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Sample records for losartan decreases vasopressin-mediated

  1. Losartan

    MedlinePlus

    ... may not decrease the risk of stroke in African Americans who have these conditions. This medication is also ... as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this ...

  2. Losartan decreases cardiac muscle fibrosis and improves cardiac function in dystrophin-deficient mdx mice.

    PubMed

    Spurney, Christopher F; Sali, Arpana; Guerron, Alfredo D; Iantorno, Micaela; Yu, Qing; Gordish-Dressman, Heather; Rayavarapu, Sree; van der Meulen, Jack; Hoffman, Eric P; Nagaraju, Kanneboyina

    2011-03-01

    Recent studies showed that chronic administration of losartan, an angiotensin II type I receptor antagonist, improved skeletal muscle function in dystrophin-deficient mdx mice. In this study, C57BL/10ScSn-Dmd(mdx)/J female mice were either untreated or treated with losartan (n = 15) in the drinking water at a dose of 600 mg/L over a 6-month period. Cardiac function was assessed via in vivo high frequency echocardiography and skeletal muscle function was assessed using grip strength testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed using picrosirius red staining and Image J analysis. Gene expression was evaluated using real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was significantly decreased in untreated (26.9% ± 3.5%) mice compared to losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was significantly reduced in losartan-treated mice (56 ± 6 vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was significantly reduced in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscles compared to untreated mdx mice. There were no significant differences in skeletal muscle function between treated and untreated groups. Chronic treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice. PMID:21304057

  3. Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

    PubMed

    Hernández-Fonseca, Juan Pablo; Durán, Anyelo; Valero, Nereida; Mosquera, Jesús

    2015-11-01

    The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1β production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1β production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection. PMID:26321474

  4. Effect of dietary fibers on losartan uptake and transport in Caco-2 cells.

    PubMed

    Iwazaki, Ayano; Takahashi, Naho; Miyake, Reiko; Hiroshima, Yuka; Abe, Mariko; Yasui, Airi; Imai, Kimie

    2016-05-01

    The objective of this study was to assess the effect of dietary fibers on the transport of losartan, an angiotensin II type 1 receptor blocker, in small intestinal cells. Using Caco-2 cells in vitro, losartan uptake and transport were evaluated in the presence of various fibers (cellulose, chitosan, sodium alginate and glucomannan). Dietary fibers caused a decrease in the uptake of losartan, with chitosan causing a significant reduction. Chitosan and glucomannan significantly reduced the transport of losartan, while cellulose or sodium alginate did not. Dietary fibers also reduced the level of free losartan; however, this did not correlate with the observed reduction in losartan uptake and transport. In summary, chitosan had the greatest inhibitory effect on losartan uptake and transport, and this potential interaction should be considered in patients taking losartan. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26748460

  5. Losartan enhances the success of myoblast transplantation.

    PubMed

    Fakhfakh, Raouia; Lamarre, Yann; Skuk, Daniel; Tremblay, Jacques P

    2012-01-01

    Duchenne muscular dystrophy is a recessive X-linked genetic disease caused by dystrophin gene mutations. Cell therapy can be a potential approach aiming to introduce a functional dystrophin in the dystrophic patient myofibers. However, this strategy produced so far limited results. Transforming growth factor-β (TGF-β) is a negative regulator of skeletal muscle development and is responsible for limiting myogenic regeneration. The combination of TGF-β signaling inhibition with myoblast transplantation can be an effective therapeutic approach in dystrophin-deficient patients. Our aim was to verify whether the success of human myoblast transplantation in immunodeficient dystrophic mice is enhanced with losartan, a molecule that downregulates TGF-β expression. In vitro, blocking TGF-β activity with losartan increased proliferation and fusion and decreased apoptosis in human myoblasts. In vivo, human myoblasts were transplanted in mice treated with oral losartan. Immunodetection of human dystrophin in tibialis anterior cross sections 1 month posttransplantation revealed more human dystrophin-positive myofibers in these mice than in nontreated dystrophic mice. Thus, blocking the TGF-β signal with losartan treatment improved the success of myoblast transplantation probably by increasing myoblast proliferation and fusion, decreasing macrophage activation, and changing the expression of myogenic regulator factors. PMID:21535912

  6. Effect of losartan therapy on endothelial function in hypertensive patients.

    PubMed

    Sosa-Canache, Beatriz; Hernández-Hernández, Rafael; Armas-Padilla, María Cristina; Armas-Hernández, María José; Cammarata-Segura, Rosalba; Pacheco, Beatriz; Guerrero, Jaime; Israili, Zafar H; Valasco, Manuel

    2007-01-01

    The aim of the study was to evaluate the effect of losartan therapy on endothelial function by measuring serum nitric oxide (NO) levels and urinary excretion of NO in patients with essential hypertension. A group of 30 untreated stage 2 hypertensive patients (15 males and 15 females; age, 51.3 +/- 1.5 years) were included in the study. Office systolic and diastolic blood pressure (BP) was measured by using a mercury sphygmomanometer according to phase I and V of Korotkoff sounds. NO levels in serum and 24-hour urine were determined at baseline and after 6 weeks of daily dosing with losartan (50-100 mg). Losartan therapy resulted in a significant fall in systolic/diastolic BP (from 169.7 +/- 4.1/105 +/- 1.8 mm Hg at baseline to 146 +/- 2.7/91 +/- 1.9 mm Hg at the end of losartan treatment; P < 0.001). The therapy also caused significant increases in both serum NO level (32.74 +/- 3.01 microM/L at baseline versus 79.04 +/- 5.17 microM/L; P < 0.001 after therapy) and urinary NO excretion (58.21 +/- 3.72 microM/L at baseline versus 113.21 +/- 8.63 microM/L; P < 0.001 after therapy). Losartan therapy also reduced serum malondialdehyde (MDA), which is a measure of oxidative stress, by 0.201 nM (15.3%; P = 0.009). Losartan at a dose of 50 to 100 mg per day was effective in reducing elevated BP. The increase in serum NO levels and urinary NO excretion and a decrease in serum MDA levels by losartan treatment indicate a reduction in oxidative stress and enhances NO availability, both of which improve endothelial function. Thus, losartan therapy improves endothelial function in hypertensive patients with essential hypertension. PMID:17414585

  7. Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma

    PubMed Central

    Pitha, Ian F.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary Ellen; Oglesby, Ericka N.; Berlinicke, Cynthia A.; Mitchell, Katherine L.; Kim, Jessica; Jefferys, Joan J.

    2015-01-01

    Purpose To determine if oral losartan treatment decreases the retinal ganglion cell (RGC) death caused by experimental intraocular pressure (IOP) elevation in mice. Methods We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry. Results Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13), while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p < 0.0001). The lower RGC loss with losartan was significantly less than the loss with spironolactone or enalapril (regression model p = 0.001; drug treatment group term p = 0.01). Both losartan and enalapril significantly lowered blood pressure (p< 0.001), but losartan was protective, while enalapril led to worse than water-treated RGC loss. RGC loss after crush injury was unaffected by losartan treatment (difference from control p = 0.9). Survival of RGC in cell culture was not prolonged by sartan treatment. Axonal transport blockade after 3 day IOP elevations was less in losartan-treated than in control glaucoma eyes (p = 0.007). Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP. Conclusions The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes

  8. Phorbol ester-induced inhibition of. beta. -adrenergic - and vasopressin-mediated responses in an established smooth muscle cell line

    SciTech Connect

    Not Available

    1986-03-01

    A-10 cells which are derived from embryonic rat thoracic aorta contain a high density of vasopressin receptors and relatively fewer ..beta..-adrenergic receptors. The effects of vasopressin binding to these cells are two-fold: a) inhibition of isoproterenol-stimulated cAMP accumulation, and; b) stimulation of phosphatidyl inositol turnover. Incubation of these cells with phorbol dibutyrate leads to an attenuation of the responses mediated by ..beta..-adrenergic agonist as well as vasopressin. This effect of phorbol ester is concentration- and time-dependent and can be observed as early as five minutes. The inactive phorbol ester (4 ..cap alpha.. phorbol 12,13-didecanoate) is ineffective in inhibiting ..beta..-adrenergic agonist and vasopressin-mediated responses. Since present evidence indicates that the enzyme protein kinase C (PK-C) is involved in both short-term and long-term regulatory processes such as secretion, smooth muscle contraction and cell growth, these data suggest that both ..beta..-adrenergic and vasopressin receptors and/or some mediator(s) of ..beta..-adrenergic and/or vasopressin responses may be phosphorylated by protein kinase C resulting in an attenuated response of these two hormones.

  9. Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome.

    PubMed

    Bhatt, Ami B; Buck, J Stewart; Zuflacht, Jonah P; Milian, Jessica; Kadivar, Samoneh; Gauvreau, Kimberlee; Singh, Michael N; Creager, Mark A

    2015-08-01

    We conducted a randomized, double-blind trial of losartan (100 mg QD) versus atenolol (50 mg QD) for 6 months in adults with Marfan syndrome. Carotid-femoral pulse wave velocity (PWV), central augmentation index (AIx), aortic diameter and left ventricular (LV) function were assessed with arterial tonometry and echocardiography. Thirty-four subjects (18 female; median age 35 years, IQR 27, 45) were randomized. Central systolic and diastolic blood pressure decreased comparably with atenolol and losartan (p = 0.64 and 0.31, respectively); heart rate decreased with atenolol (p = 0.02), but not with losartan. PWV decreased in patients treated with atenolol (-1.15 ± 1.68 m/s; p = 0.01), but not in those treated with losartan (-0.22 ± 0.59 m/s; p = 0.15; between-group difference p = 0.04). In contrast, AIx decreased in the losartan group (-9.6 ± 8.6%; p < 0.001) but not in the atenolol group (0.9 ± 6.2%, p = 0.57; between-group difference p < 0.001). There was no significant change in aortic diameters or LV ejection fraction in either treatment group. In adults with Marfan syndrome, 6 months of treatment with atenolol improves PWV, whereas losartan reduces the AIx. By improving vascular stiffness via distinct mechanisms of action, there is physiologic value to considering the use of both medications in individuals with Marfan syndrome. PMID:25795452

  10. Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

    PubMed

    Chen, Shan; Grover, Monica; Sibai, Tarek; Black, Jennifer; Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

    2015-05-01

    Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. PMID:25779879

  11. Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

    PubMed Central

    Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

    2015-01-01

    Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. PMID:25779879

  12. A Systems Level Analysis of Vasopressin-mediated Signaling Networks in Kidney Distal Convoluted Tubule Cells

    PubMed Central

    Cheng, Lei; Wu, Qi; Kortenoeven, Marleen L. A.; Pisitkun, Trairak; Fenton, Robert A.

    2015-01-01

    The kidney distal convoluted tubule (DCT) plays an essential role in maintaining body sodium balance and blood pressure. The major sodium reabsorption pathway in the DCT is the thiazide-sensitive NaCl cotransporter (NCC), whose functions can be modulated by the hormone vasopressin (VP) acting via uncharacterized signaling cascades. Here we use a systems biology approach centered on stable isotope labeling by amino acids in cell culture (SILAC) based quantitative phosphoproteomics of cultured mouse DCT cells to map global changes in protein phosphorylation upon acute treatment with a VP type II receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP). 6330 unique proteins, containing 12333 different phosphorylation sites were identified. 185 sites were altered in abundance following dDAVP. Basophilic motifs were preferential targets for upregulated sites upon dDAVP stimulation, whereas proline-directed motifs were prominent for downregulated sites. Kinase prediction indicated that dDAVP increased AGC and CAMK kinase families’ activities and decreased activity of CDK and MAPK families. Network analysis implicated phosphatidylinositol-4,5-bisphosphate 3-kinase or CAMKK dependent pathways in VP-mediated signaling; pharmacological inhibition of which significantly reduced dDAVP induced increases in phosphorylated NCC at an activating site. In conclusion, this study identifies unique VP signaling cascades in DCT cells that may be important for regulating blood pressure. PMID:26239621

  13. A Systems Level Analysis of Vasopressin-mediated Signaling Networks in Kidney Distal Convoluted Tubule Cells.

    PubMed

    Cheng, Lei; Wu, Qi; Kortenoeven, Marleen L A; Pisitkun, Trairak; Fenton, Robert A

    2015-01-01

    The kidney distal convoluted tubule (DCT) plays an essential role in maintaining body sodium balance and blood pressure. The major sodium reabsorption pathway in the DCT is the thiazide-sensitive NaCl cotransporter (NCC), whose functions can be modulated by the hormone vasopressin (VP) acting via uncharacterized signaling cascades. Here we use a systems biology approach centered on stable isotope labeling by amino acids in cell culture (SILAC) based quantitative phosphoproteomics of cultured mouse DCT cells to map global changes in protein phosphorylation upon acute treatment with a VP type II receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP). 6330 unique proteins, containing 12333 different phosphorylation sites were identified. 185 sites were altered in abundance following dDAVP. Basophilic motifs were preferential targets for upregulated sites upon dDAVP stimulation, whereas proline-directed motifs were prominent for downregulated sites. Kinase prediction indicated that dDAVP increased AGC and CAMK kinase families' activities and decreased activity of CDK and MAPK families. Network analysis implicated phosphatidylinositol-4,5-bisphosphate 3-kinase or CAMKK dependent pathways in VP-mediated signaling; pharmacological inhibition of which significantly reduced dDAVP induced increases in phosphorylated NCC at an activating site. In conclusion, this study identifies unique VP signaling cascades in DCT cells that may be important for regulating blood pressure. PMID:26239621

  14. Voluntary Oral Administration of Losartan in Rats

    PubMed Central

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-01-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents. PMID:26424254

  15. Voluntary Oral Administration of Losartan in Rats.

    PubMed

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-09-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents. PMID:26424254

  16. [Mechanism of losartan suppressing vascular calcification in rat aortic artery].

    PubMed

    Shao, Juan; Wu, Panfeng; Wu, Jiliang; Li, Mincai

    2016-08-01

    Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process. PMID:27412937

  17. Losartan

    MedlinePlus

    ... a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 ... Do not use salt substitutes containing potassium without talking to your doctor. If your doctor prescribes a low-salt or low-sodium diet, ...

  18. Losartan may inhibit the progression of liver fibrosis in chronic HCV patients

    PubMed Central

    Salama, Zakaria A.; Sadek, Ahmed; Abdelhady, Ahmed M.; Morsy, Shereif Ahmed; Esmat, Gamal

    2016-01-01

    Background Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. Methods A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1st group (n=25) was given losartan 50 mg OD for 1 year and the 2nd group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). Results In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively). Conclusions Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation. PMID:27275467

  19. Losartan attenuated lipopolysaccharide-induced lung injury by suppression of lectin-like oxidized low-density lipoprotein receptor-1

    PubMed Central

    Deng, Wang; Deng, Yue; Deng, Jia; Wang, Dao-Xin; Zhang, Ting

    2015-01-01

    Introduction: Recent study has shown that renin-angiotensin system plays an important role in the development of acute lung injury (ALI) with high level of angiotensin II (AngII) generated form AngI catalyzed by angiotensin-converting enzyme. AngII plays a major effect mainly through AT1 receptor. Therefore, we speculate inhibition of AT1 receptor may possibly attenuate the lung injury. Losartan, an antagonist of AT1 receptor for angiotensin II, attenuated lung injury by alleviation of the inflammation response in ALI, but the mechanism of losartan in ALI still remains unclear. Methods: Thirty male Sprague-Dawley rats were randomly divided into Control group, ALI group (LPS), and Losartan group (LPS + Losartan). Bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for analysis. The expressions of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), intercellular adhesion molecule-1 (ICAM-1) and caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. Results: In ALI group, TNF-α and protein level in BALF, MPO activity in lung tissue, pulmonary edema and lung injury were significantly increased. Losartan significantly reduced LPS-induced increase in TNF-α and protein level in BALF, MPO activity, pulmonary edema and lung injury in LPS-induced lung injury. The mRNA and protein expression levels of LOX-1 were significantly decreased with the administration of losartan in LPS-induced lung injury. Also, losartan blocked the protein levels of caspase-3 and ICAM-1 mediated by LOX-1 in LPS-induced lung injury. Conclusions: Losartan attenuated lung injury by alleviation of the inflammation and cell apoptosis by inhibition of LOX-1 in LPS-induced lung injury. PMID:26884836

  20. Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl4-Induced Skeletal Muscle Injury

    PubMed Central

    Hwang, Ok-Kyung; Park, Jin-Kyu; Lee, Eun-Joo; Lee, Eun-Mi; Kim, Ah-Young; Jeong, Kyu-Shik

    2016-01-01

    TGF-β1 is known to inhibit muscle regeneration after muscle injury. However, it is unknown if high systemic levels of TGF-β can affect the muscle regeneration process. In the present study, we demonstrated the effect of a CCl4 intra-peritoneal injection and losartan (an angiotensin II type 1 receptor antagonist) on skeletal muscle (gastrocnemius muscle) injury and regeneration. Male C57BL/6 mice were grouped randomly as follows: control (n = 7), CCl4-treatment group (n = 7), and CCl4 + losartan treatment group (n = 7). After CCl4 treatment for a 16-week period, the animals were sacrificed and analyzed. The expression of dystrophin significantly decreased in the muscle tissues of the control group, as compared with that of the CCl4 + losartan group (p < 0.01). p(phospho)-Smad2/3 expression significantly increased in the muscles of the control group compared to that in the CCl4 + losartan group (p < 0.01). The expressions of Pax7, MyoD, and myogenin increased in skeletal muscles of the CCl4 + losartan group compared to the corresponding levels in the control group (p < 0.01). We hypothesize that systemically elevated TGF-β1 as a result of CCl4-induced liver injury causes skeletal muscle injury, while losartan promotes muscle repair from injury via blockade of TGF-β1 signaling. PMID:26867195

  1. How the antihypertensive losartan was discovered.

    PubMed

    Bhardwaj, Gaurab

    2006-11-01

    Based on interviews and publications, this case study is a history of how DuPont scientists discovered losartan, the first angiotensin II receptor antagonist. Essential aspects of the story include: i) the discovery occurred at a young and inexperienced pharmaceutical business; ii) three bench scientists had recently graduated from PhD programmes and only the fourth had any industrial research experience; iii) pivotal to its success was the support and risk-taking of the highly experienced and recently hired head of pharmaceutical research; iv) a timely patent issued to Takeda Chemical Industries suggested a new line of research; v) a mistake made by an inexperienced pharmacologist yielded pivotal information; vi) the bench scientists were given the freedom to explore while being supported by research managers; vii) luck favoured the scientists in losartan's subreceptor-binding and metabolite; and viii) the marketing group insisted that losartan not be developed until Merck expressed an interest in the drug candidate. Today, losartan is a multibillion dollar drug. PMID:23506070

  2. Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis.

    PubMed

    Bolat, D; Oltulu, F; Uysal, A; Kose, T; Gunlusoy, B; Yigitturk, G; Turk, N S; Turan, T

    2016-09-01

    To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis. PMID:27373273

  3. Effects of licochalcon A on the pharmacokinetics of losartan and its active metabolite, EXP-3174, in rats.

    PubMed

    Choi, J S; Choi, J S; Choi, D H

    2013-11-01

    Losartan and licochalcon A interact with cytochrome P-450 (CYP) enzymes and P-glycoprotein (P-gp), and the increase in the use of health supplements may result in licochalcon A being taken concomitantly with losartan to treat or prevent cardiovascular diseases as a combination therapy. The effect of licochalcon A, a natural flavonoid, on the pharmacokinetics of losartan and its active metabolite, EXP-3174, was investigated in rats. Pharmacokinetic parameters of losartan and EXP-3174 were determined after oral administration of losartan (9 mg/kg) to rats in the presence or absence of licochalcon A (0.5, 2.5 and 10 mg/kg). The effect of licochalcon A on P-glycoprotein (P-gp) as well as CYP3A4 and 2C9 activities was also evaluated. Licochalcon A inhibited CYP3A4 and CYP2C9 enzyme activities with 50% inhibition concentrations (IC50) of 2.0 and 0.1 microM, respectively. In addition, licochalcon A significantly enhanced the cellular accumulation of rhodamine-123 in a concentration-dependent manner in MCF-7/ADR cells overexpressing P-gp. The pharmacokinetic parameters of losartan were significantly altered by licochalcon A. Licochalcon A (2.5 mg/kg or 10 mg/kg) increased AUC0-infinity of losartan by 33.4-63.2% and Cmax of losartan by 34.0-62.8%. The total body clearance (CL/F) was significantly decreased (2.5 mg/kg, p < 0.05; 10 mg/kg, p < 0.01) by licochalcon A. Consequently, the absolute bioavailability of losartan in the presence of licochalcon A increased significantly (2.5 mg/kg, p < 0.05; 10 mg/kg, p < 0.01) compared to that in the control group. The relative bioavailability (R.B.) of losartan was 1.15- to 1.63-fold greater than that of the control group. However, there was no significant change in Tmax and t1/2 of losartan in the presence of licochalcon A. Licochalcon A (10 mg/kg) increased the AUC0-infinity of EXP-3174 but this was not significant. Furthermore, concurrent use of licochalcon A (10 mg/kg) significantly decreased the metabolite-parent AUC ratio (M

  4. Combination Therapy with Losartan and α-Tocopherol in Acute Ureteral Obstruction-Induced Renal Excretory Dysfunction and Acidification Defect

    PubMed Central

    Gheitasi, Izadpanah; Moosavi, Seyed Mostafa

    2014-01-01

    Background: Previous study by the authors showed that a-tocopherol prevents oxidative stress but would not improve depressed excretory variables in post-obstructed kidney (POK) after release of 24-h unilateral ureteral obstruction (UUO). This study is a supplementary investigation on the effects of a-tocopherol combined with an antagonist of angiotensin-II type-1 (AT1) receptor on renal dysfunction following release of acute UUO. Methods: The left ureter was ligated in different groups of male Sprague-Dawley rats that received normal saline, losartan or losartan/a-tocopherol (n=6 in each group). After releasing 24-h UUO, urine of each kidney was separately collected under paraffin during 1-3 h of post-release period and then both kidneys were removed for measuring malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP). Results: Losartan-treatment decreased MDA and increased FRAP, creatinine-clearance and sodium-reabsorption in POK, while co-treatment with losartan and a-tocopherol not only augmented improvement in these variables but also elevated potassium-excretion, free-water reabsorption and urine-osmolality. However, UUO-induced fall in urinary pCO2 and rise in pH and bicarbonate-excretion of POK were ameliorated equally with losartan and losartan/a-tocopherol. Conclusion: Activation of AT1-receptor contributes to the development of renal distal acidification defect induced by acute ureteral obstruction. The co-treatment with losartan and a-tocopherol showed that their effects on preventing oxidative stress along with ameliorating glomerular filtration and tubular fluid-delivery in POK could lead to improvement in tubular transport of sodium and potassium as well as urine-concentrating ability at the early post-release period. PMID:25031488

  5. An association of losartan-hydrochlorothiazide, but not losartan-furosemide, completely arrests progressive injury in the remnant kidney.

    PubMed

    Arias, Simone Costa Alarcon; Souza, Renata Alves; Malheiros, Denise Maria Avancini Costa; Fanelli, Camilla; Fujihara, Clarice Kazue; Zatz, Roberto

    2016-01-15

    We have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease. PMID:26538442

  6. Development of a CP 31P NMR broadline simulation methodology for studying the interactions of antihypertensive AT1 antagonist losartan with phospholipid bilayers.

    PubMed

    Fotakis, Charalambos; Christodouleas, Dionisios; Chatzigeorgiou, Petros; Zervou, Maria; Benetis, Nikolas-Ploutarch; Viras, Kyriakos; Mavromoustakos, Thomas

    2009-03-18

    A cross-polarization (CP) (31)P NMR broadline simulation methodology was developed for studying the effects of drugs in phospholipids bilayers. Based on seven-parameter fittings, this methodology provided information concerning the conformational changes and dynamics effects of losartan in the polar region of the dipalmitoylphosphatidylcholine bilayers. The test molecule for this study was losartan, an antihypertensive drug known to exert its effect on AT(1) transmembrane receptors. The results were complemented and compared with those of differential scanning calorimetry, solid-state (13)C NMR spectroscopy, Raman spectroscopy, and electron spin resonance. More specifically, these physical chemical methodologies indicated that the amphipathic losartan molecule interacts with the hydrophilic-head zone of the lipid bilayers. The CP (31)P NMR broadline simulations showed that the lipid molecules in the bilayers containing losartan displayed greater collective tilt compared to the tilt displayed by the load-free bilayers, indicating improved packing. The Raman results displayed a decrease in the trans/gauche ratio and increased intermolecular interactions of the acyl chains in the liquid crystalline phase. Additional evidence, suggesting that losartan possibly anchors in the realm of the headgroup, was derived from upfield shift of the average chemical shift sigma(iso) of the (31)P signal in the presence of losartan and from shift of the observed peak at 715 cm(-1) attributed to C-N stretching in the Raman spectra. PMID:19289049

  7. A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

    PubMed Central

    Wells, Thomas G.; Shahinfar, Shahnaz; Massaad, Rachid; Dankner, Wayne M.; Lam, Chun; Santoro, Emanuela Palumbo; McCrary Sisk, Christine; Blaustein, Robert O.

    2014-01-01

    Background and objectives Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6–16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years. Design, setting, participants, & measurements This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension. Patients were randomized to losartan at the following dosages: 0.1 mg/kg per day (low), 0.3 mg/kg per day (medium), or 0.7 mg/kg per day (high). Losartan was titrated to the next dose level (to a 1.4 mg/kg per day maximum dosage, not exceeding 100 mg/d, which was not one of the three original doses offered at randomization) at weeks 3, 6, and 9 for patients who did not attain their goal BP and were not taking the highest dose. Dose response was evaluated by analyzing the slope of change in sitting systolic BP (SBP; primary end point) and diastolic BP (DBP; secondary end point) after 3 weeks compared with baseline. Adverse events (AEs) were recorded throughout. Results Of the 101 patients randomized, 99 were included in the analysis (low dose, n=32; medium dose, n=34; and high dose, n=33). Mean sitting BP decreased from baseline in the low-, medium-, and high-dose groups by 7.3, 7.6, and 6.7 mmHg, respectively, for SBP and 8.2, 5.1, and 6.7 mmHg, respectively, for DBP after 3 weeks. No dose-response relationship was established by the slope analysis on SBP (P=0.75) or DBP (P=0.64). The BP-lowering effect was observed throughout the 2-year extension. The incidence of AEs was low and comparable between groups. Conclusions Hypertensive children aged 6 months to 6 years treated with losartan 0.1–0.7 mg/kg per day had clinically significant decreases from baseline in SBP and DBP, yet no dose-response relationship was evident. Losartan, at a dosage up to 1.4 mg/kg per day, was well tolerated. PMID:24875194

  8. Angiotensin II type 1 receptor blocker losartan prevents and rescues cerebrovascular, neuropathological and cognitive deficits in an Alzheimer's disease model.

    PubMed

    Ongali, Brice; Nicolakakis, Nektaria; Tong, Xin-Kang; Aboulkassim, Tahar; Papadopoulos, Panayiota; Rosa-Neto, Pedro; Lecrux, Clotilde; Imboden, Hans; Hamel, Edith

    2014-08-01

    Angiotensin II (AngII) receptor blockers that bind selectively AngII type 1 (AT1) receptors may protect from Alzheimer's disease (AD). We studied the ability of the AT1 receptor antagonist losartan to cure or prevent AD hallmarks in aged (~18months at endpoint, 3months treatment) or adult (~12months at endpoint, 10months treatment) human amyloid precursor protein (APP) transgenic mice. We tested learning and memory with the Morris water maze, and evaluated neurometabolic and neurovascular coupling using [(18)F]fluoro-2-deoxy-D-glucose-PET and laser Doppler flowmetry responses to whisker stimulation. Cerebrovascular reactivity was assessed with on-line videomicroscopy. We measured protein levels of oxidative stress enzymes (superoxide dismutases SOD1, SOD2 and NADPH oxidase subunit p67phox), and quantified soluble and deposited amyloid-β (Aβ) peptide, glial fibrillary acidic protein (GFAP), AngII receptors AT1 and AT2, angiotensin IV receptor AT4, and cortical cholinergic innervation. In aged APP mice, losartan did not improve learning but it consolidated memory acquisition and recall, and rescued neurovascular and neurometabolic coupling and cerebrovascular dilatory capacity. Losartan normalized cerebrovascular p67phox and SOD2 protein levels and up-regulated those of SOD1. Losartan attenuated astrogliosis, normalized AT1 and AT4 receptor levels, but failed to rescue the cholinergic deficit and the Aβ pathology. Given preventively, losartan protected cognitive function, cerebrovascular reactivity, and AT4 receptor levels. Like in aged APP mice, these benefits occurred without a decrease in soluble Aβ species or plaque load. We conclude that losartan exerts potent preventive and restorative effects on AD hallmarks, possibly by mitigating AT1-initiated oxidative stress and normalizing memory-related AT4 receptors. PMID:24807206

  9. Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model

    PubMed Central

    Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

    2015-01-01

    Objective: To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Methods: Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. Results: After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Conclusions: Losartan can alleviate experimental atherosclerosis induced by hyperuricemia. PMID:26617751

  10. The Association of Losartan and Ramipril Therapy With Kidney and Cardiovascular Outcomes in Patients With Chronic Kidney Disease

    PubMed Central

    Hsing, Shih-Chun; Lu, Kuo-Cheng; Sun, Chien-An; Chien, Wu-Chien; Chung, Chi-Hsiang; Kao, Sen-Yeong

    2015-01-01

    Abstract The aim of this nation-wide cohort study was to assess the association of using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) therapy on the prognosis of hypertensive patients with chronic kidney disease (CKD). We used Cox's proportional hazard regression model to estimate hazard ratios (HRs) for the risk of end-stage renal disease (ESRD), all-cause mortality, cardiovascular mortality, and first hospitalization for cardiovascular disease (CVD) for losartan and ramipril versus conventional antihypertensive agents. In total, 136,266 hypertensive patients with CKD in Taiwan were followed up from 2001 to 2008. In an average follow-up of 5.9 years, 7364 (5.40%) patients reached ESRD, 4165 (3.06%) patients died, and 6163 (4.52%) patients had their first hospitalization for CVD. Use of losartan or ramipril was associated with a lower risk of the endpoints compared with the conventional group. In the losartan group, the risks of ESRD, all- and cardiovascular-cause mortality, and first hospitalization for CVD were decreased by 9.2% (P = 0.01), 24.6% (P < 0.001), 12.4% (P = 0.03), and 36.0% (P = 0.01), respectively. In the ramipril group, these risks decreased by 7.6% (P = 0.02) for ESRD, 56.9% (P < 0.001) for all-cause mortality, 7.5% (P = 0.04) for cardiovascular mortality, and 24.7% (P < 0.001) for first hospitalization. This study indicated that losartan and ramipril had distinct association on the prognosis of hypertensive patients with CKD, and was first to disclose that the mean time to reach each endpoint for patients in the losartan, ramipril, and conventional group was not significantly different. However, further study is needed to confirm results of the present study. PMID:26632888

  11. Effects of Losartan and Vanillic Acid Co-Administration on Ischemia-Reperfusion-Induced Oxidative Stress in Isolated Rat Heart

    PubMed Central

    Dianat, Mahin; Hamzavi, Gholam Reza; Badavi, Mohammad; Samarbafzadeh, Alireza

    2014-01-01

    Background: Experimental studies have demonstrated that angiotensin II (ANG-II)-induced oxidative stress contributes to the pathogenesis of I/R injury. Objectives: This study was aimed to investigate the protective effects of co-administration of losartan, as a selective ANG-II type 1 receptor (AT1R) blocker, and vanillic acid (VA), as an antioxidant, in I/R-induced oxidative stress in isolated rat heart. Materials and Methods: Adult male Wistar rats were randomly divided to sham, control, and five treatment groups (n = 10). Two doses of VA (5 and 10 mg/kg), one dose of losartan (20 mg/kg) alone, and one dose of losartan in combination with either doses of VA were administered orally for 10 days. The hearts were isolated and exposed to 30 minutes ischemia and 60 minutes reperfusion, using Langendorff apparatus. I/R-induced myocardial injury was assessed by estimating the release of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and myocardial creatine kinase (CK-MB) in coronary effluent at 5, 15, and 60 minutes of reperfusion. The oxidative stress in the hearts was assessed by estimating malondialdehyde (MDA). The effects of treatments on endogenous antioxidant enzymes were assessed by measuring superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). Results: There was a more significant decrease in the levels of LDH, CPK, CK-MB, and MDA as well as increase in the levels of SOD, CAT and GPx in groups that had received combined treatment in comparison to VA or losartan alone. Conclusions: It may be concluded that combination of losartan with higher dose of VA decreases ischemic markers and lipid peroxidation and augments endogenous antioxidant and hence, protects myocardium against I/R-induced oxidative stress injuries. PMID:25237570

  12. Losartan and enalapril are comparable in reducing proteinuria in children.

    PubMed

    Webb, Nicholas J A; Shahinfar, Shahnaz; Wells, Thomas G; Massaad, Rachid; Gleim, Gilbert W; Santoro, Emanuela P; Sisk, Christine M; Lam, Chun

    2012-10-01

    Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers delay progression of chronic kidney disease and have antiproteinuric effects beyond their effects on blood pressure. They are routinely used in adults; however, their efficacy and safety in children, in whom the causes of chronic kidney disease are significantly different relative to adults, is uncertain. Here we assessed an open-label extension of a previous 3-month blinded trial, in which the efficacy and tolerability of losartan was compared to placebo or amlodipine in 306 normotensive and hypertensive children with proteinuria. In this study, 268 children were re-randomized to losartan or enalapril and followed until 100 patients completed 3 years of follow-up for proteinuria and renal function. The least squares percent mean reduction from baseline in the urinary protein/creatinine ratio was 30.01% for losartan and 40.45% for enalapril. The least squares mean change from baseline in eGFR was 3.3 ml/min per 1.73 m2 for losartan and 7.0 ml/min per 1.73 m2 for enalapril. The incidence of specific adverse events such as hyperkalemia and renal dysfunction was low and similar in both groups. Both were generally well tolerated and, overall, fewer drug-related adverse events occurred with losartan than with enalapril. Thus, in children with proteinuria, losartan and enalapril significantly reduced proteinuria without any appreciable changes in eGFR, effects that were maintained throughout the study. Both losartan and enalapril were generally well tolerated. PMID:22739977

  13. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    SciTech Connect

    Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan; Wen Fuqiang

    2010-05-15

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  14. Life or death by NFκB, Losartan promotes survival in dy2J/dy2J mouse of MDC1A

    PubMed Central

    Elbaz, M; Yanay, N; Laban, S; Rabie, M; Mitrani-Rosenbaum, S; Nevo, Y

    2015-01-01

    Inflammation and fibrosis are well-defined mechanisms involved in the pathogenesis of the incurable Laminin α2-deficient congenital muscular dystrophy (MDC1A), while apoptosis mechanism is barely discussed. Our previous study showed treatment with Losartan, an angiotensin II type I receptor antagonist, improved muscle strength and reduced fibrosis through transforming growth factor beta (TGF-β) and mitogen-activated protein kinases (MAPK) signaling inhibition in the dy2J/dy2J mouse model of MDC1A. Here we show for the first time that Losartan treatment up-regulates and shifts the nuclear factor kappa B (NFκB) signaling pathway to favor survival versus apoptosis/damage in this animal model. Losartan treatment was associated with significantly increased serum tumor necrosis factor alpha (TNF-α) level, p65 nuclei accumulation, and decreased muscle IκB-β protein level, indicating NFκB activation. Moreover, NFκB anti-apoptotic target genes TNF receptor-associated factor 1 (TRAF1), TNF receptor-associated factor 2 (TRAF2), cellular inhibitor of apoptosis (cIAP2), and Ferritin heavy chain (FTH1) were increased following Losartan treatment. Losartan induced protein expression toward a pro-survival profile as BCL-2 expression levels were increased and Caspase-3 expression levels were decreased. Muscle apoptosis reduction was further confirmed using terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay. Thus, along with TGF-β and MAPK signaling, NFκB serves as an important regulatory pathway which following Losartan treatment promotes survival in the dy2J/dy2J mouse model of MDC1A. PMID:25766329

  15. Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy

    PubMed Central

    Srivastava, Anand; Adams-Huet, Beverley; Vega, Gloria L; Toto, Robert D

    2016-01-01

    Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo −24.6%, los −38.2%, spiro −51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (−20.9% vs +34.3%, p<0.01), V+I C(−18.8% vs +21.3%, p<0.01), and V+I-ApoB (−13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. Trial registration number NCT00381134; Results. PMID:27388615

  16. A case of losartan-induced severe hyponatremia

    PubMed Central

    Das, Saibal; Bandyopadhyay, Sanjib; Ramasamy, Anand; Prabhu, V. Vinoth; Pachiappan, Sudhakar

    2015-01-01

    This case report outlines a very rare case of losartan-induced severe hyponatremia in a 73-year-old type 2 diabetic patient. The patient was initiated with 50 mg daily oral losartan monotherapy for newly diagnosed moderate hypertension. After 3.5 months of taking the drug, he presented to the emergency department in a drowsy state with severe generalized weakness and occasional palpitations. He was a known diabetic for the last 3 years and well controlled by oral metformin alone. On examination, his serum sodium level was found to be 123 meq/L. There were no evidences of any other possible metabolic, infective, organic or other pathologic causes giving rise to that condition, except losartan itself. De-challenge was done and he was treated vigorously resulting in reversal of the diseased state. Naranjo adverse drug reaction probability scale suggested that it was “probable” that oral losartan was responsible for the development of severe hyponatremia in this patient. PMID:26816476

  17. Involvement of the HIF-1α and Wnt/β-catenin pathways in the protective effects of losartan on fatty liver graft with ischaemia/reperfusion injury.

    PubMed

    Yang, Ying-Ying; Lee, Pei-Chang; Huang, Yi-Tsau; Lee, Wei-Ping; Kuo, Ying-Ju; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Lee, Tzung-Yan; Lin, Han-Chieh

    2014-01-01

    Besides cardioprotective effects, the AT1R (angiotensin-II type 1 receptor) antagonist losartan protects the liver from IRI [IR (ischaemia/reperfusion) injury], but the mechanism has not been fully determined. The HIF (hypoxia inducible factor)-1α and Wnt/β-catenin signalling pathways have been reported to be involved in the mechanism of liver IRI. Therefore the aim of the present study was to determine whether the Wnt/HIF axis is part of the mechanism of the positive effect of AngII inhibition by losartan in liver IRI in rats. Various measurements were made in MCD/HF-NASH (methionine- and choline-deficient-diet/high-fat-diet-induced non-alcoholic steatohepatitis) rats with liver IRI. Acute losartan pre-administration markedly reversed the IR-suppressed levels of the hepatic-protective factors IL (interleukin)-6, IFN (interferon)-γ, Wnt3a, β-catenin and HIF-1α, and decreased hepatic blood flow and IR-elevated serum ALT (alanine aminotransferase), hepatic TNF (tumour necrosis factor)-α, IL-1α, hepatic congestion, vacuolization and necrosis, hepatic Suzuki IRI scores, necrotic index and levels of TBARS (thiobarbituric acid-reacting substances) in MCD/HF-NASH rats. Furthermore, acute Wnt3a pre-treatment significantly inhibited IR-elevated serum ALT, hepatic Suzuki IRI scores and TBARS, and restored the IR-depleted β-catenin/HIF-1α activity in MCD/HF-NASH rats. Simultaneous acute sFRP2 (secreted frizzled-related protein 2; a Wnt3a inhibitor) pre-treatment eliminated the losartan-related beneficial effects in MCD/HF-NASH rats with liver IRI, which was accompanied by a decrease in hepatic HIF-1α/β-catenin activity. Losartan-induced up-regulation of HIF-1α and Wnt/β-catenin signalling was associated with the recovery of IR-inhibited hepatic Bcl-2, Mn-SOD (manganese superoxide), Cu/Zn-SOD (copper/zinc superoxide) and GSH levels, and the suppression of IR-increased hepatic catalase and caspase 3/caspase 8 levels in MCD/HF-NASH rats. In conclusion, up

  18. The angiotensin II receptor antagonist, losartan, enhances regulator of G protein signaling 2 mRNA expression in vascular smooth muscle cells of Wistar rats.

    PubMed

    Wu, Yaqiong; Nakagawa, Suguru; Takahashi, Hidenori; Kawabata, Yukari; Suzuki, Etsu; Uehara, Yoshio

    2016-05-01

    Angiotensin II (Ang II) reportedly enhances regulator of G-protein signaling 2 (RGS2), thus making a negative feedback loop for Ang II signal transduction. However, few studies have reported whether Ang II receptor (ATR) antagonists influence RGS2 mRNA expression. We investigated RGS2 mRNA expression when Ang II binding to ATR was blocked with Ang II subtype-1 receptor (AT1R) blockers using vascular smooth muscle cells from the thoracic aorta of male Wistar rats. RGS2 mRNA expression significantly increased with Ang II stimulation, and this increase was almost completely abolished by olmesartan, a potent AT1R-specific blocker. Ang II subtype-2 receptor (AT2R) was not involved in Ang II-mediated RGS expression. In contrast, the AT1R blocker, losartan, partially decreased Ang II-mediated RGS2 mRNA expression because this antagonist directly stimulated RGS2 mRNA expression in Ang II-free medium. EXP3174, which is an active metabolite of losartan, almost completely blunted Ang II-mediated RGS2 mRNA expression without direct stimulation of RGS2 mRNA expression. Moreover, pretreatment with olmesartan abolished Ang II-mediated RGS2 mRNA expression. Treatment with a protein kinase C inhibitor partially decreased losartan-mediated RGS2 mRNA expression. These results suggest that AT1R blockers inhibit RGS2 mRNA expression in response to Ang II via an AT1R-mediated mechanism. However, the AT1R blocker, losartan, behaves as a direct agonist for RGS2 mRNA expression via AT1R through protein kinase C-dependent and -independent pathways. In conclusion, losartan exhibits dual effects on RGS2 mRNA expression, and the direct upregulation of RGS2 mRNA expression may provide a new strategy for the treatment of hypertension. PMID:26763849

  19. Negligible Pharmacokinetic Interaction of Red Ginseng and Losartan, an Antihypertensive Agent, in Sprague-Dawley Rats.

    PubMed

    Ryu, Sung Ha; Kim, Yong Soon; Jang, Hyun-Jun; Kim, Kyu-Bong

    2015-01-01

    Red ginseng (RG) is one of the top selling herbal medicines in Korea, but is not recommended in hypertensive patients. In this study, the pharmacokinetic (PK) interaction between RG and losartan, an antihypertensive drug, was examined. RG was orally administered for 2 wk to male Sprague-Dawley (S-D) rats at either control (0), 0.5, 1, or 2 g/kg/d for 2 wk. After the last administration of RG and 30 min later, all animals were treated with 10 mg/kg losartan by oral route. In addition, some S-D rats were administered RG orally for 21 d at 2 g/kg followed by losartan intravenously (iv) at 10 mg/kg/d. Post losartan administration, plasma samples were collected at 5, 15, and 30 min and 1, 1.5, 2, 3, 6, 12, and 24 h. Plasma concentrations of losartan and E-3174, the active metabolite of losartan, were analyzed by a high-pressure liquid chromatography-tandem mass spectrometer system (LC-MS/MS). Oral losartan administration showed dose-dependent pharmacokinetics (PK) increase with time to maximum plasma, but this was not significant between different groups. There was no significant change in tmax with E-3174 PK. With iv losartan, pharmacokinetics showed elevation of area under the plasma concentration-time curve from time zero extrapolated to infinitity. There was not a significant change in AUCinf with E-3174 PK. Therefore, RG appeared to interfere with biotransformation of losartan, as RG exerted no marked effect on E-3174 PK in S-D rats. Data demonstrated that oral or iv treatment with losartan in rats pretreated with RG for 2 wk showed that losartan PK was affected but E-3174 PK remained unchanged among different dose groups. These results suggested that RG induces negligible influence on losartan and E-3174 PK in rats. PMID:26514876

  20. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    PubMed Central

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  1. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms.

    PubMed

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-09-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  2. Significance of metabolites in bioequivalence: losartan potassium as a case study.

    PubMed

    Charoo, Naseem Ahmad; Cristofoletti, Rodrigo; Khatri, Aamer Roshanali; Ali, Areeg Anwer

    2014-06-01

    Estimation of metabolite data as a supportive evidence of comparable therapeutic outcome is recommended by various guidance documents. However, a consensus on using it solely to establish bioequivalence (BE) is lacking as parent drug is believed to detect pharmacokinetic differences between test and reference formulations better. Four BE studies of losartan potassium reported in the literature are reviewed. In all the four studies, 90% confidence intervals (CIs) of geometric mean ratios of the test and reference formulations for maximum blood drug concentration (Cmax ) of losartan potassium were outside the acceptable range of 80%-125%, whereas, 90% CIs for its active metabolite, losartan carboxylic acid (LCA), were within the acceptance criteria. Although BE with respect to area under the plasma concentration versus time profile curve was demonstrated in all the cases, BE with respect to Cmax could not be established. However, marketing authorization in all the four cases was granted based on scientific evidence that LCA is 10-40 times more potent than losartan, LCA exhibited higher plasma concentration levels than losartan, pharmacodynamic effects correlate with LCA, and losartan shows wide therapeutic index. Further, widened CI limits for losartan were accepted. Losartan presents an opportunity in the diligence of the principles of quality risk management for selecting moiety on which BE decision must be based. PMID:24700383

  3. [Losartan for the correction of thrombocyte activity in patients suffering from arterial hypertension with metabolic syndrome].

    PubMed

    Simonenko, V B; medvedev, i N; Kumova, T A

    2008-01-01

    The aim of the study was to evaluate therapeutic effects of losartan on intravascular thrombocyte activity (ITA) in patients suffering from arterial hypertension with metabolic syndrome (MS). The subjects of the study were 35 patients administered losartan 50 mg a day for 4 months. The dynamics of the following parameters were evaluated: anthropometric parameters, blood lipids, lipid peroxidation in blood plasma and thrombocytes, the anti-oxidative protection of the liquid part of blood and platelets, and ITA. Student criterion was used for statistical analysis. In patients with AH and MS losartan had a positive effect on peroxidation syndrome and optimized ITA. To maintain the positive effects, prolonged administration of losartan is needed. In order to lower body mass in AH patients with MS losartan should be used in combination with non-drug means. PMID:18326282

  4. Losartan prevents acquired epilepsy via TGF-β signaling suppression

    PubMed Central

    Bar-Klein, Guy; Cacheaux, Luisa P.; Kamintsky, Lyn; Prager, Ofer; Weissberg, Itai; Schoknecht, Karl; Cheng, Paul; Kim, Soo Young; Wood, Lydia; Heinemann, Uwe; Kaufer, Daniela; Friedman, Alon

    2014-01-01

    Objective Acquired epilepsy is frequently associated with structural lesions following trauma, stroke and infections. While seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin-mediated transforming growth factor β (TGF-β) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin-mediated TGF-β signaling and tested the efficacy of blocking the TGF-β pathway in preventing epilepsy. Methods We addressed the role of TGF-β signaling in epiletogenesis in two different rat models of vascular injury, combining in vitro and in vivo biochemical assays, gene expression, magnetic resonance and direct optical imaging for blood-brain barrier (BBB) permeability and vascular reactivity. Long-term electrocorticographic (ECoG) recordings were acquired in freely behaving animals. Results We demonstrate that serum-derived albumin preferentially induces activation of the activin receptor-like kinase 5 (ALK5) pathway of TGF-β receptor I in astrocytes. We further show that the angiotensin II type 1 receptor antagonist (AT1), losartan, previously identified as a blocker of peripheral TGF-β signaling, effectively blocks albumin-induced TGF-β activation in the brain. Most importantly, losartan prevents the development of delayed recurrent spontaneous seizures, an effect that persists weeks after drug withdrawal. Interpretation TGF-β signaling, activated in astrocytes by serum-derived albumin, is involved in epileptogenesis. We propose losartan, an FDA-approved drug, as an efficient anti-epileptogenic therapy for epilepsy associated with vascular injury. PMID:24659129

  5. In vitro availability of atorvastatin in presence of losartan.

    PubMed

    Arayne, M Saeed; Sultana, Najma; Haroon, Urooj; Qureshi, Faiza; Ali, Syed Asif

    2006-04-01

    Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are a group of cholesterol lowering agents that have become the largest selling drugs in the world. They are of proven clinical benefit in coronary heart disease, at least in those patients who do not have overt chronic heart failure (CHF). Co-administration of statins with angiotensin II receptor blockers (ARBs) is most common, since there is strong synergy between hypertension and hypercholesterolemia in terms of risk factors for the development of cardiovascular diseases. In present paper, we describe the in vitro availability of atorvastatin, a potent HMG-CoA reductase inhibitor, in presence of losartan potassium, which is a non-peptide angiotensin II receptor antagonist. These studies were carried out at 37, 48 and 60 degrees C in different pH environments simulating human body compartments. It was observed that in pH 1, 7.4 and 9 the availability of atorvastatin was very high while losartan was not at all available. However in pH 4 these effects were reversed and atorvastatin was not available at all. At 48 degrees C the availability of atorvastatin was high and that of losartan was depressed at pH 9, whereas the later was not available at pH 1, 4 and 7.4 at all. Likewise at 60 degrees C, the availability of atorvastatin at pH 7.4 and 9 was high, whereas the charge-transfer complex formed between the two drugs was broken at pH 1 at this temperature and the entire drug was available. On the other hand the availability of losartan at pH 4 and 9 was high while it was not available at pH 1 and 7.4. The availability of atorvastatin was maximum in simulated gastric juice as compared to buffer of pH 7.4 and 9. This high availability of one drug in presence of other is attributed to the formation of a charge-transfer complex, which was stable at elevated temperatures, except at 60 degrees C in pH 1. PMID:16751125

  6. Different initiatives across Europe to enhance losartan utilization post generics: impact and implications

    PubMed Central

    Moon, James C.; Godman, Brian; Petzold, Max; Alvarez-Madrazo, Samantha; Bennett, Kathleen; Bishop, Iain; Bucsics, Anna; Hesse, Ulrik; Martin, Andrew; Simoens, Steven; Zara, Corinne; Malmström, Rickard E.

    2014-01-01

    Introduction: There is an urgent need for health authorities across Europe to fully realize potential savings from increased use of generics to sustain their healthcare systems. A variety of strategies were used across Europe following the availability of generic losartan, the first angiotensin receptor blocker (ARB) to be approved and marketed, to enhance its prescribing vs. single-sourced drugs in the class. Demand-side strategies ranged from 100% co-payment for single-sourced ARBs in Denmark to no specific measures. We hypothesized this heterogeneity of approaches would provide opportunities to explore prescribing in a class following patent expiry. Objective: Contrast the impact of the different approaches among European countries and regions to the availability of generic losartan to provide future guidance. Methodology: Retrospective segmented regression analyses applying linear random coefficient models with country specific intercepts and slopes were used to assess the impact of the various initiatives across Europe following the availability of generic losartan. Utilization measured in defined daily doses (DDDs). Price reductions for generic losartan were also measured. Results: Utilization of losartan was over 90% of all ARBs in Denmark by the study end. Multiple measures in Sweden and one English primary care group also appreciably enhanced losartan utilization. Losartan utilization actually fell in some countries with no specific demand-side measures. Considerable differences were seen in the prices of generic losartan. Conclusion: Delisting single-sourced ARBs produced the greatest increase in losartan utilization. Overall, multiple demand-side measures are needed to change physician prescribing habits to fully realize savings from generics. There is no apparent “spill over” effect from one class to another to influence future prescribing patterns even if these are closely related. PMID:25339902

  7. Population impact of losartan use on stroke in the European Union (EU): projections from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.

    PubMed

    Dahlöf, B; Burke, T A; Krobot, K; Carides, G W; Edelman, J M; Devereux, R B; Diener, H-C

    2004-06-01

    The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study was designed to compare losartan- vs atenolol-based antihypertensive treatment on cardiovascular morbidity and mortality in a population of 9193 hypertensive patients with left ventricular hypertrophy (LVH). In LIFE, the losartan-based treatment further reduced the primary composite end point (cardiovascular death, myocardial infarction, or stroke) by 13% (risk reduction (RR) 0.87, 95% confidence interval (CI) 0.77-0.98, P=0.021). The further reduction in stroke with losartan (RR 0.75, 95% CI 0.63-0.89, P=0.001) was the major contributing factor to the reduction in the primary end point. Our objective was to project the reduction in stroke observed with a losartan- vs an atenolol-based antihypertensive treatment regimen in the LIFE study to the European Union (EU) population. The number of stroke events averted was estimated by identifying the number of persons in the EU expected to meet the LIFE inclusion criteria, and multiplying this figure by the cumulative incidence risk difference in stroke from LIFE at 5.5 years. The age- and gender-specific prevalence of hypertension, electrocardiographically (ECG)-diagnosed LVH among those with hypertension (inclusion criteria), and heart failure among those with LVH and hypertension (exclusion criteria) were applied to the EU census estimates. We conservatively projected that an estimated 7.8 million individuals aged 55-80 years in the EU are affected by hypertension and ECG-diagnosed LVH. Use of a losartan-based antihypertensive treatment in this population is projected to prevent approximately 125 000 first strokes over a 5.5-year period. A population-wide prevention strategy of using losartan in patients with LVH and hypertension has the potential to have a major public health impact by reducing the morbidity and mortality of stroke in the EU. PMID:15029217

  8. A Simple Spectrofluorimetric Method for the Determination of Losartan in Some Tablet Dosage Forms

    NASA Astrophysics Data System (ADS)

    Taher, M. A.; Asadollahzadeh, H.; Fazelirad, H.

    2015-11-01

    A very simple and sensitive spectrofluorimetric method was developed for the direct determination of losartan in some commercial tablets. The suggested method is based on the linear relationship between 0.1-5.0 μg/ml of losartan and its fluorescence intensity at 400 nm in acidic medium. The detection limit and relative standard deviation (for ten repetitive measurements of 2.0 μg/ml) were obtained as 12.0 ng/ml and 1.35%, respectively. The recommended method was successfully applied for the determination of losartan in three types of commercial tablets from different brands.

  9. A Method for Content Uniformity Determination of Atenolol and Losartan Potassium in Combined Tablet Dosage Form

    PubMed Central

    Shah, S. A.; Vyas, R. B.; Vyas, B. A.; Maniyar, N. R.; Chauhan, R. S.; Shah, D. R.

    2010-01-01

    A simple, accurate, rapid, specific and reproducible UV spectrophotometric method was developed for estimation of content uniformity of atenolol and losartan potassium in its combined tablet dosage form. The method involves formation and solving the simultaneous equation using 226.4 and 254 nm as two wavelengths for atenolol and losartan, respectively. Developed method was employed to determine the atenolol and losartan content in ten individual tablet units of five market formulations. Methanol was used as solvent. The method was validated. From the results, it was concluded that all brands are within the content uniformity limit, 85-115%. PMID:21969756

  10. Losartan/hydrochlorothiazide combination therapy surpasses high-dose angiotensin receptor blocker in the reduction of morning home blood pressure in patients with morning hypertension.

    PubMed

    Hanayama, Yoshihisa; Uchida, Haruhito Adam; Nakamura, Yoshio; Makino, Hirofumi

    2012-01-01

    Angiotensin receptor blockers (ARBs) are the first-line antihypertensive agents. In clinical practice, it is often difficult to achieve the recommended blood pressure level by ARBs in their ordinal dosages alone. This study examined the practical efficacy of a combination therapy of ARB with thiazide diuretics for lowering morning home blood pressure (MHBP) in comparison to high-dose ARB therapy in patients with morning hypertension administered an ordinal dosage of ARB. This study was performed in a prospective, randomized, open-labeled and blind-endpoint fashion. Patients were considered to have morning hypertension when their self-measured systolic MHBPs were 135mmHg or higher, irrespective of their diastolic MHBP and office blood pressures (OBPs). Forty-eight outpatients with morning hypertension receiving the ordinal dosage of ARB were given either losartan/hydrochlorothiazide (n = 26) or high-dose ARB (n = 22) in place of their previously prescribed ARB. No change in any medication was permitted during this period. Decreases of both systolic and diastolic MHBP after 3 months of treatment were significantly greater in the losartan/hydrochlorothiazide group than in the high-dose ARB group (p < 0.05, respectively). The ratio of adverse events was somewhat high (23.1% in the losartan/hydrochlorothiazide group, 9.1% in the high-dose ARB group, respectively). However, there were no significant differences in any particular adverse event between groups. This study suggested losartan/hydrochlorothiazide might be superior to high-dose ARB for reducing morning home blood pressure. PMID:23254579

  11. Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY)

    PubMed Central

    Tomita, Kengo; Kawai, Toshihide; Yokoyama, Hirokazu; Shimada, Akira; Kikuchi, Masahiro; Hirose, Hiroshi; Ebinuma, Hirotoshi; Irie, Junichiro; Ojiro, Keisuke; Oikawa, Yoichi; Itoh, Hiroshi; Hibi, Toshifumi

    2013-01-01

    Aim. This study compared the effects of telmisartan and losartan on nonalcoholic fatty liver disease (NAFLD) and biochemical markers of insulin resistance in hypertensive NAFLD patients with type 2 diabetes mellitus. Methods. This was a randomized, open-label, parallel-group comparison of therapy with telmisartan or losartan. Nineteen hypertensive NAFLD patients with type 2 diabetes were randomly assigned to receive telmisartan at a dose of 20 mg once a day (n = 12) or losartan at a dose of 50 mg once a day (n = 7) for 12 months. Body fat area as determined by CT scanning and hepatic fat content based on the liver-to-spleen (L/S) ratio, as well as several parameters of glycemic and lipid metabolism, were compared before and after 12 months. Results. The telmisartan group showed a significant decline in serum free fatty acid (FFA) level (from 0.87 ± 0.26 to 0.59 ± 0.22 mEq/L (mean ± SD), P = 0.005) and a significant increase in L/S ratio (P = 0.049) evaluated by CT scan, while these parameters were not changed in the losartan group. Conclusion. Although there was no significant difference in improvement in liver enzymes with telmisartan and losartan treatment in hypertensive NAFLD patients with type 2 diabetes after 12 months, it is suggested that telmisartan may exert beneficial effects by improving fatty liver. PMID:23997767

  12. Randomized, Double-Blind, Controlled Study of Losartan in Children with Proteinuria

    PubMed Central

    Lam, Chun; Loeys, Tom; Shahinfar, Shahnaz; Strehlau, Juergen; Wells, Thomas G.; Santoro, Emanuela; Manas, Denise; Gleim, Gilbert W.

    2010-01-01

    Background and objectives: No large, randomized, double-blind trials in children with proteinuria treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported. Design, setting, participants, & measurements: This 12-week, double-blind, multinational study investigated the effects of losartan 0.7 to 1.4 mg/kg per day compared with placebo (normotensive stratum) or amlodipine 0.1 to 0.2 mg/kg per day up to 5 mg/d (hypertensive stratum) on proteinuria (morning-void urinary protein-creatinine ratio, baseline ≥0.3 g/g) in 306 children up to 17 years of age. Results: Twelve weeks of treatment with losartan significantly reduced proteinuria compared with amlodipine/placebo: losartan −35.8% (95% confidence interval: −27.6% to −43.1%) versus amlodipine/placebo 1.4% (95% confidence interval: −10.3% to 14.5%), P ≤ 0.001. Significance remained after adjustment for differences across treatment groups in change in BP (losartan produced incremental systolic and diastolic BP reductions versus amlodipine of 5.4 and 4.6 mmHg, respectively; and versus placebo of 3.8 and 4.0 mmHg, respectively). Proteinuria reduction was consistently observed in the normotensive (−34.4% losartan; 2.6% placebo) and hypertensive (−41.5% losartan; 2.4% amlodipine) strata, and in all prespecified subgroups, including age, gender, race, Tanner stage, weight, prior therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, as well as among the most common etiologies of proteinuria. Adverse event incidence was low and comparable in all groups. Conclusions: Losartan significantly lowered proteinuria and was well tolerated after 12 weeks in children aged 1 to 17 years with proteinuria with or without hypertension, a population that has not previously been rigorously studied. PMID:20089489

  13. One-year effectiveness and safety of open-label losartan/hydrochlorothiazide combination therapy in Japanese patients with hypertension uncontrolled with ARBs or ACE inhibitors.

    PubMed

    Kita, Toshihiro; Yokota, Naoto; Ichiki, Yoshinari; Ayabe, Takao; Etoh, Takuma; Tamaki, Noboru; Kato, Johji; Eto, Tanenao; Kitamura, Kazuo

    2010-04-01

    The long-term antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been appropriately evaluated in Japan. In this study, treated hypertensive patients taking angiotensin-receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) regimens not at blood pressure (BP) goals proposed by the Japanese Society of Hypertension (JSH) were switched to losartan/HCTZ combinations and followed for 1 year. Data analysis included 244 patients aged 64.5+/-10.7 years, 56% male, 27% with diabetes mellitus and 36% with dyslipidemia. Pre-switching BP 157+/-16/88+/-10 mm Hg promptly decreased and maintained a steady state, reaching 132+/-15/77+/-9 mm Hg (P<0.001) 1 year later. After 1 year of treatment, 50% of patients cleared the goals of the JSH guideline for systolic BP and 79% for diastolic BP. Patients with maximal doses of ARBs tended to show larger decreases in BP (159+/-11/90+/-10 to 128+/-10/75+/-8 mm Hg, P<0.001, n=32). Clinical and laboratory adverse events were reported for 29 patients (11%), but serious abnormalities were not observed. In particular, plasma levels of uric acid (UA) were well-maintained for 1 year, and significant decreases in UA were observed in patients with higher levels of UA (>/=7.0 mg dl(-1)). Losartan/HCTZ combinations showed strong and steady hypotensive abilities and acceptable safety and tolerability in patients currently not at BP goals with regimens including ARBs or ACEIs in Japan. PMID:20075934

  14. Effects of losartan vs candesartan in reducing cardiovascular events in the primary treatment of hypertension

    PubMed Central

    Kjeldsen, S E; Stålhammar, J; Hasvold, P; Bodegard, J; Olsson, U; Russell, D

    2010-01-01

    Although angiotensin receptor blockers have different receptor binding properties no comparative studies with cardiovascular disease (CVD) end points have been performed within this class of drugs. The aim of this study was to test the hypothesis that there are blood pressure independent CVD-risk differences between losartan and candesartan treatment in patients with hypertension without known CVD. Seventy-two primary care centres in Sweden were screened for patients who had been prescribed losartan or candesartan between the years 1999 and 2007. Among the 24 943 eligible patients, 14 100 patients were diagnosed with hypertension and prescribed losartan (n=6771) or candesartan (n=7329). Patients were linked to Swedish national hospitalizations and death cause register. There was no difference in blood pressure reduction when comparing the losartan and candesartan groups during follow-up. Compared with the losartan group, the candesartan group had a lower adjusted hazard ratio for total CVD (0.86, 95% confidence interval (CI) 0.77–0.96, P=0.0062), heart failure (0.64, 95% CI 0.50–0.82, P=0.0004), cardiac arrhythmias (0.80, 95% CI 0.65–0.92, P=0.0330), and peripheral artery disease (0.61, 95% CI 0.41–0.91, P=0.0140). No difference in blood pressure reduction was observed suggesting that other mechanisms related to different pharmacological properties of the drugs may explain the divergent clinical outcomes. PMID:19890371

  15. Spectrophotometric and HPLC Methods for Simultaneous Estimation of Amlodipine Besilate, Losartan Potassium and Hydrochlorothiazide in Tablets

    PubMed Central

    Wankhede, S. B.; Raka, K. C.; Wadkar, S. B.; Chitlange, S. S.

    2010-01-01

    Two UV-spectrophotometric and one reverse phase high performance liquid chromatography methods have been developed for the simultaneous estimation of amlodipine besilate, losartan potassium and hydrochlorothiazide in tablet dosage form. The first UV spectrophotometric method was a determination using the simultaneous equation method at 236.5, 254 and 271 nm over the concentration range 5-25, 10-50 and 5-25 μg/ml for amlodipine besilate, losartan potassium and hydrochlorothiazide, respectively. The second UV method was a determination using the area under curve method at 231.5-241.5, 249-259 and 266-276 nm over the concentration range of 5-25, 5-25 and 10-50 μg/ml for amlodipine besilate, hydrochlorothiazide and losartan potassium, respectively. In reverse phase high performance liquid chromatography analysis is carried out using 0.025 M phosphate buffer (pH 3.7):acetonitrile (57:43 v/v) as the mobile phase and Kromasil C18 (4.6 mm i.d×250 mm) column as stationery phase with detection wavelength of 232 nm linearity was obtained in the concentration range of 2-14, 20-140 and 5-40 μg/ml for amlodipine besilate, losartan potassium and hydrochlorothiazide, respectively. Both UV-spectrophotometric and reverse phase high performance liquid chromatography methods were statistically validated and can be used for analysis of combined dose tablet formulation containing amlodipine besilate, losartan potassium and hydrochlorothiazide. PMID:20582208

  16. Effect of losartan and atenolol on insulin sensitivity in nondiabetic hypertensive patients

    PubMed Central

    Bharati, Sandesh Madhukar; Singh, Nishith

    2016-01-01

    Objective: To study the effects of losartan and atenolol on glucometabolic parameters in nondiabetic hypertensive patients. Materials and Methods: In a prospective, open-label, parallel group study, nondiabetic patients with mild to moderate hypertension were randomized to either losartan (titrated from 50 to 100 mg/day, n = 20) or atenolol (titrated from 25 mg to 100 mg/day, n = 20) for period of 24 weeks. At baseline, 12 and 24 weeks fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment for insulin resistance (HOMA-IR) apart from lipid parameters, mean systolic, and diastolic blood pressures levels were determined. Results: At the end of study, losartan significantly (P < 0.05) reduced FPG, FPI, and HOMA-IR compared to atenolol and baseline. While atenolol increased the HOMA-IR levels significantly compared to the baseline. Conclusions: Losartan improved the insulin sensitivity while atenolol worsened it. Losartan is better than atenolol for its effects on the glucose-insulin metabolism. PMID:27440952

  17. Managing blood pressure control in Asian patients: safety and efficacy of losartan

    PubMed Central

    Cheung, Tommy Tsang; Cheung, Bernard Man Yung

    2014-01-01

    Hypertension is common in Asian populations and is a major cause of cardiovascular diseases. The prevalence of hypertension is increasing in many Asian countries. The overall prevalence of hypertension in India and the People’s Republic of China has been estimated to be 20.6% in men and 22.6% in women. However, the rates of detection, treatment, and control of hypertension remain low in Asia. This reflects a low level of literacy and education, as well as a low level of access to medical care. To overcome these obstacles, strategies targeted at education, promotion, and optimization of medical care, are crucial to achieve target blood pressure control. Angiotensin receptor blockers are one of the first-line treatments for essential hypertension because they confer better cardiovascular outcomes. Losartan has been widely evaluated for the management of hypertension. Although some studies suggested that the blood pressure-lowering effect of losartan is perhaps lower than for other angiotensin receptor blockers, losartan has been demonstrated to be beneficial in terms of renal protection in patients with diabetes, heart failure resulting from either systolic or diastolic dysfunction, and diuretic-induced hyperuricemia. However, most of these data were obtained from Caucasian populations. The efficacy and safety of losartan in Asian populations may be different because of genetic and ethnic variations. Therefore, the efficacy and safety of losartan in Asian patients with hypertension warrant further study. PMID:24672231

  18. [REGRESSION OF LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH ESSENTIAL HYPERTENSION AND LONG-TERM THERAPY WITH LOSARTAN].

    PubMed

    Dotsenko, S Y; Tokarenko, A A; Tokarenko, I I

    2015-01-01

    In 106 patients with essential hypertension stage II losartan effectively lowers systolic and diastolic blood pressure during the day, thus contributing to the normalization of the circadian blood pressure profile in patients with initial breach, and does not affect the normal circadian rhythm. Long losartan promotes regression remodeling processes of cardiac muscle and reduce preload and afterload. PMID:27491145

  19. SMAD4 mutations causing Myhre syndrome result in disorganization of extracellular matrix improved by losartan

    PubMed Central

    Piccolo, Pasquale; Mithbaokar, Pratibha; Sabatino, Valeria; Tolmie, John; Melis, Daniela; Schiaffino, Maria Cristina; Filocamo, Mirella; Andria, Generoso; Brunetti-Pierri, Nicola

    2014-01-01

    Myhre syndrome (MS, MIM 139210) is a connective tissue disorder that presents with short stature, short hands and feet, facial dysmorphic features, muscle hypertrophy, thickened skin, and deafness. Recurrent missense mutations in SMAD4 encoding for a transducer mediating transforming growth factor β (TGF-β) signaling are responsible for MS. We found that MS fibroblasts showed increased SMAD4 protein levels, impaired matrix deposition, and altered expression of genes encoding matrix metalloproteinases and related inhibitors. Increased TGF-β signaling and progression of aortic root dilation in Marfan syndrome can be prevented by the antihypertensive drug losartan, a TGF-β antagonists and angiotensin-II type 1 receptor blocker. Herein, we showed that losartan normalizes metalloproteinase and related inhibitor transcript levels and corrects the extracellular matrix deposition defect in fibroblasts from MS patients. The results of this study may pave the way toward therapeutic applications of losartan in MS. PMID:24398790

  20. Long-Term Treatment with Losartan Attenuates Seizure Activity and Neuronal Damage Without Affecting Behavioral Changes in a Model of Co-morbid Hypertension and Epilepsy.

    PubMed

    Tchekalarova, Jana D; Ivanova, Natasha; Atanasova, Dimitrina; Pechlivanova, Daniela M; Lazarov, Nikolai; Kortenska, Lidia; Mitreva, Rumiana; Lozanov, Valentin; Stoynev, Alexander

    2016-08-01

    Over the last 10 years, accumulated experimental and clinical evidence has supported the idea that AT1 receptor subtype is involved in epilepsy. Recently, we have shown that the selective AT1 receptor antagonist losartan attenuates epileptogenesis and exerts neuroprotection in the CA1 area of the hippocampus in epileptic Wistar rats. This study aimed to verify the efficacy of long-term treatment with losartan (10 mg/kg) after kainate-induced status epilepticus (SE) on seizure activity, behavioral and biochemical changes, and neuronal damage in a model of co-morbid hypertension and epilepsy. Spontaneous seizures were video- and EEG-monitored in spontaneously hypertensive rats (SHRs) for a 16-week period after SE. The behavior was analyzed by open field, elevated plus maze, sugar preference test, and forced swim test. The levels of serotonin in the hippocampus and neuronal loss were estimated by HPLC and hematoxylin and eosin staining, respectively. The AT1 receptor antagonism delayed the onset of seizures and alleviated their frequency and duration during and after discontinuation of treatment. Losartan showed neuroprotection mostly in the CA3 area of the hippocampus and the septo-temporal hilus of the dentate gyrus in SHRs. However, the AT1 receptor antagonist did not exert a substantial influence on concomitant with epilepsy behavioral changes and decreased 5-HT levels in the hippocampus. Our results suggest that the antihypertensive therapy with an AT1 receptor blocker might be effective against seizure activity and neuronal damage in a co-morbid hypertension and epilepsy. PMID:26464042

  1. Effect of centrally administered losartan on gastric and duodenal ulcers in rats.

    PubMed

    Merai, Ankitkumar Harshadrai; Asad, Mohammed; Prasad, V Satya

    2009-01-01

    The effect of centrally administered losartan, an AT(1) receptor antagonist, on gastric acid secretion and gastric cytoprotection was studied using different models of gastric ulcers, such as acetic acid-induced chronic gastric ulcers, pylorus ligation, ethanol-induced and stress-induced acute gastric ulcers and cysteamine hydrochloride-induced duodenal ulcer. Losartan was administered intracerebroventrically (i.c.v.) at 2 different doses (125 and 250 microg/kg). Both doses of losartan increased the healing of acetic acid-induced chronic gastric ulcers. In pylorus-ligated rats, a significant reduction in free acidity, total acidity and ulcer index was observed with high dose (250 microg/kg, i.c.v.), while low dose (125 microg/kg, i.c.v.) produced reduction only in free acidity and ulcer index. Both doses also produced a significant antiulcer effect in ethanol-induced and stress-induced gastric ulcers. Losartan also reduced ulcer area in cysteamine-induced duodenal ulcer. We conclude that AT(1) receptor antagonism in the brain increases healing of gastric ulcers and reduces gastric acid secretion and increases gastric mucin content. PMID:19602912

  2. RP-HPLC Method for the Determination of Losartan Potassium and Ramipril in Combined Dosage Form

    PubMed Central

    Rao, K. Srinivasa; Srinivas, K.

    2010-01-01

    A simple, specific and accurate reverse phase liquid chromatographic method was developed for the simultaneous determination of losartan potassium and ramipril in table dosage forms. A hypersil ODS C18, 4.6×250 mm, 5 μm column in isocratic mode, with mobile phase acetonitrile:methanol:10 mM tetra butyl ammonium hydrogen sulphate in water in the ratio of 30:30:40% v/v/v was used. The flow rate was 1.0 ml/min and effluent was monitored at 210 nm. The retention times of losartan potassium and ramipril were 4.7 and 3.3 min, respectively. The linearity range for losartan potassium and ramipril were in the range of 0.04-100 μg/ml and 0.2-300 μg/ml, respectively. The proposed method was also validated and successfully applied to the estimation of losartan potassium and ramipril in combined tablet formulations. PMID:20582199

  3. Development and validation of an UV derivative spectrophotometric determination of Losartan potassium in tablets.

    PubMed

    Lastra, Olga C; Lemus, Igor G; Sánchez, Hugo J; Pérez, Renato F

    2003-09-19

    Development and validation of an analytical UV derivative spectrophotometric method to quantify Losartan potassium used as a single active principle in pharmaceutical forms were done. Pharmacopeias have not yet provided an official method for its quantification. A study was carried out of all the parameters established by USP XXIV to validate an analytical method for a solid pharmaceutical form, i.e. linearity, range, accuracy, precision and specificity. All these parameters were found in accordance with the acceptance criteria of Comité de Guías Oficiales de Validación de la Dirección General de Control de Insumos para la Salud de México. Based on the spectrophotometric characteristics of Losartan potassium, a signal at 234 nm of the first derivative spectrum (1D234) was found adequate for quantification. The linearity between signal 1D234 and concentration of Losartan potassium in the range of 4.00-6.00 mg l(-1) in aqueous solutions presents a square correlation coefficient (r2) of 0.9938. The mean recovery percentage was 100.7+/-1.1% and the precision expressed as relative standard deviation (R.S.D.) 0.88%. In addition, the proposed method is simple, easy to apply, low-cost, does not use polluting reagents and requires relatively inexpensive instruments. Then, it is a good alternative to existing methods for determining Losartan potassium in tablets provided that the pharmaceutical dosage form does not contain hydrochlorothiazide as second drug. PMID:12972082

  4. Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes

    PubMed Central

    Mauer, Michael; Zinman, Bernard; Gardiner, Robert; Suissa, Samy; Sinaiko, Alan; Strand, Trudy; Drummond, Keith; Donnelly, Sandra; Goodyer, Paul; Gubler, Marie Claire; Klein, Ronald

    2010-01-01

    Background Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether early administration of drugs that block the renin-angiotensin system slows their progression. Methods The Renin Angiotensin System Study [RASS] was a multicenter controlled trial in 285 normoalbuminuric, normotensive type 1 diabetic patients who were randomized to losartan (100mg daily), enalapril (20mg daily) or placebo and followed for 5 years. The primary endpoint was change in glomerular mesangial fractional volume in kidney biopsies. The retinopathy endpoint was a 2-step or greater progression in retinopathy severity scale. Intention-to-treat data analyses used linear and logistic regression models. Results Ninety and 82% of patients had complete renal biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over 5 years in placebo (0.016 units) was not significantly different from enalapril (p=0.38) or losartan (p=0.26), nor were there significant changes in other biopsy assessed renal structural variables. Five-year cumulative microalbuminuria incidence was higher for losartan than placebo (14% vs. 4%; logrank p=0.015) but not for enalapril (6% vs. 4%; logrank p=0.96). Two-step or more retinopathy progression incidence was reduced by 65% in the enalapril (O.R. 0.35; 95% C.I., 0.14–0.85) and 70% in the losartan group (O.R. 0.30; 95% C.I., 0.12–0.73) independent of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 enalapril, 6 losartan and 4 placebo patients. Conclusions Early renin-angiotensin system blockade did not modify nephropathy progression in type 1 diabetic patients, but had important effects in slowing retinopathy. PMID:19571282

  5. AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease.

    PubMed

    Liu, Tian-Jing; Shi, Yong-Yan; Wang, En-Bo; Zhu, Tong; Zhao, Qun

    2016-02-01

    Angiotensin II, which is the main effector of the renin‑angiotensin system, has an important role in intestinal inflammation via the angiotensin II type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored according to a microscopic scoring system, and reverse transcription-quantitative polymerase chain reaction were performed in order to investigate colonic inflammation. In addition, intestinal epithelial barrier permeability was evaluated, and intestinal epithelial cell (IEC) apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and apoptosis-related protein expression levels were detected by western blotting. Losartan was able to attenuate TNBS-induced body weight loss and colonic damage. Furthermore, T helper 1-mediated proinflammatory cytokines were suppressed by losartan, and gut permeability was largely preserved. TUNEL staining revealed reduced IEC apoptosis in the losartan-treated mice. Losartan also increased the B-cell lymphoma 2 (Bcl2)/Bcl-2-associated X protein (Bax) ratio and suppressed caspase-3 induction. These results suggested that the AT1R blocker losartan may attenuate TNBS-induced colitis by inhibiting the apoptosis of IECs. The effects of losartan were partially mediated through increasing the Bcl-2/Bax ratio and subsequently suppressing the induction of the proapoptotic mediator caspase-3. PMID:26676112

  6. Modulating effect of losartan potassium on the mutagenicity and recombinogenicity of doxorubicin in somatic cells of Drosophila melanogaster.

    PubMed

    Silva-Oliveira, R G; Orsolin, P C; Nepomuceno, J C

    2016-09-01

    Losartan potassium is an antihypertensive drug in the angiotensin II receptor antagonist (ARA) class. Some studies claim that, in addition to regulating blood pressure, this class of drug has anticancer properties. The objective of this study was to evaluate the genotoxic and antigenotoxic potential of losartan potassium using the SMART (Somatic Mutation and Recombination Test) assay on the somatic cells of Drosophila melanogaster, as well as the possible modulating effects of this drug, when associated with doxorubicin (DXR). Third instar larvae, descendents of standard and high bioactivation (ST and HB) crosses, were chronically treated with different concentrations of losartan potassium (0.25; 0.5; 1; 2; and 4 mM) alone or in association (co-treatment) with doxorubicin (DXR 0.125 mg/mL). The results showed an absence of a mutagenic effect of losartan potassium. In the co-treatment of losartan with DXR, the results showed that losartan is capable of reducing the number of mutant spots induced by DXR without altering the recombinogenic effect of the chemotherapeutic agent. Antiproliferative action appears to be the main mechanism involved in reducing the frequency of mutant spots and consequent modulation of alterations induced by DXR, although this parameter has not been directly assessed in this study. PMID:27394655

  7. Functional interaction between losartan and central tachykinin NK3 receptors in the conscious rat.

    PubMed Central

    Picard, P; Chrétien, L; Couture, R

    1995-01-01

    1. The cardiovascular and behavioural effects elicted by the intracerebroventricular (i.c.v.) injection of substance P (SP), neurokinin A (NKA), [MePhe7]neurokinin B ([MePhe7]NKB) or angiotensin II (AII) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for angiotensin AT1 (losartan and its active metabolite EXP 3174), angiotensin AT2 (PD 123,319) or tachykinin NK3 (R 486) receptors. 2. I.c.v. administration of 25 pmol AII evoked an increase in mean arterial blood pressure (MAP) and water intake behaviour, accompanied by a transient bradycardia, whereas 25 pmol [MePhe7]NKB caused a transient increase in MAP and heart rate (HR) concurrently with marked wet dog shake behaviour. At the same dose, SP and NKA were more potent than [MePhe7]NKB in increasing MAP and HR, but did not produce water intake or wet dog shake behaviours. 3. Losartan (650 pmol, i.c.v.) reduced significantly the cardiovascular and behavioural responses to AII or [MePhe7]NKB, but not to SP or NKA. While 65 pmol losartan was inactive, 260 pmol inhibited selectively the central effects of AII. Whereas EXP 3174 (6.5 nmol) blocked both AII and [MePhe7]NKB-mediated responses, the dose of 650 pmol blocked only the responses to AII. 4. The central responses to AII and [MePhe7]NKB were not affected by PD 123,319 (650 pmol). On the other hand, the [MePhe7]NKB-induced central effects were significnatly reduced by R 486 (650 pmol). The NK3-selective antagonist had no effect against AII. 5. This study provides functional evidence, to support earlier binding data, that losartan (and to some extent its active metabolite EXP 3174) interact with the tachykinin NK3 receptor in rat brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7541280

  8. The antioxidant effect of angiotensin II receptor blocker, losartan, in streptozotocin-induced diabetic rats.

    PubMed

    Kamper, Maria; Tsimpoukidi, Olia; Chatzigeorgiou, Antonios; Lymberi, Maria; Kamper, Elli F

    2010-07-01

    We determined the effect of a short-term angiotensin II signaling blockade on vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide (NO), and malondialdehyde (MDA) (index of lipid peroxidation) levels in the systemic circulation and on peroxynitrite generation and insulitis development in the streptozotocin (STZ) diabetic rats' pancreas. Diabetes was induced in Wistar rats by intraperitoneal STZ injection. Diabetic rats were treated for 1 week with losartan (20 mg/kg/body weight/day in the drinking water), and pancreas and blood were collected for histochemical, immunohistochemical, and biochemical studies. Diabetic rats showed greater VEGF, sICAM-1, NO, and MDA levels, a high score of insulitis, increased nitrotyrosine staining, and markedly reduced pancreatic insulin content when compared with controls. Losartan treatment suppressed the excessive NO and lipid peroxidation production systemically without restoring them to that of healthy subjects and reduced VEGF levels while leaving sICAM-1 levels unchanged. The insulitis score and nitrotyrosine staining were reduced, whereas the pancreatic islets and the beta-cell area were increased significantly in the treated group, indicating the reduction of inflammation and nitrosative stress and an early regeneration of beta-cell mass in the pancreas. Conclusively, in the STZ diabetic rat model, even a short-term losartan treatment improves oxidative and nitrosative stress systemically and locally, improving the islets' environment and accelerating beta-cell regeneration. PMID:20621034

  9. The Fixed-Dose Combination of Losartan/Hydrochlorothiazide Elicits Potent Blood Pressure Lowering During Nighttime in Obese Hypertensive Patients

    PubMed Central

    Ibuki, Chikao; Seino, Yoshihiko; Otsuka, Toshiaki; Mizuno, Kyoichi

    2014-01-01

    Background Hypertension is one of the most powerful predictor of the future cardiovascular events, and antihypertensive therapy adopting multiple drug regimen is often needed to obtain the appropriate blood pressure (BP) control. To clarify the blood pressure-lowering effect of the fixed-dose combination (FDC) of an angiotensin receptor blocker (ARB) and diuretic agent in poorly controlled hypertensive patients, we intended a multicenter prospective observational study (Investigation for Normalized Blood pressure control with the Appropriate medication: INBA) by means of the sequential ambulatory blood pressure monitoring (ABPM). Methods One hundred and thirteen hypertensive patients who had not achieved the target BP control proposed in the guidelines with medication containing any ARB but without diuretic agents (54 men; mean age, 66 years old; mean office systolic/diastolic BP (SBP/DBP), 158/82 mmHg) were enrolled. Daytime and nighttime blood pressures were assessed with ABPM before and at 12 weeks after switching the ARB to the FDC of 50 mg of losartan, and 12.5 mg of hydrochlorothiazide (HCTZ). Results Daytime SBP/DBP (mean ± SD) decreased from 151 ± 14/88 ± 8 mmHg to 140 ± 11/82 ± 8 mmHg (P < 0.001, P < 0.001, respectively), and nocturnal SBP/DBP from 138 ± 18/78 ± 9 mmHg to 125 ± 14/72 ± 9 mmHg (P < 0.001, P < 0.001, respectively) during the 12 weeks treatment. Pulse rate did not change irrespective of the time window. Among various parameters (age, history of hypertension, body mass index (BMI), serum potassium, uric acid, estimated glomerular filtration rate, plasma B-type natriuretic peptide), BMI alone showed significant negative correlation with 12-weeks reduction in nocturnal SBP (r = -0.43, P < 0.05). No parameters correlated with reduction in daytime SBP during this period. Patients with BMI ≥ median (25.8 kg/m2) showed significantly greater reduction in nocturnal SBP for 12 weeks than patients with BMI < median (20.1 ± 15.6 mmHg vs 6.1

  10. Ecotoxicological evaluation of propranolol hydrochloride and losartan potassium to Lemna minor L. (1753) individually and in binary mixtures.

    PubMed

    Godoy, Aline A; Kummrow, Fábio; Pamplin, Paulo Augusto Z

    2015-07-01

    Antihypertensive pharmaceuticals, including the beta-blockers, are one of the most detected therapeutic classes in the environment. The ecotoxicity of propranolol hydrochloride and losartan potassium was evaluated, both individually and combined in a binary mixture, by using the Lemna minor growth inhibition test. The endpoints evaluated in the single-pharmaceutical tests were frond number, total frond area and fresh weight. For the evaluation of the mixture toxicity, the selected endpoint was frond number. Water quality criteria values (WQC) were derived for the protection of freshwater and saltwater pelagic communities regarding the effects induced by propranolol and losartan using ecotoxicological data from the literature, including our data. The risks associated with both pharmaceutical effects on non-target organisms were quantified through the measured environmental concentration (MEC)/predicted-no-effect concentration (PNEC) ratios. For propranolol, the total frond area was the most sensitive endpoint (EC50 = 77.3 mg L(-1)), while for losartan there was no statistically significant difference between the endpoints. Losartan is only slightly more toxic than propranolol. Both concentration addition and independent action models overestimated the mixture toxicity of the pharmaceuticals at all the effect concentration levels evaluated. The joint action of both pharmaceuticals showed an antagonistic interaction to L. minor. Derived WQC assumed lower values for propranolol than for losartan. The MEC/PNEC ratios showed that propranolol may pose a risk for the most sensitive aquatic species, while acceptable risks posed by losartan were estimated for most of aquatic matrices. To the authors knowledge these are the first data about losartan toxicity for L. minor. PMID:25847105

  11. Losartan Attenuates Myocardial Endothelial-To-Mesenchymal Transition in Spontaneous Hypertensive Rats via Inhibiting TGF-β/Smad Signaling

    PubMed Central

    Wu, Miao; Peng, Zhenyu; Zu, Changhao; Ma, Jing; Lu, Shijuan; Zhong, Jianghua; Zhang, Saidan

    2016-01-01

    Background Losartan plays an important role in the inhibition of myocardial fibrosis. But the underlying mechanism is not entirely clear. Emerging evidences have indicated that endothelial-to-mesenchymal transition (EndMT) plays a crucial role in cardiac fibrosis. Here the present study aims to first investigated the effect of Losartan on EndMT in cardiac fibrosis of spontaneous hypertensive rats (SHRs). Methods Male SHRs were randomly divided into three groups and fed for 12 weeks, namely the SHR group (Group S), the Losartan-treated group (Group L) and the Prazosin-treated group (Group P). Wistar-Kyoto rats served as controls (Group W). The histological changes were evaluated by Masson’s trichrome. Co-expression of CD31 and fibroblast-specific protein 1 (FSP1) were used as the markers of EndMT through immunofluorescence. The expressions of FSP1, CD31, TGF-β, Smad were detected by Western blot analysis. Results It was identified that elevated blood pressure induced a significant increase in myocardial fibrosis and EndMT in SHRs, which was reversed by Losartan and Prazosin treatment. Furthermore, the activity of TGF-β/Smad signaling was detected in the four groups. TGF-β/Smad signaling was activated in SHRs and suppressed by Losartan or Prazosin treatment. Losartan exhibited more efficiently than Prazosin in inhibiting TGF-β/Smad signaling activation, EndMT and myocardial fibrosis. Conclusion These results showed that EndMT played an important role in promoting hypertensive cardiac fibrosis, and that losartan could suppress cardiac fibrosis through the inhibition of EndMT via classical TGF-β/Smad pathway. PMID:27176484

  12. Effectiveness of Losartan-Loaded Hyaluronic Acid (HA) Micelles for the Reduction of Advanced Hepatic Fibrosis in C3H/HeN Mice Model

    PubMed Central

    Thomas, Reju George; Moon, Myeong Ju; Kim, Jo Heon; Lee, Jae Hyuk; Jeong, Yong Yeon

    2015-01-01

    Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis. PMID:26714035

  13. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy

    PubMed Central

    Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  14. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

    PubMed

    Karanovic, Danijela; Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  15. Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study.

    PubMed

    McInnes, G; Burke, T A; Carides, G

    2006-01-01

    The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with left ventricular hypertrophy (LVH), mainly due to a highly significant 25% reduction in the relative risk of stroke compared with an atenolol-based regimen, for a similar reduction in blood pressure. The aim of this economic evaluation was to estimate the cost-effectiveness of losartan compared with atenolol from a UK national health system perspective. Quality-adjusted survival and direct medical costs were modelled beyond the trial using the within-trial incidence of stroke. Survival with stroke, study medication use and quality of life by stroke status were taken directly from the LIFE trial. The LIFE data were supplemented with UK data on lifetime direct medical costs of stroke and life expectancy in individuals without stroke. No additional stroke events or use of study treatment were assumed beyond the trial. Costs and benefits were discounted using current UK Treasury rates. In the base-case analysis, the reduction in stroke-related costs (by 968 sterling pound) offset 86% of the increase in study medication costs (1128 sterling pound) among losartan-treated patients. The incremental cost-effectiveness ratio (ICER) for losartan versus atenolol in hypertensive patients with LVH was 2130 sterling pound per quality-adjusted life year (QALY) gained (3195 Euro/QALY), and this increased to 11,352 sterling pound per QALY gained (16,450 Euro/QALY) when the costs of stroke beyond the first 5 years were excluded. Thus, the clinical benefit of losartan was achieved at a cost well within reported thresholds for cost-effectiveness. PMID:16357874

  16. Influence of cyclosporine A on glomerular growth and the effect of mizoribine and losartan on cyclosporine nephrotoxicity in young rats

    PubMed Central

    Kim, Ji Hong; Lee, Yeon Hee; Lim, Beom Jin; Jeong, Hyeon Joo; Kim, Pyung Kil; Shin, Jae Il

    2016-01-01

    The aim of this study was to evaluate the influence of cyclosporine A (CsA) on glomerular growth and the effect of mizoribine (MZR) and losartan (LSAR) on CsA-induced nephropathy in young rats. Six-week-old male Sprague-Dawley rats maintained on a low salt diet were given CsA (15 mg/kg), CsA and LSRT (30 mg/kg/day), CsA and MZR (5 mg/kg), or a combination of CsA, LSRT, and MZR for 4 and 7 weeks (two experiments) and compared with control group (olive oil-treated). Histopathology and glomerular size, inflammatory and fibrotic factors were studied. The score of acute CsA toxicity significantly decreased in the CsA + MZR group compared to the CsA group (p < 0.01). MZR and MZR + LSRT reduced tubulointerstitial fibrosis and TGF-β1 mRNA expression at 7 weeks. Osteopontin (OPN) mRNA expression was decreased at 7 weeks in MZR + LSRT (p < 0.01). Glomerular area decreased CsA group and recovered in MZR (p < 0.01) and MZR + LSRT (p < 0.01) at 7weeks. This study demonstrated that MZR and LSRT had suppressive effects on inflammatory process in chronic CsA nephropathy and led to improvement of tubular damage, tubulointerstitial fibrosis and arteriolopathy by down regulation of OPN and TGF-β1 and glomerular size contraction. PMID:26947764

  17. Comparison of the effects of levocetirizine and losartan on diabetic nephropathy and vascular dysfunction in streptozotocin-induced diabetic rats.

    PubMed

    Anbar, Hanan S; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M

    2016-06-01

    This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress, nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated. Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to body weight ratio, serum albumin, urinary proteins and creatinine clearance). Moreover, levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by losartan. Moreover, levocetirizine, similar to losartan, reduced the enhanced responsiveness of diabetic aorta to phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of levocetirizine on diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular hypertrophy by levocetirizine than by losartan. In conclusion, levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than, losartan in streptozotocin-diabetic rats. PMID:27012991

  18. Impact of therapy initiation with amlodipine or losartan on hemodynamic endpoints and JNC-VI blood pressure stage.

    PubMed

    Putnam, David; Griffis, Deborah; McLaughlin, Trent P; Arocho, Raul; Tang, Simon

    2006-01-01

    The relative efficacy of long-acting calcium channel antagonists and angiotensin II receptor blocking agents has been described in clinical trials; however, their effectiveness in an actual practice setting has not been well studied. This study assessed the effectiveness of 2 commonly prescribed antihypertensives, amlodipine and losartan, either as monotherapy or as add-on for patients insufficiently controlled on beta-blocker or diuretic therapy. This was a retrospective, observational study that utilized electronic medical records. Hypertensive patients more than 40 years old who were new users of amlodipine or losartan were included in the study. Patients with congestive heart failure or those using antihypertensives other than diuretics or beta-blockers were excluded. Blood pressure (BP) readings were followed up to 6 months after enrollment. Univariate and multivariate regression models were used to assess the impact of amlodipine or losartan therapy on hemodynamic end points and on JNC-VI BP stage. A total of 346 patients met the entry criteria. Of these, 275 (79.5%) amlodipine and 71 (20.5%) were prescribed losartan. Mean changes in systolic and diastolic blood pressure were greater for patients receiving amlodipine in univariate and multivariate analyses (reduction of 20/8 and 11/4 mm Hg, respectively; P<0.05). Mean change in pulse pressure trended strongly in favor of amlodipine (11.8 mm Hg vs. 7 mm Hg, P = 0.08). Univariate analysis indicated that amlodipine-treated patients were more likely to move to a better JNC-VI BP stage, where as losartan-treated patients, on average, moved to a worse stage. Amlodipine therapy was superior to losartan therapy among this population of hypertensive patients. PMID:16645423

  19. Simultaneous Determination and Pharmacokinetic Study of Losartan, Losartan Carboxylic Acid, Ramipril, Ramiprilat, and Hydrochlorothiazide in Rat Plasma by a Liquid Chromatography/Tandem Mass Spectrometry Method

    PubMed Central

    Dubey, Ramkumar; Ghosh, Manik

    2015-01-01

    The monitoring of the plasmatic concentrations of cardiovascular drugs is crucial for understanding their pharmacokinetics and pharmacodynamics. A simple, sensitive, specific, and high-throughput liquid chromatography/tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous estimation and pharmacokinetic study of losartan (LOS), losartan carboxylic acid (LCA), ramipril (RAM), ramiprilate (RPT), and hydrochlorothiazide (HCZ) in rat plasma using irbesartan (IBS) and metolazone (MET) as internal standards (ISs). After solid phase extraction (SPE), analytes and ISs were separated on an Agilent Poroshell 120, EC-C18 (50 mm × 4.6 mm, i.d., 2.7 μm) column with a mobile phase consisting of methanol/water (85:15, v/v) containing 5 mmol/L ammonium formate and 0.1% formic acid at a flow rate of 0.4 mL/min. The precursor → product ion transitions for the analytes and ISs were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) mode and switching the electrospray ionization (ESI) mode during chromatography from positive (to detect LOS, LCA, RAM, RPT, and IBS) to negative (to detect HCZ and MET). The method was validated as per the FDA guidelines and it exhibited sufficient specificity, accuracy, and precision. The method was found to be linear in the range of 3–3000 ng/mL for LOS and LCA, 0.1–200 ng/mL for RAM and RPT, and 1–1500 ng/mL for HCZ. The described method was successfully applied to the preclinical pharmacokinetic study of analytes after oral administration of a mixture of LOS (10 mg/kg), RAM (1 mg/kg), and HCZ (2.5 mg/kg) in rats. PMID:26839805

  20. Comparative Evaluation of Enalapril and Losartan in Pharmacological Correction of Experimental Osteoporosis and Fractures of Its Background

    PubMed Central

    Rajkumar, D. S. R.; Faitelson, A. V.; Gudyrev, O. S.; Dubrovin, G. M.; Pokrovski, M. V.; Ivanov, A. V.

    2013-01-01

    In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing. PMID:23401845

  1. Comparative evaluation of enalapril and losartan in pharmacological correction of experimental osteoporosis and fractures of its background.

    PubMed

    Rajkumar, D S R; Faitelson, A V; Gudyrev, O S; Dubrovin, G M; Pokrovski, M V; Ivanov, A V

    2013-01-01

    In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing. PMID:23401845

  2. Losartan, an orally active angiotensin (AT1) receptor antagonist: a review of its efficacy and safety in essential hypertension.

    PubMed

    McIntyre, M; Caffe, S E; Michalak, R A; Reid, J L

    1997-01-01

    Losartan potassium, an angiotensin II receptor antagonist, is the first of a new class of agents to be introduced for the treatment of hypertension. In this review, we describe the clinical pharmacology of losartan, including its pharmacokinetics in healthy, male volunteers and special patient groups, such as the elderly, patients with liver disease and patients with renal impairment. We also review its pharmacodynamics, including safety and tolerability; specificity of action; and the effect of salt depletion. We then review the studies examining clinical efficacy and safety in hypertension. PMID:9336021

  3. Electrochemical degradation of the antihypertensive losartan in aqueous medium by electro-oxidation with boron-doped diamond electrode.

    PubMed

    Salazar, Claudio; Contreras, Nicole; Mansilla, Héctor D; Yáñez, Jorge; Salazar, Ricardo

    2016-12-01

    In this work the electrochemical oxidation of losartan, an emerging pharmaceutical pollutant, was studied. Electrochemical oxidation was carried out in batch mode, in an open and undivided cell of 100cm(3) using a boron-doped diamond (BDD)/stainless steel system. With Cl(-) medium 56% of mineralization was registered, while with the trials containing SO4(2-) as supporting electrolyte a higher mineralization yield of 67% was reached, even obtaining a total removal of losartan potassium at 80mAcm(-2) and 180min of reaction time at pH 7.0. Higher losartan potassium concentrations enhanced the mineralization degree and the efficiency of the electrochemical oxidation process. During the mineralization up to 4 aromatic intermediates were identified by ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Moreover, short-linear carboxylic acids, like oxalic, succinic and oxamic were detected and quantified by ion-exclusion HPLC. Finally, the ability of the electrochemical oxidation process to mineralize dissolved commercial tablets containing losartan was achieved, obtaining TOC removal up to 71% under optimized conditions (10mAcm(-2), 0.05M Na2SO4, pH 7.0 and 25°C and 360min of electrolysis). PMID:27180209

  4. Application of back-propagation artificial neural network and curve estimation in pharmacokinetics of losartan in rabbit

    PubMed Central

    Lin, Bin; Lin, Gaotong; Liu, Xianyun; Ma, Jianshe; Wang, Xianchuan; Lin, Feiyan; Hu, Lufeng

    2015-01-01

    In order to develop pharmacokinetic model, a well-known multilayer feed-forward algorithm back-propagation artificial neural networks (BP-ANN) was applied to the pharmacokinetics of losartan in rabbit. The plasma concentrations of losartan in twelve rabbits, which were divided into two groups and given losartan 2 mg/kg by intravenous (Iv) and intragastrical (Ig) administration, were determined by LC-MS. The BP-ANN model included one input layer, hidden layers, and one output layer was constructed and compared with curve estimation based on the time-concentration data of losartan. The results showed the BP-ANN model had high goodness of fit index and good coherence (R > 0.99) between forecasted concentration and measured concentration both in Iv and Ig administration. The residuals of each concentrations generated by BP-ANN model were all smaller than Curve estimation. The pharmacokinetic result showed there was no significant difference between measured and simulated pharmacokinetic parameters including AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞), T1/2 V and Cmax (P > 0.05). In conclusion, the BP-ANN model has remarkably accurate predictions ability, which better than Curve estimation, and can be used as a utility tool in pharmacokinetic experiment. PMID:26885213

  5. Telmisartan vs losartan plus hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension--a randomised ABPM study.

    PubMed

    Neutel, J M; Kolloch, R E; Plouin, P F; Meinicke, T W; Schumacher, H

    2003-08-01

    The objective of this prospective, randomised, open-label, blinded-end point parallel-group, multicentre study was to show that telmisartan 80 mg is not inferior to a fixed-dose combination of losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg in patients with mild-to-moderate hypertension. The criterion for noninferiority was a treatment difference of < or =3.0 mmHg in the reduction of 24-h mean ambulatory diastolic blood pressure (DBP) from the end of the 4-week placebo washout period to the end of the 6-week active treatment period. In the intent-to-treat analysis, the mean reduction in 24-h DBP was 8.3+/-6.7 mmHg among telmisartan-treated patients (n=332) and 10.3+/-6.3 mmHg among losartan/HCTZ-treated patients (n=350). The mean adjusted difference in 24-h DBP between the two treatment groups was 1.9 mmHg, allowing rejection of the a priori null hypothesis of a treatment difference of >3 mmHg. The reduction in mean 24-h systolic blood pressure was 13.2+/-10.2 mmHg with telmisartan and 17.1+/-10.3 mmHg with losartan/HCTZ. Both drugs provided effective control over the 24-h dosing interval. Analyses of morning (0600-1159) ambulatory blood pressure monitoring DBP means and trough cuff DBP confirmed the noninferiority hypothesis of the protocol for telmisartan 80 mg vs losartan 50 mg/HCTZ 12.5 mg. The reductions in office blood pressures measured at trough in patients treated with telmisartan were -16.3/-9.6 and -18.5/-11.1 mmHg in the patients treated with losartan/HCTZ (difference -2.4/-1.2 mmHg). There were no differences between the side-effect profiles of the two treatments. PMID:12874615

  6. Control of size in losartan/copper(II) coordination complex hydrophobic precipitate.

    PubMed

    Denadai, Ângelo M L; Da Silva, Jeferson G; Guimarães, Pedro P G; Gomes, Leonardo Bertolini S; Mangrich, Antonio S; de Rezende, Edivaltrys I P; Daniel, Izabela M P; Beraldo, Heloísa; Sinisterra, Rubén D

    2013-10-01

    Reaction of highly soluble orally active, non-peptide antihypertensive drug losartan with copper(II) leads to the spontaneous formation of a very insoluble 2:1 covalent complex, which self assembles in a hydrophobic supramolecular structure of nanometric dimensions. Thermal analysis showed that Los/Cu(II) complex presents intermediate stability in comparison with its precursors KLos and Cu(OAc)2·H2O. Isothermal titration calorimetry indicated complexation to be a stepwise process, driven by enthalpy and entropy. Zeta potential and DLS measurements showed that it is possible to control the size and charge of nanoprecipitates by adjusting the relative concentration of Los(-) and Cu(II). PMID:23910296

  7. Comparison of the transplacental transfer of enalapril, captopril and losartan in sheep.

    PubMed Central

    Stevenson, K M; Gibson, K J; Lumbers, E R

    1995-01-01

    1. The transplacental transfers of three drugs (enalapril, captopril and losartan) which block the renin angiotensin system and have different lipophilicities were studied in chronically catheterized foetal sheep (125-139 days gestation). 2. The ability of the foeto-placental unit to convert enalapril to enalaprilat was studied in two chronically catheterized foetuses. Enalapril (3 mg kg-1, 7.9 mumol kg-1) given i.v. to the foetuses abolished the foetal pressor response to 5 micrograms angiotensin I (AI) in one foetus and attenuated the pressor response in the other. 3. Enalapril (100 mg, 5.7 mumol kg-1) given i.v. to the ewe (n = 5) abolished the maternal pressor response to 2.5 micrograms AI (n = 1) and attenuated the maternal pressor response to 5 micrograms AI (n = 5, P < 0.001). The foetal pressor response to 5 micrograms AI (n = 2) and 10 micrograms AI (n = 3) did not change. The maternal and foetal pressor responses to angiotensin II (AII; n = 5) did not change. 4. Foetal pressor responses to 5 micrograms AI (n = 1) and 10 micrograms AI (n = 2) were attenuated within 11 min of their mothers (n = 3) being given i.v. captopril (15 mg, 1.5 mumol kg-1). Foetal pressor responses to 5 micrograms AII (n = 1) and to 10 micrograms AII (n = 2) did not change. 5. Losartan (100 mg, kg-1, 21.7 mumol kg-1) given i.v. to the foetus (n = 9) attenuated the foetal pressor response to 5 micrograms AII (P < 0.001) but the maternal pressor response to 5 micrograms AII did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7606354

  8. In vitro and in vivo studies on chitosan beads of losartan Duolite AP143 complex, optimized by using statistical experimental design.

    PubMed

    Madgulkar, Ashwini; Bhalekar, Mangesh; Swami, Megha

    2009-01-01

    The aim of the present research work was to develop release modulated beads of losartan potassium complexed with anion exchange resin, Duolite AP143 (cholestyramine). Chitosan was selected as a hydrophilic polymer for the formation of beads which could sustain the release of the drug up to 12 h, along with drug resin complex (DRC). Chitosan beads were prepared using an in-liquid curing method by ionotropic cross-linking or interpolymer linkage with sodium tripolyphosphate (TPP). The formulation of the beads was optimized for entrapment efficiency and drug release using 3(2) full factorial design. The independent variables selected were DRC/chitosan and percent of TPP. The optimization model was validated for its performance characteristics. Studies revealed that as the concentration of chitosan and TPP was increased, entrapment efficiency and the drug release were found to increase and decrease, respectively. The swelling capacity of chitosan-TPP beads decreased with increasing concentration of TPP. The effect of chitosan concentration and percentage of TPP solution used for cross-linking on entrapment efficiency and drug release rate was extensively investigated. Optimized beads were subjected to in vivo studies in Wistar albino rats to determine the mean arterial blood pressure and compared with marketed formulation. The pharmacodynamic study demonstrates steady blood pressure control for optimized formulation as compared to fluctuated blood pressure for the marketed formulation. PMID:19495989

  9. The Role of CYP2C8 and CYP2C9 Genotypes in Losartan-Dependent Inhibition of Paclitaxel Metabolism in Human Liver Microsomes.

    PubMed

    Mukai, Yuji; Senda, Asuna; Toda, Takaki; Eliasson, Erik; Rane, Anders; Inotsume, Nobuo

    2016-06-01

    The aim of the present study was to further investigate a previously identified metabolic interaction between losartan and paclitaxel, which is one of the marker substrates of CYP2C8, by using human liver microsomes (HLMs) from donors with different CYP2C8 and CYP2C9 genotypes. Although CYP2C8 and CYP2C9 exhibit genetic linkage, previous studies have yet to determine whether losartan or its active metabolite, EXP-3174 which is specifically generated by CYP2C9, is responsible for CYP2C8 inhibition. Concentrations of 6α-hydroxypaclitaxel and EXP-3174 were measured by high-performance liquid chromatography after incubations with paclitaxel, losartan or EXP-3174 in HLMs from seven donors with different CYP2C8 and CYP2C9 genotypes. The half maximal inhibitory concentration (IC50 ) values were not fully dependent on CYP2C8 genotypes. Although the degree of inhibition was small, losartan significantly inhibited the production of 6α-hydroxypaclitaxel at a concentration of 1 μmol/L in only HL20 with the CYP2C8*3/*3 genotype. HLMs with either CYP2C9*2/*2 or CYP2C9*1/*3 exhibited a lower losartan intrinsic clearance (Vmax /Km ) than other HLMs including those with CYP2C9*1/*1 and CYP2C9*1/*2. Significant inhibition of 6α-hydroxypaclitaxel formation by EXP-3174 could only be found at levels that were 50 times higher (100 μmol/L) than the maximum concentration generated in the inhibition study using losartan. These results suggest that the metabolic interaction between losartan and paclitaxel is dependent on losartan itself rather than its metabolite and that the CYP2C8 inhibition by losartan is not affected by the CYP2C9 genotype. Further study is needed to define the effect of CYP2C8 genotypes on losartan-paclitaxel interaction. PMID:26551762

  10. Insights into the molecular basis of action of the AT1 antagonist losartan using a combined NMR spectroscopy and computational approach.

    PubMed

    Zervou, Maria; Cournia, Zoe; Potamitis, Constantinos; Patargias, George; Durdagi, Serdar; Grdadolnik, Simona Golic; Mavromoustakos, Thomas

    2014-03-01

    The drug:membrane interactions for the antihypertensive AT1 antagonist losartan, the prototype of the sartans class, are studied herein using an integrated approach. The pharmacophore arrangement of the drug was revealed by rotating frame nuclear Overhauser effect spectroscopy (2D ROESY) NMR spectroscopy in three different environments, namely water, dimethyl sulfoxide (DMSO), and sodium dodecyl sulfate (SDS) micellar solutions mimicking conditions of biological transport fluids and membrane lipid bilayers. Drug association with micelles was monitored by diffusion ordered spectroscopy (2D DOSY) and drug:micelle intermolecular interactions were characterized by ROESY spectroscopy. The localisation of the drug in the micellar environment was investigated by introducing 5-doxyl and 16-doxyl stearic acids. The use of spin labels confirmed that losartan resides close to the micelle:water interface with the hydroxymethyl group and the tetrazole heterocyclic aromatic ring facing the polar surface with the potential to interact with SDS charged polar head groups in order to increase amphiphilic interactions. The spontaneous insertion, the diffusion pathway and the conformational features of losartan were monitored by Molecular Dynamics (MD) simulations in a modeled SDS micellar aggregate environment and a long exploratory MD run (580ns) in a phospholipid dipalmitoylphosphatidylcholine (DPPC) bilayer with the AT1 receptor embedded. MD simulations were in excellent agreement with experimental results and further revealed the molecular basis of losartan:membrane interactions in atomic-level detail. This applied integrated approach aims to explore the role of membranes in losartan's pathway towards the AT1 receptor. PMID:24374319

  11. Enhanced spectrophotometric determination of Losartan potassium based on its physicochemical interaction with cationic surfactant

    NASA Astrophysics Data System (ADS)

    Abdel-Fattah, Laila; Abdel-Aziz, Lobna; Gaied, Mariam

    2015-02-01

    In this study, a simple and sensitive spectrophotometric method was developed for determination of Losartan potassium (LST K), an angiotensin-II receptor (type AT1) antagonist, in presence of cationic surfactant cetyltrimethylammonium bromide (CTAB). The physicochemical interaction of LST K with CTAB was investigated. The effect of cationic micelles on the spectroscopic and acid-base properties of LST K was studied at pH 7.4. The binding constant (Kb) and the partition coefficient (Kx) of LST K-CTAB were 1.62 × 105 M-1 and 1.38 × 105; respectively. The binding of LST K to CTAB micelles implied a shift in drug acidity constant (ΔpKa = 0.422). The developed method is linear over the range 0.5-28 μg mL-1. The accuracy was evaluated and was found to be 99.79 ± 0.509% and the relative standard deviation for intraday and interday precision was 0.821 and 0.963; respectively. The method was successfully applied to determine LST K in pharmaceutical formulations.

  12. Formulation and optimization of mucoadhesive buccal patches of losartan potassium by using response surface methodology

    PubMed Central

    Ikram, Md.; Gilhotra, Neeraj; Gilhotra, Ritu Mehra

    2015-01-01

    Background: This study was undertaken with an aim to systematically design a model of factors that would yield an optimized sustained release dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology (RSM) by employing 32 full factorial design. Materials and Methods: Mucoadhesive buccal patches were prepared using different grades of hydroxypropyl methylcellulose (HPMC) (K4M and K100M) and polyvinylpyrrolidone-K30 by solvent casting method. The amount of the release retardant polymers – HPMC K4M (X1) and HPMC K100M (X2) was taken as an independent variable. The dependent variables were the burst release in 30 min (Y1), cumulative percentage release of drug after 8 h (Y2) and swelling index (Y3) of the patches. In vitro release and swelling studies were carried out and the data were fitted to kinetic equations. Results: The physicochemical, bioadhesive, and swelling properties of patches were found to vary significantly depending on the viscosity of the polymers and their combination. Patches showed an initial burst release preceding a more gradual sustained release phase following a nonfickian diffusion process. Discussion: The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared, facilitated with the RSM. PMID:26682205

  13. Enhanced spectrophotometric determination of Losartan potassium based on its physicochemical interaction with cationic surfactant.

    PubMed

    Abdel-Fattah, Laila; Abdel-Aziz, Lobna; Gaied, Mariam

    2015-02-01

    In this study, a simple and sensitive spectrophotometric method was developed for determination of Losartan potassium (LST K), an angiotensin-II receptor (type AT1) antagonist, in presence of cationic surfactant cetyltrimethylammonium bromide (CTAB). The physicochemical interaction of LST K with CTAB was investigated. The effect of cationic micelles on the spectroscopic and acid-base properties of LST K was studied at pH 7.4. The binding constant (Kb) and the partition coefficient (Kx) of LST K-CTAB were 1.62×10(5) M(-1) and 1.38×10(5); respectively. The binding of LST K to CTAB micelles implied a shift in drug acidity constant (ΔpKa=0.422). The developed method is linear over the range 0.5-28 μg mL(-1). The accuracy was evaluated and was found to be 99.79±0.509% and the relative standard deviation for intraday and interday precision was 0.821 and 0.963; respectively. The method was successfully applied to determine LST K in pharmaceutical formulations. PMID:25315864

  14. Simultaneous Determination of Hydrochlorothiazide and Losartan Potassium in Osmotic Pump Tablets by Microemulsion Liquid Chromatography.

    PubMed

    Li, Liangxing; Lai, Caiyun; Xuan, Xueyi; Gao, Chongkai; Li, Ning

    2016-09-01

    A rapid and efficient oil-in-water microemulsion liquid chromatographic (MELC) method has been optimized and validated for the determination of hydrochlorothiazide (HCT) and losartan potassium (LOP) in osmotic pump tablets. Samples were injected into a C18 (150 mm × 4.6 mm ID, 5 µm particle size) analytical column, which was maintained at 30°C. The most effective MELC system had a mobile phase consisting of 95% (v/v) of 3.0% (w/w) SDS, 6.0% (w/w) n-butanol, 0.8% (w/w) n-octane, 90.2% (w/w) water and 5% (v/v) acetonitrile (pH 5). The flow rate was 1.0 mL min(-1) and UV detection was performed at 265 nm. Linearity ranged from 2.5 to 12.5 µg mL(-1) for HCT and 10.0-60.0 µg mL(-1) for LOP (r > 0.999 for both drugs). The proposed method was rapid, precise (RSDs < 1.4%) and accurate (98.9% recovery for HCT and 101% recovery for LOP). It is applicable to simultaneous determination of HCT and LOP in osmotic pump tablets. PMID:27334292

  15. Comparison of the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus.

    PubMed

    Derosa, Giuseppe; Querci, Fabrizio; Franzetti, Ivano; Dario Ragonesi, Pietro; D'Angelo, Angela; Maffioli, Pamela

    2015-10-01

    The aim of this study was to evaluate the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus. We enrolled 148 normocholesterolemic patients with mild-to-moderate hypertension and type 2 diabetes mellitus. Patients were treated with barnidipine, 20 mg day(-1), in combination with losartan, 100 mg day(-1), or with telmisartan+hydrochlorothiazide, 80/12.5 mg day(-1), for 6 months. We assessed blood pressure (BP) on a monthly basis; additionally, blood samples were collected to assess, at baseline and after 6 months, the following parameters: fasting plasma glucose; glycated hemoglobin; fasting plasma insulin; HOMA index; and some adipocytokines, such as adiponectin (ADN), resistin, leptin, visfatin and vaspin. Patients were also subjected to an euglycemic hyperinsulinemic clamp to assess the M value and glucose infusion rate to ascertain their insulin sensitivity. One hundred and forty-one patients completed the study. The BP was reduced in both groups, although the reduction was greater with barnidipine+losartan (P<0.001 vs. baseline and P<0.01 vs. telmisartan+hydrochlorothiazide). Barnidipine+losartan increased the M value and glucose infusion rate during the euglycemic hyperinsulinemic clamp (P<0.05 vs. baseline and vs. telmisartan+hydrochlorothiazide). With respect to the levels of adipocytokines, ADN was increased (P<0.05), and resistin and leptin were reduced from baseline with barnidipine+losartan (P<0.05 vs. baseline), but they were not reduced with telmisartan+hydrochlorothiazide. Visfatin and vaspin were reduced by barnidipine+losartan compared with baseline (P<0.05). The adipocytokine levels obtained with barnidipine+losartan were significantly better than those obtained with telmisartan+hydrochlorothiazide (P<0.05 for all parameters). In addition to providing a greater BP reduction, barnidipine+losartan improved the insulin

  16. Ionotropic Cross-linked Carbo-protein Micro Matrix System: An Approach for Improvement of Drug Release, Compaction and Tableting behavior of Losartan Potassium.

    PubMed

    Khandai, Madhusmruti; Chakraborty, Santanu; Ghosh, Ashoke Kumar

    2015-01-01

    The aim of the present research work is to develop carbo-protein polymeric complex based sustain release microspheres of losartan potassium and investigate the ability of this dosage form to improve the flowability, compressibility and tableting properties of losartan potassium. The influence of silk sericin, alginate and its blend on various physicochemical parameters and in vitro drug release pattern were studied to optimize the concentration of polymeric blend required for 12 h. sustain release. Optimized batch was subjected to different flowability, compressibility and tableting properties studies to observe the effects of carbo-protein microspheres on flow properties. Results indicated that the concentration of sericin was found to be the main influential factor for prolonged drug release. Different micromeritic studies revealed that the poor flowability and compressibility properties of pure losartan potassium were significantly improved by this algino-sericin microspheric dosage form. Research findings also revealed that plasticity, die filling behavior and tableting properties of the pure drug were significantly improved by this microsphere formulation. So these prospective results concluded that carbo-protein polymeric microspheres helps to sustain the drug release for prolong hours as well as improve the flowability, compressibility and tableting properties of losartan potassium. PMID:25760869

  17. ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension.

    PubMed

    Mallion, J; Siche, J; Lacourcière, Y

    1999-10-01

    The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week, multinational, multicentre, randomised, double-blind, double-dummy, parallel-group study of 223 patients with mild-to-moderate hypertension, defined as clinic diastolic blood pressure (DBP) >/=95 and /=140 and /=85 mm Hg. After a 4-week single-blind placebo run-in, eligible patients were randomised to receive telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebo. Ambulatory blood pressure monitoring (ABPM) after 6 weeks of double-blind therapy showed that all active treatments produced significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placebo. During the 18-to-24 h period after dosing, the reductions in SBP/DBP with telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those observed for losartan 50 mg (6.0/3.7 mm Hg), and losartan was no better than placebo. Also for the 24-h mean blood pressure, telmisartan 40 mg and 80 mg were significantly (P< 0.05) better than losartan 50 mg. Compared with losartan, telmisartan 80 mg produced significantly (P < 0.05) greater reductions in both SBP and DBP during all monitored periods of the 24-h period, while telmisartan 40 mg produced significantly greater reductions in SBP and DBP in the night-time period (10.01 pm to 5.59 am) (P < 0.05) and in DBP in the morning period (6.00 am to 11.59 am) (P < 0.05). All treatments were comparably well tolerated. Telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension, producing sustained 24-h blood pressure control which compared favourably with losartan. PMID:10516734

  18. Does the addition of losartan improve the beneficial effects of ACE inhibitors in patients with anterior myocardial infarction? A pilot study

    PubMed Central

    Di, P; Bucca, V; Scalzo, S; Cannizzaro, S; Giubilato, A; Paterna, S

    1999-01-01

    OBJECTIVE—To verify the efficacy of the combination of captopril (75 mg day) and losartan (25 mg/day) in early postinfarction phases of reperfused anterior acute myocardial infarction.
DESIGN AND PATIENTS—99 patients, hospitalised for suspected anterior acute myocardial infarction within four hours from the onset of symptoms, were randomised into two groups: group A included 50 patients who received captopril 75 mg/day and placebo; group B included 49 patients who received captopril 75 mg/day within three days of admission plus losartan 12.5 mg, as a first dose, and 25 mg/day successively. An additional 23 patients with anterior acute myocardial infarction received losartan 25 mg alone and acted as controls (group C) to check the effects of losartan on plasma angiotensin II (AII) concentrations. Noradrenaline (norepinephrine) (NA) and AII plasma concentrations were measured on the third and 10th day after admission in 93 patients (35 from group A, 35 from group B, and 23 from group C). 90 days after admission patients underwent echocardiography to determine end systolic volume (ESV) and ejection fraction (EF).
RESULTS—Patients in groups A and B were similar with regard to age, sex, creatine kinase peak, EF, ESV, and risk factors. Group B (captopril plus losartan) patients showed a significant reduction in mean (SD) systolic blood pressure within the group (basal 128 (10) mm Hg; 10 days after admission 105 (9) mm Hg, p < 0.001), and in comparison with group A (captopril) patients (basal 127 (11) mm Hg; 10 days after admission 116 (10) mm Hg, p < 0.001). Diastolic blood pressure was also lower in group B patients versus group A (66 (11) v 77 (11) mm Hg). Group C (losartan) patients also showed a significant reduction in systolic blood pressure (131 (13) mm Hg down to 121 (12) mm Hg, p < 0.001). Neither NA nor AII plasma concentrations in groups A and B differed significantly in basal samples (NA 673 (138) v 675

  19. The novel acid degradation products of losartan: Isolation and characterization using Q-TOF, 2D-NMR and FTIR.

    PubMed

    Kumar Pandey, Avadhesh; Rapolu, Ravi; Raju, Ch Krishnam; Sasalamari, Gururaj; Kumar Goud, Sanath; Awasthi, Atul; Navalgund, Sameer G; Surendranath, Koduru V

    2016-02-20

    Forced degradation of losartan potassium in acidic condition resulted into three potential unknown impurities. These unknown degradation products marked as LD-I, LD-II and LD-III were analyzed using a new reverse-phase high performance liquid chromatography (HPLC), eluting at 3.63, 3.73 and 3.91 relative retention times with respect to losartan potassium (LOS) peak. All three were isolated from reaction mass using preparative HPLC and their structures were elucidated using LC-MS/MS, multidimensional NMR and FTIR spectroscopic techniques, as 5(2),11(2)-dibutyl-5(4),11(4)-dichloro-1(1)H,5(1)H,7(1)H,11(1)H-1(5,1),7(1,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane,(Z)-5(2),11(2)-dibutyl-5(4),11(4)-dichloro-1(1)H,5(1)H,7(2)H,11(1)H-1(5,1),7(2,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane, and 5(2),11(2)-dibutyl-5(4),11(4)-dichloro-1(2)H,5(1)H,7(2)H,11(1)H-1(5,2),7(2,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane, respectively. To best of our knowledge, all three degradation products are novel impurities which are not discussed at any form of publication yet. PMID:26704631

  20. Transcriptome-based analysis of kidney gene expression changes associated with diabetes in OVE26 mice, in the presence and absence of losartan treatment.

    PubMed

    Komers, Radko; Xu, Bei; Fu, Yi; McClelland, Aaron; Kantharidis, Phillip; Mittal, Amit; Cohen, Herbert T; Cohen, David M

    2014-01-01

    Diabetes is among the most common causes of end-stage renal disease, although its pathophysiology is incompletely understood. We performed next-generation sequencing-based transcriptome analysis of renal gene expression changes in the OVE26 murine model of diabetes (age 15 weeks), relative to non-diabetic control, in the presence and absence of short-term (seven-day) treatment with the angiotensin receptor blocker, losartan (n = 3-6 biological replicates per condition). We detected 1438 statistically significant changes in gene expression across conditions. Of the 638 genes dysregulated in diabetes relative to the non-diabetic state, >70% were downregulation events. Unbiased functional annotation of genes up- and down-regulated by diabetes strongly associated (p<1 × 10(-8)) with terms for oxidative stress and for endoplasmic reticulum stress/protein folding. Most of the individual gene products up- or down-regulated with diabetes were unaffected by losartan treatment; however, of the gene products dysregulated in diabetes and influenced by losartan treatment, the vast majority of changes were in the direction of amelioration rather than exacerbation of the diabetic dysregulation. This group of losartan-protected genes associated strongly with annotation terms for endoplasmic reticulum stress, heat shock proteins, and chaperone function, but not oxidative stress; therefore, the losartan-unaffected genes suggest avenues for additional therapeutic opportunity in diabetes. Interestingly, the gene product most highly upregulated by diabetes (>52-fold), encoded by the cationic amino acid transporter Slc7a12, and the gene product most highly downregulated by diabetes (>99%)--encoded by the "pseudogene" Gm6300--are adjacent in the murine genome, are members of the SLC7 gene family, and are likely paralogous. Therefore, diabetes activates a near-total genetic switch between these two paralogs. Other individual-level changes in gene expression are potentially relevant to

  1. Transcriptome-Based Analysis of Kidney Gene Expression Changes Associated with Diabetes in OVE26 Mice, in the Presence and Absence of Losartan Treatment

    PubMed Central

    Komers, Radko; Xu, Bei; Fu, Yi; McClelland, Aaron; Kantharidis, Phillip; Mittal, Amit; Cohen, Herbert T.; Cohen, David M.

    2014-01-01

    Diabetes is among the most common causes of end-stage renal disease, although its pathophysiology is incompletely understood. We performed next-generation sequencing-based transcriptome analysis of renal gene expression changes in the OVE26 murine model of diabetes (age 15 weeks), relative to non-diabetic control, in the presence and absence of short-term (seven-day) treatment with the angiotensin receptor blocker, losartan (n = 3–6 biological replicates per condition). We detected 1438 statistically significant changes in gene expression across conditions. Of the 638 genes dysregulated in diabetes relative to the non-diabetic state, >70% were downregulation events. Unbiased functional annotation of genes up- and down-regulated by diabetes strongly associated (p<1×10−8) with terms for oxidative stress and for endoplasmic reticulum stress/protein folding. Most of the individual gene products up- or down-regulated with diabetes were unaffected by losartan treatment; however, of the gene products dysregulated in diabetes and influenced by losartan treatment, the vast majority of changes were in the direction of amelioration rather than exacerbation of the diabetic dysregulation. This group of losartan-protected genes associated strongly with annotation terms for endoplasmic reticulum stress, heat shock proteins, and chaperone function, but not oxidative stress; therefore, the losartan-unaffected genes suggest avenues for additional therapeutic opportunity in diabetes. Interestingly, the gene product most highly upregulated by diabetes (>52-fold), encoded by the cationic amino acid transporter Slc7a12, and the gene product most highly downregulated by diabetes (>99%) – encoded by the “pseudogene” Gm6300 – are adjacent in the murine genome, are members of the SLC7 gene family, and are likely paralogous. Therefore, diabetes activates a near-total genetic switch between these two paralogs. Other individual-level changes in gene expression are potentially

  2. Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets

    PubMed Central

    Jayasree, J.; Sivaneswari, S.; Hemalatha, G.; Preethi, N.; Mounika, B.; Murthy, S. Vasudeva

    2014-01-01

    Objective: The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Materials and Methods: Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results and Discussion: Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer — Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Conclusion: Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability. PMID:25426439

  3. Importance of baseline distribution of proteinuria in renal outcomes trials: lessons from the reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL) study.

    PubMed

    Zhang, Zhongxin; Shahinfar, Shahnaz; Keane, William F; Ramjit, Denise; Dickson, Tania Z; Gleim, Gilbert W; Mogensen, Carl Erik; de Zeeuw, Dick; Brenner, Barry M; Snapinn, Steven M

    2005-06-01

    A key issue in the analysis of outcome trials is the adjustment for baseline covariates that influence the primary outcome. Imbalance of an important covariate between treatment groups at baseline is of considerable concern if one treatment group is favored over another with respect to the hypothesis testing outcome. With the use of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study database as an example, the influence of baseline proteinuria on the primary composite endpoint, ESRD, and ESRD or death after adjusting for baseline proteinuria as a continuous covariate was examined. Increasing baseline proteinuria was associated with increased risk for renal events, confirming that proteinuria is an important covariate for renal outcomes. When the randomization was stratified according proteinuria <2000 mg/g or >/=2000 mg/g, within the higher proteinuria stratum (>/=2000 mg/g), patients in the losartan group had a higher baseline mean proteinuria value. When the imbalance was adjusted, an increase in the magnitude and the significance of the risk reduction with losartan for each outcome was observed. No apparent interaction between treatment effect and baseline proteinuria was found, and there was no heterogeneity in the treatment response in patients with different baseline proteinuria levels. After proteinuria was adjusted as a continuous variable, greater treatment effects were observed in the RENAAL study. This effect was due solely to the imbalance in baseline proteinuria. Considering the importance of proteinuria as a risk factor, adjustment for baseline proteinuria as a continuous covariate should be prespecified in the design and analysis of clinical trials involving renal outcomes, even when patients are stratified on the basis of level of proteinuria. PMID:15872078

  4. Neuronal activation in the central nervous system of rats in the initial stage of chronic kidney disease-modulatory effects of losartan and moxonidine.

    PubMed

    Palkovits, Miklós; Šebeková, Katarína; Klenovics, Kristina Simon; Kebis, Anton; Fazeli, Gholamreza; Bahner, Udo; Heidland, August

    2013-01-01

    The effect of mild chronic renal failure (CRF) induced by 4/6-nephrectomy (4/6NX) on central neuronal activations was investigated by c-Fos immunohistochemistry staining and compared to sham-operated rats. In the 4/6 NX rats also the effect of the angiotensin receptor blocker, losartan, and the central sympatholyticum moxonidine was studied for two months. In serial brain sections Fos-immunoreactive neurons were localized and classified semiquantitatively. In 37 brain areas/nuclei several neurons with different functional properties were strongly affected in 4/6NX. It elicited a moderate to high Fos-activity in areas responsible for the monoaminergic innervation of the cerebral cortex, the limbic system, the thalamus and hypothalamus (e.g. noradrenergic neurons of the locus coeruleus, serotonergic neurons in dorsal raphe, histaminergic neurons in the tuberomamillary nucleus). Other monoaminergic cell groups (A5 noradrenaline, C1 adrenaline, medullary raphe serotonin neurons) and neurons in the hypothalamic paraventricular nucleus (innervating the sympathetic preganglionic neurons and affecting the peripheral sympathetic outflow) did not show Fos-activity. Stress- and pain-sensitive cortical/subcortical areas, neurons in the limbic system, the hypothalamus and the circumventricular organs were also affected by 4/6NX. Administration of losartan and more strongly moxonidine modulated most effects and particularly inhibited Fos-activity in locus coeruleus neurons. In conclusion, 4/6NX elicits high activity in central sympathetic, stress- and pain-related brain areas as well as in the limbic system, which can be ameliorated by losartan and particularly by moxonidine. These changes indicate a high sensitivity of CNS in initial stages of CKD which could be causative in clinical disturbances. PMID:23818940

  5. Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse.

    PubMed

    Lovric-Bencic, Martina; Sikiric, Predrag; Hanzevacki, Jadranka S; Seiwerth, Sven; Rogic, Dunja; Kusec, Vesna; Aralica, Gorana; Konjevoda, Pasko; Batelja, Lovorka; Blagaic, Alenka B

    2004-05-01

    Overall, doxorubicine-congestive heart failure (CHF) (male Wistar rats and NMRI mice; 6 challenges with doxorubicine (2.5 mg/kg, i.p.) throughout 15 days and then a 4-week-rest period) is consistently deteriorating throughout next 14 days, if not reversed or ameliorated by therapy (/kg per day): a stable gastric pentadecapeptide BPC157 (GEPPPGKPADDAGLV, MW 1419, promisingly studied for inflammatory bowel disease (Pliva; PL 10, PLD-116, PL 14736)) (10 microg, 10 ng), losartan (0.7 mg), amlodipine (0.07 mg), given intragastrically (i.g.) (once daily, rats) or in drinking water (mice). Assessed were big endothelin-1 (BET-1) and plasma enzyme levels (CK, MBCK, LDH, AST, ALT) before and after 14 days of therapy and clinical status (hypotension, increased heart rate and respiratory rate, and ascites) every 2 days. Controls (distilled water (5 ml/kg, i.g., once daily) or drinking water (2 ml/mouse per day) given throughout 14 days) exhibited additionally increased BET-1 and aggravated clinical status, while enzyme values maintained their initial increase. BPC157 (10 microg/kg) and amlodipine treatment reversed the increased BET-1 (rats, mice), AST, ALT, CK (rats, mice), and LDH (mice) values. BPC157 (10 ng/kg) and losartan opposed further increase of BET-1 (rats, mice). Losartan reduces AST, ALT, CK, and LDH serum values. BPC157 (10 ng/kg) reduces AST and ALT serum values. Clinical status of CHF-rats and -mice is accordingly improved by the BPC157 regimens and amlodipine. PMID:15153646

  6. Ramipril and Losartan Exert a Similar Long-Term Effect upon Markers of Heart Failure, Endogenous Fibrinolysis, and Platelet Aggregation in Survivors of ST-Elevation Myocardial Infarction: A Single Centre Randomized Trial

    PubMed Central

    Marinšek, Martin; Sinkovič, Andreja

    2016-01-01

    Introduction. Blocking the renin-angiotensin-aldosterone system in ST-elevation myocardial infarction (STEMI) patients prevents heart failure and recurrent thrombosis. Our aim was to compare the effects of ramipril and losartan upon the markers of heart failure, endogenous fibrinolysis, and platelet aggregation in STEMI patients over the long term. Methods. After primary percutaneous coronary intervention (PPCI), 28 STEMI patients were randomly assigned ramipril and 27 losartan, receiving therapy for six months with dual antiplatelet therapy (DAPT). We measured N-terminal proBNP (NT-proBNP), ejection fraction (EF), plasminogen-activator-inhibitor type 1 (PAI-1), and platelet aggregation by closure times (CT) at the baseline and after six months. Results. Baseline NT-proBNP ≥ 200 pmol/mL was observed in 48.1% of the patients, EF < 55% in 49.1%, and PAI-1 ≥ 3.5 U/mL in 32.7%. Six-month treatment with ramipril or losartan resulted in a similar effect upon PAI-1, NT-proBNP, EF, and CT levels in survivors of STEMI, but in comparison to control group, receiving DAPT alone, ramipril or losartan treatment with DAPT significantly increased mean CT (226.7 ± 80.3 sec versus 158.1 ± 80.3 sec, p < 0.05). Conclusions. Ramipril and losartan exert a similar effect upon markers of heart failure and endogenous fibrinolysis, and, with DAPT, a more efficient antiplatelet effect in long term than DAPT alone. PMID:27064499

  7. Effects of Losartan-based therapy on the incidence of end-stage renal disease and associated costs in type 2 diabetes mellitus: A retrospective cost-effectiveness analysis in the United Kingdom

    PubMed Central

    Vora, Jiten; Carides, George; Robinson, Paul

    2005-01-01

    Background: In the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, the primary composite end point was the 2-fold increase in baseline serum creatinine concentration, the development of end-stage renal disease (ESRD), or death. The effects of losartan used for the prevention or delay of progression of diabetic nephropathy to ESRD were compared with those of conventional anti-hypertensive treatment (control) (calcium channel blockers, diuretics, α-blockers, β-blockers, and centrally acting agents), but not angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists (AIIAs), in 1513 adults with type 2 diabetes mellitus (DM-2) and nephropathy. Both treatment groups received conventional antihypertensive therapy (calcium channel blockers, diuretics, α-blockers, β-blockers, and/or centrally acting agents). ACE inhibitors and AIIAs were not allowed during the study period. The relative risk (RR) for composite outcome was 25% less, and the RR for ESRD was 28% less, in the losartantreated group compared with the control group. Objective: The aim of this retrospective cost-effectiveness analysis was to use data from the RENAAL study to determine the survival benefits and lifetime direct medical costs of a losartan-based regimen for the prevention of ESRD in patients with DM-2 and nephropathy in the setting of the UK National Health Service (NHS). Methods: This analysis used life-years saved as the effectiveness measure. The effect of losartan-based treatment on ESRD risk was confined to the trial period (3.5 years). However, survival and the lifetime direct medical costs of managing ESRD were projected beyond the trial period to incorporate the full effects of ESRD on survival and resource use. The effect of altering key variables was examined using 1-way sensitivity analyses. Results: ESRD-related costs were significantly lower in patients receiving losartan-based treatment

  8. INTRACEREBROVENTRICULAR LOSARTAN INFUSION MODULATES ANGIOTENSIN TYPE 1 RECEPTOR EXPRESSION IN THE SUBFORNICAL ORGAN AND DRINKING BEHAVIOUR IN BILE DUCT LIGATED RATS

    PubMed Central

    Walch, Joseph D; Carreño, Flávia Regina; Cunningham, J. Thomas

    2013-01-01

    Bile duct ligation (BDL) causes congestive liver failure that initiates hemodynamic changes including peripheral vasodilation and generalized edema. Peripheral vasodilation is hypothesized to then activate compensatory mechanisms including increased drinking behavior and neurohumoral activation. This study tested the hypothesis that changes in the expression of AT1R mRNA and protein in the lamina terminalis is associated with BDL induced hypoosmolality in the rat. All rats received either BDL or sham ligation surgery. The rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. Angiotensin type 1 receptor (AT1R) expression in the lamina terminalis was assessed by western blot and quantitative real-time PCR (RT-qPCR). Average baseline water intake significantly increased in BDL rats compared to sham and upregulation of AT1R protein and AT1aR mRNA were observed in the subfornical organ (SFO) of BDL rats. Separate groups of BDL and sham ligated rats were instrumented with minipumps filled with either losartan (2.0 µg/µl) or 0.9% saline for chronic intracerebroventricular (ICV) or subcutaneous (SC) chronic infusion. Chronic ICV losartan infusion attenuated the increased drinking behavior and prevented the increased abundance of AT1R protein in the SFO in BDL rats. Chronic SC did not affect water intake or AT1R abundance in the SFO. The data presented here indicate a possible role of increased central AT1R expression in the regulation of drinking behavior during congestive cirrhosis. PMID:23243146

  9. Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma

    PubMed Central

    Arrieta, O; Guevara, P; Escobar, E; García-Navarrete, R; Pineda, B; Sotelo, J

    2005-01-01

    Angiotensin II (Ang II) is a main effector peptide in the renin–angiotensin system and participates in the regulation of vascular tone. It also has a role in the expression of growth factors that induce neovascularisation which is closely associated to the growth of malignant gliomas. We have shown that the selective blockage of the AT1 receptor of angiotensin inhibites tumour growth, cell proliferation and angiogenesis of C6 rat glioma. The aim of this study was to study the effects of the blockage of AT1 receptor on the synthesis of growth factors, and in the genesis of apoptosis in cultured C6 glioma cells and in rats with C6 glioma. Administration of losartan at doses of 40 or 80 mg kg−1 to rats with C6 glioma significantly decreased tumoral volume and production of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast growth factor. It also induced apoptosis in a dose-dependent manner. Administration of Ang II increased cell proliferation of cultured C6 cells which decreased by the administration of losartan. Our results suggest that the selective blockage of AT1 diminishes tumoral growth through inhibition of growth factors and promotion of apoptosis. PMID:15785746

  10. Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy

    PubMed Central

    Lacro, Ronald V.; Guey, Lin T.; Dietz, Harry C.; Pearson, Gail D.; Yetman, Anji T.; Gelb, Bruce D.; Loeys, Bart L.; Benson, D. Woodrow; Bradley, Timothy J.; De Backer, Julie; Forbus, Geoffrey A.; Klein, Gloria L.; Lai, Wyman W.; Levine, Jami C.; Lewin, Mark B.; Markham, Larry W.; Paridon, Stephen M.; Pierpont, Mary Ella; Radojewski, Elizabeth; Selamet Tierney, Elif Seda; Sharkey, Angela M.; Wechsler, Stephanie Burns; Mahony, Lynn

    2013-01-01

    Background The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. Methods and results Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area–adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. Conclusions Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome. PMID:23622922

  11. Does clozapine decrease smoking?

    PubMed

    de Leon, Jose; Diaz, Francisco J; Josiassen, Richard C; Cooper, Thomas B; Simpson, George M

    2005-06-01

    McEvoy et al.'s study in 1999, which used cotinine levels but had limited power, suggested that clozapine treatment may be associated with a mild smoking decrease (particularly when plasma clozapine levels are > 150 ng/ml). Some naturalistic studies also suggest that clozapine treatment may be associated with a mild smoking decrease. The present study included 38 schizophrenic daily smokers from a double-blind clozapine trial. Five analyses were tested for significant decreases in plasma cotinine levels from a haloperidol baseline to: (1) the end of clozapine trials regarding clozapine doses (100, 300 or 600 mg/day), (2) the end of the clozapine trial where the highest plasma clozapine level was achieved, (3) the end of the clozapine trial where a clozapine level in the 150-450 ng/ml range was achieved, (4) the end of the first clozapine trial regardless of clozapine dose, and (5) the end of the last clozapine trial in the study. The first and straightforward analysis by dose showed no clozapine effects on smoking. The second and the third analyses (an attempt to mimic the design by McEvoy et al. [McEvoy, J.P., Freudenreich, O., Wilson, W.H., 1999. Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol. Psychiat. 46, 125-129.]) also indicated that there was not a significant effect of clozapine on smoking. The fourth and five analyses were also negative. None of the five analyses in our clozapine trial demonstrated that clozapine had major effects on smoking. This study cannot rule out that in some subjects, clozapine treatment may be associated with a small decrease in smoking. New prospective longitudinal studies using repeated cotinine and clozapine levels are needed to explore whether clozapine may reduce smoking in some patients. PMID:15951089

  12. Effects of the combinations of amlodipine/valsartan versus losartan/hydrochlorothiazide on left ventricular hypertrophy as determined with magnetic resonance imaging in patients with hypertension

    PubMed Central

    Bruder, Oliver; Jensen, Christoph J.; Bell, Michael; Rummel, Reinhard; Boehm, Guenter; Klebs, Sven; Sieder, Christian; Senges, Jochen

    2012-01-01

    Background Left ventricular hypertrophy (LVH), a marker of cardiac end-organ damage, is frequently found in patients with arterial hypertension and is associated with cardiovascular and cerebrovascular morbidity and mortality. Therefore, LVH regression is an important treatment goal. For amlodipine plus valsartan (A/V) no specific study on LVH has been reported to date. Methods Prospective, open-label, randomized parallel-group study. Patients with essential hypertension and LVH were randomized to 52-week treatment with A/V 10/160 mg (n = 43) or the active comparator losartan/HCT 100/25 mg (L/H, n = 47). Add-on medication was allowed in case of inadequate blood pressure control. LV parameters were measured by cardiovascular magnetic resonance imaging (MRI), and adjudicated in a blinded manner. Study identifiers were NCT00446563 and EudraCT 2006-001977-17. Results In addition to the study treatment, 35% of patients in the A/V group and 49% in the L/H group received additional antihypertensive medication. Compared to baseline, both treatments reduced measures of LVH significantly after 52 weeks (e.g. LV mass index in the A/V group from 64.7 g/m2 by −3.5 g/m2, in the L/H group from 69.1 g/m2 by −4.4 g/m2, p < 0.01 for both). LV ejection fraction and LV volumes were not significantly changed by any regimen. A/V and L/H treatments were well tolerated. Conclusions Both regimen were effective in reducing LV mass compared to baseline and were well tolerated.

  13. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial.

    PubMed

    Eijkelkamp, Wouter B A; Zhang, Zhongxin; Remuzzi, Giuseppe; Parving, Hans-Henrik; Cooper, Mark E; Keane, William F; Shahinfar, Shahnaz; Gleim, Gilbert W; Weir, Matthew R; Brenner, Barry M; de Zeeuw, Dick

    2007-05-01

    Albuminuria reduction could be renoprotective in hypertensive patients with diabetic nephropathy. However, the current use of renin-angiotensin-system intervention is targeted to BP only. Therefore, this study investigated the adequacy of this approach in 1428 patients with hypertension and diabetic nephropathy from the placebo-controlled Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. Investigated were the extent of discordance in treatment effects on systolic BP (SBP) and albuminuria and its association with renal outcome in a multivariate Cox model. Among patients with a reduced SBP during treatment, a lack of albuminuria reduction was observed in 37, 26, and 51% (total, losartan, and placebo, respectively) at month 6. SBP or albuminuria reduction was associated with a lower risk for ESRD, whereas combined SBP and albuminuria reduction was associated with the lowest risk for events. Across all categories of SBP change, a progressively lower ESRD hazard ratio was observed with a larger albuminuria reduction. A lower residual level of albuminuria was also associated with lower ESRD risk. In conclusion, changes in albuminuria are not concordant in a substantial proportion of patients when titrated for BP. Meanwhile, the ESRD risk showed a clear dependence on albuminuria reduction. The ESRD risk also showed dependence on the residual level of albuminuria, even in patients who reached the current SBP target. Antihypertensive treatment that is aimed at improving renal outcomes in patients with diabetic nephropathy may therefore require a dual strategy, targeting both SBP and albuminuria reduction. PMID:17409317

  14. Effects of salvianolic acid B and tanshinone IIA on the pharmacokinetics of losartan in rats by regulating the activities and expression of CYP3A4 and CYP2C9.

    PubMed

    Wang, Rong; Zhang, Hai; Wang, Yujie; Yu, Xiaoyan; Yuan, Yongfang

    2016-03-01

    Losartan (LST) is a common chemical drug used to treat high blood pressure and reduce the risk of stroke in certain people with heart disease. Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge, has been widely used for prevention and treatment of various cardiovascular and cerebrovascular diseases. There are more than 35 formulations containing Danshen indexed in the 2010 Chinese Pharmacopoeia, which are often combined with LST to treat cardiovascular and cerebrovascular diseases in the clinic. The effects of the two major components of Danshen, salvianolic acid B (SA-B) and tanshinone IIA (Tan IIA), on the pharmacokinetics of losartan and its metabolite, EXP3174, in rats were investigated by liquid chromatography coupled with mass spectrometry (LC-MS). Male Sprague-Dawley rats were randomly assigned to 3 groups: LST, LST+SA-B and LST+Tan IIA, and the main pharmacokinetic parameters were estimated after oral administration of LST, LST+SA-B and LST+Tan IIA. It was found that there are significant differences in the pharmacokinetic parameters among the three groups: Cmax, t1/2, AUC, AUMC in the LST+SA-B group was smaller than those in group LST, while larger in group LST+Tan IIA. Further, the effects of SA-B and Tan IIA on the metabolism of losartan was also investigated using rat liver microsomes in vitro. The results indicated that SA-B can induce the metabolism of LST, while Tan IIA can inhibit the metabolism of LST in rat liver microsomes in vitro by regulating activities of CYP450 enzymes. In addition, the effect of SA-B and Tan IIA on CYP3A4 and CYP2C9 expression was studied in Chang liver cells by western-blotting and Real-time PCR. It was concluded that the two components of Danshen, SA-B and Tan IIA have different influences on the metabolism of LST: SA-B can obviously speed up the metabolism of LST by inducing CYP3A4/CYP2C9 activities and expression, however, Tan IIA can slow down the metabolism of LST by inhibiting CYP3A4/CYP2C

  15. Calbindins decreased after space flight

    NASA Technical Reports Server (NTRS)

    Sergeev, I. N.; Rhoten, W. B.; Carney, M. D.

    1996-01-01

    Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins

  16. Bronchial hyperresponsiveness decreases through childhood.

    PubMed

    Riiser, Amund; Hovland, Vegard; Mowinckel, Petter; Carlsen, Kai-Håkon; Carlsen, Karin Lødrup

    2012-02-01

    Limited knowledge exists about development of bronchial hyperresponsiveness (BHR) through adolescence. We aimed to assess changes in and risk factors for BHR in adolescence. From a Norwegian birth cohort 517 subjects underwent clinical examinations, structured interviews and methacholine challenges at age 10 and 16. BHR was divided into four categories: no BHR (cumulative methacholine dose required to reduce FEV(1) by 20% (PD(20)) >16 μmol), borderline BHR (PD(20) ≤16 and >8 μmol), mild to moderate BHR (PD(20) ≤8 and >1 μmol), and severe BHR (PD(20) ≤ 1 μmol). Logistic regression analysis was used to assess risk factors and possible confounders. The number of children with PD(20) ≤ 8 decreased from 172 (33%) to 79 (15%) from age 10-16 (p < 0.001). Most children (n = 295, 57%) remained in the same BHR (category) from age 10-16 (50% with no BHR), whereas the majority 182 (82%) of the 222 children who changed BHR category, had decreased severity at age 16. PD(20) ≤ 8 at age 10 was the major risk factor for PD(20) ≤ 8 6 years later (odds ratio 6.3), without significant confounding effect (>25% change) of gender, active rhinitis, active asthma, height, FEV(1)/FVC, or allergic sensitization. BHR decreased overall in severity through adolescence, was stable for the majority of children and only a minority (8%) had increased BHR from age 10 to 16. Mild to moderate and severe BHR at age 10 were major risk factors for PD(20) ≤ 8 at 16 years and not modified by asthma or body size. PMID:22015380

  17. Decreasing Fires in Mediterranean Europe

    PubMed Central

    Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

    2016-01-01

    Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980’s, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts. PMID:26982584

  18. Decreasing Fires in Mediterranean Europe.

    PubMed

    Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

    2016-01-01

    Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts. PMID:26982584

  19. [Decreasing incidence of stent thrombosis].

    PubMed

    Lemesle, G; Delhaye, C

    2011-12-01

    Stent thrombosis (ST) remains a major pitfall of stent implantation in contemporary percutaneous coronary intervention (PCI) leading to high rates of death and non-fatal myocardial infarction. Many predictors of ST have been reported worldwide but the strongest have to be highlighted regarding the catastrophic prognosis of such an event. Because platelet aggregation has a pivotal role in ST pathogenesis, the new antiplatelet regimens combining aspirin and P2Y12 receptor inhibitors have led to a remarkable decrease in the ST incidence, especially in the setting of acute coronary syndrome (ACS). In this article, our purpose is to review the evolution of ST incidence since first stent use in PCI. We will also overview the main predictors of ST focusing on ACS and clopidogrel low response. PMID:22054519

  20. Application of modified stir bar with nickel:zinc sulphide nanoparticles loaded on activated carbon as a sorbent for preconcentration of losartan and valsartan and their determination by high performance liquid chromatography.

    PubMed

    Pebdani, Arezou Amiri; Dadfarnia, Shayesteh; Shabani, Ali Mohammad Haji; Khodadoust, Saeid; Haghgoo, Soheila

    2016-03-11

    In this study, the stir bar was coated for the first time with the ​nicel:zins sulphide nanoparticles (Ni:ZnS NPs) loaded on activated carbon (AC) (Ni:ZnS-AC) as well as 1-ethyl-3-methylimidazolium hexafluorophosphate ionic liquid (IL) using sol gel technique and was used for stir bar sorptive extraction (SBSE) of losartan (LOS) and valsartan (VAL) as the model compounds. The extracted analytes were then quantified by high performance liquid chromatography (HPLC) equipped with an ultra violet detector. The best extraction performance for LOS and VAL was obtained through the optimization of the parameters affecting SBSE including pH of sample solution, ionic strength, extraction time, volume of desorption solvent, desorption time, and stirring speed. The fractional factorial design (FFD) was used to find the most important parameters, which were then optimized by the central composite design (CCD) and the desirability function (DF). Under the optimal experimental conditions, wide linear ranges of 0.4-50μgL(-1) and 0.5-50μgL(-1) and good RSDs (at level of 5μgL(-1) and n=6) of 4.4 and 4.9% were obtained for LOS and VAL, respectively. With the enrichment factors (EFs) of 188.6 and 184.8-fold, the limits of detection (LODs, S/N=3) of the developed method were found to be 0.12 and 0.15μgL(-1) for LOS and VAL, respectively. The developed method was successfully applied to the determination of LOS and VAL in urine and plasma matrices. PMID:26877174

  1. Decreased gallium uptake in acute hematogenous osteomyelitis

    SciTech Connect

    Ang, J.G.; Gelfand, M.J.

    1983-07-01

    Decreased radiopharmaceutical uptake was noted on both bone and gallium scans in the case of acute hematogenous osteomyelitis of the right ilium (acetabular roof). This combination of findings is probably rare. The mechanism of decreased gallium uptake is unknown, but may be related to decreased blood flow.

  2. Red blood cell decreases of microgravity

    NASA Technical Reports Server (NTRS)

    Johnson, P. C.

    1985-01-01

    Postflight decreases in red blood cell mass (RBCM) have regularly been recorded after exposure to microgravity. These 5-25 percent decreases do not relate to the mission duration, workload, caloric intake or to the type of spacecraft used. The decrease is accompanied by normal red cell survivals, increased ferritin levels, normal radioactive iron studies, and increases in mean red blood cell volume. Comparable decreases in red blood cell mass are not found after bed rest, a commonly used simulation of the microgravity state. Inhibited bone marrow erythropoiesis has not been proven to date, although reticulocyte numbers in the peripheral circulation are decreased about 50 percent. To date, the cause of the microgravity induced decreases in RBCM is unknown. Increased splenic trapping of circulating red blood cells seem the most logical way to explain the results obtained.

  3. Using a Nonaversive Procedure to Decrease Refusals.

    ERIC Educational Resources Information Center

    Spooner, Fred; And Others

    1990-01-01

    A nonaversive technique was used to teach a severely handicapped woman to decrease her refusals. The technique employed precision teaching via precise daily measurement strategies, environmental analysis, and a focus on building appropriate behavior. (JDD)

  4. Computerized medication administration records decrease medication occurrences.

    PubMed

    Wilson, A L; Hill, J J; Wilson, R G; Nipper, K; Kwon, I W

    1997-04-01

    Studies have demonstrated that medication errors occur at a number of locations in the continuum between ordering of drug therapy and administration of the medication. Computer management of patient medication profiles offers the opportunity to enhance communication between pharmacists and nurses, and to decrease medication errors and delays in delivery of therapy. A number of authors have postulated that computerization of medication profiles would enhance medication delivery accuracy and timeliness, but no study has demonstrated this improvement. We report the results of a retrospective analysis undertaken to assess the improvements resulting from sharing a computerized medication record. We used a broader definition of medication occurrences that includes the more traditional definition, and averted errors, delays in delivery of medications and information, and disagreements between pharmacy and nursing medication profiles. We compared medication occurrences reported through an existing internal system between two periods; the first when separate pharmacy and nursing medication records were used, and the second period when a shared medication record was used by pharmacy and nursing. Average medication occurrences per admission decreased from 0.1084 to 0.0658 (p < 0.01). Medication occurrences per dose decreased from 0.0005 to 0.0003 (p < 0.01). The use of a shared medication record by pharmacy and nursing led to a statistically significant decrease in medication occurrences. Information shared between the two professions allowed timely resolution of discrepancies in medication orders, leading to better execution of drug therapy, decreased medication occurrences, and increased efficiency. PMID:10166241

  5. Shock drift mechanism for Forbush decreases

    NASA Technical Reports Server (NTRS)

    Cheng, Andrew F.; Sarris, E. T.; Dodopoulos, C.

    1990-01-01

    Consideration is given to the way in which Forbush decreases can arise from variable drifts in nonuniform shocks, where the variation in shock strength along the shock front causes both the shock drift distance and the energy gain to become variable. More particles can then be transported out of a given region of space and energy interval than were transported in, so a spacecraft passing through this region can observe a Forbush decrease in this energy interval despite shock energization and compression. A simple example of how this can occur is presented.

  6. Shock drift mechanism for Forbush decreases

    SciTech Connect

    Cheng, A.F.; Sarris, E.T.; Dodopoulos, C. Thrace Democritus Univ., Xanthe )

    1990-02-01

    Consideration is given to the way in which Forbush decreases can arise from variable drifts in nonuniform shocks, where the variation in shock strength along the shock front causes both the shock drift distance and the energy gain to become variable. More particles can then be transported out of a given region of space and energy interval than were transported in, so a spacecraft passing through this region can observe a Forbush decrease in this energy interval despite shock energization and compression. A simple example of how this can occur is presented. 20 refs.

  7. Rosa damascena decreased mortality in adult Drosophila.

    PubMed

    Jafari, Mahtab; Zarban, Asghar; Pham, Steven; Wang, Thomas

    2008-03-01

    The effects of a rose-flower extract, Rosa damascena, on the mortality rate of Drosophila melanogaster was evaluated in this study. R. damascena is a potent antioxidant that has many therapeutic uses in addition to its perfuming effects. Supplementing Drosophila with this rose extract resulted in a statistically significant decrease in mortality rate in male and female flies. Moreover, the observed anti-aging effects were not associated with common confounds of anti-aging properties, such as a decrease in fecundity or metabolic rate. PMID:18361732

  8. Temporal Decrease in Upper Atmospheric Chlorine

    NASA Technical Reports Server (NTRS)

    Froidevaux, L.; Livesey, N. J.; Read, W. G.; Salawitch, R. J.; Waters, J. W.; Drouin, B.; MacKenzie, I. A.; Pumphrey, H. C.; Bernath, P.; Boone, C.; Nassar, R.; Montzka, S.; Elkins, J.; Cunnold, D.; Waugh, D.

    2006-01-01

    We report a steady decrease in the upper stratospheric and lower mesospheric abundances of hydrogen chloride (HCl) from August 2004 through January 2006, as measured by the Microwave Limb Sounder (MLS) aboard the Aura satellite. For 60(deg)S to 60(deg)N zonal means, the average yearly change in the 0.7 to 0.1 hPa (approx.50 to 65 km) region is -27 +/- 3 pptv/year, or -0.78 +/- 0.08 percent/year. This is consistent with surface abundance decrease rates (about 6 to 7 years earlier) in chlorine source gases. The MLS data confirm that international agreements to reduce global emissions of ozone-depleting industrial gases are leading to global decreases in the total gaseous chlorine burden. Tracking stratospheric HCl variations on a seasonal basis is now possible with MLS data. Inferred stratospheric total chlorine (CITOT) has a value of 3.60 ppbv at the beginning of 2006, with a (2-sigma) accuracy estimate of 7%; the stratospheric chlorine loading has decreased by about 43 pptv in the 18-month period studied here. We discuss the MLS HCl measurements in the context of other satellite-based HCl data, as well as expectations from surface chlorine data. A mean age of air of approx. 5.5 years and an age spectrum width of 2 years or less provide a fairly good fit to the ensemble of measurements.

  9. Decreasing Smoking Behavior through Subliminal Stimulation Treatments.

    ERIC Educational Resources Information Center

    Glover, Elbert D.

    1979-01-01

    Determines whether subliminal perception can be used as a means for altering cigarette smoking behavior. Smoking behavior was not altered through subliminal perception as carried out in this study. There was evidence that smoking behavior was altered, but it was an unpredicted change. Some subjects decreased smoking patterns. (Author)

  10. Does toxic fescue decrease bull fertility?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Knowledge of the detrimental effects of toxic tall fescue on bull reproductive performance is minimal. In natural breeding, reduced bull performance could decrease the pregnancy rate of the cowherd. Scientists from ARS in Booneville, AR, and the University of Arkansas investigated the influence of f...

  11. Aggregate Unemployment Decreases Individual Returns to Education

    ERIC Educational Resources Information Center

    Ammermueller, Andreas; Kuckulenz, Anja; Zwick, Thomas

    2009-01-01

    Aggregate unemployment may affect individual returns to education through qualification-specific responses in participation and wage bargaining. This paper shows that an increase in regional unemployment by 1% decreases returns to education by 0.005 percentage points. This implies that higher skilled employees are better sheltered from labour…

  12. Decreasing informal caregiver burden with social media.

    PubMed

    Watkins, Tammi

    2014-05-01

    In 2008, there were 44 million informal family caregivers and the number is expected to rise in the next decade. Hospice clinicians need to explore ways to decrease the burden of care for these informal caregivers. The use of electronic technology and social media may be a key component in improving support at end of life in the home setting. PMID:24802601

  13. Brain glycogen decreases during prolonged exercise

    PubMed Central

    Matsui, Takashi; Soya, Shingo; Okamoto, Masahiro; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

    2011-01-01

    Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30–120 min) at moderate intensity (20 m min−1) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37–60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise. PMID:21521757

  14. Decreasing trend of groundwater in Turkey

    NASA Astrophysics Data System (ADS)

    Sarachi, S.; Moghim, S.; Famiglietti, J. S.

    2010-12-01

    In these days the increasing demand for water has created problems for availability of its resources. Some recent issues like population growth, global warming and inefficient methods of water consumption, generated the need to find sources of water other than surface water such as ground water. Excess using of groundwater in most parts of the world causes depletion of ground water in those areas. Scientists are trying to find efficient means to quantify these trends. GRACE (Gravity Recovery and Climate Experiment) including two satellites launched in March 2002, is making measurements of the Earth's gravity field which is used to display the change of storage of the water on the Earth. GRACE makes it possible to find the trend of the change of storage all over the world.It can show specific areas in the world that have dramatic decreasing trend of water storage. One of these regions that have been considered in this study is Turkey in western Asia, as one of the countries deeply affected by global warming. Turkey is identified as one of the first places where desertification will start in Europe, according to estimates by the UN Environment Program (UNEP). Turkey has 25 underground water tables and they had a decrease in level of 27 meters in the past 25 years (Turkey water report 2009). In this paper the change of the ground water is evaluated by applying the GRACE storage anomalies and the mass conservation equation that concludes the reduction trend in groundwater. The results clarify that decreasing trend of groundwater is more noticeable during recent years, particularly since 2006. Our results show that in recent years the average decrease in ground water level is 2.5 cm per year and the maximum decrease occurred in May 2007 with the value of about 7.9 cm. KEY WORDS: water resources; Ground water; Turkey; GRACE

  15. Decreased subcortical cholinergic arousal in focal seizures

    PubMed Central

    Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal

    2015-01-01

    SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258

  16. Construction noise decreases reproductive efficiency in mice.

    PubMed

    Rasmussen, Skye; Glickman, Gary; Norinsky, Rada; Quimby, Fred W; Tolwani, Ravi J

    2009-07-01

    Excessive noise is well known to impair rodent health. To better understand the effect of construction noise and to establish effective noise limits during a planned expansion of our vivarium, we analyzed the effects of construction noise on mouse gestation and neonatal growth. Our hypothesis was that high levels of construction noise would reduce the number of live births and retard neonatal growth. Female Swiss Webster mice were individually implanted with 15 B6CBAF1/J embryos and then exposed to 70- and 90-dBA concrete saw cutting noise samples at defined time points during gestation. In addition, groups of mice with litters were exposed to noise at 70, 80, or 90 dBA for 1 h daily during the first week after parturition. Litter size, birth weight, incidence of stillborn pups, and rate of neonatal weight gain were analyzed. Noise decreased reproductive efficiency by decreasing live birth rates and increasing the number of stillborn pups. PMID:19653943

  17. Are urban noise pollution levels decreasing?

    PubMed

    Arana, M

    2010-04-01

    The majority of acoustic impact studies developed over the last 50 years have used a similar acoustic parameter (L(eq), L(dn)) but the noise mapping methodology has been very uneven. The selection of the measurement points, the measurement periods, or the evaluation indices have not followed a unique criterion. Therefore, it is not possible to compare the sound pollution levels between different cities from those studies, at least in a rigorous sense. Even more, different studies carried out in the same city by different researchers during different years and using different methodologies are not conclusive whether the acoustic pollution increases or decreases. The present paper shows results, with statistical significance, about the evolution of the acoustic pollution obtained for two Spanish cities, Pamplona and Madrid. In both cases, it can be concluded that noise pollution decreases over time (P<0.01). PMID:20369990

  18. Construction Noise Decreases Reproductive Efficiency in Mice

    PubMed Central

    Rasmussen, Skye; Glickman, Gary; Norinsky, Rada; Quimby, Fred W; Tolwani, Ravi J

    2009-01-01

    Excessive noise is well known to impair rodent health. To better understand the effect of construction noise and to establish effective noise limits during a planned expansion of our vivarium, we analyzed the effects of construction noise on mouse gestation and neonatal growth. Our hypothesis was that high levels of construction noise would reduce the number of live births and retard neonatal growth. Female Swiss Webster mice were individually implanted with 15 B6CBAF1/J embryos and then exposed to 70- and 90-dBA concrete saw cutting noise samples at defined time points during gestation. In addition, groups of mice with litters were exposed to noise at 70, 80, or 90 dBA for 1 h daily during the first week after parturition. Litter size, birth weight, incidence of stillborn pups, and rate of neonatal weight gain were analyzed. Noise decreased reproductive efficiency by decreasing live birth rates and increasing the number of stillborn pups. PMID:19653943

  19. Joint Impedance Decreases during Movement Initiation

    PubMed Central

    Ludvig, Daniel; Antos, Stephen A.; Perreault, Eric J.

    2013-01-01

    The mechanical properties of the joint influence how we interact with our environment and hence are important in the control of both posture and movement. Many studies have investigated how the mechanical properties—specifically the impedance—of different joints vary with different postural tasks. However, studies on how joint impedance varies with movement remain limited. The few studies that have investigated how impedance varies with movement have found that impedance is lower during movement than during posture. In this study we investigated how impedance changed as people transitioned from a postural task to a movement task. We found that subjects’ joint impedances decreased at the initiation of movement, prior to increasing at the cessation of movement. This decrease in impedance occurred even though the subjects’ torque and EMG levels increased. These findings suggest that during movement the central nervous system may control joint impedance independently of muscle activation. PMID:23366632

  20. Decrease in major amputations in Germany.

    PubMed

    Santosa, Frans; Moysidis, Theodoros; Kanya, Susanne; Babadagi-Hardt, Zeynep; Luther, Bernd; Kröger, Knut

    2015-06-01

    A decrease in rate of amputation has been reported from many countries. This study aims to study the trends in amputation rates in Germany. On the basis of DRG-system, detailed lists of all amputations coded as minor amputations (OPS 5-864) and major amputations (OPS 5-865) performed between 2005 and 2010 were provided by the Federal Statistical Office. There was a significant decrease in age-adjusted major amputation rates per 100 000 population in Germany from 27·0 in 2005 to 22·9 in 2010 (15·2%, P ≪ 0·001) in males and from 19·7 in 2005 to 14·4 in 2010 (26·9%, P ≪ 0·001) in females. Overall, minor amputation rates did not show such a decrease but increased in males (from 47·4 in 2005 to 57·8 in 2010, 21·9%, P ≪ 0·001) and remained almost unchanged in females (23·1 in 2005 and 23·9 in 2010, not significant). Reduction in major amputation rates were even more pronounced in people above 80 years, especially in males from 216 to 150 (30·5%) and in females from 168 to 117 (30·4%). The present data demonstrate an increasing overall burden of foot lesions as indicated by an increase in incidence of minor amputations but an ongoing success in the fight against amputation, resulting in a significant decrease in major amputation rates in Germany, in the 6-year period from 2005 to 2010. PMID:23738682

  1. Does precision decrease with set size?

    PubMed Central

    Mazyar, Helga; van den Berg, Ronald; Ma, Wei Ji

    2012-01-01

    The brain encodes visual information with limited precision. Contradictory evidence exists as to whether the precision with which an item is encoded depends on the number of stimuli in a display (set size). Some studies have found evidence that precision decreases with set size, but others have reported constant precision. These groups of studies differed in two ways. The studies that reported a decrease used displays with heterogeneous stimuli and tasks with a short-term memory component, while the ones that reported constancy used homogeneous stimuli and tasks that did not require short-term memory. To disentangle the effects of heterogeneity and short-memory involvement, we conducted two main experiments. In Experiment 1, stimuli were heterogeneous, and we compared a condition in which target identity was revealed before the stimulus display with one in which it was revealed afterward. In Experiment 2, target identity was fixed, and we compared heterogeneous and homogeneous distractor conditions. In both experiments, we compared an optimal-observer model in which precision is constant with set size with one in which it depends on set size. We found that precision decreases with set size when the distractors are heterogeneous, regardless of whether short-term memory is involved, but not when it is homogeneous. This suggests that heterogeneity, not short-term memory, is the critical factor. In addition, we found that precision exhibits variability across items and trials, which may partly be caused by attentional fluctuations. PMID:22685337

  2. Interstitial pericytes decrease in aged mouse kidneys.

    PubMed

    Stefanska, Ania; Eng, Diana; Kaverina, Natalya; Duffield, Jeremy S; Pippin, Jeffrey W; Rabinovitch, Peter; Shankland, Stuart J

    2015-06-01

    With increasing age, the kidney undergoes characteristic changes in the glomerular and tubulo-interstitial compartments, which are ultimately accompanied by reduced kidney function. Studies have shown age-related loss of peritubular vessels. Normal peritubular vessel tone, function and survival depend on neighboring pericytes. Pericyte detachment leads to vascular damage, which can be accompanied by their differentiation to fibroblasts and myofibroblasts, a state that favors matrix production. To better understand the fate of pericytes in the aged kidney, 27 month-old mice were studied. Compared to 3 month-old young adult mice, aged kidneys showed a substantial decrease in capillaries, identified by CD31 staining, in both cortex and medulla. This was accompanied by a marked decrease in surrounding NG2+ / PDGFRβ+ pericytes. This decrease was more pronounced in the medulla. Capillaries devoid of pericytes were typically dilated in aged mice. Aged kidneys were also characterized by interstitial fibrosis due to increased collagen-I and -III staining. This was accompanied by an increase in the number of pericytes that acquired a pro-fibrotic phenotype, identified by increased PDGFRβ+ / αSMA+ staining. These findings are consistent with the decline in kidney interstitial pericytes as a critical step in the development of changes to the peritubular vasculature with aging, and accompanying fibrosis. PMID:26081073

  3. Interstitial pericytes decrease in aged mouse kidneys

    PubMed Central

    Stefanska, Ania; Eng, Diana; Kaverina, Natalya; Duffield, Jeremy S.; Pippin, Jeffrey W.; Rabinovitch, Peter; Shankland, Stuart J.

    2015-01-01

    With increasing age, the kidney undergoes characteristic changes in the glomerular and tubulo-interstitial compartments, which are ultimately accompanied by reduced kidney function. Studies have shown age-related loss of peritubular vessels. Normal peritubular vessel tone, function and survival depend on neighboring pericytes. Pericyte detachment leads to vascular damage, which can be accompanied by their differentiation to fibroblasts and myofibroblasts, a state that favors matrix production. To better understand the fate of pericytes in the aged kidney, 27 month-old mice were studied. Compared to 3 month-old young adult mice, aged kidneys showed a substantial decrease in capillaries, identified by CD31 staining, in both cortex and medulla. This was accompanied by a marked decrease in surrounding NG2+/PDGFRß+ pericytes. This decrease was more pronounced in the medulla. Capillaries devoid of pericytes were typically dilated in aged mice. Aged kidneys were also characterized by interstitial fibrosis due to increased collagen-I and -III staining. This was accompanied by an increase in the number of pericytes that acquired a pro-fibrotic phenotype, identified by increased PDGFRß+/αSMA+ staining. These findings are consistent with the decline in kidney interstitial pericytes as a critical step in the development of changes to the peritubular vasculature with aging, and accompanying fibrosis. PMID:26081073

  4. Bone Marrow Stress Decreases Osteogenic Progenitors.

    PubMed

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential. PMID:26220824

  5. Decreased fibrinolytic activity in juvenile chronic arthritis.

    PubMed Central

    Mussoni, L; Pintucci, G; Romano, G; De Benedetti, F; Massa, M; Martini, A

    1990-01-01

    The basal fibrinolytic activity in 17 children with active juvenile chronic arthritis (JCA) was investigated. It was found that patients with JCA, and particularly those with the systemic form, show decreased plasma fibrinolytic activity and a marked increase in plasminogen activator inhibitor. Additionally, it was found that patients with systemic JCA, but not those with the polyarticular or pauciarticular form, have increased circulating levels of tissue-type plasminogen activator, and endothelial cell protein, suggesting possible endothelial cell participation in systemic JCA. PMID:2125408

  6. Method for decreasing permeability around a wellbore

    SciTech Connect

    Richardson, W.C.; Whittington, L.E.; Morrow, L.R.

    1988-01-26

    A method for decreasing formation permeability in an underground formation around a wellbore is described comprising: injecting an aqueous solution having a pH of about 0.9 to about 3.5 into the formation surrounding a wellbore, the aqueous solution comprising about 2% to about 20% by weight of lignosulfonate, about 2% to about 20% by weight of monomer of acrylic acid, a sufficient amount of an initiator of persulfate to copolymerize the lignosulfonate and the monomer, and about 0% to about 3.0% by weight of a metal slat having a cation of iron, titanium, vanadium, chromium or molybdenum.

  7. Dexmedetomidine decreases the oral mucosal blood flow.

    PubMed

    Kawaai, Hiroyoshi; Yoshida, Kenji; Tanaka, Eri; Togami, Kohei; Tada, Hitoshi; Ganzberg, Steven; Yamazaki, Shinya

    2013-12-01

    There is an abundance of blood vessels in the oral cavity, and intraoperative bleeding can disrupt operations. There have been some interesting reports about constriction of vessels in the oral cavity, one of which reported that gingival blood flow in cats is controlled by sympathetic α-adrenergic fibres that are involved with vasoconstriction. Dexmedetomidine is a sedative and analgesic agent that acts through the α-2 adrenoceptor, and is expected to have a vasoconstrictive action in the oral cavity. We have focused on the relation between the effects of α-adrenoceptors by dexmedetomidine and vasoconstriction in oral tissues, and assessed the oral mucosal blood flow during sedation with dexmedetomidine. The subjects comprised 13 healthy male volunteers, sedated with dexmedetomidine in a loading dose of 6 μg/kg/h for 10 min and a continuous infusion of 0.7 μg/kg/h for 32 min. The mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and palatal mucosal blood flow (PMBF) were measured at 0, 5, 10, 12, 22, and 32 min after the start of the infusion. The HR, CO, and PBMF decreased significantly during the infusion even though there were no differences in the SV. The SVR increased significantly but the PMBF decreased significantly. In conclusion, PMBF was reduced by the mediating effect of dexmedetomidine on α-2 adrenoceptors. PMID:23958351

  8. Rapid weight loss decreases serum testosterone.

    PubMed

    Karila, T A M; Sarkkinen, P; Marttinen, M; Seppälä, T; Mero, A; Tallroth, K

    2008-11-01

    To investigate the effects of a rapid weight reduction program under authentic pre-competition conditions, eighteen elite wrestlers were studied with dual-energy X-ray absorptiometry (DXA) before and after two to three weeks' weight reduction regimens. In order to establish the degree of dehydration and hormonal status, blood samples were collected to obtain blood chemistry, electrolytes and endocrinological parameters after both DXA measurements. The mean weight loss was 8.2 +/- 2.3 % and it was constituted by the mean reductions of fat mass of 16 +/- 6.9 % (p < or = 0.001) and lean body mass of 7.9 +/- 2.5 %. The rapid weight reduction caused significant dehydration which was noticed as increased blood hemoglobin (7.8 +/- 5.9 %, p < or = 0.001), hematocrit (11.3 +/- 6.8 %, p < or = 0.001), and serum creatinine (35 +/- 23 %, p < or = 0.001). There was a significant decrease in serum testosterone (63 +/- 33 %, p < or = 0.001) and luteinizing hormone (54 +/- 47 %, p < or = 0.001) concentrations. A reduced body weight correlated with decreased serum testosterone concentration (r = 0.53, p < or = 0.024). Serum sex hormone binding globulin concentration increased significantly (40 +/- 21 %, p < or = 0.001). The results suggest that even short-term weight reduction may have marked effects on body composition, blood chemistry and hormonal parameters. It may constitute a possible health risk at least in a growing adolescent athlete. PMID:18516767

  9. Statins Decrease Oxidative Stress and ICD Therapies

    PubMed Central

    Bloom, Heather L.; Shukrullah, Irfan; Veledar, Emir; Gutmann, Rebecca; London, Barry; Dudley, Samuel C.

    2010-01-01

    Recent studies demonstrate that statins decrease ventricular arrhythmias in internal cardioverter defibrillator (ICD) patients. The mechanism is unknown, but evidence links increased inflammatory and oxidative states with increased arrhythmias. We hypothesized that statin use decreases oxidation. Methods. 304 subjects with ICDs were surveyed for ventricular arrhythmia. Blood was analyzed for derivatives of reactive oxygen species (DROMs) and interleukin-6 (IL-6). Results. Subjects included 252 (83%) men, 58% on statins, 20% had ventricular arrhythmias. Average age was 63 years and ejection fraction (EF) 20%. ICD implant duration was 29 ± 27 months. Use of statins correlated with lower ICD events (r = 0.12, P = .02). Subjects on statins had lower hsCRP (5.2 versus 6.3; P = .05) and DROM levels (373 versus 397; P = .03). Other factors, including IL-6 and EF did not differ between statin and nonstatin use, nor did beta-blocker or antiarrhythmic use. Multivariate cross-correlation analysis demonstrated that DROMs, statins, IL-6 and EF were strongly associated with ICD events. Multivariate regression shows DROMs to be the dominant predictor. Conclusion. ICD event rate correlates with DROMs, a measure of lipid peroxides. Use of statins is associated with reduced DROMs and fewer ICD events, suggesting that statins exert their effect through reducing oxidation. PMID:20369058

  10. Tracheoesophageal fistula length decreases over time.

    PubMed

    Jiang, Nancy; Kearney, Ann; Damrose, Edward J

    2016-07-01

    The objectives of this study were to demonstrate that the length of the tracheoesophageal voice prosthesis changes over time and to determine whether the prosthesis length over time increased, decreased, or showed no predictable change in size. A retrospective chart review was performed at a tertiary care referral center. Patients who underwent either primary or secondary tracheoesophageal puncture between January 2006 and August 2014 were evaluated. Patients were excluded if the tracheoesophageal prosthesis size was not consistently recorded or if they required re-puncturing for an extruded prosthesis. Data analyzed included patient demographics and the length of the tracheoesophageal voice prosthesis at each change. A total of 37 patients were identified. The mean age was 64 years. Seventy-six percent were male. 24 % underwent primary tracheoesophageal puncture and 76 % underwent secondary tracheoesophageal puncture. The length of the prosthesis decreased over time (median Kendall correlation coefficient = -0.60; mean = -0.44) and this correlation between length and time was significant (p = 0.00085). Therefore, in conclusion, tracheoesophageal prosthesis length is not constant over time. The tracheoesophageal wall thins, necessitating placement of shorter prostheses over time. Patients with a tracheoesophageal voice prosthesis will require long-term follow-up and repeat sizing of their prosthesis. Successful tracheoesophageal voicing will require periodic reevaluation of these devices, and insurers must, therefore, understand that long-term professional care will be required to manage these patients and their prostheses. PMID:26951219

  11. Lifestyle decreases risk factors for cardiovascular diseases.

    PubMed

    Slavícek, Jaroslav; Kittnar, Otomar; Fraser, Gary E; Medová, Eva; Konecná, Jana; Zizka, Robert; Dohnalová, Alena; Novák, Vladimir

    2008-12-01

    The morbidity and mortality of cardiovascular diseases is high in the developed countries. The lifestyle changes are capable to decrease it by 50%. The aim of the present study was to measure the parameters of some risk factors before and after a one-week NEW START rehabilitative retreat. 1349 volunteers, 320 men, 1029 woman, mean age 51 +/- 14.5 (SD) years participated in 30 rehabilitative retreats from 1999-2006 in the Czech Republic, using a low-fat, low-energy, lacto-ovo-vegetarian diet and exercise, in a stress-free environment. Body weight, height, BMI, blood pressure, heart rate, serum cholesterol and blood glucose were measured. Body weight decreased in 1223 measured persons from 71.2 +/- 14.38 (SD) to 70.6 +/- 14.02 kg (p<0.0001), BMI (1,046 measured persons) from 25.1 +/- 4.60 (SD) to 24.8+4.49 (SD) kg/m2 (p<0.0001), systolic blood pressure (1,218 persons) from 129.8 +/- 23.02 (SD) to 123.8 +/- 21.52 (SD) mmHg (p<0.0001), diastolic blood pressure (1210 persons) from 79.8 +/- 12.7 (SD) to 77.5 +/- 11.6 (SD) mmHg (p<0.0001), serum cholesterol (998 persons) from 4.86 +/- 0.95 (SD) to 4.32 +/- 0.77 (SD) mmol (p<0.0001), blood glucose (544 persons) from 4.31 +/- 1.59 (SD) to 3.88 +/- 1.33 (SD) mmol (p<0.0001). Heart rate was not significantly decreased. The parameters were lower in lacto-ovo vegetarians and Seventh-day Adventists than in controls who never observed the diet and avail the lifestyle programs. The parameters were nonsignificantly changed one year after finishing the retreat in the sample of 68 persons showing the positive effect of retreats. Our results showed, that the intake of a low-fat, low-energy diet, over the course of one week in a stress-free environment, had positive impact on the risk factors of cardiovascular diseases. PMID:19256282

  12. Cosmic ray decreases and magnetic clouds

    NASA Technical Reports Server (NTRS)

    Cane, H. V.

    1993-01-01

    A study has been made of energetic particle data, obtained from IMP 8, in conjunction with solar wind field and plasma data at the times of reported magnetic clouds. It is shown that magnetic clouds can cause a depression of the cosmic ray flux but high fields are required. A depression of 3 percent in a neutron monitor requires a field of about 25 nT. Such high fields are found only in a subset of coronal ejecta. The principal cause for Forbush decreases associated with energetic shocks is probably turbulence in the postshock region, although some shocks will be followed by an ejecta with a high field. Each event is different. The lower-energy particles can help in identifying the dominant processes in individual events.

  13. Adolescent impatience decreases with increased frontostriatal connectivity

    PubMed Central

    van den Bos, Wouter; Rodriguez, Christian A.; Schweitzer, Julie B.; McClure, Samuel M.

    2015-01-01

    Adolescence is a developmental period associated with an increase in impulsivity. Impulsivity is a multidimensional construct, and in this study we focus on one of the underlying components: impatience. Impatience can result from (i) disregard of future outcomes and/or (ii) oversensitivity to immediate rewards, but it is not known which of these evaluative processes underlie developmental changes. To distinguish between these two causes, we investigated developmental changes in the structural and functional connectivity of different frontostriatal tracts. We report that adolescents were more impatient on an intertemporal choice task and reported less future orientation, but not more present hedonism, than young adults. Developmental increases in structural connectivity strength in the right dorsolateral prefrontal tract were related to increased negative functional coupling with the striatum and an age-related decrease in discount rates. Our results suggest that mainly increased control, and the integration of future-oriented thought, drives the reduction in impatience across adolescence. PMID:26100897

  14. Cosmic ray decreases and magnetic clouds

    NASA Technical Reports Server (NTRS)

    Cane, H. V.

    1992-01-01

    Energetic particle data, obtained from IMP 8, in conjunction with solar wind field and plasma data at the times of reported magnetic clouds was studied. It is shown that magnetic clouds can cause a depression of the cosmic ray flux but high fields are required. A depression of 3 percent in a neutron monitor requires a field of about 25 nT. Such high fields are found only in a subset of coronal ejecta. The principal cause for Forbush decreases associated with energetic shocks is probably turbulence in the post-shock region although some shocks will be followed by an ejecta with a high field. Each event is different. The lower energy particles can help in identifying the dominant processes in individual events.

  15. Decreased interoceptive accuracy following social exclusion.

    PubMed

    Durlik, Caroline; Tsakiris, Manos

    2015-04-01

    The need for social affiliation is one of the most important and fundamental human needs. Unsurprisingly, humans display strong negative reactions to social exclusion. In the present study, we investigated the effect of social exclusion on interoceptive accuracy - accuracy in detecting signals arising inside the body - measured with a heartbeat perception task. We manipulated exclusion using Cyberball, a widely used paradigm of a virtual ball-tossing game, with half of the participants being included during the game and the other half of participants being ostracized during the game. Our results indicated that heartbeat perception accuracy decreased in the excluded, but not in the included, participants. We discuss these results in the context of social and physical pain overlap, as well as in relation to internally versus externally oriented attention. PMID:25701592

  16. Incomplete and transitory decrease of glycolysis

    PubMed Central

    Schoors, Sandra; Cantelmo, Anna Rita; Georgiadou, Maria; Stapor, Peter; Wang, Xingwu; Quaegebeur, Annelies; Cauwenberghs, Sandra; Wong, Brian W; Bifari, Francesco; Decimo, Ilaria; Schoonjans, Luc; De Bock, Katrien; Dewerchin, Mieke; Carmeliet, Peter

    2014-01-01

    During vessel sprouting, a migratory endothelial tip cell guides the sprout, while proliferating stalk cells elongate the branch. Tip and stalk cell phenotypes are not genetically predetermined fates, but are dynamically interchangeable to ensure that the fittest endothelial cell (EC) leads the vessel sprout. ECs increase glycolysis when forming new blood vessels. Genetic deficiency of the glycolytic activator PFKFB3 in ECs reduces vascular sprouting by impairing migration of tip cells and proliferation of stalk cells. PFKFB3-driven glycolysis promotes the tip cell phenotype during vessel sprouting, since PFKFB3 overexpression overrules the pro-stalk activity of Notch signaling. Furthermore, PFKFB3-deficient ECs cannot compete with wild-type neighbors to form new blood vessels in chimeric mosaic mice. In addition, pharmacological PFKFB3 blockade reduces pathological angiogenesis with modest systemic effects, likely because it decreases glycolysis only partially and transiently. PMID:24335389

  17. Decreasing dangerous infant behaviors through parent instruction.

    PubMed Central

    Mathews, J R; Friman, P C; Barone, V J; Ross, L V; Christophersen, E R

    1987-01-01

    One adult and three adolescent mothers with 1-year-old infants were taught to reduce their infants' potential for injury in the home. After being taught to increase their positive interactions with their infants, the mothers were taught to child-proof the home, to use playpen time-out for potentially dangerous behaviors, and to give positive attention for safe behaviors. A multiple baseline design across subjects was used to evaluate functional control. Potentially dangerous behaviors, observed during 10 min of free play, decreased from variable and, at times, high rates during baseline to stable near-zero rates after treatment. These target behaviors remained low at a 7-month follow-up assessment. PMID:3610895

  18. Decreased adult neurogenesis in hibernating Syrian hamster.

    PubMed

    León-Espinosa, Gonzalo; García, Esther; Gómez-Pinedo, Ulises; Hernández, Félix; DeFelipe, Javier; Ávila, Jesús

    2016-10-01

    Generation of new neurons from adult neural stem cells occurs in the dentate gyrus (DG) of the hippocampus and the lateral walls of the lateral ventricles. In this article, we study the neurogenesis that takes place during the hibernation of the Syrian hamster (Mesocricetus auratus). Using a variety of standard neurogenesis markers and 5-bromo-2-deoxyuridine (BrdU) incorporation, we describe a preferential decrease in the proliferation of newborn neurons in the subventricular zone (SVZ) of the hibernating hamsters (torpor) rather than in the hippocampus. Furthermore, we demonstrate that the proliferative capacity is recovered after 3-4days of torpor when arousal is triggered under natural conditions (i.e., not artificially provoked). In addition, we show that tau3R, a tau isoform with three microtubule-binding domains, is a suitable marker to study neurogenesis both in the SVZ and subgranular zone (SGZ) of the Syrian hamster brain. PMID:27436535

  19. Climate warming will not decrease winter mortality

    NASA Astrophysics Data System (ADS)

    Staddon, Philip L.; Montgomery, Hugh E.; Depledge, Michael H.

    2014-03-01

    It is widely assumed by policymakers and health professionals that the harmful health impacts of anthropogenic climate change will be partially offset by a decline in excess winter deaths (EWDs) in temperate countries, as winters warm. Recent UK government reports state that winter warming will decrease EWDs. Over the past few decades, however, the UK and other temperate countries have simultaneously experienced better housing, improved health care, higher incomes and greater awareness of the risks of cold. The link between winter temperatures and EWDs may therefore no longer be as strong as before. Here we report on the key drivers that underlie year-to-year variations in EWDs. We found that the association of year-to-year variation in EWDs with the number of cold days in winter ( <5 °C), evident until the mid 1970s, has disappeared, leaving only the incidence of influenza-like illnesses to explain any of the year-to-year variation in EWDs in the past decade. Although EWDs evidently do exist, winter cold severity no longer predicts the numbers affected. We conclude that no evidence exists that EWDs in England and Wales will fall if winters warm with climate change. These findings have important implications for climate change health adaptation policies.

  20. Ceruloplasmin decreases respiratory burst reaction during pregnancy.

    PubMed

    Varfolomeeva, Elena Y; Semenova, Elena V; Sokolov, Alexey V; Aplin, Kirill D; Timofeeva, Kseniya E; Vasilyev, Vadim B; Filatov, Michael V

    2016-08-01

    Testing of pregnant women reveals weakening of neutrophil-mediated effector functions, such as reactive oxygen species generation. This study provides data confirming the phenomenon, gained through application of the flow cytometry technique. Key factors influencing neutrophil functional activity in blood plasma of pregnant women have not been detected so far. At the same time, concentration of ceruloplasmin - a copper-containing glycoprotein - is known to increase in blood significantly during pregnancy. We observed the negative correlation between ceruloplasmin concentration in blood plasma of pregnant women and the intensity of respiratory burst of neutrophils. Fractionation of plasma using gel-filtration revealed that ceruloplasmin-containing fraction demonstrated suppression of the respiratory burst reaction. Partial elimination of ceruloplasmin from the blood of pregnant women, performed with the help of specific antibodies and followed by immunoprecipitation, leads to an increased respiratory burst reaction. On the contrary, addition of ceruloplasmin to blood samples of healthy donors noticeably decreases the respiratory burst reaction. The results presented prove that change in ceruloplasmin level in plasma is necessary and sufficient for modulating the ability of neutrophils to produce reactive oxygen species during pregnancy. PMID:27266720

  1. Future Avenues to Decrease Uremic Toxin Concentration.

    PubMed

    Vanholder, Raymond C; Eloot, Sunny; Glorieux, Griet L R L

    2016-04-01

    In this article, we review approaches for decreasing uremic solute concentrations in chronic kidney disease and in particular, in end-stage renal disease (ESRD). The rationale to do so is the straightforward relation between concentration and biological (toxic) effect for most toxins. The first section is devoted to extracorporeal strategies (kidney replacement therapy). In the context of high-flux hemodialysis and hemodiafiltration, we discuss increasing dialyzer blood and dialysate flows, frequent and/or extended dialysis, adsorption, bioartificial kidney, and changing physical conditions within the dialyzer (especially for protein-bound toxins). The next section focuses on the intestinal generation of uremic toxins, which in return is stimulated by uremic conditions. Therapeutic options are probiotics, prebiotics, synbiotics, and intestinal sorbents. Current data are conflicting, and these issues need further study before useful therapeutic concepts are developed. The following section is devoted to preservation of (residual) kidney function. Although many therapeutic options may overlap with therapies provided before ESRD, we focus on specific aspects of ESRD treatment, such as the risks of too-strict blood pressure and glycemic regulation and hemodynamic changes during dialysis. Finally, some recommendations are given on how research might be organized with regard to uremic toxins and their effects, removal, and impact on outcomes of uremic patients. PMID:26500179

  2. Exogenous spatial attention decreases audiovisual integration.

    PubMed

    Van der Stoep, N; Van der Stigchel, S; Nijboer, T C W

    2015-02-01

    Multisensory integration (MSI) and spatial attention are both mechanisms through which the processing of sensory information can be facilitated. Studies on the interaction between spatial attention and MSI have mainly focused on the interaction between endogenous spatial attention and MSI. Most of these studies have shown that endogenously attending a multisensory target enhances MSI. It is currently unclear, however, whether and how exogenous spatial attention and MSI interact. In the current study, we investigated the interaction between these two important bottom-up processes in two experiments. In Experiment 1 the target location was task-relevant, and in Experiment 2 the target location was task-irrelevant. Valid or invalid exogenous auditory cues were presented before the onset of unimodal auditory, unimodal visual, and audiovisual targets. We observed reliable cueing effects and multisensory response enhancement in both experiments. To examine whether audiovisual integration was influenced by exogenous spatial attention, the amount of race model violation was compared between exogenously attended and unattended targets. In both Experiment 1 and Experiment 2, a decrease in MSI was observed when audiovisual targets were exogenously attended, compared to when they were not. The interaction between exogenous attention and MSI was less pronounced in Experiment 2. Therefore, our results indicate that exogenous attention diminishes MSI when spatial orienting is relevant. The results are discussed in terms of models of multisensory integration and attention. PMID:25341648

  3. Aneurysm strength can decrease under calcification.

    PubMed

    Volokh, Konstantin Y; Aboudi, Jacob

    2016-04-01

    Aneurysms are abnormal dilatations of vessels in the vascular system that are prone to rupture. Prediction of the aneurysm rupture is a challenging and unsolved problem. Various factors can lead to the aneurysm rupture and, in the present study, we examine the effect of calcification on the aneurysm strength by using micromechanical modeling. The calcified tissue is considered as a composite material in which hard calcium particles are embedded in a hyperelastic soft matrix. Three experimentally calibrated constitutive models incorporating a failure description are used for the matrix representation. Two constitutive models describe the aneurysmal arterial wall and the third one - the intraluminal thrombus. The stiffness and strength of the calcified tissue are simulated in uniaxial tension under the varying amount of calcification, i.e. the relative volume of the hard inclusion within the periodic unit cell. In addition, the triaxiality of the stress state, which can be a trigger for the cavitation instability, is tracked. Results of the micromechanical simulation show an increase of the stiffness and a possible decrease of the strength of the calcified tissue as compared to the non-calcified one. The obtained results suggest that calcification (i.e. the presence of hard particles) can significantly affect the stiffness and strength of soft tissue. The development of refined experimental techniques that will allow for the accurate quantitative assessment of calcification is desirable. PMID:26717251

  4. Forbush decreases observed by Daejeon neutron monitor

    NASA Astrophysics Data System (ADS)

    Kang, Jeongsoo; Oh, Suyeon; Yi, Yu; Kim, Yongkyun

    2016-02-01

    The neutron monitor (NM) is a ground-based detector designed to estimate the cosmic ray intensity by measuring secondary particles. In October 2011, an NM64-type NM with a vertical cutoff rigidity of 11.2 GV was installed at Daejeon in Korea. It has produced reliable cosmic ray data after detector stabilization. In order to examine the reliability of cosmic ray data collected by the Daejeon NM, we select Forbush decreases (FDs) that occurred during the three years of 2012-2014. We also analyze the FDs at the Oulu NM in Finland in order to identify and compare them. We identify 37 FDs at both Daejeon and Oulu NMs. Student t-test analysis reveals that FDs at Daejeon have smaller intensity variation of main phase and shorter duration of main phase than those at the Oulu NM. Of the 37 FDs, 17 are simultaneous and 20 are non-simultaneous. The intensity variation of simultaneous FDs is larger than that of non-simultaneous FDs at both NMs with high confidence levels in the Student t-test. Most of the non-simultaneous FDs that have an onset time in the dayside hold typical properties of non-simultaneous FDs. Our study results demonstrate that the Daejeon NM can provide cosmic ray data of reliability comparable to that of the Oulu NM. As one of only a few NMs worldwide with a high vertical cutoff rigidity exceeding 10.0 GV, the Daejeon NM will continue to provide important information on higher-energy cosmic ray spectra.

  5. Antihypertensive drugs decrease risk of Alzheimer disease

    PubMed Central

    Xia, Jin; Yao, Wenliang; Furberg, Curt D.; Xue, Qian-Li; Mercado, Carla I.; Fitzpatrick, Annette L.; Fried, Linda P.; Kawas, Claudia H.; Sink, Kaycee M.; Williamson, Jeff D.; DeKosky, Steven T.; Carlson, Michelle C.

    2013-01-01

    Objectives: The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or β-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI). Methods: Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders. Results: Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31–0.82), 0.31 in ARB (95% CI 0.14–0.68), 0.50 in ACE-I (95% CI 0.29–0.83), 0.62 in CCB (95% CI 0.35–1.09), and 0.58 in BB (95% CI 0.36–0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20–0.73). Conclusions: Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI. PMID:23911756

  6. Stop signals decrease choices for palatable foods through decreased food evaluation

    PubMed Central

    Veling, Harm; Aarts, Henk; Stroebe, Wolfgang

    2013-01-01

    The present study explores whether presenting specific palatable foods in close temporal proximity of stop signals in a go/no-go task decreases subsequent evaluations of such foods among participants with a relatively high appetite. Furthermore, we tested whether any decreased evaluations could mediate subsequent food choice. Participants first received a go/no-go task in which palatable foods were consistently linked to go cues or no-go cues within participants. Next, evaluation of the palatable foods was measured as well as food choice. Replicating previous work, results show that among participants with a relatively high appetite palatable foods associated with no-go cues are less often chosen as snacks compared to when these foods are associated with go cues, whereas this manipulation did not affect participants with a relatively low appetite. Moreover, this effect was completely mediated by decreased evaluation of the palatable foods that had been associated with the no-go cues, whereas evaluation of the foods associated with go cues did not mediate this effect. Results further showed that the devaluation effect of foods associated with no-go cues was independent of the amount of pairings (4 vs. 12 vs. 24) with the no-go cues. The current findings suggest that decreased food evaluation is a mechanism that explains effects of stop signals on food choice. PMID:24324451

  7. Decreasing child mortality, spatial clustering and decreasing disparity in North-Western Burkina Faso.

    PubMed

    Becher, Heiko; Müller, Olaf; Dambach, Peter; Gabrysch, Sabine; Niamba, Louis; Sankoh, Osman; Simboro, Seraphin; Schoeps, Anja; Stieglbauer, Gabriele; Yé, Yazoume; Sié, Ali

    2016-04-01

    Within relatively small areas, there exist high spatial variations of mortality between villages. In rural Burkina Faso, with data from 1993 to 1998, clusters of particularly high child mortality were identified in the population of the Nouna Health and Demographic Surveillance System (HDSS), a member of the INDEPTH Network. In this paper, we report child mortality with respect to temporal trends, spatial clustering and disparity in this HDSS from 1993 to 2012. Poisson regression was used to describe village-specific child mortality rates and time trends in mortality. The spatial scan statistic was used to identify villages or village clusters with higher child mortality. Clustering of mortality in the area is still present, but not as strong as before. The disparity of child mortality between villages has decreased. The decrease occurred in the context of an overall halving of child mortality in the rural area of Nouna HDSS between 1993 and 2012. Extrapolated to the Millennium Development Goals target period 1990-2015, this yields an estimated reduction of 54%, which is not too far off the aim of a two-thirds reduction. PMID:26821122

  8. Anterior Hip Joint Force Increases with Hip Extension, Decreased Gluteal Force, or Decreased Iliopsoas Force

    PubMed Central

    Lewis, Cara L.; Sahrmann, Shirley A.; Moran, Daniel W.

    2008-01-01

    Abnormal or excessive force on the anterior hip joint may cause anterior hip pain, subtle hip instability and a tear of the acetabular labrum. We propose that both the pattern of muscle force and hip joint position can affect the magnitude of anterior joint force and thus possibly lead to excessive force and injury. The purpose of this study was to determine the effect of hip joint position and of weakness of the gluteal and iliopsoas muscles on anterior hip joint force. We used a musculoskeletal model to estimate hip joint forces during simulated prone hip extension and supine hip flexion under 4 different muscle force conditions and across a range of hip extension and flexion positions. Weakness of specified muscles was simulated by decreasing the modeled maximum force value for the gluteal muscles during hip extension and the iliopsoas muscle during hip flexion. We found that decreased force contribution from the gluteal muscles during hip extension and the iliopsoas muscle during hip flexion resulted in an increase in the anterior hip joint force. The anterior hip joint force was greater when the hip was in extension than when the hip was in flexion. Further studies are warranted to determine if increased utilization of the gluteal muscles during hip extension and of the iliopsoas muscle during hip flexion, and avoidance of hip extension beyond neutral would be beneficial for people with anterior hip pain, subtle hip instability, or an anterior acetabular labral tear. PMID:17707385

  9. Resolvins Decrease Oxidative Stress Mediated Macrophage and Epithelial Cell Interaction through Decreased Cytokine Secretion

    PubMed Central

    Cox, Ruan; Phillips, Oluwakemi; Fukumoto, Jutaro; Fukumoto, Itsuko; Tamarapu Parthasarathy, Prasanna; Mandry, Maria; Cho, Young; Lockey, Richard; Kolliputi, Narasaiah

    2015-01-01

    Background Inflammation is a key hallmark of ALI and is mediated through ungoverned cytokine signaling. One such cytokine, interleukin-1beta (IL-1β) has been demonstrated to be the most bioactive cytokine in ALI patients. Macrophages are the key players responsible for IL-1β secretion into the alveolar space. Following the binding of IL-1β to its receptor, “activated” alveolar epithelial cells show enhanced barrier dysfunction, adhesion molecule expression, cytokine secretion, and leukocyte attachment. More importantly, it is an important communication molecule between the macrophage and alveolar epithelium. While the molecular determinants of this inflammatory event have been well documented, endogenous resolution processes that decrease IL-1β secretion and resolve alveolar epithelial cell activation and tissue inflammation have not been well characterized. Lipid mediator Aspirin-Triggered Resolvin D1 (AT-RvD1) has demonstrated potent pro-resolutionary effects in vivo models of lung injury; however, the contribution of the alveoli to the protective benefits of this molecule has not been well documented. In this study, we demonstrate that AT-RvD1 treatment lead to a significant decrease in oxidant induced macrophage IL-1β secretion and production, IL-1β-mediated cytokine secretion, adhesion molecule expression, leukocyte adhesion and inflammatory signaling. Methods THP-1 macrophages were treated with hydrogen peroxide and extracellular ATP in the presence or absence of AT-RvD1 (1000–0.1 nM). A549 alveolar-like epithelial cells were treated with IL-1β (10 ng/mL) in the presence or absence of AT-RvD1 (0.1 μM). Following treatment, cell lysate and cell culture supernatants were collected for Western blot, qPCR and ELISA analysis of pro-inflammatory molecules. Functional consequences of IL-1β induced alveolar epithelial cell and macrophage activation were also measured following treatment with IL-1β ± AT-RvD1. Results Results demonstrate that

  10. Concurrent working memory task decreases the Stroop interference effect as indexed by the decreased theta oscillations.

    PubMed

    Zhao, Y; Tang, D; Hu, L; Zhang, L; Hitchman, G; Wang, L; Chen, A

    2014-03-14

    Working memory (WM) tasks may increase or decrease the interference effect of concurrently performed cognitive control tasks. However, the neural oscillatory correlates of this modulation effect of WM on the Stroop task are still largely unknown. In the present study, behavioral and electroencephalographic (EEG) data were recorded from 32 healthy participants during their performance of the single Stroop task and the same task with a concurrent WM task. We observed that the Stroop interference effect represented in both response times (RTs) and theta-band event-related spectral perturbation (ERSP) magnitude reduced under the dual-task condition compared with the single-task condition. The reduction of interference in theta-band ERSP was further positively correlated with interference reduction in RTs, and was mainly explained by the source in the left middle frontal gyrus. In conclusion, the present study suggests that the effect of concurrent WM tasks on the reduction of the Stroop interference effect can be indexed by EEG oscillations in theta-band rhythm in the centro-frontal regions and this modulation was mediated by the reduced cognitive control under the concurrent WM task. PMID:24406438

  11. Recovery of Neonatal Head Turning to Decreased Sound Pressure Level.

    ERIC Educational Resources Information Center

    Tarquinio, Nancy; And Others

    1990-01-01

    Investigated newborns' responses to decreased sound pressure level (SPL) by means of a localized head turning habituation procedure. Findings, which demonstrated recovery of neonatal head turning to decreased SPL, were inconsistent with the selective receptor adaptation model. (RH)

  12. The Continuing Incidence of Natural Decrease in American Counties

    ERIC Educational Resources Information Center

    Johnson, Kenneth M.

    2011-01-01

    In 2002, more American counties (985) experienced natural decrease than at any time in the nation's history. The incidence of natural decrease has diminished since then, but remains near record levels. It is most common in rural areas remote from metropolitan centers. Spatial concentrations exist in the Great Plains, Corn Belt, and East Texas,…

  13. Decreases in Human Semen Quality with Age Among Healthy Men

    SciTech Connect

    Eskenazi, B.; Wyrobek, A.J.; Kidd, S.A.; Moore, L.; Young, S.S.; Moore, D.

    2001-12-01

    The objective of this report is to characterize the associations between age and semen quality among healthy active men after controlling for identified covariates. Ninety-seven healthy, nonsmoking men between 22 and 80 years without known fertility problems who worked for or retired from a large research laboratory. There was a gradual decrease in all semen parameters from 22-80 years of age. After adjusting for covariates, volume decreased 0.03 ml per year (p = 0.001); sperm concentration decreased 2.5% per year (p = 0.005); total count decreased 3.6% per year of age (p < 0.001); motility decreased 0.7% per year (P < 0.001); progressive motility decreased 3.1% per year (p < 0.001); and total progressively motile sperm decreased 4.8% per year (p < 0.001). In a group of healthy active men, semen volume, sperm concentration, total sperm count, and sperm motility decrease continuously between 22-80 years of age, with no evidence of a threshold.

  14. 29 CFR 4043.22 - Amendment decreasing benefits payable.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Amendment decreasing benefits payable. 4043.22 Section 4043.22 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION PLAN TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing...

  15. 29 CFR 4043.22 - Amendment decreasing benefits payable.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event....

  16. 29 CFR 4043.22 - Amendment decreasing benefits payable.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event....

  17. 29 CFR 4043.22 - Amendment decreasing benefits payable.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event....

  18. 29 CFR 4043.22 - Amendment decreasing benefits payable.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... TERMINATIONS REPORTABLE EVENTS AND CERTAIN OTHER NOTIFICATION REQUIREMENTS Post-Event Notice of Reportable Events § 4043.22 Amendment decreasing benefits payable. (a) Reportable event. A reportable event occurs... contributions with respect to any participant may be decreased. (b) Waivers. Notice is waived for this event....

  19. Tigecycline Treatment Causes a Decrease in Fibrinogen Levels

    PubMed Central

    Zhang, Qian; Zhou, Suming

    2014-01-01

    The objective of this study was to assess the impact of tigecycline treatment on coagulation parameters, specifically fibrinogen, in patients with severe infections. We examined 20 cases of tigecycline-treated patients with severe infections, including hospital-acquired pneumonia, complicated intra-abdominal infections, complicated skin and soft tissue infections, and bloodstream infections. We monitored the relative markers of coagulation and renal and liver function before, during, and after treatment. Fibrinogen (FIB) levels decreased significantly after the use of tigecycline and normalized after the cessation of treatment. FIB levels significantly decreased in the patients treated with the recommended dose or a higher treatment dose. The FIB levels decreased more in the higher-treatment-dose group. There was no difference in the decrease in FIB levels or the FIB level recovery by age. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged after tigecycline use. The TT decreased after the cessation of treatment, and the PT and APTT also decreased but not to a significant level. There was no change in platelet, alanine aminotransferase (ALT), or creatinine (Cr) levels associated with treatment. The use of tigecycline was associated with decreased FIB levels, which returned to normal after the cessation of treatment. A high-dose treatment group showed greater decreases in FIB levels than did patients treated with the recommended dose. The decline in FIB was not related to patient age. The use of tigecycline was associated with prolonged PT, APTT, and TT. PMID:25547356

  20. 75 FR 55944 - Walnuts Grown in California; Decreased Assessment Rate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... Agricultural Marketing Service 7 CFR Part 984 Walnuts Grown in California; Decreased Assessment Rate AGENCY... decreases the assessment rate established for the California Walnut Board (Board) for the 2010-11 and... program. The marketing year begins September 1 and ends August 31. The assessment rate will remain...

  1. Nitrate leaching concentrations in the Netherlands decreased more than expected

    NASA Astrophysics Data System (ADS)

    Boumans, Leo; Fraters, Dico; Wattel, Esther

    2014-05-01

    The implementation of EU environmental directives and national policies into measures has led to a decrease in nitrogen (N) surplus in agriculture, notably at dairy farms in the 1995-2002 period. In addition, N emissions to air from agricultural fields have been reduced, and atmospheric N deposition on nature areas subsequently lessened. The nitrate concentrations in root zone leaching at dairy farms and nature areas in the Sand region of the Netherlands also decreased. These decreases were larger than would be expected based on the decreases in net loads. We have formulated and tested hypotheses to explain these extra decreases at farms and in nature areas. Dairy farms cover about 60% of the area in the sandy region of the Netherlands. They have shown a nitrate leaching decrease of 100 mg/l during the 1992-2010 period (67%). The N-surplus at dairy farms decreased from about 340 to 180 kg/ha in this period (47%). Other farm management factors may have caused the additional decrease in root zone leaching concentration on farm level. The main potential factors are the ratio grassland - arable land, the grazing intensity and the ratio artificial fertilizer N - manure N. There are no indications that the ratio grassland - arable land or the ratio artificial fertilizer N - manure N significantly changed between 1992 and 2010. The mowing percentage, as an indicator for grazing intensity, increased from about 180 to 290% in the study period. About 80% (80 mg/l) of the decrease at dairy farms can be attributed to a lower N-surplus and about 20% (20 mg/l) is postulated to be caused by an increasing mowing percentage or less fodder grazing. Nature areas cover about 20% of the area in the Sand region. Nitrate concentrations in root zone leaching in nature areas showed a decrease of 55% in 2010 compared to 1990. Yet in rainwater, the concentration decrease is only 40%. Several factors may cause an additional decrease in nitrate concentration particularly an increase of plant

  2. Sham-feeding decreases cardiac output in normal subjects.

    PubMed

    Andersen, H B; Jensen, E W; Madsbad, S; Nielsen, S L; Burcharth, F; Christensen, N J

    1992-07-01

    The cardiovascular effect of sham-feeding was measured in seven healthy non-obese human subjects by the Fick principle using the carbon dioxide rebreathing method. The subjects were resting in the sitting position and were exposed to the sight and smell but not the taste of a breakfast meal. Cardiac output decreased significantly from a mean value of 4.0 1 min-1 to 3.5 1 min-1 during sham-feeding (Friedman, P = 0.004). The cardiac output returned to basal values in all seven subjects when the sensory stimulus was removed. The decrease in cardiac output was due to a decreased stroke volume, whereas heart rate and blood pressure did not change. The mechanism of the decrease in cardiac output during sham-feeding remains to be established. PMID:1505165

  3. Punishment and Alternative Strategies for Decreasing a Behavior.

    ERIC Educational Resources Information Center

    Vought, James J.

    1984-01-01

    Provides an overview on the subject of punishment and alternative procedures to decelerate a behavior. Describes differential reinforcement, extinction, satiation, corrective feedback, using peers as models and rearranging the environment as positive and nonaversive procedures for decreasing a behavior. (LLL)

  4. Developmental Triclosan Exposure Decreases Maternal and Offspring Thyroxine in Rats*

    EPA Science Inventory

    Epidemiological and laboratory data have demonstrated that disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring. In a short-term exposure paradigm, triclosan decreased systemic thyroxine (T4) concentr...

  5. Decreasing the spectral radius of a graph by link removals.

    PubMed

    Van Mieghem, Piet; Stevanović, Dragan; Kuipers, Fernando; Li, Cong; van de Bovenkamp, Ruud; Liu, Daijie; Wang, Huijuan

    2011-07-01

    The decrease of the spectral radius, an important characterizer of network dynamics, by removing links is investigated. The minimization of the spectral radius by removing m links is shown to be an NP-complete problem, which suggests considering heuristic strategies. Several greedy strategies are compared, and several bounds on the decrease of the spectral radius are derived. The strategy that removes that link l=i~j with largest product (x(1))(i)(x(1))(j) of the components of the eigenvector x(1) belonging to the largest adjacency eigenvalue is shown to be superior to other strategies in most cases. Furthermore, a scaling law where the decrease in spectral radius is inversely proportional to the number of nodes N in the graph is deduced. Another sublinear scaling law of the decrease in spectral radius versus the number m of removed links is conjectured. PMID:21867251

  6. The method of decreasing of chemical activity of coals

    SciTech Connect

    Korobetskii, I.A.; Nazimov, S.A.

    1998-07-01

    The investigations of the tendency of coal products to self-ignite show the decreasing of chemical activity of this product after its modification in cool oxygen plasma. A new method for the passivation of coal products was suggested.

  7. Method of decreasing of chemical activity of coals

    SciTech Connect

    Korobetskii, I.A.; Nazimov, S.A.

    1998-04-01

    The investigations of tendency of coal products to selfignition show the decreasing of chemical activity of this product after its modification in cool oxygen plasma. Was suggested a new method of coal products passivation.

  8. Cantharidin decreases in vitro digestion of alfalfa and smooth bromegrass.

    PubMed

    Lenssen, A W; Blodgett, S L; Higgins, R A; Nagaraja, T G; Posler, G L; Broce, A B

    1990-10-01

    Blister beetles (Coleoptera:Meloidae) containing the toxin cantharidin can be incorporated with alfalfa (Medicago sativa L) during forage conservation. Cantharidin inadvertently ingested with animal feed may cause illness or death. Little information is available on the effects of cantharidin on ruminant microbial digestion. The objective of our study was to determine cantharidin effects on digestibility of alfalfa and smooth bromegrass (Bromus inermis Leyss) by measuring in vitro digestible dry matter (IVDDM) and cell wall digestion (CWD). Alfalfa dry matter digestibility, measured after IVDDM at 48 and 96 h fermentation periods, decreased as cantharidin concentration increased. Increasing cantharidin concentration also significantly reduced IVDDM of smooth bromegrass at 24 and 96 h digestion time. The CWD of alfalfa and smooth bromegrass decreased as cantharidin concentration increased. These results indicate that ingestion of cantharidin by ruminants may decrease microbial digestion of fibrous feeds and therefore may decrease the efficiency of feed utilization by ruminants. PMID:2238434

  9. Forbush Decrease Prediction Based on Remote Solar Observations

    NASA Astrophysics Data System (ADS)

    Dumbovic, Mateja; Vrsnak, Bojan; Calogovic, Jasa

    2016-04-01

    We study the relation between remote observations of coronal mass ejections (CMEs), their associated solar flares and short-term depressions in the galactic cosmic-ray flux (so called Forbush decreases). Statistical relations between Forbush decrease magnitude and several CME/flare parameters are examined. In general we find that Forbush decrease magnitude is larger for faster CMEs with larger apparent width, which is associated with stronger flares that originate close to the center of the solar disk and are (possibly) involved in a CME-CME interaction. The statistical relations are quantified and employed to forecast expected Forbush decrease magnitude range based on the selected remote solar observations of the CME and associated solar flare. Several verification measures are used to evaluate the forecast method. We find that the forecast is most reliable in predicting whether or not a CME will produce a Forbush decrease with a magnitude >3 %. The main advantage of the method is that it provides an early prediction, 1-4 days in advance. Based on the presented research, an online forecast tool was developed (Forbush Decrease Forecast Tool, FDFT) available at Hvar Observatory web page: http://oh.geof.unizg.hr/FDFT/fdft.php. We acknowledge the support of Croatian Science Foundation under the project 6212 „Solar and Stellar Variability" and of European social fond under the project "PoKRet".

  10. Thermoregulatory set point decreases after hemorrhage in rats.

    PubMed

    Brown, Justin W; Whitehurst, Marvin E; Gordon, Christopher J; Carroll, Robert G

    2005-03-01

    Hemorrhage in rats causes a drop in body core temperature that is proportional to the hemorrhage volume. We tested the hypothesis that the hemorrhagic hypothermia is due to a downward shift in the thermoregulatory set point. If so, rats subjected to hemorrhage would prefer a cooler ambient temperature to enhance heat loss during the posthemorrhage period. Male Sprague-Dawley rats were fitted with carotid arterial catheters and biotelemetry temperature probes. Two days later, rats were placed in a temperature gradient chamber that allowed the rat to move between ambient temperatures of 15 degrees C to 40 degrees C. Rat location within the gradient was recorded as the selected ambient temperature. After 48 h, a 24 mL/kg hemorrhage was induced via the carotid cannula followed by a 24-h recovery period in the gradient. Body core and selected ambient temperatures significantly decreased after hemorrhage. Within 50 min, selected ambient temperature decreased by 11 degrees C, and returned to normal 100 min after hemorrhage. Within 80 min after hemorrhage, core temperature decreased by 2.3 degrees C, and returned to normal by 8 h after hemorrhage. Expanded analysis of the first hour after hemorrhage showed that reduction in selected ambient temperature preceded the drop in body core temperature. Importantly, the decrease in selected ambient temperature persisted even during the peak decrease in body core temperature. These results indicate that a decrease in thermoregulatory set point contributes to the drop in body core temperature after hemorrhage. PMID:15718921

  11. The decrease in mid-stratospheric tropical ozone since 1991

    NASA Astrophysics Data System (ADS)

    Nedoluha, G. E.; Siskind, D. E.; Lambert, A.; Boone, C.

    2015-04-01

    While global stratospheric O3 has begun to recover, there are localized regions where O3 has decreased since 1991. Specifically, we use measurements from the Halogen Occultation Experiment (HALOE) for the period 1991-2005 and the NASA Aura Microwave Limb Sounder (MLS) for the period 2004-2013 to demonstrate a significant decrease in O3 near ~ 10 hPa in the tropics. O3 in this region is very sensitive to variations in NOy, and the observed decrease can be understood as a spatially localized, yet long-term increase in NOy. In turn, using data from MLS and from the Atmospheric Chemistry Experiment (ACE), we show that the NOy variations are caused by decreases in N2O which are likely linked to long-term variations in dynamics. To illustrate how variations in dynamics can affect N2O and O3, we show that by decreasing the upwelling in the tropics, more of the N2O can photodissociate with a concomitant increase in NOy production (via N2O + O(1D) → 2NO) at 10 hPa. Ultimately, this can cause an O3 decrease of the observed magnitude.

  12. The decrease in mid-stratospheric tropical ozone since 1991

    NASA Astrophysics Data System (ADS)

    Nedoluha, G. E.; Siskind, D. E.; Lambert, A.; Boone, C.

    2015-01-01

    While global stratospheric O3 has begun to recover, there are localized regions where O3 has decreased since 1991. Specifically, we use measurements from the Halogen Occultation Experiment (HALOE) for the period 1991-2005 and the NASA/Aura Microwave Limb Sounder (MLS) for the period 2004-2013 to demonstrate a significant decrease in O3 near ~10 hPa in the tropics. O3 in this region is very sensitive to variations in NOy, and the observed decrease can be understood as a spatially localized, yet long term increase in NOy. In turn, using data from MLS and from the Atmospheric Chemistry Experiment (ACE), we show that the NOy variations are caused by decreases in N2O which are likely linked to long term variations in dynamics. To illustrate how variations in dynamics can affect N2O and O3, we show that by decreasing the upwelling in the tropics, more of the N2O can photodissociate with a concomitant increase in NOy production (via N2O+O(1D → 2 NO) at 10 hPa. Ultimately, this can cause an O3 decrease of the observed magnitude.

  13. Cosmic ray decreases and shock structure: A multispacecraft study

    NASA Technical Reports Server (NTRS)

    Cane, H. V.; Richardson, I. G.; Von Rosenvinge, T. T.; Wibberenz, G.

    1994-01-01

    We examine greater than 60-MeV/amu ion data from three spacecraft (IMP 8 and Helios 1 and 2) at the time of a number of short term (less than 20-day duration) cosmic ray decreases (greater than 1 GeV) detected by ground-based neutron monitors in the years 1976 to 1979. The multispacecraft data allow us to investigate the structure of the modulation region and in particular the relative importance, as a function of location, of the shock and shock driver (ejecta) in causing the reduction in particle densities. Although the shocks contributing to cosmic ray decrease often have particle enhancements associated with them in the greater than 60-meV/amu data, this is not the case for three of the events discussed in this paper where a shock-associated decrease is also evident. Whereas the shock can cause an increase or decrease at low (i.e., less than neutron monitor) energies, the reduction of particle densities in the driver, if it is intercepted, is usually evident at all energies. Thus the overall shape of a decrease at greater than 60 MeV/amu depends primarily on whether the ejecta is intercepted. We find that the particle density inside ejecta increases with increasing radical distance from the Sun. In many of the events in this study, entry and exit of ejecta are accompanied by abrupt changes in the decrease and recovery rates which indicate that the effect of the ejecta is local. In contrast, the effect of the shock lasts many days after the shock has passed by and is evident at large angular distances from the longitude of the solar source, i.e., the effect of the shock is nonlocal. Within 1 AU there seems to be no radial dependence of the shock effect. One cosmic ray decrease seen at Earth, which had an unusual profile, can be understood if the median plane of the ejecta was inclined to the ecliptic.

  14. Decreased plasma isoleucine concentrations after upper gastrointestinal haemorrhage in humans.

    PubMed Central

    Dejong, C H; Meijerink, W J; van Berlo, C L; Deutz, N E; Soeters, P B

    1996-01-01

    BACKGROUND: A decrease in arterial isoleucine values after intragastric blood administration in pigs has been observed. This contrasted with increased values of most other amino acids, ammonia, and urea. After an isonitrogenous control meal in these pigs all amino acids including isoleucine increased, and urea increased to a lesser extent, suggesting a relation between the arterial isoleucine decrease and uraemia after gastrointestinal haemorrhage. METHODS: To extend these findings to humans, plasma amino acids were determined after gastrointestinal haemorrhage in patients with peptic ulcers (n = 9) or oesophageal varices induced by liver cirrhosis (n = 4) and compared with preoperative patients (n = 106). RESULTS: After gastrointestinal haemorrhage, isoleucine decreased in all patients by more than 60% and normalised within 48 hours. Most other amino acids increased and also normalised within 48 hours. Uraemia occurred in both groups, hyperammonaemia was seen in patients with liver cirrhosis. CONCLUSIONS: These results confirm previous findings in animals and healthy volunteers that plasma isoleucine decreases after simulated upper gastrointestinal haemorrhage. This supports the hypothesis that the absence of isoleucine in blood protein causes decreased plasma isoleucine values after gastrointestinal haemorrhage, and may be a contributory factor to uraemia and hyperammonaemia in patients with normal and impaired liver function, respectively. Intravenous isoleucine administration after gastrointestinal haemorrhage could be beneficial and will be the subject of further research. PMID:8881800

  15. Cobalamin inactivation decreases purine and methionine synthesis in cultured lymphoblasts.

    PubMed

    Boss, G R

    1985-07-01

    The megaloblastic anemia of cobalamin deficiency appears secondary to decreased methionine synthetase activity. Decreased activity of this enzyme should cause 5-methyltetrahydrofolate to accumulate intracellularly, and consequently, decrease purine and DNA synthesis; this is the basis of the "methylfolate trap" hypothesis of cobalamin deficiency. However, only some of the clinical and biochemical manifestations of cobalamin deficiency can be explained by the methylfolate trap. We investigated cobalamin deficiency by treating cultured human lymphoblasts with N2O since N2O inhibits methionine synthetase activity by inactivating cobalamin. We found that 4 h of N2O exposure reduced rates of methionine synthesis by 89%. Rates of purine synthesis were not significantly reduced by N2O when folate and methionine were present at 100 microM in the medium; however, at the physiologic methionine concentration of 10 microM, N2O decreased rates of purine synthesis by 33 and 57% in the presence of 100 microM folate and in the absence of folate, respectively. The dependency of rates of purine synthesis on methionine availability would be expected in cells with restricted methionine synthetic capacity because methionine is the immediate precursor of S-adenosylmethionine, a potent inhibitor of 5-methyltetrahydrofolate synthesis; methionine serves as a source of formate for purine synthesis; and rates of purine synthesis are dependent on the intracellular availability of essential amino acids. We conclude that cobalamin inactivation decreases purine synthesis by both methylfolate trapping and reduction of intracellular methionine synthesis. PMID:2862163

  16. Secular period decreasing of detached chromospherically active binaries

    NASA Astrophysics Data System (ADS)

    Luo, Chang Qing; Zhang, Xiao Bin; Deng, Li Cai; Luo, Yang Ping; Luo, Zhi Quan; Yang, Shu Zheng

    2010-05-01

    The long-term orbital period changes of a large sample of detached chromospherically active binaries (CABs) were studied. Eleven such systems were found to be undergoing secular period decreases with the rates of -6.3×10-9 to -1.1×10-6 days per year. The period decreasing rates are found to vary depending on the orbital period. The longer the orbital period is, the more rapidly the period decreases. Following Stepien (Mon. Not. R. Astron. Soc. 274:1019, 1995), the period decreasing rate predicted by angular momentum loss (AML) caused by magnetic wind is computed for each system. A comparison between the observed and calculated period decreasing rates shows that the former values are obviously larger than the latter by 1-3 orders of magnitude. It suggests that the magnetic wind is not likely the determinant mechanism driving the AML in these systems. Finally, the orbital angular momentum (AM) and the rate of AML, dot{J} , are computed for each system. It shows that the AM have a similar change with the orbital period like d P/d t does, but logdot{J}/J presents no strict changing with the kinematical ages.

  17. Decrease rate of the renal diameter in chronic hemodialysis patients.

    PubMed

    Aoyagi, Teiichiro; Tachibana, Masaaki; Naganuma, Shinji

    2013-01-01

    We here present the results of ultrasonographic (US) evaluations on the alteration of renal diameter of chronic HD patients. Of 109 outpatient HD patients who had neither severe acquired cystic disease of the kidney nor hereditary polycystic kidney disease, we performed US two or three times to measure their maximum renal diameter (mean of both kidneys), and the yearly alteration rate was calculated. The average interval of the two measurements was 35.9 months, and the average HD duration from the HD induction to the first measurement was 29.5 months. The average decrease rate of renal diameter was 4.34 ± 0.4 (SE) mm/year. No statistical difference was seen on the decrease rate in relation to gender, age and original disease (among three groups, glomerulonephritis and IgA nephropathy, diabetes, and others including hypertension). However, the decrease rate was large when the first measurement was close to the induction of hemodialysis, suggesting that the alteration rate reduced according to the hemodialysis vintage (5.3 ± 0.8 mm/year, first measurement not more than 10 months after induction of HD and 1.5 ± 1.6 mm/year, first measurement more than 80 months after induction of HD). Renal diameter decreased approximately 4.3 mm each year, and the decrease rate slowed as the length of time on dialysis increased. PMID:24967236

  18. Social Branding to Decrease Smoking Among Young Adults in Bars

    PubMed Central

    Lee, Youn Ok; Hong, Juliette; Neilands, Torsten B.; Jordan, Jeffrey W.; Glantz, Stanton A.

    2014-01-01

    Objectives. We evaluated a Social Branding antitobacco intervention for “hipster” young adults that was implemented between 2008 and 2011 in San Diego, California. Methods. We conducted repeated cross-sectional surveys of random samples of young adults going to bars at baseline and over a 3-year follow-up. We used multinomial logistic regression to evaluate changes in daily smoking, nondaily smoking, and binge drinking, controlling for demographic characteristics, alcohol use, advertising receptivity, trend sensitivity, and tobacco-related attitudes. Results. During the intervention, current (past 30 day) smoking decreased from 57% (baseline) to 48% (at follow-up 3; P = .002), and daily smoking decreased from 22% to 15% (P < .001). There were significant interactions between hipster affiliation and alcohol use on smoking. Among hipster binge drinkers, the odds of daily smoking (odds ratio [OR] = 0.44; 95% confidence interval [CI] = 0.30, 0.63) and nondaily smoking (OR = 0.57; 95% CI = 0.42, 0.77) decreased significantly at follow-up 3. Binge drinking also decreased significantly at follow-up 3 (OR = 0.64; 95% CI = 0.53, 0.78). Conclusions. Social Branding campaigns are a promising strategy to decrease smoking in young adult bar patrons. PMID:24524502

  19. Recent decrease in typhoon destructive potential and global warming implications

    PubMed Central

    Lin, I-I; Chan, Johnny C.L.

    2015-01-01

    Typhoons (tropical cyclones) severely impact the half-billion population of the Asian Pacific. Intriguingly, during the recent decade, typhoon destructive potential (Power Dissipation Index, PDI) has decreased considerably (by ∼35%). This decrease, paradoxically, has occurred despite the increase in typhoon intensity and ocean warming. Using the method proposed by Emanuel (in 2007), we show that the stronger negative contributions from typhoon frequency and duration, decrease to cancel the positive contribution from the increasing intensity, controlling the PDI. Examining the typhoons' environmental conditions, we find that although the ocean condition became more favourable (warming) in the recent decade, the atmospheric condition ‘worsened' at the same time. The ‘worsened' atmospheric condition appears to effectively overpower the ‘better' ocean conditions to suppress PDI. This stronger negative contribution from reduced typhoon frequency over the increased intensity is also present under the global warming scenario, based on analysis of the simulated typhoon data from high-resolution modelling. PMID:25990561

  20. Secular period decreasing of 17 detached chromospherically active binaries

    NASA Astrophysics Data System (ADS)

    Luo, C. Q.; Luo, Y. P.; Zhang, X. B.; Deng, L. C.; Luo, Z. Q.; Yang, S. Z.

    2008-10-01

    The long-term orbital period changes of detached chromospheric active binaries were surveyed. 17 of such systems are found to be undergoing secular period decreasing with the rates (dP/dt) of -3.05 × 10-9 to -3.77 × 10-5 days per year. The longer the orbital period, the more rapidly the period decreases. Following Stepien (1995), the period decreasing rate due to the angular momentum loss (AML) caused by magnetic wind is computed for each system. A comparison shows that the observed dP/dt's are obviously higher than that of the theoretical predictions by 1-3 orders of magnitude. It suggests that the magnetic wind is not likely the determinant mechanism driving the AML in close binaries.

  1. Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

    SciTech Connect

    Mackey, W.C.; Connolly, R.J.; Callow, A.D.; Keough, E.M.; Ramberg-Laskaris, K.; McCullough, J.L.; O'Donnell, T.F. Jr.; Melaragno, A.; Valeri, C.R.; Weiblen, B.

    1984-07-01

    The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotid interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency.

  2. MDMA DECREASES THE EFFECTS OF SIMULATED SOCIAL REJECTION

    PubMed Central

    Frye, Charles G.; Wardle, Margaret C.; Norman, Greg J.; de Wit, Harriet

    2014-01-01

    3-4-methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N = 36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called “Cyberball” during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments. PMID

  3. [The morbidity of students and the ways of its decreasing].

    PubMed

    Medvedkova, N I; Medvedkov, V D; Ashirova, S V

    2012-01-01

    The lower level of health of youth and unfavorable ecological environment inputs drastically into children morbidity. Hence, the important value has rationalization of life style and decrease of parents 'morbidity. The article presents the main components of the total structure of students' morbidity and outlines the ways of its decreasing. The changes in the education process and health of students, special medical group and students, released of physical exercises are demonstrated. The dynamics of morbidity of students over 20 years in the ecologically relatively clean environment and in industrial megalopolis is analyzed. PMID:23373343

  4. Decreased frontal lobe function in people with Internet addiction disorder

    PubMed Central

    Liu, Jun; Esmail, Fatema; Li, Lingjiang; Kou, Zhifeng; Li, Weihui; Gao, Xueping; Wang, Zhiyuan; Tan, Changlian; Zhang, Yan; Zhou, Shunke

    2013-01-01

    In our previous studies, we showed that frontal lobe and brainstem functions were abnormal in on-line game addicts. In this study, 14 students with Internet addiction disorder and 14 matched healthy controls underwent proton-magnetic resonance spectroscopy to measure cerebral function. Results demonstrated that the ratio of N-acetylaspartate to creatine decreased, but the ratio of cho-line-containing compounds to creatine increased in the bilateral frontal lobe white matter in people with Internet addiction disorder. However, these ratios were mostly unaltered in the brainstem, suggesting that frontal lobe function decreases in people with Internet addiction disorder. PMID:25206643

  5. Decrease in blood histamine in drug-treated parkinsonian patients.

    PubMed

    Coelho, M H; Silva, I J; Azevedo, M S; Manso, C F

    1991-04-01

    Blood histamine and serum histaminase activity were determined in a group of patients with Parkinson disease (PD) and in a group of healthy controls. Untreated PD patients present significantly higher blood histamine than normal controls. Therapy with L-dopa + cardidopa results in a significant decrease in blood histamine. This decrease becomes more accentuated when anticholinergics are added to this therapy. No significant changes were detected in plasma histaminase. The authors suggest, as a hypothesis, that the CNS contributes to blood histamine concentration and that its rise is the result of increased neuronal destruction. PMID:1910360

  6. Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

    NASA Technical Reports Server (NTRS)

    Tempel, G. E.; Musacchia, X. J.; Jones, S. B.

    1977-01-01

    Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

  7. Decreased frontal lobe function in people with Internet addiction disorder.

    PubMed

    Liu, Jun; Esmail, Fatema; Li, Lingjiang; Kou, Zhifeng; Li, Weihui; Gao, Xueping; Wang, Zhiyuan; Tan, Changlian; Zhang, Yan; Zhou, Shunke

    2013-12-01

    In our previous studies, we showed that frontal lobe and brainstem functions were abnormal in on-line game addicts. In this study, 14 students with Internet addiction disorder and 14 matched healthy controls underwent proton-magnetic resonance spectroscopy to measure cerebral function. Results demonstrated that the ratio of N-acetylaspartate to creatine decreased, but the ratio of cho-line-containing compounds to creatine increased in the bilateral frontal lobe white matter in people with Internet addiction disorder. However, these ratios were mostly unaltered in the brainstem, suggesting that frontal lobe function decreases in people with Internet addiction disorder. PMID:25206643

  8. [Is it possible to decrease cholesterol levels with dietary supplements?].

    PubMed

    Rodondi, Pierre-Yves; Degoumois, Florence; Marques-Vidal, Pedro; Rodondi, Nicolas

    2016-03-01

    Patients often use dietary supplements for cardiovascular prevention. An US study showed that 75% of patients with cardiovascular disease used dietary supplements. Red yeast rice, phytosterols and fibers can significantly decrease LDL. The level of monacolin in red yeast rice can vary between products and toxins can sometimes be found. Prospective studies showed that fibers could decrease cardiovascular risk. Others substances, like guggul, soy and artichoke leaf extracts, did not show a clear benefit for cardiovascular prevention. Measurements of cholesterol levels can help the physician to discuss with his patient about the effects of some dietary supplements. PMID:27089602

  9. Decrease of summer tropospheric ozone concentrations in Antarctica

    NASA Technical Reports Server (NTRS)

    Schnell, R. C.; Stone, R. S.; Liu, S. C.; Oltmans, S. J.; Hofmann, D. J.

    1991-01-01

    It is shown here that surface ozone concentrations at the South Pole in the austral summer decreased by 17 percent over the period 1976-90. Over the same period, solar irradiance at the South Pole in January and February decreased by 7 percent as a result of a 25 percent increase in cloudiness. It is suggested that the trend in the summer ozone concentrations is caused by enhanced photochemical destruction of ozone in the lower troposphere caused by the increased penetration of UV radiation associated with stratospheric ozone depletion, coupled with enhanced transport of ozone-poor marine air from lower latitudes to the South Pole.

  10. Decreased NAA in Gray Matter is Correlated with Decreased Availability of Acetate in White Matter in Postmortem Multiple Sclerosis Cortex

    PubMed Central

    Li, S.; Clements, R.; Sulak, M.; Gregory, R.; Freeman, E.; McDonough, J.

    2013-01-01

    Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids. PMID:24078261

  11. 34 CFR 300.810 - Decrease in funds.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Decrease in funds. 300.810 Section 300.810 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN...

  12. Decreased interpretation of nonverbal cues in rape victims.

    PubMed

    Giannini, A J; Price, W A; Kniepple, J L

    The ability to receive nonverbal facial cues was tested in twelve female victims of multiple nonserial rapes and matched controls. Subjects attempted to interpret nonverbal messages transmitted by male and female senders who were covertly taped while involved in a gambling task. Rape victims had significantly decreased ability to interpret the nonverbal facial cues of both male and female senders. PMID:3557809

  13. Intravenous theophylline rapidly decreases post-lumbar puncture headaches.

    PubMed

    Ergün, Ufuk; Ünal-Artık, H Aybüke; İnan, Leven E; Yoldaş, Tahir

    2016-09-01

    When managing therapy for the post-lumbar puncture headaches (PLPHs), an efficacious, fast-acting, practical and safe method is preferred. Invasive methods have known complications and oral medications might be problematic when nausea and vomiting occurs with severe headaches. The aim of this study was to highlight the brief initial time for a remarkable decrease of PLPH pain levels after the administration of IV theophylline infusion. We observed that IV theophylline infusion has a rapid and marked effect on decreasing pain in PLPHs. At 30 min of theophylline infusion, mean VAS levels were decreased by 47.1 % and at 60 min of infusion, the decrease of pain was 61.9 %. We conclude that IV theophylline infusion is a rapidly effective, noninvasive, practical and low-cost way to treat PLPHs. To the best of our knowledge, this is the first study to highlight both the efficacy and the speed of the effect of pain relief in PLPHs. PMID:26563407

  14. Downsizing a database platform for increased performance and decreased costs

    SciTech Connect

    Miller, M.M.; Tolendino, L.F.

    1993-06-01

    Technological advances in the world of microcomputers have brought forth affordable systems and powerful software than can compete with the more traditional world of minicomputers. This paper describes an effort at Sandia National Laboratories to decrease operational and maintenance costs and increase performance by moving a database system from a minicomputer to a microcomputer.

  15. 78 FR 45841 - Olives Grown in California; Decreased Assessment Rate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-30

    ..., 2013, (78 FR 24979, Doc. No. AMS-FV- 12-0076, FV13-932-1 IR), Sec. 932.230 was amended by decreasing..., as published in the Federal Register (78 FR 24979, April 29, 2013) will tend to effectuate the... Part 932, which was published at 78 FR 24979 on April 29, 2013, is adopted as a final rule,...

  16. Does Early Reading Failure Decrease Children's Reading Motivation?

    ERIC Educational Resources Information Center

    Morgan, Paul L.; Fuchs, Douglas; Compton, Donald L.; Cordray, David S.; Fuchs, Lynn S.

    2008-01-01

    The authors used a pretest-posttest control group design with random assignment to evaluate whether early reading failure decreases children's motivation to practice reading. First, they investigated whether 60 first-grade children would report substantially different levels of interest in reading as a function of their relative success or failure…

  17. 78 FR 62959 - Kiwifruit Grown in California; Decreased Assessment Rate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... Marketing Service, USDA. ACTION: Interim rule with request for comments. SUMMARY: This rule decreases the... Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612), the Agricultural Marketing Service (AMS) has considered... Marketing Service. BILLING CODE 3410-02-P...

  18. 75 FR 10409 - Tomatoes Grown in Florida; Decreased Assessment Rate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-08

    ... November 4, 2009, and effective on November 5, 2009 (74 FR 57057; Doc. No. AMS-FV-09-0063, FV09-966-2 IFR... small entities. This rule continues in effect the action that decreased the assessment rate established... (74 FR 57057, November 4, 2009) will tend to effectuate the declared policy of the Act. List...

  19. The Frequency of Decreased Visual Acuity in Orbital Fractures.

    PubMed

    Kim, Yeon Soo; Kim, Joo Ho; Hwang, Kun

    2015-07-01

    The aim of this systematic review is to summarize and evaluate the effect of orbital fractures (blowout fractures and nonblowout fractures) on visual acuity. In PubMed search and Scopus search, the terms "orbital fracture OR maxillofacial injury OR facial trauma OR craniofacial fracture," and "visual acuity OR functional outcome OR visual outcome OR improving document of visual acuity OR blindness OR optic nerve neuropathy" were used, which resulted in 1634 and 1152 papers, respectively. Of the 2226 titles excluding 560 duplicated titles, 227 abstracts were reviewed. Of the 227 abstracts reviewed, the authors found 56 potentially relevant full-text articles, of which 5 studies met our inclusion criteria. The odds ratio and 95% confidence intervals from each study were abstracted. The statistical analysis was performed with review manager (The Nordic Cochrane Centre). A summary of 5 studies affirmed that 43 patients among 532 orbital fractures (8.1%) had decreased visual acuity. Twelve patients among 159 blowout fractures (7.5%) had decreased visual acuity. Thirty-one patients among 373 orbital fractures other than pure blowout fractures (8.3%) had decreased visual acuity. In orbital fractures other than pure blowout fractures, the frequency of decreased visual acuity was higher than pure blowout fractures (n = 532, odds ratio, 2.23, 95% confidence interval = 1.06-4.70). Surgeons should acknowledge this with patients before surgery. PMID:26114513

  20. Ensiling carinata meal with forages to decrease glucosinolate concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Carinata meal (CM) has high quality protein, but it also has high glucosinolate concentrations which limits its use as a feedstuff. Our objective was to determine if ensiling CM with forages would decrease glucosinolates without compromising fermentation. Two trials were conducted, one on ensiling C...

  1. Dietary management to decrease methane emissions from beef feedlots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methane is a powerful greenhouse gas that can be produced within the digestive tract of domestic (cattle, sheep), and undomesticated (bison, deer, elk) ruminants. This publicatoin gives a brief review of research on dietary procedures that have been tested to decrease enteric methane emissions fro...

  2. Shear-induced Volume Decrease in MDCK Cells

    PubMed Central

    Heo, Jinseok; Sachs, Frederick; Wang, Jianbin; Hua, Susan Z.

    2013-01-01

    Using a microfluidic cell volume sensor we measured the change in the cell volume of Madin-Darby Canine Kidney (MDCK) cells induced by shear stress. An increase in shear stress from 0.2 to 2.0 dyn/cm2 resulted in a volume decrease to a steady state volume ~ 20 – 30 % smaller than the initial resting cell volume. Independent experiments based on fluorescence quenching confirmed the volume reduction. This shear-induced cell shrinkage was irreversible on the time scale of the experiment (~ 30 min). Treatment of 0.1 μM Hg2+ significantly inhibited the volume decrease, suggesting that the shear-induced cell shrinkage is associated with water efflux through aquaporins. The volume decrease cannot be inhibited by 75 mM TEA, 100 μM DIDS, or 100 μM Gd3+ suggesting that volume reduction is not directly mediated by K+ and Cl− channels that typically function during regulatory volume decrease (RVD), nor is it through cationic stretch-activated ion channels (SACs). The process also appears to be Ca2+ independent because it was insensitive to intracellular Ca2+ level. Since cell volume is determined by the intracellular water content, we postulate that the shear induced reductions in cell volume may arise from increased intracellular hydrostatic pressure as the cell is deformed under flow, which promotes the efflux of water. The increase in internal pressure in a deformable object under the flow is supported by the finite element mechanical model. PMID:22759987

  3. Decreased Gene Expressions of Insulin Signal Molecules in Canine Hyperadrenocorticism

    PubMed Central

    NOZAWA, Satoshi; ODA, Hitomi; AKIYAMA, Ran; UEDA, Kaori; SAEKI, Kaori; SHONO, Saori; MARUYAMA, Natsuki; MURATA, Atsuki; TAZAKI, Hiroyuki; MORI, Akihiro; MOMOTA, Yutaka; AZAKAMI, Daigo; SAKO, Toshinori; ISHIOKA, Katsumi

    2014-01-01

    ABSTRACT Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, in which excess glucocorticoid causes insulin resistance. Disturbance of insulin action may be caused by multiple factors, including transcriptional modulation of insulin signal molecules which lie downstream of insulin binding to insulin receptors. In this study, gene expressions of insulin signal molecules were examined using neutrophils of the HAC dogs (the untreated dogs and the dogs which had been treated with trilostane). Insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B/Akt kinase (Akt)-2 and protein kinase C (PKC)-lambda were analyzed in the HAC dogs and compared with those from normal dogs. The IRS-1 gene expressions decreased by 37% and 35% of the control dogs in the untreated and treated groups, respectively. The IRS-2 gene expressions decreased by 61% and 72%, the PI3-K gene expressions decreased by 47% and 55%, and the Akt-2 gene expressions decreased by 45% and 56% of the control dogs, similarly. Collectively, gene expressions of insulin signal molecules are suppressed in the HAC dogs, which may partially contribute to the induction of insulin resistance. PMID:24829079

  4. Decreased reproductive rates in sheep fed a high selenium diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High Se-containing forages grow on seleniferous soils in many parts of the United States and throughout the world. Selenium is an essential trace element that is required for many physiological processes but can also be either acutely or chronically toxic to livestock. Anecdotal reports of decrease...

  5. Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis

    PubMed Central

    Fan, Xiaoqiang; Zhang, Xiu; Shen, Jie; Zhao, Haibin; Yu, Xuetao; Chen, Yong’an; Zhuang, Zhuonan; Deng, Xiaolong; Feng, Hua; Wang, Yunfei; Peng, Long

    2016-01-01

    Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 expression was found to be suppressed both at mRNA and protein levels in cell line models as well as in clinical samples; decreased TUSC3 expression was associated with higher pathological TNM staging and poorer outcome. In three pairs of cell lines with different NF-κB activity, TUSC3 expression was found to be reversely correlated with NF-κB activity. TUSC3-silenced pancreatic cancer cell line exhibited enhanced potential of proliferation, migration and invasion. In an orthotopic implanted mice model, TUSC3 silenced cells exhibited more aggressive phenotype with more liver metastasis. In conclusion, the current study shows that decreased immunological TUSC3 staining is a factor prognostic of poor survival in pancreatic cancer patients and decreased TUSC3 promotes pancreatic cancer cell proliferation, invasion and metastasis. The reverse correlation between NF-κB activity and TUSC3 expression may suggest a novel regulation pattern for this molecule. PMID:26871953

  6. Cortisol decreases and serotonin and dopamine increase following massage therapy.

    PubMed

    Field, Tiffany; Hernandez-Reif, Maria; Diego, Miguel; Schanberg, Saul; Kuhn, Cynthia

    2005-10-01

    In this article the positive effects of massage therapy on biochemistry are reviewed including decreased levels of cortisol and increased levels of serotonin and dopamine. The research reviewed includes studies on depression (including sex abuse and eating disorder studies), pain syndrome studies, research on auto-immune conditions (including asthma and chronic fatigue), immune studies (including HIV and breast cancer), and studies on the reduction of stress on the job, the stress of aging, and pregnancy stress. In studies in which cortisol was assayed either in saliva or in urine, significant decreases were noted in cortisol levels (averaging decreases 31%). In studies in which the activating neurotransmitters (serotonin and dopamine) were assayed in urine, an average increase of 28% was noted for serotonin and an average increase of 31% was noted for dopamine. These studies combined suggest the stress-alleviating effects (decreased cortisol) and the activating effects (increased serotonin and dopamine) of massage therapy on a variety of medical conditions and stressful experiences. PMID:16162447

  7. Decrease of the Atmospheric Co-Rotation with Height

    ERIC Educational Resources Information Center

    Membrado, M.; Pacheco, A. F.

    2010-01-01

    Considering our atmosphere as a steady viscous gaseous envelope that co-rotates with the Earth, we obtain a solution for the form in which this induced rotational effect decreases as a function of the distances to the centre of the Earth and to the rotation axis. (Contains 1 figure.)

  8. Selenium bond decreases ON resistance of light-activated switch

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Vitrified amorphous selenium bond decreases the ON resistance of a gallium arsenide-silicon light-activated, low-level switch. The switch is used under a pulse condition to prolong switch life and minimize errors due to heating, devitrification, and overdrawing.

  9. Decrease of atmospheric neutron counts observed during thunderstorms.

    PubMed

    Alekseenko, V; Arneodo, F; Bruno, G; Di Giovanni, A; Fulgione, W; Gromushkin, D; Shchegolev, O; Stenkin, Yu; Stepanov, V; Sulakov, V; Yashin, I

    2015-03-27

    We report here, in brief, some results of the observation and analysis of sporadic variations of atmospheric thermal neutron flux during thunderstorms. The results obtained with unshielded scintillation neutron detectors show a prominent flux decrease correlated with meteorological precipitations after a long dry period. No observations of neutron production during thunderstorms were reported during the three-year period of data recording. PMID:25860750

  10. ASCORBID ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

    EPA Science Inventory

    ABSTRACT
    Evidence suggests that the antioxidant ascorbic acid (AA), plays an essential role in defending against oxidant attack in the airways. Decreased levels of AA have been reported in asthmatics but not at the site directly proximal to asthma pathology, i.e. the bronchial...

  11. ASCORBIC ACID IS DECREASED IN INDUCED SPUTUM OF MILD ASTHMATICS

    EPA Science Inventory

    Asthma is primarily an airways inflammatory disease, and the bronchial airways have been shown to be particularly susceptible to oxidant-induced tissue damage. The antioxidant ascorbic acid (AA) plays an essential role in defending against oxidant attack in the airways. Decreased...

  12. Decreasing Discipline Referrals for African American Males in Middle School

    ERIC Educational Resources Information Center

    Moore, Earl, Jr.; Ratchford, Vicky F.

    2007-01-01

    Brogden Middle School (BMS) is located approximately 15 miles south of Goldsboro, North Carolina, a city of approximately 40,000 citizens and the home of a military base. To decrease the number of discipline referrals of African American males, 10 students who had the most frequent discipline referrals during their seventh-grade year were…

  13. Decreased femoral arterial flow during simulated microgravity in the rat

    NASA Technical Reports Server (NTRS)

    Roer, Robert D.; Dillaman, Richard M.

    1994-01-01

    To determine whether the blood supply to the hindlimbs of rats is altered by the tail-suspension model of weightlessness, rats were chronically instrumented for the measurement of femoral artery flow. Ultrasonic transit-time flow probes were implanted into 8-wk-old Wistar-Furth rats under ketamine-xylazine anesthesia, and, after 24 h of recovery, flow was measured in the normal ambulatory posture. Next, rats were suspended and flow was measured immediately and then daily over the next 4-7 days. Rats were subsequently returned to normal posture, and flow was monitored daily for 1-3 days. Mean arterial flow decreased immediately on the rats being suspensed and continued to decrease until a new steady state of approximately 60% of control values was attained at 5 days. On the rats returning to normal posture, flow increased to levels observed before suspension. Quantile-quantile plots of blood flow data revealed a decrease in flow during both systole and diastole. The observed decrease in hindlimb blood flow during suspension suggests a possible role in the etiology of muscular atrophy and bone loss in microgravity.

  14. Does Child Labor Decrease when Parental Incomes Rise?

    ERIC Educational Resources Information Center

    Rogers, Carol Ann; Swinnerton, Kenneth A.

    2004-01-01

    When parents and children care about each other's utility, increases in parental income need not always lead to decreases in child labor. Adults raised in poor families make altruistic transfers to their elderly parents, which the parents take as repayment for income lost when their children were young and spent some time in school instead of…

  15. Forbush Decrease Prediction Based on Remote Solar Observations

    NASA Astrophysics Data System (ADS)

    Dumbović, M.; Vršnak, B.; Čalogović, J.

    2016-01-01

    We employ remote observations of coronal mass ejections (CMEs) and the associated solar flares to forecast the CME-related Forbush decreases, i.e. short-term depressions in the galactic cosmic-ray flux. The relation between the Forbush effect at Earth and remote observations of CMEs and associated solar flares is studied via a statistical analysis. Relations between Forbush decrease magnitude and several CME/flare parameters were found: the initial CME speed, apparent width, source position, associated solar-flare class, and the effect of successive-CME occurrence. Based on the statistical analysis, remote solar observations are employed to forecast a Forbush-decrease. For this purpose, an empirical probabilistic model is constructed that uses selected remote solar observations of the CME and associated solar flare as input and gives the expected Forbush-decrease magnitude range as output. The forecast method is evaluated using several verification measures, indicating that as the forecast tends to be more specific, it is less reliable, which is its main drawback. However, the advantages of the method are that it provides an early prediction and that the input does not necessarily depend on using a spacecraft.

  16. Use of an Explicit Rule Decreases Procrastination in University Students

    ERIC Educational Resources Information Center

    Johnson, Paul E.; Perrin, Christopher J.; Salo, Allen; Deschaine, Elyssa; Johnson, Beth

    2016-01-01

    The procrastination behavior of students from a small rural university was decreased by presenting them with a rule indicating that a sooner final due date for a writing assignment would be contingent on procrastination during earlier phases of the paper. A counterbalanced AB BA design was used to measure the effects of the rule-based treatment…

  17. 78 FR 24979 - Olives Grown in California; Decreased Assessment Rate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-29

    ... Service 7 CFR Part 932 Olives Grown in California; Decreased Assessment Rate AGENCY: Agricultural... assessment rate established for the California Olive Committee (Committee) for the 2013 and subsequent fiscal... began January 1 and ends December 31. The assessment rate will remain in effect indefinitely...

  18. 76 FR 11937 - Olives Grown in California; Decreased Assessment Rate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-04

    ... Service 7 CFR Part 932 Olives Grown in California; Decreased Assessment Rate AGENCY: Agricultural... assessment rate established for the California Olive Committee (Committee) for 2011 and subsequent fiscal... January 1 and ends December 31. The assessment rate will remain in effect indefinitely unless...

  19. Baroreflex Sensitivity Decreases During 90-Day Bed Rest

    NASA Technical Reports Server (NTRS)

    Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

    2008-01-01

    Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

  20. Decreased Expression of DREAM Promotes the Degeneration of Retinal Neurons

    PubMed Central

    Chintala, Shravan; Cheng, Mei; Zhang, Xiao

    2015-01-01

    The intrinsic mechanisms that promote the degeneration of retinal ganglion cells (RGCs) following the activation of N-Methyl-D-aspartic acid-type glutamate receptors (NMDARs) are unclear. In this study, we have investigated the role of downstream regulatory element antagonist modulator (DREAM) in NMDA-mediated degeneration of the retina. NMDA, phosphate-buffered saline (PBS), and MK801 were injected into the vitreous humor of C57BL/6 mice. At 12, 24, and 48 hours after injection, expression of DREAM in the retina was determined by immunohistochemistry, western blot analysis, and electrophoretic mobility-shift assay (EMSA). Apoptotic death of cells in the retina was determined by terminal deoxynucleotidyl transferace dUTP nick end labeling (TUNEL) assays. Degeneration of RGCs in cross sections and in whole mount retinas was determined by using antibodies against Tuj1 and Brn3a respectively. Degeneration of amacrine cells and bipolar cells was determined by using antibodies against calretinin and protein kinase C (PKC)-alpha respectively. DREAM was expressed constitutively in RGCs, amacrine cells, bipolar cells, as well as in the inner plexiform layer (IPL). NMDA promoted a progressive decrease in DREAM levels in all three cell types over time, and at 48 h after NMDA-treatment very low DREAM levels were evident in the IPL only. DREAM expression in retinal nuclear proteins was decreased progressively after NMDA-treatment, and correlated with its decreased binding to the c-fos-DRE oligonucleotides. A decrease in DREAM expression correlated significantly with apoptotic death of RGCs, amacrine cells and bipolar cells. Treatment of eyes with NMDA antagonist MK801, restored DREAM expression to almost normal levels in the retina, and significantly decreased NMDA-mediated apoptotic death of RGCs, amacrine cells, and bipolar cells. Results presented in this study show for the first time that down-regulation of DREAM promotes the degeneration of RGCs, amacrine cells, and

  1. Relaxin Decreases the Severity of Established Hepatic Fibrosis in Mice

    PubMed Central

    Bennett, Robert G.; Heimann, Dean G.; Singh, Sudhir; Simpson, Ronda L.; Tuma, Dean J.

    2013-01-01

    Background Hepatic fibrosis is characterized by excess collagen deposition, decreased extracellular matrix degradation, and activation of the hepatic stellate cells. The hormone relaxin has shown promise in the treatment of fibrosis in a number of tissues, but the effect of relaxin on established hepatic fibrosis is unknown. Aims The aim of this study was to determine the effect of relaxin on an in vivo model after establishing hepatic fibrosis. Methods Male mice were made fibrotic by carbon tetrachloride treatment for 4 weeks, followed by treatment with two doses of relaxin (25 or 75 ug/kg/day) or vehicle for 4 weeks, with continued administration of carbon tetrachloride. Results Relaxin significantly decreased total hepatic collagen and smooth muscle actin content at both doses, and suppressed collagen I expression at the higher dose. Relaxin increased the expression of the matrix metalloproteinases MMP13 and MMP3, decreased expression of MMP2 and tissue inhibitor of metalloproteinases 2 (TIMP2), and increased the overall level of collagen degrading activity. Relaxin decreased TGFβ-induced Smad2 nuclear localization in mouse hepatic stellate cells. Conclusions The results suggest that relaxin reduced collagen deposition and HSC activation in established hepatic fibrosis despite the presence of continued hepatic insult. This reduced fibrosis was associated with increased expression of the fibrillar collagen-degrading enzyme MMP13, decreased expression of TIMP2, and enhanced collagen degrading activity, and impaired TGFβ signaling, consistent with relaxin's effects on activated fibroblastic cells. The results suggest that relaxin may be an effective treatment for the treatment of established hepatic fibrosis. PMID:23870027

  2. Age and Helicobacter pylori decrease gastric mucosal surface hydrophobicity independently

    PubMed Central

    Hackelsberger, A; Platzer, U; Nilius, M; Schultze, V; Gunther, T; Dominguez-Munoz, J; Malfertheiner, P

    1998-01-01

    Background—Gastric mucosal surface hydrophobicity (GMSH) is an essential component of the mucosal defence system that is decreased by Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs). Gastric ulcers occur predominantly in elderly subjects, and may thus reflect diminished mucosal resistance. 
Aims—To investigate whether aging decreases GMSH. 
Patients—One hundred and twenty patients without peptic ulcer disease were divided into three age groups: I (41 years or below); II (41-64 years); and III (65 years or above). 
Methods—Biopsy specimens were taken from the antrum, corpus, and cardia for histology (Sydney system), urease testing for H pylori, and for contact angle measurement of GMSH with a goniometer. The presence of specific H pylori antibodies was checked by immunoblotting. 
Results—Fifty two patients (43%) were infected, and 68 were uninfected with H pylori. GMSH at all biopsy sites was lower in H pylori infected subjects (p=0.0001), but also decreased with age independently of infection status (p=0.0001). The most notable decrease in GMSH occurred between age groups I and II in those with, and between age groups II and III in those without, H pylori infection. GMSH was greater in antral than in corpus mucosa in both infected (p=0.0001) and uninfected patients (p=0.0003). 
Conclusions—A physiological decrease in GMSH with aging may contribute to the risk of ulcer development in the elderly, and may act synergistically with H pylori and/or NSAIDs on gastric mucosal defence. 

 Keywords: gastric mucosal defence; surface hydrophobicity; aging; Helicobacter pylori PMID:9824570

  3. Acutely Decreased Thermoregulatory Energy Expenditure or Decreased Activity Energy Expenditure Both Acutely Reduce Food Intake in Mice

    PubMed Central

    Kaiyala, Karl J.; Morton, Gregory J.; Thaler, Joshua P.; Meek, Thomas H.; Tylee, Tracy; Ogimoto, Kayoko; Wisse, Brent E.

    2012-01-01

    Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1) increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2) exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21°C to 28°C) rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40±1%) and dark cycle energy expenditure (15±3%) at normal ambient temperature (21°C). Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65±7%), thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14±2% at 21°C; 21±4% at 28°C), while food intake was reduced during the dark cycle (0.9±0.1 g) in mice housed at 28°C, but during the light cycle (0.3±0.1 g) in mice housed at 21°C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R2 = 0.51, p<0.01). We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure. PMID:22936977

  4. Mars Secular Obliquity Decrease and the Layered Terrain

    NASA Technical Reports Server (NTRS)

    Rubincam, D. P.

    2000-01-01

    Mars may have substantially decreased its average axial tilt over geologic time due to the waxing and waning of water ice caps through the phenomenon of climate friction (also called obliquity-oblateness feedback). Depending upon Mars' climate and internal structure, water caps of the order of 10(exp 17) - 10(exp 18) kg cycling with the obliquity oscillations could have either increased or decreased the average obliquity by possibly tens of degrees over the age of the solar system. Gravity and topography observations by the Mars Global Surveyor indicate that the south polar cap is mostly uncompensated, so that Mars may be largely rigid on the obliquity timescale. Further, Mars may be a water-rich planet, so that there is a large phase angle between insolation forcing and the size of the obliquity-driven water caps. A stiff, water-rich planet implies an obliquity decrease over the eons. Such a decrease might account for the apparent youthfulness of the polar layered terrain. The idea is that fewer volatiles were available to be cycled into and out of the terrain at high mean obliquity, because of the eveness of insolation between equator and pole, and because of small insolation variations as the obliquity oscillated; so that the movement of volatiles and dust produced thin layers or perhaps no layers at all. As the average obliquity decreased, the insolation contrast between high and low latitudes increased, plus the insolation variations over the obliquity cycle grew somewhat bigger, so that more volatiles and dust might have shuttled into and out of the polar regions, forming the observed thick layers late in Mars' history. It may also be that the average tilt has decreased to the point where the climate friction mechanism is starving itself: more and more water has gotten locked up in the polar regions, making less available for cycling with the oscillations. And the layer-forming mechanism may be starving too: not only less water, but also at low average

  5. Lidocaine decreases the xylazine-evoked contractility in pregnant cows.

    PubMed

    Piccinno, M; Rizzo, A; Mutinati, M; D'Onghia, G; Sciorsci, R L

    2016-08-01

    The objective of this in vitro study was to evaluate and compare the effects of xylazine on basal uterine contractility of bovine pregnant uterine strips and that of lidocaine on xylazine-sensitized bovine pregnant uterine strips, at different stages of pregnancy. Basal contractility was evaluated in an isolated organ bath and the functionality of the strips throughout the experiment was evaluated using a dose of carbachol (10(-5)M). Uterine motility, expressed with amplitude, frequency of contractions as well as the area under the curve, was recorded in different stages of pregnancy and data were collected at 15-min intervals (5-min before and 5-min after xylazine administration and 5-min after lidocaine addition on the plateau contraction induced by xylazine). Uterine motility increased in all the stages of pregnancy after xylazine addition and gradually decreased after treatment with lidocaine. These data suggest that lidocaine might decrease the tonic effect induced by xylazine on bovine pregnant uteri. PMID:27474006

  6. Knots cascade detected by a monotonically decreasing sequence of values

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Ricca, Renzo L.

    2016-04-01

    Due to reconnection or recombination of neighboring strands superfluid vortex knots and DNA plasmid torus knots and links are found to undergo an almost identical cascade process, that tend to reduce topological complexity by stepwise unlinking. Here, by using the HOMFLYPT polynomial recently introduced for fluid knots, we prove that under the assumption that topological complexity decreases by stepwise unlinking this cascade process follows a path detected by a unique, monotonically decreasing sequence of numerical values. This result holds true for any sequence of standardly embedded torus knots T(2, 2n + 1) and torus links T(2, 2n). By this result we demonstrate that the computation of this adapted HOMFLYPT polynomial provides a powerful tool to measure topological complexity of various physical systems.

  7. Psychological stress may induce increased humoral and decreased cellular immunity.

    PubMed

    Paik, I H; Toh, K Y; Lee, C; Kim, J J; Lee, S J

    2000-01-01

    Stress alters immune function and affects different immune cell populations in different ways. The authors examined whether psychological stress has different effects on the production of macrophage, T-helper 1(Th1) cell, and T-helper 2(Th2) cell-derived cytokines. Forty-two college students were recruited and their blood was sampled on the day they were to take a stressful academic examination and again 4 weeks after the examination. The stress from the academic examination significantly increased IL-1 beta, IL-6, and IL-10 and decreased IFN-gamma production. These findings suggest that examination stress may increase Th2 cell-mediated humoral immunity and macrophage activities and may decrease Th1 cell-mediated cellular immunity. PMID:11209594

  8. Playing prosocial video games increases empathy and decreases schadenfreude.

    PubMed

    Greitemeyer, Tobias; Osswald, Silvia; Brauer, Markus

    2010-12-01

    Past research provided abundant evidence that exposure to violent video games increases aggressive tendencies and decreases prosocial tendencies. In contrast, research on the effects of exposure to prosocial video games has been relatively sparse. The present research found support for the hypothesis that exposure to prosocial video games is positively related to prosocial affect and negatively related to antisocial affect. More specifically, two studies revealed that playing a prosocial (relative to a neutral) video game increased interpersonal empathy and decreased reported pleasure at another's misfortune (i.e., schadenfreude). These results lend further credence to the predictive validity of the General Learning Model (Buckley & Anderson, 2006) for the effects of media exposure on social tendencies. PMID:21171755

  9. Effectiveness of public health programs for decreasing alcohol consumption

    PubMed Central

    Kelly-Weeder, Susan; Phillips, Kathryn; Rounseville, Shannon

    2012-01-01

    Excessive alcohol consumption and the associated negative consequences are a major public health concern in the United States and throughout the world. Historically, there have been numerous attempts to develop policies and prevention programs aimed at decreasing high-risk alcohol use. Policy initiatives have demonstrated considerable effectiveness and include changes in the minimum legal drinking age, reductions in acceptable legal limits for blood alcohol concentration while operating a motor vehicle, as well as decreasing availability and access to alcohol for underage individuals. Primary prevention programs that have used exclusively educational approaches have received mixed results. Increasing effectiveness has been associated with prevention programs that have utilized a multi-component approach and have included educational initiatives with environmental changes. PMID:23180975

  10. Knots cascade detected by a monotonically decreasing sequence of values.

    PubMed

    Liu, Xin; Ricca, Renzo L

    2016-01-01

    Due to reconnection or recombination of neighboring strands superfluid vortex knots and DNA plasmid torus knots and links are found to undergo an almost identical cascade process, that tend to reduce topological complexity by stepwise unlinking. Here, by using the HOMFLYPT polynomial recently introduced for fluid knots, we prove that under the assumption that topological complexity decreases by stepwise unlinking this cascade process follows a path detected by a unique, monotonically decreasing sequence of numerical values. This result holds true for any sequence of standardly embedded torus knots T(2, 2n + 1) and torus links T(2, 2n). By this result we demonstrate that the computation of this adapted HOMFLYPT polynomial provides a powerful tool to measure topological complexity of various physical systems. PMID:27052386