. Owing to the ineffectiveness of vasopressin, we eventually made a diagnosis of nephrogenic diabetes insipidus. Laparoscopic adrenalectomy and intraoperative kidney biopsy were subsequently performed. The pathologic finding of kidney biopsy revealed a decrease in aquaporin-2 on immunohistochemical stain. PMID:26885483

  2. Effect of PAC dosage in a pilot-scale PAC-MBR treating micro-polluted surface water.

    PubMed

    Hu, Jingyi; Shang, Ran; Deng, Huiping; Heijman, Sebastiaan G J; Rietveld, Luuk C

    2014-02-01

    To address the water scarcity issue and advance the traditional drinking water treatment technique, a powdered activated carbon-amended membrane bioreactor (PAC-MBR) is proposed for micro-polluted surface water treatment. A pilot-scale study was carried out by initially dosing different amounts of PAC into the MBR. Comparative results showed that 2g/L performed the best among 0, 1, 2 and 3g/L PAC-MBR regarding organic matter and ammonia removal as well as membrane flux sustainability. 1g/L PAC-MBR exhibited a marginal improvement in pollutant removal compared to the non-PAC system. The accumulation of organic matter in the bulk mixture of 3g/L PAC-MBR led to poorer organic removal and severer membrane fouling. Molecular weight distribution of the bulk liquid in 2g/L PAC-MBR revealed the synergistic effects of PAC adsorption/biodegradation and membrane rejection on organic matter removal. Additionally, a lower amount of soluble extracellular polymer substances in the bulk can be secured in 21 days operation. PMID:24412856

  3. Diabetes impairs the vascular effects of aldosterone mediated by G protein-coupled estrogen receptor activation

    PubMed Central

    Ferreira, Nathanne S.; Cau, Stêfany B. A.; Silva, Marcondes A. B.; Manzato, Carla P.; Mestriner, Fabíola L. A. C.; Matsumoto, Takayuki; Carneiro, Fernando S.; Tostes, Rita C.

    2015-01-01

    Aldosterone promotes non-genomic effects in endothelial and vascular smooth muscle cells via activation of mineralocorticoid receptors (MR) and G protein-coupled estrogen receptors (GPER). GPER activation is associated with beneficial/protective effects in the vasculature. Considering that vascular dysfunction plays a major role in diabetes-associated complications, we hypothesized that the beneficial effects mediated by vascular GPER activation, in response to aldosterone, are decreased in diabetes. Mesenteric resistance arteries from female, 14–16 weeks-old, control and diabetic (db/db) mice were used. Phenylephrine (PhE)-induced contractions were greater in arteries from db/db vs. control mice. Aldosterone (10 nM) increased maximal contractile responses to PhE in arteries from control mice, an effect elicited via activation of GPER. Although aldosterone did not increase PhE responses in arteries from db/db mice, blockade of GPER, and MR decreased PhE-induced contractile responses in db/db mesenteric arteries. Aldosterone also reduced the potency of acetylcholine (ACh)-induced relaxation in arteries from both control and db/db mice via MR-dependent mechanisms. GPER antagonism further decreased ACh-induced relaxation in the control group, but did not affect ACh responses in the diabetic group. Aldosterone increased extracellular signal-regulated kinase 1/2 phosphorylation in arteries from control and db/db mice by a GPER-dependent mechanism. GPER, but not MR, gene, and protein expression, determined by RT-PCR and immunoblotting/immunofluorescence assays, respectively, were increased in arteries from db/db mice vs. control arteries. These findings indicate that aldosterone activates both vascular MR and GPER and that the beneficial effects of GPER activation are decreased in arteries from diabetic animals. Our results further elucidate the mechanisms by which aldosterone influences vascular function and contributes to vascular dysfunction in diabetes. Financial

  4. Impact of volumetric ultrasound on PACS

    NASA Astrophysics Data System (ADS)

    Horii, Steven; Goldszal, Alberto; Redfern, Regina; Coleman, Beverly; Langer, Jill; Morton, Dan; Rowling, Susan; Boonn, William; Iyoob, Christopher

    2006-03-01

    The purpose of this study was to determine if the size of ultrasound examinations was increasing over time. The primary reasons for this are believed to be an increased number of images per study, the incorporation of "cine loops", and increased use of color flow Doppler. The result of this study, if it supports the hypothesis that ultrasound study size is increasing, would be directly applicable to planning for future expansion of storage in the Ultrasound PACS. Data were obtained from the ultrasound PACS server for number of studies, number of images, and total stored volume for sampled months (January and July of 2003 - 2006). The investigators believed that these months would provide a reasonable sample of study size as examination types did not vary significantly from month to month (based on Departmental statistics). The Radiology Department's information system (RIS) was used to determine total yearly ultrasound examination volume to determine the trend over time. Because no protected health information (PHI) was to be used in this study, the investigators believed that no IRB approval was necessary. The number of studies done per month was more variable than the investigators had believed. One month in particular (July, 2003) had an anomalously large number of studies. However, despite this, computations of the number of images per study, the total data volume per study, and the average amount of data per image did show an increasing trend as expected. Also, the total volume of data stored showed an increasing trend over the study time period. The investigators' hypothesis that examination size is increasing has been demonstrated to be true for the months sampled. From Departmental data, the investigators know that the most recent ultrasound yearly volume increased approximately ten percent over the previous year, and that trend was also seen for the study period (from 7-10 percent per year increase in volume). With the information that the examination size

  5. Effect of hydration on plasma vasopressin, renin, and aldosterone responses to head-up tilt

    NASA Technical Reports Server (NTRS)

    Harrison, M. H.; Geelen, G.; Keil, L. C.; Wade, C. A.; Hill, L. C.

    1986-01-01

    If plasma vasopressin (PVP), plasma renin (PRA), and plasma aldosterone (PA) responses to change in posture are mediated only by alterations in intrathoracic baroreceptor activity hydration status should have minimal influence on these responses. To test this hypothesis, six male subjects underwent 45 min of 70 deg head-up tilt (HUT) following 26 h dehydration, and again, 105 min later, following rehydration. Compared with preceding supine hydrated control values, PVP, PRA, and PA increased (p less than 0.001) during dehydrated HUT, but only PVP and PRA increased during rehydrated HUT (p less than 0.001). The dissociation during rehydrated HUT of PRA and PA may have been related more to the reduction (p less than 0.001) in plasma potassium concentration than to the accompanying decrease (p less than 0.001) in plasma osmolality and sodium concentration. Although increases in PVP and PRA during HUT were attenuated (p less than 0.01) following rehydration, this attenuation was associated with the absence of symptoms of overt hypotension following rehydration. However, since rehydration did not abolish the increases in PVP and PRA induced by HUT, it is concluded that the present observations support the concept of intrathoracic baroreceptor involvement in the regulation of vasopressin secretion and renin release.

  6. Regulation of Na+ channels in frog lung epithelium: a target tissue for aldosterone action.

    PubMed

    Fischer, H; Clauss, W

    1990-04-01

    Sodium transport across isolated lung tissue of the frog Xenopus laevis was measured in Ussing chambers under voltage-clamp conditions. Perfusing the lungs with NaCl-Ringer's solutions on both sides, a basal distinct amiloride-blockable Na+ current was present. Incubating the lungs with 1 mumol/l aldosterone from the pleural side raised the short circuit current after a 1-h latent period. Maximal values were reached after 4-5 h of aldosterone treatment, at which time the transepithelial Na+ current was more than doubled compared to the control. The stimulatory effect was totally inhibited when the aldosterone treatment was preceded by incubation of the lung tissues with spironolactone in 2000-fold excess. In the presence of amiloride (0.5-8 mumol/l) in the alveolar compartment, a Lorentzian noise component appeared in the power spectrum of the fluctuations in the short circuit current. This enabled the calculation of single Na+ channel current and Na+ channel density under both experimental conditions. Aldosterone stimulation did not change single Na+ channel current. On the other hand, the number of conducting Na+ channels increased in parallel with the transepithelial Na+ transport. This suggests that the alveolar epithelium may be a physiological target tissue for aldosterone. Since fluid absorption in the lung is secondary to active Na+ transport, aldosterone may be a potent regulator for maintaining the relatively fluid-free state of the lumen of the lung in some cases of fluid accumulation. PMID:2162035

  7. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity

    PubMed Central

    Leopold, Jane A.; Dam, Aamir; Maron, Bradley A.; Scribner, Anne W.; Liao, Ronglih; Handy, Diane E.; Stanton, Robert C.; Pitt, Bertram; Loscalzo, Joseph

    2013-01-01

    Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanism by which aldosterone promotes endothelial dysfunction remains unknown. Glucose-6-phosphate dehydrogenase (G6pd), the principal source of Nadph, modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). In these studies, we show that aldosterone (10−9-10−7 mol/l) decreases endothelial G6pd expression and activity in vitro resulting in increased oxidant stress and decreased cGMP levels similar to what is observed in G6pd-deficient cells. Aldosterone decreases G6pd expression by protein kinase A activation to increase expression of Crem, which interferes with Creb binding to the G6pd promoter. In vivo, infusion of aldosterone decreases vascular G6pd expression and impairs vascular reactivity. These effects are abrogated by spironolactone or vascular gene transfer of G6pd. These studies demonstrate that aldosterone induces a G6pd-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6pd activity. PMID:17273168

  8. Aldosterone: A forgotten mediator of the relationship between psychological stress and heart disease

    PubMed Central

    Kubzansky, Laura D.; Adler, Gail K.

    2011-01-01

    Numerous studies support the notion that cumulative exposure to chronic stress is a risk factor for cardiovascular disease (CVD). Various stress-related hormones have been proposed as potential mediators of the relationship between psychological stress and CVD, including catecholamines and more indirectly, cortisol. Somewhat surprisingly, although aldosterone is also released in response to hypothalamic–pituitary–adrenal (HPA) axis activation, it has not been considered as relevant for this relationship. In the present review we will consider aldosterone as a potentially important mediator of the relationship between negative affective states and CVD. First, we will briefly review the known functions and roles of aldosterone, and then consider its actions in both the brain and the periphery. We will then review the available literature on the role of aldosterone in CVD, and also consider links between aldosterone and various forms of chronic psychological stress. Finally we will present an integrated model of how aldosterone may mediate effects of chronic stress on CVD, recommend new directions for research, and identify important methodological and design issues for this work. PMID:19631234

  9. Trip Report: RAM-PAC International

    SciTech Connect

    Jaques, Al; /Fermilab

    1988-09-09

    In the final design of the DO Detector, the three cryostats (CC and both EC's) will ride on a pair of hardened ways so as to move the EC's out and away from the CC cryostat to provide access between cryostats for repairs and such. Each of the cryostats sits on a carriage which has a pair of Tychoway rollers placed at each corner to roll on the hardened ways. When in position, the full weight of the cryostats is to be relieved from the rollers with the use of a pair of 90-ton jacks flanking the pair of rollers at each corner. Due to confined space, these jacks had to be custom made, triple cylinder, single block units. Five manufacturers were presented with the problem and three came back with proposals. All three satisfied the technical requirements but Ram-Pac International was easily the lowest priced.

  10. Novel class of highly selective divanillin-based PACs

    NASA Astrophysics Data System (ADS)

    Medina, Arturo N.; Ferreira, Lawrence; Tadros, Sobhy P.; Sizensky, Joseph J.; Fregeolle, M.; Blakeney, Andrew J.; Toukhy, Medhat A.

    1996-06-01

    A new class of diazonaphthoquinone (DNQ) photoactive compounds (PACs) based on the divanillin core is introduced in this paper. The general structure of these PAC backbones is shown in Formula 1. The divanillin structure possesses unique electronic characteristics which influence its DNQ-SO2Cl esterification reactions to be highly selective. The most reactive site for esterification in Formula 1 is one of the divanillin hydroxyls despite the typically higher steric hindrance. Surprisingly, the esterification product is then significantly deactivated towards esterification at the other previously equivalent divanillin OH. The result of using 3 equivalents of DNQ-SO2Cl to esterify tetraphenolic species is the formation of high percentages of the specific triester in which the second divanillyl OH remains unesterified. The deactivation of the second divanillin OH after the initial esterification indicates some interaction between the two o,o-biphenol rings despite its inability to be coplanar for conjugation of (pi) electrons because of steric hindrance. Possible explanations for this interaction are explored using molecular simulation tools. Diverse members of the divanillin PAC family have been prepared from phenols of varying structure and hydrophobicities. These PACs were tested lithographically and the results correlated with PAC backbone structure. The characteristic dissolution rate behavior of the resist formulations based on triesterified PACs, measured as a function of exposure dose, generally show high discrimination and strong inhibition, even with the more hydrophilic PACs. These formulations typically exhibited high resolution, wide focus latitude, and exposure margins greater than 2.0 in lithographic screening.

  11. PAC investigation on the Zr-rich region of the PZT phase diagram

    NASA Astrophysics Data System (ADS)

    Alonso, R. E.; Ayala, A. P.; López García, A. R.; Eiras, J. A.

    2007-02-01

    Previous studies using perturbed angular correlation (PAC) spectroscopy in the PbZr 1-xTi xO 3 (PZT) family of compounds show that whereas PbZrO 3 is characterized by a single probes site with a very well-defined hyperfine interaction, in PZT with x⩾0.1 the probes occupy two distributed sites. In this work, we investigate the Zr-rich region of the PZT phase diagram from x=0.02 up to x=0.08 using PAC in order to correlate the hyperfine parameters with the antiferroelectric-ferroelectric phase transition reported to occur at x=0.05. Two static electric quadrupole interactions, one of them fairly distributed, were detected over the whole Ti concentration range, and an abrupt change in the hyperfine parameters for 0.02< x<0.04 is observed. The behaviour of these parameters and the existence of two probe sites is discussed.

  12. Chronic Aldosterone Administration Causes NOX2-Mediated Increases In Reactive Oxygen Species Production and Endothelial Dysfunction in the Cerebral Circulation

    PubMed Central

    CHRISSOBOLIS, Sophocles; DRUMMOND, Grant R.; FARACI, Frank M.; SOBEY, Christopher G.

    2014-01-01

    Objective An elevated plasma aldosterone level is an independent cardiovascular risk factor. Although excess aldosterone promotes cardiovascular disease, no studies have examined the effect of increased plasma aldosterone on the cerebral circulation. A major source of vascular reactive oxygen species (ROS) during cardiovascular disease is the NADPH oxidases. Because NOX2-containing NADPH oxidase (NOX2 oxidase) is highly expressed in cerebral endothelium, we postulated that it might contribute to ROS generation and vascular dysfunction in response to aldosterone. Here we examined the effect of aldosterone and NOX2 oxidase on ROS production and endothelial dysfunction in the cerebral circulation, and whether the effects of aldosterone are exacerbated in aged mice. Methods and Results In adult (average age ~24–25 wk) wild-type (WT) and Nox2-deficient (Nox2−/y) mice, neither vehicle nor aldosterone (0.28 mg/kg/day for 14 days) affected blood pressure (measured using tail-cuff). By contrast, aldosterone treatment reduced dilation of the basilar artery (measured using myography) to the endothelium-dependent agonist acetylcholine in WT mice (P<0.05), but had no such effect in NOX2−/y mice (P>0.05). Aldosterone increased basal and phorbol-dibutyrate stimulated superoxide production (measured using L-012-enhanced chemiluminesence) in cerebral arteries from WT but not Nox2−/y mice. In aged WT mice (average age ~70 wk), aldosterone treatment increased blood pressure, but had a similar effect on cerebral artery superoxide levels as in adult WT mice. Conclusions These data indicate that NOX2 oxidase mediates aldosterone-induced increases in ROS production and endothelial dysfunction in cerebral arteries from adult mice independently of blood pressure changes. Aldosterone-induced hypertension is augmented during aging. PMID:24991871

  13. Gastrointestinal potassium binding-more than just lowering serum [K(+)]: patiromer, potassium balance, and the renin angiotensin aldosterone axis.

    PubMed

    Emmett, Michael; Mehta, Ankit

    2016-09-01

    Hyperkalemia limits the use of renin-angiotensin-aldosterone axis (RAAS) blockers in patients with renal insufficiency. This can be managed by efforts to increase kaliuresis and by gastrointestinal potassium binding with sodium polystyrene sulfonate, a relatively ineffective agent. Now with the availability of patiromer, RAAS blockers can be used more liberally. In addition, potassium reduction decreases aldosterone, which may be beneficial. Adverse nonepithelial aldosterone effects such as endothelial dysfunction and cardiac fibrosis may be ameliorated. PMID:27521112

  14. Fenofibrate inhibits aldosterone-induced apoptosis in adult rat ventricular myocytes via stress-activated kinase-dependent mechanisms

    PubMed Central

    De Silva, Deepa S.; Wilson, Richard M.; Hutchinson, Christoph; Ip, Peter C.; Garcia, Anthony G.; Lancel, Steve; Ito, Masa; Pimentel, David R.; Sam, Flora

    2009-01-01

    Aldosterone induces extracellular signal-regulated kinase (ERK)-dependent cardiac remodeling. Fenofibrate improves cardiac remodeling in adult rat ventricular myocytes (ARVM) partly via inhibition of aldosterone-induced ERK1/2 phosphorylation and inhibition of matrix metalloproteinases. We sought to determine whether aldosterone caused apoptosis in cultured ARVM and whether fenofibrate ameliorated the apoptosis. Aldosterone (1 μM) induced apoptosis by increasing terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive nuclei in ARVM. Spironolactone (100 nM), an aldosterone receptor antagonist, but not RU-486, a glucocorticoid receptor, inhibited aldosterone-mediated apoptosis, indicating that the mineralocorticoid receptor (MR) plays a role. SP-600125 (3 μM)—a selective inhibitor of c-Jun NH2-terminal kinase (JNK)—inhibited aldosterone-induced apoptosis in ARVM. Although aldosterone increased the expression of both stress-activated protein kinases, pretreatment with fenofibrate (10 μM) decreased aldosterone-mediated apoptosis by inhibiting only JNK phosphorylation and the aldosterone-induced increases in Bax, p53, and cleaved caspase-3 and decreases in Bcl-2 protein expression in ARVM. In vivo studies demonstrated that chronic fenofibrate (100 mg·kg body wt−1·day−1) inhibited myocardial Bax and increased Bcl-2 expression in aldosterone-induced cardiac hypertrophy. Similarly, eplerenone, a selective MR inhibitor, used in chronic pressure-overload ascending aortic constriction inhibited myocardial Bax expression but had no effect on Bcl-2 expression. Therefore, involvement of JNK MAPK-dependent mitochondrial death pathway mediates ARVM aldosterone-induced apoptosis and is inhibited by fenofibrate, a peroxisome proliferator-activated receptor (PPAR)α ligand. Fenofibrate mediates beneficial effects in cardiac remodeling by inhibiting programmed cell death and the stress-activated kinases. PMID:19395558

  15. Centralized vs. Distributed PACS for Intensive Care Units

    NASA Astrophysics Data System (ADS)

    Cho, Paul S.; Huang, H. K.; Tillisch, Jan

    1989-05-01

    One clinical environment which can immediately benefit from the implementation of a radiologic PACS is the intensive care unit (ICU). Our previous study has demonstrated the feasibility and timeliness of routine image transmission to an ICU. In anticipation of future expansion of this service, we have investigated two different models for a hospital-wide ICU PACS. These models included a centralized and a distributed processing PACS configuration. Their comparison indicated that although the distributed model offers some major advantages over the centralized model, the latter may hold a rightful place in the inter-departmental service, especially if the cost issue is a critical factor.

  16. Different effects of progesterone and estradiol on chimeric and wild type aldosterone synthase in vitro

    PubMed Central

    2013-01-01

    Background Familial hyperaldosteronism type I (FH-I) is caused by the unequal recombination between the 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in the generation of a CYP11B1/B2 chimeric gene and abnormal adrenal aldosterone production. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Aldosterone levels rise during pregnancy, yet in pregnant women with FH-1, their hypertensive condition either remains unchanged or may even improve. The purpose of this study was to investigate in vitro whether female sex steroids modulate the activity of chimeric (ASCE) or wild type (ASWT) aldosterone synthase enzymes. Methods We designed an in vitro assay using HEK-293 cell line transiently transfected with vectors containing the full ASCE or ASWT cDNAs. Progesterone or estradiol effects on AS enzyme activities were evaluated in transfected cells incubated with deoxycorticosterone (DOC) alone or DOC plus increasing doses of these steroids. Results In our in vitro model, both enzymes showed similar apparent kinetic parameters (Km = 1.191 microM and Vmax = 27.08 microM/24 h for ASCE and Km = 1.163 microM and Vmax = 36.98 microM/24 h for ASWT; p = ns, Mann–Whitney test). Progesterone inhibited aldosterone production by ASCE- and ASWT-transfected cells, while estradiol demonstrated no effect. Progesterone acted as a competitive inhibitor for both enzymes. Molecular modelling studies and binding affinity estimations indicate that progesterone might bind to the substrate site in both ASCE and ASWT, supporting the idea that this steroid could regulate these enzymatic activities and contribute to the decay of aldosterone synthase activity in chimeric gene-positive patients. Conclusions Our results show an inhibitory action of progesterone in the aldosterone synthesis by chimeric or wild type aldosterone synthase enzymes. This is a novel regulatory mechanism of progesterone

  17. Effect of canrenone and amiloride on the prooxidative effect induced by aldosterone in human mononuclear leukocytes in vitro.

    PubMed

    Fiore, C; Sartorato, P; Pagnin, E; Ragazzi, E; Calò, L A; Armanini, D

    2009-12-01

    Clinical studies have demonstrated that aldosterone receptor antagonists do improve the survival of patients with chronic heart diseases and in vitro studies have shown that canrenone blocks the proinflammatory effect of aldosterone in mononucler leukocytes (MNL). The aim of the study was to compare, in the model of human MNL, the effect of potassium-sparing diuretics amiloride and canrenone, on the protein expression of p22phox, a NADPH-oxidase system subunit, that is a principal marker of production of superoxide anions. MNL were isolated from 10 informed healthy volunteers (5 males and 5 females, age range 24-36 yr) and the proteins extracted. p22phox protein expression was evaluated by Western blot and quantified using a densitometric semiquantitative analysis. The experiments showed that aldosterone (10(-8) M) enhances the protein expression of p22phox and that its effect is reversed by co-incubation with canrenone (10(-6) M), while incubation with amiloride (10(-6) M) reduced the prooxidative effect of aldosterone at a significantly lower extent than canrenone. Co-incubation with canrenone, amiloride, and aldosterone together produced the same effect as aldosterone plus canrenone. Incubation with cortisol (40(-8) M) was not effective. These data confirm the prooxidative effect of aldosterone in MNL. The addition of aldosterone-receptor antagonist canrenone produced a higher inhibition than sodium channel blocker amiloride on the effect of aldosterone on p22phox protein expression. PMID:19509473

  18. Aldosterone predicts major adverse cardiovascular events in patients with acute myocardial infarction

    PubMed Central

    Yuyun, Matthew Fomonyuy; Jutla, Sandeep K; Quinn, Paulene A; Ng, Leong L

    2012-01-01

    Objective Aldosterone is associated with increased mortality in chronic heart failure patients and correlates with adverse outcomes after an acute myocardial infarction (AMI) in smaller cohorts. We evaluated the prognostic significance of plasma aldosterone in a large cohort of post-AMI patients in relation to major adverse cardiovascular events (MACE). Design A prospective cohort study. Setting University Hospitals of Leicester, UK. Patients Consecutive 955 patients admitted with AMI. Plasma aldosterone levels were measured in these patients. Main outcome measures During the 2 years follow-up, MACE which was a composite of all-cause mortality, myocardial reinfarction, and hospitalisation for heart failure as well as secondary endpoints (all-cause mortality and a combination of all-cause mortality and hospitalisation for heart failure), were ascertained. Results MACE occured in N=261, 27.3%, all-cause mortality (N=114, 11.9%) and a combination of all-cause mortality and hospitalisation for heart failure (N=176, 18.4%). Patients with MACE had significantly higher median levels of aldosterone than those without (1150.1 vs 950.4 pmol/l, p=0.0118). The multivariate adjusted HR (95% CI) for log aldosterone on MACE was 1.26 (1.01 to 1.56), p=0.041; all-cause mortality 1.60 (1.13 to 2.27), p=0.008; and combination of all-cause mortality and heart failure 1.50 (1.14 to 1.97), p=0.003. Conclusions The prognostic significance of aldosterone for a variety of endpoints in this large cohort of post-AMI patients is not new and adds to the findings by others. The magnitude of the increase in aldosterone secretion post infarction is higher than previously believed.

  19. Effects of acrolein on aldosterone release from zona glomerulosa cells in male rats.

    PubMed

    Wang, Kai-Lee; Huang, Wen-Ching; Chou, Jou-Chun; Weng, Ting-Chun; Hu, Sindy; Lieu, Fu-Kong; Lai, Wei-Ho; Idova, Galina; Wang, Paulus S; Wang, Shyi-Wu

    2016-07-01

    A positive correlation between smoking and hypertension has been well established. Acrolein is a major toxic volatile compound found in cigarette smoke. Human exposure to low levels of acrolein is unavoidable due to its production in daily activities, such as smoke from industrial, hot oil cooking vapors, and exhaust fumes from vehicles. The toxicity and the action mechanism of acrolein to induce apoptosis have been extensively studied, but the effects of acrolein on hypertension are still unknown. The present study aimed to examine the effects of acrolein on aldosterone release both in vivo and in vitro. Male rats were divided into three groups, and intraperitoneally injected with normal saline, or acrolein (2mg/kg) for 1 (group A-1) or 3 (group A-3) days, respectively. After sacrificing, rat blood samples were obtained to measure plasma aldosterone and angiotensin II (Ang II) levels. Zona glomerulosa (ZG) cells were prepared from rat adrenal cortex, and were incubated with or without stimulants. We found that the serum aldosterone was increased by 1.2-fold (p<0.05) in A-3 group as compared to control group. Basal aldosterone release from ZG cells in A-3 group was also increased significantly. Moreover, acrolein enhanced the stimulatory effects of Ang II and 8-bromo-cyclic AMP on aldosterone secretion from ZG cells prepared in both A-1 and A-3 groups. Furthermore, the enzyme activity of P450scc, the rate-limiting step of aldosterone synthesis, was elevated after acrolein injection. Plasma level of Ang II was increased in both A-1 and A-3 groups. These results suggested that acrolein exposure increased aldosterone production, at least in part, through elevating the level of plasma Ang II and stimulating steroidogenesis pathways. PMID:26980145

  20. Disabled-2 is expressed in adrenal zona glomerulosa and is involved in aldosterone secretion.

    PubMed

    Romero, Damian G; Yanes, Licy L; de Rodriguez, Angela F; Plonczynski, Maria W; Welsh, Bronwyn L; Reckelhoff, Jane F; Gomez-Sanchez, Elise P; Gomez-Sanchez, Celso E

    2007-06-01

    The differentiation of the adrenal cortex into functionally specific zones is probably due to differential temporal gene expression during fetal growth, development, and adulthood. In our search for adrenal zona glomerulosa-specific genes, we found that Disabled-2 (Dab2) is expressed in the zona glomerulosa of the rat adrenal gland using a combination of laser capture microdissection, mRNA amplification, cDNA microarray hybridization, and real-time RT-PCR. Dab2 is an alternative spliced mitogen-regulated phosphoprotein with features of an adaptor protein and functions in signal transduction, endocytosis, and tissue morphogenesis during embryonic development. We performed further studies to analyze adrenal Dab2 localization, regulation, and role in aldosterone secretion. We found that Dab2 is expressed in the zona glomerulosa and zona intermedia of the rat adrenal cortex. Low-salt diet treatment increased Dab2-long isoform expression at the mRNA and protein level in the rat adrenal gland, whereas high-salt diet treatment did not cause any significant modification. Angiotensin II infusion caused a transient increase in both Dab2 isoform mRNAs in the rat adrenal gland. Dab2 overexpression in H295R human adrenocortical cells caused an increase in aldosterone synthase expression and up-regulated aldosterone secretion under angiotensin II-stimulated conditions. In conclusion, Dab2 is an adrenal gland zona glomerulosa- and intermedia-expressed gene that is regulated by aldosterone secretagogues such as low-salt diet or angiotensin II and is involved in aldosterone synthase expression and aldosterone secretion. Dab2 may therefore be a modulator of aldosterone secretion and be involved in mineralocorticoid secretion abnormalities. PMID:17303656

  1. Disaster-hardened imaging POD for PACS

    NASA Astrophysics Data System (ADS)

    Honeyman-Buck, Janice; Frost, Meryll

    2005-04-01

    operated on emergency power, a limited, but effective number of studies could be performed. However, in a digital department, there is a reliance on the network infrastructure to deliver images to viewing locations. The system developed for our institution uses several imaging PODS, a name we chose because it implied to us a safe, contained environment. Each POD is on both the standard and the emergency power systems. All the vendor equipment that produces images is on a private, stand-alone network controlled either by a simple or a managed switch. Included in each POD is a dry-process DICOM printer that is rarely used during normal operations and a display workstation. One node on the private network is a PACS application processor (AP) with two network interface cards, one for the private network, one for the standard PACS network. During ordinary daily operations, all acquired images pass through this AP and are routed to the PACS archives, web servers, and workstations. However, if the power and network to much of the hospital were to fail, the stand-alone POD could still function. Images are routed to the AP, but cannot forward to the main network. However, they can be routed to the printer and display in the POD. They are also stored on the AP to continue normal routing when the infrastructure is restored. Results: The imaging PODS have been tested in actual disaster testing where the infrastructure was intentionally removed and worked as designed. To date, we have not had to use them in a real-life scenario and we hope we never do, but we feel we have a reasonable level of emergency imaging capability if we ever need it. Conclusions: Our testing indicates our PODS are a viable way to continue medical imaging in the face of an emergency with a major part of our network and electrical infrastructure destroyed.

  2. Product Related Advantages of a Structured PACS Architecture

    PubMed Central

    Greinacher, C.F.C.; Fuchs, D.; Perry, J.

    1986-01-01

    Most of the previously described PACS solutions are either developed and evaluated by the users themselves or they are pilot projects evaluated in close cooperation between a user and one or several manufacturers. Many of the prerequisites that will have to be met by future PACS are of minor interest in these pilot projects; e.g. minimization of costs, compatibility between different manufacturers' equipment, feasibility of systems engineering and customizing of a standard product, serviceability of different manufacturers' subsystems, stepwise introduction of the system into the daily routine and failsafety of the system. The paper shows a structured PACS architecture as a prerequisite to make PACS a high quality system from the user's point of view.

  3. Radiology information system control of a DICOM-based PACS

    NASA Astrophysics Data System (ADS)

    Behlen, Fred M.; Montner, Steven M.; Hoffmann, Kenneth R.; MacMahon, Heber; Weldy, James B.; Sayre, Richard E.

    1997-05-01

    PACS implementations require IS data for efficient operation and coherent information management. The images contributing to a radiology report in a practical multi-vendor PACS implementation may be derived from more than one DICOM study, and it is the Radiology Information System (RIS) that is responsible for the report. Flows of existing RIS-based information were studied and the required set of messages between the PACS archive and the RIS was defined. An archive providing the required functionality using standard and extended DICOM protocols was specified and acquired. The DICOM interface for the RIS was developed in-house using the M(MUMPS) programming language native to the RIS. We found that close integration of a RIS and PACS can be provided using DICOM protocols employing extensions compatible with the standard. The DICOM interfaces for textural data can be implemented in a MUMPS-based RIS without the need for an external interface 'box'.

  4. On stochastic approximation algorithms for classes of PAC learning problems

    SciTech Connect

    Rao, N.S.V.; Uppuluri, V.R.R.; Oblow, E.M.

    1994-03-01

    The classical stochastic approximation methods are shown to yield algorithms to solve several formulations of the PAC learning problem defined on the domain [o,1]{sup d}. Under some assumptions on different ability of the probability measure functions, simple algorithms to solve some PAC learning problems are proposed based on networks of non-polynomial units (e.g. artificial neural networks). Conditions on the sizes of these samples required to ensure the error bounds are derived using martingale inequalities.

  5. Why PACS is no longer a four-letter word.

    PubMed

    Chopra, R M

    2000-01-01

    The real value of PACS is not realized until widespread adoption exists among physicians other than interpreting radiologists. Referring physicians at the office level, in the operating room and in other departments must be willing to embrace the reading of images on monitors. That takes time. The payoff for a PACS system is therefore not realized until sometime in the future. Given the huge up-front capital expenditure required of PACS solutions, it is no wonder that the decision has historically been a difficult one to make. Enter the application service provider (ASP). The marriage of the ASP model to PACS seems to be one of the true "killer apps" currently available in the healthcare technology space. An ASP can host and maintain the software inherent in PACS solutions. Images are centrally archived over the short-, medium-, and long-term timeframe, utilizing state-of-art data management facilities. Some ASPs also provide the necessary bandwidth to office sites and the small amount of hardware that is required onsite, such as viewing stations or monitors. Costs for Internet-based image management under the ASP model rely on a pay-as-you-go formula, which may include all software, support, required hardware and bandwidth as part of the service. There may be a minor up-front fee for installation. The ASP pricing model eliminates the huge gamble an organization takes on "big iron" PACS purchases. Those benefits rely on the first rule of finance: a dollar today is worth more than a dollar tomorrow. PACS and ASPs were made for one another. Because the financial benefits of PACS are realized over time, the timing of cash flows is extremely important. Other benefits inherent in the ASP model such as scalability, diminished need for IT personnel, software version integrity and better pricing because of economies of scale are attractive also. PMID:11151321

  6. Aldosterone induces fibrosis, oxidative stress and DNA damage in livers of male rats independent of blood pressure changes

    SciTech Connect

    Queisser, Nina; Happ, Kathrin; Link, Samuel; Jahn, Daniel; Zimnol, Anna; Geier, Andreas; Schupp, Nicole

    2014-11-01

    Mineralocorticoid receptor blockers show antifibrotic potential in hepatic fibrosis. The mechanism of this protective effect is not known yet, although reactive oxygen species seem to play an important role. Here, we investigated the effects of elevated levels of aldosterone (Ald), the primary ligand of the mineralocorticoid receptor, on livers of rats in a hyperaldosteronism model: aldosterone-induced hypertension. Male Sprague–Dawley rats were treated for 4 weeks with aldosterone. To distinguish if damage caused in the liver depended on increased blood pressure or on increased Ald levels, the mineralocorticoid receptor antagonist spironolactone was given in a subtherapeutic dose, not normalizing blood pressure. To investigate the impact of oxidative stress, the antioxidant tempol was administered. Aldosterone induced fibrosis, detected histopathologically, and by expression analysis of the fibrosis marker, α-smooth muscle actin. Further, the mRNA amount of the profibrotic cytokine TGF-β was increased significantly. Fibrosis could be reduced by scavenging reactive oxygen species, and also by blocking the mineralocorticoid receptor. Furthermore, aldosterone treatment caused oxidative stress and DNA double strand breaks in livers, as well as the elevation of DNA repair activity. An increase of the transcription factor Nrf2, the main regulator of the antioxidative response could be observed, and of its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. All these effects of aldosterone were prevented by spironolactone and tempol. Already after 4 weeks of treatment, aldosteroneinfusion induced fibrosis in the liver. This effect was independent of elevated blood pressure. DNA damage caused by aldosterone might contribute to fibrosis progression when aldosterone is chronically increased. - Highlights: • Aldosterone has direct profibrotic effects on the liver independent of blood pressure. • Fibrosis is mediated by the mineralocorticoid receptor and

  7. Aldosterone and myocardial extracellular matrix expansion in type 2 diabetes mellitus.

    PubMed

    Rao, Ajay D; Shah, Ravi V; Garg, Rajesh; Abbasi, Siddique A; Neilan, Tomas G; Perlstein, Todd S; Di Carli, Marcelo F; Jerosch-Herold, Michael; Kwong, Raymond Y; Adler, Gail K

    2013-07-01

    Myocardial extracellular matrix expansion and reduced coronary flow reserve (CFR) occur in patients with type 2 diabetes mellitus without heart failure or coronary artery disease. Because aldosterone is implicated in the pathophysiology of cardiac fibrosis and vascular injury, the aim of this study was to test the hypothesis that aldosterone is associated with extracellular matrix expansion and reduced CFR in type 2 diabetes mellitus. Patients with type 2 diabetes mellitus without evidence of coronary artery disease were recruited. Blood pressure, lipid management, and glycemic control were optimized over 3 months. Cardiac magnetic resonance imaging with T1 mapping was used to measure myocardial extracellular volume (ECV). Cardiac positron emission tomography was used to assess CFR. On a liberal, 250 mEq/day sodium diet, 24-hour urinary aldosterone and change in serum aldosterone with angiotensin II stimulation were measured. Fifty-three participants with type 2 diabetes (68% men, mean age 53 ± 7 years, mean body mass index 32.2 ± 4.3 kg/m², mean glycosylated hemoglobin 6.8 ± 0.7%, mean systolic blood pressure 126 ± 14 mm Hg) without infarction or ischemia by cardiac magnetic resonance and positron emission tomography were studied. Subjects had impaired CFR (2.51 ± 0.83) and elevated ECV (0.36 ± 0.05), despite normal echocardiographic diastolic function and normal left ventricular function. Myocardial ECV, but not CFR, was positively associated with 24-hour urinary aldosterone excretion (r = 0.37, p = 0.01) and angiotensin II-stimulated aldosterone increase (r = 0.35, p = 0.02). In a best-overall multivariate model (including age, gender, body mass index, glycosylated hemoglobin, and blood pressure), 24-hour urinary aldosterone was the strongest predictor of myocardial ECV (p = 0.004). In conclusion, in patients with type 2 diabetes mellitus without coronary artery disease, aldosterone is associated with myocardial extracellular matrix expansion. These

  8. The Renin-Angiotensin-Aldosterone System in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

    PubMed

    Delgado, Graciela E; Siekmeier, Rüdiger; Krämer, Bernhard K; Grübler, Martin; Tomaschitz, Andreas; März, Winfried; Kleber, Marcus E

    2016-01-01

    High concentrations of renin and aldosterone are risk factors for cardiovascular diseases (CVD) which are the leading cause of morbidity and mortality worldwide. Enhanced activation of the renin-angiotensin-aldosterone system (RAAS) by cigarette smoking has been reported. The aim of our study was to analyze the effect of cigarette smoking on parameters of the RAAS in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study as well as the utility of RAAS parameter for risk prediction. We determined the concentration of aldosterone, renin, angiotensin-I and angiotensin-II in participants of the LURIC study. Smoking status was assessed by a questionnaire and the measurement of plasma cotinine concentration. Parameters were log transformed before entering analyses, where appropriate. We used a multivariate Cox regression analysis to assess the effect of parameters on mortality. From the 3316 LURIC participants 777 were AS and 1178 NS. Within a median observation period of 10 years 221 (28.4 %) AS and 302 (25.6 %) NS died. After adjustment for age, gender, and the use of anti-hypertensive medication, only angiotensin-I was significantly different in AS compared to NS with an estimated marginal mean (95 % CI) of 1607 (1541-1673) ng/L and 1719 (1667-1772) ng/L, respectively. For both NS and AS renin and angiotensin-II were directly associated with mortality in the multivariate Cox regression analysis. Angiotensin-I was only associated with increased risk for mortality in NS (HR (95 % CI) of 0.69 (0.53-0.89)). We conclude that increased renin and angiotensin-II are independent predictors of mortality in AS and NS, while angiotensin-I was associated with reduced risk of death in NS only. PMID:27334735

  9. Alterations in vascular function in primary aldosteronism: a cardiovascular magnetic resonance imaging study.

    PubMed

    Mark, P B; Boyle, S; Zimmerli, L U; McQuarrie, E P; Delles, C; Freel, E M

    2014-02-01

    Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV). We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass. Subjects with PA had significantly lower aortic distensibility and higher PWV compared with EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including ageing. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular ageing. As expected, aortic distensibility and PWV were closely correlated. These results demonstrate that PA patients display increased arterial stiffness compared with EH, independent of vascular ageing. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study. PMID:23884211

  10. Adipogenesis and aldosterone: a study in lean tryptophan-depleted rats.

    PubMed

    Pokusa, Michal; Hlavacova, Natasa; Csanova, Agnesa; Franklin, Michael; Zorad, Stefan; Jezova, Daniela

    2016-07-01

    Next to epithelial tissues, mineralocorticoid receptors are also expressed in adipose tissue and are involved in the process of adipogenesis. Mineralocorticoid receptors in adipose tissue are likely to be activated mainly by glucocorticoids. The aim of the present study was to test the hypothesis that the processes related to adipogenesis are modified under the conditions associated with high circulating aldosterone. We have made advantage of a model of depression based on tryptophan depletion in which we have previously demonstrated that the elevation of serum aldosterone precedes that of corticosterone. Sixty adult female Sprague-Dawley rats were fed either a low tryptophan diet or control diet for 4 (elevation of aldosterone only), 7 and 14 days (broader neuroendocrine activation) respectively. Gene expression of several adipogenic factors, CD31, interleukin-6, adiponectin, resistin and leptin were evaluated. Levels of mRNAs coding for adipogenic, angiogenic and inflammatory factors in adipose tissue were elevated at 4 and 7 days of tryptophan depletion. Additionally, gene expression of aldosterone sensing 11-β-hydroxysteroid dehydrogenase 2 and mineralocorticoid receptors were elevated. All changes disappeared at 14 days of tryptophan depletion. Synchronously an increase of adipose tissue mass was observed. Although direct evidence is not provided, observed changes in gene expression may be related to the action of aldosterone on mineralocorticoid receptors. Our findings represent the first data on any changes in gene expression in adipose tissue in animal models of depression. PMID:27253873

  11. Aldosterone and the mineralocorticoid receptor in the cerebral circulation and stroke

    PubMed Central

    2012-01-01

    Ischemic stroke is a leading cause of morbidity and mortality worldwide. Elevated plasma aldosterone levels are an independent cardiovascular risk factor and are thought to contribute to hypertension, a major risk factor for stroke. Evidence from both experimental and human studies supports a role for aldosterone and/or the mineralocorticoid receptor (MR) in contributing to detrimental effects in the cerebral vasculature and to the incidence and outcome of ischemic stroke. This article reviews the evidence, including the protective effects of MR antagonism. Specifically, the effects of aldosterone and/or MR activation on cerebral vascular structure and on immune cells will be reviewed. The existing evidence suggests that aldosterone and the MR contribute to cerebral vascular pathology and to the incidence and outcome of stroke. We suggest that further research into the signaling mechanisms underlying the effects of aldosterone and MR activation in the brain and its vasculature, especially with regard to cell-specific actions, will provide important insight into causes and potential treatments for cerebrovascular disease and stroke. PMID:23110876

  12. Aldosterone and mineralocorticoid receptor antagonists modulate elastin and collagen deposition in human skin.

    PubMed

    Mitts, Thomas F; Bunda, Severa; Wang, Yanting; Hinek, Aleksander

    2010-10-01

    We have shown that the steroid hormone aldosterone, recognized for its action on the kidney and the cardiovascular system, also modulates deposition of extracellular matrix in human skin. We have shown that treatment of primary cultures of normal skin fibroblasts with aldosterone (10 n-1 μM), in addition to stimulation of collagen type I expression, induces elastin gene expression and elastic fiber deposition. We have further shown that the elastogenic effect of aldosterone, which can be enhanced in the presence of mineralocorticoid receptor (MR) antagonists spironolactone and eplerenone, is executed in a MR-independent manner via amplification of IGF-I receptor-mediated signaling. Because aldosterone applied alone stimulates both collagen and elastin deposition in cultures of fibroblasts and in cultures of skin explants derived from dermal stretch marks, we postulate that this steroid should be used in the treatment of damaged skin that loses its volume and elasticity. Moreover, aldosterone applied in conjunction with spironolactone or eplerenone induces matrix remodeling and exclusively enhances elastogenesis in cultures of fibroblasts and explants derived from dermal scars and keloids. We therefore propose that intra-lesional injection of these factors should be considered in therapy for disfiguring dermal lesions and especially in prevention of their recurrence after surgical excision. PMID:20535129

  13. Learn from experience: insights of 200+ PACS customers.

    PubMed

    Swaton, Norm

    2002-01-01

    This article is based on a PACS study published in June 2001 by KLAS Enterprises. The study offers unique insight into the performance, underlying technology, product depth and breadth, and "real world" issues facing 10 of the leading PACS vendors and their clients as rated at more than 200 of their client sites by CIOs, department directors and vendor executives. The driving force behind this report reflects the heightened interest in PACS systems in general and PACS' contributions to the benefits associated with an electronic medical record. This research was sponsored by 10 healthcare provider organizations (not vendors), ranging from a 150-bed acute-care hospital to a seven-hospital IDN. Most of the data in the report focuses on the use of PACS in the radiology department, since comparatively few sites are using PACS systems in other departments, such as cardiology or pathology. The participating vendors supplied their customer lists, which contributed to the majority of clients surveyed. Clients surveyed in the study vary widely in size, ranging from 50 to 2,000 beds, with about 46 percent of those surveyed having a hospital size of more than 400 beds. The customers represent a broad cross-section of PACS clients, ranging from 10 percent to 95 percent filmless, with large-scale users making up the majority of respondents. Each of the customers were asked to numerically rate their vendor on 28 aspects of performance, as well as to answer 12 questions relating to customer satisfaction. Based on study results, success with PACS can be distilled into some basic principles. There are other issues that will help with a successful PACS selection and implementation, but the following list should help anyone get started. If you are able to focus on and accomplish these few things, you stand a better chance of building and meeting your business case. Pre-sell your PACS concept to the radiologists, technicians, IS/IT staff supporting it and to the referring physicians

  14. Protein kinase D1 modulates aldosterone-induced ENaC activity in a renal cortical collecting duct cell line.

    PubMed

    McEneaney, Victoria; Dooley, Ruth; Yusef, Yamil R; Keating, Niamh; Quinn, Ursula; Harvey, Brian J; Thomas, Warren

    2010-08-30

    Aldosterone treatment of M1-CCD cells stimulated an increase in epithelial Na(+) channel (ENaC) alpha-subunit expression that was mainly localized to the apical membrane. PKD1-suppressed cells constitutively expressed ENaCalpha at low abundance, with no increase after aldosterone treatment. In the PKD1-suppressed cells, ENaCalpha was mainly localized proximal to the basolateral surface of the epithelium both before and after aldosterone treatment. Apical membrane insertion of ENaCbeta in response to aldosterone treatment was also sensitive to PKD1 suppression as was the aldosterone-induced rise in the amiloride-sensitive, trans-epithelial current (I(TE)). The interaction of the mineralocorticoid receptor (MR) with specific elements in the promoters of aldosterone responsive genes is stabilized by ligand interaction and phosphorylation. PKD1 suppression inhibited aldosterone-induced SGK-1 expression. The nuclear localization of MR was also blocked by PKD1 suppression and MEK antagonism implicating both these kinases in MR nuclear stabilization. PKD1 thus modulates aldosterone-induced ENaC activity through the modulation of sub-cellular trafficking and the stabilization of MR nuclear localization. PMID:20434520

  15. Effect of bedrest on circadian rhythms of plasma renin, aldosterone, and cortisol

    NASA Technical Reports Server (NTRS)

    Chavarri, M.; Ganguly, A.; Luetscher, J. A.; Zager, P. G.

    1977-01-01

    Previous studies of normal men after 5 d of bedrest showed that circulatory instability on head-up tilt or standing is preceded by increased plasma renin activity (PRA) at bedrest. In the present study, the circadian rhythms of PRA, aldosterone, and cortisol have been observed in five normal men on a constant diet. In ambulatory controls, PRA and aldosterone increased normally after standing. On the third morning of bedrest, PRA was higher than before, and at noon, PRA was higher than in standing controls. The nocturnal peaks of PRA resulting from episodic renin secretion during sleep were higher after bedrest. Plasma aldosterone was also increased by bedrest. The findings are compatible with the theory that intermittent beta-adrenergic nerve activity during sleep is increased after bedrest, but other factors, such as loss of body sodium and a lower plasma volume, may also be involved.

  16. Diagnosing and Managing Primary Aldosteronism in Hypertensive Patients: a Case-Based Approach.

    PubMed

    Carey, Robert M

    2016-10-01

    Primary aldosteronism with a prevalence of 8 % of hypertension and 20 % of pharmacologically resistant hypertension is the most common secondary cause of hypertension. Yet, the diagnosis is missed in the vast majority of patients. Current clinical practice guidelines recommend screening for primary aldosteronism in patients with sustained elevation of blood pressure (BP) ≥150/100 mmHg if possible prior to initiation of antihypertensive therapy, and in patients with resistant hypertension, spontaneous or diuretic-induced hypokalemia, adrenal incidentaloma, obstructive sleep apnea, a family history of early onset of hypertension or cerebrovascular accident aldosteronism. Clinical and laboratory methods of screening, confirmatory testing, subtype classification, and medical and surgical management are systematically reviewed and illustrated with a clinical case. PMID:27566330

  17. [Primary aldosteronism is an underdiagnosed cause of hypertension. Important to find undiagnosed patients--effective treatment available].

    PubMed

    Ragnarsson, Oskar; Muth, Andreas; Johannsson, Gudmundur; Wängberg, Bo

    2015-01-01

    Primary aldosteronism is the most common cause of secondary hypertension with an estimated prevalence of 5-13 % among patients with hypertension. The most common causes are aldosterone producing adrenal adenoma and idiopathic adrenal hyperplasia. Patients with primary aldosteronism have a higher prevalence of cardiovascular morbidity and mortality compared to patients with essential hypertension. An effective treatment is available for patients with primary aldosteronism, with mineralocorticoid receptor antagonists in bilateral, and minimal invasive adrenal surgery in unilateral disease, which emphasizes the importance of early detection, adequate diagnostic work-up and treatment. In this paper we give a short review of the etiology, pathophysiology, co-morbidities, screening, diagnostic work-up, treatment, and treatment outcomes of primary aldosteronism. PMID:26625102

  18. Long-term treatment with aldosterone slows the progression of age-related hearing loss.

    PubMed

    Halonen, Joshua; Hinton, Ashley S; Frisina, Robert D; Ding, Bo; Zhu, Xiaoxia; Walton, Joseph P

    2016-06-01

    Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in significant declines in workplace productivity, quality of life, cognition and abilities to communicate effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role in the maintenance of key ion pumps, including the Na-K(+)-Cl co-transporter 1 or NKCC1, which is involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone (1 μM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not dose-dependent (dosing range from 1 nM to 100 μM). In the current study we measured behavioral and electrophysiological hearing function in middle-aged mice following long-term systemic treatment with aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1 protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a functional measure of hearing, and the auditory brainstem response was used as an objective measure of peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of aldosterone on age-related hearing loss and pave the way for translational drug development, using aldosterone as a key component to prevent or slow down the progression of ARHL. PMID:27157488

  19. [Respective roles of cortisol, aldosterone and angiotensin II during pathophysiology of atherosclerosis].

    PubMed

    Ayari, Hanène

    2013-01-01

    The involvement of angiotensin II, cortisol and aldosterone in increased cardiovascular risk is well known but their interactions within arterial wall and during atheroma formation are not established. In fact, mild cortisol excess is associated with a higher prevalence of cardiovascular events, increased intima media thickness, a higher frequency of atherosclerotic plaques and increased mortality. Conversely, remission from hypercortisolism is followed by improvement in cardiovascular risk markers as intima-media thickness or arterial distensibility, suggesting a strong link between cortisol excess and adverse vascular remodeling. On the other hand, implication of renin-angiotensin system (RAS) in atheromatous remodeling is well documented. The RAS also includes aldosterone, a mineralocorticoid which secretion is mainly and strongly stimulated by angiotensin II, and which receptor (MR) can also be activated by cortisol given that MR affinity is similar for both aldosterone and cortisol. The role of aldosterone in arterial remodeling is still very controversial. Aldosterone treatment associated with a high salt diet induced not only hypertension but also oxidative stress, collagen synthesis and vascular inflammation. However in models without salt loading or arterial hypertension, such as the treatment with deoxycorticosterone acetate in dogs, no alterations in aortic structure were observed and moreover, the MR blockade with eplerenone did not attenuate atherosclerosis in the aorta of diabetic Apo-E KO mice. It stems that among the different effects and mechanisms described in cell experiments, it is not known which are indeed operating in situ in human vessels and thus, if local cortisol is deleterious or beneficial and, if activation of MR by aldosterone or cortisol is important in vascular remodeling and atherogenesis. RAS blocker treatment would be particularly beneficial in essential hypertensive patients with low plasma renin, to attenuate both angiotensin

  20. Regulation of hypothalamic renin-angiotensin system and oxidative stress by aldosterone

    PubMed Central

    Huang, Bing S; Zheng, Hong; Tan, Junhui; Patel, Kaushik P; Leenen, Frans HH

    2011-01-01

    In rats with salt-induced hypertension or post myocardial infarction (MI), AT1 receptor (AT1R) densities and oxidative stress increase and neuronal nitric oxide synthase (nNOS) levels decrease in the paraventricular nucleus (PVN). The present study was designed to determine whether these changes may depend on activation of the aldosterone – “ouabain” neuromodulatory pathway. After intracerebroventricular (icv) infusion of aldosterone (20ng/h) for 14 days, blood pressure (BP) and heart rate (HR) were recorded in conscious Wistar rats, and mRNA and protein for nNOS, endothelial NOS (eNOS), AT1R and NADPH oxidase subunits were assessed in brain tissue. BP and HR were significantly increased by aldosterone. Aldosterone significantly increased mRNA and protein of AT1R, P22phox, P47phox, P67phox and Nox2, and decreased nNOS but not eNOS mRNA and protein in the PVN, and increased angiotensin converting enzyme (ACE) and AT1R binding densities in the PVN and SON. The increases in BP and HR as well as changes in mRNA, proteins and ACE and AT1R binding densities were all largely prevented by concomitant icv infusion of Digibind (to bind “ouabain”) or benzamil (to block presumably epithelial sodium channels). These data indicate that aldosterone via “ouabain” increases in the PVN ACE, AT1R and oxidative stress but decreases nNOS, and suggest that endogenous aldosterone may cause this similar pattern of changes observed in salt sensitive hypertension and heart failure post MI. PMID:21824999

  1. GPER is involved in the stimulatory effects of aldosterone in breast cancer cells and breast tumor-derived endothelial cells.

    PubMed

    Rigiracciolo, Damiano Cosimo; Scarpelli, Andrea; Lappano, Rosamaria; Pisano, Assunta; Santolla, Maria Francesca; Avino, Silvia; De Marco, Paola; Bussolati, Benedetta; Maggiolini, Marcello; De Francesco, Ernestina Marianna

    2016-01-01

    Aldosterone induces relevant effects binding to the mineralcorticoid receptor (MR), which acts as a ligand-gated transcription factor. Alternate mechanisms can mediate the action of aldosterone such as the activation of epidermal growth factor receptor (EGFR), MAPK/ERK, transcription factors and ion channels. The G-protein estrogen receptor (GPER) has been involved in the stimulatory effects of estrogenic signalling in breast cancer. GPER has been also shown to contribute to certain responses to aldosterone, however the role played by GPER and the molecular mechanisms implicated remain to be fully understood. Here, we evaluated the involvement of GPER in the stimulatory action exerted by aldosterone in breast cancer cells and breast tumor derived endothelial cells (B-TEC). Competition assays, gene expression and silencing studies, immunoblotting and immunofluorescence experiments, cell proliferation and migration were performed in order to provide novel insights into the role of GPER in the aldosterone-activated signalling. Our results demonstrate that aldosterone triggers the EGFR/ERK transduction pathway in a MR- and GPER-dependent manner. Aldosterone does not bind to GPER, it however induces the direct interaction between MR and GPER as well as between GPER and EGFR. Next, we ascertain that the up-regulation of the Na+/H+ exchanger-1 (NHE-1) induced by aldosterone involves MR and GPER. Biologically, both MR and GPER contribute to the proliferation and migration of breast and endothelial cancer cells mediated by NHE-1 upon aldosterone exposure. Our data further extend the current knowledge on the molecular mechanisms through which GPER may contribute to the stimulatory action elicited by aldosterone in breast cancer. PMID:26646587

  2. GPER is involved in the stimulatory effects of aldosterone in breast cancer cells and breast tumor-derived endothelial cells

    PubMed Central

    Rigiracciolo, Damiano Cosimo; Scarpelli, Andrea; Lappano, Rosamaria; Pisano, Assunta; Santolla, Maria Francesca; Avino, Silvia; De Marco, Paola; Bussolati, Benedetta; Maggiolini, Marcello; De Francesco, Ernestina Marianna

    2016-01-01

    Aldosterone induces relevant effects binding to the mineralcorticoid receptor (MR), which acts as a ligand-gated transcription factor. Alternate mechanisms can mediate the action of aldosterone such as the activation of epidermal growth factor receptor (EGFR), MAPK/ERK, transcription factors and ion channels. The G-protein estrogen receptor (GPER) has been involved in the stimulatory effects of estrogenic signalling in breast cancer. GPER has been also shown to contribute to certain responses to aldosterone, however the role played by GPER and the molecular mechanisms implicated remain to be fully understood. Here, we evaluated the involvement of GPER in the stimulatory action exerted by aldosterone in breast cancer cells and breast tumor derived endothelial cells (B-TEC). Competition assays, gene expression and silencing studies, immunoblotting and immunofluorescence experiments, cell proliferation and migration were performed in order to provide novel insights into the role of GPER in the aldosterone-activated signalling. Our results demonstrate that aldosterone triggers the EGFR/ERK transduction pathway in a MR- and GPER-dependent manner. Aldosterone does not bind to GPER, it however induces the direct interaction between MR and GPER as well as between GPER and EGFR. Next, we ascertain that the up-regulation of the Na+/H+ exchanger-1 (NHE-1) induced by aldosterone involves MR and GPER. Biologically, both MR and GPER contribute to the proliferation and migration of breast and endothelial cancer cells mediated by NHE-1 upon aldosterone exposure. Our data further extend the current knowledge on the molecular mechanisms through which GPER may contribute to the stimulatory action elicited by aldosterone in breast cancer. PMID:26646587

  3. KCNQ1 A340E impairs electrolyte homeostasis independently of the renin-angiotensin-aldosterone system in mice.

    PubMed

    Pan, Q; Sang, Y; Sun, C; Li, G; Wang, Y

    2016-01-01

    KCNQ1 (KvLQT1) is the pore-forming a-subunit of the potassium channel. To uncover its role in electrolyte metabolism, we investigated the effects of KCNQ1 A340E, a loss-of-function mutant, on J343 mice. Compared with the normal controls (C57BL/6J mice) bearing the wild-type KCNQ1 gene, J343 mice bearing KCNQ1 A340E demonstrated a much higher 24-h intake of electrolytes (potassium, sodium, and chloride). However, they suffered from significant electrolyte loss through both the feces and urine during a period of 24 h. Unbalance in electrolyte metabolism disrupted the electrolyte homeostasis in the J343 mice, which was characterized by the comparatively lower level of serum potassium (J343 vs C57BL/6J: 12.06 ± 1.47 vs 14.44 ± 3.58 mM, P = 0.01) and higher levels of serum sodium (J343 vs C57BL/6J: 148.05 ± 4.47 vs 115.15 ± 17.25 mM, P = 4.20 x 10(-4)) and chloride (J343 vs C57BL/6J: 118.0 ± 4.47 vs 85.21 ± 11.90 mM, P = 2.47 x 10(-5)). Between the J343 and C57BL/6J mice, there was no statistically significant difference in KCNQ1 expression in the gastrointestinal tract and kidney. Normal concentrations of plasma renin, angiotensin I, and aldosterone were also detected in both lines of mice. KCNQ1, therefore, is suggested to play a central role in electrolyte metabolism. KCNQ1 A340E, with the loss-of-function phenotype, may dysregulate electrolyte homeostasis in mice independently of the activity of the renin-angiotensin-aldosterone system. PMID:27525866

  4. Java-based cryptosystem for PACS and tele-imaging

    NASA Astrophysics Data System (ADS)

    Tjandra, Donny; Wong, Stephen T. C.; Yu, Yuan-Pin

    1998-07-01

    Traditional PACS systems are based on two-tier client server architectures, and require the use of costly, high-end client workstations for image viewing. Consequently, PACS systems using the two-tier architecture do not scale well as data increases in size and complexity. Furthermore, use of dedicated viewing workstations incurs costs in deployment and maintenance. To address these issues, the use of digital library technologies, such as the World Wide Web, Java, and CORBA, is being explored to distribute PACS data to serve a broader range of healthcare providers in an economic and efficient manner. Integration of PACS systems with digital library technologies allows access to medical information through open networks such as the Internet. However, use of open networks to transmit medical data introduces problems with maintaining privacy and integrity of patient information. Cryptography and digital timestamping is used to protect sensitive information from unauthorized access or tampering. A major concern when using cryptography and digital timestamping is the performance degradation associated with the mathematical calculations needed to encrypt/decrypt an image dataset, or to calculate the hash value of an image. The performance issue is compounded by the extra layer associated with the CORBA middleware, and the use of programming languages interpreted at the client side, such as Java. This paper study the extent to which Java-based cryptography and digital timestamping affects performance in a PACS system integrated with digital library technologies.

  5. PACS project management utilizing web-based tools

    NASA Astrophysics Data System (ADS)

    Patel, Sunil; Levin, Brad; Gac, Robert J., Jr.; Harding, Douglas, Jr.; Chacko, Anna K.; Radvany, Martin; Romlein, John R.

    2000-05-01

    As Picture Archiving and Communications Systems (PACS) implementations become more widespread, the management of deploying large, multi-facility PACS will become a more frequent occurrence. The tools and usability of the World Wide Web to disseminate project management information obviates time, distance, participant availability, and data format constraints, allowing for the effective collection and dissemination of PACS planning, implementation information, for a potentially limitless number of concurrent PACS sites. This paper will speak to tools, such as (1) a topic specific discussion board, (2) a 'restricted' Intranet, within a 'project' Intranet. We will also discuss project specific methods currently in use in a leading edge, regional PACS implementation concerning the sharing of project schedules, physical drawings, images of implementations, site-specific data, point of contacts lists, project milestones, and a general project overview. The individual benefits realized for the end user from each tool will also be covered. These details will be presented, balanced with a spotlight on communication as a critical component of any project management undertaking. Using today's technology, the web arguably provides the most cost and resource effective vehicle to facilitate the broad based, interactive sharing of project information.

  6. Clinical experience with PACS at Northwestern: year two

    NASA Astrophysics Data System (ADS)

    Channin, David S.; Hawkins, Rodney C.; Enzmann, Dieter R.

    2001-08-01

    We have previously described the PACS configuration at Northwestern Memorial Hospital (NMH). As opposed to an imaging modality, PACS is an evolving system that continuously grows and changes to meet the needs of the institution. The NMH PACS has grown significantly in the past year and has undergone significant architectural enhancements. This growth and evolutionary change will be described and discussed. The system now contains over 339,000 studies consisting of over 13 million images. There are now two short-term RAID storage units that provide for twice as much fast storage. There are also two magneto-optical disk jukeboxes providing long-term archive. We have deployed a redundant database to improve reliability of the system in the event of database failure. The number of modalities connected to the system has increased and will be summarized. Statistics describing utilization of the PACS will be shown. Lastly, we will discuss our plans for exploiting the application service provider model in our PACS environment.

  7. DICOM modality worklist: an essential component in a PACS environment.

    PubMed

    Gale, M E; Gale, D R

    2000-08-01

    The development and acceptance of the digital communication in medicine (DICOM) standard has become a basic requirement for the implementation of electronic imaging in radiology. DICOM is now evolving to provide a standard for electronic communication between radiology and other parts of the hospital enterprise. In a completely integrated filmless radiology department, there are 3 core computer systems, the picture archiving and communication system (PACS), the hospital or radiology information system (HIS, RIS), and the acquisition modality. Ideally, each would have bidirectional communication with the other 2 systems. At a minimum, a PACS must be able to receive and acknowledge receipt of image and demographic data from the modalities. Similarly, the modalities must be able to send images and demographic data to the PACS. Now that basic DICOM communication protocols for query or retrieval, storage, and print classes have become established through both conformance statements and intervendor testing, there has been an increase in interest in enhancing the functionality of communication between the 3 computers. Historically, demographic data passed to the PACS have been generated manually at the modality despite the existence of the same data on the HIS or RIS. In more current sophisticated implementations, acquisition modalities are able to receive patient and study-related data from the HIS or RIS. DICOM Modality Worklist is the missing electronic link that transfers this critical information between the acquisition modalities and the HIS or RIS. This report describes the concepts, issues, and impact of DICOM Modality Worklist implementation in a PACS environment. PMID:15359747

  8. Supercritical fluid extraction (SFE) of cranberries does not extract oligomeric proanthocyanidins (PAC) but does alter the chromatography and bioactivity of PAC fractions extracted from SFE residues.

    PubMed

    Feliciano, Rodrigo P; Meudt, Jennifer J; Shanmuganayagam, Dhanansayan; Metzger, Brandon T; Krueger, Christian G; Reed, Jess D

    2014-08-01

    Supercritical fluid extraction (SFE) removed lipophilic compounds and low molecular weight flavonoids from cranberries. However, SFE did not extract proanthocyanidins (PAC). The SFE PAC-enriched residue was submitted to fractionation on Sephadex LH-20 using ethanol, ethanol/methanol, and 80% acetone. PAC degree of polymerization (DP) and ratios of "A-type" to "B-type" interflavan bonds were compared with those of PAC fractions without SFE. Mass spectrometry showed that when SFE was used, PAC distribution was shifted toward higher DP and contained higher amounts of two and three "A-type" bonds compared to PAC fractions without SFE. The 80% acetone fraction with SFE had significantly greater extraintestinal pathogenic Escherichia coli (ExPEC) agglutination and significantly lower ExPEC invasion of enterocytes than the fraction without SFE. Cranberry PAC with higher numbers of "A-type" interflavan bonds are more bioactive in agglutinating ExPEC and inhibiting ExPEC enterocyte invasion. PMID:25019644

  9. Low Na, High K Diet and the Role of Aldosterone in BK-Mediated K Excretion

    PubMed Central

    Cornelius, Ryan J.; Wen, Donghai; Li, Huaqing; Yuan, Yang; Wang-France, Jun; Warner, Paige C.; Sansom, Steven C.

    2015-01-01

    A low Na, high K diet (LNaHK) is associated with a low rate of cardiovascular (CV) disease in many societies. Part of the benefit of LNaHK relies on its diuretic effects; however, the role of aldosterone (aldo) in the diuresis is not understood. LNaHK mice exhibit an increase in renal K secretion that is dependent on the large, Ca-activated K channel, (BK-α with accessory BK-β4; BK-α/β4). We hypothesized that aldo causes an osmotic diuresis by increasing BK-α/β4-mediated K secretion in LNaHK mice. We found that the plasma aldo concentration (P[aldo]) was elevated by 10-fold in LNaHK mice compared with control diet (Con) mice. We subjected LNaHK mice to either sham surgery (sham), adrenalectomy (ADX) with low aldo replacement (ADX-LA), or ADX with high aldo replacement (ADX-HA). Compared to sham, the urinary flow, K excretion rate, transtubular K gradient (TTKG), and BK-α and BK-β4 expressions, were decreased in ADX-LA, but not different in ADX-HA. BK-β4 knockout (β4KO) and WT mice exhibited similar K clearance and TTKG in the ADX-LA groups; however, in sham and ADX-HA, the K clearance and TTKG of β4KO were less than WT. In response to amiloride treatment, the osmolar clearance was increased in WT Con, decreased in WT LNaHK, and unchanged in β4KO LNaHK. These data show that the high P[aldo] of LNaHK mice is necessary to generate a high rate of BK-α/β4-mediated K secretion, which creates an osmotic diuresis that may contribute to a reduction in CV disease. PMID:25607984

  10. mPGES-1 deletion impairs aldosterone escape and enhances sodium appetite

    PubMed Central

    Jia, Zhanjun; Aoyagi, Toshinori; Kohan, Donald E.

    2010-01-01

    Aldosterone (Aldo) is a major sodium-retaining hormone that reduces renal sodium excretion and also stimulates sodium appetite. In the face of excess Aldo, the sodium-retaining action of this steroid is overridden by an adaptive regulatory mechanism, a phenomenon termed Aldo escape. The underlying mechanism of this phenomenon is not well defined but appeared to involve a number of natriuretic factors such prostaglandins (PGs). Here, we investigated the role of microsomal prostaglandin E synthase-1 (mPGES-1) in the response to excess Aldo. A 14-day Aldo infusion at 0.35 mg·kg−1·day−1 via an osmotic minipump in conjunction with normal salt intake did not produce obvious disturbances in fluid metabolism in WT mice as suggested by normal sodium and water balance, plasma sodium concentration, hematocrit, and body weight, despite the evidence of a transient sodium accumulation on days 1 or 2. In a sharp contrast, the 14-day Aldo treatment in mPGES-1 knockoute (KO) mice led to increased sodium and water balance, persistent reduction of hematocrit, hypernatremia, and body weight gain, all evidence of fluid retention. The escaped wild-type (WT) mice displayed a remarkable increase in urinary PGE2 excretion in parallel with coinduction of mPGES-1 in the proximal tubules, accompanied by a remarkable, widespread downregulation of renal sodium and water transporters. The increase in urinary PGE2 excretion together with the downregulation of renal sodium and water transporters were all significantly blocked in the KO mice. Interestingly, compared with WT controls, the KO mice exhibited consistent increases in sodium and water intake during Aldo infusion. Together, these results suggest an important role of mPGES-1 in antagonizing the sodium-retaining action of Aldo at the levels of both the central nervous system and the kidney. PMID:20335314

  11. Changes in technologist productivity with implementation of an enterprisewide PACS.

    PubMed

    Reiner, Bruce; Siegel, Eliot; Scanlon, Mary

    2002-03-01

    The purpose of this report is to determine what effect filmless operation has on technologist productivity when compared with traditional film-based operation. Retrospective data on technologist productivity was collected from the study institution before and after implementation of PACS using workload reports and payroll records. Departmentwide technologist productivity was defined as the number of examinations per full-time equivalent (exams/FTE) and correlated with local and nationwide standards operating in traditional film-based operations. During film-based operation, technologist productivity was comparable between the study institution and nationwide standards, allowing for the unique examination volumes and modality mix. After implementation of a large-scale PACS, technologist productivity was found to increase 34% above that of national standards and 48% that of the local control site. Implementation of an enterprisewide PACS offers the potential to significantly improve departmentwide technologist productivity when compared with traditional film-based operation. PMID:12134211

  12. Distribution of workload over the working day in a PACS

    NASA Astrophysics Data System (ADS)

    Wilson, Dennis L.; Smith, Donald V.

    1994-05-01

    A new radiological exam spawns a collection of image movements in a PACS system. Historical images are fetched, images are moved to workstations for diagnosis, selected images are moved to other workstations for clinicians and for consultations. The distributions of the new images over the working day will establish the image load to which the PACS system must respond. At Madigan Army Medical Center 10.1% of the daily load of images occurs in the busiest hour of the day. Individual days may have an hour that has up to 15% of the average daily load. The PACS system must be able to handle the images that are spawned by the average 10.1% busy hour load with margin to be able to handle a 50% overload with acceptable degradation of the performance of the system.

  13. PACS-Based Computer-Aided Detection and Diagnosis

    NASA Astrophysics Data System (ADS)

    Huang, H. K. (Bernie); Liu, Brent J.; Le, Anh HongTu; Documet, Jorge

    The ultimate goal of Picture Archiving and Communication System (PACS)-based Computer-Aided Detection and Diagnosis (CAD) is to integrate CAD results into daily clinical practice so that it becomes a second reader to aid the radiologist's diagnosis. Integration of CAD and Hospital Information System (HIS), Radiology Information System (RIS) or PACS requires certain basic ingredients from Health Level 7 (HL7) standard for textual data, Digital Imaging and Communications in Medicine (DICOM) standard for images, and Integrating the Healthcare Enterprise (IHE) workflow profiles in order to comply with the Health Insurance Portability and Accountability Act (HIPAA) requirements to be a healthcare information system. Among the DICOM standards and IHE workflow profiles, DICOM Structured Reporting (DICOM-SR); and IHE Key Image Note (KIN), Simple Image and Numeric Report (SINR) and Post-processing Work Flow (PWF) are utilized in CAD-HIS/RIS/PACS integration. These topics with examples are presented in this chapter.

  14. Integrated modality, PACS, and RIS environment using the DICOM standard

    NASA Astrophysics Data System (ADS)

    Bao, Yongjian; Reyinger, Juergen; Rechid, Renas

    1998-07-01

    Interoperability of imaging devices (Modality), PACS and RIS is a crucial point determining the effectiveness and the performance of a digital diagnostic radiology department. This paper represents an integrated environment of Modality, PACS and RIS based on a communication interface using the DICOM standard. In the environment, RIS acts as the master system and provides overall image management and move control functions. This allows a considerably simplified interface design and an employment of standard DICOM services for the implementation. All important RIS - PACS inter-operation functions like Image Pre-fetching, Auto-Routing, Report Delivery, etc., are supported. Using the DICOM Standard, the system integration has been achieved with an open communication protocol and therefore is expected to be supported by various vendors.

  15. Tablet PC as a mobil PACS terminal using wireless LAN

    NASA Astrophysics Data System (ADS)

    Tsao, Bo-Shen; Ching, Yu-Tai; Lee, Wen-Jeng; Chen, Shyh-Jye; Chang, Chia-Hung; Chen, Chien-Jung; Yen, York; Lee, Yuan-Ten

    2003-05-01

    A PACS mobile terminal has applications in ward round, emergency room and remote teleradiology consultation. Personal Digital Assistants (PDAs) have the highest mobility and are used for many medical applications. However, their roles are limited in the field of radiology due to small screen size. In this study, we built a wireless PACS terminal using a hand-held tablet-PC. A tablet PC (X-pilot, LEO systems, Taiwan) running the WinCE operating systems was used as our mobile PACS terminal. This device is equipped with 800×600 resolution 10.4 inch TFT monitor. The network connection between the tablet PC and the server was linked via wireless LAN (IEEE 802.11b).

  16. Monitoring the accuracy of a PACS image database.

    PubMed

    Blado, Maria Elissa; Tomlinson, Abigail

    2002-01-01

    "What you don't know won't hurt you" is a proverb that does not apply to a database on which patient lives depend. One of the core components of the picture Archiving and communications system (PACS) is an image database that contains the location and state of images and their corresponding demographic information. An image associated with the wrong patient name has potentially devastating implications, especially if the error is not caught early. This article describes how Texas Children's Hospital addresses the challenge of ensuring the accuracy of data of our PACS image database. It presents the routine checks that our PACS analysts perform every three hours and on a daily and monthly basis. These include steps involved in "fixing" exam data when an examination has missing or incorrect demographic information. In addition, this report compares how our institution assured accuracy of our film-based archive before PACS. Human error is the source of most inaccuracies in the image database, and automation such as bar code scanners and DICOM Modality Work List management have decreased their frequency, but without totally eliminating them. Some errors are routinely generated by the nature of radiology imaging operations and the limitations of devices for automating those operations. For example, computed tomography exams of the head, chest, and abdomen are routinely acquired during the same scan but must be separated into different exams for interpretation by different physicians. Factors contributing to inaccurate information include major system modifications, such as software or hardware upgrades, service interruptions, inaccurate problem descriptions provided by the user to the PACS analyst, and steps taken by the PACS analyst or technologist to correct errors. PMID:12105704

  17. Humidity response of the Eberline model PAC-7 alpha instrument

    SciTech Connect

    McAtee, J.L.

    1981-04-01

    Response of the Eberline Model PAC-7 alpha instrument under varying relative humidity (RH) and temperature conditions was studied in an environmental chamber. Electric discharges resulting in spurious counts or in instrument paralysis occurred at 35 to 50% RH. Improvement in the RH level tolerated by the PAC-7 alpha instrument was obtained by conformal coating of the high-voltage region of the printed circuit (PC) board. Following this treatment, electric discharges occurred only at relatively high humidity levels and then as a result of high-voltage breakdown within the AC-24C probe rather than within the PC board.

  18. The Photoconductor Array Camera & Spectrometer (PACS) instrument for Herschel.

    NASA Astrophysics Data System (ADS)

    Ali, Babar; Frayer, D. T.; Fadda, D.; Appleton, P.; Latter, B.

    2007-05-01

    PACS is one of three science instruments for ESA ’ s Herschel Space Observatory (HSO, formerly known as FIRST). It operates either as an imaging photometer or an integral field spectrometer over the spectral band from 57 to 210 µm. PACS is being designed and built by a consortium of institutes and university departments from across Europe under the leadership of Principal Investigator Albrecht Poglitsch located at Max-Planck-Institute for Extraterrestrial Physics (MPE), Garching, Germany. Consortium members are: Austria: UVIE; Belgium: IMEC, KUL, CSL; France: CEA, OAMP; Germany: MPE, MPIA; Italy: IFSI, OAP/OAT, OAA/CAISMI, LENS, SISSA; Spain: IAC.

  19. Picture archiving and communication system (PACS): medical perspectives.

    PubMed

    Osteaux, M; Van den Broeck, R; Verhelle, F; de Mey, J

    1997-06-01

    PACS represents the natural evolution from the digital new modalities (US, CT, MRI,...) to a global digital environment, where the film based activities are progressively replaced by their digital counterpart. The advantages of the technique, as well as the drawbacks of the first implementations, are described. The "second generation" PACS concept is presented (modular architecture, progressive implementation, multivendor environment, integration with the Hospital Information System, standardization,...). As "case study", the example of the A.Z.-V.U.B. Hospital Implementation is described. PMID:9260397

  20. Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone

    PubMed Central

    Muñoz-Durango, N.; Vecchiola, A.; Gonzalez-Gomez, L. M.; Simon, F.; Riedel, C. A.; Fardella, C. E.; Kalergis, A. M.

    2015-01-01

    The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models. PMID:26448944

  1. The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

    PubMed

    Vaidya, A; Brown, J M; Williams, J S

    2015-09-01

    There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent. PMID:25631218

  2. Impairment of endothelial progenitor cell function and vascularization capacity by aldosterone in mice and humans

    PubMed Central

    Thum, Thomas; Schmitter, Kerstin; Fleissner, Felix; Wiebking, Volker; Dietrich, Bernd; Widder, Julian D.; Jazbutyte, Virginija; Hahner, Stefanie; Ertl, Georg; Bauersachs, Johann

    2011-01-01

    Aims Hyperaldosteronism is associated with vascular injury and increased cardiovascular events. Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in endothelial repair and vascular homeostasis. We hypothesized that hyperaldosteronism impairs EPC function and vascularization capacity in mice and humans. Methods and results We characterized the effects of aldosterone and mineralocorticoid receptor (MR) blockade on EPC number and function as well as vascularization capacity and endothelial function. Treatment of human EPC with aldosterone induced translocation of the MR and impaired multiple cellular functions of EPC, such as differentiation, migration, and proliferation in vitro. Impaired EPC function was rescued by pharmacological blockade or genetic ablation of the MR. Aldosterone protein kinase A (PKA) dependently increased reactive oxygen species formation in EPC. Aldosterone infusion in mice impaired EPC function, EPC homing to vascular structures and vascularization capacity in a MR-dependent but blood pressure-independent manner. Endothelial progenitor cells from patients with primary hyperaldosteronism compared with controls of similar age displayed reduced migratory potential. Impaired EPC function was associated with endothelial dysfunction. MR blockade in patients with hyperaldosteronism improved EPC function and arterial stiffness. Conclusion Endothelial progenitor cells express a MR that mediates functional impairment by PKA-dependent increase of reactive oxygen species. Normalization of EPC function may represent a novel mechanism contributing to the beneficial effects of MR blockade in cardiovascular disease prevention and treatment. PMID:20926363

  3. The Other Side of the RAAS: Aldosterone Improves Migration of Cardiac Progenitor Cells.

    PubMed

    Könemann, Stephanie; Wenzel, Kristin; Ameling, Sabine; Grube, Karina; Hammer, Elke; Könemann, Raik; Samal, Rasmita; Völker, Uwe; Felix, Stephan B

    2015-11-01

    Stem cell therapy is a promising new option for patients suffering from heart failure. Though many clinical studies show encouraging results, little is known about the signals which cause stem cells to home to diseased but not to healthy hearts. We hypothesized that aldosterone as one of the main players of heart failure functions as an attractant for progenitor cells and stimulates their migration. Stem cell antigen-1 (Sca-1) positive cells were isolated from the hearts of wild type FVB mice via magnetic cell sorting. The migration rate of the cells was determined using aldosterone as an attractant in a modified Boyden chamber (n = 5). Aldosterone led to a dose dependent increase in migration rate and this effect could be prevented by adding its blocker eplerenone. The mineralocorticoid receptor could be detected on Sca-1+ cells via western blot and immunofluorescence. Therefore, aldosterone seems to play a role in stem cell migration and there the effect is most likely mediated by the mineralocorticoid receptor. PMID:25854326

  4. In vivo left ventricular function and collagen expression in aldosterone/salt-induced hypertension.

    PubMed

    Ramirez-Gil, J F; Delcayre, C; Robert, V; Wassef, M; Trouve, P; Mougenot, N; Charlemagne, D; Lechat, P

    1998-12-01

    Cardiac fibrosis is linked to aldosterone-induced hypertension, but the effects on in vivo left ventricular (LV) function are not established. We studied the relations between in vivo LV function and aldosterone/salt cardiac fibrosis. Adult guinea pigs (GPs) were treated for 3 months with an aldosterone infusion and high-salt diet. This treatment induced arterial hypertension (+35%) and moderate LV hypertrophy (LVH; +60%) without right ventricular (RV) hypertrophy. Echo-Doppler LV assessment demonstrated unaltered cardiac output, stroke volume, or LV relaxation. Type I collagen messenger RNA (mRNA) was significantly increased in both ventricles (LV, +48%; RV, +77%) and accompanied by a significant increase in total collagen deposition (LV, from 0.52% in controls to 4.4% in treated GPs; RV, from 0.82 to 5.5% in treated GPs). Plasma norepinephrine levels increased 2.6-fold (p < 0.01) and correlated with the increase in collagen deposition in both ventricles. Collagen content was not correlated with hypertension or LVH. We conclude that aldosterone administration induces cardiac collagen accumulation and a sympathetic stimulation, which might preserve systolic and diastolic function. PMID:9869498

  5. Aldosterone increases the apical Na sup + permeability of toad bladder by two different mechanisms

    SciTech Connect

    Asher, C.; Garty, H. )

    1988-10-01

    The aldosterone-induced augmentation of Na{sup +} transport in toad bladder was analyzed by comparing the hormonal actions on the transepithelial short-circuit current and on the amiloride-sensitive {sup 22}Na{sup +} uptake in isolated membrane vesicles. Incubating bladders with 0.5 {mu}M aldosterone for 3 hr evoked more than a 2-fold increase of the short-circuit current but had no effect on the amiloride-sensitive Na{sup +} transport in apical vesicles derived from the treated tissue. A longer incubation produced an additional augmentation of the short-circuit current, which was accompanied by about a 3-fold increase of the channel activity in isolated membranes. The stimulatory effect of aldosterone sustained in vesicles was inhibited by the antagonist spironolactone and the protein synthesis inhibitor cycloheximide. It is suggested that aldosterone elevates the apical Na{sup +} permeability of target epithelia by two different mechanisms: a relatively fast effect which is insensitive to triiodothyronine or butyrate and is not sustained by the isolated membrane, and a slower or later response blocked by these reagents, which is preserved by the isolated membrane. The data also indicate that these processes are mediated by different nuclear receptors.

  6. Delayed diagnosis of primary aldosteronism in patients with autosomal dominant polycystic kidney diseases.

    PubMed

    Kao, Chih-Chin; Wu, Vin-Cent; Kuo, Chin-Chi; Lin, Yen-Hung; Hu, Ya-Hui; Tsai, Yao-Chou; Wu, Che-Hsiung; Wu, Kwan-Dun

    2013-06-01

    Hypertension is a frequent early manifestation of autosomal dominant polycystic kidney disease (ADPKD). Several mechanisms can cause hypertension in ADPKD patients, although, primary aldosteronism (PA) as a possible manifestation of hypertension in ADPKD is extremely rare. We retrospectively reviewed the Taiwan Primary Aldosteronism Investigation (TAIPAI) database, which listed a total of 346 patients diagnosed with PA. Of these 346 patients, only three cases of concurrent PA and ADPKD were identified. These patients presented with hypertensive crisis and hypokalemia, and subsequent testing revealed aldosterone-producing adenomas (APAs) that were removed by laparoscopic adrenalectomy. Postoperatively, aldosterone-renin ratios (ARRs) and potassium levels normalized, and blood pressure improved. The diagnosis of PA in ADPKD is extremely challenging because multiple renal cysts can obscure the identification of adrenal adenomas, and ADPKD is associated with hypertension in almost all cases.(1) Because of frequent delays in the diagnosis of PA in ADPKD patients, future prospective studies to screen PA in hypertensive ADPKD patients may be necessary to evaluate the exact prevalence of coexistence of PA and ADPKD. PMID:22791703

  7. Role of mineralocorticoid receptor and renin-angiotensin-aldosterone system in adipocyte dysfunction and obesity.

    PubMed

    Feraco, Alessandra; Armani, Andrea; Mammi, Caterina; Fabbri, Andrea; Rosano, Giuseppe M C; Caprio, Massimiliano

    2013-09-01

    The mineralocorticoid receptor (MR) classically mediates aldosterone effects on salt homeostasis and blood pressure regulation in epithelial target tissues. In recent years, functional MRs have been identified in non classical targets of aldosterone actions, in particular in adipose tissue, where they mediate the effects of aldosterone and glucocorticoids in the control of adipogenesis, adipose expansion and its pro-inflammatory capacity. In this context, inappropriate MR activation has been demonstrated to be a causal factor in several pathologic conditions such as vascular inflammation, endothelial dysfunction, insulin resistance and obesity. The aim of this review is to summarize the latest developments in this rapidly developing field, and will focus on the role of MR and renin-angiotensin-aldosterone system (RAAS) as potential leading characters in the early steps of adipocyte dysfunction and obesity. Indeed modulation of MR activity in adipose tissue has promise as a novel therapeutic approach to treat obesity and its related metabolic complications. This article is part of a Special Issue entitled 'CSR 2013'. PMID:23454117

  8. Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis.

    PubMed

    Zhou, Xiaoli; Chen, Kai; Wang, Yongjun; Schuman, Mariano; Lei, Han; Sun, Zhongjie

    2016-06-01

    Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate-limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/-) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency-induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/-) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency-induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis. PMID:26471128

  9. Aldosterone-induced oxidative stress and inflammation in the brain are mediated by the endothelial cell mineralocorticoid receptor.

    PubMed

    Dinh, Quynh N; Young, Morag J; Evans, Megan A; Drummond, Grant R; Sobey, Christopher G; Chrissobolis, Sophocles

    2016-04-15

    Elevated aldosterone levels, which promote cerebral vascular oxidative stress, inflammation, and endothelial dysfunction, may increase stroke risk, independent of blood pressure and other risk factors. The main target receptor of aldosterone, the mineralocorticoid receptor (MR), is expressed in many cell types, including endothelial cells. Endothelial cell dysfunction is thought to be an initiating step contributing to cardiovascular disease and stroke; however the importance of MR expressed on endothelial cells in the brain is unknown. Here we have examined whether endothelial cell MR mediates cerebral vascular oxidative stress and brain inflammation during aldosterone excess. In male mice, aldosterone (0.72mg/kg/day, 14 days) caused a small increase (~14mmHg) in blood pressure. The MR blocker spironolactone (25mg/kg/d, ip) abolished this increase, whereas endothelial cell MR-deficiency had no effect. Aldosterone increased superoxide production capacity in cerebral arteries, and also mRNA expression of the pro-inflammatory cytokines chemokine (C-C motif) ligand 7 (CCL7), CCL8 and interleukin (IL)-1β in the brain. These increases were prevented by both spironolactone treatment and endothelial cell MR-deficiency; whereas IL-1β expression was blocked by spironolactone only. Endothelial cell MR mediates aldosterone-induced increases in cerebrovascular superoxide levels and chemokine expression in the brain, but not blood pressure or brain IL-1β. Endothelial cell-targeted MR antagonism may represent a novel approach to treat cerebrovascular disease and stroke, particularly during conditions of aldosterone excess. PMID:26923165

  10. Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor and alpha-adducin gene polymorphisms.

    PubMed

    Mulatero, Paolo; Williams, Tracy A; Milan, Alberto; Paglieri, Cristina; Rabbia, Franco; Fallo, Francesco; Veglio, Franco

    2002-07-01

    Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA is most frequently presented as moderate to severe hypertension, but the clinical and biochemical features vary widely. The aim of our study was to identify genetic variants that influence the phenotype of patients with PA. We hypothesized that genetic variants potentially affecting aldosterone production (aldosterone synthase, CYP11B2), renal proximal tubule reabsorption (alpha-adducin), or the mechanisms of counterbalance leading to vasodilatation and sodium excretion (bradykinin B(2)-receptor, B(2)R) could influence the clinical and biochemical characteristics of patients with PA. We studied three polymorphisms of these genes (C-344T of CYP11B2, G460W of alpha-adducin, and C-58T of B(2)R) in 167 primary aldosteronism patients (56 with aldosterone-producing adenoma and 111 with idiopathic hyperaldosteronism). B(2)R and alpha-adducin genotypes were strong independent predictors of both systolic and diastolic blood pressure levels; plasma renin activity and aldosterone also play a marginal role on BP levels. Body mass index, age, sex, and CYP11B2 genotype displayed no significant effect on the clinical parameters of our population. In particular, alpha-adducin and B(2)R polymorphisms accounted for 13.2% and 11.0% of the systolic and diastolic blood pressure variance, respectively. These data suggest that genetic variants of alpha-adducin and the bradykinin B(2)-R influence the blood pressure levels in patients with primary aldosteronism. PMID:12107246

  11. Angiotensin 1-7 Is a Negative Modulator of Aldosterone Secretion In Vitro and In Vivo.

    PubMed

    Shefer, Gabi; Marcus, Yonit; Knoll, Esther; Dolkart, Oleg; Foichtwanger, Shulamit; Nevo, Nava; Limor, Rona; Stern, Naftali

    2016-08-01

    Angiotensin (1-7) [Ang 1-7] is a 7 amino acid peptide generated predominantly from Ang II by the action of Ang-converting enzyme 2. We previously showed that Ang 1-7 reduced plasma aldosterone and plasma renin activity in high fructose-fed rats, and that the reduction in circulating aldosterone seemed to accord a parallel reduction in plasma renin activity. Here, we tested the possibility that Ang 1-7 affects aldosterone secretion acting directly in glomerulosa cells. First, as detected by immunofluorescence, the receptor for Ang 1-7, Mas1 is localized predominantly at the rat adrenal subcapsular region. Second, in isolated rat glomerulosa cells incubates, Ang 1-7 attenuated the aldosterone response to Ang II, with the strongest effect seen on Ang II (10(-9) M) (control 22±2.5 pg/10(5) cells; Ang II [10(-9) M] 189±11 pg/10(5) cells; Ang II [10(-9) M]+Ang 1-7 [10(-6) M] 33±3.6 pg/10(5) cells; P<0.001) and the largest effect on adrenocorticotropic hormone (10(-8) M) (control 30±3.4 pg/10(5) cells; ACTH [10(-8) M] 409±32.5 pg/10(5) cells; ACTH [10(-8) M]+Ang 1-7 [10(-6) M] 280±12.5 pg/10(5) cells; P<0.001). In contrast, Ang 1-7 did not affect the aldosterone response to potassium (K(+)). In rats subjected to a low-salt diet for 7 days, continuous infusion of Ang 1-7 (576 μg/kg per day) resulted in a lesser rise in aldosterone (salt deplete+Ang 1-7, 16.4±4.8 ng/dL) compared with rats receiving vehicle (salt deplete+vehicle, 27.6±5.3 ng/dL; P<0.01) but did not modify plasma renin activity. Taken together, these results indicate that Ang 1-7 can act as a negative modulator of aldosterone secretion in vitro and in vivo. PMID:27245181

  12. Role of Renin-Angiotensin-Aldosterone System in Metabolic Syndrome and Obesity-related Hypertension.

    PubMed

    Kamide, K

    2014-08-12

    Several recent clinical trials show that blocking agents of the renin-angiotensin-aldosterone system (RAAS) reduce cardiovascular events in patients with metabolic syndrome based on insulin resistance and obesity, especially accumulated visceral fat. Our laboratory has focused on the relationship between the vascular RAAS and the action of insulin on the vasculature. We first revealed that the addition of insulin to cultured vascular smooth muscle cells (VSMC) markedly increases angiotensinogen and angiotensin II (Ang II) expression and production. Insulin addition also induces VSMC growth that is inhibited by the blockade of the RAAS by either ACEI or ARB which suggests a role for the RAAS in insulin-mediated growth. Insulin has a quite different effect on cultured vascular endothelial cells (EC) as it reduces angiotensinogen and renin expression. However, insulin added to EC induces a marked activation of ACE and the activated ACE promotes the conversion of Ang I to Ang II and cell growth under conditions of high insulin concentration. Ang II induces the progression of atherosclerosis through the production of oxidative stress that blocks insulin signaling and accelerates atherosclerosis. In this paper, we attempt to clarify the relationship between insulin resistance, the RAAS, and oxidative stress in vascular tissues to mimic in vivo conditions found in patients with metabolic syndrome and obesity-related hypertension as previously I reviewed in "Current Hypertension Reviews" in 2010 [1]. In addition, I update the relationships between vascular RAAS and insulin resistance for the last 4 years. JSH-2014 [2] states that the target goals of blood pressure (BP) for diabetes patients is lower than 130/80 mmHg, whereas updated JNC 8 [3] and ESH-ESC 2013 [4] recommends the target BP was changed to <140/90 mmHg for hypertensive patients with diabetes. Patients with diabetes and hypertension have reduced mortality as well as improved cardiovascular and cerebrovascular

  13. Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action

    PubMed Central

    Roy, Ankita; Al-Qusairi, Lama; Donnelly, Bridget F.; Ronzaud, Caroline; Marciszyn, Allison L.; Gong, Fan; Chang, Y.P. Christy; Butterworth, Michael B.; Pastor-Soler, Núria M.; Hallows, Kenneth R.; Staub, Olivier; Subramanya, Arohan R.

    2015-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) is important for renal salt handling and blood-pressure homeostasis. The canonical NCC-activating pathway consists of With-No-Lysine (WNK) kinases and their downstream effector kinases SPAK and OSR1, which phosphorylate NCC directly. The upstream mechanisms that connect physiological stimuli to this system remain obscure. Here, we have shown that aldosterone activates SPAK/OSR1 via WNK1. We identified 2 alternatively spliced exons embedded within a proline-rich region of WNK1 that contain PY motifs, which bind the E3 ubiquitin ligase NEDD4-2. PY motif–containing WNK1 isoforms were expressed in human kidney, and these isoforms were efficiently degraded by the ubiquitin proteasome system, an effect reversed by the aldosterone-induced kinase SGK1. In gene-edited cells, WNK1 deficiency negated regulatory effects of NEDD4-2 and SGK1 on NCC, suggesting that WNK1 mediates aldosterone-dependent activity of the WNK/SPAK/OSR1 pathway. Aldosterone infusion increased proline-rich WNK1 isoform abundance in WT mice but did not alter WNK1 abundance in hypertensive Nedd4-2 KO mice, which exhibit high baseline WNK1 and SPAK/OSR1 activity toward NCC. Conversely, hypotensive Sgk1 KO mice exhibited low WNK1 expression and activity. Together, our findings indicate that the proline-rich exons are modular cassettes that convert WNK1 into a NEDD4-2 substrate, thereby linking aldosterone and other NEDD4-2–suppressing antinatriuretic hormones to NCC phosphorylation status. PMID:26241057

  14. Characterization of aldosterone-induced potassium secretion in rat distal colon.

    PubMed Central

    Sweiry, J H; Binder, H J

    1989-01-01

    The role of apical and basolateral membranes in aldosterone-induced active potassium (K) secretion in rat distal colon was investigated by measuring mucosal-to-serosal (Jms) and serosal-to-mucosal (Jsm) 42K fluxes (mueq.h-1.cm-2) across isolated stripped mucosa under short-circuit conditions in normal and secondary-hyperaldosterone animals. In normal colons mucosal tetraethylammonium (TEA; 30 mM) or barium (Ba; 5 mM), but not cesium (Cs; 15 mM), reduced Jsm without affecting Jms. In aldosterone animals (a) net K secretion (-0.54 +/- 0.11) was converted to net K absorption (0.63 +/- 0.15) by mucosal TEA, which produced a marked reduction in Jsm (0.82 +/- 0.07) and an increase in Jms (0.35 +/- 0.07). In contrast mucosal Ba resulted in a relatively smaller reduction in JK(sm) without altering JK(ms), whereas mucosal Cs was ineffective; (b) serosal bumetanide or the removal of serosal Na or Cl markedly inhibited JK(sm and abolished net K secretion; and (c) serosal ouabain (1 mM) produced qualitatively similar effects to those of serosal bumetanide. These results demonstrate that (a) normal rat distal colon contains apical TEA- and Ba-sensitive K channels; (b) aldosterone induces TEA-sensitive and Ba-sensitive apical K channels; (c) aldosterone-induced K secretion requires both the Na,K-pump and Na-K-2Cl cotransport for K uptake across the basolateral membrane; and (d) alteration of any of these processes results in inhibition of aldosterone-induced active K secretion simultaneously with stimulation of K absorption. Images PMID:2921323

  15. Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates

    PubMed Central

    Martinerie, Laetitia; Viengchareun, Say; Delezoïde, Anne-Lise; Jaubert, Francis; Sinico, Martine; Prevot, Sophie; Boileau, Pascal; Meduri, Géri; Lombès, Marc

    2009-01-01

    The human neonatal period is characterized by renal immaturity with impaired capacity to regulate water and sodium homeostasis, resembling partial aldosterone resistance. Since aldosterone effects are mediated by the mineralocorticoid receptor (MR), we postulated that this hormonal unresponsiveness could be related to low MR expression in the distal nephron. We measured aldosterone and renin levels in umbilical cord blood of healthy newborns. We used qPCR and immunohistochemistry to analyze the expression of MR and key players of the mineralocorticoid signaling pathway, during human and mouse renal development. High aldosterone and renin levels were found at birth. MR mRNA was detected in mouse kidney at day 16 postcoitum (E16), peaking at E18, but its expression was surprisingly very low at birth, rising progressively afterwards. Similar biphasic temporal expression was observed during human renal embryogenesis, with a transient expression between 15 and 24 weeks of gestation but an undetectable immunoreactive MR in late gestational and neonatal kidneys. This cyclic MR expression was tightly correlated with the evolution of the 11β–hydroxysteroid dehydrogenase type 2 and the epithelial sodium channel α-subunit. In contrast, glucocorticoid and vasopressin receptors, and aquaporin 2 followed a progressive and sustained evolution during renal maturation. Our study provides first evidence for a low renal MR expression level at birth, despite high aldosterone levels, which could account for compromised postnatal sodium handling. Elucidation of regulatory mechanisms governing MR expression should lead to new strategies for the management of sodium waste in preterms and neonates. PMID:19477942

  16. Parents as Agents of Change (PAC) in pediatric weight management: The protocol for the PAC randomized clinical trial

    PubMed Central

    2012-01-01

    Background There is an urgent need to develop and evaluate weight management interventions to address childhood obesity. Recent research suggests that interventions designed for parents exclusively, which have been named parents as agents of change (PAC) approaches, have yielded positive outcomes for managing pediatric obesity. To date, no research has combined a PAC intervention approach with cognitive behavioural therapy (CBT) to examine whether these combined elements enhance intervention effectiveness. This paper describes the protocol our team is using to examine two PAC-based interventions for pediatric weight management. We hypothesize that children with obesity whose parents complete a CBT-based PAC intervention will achieve greater reductions in adiposity and improvements in cardiometabolic risk factors, lifestyle behaviours, and psychosocial outcomes than children whose parents complete a psycho-education-based PAC intervention (PEP). Methods/Design This study is a pragmatic, two-armed, parallel, single-blinded, superiority, randomized clinical trial. The primary objective is to examine the differential effects of a CBT-based PAC vs PEP-based PAC intervention on children’s BMI z-score (primary outcome). Secondary objectives are to assess intervention-mediated changes in cardiometabolic, lifestyle, and psychosocial variables in children and parents. Both interventions are similar in frequency of contact, session duration, group facilitation, lifestyle behaviour goals, and educational content. However, the interventions differ insofar as the CBT-based intervention incorporates theory-based concepts to help parents link their thoughts, feelings, and behaviours; these cognitive activities are enabled by group leaders who possess formal training in CBT. Mothers and fathers of children (8–12 years of age; BMI ≥85th percentile) are eligible to participate if they are proficient in English (written and spoken) and agree for at least one parent to attend

  17. Want to Teach about SuperPACs? What We Can Learn from Stephen Colbert

    ERIC Educational Resources Information Center

    Stoddard, Jeremy

    2012-01-01

    The emergence of the SuperPACs in American politics is a major issue in the current election. SuperPACs, and the media campaigns they fund, also present a major challenge for media and democratic education. This article explores the issues surrounding SuperPACs and the rise of media in elections and politics in general, and presents some starting…

  18. Full PACS installation in Seoul National University Hospital, Korea

    NASA Astrophysics Data System (ADS)

    Lim, HyunWoo; Kim, DongOok; Ahn, JinYoung; Lee, DongHyuk; Lee, JinHyung; Park, HeeJung; Kim, JongHyo; Han, Jungu

    2002-05-01

    Seoul National University Hospital (SNUH) is composed of two buildings and has more than 1500 beds for patients needing hospitalization. Marotech has provided full PACS to SNUH with total HIS Integration in this year. In this paper, the installation process and management experience for seven months will be presented. At SNUH, 1643.8 exams were held per day during seven month after PACS installation. It is about 40 Gigabytes per day. Two acquisition servers (ACQ 1, 2), two database servers (DB 1, 2), two storage servers (LTA, network attached storage-NAS), one backup server (DLT) totally 8 servers were installed. SNUH has 11 CRs, 4 CTs, 3 MRIs, 9 NMs, 4 RFs, 20 USs, 7 ESs, 4 SCs, 5 XAs, and 5 Film Ditigers. All these modalities were integrated with PACS. DICOM 3.0 standard was conformed for images. DICOM Gateways were installed for modalities that do not support DICOM. The doctor can query and view Endoscopes, pathologic and anatomic data as well as radiological data. All the past five years exams is accessed less than 10 Seconds via on-line. Through the cooperation with SNUH and Marotech, HIS and PACS work together in stable state. These systems were integrated with HL7 standards and IHE.

  19. Enterprise-scale image distribution with a Web PACS.

    PubMed

    Gropper, A; Doyle, S; Dreyer, K

    1998-08-01

    The integration of images with existing and new health care information systems poses a number of challenges in a multi-facility network: image distribution to clinicians; making DICOM image headers consistent across information systems; and integration of teleradiology into PACS. A novel, Web-based enterprise PACS architecture introduced at Massachusetts General Hospital provides a solution. Four AMICAS Web/Intranet Image Servers were installed as the default DICOM destination of 10 digital modalities. A fifth AMICAS receives teleradiology studies via the Internet. Each AMICAS includes: a Java-based interface to the IDXrad radiology information system (RIS), a DICOM autorouter to tape-library archives and to the Agfa PACS, a wavelet image compressor/decompressor that preserves compatibility with DICOM workstations, a Web server to distribute images throughout the enterprise, and an extensible interface which permits links between other HIS and AMICAS. Using wavelet compression and Internet standards as its native formats, AMICAS creates a bridge to the DICOM networks of remote imaging centers via the Internet. This teleradiology capability is integrated into the DICOM network and the PACS thereby eliminating the need for special teleradiology workstations. AMICAS has been installed at MGH since March of 1997. During that time, it has been a reliable component of the evolving digital image distribution system. As a result, the recently renovated neurosurgical ICU will be filmless and use only AMICAS workstations for mission-critical patient care. PMID:9735424

  20. Millennium regional PACS management: strategies for successful implementation

    NASA Astrophysics Data System (ADS)

    Levin, Brad; Romlein, John R.; Gac, Robert J., Jr.; Chacko, Anna K.; Radvany, Martin

    2000-05-01

    With the advent of the new Millennium, Picture Archive and Communications System (PACS) technology has matured to levels sufficient to support open systems based, regional implementations. This shifts the site-centric PACS paradigm into broader scale, impacting facilities, workflow, business plans and ultimately patient care on a regional basis. Prudent and effective management of a regional implementation is critical to overall project success based upon a number of competing influences fundamental to the PACS including network infrastructure, clinical workflow, acquisition modalities, planning documentation, site preparation, acceptance testing, project communication, interface integration issues, etc. Risk mitigation is possible by understanding and managing the interrelationships of these influences through a phased approach with embedded management controls. The overall phases of regional implementation are not unlike site-centric implementations, consisting of Discovery, Planning, Preparation, Installation; Acceptance and Warranty/Maintenance; however, details which manifest over time are what provide significant management challenges. When balanced using a culturally reinforced policy of open, frequent and hands-on communication, regional PACS projects can be successfully implemented maintaining budget, schedule and scope thresholds.

  1. Preprocessing functions for computed radiography images in a PACS environment

    NASA Astrophysics Data System (ADS)

    McNitt-Gray, Michael F.; Pietka, Ewa; Huang, H. K.

    1992-05-01

    In a picture archiving and communications system (PACS), images are acquired from several modalities including computed radiography (CR). This modality has unique image characteristics and presents several problems that need to be resolved before the image is available for viewing at a display workstation. A set of preprocessing functions have been applied to all CR images in a PACS environment to enhance the display of images. The first function reformats CR images that are acquired with different plate sizes to a standard size for display. Another function removes the distracting white background caused by the collimation used at the time of exposure. A third function determines the orientation of each image and rotates those images that are in nonstandard positions into a standard viewing position. Another function creates a default look-up table based on the gray levels actually used by the image (instead of allocated gray levels). Finally, there is a function which creates (for chest images only) the piece-wise linear look-up tables that can be applied to enhance different tissue densities. These functions have all been implemented in a PACS environment. Each of these functions have been very successful in improving the viewing conditions of CR images and contribute to the clinical acceptance of PACS by reducing the effort required to display CR images.

  2. PACS implementation dramatically impacts people and radiology work processes

    NASA Astrophysics Data System (ADS)

    Ouvry, Ann

    1997-05-01

    The technology is not the bottleneck anymore in PACS implementation, it has become clear that the key to the success of PACS is understanding the current process, the end-user requirements, and how these processes will change with the introduction of PACS. We will discuss how implementation of PACS changed the working procedures in the Radiology department of Visby Hospital. Visby Hospital in Gotland, Sweden has approximately 160 beds. The Radiology department performs approximately 33,000 examinations per year and is capable of offering a broad range of diagnostic imaging services including CT and MRI. When a new facility was built in 1994, the decision was made to go for filmless operation and a modern information infrastructure. The new facility went operational by the end of 1994, in August 1995 almost filmless operation was reached. Continuing effort and attention is being paid to further simplify the workflow and working procedures in the Radiology department, and to improve the services offered to referring physicians. Although the project aimed at filmless operation, the main goal was to organize for efficient operation and excellent service, thereby maintaining high quality standards and employee satisfaction.

  3. PACS and diagnostic imaging service delivery--a UK perspective.

    PubMed

    Sutton, Laurence N

    2011-05-01

    This review sets out the current position with regard to the implementation of PACS throughout the United Kingdom and the impact this has had on improving patient care. In December 2007 England had implemented full hospital-wide PACS in all hospitals: a major achievement in the relatively short time period of three years. The different approaches used by each country of the UK to achieve full national PACS are described in addition to the current issues with the sharing of images and reports across different healthcare organisations with regard to technical solutions, clinical safety and governance. The review gives insight into the changing methods of service delivery to address increasing demand pressures on diagnostic imaging services and how the national PACS implementation, specifically in England, has made a significant contribution to measures to improve efficiencies. The role of Teleradiology is discussed in the context of supporting local patient services rather than undermining them and the concept of cross-healthcare reporting 'Grids' is described. Finally, in the summary it is recognised that the vast wealth of knowledge accumulated during the national implementations has placed the UK in a strong position to facilitate full national data sharing across all healthcare organisations to improve patient care. PMID:21600402

  4. NARSTO PAC2001 CESSNA VOC PM OZONE MET DATA

    Atmospheric Science Data Center

    2014-04-25

    NARSTO PAC2001 CESSNA VOC PM OZONE MET DATA Project Title:  NARSTO Discipline:  ... Temperature Probe Humidity Probe Wind Sensor UV Ozone Detector Optical Counter GC Location:  Lower Fraser ... Air Temperature Humidity Upper Level Winds Ozone Aerosol Particle Properties Volatile Organic Compounds ...

  5. NARSTO PAC2001 CONVAIR PM OZONE MET DATA

    Atmospheric Science Data Center

    2014-04-25

    NARSTO PAC2001 CONVAIR PM OZONE MET DATA Project Title:  NARSTO Discipline:  ... Temperature Probe Humidity Probe Wind Sensor UV Ozone Detector Optical Counter Location:  Lower Fraser ... Air Temperature Humidity Upper Level Winds Ozone Aerosol Particle Properties Order Data:  ASDC Order ...

  6. Assessing The Impact Of Computed Radiography And PACS

    NASA Astrophysics Data System (ADS)

    Hedgcock, Marcus W.; Kehr, Katherine

    1989-05-01

    Our institution (San Francisco VA Medical Center) is a VA pilot center for total digital imaging and PACS. Quantitative information about PACS impact on health care is limited, because no centers have done rigorous preimplementation studies. We are gathering quantitative service delivery and cost data before, during, and after stepwise implementation of computed radiography and PACS at our institution to define the impact on imaging service delivery. We designed a simple audit method using the x-ray request and time clocks to determine patient waiting time, imaging time, film use, image availability to the radiologist, matching of current with previous images, image availability to clinicians, and time to final interpretation. Our department model is a multichannel, mulitserver patient queue. Our current radiograph file is space limited, containing only one year of images; older images are kept in a remote file area in another building. In addition, there are 16 subfile areas within the Radiology Service and the medical center. Our preimplementation audit showed some long waiting times (40 minutes, average 20) and immediate retrieval of prior films in only 42% of cases, with an average retrieval time of 22 hours. Computed radiography and the optical archive have the potential to improve these figures. The audit will be ongoing and automated as implementation of PACS progresses, to measure service improvement and learning curve with the new equipment. We present the audit format and baseline preimplementation figures.

  7. PACS 2000: quality control using the task allocation chart

    NASA Astrophysics Data System (ADS)

    Norton, Gary S.; Romlein, John R.; Lyche, David K.; Richardson, Ronald R., Jr.

    2000-05-01

    Medical imaging's technological evolution in the next century will continue to include Picture Archive and Communication Systems (PACS) and teleradiology. It is difficult to predict radiology's future in the new millennium with both computed radiography and direct digital capture competing as the primary image acquisition methods for routine radiography. Changes in Computed Axial Tomography (CT) and Magnetic Resonance Imaging (MRI) continue to amaze the healthcare community. No matter how the acquisition, display, and archive functions change, Quality Control (QC) of the radiographic imaging chain will remain an important step in the imaging process. The Task Allocation Chart (TAC) is a tool that can be used in a medical facility's QC process to indicate the testing responsibilities of the image stakeholders and the medical informatics department. The TAC shows a grid of equipment to be serviced, tasks to be performed, and the organization assigned to perform each task. Additionally, skills, tasks, time, and references for each task can be provided. QC of the PACS must be stressed as a primary element of a PACS' implementation. The TAC can be used to clarify responsibilities during warranty and paid maintenance periods. Establishing a TAC a part of a PACS implementation has a positive affect on patient care and clinical acceptance.

  8. Maxadilan, a PAC1 receptor agonist from sand flies

    PubMed Central

    Lerner, Ethan A.; Iuga, Aurel O.; Reddy, Vemuri B.

    2007-01-01

    In 1991, a potent 61 amino acid vasodilator peptide, named maxadilan, was isolated from the salivary glands of the sand fly. Subsequently, it was shown that this peptide specifically and potently activated the mammalian PAC1 receptor, one of the three receptors for PACAP. These studies and the link between maxadilan and leishmaniasis are discussed. PMID:17681401

  9. PACS model based on digital watermarking and its core algorithms

    NASA Astrophysics Data System (ADS)

    Que, Dashun; Wen, Xianlin; Chen, Bi

    2009-10-01

    PACS model based on digital watermarking is proposed by analyzing medical image features and PACS requirements from the point of view of information security, its core being digital watermarking server and the corresponding processing module. Two kinds of digital watermarking algorithm are studied; one is non-region of interest (NROI) digital watermarking algorithm based on wavelet domain and block-mean, the other is reversible watermarking algorithm on extended difference and pseudo-random matrix. The former belongs to robust lossy watermarking, which embedded in NROI by wavelet provides a good way for protecting the focus area (ROI) of images, and introduction of block-mean approach a good scheme to enhance the anti-attack capability; the latter belongs to fragile lossless watermarking, which has the performance of simple implementation and can realize tamper localization effectively, and the pseudo-random matrix enhances the correlation and security between pixels. Plenty of experimental research has been completed in this paper, including the realization of digital watermarking PACS model, the watermarking processing module and its anti-attack experiments, the digital watermarking server and the network transmission simulating experiments of medical images. Theoretical analysis and experimental results show that the designed PACS model can effectively ensure confidentiality, authenticity, integrity and security of medical image information.

  10. The effect of acute haemorrhage in the dog and man on plasma-renin concentration

    PubMed Central

    Brown, J. J.; Davies, D. L.; Lever, A. F.; Robertson, J. I. S.; Verniory, A.

    1966-01-01

    1. The effect of acute haemorrhage on the plasma renin concentration was studied in the dog and man. 2. Plasma-renin concentration was regularly increased after the larger bleeds; after the smaller haemorrhages plasma-renin concentration remained unchanged. 3. The results are discussed in relation to current hypotheses concerning the control of renin and aldosterone secretion. PMID:4287431

  11. Integration of a clinical trial database with a PACS

    NASA Astrophysics Data System (ADS)

    van Herk, M.

    2014-03-01

    Many clinical trials use Electronic Case Report Forms (ECRF), e.g., from OpenClinica. Trial data is augmented if DICOM scans, dose cubes, etc. from the Picture Archiving and Communication System (PACS) are included for data mining. Unfortunately, there is as yet no structured way to collect DICOM objects in trial databases. In this paper, we obtain a tight integration of ECRF and PACS using open source software. Methods: DICOM identifiers for selected images/series/studies are stored in associated ECRF events (e.g., baseline) as follows: 1) JavaScript added to OpenClinica communicates using HTML with a gateway server inside the hospitals firewall; 2) On this gateway, an open source DICOM server runs scripts to query and select the data, returning anonymized identifiers; 3) The scripts then collects, anonymizes, zips and transmits selected data to a central trial server; 4) Here data is stored in a DICOM archive which allows authorized ECRF users to view and download the anonymous images associated with each event. Results: All integration scripts are open source. The PACS administrator configures the anonymization script and decides to use the gateway in passive (receiving) mode or in an active mode going out to the PACS to gather data. Our ECRF centric approach supports automatic data mining by iterating over the cases in the ECRF database, providing the identifiers to load images and the clinical data to correlate with image analysis results. Conclusions: Using open source software and web technology, a tight integration has been achieved between PACS and ECRF.

  12. Medical image security in a HIPAA mandated PACS environment.

    PubMed

    Cao, F; Huang, H K; Zhou, X Q

    2003-01-01

    Medical image security is an important issue when digital images and their pertinent patient information are transmitted across public networks. Mandates for ensuring health data security have been issued by the federal government such as Health Insurance Portability and Accountability Act (HIPAA), where healthcare institutions are obliged to take appropriate measures to ensure that patient information is only provided to people who have a professional need. Guidelines, such as digital imaging and communication in medicine (DICOM) standards that deal with security issues, continue to be published by organizing bodies in healthcare. However, there are many differences in implementation especially for an integrated system like picture archiving and communication system (PACS), and the infrastructure to deploy these security standards is often lacking. Over the past 6 years, members in the Image Processing and Informatics Laboratory, Childrens Hospital, Los Angeles/University of Southern California, have actively researched image security issues related to PACS and teleradiology. The paper summarizes our previous work and presents an approach to further research on the digital envelope (DE) concept that provides image integrity and security assurance in addition to conventional network security protection. The DE, including the digital signature (DS) of the image as well as encrypted patient information from the DICOM image header, can be embedded in the background area of the image as an invisible permanent watermark. The paper outlines the systematic development, evaluation and deployment of the DE method in a PACS environment. We have also proposed a dedicated PACS security server that will act as an image authority to check and certify the image origin and integrity upon request by a user, and meanwhile act also as a secure DICOM gateway to the outside connections and a PACS operation monitor for HIPAA supporting information. PMID:12620309

  13. Expression of the beacon gene in the rat adrenal gland: direct inhibitory effect of beacon[47-73] on aldosterone secretion from dispersed adrenal zona glomerulosa cells.

    PubMed

    Ziolkowska, Agnieszka; Rucinski, Marcin; Neri, Giuliano; Di Liddo, Rosa; Nussdorfer, Gastone G; Malendowicz, Ludwik K

    2004-02-01

    Beacon gene was recently identified in the rat hypothalamus, and there is evidence that beacon may be involved in the functional regulation of neuroendocrine axes. Reverse transcription-polymerase chain reaction and immunocytochemistry showed the expression of beacon mRNA and protein in the rat adrenal gland, especially in the cortex. Beacon[47-73], at a concentration over 10(-7) M decreased basal aldosterone secretion from dispersed rat zona glomerulosa (ZG) cells, without affecting the ACTH-stimulated one. Basal and agonist-stimulated corticosterone secretion from dispersed zona fasciculata-reticularis cells and catecholamine release from adrenomedullary slices were unaffected by beacon[47-73]. The suppressive effect of beacon[47-73] on aldosterone secretion from ZG cells was abolished by either H-89 or calphostin-C, which are inhibitors of protein kinase A and C signaling cascades. Taken together, these findings allow us to suggest that beacon can be included in the group of regulatory peptides involved in the fine tuning of ZG secretory activity. PMID:14719126

  14. Discovery and in Vivo Evaluation of Potent Dual CYP11B2 (Aldosterone Synthase) and CYP11B1 Inhibitors.

    PubMed

    Meredith, Erik L; Ksander, Gary; Monovich, Lauren G; Papillon, Julien P N; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F; Jeng, Arco Y; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; LaSala, Daniel

    2013-12-12

    Aldosterone is a key signaling component of the renin-angiotensin-aldosterone system and as such has been shown to contribute to cardiovascular pathology such as hypertension and heart failure. Aldosterone synthase (CYP11B2) is responsible for the final three steps of aldosterone synthesis and thus is a viable therapeutic target. A series of imidazole derived inhibitors, including clinical candidate 7n, have been identified through design and structure-activity relationship studies both in vitro and in vivo. Compound 7n was also found to be a potent inhibitor of 11β-hydroxylase (CYP11B1), which is responsible for cortisol production. Inhibition of CYP11B1 is being evaluated in the clinic for potential treatment of hypercortisol diseases such as Cushing's syndrome. PMID:24900631

  15. Changes in serum aldosterone are associated with changes in obesity-related factors in normotensive overweight and obese young adults.

    PubMed

    Cooper, Jennifer N; Fried, Linda; Tepper, Ping; Barinas-Mitchell, Emma; Conroy, Molly B; Evans, Rhobert W; Mori Brooks, Maria; Woodard, Genevieve A; Sutton-Tyrrell, Kim

    2013-10-01

    Recent data suggest excess circulating aldosterone promotes cardiometabolic decline. Weight loss may lower aldosterone levels, but little longitudinal data is available in normotensive adults. We aimed to determine whether, independent of changes in sodium excretion, reductions in serum aldosterone are associated with favorable changes in obesity-related factors in normotensive overweight/obese young adults. We studied 285 overweight/obese young adult participants (body mass index ≥ 25 and<40 kg m⁻², age 20-45 years) in a clinical trial examining the effects of a 1-year diet and physical activity intervention with or without sodium restriction on vascular health. Body weight, serum aldosterone, 24-h sodium and potassium excretion and obesity-related factors were measured at baseline, 6, 12 and 24 months. Weight loss was significant at 6 (7%), 12 (6%) and 24 months (4%; all P<0.0001). Decreases in aldosterone were associated with decreases in C-reactive protein, leptin, insulin, homeostasis assessment of insulin resistance, heart rate, tonic cardiac sympathovagal balance and increases in adiponectin (all P<0.05) in models adjusting for baseline age, sex, race, intervention arm, time since baseline, and sodium and potassium excretion. Weight loss and reductions in thigh intermuscular fat (intermuscular adipose tissue area; IMAT) were associated with decreases in aldosterone in the subgroup (n=98) with metabolic syndrome (MetS) at baseline (MetS × weight loss, P=0.04; MetS × change in IMAT, P=0.04). Favorable changes in obesity-related factors are associated with reductions in aldosterone in young adults with no risk factors besides excess weight, an important finding, given aldosterone's emergence as an important cardiometabolic risk factor. PMID:23657296

  16. Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway

    PubMed Central

    Feng, Xiuyan; Zhang, Yiqian; Shao, Ningjun; Wang, Yanhui; Zhuang, Zhizhi; Wu, Ping; Lee, Matthew J.; Liu, Yingli; Wang, Xiaonan; Zhuang, Jieqiu; Delpire, Eric; Gu, Dingying

    2015-01-01

    Thiazide-sensitive sodium chloride cotransporter (NCC) plays an important role in maintaining blood pressure. Aldosterone is known to modulate NCC abundance. Previous studies reported that dietary salts modulated NCC abundance through either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine-rich kinase) or WNK4-extracellular signal-regulated kinase-1 and -2 (ERK1/2) signaling pathways. To exclude the influence of SPAK signaling pathway on the role of the aldosterone-mediated ERK1/2 pathway in NCC regulation, we investigated the effects of dietary salt changes and aldosterone on NCC abundance in SPAK knockout (KO) mice. We found that in SPAK KO mice low-salt diet significantly increased total NCC abundance while reducing ERK1/2 phosphorylation, whereas high-salt diet decreased total NCC while increasing ERK1/2 phosphorylation. Importantly, exogenous aldosterone administration increased total NCC abundance in SPAK KO mice while increasing DUSP6 expression, an ERK1/2-specific phosphatase, and led to decreasing ERK1/2 phosphorylation without changing the ratio of phospho-T53-NCC/total NCC. In mouse distal convoluted tubule (mDCT) cells, aldosterone increased DUSP6 expression while reducing ERK1/2 phosphorylation. DUSP6 Knockdown increased ERK1/2 phosphorylation while reducing total NCC expression. Inhibition of DUSP6 by (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased ERK1/2 phosphorylation and reversed the aldosterone-mediated increments of NCC partly by increasing NCC ubiquitination. Therefore, these data suggest that aldosterone modulates NCC abundance via altering NCC ubiquitination through a DUSP6-dependent ERK1/2 signal pathway in SPAK KO mice and part of the effects of dietary salt changes may be mediated by aldosterone in the DCTs. PMID:25761881

  17. Aldosterone alters the participation of endothelial factors in noradrenaline vasoconstriction differently in resistance arteries from normotensive and hypertensive rats.

    PubMed

    Xavier, Fabiano E; Blanco-Rivero, Javier; Avendaño, María Soledad; Sastre, Esther; Yela, Rubén; Velázquez, Kyra; Salaíces, Mercedes; Balfagón, Gloria

    2011-03-11

    This study analyzed the effect of aldosterone (0.05mg/kg per day, 3 weeks) on vasoconstriction induced by noradrenaline in mesenteric resistance arteries from WKY rats and SHR. Contraction to noradrenaline was measured in mesenteric resistance arteries from untreated and aldosterone-treatedrats from both strains. Participation of nitric oxide (NO), superoxide anions, thromboxane A(2) (TxA(2)) and prostacyclin in this response was determined. 6-keto-prostaglandin (PG)F1alpha and thromboxane B(2) (TxB(2)) releases were determined by enzyme immunoassay. NO and superoxide anion release were also determined by fluorescence and chemiluminiscence, respectively. Aldosterone did not modify noradrenaline-induced contraction in either strain. In mesenteric resistance arteries from both aldosterone-treated groups, endothelium removal or preincubation with NO synthesis inhibitor L-NAME increased the noradrenaline-induced contraction, while incubation with the superoxide anion scavenger tempol decreased it. Preincubation with either the COX-1/2 or COX-2 inhibitor (indomethacin and NS-398, respectively) decreased the noradrenaline contraction in aldosterone-treated animals, while this response was not modified by COX-1 inhibitor SC-560. TxA(2) synthesis inhibitor (furegrelate), or TxA2 receptor antagonist (SQ 29 548) also decreased the noradrenaline contraction in aldosterone-treated animals. In untreated SHR, but not WKY rats, this response was increased by L-NAME, and reduced by tempol, indomethacin, NS-398 or SQ 29 548. Aldosterone treatment did not modify NO or TxB(2) release, but it did increase superoxide anion and 6-keto-PGF(1alpha) release in mesenteric resistance arteries from both strains. In conclusion, chronic aldosterone treatment reduces smooth muscle contraction to alpha-adrenergic stimuli, producing a new balance in the release of endothelium-derived prostanoids and NO. PMID:21262224

  18. Effects of stress, circadian rhythms, and dietary sodium on brain cell-nuclear uptake of aldosterone and corticosterone

    SciTech Connect

    Yongue, B.G.

    1985-01-01

    The binding of the adrenal steroid hormones aldosterone (ALD) and corticosterone (CORT) in brain cell-nuclei has been implicated as a necessary step in the behavioral and physiological actions of these hormones. In vivo uptake of radioactively labeled ALD and CORT in adrenalectomized (ADX) rats indicates a strong cell-nuclear localization of both of these hormones in limbic brain regions (such as hippocampus, septum and amygdala). Research using sub-cellular fractionation and radioimmunoassay (RIA), has confirmed both the presence of endogenously secreted CORT in cell-nuclei and its limbic localization in the brains of adrenal-intact rats. In this study, environmental and dietary factors were manipulated to induce variation in serum ALD and CORT. A series of experiments employing sub-cellular fractionation and RIA were performed, which reveal that: (1) endogenously secreted ALD and CORT, are concentrated by cell-nuclei of the brain in adrenal-intact rats, (2) the majority of the corticosteroids measured in ethanol extracts of brain cell-nuclei are associated with receptor molecules, and (3) the regional distribution of endogenously secreted ALD differs markedly from the predominantly limbic pattern predicted from in vivo uptake of labeled ALD in ADX rats. Instead, brain cell-nuclear ALD is heavily concentrated in the hypothalamus, which supports the hypothesized relationship between the interaction of ALD and angiotensin in the brain and the behavioral regulation of fluid/electrolyte balance.

  19. The Epidermal Growth Factor Receptor Is Involved in Angiotensin II But Not Aldosterone/Salt-Induced Cardiac Remodelling

    PubMed Central

    Griol-Charhbili, Violaine; Escoubet, Brigitte; Sadoshima, Junichi; Farman, Nicolette; Jaisser, Frederic

    2012-01-01

    Experimental and clinical studies have shown that aldosterone/mineralocorticoid receptor (MR) activation has deleterious effects in the cardiovascular system; however, the signalling pathways involved in the pathophysiological effects of aldosterone/MR in vivo are not fully understood. Several in vitro studies suggest that Epidermal Growth Factor Receptor (EGFR) plays a role in the cardiovascular effects of aldosterone. This hypothesis remains to be demonstrated in vivo. To investigate this question, we analyzed the molecular and functional consequences of aldosterone exposure in a transgenic mouse model with constitutive cardiomyocyte-specific overexpression of a mutant EGFR acting as a dominant negative protein (DN-EGFR). As previously reported, Angiotensin II-mediated cardiac remodelling was prevented in DN-EGFR mice. However, when chronic MR activation was induced by aldosterone-salt-uninephrectomy, cardiac hypertrophy was similar between control littermates and DN-EGFR. In the same way, mRNA expression of markers of cardiac remodelling such as ANF, BNF or β-Myosin Heavy Chain as well as Collagen 1a and 3a was similarly induced in DN-EGFR mice and their CT littermates. Our findings confirm the role of EGFR in AngII mediated cardiac hypertrophy, and highlight that EGFR is not involved in vivo in the damaging effects of aldosterone on cardiac function and remodelling. PMID:22291909

  20. An additional child case of an aldosterone-producing adenoma with an atypical presentation of peripheral paralysis due to hypokalemia.

    PubMed

    Dinleyici, E C; Dogruel, N; Acikalin, M F; Tokar, B; Oztelcan, B; Ilhan, H

    2007-11-01

    Aldosterone-producing adenoma, which is characterized by hypertension, hypokalemia, and elevated aldosterone levels with suppressed plasma renin activity, is a rare condition during childhood and is also potentially curable. To the best of our knowledge, nearly 25 cases of childhood aldosterone-secreting adenoma have been reported in the literature to date. Here we describe a 13-yr-old girl with primary hyperaldosteronism secondary to aldosterone-secreting adenoma. The patient was admitted to our hospital with the neuromuscular complaints of muscle weakness and inability to walk due to hypokalemia. She had been misdiagnosed as having hypokalemic periodic paralysis 2 months before admission and her symptoms had radically improved with potassium supplementation. However, her blood pressure levels had increased and her symptoms reappeared 2 days prior to being observed during hospitalization in our institution. Laboratory examinations revealed hypokalemia (2.1 mEq/l), and increased serum aldosterone levels with suppressed plasma renin activity. Abdominal ultrasonography and abdominal magnetic resonance imaging revealed left adrenal mass. Laparoscopic adrenalectomy was performed and histopathological examinations showed benign adrenal adenoma. Serum aldosterone levels and blood pressure levels returned to normal after surgical intervention. This case demonstrates the importance of a systemic evaluation including blood pressure monitorization of children with hypokalemia as intermittent hypertension episodes may be seen; cases without hypertension may be misdiagnosed as rheumatological or neurological disorders such as hypokalemic periodic paralysis, as in our case. PMID:18075291

  1. New approaches to hyperkalemia in patients with indications for renin angiotensin aldosterone inhibitors: Considerations for trial design and regulatory approval.

    PubMed

    Zannad, Faiez; Rossignol, Patrick; Stough, Wendy Gattis; Epstein, Murray; Alonso Garcia, Maria de Los Angeles; Bakris, George L; Butler, Javed; Kosiborod, Mikhail; Berman, Lance; Mebazaa, Alexandre; Rasmussen, Henrik S; Ruilope, Luis M; Stockbridge, Norman; Thompson, Aliza; Wittes, Janet; Pitt, Bertram

    2016-08-01

    Hyperkalemia is a common clinical problem, especially in patients with chronic kidney disease, diabetes mellitus, or heart failure. Treatment with renin angiotensin aldosterone system inhibitors exacerbates the risk of hyperkalemia in these patients. Concern about hyperkalemia can result in the failure to initiate, suboptimal dosing, or discontinuation of renin angiotensin aldosterone system inhibitor therapy in patients; effective treatments for hyperkalemia might mitigate such undertreatment. New treatments for hyperkalemia in development may offer better efficacy, tolerability and safety profiles than do existing approved treatments. These compounds might enable more eligible patients to receive renin angiotensin aldosterone system inhibitor therapy or to receive renin angiotensin aldosterone system inhibitors at target doses. The evidence needed to support a treatment claim (reduction in serum potassium) differs from that needed to support a prevention claim (preventing hyperkalemia to allow renin angiotensin aldosterone system inhibitor treatment). Thus, several issues related to clinical trial design and drug development need to be considered. This paper summarizes and expands upon a discussion at the Global Cardiovascular Clinical Trialists 2014 Forum and examines methodologic considerations for trials of new potassium binders for the prevention and management of hyperkalemia in patients with renin angiotensin aldosterone system inhibitor indications. PMID:27140336

  2. Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney.

    PubMed

    Stowasser, Michael; Gordon, Richard D

    2016-10-01

    In the 60 years that have passed since the discovery of the mineralocorticoid hormone aldosterone, much has been learned about its synthesis (both adrenal and extra-adrenal), regulation (by renin-angiotensin II, potassium, adrenocorticotrophin, and other factors), and effects (on both epithelial and nonepithelial tissues). Once thought to be rare, primary aldosteronism (PA, in which aldosterone secretion by the adrenal is excessive and autonomous of its principal regulator, angiotensin II) is now known to be the most common specifically treatable and potentially curable form of hypertension, with most patients lacking the clinical feature of hypokalemia, the presence of which was previously considered to be necessary to warrant further efforts towards confirming a diagnosis of PA. This, and the appreciation that aldosterone excess leads to adverse cardiovascular, renal, central nervous, and psychological effects, that are at least partly independent of its effects on blood pressure, have had a profound influence on raising clinical and research interest in PA. Such research on patients with PA has, in turn, furthered knowledge regarding aldosterone synthesis, regulation, and effects. This review summarizes current progress in our understanding of the physiology of aldosterone, and towards defining the causes (including genetic bases), epidemiology, outcomes, and clinical approaches to diagnostic workup (including screening, diagnostic confirmation, and subtype differentiation) and treatment of PA. PMID:27535640

  3. Renin–angiotensin–aldosterone system (RAAS) pharmacogenomics: implications in heart failure management

    PubMed Central

    Beitelshees, Amber L.

    2016-01-01

    Blockade of the renin–angiotensin–aldosterone system (RAAS) with ACE inhibitors has been a cornerstone of heart failure therapy for over 15 years. More recently, further blockade of RAAS with aldosterone antagonists and angiotensin receptor blockers (ARBs) has been studied. While these therapies have certainly improved outcomes in the treatment of heart failure, morbidity and mortality remain extremely high. Furthermore, polypharmacy and complex regimens of seven medications on average is the norm for management of heart failure. This results in increased costs, patient burden, and uncertainty as to the best course of therapy. The ability to personalize patients’ therapeutic regimens using pharmacogenomics has the potential of providing more effective and efficient use of RAAS-modulating medications. This review highlights the implications of major RAAS pharmacogenetic studies, while outlining future directions for translation to practice. PMID:18351457

  4. Use of computed tomography in diagnosing the cause of primary aldosteronism

    SciTech Connect

    White, E.A.; Schambelan, M.; Rost, C.R.; Biglieri, E.G.; Moss, A.A.; Korobkin, M.

    1980-12-25

    Computed tomography (CT) was performed in 22 consecutive patients with primary aldosteronism to evaluate the usefulness of this technique in diagnosing and locating aldosterone-producing adenomas. Sixteen patients had severe hypokalemia, hyperaldosteronism, and elevated plasma levels of 18-hydroxycorticosterone suggestive of an adenoma. In 12 of these 16, a unilateral adrenal mass was demonstrated clearly, and in all 11 who had surgery an adenoma was confirmed. In the other four patients in this group, one adrenal gland was normal and the other was either not seen adequately or had minor abnormalities that could not be definitely classified; and adenoma was found in the poorly visualized gland in each of the two patients who had surgery. The remaining six patients, who had milder biochemical abnormalities suggestive of idiopathic hyperaldosteronism, had bilateral adrenal enlargement or normal-appearing glands on scan and were not surgically explored.

  5. Hypokalemia-Induced Rhabdomyolysis by Primary Aldosteronism Coexistent With Sporadic Inclusion Body Myositis

    PubMed Central

    Lee, Jong Ha; Chon, Suk

    2015-01-01

    We describes a patient with hypokalemia-induced rhabdomyolysis due to primary aldosteronism (PA), who suffered from slowly progressive muscle weakness after laparoscopic adrenalectomy, and was later diagnosed with coexisting sporadic inclusion body myositis (sIBM). A 54-year-old Asian male presented with severe muscle weakness of both lower extremities. Laboratory findings showed profound hypokalemia, and extreme elevation of the serum creatine phosphokinase levels, suggestive of hypokalemia-induced rhabdomyolysis. Further evaluation strongly suggested PA by an aldosterone-producing adenoma, which was successfully removed surgically. However, muscle weakness slowly progressed one year after the operation and a muscle biopsy demonstrated findings consistent with sIBM. This case is the first report of hypokalemia-induced rhabdomyolysis by PA coexistent with sIBM, to the best of our knowledge. PMID:26605182

  6. The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin-aldosterone system in response to low dietary salt intake in vivo.

    PubMed

    Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki; Pavenstädt, Hermann; Narumiya, Shuh; Jensen, Boye L; Nüsing, Rolf M

    2012-11-15

    Increased cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis have been shown to be prerequisites for renal renin release after Na(+) deprivation. To answer the question of whether EP4 receptor type of PGE(2) mediates renin regulation under a low-salt diet, we examined renin regulation in EP4(+/+), EP4(-/-), and in wild-type mice treated with EP4 receptor antagonist. After 2 wk of a low-salt diet (0.02% wt/wt NaCl), EP4(+/+) mice showed diminished Na(+) excretion, unchanged K(+) excretion, and reduced Ca(2+) excretion. Diuresis and plasma electrolytes remained unchanged. EP4(-/-) exhibited a similar attenuation of Na(+) excretion; however, diuresis and K(+) excretion were enhanced, and plasma Na(+) concentration was higher, whereas plasma K(+) concentration was lower compared with control diet. There were no significant differences between EP4(+/+) and EP4(-/-) mice in blood pressure, creatinine clearance, and plasma antidiuretic hormone (ADH) concentration. Following salt restriction, plasma renin and aldosterone concentrations and kidney renin mRNA level rose significantly in EP4(+/+) but not in EP4(-/-) and in wild-type mice treated with EP4 antagonist ONO-AE3-208. In the latter two groups, the low-salt diet caused a significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX-2 followed by enhanced renal PGE(2) synthesis, which stimulates the renin-angiotensin-aldosterone system by activation of EP4 receptor. Most likely, defects at the step of EP4 receptor block negative feedback mechanisms on the renal COX system, leading to persistently high PGE(2) levels, diuresis, and K(+) loss. PMID:22993066

  7. Fuel Fabrication for Surrogate Sphere-Pac Rodlet

    SciTech Connect

    Del Cul, G.D.

    2005-07-19

    Sphere-pac fuel consists of a blend of spheres of two or three different size fractions contained in a fuel rod. The smear density of the sphere-pac fuel column can be adjusted to the values obtained for light-water reactor (LWR) pellets (91-95%) by using three size fractions, and to values typical of the fast-reactor oxide fuel column ({approx}85%) by using two size fractions. For optimum binary packing, the diameters of the two sphere fractions must differ by at least a factor of 7 (ref. 3). Blending of spheres with smaller-diameter ratios results in difficult blending, nonuniform loading, and lower packing fractions. A mixture of about 70 vol% coarse spheres and 30 vol% fine spheres is needed to obtain high packing fractions. The limiting smear density for binary packing is 86%, with about 82% achieved in practice. Ternary packing provides greater smear densities, with theoretical values ranging from 93 to 95%. Sphere-pac technology was developed in the 1960-1990 period for thermal and fast spectrum reactors of nearly all types (U-Th and U-Pu fuel cycles, oxide and carbide fuels), but development of this technology was most strongly motivated by the need for remote fabrication in the thorium fuel cycle. The application to LWR fuels as part of the DOE Fuel Performance Improvement Program did not result in commercial deployment for a number of reasons, but the relatively low production cost of existing UO{sub 2} pellet fuel is probably the most important factor. In the case of transmutation fuels, however, sphere-pac technology has the potential to be a lower-cost alternative while also offering great flexibility in tailoring the fuel elements to match the exact requirements of any particular reactor core at any given time in the cycle. In fact, the blend of spheres can be adjusted to offer a different composition for each fuel pin or group of pins in a given fuel element. Moreover, it can even provide a vertical gradient of composition in a single fuel pin. For

  8. Decongestion Strategies and Renin-Angiotensin-Aldosterone System Activation in Acute Heart Failure

    PubMed Central

    Mentz, Robert J.; Stevens, Susanna R.; DeVore, Adam D.; Lala, Anuradha; Vader, Justin M.; AbouEzzeddine, Omar F.; Khazanie, Prateeti; Redfield, Margaret M.; Stevenson, Lynne W.; O'Connor, Christopher M.; Goldsmith, Steven R.; Bart, Bradley A.; Anstrom, Kevin J.; Hernandez, Adrian F.; Braunwald, Eugene; Felker, G. Michael

    2014-01-01

    Background High dose diuretics in patients with acute heart failure (AHF) are thought to activate the renin-angiotensin-aldosterone system (RAAS), and alternative decongestion strategies, such as ultrafiltration (UF), have been proposed to mitigate this RAAS activation. Methods We analyzed 427 AHF patients enrolled in the DOSE-AHF and CARRESS-HF trials. We assessed the relationship between two markers of RAAS activation (plasma renin activity [PRA] and aldosterone) from baseline to 72-96h and decongestion strategy; high vs. low-dose and continuous infusion vs. bolus furosemide for DOSE-AHF and UF vs. stepped pharmacologic care for CARRESS-HF. We determined the relationship between RAAS biomarkers and 60-day outcomes. Results Patients with greater RAAS activation at baseline had lower blood pressures, lower serum sodium, and higher BUN. Continuous infusion furosemide and UF were associated with greater PRA increases (median +1.66 vs. +0.66 ng/mL/h with continuous vs. bolus, P=0.021; +4.05 vs. +0.56 ng/mL/h with UF vs. stepped care, P=0.014). There was no significant difference in RAAS biomarker change with high vs. low-dose diuretics (both P>0.5). Neither baseline log PRA nor log aldosterone was associated with increased death/HF hospitalization (HR for a doubling 1.05; 95% CI: 0.98-1.13, P=0.18 and HR 1.13; 95% CI: 0.99-1.28, P=0.069, respectively). The change in RAAS biomarkers from baseline to 72-96 h was not associated with outcomes (both P>0.5). Conclusions High-dose loop diuretics did not result in greater RAAS activation than low-dose diuretics. UF resulted in greater PRA increase than stepped pharmacologic care. Neither PRA nor aldosterone was significantly associated with short-term outcomes in this cohort. PMID:25543972

  9. Transdermal contraception and the renin-angiotensin-aldosterone system in premenopausal women.

    PubMed

    Odutayo, Ayodele; Cherney, David; Miller, Judith; Ahmed, Sofia B; Lai, Vesta; Dunn, Sheila; Pun, Nicole; Moineddin, Rahim; Hladunewich, Michelle A

    2015-03-15

    The oral contraceptive pill (OCP) activates the renin-angiotensin-aldosterone system (RAAS) through first-pass hepatic metabolism. Although usually benign, RAAS activation may have detrimental effects on renal and hemodynamic function in some women. Since combined hormonal contraception with the transdermal patch (EVRA) does not undergo first-pass hepatic metabolism, we hypothesized that the RAAS response would be different from that of OCP subjects. Thirty-five nonsmoking, premenopausal women (15 control subjects, 10 OCP subjects, and 10 contraceptive patch subjects) without evidence of cardiovascular disease, renal disease, or diabetes were studied. Baseline angiotensinogen, renin, angiotensin II, aldosterone, and plasma renin activity were assessed along with hormonal and hemodynamic responses to simulated orthostatic stress using incremental lower body negative pressure (LBNP; -15, -25, and -40 mmHg). Baseline levels of angiotensinogen, angiotensin II, and plasma renin activity were significantly higher in OCP subjects compared with normotensive control and contraceptive patch subjects (P < 0.05), whereas aldosterone was significantly higher in OCP versus control subjects only (P < 0.05). Plasma renin levels were significantly lower at baseline in contraceptive patch subjects compared with normotensive control and OCP subjects (P < 0.05). In response to LBNP, increases in renin, angiotensin II, and aldosterone were attenuated in contraceptive patch subjects in conjunction with an exaggerated decline in mean arterial pressure (P < 0.05 vs. control and OCP subjects). The contraceptive patch in healthy premenopausal women is associated with an impaired ability to maintain blood pressure in response to LBNP, possibly due to insensitivity of the endogenous RAAS. Further evaluation may be beneficial in women with kidney disease. PMID:25587124

  10. Plasma immunoreactive gamma melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension.

    PubMed Central

    Griffing, G T; Berelowitz, B; Hudson, M; Salzman, R; Manson, J A; Aurrechia, S; Melby, J C; Pedersen, R C; Brownie, A C

    1985-01-01

    A non-ACTH aldosterone-stimulating factor(s) has been implicated in the pathogenesis of idiopathic hyperaldosteronism (IHA). Although this factor has not been fully characterized, some evidence suggests that it may be related to a pro-gamma-melanotropin (pro-gamma-MSH), derived from the NH2-terminal region of pro-opiomelanocortin. In the present study, plasma immunoreactive (IR-) gamma-MSH levels at 0800 h in patients with IHA were evaluated (90 +/- 17 fmol/ml; range: 13-173 fmol/ml) and found to be significantly higher (P less than 0.05) than those in subjects with aldosterone-producing adenomas (33 +/- 8 fmol/ml), essential hypertension (33 +/- 6 fmol/ml), and normotensive controls (19 +/- 2 fmol/ml). Seven of nine IHA subjects had circulating IR-gamma-MSH levels above the normal range (greater than 35 fmol/ml). In plasmas sampled at 1200 h, IR-gamma-MSH was significantly higher in patients with IHA (95 +/- 26 fmol/ml) and adenomas (63 +/- 23 fmol/ml), as compared with essential hypertensives (31 +/- 6 fmol/ml) and normotensives (19 +/- 3 fmol/ml). Mean plasma IR-ACTH, plasma cortisol, and urinary cortisol levels did not differ significantly between any of these groups. In order to evaluate the effect of a pro-gamma-MSH in vitro, adrenal adenoma tissue was obtained from two patients, one with elevated IR-gamma-MSH (61 fmol/ml) and a second with low IR-gamma-MSH (12 fmol/ml). Aldosterone secretion by dispersed adenoma cells from the former, but not the latter, underwent a fourfold dose-dependent (10(-14)-10(-9) M) increase in response to human Lys-gamma 3-MSH. These data suggest that a pro-gamma-MSH may be implicated as a pathogenic factor in a subset of patients with primary aldosteronism, particularly among those differentially diagnosed as having IHA. Images PMID:4019776

  11. Role of Nongenomic Signaling Pathways Activated by Aldosterone During Cardiac Reperfusion Injury.

    PubMed

    Ashton, Anthony W; Le, Thi Y L; Gomez-Sanchez, Celso E; Morel-Kopp, Marie-Christine; McWhinney, Brett; Hudson, Amanda; Mihailidou, Anastasia S

    2015-08-01

    Aldosterone (Aldo) activates both genomic and nongenomic signaling pathways in the cardiovascular system. Activation of genomic signaling pathways contributes to the adverse cardiac actions of Aldo during reperfusion injury; however, the extent nongenomic signaling pathways contribute has been difficult to identify due to lack of a specific ligand that activates only nongenomic signaling pathways. Using a pegylated aldosterone analog, aldosterone-3-carboxymethoxylamine-TFP ester conjugated to methoxypegylated amine (Aldo-PEG), we are able for the first time to distinguish between nongenomic and genomic cardiac actions of Aldo. We confirm Aldo-PEG activates phosphorylation of ERK1/2 in rat cardiomyocyte H9c2 cells similar to Aldo and G protein-coupled receptor 30 (GPR30 or GPER) agonist G1. GPER antagonist, G36, but not mineralocorticoid receptor (MR) antagonist spironolactone, prevented ERK1/2 phosphorylation by Aldo, Aldo-PEG, and G1. The selective nongenomic actions of Aldo-PEG are confirmed, with Aldo-PEG increasing superoxide production in H9c2 cells to similar levels as Aldo but having no effect on subcellular localization of MR. Striatin serves as a scaffold for GPER and MR, with GPER antagonist G36, but not spironolactone, restoring MR-striatin complexes. Aldo-PEG had no effect on MR-dependent transcriptional activation, whereas Aldo increased transcript levels of serum-regulated kinase 1 and plasminogen activator inhibitor-1. Using our ex vivo experimental rat model of myocardial infarction, we found aggravated infarct size and apoptosis by Aldo but not Aldo-PEG. Our studies confirm that in the heart, activation of nongenomic signaling pathways alone are not sufficient to trigger the deleterious effects of aldosterone during myocardial reperfusion injury. PMID:26121234

  12. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells.

    PubMed

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B

    2014-08-25

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24 h significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention. PMID:25038520

  13. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells

    PubMed Central

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B.

    2014-01-01

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24hr significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention. PMID:25038520

  14. Synthesis of annulated pyridines as inhibitors of aldosterone synthase (CYP11B2).

    PubMed

    Martin, Rainer E; Lehmann, Johannes; Alzieu, Thibaut; Lenz, Mario; Carnero Corrales, Marjorie A; Aebi, Johannes D; Märki, Hans Peter; Kuhn, Bernd; Amrein, Kurt; Mayweg, Alexander V; Britton, Robert

    2016-07-01

    A series of cyclopenta[c]pyridine aldosterone synthase (AS) inhibitors were conveniently accessed using batch or continuous flow Kondrat'eva reactions. Preparation of the analogous cyclohexa[c]pyridines led to the identification of a potent and more selective AS inhibitor. The structure-activity-relationship (SAR) in this new series was rationalized using binding mode models in the crystal structure of AS. PMID:27245438

  15. Molecular identity and gene expression of aldosterone synthase cytochrome P450

    SciTech Connect

    Okamoto, Mitsuhiro . E-mail: mokamoto@mr-mbio.med.osaka-u.ac.jp; Nonaka, Yasuki; Takemori, Hiroshi; Doi, Junko

    2005-12-09

    11{beta}-Hydroxylase (CYP11B1) of bovine adrenal cortex produced corticosterone as well as aldosterone from 11-deoxycorticosterone in the presence of the mitochondrial P450 electron transport system. CYP11B1s of pig, sheep, and bullfrog, when expressed in COS-7 cells, also performed corticosterone and aldosterone production. Since these CYP11B1s are present in the zonae fasciculata and reticularis as well as in the zona glomerulosa, the zonal differentiation of steroid production may occur by the action of still-unidentified factor(s) on the enzyme-catalyzed successive oxygenations at C11- and C18-positions of steroid. In contrast, two cDNAs, one encoding 11{beta}-hydroxylase and the other encoding aldosterone synthase (CYP11B2), were isolated from rat, mouse, hamster, guinea pig, and human adrenals. The expression of CYP11B1 gene was regulated by cyclic AMP (cAMP)-dependent signaling, whereas that of CYP11B2 gene by calcium ion-signaling as well as cAMP-signaling. Salt-inducible protein kinase, a cAMP-induced novel protein kinase, was one of the regulators of CYP11B2 gene expression.

  16. Azilsartan, aliskiren, and combination antihypertensives utilizing renin-angiotensin-aldosterone system antagonists.

    PubMed

    Lanier, Gregg; Sankholkar, Kedar; Aronow, Wilbert S

    2014-01-01

    Health care providers managing hypertension (HTN) have a large selection of pharmacologic agents to choose from, including several different classes of drugs and many similar drugs within each class. Antagonism of the renin-angiotensin-aldosterone system has been shown to be very effective for HTN, especially in patients with cardiovascular disease, diabetes, and heart failure. Within this group, there have been 2 new agents recently introduced to the US market and approved by the Food and Drug Administration. It is important for the HTN specialist to be familiar with the merits of these 2 drugs: the angiotensin receptor blocker Edarbi (azilsartan) and the renin inhibitor Tekturna (aliskiren). Additionally, there have been several new, fixed-dose combination antihypertensives introduced to the market since 2006 that use a renin-angiotensin-aldosterone antagonist. Seven of these combine 2 drugs together in a single pill: Edarbyclor (azilsartan/chlorthalidone), Exforge (amlodipine/valsartan), Azor (olmesartan/amlodipine), Twynsta (amlodipine/telmisartan), Tekturna HCT [aliskiren/hydrochlorothiazide (HCTZ)], Valturna (aliskiren/valsartan), Tekamlo (aliskiren/amlodipine). Three triple-drug combination medications have also been introduced recently: Exforge HCT (amlodipine/valsartan/HCTZ), Tribenzor (olmesartan/amlodipine/HCTZ), and Amturnide (aliskiren/amlodipine/hydrocholorothiazide). This review will summarize the trial data and important pharmacologic merits of these 2 new renin-angiotensin-aldosterone antagonists and the advantages of initiating treatment with one of the new fixed-dose, combination drugs approved over the last 5 years. PMID:22975662

  17. Mild Adrenal Steroidogenic Defects and ACTH-Dependent Aldosterone Secretion in High Blood Pressure: Preliminary Evidence

    PubMed Central

    Martin Martins, João; do Vale, Sónia; Martins, Ana Filipa

    2014-01-01

    Introduction. Adrenal glands play a major role in the control of blood pressure and mild defects of steroidogenesis and/or inappropriate control of mineralocorticoid production have been reported in high blood pressure (HBP). Patients and Methods. We used a specific protocol for the evaluation of 100 consecutive patients with inappropriate or recent onset HBP. Specific methods were used to confirm HBP and to diagnose secondary forms of HBP. In addition we tested adrenal steroidogenesis with the common cosyntropin test, modified to include the simultaneous measurement of renin and aldosterone besides 17-hydroxyprogesterone (17OHP) and 11-deoxycortisol (S). Results. Secondary forms of HBP were diagnosed in 32 patients, including 14 patients with primary hyperaldosteronism (PA) (14%) and 10 patients with pheochromocytoma (10%). Mild defects of the 21-hydroxylase (21OHD) and 11-hydroxylase (11OHD) enzymes were common (42%). ACTH-dependent aldosterone secretion was found in most patients (54%) and characteristically in those with mild defects of adrenal steroidogenesis (>60%), PA (>75%), and otherwise in patients with apparent essential HBP (EHBP) (32%). Discussion. Mild defects of adrenal steroidogenesis are common in patients with HBP, occurring in almost half of the patients. In those patients as well as in patients with apparent EHBP, aldosterone secretion is commonly dependent on ACTH. PMID:25580122

  18. The renin–angiotensin–aldosterone system in adolescent offspring born prematurely to mothers with preeclampsia

    PubMed Central

    Washburn, Lisa K; Brosnihan, K Bridget; Chappell, Mark C; Diz, Debra I; Gwathmey, TanYa M; Nixon, Patricia A; Russell, Gregory B; Snively, Beverly M; O’Shea, T Michael

    2014-01-01

    Hypothesis/introduction Preeclampsia is associated with alterations in the maternal renin–angiotensin–aldosterone system (RAAS), increased blood pressure (BP), and cardiovascular risk in the offspring. We hypothesized that preeclampsia is associated with alterations in the RAAS in the offspring that persist into adolescence. Materials and methods We compared components of the circulating (n = 111) and renal (n = 160) RAAS in adolescents born prematurely with very low birth weight (VLBW) of preeclamptic (PreE) and normotensive (NoHTN) pregnancies. Multivariable linear regression was used to evaluate potential confounding and intermediate variables. Analyses were stratified by sex. Results Adjusting for race and antenatal steroid exposure, male offspring of PreE mothers had higher circulating aldosterone than those of NoHTN mothers (adjusted mean difference = 109; 95% confidence limits: −9, 227 pmol/L). Further adjustment for current BMI attenuated this difference (adjusted mean difference: 93; 95% confidence limits: −30, 215 pmol/L). Conclusion Among male preterm VLBW infants, maternal preeclampsia is associated with increased circulating aldosterone level in adolescence, which appears to be mediated in part by higher BMI. PMID:24737639

  19. Ambulatory Blood Pressure Monitoring-Derived Short-Term Blood Pressure Variability in Primary Aldosteronism.

    PubMed

    Grillo, Andrea; Bernardi, Stella; Rebellato, Andrea; Fabris, Bruno; Bardelli, Moreno; Burrello, Jacopo; Rabbia, Franco; Veglio, Franco; Fallo, Francesco; Carretta, Renzo

    2015-08-01

    The aim of this study was to investigate the short-term blood pressure (BP) variability (BPV) derived from ambulatory blood pressure monitoring (ABPM) in patients with primary aldosteronism (PA), either idiopathic hyperaldosteronism (IHA) or aldosterone-producing adenoma (APA), in comparison with patients with essential hypertension (EH) and normotensive (NT) controls. Thirty patients with PA (16 with IHA and 14 with APA), 30 patients with EH, and 30 NT controls, matched for sex, age, body mass index, and antihypertensive therapy, were studied. The standard deviation (SD) of 24-hour, daytime, and nighttime BP; 24-hour weighted SD of BP; and 24-hour BP average real variability were not different between patients with PA and those with EH (P=not significant). All BPV indices were higher in patients with PA, either IHA or APA subtypes, and patients with EH, compared with NT controls (P<.001 to P<.05). ABPM-derived short-term BPV is increased in patients with PA, and it may represent an additional cardiovascular risk factor in this disease. The role of aldosterone excess in BPV has to be clarified. PMID:25880017

  20. PACS workstation for computer-assisted image diagnosis

    NASA Astrophysics Data System (ADS)

    Hosoba, Minoru; Horino, Masato; Takemura, Kunihiko; Wani, Hidenobu; Hidaka, Akinari; Hatabu, Hiroto; Kasagi, Kanji; Konishi, Junji

    1990-08-01

    Major two functions that a PACS workstation is considered to be equipped with are 1) efficient retrieval of image data and 2) supporting or consultation of writing reports, as radiologists have to diagnose increasing number of digital images in routine clinical studies. The authors developed a prototype PACS workstation with high speed image retrieving architecture and computer aided diagnosis and reporting function by using an artificial intelligence technology (AIPACS workstation). When physician selects the patient and his studies, the system performs feature extraction and generates diagnostic report by the inference engine with backward reasoning using the knowledge installed as production rules. Clinical application to the system for thyroid diagnosis showed good correlation with the diagnosis done by the physician.

  1. Use of plasma metanephrine to aid adrenal venous sampling in combined aldosterone and cortisol over-secretion

    PubMed Central

    Goupil, Rémi; Wolley, Martin; Ungerer, Jacobus; McWhinney, Brett; Mukai, Kuniaki; Naruse, Mitsuhide; Gordon, Richard D

    2015-01-01

    Summary In patients with primary aldosteronism (PA) undergoing adrenal venous sampling (AVS), cortisol levels are measured to assess lateralization of aldosterone overproduction. Concomitant adrenal autonomous cortisol and aldosterone secretion therefore have the potential to confound AVS results. We describe a case where metanephrine was measured during AVS to successfully circumvent this problem. A 55-year-old hypertensive male had raised plasma aldosterone/renin ratios and PA confirmed by fludrocortisone suppression testing. Failure of plasma cortisol to suppress overnight following dexamethasone and persistently suppressed corticotrophin were consistent with adrenal hypercortisolism. On AVS, comparison of adrenal and peripheral A/F ratios (left 5.7 vs peripheral 1.0; right 1.7 vs peripheral 1.1) suggested bilateral aldosterone production, with the left gland dominant but without contralateral suppression. However, using aldosterone/metanephrine ratios (left 9.7 vs peripheral 2.4; right 1.3 vs peripheral 2.5), aldosterone production lateralized to the left with good contralateral suppression. The patient underwent left laparoscopic adrenalectomy with peri-operative glucocorticoid supplementation to prevent adrenal insufficiency. Pathological examination revealed adrenal cortical adenomas producing both cortisol and aldosterone within a background of aldosterone-producing cell clusters. Hypertension improved and cured of PA and hypercortisolism were confirmed by negative post-operative fludrocortisone suppression and overnight 1 mg dexamethasone suppression testing. Routine dexamethasone suppression testing in patients with PA permits detection of concurrent hypercortisolism which can confound AVS results and cause unilateral PA to be misdiagnosed as bilateral with patients thereby denied potentially curative surgical treatment. In such patients, measurement of plasma metanephrine during AVS may overcome this issue. Learning points Simultaneous autonomous

  2. Renin–angiotensin–aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease

    SciTech Connect

    Chen, Wei-Jen; Huang, Ya-Li; Shiue, Horng-Sheng; Chen, Tzen-Wen; Lin, Yuh-Feng; Huang, Chao-Yuan; Lin, Ying-Chin; Han, Bor-Cheng; Hsueh, Yu-Mei

    2014-09-01

    A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin–angiotensin–aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruited from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[− 20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[− 344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96–2.01), of CKD; while those with the AGT(A[− 20]C) CC genotype had an inverse OR of CKD (0.20 (0.05–0.81)), and a high-risk genotype was defined as A/A + A/C for AGT(A[− 20C]) and T/T for CYP11B2(C[− 344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status. - Highlights: • AGT(− 20 C) and CYP11B2(− 344 T) genotypes were significantly associated with CKD. • Combined effect of high-risk genotypes and high urinary total arsenic on OR of CKD. • Combined

  3. Integration of implant planning workflows into the PACS infrastructure

    NASA Astrophysics Data System (ADS)

    Gessat, Michael; Strauß, Gero; Burgert, Oliver

    2008-03-01

    The integration of imaging devices, diagnostic workstations, and image servers into Picture Archiving and Communication Systems (PACS) has had an enormous effect on the efficiency of radiology workflows. The standardization of the information exchange between the devices with the DICOM standard has been an essential precondition for that development. For surgical procedures, no such infrastructure exists. With the increasingly important role computerized planning and assistance systems play in the surgical domain, an infrastructure that unifies the communication between devices becomes necessary. In recent publications, the need for a modularized system design has been established. A reference architecture for a Therapy Imaging and Model Management System (TIMMS) has been proposed. It was accepted by the DICOM Working Group 6 as the reference architecture for DICOM developments for surgery. In this paper we propose the inclusion of implant planning systems into the PACS infrastructure. We propose a generic information model for the patient specific selection and positioning of implants from a repository according to patient image data. The information models are based on clinical workflows from ENT, cardiac, and orthopedic surgery as well as technical requirements derived from different use cases and systems. We show an exemplary implementation of the model for application in ENT surgery: the selection and positioning of an ossicular implant in the middle ear. An implant repository is stored in the PACS. It makes use of an experimental implementation of the Surface Mesh Module that is currently being developed as extension to the DICOM standard.

  4. Dicoogle - an open source peer-to-peer PACS.

    PubMed

    Costa, Carlos; Ferreira, Carlos; Bastião, Luís; Ribeiro, Luís; Silva, Augusto; Oliveira, José Luís

    2011-10-01

    Picture Archiving and Communication Systems (PACS) have been widely deployed in healthcare institutions, and they now constitute a normal commodity for practitioners. However, its installation, maintenance, and utilization are still a burden due to their heavy structures, typically supported by centralized computational solutions. In this paper, we present Dicoogle, a PACS archive supported by a document-based indexing system and by peer-to-peer (P2P) protocols. Replacing the traditional database storage (RDBMS) by a documental organization permits gathering and indexing data from file-based repositories, which allows searching the archive through free text queries. As a direct result of this strategy, more information can be extracted from medical imaging repositories, which clearly increases flexibility when compared with current query and retrieval DICOM services. The inclusion of P2P features allows PACS internetworking without the need for a central management framework. Moreover, Dicoogle is easy to install, manage, and use, and it maintains full interoperability with standard DICOM services. PMID:20981467

  5. Toshiba General Hospital PACS for routine in- and outpatient clinics

    NASA Astrophysics Data System (ADS)

    Toshimitsu, Akihiro; Okazaki, Nobuo; Kura, Hiroyuki; Nishihara, Eitaro; Tsubura, Shinichi

    1996-05-01

    The Toshiba General Hospital introduced a departmental RIS/PACS (Radiology Information System/Picture Archiving and Communication System) in the radiology department in May, 1993. It has been used routinely since that time. In order to provide efficient means for clinicians to find and read many images, the system has been expanded to the neurosurgery and urology clinics and wards since May, 1995, and five image referring workstations now provide digital images to clinicians. In this paper we discuss an algorithm for image migration, one of the key issues to accomplish the expansion to outpatient clinics successfully, and propose the WYWIWYG (what you want is what you get) image transfer logic. This is the logic used to transfer images that physicians require refer without increasing the traffic between the image server and referring workstations. We accomplish the WYWIWYG logic by prioritizing exams the physicians have not yet viewed and by finding historical exams according to the modality, anatomy, and marking. Clinicians gave us comments from their first use of the system and suggested that the PACS enables clinicians to review images more efficiently compared to a film-based system. Our experience suggests that it is a key to the effective application of PACS in outpatient clinics to incorporate consideration patterns of clinicians on the migration algorithm.

  6. Protecting clinical data in PACS, teleradiology systems, and research environments

    NASA Astrophysics Data System (ADS)

    Meissner, Marion C.; Collmann, Jeff R.; Tohme, Walid G.; Mun, Seong K.

    1997-05-01

    As clinical data is more widely stored in electronic patient record management systems and transmitted over the Internet and telephone lines, it becomes more accessible and therefore more useful, but also more vulnerable. Computer systems such as PACS, telemedicine applications, and medical research networks must protect against accidental or deliberate modification, disclosure, and violation of patient confidentiality in order to be viable. Conventional wisdom in the medical field and among lawmakers legislating the use of electronic medical records suggests that, although it may improve access to information, an electronic medical record cannot be as secure as a traditional paper record. This is not the case. Information security is a well-developed field in the computer and communications industry. If medical information systems, such as PACS, telemedicine applications, and research networks, properly apply information security techniques, they can ensure the accuracy and confidentiality of their patient information and even improve the security of their data over a traditional paper record. This paper will elaborate on some of these techniques and discuss how they can be applied to medical information systems. The following systems will be used as examples for the analysis: a research laboratory at Georgetown University Medical Center, the Deployable Radiology system installed to support the US Army's peace- keeping operation in Bosnia, a kidney dialysis telemedicine system in Washington, D.C., and various experiences with implementing and integrating PACS.

  7. Hospital-integrated PACS at the University Hospital of Geneva

    NASA Astrophysics Data System (ADS)

    Ratib, Osman M.; Ligier, Yves; Hochstrasser, Denis; Scherrer, Jean-Raoul

    1991-07-01

    The PACS under development at the University Hospital of Geneva is a hospital-wide image management system for radiological as well as non-radiological medical images which is part of one of the widest hospital information systems (HIS) in Switzerland (Diogene system). It is based on a multi-vendor open architecture and a set of widely available industry standards, namely: Unix as the operating system, TCP-IP as network protocol and an SQL-based distributed database (INGRES) that handles both the PACS and the HIS. The PACS is based on a distributed architecture of servers of two types: the archive servers connected to the sources of images and equipped with large optical disk libraries (jukeboxes) and display servers distributed over the hospital. A standard image storage format was developed based on the ACR-NEMA standard. This file format (the PAPYRUS format) allows storage of sets of images as a sequence of ACR-NEMA messages in an 'encapsulated' file structure. In order to provide a more uniform user interface on a variety of different workstations, a common platform for image display and manipulation called OSIRIS is developed based on X-11 windowing system and OSF/Motif extension. Such a platform is designed to be portable to any computer running Unix and equipped with a graphic display system running X-11. Because this software is written in the object-oriented language C++, it is easily expandable and easily adaptable to different needs and requirements.

  8. PACS according to Murphy: what can and will go wrong

    NASA Astrophysics Data System (ADS)

    Honeyman-Buck, Janice C.; Arreola, Manuel; Frost, Meryll M.

    2002-05-01

    A multi-institutional PACS and electronic radiology practice is in daily operation based at the University of Florida. This system is evolving constantly as technology advances and users become more sophisticated. As the technology advances, however, more things can and do go wrong. The PACS quality control and working groups at the University have compile the problems that have been encountered is this rapidly changing environment and have designed tools or procedures to either eliminate the problems or to minimize their impact on the operation of the system. As a result, a series of automated tools have been created to correct mislabeled images, to monitor the correct operation of the system, and to inform support of problems as soon as they are discovered. In the case where automated tools cannot solve the problem, protocols have been designed and procedures developed to identify issues and resolve them before time is wasted or the system fails. Not every problem can be anticipated and solved prior to it occurring, but this work can help alert new users and perhaps even experienced users to unanticipated disasters with PACS and other technologies associated with an electronic radiology practice.

  9. Effects of captopril in acute and chronic heart failure. Correlations with plasma levels of noradrenaline, renin, and aldosterone.

    PubMed Central

    Wenting, G J; Man in't veld, A J; Woittiez, A J; Boomsma, F; Laird-Meeter, K; Simoons, M L; Hugenholtz, P G; Schalekamp, M A

    1983-01-01

    The angiotensin-converting enzyme inhibitor, captopril, was given to 19 patients with severe heart failure. Seven patients had acute myocardial infarction and the remainder had chronic myocardial damage caused by ischaemia or valvular disease. Cardiac filling pressures were raised in all, the pulmonary capillary "wedge" pressure being 17 mmHg or more. Captopril, 50 mg orally, raised stroke volume and cardiac output, and reduced heart rate, cardiac filling pressures, systemic arterial pressure, and the plasma concentrations of aldosterone and noradrenaline. These changes were attended by clinical improvement. Decrements in cardiac filling pressures, systemic arterial pressure, and total peripheral resistance were positively correlated with pretreatment plasma renin. Long-term treatment with captopril was offered to 14 patients. Four patients with severe coronary disease died suddenly after initial clinical improvement. In nine patients haemodynamic measurements were repeated after three months. The results showed sustained effects on cardiac output and filling pressures but there was no loss of body weight. The haemodynamic effects were at least as good as with previous vasodilators. The fall in systemic arterial pressure, however, was greater with captopril. Captopril may become a valuable adjunct to the treatment of acute and chronic heart failure, but more information about its effect on coronary blood flow is required. PMID:6336940

  10. Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensin-aldosterone system

    PubMed Central

    Jin, Ze-Ning; Wei, Yong-Xiang

    2016-01-01

    Background Obstructive sleep apnea (OSA) is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin–angiotensin–aldosterone system (RAAS). We meta-analyzed the effects of OSA on plasma levels of RAAS components. Methods Full-text studies published on MEDLINE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index ≥ 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the I2 statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. Results The meta-analysis included 13 studies, of which 10 reported results on renin (n = 470 cases and controls), 7 on angiotensin II (AngII, n = 384), and 9 on aldosterone (n = 439). AngII levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI: 2.00–4.79, P < 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension (mean differences = 1.32 ng/dL, 95% CI: 0.58–2.07, P = 0.0005). Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL (95% CI: 0.88–1.82, P < 0.00001) emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. Conclusions OSA is associated with higher AngII and aldosterone levels, especially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity. PMID:27403143

  11. In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron.

    PubMed

    Nesterov, Viatcheslav; Krueger, Bettina; Bertog, Marko; Dahlmann, Anke; Palmisano, Ralf; Korbmacher, Christoph

    2016-06-01

    The epithelial sodium channel (ENaC) is rate limiting for Na(+) absorption in the aldosterone-sensitive distal nephron comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT), and the entire collecting duct. Liddle syndrome (pseudohyperaldosteronism), a severe form of salt-sensitive hypertension, is caused by gain-of-function mutations of ENaC, but the precise tubular site of increased ENaC function is unknown. In the cortical collecting duct (CCD), ENaC is known to be regulated by aldosterone. In contrast, we recently reported aldosterone-independent ENaC regulation in the early part of the aldosterone-sensitive distal nephron. Here, we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice homozygous for Liddle syndrome mutation or from wild-type control mice. Whole-cell patch-clamp recordings were used to measure amiloride-sensitive ENaC currents in nephron fragments from mice maintained on different sodium diets to vary plasma aldosterone levels. Our data indicate that in mice with Liddle syndrome, the primary site of increased Na(+) reabsorption is the DCT2/CNT. In addition, increased aldosterone responsiveness of ENaC in CNT/CCD may contribute to salt-sensitive hypertension in Liddle syndrome. Single channel properties of ENaC were similar in Liddle syndrome mutation and wild-type mice, but ENaC expression at the apical membrane was increased in Liddle syndrome mutation when compared with wild-type mice, in particular, in animals maintained on a high salt diet. Our findings highlight the importance of ENaC function and regulation in the early part of the aldosterone-sensitive distal nephron for the maintenance of sodium balance and blood pressure control. PMID:27170740

  12. Dietary Salt Intake Is a Determinant of Cardiac Changes After Treatment of Primary Aldosteronism: A Prospective Study.

    PubMed

    Catena, Cristiana; Colussi, GianLuca; Novello, Marileda; Verheyen, Nicolas D; Bertin, Nicole; Pilz, Stefan; Tomaschitz, Andreas; Sechi, Leonardo A

    2016-07-01

    Primary aldosteronism is associated with increased left ventricular (LV) mass independently of blood pressure. Previous studies suggest that elevated aldosterone causes cardiac damage only in the presence of an inappropriate salt status. We examined the relevance of dietary salt intake on cardiac changes in patients with primary aldosteronism before and after treatment. Sixty-five patients with tumoral or idiopathic primary aldosteronism were recruited at a University medical center and followed after either surgical (n=30) or medical (n=35) treatment. At baseline and 1 year after treatment, cardiac morphology and functional variables were measured by echocardiography together with duplicate 24-hour urinary sodium collections. At baseline, LV mass index was associated with urinary sodium excretion and plasma aldosterone levels. During follow-up, blood pressure (from 167/102-135/83 mm Hg; P<0.001) and LV mass index (from 50.5±13.0-44.4±8.9 g/m(2.7); P<0.001) decreased significantly with nonsignificant changes in LV geometry and functional properties. At the end of follow-up, percentage decrease in LV mass index was significantly greater in patients who had >10% reduction in urinary sodium excretion (15.0±12.5%) than in the remaining patients (5.5±9.3%; P<0.001). Changes in LV mass index induced by both surgical and medical treatment were directly and independently correlated with changes in blood pressure (β=0.419; P=0.009) and urinary sodium excretion (β=0.334; P=0.012) observed at follow-up. These findings strongly support the hypothesis that dietary salt intake has a crucial role in aldosterone-related LV changes and could contribute to cardiac damage in patients with primary aldosteronism. PMID:27245179

  13. A WEB-based telePACS using an asymmetric satellite system.

    PubMed

    Hwang, S C; Lee, M H

    2000-09-01

    We have developed a WWW-based TelePACS that can access every permitted PACS server via the Internet. Java programming techniques were used to implement the system, which can access and retrieve medical information and images through Web browsers only such as Netscape without specific tools. We also have developed a consolidator that performs as a manager to connect a conventional PACS server to a Web-based TelePACS server. We have developed the Asymmetric Satellite Data Communication System (ASDCS) as a fast communication system. The ASDCS uses a receive-only satellite link for data delivery and a terrestrial network for control communication. In conclusion, we were able to develop a cost-effective and fast PACS using Web technology. Web technology expanded the scope of use for a dedicated PACS from intrahospital to public use. PMID:11026591

  14. Development of hospital-integrated large-scale PACS in Seoul National University Hospital

    NASA Astrophysics Data System (ADS)

    Kim, JongHyo; Yeon, Kyoung M.; Han, Man Chung; Lee, Dong Hyuk; Cho, Han I.

    1997-05-01

    The SNUH has started a PACS project with three main goals: to develop a fully hospital-integrated PACS, to develop a cost effective PACS using open systems architecture, and to extend PACS' role to the advanced application such as image guided surgery, multi-media assisted education and research. In order to achieve these goals, we have designed a PACS architecture which takes advantage of client-server computing, high speed communication network, computing power of up-to-date high-end PC, and advanced image compression method. We have installed ATM based communication network in radiology department and in-patient wards, and implemented DICOM compliant acquisition modules, image storage and management servers, and high resolution display workstations based on high-end PC and Microsoft Windows 95 and Windows NT operating systems. The SNUH PACS is in partial scale operation now, and will be expanded to full scale by the end of 1998.

  15. Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma

    PubMed Central

    Nitta, E; Hirooka, K; Tenkumo, K; Fujita, T; Nishiyama, A; Nakamura, T; Itano, T; Shiraga, F

    2013-01-01

    Glaucoma is conventionally defined as a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Although glaucoma is often associated with elevated intraocular pressure (IOP), significant IOP reduction does not prevent progression of the disease in some glaucoma patients. Thus, exploring IOP-independent mechanisms of RGC loss is important. We describe chronic systemic administration of aldosterone and evaluate its effect on RGCs in rat. Aldosterone was administered via an osmotic minipump that was implanted subcutaneously into the mid-scapular region. Although systemic administration of aldosterone caused RGC loss associated with thinning of the retinal nerve fiber layer without elevated IOP, the other cell layers appeared to be unaffected. After chronic administration of aldosterone, RGC loss was observed at 2 weeks in the peripheral retina and at 4 weeks in the central retina. However, administration of mineralocorticoid receptor blocker prevented RGC loss. These results demonstrate aldosterone is a critical mediator of RGC loss that is independent of IOP. We believe this rat normal-tension glaucoma (NTG) animal model not only offers a powerful system for investigating the mechanism of neurodegeneration in NTG, but can also be used to develop therapies directed at IOP-independent mechanisms of RGC loss. PMID:23828574

  16. Myocardial pathology induced by aldosterone is dependent on non-canonical activities of G protein-coupled receptor kinases

    PubMed Central

    Cannavo, Alessandro; Liccardo, Daniela; Eguchi, Akito; Elliott, Katherine J.; Traynham, Christopher J.; Ibetti, Jessica; Eguchi, Satoru; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe; Koch, Walter J.

    2016-01-01

    Hyper-aldosteronism is associated with myocardial dysfunction including induction of cardiac fibrosis and maladaptive hypertrophy. Mechanisms of these cardiotoxicities are not fully understood. Here we show that mineralocorticoid receptor (MR) activation by aldosterone leads to pathological myocardial signalling mediated by mitochondrial G protein-coupled receptor kinase 2 (GRK2) pro-death activity and GRK5 pro-hypertrophic action. Moreover, these MR-dependent GRK2 and GRK5 non-canonical activities appear to involve cross-talk with the angiotensin II type-1 receptor (AT1R). Most importantly, we show that ventricular dysfunction caused by chronic hyper-aldosteronism in vivo is completely prevented in cardiac Grk2 knockout mice (KO) and to a lesser extent in Grk5 KO mice. However, aldosterone-induced cardiac hypertrophy is totally prevented in Grk5 KO mice. We also show human data consistent with MR activation status in heart failure influencing GRK2 levels. Therefore, our study uncovers GRKs as targets for ameliorating pathological cardiac effects associated with high-aldosterone levels. PMID:26932512

  17. Narrative Review: The Emerging Clinical Implications of the Role of Aldosterone in the Metabolic Syndrome and Resistant Hypertension

    PubMed Central

    Sowers, James R.; Whaley-Connell, Adam; Epstein, Murray

    2010-01-01

    The prevalence of obesity, diabetes, hypertension, and cardiovascular and chronic kidney disease is increasing in developed countries. Obesity, insulin resistance, and hypertension commonly cluster with other risk factors for cardiovascular and chronic kidney disease to form the metabolic syndrome. Emerging evidence supports a paradigm shift in our understanding of the renin–angiotensin–aldosterone system and in aldosterone's ability to promote insulin resistance and participate in the pathogenesis of the metabolic syndrome and resistant hypertension. Recent data suggest that excess circulating aldosterone promotes the development of both disorders by impairing insulin metabolic signaling and endothelial function, which in turn leads to insulin resistance and cardiovascular and renal structural and functional abnormalities. Indeed, hyperaldosteronism is associated with impaired pancreatic β-cell function, skeletal muscle insulin sensitivity, and elevated production of proinflammatory adipokines from adipose tissue, which results in systemic inflammation and impaired glucose tolerance. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated in part by aldosterone acting on the mineralocorticoid receptor. Although we have known that mineralocorticoid receptor blockade attenuates cardiovascular and renal injury, only recently have we learned that mineralocorticoid receptor blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation. In summary, aldosterone excess has detrimental metabolic effects that contribute to the metabolic syndrome and endothelial dysfunction, which in turn contribute to the development of resistant hypertension as well as cardiovascular disease and chronic kidney disease. PMID:19487712

  18. Hypoadiponectinemia and aldosterone excess are associated with lack of blood pressure control in subjects with resistant hypertension.

    PubMed

    de Faria, Ana P C; Demacq, Caroline; Figueiredo, Valéria N; Moraes, Carolina H; Santos, Rodrigo C; Sabbatini, Andréa R; Barbaro, Natália R; Boer-Martins, Leandro; Fontana, Vanessa; Moreno, Heitor

    2013-12-01

    Obesity, arterial stiffness and high aldosterone levels can interact to cause resistant hypertension (RHTN). Lower adiponectin (APN) levels may be significantly associated with hypertension. However, the importance of hypoadiponectinemia as a complicating factor in the lack of blood pressure (BP) control in individuals with RHTN has not been demonstrated. Ninety-six RHTN patients were classified into uncontrolled (UCRHTN, n = 44) and controlled (CRHTN, n = 52) subgroups. Their APN and aldosterone levels, office and ambulatory BP (ABPM) measurements, endothelium-dependent brachial artery responses (flow-mediated dilation (FMD)), left ventricular mass index (LVMI) and pulse wave velocity (PWV) were evaluated. The UCRHTN subgroup had increased aldosterone levels, as well as higher LVMI and PWV. In addition, lower APN levels and impaired FMD response were found in this subgroup. The brachial and ABPM pulse pressures were inversely associated with the APN levels (r = -0.45, P = 0.002; r = -0.33, P = 0.03, respectively), as were the aldosterone levels and the PWV (r = -0.38, P = 0.01; r = -0.36, P = 0.02, respectively) in UCRHTN patients. The PWV was only significantly influenced by the APN level in the UCRHTN subgroup in the multivariate regression analysis. None of the correlations mentioned above were observed in the CRHTN subgroup. Hypoadiponectinemia and high aldosterone levels may therefore be implicated in resistance to antihypertensive therapy related to arterial stiffness. PMID:23966059

  19. How can the impact of PACS on inpatient length of hospital stay be established?

    NASA Astrophysics Data System (ADS)

    Bryan, Stirling; Muris, Nicole; Keen, Justin; Weatherburn, Gwyneth C.; Buxton, Martin J.

    1994-05-01

    Many have argued that the introduction of a large-scale PACS system into a hospital will bring about reductions in the length of inpatient hospital stays. There is currently no convicting empirical evidence to support such claims. As part of the independent evaluation exercise being undertaken alongside the Hammersmith Hospital PACS implementation, an assessment is being made of the impact of PACS on length of stay for selected patient groups. This paper reports the general research methods being employed to undertake this assessment and provides some baseline results from the analysis of total hip replacement patients and total knee replacement patients treated prior to the introduction of PACS.

  20. Educational RIS/PACS simulator integrated with the HIPAA compliant auditing (HCA) toolkit

    NASA Astrophysics Data System (ADS)

    Zhou, Zheng; Liu, Brent J.; Huang, H. K.; Zhang, J.

    2005-04-01

    Health Insurance Portability and Accountability Act (HIPAA), a guideline for healthcare privacy and security, has been officially instituted recently. HIPAA mandates healthcare providers to follow its privacy and security rules, one of which is to have the ability to generate audit trails on the data access for any specific patient on demand. Although most current medical imaging systems such as PACS utilize logs to record their activities, there is a lack of formal methodology to interpret these large volumes of log data and generate HIPAA compliant auditing trails. In this paper, we present a HIPAA compliant auditing (HCA) toolkit for auditing the image data flow of PACS. The toolkit can extract pertinent auditing information from the logs of various PACS components and store the information in a centralized auditing database. The HIPAA compliant audit trails can be generated based on the database, which can also be utilized for data analysis to facilitate the dynamic monitoring of the data flow of PACS. In order to demonstrate the HCA toolkit in a PACS environment, it was integrated with the PACS Simulator, that was presented as an educational tool in 2003 and 2004 SPIE. With the integration of the HCA toolkit with the PACS simulator, users can learn HIPAA audit concepts and how to generate audit trails of image data access in PACS, as well as trace the image data flow of PACS Simulator through the toolkit.

  1. Process development and fabrication for sphere-pac fuel rods. [PWR; BWR

    SciTech Connect

    Welty, R.K.; Campbell, M.H.

    1981-06-01

    Uranium fuel rods containing sphere-pac fuel have been fabricated for in-reactor tests and demonstrations. A process for the development, qualification, and fabrication of acceptable sphere-pac fuel rods is described. Special equipment to control fuel contamination with moisture or air and the equipment layout needed for rod fabrication is described and tests for assuring the uniformity of the fuel column are discussed. Fuel retainers required for sphere-pac fuel column stability and instrumentation to measure fuel column smear density are described. Results of sphere-pac fuel rod fabrication campaigns are reviewed and recommended improvements for high throughput production are noted.

  2. Parallel Synthesis and Biological Evaluation of 837 Analogues of Procaspase-Activating Compound 1 (PAC-1)

    PubMed Central

    Hsu, Danny C.; Roth, Howard S.; West, Diana C.; Botham, Rachel C.; Novotny, Chris J.; Schmid, Steven C.; Hergenrother, Paul J.

    2011-01-01

    Procaspase-Activating Compound 1 (PAC-1) is an ortho-hydroxy N-acyl hydrazone that enhances the enzymatic activity of procaspase-3 in vitro and induces apoptosis in cancer cells. An analogue of PAC-1, called S-PAC-1, was evaluated in a veterinary clinical trial in pet dogs with lymphoma and found to have considerable potential as an anticancer agent. With the goal of identifying more potent compounds in this promising class of experimental therapeutics, a combinatorial library based on PAC-1 was created, and the compounds were evaluated for their ability to induce death of cancer cells in culture. For library construction, 31 hydrazides were condensed in parallel with 27 aldehydes to create 837 PAC-1 analogues, with an average purity of 91%. The compounds were evaluated for their ability to induce apoptosis in cancer cells, and through this work, six compounds were discovered to be substantially more potent than PAC-1 and S-PAC-1. These six hits were further evaluated for their ability to relieve zinc-mediated inhibition of procaspase-3 in vitro. In general, the newly identified hit compounds are two- to four-fold more potent than PAC-1 and S-PAC-1 in cell culture, and thus have promise as experimental therapeutics for treatment of the many cancers that have elevated expression levels of procaspase-3. PMID:22007686

  3. Development and evaluation of HIS-RIS-modality-PACS coupling: remote operation of PACS display terminal from HIS terminal in outpatient clinics

    NASA Astrophysics Data System (ADS)

    Kondoh, Hiroshi; Takeshi, Washiashi; Sasagaki, Michihiro; Nakamura, Hironobu; Inamura, Kiyonari; Matsumura, Yasushi; Takeda, Hiroshi

    1998-07-01

    Purpose: To evaluate the clinical acceptability of personal computer (PC)-based PACS in daily practice of HIS-RIS- Modality-PACS coupling. Materials And Methods: We are developing a hospital-wide PC-based PACS which uses HIS/RIS network. PACS servers are connecting to HIS-RIS network and store images on hard disks and magneto-optical disk (MOD) juke-boxes from 8 FCRs and 3 CT scanners. We developed the remote control software of PACS terminal from HIS terminal for physicians' easy operation in the out-patent clinics. We investigated the network workloads and display time in the daily work. Clinicians' opinion was recorded on a 5-point scale for image quality, response, and function. Result: The network workload is under the limitation and display time is within twenty-six seconds. The quality was acceptable in 54%. The response was acceptable in 25%. The function of PACS was acceptable in 40%. Conclusion: PC-based HIS/RIS/PACS coupling has possibility of acceptance.

  4. Mizoribine Ameliorates Renal Injury and Hypertension along with the Attenuation of Renal Caspase-1 Expression in Aldosterone-Salt-Treated Rats

    PubMed Central

    Doi, Toshiki; Doi, Shigehiro; Nakashima, Ayumu; Ueno, Toshinori; Yokoyama, Yukio; Kohno, Nobuoki; Masaki, Takao

    2014-01-01

    Aldosterone-salt treatment induces not only hypertension but also extensive inflammation that contributes to fibrosis in the rat kidney. However, the mechanism underlying aldosterone-salt-induced renal inflammation remains unclear. Pyroptosis has recently been identified as a new type of cell death that is accompanied by the activation of inflammatory cytokines. We hypothesized that aldosterone-salt treatment could induce inflammation through pyroptosis and that mizoribine, an effective immunosuppressant, would ameliorate the renal inflammation that would otherwise cause renal fibrosis. Ten days after recovery from left uninephrectomy, rats were given drinking water with 1% sodium chloride. The animals were divided into three groups (n = 7 per group): (1) vehicle infusion group, (2) aldosterone infusion group, or (3) aldosterone infusion plus oral mizoribine group. Aldosterone-salt treatment increased the expression of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 and caspase-1, and also increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. However, the oral administration of mizoribine attenuated these alterations. Furthermore, mizoribine inhibited hypertension and renal fibrosis, and also attenuated the aldosterone-induced expression of serum/glucocorticoid-regulated kinase and α epithelial sodium channel. These results suggest that caspase-1 activation plays an important role in the development of inflammation induced by aldosterone-salt treatment and that it functions as an anti-inflammatory strategy that protects against renal injury and hypertension. PMID:24695748

  5. Pacific Tracker 2 - expert system (PacTrac2-ES) behavioural assessment and intervention tool for the Pacific Kids DASH for Health (PacDASH) study.

    PubMed

    Novotny, Rachel; Nigg, Claudio; McGlone, Katalina; Renda, Gloria; Jung, Noah; Matsunaga, Masako; Karanja, Njeri

    2013-10-01

    The Pacific Tracker (PacTrac) is a computer program designed to analyse food intakes of individuals from the Pacific Region. PacTrac's original output included servings of daily intake of food groups according to the United States Food Guide Pyramid, nutrient intake recommendations, and a comparison to other national nutrition recommendations. PacTrac was made available for public use through the Hawaii Foods website (hawaiifoods.hawaii.edu). PacTrac2 is an updated and expanded version of PacTrac that uses the United States MyPyramid/MyPlate food groups in household units of daily intake, rather than servings. In addition, the PacTrac2 includes a physical activity analysis tool which quantifies minutes of physical activities and their intensities based on energy estimates from the compendium of physical activity and research on children. An Expert System (ES) - a computerised decision tree to guide behaviour change - was developed using information on self-efficacy and stage of readiness to change, and the fruit and vegetable intake and physical activity information from PacTrac2. The ES produces reports for the child, the parent/guardian, and the child's physician with child-specific strategies, targeted behavioural information, and feedback tailored to the child. PacTrac2-ES was designed for the Pacific Kids DASH for Health (PacDASH) intervention study, conducted in the Kaiser Permanente health care system in Hawaii. The intervention is based on the child's self-efficacy and stage of readiness to change intake of fruits and vegetables and physical activity, with a goal of maintaining body weight to prevent obesity. The intervention is complemented with stage-based mailers addressing the environment for physical activity and fruit and vegetable intake and newsletters that address related behaviours (sedentary activity and a DASH eating approach). This project is the first to expand the PacTrac to contain children's foods and physical activities from the Pacific

  6. Galaxy formation from deep surveys with Herschel-PACS

    NASA Astrophysics Data System (ADS)

    Lutz, D.

    2011-11-01

    Deep far-infrared photometric surveys studying galaxy evolution and the nature of the cosmic infrared background are a key strength of the Herschel mission. The PACS Evolutionary Probe (PEP) guaranteed time key program obtains deep photometric surveys of some of the key extragalactic multiwavelength fields at wavelengths between 70 and 160 μm. This contribution gives an overview of first science results, illustrating the potential of Herschel in providing calorimetric star formation rates for various high redshift galaxy populations, thus testing and superseding previous extrapolations from other wavelengths, and enabling a wide range of galaxy evolution studies.

  7. PAC studies on impurities in ZnO

    NASA Astrophysics Data System (ADS)

    Deubler, S.; Meier, J.; Schütz, R.; Witthuhn, W.

    1992-01-01

    Acceptor-donor pairs in ZnO are studied by the perturbed angular correlation spectroscopy (PAC) using radioactive 111In/ 111Cd probe atoms. In undoped ZnO the trapping of O-vacancies as well as the trapping of Zn-interstitials at the probe atoms which are located at substitutional Zn sites is observed after different sample treatments. In Cu-, Li-, and Na-doped ZnO the acceptor impurities form complexes with the In donors. The structure of these complexes is given and compared with theoretical calculations.

  8. New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension.

    PubMed

    Monge, Matthieu; Lorthioir, Aurélien; Bobrie, Guillaume; Azizi, Michel

    2013-12-01

    There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension. PMID:24222656

  9. Hypokalemic myopathy associated with primary aldosteronism and glycyrrhizine-induced pseudoaldosteronism.

    PubMed

    Ishikawa, S; Saito, T; Okada, K; Atsumi, T; Kuzuya, T

    1985-12-01

    Enzymatic and histological features of muscular disorders associated with primary aldosteronism and glycyrrhizine-induced pseudoaldosteronism were studied. Among 10 patients with primary aldosteronism and 3 patients with pseudoaldosteronism, 5 patients were admitted to our hospital because of muscular weakness. The serum potassium (K) level was 1.86 +/- 0.21 mEq/l in a myopathy group on admission, a value significantly less than that of the 2.74 +/- 0.10 mEq/l in a non-myopathy group (p less than 0.01). Serum creatine phosphokinase (CPK), glutamate-oxyloacetate transaminase (GOT), and lactate dehydrogenase (LDH) were increased in the myopathy group compared to the non-myopathy group; serum CPK was 1412.6 +/- 902.6 vs. 22.8 +/- 5.0 mU/ml, serum GOT was 186.4 +/- 75.3 vs. 24.2 +/- 5.4 mU/ml (p less than 0.05), and serum LDH was 1133.4 +/- 377.3 vs. 387.6 +/- 42.5 mU/ml (p less than 0.05) in the groups with and without myopathy. Analysis of CPK isozymes revealed that the MM type exceeded 95%. The elevated serum CPK, GOT and LDH rapidly decreased to the normal range and muscular strength completely improved within 6 to 13 days after hospitalization, when the serum K level remained below than normal. Light microscopic finding of damaged muscle showed the diffuse necrosis and vacuolization of muscle fibers. Electron microscopic study clearly demonstrated complete dissolution of myofilaments with disappearance of sarcoplasmic reticulum and T-tubules in the necrotic muscle fibers. These results indicate that muscular lesions may occur in primary aldosteronism and pseudoaldosteronism when the serum K level is decreased to below 2.0 mEq/l. This myopathy is not periodic paralysis but hypokalemic myopathy. The mechanism by which K deficiency causes muscular damage remains unknown. PMID:3914413

  10. ALDOSTERONISM AND PERIPHERAL BLOOD MONONUCLEAR CELL ACTIVATION: A NEUROENDOCRINE-IMMUNE INTERFACE

    PubMed Central

    Ahokas, Robert A.; Warrington, Kenneth J.; Gerling, Ivan C.; Sun, Yao; Wodi, Linus A.; Herring, Paula A.; Lu, Li; Bhattacharya, Syamal K.; Postlethwaite, Arnold E.; Weber, Karl T.

    2010-01-01

    Summary Aldosteronism eventuates in a proinflammatory/fibrogenic vascular phenotype of the heart and systemic organs. It remains uncertain whether peripheral blood mononuclear cells (PBMC) are activated prior to tissue invasion by monocytes/macrophages and lymphocytes as is the case for responsible pathogenic mechanisms. Uninephrectomized rats, treated for 4 wks with dietary 1%NaCl and aldosterone (0.75 μg/h, ALDOST) ± spironolactone (Spi, 100 mg/kg/daily gavage), were compared to unoperated/-untreated and uninephrectomized/salt-treated controls. Before intramural coronary vascular lesions appeared at wk 4 ALDOST, we found: 1) a reduction of PBMC cytosolic free [Mg2+]i, together with intracellular Mg2+ and Ca2+ loading while plasma and cardiac tissue Mg2+ were no different from controls; 2) increased H2O2 production by monocytes and lymphocytes together with upregulated PBMC gene expression of oxidative stress-inducible tyrosine phosphatase and Mn2+-superoxide dismutase, and the presence of 3-nitrotyrosine in CD4+ and ED-1-positive inflammatory cells that had invaded intramural coronary arteries; 3) B cell activation, including transcription of immunoglobulins, ICAM-1, CC and CXC chemokines and their receptors; 4) expansion of B lymphocyte subset and MHC Class II-expressing lymphocytes; and 5) autoreactivity with gene expression for antibodies to acetylcholine receptors and a downregulation of RT-6.2, which is in keeping with cell activation and associated with autoimmunity. Spi co-treatment attenuated the rise in intracellular Ca2+, the appearance of oxi/nitrosative stress in PBMC and invading inflammatory cells, and alterations in PBMC transcriptome. Thus, aldosteronism is associated with an activation of circulating immune cells induced by iterations in PBMC divalent cations and transduced by oxi/nitrosative stress. ALDO receptor antagonism modulates this neuroendocrine-immune interface. PMID:14576195

  11. Intracellular Molecular Differences in Aldosterone- Compared to Cortisol-Secreting Adrenal Cortical Adenomas

    PubMed Central

    Seidel, Eric; Scholl, Ute I.

    2016-01-01

    The adrenal cortex is a major site of steroid hormone production. Two hormones are of particular importance: aldosterone, which is produced in the zona glomerulosa in response to volume depletion and hyperkalemia, and cortisol, which is produced in the zona fasciculata in response to stress. In both cases, acute stimulation leads to increased hormone production, and chronic stimulation causes hyperplasia of the respective zone. Aldosterone- and cortisol-producing adenomas (APAs and CPAs) are benign tumors of the adrenal cortex that cause excess hormone production, leading to primary aldosteronism and Cushing’s syndrome, respectively. About 40% of the APAs carry somatic heterozygous gain-of-function mutations in the K+ channel KCNJ5. These mutations lead to sodium permeability, depolarization, activation of voltage-gated Ca2+ channels, and Ca2+ influx. Mutations in the Na+/K+-ATPase subunit ATP1A1 and the plasma membrane Ca2+-ATPase ATP2B3 similarly cause Na+ or H+ permeability and depolarization, whereas mutations in the Ca2+ channel CACNA1D directly lead to increased calcium influx. One in three CPAs carries a recurrent gain-of-function mutation (L206R) in the PRKACA gene, encoding the catalytic subunit of PKA. This mutation causes constitutive PKA activity by abolishing the binding of the inhibitory regulatory subunit to the catalytic subunit. These mutations activate pathways that are relatively specific to the respective cell type (glomerulosa versus fasciculata), and there is little overlap in mutation spectrum between APAs and CPAs, but co-secretion of both hormones can occur. Mutations in CTNNB1 (beta-catenin) and GNAS (Gsα) are exceptions, as they can cause both APAs and CPAs through pathways that are incompletely understood. PMID:27445978

  12. The effect of wireless LAN-based PACS device for portable imaging modalities.

    PubMed

    Lee, Hak Jong; Lee, Kyoung Ho; Hwang, Sung Il; Kim, Hyun-Chul; Seo, Eun Hee; Kim, Tae Gee; Ha, Kyoo-Seob

    2010-04-01

    The aim of this study was to develop wireless Picture Archiving and Communication System (PACS) device and to analyze its effect on image transfer from portable imaging modalities to the main PACS server. Using a laptop computer equipped with wireless local area network (LAN), the authors developed a wireless PACS device with DICOM modality worklist and DICOM storage server modules. This laptop computer could be easily fixed to portable imaging modalities such as ultrasound machines. From May to August 2007, 112 portable examinations were evaluated. Of these, 62 were done with wireless LAN-based PACS device, and 50 were done without wireless PACS device. To evaluate the impact of the wireless LAN-based PACS device on productivity and workflow, we analyzed the mean time delay and standard deviations (SD) both in cases where wireless LAN-based PACS device was used and in cases where it was not used. Statistical analysis was performed using a t test. The mean time interval from image acquisition to storage in the main PACS when the wireless LAN-based PACS device was used was 342.4 s (5 min and 42.4 s, SD = 509.2 s). When the wireless PACS was not used, the mean time interval was 2,305.5 s (38 min and 25.5 s, SD = 1,371.8 s). The mean time interval was statistically different between the two groups (t test, p < 0.001). The wireless LAN-based PACS device could help in reducing the storage intervals of images obtained by portable machines and in promoting effective and rapid treatment of patients who have undergone portable imaging examinations. PMID:19137373

  13. The past, present and future of renin–angiotensin aldosterone system inhibition☆

    PubMed Central

    Mentz, Robert J.; Bakris, George L.; Waeber, Bernard; McMurray, John J.V.; Gheorghiade, Mihai; Ruilope, Luis M.; Maggioni, Aldo P.; Swedberg, Karl; Piña, Ileana L.; Fiuzat, Mona; O’Connor, Christopher M.; Zannad, Faiez; Pitt, Bertram

    2014-01-01

    The renin–angiotensin aldosterone system (RAAS) is central to the pathogenesis of cardiovascular disease. RAAS inhibition can reduce blood pressure, prevent target organ damage in hypertension and diabetes, and improve outcomes in patients with heart failure and/or myocardial infarction. This review presents the history of RAAS inhibition including a summary of key heart failure, myocardial infarction, hypertension and atrial fibrillation trials. Recent developments in RAAS inhibition are discussed including implementation and optimization of current drug therapies. Finally, ongoing clinical trials, opportunities for future trials and issues related to the barriers and approvability of novel RAAS inhibitors are highlighted. PMID:23121914

  14. Renin-angiotensin-aldosterone-kinin system influences on diabetic vascular disease and cardiomyopathy.

    PubMed

    Flack, J M; Hamaty, M; Staffileno, B A

    1998-01-01

    Diabetes mellitus is associated with an inordinately high risk of virtually all manifestations of cardiovascular-renal disease including atherosclerotic coronary and peripheral vascular disease, congestive heart failure, stroke, nephropathy, and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the pathogenesis and clinical expression of these cardiovascular-renal sequelae. Thus, pharmacological modulation of the RAAK system is an attractive therapeutic target in diabetes mellitus. Indeed, emerging data from human clinical studies appear to confirm this thesis. PMID:9930381

  15. Specific action of the lipoxygenase pathway in mediating angiotensin II-induced aldosterone synthesis in isolated adrenal glomerulosa cells.

    PubMed Central

    Nadler, J L; Natarajan, R; Stern, N

    1987-01-01

    Angiotensin II (AII) in adrenal glomerulosa cells activates phospholipase C resulting in the formation of inositol phosphates and diacylglycerol rich in arachidonic acid (AA). Although glomerulosa cells can metabolize AA via cyclooxygenase (CO), this pathway plays little role in aldosterone synthesis. Recent evidence suggests that the lipoxygenase (LO) pathway may be important for hormonal secretion in endocrine tissues such as the islet of Langerhans. However, the capacity of the glomerulosa cell to synthesize LO products and their role in aldosterone secretion is not known. To study this, the effect of nonselective and selective LO inhibitors on AII, ACTH, and potassium-induced aldosterone secretion and LO product formation was evaluated in isolated rat glomerulosa cells. BW755c, a nonselective LO inhibitor dose dependently reduced the AII-stimulated level of aldosterone without altering AII binding (91 +/- 6 to 36 +/- 4 ng/10(6) cells/h 10(-4) M, P less than 0.001). The same effect was observed with another nonselective LO blocker, phenidone, and a more selective 12-LO inhibitor, Baicalein. In contrast U-60257, a selective 5-LO inhibitor did not change the AII-stimulated levels of aldosterone (208 +/- 11% control, AII 10(-9) M vs. 222 +/- 38%, AII + U-60257). The LO blockers action was specific for AII since neither BW755c nor phenidone altered ACTH or K+-induced aldosterone secretion. AII stimulated the formation of the 12-LO product 12-hydroxyeicosatetraenoic acid (12-HETE) as measured by ultraviolet detection and HPLC in AA loaded cells and by a specific RIA in unlabeled cells (501 +/- 50 to 990 +/- 10 pg/10(5) cells, P less than 0.02). BW755c prevented the AII-mediated rise in 12-HETE formation. In contrast, neither ACTH nor K+ increased 12-HETE levels. The addition of 12-HETE or its unstable precursor 12-HPETE (10(-9) or 10(-8) M) completely restored AII action during LO blockade. AII also produced an increase in 15-HETE formation, but the 15-LO products

  16. Bridging in vitro and in vivo metabolism and transport of faldaprevir in human using a novel cocultured human hepatocyte system, HepatoPac.

    PubMed

    Ramsden, Diane; Tweedie, Donald J; Chan, Tom S; Taub, Mitchell E; Li, Yongmei

    2014-03-01

    An increased appreciation of the importance of transporter and enzyme interplay in drug clearance and a desire to delineate these mechanisms necessitates the utilization of models that contain a full complement of enzymes and transporters at physiologically relevant activities. Additionally, the development of drugs with longer half-lives requires in vitro systems with extended incubation times that allow characterization of metabolic pathways for low-clearance drugs. A recently developed coculture hepatocyte model, HepatoPac, has been applied to meet these challenges. Faldaprevir is a drug in late-stage development for the treatment of hepatitis C. Faldaprevir is a low-clearance drug with the somewhat unique characteristic of being slowly metabolized, producing two abundant hydroxylated metabolites (M2a and M2b) in feces (∼40% of the dose) without exhibiting significant levels of circulating metabolites in humans. The human HepatoPac model was investigated to characterize the metabolism and transport of faldaprevir. In human HepatoPac cultures, M2a and M2b were the predominant metabolites formed, with extents of formation comparable to in vivo. Direct glucuronidation of faldaprevir was shown to be a minor metabolic pathway. HepatoPac studies also demonstrated that faldaprevir is concentrated in liver with active uptake by multiple transporters (including OATP1B1 and Na(+)-dependent transporters). Overall, human HepatoPac cultures provided valuable insights into the metabolism and disposition of faldaprevir in humans and demonstrated the importance of enzyme and transporter interplay in the clearance of the drug. PMID:24366904

  17. Generating an in vitro-in vivo correlation for metabolism and liver enrichment of a hepatitis C virus drug, faldaprevir, using a rat hepatocyte model (HepatoPac).

    PubMed

    Ramsden, Diane; Tweedie, Donald J; St George, Roger; Chen, Lin-Zhi; Li, Yongmei

    2014-03-01

    Hepatocytes provide an integrated model to study drug metabolism and disposition. As a result of a loss of polarity or a significant decrease in the expression of enzymes and transporters, suspended and sandwich-cultured hepatocytes have limitations in determining hepatocellular drug concentrations. Underprediction of the extent of glucuronidation is also a concern for these hepatocyte models. Faldaprevir is a hepatitis C virus protease inhibitor in late-stage development that has demonstrated significant liver enrichment in in vivo rat models based on quantitative whole-body autoradiography (QWBA) and liver-to-plasma area under-the-curve ratio. In bile duct cannulated rats, the primary biliary metabolite was a glucuronide. Owing to ethical concerns, it is difficult to assess liver enrichment in humans, and a lack of in vitro and in vivo correlation of glucuronidation has been reported. The current study was conducted to verify whether a hepatocyte model, rat HepatoPac, could overcome some of these limitations and provide validity for follow-up studies with human HepatoPac. With rat HepatoPac, liver enrichment values averaged 34-fold and were consistent with rat QWBA (26.8-fold) and in vivo data (42-fold). In contrast, liver enrichment in suspended hepatocytes was only 2.8-fold. Furthermore, the extent of faldaprevir glucuronidation in HepatoPac studies was in agreement with in vivo results, with glucuronidation as the major pathway (96%). Suspended rat hepatocytes did not generate the glucuronide or two key hydroxylated metabolites that were observed in vivo. Overall, our studies suggest that HepatoPac is a promising in vitro model to predict in vivo liver enrichment and metabolism, especially for glucuronidation, and has demonstrated superiority over suspended hepatocytes. PMID:24366905

  18. Enhanced superoxide anion production in activated peritoneal macrophages from English sole (Pleuronectes vetulus) exposed to PACs

    SciTech Connect

    Clemons, E.; Arkoosh, M.; Casillas, E.

    1995-12-31

    In fish, as in mammals, macrophages play a vital role in the destruction of infective organisms. The purpose of this study was to determine if peritoneal macrophages (M{O}s) from English sole (Pleuronectes vetulus), a marine benthic fish, have an altered ability to produce cytotoxic reactive oxygen intermediates (ROIs) after exposure to polycyclic aromatic compounds (PACs). ROIs are the principle product of M{O}s used to destroy engulfed organisms. Assay conditions, including the concentration of M{O}s, type of in vitro stimulant, tissue culture media, and incubation time were optimized to measure the production of superoxide anion (O{sub 2}{minus}), the progenitor ROI, in English sole M{O}s. English sole were injected with an organic solvent extract of a PAH-contaminated sediment, equivalent to 20g sediment/kg fish, via their dorsal lymphatic sinus, and peritoneal M{O}s were harvested on days 1, 3, 5, 7, and 14 post injection. Activated peritoneal M{O}s from English sole injected with the sediment extract produced significantly more superoxide radicals after stimulation in vitro with either opsonized zymosan (OZ) or phorbol myristate acetate (PMA) than the vehicle injected or control fish. Specifically, activated peritoneal M{O}s stimulated with PMA in vitro produced greater amounts (compared to controls) of O{sub 2}{minus} on days 7 and 14 after exposure, whereas the same cells stimulated with OZ showed heightened production only on day 7 after exposure. No differences in the basal amounts of O{sub 2}{minus} production from activated peritoneal M{O}s between the treatment groups were observed. This study shows that exposure of English sole to PACs altered production of O{sub 2}{minus} by macrophages, however, the consequence to the immunocompetence of exposed fish remains to be elucidated.

  19. RadSearch: a RIS/PACS integrated query tool

    NASA Astrophysics Data System (ADS)

    Tsao, Sinchai; Documet, Jorge; Moin, Paymann; Wang, Kevin; Liu, Brent J.

    2008-03-01

    Radiology Information Systems (RIS) contain a wealth of information that can be used for research, education, and practice management. However, the sheer amount of information available makes querying specific data difficult and time consuming. Previous work has shown that a clinical RIS database and its RIS text reports can be extracted, duplicated and indexed for searches while complying with HIPAA and IRB requirements. This project's intent is to provide a software tool, the RadSearch Toolkit, to allow intelligent indexing and parsing of RIS reports for easy yet powerful searches. In addition, the project aims to seamlessly query and retrieve associated images from the Picture Archiving and Communication System (PACS) in situations where an integrated RIS/PACS is in place - even subselecting individual series, such as in an MRI study. RadSearch's application of simple text parsing techniques to index text-based radiology reports will allow the search engine to quickly return relevant results. This powerful combination will be useful in both private practice and academic settings; administrators can easily obtain complex practice management information such as referral patterns; researchers can conduct retrospective studies with specific, multiple criteria; teaching institutions can quickly and effectively create thorough teaching files.

  20. Impact of PACS On The Organization Of Radiology Departments

    NASA Astrophysics Data System (ADS)

    Zielonka, Jason S.

    1983-05-01

    The radiologist serves as a consultant to other physicians in the practice of clinical medicine; the image obtained and the reported interpretation of that image represent the service rendered and are therefore of major importance (medically, legally and economically) to the radiologist. Because many radiology departments are organized along subspecialty lines or (in the case of a single department serving several institutions) along combined institutional and subspecialty lines, many patients may undergo diagnostic evaluation sequences in which several studies are performed and multiple simultaneous consultations may result. In the past, the lack of availability of multiple copies of the study (for multiple interested parties) has prevented the effective tailoring of subsequent examinations until the prior exam results were available; the advent of digital networks for PACS may result in a significant change in this procedure and, accordingly, in the pattern of interpretation, internal referral and organization of radiology departments. In addition, since clinicians may have access to studies directly and, possibly, prior to official interpretation, the nature of the relationship between the clinician and the radiologist may be altered by PACS.

  1. ATM-distributed PACS server for ICU application

    NASA Astrophysics Data System (ADS)

    Lee, Joseph K.; Wong, Albert W. K.; Huang, H. K.; Bazzill, Todd M.; Zhang, Jianguo; Andriole, Katherine P.

    1996-05-01

    In order for PACS (Picture Archiving and Communications System) to better serve our intensive care units (ICUs), we, at University of California, San Francisco, have designed and developed a client/server application that is specifically tailored to provide fast, reliable access to our PACS data from diagnostic viewing stations in the ICUs. One of our utmost design criteria is to ensure consistent delivery of high speed, high performance data throughput, and yet, the system should be cost-effective and render minimal maintenance. As high technology advances, we are able to utilize powerful mass storage device such as raid disk, which serves as a central image repository, to store images and data. We are also able to utilize Asynchronous Transfer Mode (ATM) technology, which is regarded as the prevailing technology for reliable, high speed data communications, to transfer large imagery data sets across systems and networks. This paper describes the design and mechanism of how ICU viewing stations take advantages of sharing a high performance raid disk, and ATM technology in data transfer for timely delivery of images in a clinical setting.

  2. Integration of content-based image retrieval system with PACS

    NASA Astrophysics Data System (ADS)

    Ghanem, Ahmed M.; Rasmy, M. Emad M.; Kadah, Yasser M.

    2001-08-01

    Content-based image retrieval (CBIR) provides a flexible means of searching a digital image library based on the description of the desired image. In this paper, we integrate CBIR, RIS, and HIS in PACS to allow retrieving images of similar features. Once the system finds the related images, the embedded CBIR retrieves the radiological reports and medical records of the output images, which can be used to increase diagnostic accuracy. The CBIR system is implemented on a separate server based on multi-resolution image matching. To reduce the retrieval loading on the server and network shanks, a procedure to use copies of images that are temporarily located in some workstations in the PACS is applied. These copies are stored on a temporary database space created on the different workstations. A new image retrieval management server contains image IDs in the database and the IP addresses of the workstations containing temporary image copies. Data on the management server are continuously updated with each addition or retrieval operation. When a display workstation needs a specific image, it sends a request with the required image ID to the management server, which in turn replies with the IP of the workstation containing the inquired image ID.

  3. Automatic programming of binary morphological machines by PAC learning

    NASA Astrophysics Data System (ADS)

    Barrera, Junior; Tomita, Nina S.; Correa da Silva, Flavio S.; Terada, Routo

    1995-08-01

    Binary image analysis problems can be solved by set operators implemented as programs for a binary morphological machine (BMM). This is a very general and powerful approach to solve this type of problem. However, the design of these programs is not a task manageable by nonexperts on mathematical morphology. In order to overcome this difficulty we have worked on tools that help users describe their goals at higher levels of abstraction and to translate them into BMM programs. Some of these tools are based on the representation of the goals of the user as a collection of input-output pairs of images and the estimation of the target operator from these data. PAC learning is a well suited methodology for this task, since in this theory 'concepts' are represented as Boolean functions that are equivalent to set operators. In order to apply this technique in practice we must have efficient learning algorithms. In this paper we introduce two PAC learning algorithms, both are based on the minimal representation of Boolean functions, which has a straightforward translation to the canonical decomposition of set operators. The first algorithm is based on the classical Quine-McCluskey algorithm for the simplification of Boolean functions, and the second one is based on a new idea for the construction of Boolean functions: the incremental splitting of intervals. We also present a comparative complexity analysis of the two algorithms. Finally, we give some application examples.

  4. Predicting PACS Colt Sole Requirements From Radiologists' Reading Habits

    NASA Astrophysics Data System (ADS)

    Rogers, Diane C.; Johnston, R. Eugene; Brenton, Brad; Staab, E. V.; Thompson, Bob; Perry, J. R.

    1985-09-01

    In order to define and direct our research efforts toward the development of an effective and efficient PACS display console,we have begun a series of observational studies of radiologists' reading patterns of CT images displayed on film. Preliminary findings indicate that a three-stage process occurs. In each stage specific behaviors have been identified, and some preliminary quantitative aspects have been determined. Depending on the stage when they occur, individual behaviors may serve multiple and/or different functions. We suggest that while certain functions may be necessary, certain specific behaviors might better be replaced by other behaviors. It appears that the manner in which radiologists read hardcopy is, in part, due to habit and, in part, due to limitations imposed by the image display modality. These habits may not necessarily be efficient or necessary with an electronic display. Radiologists have accepted the constraints imposed on them by film, and developed reading habits to operate within these constraints. Guided by our preliminary data, we are developing our concepts of what are the essential requirements of a PACS display.

  5. ACS/WFC Revised Geometric Distortion for DrizzlePac

    NASA Astrophysics Data System (ADS)

    Kozhurina-Platais, V.; Borncamp, D.; Anderson, J.; Grogin, N.; Hack, M.

    2015-06-01

    The goal of the ACS/WFC astrometric calibration for DrizzlePac is to provide a coordinate system free of distortion to a precision level of ˜0.1 pixels (˜ 5mas). The astrometric calibration of ACS/WFC is based on the astrometric standard field in the vicinity of globular cluster 47 Tuc. We used a polynomial model to derive the geometric distortion in the WFC channel relative to the distortion-free coordinates, which now accounts for proper motions of stars in the astrometric field. A new and straightforward representation of time-dependent distortion in the linear terms is now implemented in the IDCTAB reference file and in the STScI software DrizzlePac to obtain simultaneously the ACS/WFC geometric distortion and its time-dependent correction. As a result, the geometric distortion can be corrected down to a precision level of 0.02 pix (1mas), which allows now for improvement of the alignment and registration of the ACS/WFC images with accuracy of ˜0.05 pix (2.5mas) or better.

  6. Planning, expectation, and image evaluation for PACS at the University of Iowa Hospitals and Clinics

    NASA Astrophysics Data System (ADS)

    Franken, E. A., Jr.; Smith, Wilbur L.; Berbaum, Kevin S.; Owen, David A.; Hilsenrath, Peter

    1990-08-01

    Our strategy in studying PACS is to evaluate its clinical implementation working with equipment supplied by an established manufacturer. Fiscal and personnel resources required to design and integrate the hardware components and operational software to develop a functional PACS precluded a bottom up development approach at our institution. Imaging equipment vendors possess more abundant design development resources for this task and therefore can support a more rapid development of the initial components of PACS. For this reason we have chosen to serve as a beta test site to study the viability of the basic PACS components in a clinical setting. Our efforts primarily focus on: (1) image quality; (2) cost effectiveness; (3) PACS/HIS/RIS integration; (4) equipment and software reliability; and (5) overall system performance. The results of our studies are shared with the vendor for future PACS development and refi nement. To attain our investigational goals we have formed an interdisciplinary team of Radiologists, Perceptual Psychologist, Economist, Electrical and Industrial Engineers, Hospital Information System personnel and key departmental administrative staff. For several reasons Pediatric Radiology was targeted as the initial area for our PACS study: a small area representative of the overall operation,tight operational controls and willingness of physicians. We used a step-wise approach, the first step being the installation of PACS exclusively within the physical confines of Pediatric Radiology.

  7. Experience report: a multivendor ultrasounds mini-PACs--engineering and clinical issues

    NASA Astrophysics Data System (ADS)

    Horii, Steven C.; Coleman, Beverly; Mezrich, Reuben S.; Feingold, Eric R.; Nisenbaum, Harvey; Arger, Peter H.; Langer, Jill; Rowling, Susan; Jacobs, Jill; Black, Mark H.; Daniels, James, II

    1997-05-01

    The authors have been operating an ultrasound miniPACS for approximately two years. In the last six months, the system was more than doubled in size with inclusion of a teleradiology component and connection to PACS hardware from other vendors. This paper presents the engineering, operational, and clinical challenges posed by this integration and the logistical and systems approaches to meeting those challenges.

  8. Properties And Coefficient Program For The Calculation Of Thermodynamic Data (PAC2)

    NASA Technical Reports Server (NTRS)

    Mcbride, B. J.

    1989-01-01

    Program calculates ideal gas thermodynamic properties for any species for which molecular constant data available, and offers user choice of methodologies for performing thermodynamic calculations. PAC2 updated to PAC4. Improvements include increased user friendliness and ability to extrapolate thermodynamic properties for gases to higher temperatures using Wilhoit's formulas.

  9. Thermal-hydraulic/heat transfer code development for sphere-pac-fueled LMFBRs. [COBRA-3SP code

    SciTech Connect

    Morris, D.G.

    1980-06-01

    Sphere-pac fuel has received much attention recently in light of the development of proliferation-resistant fuel cycles for the Fast Breeder Reactor Program in the United States. However, for sphere-pac fuel to be a viable alternative to conventional pellet fuel, a means to analyze the thermal behavior of sphere-pac-fueled pin bundles is needed. To meet this need, a thermal-hydraulic/heat transfer computer code has been developed for sphere-pac-fueled fast breeder reactors. The code, COBRA-3SP, is a modified version of COBRA-3M incorporating a three-region sphere-pac fuel pin model which permits fuel restructuring. With COBRA-3SP, steady-state and transient analysis of sphere-pac-fueled pin bundles is possible. The validity of the sphere-pac fuel pin model has been verified using experimental results of irradiated sphere-pac fuel.

  10. Altered Circadian Food Anticipatory Activity Rhythms in PACAP Receptor 1 (PAC1) Deficient Mice

    PubMed Central

    Hannibal, Jens; Georg, Birgitte; Fahrenkrug, Jan

    2016-01-01

    Light signals from intrinsically photosensitive retinal ganglion cells (ipRGCs) entrain the circadian clock and regulate negative masking. Two neurotransmitters, glutamate and Pituitary Adenylate Cyclase Activating Polypeptide (PACAP), found in the ipRGCs transmit light signals to the brain via glutamate receptors and the specific PACAP type 1 (PAC1) receptor. Light entrainment occurs during the twilight zones and has little effect on clock phase during daytime. When nocturnal animals have access to food only for a few hours during the resting phase at daytime, they adapt behavior to the restricted feeding (RF) paradigm and show food anticipatory activity (FAA). A recent study in mice and rats demonstrating that light regulates FAA prompted us to investigate the role of PACAP/PAC1 signaling in the light mediated regulation of FAA. PAC1 receptor knock out (PAC1-/-) and wild type (PAC1+/+) mice placed in running wheels were examined in a full photoperiod (FPP) of 12:12 h light/dark (LD) and a skeleton photoperiod (SPP) 1:11:1:11 h L:DD:L:DD at 300 and 10 lux light intensity. Both PAC1-/- mice and PAC1+/+ littermates entrained to FPP and SPP at both light intensities. However, when placed in RF with access to food for 4–5 h during the subjective day, a significant change in behavior was observed in PAC1-/- mice compared to PAC1+/+ mice. While PAC1-/- mice showed similar FAA as PAC1+/+ animals in FPP at 300 lux, PAC1-/- mice demonstrated an advanced onset of FAA with a nearly 3-fold increase in amplitude compared to PAC1+/+ mice when placed in SPP at 300 lux. The same pattern of FAA was observed at 10 lux during both FPP and SPP. The present study indicates a role of PACAP/PAC1 signaling during light regulated FAA. Most likely, PACAP found in ipRGCs mediating non-image forming light information to the brain is involved. PMID:26757053

  11. Altered Circadian Food Anticipatory Activity Rhythms in PACAP Receptor 1 (PAC1) Deficient Mice.

    PubMed

    Hannibal, Jens; Georg, Birgitte; Fahrenkrug, Jan

    2016-01-01

    Light signals from intrinsically photosensitive retinal ganglion cells (ipRGCs) entrain the circadian clock and regulate negative masking. Two neurotransmitters, glutamate and Pituitary Adenylate Cyclase Activating Polypeptide (PACAP), found in the ipRGCs transmit light signals to the brain via glutamate receptors and the specific PACAP type 1 (PAC1) receptor. Light entrainment occurs during the twilight zones and has little effect on clock phase during daytime. When nocturnal animals have access to food only for a few hours during the resting phase at daytime, they adapt behavior to the restricted feeding (RF) paradigm and show food anticipatory activity (FAA). A recent study in mice and rats demonstrating that light regulates FAA prompted us to investigate the role of PACAP/PAC1 signaling in the light mediated regulation of FAA. PAC1 receptor knock out (PAC1-/-) and wild type (PAC1+/+) mice placed in running wheels were examined in a full photoperiod (FPP) of 12:12 h light/dark (LD) and a skeleton photoperiod (SPP) 1:11:1:11 h L:DD:L:DD at 300 and 10 lux light intensity. Both PAC1-/- mice and PAC1+/+ littermates entrained to FPP and SPP at both light intensities. However, when placed in RF with access to food for 4-5 h during the subjective day, a significant change in behavior was observed in PAC1-/- mice compared to PAC1+/+ mice. While PAC1-/- mice showed similar FAA as PAC1+/+ animals in FPP at 300 lux, PAC1-/- mice demonstrated an advanced onset of FAA with a nearly 3-fold increase in amplitude compared to PAC1+/+ mice when placed in SPP at 300 lux. The same pattern of FAA was observed at 10 lux during both FPP and SPP. The present study indicates a role of PACAP/PAC1 signaling during light regulated FAA. Most likely, PACAP found in ipRGCs mediating non-image forming light information to the brain is involved. PMID:26757053

  12. Measurement of Aerosol and Cloud Particles with PACS and HARP Hyperangular Imaging Polarimeters

    NASA Astrophysics Data System (ADS)

    Martins, J.; Fernandez-Borda, R.; Remer, L. A.; Sparr, L.; Buczkowski, S.; Munchak, L. A.

    2013-12-01

    PACS is new hyper-angular imaging polarimeter for aeorosol and cloud measurerents designed to meet the requirements of the proposed ACE decadal survey mission. The full PACS system consists of three wide field of view (110deg cross track) telescopes covering the UV, VNIR, and SWIR spectral ranges with angular coverage between +55 deg forward to -55deg backwards. The angular density can be selected to cover up to 100 different viewing angles at selected wavelengths. PACS_VNIR is a prototype airborne instrument designed to demonstrate PACS capability by deploying just one of the three wavelength modules of the full PACS. With wavelengths at 470, 550, 675, 760 and 875nm, PACS_VNIR flew for the first time during the PODEX experiment in January/February 2013 aboard the NASA ER-2 aircraft. PACS SWIR (1.64, 1.88, 2.1, and 2.25um) is currently under construction and should be operational in the lab by Fall/2013. PACS_ UV has been fully designed, but is not yet under construction. During the PODEX flights PACS_VNIR collected data for aerosol and clouds over variable surface types including, water, vegetation, urban areas, and snow. The data is currently being calibrated, geolocated and prepared for the inversion of geophysical parameters including water cloud size distribution and aerosol microphysical parameters. The large density of angles in PACS allows for the characterization of cloudbow features in relatively high spatial resolution in a pixel to pixel basis. This avoids the need for assumptions of cloud homogeneity over any distance. The hyperangle capability also allows detailed observation of cloud ice particles, surface characterization, and optimum selection of the number of angles desired for aerosol retrievals. The aerosol and cloud retrieval algorithms under development for the retrieval of particle microphysical properties from the PACS data will be discussed in this presentation. As an extension of the PACS concept we are currently developing the HARP (Hyper

  13. Fault tolerance techniques to assure data integrity in high-volume PACS image archives

    NASA Astrophysics Data System (ADS)

    He, Yutao; Huang, Lu J.; Valentino, Daniel J.; Wingate, W. Keith; Avizienis, Algirdas

    1995-05-01

    Picture archiving and communication systems (PACS) perform the systematic acquisition, archiving, and presentation of large quantities of radiological image and text data. In the UCLA Radiology PACS, for example, the volume of image data archived currently exceeds 2500 gigabytes. Furthermore, the distributed heterogeneous PACS is expected to have near real-time response, be continuously available, and assure the integrity and privacy of patient data. The off-the-shelf subsystems that compose the current PACS cannot meet these expectations; therefore fault tolerance techniques had to be incorporated into the system. This paper is to report our first-step efforts towards the goal and is organized as follows: First we discuss data integrity and identify fault classes under the PACS operational environment, then we describe auditing and accounting schemes developed for error-detection and analyze operational data collected. Finally, we outline plans for future research.

  14. Picture Archiving and Communication System (PACS) implementation, integration & benefits in an integrated health system.

    PubMed

    Mansoori, Bahar; Erhard, Karen K; Sunshine, Jeffrey L

    2012-02-01

    The availability of the Picture Archiving and Communication System (PACS) has revolutionized the practice of radiology in the past two decades and has shown to eventually increase productivity in radiology and medicine. PACS implementation and integration may bring along numerous unexpected issues, particularly in a large-scale enterprise. To achieve a successful PACS implementation, identifying the critical success and failure factors is essential. This article provides an overview of the process of implementing and integrating PACS in a comprehensive health system comprising an academic core hospital and numerous community hospitals. Important issues are addressed, touching all stages from planning to operation and training. The impact of an enterprise-wide radiology information system and PACS at the academic medical center (four specialty hospitals), in six additional community hospitals, and in all associated outpatient clinics as well as the implications on the productivity and efficiency of the entire enterprise are presented. PMID:22212425

  15. PACS--and beyond. A journey to the digital promised land.

    PubMed

    Viau, Mark A

    2004-01-01

    A successful picture archiving and communication system (PACS) integration depends on much more than the technology; marketing also plays a large role. This fact was evident from the inception of the PACS project at Boca Raton Community Hospital (BRCH). Strategic and effective marketing efforts should target technologists, nurses, physicians (including radiologists), administration, and colleagues in other departments. The buy-in of these users is critical to the project's success. BRCH's first marketing effort took place during the initial PACS presentation made to the hospital's board of directors. Once approval was given and a 6-month implementation target was set, a strategic and effective marketing/education plan commenced. Posters, brochures, t-shirts, and promotional items were distributed in a coordinated effort to target hospital staff and referring physician offices. Through its "Got PACS?" branding and other identity materials, BRCH implemented a marketing plan that informed, educated, and engaged PACS users. PMID:15259686

  16. Transition from partial to full PACS at a 450,000 exams/year hospital

    NASA Astrophysics Data System (ADS)

    Ro, Duk-Woo; Byun, Hong Sik; Choo, In W.; Kim, Bo K.; Lim, Jae H.

    1997-05-01

    The purpose of this paper is to describe the transition of a 1,100 beds tertiary hospital from 50 percent softcopy operation to full PACS operation. For the past 2 years, radiologists and clinicians have been using PACS to provide softcopy services to the outpatient clinics and inpatient wards of orthopedics surgery, neurosurgery and neurology as well as emergency room, surgical intensive care unit, medical intensive unit, pediatrics intensive care unit and neonatal intensive care unit. The examinations requested by these departments account for about 50 percent of hospital's radiological exams. In September 1996, we began the second phase of PACS implementation and installed additional workstations in the remaining wards and clinics, interfaced to PACS additional imaging modalities, and increased the capacity of both the image server and optical juke boxes. As of January 1997, we are in the final phase of moving away from conventional film system to full PACS operation.

  17. Derivatives of Procaspase-Activating Compound 1 (PAC-1) and Anticancer Activities

    PubMed Central

    Roth, Howard S.; Hergenrother, Paul J.

    2016-01-01

    PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an in-depth discussion of four derivatives on which extensive studies have been performed. PMID:26630918

  18. Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.

    PubMed

    Roth, Howard S; Hergenrother, Paul J

    2016-01-01

    PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an indepth discussion of four derivatives on which extensive studies have been performed. PMID:26630918

  19. Aldosterone antagonism fails to attenuate age-associated left ventricular fibrosis.

    PubMed

    Hwang, Hyun Seok; Cirrincione, Georgina; Thomas, D Paul; McCormick, Richard J; Boluyt, Marvin O

    2007-04-01

    Collagen accumulates disproportionately in cardiac remodeling induced by hypertension and associated with advancing age. Spironolactone (Spiro), an aldosterone antagonist, attenuates the accumulation of collagen induced by hypertension. It was hypothesized that Spiro would attenuate the age-associated increase in percent collagen in the heart. Female Fisher 344 rats at 3 months (Y), 12 months (M), and 21 months (O) of age were treated with Spiro (30 mg/kg/d) or vehicle (Veh) for 2 months, yielding six groups: Y-Veh, Y-Spiro, M-Veh, M-Spiro, O-Veh, and O-Spiro. Hearts were harvested for immunoblotting, RNA blotting, and biochemical analysis. Percent collagen in the left ventricle and septum was greatest in the oldest rats. Spiro did not significantly attenuate the age-associated increase in collagen fraction or the age-associated increases in expression of atrial natriuretic factor and beta-myosin heavy chain messenger RNA. Chronic aldosterone antagonism does not attenuate the age-associated increase in collagen fraction in the female Fisher 344 rat heart. PMID:17452731

  20. Harvest and primary culture of the murine aldosterone-sensitive distal nephron

    PubMed Central

    Labarca, Mariana; Nizar, Jonathan M.; Walczak, Elisabeth M.; Dong, Wuxing; Pao, Alan C.

    2015-01-01

    The aldosterone-sensitive distal nephron (ASDN) exhibits axial heterogeneity in structure and function from the distal convoluted tubule to the medullary collecting duct. Ion and water transport is primarily divided between the cortex and medulla of the ASDN, respectively. Transcellular transport in this segment is highly regulated in health and disease and is integrated across different cell types. We currently lack an inexpensive, high-yield, and tractable technique to harvest and culture cells for the study of gene expression and physiological properties of mouse cortical ASDN. To address this need, we harvested tubules bound to Dolichos biflorus agglutinin lectin-coated magnetic beads from the kidney cortex and characterized these cell preparations. We determined that these cells are enriched for markers of distal convoluted tubule, connecting tubule, and cortical collecting duct, including principal and intercalated cells. In primary culture, these cells develop polarized monolayers with high resistance (1,000-1,500 Ω * cm2) and maintain expression and activity of key channels. These cells demonstrate an amiloride-sensitive short-circuit current that can be enhanced with aldosterone and maintain measurable potassium and anion secretion. Our method can be easily adopted to study the biology of the ASDN and to investigate phenotypic differences between wild-type and transgenic mouse models. PMID:25810438

  1. Renal Resistive Index Predicts Postoperative Blood Pressure Outcome in Primary Aldosteronism.

    PubMed

    Iwakura, Yoshitsugu; Ito, Sadayoshi; Morimoto, Ryo; Kudo, Masataka; Ono, Yoshikiyo; Nezu, Masahiro; Takase, Kei; Seiji, Kazumasa; Ishidoya, Shigeto; Arai, Yoichi; Funamizu, Yasuharu; Miki, Takashi; Nakamura, Yasuhiro; Sasano, Hironobu; Satoh, Fumitoshi

    2016-03-01

    The renal resistive index (RI) calculated by Doppler ultrasonography has been reported to be correlated with renal structural changes and outcomes in patients with essential hypertension or renal disease. However, little is known about this index in primary aldosteronism. In this prospective study, we examined the utility of this index to predict blood pressure (BP) outcome after adrenalectomy in patients with primary aldosteronism. We studied 94 patients with histopathologically proven aldosteronoma who underwent surgery. Parameters on renal function, including renal flow indices, were examined and followed up for 12 months postoperatively. The renal RI of the main, hilum, and interlobar arteries was significantly higher in patients with aldosteronoma compared with 100 control patients. BP, estimated glomerular filtration rate, and urinary albumin excretion significantly decreased after adrenalectomy. The resistive indices of all compartment arteries were significantly reduced 1 month after adrenalectomy and remained stable for 12 months. Patients whose interlobar RI was in the highest tertile at baseline had higher systolic BP after adrenalectomy than those whose RI was in the lowest tertile. Logistic regression analysis demonstrated that the RI of the interlobar and hilum arteries could be an independent predictive marker for intractable hypertension (systolic BP ≥140 mm Hg, increased BP, taking ≥3 antihypertensive agents, or increased number of agents) even after adrenalectomy. Therefore, in patients with aldosteronoma, the renal RI indicates partially reversible renal hemodynamics and renal structural damages that would influence postoperative BP outcome. PMID:26865201

  2. Renin-angiotensin-aldosterone system blockade in chronic kidney disease: current strategies and a look ahead.

    PubMed

    Viazzi, Francesca; Bonino, Barbara; Cappadona, Francesca; Pontremoli, Roberto

    2016-08-01

    The Renin-Angiotensin-Aldosterone System (RAAS) is profoundly involved in the pathogenesis of renal and cardiovascular organ damage, and has been the preferred therapeutic target for renal protection for over 30 years. Monotherapy with either an Angiotensin Converting Enzime Inhibitor (ACE-I) or an Angiotensin Receptor Blocker (ARB), together with optimal blood pressure control, remains the mainstay treatment for retarding the progression toward end-stage renal disease. Combining ACE-Is and ARBs, or either one with an Aldosterone Receptor Antagonist (ARA), has been shown to provide greater albuminuria reduction, and to possibly improve renal outcome, but at an increased risk of potentially severe side effects. Moreover, combination therapy has failed to provide additional cardiovascular protection, and large prospective trials on hard renal endpoints are lacking. Therefore this treatment should, at present, be limited to selected patients with residual proteinuria and high renal risk. Future studies with novel agents, which directly act on the RAAS at multiple levels or have a more favourable side effect profile, are greatly needed to further explore and define the potential for and the limitations of profound pharmacologic RAAS inhibition. PMID:26984204

  3. Aldosterone-secreting adrenal cortical carcinoma. A case report and review of the literature.

    PubMed

    Griffin, Adrienne Carruth; Kelz, Rachel; LiVolsi, Virginia A

    2014-09-01

    Adrenal cortical carcinomas (ACC) are rare, typically aggressive malignant neoplasms with a reported incidence of 1-2 cases per 1 million population and account for 0.05-0.2 % of all malignancies. The majority of these tumors are functional with approximately 60 % of patients experiencing endocrine symptomatology typically characterized by Cushing's syndrome (40 %) or a mixed hormonal picture of Cushing syndrome seen in association with virilization. Rarely, patients present with a pure hormonal syndrome of feminization or hyperaldosteronism, 6 and 2.5 %, respectively. We report a case of a 76-year-old woman presenting with recently diagnosed hypertension secondary to primary hyperaldosteronism. The patient underwent laparoscopic converted to an open adrenalectomy and a diagnosis of adrenocortical carcinoma (aldosteronoma clinical) was rendered. This case and review of the literature highlight that while rare, aldosterone-secreting adrenal cortical carcinomas may occur. In this case report, we discuss the clinical presentation, pathologic findings, and review the literature for adrenal cortical carcinomas and aldosterone-secreting adrenal cortical carcinomas. PMID:24682757

  4. Aldosterone and angiotensin II induce protein aggregation in renal proximal tubules

    PubMed Central

    Cheema, Muhammad U; Poulsen, Ebbe T; Enghild, Jan J; Hoorn, Ewout; Fenton, Robert A; Praetorius, Jeppe

    2013-01-01

    Renal tubules are highly active transporting epithelia and are at risk of protein aggregation due to high protein turnover and/or oxidative stress. We hypothesized that the risk of aggregation was increased upon hormone stimulation and assessed the state of the intracellular protein degradation systems in the kidney from control rats and rats receiving aldosterone or angiotensin II treatment for 7 days. Control rats formed both aggresomes and autophagosomes specifically in the proximal tubules, indicating a need for these structures even under baseline conditions. Fluorescence sorted aggresomes contained various rat keratins known to be expressed in renal tubules as assessed by protein mass spectrometry. Aldosterone administration increased the abundance of the proximal tubular aggresomal protein keratin 5, the ribosomal protein RPL27, ataxin-3, and the chaperone heat shock protein 70-4 with no apparent change in the aggresome–autophagosome markers. Angiotensin II induced aggregation of RPL27 specifically in proximal tubules, again without apparent change in antiaggregating proteins or the aggresome–autophagosome markers. Albumin endocytosis was unaffected by the hormone administration. Taken together, we find that the renal proximal tubules display aggresome formation and autophagy. Despite an increase in aggregation-prone protein load in these tubules during hormone treatment, renal proximal tubules seem to have sufficient capacity for removing protein aggregates from the cells. PMID:24303148

  5. ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions.

    PubMed

    Mulatero, P; Schiavi, F; Williams, T A; Monticone, S; Barbon, G; Opocher, G; Fallo, F

    2016-06-01

    Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia is the most common subtype of primary aldosteronism (PA). The pathogenesis of IHA is still unknown, but the bilateral disease suggests a potential predisposing genetic alteration. Heterozygous germline mutations of armadillo repeat containing 5 (ARMC5) have been shown to be associated with hypercortisolism due to sporadic primary bilateral macronodular adrenal hyperplasia and are also observed in African-American PA patients. We investigated the presence of germline ARMC5 mutations in a group of PA patients who had bilateral computed tomography-detectable adrenal alterations. We sequenced the entire coding region of ARMC5 and all intron/exon boundaries in 39 patients (37 Caucasians and 2 black Africans) with confirmed PA (8 unilateral, 27 bilateral and 4 undetermined subtype) and bilateral adrenal lesions. We identified 11 common variants, 5 rare variants with a minor allele frequency <1% and 2 new variants not previously reported in public databases. We did not detect by in silico analysis any ARMC5 sequence variations that were predicted to alter protein function. In conclusion, ARMC5 mutations are not present in a fairly large series of Caucasian patients with PA associated to bilateral adrenal disease. Further studies are required to definitively clarify the role of ARMC5 in the pathogenesis of adrenal nodules and aldosterone excess in patients with PA. PMID:26446392

  6. DICOM-compliant PACS with CD-based image archival

    NASA Astrophysics Data System (ADS)

    Cox, Robert D.; Henri, Christopher J.; Rubin, Richard K.; Bret, Patrice M.

    1998-07-01

    This paper describes the design and implementation of a low- cost PACS conforming to the DICOM 3.0 standard. The goal was to provide an efficient image archival and management solution on a heterogeneous hospital network as a basis for filmless radiology. The system follows a distributed, client/server model and was implemented at a fraction of the cost of a commercial PACS. It provides reliable archiving on recordable CD and allows access to digital images throughout the hospital and on the Internet. Dedicated servers have been designed for short-term storage, CD-based archival, data retrieval and remote data access or teleradiology. The short-term storage devices provide DICOM storage and query/retrieve services to scanners and workstations and approximately twelve weeks of 'on-line' image data. The CD-based archival and data retrieval processes are fully automated with the exception of CD loading and unloading. The system employs lossless compression on both short- and long-term storage devices. All servers communicate via the DICOM protocol in conjunction with both local and 'master' SQL-patient databases. Records are transferred from the local to the master database independently, ensuring that storage devices will still function if the master database server cannot be reached. The system features rules-based work-flow management and WWW servers to provide multi-platform remote data access. The WWW server system is distributed on the storage, retrieval and teleradiology servers allowing viewing of locally stored image data directly in a WWW browser without the need for data transfer to a central WWW server. An independent system monitors disk usage, processes, network and CPU load on each server and reports errors to the image management team via email. The PACS was implemented using a combination of off-the-shelf hardware, freely available software and applications developed in-house. The system has enabled filmless operation in CT, MR and ultrasound within

  7. Suppression of adrenal βarrestin1-dependent aldosterone production by ARBs: head-to-head comparison

    PubMed Central

    Dabul, Samalia; Bathgate-Siryk, Ashley; Valero, Thairy Reyes; Jafferjee, Malika; Sturchler, Emmanuel; McDonald, Patricia; Koch, Walter J.; Lymperopoulos, Anastasios

    2015-01-01

    The known angiotensin II (AngII) physiological effect of aldosterone synthesis and secretion is mediated by either Gq/11 proteins or βarrestin1 (βarr1), both of which can couple to its type 1 receptors (AT1Rs), present in adrenocortical zona glomerulosa (AZG) cell membranes. In the present study, we examined the relative potencies of all the currently used in the clinic AT1R antagonist drugs (angiotensin receptor blockers, ARBs, or sartans) at preventing activation of these two signaling mediators (G proteins and βarrs) at the AngII-bound AT1R and, consequently, at suppression of aldosterone in vitro. All ARBs were found to be potent inhibitors of G protein activation at the AT1R. However, candesartan and valsartan were the most potent at blocking AngII-induced βarr activation at this receptor, among the tetrazolo-biphenyl-methyl derivatives, translating into excellent efficacies at aldosterone suppression in H295R cells. Conversely, irbesartan and losartan were largely G protein-selective inhibitors at the AT1R, with very low potency towards βarr inhibition. As a result, they were very weak suppressors of βarr1-dependent aldosterone production in H295R cells. These findings provide important pharmacological insights into the drug class of ARBs and medicinal chemistry insights for future drug development in the field of AngII antagonism. PMID:25631300

  8. [The effect of dopaminergic stimulation and inhibition on the urinary excretion of aldosterone and kallikrein in spontaneously hypertensive rats].