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Sample records for angiotensin-receptor blocker telmisartan

  1. Angiotensin receptor blocker telmisartan suppresses renal gluconeogenesis during starvation

    Directory of Open Access Journals (Sweden)

    Tojo A

    2015-02-01

    Full Text Available Akihiro Tojo, Saaya Hatakeyama, Satoshi Kinugasa, Masaomi Nangaku Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan Abstract: The kidney plays an important role in gluconeogenesis during starvation. To clarify the anti-diabetic action of angiotensin receptor blockers, we examined the effects of telmisartan on the sodium-glucose co-transporters (SGLT and the pathways of renal gluconeogenesis in streptozotocin-induced diabetes mellitus (DM rats. At 4 weeks, the DM rats treated with/without telmisartan for 2 weeks and normal control rats were used for the study after a 24-hour fast. SGLT2 expressed on the brush border membrane of the proximal convoluted tubules increased in the DM rats, but decreased in the rats treated with telmisartan. The expression of restriction enzymes of gluconeogenesis, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased in the proximal tubules in the DM rats, whereas these enzymes decreased in the kidneys of the rats treated with telmisartan. The elevated cytoplasmic glucose-6-phosphate and glucose levels in the kidney of DM rats significantly decreased in those treated with telmisartan, whereas those levels in the liver did not show significant change. Meanwhile, the high plasma glucose levels in the DM rats during the intravenous insulin tolerance tests were ameliorated by telmisartan. The increased fasting plasma glucose levels after 24 hours of starvation in the DM rats thus returned to the control levels by telmisartan treatment. In conclusion, the increased renal SGLT2 expression, elevated renal gluconeogenesis enzymes and extent of insulin-resistance in the DM rats were ameliorated by telmisartan therapy, thus resulting in decreased plasma glucose levels after 24 hours of fasting. Keywords: SGLT2, renal gluconeogenesis, diabetes, angiotensin II

  2. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial

    DEFF Research Database (Denmark)

    NN, NN; Yusuf, S; Teo, K;

    2008-01-01

    BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular...... group). INTERPRETATION: Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no significant effect on the primary outcome of this study, which included hospitalisations for heart failure, it modestly reduced the risk of the composite outcome...

  3. Angiotensin-receptor blockers as therapy for mildto- moderate hypertension-associated non-alcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Eugen Florin Georgescu; Reanina Ionescu; Mihaela Niculescu; Laurentiu Mogoanta; Liliana Vancica

    2009-01-01

    AIM: To evaluate insulin resistance, cytolysis and nonalcoholic steatohepatitis (NASH) score (NAS) using the Kleiner and Brunt criteria in 54 patients with NASH and mild-to-moderate hypertension, treated with telmisartan vs valsartan for 20 mo. METHODS: All patients met the NCEP-ATP Ⅲ criteria for metabolic syndrome. Histology confirmed steatohepatitis, defined as a NAS greater than five up to 3 wk prior inclusion, using the current criteria. Patients with viral hepatitis, chronic alcohol intake, drug abuse or other significant immune or metabolic hepatic pathology were excluded. Subjects were randomly as -signed either to the valsartan (V) group (standard dose 80 mg o.d., n = 26), or to the telmisartan (T) group (standard dose 20 mg o.d., n = 28). Treatment had to be taken daily at the same hour with no concomitant medication or alcohol consumption allowed. Neither the patient nor the medical staff was aware of treatment group allocation. Paired liver biopsies obtained at inclusion (visit 1) and end of treatment (EOT) were assessed by a single blinded pathologist, not aware of patient or treatment group. Blood pressure, BMI, ALT, AST, HOMA-IR, plasma triglycerides (TG) and total cholesterol (TC) were evaluated at inclusion and every 4 mo until EOT (visit 6). RESULTS: At EOT we noticed a significant decrease in ALT levels vs inclusion in all patients and this decrease did not differ significantly in group T vs group V. HOMA-IR significantly decreased at EOT vs inclusion in all patients but in group T, the mean HOMA-IR decrease per month was higher than in group V. NAS significantly diminished at EOT in all patients with a higher decrease in group T vs group V. CONCLUSION: Angiotensin receptor blockers seem to be efficient in hypertension-associated NASH. Telmisartan showed a higher efficacy regarding insulin resistance and histology, perhaps because of its specific PPAR-gamma ligand effect.

  4. A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention

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    Ji-Guang Wang

    2009-07-01

    Full Text Available Ji-Guang WangCentre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaAbstract: Stroke is a leading cause of death and disability worldwide. The importance of lowering blood pressure for reducing the risk of stroke is well established. However, not all the benefits of antihypertensive treatments in stroke can be accounted for by reductions in BP and there may be differences between antihypertensive classes as to which provides optimal protection. Dihydropyridine calcium channel blockers, such as amlodipine, and angiotensin receptor blockers, such as valsartan, represent the two antihypertensive drug classes with the strongest supportive data for the prevention of stroke. Therefore, when combination therapy is required, a combination of these two antihypertensive classes represents a logical approach.Keywords: stroke, angiotensin, calcium channel, cerebrovascular, hypertension, blood pressure

  5. Role of angiotensin receptor blockers in patients with left ventricular dysfunction : lessons from CHARM and VALIANT

    NARCIS (Netherlands)

    Voors, AA; van Veldhuisen, DJ

    2004-01-01

    The role of angiotensin receptor blockers (ARBs) in patients with left ventricular dysfunction has changed after the VALIANT and CHARM trials. CHARM proved that candesartan is a good alternative for patients with chronic heart failure who cannot tolerate ACE-inhibitors. Moreover, VALIANT demonstrate

  6. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis

    OpenAIRE

    Li, Nien-Chen; Lee, Austin; Whitmer, Rachel A.; Kivipelto, Miia; Lawler, Elizabeth; Kazis, Lewis E; Wolozin, Benjamin

    2010-01-01

    Objective To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases. Design Prospective cohort analysis. Setting Administrative database of the US Veteran Affairs, 2002-6. Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease. Main outcome measures Time to incident Alzheimer’s disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and ...

  7. Use of ACE Inhibitors and Angiotensin Receptor Blockers and Primary Breast Cancer Outcomes

    OpenAIRE

    Chae, Young Kwang; Brown, Erika N.; Lei, Xiudong; Melhem-Bertrandt, Amal; Giordano, Sharon H.; Litton, Jennifer K.; Hortobagyi, Gabriel N; Gonzalez-Angulo, Ana M.; Chavez-MacGregor, Mariana

    2013-01-01

    BACKGROUND: ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may have anti-tumor properties. We investigated whether the use of ACEI/ARBs affects the clinical outcomes of primary breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. METHODS: We included 1449 patients with diagnosis of invasive primary breast cancer diagnosed at the MD Anderson Cancer Center between 1995 and 2007 who underwent neoadjuvant chemotherapy. Of them, 160 (11%) patie...

  8. Different angiotensin receptor blockers and incidence of diabetes: a nationwide population-based cohort study

    OpenAIRE

    Chang, Chia-Hsuin; Chang, Yi-Cheng; Wu, Li-Chiu; Lin, Jou-Wei; Chuang, Lee-Ming; Lai, Mei-Shu

    2014-01-01

    Background Angiotensin receptor blockers (ARBs) have been shown to exert various peroxisome proliferator-activated receptor gamma (PPARγ) binding activities and insulin-sensitizing effects. The objective of this study was to investigate the association of different ARBs with new-onset diabetes mellitus. Methods In the respective cohort, a total of 492,530 subjects who initiated ARB treatment between January 2004 and December 2009 were identified from Taiwan National Health Insurance Database....

  9. Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b

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    Lee Robert E

    2006-01-01

    Full Text Available Abstract Background There have been indications that common Angiotensin Receptor Blockers (ARBs may be exerting anti-inflammatory actions by directly modulating the immune system. We decided to use molecular modelling to rapidly assess which of the potential targets might justify the expense of detailed laboratory validation. We first studied the VDR nuclear receptor, which is activated by the secosteroid hormone 1,25-dihydroxyvitamin-D. This receptor mediates the expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing hormone and the Parathyroid Hormone (PTH. Additionally we examined Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma, which affects the function of phagocytic cells, and the C-CChemokine Receptor, type 2b, (CCR2b, which recruits monocytes to the site of inflammatory immune challenge. Results Telmisartan was predicted to strongly antagonize (Ki≈0.04nmol the VDR. The ARBs Olmesartan, Irbesartan and Valsartan (Ki≈10 nmol are likely to be useful VDR antagonists at typical in-vivo concentrations. Candesartan (Ki≈30 nmol and Losartan (Ki≈70 nmol may also usefully inhibit the VDR. Telmisartan is a strong modulator of PPARgamma (Ki≈0.3 nmol, while Losartan (Ki≈3 nmol, Irbesartan (Ki≈6 nmol, Olmesartan and Valsartan (Ki≈12 nmol also seem likely to have significant PPAR modulatory activity. Olmesartan andIrbesartan (Ki≈9 nmol additionally act as antagonists of a theoretical modelof CCR2b. Initial validation of this CCR2b model was performed, and a proposed model for the AngiotensinII Type1 receptor (AT2R1 has been presented. Conclusion Molecular modeling has proven valuable to generate testable hypotheses concerning receptor/ligand binding and is an important tool in drug design. ARBs were designed to act as antagonists for AT2R1, and it was not surprising to discover their affinity for the structurally similar CCR2b. However, this study also found evidence that ARBs modulate the

  10. Initial reduction of oxidative stress by angiotensin receptor blocker contributes long term outcomes after percutaneous coronary intervention

    OpenAIRE

    Noro, Tadanori; Takehara, Naofumi; Sumitomo, Kazuhiro; Takeuchi, Toshiharu; Ishii, Yoshinao; Kato, Jun-ichi; Kawabe, Jun-ichi; Hasebe, Naoyuki

    2014-01-01

    Background: It remains unclear whether administration of ARB with reactive oxygen species (ROS) scavenging effects improves the prognosis of patients undergoing PCI. Objectives: This study investigated whether the pre-intervention antioxidant effect of angiotensin receptor blocker (ARB) affects long-term outcomes in patients after successful percutaneous coronary intervention (PCI) without early adverse events. Methods: Fifty-two patients who underwent elective PCI were randomly assigned for ...

  11. Combined therapeutic benefit of mitochondria-targeted antioxidant, MitoQ10, and angiotensin receptor blocker, losartan, on cardiovascular function

    OpenAIRE

    McLachlan, Jennifer; Beattie, Elisabeth; Murphy, Michael P; Koh-Tan, Caline H.H.; Olson, Erin; Beattie, Wendy; Dominiczak, Anna F.; Nicklin, Stuart A.; Graham, Delyth

    2014-01-01

    Objective: Mitochondria-derived reactive oxygen species (ROS) play important roles in the development of cardiovascular disease highlighting the need for novel targeted therapies. This study assessed the potential therapeutic benefit of combining the mitochondria-specific antioxidant, MitoQ10, with the low-dose angiotensin receptor blocker (ARB), losartan, on attenuation of hypertension and left ventricular hypertrophy. In parallel, we investigated the impact of MitoQ10 on cardiac hypertro...

  12. Long-term use of angiotensin receptor blockers and the risk of cancer.

    Directory of Open Access Journals (Sweden)

    Laurent Azoulay

    Full Text Available The association between angiotensin receptor blockers (ARBs and cancer is controversial with meta-analyses of randomized controlled trials and observational studies reporting conflicting results. Thus, the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers, namely, lung, colorectal, breast and prostate cancers, and to explore these effects separately for each cancer type. We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom (UK General Practice Research Database. We assembled a cohort of patients prescribed antihypertensive agents between 1995, the year the first ARB (losartan entered the UK market, and 2008, with follow-up until December 31, 2010. Cases were patients newly-diagnosed with lung, colorectal, breast and prostate cancer during follow-up. We used conditional logistic regression to estimate adjusted rate ratios (RRs and 95% confidence intervals (CIs of cancer incidence, comparing ever use of ARBs with ever use of diuretics and/or beta-blockers. The cohort included 1,165,781 patients, during which 41,059 patients were diagnosed with one of the cancers under study (rate 554/100,000 person-years. When compared to diuretics and/or beta-blockers, ever use of ARBs was not associated with an increased rate of cancer overall (RR: 1.00; 95% CI: 0.96-1.03 or with each cancer site separately. The use of angiotensin-converting enzyme inhibitors and calcium channel blockers was associated with an increased rate of lung cancer (RR: 1.13; 95% CI: 1.06-1.20 and RR: 1.19; 95% CI: 1.12-1.27, respectively. This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites. Additional research is needed to further investigate a potentially increased risk of lung cancer with angiotensin-converting enzyme inhibitors and calcium channel blockers.

  13. The importance of short-term off-target effects in estimating the long-term renal and cardiovascular protection of angiotensin receptor blockers

    DEFF Research Database (Denmark)

    Smink, P A; Miao, Y; Eijkemans, M J C;

    2014-01-01

    Angiotensin receptor blockers (ARBs) have multiple effects that may contribute to their efficacy on renal/cardiovascular outcomes. We developed and validated a risk score that incorporated short-term changes in multiple risk markers to predict the ARB effect on renal/cardiovascular outcomes. The ...

  14. Cardiovascular risk reduction in hypertension: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers. Where are we up to?

    Science.gov (United States)

    Sindone, A; Erlich, J; Lee, C; Newman, H; Suranyi, M; Roger, S D

    2016-03-01

    Previously, management of hypertension has concentrated on lowering elevated blood pressure. However, the target has shifted to reducing absolute cardiovascular (CV) risk. It is estimated that two in three Australian adults have three or more CV risk factors at the same time. Moderate reductions in several risk factors can, therefore, be more effective than major reductions in one. When managing hypertension, therapy should be focused on medications with the strongest evidence for CV event reduction, substituting alternatives only when a primary choice is not appropriate. Hypertension management guidelines categorise angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) interchangeably as first-line treatments in uncomplicated hypertension. These medications have different mechanisms of action and quite different evidence bases. They are not interchangeable and their prescription should be based on clinical evidence. Despite this, currently ARB prescriptions are increasing at a higher rate than those for ACEI and other antihypertensive classes. Evidence that ACEI therapy prevents CV events and death, in patients with coronary artery disease or multiple CV risk factors, emerged from the European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA) and Heart Outcomes Prevention Evaluation (HOPE) trials respectively. The consistent benefit has been demonstrated in meta-analyses. The clinical trial data for ARB are less consistent, particularly regarding CV outcomes and mortality benefit. The evidence supports the use of ACEI (Class 1a) compared with ARB despite current prescribing trends. PMID:26968600

  15. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Science.gov (United States)

    Benter, Ibrahim F.; Babiker, Fawzi; Al-Rashdan, Ibrahim; Yousif, Mariam; Akhtar, Saghir

    2013-01-01

    Aims. We evaluated the effects of RU28318 (RU), a selective mineralocorticoid receptor (MR) antagonist, Captopril (Capt), an angiotensin converting enzyme inhibitor, and Losartan (Los), an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R-) induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving −dP/dt (a measure of diastolic function) when administered to diabetic hearts after ischemia. PMID:24066305

  16. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Ibrahim F. Benter

    2013-01-01

    Full Text Available Aims. We evaluated the effects of RU28318 (RU, a selective mineralocorticoid receptor (MR antagonist, Captopril (Capt, an angiotensin converting enzyme inhibitor, and Losartan (Los, an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R- induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I followed by a period of 30 min of reperfusion (R. Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple. Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving -dP/dt (a measure of diastolic function when administered to diabetic hearts after ischemia.

  17. Trends in co-prescribing of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in Ireland.

    LENUS (Irish Health Repository)

    Wan Md Adnan, Wan A H

    2011-03-01

    (i) To examine the trends in co-prescribing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) therapy and (ii) to examine the influence of major clinical trials (CALM, COOPERATE, VALIANT and ONTARGET) on co-prescribing.

  18. Use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta-analysis.

    Science.gov (United States)

    Raimondi, Sara; Botteri, Edoardo; Munzone, Elisabetta; Cipolla, Carlo; Rotmensz, Nicole; DeCensi, Andrea; Gandini, Sara

    2016-07-01

    Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta-blocker (BB) drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta-analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study-specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between-study heterogeneity by meta-regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26-0.73 with I(2)  = 78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19-1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC-specific survival. Clinical trials addressing this hypothesis are warranted. PMID:26916107

  19. Angiotensin-Receptor Blocker, Angiotensin-Converting Enzyme Inhibitor, and Risks of Atrial Fibrillation: A Nationwide Cohort Study.

    Science.gov (United States)

    Hsieh, Yu-Cheng; Hung, Chen-Ying; Li, Cheng-Hung; Liao, Ying-Chieh; Huang, Jin-Long; Lin, Ching-Heng; Wu, Tsu-Juey

    2016-05-01

    Both angiotensin-receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have protective effects against atrial fibrillation (AF). The differences between ARB and ACEI in their effects on the primary prevention of AF remain unclear. This study compared ARB and ACEI in combined antihypertensive medications for reducing the risk of AF in patients with hypertension, and determined which was better for AF prevention in a nationwide cohort study.Patients aged ≥55 years and with a history of hypertension were identified from Taiwan National Health Insurance Research Database. Medical records of 25,075 patients were obtained, and included 6205 who used ARB, 8034 who used ACEI, and 10,836 nonusers (no ARB or ACEI) in their antihypertensive regimen. Cox regression models were applied to estimate the hazard ratio (HR) for new-onset AF.During an average of 7.7 years' follow-up, 1619 patients developed new-onset AF. Both ARB (adjusted HR: 0.51, 95% CI 0.44-0.58, P reduced the risk of AF compared to nonusers. Subgroup analysis showed that ARB and ACEI were equally effective in preventing new-onset AF regardless of age, gender, the presence of heart failure, diabetes, and vascular disease, except for those with prior stroke or transient ischemic attack (TIA). ARB prevents new-onset AF better than ACEI in patients with a history of stroke or TIA (log-rank P = 0.012).Both ARB and ACEI reduce new-onset AF in patients with hypertension. ARB prevents AF better than ACEI in patients with a history of prior stroke or TIA. PMID:27196491

  20. Telmisartan and cardioprotection

    Directory of Open Access Journals (Sweden)

    Akhrass PR

    2011-11-01

    Full Text Available Philippe R Akhrass, Samy I McFarlaneState University of New York, Downstate Medical Center, Brooklyn, NY, USAAbstract: Cardiovascular risk reduction has been the target of several large clinical trials in the last decade. As the activation of the renin-angiotensin-aldosterone system (RAAS plays a central role in the pathogenesis of atherosclerosis and cardiovascular disease, RAAS blockade has been suggested to be among the most efficient cardioprotective interventions, as revealed with the angiotensin converting enzyme (ACE inhibitors trials. The angiotensin receptor blockers' (ARBs efficacy in lowering blood pressure has been very well established. Telmisartan is however the first ARB to show a promising role in reducing cardiovascular risk in high-risk patients. This article will highlight the role of telmisartan in cardioprotection, underlying specifically the results of two major randomized controlled trials: ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial and TRANSCEND (Telmisartan Randomized AssessmeNt Study in aCE-iNtolerant subjects with cardiovascular Disease.Keywords: telmisartan, cardioprotection, ONTARGET, TRANSCEND

  1. The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial

    DEFF Research Database (Denmark)

    Sandset, Else Charlotte; Bath, Philip M W; Boysen, Gudrun;

    2011-01-01

    BACKGROUND: Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised...... blood pressure. METHODS: Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included...... within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked...

  2. The impact of dose of the angiotensin-receptor blocker valsartan on the post-myocardial infarction ventricular remodeling: study protocol for a randomized controlled trial

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    Cho Young-Rak

    2011-11-01

    Full Text Available Abstract Background Angiotensin-converting enzyme inhibitors and the angiotensin-receptor blocker valsartan ameliorate ventricular remodeling after myocardial infarction (MI. Based on previous clinical trials, a maximum clinical dose is recommended in practical guidelines. Yet, has not been clearly demonstrated whether the recommended dose is more efficacious compared to the lower dose that is commonly used in clinical practice. Method/Design Valsartan in post-MI remodeling (VALID is a randomized, open-label, single-blinded multicenter study designed to compare the efficacy of different clinical dose of valsartan on the post-MI ventricular remodeling. This study also aims to assess neurohormone change and clinical parameters of patients during the post-infarct period. A total of 1116 patients with left ventricular dysfunction following the first episode of acute ST-elevation MI are to be enrolled and randomized to a maximal tolerable dose (up to 320 mg/day or usual dose (80 mg/day of valsartan for 12 months in 2:1 ratio. Echocardiographic analysis for quantifying post-MI ventricular remodeling is to be conducted in central core laboratory. Clinical assessment and laboratory test are performed at fixed times. Discussion VALID is a multicenter collaborative study to evaluate the impact of dose of valsartan on the post-MI ventricular remodeling. The results of the study provide information about optimal dosing of the drug in the management of patients after MI. The results will be available by 2012. Trial registration NCT01340326

  3. Telmisartan

    Science.gov (United States)

    ... It works by blocking the action of certain natural substances that tighten the blood vessels, allowing the ... Telmisartan controls high blood pressure but does not cure it. Your blood pressure may decrease during the ...

  4. Telmisartan protects against diabetic vascular complications in a mouse model of obesity and type 2 diabetes, partially through peroxisome proliferator activated receptor-γ-dependent activity

    International Nuclear Information System (INIS)

    Highlights: → Telmisartan, an angiotensin receptor blocker, acts as a partial PPARγ agonist. → The protective effects of telmisartan against diabetic vascular injury were associated with attenuation of vascular NFκB activation and TNF α. → PPARγ activity of telmisartan was involved in the normalization of vascular PPARγ downregulation in diabetic mice. → We provided the first evidence indicating that PPARγ activity of telmisartan contributed to the protective effects of telmisartan against diabetic vascular complication. -- Abstract: Experimental and clinical data support the notion that peroxisome proliferator-activated receptor γ (PPARγ) activation is associated with anti-atherosclerosis as well as anti-diabetic effect. Telmisartan, an angiotensin receptor blocker (ARB), acts as a partial PPARγ agonist. We hypothesized that telmisartan protects against diabetic vascular complications, through PPARγ activation. We compared the effects of telmisartan, telmisartan combined with GW9662 (a PPARγ antagonist), and losartan with no PPARγ activity on vascular injury in obese type 2 diabetic db/db mice. Compared to losartan, telmisartan significantly ameliorated vascular endothelial dysfunction, downregulation of phospho-eNOS, and coronary arterial remodeling in db/db mice. More vascular protective effects of telmisartan than losartan were associated with greater anti-inflammatory effects of telmisartan, as shown by attenuation of vascular nuclear factor kappa B (NFκB) activation and tumor necrosis factor α. Coadministration of GW9662 with telmisartan abolished the above mentioned greater protective effects of telmisartan against vascular injury than losartan in db/db mice. Thus, PPARγ activity appears to be involved in the vascular protective effects of telmisartan in db/db mice. Moreover, telmisartan, but not losartan, prevented the downregulation of vascular PPARγ in db/db mice and this effect of telmisartan was cancelled by the coadministration

  5. Telmisartan protects against diabetic vascular complications in a mouse model of obesity and type 2 diabetes, partially through peroxisome proliferator activated receptor-{gamma}-dependent activity

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Kensuke; Nakamura, Taishi; Kataoka, Keiichiro [Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto (Japan); Yasuda, Osamu [Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital, Kumamoto (Japan); Fukuda, Masaya; Tokutomi, Yoshiko; Dong, Yi-Fei [Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto (Japan); Ogawa, Hisao [Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto (Japan); Kim-Mitsuyama, Shokei, E-mail: kimmitsu@gpo.kumamoto-u.ac.jp [Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto (Japan)

    2011-07-08

    Highlights: {yields} Telmisartan, an angiotensin receptor blocker, acts as a partial PPAR{gamma} agonist. {yields} The protective effects of telmisartan against diabetic vascular injury were associated with attenuation of vascular NF{kappa}B activation and TNF {alpha}. {yields} PPAR{gamma} activity of telmisartan was involved in the normalization of vascular PPAR{gamma} downregulation in diabetic mice. {yields} We provided the first evidence indicating that PPAR{gamma} activity of telmisartan contributed to the protective effects of telmisartan against diabetic vascular complication. -- Abstract: Experimental and clinical data support the notion that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) activation is associated with anti-atherosclerosis as well as anti-diabetic effect. Telmisartan, an angiotensin receptor blocker (ARB), acts as a partial PPAR{gamma} agonist. We hypothesized that telmisartan protects against diabetic vascular complications, through PPAR{gamma} activation. We compared the effects of telmisartan, telmisartan combined with GW9662 (a PPAR{gamma} antagonist), and losartan with no PPAR{gamma} activity on vascular injury in obese type 2 diabetic db/db mice. Compared to losartan, telmisartan significantly ameliorated vascular endothelial dysfunction, downregulation of phospho-eNOS, and coronary arterial remodeling in db/db mice. More vascular protective effects of telmisartan than losartan were associated with greater anti-inflammatory effects of telmisartan, as shown by attenuation of vascular nuclear factor kappa B (NF{kappa}B) activation and tumor necrosis factor {alpha}. Coadministration of GW9662 with telmisartan abolished the above mentioned greater protective effects of telmisartan against vascular injury than losartan in db/db mice. Thus, PPAR{gamma} activity appears to be involved in the vascular protective effects of telmisartan in db/db mice. Moreover, telmisartan, but not losartan, prevented the downregulation of

  6. The Effect of an Angiotensin Receptor Blocker on Arterial Stiffness in Type 2 Diabetes Mellitus Patients with Hypertension

    OpenAIRE

    Ji Hyun Kim; Su Jin Oh; Jung Min Lee; Eun Gyoung Hong; Jae Myung Yu; Kyung Ah Han; Kyung Wan Min; Hyun Shik Son; Sang Ah Chang

    2011-01-01

    Background Hypertension and type 2 diabetes mellitus are major risk factors for cardiovascular disease. This study analyzed the changes in central aortic waveforms and pulse wave velocity as well as related parameters after treatment with valsartan, an angiotensin II type 1 receptor blocker, in patients with type 2 diabetes and hypertension. Methods We used pulse wave analysis to measure central aortic waveform in a total of 98 subjects. In 47 of these patients, pulse wave velocity measuremen...

  7. The Effect of an Angiotensin Receptor Blocker on Arterial Stiffness in Type 2 Diabetes Mellitus Patients with Hypertension

    Directory of Open Access Journals (Sweden)

    Ji Hyun Kim

    2011-06-01

    Full Text Available BackgroundHypertension and type 2 diabetes mellitus are major risk factors for cardiovascular disease. This study analyzed the changes in central aortic waveforms and pulse wave velocity as well as related parameters after treatment with valsartan, an angiotensin II type 1 receptor blocker, in patients with type 2 diabetes and hypertension.MethodsWe used pulse wave analysis to measure central aortic waveform in a total of 98 subjects. In 47 of these patients, pulse wave velocity measurements were obtained before and after 12 weeks of treatment with valsartan.ResultsIn the central aortic waveform analysis, the aortic pulse pressure and augmentation index were significantly decreased after valsartan treatment, as was the aortic pulse wave velocity. Factors contributing to the improvement in pulse wave velocity were the fasting blood glucose and haemoglobin A1c levels.ConclusionShort-term treatment with valsartan improves arterial stiffness in patients with type 2 diabetes and hypertension, and the glucose status at baseline was associated with this effect.

  8. Beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine, diuretics, aldosterone antagonist, ivabradine, devices and digoxin (BANDAID(2) ): an evidence-based mnemonic for the treatment of systolic heart failure.

    Science.gov (United States)

    Chia, N; Fulcher, J; Keech, A

    2016-06-01

    Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline-based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice, which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID (2) , standing for beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine (or potentially neprilysin inhibitor), diuretics, aldosterone antagonist, ivabradine, devices (automatic implantable cardioverter defibrillator, cardiac resynchronisation therapy or both) and digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence-based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition. PMID:26109136

  9. Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells.

    Science.gov (United States)

    Kozako, Tomohiro; Soeda, Shuhei; Yoshimitsu, Makoto; Arima, Naomichi; Kuroki, Ayako; Hirata, Shinya; Tanaka, Hiroaki; Imakyure, Osamu; Tone, Nanako; Honda, Shin-Ichiro; Soeda, Shinji

    2016-05-01

    Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator-activated receptor-γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV-1 carriers (ACs) or via caspase-independent cell death in acute-type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase-dependent and -independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth-inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients. PMID:27419050

  10. Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan

    Directory of Open Access Journals (Sweden)

    Huang Shiou-Huei

    2012-05-01

    Full Text Available Abstract Background A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs] to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. Methods Using the Taiwan’s Longitudinal Health Insurance Database (2005, we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. Results The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088 and in ARBs after price adjustments in 2001 (173.4%, p  Conclusions Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs

  11. Ambulatory blood pressure response to triple therapy with an angiotensin-receptor blocker (ARB, calcium-channel blocker (CCB, and HCTZ versus dual therapy with an ARB and HCTZ

    Directory of Open Access Journals (Sweden)

    Duprez D

    2011-11-01

    Full Text Available Daniel Duprez1, Keith Ferdinand2, Das Purkayastha3, Rita Samuel3, Richard Wright41University of Minnesota, Minneapolis, MN, 2Atlanta Clinical Research Centers, Atlanta, GA, 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, 4Pacific Heart Institute, Santa Monica, CA, USABackground: Stage 2 hypertension often requires combination antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM is a useful tool for assessing antihypertensive drugs and their combinations.Objective: To compare the effect of a moderate dose of angiotensin receptor blocker/calcium channel blocker (ARB/CCB combined with a diuretic versus a maximal dose of ARB with a diuretic on 24-hour ambulatory blood pressure monitoring (ABPM and other derived ambulatory blood pressure (ABP parameters.Methods: The EXforge As compared to Losartan Treatment ABPM substudy was a randomized, double-blind, parallel-group, active-control, forced-titration study of patients with Stage 2 hypertension that compared the efficacy of initial treatment with valsartan/amlodipine 160/5 mg (n = 48 or losartan 100 mg (n = 36. At week 3, hydrochlorothiazide (HCTZ 25 mg was added in both treatment groups. ABP was measured at baseline and at week 6. Additionaly, 24-hour ABP, nighttime (10 pm to 6 am and daytime (6 am to 10 pm ABP, and ABP load (percentage of readings above 140/90 mmHg were determined.Results: Eighty-four patients (48 ARB/CCB/HCTZ, 36 ARB/HCTZ had ABPM at baseline and at week 6. Reductions of systolic/diastolic ABP were greater in the ARB/CCB/HCTZ group than in the ARB/HCTZ group for 24-hour mean ABP (–22.0/–13.3 versus –17.4/–8.1 mmHg, as well as nighttime ABP (–22.2/–13.3 versus –16.2/–7.4 mmHg, daytime ABP (–21.9/–13.0 versus –18.1/–8.6 mmHg, ABP in the last 4 hours of the dosing period (–21.5/–13.5 versus –17.0/–7.7 mmHg, and ABP load (21.7%/12.8% versus 30.8%/20.0%.Conclusion: Initiating antihypertensive treatment with moderate doses of ARB

  12. Telmisartan to prevent recurrent stroke and cardiovascular events

    DEFF Research Database (Denmark)

    Yusuf, Salim; Diener, Hans-Christoph; Sacco, Ralph L; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo; Iversen, Helle Klingenberg

    2008-01-01

    BACKGROUND: Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood...... pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. METHODS: In a multicenter trial involving 20,332 patients who recently had an...... ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening...

  13. Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques

    International Nuclear Information System (INIS)

    Introduction: Telmisartan is a widely used, long-acting antihypertensive agent. Known to be a selective angiotensin II type 1 (AT1) receptor (AT1R) blocker (ARB), telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and inhibits centrally mediated effects of angiotensin II in rats following peripheral administration, although the brain penetration of telmisartan remains unclear. We investigated the brain concentration and localization of telmisartan using 11 C-labeled telmisartan and positron emission tomography (PET) in conscious rhesus macaques. Methods: Three male rhesus macaques were bolus intravenously administered [11 C]telmisartan either alone or as a mixture with unlabeled telmisartan (1 mg/kg). Dynamic PET images were acquired for 95 min following administration. Blood samples were collected for the analysis of plasma concentration and metabolites, and brain and plasma concentrations were calculated from detected radioactivity using the specific activity of the administered drug preparation, in which whole blood radioactivity was used for the correction of intravascular blood radioactivity in brain. Results: Telmisartan penetrated into the brain little but enough to block AT1R and showed a consistently increasing brain/plasma ratio within the PET scanning period, suggesting slow clearance of the compound from the brain compared to the plasma clearance. Brain/plasma ratios at 30, 60, and 90 min were 0.06, 0.13, and 0.18, respectively. No marked localization according to the AT1R distribution was noted over the entire brain, even on tracer alone dosing. Conclusions: Telmisartan penetrated into the brain enough to block AT1R and showed a slow clearance from the brain in conscious rhesus macaques, supporting the long-acting and central responses of telmisartan as a unique property among ARBs.

  14. Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial.

    Directory of Open Access Journals (Sweden)

    Matthias Huber

    Full Text Available Treatment of hypertension in hemodialysis (HD patients is characterised by lack of evidence for both the blood pressure (BP target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients.Clinicaltrialsregister.eu 2005-005021-60.

  15. A PROSPECTIVE STUDY OF EFFECT OF TELMISARTAN (ANGIOTENSIN II RECEPTOR BLOCKER ON METABOLIC PARAMETERS IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Somesekhar

    2016-04-01

    Full Text Available BACKGROUND The metabolic syndrome is currently a major worldwide epidemic. It strongly associates with obesity, insulin resistance, type 2 diabetes, and cardiovascular diseases, which are major pathologies contributing to mortality and morbidity worldwide. The effect of PPAR-y on metabolic syndrome is significant it is critical regulator of adipogenesis the gain in PPAR-y is resulted in obesity but loss of PPAR–y by mutation is associated with loss of weight and insulin resistance. Telmisartan is an orally active, long-acting, non-peptide angiotensin type 1 (ATI receptor blocker. In addition to this, it has been identified as partial agonist/selective modulator of the nuclear hormone receptor PPAR-y. MATERIAL AND METHOD This is a prospective, randomised and open labelled 16 weeks study conducted in the Dept. of General Medicine, Konaseema Institute of Medical Science, Amalapuram. Present study is designed to study the effect of telmisartan on various metabolic parameters in hypertensive patients who fulfilled the criteria of metabolic syndrome. RESULT There was statistically significant change in all parameters most important was lipid profile; LDL concentration was decreased from 139.2 mg/dL to 120.2 mg/dL. Baseline triglyceride concentration was 161.0 mg/dL which was changed 152.8 mg/dL Total cholesterol was decreased from 203.2 to 193.8 mg/dL. CONCLUSION In our study, we have also found that use of telmisartan is associated with decrease in lipid concentration in addition to its effect on blood pressure regulation. But a long term study with high dose required of this drug is required because safety profile of this drug is better than thiazolidinedione. Financial part of this study is our limitation.

  16. Diabetic Retinal Neurodegeneration Is Associated With Mitochondrial Oxidative Stress and Is Improved by an Angiotensin Receptor Blocker in a Model Combining Hypertension and Diabetes

    OpenAIRE

    Silva, Kamila C.; Rosales, Mariana A.B.; Biswas, Subrata K.; Lopes de Faria, Jose B.; Lopes de Faria, Jacqueline M.

    2009-01-01

    OBJECTIVE Diabetic retinopathy displays the features of a neurodegenerative disease. Oxidative stress is involved in the pathogenesis of diabetic retinopathy. This investigation sought to determine whether hypertension exacerbates the oxidative stress, neurodegeneration, and mitochondrial dysfunction that exists in diabetic retinopathy and whether these changes could be minimized by the angiotensin II type 1 (AT1) receptor blocker (ARB) losartan. RESEARCH DESIGN AND METHODS Diabetes was induc...

  17. A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial: study protocol for a randomized double-blind controlled trial

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    Figueiredo Neto José A

    2011-02-01

    Full Text Available Abstract Background Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials

  18. Distinct properties of telmisartan on agonistic activities for peroxisome proliferator-activated receptor γ among clinically used angiotensin II receptor blockers: drug-target interaction analyses.

    Science.gov (United States)

    Kakuta, Hirotoshi; Kurosaki, Eiji; Niimi, Tatsuya; Gato, Katsuhiko; Kawasaki, Yuko; Suwa, Akira; Honbou, Kazuya; Yamaguchi, Tomohiko; Okumura, Hiroyuki; Sanagi, Masanao; Tomura, Yuichi; Orita, Masaya; Yonemoto, Takako; Masuzaki, Hiroaki

    2014-04-01

    A proportion of angiotensin II type 1 receptor blockers (ARBs) improves glucose dyshomeostasis and insulin resistance in a clinical setting. Of these ARBs, telmisartan has the unique property of being a partial agonist for peroxisome proliferator-activated receptor γ (PPARγ). However, the detailed mechanism of how telmisartan acts on PPARγ and exerts its insulin-sensitizing effect is poorly understood. In this context, we investigated the agonistic activity of a variety of clinically available ARBs on PPARγ using isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) system. Based on physicochemical data, we then reevaluated the metabolically beneficial effects of telmisartan in cultured murine adipocytes. ITC and SPR assays demonstrated that telmisartan exhibited the highest affinity of the ARBs tested. Distribution coefficient and parallel artificial membrane permeability assays were used to assess lipophilicity and cell permeability, for which telmisartan exhibited the highest levels of both. We next examined the effect of each ARB on insulin-mediated glucose metabolism in 3T3-L1 preadipocytes. To investigate the impact on adipogenesis, 3T3-L1 preadipocytes were differentiated with each ARB in addition to standard inducers of differentiation for adipogenesis. Telmisartan dose-dependently facilitated adipogenesis and markedly augmented the mRNA expression of adipocyte fatty acid-binding protein (aP2), accompanied by an increase in the uptake of 2-deoxyglucose and protein expression of glucose transporter 4 (GLUT4). In contrast, other ARBs showed only marginal effects in these experiments. In accordance with its highest affinity of binding for PPARγ as well as the highest cell permeability, telmisartan superbly activates PPARγ among the ARBs tested, thereby providing a fresh avenue for treating hypertensive patients with metabolic derangement. PMID:24424487

  19. Telmisartan induced urticarial vasculitis.

    Science.gov (United States)

    Mahajan, Vikram K; Singh, Ravinder; Gupta, Mrinal; Raina, Rashmi

    2015-01-01

    A 53-year-old man developed urticarial vasculitis following ingestion of telmisartan and hydrochlorothiazide combination for hypertension. Treatment with prednisolone and cetirizine was curative, but his lesions recurred when he continued telmisartan and hydrochlorothiazide against medical advice. Re-challenge with the same doses of telmisartan precipitated similar lesions with telmisartan and not with hydrochlorothiazide. This uncommon cutaneous adverse reaction of angiotensin II receptor blockers has implication for the clinicians as more such cases may become apparent with their wider use than in premarketing studies. PMID:26600649

  20. Telmisartan induced urticarial vasculitis

    Directory of Open Access Journals (Sweden)

    Vikram K Mahajan

    2015-01-01

    Full Text Available A 53-year-old man developed urticarial vasculitis following ingestion of telmisartan and hydrochlorothiazide combination for hypertension. Treatment with prednisolone and cetirizine was curative, but his lesions recurred when he continued telmisartan and hydrochlorothiazide against medical advice. Re-challenge with the same doses of telmisartan precipitated similar lesions with telmisartan and not with hydrochlorothiazide. This uncommon cutaneous adverse reaction of angiotensin II receptor blockers has implication for the clinicians as more such cases may become apparent with their wider use than in premarketing studies.

  1. Telmisartan Ameliorates Fibrocystic Liver Disease in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    Science.gov (United States)

    Yoshihara, Daisuke; Kugita, Masanori; Sasaki, Mai; Horie, Shigeo; Nakanishi, Koichi; Abe, Takaaki; Aukema, Harold M.; Yamaguchi, Tamio; Nagao, Shizuko

    2013-01-01

    Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the

  2. Effect of angiotensin receptor blocker on the expressions of NF-κB PPARγ in adipose tissue of high-fat- diet induced insulin resistant rats%血管紧张素受体阻断剂对高脂诱导的胰岛素抵抗大鼠脂肪组织NF-κB、PPARγ/表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘晓玲; 袁莉; 郭彩红; 黄艳; 杜爱民; 张利莉

    2009-01-01

    The expressions of NF-κB and PPARγ were increased in adipose tissue of insulin resistant rats.The angiotensin receptor blocker decreased NF-κB protein expression by 21%,increased PPARγ protein expression by 28%and diminished adipocyte size,suggesting that these findings may be involved in the improvement of obesity-induced inflammation and insulin resisitance.%胰岛素抵抗大鼠脂肪组织中NF-κB、PPARγ表达增加,血管紧张素受体阻断剂可降低脂肪组织NF-κB蛋白表达21%,增加PPART蛋白表达28%,减小肪细胞体积,这可能是阻断肾素血管紧张素系统改善肥胖脂肪组织炎症和胰岛素抵抗的分子机制之一.

  3. Comparative review of the blood pressure-lowering and cardiovascular benefits of telmisartan and perindopril

    Directory of Open Access Journals (Sweden)

    Wang JG

    2014-04-01

    that the benefits are not a “class effect”, and vary between the different drugs within each class. Hence, the best approach for treatments tailored to individual patient needs should be evidence-based specific drugs, rather than a drug-class recommendation for achieving therapeutic targets. Keywords: hypertension, antihypertensive therapy, clinical outcome, renin–angiotensin system inhibitors, angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker

  4. Angiotensin Receptors, Autoimmunity, and Preeclampsia1

    OpenAIRE

    Xia, Yang; Zhou, Cissy Chenyi; RAMIN, Susan M.; Kellems, Rodney E.

    2007-01-01

    Preeclampsia is a pregnancy-induced hypertensive disorder that causes substantial maternal and fetal morbidity and mortality. Despite being a leading cause of maternal death and a major contributor to maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are poorly understood. Recent studies indicate that women with preeclampsia have autoantibodies that activate the angiotensin receptor, AT1, and that autoantibody-mediated receptor activation contri...

  5. Prospects for angiotensin receptor blockers in diabetic retinopathy

    DEFF Research Database (Denmark)

    Sjølie, Anne Katrin

    2007-01-01

    Retinopathy is the most common microvascular complication of diabetes mellitus, and is an important cause of blindness worldwide. Clinical trials have demonstrated that tight metabolic control inhibits the progression of retinopathy. Good blood pressure control has been shown to be protective in...... type 2 diabetes, and it may also reduce proliferative retinopathy in type 1 diabetes. However, such control is often difficult to achieve in clinical practice, and may be associated with problems such as hypoglycaemia. New therapies are therefore needed to reduce the risk of retinopathy. There is...... growing evidence that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of diabetic retinopathy, and this has led to interest in RAS inhibitors as agents to prevent retinopathy. Several trials have suggested that ACE inhibitor therapy can inhibit progression of retinopathy...

  6. Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy

    OpenAIRE

    Mehdi, Uzma F.; Adams-Huet, Beverley; Raskin, Philip; Vega, Gloria L.; Toto, Robert D.

    2009-01-01

    Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We co...

  7. Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil

    Directory of Open Access Journals (Sweden)

    Carlos Ferrario

    2009-03-01

    Full Text Available Carlos FerrarioHypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USAAbstract: Endothelial dysfunction is the common link between cardiovascular disease risk factors and the earliest event in the cascade of incidents that results in target organ damage. Angiotensin II, the terminal pressor effector arm of the renin-angiotensin-aldosterone system, increases blood pressure (BP by vasoconstriction and sodium and fluid retention, and has a pro-oxidative action that induces endothelial dysfunction and contributes to vascular remodeling. Angiotensin receptor blockers (ARBs reduce BP and morbidity and mortality in patients with hypertension, ventricular hypertrophy, diabetes mellitus, and renal disease. Olmesartan medoxomil is a long-acting, well-tolerated, effective ARB that prevents or reverses endothelial dysfunction in animal models of atherosclerosis, hypertension, diabetes, nephropathy, and retinopathy. Olmesartan medoxomil, a prodrug of olmesartan approved for the treatment of hypertension, has been shown to ameliorate endothelial dysfunction in patients with hypertension or diabetes. In randomized studies, the drug reduces vascular inflammation and the volume of large atherosclerotic plaques, increases the number of regenerative endothelial progenitor cells in the peripheral circulation, improves endothelium-dependent relaxation, and restores the normal resistance vessel morphology. Importantly, the impact of olmesartan medoxomil on endothelial dysfunction is thought to be independent of BP lowering.Keywords: endothelial dysfunction, angiotensin receptor blocker, olmesartan medoxomil, hypertension, atherosclerosis 

  8. [Angiotensin-receptor- and neprilysin-inhibition: a new option against heart failure].

    Science.gov (United States)

    Bruhn, Claudia

    2016-01-01

    The molecular combination of sacubitril and valsartan (Entresto) is a new drug for reducing the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. It is usually administered in conjunction with other heart failure therapies, instead of an ACE inhibitor or an angiotensin-receptor blocker (ARB). In studies, sacubitril/ valsartan was superior to enalapril in reducing the risks of death and hospitalization for heart failure. Possible side effects of sacubitril/valsartan are hypotension, angioedema, impaired renal function and elevation in serum potassium levels. The drug should not be used in times of pregnancy and breast feeding, in patients with servere hepatic impairment (Child-Pugh C) and in combination with aliskiren in patients with diabetes. PMID:26975167

  9. Telmisartan induced urticarial vasculitis

    OpenAIRE

    Mahajan, Vikram K.; Ravinder Singh; Mrinal Gupta; Rashmi Raina

    2015-01-01

    A 53-year-old man developed urticarial vasculitis following ingestion of telmisartan and hydrochlorothiazide combination for hypertension. Treatment with prednisolone and cetirizine was curative, but his lesions recurred when he continued telmisartan and hydrochlorothiazide against medical advice. Re-challenge with the same doses of telmisartan precipitated similar lesions with telmisartan and not with hydrochlorothiazide. This uncommon cutaneous adverse reaction of angiotensin II receptor bl...

  10. A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention

    OpenAIRE

    Ji-Guang Wang

    2009-01-01

    Ji-Guang WangCentre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaAbstract: Stroke is a leading cause of death and disability worldwide. The importance of lowering blood pressure for reducing the risk of stroke is well established. However, not all the benefits of antihypertensive treatments in stroke can be accounted for by reductions in BP and there may be differences between antihypertensive classes as to w...

  11. Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ The benefits of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) beyond blood pressure reduction have been proven through many large studies (HOPE, LIFE) in high risk CVD patients;1 post hoc studies have shown reductions in new onset type 2 diabetes mellitus (DM).

  12. Effects of Different Doses of Telmisartan on Paroxysmal Atrial Fibrillation%不同剂量的替米沙坦对阵发性心房颤动的影响

    Institute of Scientific and Technical Information of China (English)

    王志敬; 周茂峰; 周辉; 许东伟

    2011-01-01

    Objective:To investigate effects of different doses of telmisartan on the prevention of paroxysmal atrial fibrillation and explore dose-response relations and mechanisms. Methods: A total of 123 hypertensive patients with cardiac insufficiency or left ventricular hypertrophy or coronary heart disease, who were met the inclusion criteria, were randomly divided into telmisartan 20mg (n = 30), 40mg (n = 30), 80mg (n = 31 ) and the control group (n = 32), respectively. Patients in telmisartan groups and control group were treated with the same dosage and administration duration of amiodarone. Patients in the control group were administered other antihypertensive drugs excluding angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). All the patients were followed up for six months. The numbers of cases of atrial fibrillation recurrence, episodes of atrial fibrillation, time of the first atrial fibrillation recurrence and changes of left atrial and ventricular dimension were recorded. Results: There was more prolonged first recurrence time (P<0.05), less episodes of atrial fibrillation and numbers of cases of atrial fibrillation recurrence (P<0. 05) in telmisartan 80mg group compared with those of the control group in six months. Left ventricular end diastolic and left atrial dimension showed similar results between telmisartan 80mg group and control group during the three-month tracing period (P>0. 05) while reduced significantly in six months (P<0.05). All of the indicators mentioned above in telmisartan 20mg and 40mg group were not significantly different from the control group (P>0. 05). Conclusions: Different doses of telmisartan have different effects on preventing atrial fibrillation recurrence and there are dose-response relations between telmisartan and its effect. The mechanism of effects is primarily relevant to degrees of inhibition of atrial and ventricular remodeling.%目的:观察不同剂量的替米沙坦对

  13. 血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂对扩张型心肌病内皮功能的影响%Effects of Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker to Endothelium Function in Idiopathic Dilated Cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    陈嫦娥

    2014-01-01

    目的:探讨血管紧张素转换酶抑制剂(angiotension converting enzyme inhibitor,ACEI)达爽和血管紧张素受体拮抗剂(angiotension receptor blocker,ARB)安博维对扩张型心肌病患者内皮功能的影响。方法:采用超声肱动脉内径测量法,对20例正常人和24例扩张型心肌病患者服用达爽或安博维治疗前后肱动脉内径在反应性充血后和含服硝酸甘油后的百分变化率进行比较,分析ACE-I和ARB对扩张型心肌病内皮功能的影响。结果:治疗前扩张型心肌病患者肱动脉内径在反应性充血前后变化较小,但与对照组比较差异均有统计学意义(P0.05)。结论:ACE-I和ARB均可改善扩张型心肌病的内皮功能,两者在治疗效果上差异不明显。%Objective:To evaluate the effects of angiotension converting enzyme inhibitor(ACEI) imidapril or angiotension receptor blocker (ARB)irbesartan on the endothelial function in patients with idiopathic dilated cardiomyopathy by transthoracic echocardiography.Method:Twenty-four patients with idiopathic dilated cardiomyopathy and 20 healthy subjects were included in this study. Brachial artery endothelium dependent dilation function [flow-mediated dilation(FMD)] and nitroglycerin-induced percent changes in the brachial artery diameter were measured by two-dimensional ultrasound before and after the treatment of imidapril or irbesartan and the effect of ACE-I and ARB on endothelial function in dicated cordiomyopathy were analyzed. Result:The treatment of dilated cardiomyopathy patients in the brachial artery diameter had smaller changes before and after the reactive hyperemia,but with the control group had significant difference(P0.05).Conclusion:ACE-I and ARB can improve the endothelial function in patients with dilated cardiomyopathy,the treatment effect is not obvious difference.

  14. Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats

    Institute of Scientific and Technical Information of China (English)

    En-tong YI; Rui-xia LIU; Yan WEN; Cheng-hong YIN

    2012-01-01

    Aim: To evaluate the antifibrotic effect of telmisartan,an angiotensin Ⅱ receptor blocker,in bile duct-ligated rats.Methods: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats,model rats underwent common bile duct ligation (BDL),and BDL rats treated with telmisartan (8 mg/kg,po,for 4 weeks).The animals were sacrificed on d 29,and liver histology was examined,the Knodell and Ishak scores were assigned,and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining.The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot,respectively.Results: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35,P=0.015).However,there was no significant difference in inflammation between the two groups,both of which showed moderate inflammation.Histologically,treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis.Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS,and decreased the mRNA levels of ACE,angiotensin Ⅱ type 1 receptor (AT1-R),collagen type Ⅲ,and transforming growth factor β1 (TGF-β1).Moreover,treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins,and inhibited the expression levels of ACE and AT1-R protein.Conclusion: Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.

  15. β受体阻滞剂分别联合血管紧张素受体拮抗剂和钙离子拮抗剂治疗江门地区中青年高血压的临床效果观察%Curative Effect of Beta-blockers Respectively Combination of Angiotensin Receptor Blockers and Calcium Antagonists in the Treatment of Young and Middle-Aged High Blood Pressure in Jiangmen

    Institute of Scientific and Technical Information of China (English)

    黄享贞; 钟洁霞

    2015-01-01

    目的:比较β受体阻滞剂分别联合血管紧张素受体拮抗剂(ARB)和钙离子拮抗剂(CCB)治疗江门地区中青年高血压的治疗效果。方法:选取2012年12月-2014年12月收治的江门地区中青年高血压患者300例,随机数字表法分为观察组和对照组各150例。观察组患者给予ARB联合β受体阻滞剂治疗,对照组给予CCB联合β受体阻滞剂治疗,观察两组治疗前后的血压、心率变化情况以及降压疗效和症状改变情况。结果:治疗8周后两组患者的血压、心率均较治疗前下降(P0.05),观察组心率下降较对照组明显,差异有统计学意义(P0.05),heart rate decline in treatment group and control group,the difference was statistically significant(P<0.05).In terms of hypertension treatment,observation group total effective rate was 94.67%,control group total effective rate was 82.00%, total effective rate of observation group was obviously higher than that of control group,the difference was statistically significant (P<0.05).In terms of symptom improvement,observation group total effective rate was 96.67%,control group total effective rate was 84.67%,total effective observation group was obviously higher than that of control group,the difference was statistically significant(P<0.05).Conclusion:The application of combined beta-blockers ARB can significantly reduce the diastolic and systolic blood pressure of patients,slow heart rate,and in terms of antihypertensive effects and symptoms improve curative effect is good,worthy of clinical promotion.

  16. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers

    DEFF Research Database (Denmark)

    Lambers Heerspink, Hiddo J; Holtkamp, Frank A; Parving, Hans-Henrik;

    2012-01-01

    intake during treatment, measured as the 24-h urinary sodium/creatinine ratio of 1177 patients with available 24-h urinary sodium measurements. ARB compared to non-RAASi-based therapy produced the greatest long-term effects on renal and cardiovascular events in the lowest tertile of sodium intake....... Compared to non-RAASi, the trend in risk for renal events was significantly reduced by 43%, not changed, or increased by 37% for each tertile of increased sodium intake, respectively. The trend for cardiovascular events was significantly reduced by 37%, increased by 2% and 25%, respectively. Thus...

  17. Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade

    OpenAIRE

    Shang, Fenqing; Zhang, Jiao; Li, Zhao; Zhang, Jin; Yin, Yanjun; Wang, Yaqiong; Marin, Traci L.; Gongol, Brendan; Xiao, Han; Zhang, You-Yi; Chen, Zhen; Shyy, John Y-J; Lei, Ting

    2016-01-01

    Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose) polymerase 1 (PARP1). Biguanides and angiotensin II receptor blockers (ARBs) such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs), diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated pro...

  18. [AT1-blockers in the treatment of hypertension: summary].

    Science.gov (United States)

    Jr, Jiří Widimský

    2016-02-01

    Angiotensin receptor antagonists (AT(1)-blockers) are considered as one of the major classes of antihypertensive drugs suitable for monotherapy as well as for combination treatment. AT(1)-blockers have comparable antihypertensive efficacy with other major classes of antihypertensive drugs. AT(1)-blockers are considered by current guidelines of Czech society of hypertension altogether with ACE-inhibitors and calcium channel blockers as universal antihypertensive drug class. AT(1)-blockers has the lowest profile of side-effects among all antihypertensive drug classes and thus very high persistence to therapy. Mechanisms of antihypertensive effects of AT(1)-blockers are discussed altogether with the results of large clinical trials and indications in the treatment of hypertension. PMID:27172437

  19. New standards in hypertension and cardiovascular risk management: focus on telmisartan

    Directory of Open Access Journals (Sweden)

    Domenico Galzerano

    2010-03-01

    Full Text Available Domenico Galzerano1, Cristina Capogrosso4, Sara Di Michele2, Antonio Galzerano1, Paola Paparello1, Diana Lama3, Carlo Gaudio21Department of Cardiology, San Gennaro Hospital, Naples, Italy; 2Department of Heart and Great Vessels, A. Reale, La Sapienza University, Rome, Italy; 3V Division of Internal Medicine, II University, Naples, Italy; 4Cardiology Division, San Giovanni Bosco Hospital, Naples, ItalyAbstract: Blockade of the renin–angiotensin system is an important approach in managing high blood pressure, and has increasingly been shown to affect cardiovascular disease processes mediated by angiotensin II throughout the cardiovascular and renal continua. Telmisartan is an angiotensin II receptor blocker (ARB displaying unique pharmacologic properties, including a longer half life than any other ARB, that result in large and sustained reductions of blood pressure. In patients with mild-to-moderate hypertension, telmisartan has proved superior to other antihypertensive agents (valsartan, losartan, ramipril, perindopril, and atenolol in controlling blood pressure particularly towards the end of the dosing interval. There is also clinical evidence that telmisartan reduces left ventricular hypertrophy, reduces arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET® study has demonstrated that telmisartan has similar cardiovascular protective effects to ramipril in a large, high-risk patient population but was better tolerated. The powerful and sustained blood pressure control apparent in clinical trials, together with cardiovascular protection and tolerability demonstrated in ONTARGET® means that telmisartan may be a preferred option for patients with hypertension.Keywords: angiotensin II receptor blocker, cardiovascular disease, hypertension, renin–angiotensin system, telmisartan

  20. Telmisartan attenuates chronic ciclosporin A nephrotoxicity in a pig model

    DEFF Research Database (Denmark)

    Cibulskyte, Donata; pedersen, michael; Hørlyck, Arne;

    2007-01-01

    BACKGROUND: We have previously demonstrated renal enlargement in pigs treated with ciclosporin A (CsA) 10 mg/kg/day orally for 6 months. The aim of the study was to investigate the effect of oral CsA (10 mg/kg/day) for 12 months on kidney structure and function and the potential renoprotective role...... of angiotensin II (Ang II) receptor blocker telmisartan on chronic CsA nephrotoxicity in pigs. METHODS: Fourteen Göttingen minipigs aged 12-14 months were included: pigs received either CsA 10 mg/kg/day (n = 7) or CsA 10 mg/kg/day + telmisartan 40 mg/day (n = 7) orally for 12 months. At week 0, 12...

  1. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Danon, Abraham; Apte, Ron N.; Fleisher-Berkovich, Sigal

    2016-01-01

    The circulating renin-angiotensin system (RAS), including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R)) some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer’s disease (AD) models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker) on tumor necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and nitric oxide (NO) release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD) mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor). Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS) -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia) both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the progression

  2. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

    Directory of Open Access Journals (Sweden)

    Nofar Torika

    Full Text Available The circulating renin-angiotensin system (RAS, including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker on tumor necrosis factor-α (TNF-α, interleukin 1-β (IL1-β and nitric oxide (NO release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor. Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the

  3. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Danon, Abraham; Apte, Ron N; Fleisher-Berkovich, Sigal

    2016-01-01

    The circulating renin-angiotensin system (RAS), including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R)) some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD) models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker) on tumor necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and nitric oxide (NO) release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD) mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor). Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS) -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia) both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the progression of

  4. Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet.

    Science.gov (United States)

    Yanagihara, Hayato; Ushijima, Kentaro; Arakawa, Yusuke; Aizawa, Ken-Ichi; Fujimura, Akio

    2016-07-01

    Although telmisartan, an angiotensin II receptor blocker (ARB), has an agonistic action for proliferator-activated receptor (PPAR)-γ in vitro, it remains to be determined whether telmisartan exerts such an action in vivo using a non-toxic dose (hypertriglyceridemia and renal damage, which were improved by ARBs. Protective effects of telmisartan and olmesartan did not significantly differ. In addition, in vitro study showed that 1 μM of telmisartan did not elevate the mRNA expression of adipose protein 2, which is a PPAR-γ-stimulated adipogenic marker gene, in preadipocytes with 3% albumin. To obtain 1 μM of plasma concentration, oral dose of telmisartan was calculated to be 6 mg/kg, which indicates that PPAR-γ agonistic action is negligible with a non-toxic dose of telmisartan (hypertriglyceridemia and renal damage in SHR fed a HFD. As beneficial effects of telmisartan and olmesartan did not significantly differ, these were mediated through the PPAR-γ-independent actions. PMID:27430988

  5. Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy

    Science.gov (United States)

    Mehdi, Uzma F.; Adams-Huet, Beverley; Raskin, Philip; Vega, Gloria L.

    2009-01-01

    Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio ≥300 mg/g) who all received lisinopril (80 mg once daily). We randomly assigned the patients to placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 wk. We obtained blood and urine albumin, urea, creatinine, electrolytes, A1c, and ambulatory BP at baseline, 24, and 48 wk. Compared with placebo, the urine albumin-to-creatinine ratio decreased by 34.0% (95% CI, −51.0%, −11.2%, P = 0.007) in the group assigned to spironolactone and by 16.8% (95% CI, −37.3%, +10.5%, P = 0.20) in the group assigned to losartan. Clinic and ambulatory BP, creatinine clearance, sodium and protein intake, and glycemic control did not differ between groups. Serum potassium level was significantly higher with the addition of either spironolactone or losartan. In conclusion, the addition of spironolactone, but not losartan, to a regimen including maximal ACE inhibition affords greater renoprotection in diabetic nephropathy despite a similar effect on BP. These results support the need to conduct a long-term, large-scale, renal failure outcomes trial. PMID:19926893

  6. Angiotensin II Receptor Blocker Ameliorates Stress-Induced Adipose Tissue Inflammation and Insulin Resistance

    OpenAIRE

    Motoharu Hayashi; Kyosuke Takeshita; Yasuhiro Uchida; Koji Yamamoto; Ryosuke Kikuchi; Takayuki Nakayama; Emiko Nomura; Xian Wu Cheng; Tadashi Matsushita; Shigeo Nakamura; Toyoaki Murohara

    2014-01-01

    A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restra...

  7. Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells

    Directory of Open Access Journals (Sweden)

    Juan Li

    2014-03-01

    Full Text Available Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis.

  8. Effects and mechanism of telmisartan on prevention of atrial fibrillation recurrence in hypertensive patients with paroxysmal atrial fibrillation%替米沙坦预防高血压并阵发性房颤患者房颤复发的效果及机制

    Institute of Scientific and Technical Information of China (English)

    王志敬; 周茂峰; 许东伟; 周辉; 孙波

    2011-01-01

    Objective To investigate the effects and mechanism of telmisartan on prevention of atrial fibrillation recurrence in hypertensive patients with paroxysmal atrial fibrillation. Methods A total of 186 hypertensive patients with paroxysmal atrial fibrillation were randomly divided into the observation group ( n = 91 ) and the control group ( n = 95 ), all the patients were treated with amiedarone and telmisartan 20-80 mg/d were administered simultaneously in the observation group, course of the treatment was six months; patients were given calcium antagonists, beta-blockers or diuretics as additional treatment if their blood pressures were not well controlled, while patients of the control group did not receive antihypertensive drugs including angiotensin converting enzyme inhibitors and angiotensin receptor blockers. During the follow-up time, changes of blood pressure, numbers of cases of atrial fibrillation recurrence, episodes of atrial fibrillation, time of the first atrial fibrillation recurrence and changes of left ventricular end diastolic dimension(LVEDD) and left atrial dimension (LAD) were recorded. Results There were no significant differences in blood pressure between two groups; there was more prolonged first recurrence time, less episodes of atrial fibrillation and numbers of cases of atrial fibrillation recurrence in the observation group compared to those of the control group; LVEDD and LAD of the observation group significantly reduced compared with those of the control group at the end of 6 months( P < 0.05). Conclusions Telmisartan can prevent atrial fibrillation recurrence in the hypertensive patients with paroxysmal atrial fibrillation, the meeharism may be inhibition of atrial remodeling.%目的 探讨替米沙坦预防高血压病并阵发性房颤患者房颤复发的效果及其作用机制.方法 将186例高血压并阵发性房颤患者随机分为观察组91例和对照组95例,两组均口服胺碘酮,在此基础上观

  9. Rational Design, Efficient Synthesis, Biological Evaluation of New Ν,Ν'-bis-substituted Butylimidazole Analogs as Potent Angiotensin Receptor Blockers

    Czech Academy of Sciences Publication Activity Database

    Agelis, G.; Resvani, A.; Koukoulitsa, C.; Afantitis, A.; Melagraki, G.; Siafaka, A.; Gkini, E.; Tůmová, Tereza; Spyridaki, K.; Kalavrizioti, D.; Androutsou, M-E.; Slaninová, Jiřina; Liapakis, G.; Vlahakos, D.; Mavromoustakos, T.; Matsoukas, J.

    2012-01-01

    Roč. 18, S1 (2012), S123-S123. ISSN 1075-2617. [European Peptide Symposium /32./. 02.09.2012-07.09.2012, Athens] Institutional research plan: CEZ:AV0Z40550506 Keywords : angiotensin II AT1 receptor * in vitro * antagonism * inhibitor * in vitro antagonism * synthesis Subject RIV: CE - Biochemistry

  10. The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Masashi Nishida

    2012-03-01

    Full Text Available Background: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1. The effects of the apelin/APJ system on renal fibrosis still remain unclear. Methods: We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO model. Results: We obtained the following results: (1 At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS in the UUO kidney were increased compared to those in the nonobstructed kidney. (2 AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3 Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4 Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group. Conclusion: These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis.

  11. Cognitive enhancing effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on learning and memory

    Directory of Open Access Journals (Sweden)

    V S Nade

    2015-01-01

    Conclusion: The results suggest that the cognitive enhancing effect of ACEI and ARBs may be due to inhibition of AChE or by regulation of antioxidant system or increase in formation of angiotensin IV.

  12. Role of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in hypertension of chronic kidney disease and renoprotection. Study results

    OpenAIRE

    Baltatzi, M; Savopoulos, Ch; Hatzitolios, A

    2011-01-01

    Chronic kidney disease (CKD) is a global health problem associated with considerable morbidity and mortality and despite advances in the treatment of end stage renal disease (ESRD) mechanisms to prevent and delay its progression are still being sought. The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in many of the pathophysiologic changes that lead to progression of renal disease. Traditionally RAAS was considered as an endocrine system and its principal role was to maint...

  13. Comparison of the efficacy and tolerability of telmisartan and enalapril in patients of mild to moderate essential hypertension

    Directory of Open Access Journals (Sweden)

    Akat Pramod

    2010-01-01

    Full Text Available Background : Theoretically, angiotensin II receptor blockers (ARBs have certain advantages over angiotensin-converting enzyme inhibitors, but the contribution of these advantages to the clinical effect of ARBs is not known. Objective : To compare the efficacy and tolerability of telmisartan with enalapril in patients of essential hypertension. Materials and Methods : Patients of mild to moderate hypertension were randomized to receive either 40 mg of telmisartan or enalapril 10 mg once a day orally for 12 weeks. At each visit, the systolic blood pressure (BP, diastolic BP and heart rate of each patient were recorded. Investigations such as hemogram hemoglobin, total leucocytes count (Hb, TLC, serum creatinine, serum glutamic oxaloacetic transaminase, serum glutamic pyruric transaminase (SGOT, SGPT random blood sugar and urine examination were performed at baseline and after 12 weeks of the treatment period. Results : The mean reduction in systolic BP in the telmisartan/enalapril group was 26.38 ± 10.98/26.74 ± 8.24 mmHg while the mean reduction in diastolic BP in the telmisartan/enalapril group was 14 ± 2.98/9.71 ± 4.23 mmHg, respectively, at 12 weeks. When the reduction in systolic BP in the two groups was compared, there was no significant difference between the groups (P > 0.05. However, the mean reduction in diastolic BP achieved with telmisartan at 12 weeks was significantly higher (P < 0.001 than that achieved with enalapril after the corresponding period. The overall frequency of adverse-effects was similar. However, in the enalapril group, the incidence of dry cough was higher as compared to that in the telmisartan group (11.43% vs. 0%, respectively; P < 0.05. Conclusion : Telmisartan produces a greater reduction in diastolic BP than enalapril and is free from the adverse-effect of dry cough that is commonly encountered with enalapril.

  14. Telmisartan attenuates the inflamed mesenteric adipose tissue in spontaneous colitis by mechanisms involving regulation of neurotensin/microRNA-155 pathway.

    Science.gov (United States)

    Li, Yi; Zuo, Lugen; Zhu, Weiming; Gong, Jianfeng; Zhang, Wei; Guo, Zhen; Gu, Lili; Li, Ning; Li, Jieshou

    2015-02-15

    Mesenteric adipose tissue hypertrophy is unique to Crohn's disease while the molecular basis of the crosstalk between MAT and the intestinal inflammation is largely unknown. Telmisartan is an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-receptor-γ agonist which has beneficial effects on fat distribution and pro-inflammatory adipokine expression. We evaluated the effect of telmisartan upon mesenteric adipose tissue alterations and inflammatory features in IL-10(-)/(-) mice. We found that treatment with telmisartan significantly ameliorated the severity of colitis in IL-10(-)/(-) mice. Additionally, administration of telmisartan was associated with restoration of mesenteric adipose tissue adipocyte morphology and the expression of adipokines. Furthermore, telmisartan treatment suppressed the neurotensin/microRNA-155 pathway in mesenteric adipose tissue from spontaneous colitis which was confirmed by an in vitro study using cultured mesenteric adipose tissue from Crohn's disease patients. Administration of telmisartan showed promising results in spontaneous colitis which was associated with the attenuated mesenteric adipose tissue alteration which at least in part, was associated with its activity in the regulation of the neurotensin/microRNA-155 pathway. These results support the hypothesis that regulating the abnormal immune response in adipose tissue is an important target for the treatment of Crohn's disease. PMID:25576685

  15. Angiotensin Receptor Blockade Increases Pancreatic Insulin Secretion and Decreases Glucose Intolerance during Glucose Supplementation in a Model of Metabolic Syndrome

    OpenAIRE

    Rodriguez, Ruben; Viscarra, Jose A.; Minas, Jacqueline N.; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M.

    2012-01-01

    Renin-angiotensin system blockade improves glucose intolerance and insulin resistance, which contribute to the development of metabolic syndrome. However, the contribution of impaired insulin secretion to the pathogenesis of metabolic syndrome is not well defined. To assess the contributions of angiotensin receptor type 1 (AT1) activation and high glucose intake on pancreatic function and their effects on insulin signaling in skeletal muscle and adipose tissue, an oral glucose tolerance test ...

  16. Design and development of a self-nanoemulsifying drug delivery system for telmisartan for oral drug delivery

    OpenAIRE

    Patel, Jaydeep; Kevin, Garala; Patel, Anjali; Raval, Mihir; Sheth, Navin

    2011-01-01

    Background and Aim: Telmisartan (TEL) is an angiotensin II receptor blocker (ARB) antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water soluble TEL. Materials and Methods: The solubility of TEL in various oils was determined to identify the oil phase of a SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseud...

  17. Pilot data on telmisartan short-term effects on glucose metabolism in the olfactory tract in Alzheimer's disease

    OpenAIRE

    Imabayashi, Etsuko; Matsuda, Hiroshi; Yoshimaru, Kimiko; Kuji, Ichiei; Seto, Akira; Shimano, Yasumasa; Ito, Kimiteru; Kikuta, Daisuke; Shimazu, Tomokazu; Araki, Nobuo

    2011-01-01

    The possible effect of antihypertensive therapy on Alzheimer's disease (AD) has been studied, and angiotensin II receptor blockers (ARBs) have been suggested to exert an effect on cognitive decline. The purpose of this study is to clarify the functional effects of telmisartan, a long-acting ARB, on AD brain using prospective longitudinal 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies. For this purpose, brain glucose metabolism of four hypertensive patients with AD was e...

  18. Angiotensin-2-mediated Ca2+ signaling in the retinal pigment epithelium: role of angiotensin-receptor-associated-protein and TRPV2 channel.

    Directory of Open Access Journals (Sweden)

    Rene Barro-Soria

    Full Text Available Angiotensin II (AngII receptor (ATR is involved in pathologic local events such as neovascularisation and inflammation including in the brain and retina. The retinal pigment epithelium (RPE expresses ATR in its AT1R form, angiotensin-receptor-associated protein (Atrap, and transient-receptor-potential channel-V2 (TRPV2. AT1R and Atrap co-localize to the basolateral membrane of the RPE, as shown by immunostaining. Stimulation of porcine RPE (pRPE cells by AngII results in biphasic increases in intracellular free Ca(2+inhibited by losartan. Xestospongin C (xest C and U-73122, blockers of IP3R and PLC respectively, reduced AngII-evoked Ca(2+response. RPE cells from Atrap(-/- mice showed smaller AngII-evoked Ca(2+peak (by 22% and loss of sustained Ca(2+elevation compared to wild-type. The TRPV channel activator cannabidiol (CBD at 15 µM stimulates intracellular Ca(2+-rise suggesting that porcine RPE cells express TRPV2 channels. Further evidence supporting the functional expression of TRPV2 channels comes from experiments in which 100 µM SKF96365 (a TRPV channel inhibitor reduced the cannabidiol-induced Ca(2+-rise. Application of SKF96365 or reduction of TRPV2 expression by siRNA reduced the sustained phase of AngII-mediated Ca(2+transients by 53%. Thus systemic AngII, an effector of the local renin-angiotensin system stimulates biphasic Ca(2+transients in the RPE by releasing Ca(2+from cytosolic IP3-dependent stores and activating ATR/Atrap and TRPV2 channels to generate a sustained Ca(2+elevation.

  19. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

    OpenAIRE

    Harel, Ziv; Gilbert, Cameron; Wald, Ron; Bell, Chaim; Perl, Jeff; Juurlink, David; Beyene, Joseph; Shah, Prakesh S.

    2012-01-01

    Objective To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011. Study selection Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers w...

  20. Angiotensin receptors in an Australian marsupial, the brushtail possum Trichosurus vulpecula

    Energy Technology Data Exchange (ETDEWEB)

    Sernia, C.; Lello, P.; Thomas, W.G. (Univ. of Queensland, St Lucia (Australia))

    1990-01-01

    In this study, the binding properties of angiotensin receptors were examined in the liver, adrenal, brain, and vascular tissue of the brushtail possum, Trichosurus vulpecula. With 125I-Ile5-angiotensin II as the radioligand, the binding affinity (Ka) and receptor number (R0) were estimated for the liver (Ka = 3.60 +/- 0.31 liters/nmol; R0 = 23.8 +/- 1.30 pmol/g tissue; n = 8) and adrenal (Ka = 1.68 +/- 0.29 liters/nmol; R0 = 1.67 +/- 0.23 pmol/g tissue; n = 8). Specific binding was not found in any of seven areas of the possum brain (n = 6), whereas the expected binding was present in similar areas of the rat brain. Using angiotensin III or the antagonist Sar1-Ala8-angiotensin II as radioligands or changing the composition of the incubation buffer did not alter the outcome. Moreover, the intracerebroventricular injection of 1 and 5 nmol of angiotensin II did not elicit an increase in blood pressure which could be attributed to brain angiotensin II (AII) receptors. Ligand affinities of the adrenal and liver receptors were found to be in the following decreasing order: Val5-AII greater than Ile5-AII = Ile5-AIII greater than Sar1-Ala8-AII greater than Sar1-Gly8-AII greater than Sar1-Leu8-AII greater than Ile5-AI greater than hexapeptide greater than Phe3-Tyr8-AII. The cardiovascular AII receptor was investigated by generating dose-response curves of the pressor activity of Ile5-AII and six AII analogs infused intravenously. It was concluded that liver, adrenal, and vascular AII receptors in the marsupial possum have characteristics similar to those in eutherian mammals. However, the failure to find brain AII receptors raises the possibility that those functions mediated by such receptors in the eutherian brain are absent in the possum and perhaps other marsupials.

  1. Angiotensin receptors in an Australian marsupial, the brushtail possum Trichosurus vulpecula

    International Nuclear Information System (INIS)

    In this study, the binding properties of angiotensin receptors were examined in the liver, adrenal, brain, and vascular tissue of the brushtail possum, Trichosurus vulpecula. With 125I-Ile5-angiotensin II as the radioligand, the binding affinity (Ka) and receptor number (R0) were estimated for the liver (Ka = 3.60 +/- 0.31 liters/nmol; R0 = 23.8 +/- 1.30 pmol/g tissue; n = 8) and adrenal (Ka = 1.68 +/- 0.29 liters/nmol; R0 = 1.67 +/- 0.23 pmol/g tissue; n = 8). Specific binding was not found in any of seven areas of the possum brain (n = 6), whereas the expected binding was present in similar areas of the rat brain. Using angiotensin III or the antagonist Sar1-Ala8-angiotensin II as radioligands or changing the composition of the incubation buffer did not alter the outcome. Moreover, the intracerebroventricular injection of 1 and 5 nmol of angiotensin II did not elicit an increase in blood pressure which could be attributed to brain angiotensin II (AII) receptors. Ligand affinities of the adrenal and liver receptors were found to be in the following decreasing order: Val5-AII greater than Ile5-AII = Ile5-AIII greater than Sar1-Ala8-AII greater than Sar1-Gly8-AII greater than Sar1-Leu8-AII greater than Ile5-AI greater than hexapeptide greater than Phe3-Tyr8-AII. The cardiovascular AII receptor was investigated by generating dose-response curves of the pressor activity of Ile5-AII and six AII analogs infused intravenously. It was concluded that liver, adrenal, and vascular AII receptors in the marsupial possum have characteristics similar to those in eutherian mammals. However, the failure to find brain AII receptors raises the possibility that those functions mediated by such receptors in the eutherian brain are absent in the possum and perhaps other marsupials

  2. Expression of Astrocytic Type 2 Angiotensin Receptor in Central Nervous System Inflammation Correlates With Blood-Brain Barrier Breakdown

    DEFF Research Database (Denmark)

    Füchtbauer, Laila; Toft-Hansen, Henrik; Khorooshi, Reza;

    2010-01-01

    The blood-brain barrier (BBB), a complex of endothelial and glial barriers, controls passage of cells and solutes between the blood and central nervous system (CNS). Blood-brain barrier breakdown refers to entry of cells and/or solutes. We were interested whether the renin-angiotensin system is...... involved during BBB breakdown. We studied the type 2 angiotensin receptor AT(2) because of its suggested neuroprotective role. Two models of brain inflammation were used to distinguish solute versus cellular barrier functions. Both leukocytes and horseradish peroxidase (HRP) accumulated in the perivascular...

  3. H2 blockers

    Science.gov (United States)

    Peptic ulcer disease - H2 blockers; PUD - H2 blockers; Gastroesophageal reflux - H2 blockers ... provider about your symptoms. If you have a peptic ulcer, your provider may prescribe H2 blockers along with ...

  4. Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients

    Directory of Open Access Journals (Sweden)

    David C Evans

    2014-01-01

    Full Text Available Purpose: Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. Materials and Methods: Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB, beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. Results: Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%. Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. Conclusions: Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response.

  5. Local and systemic effects of angiotensin receptor blockade in an emphysema mouse model

    OpenAIRE

    Raupach, Tobias; Lüthje, Lars; Kögler, Harald; de Duve, Christian; Schweda, Frank; Hasenfuß, Gerd; Andreas, Stefan

    2011-01-01

    Abstract Objectives COPD with emphysema causes marked neurohumoral activation. Angiotensin II receptors are highly expressed within the lung and interfere with mechanisms involved in the progression of emphysema. This study examined the effects of an angiotensin II receptor blocker (ARB) on pulmonary and systemic manifestations of emphysema in a mouse model. Methods Female NMRI mice received five intratracheal instillations of porcine pancreatic ela...

  6. Efecto de telmisartan sobre marcadores del remodelado óseo en pacientes hipertensos Telmisartan effect's on remodelling bone markers in hypertensive patients

    Directory of Open Access Journals (Sweden)

    J. L. Pérez-Castrillón

    2012-02-01

    remodelado aunque se observó un descenso de la glucosa en pacientes con niveles de vitamina D por encima de 20 ng/ml (135 ± 53 mg/dl vs 119 ± 39 mg/dl, p = 0,01. Los pacientes tratados con IECAS disminuyen los valores de tensión arterial sistólica pero la diastólica no muestra cambios. Conclusiones: Telmisartan tiene un efecto neutro a nivel de los marcadores del remodelado óseo.Introduction: The telmisartan is an angiotensin II receptor blocker (ARB with a few own characteristics that it allows us to obtain a few additional benefits. It displays the ability to act as a partial agonist of PPARgamma. On the other hand, PPAR gamma intervenes in the control of bone remodelling though with not concordant results. The objective of this study to value the effect of telmisartan on bone markers in hypertensive patients. Subjects: A sample of 31 hypertensive patients with hypertension were included. The dose of telmisartan was of 80 mg/24 h and the period of follow-up was 12 weeks. The control group included 32 hypertensive patients treated before with IECA (enalapril-20 mg/24 h - or quinapril - 40 mg/24 hours. The following parameters were determined P1NP, β-CTX, 25OHD and PTH , osteocalcin, insulin and adiponectin. Results: The patients treated with Telmisartan shown a significantly decrease in systolic blood pressure (156 ± 19 mmHg vs 133 ± 15 mmHg, p = 0.001 and diastolic blood pressure (92 ± 9 mmHgvs 82 ± 6 mmHg, p = 0.01 . Changes were not observed in other parameter, PTHi (48 ± 22 pg/ml vs 45 ± 22 pg/ml, p > 0.05 and 25-vitamin D (21 ± 10 ng/ml vs 25 ± 8 ng/ml, p > 0.05, CTX (0.195 ± 0.12 ng/ml vs 0.221 ± 0.13 ng/ml, p > 0.05, PINP (39 ± 20 ng/ml vs 40 ± 19 ng/ml, p > 0.05, osteocalcin (11 ± 9 ng/ml vs 11 ± 5 ng/ml, p > 0.05, glucose, adiponectin, insulin and HOMA. When the patients divided in two groups depending on the levels of vitamin D (insufficient and not insufficient, with a cut of 20 ng/ml, there was changes on bone markers but a decrease of the

  7. How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

    2010-01-01

    An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time of...... heart failure diagnosis have similar prognosis.Treatment options for patients developing heart failure while already treated with ACE inhibitors/ARBs and beta-blockers are very limited if current heart failure guidelines are followed. In this review possible strategies are outlined and important areas...

  8. How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

    2010-01-01

    An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time...... of heart failure diagnosis have similar prognosis.Treatment options for patients developing heart failure while already treated with ACE inhibitors/ARBs and beta-blockers are very limited if current heart failure guidelines are followed. In this review possible strategies are outlined and important areas...

  9. Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.

    Science.gov (United States)

    Shang, Fenqing; Zhang, Jiao; Li, Zhao; Zhang, Jin; Yin, Yanjun; Wang, Yaqiong; Marin, Traci L; Gongol, Brendan; Xiao, Han; Zhang, You-Yi; Chen, Zhen; Shyy, John Y-J; Lei, Ting

    2016-01-01

    Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose) polymerase 1 (PARP1). Biguanides and angiotensin II receptor blockers (ARBs) such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs), diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated protein kinase (AMPK) phosphorylation of PARP1 and thus inhibition of PARP1 activity. The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models. Experiments using phosphorylated/de-phosphorylated PARP1 mutants show that AMPK phosphorylation of PARP1 leads to decreased PARP1 activity and attenuated protein poly(ADP-ribosyl)ation (PARylation), but increased endothelial nitric oxide synthase (eNOS) activity and silent mating type information regulation 2 homolog 1 (SIRT1) expression. Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction. PMID:26986624

  10. Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.

    Directory of Open Access Journals (Sweden)

    Fenqing Shang

    Full Text Available Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose polymerase 1 (PARP1. Biguanides and angiotensin II receptor blockers (ARBs such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs, diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated protein kinase (AMPK phosphorylation of PARP1 and thus inhibition of PARP1 activity. The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models. Experiments using phosphorylated/de-phosphorylated PARP1 mutants show that AMPK phosphorylation of PARP1 leads to decreased PARP1 activity and attenuated protein poly(ADP-ribosylation (PARylation, but increased endothelial nitric oxide synthase (eNOS activity and silent mating type information regulation 2 homolog 1 (SIRT1 expression. Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.

  11. Effect of captopril and telmisartan on methotrexate-induced hepatotoxicity in rats: impact of oxidative stress, inflammation and apoptosis.

    Science.gov (United States)

    Kelleni, Mina T; Ibrahim, Salwa A; Abdelrahman, Aly M

    2016-06-01

    Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid drug whose efficacy is limited by its hepatotoxicity. The aim of this study was to investigate the possible protective role of captopril (100 mg/kg/day, p.o. for seven days), an angiotensin converting enzyme inhibitor, and telmisartan (10 mg/kg/day p.o. for seven days), an angiotensin II receptor blocker with peroxisome proliferative receptor gamma (PPARγ) agonism, in a model of MTX (single dose 20 mg/kg i.p. at the fifth day) induced hepatotoxicity in rats. Results of the present study revealed MTX-induced hepatotoxicity as demonstrated by increased level of liver enzymes and confirmed by histopathology. Pretreatment with captopril or telmisartan produced a significant hepatic protection manifested as a significant (p nitrites and nitrates (NOx) levels; as well as a significant increase in hepatic superoxide dismutase (SOD) activity. In addition, there was a remarkable improvement in the histopathological features and a significant reduction in the expression of COX-2, iNOS and caspase-3 enzymes as compared with the MTX group. We recommend considering captopril/Telmisartan, if tolerated and not contraindicated, as preferable antihypertensive agents in patients receiving MTX in their chemotherapy protocols. PMID:27269004

  12. Combined Angiotensin Receptor Modulation in the Management of Cardio-Metabolic Disorders

    DEFF Research Database (Denmark)

    Paulis, Ludovit; Foulquier, Sébastien; Namsolleck, Pawel;

    2016-01-01

    Cardiovascular and metabolic disorders, such as hypertension, insulin resistance, dyslipidemia or obesity are linked with chronic low-grade inflammation and dysregulation of the renin-angiotensin system (RAS). Consequently, RAS inhibition by ACE inhibitors or angiotensin AT1 receptor (AT1R......) blockers is the evidence-based standard for cardiovascular risk reduction in high-risk patients, including diabetics with albuminuria. In addition, RAS inhibition reduces the new onset of diabetes mellitus. Yet, the high and increasing prevalence of metabolic disorders, and the high residual risk even....... Therefore, a concept of dual AT1R/AT2R modulation emerges as a putative means for risk reduction in cardio-metabolic diseases. The approach employing simultaneous RAS blockade (AT1R) and RAS stimulation (AT2R) is distinct from previous attempts of double intervention in the RAS by dual blockade. Dual...

  13. Disposition and metabolism of [(14)C] Sacubitril/Valsartan (formerly LCZ696) an angiotensin receptor neprilysin inhibitor, in healthy subjects.

    Science.gov (United States)

    Flarakos, Jimmy; Du, Yancy; Bedman, Timothy; Al-Share, Qusai; Jordaan, Pierre; Chandra, Priya; Albrecht, Diego; Wang, Lai; Gu, Helen; Einolf, Heidi J; Huskey, Su-Er; Mangold, James B

    2016-11-01

    1. Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor (ARNI) providing simultaneous inhibition of neprilysin (neutral endopeptidase 24.11; NEP) and blockade of the angiotensin II type-1 (AT1) receptor. 2. Following oral administration, [(14)C]LCZ696 delivers systemic exposure to valsartan and AHU377 (sacubitril), which is rapidly metabolized to LBQ657 (M1), the biologically active neprilysin inhibitor. Peak sacubitril plasma concentrations were reached within 0.5-1 h. The mean terminal half-lives of sacubitril, LBQ657 and valsartan were ∼1.3, ∼12 and ∼21 h, respectively. 3. Renal excretion was the dominant route of elimination of radioactivity in human. Urine accounted for 51.7-67.8% and feces for 36.9 to 48.3 % of the total radioactivity. The majority of the drug was excreted as the active metabolite LBQ657 in urine and feces, total accounting for ∼85.5% of the total dose. 4. Based upon in vitro studies, the potential for LCZ696 to inhibit or induce cytochrome P450 (CYP) enzymes and cause CYP-mediated drug interactions clinically was found to be low. PMID:26931777

  14. Pharmacokinetic drug-drug interaction assessment between LCZ696, an angiotensin receptor neprilysin inhibitor, and hydrochlorothiazide, amlodipine, or carvedilol.

    Science.gov (United States)

    Hsiao, Hsiu-Ling; Langenickel, Thomas Heiko; Greeley, Michael; Roberts, John; Zhou, Wei; Pal, Parasar; Rebello, Sam; Rajman, Iris; Sunkara, Gangadhar

    2015-11-01

    LCZ696 is a first-in-class angiotensin receptor neprilysin inhibitor in development for treatments of hypertension and heart failure indications. In 3 separate studies, pharmacokinetic drug-drug interactions (DDIs) potential was assessed when LCZ696 was coadministered with hydrochlorothiazide (HCTZ), amlodipine, or carvedilol. The studies used a open-label, single-sequence, 3-period, crossover design in healthy subjects. Blood samples were collected to determine the pharmacokinetic parameters of LCZ696 analytes (AHU377, LBQ657, and valsartan), HCTZ, amlodipine, or carvedilol (R[+]- and S[-]-carvedilol) for statistical analysis. When coadministered LCZ696 with HCTZ, the 90% CIs of the geometric mean ratios of AUCtau,ss of HCTZ and that of LBQ657 were within a 0.80-1.25 interval, whereas HCTZ Cmax,ss decreased by 26%, LBQ657 Cmax,ss increased by 19%, and the AUCtau,ss and Cmax,ss of valsartan increased by 14% and 16%, respectively. Pharmacokinetics of amlodipine, R(+)- and S(-)-carvedilol, or LBQ657 were not altered after coadministration of LCZ696 with amlodipine or carvedilol. Coadministration of LCZ696 400 mg once daily (qd) with HCTZ 25 mg qd, amlodipine 10 mg qd, or carvedilol 25 mg twice a day (bid) had no clinically relevant pharmacokinetic drug-drug interactions. LCZ696, HCTZ, amlodipine, and carvedilol were safe and well tolerated when given alone or concomitantly in the investigated studies. PMID:27137712

  15. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium channel blockers are a type of medicine used ...

  16. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

    International Nuclear Information System (INIS)

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis

  17. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Hideki, E-mail: hkimura@u-fukui.ac.jp [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Mikami, Daisuke; Kamiyama, Kazuko [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Sugimoto, Hidehiro [Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Kasuno, Kenji; Takahashi, Naoki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yoshida, Haruyoshi [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Division of Nephrology, Obama Municipal Hospital, Obama, Fukui (Japan); Iwano, Masayuki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)

    2014-11-14

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  18. SECOND ORDER DERIVATIVE SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION OF TELMISARTAN AND METOPROLOL IN TABLET DOSAGE FORM

    OpenAIRE

    Patel Prashant B.; Marolia Bhavin P.; Shah Shailesh A.; Shah Dinesh R.

    2012-01-01

    Accurate, precise, rapid and economical method was developed for the estimation of Telmisartan (TELM) and Metoprolol (METO) in bulk and tablet dosage form using second order derivative spectrophotometry. Wavelengths selected for quantitation were 299.5 nm for Telmisartan (zero crossing point of Metoprolol) and 224nm for Metoprolol (zero crossing point of Telmisartan). Linearity was observed in the concentration range of 3-15μg/ml for both Telmisartan and Metoprolol. The accuracy and precision...

  19. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure

    DEFF Research Database (Denmark)

    McMurray, John J V; Packer, Milton; Desai, Akshay S;

    2013-01-01

    AIMS: Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and...... natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor...

  20. The Effects of Telmisartan and Losartan on Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Okan Bakıner

    2013-12-01

    Full Text Available Purpose: Telmisartan has been reported to increase insulin sensitivity by acting as a partial PPAR-gamma agonist, regardless of its renin-angiotensin system inhibition, but losartan has no such activity. In this study, we compared the effects of telmisartan and losartan on insulin sensitivity among type 2 diabetic patients. Material and Method: Age-, sex- and weight-matched patients, who had been on telmisartan or losartan treatment for at least 3 months, were included. Their anthropometric measurements were performed, blood pressures were recorded. Fasting venous blood samples were obtained for analyzing the levels of glucose, HbA1C, insulin and adiponectin. HOMA-IR was calculated. An euglycemic hyperinsulinemic clamp procedure was performed in each subject and M index was calculated. Thereafter, telmisartan and losartan were withdrawn in both groups. A cross-over design was planned; following a wash-out period of 15 days, losartan group (Group 1 was given telmisartan 80 mg/day, telmisartan group (Group 2 was administered losartan 50 mg/day. After 12 weeks of therapy, all measurements, calculations and the euglycemic hyperinsulinemic clamp test were re-performed. Results: General characteristics of the patients at inclusion were similar. Nine cases in group 1 and 8 cases in Group 2 concluded the follow-up. In Group 1, among all follow-up parameters, only weight exhibited a significant decrease at final evaluation (p=0,034. In Group 2, only M value was found to increase (p=0,028. Discussion: Our findings indicated that losartan improved insulin sensitivity in patients with concomitant hypertension and type 2 diabetes, and telmisartan use resulted in more weight loss. Turk Jem 2013; 17: 92-7

  1. A review of the benefits of early treatment initiation with single-pill combinations of telmisartan with amlodipine or hydrochlorothiazide

    Directory of Open Access Journals (Sweden)

    Segura J

    2013-09-01

    Full Text Available Julian Segura, Luis Miguel Ruilope Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain Abstract: This review discusses the rationale for earlier use of single-pill combinations (SPCs of antihypertensive drugs, with a focus on telmisartan/amlodipine (T/A and telmisartan/hydrochlorothiazide (T/H SPCs. Compared with the respective monotherapies, the once-daily T/A and T/H SPCs have been shown to result in significantly higher blood pressure (BP reductions, BP goal rates, and response rates in patients at all stages of hypertension. As expected, BP reductions are highest with the highest dose (T80/A10 and T80/H25 SPCs. Subgroup analyses of the telmisartan trials have reported the efficacy of both SPCs to be consistent, regardless of the patients' age, race, and coexisting diabetes, obesity, or renal impairment. In patients with mild-to-moderate hypertension, the T/A combination provides superior 24-hour BP-lowering efficacy compared with either treatment administered as monotherapy. Similarly, the T/H SPC treatment provides superior 24-hour BP-lowering efficacy, especially in the last 6 hours relative to other renin–angiotensin system inhibitor-based SPCs. The T/A SPC is associated with a lower incidence of edema than amlodipine monotherapy, and the T/H SPC with a lower incidence of hypokalemia than hydrochlorothiazide monotherapy. Existing evidence supports the use of the T/A SPC for the treatment of hypertensive patients with prediabetes, diabetes, or metabolic syndrome, due to the metabolic neutrality of both component drugs, and the use of the T/H SPC for those patients with edema or in need of volume reduction. Keywords: calcium-channel blocker, essential hypertension, diuretic, primary care physician, renin-angiotensin system inhibitor

  2. Beta-blockers

    DEFF Research Database (Denmark)

    Arboe, Bente; Ulrik, Charlotte Suppli

    2013-01-01

    Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma.......Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma....

  3. β-Blockers and All-Cause Mortality in Adults with Episodes of Acute Bronchitis: An Observational Study.

    Directory of Open Access Journals (Sweden)

    Frans H Rutten

    Full Text Available Recent observational studies suggest that β-blockers may improve long-term prognosis in patients with chronic obstructive pulmonary disease (COPD. We assessed whether β-blocker use improves all-cause mortality in patients with episodes of acute bronchitis.An observational cohort study using data from the electronic medical records of 23 general practices in the Netherlands. The data included standardized information about daily patient contacts, diagnoses, and drug prescriptions. Cox regression was applied with time-varying treatment and covariates.The study included 4,493 patients aged 45 years and older, with at least one episode of acute bronchitis between 1996 and 2006. The mean (SD age of the patients was 66.9 (11.7 years, and 41.9% were male. During a mean (SD follow up period of 7.7 (2.5 years, 20.4% developed COPD. In total, 22.7% had cardiovascular comorbidities, resulting in significant higher mortality rates than those without (51.7% vs. 12.0%, p<0.001. The adjusted hazard ratio of cardioselective β-blocker use for mortality was 0.62 (95% confidence interval [CI], 0.50-0.77, and 1.01 (95% CI 0.75-1.36 for non-selective ones. Some other cardiovascular drugs also reduced the risk of mortality, with adjusted HRs of 0.60 (95% CI 0.46-0.79 for calcium channel blockers, 0.88 (95% CI 0.73-1.06 for ACE inhibitors/angiotensin receptor blockers, and 0.42 (95% CI 0.31-0.57 for statins, respectively.Cardiovascular comorbidities are common and increase the risk of mortality in adults with episodes of acute bronchitis. Cardioselective β-blockers, but also calcium channel blockers and statins may reduce mortality, possibly as a result of cardiovascular protective properties.

  4. Reduced expression of angiotensin II and angiotensin receptor type 1 and type 2 in resistance arteries from nasal lesions in granulomatosis with polyangiitis (Wegener's granulomatosis)

    DEFF Research Database (Denmark)

    Dimitrijevic, I; Rissler, P; Luts, L;

    2011-01-01

    OBJECTIVES: Angiotensin II (ANGII) is involved in vessel inflammation and is important in the development of cardiovascular disorders such as atherosclerosis. During active disease, patients with granulomatosis with polyangiitis (GPA; Wegener's granulomatosis) have accelerated atherosclerosis...... and ANGII inhibitors are recommended to these patients to reduce atherosclerosis. We assessed the hypothesis that the expression of ANGII and its receptors in arteries in granulomatous lesions change in GPA. METHODS: ANGII and angiotensin receptors were quantified in vessels from granulomatous lesions from...... patients with GPA using immunohistochemistry. Anti- ANGI type 1 (AT1) and type 2 (AT2) antibodies were applied on formalin-fixed and paraffin-embedded biopsies from nasal mucous membranes from eight patients with GPA and eight controls. RESULTS: ANGII expression was localized to the endothelial cells (ECs...

  5. SECOND ORDER DERIVATIVE SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION OF TELMISARTAN AND METOPROLOL IN TABLET DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Patel Prashant B.

    2012-05-01

    Full Text Available Accurate, precise, rapid and economical method was developed for the estimation of Telmisartan (TELM and Metoprolol (METO in bulk and tablet dosage form using second order derivative spectrophotometry. Wavelengths selected for quantitation were 299.5 nm for Telmisartan (zero crossing point of Metoprolol and 224nm for Metoprolol (zero crossing point of Telmisartan. Linearity was observed in the concentration range of 3-15μg/ml for both Telmisartan and Metoprolol. The accuracy and precision were determined and found to comply with ICH guidelines. The proposed method was successfully applied for the simultaneous estimation of both drugs in commercial tablet preparation.

  6. Effects of Benazapril and Telmisartan on the adiponectin expression of human preadipocytes%贝那普利、替米沙坦对人前脂肪细胞脂联素表达的影响

    Institute of Scientific and Technical Information of China (English)

    赵志强; 田凤石; 雒珞; 吴岩; 李广平

    2012-01-01

    Objective To investigate the effects of Benazapril and Telmisartan on the adiponectin expression of human preadipocytes. Methods Human omental and subcutaneous preadipocytes were isolated from abdominal adipose tissue obtained from 12 healthy adult women undergoing elective abdominal surgery. Preadipocytes were difierentiated for 14 days without any treatment ( Group NC)or in the presence of either angiotensin convening enzyme inhibitor Benazapril ( Group Benazapril), angiotensin II receptor blocker Telmisartan(Group Telmisartan). The approach of radioimmunoassay was used to detect the adiponeetin expression level. Results Benazapril and Telmisartan can increase the differentiation, improve the expression and protein excretion levels in human primary culture omental and subcutaneous preadipocytes in vitro. Conclusion Telmisartan and Benazapril have stronger effects on human omental preadipocytes in adiponectin mRNA expression and secretion. This may suggests a wide perspective of RAS blockers on metabolic syndrome with characteristic in-tra-abdominal obesity.%目的 探讨贝那普利、替米沙坦对体外原代培养的人网膜和皮下来源的前脂肪细胞脂联素(APN)表达的影响.方法 自12例行电切开腹部手术的健康成年女性腹部皮下和网膜分离前脂肪细胞,分为3组,即无干预正常对照组(NC组)、血管紧张素转换酶抑制剂类药物贝那普利组(ACEI组)和血管紧张素Ⅱ受体拮抗剂类药物替米沙坦组(ARB组),诱导分化共14 d.放射免疫法测定各组APN mRNA表达水平.结果 与NC组比较,ACEI组、ARB组体外原代培养的人网膜和皮下前脂肪细胞中APN mRNA表达明显增强.结论 贝那普利、替米沙坦可促进网膜来源的前脂肪细胞的分化,在以腹型肥胖为特征的代谢综合征干预方面可能具有广泛的应用前景.

  7. The role of AT1 and AT2 angiotensin receptors in the mechanism of apoptosis in renal tubular cells after physical exercise.

    Science.gov (United States)

    Podhorska-Okołów, M; Dziegiel, P; Gomułkiewicz, A; Dolińska-Krajewska, B; Murawska-Ciałowicz, E; Jethon, Z; Zabel, M

    2004-01-01

    Intensive physical exercise disturbs the entire homeostasis in the body and leads to changes in haemodynamic and metabolic alterations not only in skeletal muscles but also in many distant organs. In response to acute physical exercise, a decrease of the glomerular filtration may occur, followed by stimulation of the renin-angiotensin system (RAS). Recent studies have shown that both AT1 and AT2 angiotensin receptors may play a role in mediating the apoptotic process in the kidney. Our previous studies have demonstrated an occurrence of apoptosis in rat renal tubular cells after an excessive exercise. The aim of the present study was to determine the possible mechanism of exercise-induced apoptosis in rat kidney. The analysis was performed on kidneys of rats, subjected to treadmill running until exhaustion. Apoptosis was detected in paraffin sections by the TUNEL technique. The expression of AT1 and AT2 receptors in renal tubular cells was examined by immunohistochemistry and Western blot. Our results confirmed that apoptosis after physical exercise is present in renal distal tubular cells. Moreover, there was an increased expression of AT1 and AT2 receptors in distal tubular cells. These studies suggest that physical exercise may induce apoptosis by a mechanism, involving the activation of angiotensin AT1 and AT2 receptors. PMID:15638358

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

    Directory of Open Access Journals (Sweden)

    Takumi Hirata

    2013-01-01

    Full Text Available 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.

  9. Effects of telmisartan and pioglitazone on high fructose induced metabolic syndrome in rats.

    Science.gov (United States)

    Shahataa, Mary Girgis; Mostafa-Hedeab, Gomaa; Ali, Esam Fouaad; Mahdi, Emad Ahmed; Mahmoud, Fatma Abd Elhaleem

    2016-08-01

    Metabolic syndrome (MS) is a cluster of hypertension, insulin resistance, dyslipidaemia, and hyperuricemia. This study was designed to assess the effect of telmisartan and pioglitazone on high fructose induced MS. Thirty-five male albino rats were classified into 5 groups: A, normal diet; B, high-fructose diet (HFD) subdivided into B1 (HFD only), B2 (telmisartan, 5 mg/kg), B3 (pioglitazone, 10 mg/kg), and B4 (telmisartan + pioglitazone). Administration of the drugs was started after the rats had been on HFD for 4 weeks and continued for 4 weeks. Body mass (BM), blood pressure (BP), uric acid (UA), total cholesterol, triglycerides (TG), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), blood urea nitrogen (BUN), creatinine, and nitric oxide (NO) were measured and the levels of fasting glucose and fasting insulin were estimated. Compared with group B1, telmisartan treatment significantly decreased BP, BM, serum glucose, insulin, UA, urea, cholesterol, TGA, and LDL and significantly increased HDL, whereas pioglitazone treatment significantly decreased BP, serum glucose, insulin, UA, urea, creatinine, cholesterol, TGA, and LDL and significantly increased HDL. Co-administration of pioglitazone + telmisartan significantly decreased insulin, urea, and creatinine compared with telmisartan alone. Combined telmisartan + pioglitazone allowed better control of BP, hyperglycaemia, insulin resistance, and the amelioration of BM increase that may be associated with pioglitazone treatment. PMID:27245695

  10. Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects.

    Science.gov (United States)

    Gan, Lu; Jiang, Xuemin; Mendonza, Anisha; Swan, Therese; Reynolds, Christine; Nguyen, Joanne; Pal, Parasar; Neelakantham, Srikanth; Dahlke, Marion; Langenickel, Thomas; Rajman, Iris; Akahori, Mizuki; Zhou, Wei; Rebello, Sam; Sunkara, Gangadhar

    2016-01-01

    LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%. Co-administration of LCZ696 with levonorgestrel-ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUCinf of levonorgestrel. The Cmax of levonorgestrel decreased by 15%, and AUCtau,ss and Cmax,ss of valsartan decreased by 14% and 16%, respectively. Co-administration of LCZ696 with omeprazole, metformin, or levonorgestrel-ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions. PMID:27119576

  11. Comparison of efficacy of telmisartan with losartan in patients of essential hypertension with cognitive impairment

    Directory of Open Access Journals (Sweden)

    Nitin Natthuji Puram

    2016-06-01

    Conclusions: Telmisartan is as effective as losartan in controlling blood pressure and improving cognitive function in hypertensive patients with cognitive impairment. [Int J Basic Clin Pharmacol 2016; 5(3.000: 702-706

  12. FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF TELMISARTAN

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    Kapil Chauhan*, Bharat Parashar, Abhishek Chandel and Varun Thakur

    2013-04-01

    Full Text Available ABSTRACT: The patients with sudden increase blood pressure have markedly reduced function ability and extremely restless, in such cases rapid onset of action is of prime importance. So the patients would be benefited from acute treatment by using Fast dissolving drug delivery system. Telmisartan is an Anti-hypertensive drug which is insoluble in water; hence the drug may be slowly or incompletely dissolves in the gastro-intestinal tract. So the rate of dissolution and therefore its bioavailability is less (bioavailability 42%. In the present study an attempt has been made to prepare. Fast Dissolving tablets of Telmisartan by using Superdisintegrants– Crosscarmellose Sodium, Doshion ,Sodium Starch Glycolate, level of addition to increase the rate of drug release from dosage form to increase the dissolution rate and hence its bioavailability. The tablets were prepared by Direct Compression methods and the prepared blend and tablets were evaluated for their physicochemical properties and In-vitro dissolution study. The evaluation studies were performed such as Weight Variation, Thickness, Hardness, Disintegrating Time, Wetting Time, and In-vitro Drug Release and Stability Study. The Disintegration time of Fast Dissolving tablets were increased by the addition of concentration of Superdisintegrants.

  13. A Review of Antihypertensive Medications, Part II.

    Science.gov (United States)

    Felicilda-Reynaldo, Rhea Faye D; Kenneally, Maria

    2015-01-01

    Hypertension requires careful management, including lifestyle mod- ification and drug therapy. Use of angiotensin-receptor blockers, beta blockers, and calcium channel blockers is discussed. PMID:26665869

  14. Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms

    OpenAIRE

    Patel, Komal; Patel, Amit; Dave, Jayant; Patel, Chaganbhai

    2012-01-01

    Aim and Background: The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of telmisartan and metoprolol succinate in combined tablet dosage form. Materials and Methods: The method is based on the absorbance correction equations for analysis of both the drugs using methanol as solvent. Telmisartan has absorbance maxima at 296 nm and metoprolol succinate has absorbance maxima at 223 nm in methanol...

  15. In vitro interaction study of retinoic acid isomers with telmisartan and amlodipine by equilibrium dialysis method using UV spectroscopy

    Science.gov (United States)

    Varghese, Susheel John; Johny, Sojimol K.; Paul, David; Ravi, Thengungal Kochupappy

    2011-07-01

    The in vitro protein binding of retinoic acid isomers (isotretinoin and tretinoin) and the antihypertensive drugs (amlodipine and telmisartan) was studied by equilibrium dialysis method. In this study, free fraction of drugs and the % of binding of drugs in the mixture to bovine serum albumin (BSA) were calculated. The influence of retinoic acid isomers on the % of protein binding of telmisartan and amlodipine at physiological pH (7.4) and temperature (37 ± 0.5 °C) was also evaluated. The in vitro displacement interaction study of drugs telmisartan and amlodipine on retinoic acid isomers and also interaction of retinoic acid isomers on telmisartan and amlodipine were carried out.

  16. Is the fixed-dose combination of telmisartan and hydrochlorothiazide a good approach to treat hypertension?

    Directory of Open Access Journals (Sweden)

    Marc P Maillard

    2007-07-01

    Full Text Available Marc P Maillard, Michel BurnierService of Nephrology, Department of Internal Medicine, Lausanne University Hospital, SwitzerlandAbstract: Blockade of the renin-angiotensin system with selective AT1 receptor antagonists is recognized as an effective mean to lower blood pressure in hypertensive patients. Among the class of AT1 receptor antagonists, telmisartan offers the advantage of a very long half-life. This enables blood pressure control over 24 hours using once-daily administration. The combination of telmisartan with hydrochlorothiazide is a logical step because numerous previous studies have demonstrated that sodium depletion enhances the antihypertensive efficacy of drugs interfering with the activity of the renin-angiotensin system (RAS. In accordance with past experience using similar compounds blocking the RAS, several controlled studies have now demonstrated that the fixed-dose combination of telmisartan/hydrochlorothiazide is superior in lowering blood pressure than either telmisartan or hydrochlorothiazide alone. Of clinical interest also is the observation that the excellent clinical tolerance of the angiotensin II receptor antagonist is not affected by the association of the low-dose thiazide. Thus telmisartan/hydrochlorothiazide is an effective and well-tolerated antihypertensive combination. Finally, the development of fixed-dose combinations should improve drug adherence because of the one-pill-a-day regimen.Keywords: telmisartan, hydrochlorothiazide, fixed-dose combinations, antihypertensive agent, safety, compliance

  17. Use of Ophiocordyceps sinensis (syn. Cordyceps sinensis) combined with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) versus ACEI/ARB alone in the treatment of diabetic kidney disease: a meta-analysis.

    Science.gov (United States)

    Luo, Ying; Yang, Shi-kun; Zhou, Xun; Wang, Ming; Tang, Dan; Liu, Fu-you; Sun, Lin; Xiao, Li

    2015-05-01

    Ophiocordyceps sinensis (O. sinensis; syn. Cordyceps sinensis) has been used in clinical therapy for diabetic kidney disease (DKD) for more than 15 years. O. sinensis is a household name in china and it is available even in supermarket. However, the precise role of O. sinensis has not been fully elucidated with meta-analysis. The aim of this study was to review existing evidence on the effectiveness of O. sinensis for the treatment of DKD. We identified 60 trials involving 4288 participants. Overall, O. sinensis combined with ACEI/ARB had a better effect when compared to ACEI/ARB alone on 24 h UP (MD = -0.23 g/d, 95% CI: - 0.28 to -0.19, p sinensis combined with ACEI/ARB may have a more beneficial effect on the proteinuria, inflammatory, dyslipidemia status as compared to ACEI/ARB alone in DKD III-IV stage patients, while there is no evidence that O. sinensis could improve the hyperglycemia status. However, with regard to low-quality and significant heterogeneity of included trials, to further verify the current results from this meta-analysis, long-term and well-designed RCTs with high-quality study are warranted to ascertain the long-term efficacy of O. sinensis. PMID:25682973

  18. Formulation development and evaluation of fast dissolving film of telmisartan

    Directory of Open Access Journals (Sweden)

    Vaishali Y Londhe

    2012-01-01

    Full Text Available Hypertension is a major cause of concern not just in the elderly but also in the youngsters. An effort was made to formulate a fast dissolving film containing telmisartan which is used in the treatment of hypertension with a view to improve the onset of action, therapeutic efficacy, patient compliance and convenience. The major challenge in formulation of oral films of telmisatran is that it shows very less solubility in the pH range of 3-9. Various film forming agents and polyhydric alcohols were evaluated for optimizing composition of fast dissolving films. Fast dissolving films using hydroxypropyl methylcellulose, polyvinyl alcohol, glycerol, sorbitol, menthol and an alkalizer were formulated using solvent casting method. Optimized formulations were evaluated for their weight, thickness, folding endurance, appearance, tensile strength, disintegration time and dissolution profile.

  19. Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial

    Science.gov (United States)

    Wu, Jie; Duan, Shu-Wei; Sun, Xue-Feng; Li, Wen-Ge; Wang, Ya-Ping; Liu, Wen-Hu; Zhang, Jian-Rong; Lun, Li-De; Li, Xue-Mei; Zhou, Chun-Hua; Li, Ji-Jun; Liu, Shu-Wen; Xie, Yuan-Sheng; Cai, Guang-Yan; Ma, Lu; Huang, Wen; Wu, Hua; Jia, Qiang; Chen, Xiang-Mei

    2016-01-01

    Background: The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods: It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results: The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18–0.55] g/d, P 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions: Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients. Trial Registration: chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760. PMID:27503012

  20. First automatic radiosynthesis of 11C labeled Telmisartan using a multipurpose synthesizer for clinical research use

    International Nuclear Information System (INIS)

    Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist, is an antihypertensive drug. Positron emission tomography (PET) imaging with [11C]Telmisartan is expected to provide information about the whole body pharmacokinetics of telmisartan as well as the transport function of hepatic organic anion-transporting polypeptide (OATP) 1B3. We developed a first automatic preparation system of [11C]Telmisartan to applicable clinical research using a new 11C and 18F multipurpose synthesizer. Two milligrams of precursor (1) in 5 μl of 1 M KOH in 0.5 ml of dimethyl sulfoxide was reacted with [11C]CH3I for 5 min at 120 deg C. The resultant solution was hydrolyzed with 1 M NaOH at 100 deg C for 3 min. The neutralization was carried out with acetic acid, followed by purification with high-performance liquid chromatography. The desired radioactive fraction was collected and solvent was replaced by 10 ml saline containing 0.3 ml of EtOH and 0.5 ml of PEG400, and then passed through a sterile 0.22 μm filter (Millex-GV, Millipore) to a pyrogen-free vial as the final product. The yield of [11C]Telmisartan for clinical research use was 16.8±2.9% end of bombardment (EOB) as decay corrected (n=8, mean ± standard deviation (SD) in 32-36 min. The radiochemical purity of [11C]Telmisartan was >97%, and specific activity was higher than 86.3 MBq/nmol. We succeeded in the first synthesis of [11C]Telmisartan for clinical research use by appropriate quality tests. (author)

  1. A fluorescence study on the interaction of telmisartan in triblock polymers pluronic P123 and F127.

    Science.gov (United States)

    Mohanty, Maneesha Esther; Rao, Vaidya Jayathirtha; Mishra, Ashok Kumar

    2014-01-01

    Telmisartan is a poorly soluble drug used in treatment of hypertension. There is a recent interest to use pluronic for improving the solubility and bioavailability of these drugs. In this study the interaction of telmisartan with P123 and F127 has been carried out using steady state and time dependent fluorescence study. Quenching of telmisartan fluorescence by potassium iodide is controlled by interactions arising from collisions and complex formation. A comparison of the fluorescence of telmisartan in pluronics with the well understood fluorescence of 8-anilino-1-naphthalene-sulfonic acid, a known fluorescent molecular probe, indicates that telmisartan is generally present in a relatively polar microenvironment with restricted diffusive motion. PMID:24263130

  2. Impairment of physical performance after treatment with beta blockers and alpha blockers.

    OpenAIRE

    Bengtsson, C.

    1984-01-01

    An investigation was made into the effect of various types of beta blockers, an alpha blocker, a combined alpha and beta blocker, and a diuretic on physical performance in a normotensive man. Beta blockers, the alpha blocker, and the combined alpha and beta blocker significantly (p less than 0.001) reduced physical performance. Further studies are needed to confirm these findings in a larger series of subjects.

  3. How Do Beta Blocker Drugs Affect Exercise?

    Science.gov (United States)

    ... Stroke More How do beta blocker drugs affect exercise? Updated:Aug 5,2015 Beta blockers are a ... about them: Do they affect your ability to exercise? The answer can vary a great deal, depending ...

  4. Protective effect of telmisartan on rats with renal failure and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Zhi-Kui Wang; Zhen-Ying Liu; Hai-Bo Yu

    2015-01-01

    Objective:To study the protective effect of telmisartan on rats with renal failure and its mechanism. Methods:60 Wistar rats were chosen as study objective, and were divided into 4 groups randomly:15 in group A (sham operation group), 15 in group B (model group), 15 in group C (telmisartan group) and 15 in group D (telmisartan+GW9962 group). The difference of survival rate, blood-urine biochemical indexes, renal pathological change, and the expression level of PPARγ and nNOS were compared. Results:After 12 weeks, the survival rate of group A was 93.33%(14/15), that of group B was 46.67%(7/15), that of group C was 86.67%(13/15), that of group D was 60.00%(9/15), and the difference among 4 groups had statistical significance (P0.05);after 3 weeks, 6 weeks and 12 weeks, these difference was statistical significant (P<0.05). The difference of blood-urine biochemical indexes, that of renal pathological change, and that of the expression level of PPAR毭and nNOS was statistical significant (P<0.05). Conclusions:Telmisartan has protective effect on renal failure caused by 5/6 nephrectomy, which might be relative to the expression level of PPARγ and nNOS.

  5. Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate the effects of telmisartan on the blood glucose, blood lipid, blood insulin, and insulin resistance in the hypertensive patients with dyslipidemia, and also its effect on controlling blood pressure. Patients and Methods A total of 96hypertensive patients (34 females, 62 males) with dyslipidemia were included (mean age 51.2±9.6, range 42-65 years). Patients were randomized to receive either telmisartan 80 mg/day (n=46) or enalapril 10 mg/day (n=50) for 6 months. The levels of blood pressure (BP), heart rate (HR), and biochemical data were measured before therapy and at the end of the 3-month treatment and 6-month treatment, respectively. Meanwhile, insulin resistance was evaluated by using a homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-IS). Results In the telmisartan group, the mean blood pressure was obviously lower than that of pre-therapy (P<0.05), and the levels of triglyceride (TG), HOMA-IR, and HOMA-IS were all obviously lower than those of pre-therapy and of the enalapril group at the end of the 3-month-treatment period (P<0.05). After 6 months of treatment, the levels of TG, HOMA-IR, and HOMA-IS in the telmisartan group were significantly lower in comparison with those of pre-therapy, the enalapril group (P<0.01), and 3-month-treatment (P<0.05). Post-prandial12 hour blood glucose (P2HBG) in the telmisartan group decreased significantly after 6-month treatment compared with that of pre-therapy and the enalapril group (P<0.05). The level of high density lipoprotein (HDL) cholesterol was significantly higher after 6-month treatment in the telmisartan group than with pre-therapy and the enalapril group(P<0.05). Conclusions Telmisartan could not only control blood pressure steadily and effectively, but also decrease blood TG, increase HDL cholesterol and insulin sensitivity, and lower insulin resistance.

  6. Effects of telmisartan vs olmesartan on metabolic parameters, insulin resistance and adipocytokines in hypertensive obese patients Efectos de telmisartan vs olmesartan sobre parámetros antropométricos, resistencia a la insulina y adipocitoquinas en pacientes hipertensos obesos

    OpenAIRE

    D. A. De Luis; Conde, R.; M González-Sagrado; R. Aller; O. Izaola; A. Dueñas; J. L. Pérez Castrillón; Romero, E.

    2010-01-01

    Background: Angiotensin II regulates the production of adipokines. The objective was to study the effect of treatment with telmisartan versus olmesartan in hypertensiveobese and overweight patients. Subjects: A sample of 65 overweight and obese patients with mild to moderate hypertension was analyzed in a prospective way with a randomized trial. Patients were randomized to telmisartan (80 mg/day) or olmesartan (40 mg/day) for 3 months. Weight, body mass index, blood pressure, basal glucose, i...

  7. DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR SIMULTANEOUS ESTIMATION OF METOPROLOL SUCCINATE AND TELMISARTAN IN COMBINED PHARMACEUTICAL FORMULATION

    OpenAIRE

    Mayur Modi*, Rikin Shah and R.C. Mashru

    2012-01-01

    Four simple, rapid, precise, economical and accurate spectrophotometric methods have been developed for simultaneous analysis of Metoprolol succinate and Telmisartan in their combined dosage form. Method 1, First derivative simultaneous equation method (Vierodt’s method). It employs formation and solving of simultaneous equation using two wavelengths 230.2 nm (λmax of Metoprolol succinate) and 237 nm (λmax of Telmisartan) in first derivative spectra. Method 2, First derivative Q-Absorbance eq...

  8. What is a preferred angiotensin II receptor blocker-based combination therapy for blood pressure control in hypertensive patients with diabetic and non-diabetic renal impairment?

    Directory of Open Access Journals (Sweden)

    Mallat Samir G

    2012-04-01

    Full Text Available Abstract Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular (CV events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Given that most patients with hypertension require at least two antihypertensives to achieve blood pressure (BP goals, identifying the most appropriate combination regimen based on individual risk factors and comorbidities is important for risk management. Single-pill combinations (SPCs containing two or more antihypertensive agents with complementary mechanisms of action offer potential advantages over free-drug combinations, including simplification of treatment regimens, convenience and reduced costs. The improved adherence and convenience resulting from SPC use is recognised in updated hypertension guidelines. Despite a wide choice of SPCs for hypertension treatment, clinical evidence from direct head-to-head comparisons to guide selection for individual patients is lacking. However, in patients with evidence of renal disease or at greater risk of developing renal disease, such as those with diabetes mellitus, microalbuminura and high-normal BP or overt hypertension, guidelines recommend renin-angiotensin system (RAS blocker-based combination therapy due to superior renoprotective effects compared with other antihypertensive classes. Furthermore, RAS inhibitors attenuate the oedema and renal hyperfiltration associated with calcium channel blocker (CCB monotherapy, making them a good choice for combination therapy. The occurrence of angiotensin-converting enzyme (ACE inhibitor-induced cough supports the use of angiotensin II receptor blockers (ARBs for RAS blockade rather than ACE inhibitors. In this regard, ARB-based SPCs are available in combination with the diuretic, hydrochlorothiazide (HCTZ or the calcium CCB, amlodipine. Telmisartan, a long-acting ARB with preferential pharmacodynamic profile compared with several

  9. Myokardinfarkt und Beta-Blocker

    Directory of Open Access Journals (Sweden)

    Stühlinger H-G

    2003-01-01

    Full Text Available Im Rahmen eines akuten koronaren Syndroms (akuter Herzinfarkt, Angina pectoris kommt es, aufgrund eines Ungleichgewichtes zwischen Angebot und Bedarf, zu einem akuten Mangel an Sauerstoff im Herzmuskel. Ursache ist eine reduzierte Sauerstoffzufuhr durch verengte bzw. verschlossene Gefäße. Bis zur Behebung der Ursache vergehen oft mehrere Stunden. In dieser Phase muß - durch Verminderung des Sauerstoffbedarfs im Herzmuskel - eine Verlangsamung der Nekroseentwicklung erreicht werden. Das Ausmaß der Nekrose wird reduziert, somit die für die Langzeitprognose wichtige Linksventrikelfunktion verbessert. Eine Verminderung des Sauerstoffbedarfs erreicht man durch kontrollierte Frequenzsenkung mittels intravenöser Beta-Blockade. In optimaler Weise wird diese Methode durch die Anwendung eines kardioselektiven Beta-Blockers mit kurzer Halbwertszeit durchgeführt. Beta-Blocker haben nicht nur auf die Nekroseentwicklung, sondern auch auf die Inzidenz von Rhythmusstörungen - besonders in der Akutphase - Auswirkungen. Vor allem die mit dieser therapeutischen Maßnahme verbundene Reduktion von Kammerflimmern ist von großer Bedeutung.

  10. Effect of telmisartan on vascular endothelium in hypertensive and type 2 diabetic hypertensive patients

    OpenAIRE

    BARUTÇUOGLU, Burcu; PARILDAR, Zuhal; MUTAF, M. Işıl; Özmen, Dilek; ALİOĞLU, Emin; HABİF, Sara; BAYINDIR, Oya

    2010-01-01

    Hypertension and type 2 diabetes mellitus (DM) cause endothelial dysfunction and may result in cardiovascular disease. The aim of this study was to assess endothelial dysfunction in essential hypertensives, and normotensive and hypertensive type 2 diabetics and to evaluate the effect of telmisartan on endothelium in hypertensives. Materials and methods: Eighteen essential hypertensives (group 1), 16 type 2 diabetic hypertensives (group 2), 10 type 2 diabetic normotensives (group 3), and 10 c...

  11. Tissue-Specific Peroxisome Proliferator Activated Receptor Gamma Expression and Metabolic Effects of Telmisartan

    Czech Academy of Sciences Publication Activity Database

    Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Landa, Vladimír; Kazdová, L.; Pravenec, Michal; Kurtz, T. W.

    2013-01-01

    Roč. 26, č. 6 (2013), s. 829-835. ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP303/10/0505; GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : telmisartan * metabolic effects * tissue-specific Pparg knockout mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.402, year: 2013

  12. The pharmacological research of Tek-1 relevance to anti-neuroinflammation, a candidate compound based on Telmisartan

    Directory of Open Access Journals (Sweden)

    Yang Jianbo

    2015-01-01

    Full Text Available In this paper, BV-2 mouse small glial cell inflammation model induced by LPS is established. The experiment used 0.1-10 μM of telmisartan and Tek-1 to incubate with small glial cell and used telmisartan and Tek-1 to incubate with PPAR gamma special heterosexual antagonistic anti-agent GW9662. The article used ELISA method to dectect TNF-a effect on small glial cell for telmisartan and Tek-1. The article used real-time quantitative PCR method to dectect mRNA level expression effect of CD11b, CD16 and iNOS on small glial cell for telmisartan and Tek-1 and used Western Blot method to dectect MAPKs signal pathway and NF-κb signal turned guide pathway effect on small glial cell for telmisartan and Tek-1. Results show that Tek-1 had high affinity with AT1 receptor and inhibited intracellular calcium ion activation which can be for the AT1 receptor antagonists. Meanwhile, Tek-1 can partially activate PPAR gamma compared with full agonists of rosiglitazone.

  13. Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Motoharu Hayashi

    Full Text Available A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1, tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1 and glucose transporter 4 (GLUT4 in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results

  14. Beta blockers: A new role in chemotherapy

    OpenAIRE

    Nagaraja, Archana S; Sadaoui, Nouara C.; Lutgendorf, Susan K.; Ramondetta, Lois M.; Sood, Anil K

    2013-01-01

    Beta-blockers are a class of drugs widely used to treat cardiac, respiratory and other ailments. They act by blocking beta-adrenergic receptor–mediated signalling. Studies in various cancers have shown that patients taking a beta-blocker have higher survival and lower recurrence and metastasis rates. This is supported by several preclinical and in vitro studies showing that adrenergic activation modulates apoptosis, promotes angiogenesis and other cancer hallmarks, and these effects can be ab...

  15. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofi-brillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers in-volved in Alzheimer's disease therapy.

  16. Pharmacogenetics of ophthalmic topical β-blockers

    OpenAIRE

    Sidjanin, Duska J; Catherine A McCarty; Patchett, Richard; Smith, Edward; Wilke, Russell A

    2008-01-01

    Glaucoma is the second leading cause of blindness worldwide. The primary glaucoma risk factor is elevated intraocular pressure. Topical β-blockers are affordable and widely used to lower intraocular pressure. Genetic variability has been postulated to contribute to interpersonal differences in efficacy and safety of topical β-blockers. This review summarizes clinically significant polymorphisms that have been identified in the β-adrenergic receptors (ADRB1, ADRB2 and ADRB3). The implications ...

  17. Calcium channel blockers and Alzheimer's disease★

    OpenAIRE

    Tan, Yi; Deng, Yulin; Qing, Hong

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers involved in...

  18. Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue.

    Science.gov (United States)

    Li, Hao; Li, Min; Liu, Ping; Wang, YaPing; Zhang, Heng; Li, HongBin; Yang, ShiFeng; Song, Yan; Yin, YanRong; Gao, Lan; Cheng, Si; Cai, Jun; Tian, Gang

    2016-08-01

    Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogen-activated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy. PMID:27296996

  19. Cardiovascular risk reduction by reversing endothelial dysfunction: ARBs, ACE inhibitors,  or both? Expectations from The ONTARGET  Trial Programme

    Directory of Open Access Journals (Sweden)

    Luis Miguel  Ruilope

    2007-03-01

    Full Text Available Luis Miguel  Ruilope1, Josep Redón2, Roland Schmieder31Servicio de Nefrologia, Unidad de Hipertension Hospital, 12 de Octubre, Madrid, Spain; 2Department of Internal Medicine, Hospital Clinico University of Valencia, Valencia, Spain; 3Department of Nephrology and Hypertension, Friedrich-Alexander-Universitat, Erlangen-Nurnberg, GermanyAbstract: Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS, has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB and/or angiotensin-converting enzyme (ACE inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET Programme is expected to provide the ultimate evidence of whether improved endothelial func tion translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade. Completion of ONTARGET is expected in 2008. Keywords: angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, endothelial dysfunction, ONTARGET, renin–angiotensin system, telmisartan

  20. Effects of telmisartan vs olmesartan on metabolic parameters, insulin resistance and adipocytokines in hypertensive obese patients Efectos de telmisartan vs olmesartan sobre parámetros antropométricos, resistencia a la insulina y adipocitoquinas en pacientes hipertensos obesos

    Directory of Open Access Journals (Sweden)

    D. A. de Luis

    2010-04-01

    Full Text Available Background: Angiotensin II regulates the production of adipokines. The objective was to study the effect of treatment with telmisartan versus olmesartan in hypertensiveobese and overweight patients. Subjects: A sample of 65 overweight and obese patients with mild to moderate hypertension was analyzed in a prospective way with a randomized trial. Patients were randomized to telmisartan (80 mg/day or olmesartan (40 mg/day for 3 months. Weight, body mass index, blood pressure, basal glucose, insulin, total cholesterol, LDLcholesterol, HDL-cholesterol, triglycerides, HOMA, QUICKI, leptin and adiponectin were determined at basal time and after 3 months of treatment. Results: Sixty five patients gave informed consent and were enrolled in the study. Patients treated with telmisartan had a significative decrease of glucose 10.53 mg/dl (CI 95%: 2.6-18.5, insulin 2.51 mUI/L (CI 95%: 2.07-7.17 and HOMA 1.08 (CI 95%: 0.39-2.55. Patients treated with olmesartan had a significative decrease of total cholesterol 20.2 mg/dl (CI 95%: 5.8-34.9 and LDL cholesterol 22.6 mg/dl (CI 95%: 9.7-35.6. Only leptin levels have a significant decrease in telmisartan group 7.39 ng/ml (CI 95%: 1.47-13.31. Conclusion: Telmisartan improved blood pressure, glucose, insulin, HOMA and leptin in hypertensive diabetic patients. Olmesartan improved blood pressure and lipid levels.Introducción: La angiotensina II puede regular la producción de adipocitoquinas. El objetivo de nuestro trabajo fue evalaur el efecto sobre parámetros bioquímicos del tratamiento con telmisartan versus olmesartan en pacientes obesos hipertensos. Pacientes: Se analizó una muestra de 65 pacientes con hipertensión moderada severa y obesidad, mediante un ensayo clínico randomizado. Los pacientes fueron randomizados en dos ramas; telmisartan (80 mg/día u olmesartan (40 mg/día durante 3 meses. Se determinaron en el tiempo basal y tras 3 meses los siguientes parámetros; peso, índice de masa corporal, presi

  1. Detrimental effects of beta-blockers in COPD - A concern for nonselective beta-blockers

    NARCIS (Netherlands)

    van der Woude, HJ; Zaagsma, J; Postma, DS; Winter, TH; van Hulst, M; Aalbers, R

    2005-01-01

    Introduction: beta-Blockers are known to worsen FEV1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment. Design: A double-blind, placebo-controlled, randomized,

  2. Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways

    DEFF Research Database (Denmark)

    He, Hongbo; Yang, Dachun; Ma, Liqun;

    2010-01-01

    -gamma expression, whereas neither candesartan nor losartan affected PPAR-delta expression. In vivo, long-term administration of telmisartan significantly reduced visceral fat and prevented high-fat diet-induced obesity in wild-type mice and hypertensive rats but not in PPAR-delta knockout mice. Administration of...

  3. The impact of telmisartan on angiotensin converting enzyme 2 mRNA expression in monocyte-derived macrophages of diabetic hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    李永勤

    2013-01-01

    Objective To investigate the effects of telmisartan on the expression of angiotensin converting enzyme 2(ACE2) mRNA in monocyte-derived macrophages of hypertensive patients accompanied with diabetes. Methods 62 essential hypertensive patients accompanied with

  4. Prevalence of diabetic nephropathy in Type 2 Diabetes Mellitus in rural communities of Guanajuato, Mexico. Effect after 6 months of Telmisartan treatment

    Directory of Open Access Journals (Sweden)

    Priscyla Zenteno-Castillo

    2015-12-01

    Conclusions: A higher prevalence of DN than that reported in the Mexican National Health Survey (ENSANUT was found. Further research is required in a larger population sample in order to confirm the results of Telmisartan treatment.

  5. Enhancement of dissolution of Telmisartan through use of solid dispersion technique surface solid dispersion

    Directory of Open Access Journals (Sweden)

    Bhumika Patel

    2012-01-01

    Full Text Available The present study was aimed to increase the solubility of the poorly water soluble drug Telmisartan by using Surface solid dispersion (SSD made of polymers like Poloxamer 407, PEG 6000 by Solvent evaporation method. The drug was solubilized by surfactants and/or polymers then adsorbed onto the surface of extremely fine carriers to increase its surface area and to form the SSD which give the more Surface area for absorption of the drug. A 2 2 full factorial design was used to investigate for each carrier the joint influence of formulation variables: Amount of carrier and adsorbent. Saturation solubility studies shows the improvement in solubility of drug batch SSD 8 give more solubility improvement than the other batch, in-vitro dissolution of pure drug, physical mixtures and SSDs were carried out in that SSDs were found to be effective in increasing the dissolution rate of Telmisartan in form of SSD when compared to pure drug. Also FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and Surface solid dispersion. Furthermore, both DSC and X-ray diffraction showed a decrease in the melting enthalpy and reduced drug crystallinity consequently in SSDs. However, infrared spectroscopy revealed no drug interactions with the carriers.

  6. Whole-body distribution and radiation dosimetry of [11C]telmisartan as a biomarker for hepatic organic anion transporting polypeptide (OATP) 1B3

    International Nuclear Information System (INIS)

    Introduction: Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist used as an antihypertensive drug, is specifically taken up by the liver through the OATP1B3. PET imaging with [11C]telmisartan is expected to provide information about the whole body pharmacokinetics of telmisartan as well as its transport property by OATP1B3. The purpose of the study was to determine the biodistribution and radiation dosimetry of [11C]telmisartan in humans. Methods: Biodistribution of [11C]telmisartan was measured in three rats and six healthy male human volunteers. In the rat study, a dynamic emission scan was performed for 90 min. In the human study, dynamic whole-body PET images were acquired after intravenous injection of [11C]telmisartan. ROIs were defined for source organs on the PET images to measure time-course of [11C]telmisartan uptake as percentage injected dose and the number of disintegration for each organ. Radiation dosimetry was calculated with OLINDA/EXM. Results: In the rat study, most radioactivity was rapidly taken up by the liver and part of it was excreted into the biliary tract and intestine. Extrapolating from the rat data, the effective dose for the adult human being was estimated to be 3.65±0.01 microSv/MBq (n=3). In the human study, most of the tracer was taken up by the liver as well, although not as rapidly as in the rat. The activity in the gall bladder and intestine increased gradually. The effective dose for the adult human being was 4.24±0.09 microSv/MBq (n=6). Conclusions: [11C]Telmisartan is a safe PET tracer with a dosimetry profile comparable to other common 11C PET tracers.

  7. Topical beta-Blockers and Mortality

    NARCIS (Netherlands)

    Muskens, Rogier P. H. M.; Wolfs, Roger C. W.; Wittenian, Jacqueline C. M.; Hofman, Albert; de Jong, Paulus T. V. M.; Stricker, Bruno H. C.; Jansonius, Nomdo M.

    2008-01-01

    Purpose: To study the associations between long-term and short-term use of topical beta-blockers and mortality. Design: Prospective population-based cohort study. Participants: To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484

  8. In a subgroup of high-risk Asians, telmisartan was non-inferior to ramipril and better tolerated in the prevention of cardiovascular events.

    Directory of Open Access Journals (Sweden)

    Antonio L Dans

    Full Text Available BACKGROUND AND OBJECTIVES: Results of the recently published ONTARGET study (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial showed that telmisartan (80 mg/day was non-inferior to ramipril (10 mg/day in reducing cardiovascular events. Clinicians in Asia doubt tolerability of these doses for their patients. We therefore analyzed data from this study and a parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease. Our objectives were to compare Asians and non-Asians with respect to the following: 1 Effectiveness of telmisartan vs. ramipril in reducing cardiovascular events;2 Proportions who reached the full dose of telmisartan, ramipril or placebo; and3 Proportions of overall discontinuations, and discontinuations due to adverse effects. METHOD: The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to ramipril, telmisartan, or their combination. The primary composite endpoint was death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The primary outcome was the same. In this substudy, we compared Asians and non-Asians as to how well they tolerated telmisartan (given in both studies and ramipril (given in ONTARGET. RESULTS: 1 Telmisartan was non-inferior to ramipril in lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13; 2 more Asians achieved the full dose of either drug; 3 less withdrew (overall; and 4 less withdrew for adverse effects. Furthermore, telmisartan was better tolerated than ramipril. This advantage was greater among Asians. CONCLUSION AND SIGNIFICANCE: Although Asians had lower BMI than non-Asians, Asians tolerated both drugs better. Regulatory agencies require reporting of safety and effectiveness data by

  9. The fourth-generation Calcium channel blocker: Cilnidipine

    OpenAIRE

    Chandra, K. Sarat; Ramesh, G.

    2013-01-01

    Several classes of antihypertensive agents have been in clinical use, including diuretics, α-blockers, β-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockers (ARB), and organic calcium channel blockers (CCBs). All these drugs are being currently used in the treatment of Hypertension & various disease conditions of the heart either alone or in combination. Cilnidipine is a new antihypertensive drug distinguished from other L-type Ca2+ channel blocke...

  10. Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model.

    Science.gov (United States)

    El-Mahdy, Nageh Ahmed; El-Sayad, Magda El-Sayed; El-Kadem, Aya Hassan

    2016-07-01

    Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the world. Several signaling pathways are involved in the pathogenesis of DN including elevation in level of angiotensin II, formation of advanced glycation end products (AGE), activation of protein kinase c (PKC), and lipid accumulation. These pathways activate one another mutually leading to oxidative stress, increasing expression of transforming growth factor beta-1(TGF-β 1) and release of interleukins and adhesion molecules, so the aim of this study is to interrupt more than pathogenic pathway to ameliorate the progression of DN. In the present study, white male rats (N=48) were divided into six groups (8 rats each), the first two groups served as normal control and a control vehicle group while the remaining four groups were rendered diabetic by a single intraperitoneal injection of Streptozotocin (STZ) and being left for 4 weeks to develop DN. Thereafter, the rats were divided into DN group, DN group receiving Telmisartan or Sildenafil or Telmisartan Sildenafil combination. After the specified treatment period, urine samples were collected (using metabolic cages) to measure proteinuria, animals were then euthanized, blood and tissue samples were collected for measurement of Blood glucose,BUN, S.Cr, LDL, NO, TGF-β1, IL-1β, AGEPs, and SOD. The combination therapy showed significant decrease in BUN, S.Cr,LDL, TGF-β1, IL-1β, Proteinuria and AGEPs and significant increase in SOD and NO. The findings showed that combination therapy was able to ameliorate DN and that the effects were superior to the single drugs alone. PMID:27261587

  11. Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan

    OpenAIRE

    Jaiswal, Parul; Aggarwal, Geeta; Harikumar, Sasidharan Leelakumari; Singh, Kashmir

    2014-01-01

    Objective: Self-microemulsifying drug delivery system (SMEDDS) and solid-SMEDDS of telmisartan was aimed at overcoming the problems of poor solubility and bioavailability. Methodology: The formulation strategy included selection of oil phase based on saturated solubility studies and surfactant and co-surfactant screening on the basis of their emulsification ability. Ternary phase diagrams were constructed to identify the self-emulsifying region using a dilution method. The prepared formulatio...

  12. Telmisartan Attenuates Colon Inflammation, Oxidative Perturbations and Apoptosis in a Rat Model of Experimental Inflammatory Bowel Disease

    OpenAIRE

    Arab, Hany H.; Al-Shorbagy, Muhammad Y.; Abdallah, Dalaal M.; Nassar, Noha N

    2014-01-01

    Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. Telmisartan (TLM) is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphon...

  13. Histamine 2 blocker potentiates the effects of histamine 1 blocker in suppressing histamine-induced wheal

    Directory of Open Access Journals (Sweden)

    Dhanya N

    2008-01-01

    Full Text Available Background : Histamine is responsible for the wheal and flare reaction in various allergic conditions. Classical antihistamines are the drugs which block the H 1 receptors and are widely used in various allergic conditions, whereas H 2 blockers are mainly used for acid peptic disease. Although H 1 receptor-mediated actions of histamine are primarily responsible for vasodilatation, vasopermeability, and itching, it has been observed that combined blocking of both H 1 and H 2 receptors may provide better relief. Aim: To compare the efficacy of levocetirizine (H 1 blocker versus levocetirizine and ranitidine (H 2 blocker in suppressing histamine-induced wheal. Methods: Fifteen volunteers were given a single dose of levocetirizine 5 mg on day 1 and a single dose of levocetirizine 5 mg with ranitidine 150 mg twice a day on day 7. A pretest was performed by intradermal histamine prick test. After administration of the drugs, the prick test was repeated at 1 hour, 2, 3, 6, and 24 hours, and the size of the wheal measured and statistically analyzed. Results: At 1 hour, there was no statistically significant difference in the wheal size between levocetirizine alone and the combination of levocetirizine and ranitidine. Levocetirizine with ranitidine resulted in statistically significant reduction of wheal size at 2, 3, 6, and 24 hours when compared with levocetirizine alone. Conclusion: H2 blocker potentiates the effects of an H1 blocker in suppressing histamine-induced wheal.

  14. Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Telmisartan and Hydrochlorothiazide in Bulk and Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    N. Mukuntha Kumar

    2014-10-01

    Full Text Available A simple, accurate, precise and rapid RP-HPLC method has been developed and validated for the simultaneous estimation of Telmisartan and Hydrochlorothiazide in bulk and fixed-dosage formulation. The separation was achieved on ACE 5 C18 (Length 150 mm × Diameter 4.6 mm Particle size 5 μm column with gradient flow. The mobile phase at a flow rate of 1.5 mL/min consisted of Water: Acetonitrile: Orthophospharic acid (95:5:1 Mobile Phase A and Water: Acetonitrile: Orthophospharic acid (5:95:1 Mobile Phase B (Gradient ratio. The UV detection was carried out at 280 nm. The retention time of Hydrochlorothiazide and Telmisartan was found to be 4.19 and 9.12 min. respectively. The method has been validated for Specificity, Linearity, Accuracy, Precision and Robustness. The calibration curve for Telmisartan and Hydrochlorothiazide were linear from the range of 160.1-480.4 μg/mL and 25.2 - 75.7 μg/mL respectively. The mean recoveries obtained for Telmisartan and Hydrochlorothiazide were 100.1% and 99.8% respectively. The developed method was found to be Specific, accurate, Precise, Robust and rapid for the simultaneous estimation of Telmisartan and Hydrochlorothiazide in bulk Pharmaceutical Dosage Form.

  15. Involvement of Proteasome and Macrophages M2 in the Protection Afforded by Telmisartan against the Acute Myocardial Infarction in Zucker Diabetic Fatty Rats with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    C. Di Filippo

    2014-01-01

    Full Text Available This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R. At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7% and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R.

  16. Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice.

    Directory of Open Access Journals (Sweden)

    Muralikrishna Gangadharan Komala

    Full Text Available BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2 is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND METHODS: We induced diabetes using a low dose streptozotocin protocol in 7-8 week old endothelial nitric oxide (eNOS synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice. RESULTS: Diabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1, transforming growth factor β1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the

  17. Treatment for calcium channel blocker poisoning: A systematic review

    OpenAIRE

    St-Onge, M.; Dubé, P.-A.; Gosselin, S.; Guimont, C; Godwin, J; Archambault, P. M.; Chauny, J.-M.; Frenette, A. J.; Darveau, M.; Le sage, N.; Poitras, J.; Provencher, J.; Juurlink, D. N.; Blais, R

    2014-01-01

    Context Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. Objective To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. Methods Medline/Ovid, PubMed, ...

  18. DEVELOPMENT OF UV SPECTROPHOTOMETER METHOD AND IT’S VALIDATION FOR ESTIMATION OF TELMISARTAN AS API AND IN PHARMACEUTICAL DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Jaithlia Rajiv

    2011-06-01

    Full Text Available A simple, sensitive, cost effective, reproducible and specific UV spectrophotometric method was developed for the estimation of Telmisartan in tablet dosage form. The optimum conditions for the analysis of the drug were established with Methanol as solvent. The wavelength maxima (λmax for Telmisartan were found to be 296 nm. Beer’s law was obeyed in the concentration range of 2-22 µg/mL, and was validated with respect to linearity, accuracy (recovery, precision and specificity. The proposed method has been applied successfully for the analysis of the drug as API and in its tablets dosage forms.

  19. Systematic review of use of β-blockers in sepsis

    Directory of Open Access Journals (Sweden)

    Cyril Jacob Chacko

    2015-01-01

    Conclusion: There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

  20. The expression of ACE2 in porcine atrial tissue with chronic atrial fibrillation induced by rapid atrial pacing and the effect of angiotensin receptor blocker on its expression%快速心房起搏诱导猪持续性房颤心房组织ACE2表达及替米沙坦干预的影响

    Institute of Scientific and Technical Information of China (English)

    李思召; 王志荣; 张超群; 徐晤; 张辉; 郑雯

    2011-01-01

    目的 探讨猪心房颤动(房颤)心房肌组织中血管紧张素转换酶2(ACE2)的表达和替米沙坦干预的作用.方法 18只健康小猪随机分为3组,分别为正常对照组(假手术组)、快速心房起搏组(RAP组)、替米沙坦干预组(起搏+替米沙坦,ARB组),每组各6头猪.对照组安置起搏器(AOO)但不行起搏刺激,其余各组安置起搏器,给予500次/min的快速右心房起搏2周,制成慢性房颤实验模型.各组均给予相同饲料喂养.替米沙坦(1.5 mg·kg-1·d-1)混于饲料中,并提前3天应用于ARB组;2周后处死所有实验猪,免疫组化染色方法 观察心房组织ACE2蛋白表达及定位;Western Blot检测心房组织ACE2的表达变化.结果 免疫组化染色可见:RAP组心房组织ACE2阳性染色较正常对照组明显减少,ARB干预组ACE2阳性染色较RAP组明显增加,接近正常对照组.与正常对照组比较,RAP组ACE2蛋白表达明显降低(P 0. 05 ). C onclusion These findings fran tiis study indicate tiatACE levelmay play an mportent role in tie process of atrial fibrillation The effect tiat tin isarten inhibitAF incidence and shorten tie duration of Afmay be tirough up regulating tie expression of ACE.

  1. Influência do bloqueador de receptor de angiotensina (Losartana potássica na função renal e pressão arterial em cães GRMD Influence of angiotensin receptor blocker of renal function and arterial pression in GRMD dogs

    Directory of Open Access Journals (Sweden)

    Marina Brito Silva

    2009-04-01

    Full Text Available A distrofia muscular de Duchenne (DMD é uma alteração neuromuscular caracterizada por contínua necrose muscular e degeneração, com eventual fibrose e infiltração por tecido adiposo. O aumento progressivo da fibrose intersticial no músculo impede a migração das células miogênicas, necessárias para a formação muscular. O modelo canino constitui-se nas melhores fenocópias da doença em humanos, quando comparados com outros modelos animais com distrofia. O tratamento antifibrose de pacientes DMD, tendo como alvo os mediadores da citocina, TGF-beta, e o tratamento com antiinflamatórios, podem limitar a degeneração muscular e contribuir para a melhora do curso da doença. O presente estudo teve como objetivo observar os possíveis efeitos adversos na fisiologia renal, por meio de avaliação bioquímica sanguínea e da pressão arterial, verificando a viabilidade do uso do Losartan (um inibidor de TGF-beta nos cães afetados pela distrofia muscular. Foram utilizados quatro cães adultos, sendo dois machos e duas fêmeas. Utilizou-se a dose de 50mg de Losartan, administrada via oral, uma vez ao dia. Os exames clínicos, bem como alterações na função renal, o nível do potássio sérico e a pressão arterial não evidenciaram reação adversa durante todo o período do experimento. O uso de Losartan, por um período de 9 semanas, mostrou-se como uma terapia segura para o tratamento antifibrótico em cães adultos, não afetando a função renal ou pressão arterial dos animais.Duchenne muscular dystrophy (DMD is a neuromuscular disorder characterized by a continuous muscle necrosis and degeneration with eventual fibrosis and fatty tissue infiltration. Progressive increase in muscle interstitial fibrosis prevents the movement of myogenic cells, which is necessary for myotube formation. Canine model is the best phenocopies of the disease in humans when comparing with others animal models with dystrophy. Anti-fibrotic treatment of DMD patients, targeting the cytokine mediators, TGF-beta, and the treatment with antiinflammatories, may limit muscle degeneration and contribute for the improvement of the course of the illness. This work aimed to verify the possible adverse effects in renal physiology by means of evaluation sanguineous biochemist and arterial pressure, in order to verifying the viability of Losartan (a TGF-beta inhibiter in affected dogs by muscle dystrophy. It was used four adults dogs, two of each gender. A dose of 50mg of Losartan was orally given once a day. The clinical exams, the kidney function, arterial blood pressure and potassium level did not show any adverse effect through the experimental period. Losartan utilization showed to be a safe therapy for the antifibrotic treatment in adults dogs, not affecting neither the kidney function nor the arterial blood pressure.

  2. Development of dissolution test method for a telmisartan/amlodipine besylate combination using synchronous derivative spectrofluorimetry

    Directory of Open Access Journals (Sweden)

    Panikumar Durga Anumolu

    2014-04-01

    Full Text Available The dissolution process is considered an important in vitro tool to evaluate product quality and drug release behavior. Single dissolution methods for the analysis of combined dosage forms are preferred to simplify quality control testing. The objective of the present work was to develop and validate a single dissolution test for a telmisartan (TEL and amlodipine besylate (AML combined tablet dosage form. The sink conditions, stability and specificity of both drugs in different dissolution media were tested to choose a discriminatory dissolution method, which uses an USP type-II apparatus with a paddle rotating at 75 rpm, with 900 mL of simulated gastric fluid (SGF without enzymes as the dissolution medium. This dissolution methodology provided good dissolution profiles for both TEL and AML and was able to discriminate changes in the composition and manufacturing process. To quantify both drugs simultaneously, a synchronous first derivative spectrofluorimetric method was developed and validated. Drug release was analyzed by a fluorimetric method at 458 nm and 675 nm for AML and TEL, respectively. The dissolution method was validated as per ICH guidance.

  3. Preparation and Characterization of Liquisolid Compacts for Improved Dissolution of Telmisartan

    Directory of Open Access Journals (Sweden)

    Naveen Chella

    2014-01-01

    Full Text Available The objective of the present work was to obtain pH independent and improved dissolution profile for a poorly soluble drug, telmisartan using liquisolid compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle, Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations were evaluated for drug excipient interactions, change in crystallinity of drug, flow properties, and general quality control tests of tablets using Fourier transform infrared (FTIR spectroscopy, differential scanning calorimetry (DSC, X-ray diffraction (XRD, angle of repose, and various pharmacopoeial tests. In vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and 7.4. Stability studies were performed at 40°C and 75% RH for three months. The formulation was found to comply with Indian pharmacopoeial limits for tablets. FTIR studies confirmed no interaction between drug and excipients. XRD and DSC studies indicate change/reduction in crystallinity of drug. Dissolution media were selected based on the solubility studies. The optimized formulation showed pH independent release profile with significant improvement P<0.005 in dissolution compared to plain drug and conventional marketed formulation. No significant difference was seen in the tablet properties, and drug release profile after storage for 3 months.

  4. DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR SIMULTANEOUS ESTIMATION OF METOPROLOL SUCCINATE AND TELMISARTAN IN COMBINED PHARMACEUTICAL FORMULATION

    Directory of Open Access Journals (Sweden)

    Mayur Modi*, Rikin Shah and R.C. Mashru

    2012-05-01

    Full Text Available Four simple, rapid, precise, economical and accurate spectrophotometric methods have been developed for simultaneous analysis of Metoprolol succinate and Telmisartan in their combined dosage form. Method 1, First derivative simultaneous equation method (Vierodt’s method. It employs formation and solving of simultaneous equation using two wavelengths 230.2 nm (λmax of Metoprolol succinate and 237 nm (λmax of Telmisartan in first derivative spectra. Method 2, First derivative Q-Absorbance equation method. It involves, formation of Q-absorbance equation at 231.8 nm (isoabsorptive point and 237 nm (λmax of Telmisartan in first derivative spectra. Method 3, Absorbance correction method, involves measurement of absorbance at 296.6 nm for estimation of TEL and measurement of corrected absorbance at 223 nm for estimation of MET. Method 4, Combination of First derivative dual wavelength ,which uses the difference in absorbance at 282.4 nm and 284.6 nm for estimation of MET and zero crossing first derivative spectrophotometry involves measurement of amplitudes at 330 nm for estimation of TEL in first derivative spectra. Developed methods were validated according to ICH guidelines. The calibration graph follows Beer’s law in the range of 3-20 µg/ml for MET and 4-16 µg/ml for TEL with R square value greater than 0.999. Accuracy of all methods was determined by recovery studies and showed % recovery between 99 to 101%. Intraday and interday precision was checked for all methods and mean %RSD was found to be less than 2 for all the methods. The methods were successfully applied for estimation of MET and TEL in marketed formulation.

  5. Development of Solid Self Micro Emulsifying Drug Delivery System with Neusilin US2 for Enhanced Dissolution Rate of Telmisartan

    OpenAIRE

    Bhagwat Durgacharan A; D’Souza John I

    2012-01-01

    Aim of present study was to develop solid self micro emulsifying drug delivery system (S-SMEDDS) with Neusilin US2 for enhancement of dissolution rate of Telmisartan (TEL). SMEDDS was prepared using Oleic acid, Tween 80 and PEG 400 as oil, surfactant and cosurfactant respectively. For formulation of stable SMEDDS, micro emulsion region was identified by constructing pseudo ternary phase diagram containing different proportion of surfactant: co-surfactant (Km value 1:1, 2:1 and 3:1), oil and w...

  6. Telmisartan increases fatty acid oxidation in skeletal muscle through a peroxisome proliferator-activated receptor-[gamma] dependent pathway

    Czech Academy of Sciences Publication Activity Database

    Sugimoto, K.; Kazdová, L.; Qi, N.R.; Hyakukoku, M.; Křen, Vladimír; Šimáková, Miroslava; Zídek, Václav; Kurtz, T. W.; Pravenec, Michal

    2008-01-01

    Roč. 26, č. 6 (2008), s. 1209-1215. ISSN 0263-6352 R&D Projects: GA MŠk(CZ) 1M0520; GA MZd(CZ) NR8495; GA MZd NR9359; GA ČR(CZ) GA301/06/0028 Grant ostatní: -(XE) LSHG-CT-2005-019015; HHMI(US) 55005624; -(US) HL56028; -(US) HL63709 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK ; N - neverejné zdroje Keywords : telmisartan * fatty acid oxidation * PPARgamma Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.132, year: 2008

  7. Normal and Reversed-Phase HPTLC Methods for Simultaneous Estimation of Telmisartan and Metoprolol Succinate in Pharmaceutical Formulation

    OpenAIRE

    Nawale, Prajakta S.; Shirkhedkar, Atul A.; Surana, Sanjay J.; Patil, Amod S.

    2012-01-01

    Two simple precise normal-phase (Method I) and reversed-phase (Method II) HPTLC/densitometry method have been developed for simultaneous determination of telmisartan and metoprolol succinate in bulk and in combined tablet formulation. Method I was developed with aluminium plates precoated with silica gel 60F254S, and toluene : propanol : methanol : triethylamine (8 : 1 : 1 : 0.5 v/v) was used as as mobile phase. Method II was carried out using aluminium coated with RP-18 silica gel 60 F254S H...

  8. A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients

    Directory of Open Access Journals (Sweden)

    Plavnik Frida Liane

    2002-01-01

    Full Text Available OBJECTIVE: To evaluate the efficacy and tolerability of telmisartan, given once a day to patients with mild to moderate hypertension, as well as to assess the 24-hour blood pressure profile with ABPM. METHODS: Initially, 163 patients over 18 were selected, regardless of sex, with blood pressure levels >140/90mmHg at visit 1, which was confirmed at visit 2. One hundred thirty-four patients completed the study. After a 4-week placebo run-in phase, telmisartan 40mg/daily was given for 6 weeks. In those patients whose blood pressure (BP levels were lower than 140/90mmHg, the same dosage was kept for an additional period of 6 weeks. For those who had BP higher than 140/90mmHg, the dosage was increased to 80mg/daily. Sixty-two patients were included in a subgroup that underwent ABPM 3 different times during the study. RESULTS: In the overall group, blood pressure reduction ranged from 162.3±14.5/101.3±5.75 mmHg (baseline to 147.3±20.1/90.8±10.9 mmHg (week 12 (p<0.05. Mean blood pressure decreases were 14.4mmHg for systolic BP and 10.3mmHg for diastolic BP, after 12 weeks of active treatment. A subanalysis showed that 47 (35% patients took telmisartan 40mg throughout the study and 81 (65% had the dosage increased to 80mg daily. Using ABPM, an 8-mmHg reduction in systolic BP as well as a 5-mmHg reduction in diastolic BP were observed, when compared with baseline values in the final 6 hours (18-24 hours after the last dose of study medication. CONCLUSION: Our results confirm that telmisartan given once a day is effective in reducing blood pressure levels in mild to moderate hypertensive patients. This reduction occurs in a sustained and gradual manner during a 24-hour period confirmed by ABPM.

  9. Identification of a pharmacophore of SKCa channel blockers.

    Science.gov (United States)

    Dilly, Sebastien; Graulich, Amaury; Farce, Amaury; Seutin, Vincent; Liegeois, Jean-Francois; Chavatte, Philippe

    2005-12-01

    Small conductance calcium-activated potassium channels (SK) are widely expressed throughout the central nervous system (CNS) and the periphery. Three subtypes of SK channels have so far been identified in different parts of the brain. Activation of the SK channels by a rise in intracellular calcium leads to the hyperpolarisation of the membrane, reducing cell excitability. Blocking the SK channels might be beneficial in the treatment of depression, Parkinson's disease and cognitive disorders. However, few blockers of SK channels have been characterized. In this study, a pharmacophoric model of SK channels blockers is presented. It is based on a series of nonpeptidic compounds and apamin, a peptidic blocker. To create the pharmacophore model, the conformational space of nonpeptidic blockers was investigated to generate a series of distance constraints applied to a simulated annealing study of apamin. The resulting conformation was superimposed with the nonpeptidic blockers to give a pharmacophore. PMID:16408787

  10. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    Science.gov (United States)

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH

  11. Treating High Blood Pressure: Is a Beta-Blocker Drug Right for You?

    Science.gov (United States)

    ... High Blood Pressure: Is a Beta-blocker Drug Right for You? What are beta-blockers? Beta-blockers ... talk with your doctor about which drugs are right for you. If your blood pressure is slightly ...

  12. DMPD: Lipopolysaccharide-binding molecules: transporters, blockers and sensors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15241548 Lipopolysaccharide-binding molecules: transporters, blockers and sensors. ...binding molecules: transporters, blockers and sensors. PubmedID 15241548 Title Lipopolysaccharide-binding mo...lecules: transporters, blockers and sensors. Authors Chaby R. Publication Cell Mo

  13. Use of beta blockers in various clinical states

    Directory of Open Access Journals (Sweden)

    Radović Vesna V.

    2011-01-01

    Full Text Available Introduction. According to the convincing evidence, a decline in mortality rate has been achieved with beta-blockers in patients with an acute myocardial infarction and in post-infarction follow-up. In fact, there has been a clear reduction of sudden coronary death. The necessary condition for the efficiency of beta-blockers is an early use. They are also a medication of choice for angina after an infarction. The objective of this work was to evaluate the use of beta-blockers after a myocardial infarction in various clinical states and to eliminate doubts concerning their prescription. Beta blockers Even in conditions considered contraindications for administration of beta blockers such as old age, diabetes, non-Q-wave myocardial infarction, peripheral vascular disease, arterial disease, heart insufficiency, ventricular arrhythmias, renal disease, chronic obstructive pulmonary disease, asthma and depression, patients benefit from beta blockers when they are given along with a right choice of the medication and a regular follow-up of the patient. Preference is given to cardioselective beta blockers in patients with diabetes or lung disease. Beta-blockers do not cause long-term lipid alterations. Therefore, the matter of clinically significant alterations of lipids or blood glucose levels should not need further consideration as a problem of the treatment of diabetics. Discussion and conclusion. Investigations have proved that the use of beta-blockers reduces the development of cerebrovascular accidents, heart insufficiency and hypertension. Despite strong arguments and numerous recommendations, beta-blockers have not been accepted to a sufficient extent as an integral part of treatment of acute coronary syndrome and related diseases, to the detriment of many lost lives and in spite of favourable pharmaco-economic aspect.

  14. Effect of telmisartan on selected adipokines, insulin sensitivity, and substrate utilization during insulin-stimulated conditions in patients with metabolic syndrome and impaired fasting glucose

    Czech Academy of Sciences Publication Activity Database

    Wohl, P.; Krušinová, E.; Hill, M.; Kratochvílová, S.; Zídková, K.; Kopecký, J.; Neškudla, T.; Pravenec, Michal; Klementová, M.; Vrbíková, J.; Wohl, P.; Mlejnek, Petr; Pelikánová, T.

    2010-01-01

    Roč. 163, č. 4 (2010), s. 573-583. ISSN 0804-4643 R&D Projects: GA MZd(CZ) NR9359; GA MZd(CZ) NS10528 Institutional research plan: CEZ:AV0Z50110509 Keywords : telmisartan * insulin resistance * adipokines Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.482, year: 2010

  15. Influence of G-protein β-Polypeptide 3 C825T Polymorphism on Antihypertensive Response to Telmisartan and Amlodipine in Chinese Patients

    Institute of Scientific and Technical Information of China (English)

    Zan-Lin Zhang; Hui-Lan Li; Zhi-Peng Wen; Guo-Ping Yang; Wei Zhang; Xiao-Ping Chen

    2016-01-01

    Background: G-protein β-polypeptide 3 (GNB3) is a β subunit isoform of G-protein that plays important role in signal transduction of membrane G-protein coupled receptors (GPCRs).The GNB3 splice variant C825T (rs5443) is associated with risk for essential hypertension (EH) and efficacy of therapeutic drugs targeting GPCRs.It is unknown whether the polymorphism is associated with blood pressure (BP) response to telmisartan or amlodipine, two widely prescribed antihypertensive drugs.Methods: A total of 93 subjects initially diagnosed as EH were recruited and underwent a 4-week treatment with telmisartan (42 patients) or amlodipine (51 patients) monotherapy.Both baseline and after-treatment BP were measured.GNB3 C825T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism.Results: Baseline systolic BP (SBP) and diastolic BP (DBP) were comparable among C825T genotypes in both telmisartan and amlodipine treatment groups.Patients with the CT or TT genotypes showed significantly lower body mass index (BMI) as compared with CC homozygotes in both groups (P < 0.05, respectively).GNB3 825TT homozygotes showed significantly higher after-treatment DBP and mean arterial pressure (MAP) than those carrying at least one 825C allele (P < 0.01) in the telmisartan treatment group.No difference in after-treatment SBP, DBP, and MAP levels among C825T genotypes was observed in the amlodipine treatment group.No significant difference in absolute changes in BP levels was observed among the genotypes in either treatment group.Conclusion: The GNB3 C825T splice variant is associated with the DBP-lowering effect of telmisartan but not amlodipine in Chinese EH patients.

  16. The effects of dual and triple combinations of trandolapril, telmisartan, and verapamil on overt proteinuria in the patients with diabetic nephropathy.

    Science.gov (United States)

    Albayrak, Bülent; Cankaya, Erdem; Cetinkaya, Ramazan; Cerrah, Serkan; Bilen, Yusuf

    2016-01-01

    Diabetic nephropathy (DN) is one of the most important causes of the end-stage renal failure and its prevalence is found to be increasing. The presence of hypertension and progressive proteinuria is among the important findings. In this study, the effects of double and triple combinations of trandolapril, telmisartan, and verapamil on proteinuria were investigated in diabetic patients with nephropathy. Seventy-eight patients (mean age: 56.11 ± 11.26 years; 47 females and 31 males) with overt proteinuria and DN were included in this study. The patients were divided into four groups: Group I (n: 18, trandolapril + telmisartan), Group II (n: 20, trando- lapril + verapamil), Group III (n: 20, trandolapril +telmisartan + verapamil), and Group IV (n: 20, telmisartan + verapamil). At the end of a three-month therapy, within and between group compa- risons were done about the effects of the use of double or triple drug combinations on proteinuria, glomerular filtration rate (GFR), electrolytes, serum albumin, low-density lipoprotein (LDL)- cholesterol, and HbA1C. There was no significant difference among groups in terms of age, gender, diabetes duration, body mass index, and retinopathy frequency. The decreases in protei- nuria and mean arterial blood pressure (MABP) were significant in all groups. The decrease in proteinuria was independent of the decrease in MABP [the reduction rate in proteinuria was 39% (P treatment) was significant in Groups III and IV when com- pared to Groups I and II. Any adverse event, like hyperkalemia, was not observed. There was no significant difference among the groups in terms of GFR, LDL-cholesterol, albumin, and potassium. All the patients tolerated the drugs well. In conclusion, in patients with DN, both double or triple combinations of trandolapril, telmisartan and verapamil resulted in signi- ficant decreases in proteinuria and MABP. Triple combinations did not have any supe- riority over double combinations. Therefore, the suitable

  17. Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan.

    Science.gov (United States)

    Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G; Campbell, Ashley M; Saavedra, Juan M; Shewmaker, Frank P; Symes, Aviva J

    2015-10-01

    Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. PMID:26435412

  18. Study of changes in serum lipid profile and blood sugar level by perindopril and telmisartan during treatment of systemic hypertension

    Directory of Open Access Journals (Sweden)

    Manish Kumar

    2014-06-01

    Results: With perindopril initial means of TC, HDL, LDL, TGs, FBS, and PPBS in Groups A and B were 190.32, 49.76, 117.96, 165.04, 84.56, 122.60, and 188.80, 51.64, 118.52, 159.12, 93.92, 133.60, respectively. After 24 weeks, these values were 190.84, 50.68, 118.60, 163.84, 83.48, 120.20, and 190.96, 52.04, 118.28, 157.56, 93.96, 133.68, respectively (p > 0.05. With telmisartan, initial means of TC, HDL, LDL, TG, FBS, and PPBS in both groups were 188.08, 49.76, 118.84, 167.20, 83.72, 120.68, and 188.08, 46.88, 121.96, 167.84, 91.44, 131.72, respectively. After 24 weeks, these values in both groups were 189.36, 49.80, 120.04, 165.96, 82.60, 118.36 and 186.12, 45.28, 121.08, 167.72, 92.76, 129.56 respectively (p > 0.05. Conclusions: It concluded that both perindopril and telmisartan had not any significant adverse effects on plasma lipid profile and blood sugar level in both groups. [Int J Basic Clin Pharmacol 2014; 3(3.000: 454-459

  19. Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression

    Institute of Scientific and Technical Information of China (English)

    Bing-yan GUO; Yong-jun LI; Rui HAN; Shao-1ing YANG; Ying-hui SHI; De-rong HAN; Hong ZHOU; Mei WANG

    2011-01-01

    Aim:To investigate whether telmisartan(Telm)pretreatment attenuates isoproterenol(Iso)-induced postinfarction remodeling(PIR)in rats, and whether the effect of Telm is associated with cardiac expression of adiponectin.Methods:PIR was induced in male Wistar rats with two consecutive injections of Iso(80 mg/kg,sc)at an interval of 24 h.Primary Culture of ventricular myocytes from neonatal rats was prepared.Iso-induced cardiomyocyte injury was assessed based on cell growth and lactate dehydrogenase(LDH)activity.Cardiac adiponectin expression was measured using qRT-PCR and immunoblot analysis.Results:In the rats with PIR.Telm(10 mg·kg-1·d-1,po for 65 d)suppressed lso-induced increases in gravimetric parameters.cardiomyocyte diameter and collagen volume fraction,but had no effect on Iso-induced myocardial hypertrophy and interstitial fibrosis.The protective effect of Telm was associated with enhanced protein expression of cardiac adiponectin.In cultured cardiomyocytes,Telm (5-20 μmol/L)inhibited the celI death and LDH release induced by lSO(10 μmol/L).and reversed Iso-induced reduction in adiponectinprotein expression.In cardiomyocytes exposed to Iso(20 μmol/L).GW9662(30 μmol/L),a selective antagonist of PPAR-v,blocked the effects of Telm Dretreatment on adiponectin protein expression,as well as the protective effects of Telm on Iso-induced celI injUry.Conclusion:Telm attenuates Iso-induced cardiac remodeling and cell injury,which is associated with induction of cardiac adiponectin expression.

  20. Use of beta blockers in various clinical states

    OpenAIRE

    Radović Vesna V.

    2011-01-01

    Introduction. According to the convincing evidence, a decline in mortality rate has been achieved with beta-blockers in patients with an acute myocardial infarction and in post-infarction follow-up. In fact, there has been a clear reduction of sudden coronary death. The necessary condition for the efficiency of beta-blockers is an early use. They are also a medication of choice for angina after an infarction. The objective of this work was to evaluate the use of beta-blockers after a my...

  1. Refractory anaphylactoid shock potentiated by beta-blockers.

    Science.gov (United States)

    Javeed, N; Javeed, H; Javeed, S; Moussa, G; Wong, P; Rezai, F

    1996-12-01

    Allergic reactions, including anaphylactoid shock due to contrast material, are not uncommon. However, persistent anaphylactoid shock refractory to conventional therapy is rare. We present a case of refractory anaphylactoid shock during coronary angiography unresponsive to aggressive standard therapy in a patient on beta-blockers. Significant clinical improvement was noted upon administration of glucagon. Since beta-blockers are commonly used in patients with coronary artery disease, this potentially life-threatening complication has to be kept in mind with any procedure involving contrast media in patients on beta-blockers. Immediate access to glucagon by keeping it in the procedure room may be lifesaving in these situations. PMID:8958428

  2. β-Blockers in coronary artery disease management

    OpenAIRE

    Boudonas, G E

    2010-01-01

    Beta-blockers are a multiform group of drugs with multiple applications in the treatment of patients with cardiovascular disease. Their adverse actions are multiple and relate mainly to the β-adrenergic receptor blockade.

  3. Beta-blockers in cirrhosis and refractory ascites

    DEFF Research Database (Denmark)

    Kimer, Nina; Feineis, Martin; Møller, Søren;

    2015-01-01

    OBJECTIVE: It is currently discussed if beta-blockers exert harmful effects and increase mortality in patients with cirrhosis and refractory ascites. In this study, we provide an overview of the available literature in this field in combination with a retrospective analysis of 61 patients with...... trials (9 trials on propranolol, 1 case-control study and 4 retrospective analyses) were identified. One trial suggested an increased mortality in patients treated with beta-blockers and refractory ascites. The results of the remaining trials were inconclusive. No increase in mortality among beta-blocker......-treated patients was found in the present retrospective analysis. CONCLUSIONS: Treatment with beta-blockers may increase mortality in patients with cirrhosis and refractory ascites. However, the current evidence is sparse and high-quality studies are warranted to clarify the matter....

  4. Fracture risk in perimenopausal women treated with beta-blockers

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Vestergaard, Peter; Kassem, Moustapha;

    2004-01-01

    beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density...... (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study....... Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture...

  5. The Use of Calcium Channel Blockers in Skin Diseases

    Directory of Open Access Journals (Sweden)

    Özge Uzun

    2013-05-01

    Full Text Available Calcium channel blockers are a group of drugs often used to treat cardiovascular diseases, such as hypertension, angina, peripheral vascular disorders and some arrhythmias. These drugs may suppress the growth and proliferation of vascular smooth muscle cells and fibroblasts, and inhibit the synthesis of extracellular-matrix proteins,such as collagen, fibronectin, proteoglycans. Some calcium channel blockers also have immunomodulatory or dysregulatory effects on lymphocytes and can suppress superoxide generation and phagocytic activity of neutrophils. Moreover, mast cell degranulation and platelet aggregation may also be impaired. On account of these properties, calcium channel blockers have also been used for the prevention and treatment of various dermatologic diseases. In this review, we evaluated the use of calcium channel blockers in various dermatologic diseases, such as Raynaud’s phenomenon, chilblains, chronic anal fissures, vulvodynia, keloids and burn scars, calcinosis cutis, and leiomyoma.

  6. Beta blockers after myocardial infarction: have trials changed practice?

    OpenAIRE

    Baber, N S; Julian, D.G.; Lewis, J. A.; Rose, G.

    1984-01-01

    A survey of British consultant cardiologists was carried out to elicit their current practices when prescribing long term beta blockers after myocardial infarction. Sixty (72%) of the respondents reported that they used beta blockers prophylactically even in the absence of any other indications; the details of their stated policies, however, varied considerably. The favourable evidence of clinical trials in this indication appears to have been assimilated into hospital practice.

  7. Treatment with beta-adrenoceptor blockers reduces plasma melatonin concentration.

    OpenAIRE

    Cowen, P J; Bevan, J. S.; Gosden, B; Elliott, S A

    1985-01-01

    In treated hypertensive patients plasma melatonin levels were lower in subjects receiving beta-adrenoceptor blockers than those treated with diuretics. Melatonin concentrations in middle-aged and young control subjects were similar to each other and to those of the diuretic-treated patients. The results suggest that treatment with beta-adrenoceptor blockers causes a persistent reduction in plasma melatonin but it is unclear if this finding has clinical implications.

  8. Beta-blockers: friend or foe in asthma?

    OpenAIRE

    Arboe B; Ulrik CS

    2013-01-01

    Bente Arboe, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, DenmarkBackground and aim: Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma.Method: Systematic literature review.Results: No significant increase in the number of...

  9. β-Blocker treatment during pregnancy and adverse pregnancy outcomes

    DEFF Research Database (Denmark)

    Petersen, Kasper Meidahl; Jimenez-Solem, Espen; Andersen, Jon Traerup; Petersen, Morten; Brødbæk, Kasper; Køber, Lars; Torp-Pedersen, Christian; Poulsen, Henrik Enghusen

    2012-01-01

    To investigate the association between exposure to β-blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort.......To investigate the association between exposure to β-blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort....

  10. The Use of Calcium Channel Blockers in Skin Diseases

    OpenAIRE

    Özge Uzun; Mualla Polat

    2013-01-01

    Calcium channel blockers are a group of drugs often used to treat cardiovascular diseases, such as hypertension, angina, peripheral vascular disorders and some arrhythmias. These drugs may suppress the growth and proliferation of vascular smooth muscle cells and fibroblasts, and inhibit the synthesis of extracellular-matrix proteins,such as collagen, fibronectin, proteoglycans. Some calcium channel blockers also have immunomodulatory or dysregulatory effects on lymphocytes and can suppress su...

  11. Non-selective beta-blockers decrease thrombotic events in patients with heart failure

    NARCIS (Netherlands)

    De Peuter, Olav R.; Souverein, Patrick C.; Klungel, Olaf H.; Lip, Gregory Y.; Buller, Harry R.; De Boer, Anthonius; Kamphuisen, Pieter W.

    2010-01-01

    Background: Beta-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of beta-blockers. The 2002 COMET study showed superiority of carvedilol (a non-selective beta-blocker) over metoprolol (selective beta-blocker) on mortality and cardiovascular events

  12. BETA-BLOCKERS IN THE TREATMENT OF ARTERIAL HYPERTENSION: EVIDENCE BASED DATA AND REAL PRACTICE

    OpenAIRE

    M. V. Leonova

    2015-01-01

    Data of the largest meta-analyzes of beta-blockers use in arterial hypertension is presented. The role of beta-blockers among other basic groups of antihypertensive drugs (thiazide diuretics, calcium channel blockers, ACE inhibitors) is evaluated. Special considerations of beta-blockers use in hypertensive patients with diabetes mellitus and chronic heart failure are discussed. Special attention is paid to bisoprolol.

  13. Beta-blockers: friend or foe in asthma?

    Directory of Open Access Journals (Sweden)

    Arboe B

    2013-07-01

    Full Text Available Bente Arboe, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, DenmarkBackground and aim: Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma.Method: Systematic literature review.Results: No significant increase in the number of patients requiring rescue oral corticosteroid for an exacerbation of asthma has been observed after initiation of β-blocker treatment. Patients with mild to moderate reactive airway disease, probably both asthma and chronic obstructive pulmonary disease, may have a limited fall in forced expiratory volume in 1 second (FEV1 following single-dose administration of β-blocker, whereas no change in FEV1 has been reported following long-term administration. In a murine model of asthma, long-term administration of β-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect. In keeping with this, long-term administration of a nonselective β-blocker to steroid-naïve asthma patients has shown a dose-dependent improvement in airway hyperresponsiveness, and either an asymptomatic fall in FEV1 or no significant change in FEV1. Furthermore, available studies show that bronchoconstriction induced by inhaled methacholine is reversed by salbutamol in patients on regular therapy with a β-blocker. On the other hand, a recent placebo-controlled trial of propranolol and tiotropium bromide added to inhaled corticosteroids revealed no effect on airway hyperresponsiveness and a small, not statistically significant, fall in FEV1 in patients classified as having mild to moderate asthma.Conclusion: The available, although limited, evidence suggests that a dose-escalating model of β-blocker therapy to patients with asthma is well tolerated, does not

  14. Photochemical fate of beta-blockers in NOM enriched waters

    International Nuclear Information System (INIS)

    Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4–10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9 h−1 at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical (·OH) and singlet oxygen (1ΔO2), and, the direct reaction with the triplet excited state, 3NOM⁎, also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with 1ΔO2 and ·OH were measured and accounted for 0.02–0.04% and 7.2–38.9% of their loss, respectively. These data suggest that the 3NOM⁎ contributed 50.6–85.4%. Experiments with various 3NOM⁎ quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC–MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. - Highlights: ► Photochemical degradation of beta-blockers in the simulated natural waters. ► Reactive Oxygen Species play a minor role in the indirect photodegradation. ► The loss of beta-blockers results from direct reaction with 3DOM⁎.

  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.

    Science.gov (United States)

    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 (PADN 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 sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, and improved some of the adipocytokines related to insulin resistance. PMID:25994603

  16. Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Guo Zhixin

    2012-08-01

    Full Text Available Abstract Background Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2 and nicotinamide adenine dinucleotide phosphate (NADPH oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1 in aorta in type 2 diabetic rats. Methods Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ. Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4, monocyte chemoattractant protein-1(MCP-1 and connective tissue growth factor (CTGFin the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-κB in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d by gavage for 12 weeks. Results Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P Conclusions Our results suggest that telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-κB in the abdominal aorta in diabetic rats.

  17. Simultaneous determination of related substances of telmisartan and hydrochlorothiazide in tablet dosage form by using reversed phase high performance liquid chromatographic method

    OpenAIRE

    Sutirtho Mukhopadhyay; Kiran Kadam; Laxman Sawant; Dhanashree Nachane; Nancy Pandita

    2011-01-01

    Objective : Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT 1 ) receptor that is indicated for the treatment of essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and it is indicated for the treatment of edema, control of essential hypertension and management of diabetes insipidus. In the current article a new, accurate, sensitive, precise, rapid, reversed phase high performance liquid chromatography (RP-HPLC) method was d...

  18. Microalbuminuria and sRAGE in High-Risk Hypertensive Patients Treated with Nifedipine/Telmisartan Combination Treatment: A Substudy of TALENT

    Directory of Open Access Journals (Sweden)

    Colomba Falcone

    2012-01-01

    Full Text Available Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products. In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity.

  19. Microalbuminuria and sRAGE in High-Risk Hypertensive Patients Treated with Nifedipine/Telmisartan Combination Treatment: A Substudy of TALENT

    Science.gov (United States)

    Falcone, Colomba; Buzzi, Maria Paola; Bozzini, Sara; Boiocchi, Chiara; D'Angelo, Angela; Schirinzi, Sandra; Esposito, Ciro; Torreggiani, Massimo; Choi, Jasmine; Ochan Kilama, Michael; Mancia, Giuseppe

    2012-01-01

    Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR) are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products). In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE) plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity. PMID:22474401

  20. An innovative way to reinsert dislodged Arndt blocker using urological glide wire

    Science.gov (United States)

    Pillai, Rahul; Ancheri, Sneha Ann; Dharmalingam, Sathish Kumar; Sahajanandan, Raj

    2016-01-01

    The Arndt blocker is positioned in the desired bronchus using a wire loop which couples the blocker with a fiberoptic bronchoscope (FOB). The wire loop once removed cannot be reinserted in 5F and 7F blockers making repositioning of the blocker difficult. A 34-year-old female was to undergo left thoracotomy followed by laparoscopic cholecystectomy. The left lung was isolated with a 7F Arndt bronchial blocker. During one-lung ventilation, the wire loop was removed for oxygen insufflation. There was loss of lung isolation during the procedure and dislodgement of the blocker was confirmed by FOB. The initial attempts to reintroduce the blocker into the left main bronchus failed. An alternative technique using a glide wire was attempted which resulted in successful reintroduction of the Arndt blocker. The 0.032 inch zebra glide wire may be effectively used to reposition a dislodged Arndt blocker if the wire loop has been removed. PMID:27052085

  1. Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension

    Directory of Open Access Journals (Sweden)

    Takami T

    2012-09-01

    Full Text Available Takeshi Takami,1 Hiroshi Ito,2 Katsuhisa Ishii,3 Kenei Shimada,4 Katsuomi Iwakura,5 Hiroyuki Watanabe,6 Shota Fukuda,7 Junichi Yoshikawa81Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2Department of Cardiovascular Medicine, Okayama University, Graduate School of Medicine, Okayama, Japan; 3Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan; 4Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan; 5Cardiovascular Center, Sakurabashi Watanabe Hospital, Osaka, Japan; 6Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 7Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 8Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanAbstract: The urinary albumin to creatinine ratio (UACR is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi or angiotensin receptor blocker (ARB to a combination of losartan and hydrochlorothiazide on left ventricular (LV relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024, but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051. Among DM patients, there was a significant relationship between changes in UACR and changes in e′ velocity (r =

  2. α-Blocker Monotherapy and α-Blocker Plus 5-Alpha-Reductase Inhibitor Combination Treatment in Benign Prostatic Hyperplasia; 10 Years' Long-Term Results

    OpenAIRE

    Shin, Teak Jun; Kim, Chun Il; Park, Choal Hee; Kim, Byung Hoon; Kwon, Young Kee

    2012-01-01

    Purpose We compared the effects of alpha-adrenergic receptor blocker (α-blocker) monotherapy with those of combination therapy with α-blocker and 5-alpha-reductase inhibitor (5-ARI) on benign prostatic hyperplasia (BPH) progression for over 10 years. Materials and Methods A total of 620 patients with BPH who received α-blocker monotherapy (α-blocker group, n=368) or combination therapy (combination group, n=252) as their initial treatment were enrolled from January 1989 to June 2000. The inci...

  3. Effects of telmisartan on metabolic changes and insulin sensitivity in elderly patients with type 2 diabetes mellitus and hypertension%替米沙坦对老年2型糖尿病合并高血压患者糖脂代谢及胰岛素敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    于晓红; 于志宏

    2011-01-01

    目的 探讨血管紧张素受体拮抗药替米沙坦对老年2型糖尿病合并高血压患者糖脂代谢及胰岛素敏感性的作用.方法 48例老年2型糖尿病合并高血压患者按体重指数(body mass index,BMI)分为非肥胖组和肥胖组.每位患者每天空腹口服80 mg替米沙坦,共24周.测定治疗前后BMI、腰臀比(waist-to-hip ratio,WHR)、胰岛素、血糖、血脂、血压、肝功能、肾功能、血管紧张素Ⅱ,计算稳态模型胰岛素抵抗指数(HOMA-IR).结果 替米沙坦治疗前,与非肥胖组相比,肥胖组收缩压(SBP)、舒张压(DBP)、三酰甘油(triglyceride,TG)、胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,LDL-C)、空腹血糖(fasting plasma glucose,FPG)、空腹胰岛素值(fasting insulin,FINS)、HOMA指数(homeostasis model assessment - insulin resistance index,HOMA-IR)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)均升高,差异有统计学意义(P<005).非肥胖组替米沙坦治疗后,SBP、FINS、HOMA-IR水平与治疗前相比均下降,ANGⅡ水平升高,差异有统计学意义.肥胖组替米沙坦治疗后,SBP、DBP、TG、TC、FPG、FINS、HOMA-IR水平与治疗前相比均下降,差异有统计学意义(P<005).结论 替米沙坦能够有效降低老年2型糖尿病合并高血压患者的血压,明显改善其糖、脂代谢状态,增强机体对胰岛素的敏感性.%Objective To evaluate the effect of teimisartan, an angiotensin Ⅱ ATI receptor blocker (ARB), on metabolism and insulin sensitivity in elderly patients with type 2.diabetes mellitus and hypertension.Methods Subjects were divided into two groups according to the body mass index (BMI): the group of nonobese patients (n =20) and the group of obese patients (n =28).All the patients were administered telmisartan 80mg/d for 24 weeks.BMI, waist hip ratio (WHR), systolic blood pressure ( SBP),diastolic blood pressure (DBP), triglyceride (TG), total cholesterol ( TC ), low

  4. Efficacy and safety of amiodarone combined with telmisartan for prevention of paroxysmal atrial fibrillation%胺碘酮联合替米沙坦预防阵发性心房颤动的疗效与安全性

    Institute of Scientific and Technical Information of China (English)

    王志敬; 孙波; 周茂峰; 许东伟

    2011-01-01

    目的:观察胺碘酮联用替米沙坦预防阵发性心房颤动的疗效,并评价其安全性.方法:将204例高血压合并阵发性心房颤动病人用随机数字表法分为试验组与对照组.试验组与对照组病人均口服胺碘酮,第1周600 mg/d,第2周400 mg/d,第3周200mg/d,之后100 mg/d.试验组病人同时口服替米沙坦20~80 mg/d;对照组病人服用其他降压药,避免使用血管紧张素转换酶抑制剂(ACEIs)和血管紧张素受体拮抗剂(ARBs).随访6个月,观察两组病人的心房颤动发作次数、复发例数、首次复发时间以及药物不良反应(ADRs)发生率.结果:试验组和对照组分别有91和95例病人完成试验.试验组发生ADRs的例数较对照组显著增加(56 vs 41,P<0.05),主要表现为胃肠道反应发生率升高,但因严重ADRs导致的停药例数组间差异无统计学意义(P>0.05).试验组心房颤动首次复发的时间较对照组明显延长[(94.59±30.51)d vs (84.54±28.73)d,P<0.05],复发次数显著减少(32 vs 53,P<0.05); 3个月内复发例数无显著差异(15 vs 24,P>0.05),6个月内复发例数显著减少(26 vs 42,P<0.05).结论:胺碘酮与替米沙坦联用预防阵发性心房颤动安全、有效.%Objective: To observe the efficacy and safety of amidarone combined with telmisartan for prevention of paroxysmal atrial fibrillation. Methods: A total of 204 patients with hypertension and paroxysmal atrial fibrillation were randomly divided into test and control groups by digit table. Patients in the two groups took amiodarone 600 mg/d in the first week, 400 mg/d in the second week,200 mg/d in the third week and 100 mg/d afterwards. Patients in the test group were also treated with telmisartan at the dose of 20-80 mg/d simultaneously. While patients in the control group were treated with other antihy-pertensive drugs,excluding angiotensin converting enzyme inhibitorsC ACEIs) and angtotensin receptor blockersC ARBs). All the patients were

  5. The effects of dual and triple combinations of trandolapril, telmisartan, and verapamil on overt proteinuria in the patients with diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Bülent Albayrak

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is one of the most important causes of the end-stage renal failure and its prevalence is found to be increasing. The presence of hypertension and progressive proteinuria is among the important findings. In this study, the effects of double and triple combinations of trandolapril, telmisartan, and verapamil on proteinuria were investigated in diabetic patients with nephropathy. Seventy-eight patients (mean age: 56.11 ± 11.26 years; 47 females and 31 males with overt proteinuria and DN were included in this study. The patients were divided into four groups: Group I (n: 18, trandolapril + telmisartan, Group II (n: 20, trando- lapril + verapamil, Group III (n: 20, trandolapril +telmisartan + verapamil, and Group IV (n: 20, telmisartan + verapamil. At the end of a three-month therapy, within and between group compa- risons were done about the effects of the use of double or triple drug combinations on proteinuria, glomerular filtration rate (GFR, electrolytes, serum albumin, low-density lipoprotein (LDL- cholesterol, and HbA1C. There was no significant difference among groups in terms of age, gender, diabetes duration, body mass index, and retinopathy frequency. The decreases in protei- nuria and mean arterial blood pressure (MABP were significant in all groups. The decrease in proteinuria was independent of the decrease in MABP [the reduction rate in proteinuria was 39% (P <0.001 in Group I, 37% (P <0.001 in Group II, 42% (P <0.001 in Group III, and 43% (P <0.001 in Group IV; the reduction rate in MABP was 10.6% (P <0.001 in Group I, 13.7% (P <0.001 in Group II, 17.5% (P <0.001 in Group III, and 15.4% (P <0.001 in Group IV]. Decrease in HbA1C (before and after treatment was significant in Groups III and IV when com- pared to Groups I and II. Any adverse event, like hyperkalemia, was not observed. There was no significant difference among the groups in terms of GFR, LDL-cholesterol, albumin, and potassium. All the patients

  6. Safe browsing - is an ad-blocker enough?

    CERN Document Server

    CERN. Geneva

    2015-01-01

    An ad-blocker plugin in your browser stops advertisements and maybe some malware. But is it enough? Are you feeling secure while surfing the Web? If your answer is yes, think twice! What else can you do to protect yourself?

  7. Perioperative beta blockers in patients having non-cardiac surgery

    DEFF Research Database (Denmark)

    Bangalore, Sripal; Wetterslev, Jørn; Pranesh, Shruthi;

    2008-01-01

    American College of Cardiology and American Heart Association (ACC/AHA) guidelines on perioperative assessment recommend perioperative beta blockers for non-cardiac surgery, although results of some clinical trials seem not to support this recommendation. We aimed to critically review the evidenc...

  8. The role of beta-blockers in septic patients.

    Science.gov (United States)

    Hamzaoui, O; Teboul, J L

    2015-03-01

    β-blockers are widely used to treat cardiovascular diseases and in the peri-operative period in selected patients. The main benefit in terms of morbidity and/or mortality of their use is believed to be linked to specific effects on myocardial oxygen supply/demand balance, to anti-arrhythmic effects and anti-inflammatory effects. Use of β-blockers in severe sepsis is still under debate and if any, their appropriate indications remain unclear. In this article, we analyze the recent literature addressing the metabolic, immuno-modulatory and hemodynamic effects of non cardio-selective and of cardio-selective β-blockers in experimental and human sepsis in order to help clarifying the potential place of these drugs in patients with severe sepsis. From this analysis, it appears that β-adrenoceptor blocking agents may represent a therapeutic approach in patients with severe sepsis, in whom catecholaminergic hyperactivity including excessive tachycardia is supposed to play an aggravating role. However, many questions about effectiveness, safety and cardio-selectivity of the drugs and about the appropriate target population remain partially unanswered. Recently, esmolol, a short-time acting β1-adrenoceptor blocker titrated to decrease heart rate below 95 beats/min was shown to exert beneficial effects in a monocentric randomized clinical trial including selected septic patients. Further large multicenter randomized trials are required to confirm the potential benefit of such a therapy in patients with severe sepsis. PMID:24941896

  9. Photochemical fate of beta-blockers in NOM enriched waters

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ling; Xu, Haomin; Cooper, William J. [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Song, Weihua, E-mail: wsong@fudan.edu.cn [Department of Environmental Science and Engineering, Fudan University, Shanghai 200433 (China)

    2012-06-01

    Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4-10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9 h{sup -1} at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical ({center_dot}OH) and singlet oxygen ({sup 1}{Delta}O{sub 2}), and, the direct reaction with the triplet excited state, {sup 3}NOM{sup Low-Asterisk }, also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with {sup 1}{Delta}O{sub 2} and {center_dot}OH were measured and accounted for 0.02-0.04% and 7.2-38.9% of their loss, respectively. These data suggest that the {sup 3}NOM{sup Low-Asterisk} contributed 50.6-85.4%. Experiments with various {sup 3}NOM{sup Low-Asterisk} quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC-MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. - Highlights: Black-Right-Pointing-Pointer Photochemical degradation of beta-blockers in the simulated natural waters. Black-Right-Pointing-Pointer Reactive Oxygen Species play a minor role in the indirect photodegradation. Black-Right-Pointing-Pointer The loss of beta-blockers results from direct reaction with {sup 3}DOM{sup Low-Asterisk }.

  10. Treating High Blood Pressure: Is a Calcium Channel Blocker Drug Right for You?

    Science.gov (United States)

    ... Blood Pressure: Is a Calcium Channel Blocker Drug Right for You? What are calcium channel blockers? Calcium ... talk with your doctor about which drugs are right for you. If your blood pressure is slightly ...

  11. Prospective Factor Analysis of Alpha Blocker Monotherapy Failure in Benign Prostatic Hyperplasia

    OpenAIRE

    Hong, Kyoung Pyo; Byun, Young Joon; Yoon, Hana; Park, Young Yo; Chung, Woo Sik

    2010-01-01

    Purpose We aimed to determine the treatment of choice criteria for benign prostatic hyperplasia (BPH) by analyzing the factors causing alpha-adrenergic receptor blocker (α-blocker) monotherapy failure. Materials and Methods This retrospective study enrolled 129 patients with BPH who were prescribed an α-blocker. Patients were allocated to a transurethral resection of prostate (TURP) group (after having at least a 6-month duration of medication) and an α-blocker group. We compared the differen...

  12. Pre-stroke use of beta-blockers does not affect ischaemic stroke severity and outcome

    NARCIS (Netherlands)

    De Raedt, S.; Haentjens, P.; De Smedt, A.; Brouns, R.; Uyttenboogaart, Maarten; Luijckx, G. J.; De Keyser, J.

    2012-01-01

    Background and purpose: It is unclear whether pre-stroke beta-blockers use may influence stroke outcome. This study evaluates the independent effect of pre-stroke use of beta-blockers on ischaemic stroke severity and 3 months functional outcome. Methods: Pre-stroke use of beta-blockers was investiga

  13. Clinical Implication of the Renin-angiotensin-aldosterone Blockers in Chronic Kidney Disease Undergoing Hemodialysis

    OpenAIRE

    Morishita, Yoshiyuki; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    The renin-angiotensin-aldosterone system (RAAS) blockers have been widely used in chronic kidney disease patients undergoing hemodialysis; however, whether RAAS blockers have beneficial effects for cardiovascular disease in those patients has not been fully defined. This review focuses on the effects of RAAS blockers in chronic kidney disease undergoing hemodialysis for cardiovascular disease.

  14. Validated spectrofluorimetric determination of two pharmaceutical antihypertensive mixtures containing amlodipine besylate together with either candesartan cilexetil or telmisartan.

    Science.gov (United States)

    Belal, Tarek S; Mahrous, Mohamed S; Abdel-Khalek, Magdi M; Daabees, Hoda G; Khamis, Mona M

    2014-11-01

    Amlodipine besylate (AML) is available in fixed-dose combination tablets with either candesartan cilexetil (CAN) or telmisartan (TEL). This work describes a simple, selective and sensitive spectrofluorimetric method for analysis of AML/CAN and AML/TEL binary mixtures without prior separation. The method involves measurement of the native fluorescence of AML at excitation and emission wavelengths of 367 and 454 nm, respectively, in water without interference from either of the two drugs. By contrast, the intrinsic fluorescence of CAN was measured at excitation and emission wavelengths of 265 and 392 nm, respectively, in ethanol, while TEL was measured at 366 nm in 0.05 M sodium hydroxide solution using 294 nm as the excitation wavelength. The proposed spectrofluorimetric procedure was validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness, detection and quantification limits. Regression analysis showed a good correlation between fluorescence intensity and concentration over the ranges 0.1-1.4, 0.025-0.25 and 0.0025-0.05 µg/mL for AML, CAN and TEL, respectively. Limits of detection were 0.034, 0.0063 and 0.0007 µg/mL for AML, CAN and TEL, respectively. The proposed method was successfully applied for the analysis of several synthetic binary mixtures of different ratios and laboratory-prepared tablets with good recoveries, and no interference from common pharmaceutical additives was observed. PMID:24615878

  15. Simultaneous determination of related substances of telmisartan and hydrochlorothiazide in tablet dosage form by using reversed phase high performance liquid chromatographic method

    Directory of Open Access Journals (Sweden)

    Sutirtho Mukhopadhyay

    2011-01-01

    Full Text Available Objective : Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT 1 receptor that is indicated for the treatment of essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and it is indicated for the treatment of edema, control of essential hypertension and management of diabetes insipidus. In the current article a new, accurate, sensitive, precise, rapid, reversed phase high performance liquid chromatography (RP-HPLC method was developed for determination of related substances of Telmisartan and Hydrochlorthiazide in tablet dosage form. Materials and Methods : Simultaneous determination of related substances was performed on Kromasil C 18 analytical column (250 × 4.6 mm; 5΅m pertical size column at 40°C employing a gradient elution. Mobile phase consisting of solvent A (solution containing 2.0 g of potassium dihydrogen phosphate anhydrous and 1.04 g of Sodium 1- Hexane sulphonic acid monohydrate per liter of water, adjusted to pH 3.0 with orthophosphoric acid and solvent B (mixture of Acetonitrile: Methanol in the ratio 80:20 v/v was used at a flow rate of 1.0 ml min−1 . UV detection was performed at 270 nm. Results : During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. Conclusions : HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. It may find application for the routine analysis of the related substances of both Telmisartan and Hydrochlorthiazide in this combination tablets.

  16. Heart failure - tests

    Science.gov (United States)

    ... test regularly if: You are taking medicines called ACE inhibitors or ARBs (angiotensin receptor blockers) Your provider makes ... there are changes made for some medicines including: ACE inhibitors, ARBs, or certain types of water pills (amiloride, ...

  17. The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy : a randomised trial

    NARCIS (Netherlands)

    de Zeeuw, Dick; Bekker, Pirow; Henkel, Elena; Hasslacher, Christopher; Gouni-Berthold, Ioanna; Mehling, Heidrun; Potarca, Antonia; Tesar, Vladimir; Lambers Heerspink, Hiddo J.; Schall, Thomas J.

    2015-01-01

    Background Patients with type 2 diabetes and nephropathy have high cardiorenal morbidity and mortality despite optimum treatment including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Residual risk is related to residual albuminuria. We assessed whether CCX

  18. Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria

    NARCIS (Netherlands)

    Heerspink, Hiddo Lambers; Greene, Tom; Lewis, Julia B.; Raz, Itamar; Rohde, Richard D.; Hunsicker, Lawrence G.; Schwartz, Sherwyn L.; Aronoff, Stephen; Katz, Murray A.; Eisner, Gilbert M.; Mersey, James H.; Wiegmann, Thomas B.

    2008-01-01

    Background. Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized t

  19. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials

    DEFF Research Database (Denmark)

    Bilous, Rudy; Chaturvedi, Nish; Sjølie, Anne Katrin;

    2009-01-01

    BACKGROUND: Microalbuminuria in diabetes is strongly predictive of nephropathy, end-stage renal disease, and premature cardiovascular morbidity and mortality. Effective preventive therapies are therefore a clinical priority. OBJECTIVE: To determine whether the angiotensin-receptor blocker candesa...

  20. Modeling Human Blockers in Millimeter Wave Radio Links

    Institute of Scientific and Technical Information of China (English)

    Jonathan S. Lu; Daniel Steinbach; Patrick Cabrol; Philip Pietraski

    2012-01-01

    In this paper, we investigate the loss caused by multiple humans blocking millimeter wave frequencies. We model human blockers as absorbing screens of infinite height with two knife-edges, We take a physical optics approach to computing the diffraction around the absorbing screens, This approach differs to the geometric optics approach described in much of the literature. The blocking model is validated by measuring the gain from multiple-human blocking configurations on an indoor link. The blocking gains predicted using Piazzi ' s numerical integration method (a physical optics method) agree well with measurements taken from approximately 2.7 dB to -50 dB. Thereofre, this model is suitable for real human blockers, The mean prediction error for the method is approximately -1.2 dB, and the standard deviation is approximately 5 dB.

  1. HEART FAILURE, DIABETES, BETA-BLOCKERS AND RISK OF HYPOGLYCEMIA

    Directory of Open Access Journals (Sweden)

    A. A. Aleksandrov

    2008-01-01

    Full Text Available Aim. To evaluate an influence of carvedilol on risk of hypoglycemia in patients with diabetes type 2 (D2 and chronic heart failure (CHF treated with angiotensin converting enzyme (ACE inhibitors.Material and methods. 13 patients (10 men, 3 women; aged 59,8±6,7 y.o. with D2 and CHF caused by ischemic heart disease were included in the study. Before inclusion all patients were treated with ACE inhibitors and various beta-blockers (atenolol, metoprolol, bisoprolol. These beta-blockers were changed for carvedilol. Heart ultrasonography, blood pressure control, glycemia monitoring, HbA1c level determination were performed before, during and after carvedilol therapy.Results. Carvedilol reduces frequency and duration of hypoglycaemia episodes. There were not episodes of severe hypoglycaemia during carvedilol therapy.Conclusion. Carvedilol reduces risk of hypoglycemia when it is used in combination with ACE inhiditors in diabetic patients with CHF.

  2. Analysis of solar blocker through portable X-ray fluorescence

    International Nuclear Information System (INIS)

    This paper estimates the concentration of TiO2 by Energy Dispersion X-ray fluorescence (EDXRF) viewing t obtain the FPS due to the physical barrier in the composition of solar blockers, and identifies possible present metals in the samples. A portable EDXRF equipment was used and 27 commercial of different brands and solar protection factors were analysed. Also, three formulations (A, B and C) were prepared and measured estimated in FPS-30 using 5% or TiO2. The quantification was performed through calibration curves with 1% to 30% standards of TiO2. As result, it was possible to determine the contribution to physical protection in the FPS, associated to the Ti concentration present in some solar blocker samples available in the market. Also, it was possible to detect the presence of various metals in solar protectors, such as Fe, Zn, Br and Sr, and identify chemical elements which were not mentioned and their formulation as well

  3. β-adrenoceptor blocker pharmacokinetics and the oral contraceptive pill

    OpenAIRE

    Kendall, M. J.; Jack, D B; Quarterman, C P; Smith, S.R.; Zaman, R

    1984-01-01

    Higher AUC and Cmax values were obtained for metoprolol, oxprenolol and propranolol in groups receiving the low-dose oestrogen-ethinyl oestradiol oral contraceptive, but statistical significance was reached only with metoprolol AUC. The oral contraceptive had the opposite effect on acebutolol AUC and Cmax but this was not significant. The oral contraceptive had no detectable effects on the tmax and t½ values of any of the β-adrenoceptor blockers.

  4. Bei Patienten mit Metabolischem Syndrom und leichtem – mittelschwerem Hypertonus verbessert Telmisartan, aber nicht Amlodipin, die myokardiale und die vaskuläre Funktion insbesondere postprandial

    OpenAIRE

    Salmen, Bettina

    2014-01-01

    In der vorliegenden prospektiven Studie im Crossover-Design wurde untersucht, ob der AT1-Rezeptorblocker Telmisartan im Vergleich zu Amlodipin günstigere Auswirkungen auf frühe kardiovaskuläre Veränderungen bei herzgesunden Patienten mit Metabolischem Syndrom aufweist. Die Messungen erfolgten nüchtern und zusätzlich postprandial mit Echokardiographie und myokardialem Gewebedoppler. Die vaskulären Parameter wurden mittels Echo-tracking ermittelt. Nach 12-wöchiger Monotherapie zeigte sich nur m...

  5. Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis

    DEFF Research Database (Denmark)

    Bath, Philip M W; Martin, Reneé H; Palesch, Yuko;

    2009-01-01

    , small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84-1.26; P=0.81; death: OR, 1.05; 95% CI, 0.27-4.04; and stroke recurrence: OR......, 1.40; 95% CI, 0.68-2.89; P=0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mm Hg, difference 6 to 7 mm Hg and 2 to 4 mm Hg; P...

  6. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache.

    Directory of Open Access Journals (Sweden)

    Jeffrey L Jackson

    Full Text Available To compare the effectiveness and side effects of migraine prophylactic medications.We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models.PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014.We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration.Placebo controlled trials included alpha blockers (n = 9, angiotensin converting enzyme inhibitors (n = 3, angiotensin receptor blockers (n = 3, anticonvulsants (n = 32, beta-blockers (n = 39, calcium channel blockers (n = 12, flunarizine (n = 7, serotonin reuptake inhibitors (n = 6, serotonin norepinephrine reuptake inhibitors (n = 1 serotonin agonists (n = 9 and tricyclic antidepressants (n = 11. In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82, -flunarizine (-1.1 headaches/month (ha/month, 95% CI: -1.6 to -0.67, fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17, metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46, pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21, propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62, topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73 and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8. Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril, two angiotensin receptor blockers (candesartan, telmisartan, two anticonvulsants (lamotrigine, levetiracetam, and several beta-blockers (atenolol, bisoprolol, timolol. Network meta-analysis found amitriptyline to be better than several other medications including candesartan, fluoxetine, propranolol, topiramate and valproate and no different than

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

    Science.gov (United States)

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

    2014-05-01

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

  8. Novel roles of nuclear angiotensin receptors and signaling mechanisms.

    Science.gov (United States)

    Gwathmey, TanYa M; Alzayadneh, Ebaa M; Pendergrass, Karl D; Chappell, Mark C

    2012-03-01

    The renin-angiotensin system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. The dysregulation of the RAS is considered a major influence in the development and progression of cardiovascular disease and other pathologies. Indeed, experimental and clinical evidence indicates that blockade of this system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 1 receptor (AT1R) antagonists is an effective therapy to attenuate hypertension and diabetic renal injury, and to improve heart failure. Originally defined as a circulating system, multiple tissues express a complete RAS, and compelling evidence now favors an intracellular system involved in cell signaling and function. Within the kidney, intracellular expression of the three predominant ANG receptor subtypes is evident in the nuclear compartment. The ANG type 1 receptor (AT1R) is coupled to the generation of reactive oxygen species (ROS) through the activation of phosphoinositol-3 kinase (PI3K) and PKC. In contrast, both ANG type 2 (AT2R) and ANG-(1-7) (AT7R) receptors stimulate nitric oxide (NO) formation, which may involve nuclear endothelial NO synthase (eNOS). Moreover, blockade of either ACE2-the enzyme that converts ANG II to ANG-(1-7)-or the AT7 receptor exacerbates the ANG II-ROS response on renal nuclei. Finally, in a model of fetal programmed hypertension, the nuclear ROS response to ANG II is enhanced, while both AT2 and AT7 stimulation of NO is attenuated, suggesting that an imbalance in the intracellular RAS may contribute to the development of programming events. We conclude that a functional intracellular or nuclear RAS may have important implications in the therapeutic approaches to cardiovascular disease. PMID:22170620

  9. Review: Novel roles of nuclear angiotensin receptors and signaling mechanisms

    OpenAIRE

    Gwathmey, TanYa M.; Alzayadneh, Ebaa M.; Karl D. Pendergrass; Chappell, Mark C.

    2011-01-01

    The renin-angiotensin system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. The dysregulation of the RAS is considered a major influence in the development and progression of cardiovascular disease and other pathologies. Indeed, experimental and clinical evidence indicates that blockade of this system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 1 receptor (AT1R) antagonists is an effective therapy to attenuate hype...

  10. Increased serum potassium affects renal outcomes

    DEFF Research Database (Denmark)

    Miao, Y; Dobre, D; Heerspink, H J Lambers; Brenner, B M; Cooper, M E; Parving, Hans-Henrik Dyring; Shahinfar, S; Grobbee, D; de Zeeuw, D

    2011-01-01

    To assess the effect of an angiotensin receptor blocker (ARB) on serum potassium and the effect of a serum potassium change on renal outcomes in patients with type 2 diabetes and nephropathy.......To assess the effect of an angiotensin receptor blocker (ARB) on serum potassium and the effect of a serum potassium change on renal outcomes in patients with type 2 diabetes and nephropathy....

  11. C-A4-03: Risks to the Newborn Associated With In-Utero Exposure to Beta-Blockers and Calcium-Channel Blockers

    OpenAIRE

    Davis, Robert; Andrade, Susan; Rubanowice, David; McPhillips, Heather; Boudreau, Denise; Raebel, Marsha; Smith, David; Ulcickas-Yood, M; Lane, Kim; Varghese, Renny; Platt, Richard

    2010-01-01

    Background: While medication use to manage cardiovascular disease during pregnancy is widespread, data on its safety for the developing infant is scarce. We used population-based data from 5 HMOs to study risks for perinatal complications and congenital defects among infants exposed in-utero to beta -blockers and calcium-channel blockers.

  12. Vasorelaxant Effect of a Newly Synthesized Dihydropyridine Ethyl Ester (DHPEE on Rat Thoracic Aorta: Dual Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Hossein Babaei

    2011-06-01

    Full Text Available Introduction: DHPEE is a newly synthesized compound by merging the key structural elements in an angiotensin receptor blocker (Telmisartan with key structural elements in 1,4- dihydropyridine calcium channel blocker (Nifedipine. In this study, we examined dual calcium channel blocking and AT1 antagonist activity for DHPEE. Methods: The functional inhibitory characteristics of DHPEE were studied in vitro in rat thoracic aorta preparations precontracted by phenylephrine (1µM or KCl (80µM or Ang II in normal or calcium-free solutions. Results: Concentration–dependent significant relaxation was observed in aortic rings precontracted with phenylephrine, KCl or Ang II. The tension increment produced by increasing external calcium was also reduced by DHPEE. DHPEE caused a marked decrease in the maximal contractile response of the vasoactive agents and shifted their concentration-response curves to the right. Conclusion: DHPEE possesses dual characteristics and cause vasorelaxation by blocking the L-type calcium channels and blocking Ang II receptors (AT1 in rat aortic smooth muscle.

  13. Development of Solid Self Micro Emulsifying Drug Delivery System with Neusilin US2 for Enhanced Dissolution Rate of Telmisartan

    Directory of Open Access Journals (Sweden)

    Bhagwat Durgacharan A

    2012-12-01

    Full Text Available Aim of present study was to develop solid self micro emulsifying drug delivery system (S-SMEDDS with Neusilin US2 for enhancement of dissolution rate of Telmisartan (TEL. SMEDDS was prepared using Oleic acid, Tween 80 and PEG 400 as oil, surfactant and cosurfactant respectively. For formulation of stable SMEDDS, micro emulsion region was identified by constructing pseudo ternary phase diagram containing different proportion of surfactant: co-surfactant (Km value 1:1, 2:1 and 3:1, oil and water. Prepared SMEDDS was evaluated for thermodynamic stability study, dispersibility tests, globule size and zeta potential. S-SMEDDS was prepared by adsorption technique using Neusilin US2 as solid carrier. Prepared S-SMEDDS was evaluated for flow properties, drug content, reconstitution properties, FTIR, SEM, DSC and in-vitro dissolution study. Results showed that prepared liquid SMEDDS passed dispersibility test with good thermodynamic stability. Globule size was found to be 30.2 nm with polydispersity index 0.116 and -5.80 mV zeta potential. S-SMEDDS showed good flow property and drug content. Reconstitution properties of S-SMEDDS showed spontaneous micro emulsification with globule size 32.4 nm and polydispersity index 0.219 and -6.32 mV zeta potential. Results of in-vitro dissolution showed that there was enhancement of dissolution rate of TEL as compared with that of plain TEL. From the results study concluded that, Neusilin US2 can be used to develop S-SMEDDS by adsorption technique to enhance dissolution rate of poorly water soluble drug such as TEL.

  14. Development and Validation of Stability Indicating HPTLC and HPLC Methods for Simultaneous Determination of Telmisartan and Atorvastatin in Their Formulations

    Directory of Open Access Journals (Sweden)

    Kaliappan Ilango

    2013-01-01

    Full Text Available The present study describes development and subsequent validation of stability indicating HPLC and HPTLC methods for simultaneous estimation of Telmisartan (TLM and Atorvastatin (ATV in their combined formulation. The proposed RP-HPLC method utilizes a Phenomenex Luna C18 column using acetonitrile: 0.025 M ammonium acetate (38 : 52%, v/v as mobile phase (pH 3.8, flow rate of 1.0 mL/min. Quantification was achieved with UV detection at 281 nm over concentration range of 12 to 72 μg/mL for TLM and 3 to 18 μg/mL for ATV respectively. In HPTLC, separations were performed on silica gel 60 F254 using toluene-methanol-ethyl acetate-acetic acid (5 : 1 : 1 : 0.3, v/v as mobile phase. The compact bands of TLM and ATV at 0.37 ± 0.02 and 0.63 ± 0.01 respectively were scanned at 279 nm. Linear regression analysis revealed linearity in the range of 40 to 240 ng/band for TLM and 10 to 60 ng/band for ATV respectively. For both the methods, dosage form was exposed to thermal, photolytic, acid, alkali and oxidative stress. The methods distinctly separated the drugs and degradation products even in actual samples. In conclusion, the proposed HPLC and HPTLC methods were appropriate for routine quantification of TLM and ATV in tablet formulation.

  15. Beta-blockers and depression in elderly hypertension patients in primary care

    DEFF Research Database (Denmark)

    Ringoir, Lianne; Pedersen, Susanne S.; Widdershoven, Jos W M G;

    2014-01-01

    BACKGROUND AND OBJECTIVES: Previous findings regarding a possible association between beta-blocker use and depression are mixed. To our knowledge there have been no studies investigating the association of beta-blockers with depression in primary care hypertension patients without previous...... myocardial infarction. The aim of this study was to determine the relation between lipophilic beta-blocker use and depression in elderly primary care patients with hypertension. METHODS: This was a cross-sectional study in primary care practices located in the South of The Netherlands. Primary care......-squared test showed that lipophilic beta-blocker users as compared to non-beta-blockers users were more likely to be in a higher depression category. Ordinal regression showed a significant relationship between use of lipophilic beta-blockers and depression (OR=1.60, 95% CI=1.08--2.36) when adjusting...

  16. Beta-Blocker Therapy and Hemophagocytic Lymphohistiocytosis: A Case Report

    Directory of Open Access Journals (Sweden)

    C. Müller

    2010-01-01

    as indicated by high lactate dehydrogenase and alanine aminotransferase levels. A therapeutic switch from propranolol to the 1-receptor blocker metoprolol appeared to be instrumental in hemodynamic improvement and allowed discharge from hospital. However, the infant ultimately died from secondary inflammatory reactivation and intractable pulmonary obstructive disease. The autopsy results revealed HLH. Conclusion. Our case describes HLH secondary to heart failure and Downs syndrome. In this highly activated inflammatory state the beneficial hemodynamic effects of propranolol may be accompanied by immunomodulatory effects and the risk of acute liver failure. HLH occurs with a distinct pathophysiology, and specific treatment might be mandatory to increase the chance of survival.

  17. Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Krag, Aleksander

    2012-01-01

    Non-selective beta-blockers are used as a first-line treatment for primary prevention in patients with medium- to high-risk oesophageal varices. The effect of non-selective beta-blockers on mortality is debated and many patients experience adverse events. Trials on banding ligation versus non......-selective beta-blockers for patients with oesophageal varices and no history of bleeding have reached equivocal results....

  18. Metaflumizone is a novel sodium channel blocker insecticide.

    Science.gov (United States)

    Salgado, V L; Hayashi, J H

    2007-12-15

    Metaflumizone is a novel semicarbazone insecticide, derived chemically from the pyrazoline sodium channel blocker insecticides (SCBIs) discovered at Philips-Duphar in the early 1970s, but with greatly improved mammalian safety. This paper describes studies confirming that the insecticidal action of metaflumizone is due to the state-dependent blockage of sodium channels. Larvae of the moth Spodoptera eridania injected with metaflumizone became paralyzed, concomitant with blockage of all nerve activity. Furthermore, tonic firing of abdominal stretch receptor organs from Spodoptera frugiperda was blocked by metaflumizone applied in the bath, consistent with the block of voltage-dependent sodium channels. Studies on native sodium channels, in primary-cultured neurons isolated from the CNS of the larvae of the moth Manduca sexta and on Para/TipE sodium channels heterologously expressed in Xenopus (African clawed frog) oocytes, confirmed that metaflumizone blocks sodium channels by binding selectively to the slow-inactivated state, which is characteristic of the SCBIs. The results confirm that metaflumizone is a novel sodium channel blocker insecticide. PMID:17959312

  19. Extracellular magnesium and calcium blockers modulate macrophage activity.

    Science.gov (United States)

    Libako, Patrycja; Nowacki, Wojciech; Castiglioni, Sara; Mazur, Andrzej; Maier, Jeanette A M

    2016-03-01

    Magnesium (Mg) possesses anti-inflammatory properties, partly because it antagonizes calcium (Ca) and inhibits L-type Ca channels. Our aim was to determine the effects of different concentrations of extracellular Mg, with or without Ca-channel blockers, in macrophages. A macrophage-like cell line J774.E was cultured in different concentrations of extracellular Mg and exposed to i) the phorbol ester PMA to induce the production of reactive oxygen species ii) lipopolysaccharide to induce the production of pro-inflammatory cytokines, or iii) ovalbumin to study endocytosis. The Ca antagonists verapamil and/or TMB-8 were used to interfere with Ca homeostasis. Different concentrations of extracellular Mg did not impact on endocytosis, while Ca antagonists markedly decreased it. Low extracellular Mg exacerbated, whereas Ca antagonists inhibited, PMA-induced production of free radicals. Ca blockers prevented lipopolysaccharide-induced transcription and release of IL-1β, IL-6 and TNF-α, while extracellular Mg had only a marginal effect. Ca channel inhibitors markedly reduced the activity of J774.E cells, thus underscoring the critical role of Ca in the non-specific immune response, a role which was, in some instances, also modulated by extracellular Mg. PMID:27160489

  20. TLR4/MyD88/NF-κB signaling and PPAR-γ within the paraventricular nucleus are involved in the effects of telmisartan in hypertension.

    Science.gov (United States)

    Li, Hong-Bao; Li, Xiang; Huo, Chan-Juan; Su, Qing; Guo, Jing; Yuan, Zu-Yi; Zhu, Guo-Qing; Shi, Xiao-Lian; Liu, Jin-Jun; Kang, Yu-Ming

    2016-08-15

    Previous findings from our laboratory and others indicate that the main therapeutic effect of angiotensin II type 1 receptor (AT1-R) antagonists is to decrease blood pressure and exert anti-inflammatory effects in the cardiovascular system. In this study, we determined whether AT1-R antagonist telmisartan within the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and hypothalamic inflammation via both the TLR4/MyD88/NF-κB signaling pathway and peroxisome proliferator-activated receptor-γ (PPAR-γ) in the PVN in hypertensive rats. Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were treated for 4weeks through bilateral PVN infusion with the AT1-R antagonist telmisartan (TEL, 10μg/h), or losartan (LOS, 20μg/h), or the PPAR-γ antagonist GW9662 (GW, 100μg/h), or vehicle via osmotic minipump. Mean arterial pressure (MAP) was recorded by a tail-cuff occlusion method. PVN tissue and blood were collected for the measurement of AT1-R, PPAR-γ, pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6), inducible nitric oxide synthase (iNOS), TLR4, MyD88, nuclear factor-kappa B (NF-κB) activity and plasma norepinephrine (NE), respectively. Hypertensive rats exhibited significantly higher level of AT1-R and lower level of PPAR-γ in the PVN. PVN treatment with TEL attenuated MAP, improved cardiac hypertrophy, reduced TNF-α, IL-1β, IL-6, iNOS levels, and plasma NE in SHR but not in WKY rats. These results were associated with reduced TLR4, MyD88 and NF-κB levels and increased PPAR-γ level in the PVN of hypertensive rats. Our findings suggest that TLR4/MyD88/NF-κB signaling and PPAR-γ within the PVN are involved in the beneficial effects of telmisartan in hypertension. PMID:27292124

  1. Oral Ascorbic Acid in Combination with Beta-Blockers Is More Effective than Beta-Blockers Alone in the Prevention of Atrial Fibrillation after Coronary Artery Bypass Grafting

    OpenAIRE

    Eslami, Masoud; Badkoubeh, Roya Sattarzadeh; Mousavi, Mehdi; Radmehr, Hassan; Salehi, Mehrdad; Tavakoli, Nafiseh; Avadi, Mohamad Reza

    2007-01-01

    Because adrenergic beta antagonists are not sufficient to prevent atrial fibrillation after coronary artery bypass grafting, this prospective, randomized trial was designed to evaluate the effects of ascorbic acid as an adjunct to β-blockers.

  2. Beta-blocker use and clinical outcomes after primary vascular surgery

    DEFF Research Database (Denmark)

    Høgh, A; Lindholt, J S; Nielsen, H;

    2013-01-01

    To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction.......To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction....

  3. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices

    DEFF Research Database (Denmark)

    Gluud, Lise L; Klingenberg, Sarah; Nikolova, Dimitrinka;

    2007-01-01

    To compare banding ligation versus beta-blockers as primary prophylaxis in patients with esophageal varices and no previous bleeding.......To compare banding ligation versus beta-blockers as primary prophylaxis in patients with esophageal varices and no previous bleeding....

  4. Discontinuation of beta-blockers and the risk of myocardial infarction in the elderly.

    NARCIS (Netherlands)

    Teichert, M.; Smet, P.A.G.M. de; Hofman, A.; Witteman, J.C.; Stricker, B.H.C.

    2007-01-01

    BACKGROUND: It has been shown that the abrupt cessation of treatment with beta-adrenoceptor antagonists (beta-blockers) increases the risk of myocardial infarction in patients with hypertension. As beta-blockers differ in their pharmacokinetic and pharmacodynamic properties, this risk of discontinua

  5. A review on the putative association between beta-blockers and depression

    NARCIS (Netherlands)

    Verbeek, D.E.; van Riezen, J.; de Boer, R.A.; van Melle, J.P.; de Jonge, P.

    2011-01-01

    Several kinds of systematic studies have been conducted verifying the putative association between beta-blockers and depressive symptoms. However, many of these studies had important limitations in their design. In most of the studies, no effect of beta-blockers on depressive symptoms was seen. Beca

  6. Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Battes, Linda C; Pedersen, Susanne S.; Oemrawsingh, Rohit M;

    2012-01-01

    Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose-response relationship between...

  7. The use of New Generation H1 Receptor Blockers and Advantages in Terms of Reliability

    Directory of Open Access Journals (Sweden)

    Muhammed Yayla

    2013-10-01

    Full Text Available H1 receptor blockers are one of the most commonly prescribed medications in the treatment of allergic disorders. These disease have reduced life quality of people and prevalent in the world. H1 receptor blockers has been used since 1940 and lead to some adverse effects such as sedation because of their chemical and pharmacological properties. Therefore new generations have been studied for reduced their adverse effect. The aims of this review are to exhibit advantages of new produced H1 receptor blockers compared to classical antihistamines and demonstrate efficacies of clinical uses of new produced H1 antihistamines. New generation H1 receptor blockers which have been developed after 1980s has less lipophilic properties and their sedative effects are minimized compared to classical antihistamines. Also, their specificity, affinity for H1 receptors and antihistaminergic effects are higher than classical H1 receptor blockers. Although new generation H1 receptor blockers are better tolerated than classical H1 receptor blockers, some of them lead to potential cardio toxicity. Consequently new generation H1 receptor blockers are reliable and efficient drugs, they provide convenience in the treatment of allergic disorders and prevent development of phobia against drugs.

  8. The renin-angiotensin system and its blockers

    Directory of Open Access Journals (Sweden)

    Igić Rajko

    2014-01-01

    Full Text Available Research on the renin-angiotensin system (RAS has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

  9. Beta-blockers in the environment: part II. Ecotoxicity study.

    Science.gov (United States)

    Maszkowska, Joanna; Stolte, Stefan; Kumirska, Jolanta; Łukaszewicz, Paulina; Mioduszewska, Katarzyna; Puckowski, Alan; Caban, Magda; Wagil, Marta; Stepnowski, Piotr; Białk-Bielińska, Anna

    2014-09-15

    The increasing consumption of beta-blockers (BB) has caused their presence in the environment to become more noticeable. Even though BB are safe for human and veterinary usage, ecosystems may be exposed to these substances. In this study, three selected BB: propranolol, metoprolol and nadolol were subjected to ecotoxicity study. Ecotoxicity evaluation was based on a flexible ecotoxicological test battery including organisms, representing different trophic levels and complexity: marine bacteria (Vibrio fischeri), soil/sediment bacteria (Arthrobacter globiformis), green algae (Scenedesmus vacuolatus) and duckweed (Lemna minor). All the ecotoxicological studies were supported by instrumental analysis to measure deviation between nominal and real test concentrations. Based on toxicological data from the green algae test (S. vacuolatus) propranolol and metoprolol can be considered to be harmful to aquatic organisms. However, sorption explicitly inhibits the hazardous effects of BB, therefore the risks posed by these compounds for the environment are of minor importance. PMID:24975494

  10. Effect of alpha1-blockers on stentless ureteroscopic lithotripsy

    Directory of Open Access Journals (Sweden)

    Jianguo Zhu

    2016-02-01

    Full Text Available ABSTRACT Objective To evaluate the clinical efficiency of alpha1-adrenergic antagonists on stentless ureteroscopic lithotripsy treating uncomplicated lower ureteral stones. Materials and Methods From January 2007 to January 2013, 84 patients who have uncomplicated lower ureteral stones treated by ureteroscopic intracorporeal lithotripsy with the holmium laser were analyzed. The patients were divided into two groups, group A (44 patients received indwelled double-J stents and group B (40 patients were treated by alpha1-adrenergic antagonists without stents. All cases of group B were treated with alpha1 blocker for 1 week. Results The mean operative time of group A was significantly longer than group B. The incidences of hematuria, flank/abdominal pain, frequency/urgency after surgery were statistically different between both groups. The stone-free rate of each group was 100%. Conclusions The effect of alpha1-adrenergic antagonists is more significant than indwelling stent after ureteroscopic lithotripsy in treating uncomplicated lower ureteral stones.

  11. Potassium Channels Blockers from the Venom of Androctonus mauretanicus mauretanicus

    Directory of Open Access Journals (Sweden)

    Marie-France Martin-Eauclaire

    2012-01-01

    Full Text Available K+ channels selectively transport K+ ions across cell membranes and play a key role in regulating the physiology of excitable and nonexcitable cells. Their activation allows the cell to repolarize after action potential firing and reduces excitability, whereas channel inhibition increases excitability. In eukaryotes, the pharmacology and pore topology of several structural classes of K+ channels have been well characterized in the past two decades. This information has come about through the extensive use of scorpion toxins. We have participated in the isolation and in the characterization of several structurally distinct families of scorpion toxin peptides exhibiting different K+ channel blocking functions. In particular, the venom from the Moroccan scorpion Androctonus mauretanicus mauretanicus provided several high-affinity blockers selective for diverse K+ channels  (SKCa,  Kv4.x, and  Kv1.x K+ channel families. In this paper, we summarize our work on these toxin/channel interactions.

  12. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

    International Nuclear Information System (INIS)

    Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor γ activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGFβ1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis

  13. RP-HPLC METHOD FOR SIMULTATANEOUS DETERMINATION OF AMLODIPINE BESYLATE, VALSARTAN, TELMISARTAN, HYDROCHLOROTHIAZIDE AND CHLORTHALIDONE: APPLICATION TO COMMERCIALLY AVAILABLE DRUG PRODUCTS

    Directory of Open Access Journals (Sweden)

    R. A. Mhaske et al.

    2012-01-01

    Full Text Available A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of anti-hypertensive drugs Amlodipine Besylate, Valsartan, Telmisartan and diuretics Hydrochlorothiazide and Chlorthalidone. The separation was achieved on Cosmosil PAQ (150 mm × 4.6 mm 5 μm column with gradient flow. The mobile phase at a flow rate of 1.0 mL min−1 consisted of 0.05 M sodium dihydrogen phosphate buffer and acetonitrile (Gradient ratio. The UV detection was carried out at 220 nm. The method was successfully validated in accordance to ICH guidelines. Further, the validated method was applied for commercially available pharmaceutical dosage form.

  14. Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Jung [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Lee, Jue Yeon [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Lee, Seung Jin [Department of Industrial Pharmacy, College of Pharmacy, Ewha Womans University, Seoul (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Chung, Chong-Pyoung [Department of Periodontology, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Park, Yoon Jeong, E-mail: parkyj@snu.ac.kr [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Doxazocin directly up-regulated bone metabolism at a low dose. Black-Right-Pointing-Pointer Doxazocin induced osteoblastic stem cell differentiation without affecting cell proliferation. Black-Right-Pointing-Pointer This osteogenic stem cell differentiation is mediated by ERK-signal dependent pathway. -- Abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinically used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor {gamma}, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk and

  15. An investigation into sustainable construction stimulators and blockers

    Directory of Open Access Journals (Sweden)

    M Osmani

    2014-10-01

    Full Text Available The UK Government has been using a combination of regulation, economic instruments and voluntary agreements to meet targets of ethical, social and environmental performancein driving the climate change agenda. The UK is the first country worldwide to set a legally binding 80% greenhouse-gas emissions reduction target by 2050. The built environment in the UK is responsible for about 40% of carbon emissions, 32% of solid waste generation,20% of water effluents, and 40% of all energy used. As such, the construction industry has been targeted to facilitate the transition to a low-carbon economy.Indeed, sustainabilitywithin the built environment has become the forefront of all sustainable development policies in the UK. However; various studies have outlined the difficulty of translating theUK’s 80% greenhouse-gas emissions reduction target to a micro level such as construction projects. This research engaged the top 100 UK contractorsto investigate stimulators that drivethe implementation of sustainability in their projects,and assess associated blockers.Findings reveal that sustainability requirements driven by financial and business were viewed by participating contractors as being the key motivators in construction projects. Corporate Social Responsibility (CSR was viewed as a vehicle to improve social and environmental dynamics of sustainability through local community support initiatives,which in turn has increased companies’ opportunities to secure new projects, particularly from public clients. On the other hand, respondents called for clearer and inclusivelegislation; increased awareness; enhanced communication and coordination among project stakeholders; and widespread sharing and dissemination of sustainableconstruction best practice data.Keywords: UK; contractors; sustainable construction; stimulators; blockers.

  16. 替米沙坦治疗代谢综合征的荟萃分析%Meta analysis of the treatment of metabolic syndrome with telmisartan

    Institute of Scientific and Technical Information of China (English)

    李宁荫; 余静; 张小卫; 白锋

    2011-01-01

    Objective To evaluate the clinical efficacy and safety of telmisartan in the treatment of metabolic syndrome (MS). Methods Based on the principles of evidence-based medicine, corresponding inclusion and exclusion criteria, along with search strategies were developed. We searched the Cochrane Library, PubMed, EMBASE,Chinese Biomedical Literature Database, Chinese Scientific Journals Full-text Database, and Chinese Journal Fulltext Database up to September 2010 to identify randomized controlled trials (RCTs) comparing telmisartan with otherdrugs for treatment of MS. Other search methods were also adopted. Two reviewers independently evaluated the quality of the included studies,extracted data with a unified form, and analyzed the data by Cochrane Collaboratior's RevMan 5.0 software. We performed the comparisons on effects of telmisartan with those of valsartan,losartan, irbesartan and amlodipine on blood pressure, blood lipids, blood glucose, body mass index ( BMI), waist circumference, insulin, resistin, adiponectin, C-reactive protein (CIPI, heart rate, pulse wave velocity, serum creatinine, blood urea nitrogen, glomerular filtration rate, urinary protein and creatinine ratio ( UACR) was carried on.Results Seven RCTs involving 479 patients were included. The results of meta analysis suggested that telmisartan was better than valsartan in reducing systolic blood pressure ( MD= 1.79, 95 % CI0. 91-2.67). but worse than valsartan in lowering Low-density lipoprotein (MD=-10. 10, 95 % CI -13. 02 --7.18). Telmisartan was more effective than losartan in decreasing systolic blood pressure ( MD= 6.20, 95 % CI 1.80-10.60) and fasting plasma glucose (MD=10. 72, 95% CI 1.05-20. 39). Compared with irbesartan,telmisartan could significantly lower diastolic blood pressure( MD-1.00, 95 % CI0. 06-1.94 ) and fasting plasma glucose (MD= 14.00, 95 % CI 10. 95—17.05). At the same time, telmisartan could reduce insulin resistance index more significantly

  17. 替米沙坦对高血压合并糖尿病患者血浆APN及IR的影响%Effects of Telmisartan on Adiponection(APN) and Insulin Resistance in Patients with Hypertension and Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    颜安华; 郑道国; 吴利云

    2011-01-01

    Objective To investigate the effect of telmisartan on APN and insulin resistance in patients with hypertension and type 2 diabetes mellitus. Methods A total of 150 patients with hypertension and type 2 diabetes mellitus were randomly divided into telmisartan group and control group, 75 patients in each group. Patients in both groups were subjected to hypoglycemic treatment. Meanwhile, in telmisartan group, patients took 80 mg of telmisartan orally once daily; while in control group, patients took 4 mg of perindopril orally once daily. After 4 weeks, if blood pressure control is still not been satisfactory, then the oral doses of telmisartan and perindopril will be doubled. RssultS After 8 weeks of treatment, patients in both groups achieved the blood pressure goals, SBP and DBP showed no significant difference between two groups (P >0. 05) . No significant difference was observed in APN, fBS, Fins and HOMA-IR between two groups before treatment (P >0. 05) . After 16 weeks of treatment, APN in telmisartan group was significantly higher than that in control group (P >0. 05) ; while fBS showed no obvious difference between two groups (P > 0. 05) , Fins and HOMA-IR in telmisartan group were evidently lower than those in control group (P > 0. 05) . Conclusion Telmisartan has a certain role in regulating the plasma APN level in patients with hypertension and type 2 diabetes mellitus. It can also improve their insulin resistance phenomenon obviously.%目的:探讨替米沙坦对高血压合并2型糖尿病(DM2)患者脂联素(adiponectin,APN)及胰岛素抵抗(IR)的影响.方法:选择150例高血压合并DM2患者,随机分为替米沙坦组和对照组,每组75例.两组均予以降血糖治疗.同时,替米沙坦组给予替米沙坦80mg口服,1次/d;对照组给予培哚普利4mg口服,1次/d.若4周后血压控制仍不理想,则替米沙坦、培哚普利的口服剂量给予加倍.结果:两组患者在治疗8周后均实现了血压达标,治疗8周后两组患

  18. Pulmonary vasoconstrictor action of KCNQ potassium channel blockers

    Directory of Open Access Journals (Sweden)

    Balan Prabhu

    2006-02-01

    Full Text Available Abstract Background KCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+ currents mediated by KCNQ channels resemble a current underlying the resting K+ conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction. Methods The tension developed by rat and mouse intrapulmonary or mesenteric arteries was measured using small vessel myography. Contractile responses to linopirdine and XE991 were measured in intact and endothelium denuded vessels. Experiments were also carried out under conditions that prevent the contractile effects of nerve released noradrenaline or ATP, or block various Ca2+ influx pathways, in order to investigate the mechanisms underlying contraction. Results Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50 of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim. Conclusion The KCNQ channel blockers are potent and powerful constrictors of pulmonary arteries. This action may be selective for the pulmonary circulation as mesenteric arteries showed little response. The

  19. Skin prick testing in patients using beta-blockers: a retrospective analysis

    OpenAIRE

    Fung Irene N; Kim Harold L

    2010-01-01

    Abstract Rationale The use of beta-blockers is a relative contraindication in allergen skin testing yet there is a paucity of literature on adverse events in this circumstance. We examined a population of skin tested patients on beta-blockers to look for any adverse effects. Methods Charts from 2004-2008 in a single allergy clinic were reviewed for any patients taking a beta-blocker when skin tested. Data was examined for skin test reactivity, type of skin test, concomitant asthma diagnosis, ...

  20. An Analysis of Forensic Imaging in the Absence of Write-Blockers

    OpenAIRE

    Gary C. Kessler; Greg H Carlton

    2014-01-01

    Best practices in digital forensics demand use of write-blockers when creating forensic copies of digital media and this has been a core of computer forensics training for decades. The practice is so in-grained that images created without a write-blocker are immediate suspect for integrity. This paper describes a research framework to examine what occurs when a forensic image is acquired without benefit of a write-blocker in order to understand the true impact of such an eventuality. The init...

  1. Multi drug resistance to cancer chemotherapy: Genes involved and blockers

    International Nuclear Information System (INIS)

    During the last three decades, important and considerable research efforts had been performed to investigate the mechanism through which cancer cells overcome the cytotoxic effects of a variety of chemotherapeutic drugs. Most of the previously published work has been focused on the resistance of tumor cells to those anticancer drugs of natural source. Multidrug resistance (MDR) is a cellular cross-resistance to a broad spectrum of natural products used in cancer chemotherapy and is believed to be the major cause of the therapeutic failures of the drugs belonging to different naturally obtained or semisynthetic groups including vinca alkaloids, taxans, epipodophyllotoxins and certain antibiotics. This phenomenon results from overexpression of four MDR genes and their corresponding proteins that act as membrane-bound ATP consuming pumps. These proteins mediate the efflux of many structurally and functionally unrelated anticancer drugs of natural source. MDR may be intrinsic or acquired following exposure to chemotherapy. The existence of intrinsically resistant tumor cell clone before and following chemotherapeutic treatment has been associated with a worse final outcome because of increased incidence of distant metasis. In view of irreplaceability of natural product anticancer drugs as effective chemotherapeutic agents, and in view of MDR as a major obstacle to successful chemotherapy, this review is aimed to highlight the genes involved in MDR, classical MDR blockers and gene therapy approaches to overcome MDR. (author)

  2. Beta blockers and the sensitivity of the thallium treadmill test

    International Nuclear Information System (INIS)

    The effect beta blockers (BB) may have on the sensitivity of the thallium treadmill test (Th-TMT) is controversial. The purpose of this study was to test the hypothesis that BB decrease the sensitivity of the Th-TMT. Two hundred three patients over a two-year period were identified who satisfied the following criteria. All had symptom-limited upright treadmill exercise tests with stress and redistribution thallium imaging, as well as coronary angiography within two months of the Th-TMT. Of 58 patients with CAD not on BB, 52 had an abnormal Th-TMT scan (sensitivity 90 percent). In comparison, the sensitivity of the Th-TMT scan in the 88 patients with CAD receiving BB was 76 percent (p less than 0.05). We conclude that BB may significantly decrease the sensitivity of the Th-TMT. Physicians should fully appreciate the higher false negative rate (24 vs 10 percent) for patients on BB and consider cautious withdrawal prior to diagnostic studies

  3. Erythrocyte transfusion and calcium channel blockers: Effects on tumor radiosensitivity

    International Nuclear Information System (INIS)

    One approach to overcoming the radioresistance often associated with anemia is to give an erythrocyte transfusion prior to irradiation. When 0.5 ml packed erythrocytes were injected I.V. into anemic RIF-1 or SCCVII/St tumor bearing mice, just prior to X-rays, and tumor response was measured by an in vivo/in vitro survival assay, there was a 10-fold increase in cell killing in the RIF-1 tumor, compared to only a 4-fold increase for SCCVII/St. The differences in response to the treatments described may be related in part to the variation in normal hypoxic fraction, between the RIF-1 (20%) tumors. Calcium channel blockers have been shown to reduce the hypoxic fraction in some mouse tumors. Such compounds may therefore enhance the radiosensitivity produced by erythrocyte transfusion. One compound, cinnarizine, gave only a small enhancement of the radiation response in the RIF-1 tumor, compared to that for erythrocyte transfusion alone. Since the SCVII/St tumor has a greater hypoxic fraction, cinnarizine may give a greater enhancement of erythrocyte transfusion sensitization to X-rays than is observed in RIF-1 tumors. Additional results are presented and discussed with reference to adaptation to these treatments and the importance of the tumor hypoxic fractions

  4. Efficacy and safety of telmisartan in patients with mild to moderate essential hypertension%替米沙坦治疗轻中度原发性高血压疗效和安全性观察

    Institute of Scientific and Technical Information of China (English)

    汪艺; 姜蕾

    2008-01-01

    Objective To observe the efficacy and safety of telmisartan in patients of essential hypertension.Methods This study was a randomized,double-blind and parallel controlled trial.66 eligible mild and moderate hypertension patients were divided randomly into telmisartan group and perindopril group.80mg of telmisartan or 4mg of perindopril was administrated once per day,and the patients were followed up in every two weeks.This trial was continued for 8 weeks.Results After 8 weeks,the effectiveness of telmisartan and perindopril were 72.7% and 68.8%respectively,showing no significant difference between both groups.After 8 weeks,the SBP and DBP of telmisartan group decreased 11.4%and 12.3%.perindopril group decreased 8.9%and 11.1%.Also no significant difference Was observed.The side effect ratio Was significantly lower in telmisartan group(3.2%)than that in perindopril group(15.2%).The most common side effects were COUgh and mild dizziness.Conclusion Telmisartan (80 mg/d)is effective、safe and well tolerated in treatment of mild to moderate essential hypertension.%目的 观察替米沙坦治疗轻中度原发性高血压痛的疗效和安全性.方法 采用随机双盲平行对照试验的方法 将符合条件的轻中度原发性高血压患者66例分为替米沙坦组和培哚普利组各33例,2组分别口服替米沙坦80 mg和培哚普利4 mg,均1次/d,疗程共8周.结果 ①治疗8周后,替米沙坦组降压总有效率72.7%,培哚普利组总有效率68.8%,2组差异无统计学意义(P<0.05).②治疗前后收缩压、舒张压下降幅度分别为:替米沙坦组11.4%和12.3%,培哚普利组8.9%和11.1%,2组比较无统计学意义(P>0.05).③不良反应的发生率,替米沙坦组为3.2%,培哚普利组为15.2%,2组差异有统计学意义(P<0.05).结论 替米沙坦治疗轻中度原发性高血压安全有效,不良反应发生率低于培哚普利.

  5. Defining the optimal murine models to investigate immune checkpoint blockers and their combination with other immunotherapies.

    Science.gov (United States)

    Sanmamed, M F; Chester, C; Melero, I; Kohrt, H

    2016-07-01

    The recent success of checkpoint blockers to treat cancer has demonstrated that the immune system is a critical player in the war against cancer. Historically, anticancer therapeutics have been tested in syngeneic mouse models (with a fully murine immune system) or in immunodeficient mice that allow the engraftment of human xenografts. Animal models with functioning human immune systems are critically needed to more accurately recapitulate the complexity of the human tumor microenvironment. Such models are integral to better predict tumor responses to both immunomodulatory agents and directly antineoplastic therapies. In this regard, the development of humanized models is a promising, novel strategy that offers the possibility of testing checkpoint blockers' capacity and their combination with other antitumor drugs. In this review, we discuss the strengths and weaknesses of the available animal models regarding their capacity to evaluate checkpoint blockers and checkpoint blocker-based combination immunotherapy. PMID:26912558

  6. Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

    DEFF Research Database (Denmark)

    Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte;

    2013-01-01

    Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular...... carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis. Due to their effect on the portal pressure, non-selective beta-blockers are used for prevention of esophageal variceal bleeding. Recently, non-hemodynamic effects of beta-blockers have received...... reduce hepatic inflammation. Blockage of β-adrenoceptors also decrease angiogenesis by inhibition of vascular endothelial growth factors. Because gut-derived inflammation and neo-angiogenesis are important in hepatic carcinogenesis, non-selective beta-blockers can potentially reduce the development and...

  7. β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

    DEFF Research Database (Denmark)

    Jørgensen, Mads E; Hlatky, Mark A; Køber, Lars Valeur;

    2015-01-01

    IMPORTANCE: Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk. OBJECTIVE: To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy in...... antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. INTERVENTIONS: Various antihypertensive treatment regimens, chosen as part of usual care. MAIN OUTCOMES AND MEASURES: Thirty-day risk of MACEs...... (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). RESULTS: The baseline characteristics of the 14,644 patients who received β-blockers (65% female, mean [SD...

  8. Comparison of the clinical outcome of different beta-blockers in heart failure patients

    DEFF Research Database (Denmark)

    Bølling, Rasmus; Scheller, Nikolai Madrid; Køber, Lars;

    2014-01-01

    AIM: To compare survival on different beta-blockers in heart failure. METHODS AND RESULTS: We identified all Danish patients ≥35 years of age who were hospitalized with a first admission for heart failure and who initiated treatment with a beta-blocker within 60 days of discharge. The study period...... according to beta-blocker dosages, patients that received high-dose carvedilol (≥50 mg daily) had a lower all-cause mortality risk (HR 0.873, 0.789-0.966) than patients receiving high-dose (≥200 mg daily) metoprolol (reference). High-dose bisoprolol (≥10 mg daily) was associated with a greater risk of death......: Heart failure patients receiving high-dose carvedilol (≥50 mg daily) showed significantly lower all-cause mortality risk and hospitalization risk, compared with other beta-blockers....

  9. Beta-blocker therapy and cardiac events among patients with newly diagnosed coronary heart disease

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Shilane, David; Go, Alan S;

    2014-01-01

    BACKGROUND: The effectiveness of beta-blockers for preventing cardiac events has been questioned for patients who have coronary heart disease (CHD) without a prior myocardial infarction (MI). OBJECTIVES: The purpose of this study was to assess the association of beta-blockers with outcomes among...... patients with new-onset CHD. METHODS: We studied consecutive patients discharged after the first CHD event (acute coronary syndrome or coronary revascularization) between 2000 and 2008 in an integrated healthcare delivery system who did not use beta-blockers in the year before entry. We used time......-blockers among patients with new-onset CHD was associated with a lower risk of cardiac events only among patients with a recent MI....

  10. Clinical Outcomes with β-blockers for Myocardial Infarction A Meta-Analysis of Randomized Trials

    DEFF Research Database (Denmark)

    Bangalore, Sripal; Makani, Harikrishna; Radford, Martha; Thakur, Kamia; Toklu, Bora; Katz, Stuart D; DiNicolantonio, James J; Devereaux, P J; Alexander, Karen P; Wetterslev, Jorn; Messerli, Franz H

    2014-01-01

    patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion era (>50% undergoing reperfusion and/or receiving aspirin/statin) or pre-reperfusion era trials. RESULTS: Sixty trials with 102003 patients satisfied the inclusion criteria. In the acute......BACKGROUND: Debate exists regarding the efficacy of â-blockers in myocardial infarction and their required duration of usage in contemporary practice. METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating â-blockers in myocardial infarction enrolling at least 100...... myocardial infarction trials, a significant interaction (Pinteraction=0.02) was noted such that â-blockers reduced mortality in the pre-reperfusion[Incident Rate Ratio (IRR)=0.86, 95% CI 0.79-0.94] but not in the reperfusion era(IRR=0.98, 95% CI 0.92-1.05). In the pre-reperfusion era, â-blockers reduced...

  11. FLOATING MICROSPHERE AS A NOVEL TOOL FOR H2 RECEPTOR BLOCKER

    Directory of Open Access Journals (Sweden)

    Gaurang Patel

    2012-02-01

    Full Text Available H2 receptor blockers are amongst the most commonly prescribed medications in the world. Almost all the H2 blockers available in the market have severe side effects. As awareness of the local treatment in the stomach, it is necessary to develop the dosage forms which give better release in the stomach. A trend in H2 receptor blocker development has been to improve therapeutic efficacy and reduce the severity of side effects through altering dosage forms by modifying release of the formulations to optimize drug delivery. One such approach is using polymeric microspheres as carriers of drugs. A brief review of the Microsphere, Polymer can be used to formulate microspheres, various methods used to formulate microspheres, in vitro and in vivo evaluation and how H2 receptor blocker are good candidate for this dosage form are briefly given in this article.

  12. Effects of a beta-blocker on the cardiovascular response to MDMA (Ecstasy)

    OpenAIRE

    Hysek, C M; Vollenweider, F X; Liechti, M. E.

    2010-01-01

    BACKGROUND: MDMA (3,4-methylenedioxymethamphetamine, 'Ecstasy') produces tachycardia and hypertension and is rarely associated with cardiovascular and cerebrovascular complications. In clinical practice, beta-blockers are often withheld in patients with stimulant intoxication because they may increase hypertension and coronary artery vasospasm due to loss of beta(2)-mediated vasodilation and unopposed alpha-receptor activation. However, it is unknown whether beta-blockers affect the cardiovas...

  13. Lack of a pharmacokinetic interaction between nifedipine and the beta-adrenoceptor blockers metoprolol and atenolol.

    OpenAIRE

    Kendall, M. J.; Jack, D B; Laugher, S J; Lobo, J.; Rolf Smith, S

    1984-01-01

    Nifedipine, metoprolol and atenolol were administered orally to young, healthy volunteers. Each drug was given alone and nifedipine was also given with both beta-adrenoceptor blockers. Each drug was given for 3 days immediately before the study days. Plasma and urine drug concentrations were measured and the relevant pharmacokinetic parameters calculated. No pharmacokinetic interaction between nifedipine and the beta-adrenoceptor blockers was revealed.

  14. Beta-Blockers in the Management of Hypertension and/or Chronic Kidney Disease

    OpenAIRE

    Hirofumi Tomiyama; Akira Yamashina

    2014-01-01

    This minireview provides current summaries of beta-blocker use in the management of hypertension and/or chronic kidney disease. Accumulated evidence suggests that atenolol is not sufficiently effective as a primary tool to treat hypertension. The less-than-adequate effect of beta-blockers in lowering the blood pressure and on vascular protection, and the unfavorable effects of these drugs, as compared to other antihypertensive agents, on the metabolic profile have been pointed out. On the oth...

  15. Non-selective beta-blockers may reduce risk of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Thiele, Maja; Albillos, Agustín; Abazi, Rozeta;

    2015-01-01

    BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are used in patients with cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit angiogenesis and reduce bacterial translocation, which may prevent hepatocellular carcinoma (HCC). We therefore assessed the effect of NSBB...... reduce HCC-related mortality (RD -0.011; 95% CI -0.040 to 0.017). CONCLUSIONS: Non-selective beta-blockers may prevent HCC in patients with cirrhosis....

  16. Poor tolerance of beta-blockers by elderly patients with heart failure

    OpenAIRE

    Yanagisawa, Satoshi

    2010-01-01

    Satoshi Yanagisawa, Noriyuki Suzuki, Toshikazu TanakaDepartment of Cardiology, Okazaki City Hospital, Aichi, JapanAbstract: Despite the well-understood importance of beta-blocker therapy in heart failure, it is sometimes not possible to use beta-blockers in elderly patients due to poor tolerance. In this report, we describe the case of an 83-year-old patient with severe systolic heart failure complicated by aortic valve stenosis and atrial fibrillation. A simple therapeutic approach involving...

  17. Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma Model

    OpenAIRE

    Nguyen, Long P.; Omoluabi, Ozozoma; Parra, Sergio; Frieske, Joanna M.; Clement, Cecilia; Ammar-Aouchiche, Zoulikha; Ho, Samuel B.; Ehre, Camille; Kesimer, Mehmet; Knoll, Brian J.; Tuvim, Michael J; Dickey, Burton F.; Bond, Richard A.

    2007-01-01

    Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers de...

  18. Age-related differences in bitter taste and efficacy of bitter blockers.

    Directory of Open Access Journals (Sweden)

    Julie A Mennella

    Full Text Available Bitter taste is the primary culprit for rejection of pediatric liquid medications. We probed the underlying biology of bitter sensing and the efficacy of two known bitter blockers in children and adults.A racially diverse group of 154 children (3-10 years old and their mothers (N = 118 evaluated the effectiveness of two bitter blockers, sodium gluconate (NaG and monosodium glutamate (MSG, for five food-grade bitter compounds (quinine, denatonium benzoate, caffeine, propylthiouracil (PROP, urea using a forced-choice method of paired comparisons. The trial was registered at clinicaltrials.gov (NCT01407939.The blockers reduced bitterness in 7 of 10 bitter-blocker combinations for adults but only 3 of 10 for children, suggesting that efficacy depends on age and is also specific to each bitter-blocker combination. Only the bitterness of urea was reduced by both blockers in both age groups, whereas the bitterness of PROP was not reduced by either blocker in either age group regardless of TAS2R38 genotype. Children liked the salty taste of the blocker NaG more than did adults, but both groups liked the savory taste of MSG equally.Bitter blocking was less effective in children, and the efficacy of blocking was both age and compound specific. This knowledge will pave the way for evidence-based strategies to help develop better-tasting medicines and highlights the conclusion that adult panelists and genotyping alone may not always be appropriate in evaluating the taste of a drug geared for children.

  19. The use of New Generation H1 Receptor Blockers and Advantages in Terms of Reliability

    OpenAIRE

    Muhammed Yayla

    2013-01-01

    H1 receptor blockers are one of the most commonly prescribed medications in the treatment of allergic disorders. These disease have reduced life quality of people and prevalent in the world. H1 receptor blockers has been used since 1940 and lead to some adverse effects such as sedation because of their chemical and pharmacological properties. Therefore new generations have been studied for reduced their adverse effect. The aims of this review are to exhibit advantages of new produced H1 recep...

  20. Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss

    OpenAIRE

    Shen, Haiyan; Zhang, BaoPing; Shin, June-Ho; Lei, Debin; Du, Yafei; Gao, Xiang; Wang, Qiuju; Ohlemiller, Kevin K.; Piccirillo, Jay; Bao, Jianxin

    2006-01-01

    Cochlear noise injury is the second most frequent cause of sensorineural hearing loss, after aging. Because calcium dysregulation is a widely recognized contributor to noise injury, we examined the potential of calcium channel blockers to reduce noise-induced hearing loss (NIHL) in mice. We focused on two T-type calcium blockers, trimethadione and ethosuximide, which are anti-epileptics approved by the Food and Drug Administration. Young C57BL/6 mice of either gender were divided into three g...

  1. Characterization of co-blockers for simple perfect matchings in a convex geometric graph

    CERN Document Server

    Keller, Chaya

    2010-01-01

    Consider the complete convex geometric graph on $2m$ vertices, $CGG(2m)$, i.e., the set of all boundary edges and diagonals of a planar convex $2m$-gon $P$. In [C. Keller and M. Perles, On the Smallest Sets Blocking Simple Perfect Matchings in a Convex Geometric Graph], the smallest sets of edges that meet all the simple perfect matchings (SPMs) in $CGG(2m)$ (called "blockers") are characterized, and it is shown that all these sets are caterpillar graphs with a special structure, and that their total number is $m \\cdot 2^{m-1}$. In this paper we characterize the co-blockers for SPMs in $CGG(2m)$, that is, the smallest sets of edges that meet all the blockers. We show that the co-blockers are exactly those perfect matchings $M$ in $CGG(2m)$ where all edges are of odd order, and two edges of $M$ that emanate from two adjacent vertices of $P$ never cross. In particular, while the number of SPMs and the number of blockers grow exponentially with $m$, the number of co-blockers grows super-exponentially.

  2. Sequential comparison of therapy with beta-blockers and calcium channel blockers with celiprolol therapy in patients with angina pectoris, hypertension, or both

    NARCIS (Netherlands)

    Cleophas, TJM; Niemeyer, MG; Bernink, PJLM; Zwinderman, KH; Wijk, AV; Wall, EEVD

    1996-01-01

    Unlike patients with either hypertension (HT) of angina pectoris (AP) alone, patients with both HT and AP usually have a reduced left ventricular compliance and may, therefore, have an impaired capability to cope with acute hemodynamic changes generated by standard beta-blockers or calcium channel b

  3. A different dihydropyridine calcium channel blocker in hypertensive patients who developed pedal edema on dihydropyridine calcium channel blocker therapy

    Directory of Open Access Journals (Sweden)

    Ayşe Yüksel

    2014-03-01

    Full Text Available Abstract Aim. Dihydropyridine calcium channel blockers (CCB are widely preferred for the treatment of hypertension for their efficacy, metabolic neutrality and low side effect profile. However pedal edema formation limits their usage. The aim of the present study is to evaluate the incidence of pedal edema formation with a different dihydropyridine CCB in hypertensive patients who developed pedal edema during a dihydropyridine CCB therapy. Method. Fifty-eight hypertensive patients (34 female, 24 male, mean age: 65.3±10.5 in whom pedal edema developed during treatment with a dihydropyridine CCB (amlodipine 10mg/day in 40 patients, amlodipine 5mg/day in 14 patients, nifedipine GITS 30mg/day in 4 patients were enrolled. CCB which caused pedal edema was withdrawn and a different CCB (felodipine or lacidipine were initiated after the resolution of the pedal edema. CCB therapy was continued as long as the patient tolerated pedal edema. Results. At the end of one year, 44 out of 58 patients (36 [81.8%] free of pedal edema, 8 [19.2%] with pedal edema continued CCB therapy. Eleven (37.9% patients in the felodipine group and 9 (31.0% patients in the lacidipine group developed pedal edema. In 7 patients in felodipine group and in 5 patients in the lacidipine group the study drug was withdrawn due to pedal edema. In two patients, study drug was withdrawn due to intractable headache (felodipine group or due to flushing (lacidipine group. Conclusion. A different group of dihydropyridine CCB be used as an alternative therapy for hypertension whenever pedal edema develops during treatment with a dihydropyridine CCB.

  4. Effects of telmisartan on diabetic patients with paroxysmal atrial fibrillation%替米沙坦对糖尿病合并阵发性心房颤动患者的影响

    Institute of Scientific and Technical Information of China (English)

    王丽岳; 韩红彦

    2011-01-01

    目的 探讨替米沙坦对2型糖尿病并阵发性心房颤动(简称房颤)患者的影响.方法 选取93例糖尿病合并阵发性房颤患者,随机分成替米沙坦治疗组与对照组.治疗组在由原降糖药物基础上加用口服替米沙坦80me/d,对照组仅继续使用原降糖药物.观察6个月,记录治疗前后房颤发作情况,检测治疗前和治疗6个月后的左房内径、血浆血管假性血友病因子(vWF)和一氧化氮(NO)浓度.结果 治疗组维持窦性心律的情况明显优于对照组(81.3%vs 66.7%,P<0.05=.和对照组比较,治疗组6个月后内皮功能明显改善(P<0.05).结论 替米沙坦可能有利于糖尿病并阵发性房颤患者维持窦性心律及改善内皮功能.%Objective To investigate the effect of telmisartan on patients with type 2 diabetes and paroxysmal atrial fibrillation (AF). Methods Ninty-three patients with well-controlled type 2 diabetes who also suffered paroxysmal AF were randomized to treatment group ( 80 mg of telmisartan plus hypoglycemic agent) or to control group ( hypoglycemic agent only) and were followed up for 6 monthes. A 24-hour ECG were evaluated monthly. The patients were asked to report any episode of symptomatic AF and to obtain its ECG recording as early as possible. Nitric oxide (NO) and yon Willebrand factor (vWF) were quantified before and after 6month therapy. Results The situation of maintaining sinus rhythm was reported in 81.3% of the patients treated with telmisartan and in 66.7% of those treated without telmisartan, with a significant difference between treatments ( P < 0.05 ). Improvement of endothelial function of patients in telmisartan treatment group was better than that in the control group ( P < 0.05 ). Conclusion Telmisartan can improve the situation of maintaining sinus rhythm and endothelial function in diabetic patients with paroxysmal atrial fibrillation.

  5. Night-time exogenous melatonin administration may be a beneficial treatment for sleeping disorders in beta blocker patients

    OpenAIRE

    Fares, Auda

    2011-01-01

    Sleep disorders are the common side effects of beta blockers. Beta blockers have been shown to reduce the production of melatonin via specific inhibition of adrenergic beta1-receptors. Exogenous melatonin, taken in the evening as a supplement, could reduce the central nervous system (CNS) side effects (sleep disorder) associated with beta-adrenergic receptor blockers as well as the potential risk associated with reduction of the melatonin synthesis.

  6. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

    OpenAIRE

    Ivanov, Vadim; Ivanova, Svetlana; KALINOVSKY, TATIANA; NIEDZWIECKI, ALEKSANDRA; RATH, MATTHIAS

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition...

  7. Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Kontula, Kimmo; Benn, Marianne;

    2010-01-01

    OBJECTIVE: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested...

  8. Optimal use of β-blockers in high-risk hypertension: A guide to dosing equivalence

    Directory of Open Access Journals (Sweden)

    Janet B McGill

    2010-05-01

    Full Text Available Janet B McGillDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USAAbstract: Hypertension is the number one diagnosis made by primary care physicians, placing them in a unique position to prescribe the antihypertensive agent best suited to the individual patient. In individuals with diabetes mellitus, blood pressure (BP levels > 130/80 mmHg confer an even higher risk for cardiovascular and renal disease, and these patients will benefit from aggressive antihypertensive treatment using a combination of agents. β‑blockers are playing an increasingly important role in the management of hypertension in high-risk patients. β‑blockers are a heterogeneous class of agents, and this review presents the differences between β‑blockers and provides evidence-based protocols to assist in understanding dose equivalence in the selection of an optimal regimen in patients with complex needs. The clinical benefits provided by β‑blockers are only effective if patients adhere to medication treatment long term. β‑blockers with proven efficacy, once-daily dosing, and lower side effect profiles may become instrumental in the treatment of hypertensive diabetic and nondiabetic patients.Keywords: antihypertensive, blood pressure, atenolol, carvedilol, labetalol, metoprolol, nebivolol

  9. Clinical study of Telmisartan in treatment of elderly hypertension with impaired glucose tolerance%进口替米沙坦治疗老年高血压伴葡萄糖耐量异常的临床研究

    Institute of Scientific and Technical Information of China (English)

    邹文淑; 周庆蓉; 彭良君; 张雪萍

    2011-01-01

    目的 观察进口替米沙坦对老年高血压伴葡萄糖糖耐量异常患者血糖及血压的影响.方法收集我院2008年9月至2010年9月60~80岁高血压伴糖耐量异常患者160例,随机数字表法分为两组.试验组采用替米沙进口坦80 mg口服,对照组采用进口雷米普利5mg口服,均1次/日,疗程6个月.观察两组降压效果、对糖代谢的影响、肝肾功能及血脂谱的变化、咳嗽及血管神经水肿等不良反应的发生率.结果 试验组患者血糖、血脂、胰岛素抵抗较对照组有明显改善,差异有统计学意义(P<0.05).结论 进口替米沙坦除具有降压作用外,还能改善糖脂代谢,预防糖尿病的发生,患者咳嗽发生率低,耐受性好.%Objective To observe the effect of Telmisartan on blood glucose and blood pressure of elderly patients with hypertension and impaired glucose tolerance. Methods A total of 160 60 to 80-year-old patients with hypertension and impaired glucose tolerance from September 2008 to September 2010 were randomly divided into two groups. The experimental group was treated with oral administration of Telmisartan 80 mg, q. D. The control group was treated with oral administration of Ramipril 5 mg q. D. The courses of treatment were both 6 months. We observed the incidence of adverse reactions such as antihypertensive effect, effect on glucose metabolism, changes in liver and kidney function, lipid profile changes, cough and angioneurotic edema etc.. Results In Telmisartan group, the patients' glucose, blood lipids and insulin resistance significantly improved compared with that in control group. (P < 0.05). Conclusion Besides antihypertensive effect, Telmisartan can improve glucose and lipid metabolism and prevent diabetes, with low incidence of cough and good tolerance by patients.

  10. 复方丹参滴丸联合替米沙坦治疗糖尿病肾病临床观察%Compound salvia pellet combined with telmisartan in the treatment of diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    王康君; 文世林

    2009-01-01

    Objective To observe the combined treatment effect of compound salvia pellet and telmisartan on dia-betic nephropathy (DN). Methods Sixty-three clinical diabetes subjects with complications of DN were randomly divided into treatment group and control group. Both groups received basic diabetes therapy such as strict blood control, low salt and low protein diet. The control group was simply given telmisartan. Besides telmisartan, the treatment group further received compound salvia pellet treatment. After 6 months treatment, 24 h urinary albumin (uAlb), serum creatinine (Ccr) and fundus oculi were examined. Results uAlb and uAlb/Ccr was significantly reduced in both. groups. However, the reduction was much larger in treatment group than in control group(P<0.01), DN was markedly improved in both groups and the treatment group improved more significantly than control group. No side effect was observed on all the subjects in the treatment process. Conclusions Combined treatment of compound salvia pellet and telmisartan on DN is effective and safe and the combination deserves further clinical applications.%目的 观察复方丹参滴丸联合替米沙坦治疗糖尿病肾病(DN)的疗效.方法 将63例临床DN患者随机分为治疗组和对照组,两组均严格控制血糖,给予低盐、低蛋白饮食等基础治疗,对照组单纯使用替米沙坦,治疗组在替米沙坦的基础上联合复方丹参滴丸治疗6个月.观察24 h尿白蛋白(uAlb)、血肌酐(Ccr)变化.结果 两组患者uAlb和尿白蛋白/肌酐(uAlb/Ccr)比值均较治疗前显著下降,而治疗组下降显著高于对照组(P<0.01),治疗过程中无明显不良反应.结论 复方丹参滴丸联合替米沙坦治疗DN安全、高效,值得临床推广应用.

  11. PRESCRIBING PATTERN OF ANTIHYPERTENSIVES IN INDIVIDUALS WITH HYPERTENSION ALONE AND WITH COEXISTING DIABETES MELLITUS – A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    J. Keerthi Sagar*, S. Narendranath, H.S. Somashekar, S.R. Reshma, Susheela Somappa Halemani and Prabhakar Adake

    2012-06-01

    Full Text Available Objective: Analysis of prescribing pattern of antihypertensives in patients with hypertension alone and with coexisting diabetes mellitus. Materials and Methods: A cross sectional study was conducted in an outpatient and inpatient department of general medicine at JJM Medical College hospital for a period of 3 months (July 2011 to September 2011. Prescriptions of the patients were collected and relevant data was entered in the preformed proforma and analyzed.Results: A total of 210 prescriptions were analyzed using chi square test. Out of which 126 prescriptions were of patients with hypertension alone which contain calcium channel blockers (30%, beta blockers (26%, angiotensin receptor blockers (15%, angiotensin converting enzyme inhibitors (4% and fixed dose combinations of angiotensin receptor blockers with hydrochlorothiazide (11% and combination of amlodipine with hydro-chlorothiazide (2.5%.84 Prescriptions of hypertension with coexisting diabetes mellitus had calcium channel blockers (24%, angiotensin converting enzyme inhibitors (19%, angiotensin receptor blockers (13%, beta blockers (13%, and fixed dose combinations of angiotensin receptor blockers with hydrochlorothiazide (18% and combination of amlodipine with hydrochlorothiazide (6%.[χ2=17.01, p=o.oo4] Conclusion- The present study shows that angiotensin converting enzyme inhibitors because of its beneficial effects which are well known are more commonly prescribed drugs in individuals with hypertension with coexisting diabetes mellitus. Calcium channel blockers and newly introduced angiotensin receptor blockers alone or in combination with hydrochlorothiazide are preferred drugs in both the study groups. Beta blockers are less preferred in patients of hypertension with coexisting diabetes mellitus for obvious reasons.

  12. [Beta-blockers usage in cardio-vascular diseases co-existing with COPD].

    Science.gov (United States)

    Walczak, Dorota; Kowal, Aneta; Jankowska, Renata

    2012-12-01

    Chronic obstructive pulmonary disease (COPD) is one of the most frequent chronic diseases. Slightly reversable and progressive decrease in airflow through the airways is characteristic for the disease. It has been brought up last years that COPD course influences not only pulmonary system status but also many co-existing diseases in the eldery, especially cardio-vascular diseases, such as: ischaemic heart disease, hypertension, heart arrythmias, heart infarction. Wide usage and established position in the treatment of cardio-vascular diseases have the antagonists of beta-adrenergic receptors (beta-blockers). The aim of this work was the combination of the studies results quoted in the literature about the usage of beta-blockers in cardiovascular diseases co-existing with COPD. Conclusions. Nowadays there are no unambiguous recommendations for the usage of beta-blocker in patients with COPD and the decision about including them into treatment depends on the individually estimated risk of complications. PMID:23437704

  13. A novel series of pyrazolylpiperidine N-type calcium channel blockers.

    Science.gov (United States)

    Subasinghe, Nalin L; Wall, Mark J; Winters, Michael P; Qin, Ning; Lubin, Mary Lou; Finley, Michael F A; Brandt, Michael R; Neeper, Michael P; Schneider, Craig R; Colburn, Raymond W; Flores, Christopher M; Sui, Zhihua

    2012-06-15

    Selective blockers of the N-type calcium channel have proven to be effective in animal models of chronic pain. However, even though intrathecally delivered synthetic ω-conotoxin MVIIA from Conus magnus (ziconotide [Prialt®]) has been approved for the treatment of chronic pain in humans, its mode of delivery and narrow therapeutic window have limited its usefulness. Therefore, the identification of orally active, small-molecule N-type calcium channel blockers would represent a significant advancement in the treatment of chronic pain. A novel series of pyrazole-based N-type calcium channel blockers was identified by structural modification of a high-throughput screening hit and further optimized to improve potency and metabolic stability. In vivo efficacy in rat models of inflammatory and neuropathic pain was demonstrated by a representative compound from this series. PMID:22608964

  14. USE OF BETA-BLOCKERS IN THE PERIOPERATIVE PERIOD: HOW STRONG ARE THE EVIDENCES?

    Directory of Open Access Journals (Sweden)

    V. V. Samoylenko

    2015-09-01

    Full Text Available Optimization of the pharmacotherapy in preoperative period is the cornerstone of the concept of risk modification of cardiovascular complications in the perioperative period. Therefore, special attention has recently been focused on the use of beta-blockers in the postoperative period. Nowadays convincing evidence base for the use of this class of drugs in the perioperative period that was the basis for the development of clinical guidelines is accumulated. Moreover, results of large randomized trials of beta-blockers are controversial. This has resulted in significant differences in the classes of recommendations and levels of evidence.Analysis of the results of basic researches and the provisions of recommendations of the international and national professional medical societies on the use of beta-blockers in patients with cardiovascular disease to reduce the risk of cardiac complications in the perioperative period for planned extracardiac surgical procedures is presented.

  15. Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus ().

    Science.gov (United States)

    Martin-Eauclaire, Marie-France; Pimenta, Adriano M C; Bougis, Pierre E; De Lima, Maria-Elena

    2016-09-01

    Potassium (K(+)) channels are trans-membrane proteins, which play a key role in cellular excitability and signal transduction pathways. Scorpion toxins blocking the ion-conducting pore from the external side have been invaluable probes to elucidate the structural, functional, and physio-pathological characteristics of these ion channels. This review will focus on the interaction between K(+) channels and their peptide blockers isolated from the venom of the scorpion Tityus serrulatus, which is considered as the most dangerous scorpion in Brazil, in particular in Minas-Gerais State, where many casualties are described each year. The primary mechanisms of action of these K(+) blockers will be discussed in correlation with their structure, very often non-canonical compared to those of other well known K(+) channels blockers purified from other scorpion venoms. Also, special attention will be brought to the most recent data obtained by proteomic and transcriptomic analyses on Tityus serrulatus venoms and venom glands. PMID:27349167

  16. In Silico Predictions of hERG Channel Blockers in Drug Discovery

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Sørensen, Flemming Steen

    2011-01-01

    drugs with different therapeutic indications and recognized as hERG blockers were recently withdrawn due to the risk of QT prolongation, arrhythmia and Torsade de Pointes.In silico techniques can provide a priori knowledge of hERG blockers, thus reducing the costs associated with screening assays...... whereas QSAR and classification models provide a faster assessment and detection of hERG-related drug toxicity, limitation on the applicability domain of the current models and integration of data from diverse in vitro approaches are still issues to challenge.Therefore, this review will emphasize on...... current methods to predict hERG blockers and the need of consistent data to improve the quality and performance of the in silico models. Finally, integration of network-based analysis on drugs inducing potentially long-QT syndrome and arrhythmia will be discussed as a new perspective for a better...

  17. Effects of beta-blockers on heart failure with preserved ejection fraction: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Feng Liu

    Full Text Available BACKGROUND: Effects of beta-blockers on the prognosis of the heart failure patients with preserved ejection fraction (HFpEF remain controversial. The aim of this meta-analysis was to determine the impact of beta-blockers on mortality and hospitalization in the patients with HFpEF. METHODS: A search of MEDLINE, EMBASE, and the Cochrane Library databases from 2005 to June 2013 was conducted. Clinical studies reporting outcomes of mortality and/or hospitalization for patients with HFpEF (EF ≥ 40%, being assigned to beta-blockers treatment and non-beta-blockers control group were included. RESULTS: A total of 12 clinical studies (2 randomized controlled trials and 10 observational studies involving 21,206 HFpEF patients were included for this meta-analysis. The pooled analysis demonstrated that beta-blocker exposure was associated with a 9% reduction in relative risk for all-cause mortality in patients with HFpEF (95% CI: 0.87 - 0.95; P < 0.001. Whereas, the all-cause hospitalization, HF hospitalization and composite outcomes (mortality and hospitalization were not affected by this treatment (P=0.26, P=0.97, and P=0.88 respectively. CONCLUSIONS: The beta-blockers treatment for the patients with HFpEF was associated with a lower risk of all-cause mortality, but not with a lower risk of hospitalization. These finding were mainly obtained from observational studies, and further investigations are needed to make an assertion.

  18. Heart rate and use of beta-blockers in stable outpatients with coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Ph Gabriel Steg

    Full Text Available BACKGROUND: Heart rate (HR is an emerging risk factor in coronary artery disease (CAD. However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR. METHODS AND FINDINGS: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%. Mean (SD age was 64.2 (10.5 years, HR by pulse was 68.3 (10.6 bpm, and by electrocardiogram was 67.2 (11.4 bpm. Overall, 44.0% had HR ≥ 70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR ≥ 70 bpm. HR ≥ 70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents. CONCLUSIONS: Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR ≥ 70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested.

  19. Selective Kv1.3 channel blocker as therapeutic for obesity and insulin resistance

    OpenAIRE

    Upadhyay, Sanjeev Kumar; Eckel-Mahan, Kristin L.; Mirbolooki, M Reza; Tjong, Indra; Griffey, Stephen M.; Schmunk, Galina; Koehne, Amanda; Halbout, Briac; Iadonato, Shawn; Pedersen, Brian; Borrelli, Emiliana; Ping H. Wang; Mukherjee, Jogeshwar; Sassone-Corsi, Paolo; Chandy, K. George

    2013-01-01

    Obesity is a global epidemic in need of novel and safe therapeutics. We show that ShK-186, a selective blocker of the Kv1.3 potassium channel, has powerful antiobesity effects in a mouse model of diet-induced obesity. ShK-186 increases energy expenditure by activating brown adipose tissue, causes profound changes in liver metabolism and reduces obesity-induced inflammation of white adipose tissue. Our studies highlight the potential use of selective Kv1.3 blockers in the treatment of obesity ...

  20. Spiro azepane-oxazolidinones as Kv1.3 potassium channel blockers - WO2010066840

    OpenAIRE

    Wulff, Heike

    2010-01-01

    This article evaluates a patent application from Solvay Pharmaceuticals, which claims spiro azepane-oxazolidinones as novel blockers of the voltage-gated potassium channel Kv1.3 for the treatment of diabetes, psoriasis, obesity, transplant rejection and T-cell mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The patent describes a new chemotype of Kv1.3 blockers and thus illustrates the growing interest of the pharmaceutical industry in Kv1.3 as a target of im...

  1. Blockers for non-crossing spanning trees in complete geometric graphs

    CERN Document Server

    Keller, Chaya; Rivera-Campo, Eduardo; Urrutia-Galicia, Virginia

    2012-01-01

    In this paper we present a complete characterization of the smallest sets that block all the simple spanning trees (SSTs) in a complete geometric graph. We also show that if a subgraph is a blocker for all SSTs of diameter at most 4, then it must block all simple spanning subgraphs, and in particular, all SSTs. For convex geometric graphs, we obtain an even stronger result: being a blocker for all SSTs of diameter at most 3 is already sufficient for blocking all simple spanning subgraphs.

  2. Effect of telmisartan on adiponectin,TNF-α and insulin resistance in patients with type 2 diabetes complicated with hypertension%替米沙坦对2型糖尿病合并高血压患者血清APN、TNF-α及胰岛素抵抗的影响

    Institute of Scientific and Technical Information of China (English)

    葛建彬; 邹云; 顾锦华

    2012-01-01

    Objective To evaluate the effect of telmisartan on adiponectin, TNF-α and insulin resistance in patients with type 2 diabetes complicated with hypertension. Methods 80 patients who had type 2 diabetes complicated with hypertension were randomly divided into telmisartan group and control group ,40 cases in each group. Based on o-ral glucose-lowering agents,telmisartan was added in telmisartan group,while amlodipine was added in control group. APN, TNF-α, Bp and IRI were observed of the two groups before and after treatment. Results In all these patients, the blood pressure all decreased to 140/90 mmHg after 10 weeks of treatment, while SBP and DBP had no significant changes between the two groups( P > 0. 05 ). There was no significant difference in APN, TNF-a and HOMA-IR between the two groups before treatment. The HOMA-IR in telmisartan group decreased significantly than that of control group ( P 0.05).治疗前两组APN、TNF-α、HOMA-IR水平比较,差异无统计学意义(P>0.05).治疗10周后,替米沙坦组外周血APN含量较对照组明显升高(P<0.05),TNF-α含量较对照组明显降低(P<0.05),HOMA-IR较对照组明显降低(P<0.05).结论 采用替米沙坦治疗2型糖尿病合并高血压患者,在升高血清APN浓度和降低TNF-α浓度的同时,具有改善胰岛素抵抗的作用.

  3. Effects of Telmisartan and Valsartan on Insulin Resistance in Obese Hypertensive Patients%替米沙坦和缬沙坦对肥胖高血压患者胰岛素抵抗的影响

    Institute of Scientific and Technical Information of China (English)

    武欣迎; 李晶晶; 宋红萍; 韩勇

    2015-01-01

    目的:观察替米沙坦和缬沙坦对肥胖高血压患者胰岛素抵抗影响。方法肥胖标准为体重指数(BMI)≥25 kg·(m2)-1的原发性高血压患者68例,随机分为替米沙坦组33例和缬沙坦组35例,服药前及服药16周后监测血压、空腹血糖、空腹胰岛素(Fins)及胰岛素抵抗指数(HOMA-IR)。结果两组服药前后比较,收缩压/舒张压差异均有统计学意义(P0.05)。两组治疗后 Fins 和 HOMA-IR 比较差异有统计学意义(P 0. 05);( 3. 0 ± 0. 7) vs. (3. 0 ± 0. 7) ( P > 0. 05), respectively]. Conclusion In obese hypertensive patients, telmisartan and valsartan exert similar antihypertensive effect, but telmisartan may have a benefit in insulin resistance in comparison to valsartan.

  4. The putative P-gp inhibitor telmisartan does not affect the transcellular permeability and cellular uptake of the calcium channel antagonist verapamil in the P-glycoprotein expressing cell line MDCK II MDR1

    DEFF Research Database (Denmark)

    Saaby, Lasse; Tfelt-Hansen, Peer; Brodin, Birger

    2015-01-01

    Verapamil is used in high doses for the treatment of cluster headache. Verapamil has been described as a P-glycoprotein (P-gp, ABCB1) substrate. We wished to evaluate in vitro whether co administration of a P-gp inhibitor with verapamil could be a feasible strategy for increasing CNS uptake of...... verapamil. Fluxes of radiolabelled verapamil across MDCK II MDR1 monolayers were measured in the absence and presence of the putative P-gp inhibitor telmisartan (a clinically approved drug compound). Verapamil displayed a vectorial basolateral-toapical transepithelial efflux across the MDCK II MDR1...... monolayers with a permeability of 5.7 9 105 cm sec1 compared to an apical to basolateral permeability of 1.3 9 105 cm sec-1. The efflux could be inhibited with the P-gp inhibitor zosuquidar. Zosuquidar (0.4 lmol/L) reduced the efflux ratio (PB-A/PA-B) for verapamil 4.6–1.6. The presence of telmisartan...

  5. Synthesis and Effects of Novel Dihydropyridines as Dual Calcium Channel Blocker and Angiotensin Antagonist on Isolated Rat Aorta

    Directory of Open Access Journals (Sweden)

    Farzin Hadizadeh

    2010-01-01

    Full Text Available Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors (AT1 and L-type calcium channels were investigated on isolated rat aorta. Materials and MethodsAortic rings were pre-contracted with 1 µM Angiotensin II or 80 mM KCl and relaxant effects of losartan, nifedipine, 5a and 5b were evaluated by cumulative addition of these drugs to the bath solution.ResultsThe results showed that compounds 5a and 5b have both L-type calcium channel and AT1 receptor blocking activity. Their effects on AT1 receptors are 1000 and 100,000 times more than losartan respectively. The activity of compound 5b on L-type calcium channel is significantly less than nifedipine but compound 5a has comparable effect with nifedipine. ConclusionFinally we concluded that these two new Compounds can be potential candidates to be used as effective antihypertensive agents.

  6. Effects of telmisartan on insulin resistance in patients with essential hypertension%替米沙坦对高血压患者胰岛素抵抗的影响

    Institute of Scientific and Technical Information of China (English)

    杨菊

    2011-01-01

    目的 探讨替米沙坦对高血压患者胰岛素抵抗的影响.方法 分别测定高血压低危组(22例)、中危组(20例)及高危组(18例)口服替米沙坦12周前、后的血压、空腹血糖(FPG)和空腹血糖胰岛素水平(FINS),并计算胰岛素敏感指数(ISI).另取正常对照组(20例)检测以上生化指标作为正常对照.结果 治疗前中、高危组患者血压高于低危组(P<0.05);3组高血压患者FINS高于正常对照组(P<0.01);ISI低于正常对照组(P<0.01).治疗后3组血压均明显下降(P<0.01);低、中危组患者的FINS降低,而ISI增加(P<0.01),但替米沙坦对高危组患者的FINS和ISI无影响;治疗后低、中危组FINS和ISI比较,差异无统计学意义.结论 替米沙坦能改善高血压低、中危组患者的胰岛素抵抗,而对高危组患者无影响.%Objective To study the effects of telmisartan on insulin resistance in patients with essential hypertension(EH). Methods 22 low-risk EH patients and 20 moderate-risk EH patients and high-risk EH patients were treated with telmisartan for 12 weeks. Blood pressure,serum concentration of fasting insulin(FINS) and glucose(FPG) were measured respectively before and 12 weeks after the treatment and insulin sensitivity index( ISI) were calculated. 20 healthy subjects were taken as the normal control group. Results The blood pressures of moderate-risk and high risk EH patients were significantly high as compared with low-risk EH patients(P<0.05). FINS was higher and ISI was lower in EH patients than those in normal controls(all P<0.01). The blood pressures of all EH patients significantly decreased after treatments(P<0.01). Telmisartan decreased FINS level and increased ISI in low-risk and moderate-risk EH patients(all P<0.01), but had no effect on high-risk patients. There were similar effects of telmisartan on FINS and ISI in low-risk and moderate-risk EH patients. Conclusion Telmisartan can ameliorate insulin resistance in EH

  7. Telmisartan Improves Vascular Endothelial Function in Patients with Metabolic Syndrome%替米沙坦改善代谢综合征患者血管内皮功能

    Institute of Scientific and Technical Information of China (English)

    龚丽娅; 蓝光明; 黄秋霞

    2011-01-01

    Aim To investigate the effect of telmisartan on vascular endothelial function in patients with metabolic syndrome. Methods 76 cases of patients with metabolic syndrome were recruited, and randomized to receive conventional treatment (n = 38) or telmisartan (80 mg/d) on the basis of conventional treatment (n = 38 ) for 3 months. Thirty-eight healthy persons were chosen as control group. The plasma level of glucose and lipid metabolism, nitric oxide (NO) and cytokines of each group before and after treament were determined. The blood pressure and endothelial relaxation function were also measured. Results The blood glucose and blood pressure in telmisartan group and conventional group were all decreased after treatment ( P < 0. 01 ), without intergroup differences ( P > 0.05 ). In telmisartan group, the flow-mediated diameter(FMD) and NO were obviously increased(P <0. 05 and P <0. 01), and the plasma tumor necrosis factor α(TNF-α) , interleukin-6 (IL-6) and C-reactive protein (CRP) were decreased (P < 0. 05 ) , with intergroup differences( P < 0.05). No obvious changes of FMD, NO and inflammatory factors were found in conventional group. Conclusion Telmisartan can improve vascular endothelial function in patients with metabolic syndrome by raising concentration of NO and inhibiting inflammatory reaction with decreased level of cytokines.%目的 观察替米沙坦对代谢综合征患者血管内皮功能的影响.方法 76例代谢综合征患者随机分为常规组和替米沙坦组,每组38例,同时选择健康体检者38例作为对照组.替米沙坦组在常规用药的基础上加服替米沙坦80 mg/d,治疗3个月.检测三组患者治疗前后血糖、血脂代谢指标、血浆一氧化氮含量及炎症因子肿瘤坏死因子α、白细胞介素6和C反应蛋白水平,观察血压及血管内皮舒张功能变化.结果 治疗后常规组和替米沙坦组的血压、空腹血糖均明显下降(P<0.01),但两组间的血压、空腹血

  8. 替米沙坦对男性高血压患者性功能影响的研究%Effects of telmisartan on sexual function of male hypertension patients

    Institute of Scientific and Technical Information of China (English)

    臧贵明

    2013-01-01

    目的:探讨替米沙坦对男性高血压患者性功能的影响.方法:选择150例男性高血压患者为研究对象,随机分为替米沙坦组(75例)和贝那普利对照组(75例),观察并比较两组血压、勃起功能国际指数(IIEF)和性生活情况.结果:治疗后两组患者血压均明显下降(P<0.05),且治疗后两组患者血压情况仍无显著差异(P>0.05);治疗后,与贝那普利对照组比较,替米沙坦组IIEF评分[(11.28±1.32)分比(19.48±2.49)分]、性生活频率[(2.09±0.22)次/月比(6.31±0.85)次/月]明显升高,能够勃起比例(62.7%比82.7%)明显增大(P均<0.05);勃起功能情况[分正常,轻、中、重度障碍(ED),x2=6.322,P=0.0412]及主观性欲要求(分强、中、弱,x2 =7.493,P=0.0326)替米沙坦组亦明显好于贝那普利对照组.结论:替米沙坦能够在保证降压效果的基础上,改善性功能和性生活质量.%Objective:To explore influence of telmisartan on sexual function in male patients with hypertension.Methods:A total of 150 male patients with hypertension were enrolled and randomly divided into telmisartan group (n=75) and benazepril control group (n=75).Blood pressure,international index of erectile function (IIEF) and quality of sex were observed and compared between two groups.Results:After treatment,there was significant decrease in blood pressure in both groups (P<0.05),and there was still no significant difference in blood pressure between two groups (P>0.05) ; compared with benazepril control group,there were significant increase in IIEF score [(11.28±1.32) scores vs.(19.48±2.49) scores],sex life frequency [(2.09±0.22) times/month vs.(6.31± 0.85) times/month] and erectile proportion (62.7% vs.82.7%),P<0.05 all in telmisartan group; Erectile function (was divided into normal,mild disability,moderate disability and severe disability,x2 =6.322,P =0.0412)and subjective sexual desire (was divided into strong,middle and weak,x2 =7.493,P=0.0326) of

  9. Treatment with beta-blockers in nurse-led heart failure clinics

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Schou, Morten; Videbaek, Lars;

    2007-01-01

    BACKGROUND: Beta-blockers (BBs) are a cornerstone in the treatment of chronic heart failure (HF), but several surveys have documented that many patients are not offered treatment or are not titrated to target doses. In part to address this problem, specialized, nurse-led HF clinics have been...

  10. Chronic beta-blocker treatment in patients with advanced heart failure - Effects on neurohormones

    NARCIS (Netherlands)

    Teisman, ACH; van Veldhuisen, DJ; Boomsma, F; de Kam, PJ; Pinto, YM; de Zeeuw, D; van Gilst, WH

    2000-01-01

    Background: To date, the use of beta-blockers in treating patients with chronic heart failure gains support, this since several large clinical trials reported reduced mortality after chronic beta-blockade. Part of these beneficial effects may result from inhibition of deleterious neurohormone activa

  11. Beta-Blockers and the Kidney: Implications for Renal Function and Renin Release.

    Science.gov (United States)

    Epstein, Murray; And Others

    1985-01-01

    Reviews and discusses current information on the human renal response as related to beta-blockers (antihypertension agents). Topic areas considered include cardioselectivity, renal hemodynamics, systemic hemodynamics, changes with acute and chronic administration, influence of dose, and others. Implications and an 11-item multiple-choice self-quiz…

  12. SAFETY AND EFFICACY OF BETA-BLOCKERS IN THE TREATMENT OF STABLE ANGINA-PECTORIS

    NARCIS (Netherlands)

    DEMUINCK, ED; LIE, KI

    1990-01-01

    In stable exercise-induced angina pectoris, beta-blockers exert their beneficial effects mainly through a reduction in heart rate, blood pressure, and contractility. Additional beneficial effects are an improvement in myocardial oxygen supply through a redistribution of coronary flow, a lengthening

  13. Bed blockers: A study on the elderly patients in a teaching hospital in India

    Directory of Open Access Journals (Sweden)

    Praveen Kumar N

    2010-07-01

    Full Text Available A cross-sectional study of in-patients over the age of 60 years was conducted at district McGann Hospital, Shimoga on patients who were classified as bed blockers. Level of dependency and cognitive function of these patients were assessed using Barthel scale and Abbreviated mental test (AMT respectively. Median age of the study population was 67 years; majority of them were men. Most of them were admitted in the medical ward and the median time to be labeled as bed blocker was 32 days. These bed blockers were a weak group of patients with an average 3.1 pathology per case. Majority of them suffered from neurological disorders and cardiovascular disease. High level of dependence was noted with a mean Barthel score of 29.68 (Range 0 -100. Low levels of cognitive function was also noted among these patients with a mean AMT of 4.76 (Range 0 -10.These findings demonstrate that the bed blockers in McGann hospital suffer not only from genuine health problems but also have a high dependency level in activities of daily living which hamper their discharge to the community. Community based rehabilitation using an intersectoral approach may help at least the less dependent to return home.

  14. Inhibition of Escherichia coli chemotaxis by omega-conotoxin, a calcium ion channel blocker.

    OpenAIRE

    Tisa, L S; Olivera, B M; Adler, J

    1993-01-01

    Escherichia coli chemotaxis was inhibited by omega-conotoxin, a calcium ion channel blocker. With Tris-EDTA-permeabilized cells, nanomolar levels of omega-conotoxin inhibited chemotaxis without loss of motility. Cells treated with omega-conotoxin swam with a smooth bias, i.e., tumbling was inhibited.

  15. INHIBITION OF KIDNEY DISORDERS IN CARDIOVASCULAR DISEASES: THE ROLE OF ANGIOTENSIN II RECEPTOR BLOCKERS

    Directory of Open Access Journals (Sweden)

    V. V. Fomin

    2016-01-01

    Full Text Available Mechanisms of renal disorders in cardiovascular diseases are presented. The main of these mechanisms is an endothelium dysfunction. It is related with some factors: arterial hypertension, insulin resistance syndrome, diabetes type 2, dyslipidemia, obesity. Approaches to prevention of kidney disorder and cardiovascular complications are discussed with focus on usage of angiotensin II receptor blockers.

  16. Use of clopidogrel and calcium channel blockers and risk of major adverse cardiovascular events

    DEFF Research Database (Denmark)

    Schmidt, Morten; Johansen, Martin B; Robertson, Douglas J;

    2012-01-01

    Eur J Clin Invest 2011 ABSTRACT: Background  The CYP3A4 inhibition by calcium channel blockers (CCBs) may attenuate the effectiveness of clopidogrel. Using time-varying drug exposure ascertainment, we examined whether CCB use modified the association between clopidogrel use and major adverse...

  17. Monolithic integrated silicon-based slot-blocker for packet-switched networks

    OpenAIRE

    de Valicourt, Guilhem; Mestre , Miquel A.; Bramerie, Laurent; Simon, Jean-Claude; Borgne, Eric; Vivien, Laurent; Cassan, Eric; Marris-Morini, Delphine; Fédéli, Jean-Marc; Jennevé, Philippe; Mardoyan, Haik; Pointurier, Yvan; Le Liepvre, Alban; Duan, Guang-Hua; Shen, Alexandre

    2014-01-01

    We demonstrate a 16-channel, silicon-on-insulator, monolithic integrated slot-blocker. This silicon photonic circuit includes two arrayed waveguide gratings, 16 variable optical attenuators and two vertical fiber couplers. We successfully operate it with 56 Gb/s and 80 Gb/s QPSK optical packets.

  18. Comparison of beta blocker and digoxin alone and in combination for management of patients with atrial fibrillation and heart failure.

    Science.gov (United States)

    Fauchier, Laurent; Grimard, Caroline; Pierre, Bertrand; Nonin, Emilie; Gorin, Laurent; Rauzy, Bruno; Cosnay, Pierre; Babuty, Dominique; Charbonnier, Bernard

    2009-01-15

    In patients with atrial fibrillation (AF) and heart failure (HF), beta blockers and digoxin reduce the ventricular rate, but controversy exists concerning how these drugs affect prognosis in this setting. This study compared the effects of beta blocker and digoxin on mortality in patients with both AF and HF. In a single-center institution, patients with AF and HF seen between January 2000 and January 2004 were identified and followed until September 2007. Of 1,269 consecutive patients with both AF and HF, 260 were treated with a beta blocker alone, 189 with beta blocker plus digoxin, 402 with digoxin alone, and 418 without beta blocker or digoxin (control group). During a follow-up of 881+/-859 days, 247 patients died. Compared with the control group, treatment with beta blocker was associated with a decreased mortality (relative risk=0.58, 95% confidence interval 0.40 to 0.85, p=0.005 for beta blocker alone and 0.59, 95% confidence interval 0.40 to 0.87, p=0.008 for beta blocker plus digoxin). By contrast, treatment with digoxin alone was not associated with a better survival (relative risk=0.97, 95% confidence interval 0.73 to 1.30, p=NS). Results remained significant after adjustment for potential confounders and similar when we considered, separately, HF with permanent or nonpermanent AF, presence or absence of coronary disease, and patients with decreased or preserved systolic function. In conclusion, in unselected patients with AF and HF, treatments with beta blocker alone or with beta blocker plus digoxin are associated with a similar decrease in the risk of death. Digoxin alone is associated with a worse survival chance, similar to that of patients without any rate control treatment. PMID:19121446

  19. High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers

    International Nuclear Information System (INIS)

    Antibodies with high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers have been produced in rabbits by immunization with dihydropyridine-protein conjugates. Anti-dihydropyridine antibodies were found to specifically bind [3H]nitrendipine, [3H]-nimodipine, [3H]nisoldipine, and [3H]PN 200-110 (all 1,4-dihydropyridine Ca2+-channel blockers) with high affinity, while [3H]verapamil, [3H]diltiazem, and [3H]trifluoperazine were not recognized. The average dissociation constant of the [3H]nitrendipine-antibody complex was 0.06 (+/- 0.02) X 10(-9) M for an antiserum studied in detail and ranged from 0.01 to 0.24 X 10(-9) M for all antisera. Inhibition of [3H]nitrendipine binding was specific for the 1,4-dihydropyridine Ca2+-channel modifiers and the concentrations required for half-maximal inhibition ranged between 0.25 and 0.90 nM. Structurally unrelated Ca2+-channel blockers, calmodulin antagonists, inactive metabolites of nitrendipine, and UV-inactivated nisoldipine did not modify [3H]nitrendipine binding to the anti-dihydropyridine antibodies. Dihydropyridines without a bulky substituent in the 4-position of the heterocycle were able to displace [3H]nitrendipine binding, but the concentrations required for half-maximal inhibition were greater than 800 nM. In summary, anti-dihydropyridine antibodies have been shown to have high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers and to exhibit dihydropyridine binding properties similar to the membrane receptor for the 1,4-dihydropyridine Ca2+-channel blockers

  20. Calcium-channel blockers for the prevention of stroke: from scientific evidences to the clinical practice

    Directory of Open Access Journals (Sweden)

    S. Taddei

    2013-05-01

    Full Text Available AIM OF THE REVIEW The present review aims to analyze the role of calcium-channel blockers, and particularly newer molecules, as first-line therapy for cerebrovascular disease. BACKGROUND Stroke is the leading cause of disability in the general population. Among traditional cardiovascular risk factors, hypertension has a key role in the genesis of both hemorrhagic and ischemic stroke and a direct correlation exists between blood pressure values and the risk of stroke. Moreover, blood pressure reduction has been demonstrated to be the most important route to reduce stroke incidence and recurrence. However, the mere reduction of blood pressure values does not normalize the cardiovascular risk of the hypertensive patient. It is therefore necessary to use drug classes that beyond their blood pressure-lowering effect have also an additional effect in terms of organ protection. Among these, calcium-channel blockers have a crucial profile. Firstly, they are effective in inducing left ventricular hypertrophy regression, with a strength at least equal to that of ACE-inhibitors. Secondly, they have an antithrombotic and an endothelium-protecting effect, mediated by their antioxidant activity. Finally, calcium-channel blockers are the most powerful drugs in preventing vascular remodeling. For these reasons this drug class has probably the strongest antiatherosclerotic effect, and it is the first-choice treatment mainly for cerebrovascular disease. Among different available calcium-channel blockers, the newer ones seem to possess pharmacokinetic characteristics allowing a more homogeneous 24 hours coverage as compared to older molecules, and preliminary data seem to suggest a greater beneficial effect also on left ventricular hypertrophy and lower incidence of side effects. CONCLUSIONS Although blood pressure reduction is the main tool to reduce cerebrovascular risk in hypertensive patients, some drug classes, such as calciumchannel blockers, seem to provide

  1. Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator

    DEFF Research Database (Denmark)

    Hoogwegt, Madelein T; Kupper, Nina; Theuns, Dominic A M J;

    2012-01-01

    Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We...... investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD....

  2. β-Blocker use and mortality in cancer patients: systematic review and meta-analysis of observational studies.

    Science.gov (United States)

    Zhong, Shanliang; Yu, Dandan; Zhang, Xiaohui; Chen, Xiu; Yang, Sujin; Tang, Jinhai; Zhao, Jianhua; Wang, Shukui

    2016-09-01

    A number of epidemiologic studies have attempted to link the use of β blockers to mortality in cancer patients, but their findings have been inconclusive. A meta-analysis was carried out to derive a more precise estimation. Relevant studies were identified by searching PubMed and EMBASE to May 2015. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. Twenty cohort studies and four case-control studies involving 76 538 participants were included. The overall results showed that patients who used β blockers after diagnosis had an HR of 0.89 (95% CI 0.81-0.98) for all-cause mortality compared with nonusers. Those who used β blockers after diagnosis (vs. nonusers) had an HR of 0.89 (95% CI 0.79-0.99) for cancer-specific mortality. Prediagnostic use of β blockers showed no beneficial effect on all-cause mortality or cancer-specific mortality. Stratifying by cancer type, only breast cancer patients who used β blockers after diagnosis had a prolonged overall survival. A linear but nonsignificant trend was found between postdiagnostic β-blocker use and mortality of cancer patients. In conclusion, the average effect of β-blocker use after diagnosis but not before diagnosis is beneficial for the survival of cancer patients. PMID:26340056

  3. Clinical effect of Telmisartan in treatment of elderly patients with essen-tial hypertension%替米沙坦治疗老年原发性高血压患者的临床效果

    Institute of Scientific and Technical Information of China (English)

    王珊珊

    2014-01-01

    Objective To observe the effect of Telmisartan in treatment of elderly patients with essential hypertension (EH) in patients with clinical efficacy. Methods 60 EH patients in He'nan Provincial People's Hospital from June 2012 to January 2014 were selected as Telmisartan group (Telmisartan 80 mg, once a day, course of 6 months) and 30 healthy elderly people physical examined at the same time were selected as normal control group; everyone was fasting blood at initial examination and Telmisartan group were fasting blood 6 months later. The systolic and diastolic blood pressure were measured with sphygmomanometer; the high-sensitivity C reactive protein (hs-CRP) was detected with immunonephelometry; the serum fibrinogen (FIB) was detected with the fiber automatic blood coagulation analyzer;serum interleukin 6 (IL-6), interleukin 18 (IL-18), intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor alpha (TNF-α) protein levels were detected with the method of ELISA. Results In initial examination, Telmisartan group compared with the normal control group, the content of serum hs-CRP, FIB, IL-6, IL-18, ICAM-1 and TNF- α increased with a statistical significance (P < 0.01). The content of serum hs-CRP, FIB, IL-6, IL-18, ICAM-1 and TNF- α slightly increased with a statistical significance after treatment of 6 months' later compared with the normal control group (P<0.05);after treatment with Telmisartan, the contents of serum hs-CRP, FIB, IL-6, IL-18, ICAM-1 and TNF-α markedly reduced with a statistical significance (P < 0.01). Conclusion Inflammation reaction exists in elder EH patients, inflammatory factors involved in the pathophysiological process of senior primary pathogenesis of hypertension; Telmisartan can reduce the protein level of serum hs-CRP, FIB, IL-6, IL-18, ICAM-1 and TNF-α, the antihypertensive effect and anti-inflammatory effects.%目的:观察替米沙坦治疗老年原发性高血压(EH)患者的临床效果。方法选择2012年6

  4. Studies of the outcome of the treatment with beta-blockers in secondary prevention of the ischemic heart disease

    OpenAIRE

    Radović Vesna V.

    2009-01-01

    Convincing evidence of the decline of mortality has been achieved with beta-blockers in patients with an acute myocardial infarction and in post-infarction follow-up. The beta-blockers are also the most efficient antianginal medications for the decrease of ischemia in outpatients. They are highly efficient as a monotherapy for angina and are also a medication of choice for angina after the coronary. The objective of this work was an estimate of the use of beta-blockers in secondary prevention...

  5. Use of statins and beta-blockers after acute myocardial infarction according to income and education

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Nørgaard; Gislason, Gunnar H; Rasmussen, Søren;

    2007-01-01

    OBJECTIVE: To study the initiation of and long-term refill persistency with statins and beta-blockers after acute myocardial infarction (AMI) according to income and education. DESIGN AND SETTING: Linkage of individuals through national registers of hospitalisations, drug dispensation, income and...... education. PARTICIPANTS: 30 078 patients aged 30-74 years surviving first hospitalisation for AMI in Denmark between 1995 and 2001. MAIN OUTCOME MEASURES: Initiation of statin or beta-blocker treatment (out-patient claim of prescriptions within 6 months of discharge) and refill persistency (first break in...... treatment lasting at least 90 days, and re-initiation of treatment after a break). RESULTS: When simultaneously estimating the effect of income and education on initiation of treatment, the effect of education attenuated and a clear income gradient remained for both drugs. Among patients aged 30-64 years...

  6. In silico predictions of hERG channel blockers in drug discovery

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Jørgensen, Flemming Steen

    2011-01-01

    The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several...... drugs with different therapeutic indications and recognized as hERG blockers were recently withdrawn due to the risk of QT prolongation, arrhythmia and Torsade de Pointes. In silico techniques can provide a priori knowledge of hERG blockers, thus reducing the costs associated with screening assays....... Significant progress has been made in structure-based and ligand-based drug design and a number of models have been developed to predict hERG blockage. Although approaches such as homology modeling in combination with docking and molecular dynamics bring us closer to understand the drug-channel interactions...

  7. In Silico Predictions of hERG Channel Blockers in Drug Discovery

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Sørensen, Flemming Steen

    2011-01-01

    The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several...... drugs with different therapeutic indications and recognized as hERG blockers were recently withdrawn due to the risk of QT prolongation, arrhythmia and Torsade de Pointes.In silico techniques can provide a priori knowledge of hERG blockers, thus reducing the costs associated with screening assays....... Significant progress has been made in structure-based and ligand-based drug design and a number of models have been developed to predict hERG blockage.Although approaches such as homology modeling in combination with docking and molecular dynamics bring us closer to understand the drug-channel interactions...

  8. The role of aldosterone receptor blocker therapy in hypertension and heart failure

    Directory of Open Access Journals (Sweden)

    Giuseppina Santese

    2015-09-01

    Full Text Available The aldosterone receptor blocker therapy as an “add-on” to hypotensive therapy is an excellent therapeutic strategy that has proved to be particularly effective in treating refractory hypertension, hypertension with organ damage and overweight hypertensive patients. Aldosterone receptor blockers are extremely useful in inhibiting hormonal activation linked with heart failure: they have cardioprotective effects not only during full-blown heart failure, but also in its early stages, and this effect can be observed even more frequently in heart failures with metabolic syndrome. The use of molecules such as canrenone with a favorable tolerability profile ensures a better tolerability ratio by providing benefits linked to fewer drug interactions, lower incidence of side effects and improved therapy adherence.

  9. Alpha 1-blockers vs 5 alpha-reductase inhibitors in benign prostatic hyperplasia. A comparative review

    DEFF Research Database (Denmark)

    Andersen, J T

    1995-01-01

    During recent years, pharmacological treatment of symptomatic benign prostatic hyperplasia (BPH) has become the primary treatment choice for an increasing number of patients. The 2 principal drug classes employed are alpha 1-blockers and 5 alpha-reductase inhibitors. Current information from...... patients who will respond well to alpha 1-blockers have yet to be identified, and data concerning the long term effects of these drugs are not yet available. 5 alpha-Reductase inhibitors have a slow onset of effect, but treatment leads to improvement in symptoms, reduction of the size of the prostate gland...... and improvement in objective parameters for bladder outflow obstruction. Approximately 30 to 50% of patients will respond to treatment with 5 alpha-reductase inhibitors. The definitive role of pharmacological treatment in symptomatic BPH remains to be established, although it seems that patients unfit...

  10. A Meta-Analysis of Long- Versus Short-Acting Phosphodiesterase 5 Inhibitors: Comparing Combination Use With α-Blockers and α-Blocker Monotherapy for Lower Urinary Tract Symptoms and Erectile Dysfunction

    OpenAIRE

    Choi, Hoon; Kim, Hyun Jung; Bae, Jae Hyun; Kim, Jae Heon; Moon, Du Geon; Cheon, Jun; Yeo, Jeong-Kyun

    2015-01-01

    Purpose: Combination therapy with an α-1-adrenergic blocker and phosphodiesterase type 5 inhibitors (PDE5Is) has shown improvements in lower urinary tract symptoms (LUTS) with negligible side effects. Nonetheless, decisive advantages in symptom improvement were insufficient, and there were no clinical differences between long- or short-acting PDE5Is in combination with combination medication. Methods: To review the studies on α-1-adrenergic blocker monotherapy and combination therapy with lon...

  11. Individual patient data meta-analysis of beta-blockers in heart failure: rationale and design

    Directory of Open Access Journals (Sweden)

    Kotecha Dipak

    2013-01-01

    Full Text Available Abstract The Beta-Blockers in Heart Failure Collaborative Group (BB-HF was formed to obtain and analyze individual patient data from the major randomized controlled trials of beta-blockers in heart failure. Even though beta-blockers are an established treatment for heart failure, uptake is still sub-optimal. Further, the balance of efficacy and safety remains uncertain for common groups including older persons, women, those with impaired renal function and diabetes. Our aim is to provide clinicians with a thorough and definitive evidence-based assessment of these agents. We have identified 11 large randomized trials of beta-blockers versus placebo in heart failure and plan to meta-analyze the data on an individual patient level. In total, these trials have enrolled 18,630 patients. Uniquely, the BB-HF group has secured access to the individual data for all of these trials, with the participation of key investigators and pharmaceutical companies. Our principal objectives include deriving an overall estimate of efficacy for all-cause mortality and cardiovascular hospitalization. Importantly, we propose a statistically-robust sub-group assessment according to age, gender, diabetes and other key factors; analyses which are only achievable using an individual patient data meta-analysis. Further, we aim to provide an assessment of economic benefit and develop a risk model for the prognosis of patients with chronic heart failure. This paper outlines inclusion criteria, search strategies, outcome measures and planned statistical analyses. Trial registration Clinical trial registration information: http://clinicaltrials.gov/ct2/show/NCT00832442

  12. Validated HPLC and HPTLC Methods for Simultaneous Determination of Some α1 -Adrenoreceptor Blockers

    OpenAIRE

    Shrivatava, Alankar; Gupta, Vipin B.

    2012-01-01

    Alpha-blockers (alfuzosin, tamsulosin, doxazosin, prazosin and terazosin) relax the smooth muscles in the prostate and are indicated for the symptomatic treatment of benign prostatic hyperplasia due to evidence of their positive and rapid effect on lower urinary tract symptoms. Our objective was to develop and validate simultaneous estimation of these drugs. Same class of drugs may have almost same functional groups and therefore research focused on development of RPLC and HPTLC m...

  13. Ca2+ channel blockers modulate metabolism of collagens within the extracellular matrix.

    OpenAIRE

    Roth, M; Eickelberg, O.; Kohler, E.; Erne, P; Block, L H

    1996-01-01

    The extracellular matrix (ECM) is an intricate network composed of an array of macromolecules capable of regulating the functional responsiveness of cells. Its composition greatly varies among different types of tissue, and dysregulation of its metabolism may contribute to vascular remodeling during the pathogenesis of various diseases, including atherosclerosis. In view of their antiatherosclerotic effects, the role of Ca2+ channel blockers in the metabolism of ECM was examined. Nanomolar co...

  14. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers

    OpenAIRE

    Aggarwal, Bharat B.; Gupta, Subash C.; Sung, Bokyung

    2013-01-01

    TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a ...

  15. Complications of cataract surgery in patients with BPH treated with alpha 1A-blockers

    OpenAIRE

    Jan Teper, Slawomir; Dobrowolski, Dariusz; Wylegala, Edward

    2011-01-01

    The prevalence of benign prostate hyperplasia (BPH) and cataract increases with age. Both diseases may develop concomitantly and may affect almost 50% of elderly men as comorbidities. Cataract is treated surgically and it has been reported that there may be an association between use of alpha-blockers for BPH, particularly alpha1A-adrenergic receptor selective drugs, and complications of cataract surgery known as Intraoperative Floppy Iris Syndrome (IFIS). The article reviews literature publi...

  16. Applying Theoretical Approach for Predicting the Selective Calcium Channel Blockers Pharmacological Parameter by Biopartitioning Micellar Chromatography

    Institute of Scientific and Technical Information of China (English)

    WANG Su-Min; YANG Geng-Liang; LI Zhi-Wei; LIU Hai-Yan; GUO Hui-Juan

    2006-01-01

    The usefulness of biopartitioning micellar chromatography (BMC) for predicting oral drug acute toxicity and apparent bioavailability was demonstrated. A logarithmic model (an LD50 model) and the second order polynomial models (apparent bioavailability model) have been obtained using the retention data of the selective calcium channel blockers to predict pharmacological properties of compounds. The use of BMC is simple, reproducible and can provide key information about the acute toxicity and transport properties of new compounds during the drug discovery process.

  17. Pneumonia Risk and Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

    OpenAIRE

    Liu, Chia-Lin; Shau, Wen-Yi; Chang, Chia-Hsuin; Wu, Chi-Shin; Lai, Mei-Shu

    2013-01-01

    Background Recent studies have shown that use of angiotensin-converting enzyme (ACE) inhibitors may decrease pneumonia risk in various populations. We investigated the effect of ACE inhibitors and angiotensin II receptor blockers (ARBs) on pneumonia hospitalization in the general population of Taiwan. Methods We conducted a case-crossover study using the Taiwan Longitudinal Health Insurance Database for the year 2005. Data from patients hospitalized for the first time for pneumonia during 199...

  18. Effects of calcium channel blocker, nifedipine, on antidepressant activity of fluvoxamine, venlafaxine and tianeptine in mice

    OpenAIRE

    SHARMA, Ashok K.; Anjan Khadka; Navdeep Dahiya

    2015-01-01

    Background: Cardiovascular diseases are commonly associated with depression. Calcium channel blockers (CCBs) form commonly used group of drugs for the treatment of a number of cardiovascular diseases. Nifedipine, a CCB, has been shown to possess antidepressant activity and potentiate antidepressant activity of imipramine and sertraline, however, literature on its interaction with newer antidepressant drugs such as fluvoxamine, venlafaxine and tianeptine is limited. Hence, the present study wa...

  19. ENDOTHELIAL DYSFUNCTION AND ROLE NITRATES AND BETA-BLOCKERS IN ITS CORRECTION IN ISCHEMIC HEART DISEASE

    OpenAIRE

    A. N. Britov

    2016-01-01

    The role of endothelial dysfunction in the pathogenesis of ischemic heart disease and some other cardiovascular diseases is considered. The endothelial dysfunction takes place at the earliest stages of diseases. The interaction of vasodilator and vasoconstrictor factors produced by vascular endothelium is discussed. The treating effect of some medicinal products (nitrates, beta-blockers and others) is analyzed from the point of view of their correcting influence on endothelial function.

  20. Esmolol: A Unique Beta-Blocker in Maintaining Cardiovascular Stability Following Neurosurgical Procedures

    OpenAIRE

    Samad EJ Golzari; Kamyar Ghabili; Mehdi Ghaffarlou; Mahmood Eydi; Hamzeh Hosseinzadeh

    2012-01-01

    Purpose: Patients with increased intracranial pressure (ICP) are prone to severe cardiac and or cerebral complications following emergence from general anesthesia and especially post-extubation phase. Administering beta blockers including esmolol is believed to be helpful in providing a stable hemodynamic at the end of the surgery and recovery stages and reducing recovery phase length. Methods: In a double-blind prospective randomized clinical trial, 60 adult patients with ASA (American Socie...

  1. How Administration of the Beta-Blocker Propranolol Before Extinction can Prevent the Return of Fear.

    Science.gov (United States)

    Kroes, Marijn C W; Tona, Klodiana-Daphne; den Ouden, Hanneke E M; Vogel, Susanne; van Wingen, Guido A; Fernández, Guillén

    2016-05-01

    Combining beta-blockers with exposure therapy has been advocated to reduce fear, yet experimental studies combining beta-blockers with memory reactivation have had contradictory results. We explored how beta-blockade might affect the course of safety learning and the subsequent return of fear in a double-blind placebo-controlled functional magnetic resonance imaging study in humans (N=46). A single dose of propranolol before extinction learning caused a loss of conditioned fear responses, and prevented the subsequent return of fear and decreased explicit memory for the fearful events in the absence of drug. Fear-related neural responses were persistently attenuated in the dorsal medial prefrontal cortex (dmPFC), increased in the hippocampus 24 h later, and correlated with individual behavioral indices of fear. Prediction error-related responses in the ventral striatum persisted during beta-blockade. We suggest that this pattern of results is most consistent with a model where beta-blockade can prevent the return of fear by (i) reducing retrieval of fear memory, via the dmPFC and (ii) increasing contextual safety learning, via the hippocampus. Our findings suggest that retrieval of fear memory and contextual safety learning form potential mnemonic target mechanisms to optimize exposure-based therapy with beta-blockers. PMID:26462618

  2. Mortality and reinfarction among patients using different beta-blockers for secondary prevention after a myocardial infarction

    DEFF Research Database (Denmark)

    Andersen, Søren Skøtt; Hansen, Morten Lock; Gislason, Gunnar H;

    2009-01-01

    OBJECTIVES: To study differences in the clinical efficacy of various brands of beta-blocker in secondary prevention after a myocardial infarction (MI). METHODS: All patients hospitalized with a first MI between 1995 and 2002 who were still alive 30 days after discharge and had had at least one...... prescription for a beta-blocker filled were identified by individual-level linkage of nationwide registries of hospitalizations and drugs dispensed from pharmacies. A total of 32,259 MI patients were included in the study. Multivariable Cox proportional hazard models were used to analyze the risks of death and...... recurrent MI related to treatment with different beta-blockers. RESULTS: The risks for death and recurrent MI were similar in patients using different beta-blockers, except that mortality from all causes among patients with a prescription for sotalol was higher. Subgroup analyses of high-risk patients with...

  3. Effects of treatment with β-blocker and aldosterone antagonist on central and peripheral haemodynamics and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander;

    2011-01-01

    Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and...

  4. Effect of telmisartan on insulin resistance in elderly patients undergoing maintenance hemodialysis%替米沙坦对老年维持性血液透析患者胰岛素抵抗的影响

    Institute of Scientific and Technical Information of China (English)

    王瑞; 丁国华; 刘红燕

    2009-01-01

    Eleven elderly patients undergoing maintenance hemodialysis without ARB or ACEI within 4 weeks were enrolled. Anti-hypertensive agents were replaced by telmisartan gradually to maintain stable blood pressure. Before and after 6 or 12 weeks of treatment, blood biochemical profiles, fasting blood glucose, fasting plasma insulin, insulin resistance index(HOMA-IR), blood pressure, and body weight were recorded. Our results showed that telmisartan did not affect body weight, high-density lipoprotein (HDL), triglyceride (TG), SCr, BUN, Alb, K+ , and PTH, although led to a significant decrease in TC and low-density lipoprotein (LDL). Following telmisartan treatment, FPG did not change significantly, but fasting insulin decreased from 13.9±3.6 mU/ml to 9.9±2.7 or 9.1±2.3 mU/ml at 6 and 12 week (P<0.01), and HOMA-IR decreased from 3.5±1.4 to 2.4±0.8 or 2.2±0.8 at 6 and 12 week (P<0.05). These results suggest that insulin resistance in elderly patients with MHD may be improved by telmisartan.%以11例稳定规律透析且近4周未用血管紧张素IIAT1受体阻滞剂或血管紧张素转化酶抑制剂药物的老年血液透析患者为研究对象,逐步换用替米沙坦降压并使血压保持基本稳定,分别于换用替米沙坦降压治疗前及治疗6周和12周时,透析当天空腹抽血检测血生化、空腹血糖和空腹胰岛素,评估胰岛素抵抗指数,并比较治疗前后体重及血压.结果提示替米沙坦治疗后患者体重、高密度脂蛋白、甘油三酯、血肌酐、尿素氮、白蛋白、血钾和甲状旁腺索无明显变化,总胆固醇、低密度脂蛋白有所下降.空腹血糖无明显变化,但空腹胰岛素从(13.9±3.6)mU/ml下降到(9.9±2.7)mU/ml(6周)和(9.1±2.3)mU/ml(12周),均P<0.01;胰岛素抵抗指数从3.5±1.4下降至2.4±0.8(6周)和2.2±0.8(12周),均P<0.05.提示替米沙坦可改善老年血液透析患者胰岛素抵抗状态.

  5. 替米沙坦对高血压合并糖调节受损患者的影响%Influence of telmisartan on the impaired glucose regulation in patients with hypertention

    Institute of Scientific and Technical Information of China (English)

    陆玉良; 韦凡平; 程震锋

    2014-01-01

    目的:探讨替米沙坦对高血压合并糖调节受损患者的影响。方法:入选初诊为原发性高血压合并糖调节受损患者90例为研究对象,随机分为两组,观察组45例每天服用替米沙坦40~80mg,对照组45例每天服用厄贝沙坦75~150mg,共治疗12周。观察高血压患者治疗前后血压(BP)、空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)和胰岛素抵抗指数(IRI)水平的变化。结果:两组治疗后收缩压和舒张压均明显下降,与治疗前相比差异有统计学意义(P<0.05)。两组BP治疗后比较差异无统计学意义(P>0.05)。与对照组比较,观察组治疗后FPG、2hPG、HbA1c、FINS和IRI水平明显改善,两组比较差异有统计学意义(均P<0.05)。结论:替米沙坦可改善高血压合并糖调节受损患者的糖代谢。%Objective: To explore the inlfuence of telmisartan on the impaired glucose regulation (IGR) of patients with hypertention.Methods: Ninety patients with IGR and hypertension who were selected in our hospi-tal were randomly divided into two groups. The patients in study group (45 cases) were treated by taking telmis-artan 40~80 mg per day for 12 weeks and the patients in control group (45 cases) were required to take irbesartan 75~150 mg per day for 12 weeks. Their blood pressure (BP) and the insulin sensitivity including fasting plasma glucose (FPG), 2 hours postprandial glucose (2hPG), glycosylated hemoglobin, fasting insulin (FINS) and insulin resistance index (IRI) were observed and analysed after 12 weeks.Results: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased signiifcantly in both groups after treatment (P<0.05). Compared with the control group, FBG, 2hPG, HbA1c, FINS and IRI in the study group decreased after telmisartan treatment (P<0.05).Conclusion: Telmisartan can effectively improve glucose metabolism in the

  6. Clinical efficacy of beta1 selective adrenergic blockers in the treatment of neurocardiogenic syncope – a meta-analysis

    OpenAIRE

    Vallurupalli, Srikanth

    2010-01-01

    Srikanth Vallurupalli1, Smita Das21Division of General Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA; 2Department of Kinesiology and Community Health, University of Illinois College of Medicine, Champaign, IL, USABackground: Beta1 (B1) selective blockers have been widely used for the treatment of neurocardiogenic syncope though clinical trials have shown conflicting degrees of efficacy.Objective: To study the clinical efficacy of B1 selective blocker...

  7. Pre-treatment with beta blockers and the frequency of hypokalaemia in patients with acute chest pain.

    OpenAIRE

    Simpson, E; Rodger, J C; Raj, S. M.; Wong, C.; Wilkie, L; Robertson, C.

    1987-01-01

    Plasma potassium concentration was measured at admission in 1234 patients who presented with acute chest pain. One hundred and ninety five patients were on beta blockers before admission. The potassium concentrations of patients admitted early (within four hours of onset of symptoms) were compared with those admitted later (4-18 hours after onset of symptoms). There was a transient fall in plasma potassium concentrations in patients not pre-treated with beta blockers. This was not seen in pat...

  8. Primary prevention of atrial fibrillation with beta-blockers in patients with end-stage renal disease undergoing dialysis

    OpenAIRE

    Ting-Tse Lin; Jiun-Yang Chiang; Min-Tsun Liao; Chia-Ti Tsai; Juey Jen Hwang; Fu-Tien Chiang; Jiunn-Lee Lin; Lian-Yu Lin

    2015-01-01

    Current evidence suggests that beta-blocker lower the risk of development of atrial fibrillation (AF) and in-hospital stroke after cardiac surgery. This study was to assess whether beta-blockers could decrease incidence of new-onset AF in patients with end stage renal disease (ESRD). We identified patients from a nation-wide database called Registry for Catastrophic Illness, which encompassed almost 100% of the patients receiving dialysis therapy in Taiwan from 1995 to 2008. Propensity score ...

  9. Beta-Blockers, Left and Right Ventricular Function, and In-Vivo Calcium Influx in Muscular Dystrophy Cardiomyopathy

    OpenAIRE

    Alison Blain; Elizabeth Greally; Steve Laval; Andrew Blamire; Volker Straub; MacGowan, Guy A.

    2013-01-01

    Beta-blockers are used to treat acquired heart failure in adults, though their role in early muscular dystrophy cardiomyopathy is unclear. We treated 2 different dystrophic mouse models which have an associated cardiomyopathy (mdx: model for Duchenne Muscular Dystrophy, and Sgcd-/-: model for limb girdle muscular dystrophy type 2F) and wild type controls (C57 Bl10) with the beta blocker metoprolol or placebo for 8 weeks at an early stage in the development of the cardiomyopathy. Left and righ...

  10. Analgesic activity of a novel use-dependent sodium channel blocker, crobenetine, in mono-arthritic rats

    OpenAIRE

    Laird, J M A; Carter, A J; Grauert, M; Cervero, F

    2001-01-01

    Although sodium channel blockers are effective analgesics in neuropathic pain, their effectiveness in inflammatory pain has been little studied. Sodium channels are substantially up-regulated in inflamed tissue, which suggests they play a role in maintenance of chronic inflammatory pain. We have examined the effects of sodium channel blockers on mobility, joint hyperalgesia and inflammation induced by complete Freund's adjuvant injected in one ankle joint of adult rats. The clinically effecti...

  11. Preclinical evaluation of marketed sodium channel blockers in a rat model of myotonia discloses promising antimyotonic drugs

    OpenAIRE

    Desaphy, Jean-François; Carbonara, Roberta; Costanza, Teresa; Conte Camerino, Diana

    2014-01-01

    Although the sodium channel blocker mexiletine is considered the first-line drug in myotonia, some patients experiment adverse effects, while others do not gain any benefit. Other antimyotonic drugs are thus needed to offer mexiletine alternatives. In the present study, we used a previously-validated rat model of myotonia congenita to compare six marketed sodium channel blockers to mexiletine. Myotonia was induced in the rat by injection of anthracen-9-carboxylic acid, a muscle chloride chann...

  12. Two tarantula venom peptides as potent and differential Na(V) channels blockers.

    Science.gov (United States)

    Cherki, Ronit S; Kolb, Ela; Langut, Yael; Tsveyer, Lior; Bajayo, Nissim; Meir, Alon

    2014-01-01

    Voltage dependent sodium (Na(V)) channels are large membrane spanning proteins which lie in the basis of action potential generation and propagation in excitable cells and hence are essential mediators of neuronal signaling. Inhibition of Na(V) channel activity is one of the core mechanisms to treat conditions related to neuronal hyperexcitability, such as epilepsy in the clinic. Na(V) channel blockers are also extensively used to locally inhibit action potential generation and related pain perceptions in the form of local anesthetics. Here we describe the isolation, biochemical characterization, synthesis and in vitro characterization of two potent Na(V) channel blockers from the venom of the Paraphysa scrofa (Phrixotrichus auratus) tarantula spider. Both Voltage sensor toxin 3 (VSTx-3, κ-theraphotoxin-Gr4a) and GTx1-15 (Toxin Gtx1-15), were originally isolated from the venom of the related tarantula Grammostola rosea and described as K(V) and Ca(V) channel blockers, respectively. In our hands, GTx1-15 was shown to be a potent inhibitor of tetrodotoxin (TTX)-sensitive channels (IC₅₀ 0.007 μM for hNa(V)1.7 and 0.12 μM for hNa(V)1.3 channels), with very little effect on TTX-resistant (Na(V)1.5 and NaV1.8) channels. VSTx-3 was demonstrated to be a potent, TTX-sensitive sodium channel blocker and especially, potent blocker of Na(V)1.8 channels (IC₅₀ 0.19 μM for hNa(V)1.3, 0.43 μM for hNa(V)1.7 and 0.77 μM for hNa(V)1.8 channels). Such potent inhibitors with differential selectivity among Na(V) channel isoforms may be used as tools to study the roles of the different channels in processes related to hyperexcitability and as lead compounds to treat pathological pain conditions. PMID:24211312

  13. Acrolein-mediated conduction loss is partially restored by K+ channel blockers.

    Science.gov (United States)

    Yan, Rui; Page, Jessica C; Shi, Riyi

    2016-02-01

    Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K(+) channels due to myelin damage leads to conduction block, and K(+) channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K(+) channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K(+) channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases. PMID:26581866

  14. Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, biophysical and physiological relevance

    Institute of Scientific and Technical Information of China (English)

    Paul; Linsdell

    2014-01-01

    Dysfunction of the cystic fibrosis transmembrane con-ductance regulator(CFTR) chloride channel causes cys-tic fibrosis, while inappropriate activity of this channeloccurs in secretory diarrhea and polycystic kidney dis-ease. Drugs that interact directly with CFTR are there-fore of interest in the treatment of a number of diseasestates. This review focuses on one class of small mol-ecules that interacts directly with CFTR, namely inhibi-tors that act by directly blocking chloride movementthrough the open channel pore. In theory such com-pounds could be of use in the treatment of diarrheaand polycystic kidney disease, however in practice allknown substances acting by this mechanism to inhibitCFTR function lack either the potency or specificity forin vivo use. Nevertheless, this theoretical pharmaco-logical usefulness set the scene for the developmentof more potent, specific CFTR inhibitors. Biophysically,open channel blockers have proven most useful as ex-perimental probes of the structure and function of theCFTR chloride channel pore. Most importantly, the useof these blockers has been fundamental in developing afunctional model of the pore that includes a wide innervestibule that uses positively charged amino acid sidechains to attract both permeant and blocking anionsfrom the cell cytoplasm. CFTR channels are also subjectto this kind of blocking action by endogenous anionspresent in the cell cytoplasm, and recently this blocking effect has been suggested to play a role in the physio-logical control of CFTR channel function, in particular as a novel mechanism linking CFTR function dynamically to the composition of epithelial cell secretions. It has also been suggested that future drugs could target this same pathway as a way of pharmacologically increasing CFTR activity in cystic fibrosis. Studying open channel blockers and their mechanisms of action has resulted in significant advances in our understanding of CFTR as a pharmacological target in disease states, of

  15. SU-E-I-08: Investigation of Deconvolution Methods for Blocker-Based CBCT Scatter Estimation

    International Nuclear Information System (INIS)

    Purpose: To investigate whether deconvolution methods can improve the scatter estimation under different blurring and noise conditions for blocker-based scatter correction methods for cone-beam X-ray computed tomography (CBCT). Methods: An “ideal” projection image with scatter was first simulated for blocker-based CBCT data acquisition by assuming no blurring effect and no noise. The ideal image was then convolved with long-tail point spread functions (PSF) with different widths to mimic the blurring effect from the finite focal spot and detector response. Different levels of noise were also added. Three deconvolution Methods: 1) inverse filtering; 2) Wiener; and 3) Richardson-Lucy, were used to recover the scatter signal in the blocked region. The root mean square error (RMSE) of estimated scatter serves as a quantitative measure for the performance of different methods under different blurring and noise conditions. Results: Due to the blurring effect, the scatter signal in the blocked region is contaminated by the primary signal in the unblocked region. The direct use of the signal in the blocked region to estimate scatter (“direct method”) leads to large RMSE values, which increase with the increased width of PSF and increased noise. The inverse filtering is very sensitive to noise and practically useless. The Wiener and Richardson-Lucy deconvolution methods significantly improve scatter estimation compared to the direct method. For a typical medium PSF and medium noise condition, both methods (∼20 RMSE) can achieve 4-fold improvement over the direct method (∼80 RMSE). The Wiener method deals better with large noise and Richardson-Lucy works better on wide PSF. Conclusion: We investigated several deconvolution methods to recover the scatter signal in the blocked region for blocker-based scatter correction for CBCT. Our simulation results demonstrate that Wiener and Richardson-Lucy deconvolution can significantly improve the scatter estimation

  16. Comparative effects of sodium channel blockers in short term rat whole embryo culture

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, Mats F, E-mail: Mats.Nilsson@farmbio.uu.se [Department of Pharmaceutical Biosciences, Uppsala University (Sweden); Sköld, Anna-Carin; Ericson, Ann-Christin; Annas, Anita; Villar, Rodrigo Palma [AstraZeneca R and D Södertälje (Sweden); Cebers, Gvido [AstraZeneca R and D, iMed, 141 Portland Street, Cambridge, MA 02139 (United States); Hellmold, Heike; Gustafson, Anne-Lee [AstraZeneca R and D Södertälje (Sweden); Webster, William S [Department of Anatomy and Histology, University of Sydney (Australia)

    2013-10-15

    This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.

  17. Electrically enhanced microextraction for highly selective transport of three β-blocker drugs.

    Science.gov (United States)

    Seidi, Shahram; Yamini, Yadollah; Rezazadeh, Maryam

    2011-12-15

    Facilitated transport of three β-blocker drugs including atenolol (ATE), betaxolol (BET) and propranolol (PRO) was investigated under electrical field across a supported liquid membrane (SLM) using phosphoric acid derivatives as selective ion carriers, dissolved in 2-nitro phenyl octyl ether (NPOE). In the presence of di-(2-ethylhexyl) phosphate (DEHP) and tris-(2-ethylhexyl) phosphate (TEHP) in the membrane phase, the three β-blockers showed completely different transport behaviors which enabled highly selective separation of the drugs. Each β-blocker migrated from 3 mL of sample solutions, through a thin layer of specific organic solvent immobilized in the pores of a porous hollow fiber, and into a 15 μL acidic aqueous acceptor solution present inside the lumen of the fiber. The influences of fundamental parameters affecting the transport of target drugs including type of ion carrier for selective separation of each drug and its concentration in the membrane phase, extraction voltage, time of transport, pH of donor and acceptor phases, stirring speed of donor phase and salt effect were studied and optimized. After microextraction process, the extracts were analyzed by high-performance liquid chromatography with ultraviolet detection. Under optimal conditions, ATE was selectively extracted from different saliva samples with recovery of 37%, which corresponded to preconcentration factor of 74. A good linearity was achieved for calibration curve with a coefficient of determination higher than 0.997. Limits of detection and intra-day precision (n=3) were less than 2 μg L(-1) and 8.8%, respectively. PMID:21856103

  18. Enantiomeric selectivity in adsorption of chiral β-blockers on sludge.

    Science.gov (United States)

    Sanganyado, Edmond; Fu, Qiuguo; Gan, Jay

    2016-07-01

    Adsorption of weakly basic compounds by sludge is poorly understood, although it has important implications on the distribution and fate of such micropollutants in wastewater effluent and sludge. Additionally, many of these compounds are chiral, and it is likely that their interactions with sludge is stereoselective and that the process may be further modified by surfactants that coexist in these systems. Adsorption of (R) and (S)-enantiomers of five commonly used β-blockers, i.e., acebutolol, atenolol, metoprolol, pindolol and propranolol, on sludge was characterized through batch experiments. Stereoselectivity in adsorption increased with decreases in hydrophobicity of the β-blockers. The enantiomeric fraction (EF) of the amount of acebutolol, atenolol and metoprolol sorbed on sludge were 0.27, 0.55 and 0.32, respectively. Thus, Kd values of the (S)-enantiomers of acebutolol and metoprolol were approximately twice that of the (R)-enantiomer, that is, 109 ± 11 and 57 ± 8 L/kg compared to 52 ± 13 and 22 ± 8 L/kg, respectively. There was no statistically significant difference in Kd values of the enantiomers of pindolol and propranolol, suggesting stereoselectivity in adsorption was likely driven by specific polar interactions rather than hydrophobic interactions. The EF value of atenolol decreased from 0.55 ± 0.03 to 0.44 ± 0.04 after modifying the sludge with Triton X 100. These results suggested that surfactants altered adsorption of β-blockers to sludge, likely by forming ion pair complexes that promote hydrophobic interactions with the solid surfaces. PMID:27155096

  19. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    Science.gov (United States)

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  20. Evaluation of angiotensin II receptor blockers for drug formulary using objective scoring analytical tool

    Directory of Open Access Journals (Sweden)

    Lim TM

    2012-09-01

    Full Text Available Drug selection methods with scores have been developed and used worldwide for formulary purposes. These tools focus on the way in which the products are differentiated from each other within the same therapeutic class. Scoring Analytical Tool (SAT is designed based on the same principle with score and is able to assist formulary committee members in evaluating drugs either to add or delete in a more structured, consistent and reproducible manner. Objective: To develop an objective SAT to facilitate evaluation of drug selection for formulary listing purposes. Methods: A cross-sectional survey was carried out. The proposed SAT was developed to evaluate the drugs according to pre-set criteria and sub-criteria that were matched to the diseases concerned and scores were then assigned based on their relative importance. The main criteria under consideration were safety, quality, cost and efficacy. All these were converted to questionnaires format. Data and information were collected through self-administered questionnaires that were distributed to medical doctors and specialists from the established public hospitals. A convenient sample of 167 doctors (specialists and non-specialists were taken from various disciplines in the outpatient clinics such as Medical, Nephrology and Cardiology units who prescribed ARBs hypertensive drugs to patients. They were given a duration of 4 weeks to answer the questionnaires at their convenience. One way ANOVA, Kruskal Wallis and post hoc comparison tests were carried out at alpha level 0.05. Results: Statistical analysis showed that the descending order of ARBs preference was Telmisartan or Irbesartan or Losartan, Valsartan or Candesartan, Olmesartan and lastly Eprosartan. The most cost saving ARBs for hypertension in public hospitals was Irbesartan. Conclusion: SAT is a tool which can be used to reduce the number of drugs and retained the most therapeutically appropriate drugs in the formulary, to determine most

  1. The use of TNF-α blockers in psoriatic arthritis patients with latent tuberculosis infection

    OpenAIRE

    Atteno, Mariangela; Costa, Luisa; Matarese, Alessandro; Caso, Francesco; Del Puente, Antonio; Cantarini, Luca; Bocchino, Maria Luisa; Sanduzzi, Alessandro; Scarpa, Raffaele

    2014-01-01

    Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α is an essential cytokine for the host defense, and its depletion by treatment may facilitate the risk of infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in patients with PsA and concomitant latent tuberculosis infection (LTBI) comparing their outcome with non-infected PsA patients. This is a retrospective study in 321 pati...

  2. The β-blocker Nebivolol Is a GRK/β-arrestin biased agonist.

    Directory of Open Access Journals (Sweden)

    Catherine E Erickson

    Full Text Available Nebivolol, a third generation β-adrenoceptor (β-AR antagonist (β-blocker, causes vasodilation by inducing nitric oxide (NO production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR and extracellular signal-regulated kinase (ERK. Due to the pharmacological similarities between nebivolol and carvedilol, we hypothesized that nebivolol is also a GRK/β-arrestin biased agonist. We tested this hypothesis utilizing mouse embryonic fibroblasts (MEFs that solely express β2-ARs, and HL-1 cardiac myocytes that express β1- and β2-ARs and no detectable β3-ARs. We confirmed previous reports that nebivolol does not significantly alter cAMP levels and thus is not a classical agonist. Moreover, in both cell types, nebivolol induced rapid internalization of β-ARs indicating that nebivolol is also not a classical β-blocker. Furthermore, nebivolol treatment resulted in a time-dependent phosphorylation of ERK that was indistinguishable from carvedilol and similar in duration, but not amplitude, to isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to propranolol (non-selective β-AR-blocker, AG1478 (EGFR inhibitor, indicating that the signaling emanates from β-ARs and involves the EGFR. Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. We conclude that nebivolol is a β2

  3. Central origin of respiratory arrest in beta-blocker intoxication in rats

    OpenAIRE

    Langemeijer, J.J.M.; de Wildt, D J; de Groot, G.; Sangster, B.

    1987-01-01

    Propranolol HCl (7.5 mg·kg−1), timolol maleate (7.0 mg·kg−1), and sotalol HCl (10 mg·kg−1) were administered intracerebroventricularly (icv) to spontaneously breathing (SB) rats. The respiratory rate declined until the rats all died from respiratory arrest. Artificial ventilation resulted in survival of the rats for a 3-hr observation period. Intravenous (iv) administration of the same doses of the three beta blockers to SB rats did not result in either respiratory depression or death. Except...

  4. Effect of short-acting beta blocker on the cardiac recovery after cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Qian Yanning

    2011-08-01

    Full Text Available Abstract The objective of this study was to investigate the effect of beta blocker on cardiac recovery and rhythm during cardiac surgeries. Sixty surgical rheumatic heart disease patients were received esmolol 1 mg/kg or the same volume of saline prior to removal of the aortic clamp. The incidence of cardiac automatic re-beat, ventricular fibrillation after reperfusion, the heart rate after steady re-beat, vasoactive drug use during weaning from bypass, the posterior parallel time and total bypass time were decreased by esmolol treatment. In conclusion: Esmolol has a positive effect on the cardiac recovery in cardiopulmonary bypass surgeries.

  5. Intraoperative Extracorporeal Carbon Dioxide Removal During Apneic Oxygenation with an EZ-Blocker in Tracheal Surgery.

    Science.gov (United States)

    Rispoli, Marco; Nespoli, Moana Rossella; Mattiacci, Dario Maria; Esposito, Marianna; Corcione, Antonio; Buono, Salvatore

    2016-06-01

    Tracheal surgery requires continued innovation to manage the anesthetic during an open airway phase. A common approach is apneic oxygenation with continuous oxygen flow, but the lack of effective ventilation causes hypercapnia, with respiratory acidosis. We used extracorporeal carbon dioxide removal for intraoperative decapneization during apneic oxygenation in a 64-year-old woman who was scheduled for tracheal surgery because of tracheal stenosis caused by long-term intubation. Our findings demonstrate that even after 40 minutes of total apnea, using an EZ-blocker for oxygenation and external decapneization, hemodynamic and gas exchange variables never demonstrated any dangerous alterations. PMID:27075426

  6. Are there any positive effects of TNF-alpha blockers on bone metabolism?

    Directory of Open Access Journals (Sweden)

    A. Sulli

    2011-09-01

    Full Text Available Secondary osteoporosis (OP is a well-recognized complication of rheumatoid arthritis (RA. Treatment with TNF-a blockers, might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular regions. Objective: To assess the influence of anti-TNF-a therapy, on bone metabolism in RA patients. 36 RA patients were treated with stable therapy of prednisone (7.5 mg/day and methotrexate (MTX=10 mg/week. Nine of these RA patients further received etanercept (25 mg, twice/weekly and eleven infliximab (3mg/kg on 0, 2, 6, and every 8 weeks thereafter. A control group included 16 RA patients only with stable therapy (some dosage of prednisone and MTX. Quantitative Ultrasound (QUS bone densitometry was obtained at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy. Bone mineral density (BMD of the hip and lumbar spine were performed with a densitometer ( Lunar Prodigy, GE, USA at baseline and after 12 months. Soluble bone turnover markers [osteocalcin (OC, bone alkaline phospatase (ALP deoxypyridinoline/creatinine ratio (Dpd/Cr and cross-linked N-telopeptide of type I collagen / creatinine ratio (NTx/Cr] were measured using ELISA tests. Results: AD-SoS values were found increased by +4.55% after 12 months of treatment in the RA patients treated with anti-TNF-a therapy. On the contrary, the Ad-SoS levels decreased by -4.48% during the same period in the control RA group. BMD increased by +3.64% at lumbar spine and +2.90% at the hip (both p<0.001 in TNF-a blockers-treated patients and decreased by -2.89% and -3.10% (both p<0.001, respectively at lumbar spine and at the hip in RA patients without anti-TNF-a therapy. In RA patients treated with TNF-a blockers, OC and bone ALP levels were found significantly increased (p<0.01 and Dpd/Cr or NTx/Cr levels were found significantly decreased (p<0.01 at 12 months when compared to baseline values. Conclusion: During 12

  7. Effects of angiotensin Ⅱ type 1 receptor blocker on triglyceride metabolism in the liver: experiment with Zucker fatty rats%奥美沙坦对肥胖大鼠肝脏甘油三酯代谢的影响

    Institute of Scientific and Technical Information of China (English)

    冉建民; 劳干诚; 徐刚; 谢彬; 张扬; 刘薇; 冯琼; 郭坚

    2008-01-01

    目的 观察血管紧张素Ⅱ受体拮抗剂奥美沙坦对胰岛素抵抗的Zucker肥胖大鼠(ZF鼠)肝脏甘油三酯(TG)代谢的影响.方法 8周龄ZF鼠(22只)及其对照(ZL鼠,12只)分别给予含0.01%奥美沙坦饮用水治疗4周.结果 奥美沙坦在两组大鼠均明显降低了血压.ZF鼠的胰岛素敏感性指数[SI,(0.31±0.22)μU·ml-1·min-1·10-4vs(3.54±0.30)μu·ml-1·min-1·10-4,P<0.01)]和葡萄糖效应[(SG,(1.35±0.51)min-1·10-2vs(3.40±0.14)min-1·10-2,P<0.01)较ZL鼠明显减低,而血糖水平明显升高[(11.4±2.6)mmol/L vs(9.2±0.6)mmol/L,P<0.01],奥美沙坦治疗后SI和SG明显改善.ZF鼠血TG浓度为ZL鼠的6倍,奥美沙坦治疗明显降低了ZF鼠的血游离脂肪酸水平[治疗前2.70±0.69 mmol/L vs治疗后(1.98±0.43)mmol/L,P<0.01],但对血TG水平无明显影响(P>0.05).奥美沙坦使ZF鼠肝甘油三酯分泌率(TGSR)下降了50%[(0.56±0.08)mg·min-1·100 g-1 vs(0.30±0.07)mg·min-1·100 g-1,P<0.01].奥美沙坦治疗后(12.8±1.7)mg/g,肝脏甘油三酯含量比治疗前[(22.7±4.2)mg/g明显降低,P<0.01)],而肝胆固醇含量不受影响.奥美沙坦治疗后ZF鼠肝细胞脂滴沉积明显得到改善.结论 奥美沙坦对肥胖大鼠肝脏甘油三酯的产生和积累有明显的抑制作用;这一作用不依赖于药物的降压效应.%Objective To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) metabolism and mechanism thereof.Methods Zucker fatty (ZF) rats and Zucker lean (ZL) rats were fed with water containing 0.01% olmesartan medoxiomil,a hishly specific ARB for 4 weeks.Frequently sampled intravenous glucose tolerance test was conducted to calculate the area under the glucose (AUCG),insulin sensitivity index (SI),glucose effectiveness (SG),Blood glucose,TC,TG,nonesterified fatty acid (NEFA),and HDL-C were measured with standard assay kit.Triton WR-1339 technique was usod to detect the TG secretion rate (TGSR).After TGSR and FS-IVGTT the levers

  8. Dose-Finding Study of Landiolol Hydrochloride: A Short-Acting β1-Blocker for Controlling Heart Rate During Coronary Computed-Tomography Angiography in Japan

    OpenAIRE

    Hirano, Masaharu; Hara, Kazuhiro; Ikari, Yuji; Jinzaki, Masahiro; Iino, Misako; Hamada, Chikuma; Kuribayashi, Sachio

    2013-01-01

    Introduction Coronary computed-tomography angiography (CCTA) has high diagnostic performance, but it sometimes does not allow evaluation because of artifacts. Currently, the use of a β-blocker is recommended to prevent motion artifacts, but the β-blocker (metoprolol, propranolol, etc.) commonly used has a slow onset and long duration of action. Landiolol hydrochloride is an intravenous β1-blocker with a very short half-life. We investigated the efficacy and optimal dose of this drug for reduc...

  9. Effects of potassium channel and Na+-Ca2+ exchange blockers on the responses of slowly adapting pulmonary stretch receptors to hyperinflation in flecainide-treated rats

    OpenAIRE

    Matsumoto, Shigeji; Nishikawa, Toshimi; Yoshida, Shinki; Ikeda, Mizuho; Tanimoto, Takeshi; Saiki, Chikako; Takeda, Mamoru

    2001-01-01

    The effects of K+ channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na+ – Ca2+ exchange blocker, 2-[2-[4-(4-nitrobenzyloxyl) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), on the responses of slowly adapting pulmonary stretch receptor activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anaesthetized, artificially ventilated, unilaterally vagotomized rats after pretreatment with a Na+ channel blocker fleca...

  10. Rituximab is more effective than second anti-TNF therapy in rheumatoid arthritis patients and previous TNFα blocker failure

    Directory of Open Access Journals (Sweden)

    Kekow J

    2012-07-01

    Full Text Available Joern Kekow,1 Ulf Mueller-Ladner,2 Hendrik Schulze-Koops31Clinic of Rheumatology and Orthopedics, Otto-von-Guericke University of Magdeburg, Vogelsang-Gommern; 2Department of Rheumatology and Clinical Immunology, Kerckhoff Clinic, Bad Nauheim; 3Division of Rheumatology, University of Munich, Munich, GermanyPurpose: To assess the efficacy of one course of rituximab (two 1-g doses compared to an alternative tumor necrosis factor-α (TNFα blocker in rheumatoid arthritis patients who had experienced one previous TNFα blocker failure (eg, etanercept, adalimumab, or infliximab.Patients and methods: The efficacy of both treatments was studied in this retrospective, multicenter, noninterventional cohort study with 196 patients. All patients had active rheumatoid arthritis defined by a Disease Activity Score-28 of ≥3.2 despite having TNFα blocker therapy, and were followed over 6.6 months on average after switching to rituximab versus a second TNFα blocker (ie, switching to etanercept, adalimumab, or infliximab at baseline.Results: At baseline, both cohorts showed similar demographic and disease-related characteristics (including Disease Activity Score-28. At the end of observation, mean Disease Activity Score-28 was significantly lower after treatment with rituximab than with a second TNFα blocker (-1.64 [95% confidence interval: -1.92; -1.36] versus -1.19 [95% confidence interval: -1.42; -0.96], P = 0.013. This difference between the two groups was even more pronounced when patients were seropositive for rheumatoid factor (-1.66 versus -1.17, P = 0.018 and anti-cyclic citrullinated peptide antibodies (-1.75 versus -1.06, P = 0.002. More rituximab-treated patients achieved good European League Against Rheumatism response than TNFα blocker-treated patients (30% versus 15%, and less patients were nonresponders (22% versus 35% according to European League Against Rheumatism criteria (P = 0.022, chi-squared test.Conclusion: Treatment with rituximab

  11. Effect of beta-blocker therapy on functional status in patients with heart failure--a meta-analysis

    DEFF Research Database (Denmark)

    Abdulla, Jawdat; Køber, Lars; Christensen, Erik;

    2005-01-01

    BACKGROUND: The results of randomised control trials (RCTs) evaluating the effect of beta-blockers on functional status in patients with chronic heart failure are conflicting. AIM: To perform a systematic review and meta-analysis of RCTs evaluating the effect of beta-blockers on New York Heart...... Association (NYHA) classification and exercise tolerance in chronic heart failure. METHODS AND RESULTS: We selected 28 RCTs evaluating beta-blocker versus placebo in addition to ACE inhibitor therapy. Combined results of 23 RCTs showed that beta-blockers improved NYHA class by at least one class with odds...... ratio (OR) 1.80 (1.33-2.43) p<0.0001. Meta-analysis of 10 RCTs showed a significant prolongation of exercise time by 44.19 (6.62-81.75) s p=0.021. Combining 8 RCTs evaluating the maximal peak oxygen uptake and 9 RCTs evaluating 6-min walk distance showed that beta-blockers had no significant effect...

  12. [Are the theoretical drawbacks of beta-blocker treatment in pregnancy being confirmed? A review of the literature].

    Science.gov (United States)

    Tcherdakoff, P; Goupil-Colliard, M

    1983-01-01

    The use of beta-blocking drugs in the treatment of hypertension during pregnancy has been the subject of controversies on the basis of theoretical hazards due to the pharmacology and pharmacokinetic characteristics of these drugs. A review of the literature on the subject shows that: The danger of premature contractions, abortion or premature delivery does not seem to increase with the use of beta-blockers. The blood supply is not more impaired with beta-blockers than with other antihypertensive drugs according to fetal growth, birth-weight, frequency of perinatal deaths or APGAR score. Although beta-blocking drugs pass into fetal circulation, neonatal bradycardia, respiratory distress or hypoglycemia do not seem more frequent with beta-blockers. Beta-blockers pass from maternal plasma into milk but the 24 hour dose brought to the newborn by maternal feeding is so slight as to be negligible. Thus, the cumulative data and the favorable opinions of many authors, the greater efficiency of beta-blockers authorizes the use of these drugs in the treatment of hypertension in pregnancy, where it seems to improve the outcome of the pregnancy and the state of the fetus at birth. PMID:6138464

  13. Development of an amorphous surge blocker for a high voltage acceleration power supply of the neutral beam injectors

    International Nuclear Information System (INIS)

    An amorphous surge blocker for a high voltage acceleration power supply for the neutral beam injectors has been developed. Since the saturation magnetic flux density of the amorphous core is higher than that of the ferrite core, the surge blocker made of amorphous cores can be reduced in size appreciably compared to the conventional ferrite surge blocker. A 350 kV, 0.05 volt-second amorphous surge blocker was designed, fabricated and tested. The amorphous core was made by winding an amorphous tape with a film for the layer insulation and was heat-treated to recover the magnetic characteristics. The core is molded by epoxy resin and installed in a FRP insulator tube filled with SF6 gas for the insulation. The volt-second measured was higher than the designed value and the electrical breakdown along the cores and between layers was not observed. This test result shows that the amorphous surge blocker is applicable for a dc acceleration power supply for high energy neutral beam injectors. (author)

  14. MDR1基因多态性对替米沙坦血药浓度和药动力学影响研究%Effects of MDR1 Gene C3435T polymorphism on bloold concentration and pharmacokinetics of telmisartan

    Institute of Scientific and Technical Information of China (English)

    程茂良; 王珏

    2013-01-01

    目的:探讨健康志愿者和高血压患者的多药耐药基因(Multidrug resistance 1 gene,MDR1) C3435T基因多态性对替米沙坦血药浓度和药动学的影响.方法:采用聚合酶链反应(Polymerase chain reaction,PCR)和限制性内切片段多态性(Restriction fragment length polymorphism,RFLP)的方法对19名健康志愿者和61例高血压患者进行MDR1基因分型;使用HPLC-MS法测定志愿者单剂量口服40 mg替米沙坦48 h内血药浓度和高血压患者的稳态血药浓度.比较替米沙坦在不同基因型的健康志愿者单剂量药动学及高血压患者稳态血药浓度的差异.结果:在61例高血压患者中,MDRlCC型纯合子频率39.34%,TT型纯合子频率11.48%,CT型杂合子频率49.18%,C3435T发生率在健康人群和高血压患者之间没有明显的差异,C3435T的三个不同基因型志愿者Cmax、tmax、t1/2、AUC0-48、AUC0-∞和CL差异无统计学意义(P>0.05).三个基因型高血压患者的稳态血药浓度差异无统计学意义(P>0.05).结论:MDR1C3435T基因多态性对替米沙坦的血药浓度和药动学无影响.%AIM:To determine the effects of MDR1C3435T on the pharmacokinetics of telmisartan in healthy Chinese volunteers and blood concentration in hypertension patients.METHODS:The genotype on MDR1C3435T in 19 healthy Chinese volunteers who were received a single oral dose of 40 ng telmisartan and 61 hypertension patients who were received oral of 40 mg telmisartan every day after a month was detected by PCR RFLP method,the relationship of MDR1C3435T polymorphism and steady-state blood concentrations of telmisartan were determinated by HPLC-MS.The pharmacokinetics of telmisartan in health volunteers and steady-state telmisartan concentrations of patients with hypertension were compared among MDR1C3435T genotypes.RESULTS:Among the 61 cases of hypertension patients,the frequencies of C3435T CC,C3435T TT and C3435T CT were 39.34%,11.48% and 49.18

  15. Compliance, Persistence, and Switching Patterns for ACE Inhibitors and ARBs

    NARCIS (Netherlands)

    Vegter, S.; Nguyen, N.H.; Visser, S.T.; de Jong-van den Berg, LTW; Postma, M.J.; Boersma, C.

    2011-01-01

    Objectives: To investigate compliance, persistence, and switching patterns for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Study Design: Drug-utilization analysis using a large prescription database. Methods: Prescription data for more than 50,000 inciden

  16. Valsartan: the past, present and future

    DEFF Research Database (Denmark)

    Køber, Lars; Torp-Pedersen, Christian

    2005-01-01

    Valsartan (Diovan((R))) is a widely use angiotensin receptor blocker that prevents angiotensin II from binding to the subtype 1 receptor. Stimulation of the subtype 1 receptor is believed to mediate many of the deleterious effects accompanied by increased angiotensin II levels. Valsartan is effec...

  17. Azilsartan Decreases Renal and Cardiovascular Injury in the Spontaneously Hypertensive Obese Rat

    Czech Academy of Sciences Publication Activity Database

    Khan, M. A. H.; Neckář, Jan; Cummens, B.; Wahl, G.M.; Imig, J. D.

    2014-01-01

    Roč. 28, č. 4 (2014), s. 313-322. ISSN 0920-3206 R&D Projects: GA ČR(CZ) GA13-10267S Institutional support: RVO:67985823 Keywords : angiotensin receptor blocker * kidney * metabolic syndrome * heart Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.189, year: 2014

  18. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials

    DEFF Research Database (Denmark)

    Bangalore, Sripal; Kumar, Sunil; Kjeldsen, Sverre E; Makani, Harikrishna; Grossman, Ehud; Wetterslev, Jørn; Gupta, Ajay K; Sever, Peter S; Gluud, Christian; Messerli, Franz H

    2011-01-01

    The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs). We assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomised clinical tr...

  19. Exposure to candesartan during the first trimester of pregnancy in type 1 diabetes: experience from the placebo-controlled diabetic retinopathy candesartan trials

    DEFF Research Database (Denmark)

    Porta, M; Hainer, J W; Jansson, S-O;

    2011-01-01

    AIMS/HYPOTHESIS: The teratogenic consequences of angiotensin-converting enzyme inhibitors angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy are well described. However, the consequences of exposure during the first trimester are unclear, especially in diabet...

  20. Triazine-based vanilloid 1 receptor open channel blockers: design, synthesis, evaluation, and SAR analysis.

    Science.gov (United States)

    Vidal-Mosquera, Miquel; Fernández-Carvajal, Asia; Moure, Alejandra; Valente, Pierluigi; Planells-Cases, Rosa; González-Ros, José M; Bujons, Jordi; Ferrer-Montiel, Antonio; Messeguer, Angel

    2011-11-10

    The thermosensory transient receptor potential vanilloid 1 channel (TRPV1) is a polymodal receptor activated by physical and chemical stimuli. TRPV1 activity is drastically potentiated by proinflammatory agents released upon tissue damage. Given the pivotal role of TRPV1 in human pain, there is pressing need for improved TRPV1 antagonists, the development of which will require identification of new pharmacophore scaffolds. Uncompetitive antagonists acting as open-channel blockers might serve as activity-dependent blockers that preferentially modulate the activity of overactive channels, thus displaying fewer side effects than their competitive counterparts. Herein we report the design, synthesis, biological evaluation, and SAR analysis of a family of triazine-based compounds acting as TRPV1 uncompetitive antagonists. We identified the triazine 8aA as a potent, pure antagonist that inhibits TRPV1 channel activity with nanomolar efficacy and strong voltage dependency. It represents a new class of activity-dependent TRPV1 antagonists and may serve as the basis for lead optimization in the development of new analgesics. PMID:21950613

  1. The pre-synaptic blocker toosendanin does not inhibit secretion in exocrine cells

    Institute of Scientific and Technical Information of China (English)

    Zong-Jie Cui; Xue-Hui He

    2002-01-01

    AIM: Toosendanin is a pre-synaptic blocker at theneuromuscular junction and its inhibitory effect is dividedinto an initial facilitative/stimulatory phase followed by aprolonged inhibitory phase. The present study investigatedwhether the subsequent inhibitory phase was due toexhaustion of the secretory machinery as a result of extensivestimulation during the initial facilitative phase. Morespecifically, this paper examined whether toosendanin coulddirectly inhibit the secretory machinery in exocrine cells.METHODS: Rat pancreatic acinar cells were isolated bycollagenase digestion. Secretion was assessed by measuringthe amount of amylase released into the extracellular mediumas a percentage of the total present in the cells beforestimulation. Cholecystokinin (CCK)-induced increases inintracellular calcium in single cells were measured with fura-2 microfluorometry.RESULTS: Effects of toosendanin on CCK-induced amylasesecretion and calcium oscillations were investigated.Toosendanin of 87-870 tM had no effect on 10 pM-100 nMCCK-stimulated amylase secretion, nor did 8.7-870 μMtoosendanin inhibit 5 pM CCK-induced calcium oscillations.In contrast, 10 nM CCK1 receptor antagonist FK 480 completelyblocked 5 pM CCK-induced calcium oscillations.CONCLUSION: The pre-synaptic "blocker" toosendanin is aselective activator of the voltage-dependent calcium channels,but does not interfere with the secretory machinery itself.

  2. Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction

    DEFF Research Database (Denmark)

    Ersbøll, A S; Hedegaard, M; Søndergaard, L;

    2014-01-01

    OBJECTIVE: To investigate the effect on fetal growth of treatment with oral beta-blockers during pregnancy in women with congenital or acquired heart disease. DESIGN: Historical matched cohort study. SETTING: Centre for Pregnant Women with Heart Disease, Copenhagen University Hospital, Denmark....... POPULATION: A cohort of 175 women with heart disease, grouped according to beta-blocker treatment, and a cohort of 627 women from the overall population matched on seven birthweight-determining factors. METHODS: Differences between groups were tested by simple descriptive statistics and assessed using...... standard hypothesis tests. Associations were estimated by correlational analysis and multivariable regression. MAIN OUTCOME MEASURE: Proportion of infants born small for gestational age (SGA). RESULTS: More of the infants exposed to beta-blockers were SGA compared with non-exposed infants (29.4 versus 15...

  3. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Rasmussen, Jeppe Nørgaard; Abildstrøm, Steen Z;

    2006-01-01

    AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995...... and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were...... still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials...

  4. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

    Science.gov (United States)

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  5. Coronary computed tomography angiography - Tolerability of β-blockers and contrast media, and temporal changes in radiation dose

    DEFF Research Database (Denmark)

    Pedersen, Charlotte; Thomsen, Camilla F; Hosbond, Susanne Elisabeth;

    2014-01-01

    Abstract Objective: To determine the risk of administration of β-blockers, contrast induced nephropathy (CIN) and trend in x-rays use, during coronary computed tomography angiography (CCTA). Methods: A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60...... beats per minute oral and / or intravenously β-blockers were administered. Information was collected from patients on the adverse effects of β-blockers in the form of questionnaires. S-creatinine and estimated GFR (eGFR) were measured before and after contrast enhanced CCTA. Radiation exposure was....../L, p=0.09), while eGFR increased non-significantly (78 versus 79 mL/min, p=0.17). Also subgroups of patients with hypertension, hypercholesterolemia, diabetes or pre-excisting slightly impaired renal function did not develop CIN. Mean radiation exposure decreased from 17.5 to 6.7 mSv, p<0...

  6. Molecular bases of the influence of calcium influx on the heart by means of a calcium duct-blocker

    International Nuclear Information System (INIS)

    The goal of this work was to identify and purify the physiological binding places for calcium duct-blocker in the heart muscle of cattle. The following was thereby attempted: 1. to purify the plasma membranes from heart cells; 2. to develop a measuring method for the tension-dependent calcium duct with the help of tritiated calcium duct-blocker or respectively, to improve existing methods; 3. to characterize by the use of different calcium duct-blockers this ion duct; 4. to develop methods to solubilize the calcium duct out of the plasma membrane using detergents; as well as 5. to purify the dissolved calcium duct by use of various procedures such as affinity chromatography, chromatography on wheatgerm-agglutinin-substituted sepharose and density gradient centrifugation. (orig./MG)

  7. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

    Science.gov (United States)

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  8. Efficacy of Telmisartan combined with Nifedipine in patients with obesity hypertension%替米沙坦联合硝苯地平控释片对肥胖性高血压患者的疗效观察

    Institute of Scientific and Technical Information of China (English)

    吴池

    2012-01-01

    Department of Internal Medicine, Pingliang Health Center of Shanghai Yangpu District, Shanghai 200082, China Objective To observe the efficacy of Telmisartan combined with Nifedipine in patients with obesity hypertension and its effect on blood lipids and insulin resistance. Methods 190 obese patients with hypertension from June 2010 to June 2011 were randomly divided into observation group and control group, each group was 95 cases. Control group were given Nifedipine, Telmisartan were perfermed on the basis of the control group in observation group. The effect, blood lipids, body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (Fins) and insulin homeostasis assessment index (HOMA -IR) were observed in each group. Results The total effective rate was 92.63% in the observation group, 81.05% in the control group, the difference was statistically significant (^ = 4.606, P = 0.032). After treatment, The levels of TC, TG, BMI and HOMA-IR in the observation group were significantly lower than those before treatment and the control group, the differences were statistically significant (P 0.05). Conclusion The effect of Telmisartan combined with Nifedipine on blood pressure is very obvious, can decrease the blood lipid and improve the insulin resistance.%目的 观察替米沙坦联合硝苯地平控释片对肥胖性高血压患者的疗效及对患者血脂和胰岛素抵抗的影响.方法 选取2010年6月~2011年6月就诊的肥胖性高血压患者190例,随机分为观察组和对照组,两组各95例.对照组予以硝苯地平治疗,观察组在对照组基础上予以替米沙坦治疗.观察两组的疗效、血脂、体重指数(BMI)、空腹血糖(FPG)、空腹胰岛素(FIns)和稳态胰岛素评价指数(HOMA-IR).结果 观察组总有效率为92.63%,对照组总有效率为81.05%,观察组总有效率优于对照组,差异有统计学意义(x2=4.606,P=0.032).治疗后,观察组的TC、TG、BMI和HOMA-IR较治疗前和对照组明显

  9. Autoantibody-mediated angiotensin receptor activation contributes to preeclampsia through TNF-alpha signaling

    OpenAIRE

    Irani, Roxanna A.; Zhang, Yujin; Zhou, Cissy Chenyi; Blackwell, Sean C.; Hicks, M. John; Ramin, Susan M.; Kellems, Rodney E.; Xia, Yang

    2010-01-01

    Preeclampsia is a prevalent life-threatening hypertensive disorder of pregnancy whose pathophysiology remains largely undefined. Recently, a circulating maternal autoantibody, the angiotensin II type I receptor agonistic autoantibody (AT1-AA), has emerged as a contributor to disease features. Increased circulating maternal tumor necrosis factor alpha (TNF-α) is also associated with the disease, however it is unknown if this factor directly contributes to preeclamptic symptoms. Here we report ...

  10. A novel radioligand for imaging the AT1 angiotensin receptor with PET

    International Nuclear Information System (INIS)

    2-Butyl-5-methoxymethyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine (KR31173) was radiolabeled by coupling a tetrazole-protected hydroxy precursor with [11C] methyl iodide and removing the protecting group by acid hydrolysis. In mice, the highest uptake of [11C] KR31173 was in the adrenal glands, kidneys, and liver. Tissue to blood ratios were generally greater than 10:1. Uptake of the tracer in the adrenal glands, kidneys, lungs, and heart was blocked with a 1 mg/kg dose of KR31173 or MK-996

  11. A novel radioligand for imaging the AT{sub 1} angiotensin receptor with PET

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, William B. E-mail: bmathews@petscan.nm.jhu.edu; Yoo, Sung-Eun; Lee, Sung-Hou; Scheffel, Ursula; Rauseo, Paige A.; Zober, Tamas G.; Gocco, Gerard; Sandberg, Kathryn; Ravert, Hayden T.; Dannals, Robert F.; Szabo, Zsolt

    2004-07-01

    2-Butyl-5-methoxymethyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine (KR31173) was radiolabeled by coupling a tetrazole-protected hydroxy precursor with [{sup 11}C] methyl iodide and removing the protecting group by acid hydrolysis. In mice, the highest uptake of [{sup 11}C] KR31173 was in the adrenal glands, kidneys, and liver. Tissue to blood ratios were generally greater than 10:1. Uptake of the tracer in the adrenal glands, kidneys, lungs, and heart was blocked with a 1 mg/kg dose of KR31173 or MK-996.

  12. Predicting Kinase Activity in Angiotensin Receptor Phosphoproteomes Based on Sequence-Motifs and Interactions

    DEFF Research Database (Denmark)

    Bøgebo, Rikke; Horn, Heiko; Olsen, Jesper V;

    2014-01-01

    -arrestin dependent signalling. Two complimentary global phosphoproteomics studies have analyzed the complex signalling induced by the AT1aR. Here we integrate the data sets from these studies and perform a joint analysis using a novel method for prediction of differential kinase activity from phosphoproteomics data...... developed a new method for kinase-centric analysis of phosphoproteomes to pinpoint differential kinase activity in large-scale data sets....

  13. Predicting kinase activity in angiotensin receptor phosphoproteomes based on sequence-motifs and interactions.

    Directory of Open Access Journals (Sweden)

    Rikke Bøgebo

    Full Text Available Recent progress in the understanding of seven-transmembrane receptor (7TMR signalling has promoted the development of a new generation of pathway selective ligands. The angiotensin II type I receptor (AT1aR is one of the most studied 7TMRs with respect to selective activation of the β-arrestin dependent signalling. Two complimentary global phosphoproteomics studies have analyzed the complex signalling induced by the AT1aR. Here we integrate the data sets from these studies and perform a joint analysis using a novel method for prediction of differential kinase activity from phosphoproteomics data. The method builds upon NetworKIN, which applies sophisticated linear motif analysis in combination with contextual network modelling to predict kinase-substrate associations with high accuracy and sensitivity. These predictions form the basis for subsequently nonparametric statistical analysis to identify likely activated kinases. This suggested that AT1aR-dependent signalling activates 48 of the 285 kinases detected in HEK293 cells. Of these, Aurora B, CLK3 and PKG1 have not previously been described in the pathway whereas others, such as PKA, PKB and PKC, are well known. In summary, we have developed a new method for kinase-centric analysis of phosphoproteomes to pinpoint differential kinase activity in large-scale data sets.

  14. ACE inhibition is superior to angiotensin receptor blockade for renography in renal artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Karanikas, Georgios; Becherer, Alexander; Wiesner, Karoline; Dudczak, Robert; Kletter, Kurt [Department of Nuclear Medicine, University of Vienna (Austria)

    2002-03-01

    Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much more sensitive than valsartan renography in detecting a clinically significant renal artery stenosis. Furthermore, our data suggest that other effects, such as that on the prostaglandin-bradykinin system, are of at least similar importance to ACE inhibition for the high diagnostic sensitivity of captopril renography regarding renovascular hypertension. (orig.)

  15. Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial

    DEFF Research Database (Denmark)

    Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun;

    2010-01-01

    ≥140 mmHg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North...

  16. Differential roles of Angiotensinogen and Angiotensin Receptor type 1 polymorphisms in breast cancer risk.

    NARCIS (Netherlands)

    Gonzalez-Zuloet Ladd, A.M.; Arias Vasquez, A.; Siemes, C.; Yazdanpanah, M.; Coebergh, J.W.W.; Hofman, A.; Stricker, B.H.C.; Duijn, C.M. van

    2007-01-01

    While angiotensinogen (AGT) seems to have anti proliferative properties, angiotensin II (ATII) is a potent growth factor and it mediates its actions through the angiotensin type 1 receptor (AGTR1). In the AGT gene, the M235T polymorphism has been associated with the variation in angiotensinogen leve

  17. Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil

    OpenAIRE

    Carlos Ferrario

    2009-01-01

    Carlos FerrarioHypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USAAbstract: Endothelial dysfunction is the common link between cardiovascular disease risk factors and the earliest event in the cascade of incidents that results in target organ damage. Angiotensin II, the terminal pressor effector arm of the renin-angiotensin-aldosterone system, increases blood pressure (BP) by vasoconstriction and sodium and fluid retention, and has a pro...

  18. Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction.

    Science.gov (United States)

    Hioki, Hirofumi; Motoki, Hirohiko; Izawa, Atsushi; Kashima, Yuichirou; Miura, Takashi; Ebisawa, Souichirou; Tomita, Takeshi; Miyashita, Yusuke; Koyama, Jun; Ikeda, Uichi

    2016-05-01

    The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan-Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116-0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission. PMID:25863805

  19. Sodium Phosphate Rectal

    Science.gov (United States)

    ... blockers (ARBs) such as candesartan (Atacand, in Atacand HCT), eprosartan (Teveten), irbesartan (Avapro, in Avalide), losartan (Cozaar, ... Benicar, in Azor, Tribenzor), telmisartan (Micardis, in Micardis HCT, Twynsta), or valsartan (Diovan, in Diovan HCT, Exforge, ...

  20. Sodium Phosphate

    Science.gov (United States)

    ... blockers (ARBs) such as candesartan (Atacand, in Atacand HCT), eprosartan (Teveten), irbesartan (Avapro, in Avalide), losartan (Cozaar, ... in Azor and Tribenzor), telmisartan (Micardis, in Micardis HCT and Twynsta), or valsartan (Diovan, in Diovan HCT, ...

  1. Non-selective vs. selective beta-blocker treatment and the risk of thrombo-embolic events in patients with heart failure

    NARCIS (Netherlands)

    O.R. de Peuter; P.C. Souverein; O.H. Klungel; H.R. Büller; A. de Boer; P.W. Kamphuisen

    2011-01-01

    Aims Heart failure (HF) is associated with a prothrombotic state, resulting in an increased risk for thrombo-embolic events. Studies suggest a reduced prothrombotic state when non-selective beta-blockers relative to selective beta-blockers are given. We studied the influence of non-selective beta-bl

  2. Angiotensin AT1-receptor blockers and cerebrovascular protection: do they actually have a cutting edge over angiotensin-converting enzyme inhibitors?

    DEFF Research Database (Denmark)

    Oprisiu-Fournier, Roxana; Faure, Sébastien; Mazouz, Hakim;

    2009-01-01

    is presented to support the hypothesis that antihypertensive drugs that increase angiotensin II formation, such as diuretics, AT1-receptor blockers and dihydropyridines, may have greater brain anti-ischemic effects than antihypertensive drugs that decrease angiotensin II formation, such as beta-blockers...

  3. Heart rate reduction and exercise performance in recent onset heart failure with reduced ejection fraction: arguments for beta-blocker hypo-response

    OpenAIRE

    Verbrugge, Frederik Hendrik; Vrijsen, Jeroen; Vercammen, Jan; Grieten, Lars; Dupont, Matthias; Mullens, Wilfried

    2015-01-01

    Objective Beta blockers reduce all-cause mortality and readmissions in heart failure with reduced ejection fraction (HFrEF), which may be explained by their effect on heart rate (HR). This study assessed the impact of HR reduction with beta blockers on exercise capacity in recent onset HFrEF. Methods and results Fifty consecutive patients with recent onset HFrEF (

  4. Cardiovascular drugs and the risk of suicide: a nested case-control study

    DEFF Research Database (Denmark)

    Callréus, Torbjörn; Agerskov Andersen, Ulla; Hallas, Jesper; Andersen, Morten

    2007-01-01

    OBJECTIVE: During the past 30 years, various cardiovascular drugs have been implicated as causes of depression or suicide. Although the evidence for causal relationships has generally been conflicting, both beta-blockers and angiotensin-converting-enzyme inhibitors (ACE-inhibitors) have been...... current angiotensin-receptor antagonist use (OR: 3.52; 95% CI: 1.33-9.30) based on five of the cases exposed. CONCLUSION: With the exception of the imprecise risk associated with current use of angiotensin-receptor antagonists, the results from our study do not support the hypothesis that other...

  5. Inhibitory effects of calcium channel blockers on thyroid hormone uptake in neonatal rat cardiomyocytes

    OpenAIRE

    Verhoeven, F.A.; Moerings, Ellis; Lamers, Jos; Hennemann, G.; Visser, Ton; Everts, Maria

    2001-01-01

    textabstractThe effects of the Ca2+ channel blockers verapamil, nifedipine, and diltiazem on triiodothyronine (T3) and thyroxine (T4) uptake were tested in cultured cardiomyocytes from 2-day-old rats. Experiments were performed at 37 degrees C in medium with 0.5% BSA for [125I]T3 (100 pM) or 0.1% BSA for [125I]T4 (350 pM). The 15-min uptake of [125I]T3 was 0.124 +/- 0.013 fmol/pM free T3 (n = 6); [125I]T4 uptake was 0.032 +/- 0.003 fmol/pM free T4 (n = 12). Neither T3 nor T4 uptake was affect...

  6. Antioxidant effect of T-type calcium channel blockers in gastric injury.

    Science.gov (United States)

    Bilici, Dilek; Banoğlu, Z Nur; Kiziltunç, Ahmet; Avci, Bahattin; Ciftçioğlu, Akif; Bilici, Sefa

    2002-04-01

    It is known that calcium ion has an important role in the cellular function. For this reason, calcium channel blockers may have a protective action against gastric injury which is induced by various stimuli. In this study, the influence of mibefradil on ethanol-induced gastric injury was investigated in rats. Mibefradil was given at a dose 50 mg/kg intraperitoneally 30 min before administration of 1 ml absolute ethanol given by gavage. We compared this effect of mibefradil with that of omeprazol. Ethanol-induced mucosal damage was evaluated using three different approaches: analysis of biochemical parameters and pathologic and macroscopic investigation. It was found that pretreatment with mibefradil significantly reduced ethanol-induced macroscopic, pathologic, and biochemical changes in the gastric mucosa. In conclusion, it is speculated that this findings may prove important in the development of new and improved therapies for the treatment and prevention of gastric ulcers in humans. PMID:11991620

  7. Inhibition of Peripheral Nerve Scarring by Calcium Antagonists, Also Known as Calcium Channel Blockers.

    Science.gov (United States)

    Xue, Jin-Wei; Jiao, Jian-Bao; Liu, Xiao-Feng; Jiang, Yuan-Tao; Yang, Guang; Li, Chun-Yu; Yin, Wei-Tian; Ling, Li

    2016-05-01

    The aim of this research was to investigate the impact of calcium channel blockers (verapamil) on the formation of scars in the sciatic nerve anastomosis after peripheral nerve injury. One hundred twenty healthy, male Sprague-Dawley rats were selected and prepared with right sciatic nerve injury for this study. Samples were selected at the fourth and 12th weeks, respectively, after treatment and observations were made on the nerve anastomosis healing and diameter. Image analysis and statistical processing were carried out relating to the results of the study. The diameter of the anastomosis of the treatment group at weeks 4 and 12 was noticeably smaller than the control group (P regeneration. It can effectively inhibit the formation of scarring from nerve injury. It also provided an excellent microenvironment for the regeneration of nerve fibers. PMID:26488333

  8. Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro

    International Nuclear Information System (INIS)

    The effects of 2 specific calcium channel blockers, verapamil and nimodipine, on the proliferation of human glioma tumour cells were investigated in vitro. Tumour tissues for primary cell cultures were obtained bioptically from 3 patients with the histopathological diagnosis of glioblastoma. The [3H]-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation. It was found that varapamil (104-105M) and nimodipine (104-106M) significantly inhibited the [3H]-thymidine uptake in a dose-related manner. The inhibitory effect of both calcium channel antagonists was reversed by stimultancous addition of calcium chloride (5x103M). These results indicate that verapamil and nimodipine may exert an antiproliferative effect on glioma cells growth acting through a blokade of specific voltage-dependent calcium channels. (author)

  9. The effect of ions, ion channel blockers, and ionophores on uptake of vitellogenin into cockroach follicles.

    Science.gov (United States)

    Kindle, H; Lanzrein, B; Kunkel, J G

    1990-12-01

    Since calcium plays an important role in vitellogenin binding and uptake in Nauphoeta cinerea and because calcium channels have been described in follicles of this species, we investigated the effect of various ions, ionophores, and ion channel blockers on vitellogenin uptake in vitro. Calcium significantly stimulated vitellogenin uptake; this effect could be substituted best by barium and less well by strontium and magnesium. The stimulatory effect of calcium, and to a certain extent also that of barium, was dependent on the vitellogenin concentration, whereas the effect of strontium and magnesium was not. In the presence of calcium, vitellogenin uptake was inhibited by barium, strontium, and magnesium as well as by the transition elements nickel, cobalt, and zinc, but not by manganese which had a stimulatory effect. Valinomycin, verapamil, tetraethylammonium, and atropine reduced vitellogenin uptake, while amiloride and ouabain were ineffective. Our results indicate that calcium inward (and possibly potassium outward) fluxes play an important role in vitellogenin uptake. PMID:2257971

  10. In vitro and in vivo evaluation of polymethylene tetraamine derivatives as NMDA receptor channel blockers.

    Science.gov (United States)

    Saiki, Ryotaro; Yoshizawa, Yuki; Minarini, Anna; Milelli, Andrea; Marchetti, Chiara; Tumiatti, Vincenzo; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2013-07-01

    The biological activities of six symmetrically substituted 2-methoxy-benzyl polymethylene tetraamines (1-4) and diphenylethyl polymethylene tetraamines (5 and 6) as N-methyl-D-aspartate (NMDA) receptor channel blockers, were evaluated in vitro and in vivo. Although all compounds exhibited stronger channel block activities in comparison to memantine in Xenopus oocytes voltage clamped at -70 mV, only compound 2 (0.4 mg/kg intravenous injection) decreased the size of brain infarction in a photochemically induced thrombosis model mice at the same extent of memantine (10mg/kg intravenous injection). Other compounds (1, 3, 4, 5 and 6) did not decrease the size of brain infarction significantly due to the limited injection doses. The present study suggests that compound 2 could represent a valuable lead compound to design low toxicity polyamines for clinical use against stroke. PMID:23692871

  11. Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Axelsson, Anna; Iversen, Kasper; Vejlstrup, Niels;

    2015-01-01

    18 years and older) with obstructive or non-obstructive hypertrophic cardiomyopathy were randomly assigned via computer-based system to losartan (100 mg per day) or placebo for 12 months. Patients and investigators were masked to assigned treatment. The primary endpoint was change in left ventricular......, and May 1, 2013, 318 patients were screened. 133 patients (mean age 52 years [SD 13], 35% women) consented and were randomly assigned to placebo (n=69) or losartan (n=64). 124 (93%) patients completed the study and were included in the modified intention-to-treat analysis for the primary endpoint...... predictive of an adverse outcome. We aimed to assess the effect of the angiotensin II receptor blocker losartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, adult patients (aged...

  12. Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2007-01-01

    Full Text Available Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group. One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine; two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil; four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups. Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect. This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

  13. Utility of atropine in patients under beta-blocker effect during exercise stress echocardiography

    International Nuclear Information System (INIS)

    The objective is to assess the usefulness of adding atropine 0.5 to 1.0 mg by intravenous injection during peak exercise in patients under beta-blocker effect that are subjected to exercise stress echocardiography. Population: exercise stress echocardiography was performed in 73 patients receiving beta-blocking agents with basal heart rate below 60 beats per minute (BPM). Two groups were established at random: group I (18 patients that did not receive atropine during maximal exercise) and group II (50 patients from whom 28 received 0.5 mg atropine IV 30 seconds to one minute before concluding the exercise and 22 patients who received 1.0 mg atropine IV 30 seconds to one minute before its conclusion). From a demographic point of view, there were no differences between the two groups. Mean age was 59 ± 10.8 years (57% male). Most of the patients received metoprolol (87%) and no significant statistical differences in relation with the doses were found in these two groups. At the end of the exercise, the patients had a mean heart rate of 84% from their maximal heart rate (MHR). The values post-exercise were 76% at 30 seconds, 68% at 60 sec., 62% at 90 sec., and 59% of the maximal heart rate at 120 sec. When comparing the percentage of the maximal heart rate achieved in maximal exercise and the one observed during the first 120 sec. after exercise, no statistically significant difference was observed between the two groups (p > 0.05). Conclusion: during the performance of stress exercise echocardiography, the administration of intravenous atropine was of no use for incrementing the peak heart rate post-exercise in patients with significant beta-blocker effect (basal heart rate < 60 BPM)

  14. Effectiveness of β-blockers in physically active patients with hypertension: protocol of a systematic review

    Science.gov (United States)

    Tučková, Dagmar; Klugar, Miloslav; Sovová, Eliška; Sovová, Markéta; Štégnerová, Lenka

    2016-01-01

    Introduction Based on more than 5 decades of epidemiological studies, it is now widely accepted that higher physical activity patterns and levels of cardiorespiratory fitness are associated with better health outcomes. Therefore, it is necessary to consider how treatment methods affect these two components. Clinically, one very important question concerns the influence of aerobic performance on patients being treated for hypertension. The administration of β-blockers can significantly reduce maximal—and especially submaximal—aerobic exercise capacity. The objective of this review is to determine, by comparison of existing mono and combination therapy, which β-blockers are less physically limiting for patients with hypertension who are physically active. Methods A three-step strategy will be adopted in the review, following the methods used by the Joanna Briggs Institute (JBI). The initial search will be conducted using the MEDLINE and EMBASE databases. The second search will involve the listed databases for the published literature (MEDLINE, Biomedica Czechoslovaca, Tripdatabase, Pedro, EMBASE, the Cochrane Central Register of Controlled Trials, Cinahl, WoS) and the unpublished literature (Open Grey, Current Controlled Trials, MedNar, ClinicalTrials.gov, Cos Conference Papers Index, the International Clinical Trials Registry Platform of the WHO). Following the JBI methodology, analysis of title/abstracts and full texts, critical appraisal and data extraction will be carried out on selected studies using the JBI tool, MAStARI. This will be performed by two independent reviewers. If possible, statistical meta-analysis will be pooled. Statistical heterogeneity will be assessed. Subgroup analysis will be used for different age and gender characteristics. Funnel plots, Begg's rank correlation and Egger's regression test will be used to detect or correct publication bias. Ethics and dissemination The results will be disseminated by publishing in a peer

  15. Development of selective blockers for Ca2+-activated Cl- channel using Xenopus laevis oocytes with an improved drug screening strategy

    Directory of Open Access Journals (Sweden)

    Oh Soo-Jin

    2008-10-01

    Full Text Available Abstract Background Ca2+-activated Cl- channels (CaCCs participate in many important physiological processes. However, the lack of effective and selective blockers has hindered the study of these channels, mostly due to the lack of good assay system. Here, we have developed a reliable drug screening method for better blockers of CaCCs, using the endogeneous CaCCs in Xenopus laevis oocytes and two-electrode voltage-clamp (TEVC technique. Results Oocytes were prepared with a treatment of Ca2+ ionophore, which was followed by a treatment of thapsigargin which depletes Ca2+ stores to eliminate any contribution of Ca2+ release. TEVC was performed with micropipette containing chelerythrine to prevent PKC dependent run-up or run-down. Under these conditions, Ca2+-activated Cl- currents induced by bath application of Ca2+ to oocytes showed stable peak amplitude when repetitively activated, allowing us to test several concentrations of a test compound from one oocyte. Inhibitory activities of commercially available blockers and synthesized anthranilic acid derivatives were tested using this method. As a result, newly synthesized N-(4-trifluoromethylphenylanthranilic acid with trifluoromethyl group (-CF3 at para position on the benzene ring showed the lowest IC50. Conclusion Our results provide an optimal drug screening strategy suitable for high throughput screening, and propose N-(4-trifluoromethylphenylanthranilic acid as an improved CaCC blocker.

  16. Is heart rate reduction more important than target dose in chronic heart failure therapy with a beta-blocker?

    Institute of Scientific and Technical Information of China (English)

    Yong-Fang Guo; Yi An

    2011-01-01

    1 IntroductionBeta-adrenoceptor blocking agents (beta-blockers) are now well established as cornerstone therapy in patients with systolic chronic heart failure (CHF).[1] Clinical data have overwhelmingly proven the beneficial effects of beta-blocker therapy in terms of improving patient prognosis,decreasing requirements for hospitalization,and postponing disease progression.[2-4] However,it remains unclear what the optimal efficacious and safe dose for an individual patient with CHF is,and whether this can simply be inferred from the target dose for each beta-blocking agent as used in the major clinical trials.Beta-blockers are a heterogeneous class of drugs,and due to the polymorphisms of beta-adrenoceptor gene expression,there is marked individual variation in responsiveness to specific agents.[5] If pharmacodynamic markers of responsiveness to beta-blockade (such as heart rate (HR) reduction) are more important than the achievement of a target dose,could they become another potential therapeutic target in beta-blocker therapy? We provide a discussion of the question in this article.

  17. Comparative study between LMA-Proseal™ and Air-Q® Blocker for ventilation in adult eye trauma patients

    Directory of Open Access Journals (Sweden)

    Maha M.I. Youssef

    2014-07-01

    Conclusion: The Air-Q® Blocker demonstrated to be remarkably good as a ventilatory device, with adequate airway seal pressure, and improved facilitation of gastric tube insertion compared to LMA-Proseal™. Minimal pressor response was achieved after insertion with no statistical significance.

  18. Relationship between chronotropic incompetence and β-blockers based on changes in chronotropic response during cardiopulmonary exercise testing

    Directory of Open Access Journals (Sweden)

    Nami Takano

    2015-03-01

    Conclusions: An attenuated HR response may occur during the early stages of exercise. The HR response according to the presence or absence of β-blockers is clearly identifiable by comparing MCR-AT and MCR-Rc using the Wilkoff model.

  19. 替米沙坦对2型糖尿病合并高血压患者胰岛β细胞功能影响的临床观察%The Effects of Telmisartan to the Function of Beta Cell of Islet in Human New Diagnosis of Type 2 Diabetes and Hypertension

    Institute of Scientific and Technical Information of China (English)

    黄爽; 周强; 顾学林; 胡晓琼; 肖建香

    2012-01-01

    Objective: To investigate the effects of Telmisartan to the beta cell of islet in people diagnosis with type 2 diabetes combine hypertension. Methods: 70 people diagnosis with diabetes and combine mild to moderate hypertension people were divided into two groups: the telmisartan group and the amlodipine group, 35 people in each group. The base control blood glucose were given in both of the groups , in telmisartan group the telmisartan were given to control the blood pressure; the amlodipine group the amlodipine were given to control the blood pressure. The blood pressure and fasting blood glucose were observed in two weeks. The observation time is 12 weeks, before and after observation time, the HbAlc, insulin levels, glucose level after two hours after glucose challenge were detected. Calculated steady-state model according to HOMA β-cell function index (HOMA-β) and insulin resistance index (HOMA-IR). ResultS:In lower the blood pressure, there were no significantly difference between the two groups, including the SBP and DBP, P>0.05. Compared to the amlodipine group, the telmisartan improved the insulin secretion and the HOMA-βbut decreased the HOMA-IR. Conclusions:Telmisartan may make more significant improvement in patients with diabetes and high blood pressure β-cell function, with improvement in blood pressure as well as the function of islet cells.%目的:观察替米沙坦对糖尿病合并高血压患者胰岛β细胞功能的影响,探索血管紧张素Ⅱ阻断剂降压以外的胰岛功能修复作用.方法:70例糖尿病合并轻、中度高血压的患者随机分为替米沙坦治疗组和氨氯地平治疗组,每组35例患者;替米沙坦治疗组在控制血糖的治疗上给予替米沙坦进行降压治疗;氨氯地平治疗组在控制血糖的治疗上给予氨氯地平进行降压治疗;两组的观察周期均12周,每2周观察1次血压、空腹血糖、并记录低血糖及其它不良反应.治疗前后测糖

  20. ACE up the sleeve - are vascular patients medically optimized?

    LENUS (Irish Health Repository)

    Coveney, A P

    2011-03-01

    To examine the current medical management of arteriopathic patients attending a vascular surgical service at a university teaching hospital over a 6-month period. The prescribing of antiplatelets, statins, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers and beta-blockers was specifically examined. Vascular patients are often under the care of multiple specialties, and therefore the influence of different medical specialties on the patients\\' medical management was also examined.

  1. Lipid Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008393 Effects of angiotensin Ⅱ type 1 receptor blocker on triglyceride metabolism in the liver: experiment with Zucker fatty rats. RAN Jianmin(冉建民), et al. Dept Endocrinol, Guangzhou Red Cross Hosp, 4th Hosp Med Coll, Jinan Univ, Guangzhou 510220. Natl Med J China 2008;88(22):1557-1561. Objective To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) metabolism and mechanism thereof.

  2. 明胶酶与核因子-κB对大鼠心肌纤维化的作用及替米沙坦、氨氯地平的干预效果%Roles of gelatinases and NF-KB in rat myocardial fibrosis and effects of Telmisartan and Amlodipine

    Institute of Scientific and Technical Information of China (English)

    商卓; 刘丽; 王文; 马丽媛; 孟宪敏

    2011-01-01

    抑制明胶酶的过程.%Objective Myoeardial fibrosis induced by hypertension is an independent risk factor for cardiovascular diseases. The aim of this study is to explore the mechanism of pharmaceutical prevention of myoeardial fibrosis by observing the changes of gelati-nases (MMP-2, MMP-9) and nuclear factor-icB (NF-kB) during myoeardial fibrosis and intervention with Telmisartan and Amlodipine in hypertensive rats of abdominal aortic constriction ( AAC). Methods Twenty-two 8-week-old male SD rats underwent AAC and another 8 received sham operation. One week after surgery, the former were subdivided into three groups: Telmisartan (ra =8), Amlodipine (ra = 8) and AAC control ( n. = 8 ) , the first two treated byTelmisartan and Amlodipine, respectively, at 5 ing ? Kg"' ? D"1. After 8 weeks of medication, myocardial collagen volume fraction ( CVF) and type-1 and-ffl collagen were assessed by sinus red staining combined with computer image analysis. The protein levels of MMP-2, MMP-9 and NF-kB were assessed by Westemblot. Results Compared with the sham operation group, myocardial CVF, integral optical density (IOD) values of type-1 and-III collagen were significantly increased in the Telmisartan, Amlodipine and AAC control groups (/*<0.05) , lower in the treatment groups than in the AAC control (P<0.05), and lower in the Telmisartan than in the Amdlodipine group ( P < 0.05 ). The IOD value of type HI collagen was also on the rise, lower in the treatment groups than in the AAC control (P <0.05), but with no significant difference between the Telmisartan and Amlodipine groups. The activity of MMP-2 showed no significant difference between the Telmisartan and Amlodipine groups, but lower than in the two groups than in the AAC control and higher than in the sham operation group (P <0.05 ). Compared with the sham operation group, the activity of MMP-9 and the protein levels of MMP-2 and MMP-9 were remarkably increased in the Telmisartan, Amlodipine and AAC control groups (P < 0.05). The protein level of NF-kB was

  3. Patient medication adherence and physician prescribing among congestive heart failure patients of Yemen

    Directory of Open Access Journals (Sweden)

    K M Alakhali

    2013-01-01

    Full Text Available Congestive heart failure has been associated with high morbidity and mortality requiring hospitalisation and is further complicated by noncompliance and under prescriptions. We aim to determine medication adherence and percentage deviation among Asians population in general and Yemenis in particular. A cross-sectional, prospective observational study with purposive sampling was conducted at two cardiac outpatient centers in 70 congestive heart failure patients for a period of 3 months. An Arabic translated Morisky 4 item scale assessed the adherence of patients. Deviation in prescribing was determined by chart review. All 70 patients had mean age of 56.6΁16 years. Morisky 4 item scale predicted low adherence (n=33; 47.1% and overall nonadherencerate (n=38; 54.2% was slightly higher than adherence. Percentage nonadherence versus adherence was high with diuretics (53 vs. 46% and, digoxin (40 vs. 29%. The adherence percentage of angiotensin receptor blockers (9% and beta blockers (8% was low. Diuretics were the most prescribed drugs (n=69; 99%, followed by angiotensin converting enzyme inhibitors (n=51; 73%, cardiac glycoside (n=48; 69%, few patients were on angiotensin receptor blockers (n=8; 11% and (n=9; 13% beta blockers. The maximum prescribing rate deviation was seen with angiotensin receptor blockers (−89% and beta blockers (−87% followed by nitrates (−77%. Digoxin (−31% and angiotensin converting enzymes (−27% deviated comparatively less. Prescribing as well as utilisation rates generally were low resulting in nonachievement of therapeutic goals which could be resolved using multimodel approach.

  4. The safety of beta-blocker use in chronic obstructive pulmonary disease patients with respiratory failure in the intensive care unit

    OpenAIRE

    Kargin, Feyza; Takir, Huriye Berk; Salturk, Cuneyt; Goksenoglu, Nezihe Ciftaslan; Karabay, Can Yucel; Mocin, Ozlem Yazicioglu; Adiguzel, Nalan; Gungor, Gokay; Balci, Merih Kalamanoglu; Yalcinsoy, Murat; Kargin, Ramazan; Karakurt, Zuhal

    2014-01-01

    Background The safety of beta-blockers as a heart rate-limiting drug (HRLD) in patients with acute respiratory failure (ARF) due to chronic obstructive lung disease (COPD) has not been properly assessed in the intensive care unit (ICU) setting. This study aims to compare the use of beta-blocker drugs relative to non-beta-blocker ones in COPD patients with ARF due to heart rate-limiting with respect to length of ICU stay and mortality. Methods We performed a retrospective (January 2011-Decembe...

  5. Impact of β-blocker selectivity on long-term outcomes in congestive heart failure patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Kubota Y

    2015-03-01

    Full Text Available Yoshiaki Kubota, Kuniya Asai, Erito Furuse, Shunichi Nakamura, Koji Murai, Yayoi Tetsuou Tsukada, Wataru Shimizu Department of Medicine (Division of Cardiology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan Background: Chronic obstructive pulmonary disease (COPD is present in approximately one-third of all congestive heart failure (CHF patients, and is a key cause of underprescription and underdosing of β-blockers, largely owing to concerns about precipitating respiratory deterioration. For these reasons, the aim of this study was to evaluate the impact of β-blockers on the long-term outcomes in CHF patients with COPD. In addition, we compared the effects of two different β-blockers, carvedilol and bisoprolol. Methods: The study was a retrospective, non-randomized, single center trial. Acute decompensated HF patients with COPD were classified according to the oral drug used at discharge into β-blocker (n=86; carvedilol [n=52] or bisoprolol [n=34] and non-β-blocker groups (n=46. The primary endpoint was all-cause mortality between the β-blocker and non-β-blocker groups during a mean clinical follow-up of 33.9 months. The secondary endpoints were the differences in all-cause mortality and the hospitalization rates for CHF and/or COPD exacerbation between patients receiving carvedilol and bisoprolol. Results: The mortality rate was higher in patients without β-blockers compared with those taking β-blockers (log-rank P=0.039, and univariate analyses revealed that the use of β-blockers was the only factor significantly correlated with the mortality rate (hazard ratio: 0.41; 95% confidence interval: 0.17–0.99; P=0.047. Moreover, the rate of CHF and/or COPD exacerbation was higher in patients treated with carvedilol compared with bisoprolol (log-rank P=0.033. In the multivariate analysis, only a past history of COPD exacerbation significantly increased the risk of re-hospitalization due to CHF and/or COPD exacerbation (adjusted hazard

  6. Management of Agitation Following Aneurysmal Subarachnoid Hemorrhage: Is There a Role for Beta-Blockers?

    Directory of Open Access Journals (Sweden)

    Fayaz Ibrahim

    2012-01-01

    Full Text Available Introduction. Stroke is a leading cause of mortality and morbidity in the United States. About 20% of the stroke is hemorrhagic and about 50% of these is due to aneurysmal subarachnoid hemorrhage. A troublesome neuropsychiatric complication of subarachnoid hemorrhage is agitation/aggression. Case Presentation. A 45-year-old man with no prior psychiatric history, sustained subarachnoid hemorrhage. After initial stabilization for 2 days, he underwent craniotomy and clipping of anterior cerebral communicating artery aneurysm. Treatment was continued with labetalol, nimodipine, and levetiracetam. Beginning postoperative day 4, patient developed episodes of confusion and agitation/aggression. Switching of Levetiracetam to valproate did not show any improvement. Psychiatry team tried to manage him with intense nursing intervention and different medications like olanzapine, valproate, lorazepam, and haloperidol. However, patient continued to be agitated and aggressive. Switching from labetalol to metoprolol resulted in dramatic improvement within 3 days. Discussion. Antipsychotics and benzodiazepines are often not sufficiently effective in the control of agitation/aggression in patients with traumatic brain injury and similar conditions. Our case report and the literature review including a cochrane review suggests that beta-blockers may be helpful in this situation.

  7. Removal of beta-blockers from aqueous media by adsorption onto graphene oxide.

    Science.gov (United States)

    Kyzas, George Z; Koltsakidou, Anastasia; Nanaki, Stavroula G; Bikiaris, Dimitrios N; Lambropoulou, Dimitra A

    2015-12-15

    The aim of the present study is the evaluation of graphene oxide (GhO) as adsorbent material for the removal of beta-blockers (pharmaceutical compounds) in aqueous solutions. The composition and morphology of prepared materials were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Atenolol (ATL) and propranolol (PRO) were used as model drug molecules and their behavior were investigated in terms of GhO dosage, contact time, temperature and pH. Adsorption mechanisms were proposed and the pH-effect curves after adsorption were discussed. The kinetic behavior of GhO-drugs system was analyzed after fitting to pseudo-first and -second order equations. The adsorption equilibrium data were fitted to Langmuir, Freundlich and Langmuir-Freundlich model calculating the maximum adsorption capacity (67 and 116 mg/g for PRO and ATL (25 °C), respectively). The temperature effect on adsorption was tested carrying out the equilibrium adsorption experiments at three different temperatures (25, 45, 65 °C). Then, the thermodynamic parameters of enthalpy, free energy and entropy were calculated. Finally, the desorption of drugs from GhO was evaluated by using both aqueous eluants (pH2-10) and organic solvents. PMID:26282775

  8. Do calcium channel blockers increase the diagnosis of heart failure in patients with hypertension?

    Science.gov (United States)

    Shibata, Marcelo C; León, Hernando; Chatterley, Trish; Dorgan, Marlene; Vandermeer, Ben

    2010-07-15

    Calcium channel blockers (CCBs) are widely used to control hypertension. Previous work suggested that their use could increase heart failure (HF), which is 1 of the consequences of uncontrolled hypertension. Information about the effect of CCBs on incident HF in patients with hypertension is scarce. A systematic review was conducted to evaluate patients with hypertension treated with CCBs and incident HF. An electronic search of publications was conducted using 8 major databases. Studies were eligible if they (1) were randomized clinical trials, (2) performed comparisons of CCBs versus active control, (3) randomized >200 patients, (4) had follow-up periods >6 months, and (5) provided data regarding incident HF. Trials of renal transplantation patients, placebo-controlled trials, and HF trials were excluded. A total of 156,766 patients were randomized to CCBs or control, with a total of 5,049 events. The analysis indicated a significant increase in the diagnosis of HF in patients allocated to CCBs (odds ratio 1.18, 95% confidence interval 1.07 to 1.31). The effect observed was independent of incident myocardial infarction. Subgroup analyses indicated that patients with diabetes were at higher risk for developing HF (odds ratio 1.71, 95% confidence interval 1.21 to 2.41). In conclusion, the results suggest that patients with hypertension treated with CCBs have increased incident HF. PMID:20599008

  9. Radioprotective effect of calcium channel blocker, diltiazem on survival in gamma rays exposed mice

    International Nuclear Information System (INIS)

    Diltiazem, a calcium channel blocker, used widely in cardio-vascular therapy, protected mice against death and weight loss due to ionising radiation. Administration of such compound 30 minutes prior to 8.0 Gy gamma irradiation enhanced the 30 days survival of animals to 37.5 and 82.5 percent at the dose of 50 and 100 mg/kg b. wt., respectively. On the contrary, 100 per cent death was noted at the dose of 25 mg and 82.5 percent at 200 mg/kg b.wt. Pre-treatment with a dose of 100 mg/kg b.wt. enhanced 30 day survival after lethal irradiation and also inhibited the radiation induced life span shortening. Prior treatment of diltiazem accelerated the recovery of radiation induced weight loss also. Data on dose response demonstrate that higher dose of diltiazem (up to 100 mg/kg b.wt.) is more effective against lethal gamma radiation dose. However, doses above 100 mg/kg b. wt. was found to be quite ineffective in preventing mice against deleterious effects of radiation. (author)

  10. Esmolol: A Unique Beta-Blocker in Maintaining Cardiovascular Stability Following Neurosurgical Procedures

    Directory of Open Access Journals (Sweden)

    Samad EJ Golzari

    2012-08-01

    Full Text Available Purpose: Patients with increased intracranial pressure (ICP are prone to severe cardiac and or cerebral complications following emergence from general anesthesia and especially post-extubation phase. Administering beta blockers including esmolol is believed to be helpful in providing a stable hemodynamic at the end of the surgery and recovery stages and reducing recovery phase length. Methods: In a double-blind prospective randomized clinical trial, 60 adult patients with ASA (American Society of Anesthesiologist class of I-II scheduled to undergo elective neurosurgery operations were randomly divided into two groups receiving esmolol (n=30 and placebo (n=30 as IV infusion within four minutes prior to extubation continued by an IV infusion for 10 minutes after extubation. Results: There was a significant difference between two groups regarding the changes of systolic blood pressure and heart rate at all studied stages after extubation (P≤0.05. However, no significant difference existed between esmolol and control groups regarding recovery and extubation times emphasizing the fact that esmolol is of excellent early recovery and extubation profiles. Conclusion: Esmolol is advised to be used in preventing hyperdynamic status throughout extubation phase without extending recovery phase length.

  11. Polyaniline-graphene oxide nanocomposite sensor for quantification of calcium channel blocker levamlodipine.

    Science.gov (United States)

    Jain, Rajeev; Sinha, Ankita; Khan, Ab Lateef

    2016-08-01

    A novel polyaniline-graphene oxide nanocomposite (PANI/GO/GCE) sensor has been fabricated for quantification of a calcium channel blocker drug levamlodipine (LAMP). Fabricated sensor has been characterized by electrochemical impedance spectroscopy, square wave and cyclic voltammetry, Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The developed PANI/GO/GCE sensor has excellent analytical performance towards electrocatalytic oxidation as compared to PANI/GCE, GO/GCE and bare GCE. Under optimized experimental conditions, the fabricated sensor exhibits a linear response for LAMP for its oxidation over a concentration range from 1.25μgmL(-1) to 13.25μgmL(-1) with correlation coefficient of 0.9950 (r(2)), detection limit of 1.07ngmL(-1) and quantification limit of 3.57ngmL(-1). The sensor shows an excellent performance for detecting LAMP with reproducibility of 2.78% relative standard deviation (RSD). The proposed method has been successfully applied for LAMP determination in pharmaceutical formulation with a recovery from 99.88% to 101.75%. PMID:27157745

  12. Protonated form: the potent form of potassium-competitive acid blockers.

    Directory of Open Access Journals (Sweden)

    Hua-Jun Luo

    Full Text Available Potassium-competitive acid blockers (P-CABs are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.

  13. A pentasymmetric open channel blocker for Cys-loop receptor channels.

    Science.gov (United States)

    Carta, Valentina; Pangerl, Michael; Baur, Roland; Puthenkalam, Roshan; Ernst, Margot; Trauner, Dirk; Sigel, Erwin

    2014-01-01

    γ-Aminobutyric acid type A receptors (GABAA receptors) are chloride ion channels composed of five subunits, mediating fast synaptic and tonic inhibition in the mammalian brain. These receptors show near five-fold symmetry that is most pronounced in the second trans-membrane domain M2 lining the Cl- ion channel. To take advantage of this inherent symmetry, we screened a variety of aromatic anions with matched symmetry and found an inhibitor, pentacyanocyclopentdienyl anion (PCCP-) that exhibited all characteristics of an open channel blocker. Inhibition was strongly dependent on the membrane potential. Through mutagenesis and covalent modification, we identified the region α1V256-α1T261 in the rat recombinant GABAA receptor to be important for PCCP- action. Introduction of positive charges into M2 increased the affinity for PCCP- while PCCP- prevented the access of a positively charged molecule into M2. Interestingly, other anion selective cys-loop receptors were also inhibited by PCCP-, among them the Drosophila RDL GABAA receptor carrying an insecticide resistance mutation, suggesting that PCCP- could serve as an insecticide. PMID:25184303

  14. Biodegradation and cometabolic modeling of selected beta blockers during ammonia oxidation.

    Science.gov (United States)

    Sathyamoorthy, Sandeep; Chandran, Kartik; Ramsburg, C Andrew

    2013-11-19

    Accurate prediction of pharmaceutical concentrations in wastewater effluents requires that the specific biochemical processes responsible for pharmaceutical biodegradation be elucidated and integrated within any modeling framework. The fate of three selected beta blockers-atenolol, metoprolol, and sotalol-was examined during nitrification using batch experiments to develop and evaluate a new cometabolic process-based (CPB) model. CPB model parameters describe biotransformation during and after ammonia oxidation for specific biomass populations and are designed to be integrated within the Activated Sludge Models framework. Metoprolol and sotalol were not biodegraded by the nitrification enrichment culture employed herein. Biodegradation of atenolol was observed and linked to the activity of ammonia-oxidizing bacteria (AOB) and heterotrophs but not nitrite-oxidizing bacteria. Results suggest that the role of AOB in atenolol degradation may be disproportionately more significant than is otherwise suggested by their lower relative abundance in typical biological treatment processes. Atenolol was observed to competitively inhibit AOB growth in our experiments, though model simulations suggest inhibition is most relevant at atenolol concentrations greater than approximately 200 ng·L(-1). CPB model parameters were found to be relatively insensitive to biokinetic parameter selection suggesting the model approach may hold utility for describing pharmaceutical biodegradation during biological wastewater treatment. PMID:24112027

  15. Vincamine and vincanol are potent blockers of voltage-gated Na+ channels.

    Science.gov (United States)

    Erdo, S A; Molnár, P; Lakics, V; Bence, J Z; Tömösközi, Z

    1996-10-24

    The effects of three vinca derivatives on [3H]batrachotoxin binding in rat cortical synaptosomes, on the inhibition of whole-cell Na+ currents evoked in voltage-clamped cortical neurones of the rat, on the protection against veratridine-induced cell death in cortical cultures and on the maximal electroshock-induced seizures in mice were compared. Vinpocetine, vincamine and vincanol reduced [3H]batrachotoxin binding with IC50 values of 0.34, 1.9 and 10.7 microM, blocked Na+ currents with IC50 values of 44.72 and 40 microM, and protected cortical against veratridine-induced cell death with IC50 values of 0.49, 26 and 33 microM, respectively. Upon i.p. administration, vinpocetine, vincamine and vincanol attenuated maximal electric shock-induced convulsions in a dose-dependent manner with ED50 values of 27, 15.4 and 14.6 mg/kg, respectively. The present findings indicate that the three vinca derivatives are potent blockers of voltage-gated Na+ channels, a mechanism that may contribute at least in part to the pharmacological/therapeutic benefit of these drugs. PMID:8957220

  16. eNOS-dependent antisenscence effect of a calcium channel blocker in human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Toshio Hayashi

    Full Text Available Senescence of vascular endothelial cells is an important contributor to the pathogenesis of age-associated vascular disorders such as atherosclerosis. We investigated the effects of antihypertensive agents on high glucose-induced cellular senescence in human umbilical venous endothelial cells (HUVECs. Exposure of HUVECs to high glucose (22 mM for 3 days increased senescence-associated- β-galactosidase (SA-β-gal activity, a senescence marker, and decreased telomerase activity, a replicative senescence marker. The calcium channel blocker nifedipine, but not the β1-adrenergic blocking agent atenolol or the angiotensin-converting enzyme inhibitor perindopril, reduced SA-β-gal positive cells and prevented a decrease in telomerase activity in a high-glucose environment. This beneficial effect of nifedipine was associated with reduced reactive oxygen species (ROS and increased endothelial nitric oxide synthase (eNOS activity. Thus, nifedipine prevented high glucose-induced ROS generation and increased basal eNOS phosphorylation level at Ser-1177. Treatment with N (G-nitro-L-arginine (L-NAME and transfection of small interfering RNA (siRNA targeting eNOS eliminated the anti-senscence effect of nifedipine. These results demonstrate that nifedipine can prevent endothelial cell senescence in an eNOS-dependent manner. The anti-senescence action of nifedipine may represent a novel mechanism by which it protects against atherosclerosis.

  17. The effect of the molecular properties of calcium channel blockers on their elimination route

    Directory of Open Access Journals (Sweden)

    Trbojević-Stanković Jasna B.

    2015-01-01

    Full Text Available Calcium channel blockers (CCBs are among the most widely used drugs in cardiovascular medicine. In this study, nine CCBs (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem were investigated to assess the relationship between their molecular properties and elimination data obtained from literature. The descriptors of the molecular properties of CCBs were calculated using three software packages. The relationship between computed molecular properties and elimination data collected from relevant literature, initially investigated with simple linear regression analysis, showed poor correlation (R2 <0.25. Application of molecular weight or volume data as additional independent variable, multiple linear regression (MLR revealed better correlations (R2 ~ 0.38 between CCB renal and fecal elimination data and their lipophilicity. Excluding nimodipine from the calculations resulted in more acceptable correlations. The best correlations were established after computed lipophilicity descriptor and molecular weight were applied (R2 = 0.66 with acceptable probability value. [Projekat Ministarstva nauke Republike Srbije, br. TR34031

  18. Effect of beta-adrenoceptor blockers on human ether-a-go-go-related gene (HERG) potassium channels

    DEFF Research Database (Denmark)

    Dupuis, Delphine S; Klaerke, Dan A; Olesen, Søren-Peter

    2005-01-01

    Patients with congenital long QT syndrome may develop arrhythmias under conditions of increased sympathetic tone. We have addressed whether some of the beta-adrenoceptor blockers commonly used to prevent the development of these arrhythmias could per se block the cardiac HERG (Human Ether....... These data showed that HERG blockade by beta-adrenoceptor blockers occurred only at high micromolar concentrations, which are significantly above the recently established safe margin of 100 (Redfern et al., 2003).......-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) blocked the HERG channel with similar affinity, whereas the beta1-receptor antagonists metoprolol and atenolol showed weak effects. Further, the four compounds blocked HERG channels expressed in a mammalian HEK293 cell line...

  19. Cell differentiation and infectivity of Leishmania mexicana are inhibited in a strain resistant to an ABC-transporter blocker.

    Science.gov (United States)

    Silva, N; Camacho, N; Figarella, K; Ponte-Sucre, A

    2004-06-01

    We analysed whether markers of cell differentiation and infectivity differed when compared to the parental sensitive strain [NR(Gs)] in an in vitro selected Leishmania strain [NR(Gr)] resistant to Glibenclamide, an ATP-binding-cassette (ABC)-transporter blocker. The data show that the cell body area was larger in NR(Gr) compared to NR(Gs) and that functional characters associated with an infective metacyclic phenotype, such as resistance to the lytic effect of the alternative complement pathway and expression of the Meta-1 protein, were reduced. The infectivity of NR(Gr) to J774.1 macrophages was also significantly reduced. These results suggest that resistance in Leishmania against Glibenclamide, a general blocker of P-glycoproteins, could produce functional modifications that may be relevant for Leishmania differentiation, infectivity and survival. PMID:15206465

  20. Intensity-based optical fiber strain sensor using long-period fiber gratings and a core mode blocker

    International Nuclear Information System (INIS)

    We report an intensity-based fiber strain sensor using a pair of long-period fiber gratings (LPFGs) and an in-line core mode blocker. By inserting a core mode blocker fabricated by the arc discharge method between two LPFGs, a band-pass filter can be formed. We used an LED and an optical power meter to measure the transmittance near the resonance wavelength of the LPFGs and we obtained a relation between the axial strain applied on one of the LPFGs and the transmitted power. The measurement results indicate that the sensitivity of the power meter output voltage to the applied strain is 6.37 pV με−1

  1. Efficacy and tolerability of a single-pill combination of telmisartan/hydrochlorothiazide 80/25 mg in Chinese and Korean patients with moderate to severe hypertension: a subgroup analysis of a randomized, double-blind, active-controlled trial

    Institute of Scientific and Technical Information of China (English)

    ZHU Ding-liang; GAO Ping-jin; LIU Shao-wen; Myung Ho Jeong; Michaela Mattheus; Birgit Voelker

    2013-01-01

    Background Hypertension is an important issue in Asia,responsible for up to 66% of cardiovascular disease cases.This randomized controlled trial subgroup analysis compared telmisartan 80 mg (T80)/hydrochlorothiazide 25 mg (H25) singlepill combination with T80 monotherapy,specifically in Chinese and Korean patients.Methods Patients with grade 2/3 hypertension were randomized to receive telmisartan 40 mg (T40)/hydrochlorothiazide 12.5 mg (H12.5) combination or T40 monotherapy for one week,before uptitrating the dose to T80/H25 or T80,respectively,for the remaining 6 weeks.The primary endpoint was systolic blood pressure (SBP) mean change from baseline.Secondary endpoints included mean diastolic blood pressure (DBP) change from baseline,and blood pressure (BP) goal achievement.Adverse events were recorded.Results Of a total 888 patients who were treated,efficacy analyses for Chinese and Korean patients included 127 patients treated with T80/H25 and 54 patients treated with T80.At week 7,mean SBP reductions from baseline were -37.5 mmHg (1 mmHg=0.133 kPa) and-26.9 mmHg in the T80/H25 and T80 groups (adjusted mean difference,-10.6 mmHg; 95% confidence interval (CO,-15.6 to-5.7).Mean DBP reductions were-19.0 and-14.1 mmHg in the T80/H25 and T80 groups (adjusted mean difference,-4.9 mmHg; 95% CI,-8.0 to-1.8).In total,56.7% of patients receiving T80/H25 achieved BP goal (<140/90 mmHg) compared with 35.2% receiving T80.SBP goal attainment (<140 mmHg) and DBP goal attainment (<90 mmHg) were also higher in the T80/H25 group compared with the T80 group (SBP:69.3% vs.48.1%; DBP:62.2% vs.46.3%).A small number of treatment-related adverse events were observed in both T80/H25 (nine patients,6.9%) and T80 monotherapy (two patients,3.6%) groups.Conclusions In Chinese and Korean patients with moderate-to-severe hypertension,treatment with T80/H25 provided large reductions in mean SBP and DBP,and high BP goal attainment rates.This once-daily combination is

  2. Behavioural hyperactivity in rats treated with selective monoamine oxidase inhibitors and LM 5008, a selective 5-hydroxytryptamine uptake blocker.

    OpenAIRE

    Ashkenazi, R.; Finberg, J. P.; Youdim, M. B.

    1983-01-01

    The administration of 4-[2-(3-indolyl)ethyl]piperidine (LM 5008), a selective 5-hydroxytryptamine (5-HT) uptake blocker to rats pretreated with tranylcypromine (Tcp) resulted in a behavioural syndrome of locomotor hyperactivity which is indistinguishable from that following combined treatment with Tcp and L-tryptophan. A similar behavioural response was elicited by the administration of LM 5008 to rats pretreated with 5-hydroxytryptophan. The response to LM 5008 after monoamine oxidase (MAO) ...

  3. Evaluation Effects of Verapamil as a Calcium Channel Blocker on Acquisition, Consolidation and Retrieval of Memory in Mice

    OpenAIRE

    Nooshin Masoudian; Nahid Masoudian; Ali Rashidy Pour; Abbas Ali Vafaiee; Sasan Andalib; Golnaz Vaseghi

    2015-01-01

    Many factors are involved in learning and memory processes including brain nuclei, neurotransmitter systems, and the activity of ion channels. Studies showed inconsistent effects of calcium channel blockers on learning process, especially memory consolidation; however, little is known about their effect on memory acquisition and retrieval. Accordingly, the present study aimed to determine the effects of verapamil calcium channel antagonist as a representative of the phenylalkylamine group on ...

  4. The energy blockers bromopyruvate and lonidamine lead GL15 glioblastoma cells to death by different p53-dependent routes

    OpenAIRE

    Magdalena Davidescu; Lara Macchioni; Gaetano Scaramozzino; Maria Cristina Marchetti; Graziella Migliorati; Rita Vitale; Angela Corcelli; Rita Roberti; Emilia Castigli; Lanfranco Corazzi

    2015-01-01

    The energy metabolism of tumor cells relies on aerobic glycolysis rather than mitochondrial oxidation. This difference between normal and cancer cells provides a biochemical basis for new therapeutic strategies aimed to block the energy power plants of cells. The effects produced by the energy blockers bromopyruvate (3BP) and lonidamine (LND) and the underlying biochemical mechanisms were investigated in GL15 glioblastoma cells. 3BP exerts early effects compared to LND, even though both drugs...

  5. The Kv channel blocker 4-aminopyridine enhances Ag+ uptake: A scanning electrochemical microscopy study of single living cells

    OpenAIRE

    Zhan, Dongping; Fan, Fu-Ren F.; Bard, Allen J.

    2008-01-01

    We report that silver ion (Ag+) uptake is enhanced by 4-aminopyridine (4-AP), a well known voltage-sensitive potassium ion channel (Kv) blocker. Both bacterial (Escherichia coli) and mammalian (3T3 fibroblast) cells were used as model systems. Ag+ uptake was monitored with a scanning electrochemical microscope with an amperometric Ag+ ion-selective electrode (Ag+-ISE) and the respiration rates of E. coli cells were measured by oxygen reduction at an ultramicroelectrode. The results showed tha...

  6. Preventive Effects of the Angiotensin-II Receptor Blocker on Atrial Remodeling in an Ischemic Heart Failure Model of Rats

    OpenAIRE

    Yoon, Namsik; Kim, Kye Hun; Park, Keun Ho; Sim, Doo Sun; Youn, Hyun Ju; Hong, Young Joon; Park, Hyung Wook; Kim, Ju Han; Ahn, Youngkeun; Jeong, Myung Ho; Cho, Jeong Gwan; Park, Jong Chun

    2013-01-01

    Background and Objectives It is widely known that angiotensin-II receptor blockers (ARBs) have reverse remodeling effects in atrium. Although atrial fibrillation is frequent in ischemic heart failure clinically, experiments to demonstrate ARB's effects on atrial remodeling in a heart failure model are rare. Materials and Methods A heart failure model and a sham-operated group were formed in 25 Sprague-Dawley male rats of roughly 260 g in weight. Ischemic heart failure models were obtained via...

  7. Afatinib, an irreversible ErbB family blocker, with protracted temozolomide in recurrent glioblastoma: A case report

    OpenAIRE

    Alshami, Jad; Guiot, Marie-Christine; Owen, Scott; Kavan, Petr; Gibson, Neil; Solca, Flavio; Cseh, Agnieszka; Reardon, David A.; Muanza, Thierry

    2015-01-01

    There are few effective treatments for recurrent glioblastoma multiforme (GBM). We present a patient with recurrent GBM who achieved a prolonged response to treatment with afatinib, an irreversible ErbB family blocker, plus temozolomide. A 58-year-old female patient was diagnosed with multifocal primary GBM. After surgical resection, first-line therapy comprised radiotherapy and temozolomide. Following disease progression after 3 temozolomide cycles, the patient entered a phase I/II clinical ...

  8. The use of alpha-1 adrenergic blockers in children with distal ureterolithiasis: a systematic review and meta-analysis

    OpenAIRE

    Glina, F.P.; Castro, P.M.V.; Monteiro, G.G.R.; G.C. Del Guerra; S. Glina; M. Mazzurana; W.M. Bernardo

    2015-01-01

    ABSTRACT Introduction: Urinary lithiasis is the main urologic cause of emergency treatment in adult patient. In the past years, the incidence in children population has increased. However, literature about the use of alpha-1 adrenergic blockers in pediatric population with distal ureterolithiasis is still scarce. The drug acts by decreasing ureter contractions, especially in the distal portion, facilitating calculus expulsion. Objective: This review has the objective to evaluate the use of al...

  9. β1-blockers lower norepinephrine release by inhibiting presynaptic, facilitating β1-adrenoceptors in normotensive and hypertensive rats

    Directory of Open Access Journals (Sweden)

    TorillBerg

    2014-04-01

    Full Text Available Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors (AR, believed to involve the β2-subtype exclusively. However, β1-selective blockers are the most commonly used β-blockers in hypertension. Here I tested the hypothesis that β1AR may function as presynaptic, release-facilitating auto-receptors. Since β1AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET, presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β1AR-selective antagonists (CGP20712A, atenolol, metoprolol reduced norepinephrine overflow to plasma equally efficient as β2AR-selective (ICI-118551 and β1+2AR (nadolol antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood-brain barrier, reduced norepinephrine overflow after adrenalectomy, adrenalectomy+ganglion blockade, losartan or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β1AR, like β2AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1-receptor activation. β1AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β1AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as

  10. The use of alpha-1 adrenergic blockers in children with distal ureterolithiasis: a systematic review and meta-analysis

    OpenAIRE

    Glina, F.P.; Castro, P.M.V.; Monteiro, G.G.R.; G.C. Del Guerra; S Glina; M. Mazzurana; Bernardo, W.M.

    2015-01-01

    Introduction: Urinary lithiasis is the main urologic cause of emergency treatment in adult patient. In the past years, the incidence in children population has increased. However, literature about the use of alpha-1 adrenergic blockers in pediatric population with distal ureterolithiasis is still scarce. The drug acts by decreasing ureter contractions, especially in the distal portion, facilitating calculus expulsion. Objective: This review has the objective to evaluate the use of alpha-1 ad...

  11. Effects of prototypic calcium channel blockers in methadone-maintained humans responding under a naloxone discrimination procedurea

    OpenAIRE

    Oliveto, Alison; Mancino, Michael; Sanders, Nichole; Cargile, Christopher; Guise, J. Benjamin; Bickel, Warren; Gentry, W. Brooks

    2013-01-01

    Accumulating evidence suggests that L-type calcium channel blockers (CCBs) attenuate the expression of opioid withdrawal and the dihydropyridine L-type CCB isradipine has been shown to block the behavioral effects of naloxone in opioid-maintained humans. This study determined whether two prototypic L-type CCBs with differing chemical structures, the benzothiazepine diltiazem and the phenylalkamine verapamil, attenuate the behavioral effects of naloxone in methadone-maintained humans trained t...

  12. TNF-α Blocker Effect of Naringenin-Loaded Sericin Microparticles that Are Potentially Useful in the Treatment of Psoriasis

    OpenAIRE

    Theodora Chlapanidas; Sara Perteghella; Flavio Leoni; Silvio Faragò; Mario Marazzi; Daniela Rossi; Emanuela Martino; Raffaella Gaggeri; Simona Collina

    2014-01-01

    This study aims to evaluate the effect of combined use of the racemic flavanone Naringenin (NRG) and the protein sericin as TNF-α blockers. Sericin (SMs) and (R/S) NRG-loaded Sericin (SNRGMs) microparticles were prepared by spray-drying, characterized in terms of morphology and particle size distribution, and encapsulation efficiency was determined. Concerning morphology and particle size distribution of microparticles, results indicated that they were not affected by the presence of NRG. Th...

  13. Tumor Necrosis Factor-Blocker Dose Escalation in Rheumatoid Arthritis Patients in a Pharmacy Benefit Management Setting

    OpenAIRE

    Blume, Steven W; Fox, Kathleen M.; Joseph, George; Chuang, Chien-Chia; Thomas, Jessy; Gandra, Shravanthi R

    2013-01-01

    Introduction Dose escalation with tumor necrosis factor (TNF)-blockers is poorly characterized in pharmacy benefit management (PBM) settings. Methods This retrospective study used integrated pharmacy and medical claims from the PBM Medco to characterize dose escalation among rheumatoid arthritis (RA) patients treated with etanercept and adalimumab. Data from adults with RA with pharmacy claims for etanercept or adalimumab between 1/1/2007 and 12/31/2009 and continuous enrollment for ≥6 months...

  14. Telmisartan attrnuates ventilator-induced lung injury in rats%替米沙坦对大鼠呼吸机相关性肺损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    宋先斌; 肖军

    2012-01-01

    Objective To determine the effect of telmisartan on ventilator-induced lung injury ( VILI) in rats. Methods Forty healthy male SD rats were equally divided into four groups in random (A, B, C and D groups, n = 10). Group A served as control group, in which rats did not receive ventilation. Groups B, C and D received large-tide volume ventilation, but only rats from groups C and D received intraperitoneal injection with telmisartan solution (2. 5 and 5 mg/kg respectively. Telmisartan was dissolved in PBS) in 30 min before ventilation. Equal amount of PBS solution was given to rats in groups A and, B. A rat model of VILI was reproduced by volume-controlled mechanical ventilation with large tide volume ( Vt =40 ml/kg for 2 h) . Hemo-dynamic parameters and arterial blood gases of all the rats in the 4 groups were measured throughout the study period. After maintaining ventilation for 2 h, all rats were sacrificed and specimens of lung tissues and bron-choalveolar lavage fluid (BALF) were harvested. Lung pathological changes were observed by microscopy, and Smith score was estimated. The protein levels of peroxisome proliferator activated receptor-γ ( PPAR-γ) and Ang Ⅱ1 receptor (AT1R) in lung tissues were assayed with immunohistochemistry staining. Lung myeloperoxi-dase (MPO) activity and wet-dry weight ratio ( W/D) were measured. The levels of tumor necrosis factor-ot (TNF-α) and interleukin-8 (IL-8) in BALF were measured by enzyme-linked immunosorbent assay (ELISA). Results Mean Ph values in arterial blood from groups B, C and D tended to be higher than the base linevalue during the ventilation, while mean arterial pressure ( MAP) , mean partial pressure of carbon dioxide in arterial blood [ p ( C02) ] and mean partial pressure of oxygen in arterial blood [ p ( 02) ] were lower than baseline in these groups. MAP in groups C and D was significantly lower than in group B after 2 hours' ventilation( P < 0. 05 ). Smith score, mean MPO activity, mean W/D ratio

  15. Oral physiology, nutrition and quality of life in diabetic patients associated or not with hypertension and beta-blockers therapy.

    Science.gov (United States)

    Pereira, L J; Foureaux, R C; Pereira, C V; Alves, M C; Campos, C H; Rodrigues Garcia, R C M; Andrade, E F; Gonçalves, T M S V

    2016-07-01

    The relationship between type 2 diabetes oral physiology, nutritional intake and quality of life has not been fully elucidated. We assessed the impact of type 2 diabetes - exclusive or associated with hypertension with beta-blockers treatment - on oral physiology, mastication, nutrition and quality of life. This cross-sectional study was performed with 78 complete dentate subjects (15 natural teeth and six masticatory units minimum; without removable or fixed prostheses), divided into three groups: diabetics (DM) (n = 20; 45·4 ± 9·5 years), diabetics with hypertension and receiving beta-blockers treatment (DMH) (n = 19; 41·1 ± 5·1 years) and controls (n = 39; 44·5 ± 11·7 years) matched for gender, age and socioeconomic status. Blood glucose, masticatory performance, swallowing threshold, taste, food intake, stimulated and unstimulated salivary flow, pH and buffering capacity of saliva were assessed. Glycemia was higher in DM than in controls (P physiology, nutrition or quality of life. However, when hypertension and beta-blockers treatment were associated with diabetes, the salivary flow rate, chewing cycles and number of teeth decreased. PMID:27043215

  16. Beneficial effects of switching from β-blockers to nebivolol on the erectile function of hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    Michael Doumas; Alexandros Tsakiris; Stella Douma; Alkiviadis Grigorakis; Angelos Papadopoulos; Athina Hounta; Sotirios Tsiodras; Dimitrios Dimitriou; Helen Giamarellou

    2006-01-01

    Aim: To investigate the effect of substituting β-blockers with nebivolol on the erectile function of patients suffering from essential hypertension. Methods: Forty-four young and middle-aged men (31-65 years) with essential hypertension visited our outpatient clinic and took β-blocker treatment (atenolol, metoprolol or bisoprolol) for more than 6months. All the patients completed a questionnaire regarding erectile function (International Index for Erectile Function).Patients were then switched to an equipotent dose of nebivolol for 3 months and, at the end of this time period, filled out the same questionnaire. Results: Twenty-nine out of the 44 (65.9%) patients who took β-blockers (atenolol,metoprolol or bisoprolol) had exhibited erectile dysfunction (ED). Their systolic and diastolic blood pressure did not change significantly with the treatment switch. In 20 out of these 29 (69%) patients, a significant improvement in the erectile function score was exhibited after 3 months of nebivolol administration, and in 11 of these 20 patients, erectile function was normalized. Conclusion: Nebivolol seems to have a beneficial effect on ED (possibly due to increased nitric oxide availability); however, further prospective, randomized, placebo-controlled studies are needed to confirm the beneficial effects of nebivolol.

  17. Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers

    Directory of Open Access Journals (Sweden)

    Kelly Rosemary F

    2009-11-01

    Full Text Available Abstract Background Previous studies on the effects of Statins in preventing atrial fibrillation (AF after cardiac surgery have shown conflicting results. Whether statins prevent AF in patients treated with postoperative beta blockers and whether the statin-effect is dose related are unknown. Methods We retrospectively studied 1936 consecutive patients who underwent coronary artery bypass graft (CABG (n = 1493 or valve surgery (n = 443 at the Minneapolis Veterans Affairs Medical Center. All patients were in sinus rhythm before the surgery. Postoperative beta blockers were administered routinely (92% within 24 hours postoperatively. Results Mean age was 66+10 years and 68% of the patients were taking Statins. Postoperative AF occurred in 588 (30% patients and led to longer length of stay in the intensive care unit versus those without AF (5.1+7.6 days versus 2.5+2.3 days, p 20 mg daily had a 36% reduction in the risk of postoperative AF (OR 0.64, 95% CI 0.43 to 0.6; p = 0.03 in comparison to those taking lower dosages. Conclusion Among cardiac surgery patients treated with postoperative beta blockers Statin treatment reduces the incidence of postoperative AF when used at higher dosages

  18. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    Science.gov (United States)

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (Phospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs.

  19. Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans.

    Science.gov (United States)

    Gong, Yan; Wang, Zhiying; Beitelshees, Amber L; McDonough, Caitrin W; Langaee, Taimour Y; Hall, Karen; Schmidt, Siegfried O F; Curry, Robert W; Gums, John G; Bailey, Kent R; Boerwinkle, Eric; Chapman, Arlene B; Turner, Stephen T; Cooper-DeHoff, Rhonda M; Johnson, Julie A

    2016-03-01

    African Americans suffer a higher prevalence of hypertension compared with other racial/ethnic groups. In this study, we performed a pharmacogenomic genome-wide association study of blood pressure (BP) response to β-blockers in African Americans with uncomplicated hypertension. Genome-wide meta-analysis was performed in 318 African American hypertensive participants in the 2 Pharmacogenomic Evaluation of Antihypertensive Responses studies: 150 treated with atenolol monotherapy and 168 treated with metoprolol monotherapy. The analysis adjusted for age, sex, baseline BP and principal components for ancestry. Genome-wide significant variants with Pmetoprolol monotherapy, and atenolol add-on therapy: -9.3 versus -4.6, -9.6 versus -4.8, and -9.7 versus -6.4 mm Hg, respectively (3-group meta-analysis P=2.5×10(-8), β=-4.42 mm Hg per variant allele). Similarly, LRRC15 rs11313667 was validated for systolic BP response to β-blocker therapy with 3-group meta-analysis P=7.2×10(-8) and β=-3.65 mm Hg per variant allele. In this first pharmacogenomic genome-wide meta-analysis of BP response to β-blockers in African Americans, we identified novel variants that may provide valuable information for personalized antihypertensive treatment in this group. PMID:26729753

  20. L—type calcium channel blockers inhibit the development but not the expression of sensitization to morphine in mice

    Institute of Scientific and Technical Information of China (English)

    ZhanQ; ZhenJW

    2002-01-01

    The relationship between opioid actions and L-type calcium channel blockers has been well documented.However,there is no report relevant to L-type calcium channel blockers and morphinesensitization,which is suggested to be an analog of behaviors that are the characteristics of drug addiction.Here the effects of three L-type calcium channel blockers,nimodipine,nifedipine and verapamil,on morphine-induced locomotor activity,the development and the expression of sensitization to morphine were studied systematically.The results showed that both nimodipine and verapamil attenuated,while nifedipine had only a tendency to decrease morphine-induced locomotor activity.All the three drugs inhibited the development of sensitization to morphine.However,none of them showed any effects on the expression of morphine sensitization.These results indicate that blocking L-tpye calcium channel attenuates the locomotor stimulating effects of morphine and inhibits the development but not the expression of morphine-sensitization.

  1. Association of beta-Blocker Therapy With Risks of Adverse Cardiovascular Events and Deaths in Patients With Ischemic Heart Disease Undergoing Noncardiac Surgery A Danish Nationwide Cohort Study

    DEFF Research Database (Denmark)

    Andersson, C.; Merie, C.; Jorgensen, M.;

    2014-01-01

    IMPORTANCE Clinical guidelines have been criticized for encouraging the use of beta-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of beta-blockers on hard end points (ie, perioperative myocardial...... infarction, ischemic stroke, cardiovascular death, and all-cause death). OBJECTIVE To assess the association of beta-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. DESIGN, SETTING. PARTICIPANTS...... models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with beta-blocker therapy. MAIN OUTCOMES AND MEASURES Thirty-day risk of MACE and all-cause mortality. RESULTS Of 28 263 patients with ischemic heart...

  2. Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Abildstrom, Steen Z; Rasmussen, Jeppe Nørgaard;

    2005-01-01

    OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. DESIGN: Information about patients with first AMI aged > or = 30 years and the dispensing of beta-blockers and ACE inhibitors from......-diuretics and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged or = 80 years and patients not taking loop......-diuretics received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. CONCLUSIONS: Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people...

  3. 替米沙坦对原发性高血压病患者早期肾损害及肾内血液动力学的影响%Effect of telmisartan on early renal function and intrarenal hemodynamics in essential hypertension patients

    Institute of Scientific and Technical Information of China (English)

    孙亚非; 冯红旗; 张丽薇

    2012-01-01

    目的 评价替米沙坦对原发性高血压病患者早期肾功能损害和肾内血液动力学的影响.方法 选择80例原发性高血压,血肌酐(Cr)正常患者,分别测定Cr、血清胱抑素C(Cys-C)、尿白蛋白/血肌酐(Alb/Cr)来评价肾功能,用彩色多普勒超声仪测量肾动脉阻力指数(resistive index,RI)和搏动指数(pulsatility index,PI)评价肾内血液动力学.给予替米沙坦80~160 mg/d,12周后重复测量上述指标.结果 治疗后收缩压及舒张压较治疗前明显降低(P<0.01);治疗前后血肌酐均没有变化,但血清胱抑素C(P<0.05)、尿白蛋白/血肌酐显著降低(P<0.01);治疗后微量白蛋白尿阳性患者的RI和PI降低(P<0.01).结论 Cys-C、RI和PI是反映原发性高血压早期肾损害的指标.替米沙坦能降低肾动脉阻力,从而保护肾脏功能.%Objective To evaluate the effect of telmisartan on early renal function and intra-renal hemodynamics in essential hypertension patients. Methods Eighty patients with primary hypertension and normal serum creatinine (Cr) were studied. Cr,serum cystatin C (Cys-C) ,urine protein/creatinine (Alb/Cr) were examined to evaluate renal function. Renal artery resistance index ( RI) and pulsatility index( PI) were measured by color Doppler ultrasound to e-valuate renal hemodynamies. Telmisartan 80 - 160 mg/d was given,after 12 weeks,these index were measured again. Results Telmisartan reduced systolic and diastolic blood pressure significantly and decreased the Alb/Cr ratio(P<0. 01). Cr had no change(P<0. 05) ,Cys-C levels were significantly reduced(P <0.01). Telmisartan decreased PI and RI in patients with microalbumimiria( P<0. 01). Conclusion Cys-C,RI and PI is sensitive indicators of early renal damage in essential hypertension,and telmisartan can significantly reduce renal vascular resistance to improve renal function in hypertensive patients.

  4. Dose-Dependent Effect of Landiolol, a New Ultra-Short-Acting β1-Blocker, on Supraventricular Tachyarrhythmias in Postoperative Patients

    OpenAIRE

    Taenaka, Nobuyuki; Kikawa, Shinichi

    2013-01-01

    Background β-Adrenoceptor antagonists (β-blockers) have been reported to be effective for regulation of heart rate (HR) and restoring sinus rhythm in postoperative atrial fibrillation and atrial flutter, as well as in the prevention of those arrhythmias after open-heart surgery. Objectives The objectives of this study were to evaluate the dose-dependent effects of landiolol, an ultra-short-acting β1-blocker, as well as the effectiveness and safety of the drug in suppressing supraventricular t...

  5. Effect of beta-blocker therapy on the risk of infections and death after acute stroke--a historical cohort study.

    Directory of Open Access Journals (Sweden)

    Ilko L Maier

    Full Text Available BACKGROUND: Infections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans. METHODS: 625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models. RESULTS: 553 (88.3% patients were admitted with ischemic stroke, the remaining 72 (11.7% had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5-16 points. 301 (48.2% patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77-1.30, p = 0.995. Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43-0.98, p = 0.040. 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65-2.77, p = 0.425, while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20-3.10, p = 0.006. CONCLUSIONS: Beta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.

  6. Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    Wu Xiaosan

    2013-01-01

    Full Text Available Abstract Background Atrial arrhythmia (AA is the most common complication after coronary artery bypass grafting (CABG. Only beta-blockers and amiodarone have been convincingly shown to decrease its incidence. The effectiveness of magnesium on this complication is still controversial. This meta-analysis was performed to evaluate the effect of magnesium as a sole or adjuvant agent in addition to beta-blocker on suppressing postoperative AA after CABG. Methods We searched the PubMed, Medline, ISI Web of Knowledge, Cochrane library databases and online clinical trial database up to May 2012. We used random effects model when there was significant heterogeneity between trials and fixed effects model when heterogeneity was negligible. Results Five randomized controlled trials were identified, enrolling a total of 1251 patients. The combination of magnesium and beta-blocker did not significantly decrease the incidence of postoperative AA after CABG versus beta-blocker alone (odds ratio (OR 1.12, 95% confidence interval (CI 0.86-1.47, P = 0.40. Magnesium in addition to beta-blocker did not significantly affect LOS (weighted mean difference −0.14 days of stay, 95% CI −0.58 to 0.29, P = 0.24 or the overall mortality (OR 0.59, 95% CI 0.08-4.56, P = 0.62. However the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone (OR 2.80, 95% CI 1.66-4.71, P = 0.0001. Conclusions This meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered, and shows an association with more adverse events in those people who received magnesium.

  7. The effect of two beta-adrenoceptor blockers (mepindolol and atenolol) on blood lipids and platelet aggregation in normal volunteers and essential hypertensive patients.

    OpenAIRE

    Luque Otero, M; Fernandez Pinilla, C; Escriba Polo, A; Rodriguez Vazquez, M; Martell Claros, N; A Fernandez-Cruz

    1984-01-01

    beta-adrenoceptor blocking agents are widely used as treatment of essential hypertension. We studied the action of a new non cardioselective beta-adrenoceptor blocker, mepindolol, comparing its effects on blood pressure, blood lipids and platelet aggregation with those of a cardioselective beta-adrenoceptor blocker, atenolol. Blood pressure fell significantly in the patients treated with both drugs. Triglycerides rose non-significantly only in volunteers treated with mepindolol. We did not fi...

  8. Effects of eprosartan on target organ protection

    Directory of Open Access Journals (Sweden)

    Alejandro de la Sierra

    2006-03-01

    Full Text Available Alejandro de la SierraHypertension Unit, Department of Internal Medicine, Hospital Clínic, IDIBAPS, University of Barcelona, SpainAbstract: Hypertension is the most important cardiovascular risk factor for stroke. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary, although no clear differences have yet been observed between antihypertensive drug classes. However, a recent study reported the clear superiority of the angiotensin-receptor blocker eprosartan over the calcium channel blocker nitrendipine in cardiovascular protection of hypertensive patients with a previous stroke. Comparative studies using angiotensin-receptor blockers have also suggested the superiority of this class of drugs on primary stroke prevention. This effect may be linked to their beneficial actions on left ventricular hypertrophy, atrial enlargement, and supraventricular arrhythmias, endothelial dysfunction, inflammation, and remodelling, as well as a direct neuroprotective effect mediated through the stimulation of the angiotensin II type-2 receptor. In addition, a sympathoinhibition observed with the renin–angiotensin system blockers and particularly demonstrated with eprosartan, may help to explain the better cardiovascular and cerebrovascular protection in comparison with the calcium antagonist nitrendipine.Keywords: eprosartan, angiotensin-receptor blockers, hypertension, stroke, organ protection

  9. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    Directory of Open Access Journals (Sweden)

    Mugoša S

    2016-08-01

    Full Text Available Snežana Mugoša,1,2 Nataša Djordjević,3 Nina Djukanović,4 Dragana Protić,5 Zoran Bukumirić,6 Ivan Radosavljević,7 Aneta Bošković,8 Zoran Todorović5,9 1Department of Pharmacotherapy, Faculty of Pharmacy, University of Montenegro, 2Clinical Trial Department, Agency for Medicines and Medical Devices of Montenegro, Podgorica, Montenegro; 3Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 4High Medical School “Milutin Milanković”, Belgrade, 5Department of Pharmacology, Clinical Pharmacology and Toxicology, 6Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, 7Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; 8Clinic for Heart Diseases, Clinical Centre of Montenegro, Podgorica, Montenegro; 9Department of Clinical Immunology and Allergy, Medical Center “Bežanijska kosa”, Belgrade, Serbia Abstract: The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6 poor metabolizer alleles (*3, *4, *5, and *6 on a Montenegrin population and its impact on developing adverse drug reactions (ADRs of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9% patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001, with ADRs’ occurrence significantly

  10. The energy blockers 3-bromopyruvate and lonidamine: effects on bioenergetics of brain mitochondria.

    Science.gov (United States)

    Macchioni, Lara; Davidescu, Magdalena; Roberti, Rita; Corazzi, Lanfranco

    2014-10-01

    Tumor cells favor abnormal energy production via aerobic glycolysis and show resistance to apoptosis, suggesting the involvement of mitochondrial dysfunction. The differences between normal and cancer cells in their energy metabolism provide a biochemical basis for developing new therapeutic strategies. The energy blocker 3-bromopyruvate (3BP) can eradicate liver cancer in animals without associated toxicity, and is a potent anticancer towards glioblastoma cells. Since mitochondria are 3BP targets, in this work the effects of 3BP on the bioenergetics of normal rat brain mitochondria were investigated in vitro, in comparison with the anticancer agent lonidamine (LND). Whereas LND impaired oxygen consumption dependent on any complex of the respiratory chain, 3BP was inhibitory to malate/pyruvate and succinate (Complexes I and II), but preserved respiration from glycerol-3-phosphate and ascorbate (Complex IV). Accordingly, although electron flow along the respiratory chain and ATP levels were decreased by 3BP in malate/pyruvate- and succinate-fed mitochondria, they were not significantly influenced from glycerol-3-phosphate- or ascorbate-fed mitochondria. LND produced a decrease in electron flow from all substrates tested. No ROS were produced from any substrate, with the exception of 3BP-induced H(2)O(2) release from succinate, which suggests an antimycin-like action of 3BP as an inhibitor of Complex III. We can conclude that 3BP does not abolish completely respiration and ATP synthesis in brain mitochondria, and has a limited effect on ROS production, confirming that this drug may have limited harmful effects on normal cells. PMID:25194986

  11. Angiotensin II AT(1) receptor blockers as treatments for inflammatory brain disorders.

    Science.gov (United States)

    Saavedra, Juan M

    2012-11-01

    The effects of brain AngII (angiotensin II) depend on AT(1) receptor (AngII type 1 receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT(1) receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood-brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurodegerative, mood and traumatic brain disorders, and cognitive decline. In rodents, ARBs (AT(1) receptor blockers) ameliorate stress-induced disorders, anxiety and depression, protect cerebral blood flow during stroke, decrease brain inflammation and amyloid-β neurotoxicity and reduce traumatic brain injury. Direct anti-inflammatory protective effects, demonstrated in cultured microglia, cerebrovascular endothelial cells, neurons and human circulating monocytes, may result not only in AT(1) receptor blockade, but also from PPARγ (peroxisome-proliferator-activated receptor γ) stimulation. Controlled clinical studies indicate that ARBs protect cognition after stroke and during aging, and cohort analyses reveal that these compounds significantly reduce the incidence and progression of Alzheimer's disease. ARBs are commonly used for the therapy of hypertension, diabetes and stroke, but have not been studied in the context of neurodegenerative, mood or traumatic brain disorders, conditions lacking effective therapy. These compounds are well-tolerated pleiotropic neuroprotective agents with additional beneficial cardiovascular and metabolic profiles, and their use in central nervous system disorders offers a novel therapeutic approach of immediate translational value. ARBs should be tested for the prevention and therapy of neurodegenerative disorders, in particular Alzheimer's disease, affective disorders, such as co-morbid cardiovascular disease and depression, and traumatic

  12. Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer's Disease.

    Science.gov (United States)

    Saavedra, Juan M

    2016-03-01

    Alzheimer's disease is the most frequent type of dementia and diagnosed late in the progression of the illness when irreversible brain tissue loss has already occurred. For this reason, treatments have been ineffective. It is imperative to find novel therapies ameliorating modifiable risk factors (hypertension, stroke, diabetes, chronic kidney disease, and traumatic brain injury) and effective against early pathogenic mechanisms including alterations in cerebral blood flow leading to poor oxygenation and decreased access to nutrients, impaired glucose metabolism, chronic inflammation, and glutamate excitotoxicity. Angiotensin II receptor blockers (ARBs) fulfill these requirements. ARBs are directly neuroprotective against early injury factors in neuronal, astrocyte, microglia, and cerebrovascular endothelial cell cultures. ARBs protect cerebral blood flow and reduce injury to the blood brain barrier and neurological and cognitive loss in animal models of brain ischemia, traumatic brain injury, and Alzheimer's disease. These compounds are clinically effective against major risk factors for Alzheimer's disease: hypertension, stroke, chronic kidney disease, diabetes and metabolic syndrome, and ameliorate age-dependent cognitive loss. Controlled studies on hypertensive patients, open trials, case reports, and database meta-analysis indicate significant therapeutic effects of ARBs in Alzheimer's disease. ARBs are safe compounds, widely used to treat cardiovascular and metabolic disorders in humans, and although they reduce hypertension, they do not affect blood pressure in normotensive individuals. Overall, there is sufficient evidence to consider long-term controlled clinical studies with ARBs in patients suffering from established risk factors, in patients with early cognitive loss, or in normal individuals when reliable biomarkers of Alzheimer's disease risk are identified. PMID:26993513

  13. Neuroprotective effects of volume-regulated anion channel blocker DCPIB on neonatal hypoxic-ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Ammar ALIBRAHIM; Li-yan ZHAO; Christine You-jin BAE; Andrew BARSZCZYK; Christopher LF SUN; Guan-lei WANG; Hong-shuo SUN

    2013-01-01

    Aim:To evaluate the role of swelling-induced activation of volume-regulated anion channels (VRACs) in a neonatal hypoxic-ischemic injury model using the selective VRAC blocker 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on5-yl) oxobutyric acid (DCPIB).Methods:Cerebral hypoxic-ischemic injury was induced in 7-day-old mouse pups with Rice-Vannucci method.Prior to the onset of ischemia,the animals were ip administered DCPIB (10 mg/kg).The animals were sacrificed 24 h afterwards,coronal sections of the brains were cut and the areas of infarct were examined using TTC staining and an image-analysis system.Cultured PC12 cells were subjected to oxygen-glucose deprivation (OGD) for 4 h.The cellular viability was assessed using Cell Counting Kit 8.Intracellular chloride concentration [Clˉ]i was measured using 6-methoxy-N-ethylquinolinium iodide.Results:DCPIB-treated mice showed a significant reduction in hemispheric corrected infarct volume (26.65%+2.23%) compared to that in vehicle-treated mice (45.52%+1.45%,P<O.O01).DCPIB-treated mice also showed better functional recovery as they were more active than vehicle-treated mice at 4 and 24 h post injury.In cultured PC12 cells,DCPIB (10 μmol/L) significantly reduced OGD-induced cell death.Moreover,DCPIB (20 μmol/L) blocked hypotonic-induced decrease in [Clˉ]i in PC12 cells of both control and OGD groups.Conclusion:The results further support the pathophysiological role of VRACs in ischemic brain injury,and suggest DCPIB as a potential,easily administrable agent targeting VRACs in the context of perinatal and neonatal hypoxic-ischemic brain injury.

  14. Meroterpenoid Chrodrimanins Are Selective and Potent Blockers of Insect GABA-Gated Chloride Channels.

    Science.gov (United States)

    Xu, Yan; Furutani, Shogo; Ihara, Makoto; Ling, Yun; Yang, Xinling; Kai, Kenji; Hayashi, Hideo; Matsuda, Kazuhiko

    2015-01-01

    Meroterpenoid chrodrimanins, produced from Talaromyces sp. YO-2, are known to paralyze silkworm (Bombyx mori) larvae, but their target is unknown. We have investigated the actions of chrodrimanin B on ligand-gated ion channels of silkworm larval neurons using patch-clamp electrophysiology. Chrodrimanin B had no effect on membrane currents when tested alone at 1 μM. However, it completely blocked the γ-aminobutyric acid (GABA)-induced current and showed less pronounced actions on acetylcholine- and L-glutamate-induced currents, when delivered at 1 μM for 1 min prior to co-application with transmitter GABA. Thus, chrodrimanins were also tested on a wild-type isoform of the B. mori GABA receptor (GABAR) RDL using two-electrode voltage-clamp electrophysiology. Chrodrimanin B attenuated the peak current amplitude of the GABA response of RDL with an IC50 of 1.66 nM. The order of the GABAR-blocking potency of chrodrimanins B > D > A was in accordance with their reported insecticidal potency. Chrodrimanin B had no open channel blocking action when tested at 3 nM on the GABA response of RDL. Co-application with 3 nM chrodrimanin B shifted the GABA concentration response curve to a higher concentration and further increase of chrodrimanin B concentration to 10 nM; it reduced maximum current amplitude of the GABA response, pointing to a high-affinity competitive action and a lower affinity non-competitive action. The A282S;T286V double mutation of RDL, which impairs the actions of fipronil, hardly affected the blocking action of chrodrimanin B, indicating a binding site of chrodrimanin B distinct from that of fipronil. Chrodrimanin B showed approximately 1,000-fold lower blocking action on human α1β2γ2 GABAR compared to RDL and thus is a selective blocker of insect GABARs. PMID:25902139

  15. Use of the tumor necrosis factor-blockers for Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Alan BR Thomson; Milli Gupta; Hugh J Freeman

    2012-01-01

    The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago.The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses.In general,it is suggested that tumor necrosis factor-α blockers (TNFBs) are indicated (1)for persons with moderately-severe Crohn's disease or ulcerative colitis (UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause (8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate; (2) non-responsive perianal disease; and (3) severe UC not responding to a 3-d to 5-d course of steroids.Once TNFBs have been introduced and the patient is responsive,therapy given by the IV and SC rate must be continued.It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy,and when or if TNFB may be weaned and discontinued.The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed.The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB,and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic.Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high,the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

  16. Reactivity of β-blockers/agonists with aqueous permanganate. Kinetics and transformation products of salbutamol.

    Science.gov (United States)

    Rodríguez-Álvarez, Tania; Rodil, Rosario; Quintana, José Benito; Cela, Rafael

    2015-08-01

    The possible oxidation of two β-blockers, atenolol and propranolol, and one β-agonist, salbutamol, with aqueous potassium permanganate (KMnO4) was investigated by liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-QTOF-MS). Under strong oxidation conditions (2 mg L(-1) KMnO4, 24 h), only salbutamol did significantly react. In this way, the oxidation kinetics of salbutamol was further investigated at different concentrations of KMnO4, chloride, phosphate and sample pH by means of a full factorial experimental design. Depending on these factors, half-lives were in the range 1-144 min for drug and it was observed that KMnO4 concentration was the most significant factor, resulting in increased reaction rate as it is increased. Moreover, the reaction of salbutamol is also enhanced at basic pH and to a minor extent by the presence of phosphates, being both factors more relevant at low KMnO4 concentrations. The use of an accurate-mass LC-QTOF-MS system permitted the identification of a total of seven transformation products (TPs). The transformation path of the drug begins by the attack of KMnO4 on two double bonds of the aromatic ring of salbutamol via 3 + 2 and 2 + 2 addition reactions, which resulted in the ring opening and that continues with oxidative reactions to finally produce smaller size TPs, ending with tert-butyl-formamide, as the smallest TP identified. Reaction in real samples showed a slower and partial oxidation of the pharmaceutical, due to other competing water organic constituents, but still exceeding 60%. Moreover, the software predicted toxicity of TPs indicates that they are expected not to be more toxic than salbutamol, in contrast to the results obtained for the predicted toxicity of chlorination TPs, excepting predicted developmental toxicity. PMID:25965887

  17. Meroterpenoid Chrodrimanins Are Selective and Potent Blockers of Insect GABA-Gated Chloride Channels.

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    Yan Xu

    Full Text Available Meroterpenoid chrodrimanins, produced from Talaromyces sp. YO-2, are known to paralyze silkworm (Bombyx mori larvae, but their target is unknown. We have investigated the actions of chrodrimanin B on ligand-gated ion channels of silkworm larval neurons using patch-clamp electrophysiology. Chrodrimanin B had no effect on membrane currents when tested alone at 1 μM. However, it completely blocked the γ-aminobutyric acid (GABA-induced current and showed less pronounced actions on acetylcholine- and L-glutamate-induced currents, when delivered at 1 μM for 1 min prior to co-application with transmitter GABA. Thus, chrodrimanins were also tested on a wild-type isoform of the B. mori GABA receptor (GABAR RDL using two-electrode voltage-clamp electrophysiology. Chrodrimanin B attenuated the peak current amplitude of the GABA response of RDL with an IC50 of 1.66 nM. The order of the GABAR-blocking potency of chrodrimanins B > D > A was in accordance with their reported insecticidal potency. Chrodrimanin B had no open channel blocking action when tested at 3 nM on the GABA response of RDL. Co-application with 3 nM chrodrimanin B shifted the GABA concentration response curve to a higher concentration and further increase of chrodrimanin B concentration to 10 nM; it reduced maximum current amplitude of the GABA response, pointing to a high-affinity competitive action and a lower affinity non-competitive action. The A282S;T286V double mutation of RDL, which impairs the actions of fipronil, hardly affected the blocking action of chrodrimanin B, indicating a binding site of chrodrimanin B distinct from that of fipronil. Chrodrimanin B showed approximately 1,000-fold lower blocking action on human α1β2γ2 GABAR compared to RDL and thus is a selective blocker of insect GABARs.

  18. Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus

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    Mori Y

    2014-06-01

    Full Text Available Yutaka Mori,1,2 Shizuka Aritomi,3 Kazumi Niinuma,3 Tarou Nakamura,3 Kenichi Matsuura,1 Junichi Yokoyama,1 Kazunori Utsunomiya1 1Division of Diabetes and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Minato-ku, Japan; 2Department of Clinical Research, National Hospital Organization, Utsunomiya National Hospital, Utsunomiya, Japan; 3Research Center, Ajinomoto Pharmaceuticals Co, Ltd, Kanagawa, Japan Abstract: Cilnidipine (Cil, which is an L-/N-type calcium channel blocker (CCB, has been known to provide renal protection by decreasing the activity of the sympathetic nervous system (SNS and the renin–angiotensin system. In this study, we compared the effects of the combination of Cil and amlodipine (Aml, which is an L-type CCB, with an angiotensin (Ang II receptor blocker on diabetic cardiorenal damage in spontaneously type 2 diabetic rats. Seventeen-week-old Otsuka Long-Evans Tokushima Fatty rats were randomly assigned to receive Cil, Aml, valsartan (Val, Cil + Val, Aml + Val, or a vehicle (eight rats per group for 22 weeks. Antihypertensive potencies were nearly equal among the CCB monotherapy groups and the combination therapy groups. The lowering of blood pressure by either treatment did not significantly affect the glycemic variables. However, exacerbations of renal and heart failure were significantly suppressed in rats administered Cil or Val, and additional suppression was observed in those administered Cil + Val. Although Val increased the renin–Ang system, Aml + Val treatment resulted in additional increases in these parameters, while Cil + Val did not show such effects. Furthermore, Cil increased the ratio of Ang-(1–7 to Ang-I, despite the fact that Val and Aml + Val decreased the Ang-(1–7 levels. These actions of Cil + Val might be due to their synergistic inhibitory effect on the activity of the SNS, and on aldosterone secretion through N-type calcium channel antagonism and Ang II

  19. Beta-blocker therapy in patients with left ventricular systolic dysfunction and chronic obstructive lung disease in an ambulatory care setting

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    Billups SJ

    2009-12-01

    Full Text Available Objective: To evaluate beta blocker persistence six months after beta-blocker initiation or dose titration in heart failure (HF patients with COPD compared to those without COPD. Secondary objectives included comparison of beta-blocker dose achieved, changes in left ventricular ejection fraction (LVEF and incidence of hospitalizations or emergency department (ED visits during follow-up.Methods: We conducted a matched, retrospective, cohort study including 86 patients with COPD plus concomitant HF (LVEF ≤40% and 137 patients with HF alone. All patients were followed in an outpatient HF clinic. Eligible patients had a documented LVEF ≤40% and were initiated or titrated on a beta-blocker in the HF clinic. Patients were matched based on LVEF (categorized as ≤ 20% or 21-40%, gender, and age (> or ≤70 years. The primary outcome was beta blocker persistence at 6 months. Secondary outcomes were dose achieved, LVEF, and incidence of hospitalizations or ED visits. Results: There were no differences between the COPD and non-COPD groups in beta-blocker persistence at six-month follow-up (94.2% vs. 93.4% respectively, adjusted p=0.842. The proportion of patients who achieved a daily metoprolol dose equivalent of at least 100 mg was similar between the groups (adjusted p=0.188. The percent of patients with at least one ED visit or hospitalization in the six-month post-titration period was substantial but similar between the groups (53.5% and 48.2% for COPD and non-COPD patients, respectively, adjusted p=0.169. Conclusion: Our results support the use of beta-blockers in the population of heart failure patients with COPD and without reactive airway disease.

  20. Adjunctive medical therapy with α-blocker after extracorporeal shock wave lithotripsy of renal and ureteral stones: a meta-analysis.

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    Mingchao Li

    Full Text Available Although some trials assessed the efficacy and safety of the α-blocker in facilitating renal and ureteral stones expulsion after extracorporeal shock wave lithotripsy (ESWL, the role of the α-blocker in facilitating upper urinary calculi expulsion after ESWL remain controversial.To determine the efficacy and safety of the α-blocker in facilitating renal and ureteral stones expulsion after ESWL.A literature search was carried out using the PubMed database, EMBASE and the Cochrane Library database to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality. Pooled effect estimates were obtained using a fixed- and random-effects meta-analysis.The meta-analysis included 23 RCTs, α-blocker significantly enhanced expulsion rate of upper urinary tract calculi after ESWL (P<0.00001; RR 1.21; 95% CI 1.12-1.31, significantly promoted steinstrasse expulsion (P=0.03; RR 1.25; 95% CI 1.03-1.53, significantly shortened the discharge time of upper urinary tract calculi (P=0.0001; MD -2.12; 95% CI -3.20--1.04, significantly reduced the patient's pain VAS score (P=0.001; RR -1.0; 95% CI -1.61--0.39. Compared with the control group, dizziness (P=0.002; RR 5.48; 95% CI 1.91-15.77, anejaculation (P=0.02; RR 12.17; 95% CI 1.61-91.99 and headache (P=0.04; RR 4.03; 95% CI 1.04-15.72 in the α-blocker group was associated with a higher incidence.Treatment with α-blocker after ESWL appears to be effective in enhancing expulsion rate of upper urinary tract calculi, shortening the discharge time of upper urinary tract calculi, reducing the patient's pain. The side effects of α-blocker were light and few.

  1. Withholding or Continuing Beta-Blocker Treatment Before Dipyridamole Myocardial Perfusion Imaging for the Diagnosis of Coronary Artery Disease? a Randomized Clinical Trial

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    Babak Fallahi

    2013-01-01

    Full Text Available Although it has been shown that acute beta-blocker administration may reduce the presence or severity of myocardial perfusion defects with dipyridamole stress, little information is available about the potential effect of chronic beta-blocker treatment on the sensitivity of dipyridamole myocardial perfusion imaging (DMPI.Methods As a randomized clinical trial, one hundred twenty patients (103 male and 17 female with angiographically confirmed CAD who were on long-term beta blocker therapy ([greater than or equal to]3 months enrolled in a randomized clinical trial study. The patients were allocated into two groups: Group A (n=60 in whom the beta-blocker agent was discontinued for 72h before DMPI and Group B (n=60 without discontinuation of beta-blockers prior to DMPI.ResultsNo significant difference was noted between the groups concerning age, sex, type of the injected radiotracer and number of involved coronary vessels. The mean rank of total perfusion scores for whole myocardium (irrespective of reversibility or irreversibility in group B was not significantly different from that of group A, (65.75 vs. 55.25, P=0.096. Regarding the only irreversible perfusion defects, the mean rank of perfusion score in group B was higher than that of group A for whole myocardium (72 vs. 49, P=0.0001; however, no difference was noted between two groups for only reversible perfusion defects (61.0 vs. 60.0, P=0.898. The overall sensitivity of DMPI for the diagnosis of CAD in group A (91.7% was not statistically different from group B (90%.ConclusionBeta-blocker withholding before DMPI did not generally affect the sensitivity of the test for the diagnostic purposes in our study. Thus, beta-blocker withdrawal for just the purpose of diagnostic imaging is not mandatory particularly when medication discontinuation may cause the patients to face increased risk of heart events.

  2. The influence of radiation sterilisation on some {beta}-blockers in the solid state

    Energy Technology Data Exchange (ETDEWEB)

    Marciniec, B. [Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 6 Gruwaldzka Str., 60-780 Poznan (Poland); Ogrodowczyk, M., E-mail: mogrodo@ump.edu.pl [Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 6 Gruwaldzka Str., 60-780 Poznan (Poland); Czajka, B.; Hofman, M. [Department of Cooridinational Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznan (Poland)

    2011-02-20

    Research highlights: {yields} Six {beta}-blockers (acebutolol, alprenolol, atenolol, metoprolol, pindolol, propranolol) in solid phase were exposed to the ionising radiation by e-beam in doses from 25 to 400 kGy. {yields} To establish the effects of irradiation on their physico-chemical properties, the compounds were then analysed by DSC, SEM, XRD and FT-IR. {yields} For alprenolol, propranolol and metoprolol linear relations were found between the irradiation dose and the decrease in the melting point (r = 0.9446-0.9864). {yields} No changes were observed in the FT-IR spectra and in the SEM images of the compounds studied. - Abstract: Six derivatives of aryloxyalkylaminopropanol of known {beta}-adrenolytic activity (acebutolol, alprenolol, atenolol, metoprolol, pindolol, propranolol) in solid phase were exposed to the ionising radiation generated by e-beam of high-energy electrons from an accelerator ({approx}10 MeV) in doses from 25 to 400 kGy. To establish the effects of irradiation on their physico-chemical properties, the compounds were then analysed by differential scanning calorimetry (DSC), scanning electron microscope (SEM), X-ray diffraction (XRD) and FT-IR spectrometry. The standard sterilisation dose (25 kGy) was found to cause no changes in only one derivative - acebutolol, whereas in the other derivatives the irradiation caused colour changes, differences in X-ray diffraction patterns and in the character of DSC curves, including a decrease in the melting point. For each derivative one clear peak corresponding to the process of melting was observed and its position shifted towards lower temperatures with increasing dose of irradiation. For all compounds studied the value of the shift was between 0.1 and 1.0 {sup o}C. For alprenolol, propranolol and metoprolol linear relations were found between the irradiation dose and the decrease in the melting point, described by the correlation coefficient (between 0.9446 and 0.9864). No changes were observed in

  3. The influence of radiation sterilisation on some β-blockers in the solid state

    International Nuclear Information System (INIS)

    Research highlights: → Six β-blockers (acebutolol, alprenolol, atenolol, metoprolol, pindolol, propranolol) in solid phase were exposed to the ionising radiation by e-beam in doses from 25 to 400 kGy. → To establish the effects of irradiation on their physico-chemical properties, the compounds were then analysed by DSC, SEM, XRD and FT-IR. → For alprenolol, propranolol and metoprolol linear relations were found between the irradiation dose and the decrease in the melting point (r = 0.9446-0.9864). → No changes were observed in the FT-IR spectra and in the SEM images of the compounds studied. - Abstract: Six derivatives of aryloxyalkylaminopropanol of known β-adrenolytic activity (acebutolol, alprenolol, atenolol, metoprolol, pindolol, propranolol) in solid phase were exposed to the ionising radiation generated by e-beam of high-energy electrons from an accelerator (∼10 MeV) in doses from 25 to 400 kGy. To establish the effects of irradiation on their physico-chemical properties, the compounds were then analysed by differential scanning calorimetry (DSC), scanning electron microscope (SEM), X-ray diffraction (XRD) and FT-IR spectrometry. The standard sterilisation dose (25 kGy) was found to cause no changes in only one derivative - acebutolol, whereas in the other derivatives the irradiation caused colour changes, differences in X-ray diffraction patterns and in the character of DSC curves, including a decrease in the melting point. For each derivative one clear peak corresponding to the process of melting was observed and its position shifted towards lower temperatures with increasing dose of irradiation. For all compounds studied the value of the shift was between 0.1 and 1.0 oC. For alprenolol, propranolol and metoprolol linear relations were found between the irradiation dose and the decrease in the melting point, described by the correlation coefficient (between 0.9446 and 0.9864). No changes were observed in the FT-IR spectra and in the SEM images

  4. Cost of tumor necrosis factor blockers per patient with rheumatoid arthritis in a multistate Medicaid population

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    Bonafede M

    2014-09-01

    Full Text Available Machaon Bonafede,1 George J Joseph,2 Neel Shah,2 Nicole Princic,1 David J Harrison2 1Truven Health Analytics, Cambridge, MA, 2Amgen Inc., Thousand Oaks, CA, USA Background: The purpose of this study was to estimate the annual cost per treated patient for the tumor necrosis factor (TNF blockers, etanercept, adalimumab, and infliximab in rheumatoid arthritis (RA patients covered by Medicaid. Methods: The MarketScan Medicaid Multistate Database was used to identify adult RA patients who used etanercept, adalimumab, or infliximab (index agents from 2007 to 2011. The index date was the first claim preceded by 180 days and followed by 360 days of continuous enrollment. Patients with other conditions for which these agents are approved by the US Food and Drug Administration were excluded. “Continuing” patients had one or more pre-index claim for their index biologic, and "new" patients did not. Cost per treated patient was calculated in the 360 day post-index period for each index agent as the total index drug and administration cost to the payer and the costs of switched-to agents divided by the number of patients who received the index agent. Results: A total of 1,085 patients met the study criteria. Forty-eight percent received etanercept (n=521; 37% received adalimumab (n=405; and 15% received infliximab (n=159. Patient characteristics were similar across groups (mean age 47.4 years, 83% female. The annual cost per treated patient was lowest for etanercept ($18,466, followed by adalimumab ($20,983 and infliximab ($26,516. For all agents, annual costs were lower for new patients ($17,996 for etanercept, $18,992 for adalimumab, and $24,756 for infliximab than for continuing patients ($19,004 for etanercept, $24,438 for adalimumab, and $28,127 for infliximab. Conclusion: Etanercept had lower costs per treated patient than adalimumab or infliximab in both new and continuing Medicaid enrollees with RA. Keywords: cost, tumor necrosis factor

  5. Morphological and lectin histochemical characteristics of spleen under the experimental application of H1-histamine receptor blockers

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    Dudok O.V.

    2016-03-01

    Full Text Available Background. It is well known that histamine modulate immunocompetent cells cooperation, since plenty of them expose H- and H2- receptors for this biogenic amine. However, the influence of synthetic blockers of these receptors on the structure and function of the spleen – the immune system organ – remains obscure. Objective. To investigate the influence of widely used H1-receptor blocker Loratadine on the microstructure and lectin histochemistry characteristics of a rat spleen. Methods. Daily intragastric insertion of Loratadine at a dose of 0.15 mg/kg was maintained for 30 days. Thereafter (on days 10th, 30th of experiment and on days 10th, 20th and 30th after its completion tissue samples of spleen were excised and subjected to general morphology and lectin histochemistry investigation. Results. On the early stages of Loratadine administration it was detected the increased white pulp content. Further changes included the appearance of germinative centers in lymphoid follicles with simultaneous compactization of periarterial zones. Lectin histochemistry revealed the accumulation of dendritic cells, which were selectively labeled by PNA and GNA, while WGA demonstrated its suitability for differential staining of white and red pulp in the rat spleen. Conclusion. Prolonged Loratadine administration induce antigenic stimulation of the spleen. Lectins PNA and GNA can be recommended for selective labeling of activated dendritic cells, WGA – for differential staining of white and red pulp of the rat spleen. Citation: Dudok OV, Yashchenko AM, Lutsyk OD. [Morphological and lectin histochemical characteristics of spleen under the experimental application of H1-histamine receptor blockers]. Morphologia. 2016;10(1:32-7. Ukrainian.

  6. Beta-blockers, left and right ventricular function, and in-vivo calcium influx in muscular dystrophy cardiomyopathy.

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    Alison Blain

    Full Text Available Beta-blockers are used to treat acquired heart failure in adults, though their role in early muscular dystrophy cardiomyopathy is unclear. We treated 2 different dystrophic mouse models which have an associated cardiomyopathy (mdx: model for Duchenne Muscular Dystrophy, and Sgcd-/-: model for limb girdle muscular dystrophy type 2F and wild type controls (C57 Bl10 with the beta blocker metoprolol or placebo for 8 weeks at an early stage in the development of the cardiomyopathy. Left and right ventricular function was assessed with cardiac magnetic resonance imaging (MRI and in-vivo myocardial calcium influx with manganese enhanced MRI. In the mdx mice at baseline there was reduced stroke volume, cardiac index, and end-diastolic volume with preserved left ventricular ejection fraction. These abnormalities were no longer evident after treatment with beta-blockers. Right ventricular ejection fraction was reduced and right ventricular end-systolic volume increased in the mdx mice. With metoprolol there was an increase in right ventricular end-diastolic and end-systolic volumes. Left and right ventricular function was normal in the Sgcd-/- mice. Metroprolol had no significant effects on left and right ventricular function in these mice, though heart/body weight ratios increased after treatment. In-vivo myocardial calcium influx with MEMRI was significantly elevated in both models, though metoprolol had no significant effects on either. In conclusion, metoprolol treatment at an early stage in the development of cardiomyopathy has deleterious effects on right ventricular function in mdx mice and in both models no effect on increased in-vivo calcium influx. This suggests that clinical trials need to carefully monitor not just left ventricular function but also right ventricular function and other aspects of myocardial metabolism.

  7. The use of alpha-1 adrenergic blockers in children with distal ureterolithiasis: a systematic review and meta-analysis

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    F.P. Glina

    2015-12-01

    Full Text Available Introduction: Urinary lithiasis is the main urologic cause of emergency treatment in adult patient. In the past years, the incidence in children population has increased. However, literature about the use of alpha-1 adrenergic blockers in pediatric population with distal ureterolithiasis is still scarce. The drug acts by decreasing ureter contractions, especially in the distal portion, facilitating calculus expulsion. Objective: This review has the objective to evaluate the use of alpha-1 adrenergic blockers as medical expulsive treatment in children with distal ureterolithiasis. Evidence Acquisition: An electronic literature search was performed using the MEDLINE, COCHRANE, and LILACS databases. We further searched manually the references of the primary studies. Searches were concluded on October 4th, 2014. Articles were selected, independently and in pairs, by the respective titles and summaries. Any divergence was resolved by consensus. Evidence Synthesis: Alpha-1 adrenergic antagonists increased the probability of calculus expulsion by 27% (NNT=4. Calculi smaller than 5mm, increased by 33% (NNT=3. Larger than 5mm, increased by 34% (NNT=3. Conclusion: Alpha-1 adrenergic blocker use is related with a greater incidence of expulsion of ureteral calculi, smaller or greater than 5mm, and fewer episodes of pain when compared to ibuprofen. However it is necessary larger samples to enhance the power analysis of the expulsion of ureteral calculi larger than 5mm and the episodes of pain. Patient Summary: This review analyzed the outcome of alpha adrenergic antagonist in children with ureteral calculi. We conclude that it is the best medicine for use, since it helps the expulsion of the stone.

  8. Early intravenous beta-blockers in patients with acute coronary syndrome–A meta-analysis of randomized trials

    Science.gov (United States)

    Chatterjee, Saurav; Chaudhuri, Debanik; Vedanthan, Rajesh; Fuster, Valentin; Ibanez, Borja; Bangalore, Sripal; Mukherjee, Debabrata

    2014-01-01

    Background Intravenous (IV) beta-blockade is currently a Class IIa recommendation in early management of patients with acute coronary syndromes (ACS) without obvious contraindications. Methods We searched the PubMed, EMBASE and the Cochrane Register for Controlled Clinical Trials for randomized clinical trials from 1965 through December, 2011, comparing intravenous beta-blockers administered within 12 hours of presentation of ACS with standard medical therapy and/or placebo. The primary outcome assessed was the risk of short-term (in-hospital mortality-with maximum follow up duration of 90 days) all-cause mortality in the intervention group versus the comparator group. The secondary outcomes assessed were ventricular tachyarrhythmias, myocardial reinfarction, cardiogenic shock, and stroke. Pooled treatment effects were estimated using relative risk with Mantel–Haenszel risk ratio, using a random-effects model. Results Sixteen studies enrolling 73,396 participants met the inclusion / exclusion criteria. In- hospital mortality was reduced 8% with intravenous beta-blockers, RR=0.92 (95% CI, 0.86–1.00; p=0.04) when compared with controls. Moreover, intravenous beta-blockade reduced the risk of ventricular tachyarrhythmias (RR=0.61; 95 % CI 0.47–0.79; p=0.0003) and myocardial reinfarction (RR=0.73, 95 % CI 0.59–0.91; p=0.004) without increase in the risk of cardiogenic shock, (RR=1.02; 95% CI 0.77–1.35; p=0.91) or stroke (RR=0.58; 95 % CI 0.17–1.98; p=0.38). Conclusions Intravenous beta-blockers early in the course of appropriate patients with ACS appears to be associated with significant reduction in the risk of short-term cardiovascular outcomes, including a reduction in the risk of all-cause mortality. PMID:23168009

  9. The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation

    Science.gov (United States)

    Choi, Wungrak; Noh, Hyemi; Yeo, Areum; Jang, Hanmil; Ahn, Hyea Kyung; Song, Yeon Jung

    2016-01-01

    Purpose Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presented data showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. The purpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 compared to cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337 represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporine A was determined using an experimental murine dry eye model. Methods The TNF-α blocker HL036337 is a modified form of TNF receptor I. Using dry eye induced C57BL/6 mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A or HL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topically administered twice per day to dry eye induced murine corneas for 1 week. Results The optimal concentration of the TNF-α blocker HL036337 for treatment of dry eye induced corneal erosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topically applied cyclosporine A and HL036337 at 1 mg/mL. Conclusions HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dry eye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome. PMID:27478358

  10. Antineoplastic Effect of Calcium Channel Blocker-Verapamil and 5-Fluorouracil Intraperitoneal Chemotherapy on Hepatocarcinoma-Bearing Rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy on hepatocarcinoma-bearing rats,and examine the action between calcium channel blockers and cytotoxic drugs. Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of liver carcinoma-bearing rats.All experimental animals were divided into four groups.On the sixth day post implantation,in group A (control group) 6ml of saline was injected intraperitoneally once a day for 3 days.In group B(single chemotherapy group) 6ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days.In group C(combination of treatment group)both 5-Fu(75mg/kg) and verapamil (25mg/kg) were administered simultaneously as in A and B.In group D(simple verapamil group)only 6ml of verapamil(25mg/kg)was administered as above. Results Compared with groups A, B and D,The volume of cancer and the contents of liver cancer DNA and protein were significantly reduced.The rates of inhibiting cancer(89.9% in group C and 35.4% in group B)were significantly increased in groupC. Group C had significantly long survival time compared to groups A, B and D(P<0.05).By light microscopy, a number of focal necroses were found in cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitonea chemotherapy to liver cancer;The use of verapamil can not increase the toxicity of 5-Fu.

  11. Effects of telmisartan on body fat, serum lipids and insulin resistance in patients with obesity hypertension%替米沙坦对肥胖性高血压患者体脂、血脂及胰岛素抵抗的影响

    Institute of Scientific and Technical Information of China (English)

    黄国秀; 余文珊; 伍广伟; 谭文芳; 李建英; 叶伟林; 温建东; 陈健

    2011-01-01

    目的 探讨替米沙坦对肥胖性高血压患者体脂、血脂、胰岛素抵抗的影响.方法 BMI≥125 kg/m的原发性高血压患者60例,随机分成观察组和对照组,并分别给予替米沙坦和硝苯地平缓释片干预,观察干预前后BP、BMI、腰臀比(W/H)、TC、LDL-C、TG、胰岛素抵抗指数(IRI)、高敏C反应蛋白(hsCRP)等指标变化.结果 与干预前比较,干预后12、24周两组BP均下降(P<0.01),干预后24周观察组W/H、TG、IRI、hsCRP下降(P<0.01或P<0.05).观察组IRI、hsCRP的变化与SBP、DBP、BMI、W/H、TG等呈直线相关.结论 替米沙坦除良好的降压外,有一定的减轻腹型肥胖、控制TG和改善胰岛素抵抗的作用.%Objective To investigate the effects of telmisartan on serum lipids and insulin resistance in patients with obesity hypertension. Methods Sixty patients with hypertension and BMI ≥ 25 kg/m2 were randomly divided into treatment group and control group (n= 30) treated with telmisartan and nifedipine, respectively. The expression levels of BP, BMI,W/H, TG, TC, LDL-C, IRI and hsCRP were examined before and after treatment for 12 and 24 weeks. Results Compared with pre-treatment, the BP in both groups decreased significantly after treatment for 12 and 24 weeks (P < 0. 01 ).Simultaneously, the expression levels of W/H, TG, IRI, hsCRP were decreased significantly after 24 weeks in the treatment group ( P < 0. 01 or P < 0. 05 ). Correlation analysis proved that the expression levels of IRI, hsCRP were linearly related with SBP, DBP, BMI, W/H and TG. Conclusion Telmisartan can reduce BP and decrease the levels of W/H,TG, IRI with a certain extent.

  12. Anti-aging effect of simvastatin and telmisartan on retinas and its mechanism in rats%辛伐他汀和替米沙坦对大鼠视网膜衰老的延缓作用及其机制

    Institute of Scientific and Technical Information of China (English)

    王静; 康前雁

    2016-01-01

    Background Statins has prominent roles in regulating lipids,anti-inflammation,autoxidation and protecting vascular endothelial cells.Sartans can promote cell growth and the expression of cytokines.Since the pleiotropic effects of statins and sartans on a variety of cell types,it is inferred that the two medicines can delay retinal aging.Objective This study was to explore the anti-aging effect of simvastatin and telmisartan on the physiological aging of retina.Methods Sixty-six three-month-old healthy SD rats were selected in this study,and 6 of them served as the youth group and the right eyeballs were immediately enucleated.The other rats were raised until 9-month-old in the same conditions and then randomly divided into the simvastatin group,telmisartan group and the control group with 20 rats for each group.The simvastatin of 5 mg/kg and telmisartan of 8 mg/kg were given by intragastric administration once a day in the simvastatin group and the telmisartan group until 17-month-old,and the equal amount of normal saline was used in the control group in the same way.The number of survival rats was 12 in the simvastatin group,10 in the telmisartan group and 8 in the control group.The right eyes were enucleated after heart perfusion of 4% paraformaldehyde solution for the preparation of retinal paraffin sections.Retinal thickness was measured by pathological examination,and the expressions of the retinal neuron markers,including Thy-1,protein kinase C-α (PKC-ot),opsin and rhodopsin,were detected by immunofluorescence technique to evaluate the morphology of retinal ganglion cells (RGCs),bipolar cells as well as the thickness of the outer segment of photoreceptors.Results The retinal structure was clear in the rats of the youth group.However,the RGCs arrangement and inner segment (IS) and outer segment (OS) structure were abnormal in the simvastatin group,the telmisartan group and the control group.Compared with the rats of the youth group,the thickness of outer

  13. 替米沙坦对糖尿病合并高血压患者脂代谢紊乱的影响%Effects of telmisartan on glucose and lipid metabolism disorders in patients with diabetes mellitus and hypertension

    Institute of Scientific and Technical Information of China (English)

    钱虹

    2014-01-01

    Objective To discuss effects of telmisartan on glucose and lipid metabolism disorders in patients with diabetes mellitus and hypertension.Methods One hundred and twenty patients with type 2 diabetes mellitus and hypertension were divided into observation group (60 cases) and control group (60 cases).Observation group was given telmisartan and control group was given nifedipine.Blood pressure,fasting blood glucose (FBG),postpranddial blood sugar (PBG 2 h),glycated hemoglobin (HbA1 c),triglycerides (TG),total cholesterol(TC),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C),insulin (FINS),liver and kidney function and electrocardiogram of two groups before and after treatment were observed and compared.Results There were significant differences on systolic blood pressure (SBP) [observation group:(131 ± 7) mmHg; control group:(136 ± 5) mmHg],diastolic blood pressure (DBP) [observation group:(82 ±4) mmHg; control group:(91 ± 6)mmHg] of observation group compared with before treatment [observation group:SBP:(163 ± 11) mmHg,DBP:(102 ± 5) mmHg; control group:SBP:(162 ± 9) mmHg,DBP:(100 ± 3) mmHg](P < 0.05).There were significant differences on SBP,DBP between two group after treatment (P < 0.05).TC [(4.1 ± 0.9) mmol/L],TG [(1.6 ± 0.8) mmol/L],FINS [(15 ± 7) mIU/L] of observation group after treatment were lower than that of before treatment [(5.7 ± 1.7) mmol/L,(3.3 ± 1.4) mmol/L,(21 ± 13) mIU/L] (P < 0.05).There were significant differences on TG,FINS of observation group compared with control group [TG:(3.5 ± 1.4) mmol/L,FINS(22 ± 13) mlU/L] (P < 0.01).The total effective rate of observation group [88.3% (53/60)] was higher than that of control group [75.0% (45/60)] (P <0.05).Adverse effects rate of observation group [3.3% (2/60)] was lower than that of control group [15.0% (9/60)] (P < 0.01).Conclusion Telmisartan in the treatment of diabetes mellitus and hypertension is safe and effective and

  14. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Diana Machado

    Full Text Available Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction

  15. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Machado, Diana; Pires, David; Perdigão, João; Couto, Isabel; Portugal, Isabel; Martins, Marta; Amaral, Leonard; Anes, Elsa; Viveiros, Miguel

    2016-01-01

    Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a) in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b) on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction irrespective of their

  16. Dosage of angiotensin-II receptor blockers in heart failure patients following changes in Danish drug reimbursement policies

    DEFF Research Database (Denmark)

    Selmer, Christian; Lamberts, Morten; Kristensen, Søren Lund;

    2014-01-01

    PURPOSE: National reimbursement policies in Denmark were changed in November 2010 favouring a shift in angiotensin-II receptor blocker (ARB) treatment to generic losartan for heart failure (HF) patients. We examined how changes in reimbursement policies affected the fraction of HF patients up......, respectively. Individual-level linkage of nationwide registries of hospitalization and drug dispensing in Denmark was used to describe patterns of ARB prescriptions and estimate dosage before and after November 2010. Logistic regression models were used to assess the probability for being up-titrated in the...

  17. Adsorption and Photocatalytic Decomposition of the -Blocker Metoprolol in Aqueous Titanium Dioxide Suspensions: Kinetics, Intermediates, and Degradation Pathways

    OpenAIRE

    Violette Romero; Pilar Marco; Jaime Giménez; Santiago Esplugas

    2013-01-01

    This study reports the photocatalytic degradation of the β-blocker metoprolol (MET) using TiO2 suspended as catalyst. A series of photoexperiments were carried out by a UV lamp, emitting in the 250–400 nm range, providing information about the absorption of radiation in the photoreactor wall. The influence of the radiation wavelength on the MET photooxidation rate was investigated using a filter cutting out wavelengths shorter than 280 nm. Effects of photolysis and adsorption at different ini...

  18. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis

    Science.gov (United States)

    Perdigão, João; Couto, Isabel; Portugal, Isabel; Martins, Marta; Amaral, Leonard; Anes, Elsa; Viveiros, Miguel

    2016-01-01

    Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a) in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b) on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction irrespective of their

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

    OpenAIRE

    LIU, TIAN-JING; SHI, YONG-YAN; WANG, EN-BO; Zhu, Tong; Zhao, Qun

    2015-01-01

    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 acc...

  20. Effectiveness comparison of cardio-selective to non-selective β-blockers and their association with mortality and morbidity in end-stage renal disease: a retrospective cohort study

    OpenAIRE

    Shireman, Theresa I.; Mahnken, Jonathan D.; Phadnis, Milind A; Ellerbeck, Edward F.

    2016-01-01

    Background Within-class comparative effectiveness studies of β-blockers have not been performed in the chronic dialysis setting. With widespread cardiac disease in these patients and potential mechanistic differences within the class, we examined whether mortality and morbidity outcomes varied between cardio-selective and non-selective β-blockers. Methods Retrospective observational study of within class β-blocker exposure among a national cohort of new chronic dialysis patients (N = 52,922) ...