Dose-dependent effects of atorvastatin on myocardial infarction

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Barbarash O

2015-06-01

Full Text Available Olga Barbarash, Olga Gruzdeva, Evgenya Uchasova, Ekaterina Belik, Yulia Dyleva, Victoria KaretnikovaFederal State Budgetary Institution, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, the Russian Federation Background: Dyslipidemia is a key factor determining the development of both myocardial infarction (MI and its subsequent complications. Dyslipidemia is associated with endothelial dysfunction, activation of inflammation, thrombogenesis, and formation of insulin resistance. Statin therapy is thought to be effective for primary and secondary prevention of complications associated with atherosclerosis.Methods: This study examined 210 patients with Segment elevated MI (ST elevated MI who were treated with atorvastatin from the first 24 hours after MI. Group 1 (n=110 were given atorvastatin 20 mg/day. Group 2 (n=100 were given atorvastatin 40 mg/day. At days 1 and 12 after MI onset, insulin resistance levels determined by the homeostasis model assessment of insulin resistance index, lipid profiles, and serum glucose, insulin, adipokine, and ghrelin levels were measured.Results: Free fatty acid levels showed a sharp increase during the acute phase of MI. Treatment with atorvastatin 20 mg/day, and especially with 40 mg/day, resulted in a decrease in free fatty acid levels. The positive effect of low-dose atorvastatin (20 mg/day is normalization of the adipokine status. Administration of atorvastatin 20 mg/day was accompanied with a statistically significant reduction in glucose levels (by 14% and C-peptide levels (by 38%, and a decrease in the homeostasis model assessment of insulin resistance index on day 12.Conclusion: Determination of atorvastatin dose and its use during the in-hospital period and subsequent periods should take into account changes in biochemical markers of insulin resistance and adipokine status in patients with MI.Keywords: myocardial infarction, statin, insulin resistance, adipokines

Effects of atorvastatin on human c reactive protein metabolism

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Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goals were to define the mechanisms by which CRP was reduced by maximal dose atorvastatin. Eight subjects with combined hyperlipidemia (5 men and 3 postmenopausal women) were enrolled in a randomized, placebo-controlled...

Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin

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Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Liantonio, Antonella; Musaraj, Kejla; Cannone, Maria; Fonzino, Adriano; Giustino, Arcangela; De Luca, Annamaria; Romano, Rossella; Camerino, Claudia; Laghezza, Antonio; Loiodice, Fulvio; Desaphy, Jean-Francois; Conte Camerino, Diana; Pierno, Sabata

2016-01-01

Statin-induced skeletal muscle damage in rats is associated to the reduction of the resting sarcolemmal chloride conductance (gCl) and ClC-1 chloride channel expression. These drugs also affect the ClC-1 regulation by increasing protein kinase C (PKC) activity, which phosphorylate and close the channel. Also the intracellular resting calcium (restCa) level is increased. Similar alterations are observed in skeletal muscles of aged rats, suggesting a higher risk of statin myotoxicity. To verify this hypothesis, we performed a 4–5-weeks atorvastatin treatment of 24-months-old rats to evaluate the ClC-1 channel function by the two-intracellular microelectrodes technique as well as transcript and protein expression of different genes sensitive to statins by quantitative real-time-PCR and western blot analysis. The restCa was measured using FURA-2 imaging, and histological analysis of muscle sections was performed. The results show a marked reduction of resting gCl, in agreement with the reduced ClC-1 mRNA and protein expression in atorvastatin-treated aged rats, with respect to treated adult animals. The observed changes in myocyte-enhancer factor-2 (MEF2) expression may be involved in ClC-1 expression changes. The activity of PKC was also increased and further modulate the gCl in treated aged rats. In parallel, a marked reduction of the expression of glycolytic and mitochondrial enzymes demonstrates an impairment of muscle metabolism. No worsening of restCa or histological features was found in statin-treated aged animals. These findings suggest that a strong reduction of gCl and alteration of muscle metabolism coupled to muscle atrophy may contribute to the increased risk of statin-induced myopathy in the elderly. - Highlights: • This work characterizes the causes of atorvastatin related myotoxicity in aged rats. • Skeletal muscle chloride channel ClC-1 is a target of statin-induced side effects. • ClC-1 dysfunction is worsened by aging process. • Age

Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin

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Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Liantonio, Antonella; Musaraj, Kejla; Cannone, Maria; Fonzino, Adriano [Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy); Giustino, Arcangela [Department of Biomedical Sciences and Human Oncology, University of Bari - Aldo Moro, Medical School, Bari (Italy); De Luca, Annamaria; Romano, Rossella [Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy); Camerino, Claudia [Department of Medical Sciences, Neurosciences and Sense Organs, University of Bari - Aldo Moro, Bari (Italy); Laghezza, Antonio; Loiodice, Fulvio [Section of Medicinal Chemistry, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy); Desaphy, Jean-Francois [Department of Biomedical Sciences and Human Oncology, University of Bari - Aldo Moro, Medical School, Bari (Italy); Conte Camerino, Diana [Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy); Pierno, Sabata, E-mail: sabata.pierno@uniba.it [Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy)

2016-09-01

Statin-induced skeletal muscle damage in rats is associated to the reduction of the resting sarcolemmal chloride conductance (gCl) and ClC-1 chloride channel expression. These drugs also affect the ClC-1 regulation by increasing protein kinase C (PKC) activity, which phosphorylate and close the channel. Also the intracellular resting calcium (restCa) level is increased. Similar alterations are observed in skeletal muscles of aged rats, suggesting a higher risk of statin myotoxicity. To verify this hypothesis, we performed a 4–5-weeks atorvastatin treatment of 24-months-old rats to evaluate the ClC-1 channel function by the two-intracellular microelectrodes technique as well as transcript and protein expression of different genes sensitive to statins by quantitative real-time-PCR and western blot analysis. The restCa was measured using FURA-2 imaging, and histological analysis of muscle sections was performed. The results show a marked reduction of resting gCl, in agreement with the reduced ClC-1 mRNA and protein expression in atorvastatin-treated aged rats, with respect to treated adult animals. The observed changes in myocyte-enhancer factor-2 (MEF2) expression may be involved in ClC-1 expression changes. The activity of PKC was also increased and further modulate the gCl in treated aged rats. In parallel, a marked reduction of the expression of glycolytic and mitochondrial enzymes demonstrates an impairment of muscle metabolism. No worsening of restCa or histological features was found in statin-treated aged animals. These findings suggest that a strong reduction of gCl and alteration of muscle metabolism coupled to muscle atrophy may contribute to the increased risk of statin-induced myopathy in the elderly. - Highlights: • This work characterizes the causes of atorvastatin related myotoxicity in aged rats. • Skeletal muscle chloride channel ClC-1 is a target of statin-induced side effects. • ClC-1 dysfunction is worsened by aging process. • Age

Effects of atorvastatin on renal function in patients with dyslipidemia and chronic kidney disease: assessment of clinical usefulness in CKD patients with atorvastatin (ASUCA) trial.

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Kimura, Genjiro; Kasahara, Masato; Ueshima, Kenji; Tanaka, Sachiko; Yasuno, Shinji; Fujimoto, Akira; Sato, Toshiya; Imamoto, Miyuki; Kosugi, Shinji; Nakao, Kazuwa

2017-06-01

Dyslipidemia is a risk factor for the progression of chronic kidney disease (CKD). While conventional lipid lowering therapy provides a benefit to CKD management, the effect of statins on eGFR remains unclear. A prospective, multi-center, open-labeled, randomized trial. Total of 349 CKD patients with hyperlipidemia were randomized into 2 groups, and followed for 2 years. Group A included patients who were treated with atorvastatin. Group C were treated with conventional lipid lowering drugs other than statin. Primary endpoint was changes in eGFR. Secondary endpoints included changes in urinary albumin excretion, serum LDL-C, serum triglyceride, cardio-vascular events and all-cause mortality. As the primary endpoint, eGFR decreased by 2.3 ml/min/1.73 m 2 in Group A and by 2.6 ml/min/1.73 m 2 in Group C, indicating that there was no difference in change of eGFR between the two groups. As secondary endpoints, atorvastatin succeeded to reduce serum LDL-C level significantly and rapidly, but conventional therapy did not. In fact, mean LDL-C level did not reach the target level of 100 mg/dl in Group C. Serum triglyceride was lowered only by atorvastatin, but not conventional drugs. The number of cardiovascular events and all-cause mortality did not differ between in two groups. The ASUCA (Assessment of Clinical Usefulness in CKD Patients with Atorvastatin) trial demonstrated that atorvastatin failed to exhibit reno-protections compared to conventional therapy in Japanese patients with dyslipidemia and CKD. It would be due in part to the ability of atorvastatin to more potently reduce serum LDL and triglycerides compared to conventional therapy.

Atorvastatin can ameliorate left atrial stunning induced by radiofrequency ablation for atrial fibrillation.

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Xie, Ruiqin; Yang, Yingtao; Cui, Wei; Yin, Hongning; Zheng, Hongmei; Zhang, Jidong; You, Ling

2017-09-01

The objective of this study was to study the functional changes of the left atrium after radiofrequency ablation treatment for atrial fibrillation and the therapeutic effect of atorvastatin. Fifty-eight patients undergoing radiofrequency ablation for atrial fibrillation were randomly divided into non-atorvastatin group and atorvastatin group. Patients in the atorvastatin group were treated with atorvastatin 20 mg p.o. per night in addition to the conventional treatment of atrial fibrillation; patients in the non-atorvastatin group received conventional treatment of atrial fibrillation only. Echocardiography was performed before radiofrequency ablation operation and 1 week, 2 weeks, 3 weeks, and 4 weeks after operation. Two-dimensional ultrasound speckle tracking imaging system was used to measure the structural indexes of the left atrium. Results indicated that there was no significant change for indexes representing the structural status of the left atrium within a month after radiofrequency ablation (P > 0.05); however, there were significant changes for indexes representing the functional status of the left atrium. There were also significant changes in indexes reflecting left atrial strain status: the S and SRs of atorvastatin group were higher than those of non-atorvastatin group (P atorvastatin could improve left atrial function and shorten the duration of atrial stunning after radiofrequency ablation of atrial fibrillation.

Atorvastatin Use Associated With Acute Pancreatitis

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Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

2016-01-01

Abstract Few data are present in the literature on the relationship between atorvastatin use and acute pancreatitis. The aim of this study was to explore this issue in Taiwan. Using representative claims data established from the Taiwan National Health Insurance Program, this case–control study consisted of 5810 cases aged 20 to 84 years with a first-time diagnosis of acute pancreatitis during the period 1998 to 2011and 5733 randomly selected controls without acute pancreatitis. Both cases and controls were matched by sex, age, comorbidities, and index year of diagnosing acute pancreatitis. Subjects who at least received 1 prescription for other statins or nonstatin lipid-lowering drugs were excluded from the study. If subjects never had 1 prescription for atorvastatin, they were defined as never use of atorvastatin. Current use of atorvastatin was defined as subjects whose last remaining 1 tablet of atorvastatin was noted ≤7 days before the date of diagnosing acute pancreatitis. Late use of atorvastatin was defined as subjects whose last remaining 1 tablet of atorvastatin was noted >7 days before the date of diagnosing acute pancreatitis. The odds ratio with 95% confidence interval of acute pancreatitis associated with atorvastatin use was calculated by using the logistic regression analysis. The logistic regression analysis revealed that the odds ratio of acute pancreatitis was 1.67 for subjects with current use of atorvastatin (95% confidence interval 1.18, 2.38), when compared with subjects with never use of atorvastatin. The odds ratio decreased to 1.15 for those with late use of atorvastatin (95% confidence interval 0.87, 1.52), but without statistical significance. Current use of atorvastatin is associated with the diagnosis of acute pancreatitis. Clinically, clinicians should consider the possibility of atorvastatin-associated acute pancreatitis when patients present with a diagnosis of acute pancreatitis without a definite etiology but are taking

Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study

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Wieczorek-Surdacka, Ewa; Świerszcz, Jolanta; Surdacki, Andrzej

2016-01-01

Angiotensin-converting enzyme inhibitors (ACEI) and statins are widely used in patients with coronary artery disease (CAD). Our aim was to compare changes in glomerular filtration rate (GFR) over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL) cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10–40 mg for ≥3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean ± SEM: −4.2 ± 2.4, 1.1 ± 1.6, 5.2 ± 2.4 mL/min per 1.73 m2 for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman’s rho = 0.50, p = 0.001 for trend). In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: −1.3 ± 1.0, −4.7 ± 2.1, 4.8 ± 3.6 mL/min per 1.73 m2, p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend). The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD. PMID:26848655

Assessment of Atorvastatin Effectiveness on Serum PSA Level in Hypercholesterolemic Males

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Darya Khosropanah

2011-12-01

Full Text Available The previous large retrospective studies demonstrated that treatment with Statins reduces both the incidence of prostate cancer by 50% and serum Prostate Specific Antigen (PSA level up to 40%. However the main problem in those studies was the absence of control groups of men with hypercholesterolemia without Statin treatment. We performed a small prospective controlled clinical trial to assess the influence of the treatment with Atorvastatin on serum PSA in men with hypercholesterolemia referred to our educational and treatment center from October 2007 to March 2008. In this study, among the newly diagnosed males with hypercholesterolemia (LDL > 130 mg/dl, 40 patients with LDL more than 190 mg/dl were selected as a case group and were treated with Atorvastatin (20 mg/day. Among the same population and in the same period, another 40 patients with LDL between 130 and 190 mg/dl were selected as first control group and were treated only with low fat diet. Another 40 patients with normal serum cholesterol and without any treatment were selected as second control group. The lipid profile and serum PSA level of patients of all groups were tested at the first and third months after the therapy. After completion of data, the mean serum lipids and PSA level were measured in both visits and compared with each other by paired t-test. Also the mean PSA change in two visits between three groups was compared by ANOVA and Tukey HSD test. There was not any significant difference in mean baseline PSA between hypercholesterolemic and normocholesterolemic patients (P=0.547. In case group, mean PSA and LDL was reduced by 14.1% (P=0.0001 and 30% (P=0.0001 respectively by second visit. In first control group, mean PSA was not changed significantly (P=0.337, whereas mean LDL in this group was reduced by 9.6% (P= 0.0001. Similarly in the second control group mean PSA was not changed significantly (P=0.309 by second visit. In addition, mean change of PSA in case group

Atorvastatin repurposing for the treatment of cryptosporidiosis in experimentally immunosuppressed mice.

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Madbouly Taha, Noha; Salah A Yousof, Hebat-Allah; El-Sayed, Shaimaa H; Younis, Azza Ibrahim; Ismail Negm, Mohamed Sherif

2017-10-01

The present study was conducted on 200 male mice for the detection of the effect of Atorvastatin on Cryptosporidium spp. infection versus the commercially used drug Nitazoxanide in experimentally immunosuppressed mice. Atorvastatin was used alone at low dose (20 mg/kg), high dose (40 mg/kg), and combined with Nitazoxanide (1000 mg/kg) with either the low dose or high dose for five consecutive days. Parasitological assessment of the drug effect was done using Modified Z-N staining of stool samples collected from mice. Results revealed a reduction of the number of oocysts shed with percentage of reduction on the 21st day post infection by 53.7%, 67.2%, 70.1% &77.5%, respectively, compared to the infected untreated group. The Nitazoxanide treated group showed 52.7% reduction. In addition, examination of small and large intestinal contents after mice scarification revealed reduced numbers of oocysts by 56.2%-58.8%, 65.1%-65.3%, 70.6%-73.9% and 77.8%-79.9%, respectively, compared to 51.2%-54.1% in Nitazoxanide treated group. The histopathological examination of sections from duodenum, jejunum, ileum, colon, stomach and lungs also revealed a significant improvement of the histopathological changes in Atorvastatin treated groups and more remarkable improvement in the groups treated with combined drugs as compared to infected untreated group. Accordingly, the combination of Atorvastatin and Nitazoxanide showed a synergistic effect through reduction of the number of oocysts shed and improvement of the histopathological changes induced by Cryptosporidium spp. infection in the small intestine, colon, stomach and lungs of infected immunosuppressed mice in comparison to that induced by either Nitazoxanide or Atorvastatin alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Generic atorvastatin, the Belgian statin market and the cost-effectiveness of statin therapy.

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Simoens, Steven; Sinnaeve, Peter R

2013-02-01

This study examines how the market entry of generic atorvastatin influences the Belgian statin market and the cost-effectiveness of statin therapy. Using IMS Health data, the Belgian 2000-2011 statin market was analyzed in terms of total expenditure, annual price of statin treatment, and patient numbers. A simulation analysis projected statin market shares from 2012 to 2015 following market entry of generic atorvastatin. This analysis was based on three scenarios regarding the number of patients taking specific statins. Savings associated with an atorvastatin price reduction of 50-70 % were calculated. A literature review of economic evaluations assessed the cost-effectiveness of generic atorvastatin. Statin expenditure increased from €113 million in 2000 to €285 million in 2011 due to higher expenditure on atorvastatin and rosuvastatin. Although the number of patients treated with simvastatin increased by nearly 800 %, the resulting increase in expenditure was partially offset by price reductions. Atorvastatin is projected to become the dominant product in the Belgian statin market (market share of 47-66 % by 2015). Annual savings would attain €108.6-€153.7 million for a 50 % reduction in the atorvastatin price and €152.0-€215.2 million for a 70 % price reduction. The literature suggests that generic atorvastatin is cost-effective as compared to simvastatin. The limited evidence about the cost-effectiveness of rosuvastatin as compared with generic atorvastatin is inconclusive. Generic atorvastatin is cost-effective as compared to simvastatin, is projected to become the dominant product in the Belgian statin market and is expected to generate substantial savings to health care payers.

Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

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Smiderle, Lisiane [Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Lima, Luciana O.; Hutz, Mara Helena [Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Sand, Cézar Roberto Van der; Sand, Luiz Carlos Van der; Ferreira, Maria Elvira Wagner; Pires, Renan Canibal [Centro de Diagnóstico Cardiológico, Porto Alegre, RS (Brazil); Almeida, Silvana; Fiegenbaum, Marilu [Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

2014-07-15

Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

International Nuclear Information System (INIS)

Smiderle, Lisiane; Lima, Luciana O.; Hutz, Mara Helena; Sand, Cézar Roberto Van der; Sand, Luiz Carlos Van der; Ferreira, Maria Elvira Wagner; Pires, Renan Canibal; Almeida, Silvana; Fiegenbaum, Marilu

2014-01-01

Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations

Protective effect of atorvastatin on radiation-induced endothelial cell injury

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Xinze, Ran; Huaien, Zheng; Fengchao, Wang; Xi, Ran; Aiping, Wang; Jing, Han; Yanqi, Zhang; Jun, Chen [Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing (China)

2009-04-15

Objective: To explore the protective effect of atorvastatin on irradiated endothelium and the thrombomodulin (TM) expression. Methods: Cultured human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were treated by atorvastatin at the final concentration of 10 {mu}mol/ml for 10 min, and then irradiated with 2 and 25 Gy. Cell cycles status and TM expression were quantitatively measured by flow cytometry 24 hours after irradiation. Protein C activation in endothelial cells was also assessod. Results: After administration with atorvastatin for 24 h, the TM expression increased by 77%, 59% and 61% in normal control group, 2 Gy group and 25 Gy group, respectively (t=27.395, 26.420, 58.065; P=0.000). The protein C levels decreased by 23% and 34% compared with the normal group post-irradiation to 2 and 25 Gy, but increased by 79% and 76% compared with the irradiated control group after administration with atorvastatin. The rates of cell apoptosis decreased by 6% and 16% in 2 Gy and 25 Gy groups, respectively after administration with atorvastatin for 24 h (t=4.178, 17.863; P=0.000). Conclusions: Atorva statin can protect endothelia cell from irradiation-induced apeptosis by increasing TM expression and protein C activation. (authors)

Protective effect of atorvastatin on radiation-induced endothelial cell injury

International Nuclear Information System (INIS)

Ran Xinze; Zheng Huaien; Wang Fengchao; Ran Xi; Wang Aiping; Han Jing; Zhang Yanqi; Chen Jun

2009-01-01

Objective: To explore the protective effect of atorvastatin on irradiated endothelium and the thrombomodulin (TM) expression. Methods: Cultured human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were treated by atorvastatin at the final concentration of 10 μmol/ml for 10 min, and then irradiated with 2 and 25 Gy. Cell cycles status and TM expression were quantitatively measured by flow cytometry 24 hours after irradiation. Protein C activation in endothelial cells was also assessod. Results: After administration with atorvastatin for 24 h, the TM expression increased by 77%, 59% and 61% in normal control group, 2 Gy group and 25 Gy group, respectively (t=27.395, 26.420, 58.065; P=0.000). The protein C levels decreased by 23% and 34% compared with the normal group post-irradiation to 2 and 25 Gy, but increased by 79% and 76% compared with the irradiated control group after administration with atorvastatin. The rates of cell apoptosis decreased by 6% and 16% in 2 Gy and 25 Gy groups, respectively after administration with atorvastatin for 24 h (t=4.178, 17.863; P=0.000). Conclusions: Atorva statin can protect endothelia cell from irradiation-induced apeptosis by increasing TM expression and protein C activation. (authors)

Atorvastatin 10 mg plus ezetimibe 10mg compared with atorvastatin 20 mg: impact on the lipid profile in Japanese patients with abnormal glucose tolerance and coronary artery disease.

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Uemura, Yusuke; Watarai, Masato; Ishii, Hideki; Koyasu, Masayoshi; Takemoto, Kenji; Yoshikawa, Daiji; Shibata, Rei; Matsubara, Tatsuaki; Murohara, Toyoaki

2012-01-01

Oxidized low-density lipoprotein (LDL) cholesterol is a sensitive lipid marker for predicting atherosclerosis. Ezetimibe and statins are reported to decrease both LDL cholesterol and oxidized LDL cholesterol. This prospective randomized open-label crossover study compared combination therapy with atorvastatin plus ezetimibe versus high-dose atorvastatin monotherapy. Changes in serum lipids, including malondialdehyde-modified LDL (MDA-LDL) as a representative form of oxidized LDL cholesterol, and glucose metabolism were assessed. The subjects were 39 Japanese patients with coronary artery disease and type 2 diabetes or impaired glucose tolerance who were taking 10 mg/day of atorvastatin (30 men and 9 women with a mean age of 67.8 years). They were randomized to a group that first received add-on ezetimibe (10 mg/day) or a group that first received atorvastatin monotherapy at a higher dose of 20 mg/day. Both treatments were given for 12 weeks each in a crossover fashion. Add-on ezetimibe significantly decreased MDA-LDL (109.0 ± 31.9 mg/dl to 87.7 ± 29.4 mg/dl, p=0.0009), while up-titration of atorvastatin did not. The decrease with add-on ezetimibe was significantly greater than with up-titration of atorvastatin (p=0.0006). Total cholesterol and LDL cholesterol were significantly decreased by both treatments, but the percent reduction with add-on ezetimibe was significantly greater (pHigh-density lipoprotein cholesterol was significantly increased by both treatments and there was no significant difference between them. The apolipoprotein B/apolipoprotein A-I ratio and remnant-like particle cholesterol were only significantly decreased by add-on ezetimibe. Both treatments caused similar elevation of hemoglobin A(1c). In Japanese patients with type 2 diabetes or impaired glucose tolerance and coronary artery disease, adding ezetimibe (10 mg/day) to atorvastatin (10 mg/day) significantly improved the lipid profile compared with atorvastatin monotherapy at 20 mg

Effect of atorvastatin on preventing contrast-induced nephropathy

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Zhang Dongya; Zhu Jing; Chen Jianchang; Xu Weiting; Luo Xiaoyu; Zhao Liangping

2011-01-01

Objective: To study the effects of atorvastatin on contrast-induced renal function and urinary protein change in patients undergoing diagnostic and therapeutic coronary intervention. Methods: Two hundred and forty-six patients who underwent coronary angiography or percutaneous coronary intervention (PCI) were randomized to receive atorvastatin (40 mg, qn, n=123) or no atorvastatin (n=123) treatment 3 days before coronary angiography. All patients received hydrated therapy. Serum creatinine (Scr), urinary αl-microglobulin (α l -MG), and urinary albumin (mALB) were checked for evidence of tubular or glomerular damage at start, and 36 to 48 hours after the administration of a radiocontrast agent. High-sensitive C-reactive protein (hsCRP) levels, urinary α l -MG/ urinary creatinine(Ucr) and mALB/ Ucr were also assessed at the same time. Creatinine clearance(Ccr) was calculated according to Cockcroft-Gault formulas basing on serum creatinine. Results: (1) In the control group and atorvastatin-treated group, comparison with the value before coronary angiography or PCI, urinary α l -MG/ Ucr, mALB/ Ucr, Scr and hsCRP significantly increased from 36 to 48 hours after angiography or PCI (P l -MG/ Ucr significantly increased at the 2nd day after angiography or PCI in the control group (P<0.05), incidence of contrast induced nephropathy (CIN) significantly increased too (8.13% vs 0.81%, P<0.05). Conclusions: Contrast media induces light renal function damage. Pretreatment with atorvastatin 40 mg/qn for 3 days could significantly reduce procedural inflammatory reaction and prevent contrast-induced nephropathy. (authors)

Use of Atorvastatin in Lipid Disorders and Cardiovascular Disease in Chinese Patients

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Ye, Yi-Cong; Zhao, Xi-Liang; Zhang, Shu-Yang

2015-01-01

Objective: Statins are still underused for the prevention of cardiovascular disease (CVD) in China. Hence, we conducted a systemic review on the pharmacology, clinical efficacy, and adverse events of atorvastatin, as well as on patient adherence. Data Sources: We conducted a systemic search in PubMed with the following keywords: “atorvastatin” (Supplementary concept) or “atorvastatin” (All field) and (“China” [AD] or “China” [all field] or “Chinese” [All field]). Study Selection: Clinical or basic research articles on atorvastatin were included. Results: Atorvastatin is a reversible and competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, decreasing the de novo cholesterol synthesis. The pharmacokinetics of atorvastatin among Chinese is similar to those in Caucasians, and several gene polymorphisms have proved to be associated with the metabolism of atorvastatin in the Chinese population. Several international multiple-center randomized control trials have demonstrated the benefit of atorvastatin for primary and secondary prevention of CVD. None of them, however, included the Chinese, and current evidence in the population is still inadequate, due to the small sample size, low study quality, short study duration, and the use of surrogate endpoints instead of clinical endpoints. The overall incidence of adverse events observed with atorvastatin did not increase in the 10–80 mg dose range, and was similar to that observed with placebo and in patients treated with other statins, which makes atorvastatin well-tolerated in the Chinese population. Moreover, high patient adherence was observed in clinical studies. Conclusions: Based on the current available evidence, there is no significant difference between Chinese and non-Chinese population in term of pharmacology and clinical efficacy/safety. High-quality evidence is still needed to support the use of atorvastatin in high-risk Chinese population. PMID:25591572

Effects of Atorvastatin on Oxidative Stress Biomarkers and Mitochondrial Morphofunctionality in Hyperfibrinogenemia-Induced Atherogenesis

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María de la Paz Scribano

2014-01-01

Full Text Available Relationship between hyperfibrinogenemia (HF, oxidative stress, and atherogenesis was established. Effect of atorvastatin (Ator was assessed. Wistar male (6 months rats were studied: Ctr, control, without HF induction; Ctr-Ator, without HF treated with atorvastatin; AI, atherogenesis induced, and AI-Ator, atherogenesis induced and treated with atorvastatin. Atherogenesis was induced by daily adrenaline injection (0.1 mL/day/rat for 90 days; treatment started 15 days after induction. Fibrinogen (mg/dL and nitric oxide (NO were measured in plasma (mM and superoxide dismutase (SOD (U/mL in red cell lysate by spectrophotometry. Slices of aorta were analyzed by electron microscopy (EM. ANOVA and chi-square test were used; P<0.05 was established. There were no significant differences between Ctr and Ctr-Atorv in fibrinogen, NO, and SOD values. Comparing Ctr with AI an increase of fibrinogen is observed (P<0.001, but it decreased after administration of atorvastatin in AI-Ator (P<0.001. NO diminished in AI relative to Ctr and increased in AI-Ator (P<0.001. SOD showed an increase in AI and AI-Ator compared to Ctr (P<0.001. EM revealed expansion of intermembrane space and disorganization of crests in AI. In AI-Ator mitochondrial areas and diameters were similar to control. Atorvastatin normalizes HF, stabilizes NO, increases SOD, and produces a partial regression of mitochondrial lesions.

Effects of Atorvastatin on Oxidative Stress Biomarkers and Mitochondrial Morphofunctionality in Hyperfibrinogenemia-Induced Atherogenesis

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Scribano, María de la Paz; Baez, María del Carmen; Florencia, Becerra; Tarán, Mariana Denise; Franco, Signorini; Balceda, Ariel G.; Moya, Mónica

2014-01-01

Relationship between hyperfibrinogenemia (HF), oxidative stress, and atherogenesis was established. Effect of atorvastatin (Ator) was assessed. Wistar male (6 months) rats were studied: Ctr, control, without HF induction; Ctr-Ator, without HF treated with atorvastatin; AI, atherogenesis induced, and AI-Ator, atherogenesis induced and treated with atorvastatin. Atherogenesis was induced by daily adrenaline injection (0.1 mL/day/rat) for 90 days; treatment started 15 days after induction. Fibrinogen (mg/dL) and nitric oxide (NO) were measured in plasma (mM) and superoxide dismutase (SOD) (U/mL) in red cell lysate by spectrophotometry. Slices of aorta were analyzed by electron microscopy (EM). ANOVA and chi-square test were used; P < 0.05 was established. There were no significant differences between Ctr and Ctr-Atorv in fibrinogen, NO, and SOD values. Comparing Ctr with AI an increase of fibrinogen is observed (P < 0.001), but it decreased after administration of atorvastatin in AI-Ator (P < 0.001). NO diminished in AI relative to Ctr and increased in AI-Ator (P < 0.001). SOD showed an increase in AI and AI-Ator compared to Ctr (P < 0.001). EM revealed expansion of intermembrane space and disorganization of crests in AI. In AI-Ator mitochondrial areas and diameters were similar to control. Atorvastatin normalizes HF, stabilizes NO, increases SOD, and produces a partial regression of mitochondrial lesions. PMID:26556431

A comparative study of efficacy of atorvastatin, rosuvastatin, and atorvastatin + fibrates as lipid lowering agents

OpenAIRE

Karunasree Nagarur; Yamini Vadlamannati; Narasimha Rao Raja

2016-01-01

Background: Hypercholesterolemia patients are at high risk of coronary heart disease. National cholesterol education programme (NCEP) Adult Treatment Panel III guidelines provide the option of aggressively lowering Low-density cholesterol in them. Presently the standard therapy of hypercholesterolemia is by HMG co-A reductase inhibitors. Present study shows that Rosuvastatin is better than Atorvastatin, Atorvastatin and Fibrate is better than Atorvastatin monotherapy in management of hypercho...

Effect of combined administration of ginger (Zingiber officinale Roscoe) and atorvastatin on the liver of rats.

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Heeba, Gehan H; Abd-Elghany, Manal I

2010-12-01

Ginger is known to possess hypolipidemic, antioxidant and hepatoprotective properties. Combination therapy often takes advantage of complementary effects of different agents. This study investigated the combined effect of ginger extract (GE) and atorvastatin on lipid profile and on atorvastatin-induced hepatic injury. Rats were randomized into: control; GE (400 mg/kg); atorvastatin (20 mg/kg) alone or with GE or vitamin E, and atorvastatin (80 mg/kg) alone or with GE or vitamin E. Administration of 80 mg/kg atorvastatin for 4 weeks had major hepatotoxic effect whereas the lower dose (20 mg/kg) seems to cause mild liver injury. Besides lowering serum total cholesterol and hepatic superoxide dismutase (SOD) and catalase (CAT), atorvastatin significantly increased serum aminotransferases, hepatic malondialdehyde (MDA) and nitric oxide (NO). Concurrent administration of GE and atorvastatin had the opposite effect. Histopathological study revealed that GE reduced liver lesions induced by atorvastatin. The results indicate that the ability of ginger to lower serum cholesterol and to decrease aminotransferases, MDA and NO is clinically important, because its chronic administration will neither lead to side-effects nor to hepatic changes as occurs with high atorvastatin doses. Therefore, combination regimens containing GE and low dose of statins could be advantageous in treating hypercholesterolemic patients which are susceptible to liver function abnormalities. Copyright © 2010 Elsevier GmbH. All rights reserved.

Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction.

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Xian-Liang Tang

Full Text Available Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI. Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14 received oral atorvastatin (10 mg/kg/d daily for 3 wk before and 4 wk after MI, while group I (n = 12 received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF and fractional area change (FAC were higher while LV end-diastolic volume (LVEDV and LV end-systolic and end-diastolic diameters (LVESD and LVEDD were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dt(max, end-systolic elastance (Ees, and preload recruitable stroke work (PRSW and lower LV end-diastolic pressure (LVEDP. Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis.

Oxidative markers, nitric oxide and homocysteine alteration in hypercholesterolimic rats: role of atorvastatine and cinnamon.

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Amin, Kamal A; Abd El-Twab, Thanaa M

2009-10-05

To investigate the effects of atorvastatin and cinnamon on serum lipid profile, oxidative stress, antioxidant capacity, hepatic enzymes activities, nitric oxide (NO) as well as homocysteine (Hcy) in hypercholesterolemic rats, 48 male albino rats, weighing 130-190 gm were divided into 2 groups, normal group fed on basal rat chow diet (n=12) and high cholesterol group (HCD) were fed on 1% cholesterol-enriched diet for 15 day (n=36). Hypercholesterolemic rats were divided into 3 subgroups (n=12 for each) fed the same diet and treated with atorvastatine (HCD+Atorvastatin) or cinnamon extract (HCD+cinnamon) or none treated (HCD) for 3&6 weeks. Serum triglycerides (TG), Total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), ALT, AST, NO, Hcy, hepatic reduced glutathione (GSH), Malondialdehyde (MDA) and antioxidant enzymes, Superoxide dismutase (SOD) and catalase activity were measured. Results showed that HCD increased significantly TG, TC, LDL-C, ALT, AST, Hcy and hepatic MDA, while lowered significantly antioxidant enzyme activities and NO levels. Atorvastatin therapy significantly increased HDL-C, NO and antioxidant activity while decreased LDL-C, MDA and Hcy concentrations. Serum TG, TC, LDL-C, ALT, AST and hepatic MDA levels were significantly lowered meanwhile, serum HDL, NO values and hepatic antioxidant activities were significantly, higher in cinnamon-treated than untreated group. These results indicate that lipid abnormalities, oxidative injury and hyperhomocystienemia were induced by HCD and this study recommend that administration of atorvastatine or cinnamon provided protection against the lipemic-oxidative disorder and act as hypocholesterolemic, hepatoprotective agent and improve cardiovascular function through modulation of oxidative stress, NO and Hcy.

Cilostazol enhances atorvastatin-induced vasodilation of female rat aorta during aging.

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Nurullahoğlu-Atalık, K E; Kutlu, S; Solak, H; Koca, R Özen

2017-09-01

Statins have cholesterol-independent effects including an increased vascular nitric oxide activity and are commonly used by patients with cardiovascular disease. Such patients frequently have cardiovascular diseases, which may be treated with cilostazol, a platelet aggregation inhibitor. This study was designed to investigate whether combined use of cilostazol would increase the inhibitory effect of statin on vascular smooth muscle and how maturation would affect these responses. Female Wistar rats, aged 3-4 months (young) and 14-15 months (adult), were sacrificed by cervical dislocation and the thoracic aorta was dissected and cut into 3- to 4-mm-long rings. The rings were mounted under a resting tension of 1 g in a 20-ml organ bath filled with Krebs-Henseleit solution. Rings were precontracted with phenylephrine (10 -6  M), and the presence of endothelium was confirmed with acetylcholine (10 -6  M). Then, the concentration-response curves were obtained for atorvastatin alone (10 -10 to 3 × 10 -4  M; control) and in the presence of cilostazol (10 -6  M) in young and adult rat aortas. This experimental protocol was also carried out in aorta rings, which had been pretreated with N G -nitro-l-arginine methyl ester (l-NAME, 10 -4  M). Atorvastatin induced concentration-dependent relaxations in young and adult rat thoracic aorta rings precontracted with phenylephrine. The pIC 50 value of atorvastatin was significantly decreased in adult rat aortas. In addition, pretreatment of aortas with cilostazol enhanced the potency of atorvastatin in both young and adult aortas. Incubation with l-NAME did not completely eliminate the relaxations to atorvastatin in the presence of cilostazol. These results suggest that combined application of cilostazol with atorvastatin was significantly more potent than atorvastatin alone. Combined drug therapy may be efficacious in delaying the occurrence of cardiovascular events.

The total synthesis of calcium atorvastatin.

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Dias, Luiz C; Vieira, Adriano S; Barreiro, Eliezer J

2016-02-21

A practical and convergent asymmetric route to calcium atorvastatin (1) is reported. The synthesis of calcium atorvastatin (1) was performed using the remote 1,5-anti asymmetric induction in the boron-mediated aldol reaction of β-alkoxy methylketone (4) with pyrrolic aldehyde (3) as a key step. Calcium atorvastatin was obtained from aldehyde (3) after 6 steps, with a 41% overall yield.

Atorvastatin reduces cardiac and adipose tissue inflammation in rats with metabolic syndrome.

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Yamada, Yuichiro; Takeuchi, Shino; Yoneda, Mamoru; Ito, Shogo; Sano, Yusuke; Nagasawa, Kai; Matsuura, Natsumi; Uchinaka, Ayako; Murohara, Toyoaki; Nagata, Kohzo

2017-08-01

Statins are strong inhibitors of cholesterol biosynthesis and help to prevent cardiovascular disease. They also exert additional pleiotropic effects that include an anti-inflammatory action and are independent of cholesterol, but the molecular mechanisms underlying these additional effects have remained unclear. We have now examined the effects of atorvastatin on cardiac and adipose tissue inflammation in DahlS.Z-Lepr fa /Lepr fa (DS/obese) rats, which we previously established as a model of metabolic syndrome (MetS). DS/obese rats were treated with atorvastatin (6 or 20mgkg -1 day -1 ) from 9 to 13weeks of age. Atorvastatin ameliorated cardiac fibrosis, diastolic dysfunction, oxidative stress, and inflammation as well as adipose tissue inflammation in these animals at both doses. The high dose of atorvastatin reduced adipocyte hypertrophy to a greater extent than did the low dose. Atorvastatin inhibited the up-regulation of peroxisome proliferator-activated receptor γ gene expression in adipose tissue as well as decreased the serum adiponectin concentration in DS/obese rats. It also activated AMP-activated protein kinase (AMPK) as well as inactivated nuclear factor-κB (NF-κB) in the heart of these animals. The down-regulation of AMPK and NF-κB activities in adipose tissue of DS/obese rats was attenuated and further enhanced, respectively, by atorvastatin treatment. The present results suggest that the anti-inflammatory effects of atorvastatin on the heart and adipose tissue are attributable at least partly to increased AMPK activity and decreased NF-κB activity in this rat model of MetS. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of atorvastatin treatment on left ventricular diastolic function in peritoneal dialysis patients-The ALEVENT clinical trial.

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Wu, Cho-Kai; Yeh, Chih-Fan; Chiang, Jiun-Yang; Lin, Ting-Tse; Wu, Yi-Fan; Chiang, Chih-Kang; Kao, Tze-Wah; Hung, Kuan-Yu; Huang, Jenq-Wen

Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). Increased levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein, predict the development of LVDD. We hypothesized that PD patients with elevated high-sensitivity C-reactive protein levels might benefit from statin treatment for LVDD and designed a randomized clinical trial to prove the hypothesis. We screened 213 PD patients and randomly assigned 32 men and women with low-density lipoprotein cholesterol levels atorvastatin, 40 mg daily, or without. The primary end points were changes in TDI diastolic parameters or global strain imaging diastolic parameters. Atorvastatin reduced low-density lipoprotein cholesterol levels by 43% and high-sensitivity C-reactive protein levels by 45% (both P atorvastatin and control, respectively, P = .02). There was also a significant improvement in global strain imaging after atorvastatin treatment (global strain rate, -17.12 ± 1.42 vs -14.61 ± 1.78 for atorvastatin and control, respectively, P = .002 and E/SR IVR , 462.35 ± 110.54 vs 634.09 ± 116.81, P = .003). In this trial of PD patients without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels and LVDD, atorvastatin significantly improved cardiac diastolic function (ClinicalTrials.gov number, NCT01503671). Copyright © 2017. Published by Elsevier Inc.

Pharmacokinetic Drug-Drug Interaction Study Between Raltegravir and Atorvastatin 20 mg in Healthy Volunteers

NARCIS (Netherlands)

Blonk, M.I.; Beek, M. van; Colbers, A.; Schouwenberg, B.J.; Burger, D.M.

2015-01-01

BACKGROUND: Dyslipidemia is highly prevalent among patients with HIV infection and contributes to an increased risk of cardiovascular disease. We investigated the influence of a frequently used statin, atorvastatin, on the pharmacokinetics of the HIV-integrase inhibitor raltegravir and vice versa.

Can atorvastatin calcium cause asymptomatic hypercalcemia?

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Ipekçi, Süleyman Hilmi; Baldane, Süleyman; Sözen, Mehmet; Kebapçılar, Levent

2014-10-01

The use of statins may have unnatural effects. A 54-year-old woman was admitted to the hospital with an incidental finding of hypercalcemia (10.8 mg/dL). There was no disease other than hyperlipidemia, and the patient had been on a course of atorvastatin calcium 10 mg for 1.5 years. A workup investigation to diagnose the cause of hypercalcemia was completed. The investigation did not reveal any pathological diseases that may have caused the hypercalcemia. The hypercalcemia resolved after atorvastatin-calcium was stopped, and the patient developed hypercalcemia shortly after the initiation of the atorvastatin calcium. Here, we report a clinical case of recurrent hypercalcemia possibly induced by atorvastatin calcium administration.

Atorvastatin induces bile acid-synthetic enzyme Cyp7a1 by suppressing FXR signaling in both liver and intestine in mice[S

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Fu, Zidong Donna; Cui, Julia Yue; Klaassen, Curtis D.

2014-01-01

Statins are effective cholesterol-lowering drugs to treat CVDs. Bile acids (BAs), the end products of cholesterol metabolism in the liver, are important nutrient and energy regulators. The present study aims to investigate how statins affect BA homeostasis in the enterohepatic circulation. Male C57BL/6 mice were treated with atorvastatin (100 mg/kg/day po) for 1 week, followed by BA profiling by ultra-performance LC-MS/MS. Atorvastatin decreased BA pool size, mainly due to less BA in the intestine. Surprisingly, atorvastatin did not alter total BAs in the serum or liver. Atorvastatin increased the ratio of 12α-OH/non12α-OH BAs. Atorvastatin increased the mRNAs of the BA-synthetic enzymes cholesterol 7α-hydroxylase (Cyp7a1) (over 10-fold) and cytochrome P450 27a1, the BA uptake transporters Na+/taurocholate cotransporting polypeptide and organic anion transporting polypeptide 1b2, and the efflux transporter multidrug resistance-associated protein 2 in the liver. Noticeably, atorvastatin suppressed the expression of BA nuclear receptor farnesoid X receptor (FXR) target genes, namely small heterodimer partner (liver) and fibroblast growth factor 15 (ileum). Furthermore, atorvastatin increased the mRNAs of the organic cation uptake transporter 1 and cholesterol efflux transporters Abcg5 and Abcg8 in the liver. The increased expression of BA-synthetic enzymes and BA transporters appear to be a compensatory response to maintain BA homeostasis after atorvastatin treatment. The Cyp7a1 induction by atorvastatin appears to be due to suppressed FXR signaling in both the liver and intestine. PMID:25278499

Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked by Glutamate Toxicity in Hippocampal Slices.

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Ludka, Fabiana K; Dal-Cim, Tharine; Binder, Luisa Bandeira; Constantino, Leandra Celso; Massari, Caio; Tasca, Carla I

2017-07-01

Atorvastatin has been shown to exert a neuroprotective action by counteracting glutamatergic toxicity. Recently, we have shown atorvastatin also exerts an antidepressant-like effect that depends on both glutamatergic and serotonergic systems modulation. Excitotoxicity is involved in several brain disorders including depression; thus, it is suggested that antidepressants may target glutamatergic system as a final common pathway. In this study, a comparison of the mechanisms involved in the putative neuroprotective effect of a repetitive atorvastatin or fluoxetine treatment against glutamate toxicity in hippocampal slices was performed. Adult Swiss mice were treated with atorvastatin (10 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.), once a day during seven consecutive days. On the eighth day, animals were killed and hippocampal slices were obtained and subjected to an in vitro protocol of glutamate toxicity. An acute treatment of atorvastatin or fluoxetine was not neuroprotective; however, the repeated atorvastatin or fluoxetine treatment prevented the decrease in cellular viability induced by glutamate in hippocampal slices. The loss of cellular viability induced by glutamate was accompanied by increased D-aspartate release, increased reactive oxygen species (ROS) and nitric oxide (NO) production, and impaired mitochondrial membrane potential. Atorvastatin or fluoxetine repeated treatment also presented an antidepressant-like effect in the tail suspension test. Atorvastatin or fluoxetine treatment was effective in protecting mice hippocampal slices from glutamate toxicity by preventing the oxidative stress and mitochondrial dysfunction.

Effect of atorvastatin on glycaemia progression in patients with diabetes: an analysis from the Collaborative Atorvastatin in Diabetes Trial (CARDS).

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Livingstone, Shona J; Looker, Helen C; Akbar, Tahira; Betteridge, D John; Durrington, Paul N; Hitman, Graham A; Neil, H Andrew W; Fuller, John H; Colhoun, Helen M

2016-02-01

In an individual-level analysis we examined the effect of atorvastatin on glycaemia progression in type 2 diabetes and whether glycaemia effects reduce the prevention of cardiovascular disease (CVD) with atorvastatin. The study population comprised 2,739 people taking part in the Collaborative Atorvastatin Diabetes Study (CARDS) who were randomised to receive atorvastatin 10 mg or placebo and who had post-randomisation HbA1c data. This secondary analysis used Cox regression to estimate the effect of atorvastatin on glycaemia progression, defined as an increase in HbA1c of ≥ 0.5% (5.5 mmol/mol) or intensification of diabetes therapy. Mixed models were used to estimate the effect of atorvastatin on HbA1c as a continuous endpoint. Glycaemia progression occurred in 73.6% of participants allocated placebo and 78.1% of those allocated atorvastatin (HR 1.18 [95% CI 1.08, 1.29], p effect was seen in on-treatment analyses: HR 1.20 (95% CI 1.07, 1.35), p = 0.001. The net mean treatment effect on HbA1c was 0.14% (95% CI 0.08, 0.21) (1.5 mmol/mol). The effect did not increase through time. Diabetes treatment intensification alone did not differ with statin allocation. Neither baseline nor 1-year-attained HbA1c predicted subsequent CVD, and the atorvastatin effect on CVD did not vary by HbA1c change (interaction p value 0.229). The effect of atorvastatin 10 mg on glycaemia progression among those with diabetes is statistically significant but very small, is not significantly different between sexes, does not increase with duration of statin and does not have an impact on the magnitude of CVD risk reduction with atorvastatin.

Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

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Yue, Rongzheng; Zuo, Chuan; Zeng, Jing; Su, Baihai; Tao, Ye; Huang, Songmin; Zeng, Rui

2017-11-01

To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

[Effect of compound Danshen dripping pills combined with atorvastatin on restenosis after angioplasty in rabbits].

Science.gov (United States)

Song, Jieli; Zeng, Jinpei; Zhang, Yongxia; Li, Pengfei; Zhang, Lihong; Chen, Cibin

2014-08-01

To study the effect of compound Danshen dripping pills and atorvastatin on restenosis after abdominal aorta angioplasty in rabbits. Rabbit models of abdominal aorta restenosis after angioplasty were established and treated with saline (group A), compound Danshen dripping pills (group B), atorvastatin (group C), or compound Danshen dripping pills plus atorvastatin (group D). HE staining was used to determine the thickness of arterial intimal hyperplasia and assess the morphological changes of the narrowed artery. Immunohistochemistry was employed to detect the expression of nuclear factor-κB (NF-κB) and monocyte chemoattractant protein-1 (MCP-1). Compared with group A, the 3 treatment groups showed significant increased vascular cavity area and reduced intimal area and percentage of intimal hyperplasia (Ppills combined with atorvastatin produces better effects than the drugs used alone in inhibiting vascular smooth muscle cell proliferation in rabbits after abdominal aorta angioplasty possibly due to a decreased expression of MCP-1 as a result of NF-κB inhibition.

Atorvastatin helps preserve pancreatic β cell function in obese C57BL/6 J mice and the effect is related to increased pancreas proliferation and amelioration of endoplasmic-reticulum stress

Science.gov (United States)

2014-01-01

Background 3-Hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitors or statins are competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis. Currently, statins are used as first-line therapy in the treatment of diabetic dyslipidemia. However, effects of statins on β cell function remains unclear. This study aims to examine effects of atorvastatin treatment on pancreatic β cell function in obese C57BL/6 J mice and the possible mechanisms. Methods Diet-induced obesity (DIO) C57BL/6 J mice were treated with atorvastatin (30 mg/kg/day) for 58 days. β cell function was assessed by hyperglycemic clamp and the area of insulin-positive β cells was examined by immunofluorescence. Gene expression was assessed by RT-PCR, and endoplasmic reticulum (ER) stress related proteins were examined by Western blot. Additionally, cell viability and apoptosis of the cholesterol-loaded NIT-1 cells were investigated after atorvastatin treatment. Results Hyperglycemic clamp study revealed that glucose infusion rate (GIR) and insulin stimulation ratio in atorvastatin-treated DIO mice were markedly higher than control mice (P atorvastatin treatment (P atorvastatin-treated mice had significantly larger insulin-positive β cell area (P atorvastatin-treated mice (P atorvastatin protected the pancreatic β cell line of NIT-1 from cholesterol-induced apoptosis. Western blot showed increased expression of anti-apoptotic protein of B-cell lymphoma 2 (Bcl-2). Conclusion Pancreatic β cell function of obese C57BL/6 J mice was preserved after atorvastatin treatment, and this improvement may be attributed to enhanced pancreas proliferation and amelioration of pancreatic ER stress. PMID:24950764

An improved kilogram-scale preparation of atorvastatin calcium.

Science.gov (United States)

Novozhilov, Yuri V; Dorogov, Mikhail V; Blumina, Maria V; Smirnov, Alexey V; Krasavin, Mikhail

2015-01-01

If literature protocols are followed, conversion of an advanced ketal ester intermediate (available in kilogram quantities via a published Paal-Knorr synthesis) to cholesterol-lowering drug atorvastatin calcium is hampered by several process issues, particularly at the final stage where the hemi-calcium salt is obtained. We developed a high-yielding synthesis of atorvastatin calcium salt on 7 kg scale that affords >99.5% product purities by introducing the following key improvements: i. isolating the pure product of the ketal deprotection step as crystalline solid, and ii. using a convenient ethyl acetate extraction procedure to isolate the pure atorvastatin calcium at the ester hydrolysis and counter-ion exchange step. The convenient and operationally simple conversion of an advanced intermediate of atorvastatin to the clinically used hemi-calcium salt form of the drug that is superior to the methods obtainable from the literature is now available to facilitate the production of atorvastatin calcium on industrial scale. Graphical abstractStepwise ketal and tert-butyl ester group hydrolysis and a modified work-up protocol lead to a more convenient preparation of API-grade atorvastatin calcium.

Atorvastatin in the management of tinnitus with hyperlipidemias

Energy Technology Data Exchange (ETDEWEB)

Hameed, M. K.; Sheikh, Z. A.; Ahmed, A. [Armed Forces Inst. of Pathology, Rawalpindi (Pakistan). Dept. of Pathology

2014-12-15

To determine the role of atorvastatin in management of tinnitus in patients with hyperlipidemia. Study Design: Quasi-experimental study. Place and Duration of Study: ENT Department, Combined Military Hospital, Rawalpindi, from July 2011 to August 2012. Methodology: Ninety eight patients of tinnitus with sensorineural hearing loss having hyperlipidemia were included in the study. Their pre-therapy serum cholesterols were measured, and tinnitus scores were recorded on a 'Tinnitus handicap questionnaire'. They were administered tablet atorvastatin 40 mg once daily with low fat diet for 8 months. After 8 months of therapy, patients were purposefully divided into responsive and unresponsive group depending on serum cholesterol levels. Post therapy serum cholesterol levels and tinnitus scores were also recorded after 8 months and compared with pre-therapy records. Results: Serum cholesterol came to within normal limits in 51 (52%) patients (responsive group), while it remained high in 47 (48%) patients (unresponsive group). Improvement in tinnitus score in the responsive group was seen in 36 (70.5%) patients and in 2 (4.2%) patients of the unresponsive group. Improvement in tinnitus scores was compared in the two groups using Fisher's exact test and were found to be statistically better in the responsive group (p < 0.001). Conclusion: Tinnitus, in patients having hyperlipidemia, can be successfully dealt with by treating hyperlipidemia with lipid lowering agent atorvastatin. (author)

Atorvastatin in the management of tinnitus with hyperlipidemias

International Nuclear Information System (INIS)

Hameed, M.K.; Sheikh, Z.A.; Ahmed, A.

2014-01-01

To determine the role of atorvastatin in management of tinnitus in patients with hyperlipidemia. Study Design: Quasi-experimental study. Place and Duration of Study: ENT Department, Combined Military Hospital, Rawalpindi, from July 2011 to August 2012. Methodology: Ninety eight patients of tinnitus with sensorineural hearing loss having hyperlipidemia were included in the study. Their pre-therapy serum cholesterols were measured, and tinnitus scores were recorded on a 'Tinnitus handicap questionnaire'. They were administered tablet atorvastatin 40 mg once daily with low fat diet for 8 months. After 8 months of therapy, patients were purposefully divided into responsive and unresponsive group depending on serum cholesterol levels. Post therapy serum cholesterol levels and tinnitus scores were also recorded after 8 months and compared with pre-therapy records. Results: Serum cholesterol came to within normal limits in 51 (52%) patients (responsive group), while it remained high in 47 (48%) patients (unresponsive group). Improvement in tinnitus score in the responsive group was seen in 36 (70.5%) patients and in 2 (4.2%) patients of the unresponsive group. Improvement in tinnitus scores was compared in the two groups using Fisher's exact test and were found to be statistically better in the responsive group (p < 0.001). Conclusion: Tinnitus, in patients having hyperlipidemia, can be successfully dealt with by treating hyperlipidemia with lipid lowering agent atorvastatin. (author)

Effect of gemfibrozil and fenofibrate on the pharmacokinetics of atorvastatin.

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Whitfield, Lloyd R; Porcari, Anthony R; Alvey, Christine; Abel, Robert; Bullen, William; Hartman, Daniel

2011-03-01

Coadministration of statins and fibrates is beneficial in some patients by allowing simultaneous reduction of triglycerides and low-density lipoprotein cholesterol alongside elevation of high-density lipoprotein cholesterol. However, the potential for drug interactions must be taken into consideration. Gemfibrozil increases systemic exposure to various different statins, whereas similar effects are not observed with fenofibrate, suggesting it may be a more appropriate choice for coadministration with statins. Gemfibrozil is reported to cause a moderate increase in the area under the curve (AUC) of atorvastatin, but the effect of fenofibrate on atorvastatin pharmacokinetics has not been described. This study compared the effects of multiple-dose administration of gemfibrozil and fenofibrate on the single-dose pharmacokinetics of atorvastatin. Gemfibrozil coadministration led to significant increases in the AUC of atorvastatin, 2-hydroxyatorvastatin, 2-hydroxyatorvastatin lactone, and 4-hydroxyatorvastatin lactone. In contrast, fenofibrate administration did not lead to clinically meaningful changes in the AUC for atorvastatin, atorvastatin lactone, 2-hydroxyatorvastatin, or 2-hydroxyatorvastatin lactone. The absence of a significant pharmacokinetic interaction between fenofibrate and atorvastatin is consistent with recent results showing no difference in safety profile between atorvastatin as monotherapy or in combination with fenofibric acid. Together, these data suggest that atorvastatin-fenofibrate combination therapy is unlikely to pose a risk to patients.

Elucidation of the mechanism of atorvastatin-induced myopathy in a rat model.

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El-Ganainy, Samar O; El-Mallah, Ahmed; Abdallah, Dina; Khattab, Mahmoud M; Mohy El-Din, Mahmoud M; El-Khatib, Aiman S

2016-06-01

Myopathy is among the well documented and the most disturbing adverse effects of statins. The underlying mechanism is still unknown. Mitochondrial dysfunction related to coenzyme Q10 decline is one of the proposed theories. The present study aimed to investigate the mechanism of atorvastatin-induced myopathy in rats. In addition, the mechanism of the coenzyme Q10 protection was investigated with special focus of mitochondrial alterations. Sprague-Dawely rats were treated orally either with atorvastatin (100mg/kg) or atorvastatin and coenzyme Q10 (100mg/kg). Myopathy was assessed by measuring serum creatine kinase (CK) and myoglobin levels together with examination of necrosis in type IIB fiber muscles. Mitochondrial dysfunction was evaluated by measuring muscle lactate/pyruvate ratio, ATP level, pAkt as well as mitochondrial ultrastructure examination. Atorvastatin treatment resulted in a rise in both CK (2X) and myoglobin (6X) level with graded degrees of muscle necrosis. Biochemical determinations showed prominent increase in lactate/pyruvate ratio and a decline in both ATP (>80%) and pAkt (>50%) levels. Ultrastructure examination showed mitochondrial swelling with disrupted organelle membrane. Co-treatment with coenzyme Q10 induced reduction in muscle necrosis as well as in CK and myoglobin levels. In addition, coenzyme Q10 improved all mitochondrial dysfunction parameters including mitochondrial swelling and disruption. These results presented a model for atorvastatin-induced myopathy in rats and proved that mitochondrial dysfunction is the main contributor in statin-myopathy pathophysiology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antinociception induced by atorvastatin in different pain models.

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Garcia, G G; Miranda, H F; Noriega, V; Sierralta, F; Olavarría, L; Zepeda, R J; Prieto, J C

2011-11-01

Atorvastatin is a statin that inhibits the 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. Several landmark clinical trials have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. It is assumed that the beneficial effects of statin therapy are entirely due to cholesterol reduction. Statins have an additional activity (pleiotropic effect) that has been associated to their anti-inflammatory effects. The aim of the present study was to assess the antinociceptive activity of atorvastatin in five animal pain models. The daily administration of 3-100mg/kg of atorvastatin by oral gavage induced a significant dose-dependent antinociception in the writhing, tail-flick, orofacial formalin and formalin hind paw tests. However, this antinociceptive activity of atorvastatin was detectable only at high concentrations in the hot plate assay. The data obtained in the present study demonstrates the effect of atorvastatin to reduce nociception and inflammation in different animal pain models. Copyright © 2011 Elsevier Inc. All rights reserved.

Atorvastatin protects against ischemia-reperfusion injury in fructose-induced insulin resistant rats.

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Prakash, Prem; Khanna, Vivek; Singh, Vishal; Jyoti, Anupam; Jain, Manish; Keshari, Ravi Shankar; Barthwal, Manoj Kumar; Dikshit, Madhu

2011-08-01

High fructose (HFr) intake is known to cause insulin resistance syndrome (IRS), however its effect against acute coronary events remains elusive. The present study was undertaken to evaluate the effect of HFr (60%) diet on myocardial ischemia-reperfusion (MI-RP) injury and its modulation by atorvastatin treatment. Wistar rats kept on HFr/chow feeding for 10 weeks, received atorvastatin (30 mg/kg, per oral) or vehicle for two additional weeks followed by MI-RP injury. MI-RP injury was significantly augmented in HFr fed rats, as evident by the increase in infarct size (IS, 65 ± 5% vs. 43 ± 7%) and activities of cardiac injury biomarkers [serum lactate dehydrogenase (LDH, 698 ± 57 vs. 444 ± 26 U/L), creatinine kinase (CK-MB, 584 ± 58 vs. 435 ± 28 U/L) and tissue myeloperoxidase (MPO, 235 ± 15 vs. 101 ± 11 μM/min/100 mg tissue)]. Insulin resistance (plasma glucose, 64 ± 5 vs. 100 ± 5 mg/dl; AUC (0-120 min), p < 0.05), MI-RP injury (IS 20 ± 5%, LDH 292 ± 28 U/L, CK-MB 257 ± 13 U/L, MPO 95 ± 5 μM/min/100 mg tissue) and triglyceride (TG) level were significantly reduced, while myocardial Akt, p-Akt, eNOS, p-eNOS and iNOS protein expression were significantly enhanced following atorvastatin treatment in comparison to HFr fed rats. Oxidative stress marker, malondialdehyde and circulating levels of inflammatory cytokines (CRP, IL-6, IFN-γ and TNF) were significantly reduced, while total nitrite content in the tissue and plasma was significantly augmented in atorvastatin treated rats. Atorvastatin also ameliorated endothelial dysfunction and significantly enhanced aortic Akt and eNOS protein expression. Atorvastatin conferred significant protection against MI-RP injury and alleviated HFr induced IRS possibly by increasing NOS expression through Akt dependent pathway.

Renoprotective Effects of Atorvastatin in Diabetic Mice: Downregulation of RhoA and Upregulation of Akt/GSK3

Science.gov (United States)

Bruder-Nascimento, Thiago; Callera, Glaucia; Montezano, Augusto Cesar; Antunes, Tayze T.; He, Ying; Cat, Aurelie Nguyen Dinh; Ferreira, Nathanne S.; Barreto, Pedro A.; Olivon, Vânia C.; Tostes, Rita C.; Touyz, Rhian M.

2016-01-01

Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p.o., for 2 weeks). Diabetes-associated renal injury was characterized by albuminuria (albumin:creatinine ratio, db/+: 3.2 ± 0.6 vs. db/db: 12.5 ± 3.1*; *Patorvastatin-treated db/db mice. Increased ROS generation in the renal cortex of db/db mice was also inhibited by atorvastatin. ERK1/2 phosphorylation was increased in the renal cortex of db/db mice. Increased renal expression of Nox4 and proliferating cell nuclear antigen, observed in db/db mice, were abrogated by statin treatment. Atorvastatin also upregulated Akt/GSK3β phosphorylation in the renal cortex of db/db mice. Our findings suggest that atorvastatin attenuates diabetes-associated renal injury by reducing ROS generation, RhoA activity and normalizing Akt/GSK3β signaling pathways. The present study provides some new insights into molecular mechanisms whereby statins may protect against renal injury in diabetes. PMID:27649495

Comparison of Low-Dose Rosuvastatin with Atorvastatin in Lipid-Lowering Efficacy and Safety in a High-Risk Pakistani Cohort: An Open-Label Randomized Trial

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Abdul Rehman Arshad

2014-01-01

Full Text Available Background. Treatment of hyperlipidemia is helpful in both primary and secondary prevention of coronary heart disease and stroke. Aim. To compare lipid-lowering efficacy of rosuvastatin with atorvastatin. Methodology. This open-label randomized controlled trial was carried out at 1 Mountain Medical Battalion from September 2012 to August 2013 on patients with type 2 diabetes, hypertension, myocardial infarction, or stroke, meriting treatment with a statin. Those with secondary causes of dyslipidemia were excluded. Blood samples for estimation of serum total cholesterol, triglycerides, HDL-C, and LDL-C were collected after a 12-hour fast. Patients were randomly allocated to receive either atorvastatin 10 mg HS or rosuvastatin 5 mg HS daily. Lipid levels were rechecked after six weeks. Results. Atorvastatin was used in 63 patients and rosuvastatin in 66. There was a greater absolute and percent reduction in serum LDL-C levels with rosuvastatin as compared to atorvastatin (0.96 versus 0.54 mg/dL; P=0.011 and 24.34 versus 13.66%; P=0.045, whereas reduction in all other fractions was equal. Myalgias were seen in 5 (7.94% patients treated with atorvastatin and 8 (12.12% patients treated with rosuvastatin (P: 0.432. Conclusion. Rosuvastatin produces a greater reduction in serum LDL-C levels and should therefore be preferred over atorvastatin.

Healthy Aging Among Older Black and White Men: What Is the Role of Mastery?

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Latham-Mintus, Kenzie; Vowels, Ashley; Huskins, Kyle

2018-01-11

This research explores black-white differences in healthy aging and investigates whether mastery acts as a buffer against poor health for older black and white men. Using data from the Health and Retirement Study (HRS) (2008-2012), a series of binary logit models were created to assess healthy aging over a 2-year period. Healthy aging was defined as good subjective health and free of disability at both waves. Mastery was lagged, and analyses (n = 4,892) controlled for social and health factors. Black-white disparities in healthy aging were observed, where older black men had lower odds of healthy aging. Mastery was associated with higher odds of healthy aging, and race moderated the relationship between mastery and healthy aging. The predicted probability of healthy aging was relatively flat across all levels of mastery among black men, yet white men saw consistent gains in the probability of healthy aging with higher levels of mastery. In race-stratified models, mastery was not a significant predictor of healthy aging among black men. High levels of mastery are linked to positive health-often acting as a buffer against stressful life events. However, among older black men, higher levels of mastery did not necessarily equate to healthy aging. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Atorvastatin induced thrombocytopenia: A case report and review of literature

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Saibal Moitra

2016-01-01

Full Text Available A 65-year-old hypertensive male, with co-existing benign prostatic hyperplasia for last 5 years was on tab telmisartan 40 mg and tab tamsulosin 0.4 mg, both once daily. He was found dyslipidemic on a routine investigation and was put on tab atorvastatin 10 mg once daily. The patient developed a petechial rash and bleeding from gums within a week of starting atorvastatin, and his platelet count dropped to 15,000/cmm. Atorvastatin was suspected to be the offender as no other causes of thrombocytopenia could be implicated. Atorvastatin was discontinued and intravenous steroid and platelet transfusion given. Platelet count improved gradually and became normal after 10 days. Causality assessment as per the Naranjo algorithm revealed a "probable association" with atorvastatin therapy.

Effects of atorvastatin metabolites on induction of drug-metabolizing enzymes and membrane transporters through human pregnane X receptor

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Hoffart, E; Ghebreghiorghis, L; Nussler, AK; Thasler, WE; Weiss, TS; Schwab, M; Burk, O

2012-01-01

BACKGROUND AND PURPOSE Atorvastatin metabolites differ in their potential for drug interaction because of differential inhibition of drug-metabolizing enzymes and transporters. We here investigate whether they exert differential effects on the induction of these genes via activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). EXPERIMENTAL APPROACH Ligand binding to PXR or CAR was analysed by mammalian two-hybrid assembly and promoter/reporter gene assays. Additionally, surface plasmon resonance was used to analyse ligand binding to CAR. Primary human hepatocytes were treated with atorvastatin metabolites, and mRNA and protein expression of PXR-regulated genes was measured. Two-hybrid co-activator interaction and co-repressor release assays were utilized to elucidate the molecular mechanism of PXR activation. KEY RESULTS All atorvastatin metabolites induced the assembly of PXR and activated CYP3A4 promoter activity. Ligand binding to CAR could not be proven. In primary human hepatocytes, the para-hydroxy metabolite markedly reduced or abolished induction of cytochrome P450 and transporter genes. While significant differences in co-activator recruitment were not observed, para-hydroxy atorvastatin demonstrated only 50% release of co-repressors. CONCLUSIONS AND IMPLICATIONS Atorvastatin metabolites are ligands of PXR but not of CAR. Atorvastatin metabolites demonstrate differential induction of PXR target genes, which results from impaired release of co-repressors. Consequently, the properties of drug metabolites have to be taken into account when analysing PXR-dependent induction of drug metabolism and transport. The drug interaction potential of the active metabolite, para-hydroxy atorvastatin, might be lower than that of the parent compound. PMID:21913896

Abscess Formation after Septic Arthritis in the Sternoclavicular Joint of Two Healthy Men

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Henriksen, Jeppe; Tang, Mariann; Hjortdal, Vibeke

2015-01-01

Abscess formation after septic arthritis in the sternoclavicular joint is a rare phenomenon in healthy people without immune suppression, intravenous drug abuse, or diabetes. Here we report two cases with formation of abscess in two middle-aged men, with no relevant comorbidities and no obvious...... sites of infection. The abscesses were both treated surgically with debridement followed by negative pressure wound therapy and antibiotics. The cases differ in diagnostic procedures and delay of diagnosis and broach the issues of handling a rare disease....

Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I)

DEFF Research Database (Denmark)

de Zeeuw, Dick; Anzalone, Deborah A; Cain, Valerie A

2015-01-01

, angiotensin receptor blockers, or both. We randomly assigned participants to atorvastatin 80 mg, rosuvastatin 10 mg, or rosuvastatin 40 mg for 52 weeks. The primary endpoint was change from baseline to week 52 of mean UPCR in each treatment group. The study is registered with ClinicalTrials.gov, number NCT......00296374. FINDINGS: We enrolled 353 patients: 118 were assigned to rosuvastatin 10 mg, 124 to rosuvastatin 40 mg, and 111 to atorvastatin 80 mg; of these, 325 were included in the intention-to-treat population. UPCR baseline:week 52 ratio was 0·87 (95% CI 0·77-0·99; p=0·033) with atorvastatin 80 mg, 1...... with ClinicalTrials.gov, NCT00296400). In this analysis, atorvastatin 80 mg lowered UPCR significantly more than did rosuvastatin 10 mg (-15·6%, 95% CI -28·3 to -0·5; p=0·043) and rosuvastatin 40 mg (-18·2%, -30·2 to -4·2; p=0·013). Adverse events occurred in 69 (60%) of 116 patients in the rosuvastatin 10 mg...

Abscess Formation after Septic Arthritis in the Sternoclavicular Joint of Two Healthy Men

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Jeppe Henriksen

2015-01-01

Full Text Available Abscess formation after septic arthritis in the sternoclavicular joint is a rare phenomenon in healthy people without immune suppression, intravenous drug abuse, or diabetes. Here we report two cases with formation of abscess in two middle-aged men, with no relevant comorbidities and no obvious sites of infection. The abscesses were both treated surgically with debridement followed by negative pressure wound therapy and antibiotics. The cases differ in diagnostic procedures and delay of diagnosis and broach the issues of handling a rare disease.

Metabolically Healthy Obesity Is Not Associated with Food Intake in White or Black Men.

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Kimokoti, Ruth W; Judd, Suzanne E; Shikany, James M; Newby, P K

2015-11-01

Healthy obese individuals may be protected against adverse health outcomes. Diet and race might influence healthy obesity, but data on their roles and interactions on the phenotype are limited. We compared the food intake of metabolically healthy obese men to those of other weight status-metabolic health phenotypes. Men (n = 4855) aged ≥ 45 y with BMI ≥ 18.5 kg/m(2) and free of cardiovascular diseases, diabetes, and cancer were evaluated in a cross-sectional study of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study cohort. Food intake was assessed with the use of a food frequency questionnaire. Weight status-metabolic health phenotypes were defined by using metabolic syndrome (MetS) and homeostasis model assessment of insulin resistance (HOMA-IR) criteria. Mean differences in food intake among weight status-metabolic health phenotypes were compared with the use of linear regression. MetS-defined healthy obesity was present in 44% of white obese men and 58% of black obese men; the healthy obese phenotype, based on HOMA-IR, was equally prevalent in both white (20%) and black (21%) obese men. Among white men, MetS-defined healthy and unhealthy obesity were associated with lower wholegrain bread intake and higher consumption of red meat (P food intake in all models. Healthy obesity in men is not associated with a healthier diet. Future studies need to consider dietary patterns, which may better inform the holistic effect of diet on healthy obesity, in prospective analyses. © 2015 American Society for Nutrition.

Decreases in Human Semen Quality with Age Among Healthy Men

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

2001-12-01

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

Antagonistic Effect of Atorvastatin on High Fat Diet Induced Survival during Acute Chagas Disease

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Zhao, Dazhi; Lizardo, Kezia; Cui, Min Hui; Ambadipudi, Kamalakar; Lora, Jose; Jelicks, Linda A; Nagajyothi, Jyothi F

2016-01-01

Chagasic cardiomyopathy, which is seen in Chagas Disease, is the most severe and life-threatening manifestation of infection by the kinetoplastid Trypanosoma cruzi. Adipose tissue and diet play a major role in maintaining lipid homeostasis and regulating cardiac pathogenesis during the development of Chagas cardiomyopathy. We have previously reported that T. cruzi has a high affinity for lipoproteins and that the invasion rate of this parasite increases in the presence of cholesterol, suggesting that drugs that inhibit cholesterol synthesis, such as statins, could affect infection and the development of Chagasic cardiomyopathy. The dual epidemic of diabetes and obesity in Latin America, the endemic regions for Chagas Disease, has led to many patients in the endemic region of infection having hyperlipidemia that is being treated with statins such as atorvastatin. The current study was performed to examine using mice fed on either regular or high fat diet the effect of atorvastatin on T. cruzi infection-induced myocarditis and to evaluate the effect of this treatment during infection on adipose tissue physiology and cardiac pathology. Atorvastatin was found to regulate lipolysis and cardiac lipidopathy during acute T. cruzi infection in mice and to enhance tissue parasite load, cardiac LDL levels, inflammation, and mortality in during acute infection. Overall, these data suggest that statins, such as atorvastatin, have deleterious effects during acute Chagas disease. PMID:27416748

Inhibition of Autophagy Potentiates Atorvastatin-Induced Apoptotic Cell Death in Human Bladder Cancer Cells in Vitro

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Kang, Minyong; Jeong, Chang Wook; Ku, Ja Hyeon; Kwak, Cheol; Kim, Hyeon Hoe

2014-01-01

Statins are cholesterol reduction agents that exhibit anti-cancer activity in several human cancers. Because autophagy is a crucial survival mechanism for cancer cells under stress conditions, cooperative inhibition of autophagy acts synergistically with other anti-cancer drugs. Thus, this study investigates whether combined treatment of atorvastatin and autophagy inhibitors results in enhancing the cytotoxic effects of atorvastatin, upon human bladder cancer cells, T24 and J82, in vitro. To measure cell viability, we performed the EZ-Cytox cell viability assay. We examined apoptosis by flow cytometry using annexin-V/propidium iodide (PI and western blot using procaspase-3 and poly (ADP-ribose) polymerase (PARP) antibodies. To examine autophagy activation, we evaluated the co-localization of LC3 and LysoTracker by immunocytochemistry, as well as the expression of LC3 and p62/sequestosome-1 (SQSTM1) by western blot. In addition, we assessed the survival and proliferation of T24 and J82 cells by a clonogenic assay. We found that atorvastatin reduced the cell viability of T24 and J82 cells via apoptotic cell death and induced autophagy activation, shown by the co-localization of LC3 and LysoTracker. Moreover, pharmacologic inhibition of autophagy significantly enhanced atorvastatin-induced apoptosis in T24 and J82 cells. In sum, inhibition of autophagy potentiates atorvastatin-induced apoptotic cell death in human bladder cancer cells in vitro, providing a potential therapeutic approach to treat bladder cancer. PMID:24815071

Atorvastatin calcium plus amlodipine for the treatment of hypertension.

Science.gov (United States)

Delgado-Montero, Antonia; Zamorano, Jose L

2012-12-01

Hypertension (HTN) and dyslipemia (DYL) are two of the major modifiable cardiovascular (CV) risk factors, determinants in the development of cerebrovascular and coronary heart disease (CHD). Many patients have both risk factors which increase their total CV risk compared with patients with only one risk factor. Treatment guideline recommendations are poorly implemented in real practice, in part due to numerous and complicated drug regimes which hamper patient´s adherence. In this article the authors describe the first combined fixed-dose pill of an antihypertensive and a lipid-lowering agent, the single-pill combination of amlodipine besylate and atorvastatin calcium (SPAA). They summarize the pharmacokinetic and pharmacodynamic properties of both compounds and the main randomized clinical studies, as well as real-world observational studies, made with the new combined formulation. The use of the single-pill amlodipine and atorvastatin is an adequate option for the clinician to treat hypertensive patients with DYL or high CV risk burden, with proven efficacy, tolerability, cost-effectiveness, and the advantage of improving patient treatment compliance.

The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.

LENUS (Irish Health Repository)

Mc Donnell, C G

2012-02-03

Midazolam is a commonly used anaesthetic agent and is metabolised by the 3A4 isoform of the cytochrome P450 enzyme system. Atorvastatin is also metabolised by cytochrome P450 3A4 and, in vitro, atorvastatin inhibits the cytochrome P450 3A4-mediated metabolism of mexazolam. We hypothesised that concurrent administration of atorvastatin and midazolam would result in altered midazolam pharmacokinetics. Fourteen patients scheduled to undergo general anaesthesia for elective surgery were recruited in a matched pair design to receive intravenous midazolam (0.15 mg.kg-1). Of these patients, seven were taking long-term atorvastatin. Atorvastatin patients demonstrated a greater area under the curve (889.4 (standard deviation 388.6) ng-h.ml-1) vs. control patients (629.1 (standard deviation 197.2) ng-h.ml-1) (p < 0.05). Patients taking atorvastatin also demonstrated a decreased clearance (0.18 (standard deviation 0.08) l-kg. h-1) vs. control patients (0.27 (standard deviation 0.08) l-kg.h-1) (p < 0.05). This study suggests that chronically administered atorvastatin decreases the clearance of intravenously administered midazolam.

The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone

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D.T. Ito

2007-03-01

Full Text Available Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.

The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1

Science.gov (United States)

Shu, Nan; Hu, Mengyue; Ling, Zhaoli; Liu, Peihua; Wang, Fan; Xu, Ping; Zhong, Zeyu; Sun, Binbin; Zhang, Mian; Li, Feng; Xie, Qiushi; Liu, Xiaodong; Liu, Li

2016-01-01

Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats. Expressions and activities of hepatic Cyp3a and SLCO1B1 were increased in diabetic rats, which were highly correlated with hepatotoxicity. Antioxidants (glutathione and N-Acetylcysteine), Cyp3a inhibitor ketoconazole and SLCO1B1 inhibitor gemfibrozil suppressed cytotoxicity and ROS formation in primary hepatocytes of diabetic rats. In HepG2 cells, up-regulations of CYP3A4 and SLCO1B1 potentiated hepatotoxicity and ROS generation, whereas knockdowns of CYP3A4 and SLCO1B1 as well as CYP3A4/SLCO1B1 inhibitions showed the opposite effects. Phenobarbital pretreatment was used to induce hepatic Cyp3a and SLCO1B1 in rats. Phenobarbital aggravated atorvastatin-induced hepatotoxicity, while decreased plasma exposure of atorvastatin. All these findings demonstrated that the upregulations of hepatic Cyp3a and SLCO1B1 in diabetic rats potentiated atorvastatin-induced hepatotoxicity via increasing ROS formation. PMID:27624558

Atorvastatin and fenofibrate increase apolipoprotein AV and decrease triglycerides by up-regulating peroxisome proliferator-activated receptor-α

Science.gov (United States)

Huang, Xian-sheng; Zhao, Shui-ping; Bai, Lin; Hu, Min; Zhao, Wang; Zhang, Qian

2009-01-01

Background and purpose: Combining statin and fibrate in clinical practice provides a greater reduction of triglycerides than either drug given alone, but the mechanism for this effect is poorly understood. Apolipoprotein AV (apoAV) has been implicated in triglyceride metabolism. This study was designed to investigate the effect of the combination of statin and fibrate on apoAV and the underlying mechanism(s). Experimental approach: Hypertriglyceridaemia was induced in rats by giving them 10% fructose in drinking water for 2 weeks. They were then treated with atorvastatin, fenofibrate or the two agents combined for 4 weeks, and plasma triglyceride and apoAV measured. We also tested the effects of these two agents on triglycerides and apoAV in HepG2 cells in culture. Western blot and reverse transcription polymerase chain reaction was used to measure apoAV and peroxisome proliferator-activated receptor-α (PPARα) expression. Key results: The combination of atorvastatin and fenofibrate resulted in a greater decrease in plasma triglycerides and a greater increase in plasma and hepatic apoAV than either agent given alone. Hepatic expression of the PPARα was also more extensively up-regulated in rats treated with the combination. A similar, greater increase in apoAV and a greater decrease in triglycerides were observed following treatment of HepG2 cells pre-exposed to fructose), with the combination. Adding an inhibitor of PPARα (MK886) abolished the effects of atorvastatin on HepG2 cells. Conclusions and implications: A combination of atorvastatin and fenofibrate increased apoAV and decreased triglycerides through up-regulation of PPARα. PMID:19694729

Fatherhood in tall men treated with high-dose sex steroids during adolescence.

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Hendriks, A E J; Boellaard, W P A; van Casteren, N J; Romijn, J C; de Jong, F H; Boot, A M; Drop, S L S

2010-12-01

Sex steroid treatment to reduce final height of tall boys has been available since the 1950s. In women, it has been shown to interfere with fertility. In men, no such data are available. We therefore evaluated fertility and gonadal function in tall men who did or did not receive high-dose androgen treatment in adolescence. We conducted a retrospective cohort study of 116 tall men, of whom 60 had been treated. Reproductive and gonadal function was assessed by standardized interview, semen analysis, endocrine parameters, ultrasound imaging, and fatherhood. Mean age at treatment commencement was 14.2 yr, and mean follow-up was 21.2 yr. Sixty-six men (36 treated and 30 untreated) had attempted to achieve fatherhood. The probability of conceiving their first pregnancy within 1 yr was similar in treated and untreated men (26 vs. 24; Breslow P=0.8). Eleven treated and 13 untreated men presented with a left-sided varicocele (P=0.5). Testicular volume, sperm quality, and serum LH, FSH, and inhibin B levels were comparable between treated and untreated men. However, treated men had significantly reduced serum T levels, adjusted for known confounders [mean (sd) 13.3 (1.8) vs. 15.2 (1.9) nmol/liter; P=0.005). In addition, testicular volume and serum inhibin B and FSH levels in treated men were significantly correlated with age at treatment commencement. At a mean follow-up of 21 yr after high-dose androgen treatment, we conclude that fatherhood and semen quality in tall treated men are not affected. Serum testosterone levels, however, are reduced in androgen-treated men. Future research is required to determine whether declining testosterone levels may become clinically relevant for these men as they age.

Efficacy and safety of atorvastatin in South Asian patients with dyslipidemia: an open label noncomparative pilot study

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Jeetesh V Patel

2005-12-01

Full Text Available Jeetesh V Patel1, Sandeep Gupta2, Frank Lie3, Elizabeth A Hughes11Sandwell and West Birmingham Hospitals NHS Trust, West Bromwich, UK; 2Whipps Cross and St Bartholomew’s Hospitals; and 3Whipps Cross University Hospital, London, UKBackground: Rates of coronary heart disease (CHD mortality are 40% higher amongst South Asian men and women living in the UK compared with the general UK population. Despite an established excess CHD risk, little is known of the efficacy and safety of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA reductase inhibitors (statins amongst South Asian migrants.Methods and results: Hyperlipidemic South Asian patients (raised or uncontrolled lowdensity lipoprotein cholesterol [LDL-C] were recruited from two UK centers (n = 33. After a five-week period, which included dietary advice, patients received atorvastatin 10 mg/d for five weeks to achieve a target LDL-C goal of < 3.0 mmol/L, titrated to 20 mg, 40 mg, or 80 mg for a further 12 weeks as required. Significant reductions in LDL-C levels from baseline were observed after 4 weeks’ and 17 weeks’ treatment with atorvastatin (≥ 33.6%; 26.0, 41.2. Overall, 81% (95% confidence interval [CI]: 62.5, 92.6% achieved the target LDL-C after 4 weeks’ treatment with 10 mg atorvastatin. Titration to a dose of more than 20 mg was required in only one patient (40 mg at any point during the study. Nineteen patients reported at least one adverse event during the study; the majority were mild in severity and considered unrelated to atorvastatin.Conclusions: Atorvastatin was effective in achieving target lipid levels and was well tolerated. Statin therapy for high-risk South Asian individuals is likely to benefit CHD outcomes, although further and larger prospective trials are required.Keywords: hyperlipidemia, lipids, cholesterol, dyslipidemia, statins, coronary heart disease, South Asians

Clinical and laboratory characteristics of active and healthy aging (AHA) in octogenarian men.

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Rantanen, Kirsi K; Strandberg, Timo E; Stenholm, Sari S; Strandberg, Arto Y; Pitkälä, Kaisu H; Salomaa, Veikko V; Tilvis, Reijo S

2015-10-01

To investigate clinical and laboratory variables associated with good subjective and objective health ("active and healthy aging", AHA) in a cohort of octogenarian men. Cross-sectional analyses of a longitudinal study. The Helsinki Businessmen Study in Finland. A socioeconomically homogenous cohort of men (baseline n = 3293), born in 1919-1934, has been followed up from the 1960s. From 2000, the men have been regularly sent mailed questionnaires and mortality has been retrieved from national registers. In 2010 survey, AHA was defined as independently responding to the mailed survey, feeling happy without cognitive or functional impairments and without major diseases. In 2010/11, a random subgroup men was clinically investigated and survivors with healthy and nonhealthy aging were compared. By 2010, 1788 men of the baseline cohort had died, and 894 men responded to the mailed survey. 154 (17.2 %) of those fulfilled the present AHA criteria. Increasing number of criteria were negatively (P active and healthy aging over their life course, which was significantly related to markers of frailty but not to the traditional vascular risk factors.

Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia.

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Santini, Stefano A; Carrozza, Cinzia; Lulli, Paola; Zuppi, Cecilia; CarloTonolo, Gian; Musumeci, Salvatore

2003-01-01

Atorvastatin, a second generation synthetic 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia, reduces both intracellular cholesterol synthesis and serum cholesterol levels, and this could have a potential negative impact on gonadal and adrenal steroidogenesis. Hypercholesterolemia in type 2 diabetes, even when mild, must be treated in an aggressive way, due to the more strict therapeutic goals than in the non diabetic population. Since the wide use of 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor (statins) in type 2 diabetes, the main aim of our study was to evaluate the effects of "therapeutic" doses of atorvastatin on gonadal and adrenal hormones in 24 type 2 diabetic patients (16 males and 8 postmenopausal females), with mild to moderate hypercholesterolemia (LDL-cholesterol = 150.1 +/- 32.0 and 189.9 +/- 32.9 mg/dl, respectively) studied before and after a 3 months treatment with atorvastatin (20 mg/day). In all patients, lipids and serum cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstendione and sex hormone binding globulin (SHBG) were measured, with the addition, only in males, of testosterone and free testosterone index. After atorvastatin treatment a significant decrease in total and LDL cholesterol was observed (p < 0.05), while HDL-cholesterol did not significantly change ( p = N.S.), as no significant difference was found between steroid hormones measured before and after atorvastatin either in male and females. In conclusion, our data suggest that, in type 2 diabetic patients, the use of atorvastatin has no clinically important effects on either gonadal or adrenal steroid hormones.

Rhabdomyolysis caused by the moderate CYP3A4 inhibitor fluconazole in a patient on stable atorvastatin therapy: a case report and literature review.

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Hsiao, S-H; Chang, H-J; Hsieh, T-H; Kao, S-M; Yeh, P-Y; Wu, T-J

2016-10-01

Rhabdomyolysis is a severe potential adverse drug reaction of statin therapy. We report a case of rhabdomyolysis due to drug-drug interaction (DDI) between atorvastatin and fluconazole and review the literature. A 70-year-old woman received atorvastatin for hyperlipidaemia without any problem for 4 years. When intravenous fluconazole was added for treating a fungal infection, rhabdomyolysis developed 2 weeks later. Removal of atorvastatin led to the resolution of her rhabdomyolysis. Our case demonstrates that in some subjects even a moderate CYP3A4 inhibitor such as fluconazole may lead to rhabdomyolysis in subjects receiving a statin. © 2016 John Wiley & Sons Ltd.

St. John's wort impairs glucose tolerance by reducing insulin response in healthy men

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Stage, Tore Bjerregaard; Damkier, Per; Christensen, Mette Marie Hougaard

2015-01-01

The purpose of this study was to examine if the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions; A: Baseline, B: After 21 days...

Binding interaction of atorvastatin with bovine serum albumin: Spectroscopic methods and molecular docking

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Wang, Qi; Huang, Chuan-ren; Jiang, Min; Zhu, Ying-yao; Wang, Jing; Chen, Jun; Shi, Jie-hua

2016-03-01

The interaction of atorvastatin with bovine serum albumin (BSA) was investigated using multi-spectroscopic methods and molecular docking technique for providing important insight into further elucidating the store and transport process of atorvastatin in the body and the mechanism of action and pharmacokinetics. The experimental results revealed that the fluorescence quenching mechanism of BSA induced atorvastatin was a combined dynamic and static quenching. The binding constant and number of binding site of atorvastatin with BSA under simulated physiological conditions (pH = 7.4) were 1.41 × 105 M- 1 and about 1 at 310 K, respectively. The values of the enthalpic change (ΔH0), entropic change (ΔS0) and Gibbs free energy (ΔG0) in the binding process of atorvastatin with BSA at 310 K were negative, suggesting that the binding process of atorvastatin and BSA was spontaneous and the main interaction forces were van der Waals force and hydrogen bonding interaction. Moreover, atorvastatin was bound into the subdomain IIA (site I) of BSA, resulting in a slight change of the conformation of BSA.

Physical activity is not related to semen quality in young healthy men

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Mínguez-Alarcón, Lidia; Chavarro, Jorge E; Mendiola, Jaime; Gaskins, Audrey J; Torres-Cantero, Alberto M

2015-01-01

Objective To study the relation of physical activity with semen quality among healthy young men from Spain. Design Cross-sectional study. Setting University and college campuses of Murcia Region, Spain. Patients Healthy young men with untested fertility (n=215). Intervention A physical examination, blood and semen samples, and completion of a questionnaire. Main outcomes measure Semen quality parameters. Results Physical activity was not related to semen quality parameters. The adjusted percentage differences (95% confidence interval) in semen parameters comparing men in the top quartile of moderate to vigorous physical activity (≥9.5h/wk) to men in the bottom quartile (≤3h/wk) were 4.3% (−30.2, 38.9) for total sperm count, 7.2% (−30.6, 45.1) for sperm concentration, −2.42% (−6.53, 1.69) for sperm motility, and 12.6% (−12.0, 37.2) for sperm morphology. Conclusion In contrast to previous research among athletes, these data suggest that physical activity is not deleterious to testicular function, as captured by semen quality parameters in this population of healthy young men in Spain. PMID:25064411

Physical activity is not related to semen quality in young healthy men.

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Mínguez-Alarcón, Lidia; Chavarro, Jorge E; Mendiola, Jaime; Gaskins, Audrey J; Torres-Cantero, Alberto M

2014-10-01

To study the relationship of physical activity with semen quality among healthy young men from Spain. Cross-sectional study. University and college campuses of Murcia Region, Spain. Healthy young men with untested fertility (n = 215). A physical examination, blood and semen samples, and completion of a questionnaire. Semen quality parameters. Physical activity was not related to semen quality parameters. The adjusted percentage differences (95% confidence interval) in semen parameters comparing men in the top quartile of moderate-to-vigorous physical activity (≥9.5 h/wk) with men in the bottom quartile (≤3 h/wk) were 4.3% (-30.2%, 38.9%) for total sperm count, 7.2% (-30.6%, 45.1%) for sperm concentration, -2.42% (-6.53%, 1.69%) for sperm motility, and 12.6% (-12.0%, 37.2%) for sperm morphology. In contrast to previous research among athletes, these data suggest that physical activity is not deleterious to testicular function, as captured by semen quality parameters in this population of healthy young men in Spain. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

High-resolution Sonographic Measurements of Lower Extremity Bursae in Chinese Healthy Young Men

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Yong-Yan Gao

2016-01-01

Conclusions: Using HR-US imaging, we were able to analyze lower extremity bursae with high detection rates in healthy young men. The normal ranges of lower extremity bursa dimensions in healthy young men measured by HR-US in this study could be used as reference values for evaluation of bursa abnormalities in the lower extremity.

Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole

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Zhang, Jian-rong; Wang, Di-qing; Du, Jun; Qu, Guang-su; Du, Jian-lin; Deng, Song-bai; Liu, Ya-jie; Cai, Jin-xi; She, Qiang

2015-01-01

Abstract This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole. One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10 mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30 mg daily, Group B: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30 mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events. A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB2, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05). In patients diagnosed with NSTE-ACS who have had drug-eluting stent

Tales of healthy men: male reproductive bodies in biomedicine from 'Lebensborn' to sperm banks.

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Kampf, Antje

2013-01-01

Using the example of 'sperm tales', borne out of the biomedical technologies that went hand in hand with the establishment of the 'science of man' (andrology), the article engages with the epistemic evolution of interrelated biomedical theories and concepts of what constitutes a 'healthy' reproductive male body. The article asks: how has the normative ideal male body been either perpetuated or interrogated through these tales of male reproduction at the interface between scientific and medical technologies? And how were changes to the normalization of male bodies central to clinical practices and cultural understandings of health and illness? With many aspects of the medical history of male reproduction in the 20th century still unexplored, this article will focus on the growing intervention of biomedicine to 'treat' male infertility by way of the classification, standardization and normalization of male corporeality, focusing in particular on the representation and construction of men and the male body, as reflected in medical science and practice from the second half of the 20th century onwards in Germany. The article analyses the rise in importance of sperm in biomedical investigation, including a consideration of the construction of infertility as the defining force behind concepts of 'healthy men', and examines the related conceptualization of male reproductive bodies at the crossroad between 'healthy' and 'normal'. It is argued that the ideal of male reproduction as being inherently healthy has lost ground. By the late 20th century, male bodies have become vulnerable, at least as represented in medical science and technology.

Efficacy of atorvastatin therapy in prevention of postoperative atrial fibrillation in patients with ischemic heart disease

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O. A. Rubanenko

2015-11-01

Full Text Available Aim. To evaluate the efficacy of atorvastatin therapy in prevention of atrial fibrillation (AF development after coronary artery bypass graft (CABG surgery in patients with ischemic heart disease (IHD with the assessment of inflammation, sheer stress and myocardial injury indicators. Material and methods. The study included 105 patients with IHD who were divided into two groups: patients of group 1 were treated with atorvastatin (59 patients, 81% males, mean age 62.1±7.5 years; patients of group 2 received no HMG-CoA reductase inhibitors (46 patients, 89% males, and mean age 61.7±8.1 years. Results. Postoperative AF occurred more often in patients of group 2 (41.3% vs 16.9%; р=0.047. Laboratory analysis revealed the following: the levels of total leukocytes, interleukin-8, interleukin-10, C-reactive protein, fibrinogen, superoxide dismutase and troponin did not different significantly among the patients of two groups. Interleukin-6 level in preand postoperative period was significantly higher in patients of group 2 (35.4±28.5 pg/ml vs 24.1±14.8 pg/ml, р=0.03; 63.7±54.8 pg/ml vs 50.7±40.8 pg/ml, р=0.04, respectively. Conclusion. Our study has shown that atorvastatin therapy contributed to the reduction of number of new cases of AF after CABG in patients with IHD. At that, the efficacy of atorvastatin therapy correlated with the size of left atrium and the severity of inflammatory response. Patients with atorvastatin therapy had significantly lower interleukin-6 level, as a proinflammatory marker, in preand postoperational period as compared with the patients without such treatment.

Vitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial

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Lerchbaum, Elisabeth; Pilz, Stefan; Trummer, Christian; Schwetz, Verena; Pachernegg, Oliver; Heijboer, Annemieke C.; Obermayer-Pietsch, Barbara

2017-01-01

Available evidence shows an association of vitamin D with androgen levels in men. However, results from preliminary randomized controlled trials (RCTs) are conflicting. To evaluate whether vitamin D supplementation increases total testosterone (TT) levels in healthy men. The Graz Vitamin D&TT-RCT is

Late-life factors associated with healthy aging in older men.

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Bell, Christina L; Chen, Randi; Masaki, Kamal; Yee, Priscilla; He, Qimei; Grove, John; Donlon, Timothy; Curb, J David; Willcox, D Craig; Poon, Leonard W; Willcox, Bradley J

2014-05-01

To identify potentially modifiable late-life biological, lifestyle, and sociodemographic factors associated with overall and healthy survival to age 85. Prospective longitudinal cohort study with 21 years of follow-up (1991-2012). Hawaii Lifespan Study. American men of Japanese ancestry (mean age 75.7, range 71-82) without baseline major clinical morbidity and functional impairments (N = 1,292). Overall survival and healthy survival (free from six major chronic diseases and without physical or cognitive impairment) to age 85. Factors were measured at late-life baseline examinations (1991-1993). Of 1,292 participants, 1,000 (77%) survived to 85 (34% healthy) and 309 (24%) to 95 (healthy). Late-life factors associated with survival and healthy survival included biological (body mass index, ankle-brachial index, cognitive score, blood pressure, inflammatory markers), lifestyle (smoking, alcohol use, physical activity), and sociodemographic factors (education, marital status). Cumulative late-life baseline risk factor models demonstrated that age-standardized (at 70) probability of survival to 95 ranged from 27% (no factors) to 7% (≥ 5 factors); probability of survival to 100 ranged from 4% (no factors) to 0.1% (≥ 5 factors). Age-standardized (at 70) probability of healthy survival to 90 ranged from 4% (no factors) to 0.01% (≥ 5 factors). There were nine healthy survivors at 95 and one healthy survivor at 100. Several potentially modifiable risk factors in men in late life (mean age 75.7) were associated with markedly greater probability of subsequent healthy survival and longevity. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5.

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Gao, Xing; Nan, Yang; Zhao, Yuanlin; Yuan, Yuan; Ren, Bincheng; Sun, Chao; Cao, Kaiyu; Yu, Ming; Feng, Xuyang; Ye, Jing

2017-12-01

Statins have been proven to be effective in treating non-alcoholic fatty liver disease (NAFLD). Recently, it was reported that statins decreased the hepatic expression of perilipin 5 (Plin5), a lipid droplet (LD)-associated protein, which plays critical roles in regulating lipid accumulation and lipolysis in liver. However, the function and regulation mechanism of Plin5 have not yet been well-established in NAFLD treatment with statins. In this study, we observed that atorvastatin moderately reduced the expression of Plin5 in livers without changing the protein level of Plin5 in the hepatic LD fraction of mice fed with high-fat diet (HFD). Intriguingly, atorvastatin stimulated the PKA-mediated phosphorylation of Plin5 and reduced the triglyceride (TG) accumulation in hepatocytes with overexpression of wide type (Plin5-WT) compared to serine-155 mutant Plin5 (Plin5-S155A). Moreover, PKA-stimulated FA release of purified LDs carrying Plin5-WT but not Plin5-S155A. Glucagon, a PKA activator, stimulated the phosphorylation of Plin5-WT and inhibited its interaction with CGI-58. The results indicated that atorvastatin promoted lipolysis and reduced TG accumulation in the liver by increasing PKA-mediated phosphorylation of Plin5. This new mechanism of lipid-lowering effects of atorvastatin might provide a new strategy for NAFLD treatment. Copyright © 2017. Published by Elsevier B.V.

Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP

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Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei

2015-01-01

Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. PMID:26063978

Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome.

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Sathyapalan, Thozhukat; Shepherd, John; Coady, Anne-Marie; Kilpatrick, Eric S; Atkin, Stephen L

2012-11-01

It has been shown that there is an increase in oxidative stress in polycystic ovary syndrome (PCOS). Statins are considered to have a pleiotropic effect other than their lipid-lowering effect. These effects may be mediated in part by reducing oxidative stress. This randomized, double-blind, placebo-controlled study was conducted to assess the effect of atorvastatin on serum malondialdehyde (MDA) concentrations as a marker of oxidative stress in patients with PCOS. Forty medication-naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. There was a significant decrease of MDA concentrations with atorvastatin [mean (sem)] [0.29 (0.04) vs. 0.25 (0.02) μmol/liter; P polycystic ovary syndrome that was independently predicted by changes in testosterone, 25OHD, and high-sensitivity C-reactive protein.

Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

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Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

2016-01-01

Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

Autobiographical memory after acute stress in healthy young men

NARCIS (Netherlands)

Tollenaar, M.S.; Elzinga, B.M.; Spinhoven, P.; Everaerd, W.

2009-01-01

Autobiographical memories have been found to be less specific after hydrocortisone administration in healthy men, resembling memory deficits in, for example, depression. This is the first study to investigate the effects of stress-induced elevated cortisol levels on autobiographic memory specificity

Baroreflex buffering in sedentary and endurance exercise-trained healthy men.

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Christou, Demetra D; Jones, Pamela Parker; Seals, Douglas R

2003-06-01

Baroreflex buffering plays an important role in arterial blood pressure control. Previous reports suggest that baroreflex sensitivity may be altered in endurance exercise-trained compared with untrained subjects. It is unknown, however, if in vivo baroreflex buffering is altered in the endurance exercise-trained state in humans. Baroreflex buffering was determined in 36 healthy normotensive men (18 endurance exercise-trained, 41+/-5 [SEM] years; 18 untrained, 41+/-4 years) by measuring the potentiation of the systolic blood pressure responses to a phenylephrine bolus and to incremental phenylephrine infusion during compared with before ganglionic blockade with trimethaphan. The exercise-trained men had a lower resting heart rate and higher maximal oxygen consumption and heart rate variability than the sedentary control subjects (all P=0.01). Mean levels and variability of blood pressure, cardiovagal baroreflex sensitivity (change in heart rate/change in systolic blood pressure), and basal muscle sympathetic nerve activity were not different in the two groups. The systolic blood pressure responses to phenylephrine were not different in the endurance-trained and untrained men before or during ganglionic blockade (P>0.6). Measures of baroreflex buffering with the use of a phenylephrine bolus (3.9+/-0.8 versus 4.0+/-0.7, trained versus untrained, P=0.85) and incremental infusion (2.8+/-0.4 versus 2.5+/-0.6, P=0.67) were similar in the two groups. Baroreflex buffering does not differ in endurance exercise-trained compared with untrained healthy men. These results support the concept that habitual vigorous endurance exercise does not modulate in vivo baroreflex buffering in healthy humans.

Inhibition of Rho and Rac geranylgeranylation by atorvastatin is critical for preservation of endothelial junction integrity.

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Hongbing Xiao

Full Text Available BACKGROUND: Small GTPases (guanosine triphosphate, GTP are involved in many critical cellular processes, including inflammation, proliferation, and migration. GTP loading and isoprenylation are two important post-translational modifications of small GTPases, and are critical for their normal function. In this study, we investigated the role of post-translational modifications of small GTPases in regulating endothelial cell inflammatory responses and junctional integrity. METHODS AND RESULTS: Confluent human umbilical vein endothelial cell (HUVECs treated with atorvastatin demonstrated significantly decreased lipopolysaccharide (LPS-mediated IL-6 and IL-8 generation. The inhibitory effect of atorvastatin (Atorva was attenuated by co-treatment with 100 µM mevalonate (MVA or 10 µM geranylgeranyl pyrophosphate (GGPP, but not by 10 µM farnesyl pyrophosphate (FPP. Atorvastatin treatment of HUVECs produced a time-dependent increase in GTP loading of all Rho GTPases, and induced the translocation of small Rho GTPases from the cellular membrane to the cytosol, which was reversed by 100 µM MVA and 10 µM GGPP, but not by 10 µM FPP. Atorvastatin significantly attenuated thrombin-induced HUVECs permeability, increased VE-cadherin targeting to cell junctions, and preserved junction integrity. These effects were partially reversed by GGPP but not by FPP, indicating that geranylgeranylation of small GTPases plays a major role in regulating endothelial junction integrity. Silencing of small GTPases showed that Rho and Rac, but not Cdc42, play central role in HUVECs junction integrity. CONCLUSIONS: In conclusion, our studies show that post-translational modification of small GTPases plays a vital role in regulating endothelial inflammatory response and endothelial junction integrity. Atorvastatin increased GTP loading and inhibited isoprenylation of small GTPases, accompanied by reduced inflammatory response and preserved cellular junction integrity.

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

Haan, W. de; Vries-van der Weij, J. de; Hoorn, J.W.A. van der; Gautier, T.; Hoogt, C.C. van der; Westerterp, M.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Princen, H.M.G.; Rensen, P.C.N.

2008-01-01

BACKGROUND - Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, Jose W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

2008-01-01

Background-Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, José W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

2008-01-01

Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased

Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin.

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Nawawi, H; Osman, N S; Annuar, R; Khalid, B A K; Yusoff, K

2003-08-01

Adhesion molecules and cytokines are involved in the pathogenesis of intimal injury in atherosclerosis but their relationship with endothelial function remains unclear. The objectives of this study were to examine the effects of atorvastatin on soluble adhesion molecules, interleukin-6 (IL-6) and brachial artery endothelial-dependent flow mediated dilatation (FMD) in patients with familial (FH) and non-familial hypercholesterolaemia (NFH). A total of 74 patients (27 FH and 47 NFH) were recruited. Fasting lipid profiles, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-cellular adhesion molecule-1 (sVCAM-1), E-selectin, IL-6 and FMD were measured at baseline, 2 weeks, 3 and 9 months post-atorvastatin treatment (FH--80 mg/day, NFH--10 mg/day). In both groups, compared to baseline, sICAM-1 levels were significantly reduced at 2 weeks, further reduced at 3 months and maintained at 9 months (P<0.0001). The IL-6 levels were significantly reduced at 3 months and 9 months compared to baseline for FH (P<0.005) and NFH (P<0.0001). In both groups, the FMD at 2 weeks was higher than baseline (P<0.005), with progressive improvement up to 9 months. FMD was negatively correlated with sICAM-1 and IL-6. In conclusion, both low and high doses of atorvastatin lead to early progressive improvement in endothelial function in patients with primary hypercholesterolaemia. sICAM-1 and IL-6 levels reflect endothelial dysfunction in these patients.

Comparison of valsartan and benazepril when combined with atorvastatin in protecting patients with early cardio-renal syndrome (CRS).

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Peng, D-F; Tang, S-Y; Hu, Y-J; Chen, J; Peng, X; Huang, Q

2015-04-01

The aims to investigate the different protective effects of valsartan and benazepril when combined with atorvastatin in the cardio-renal functions of cardio-renal syndrome (CRS) patients. A total of 200 early CRS patients were enrolled in the present study, including 104 males and 96 females, with an average age of 62.2 ± 7.7 years. The same group of patients were set as the control group prior to treatment, and then randomly divided into two groups; the A group was treated with valsartan (80 mg/d) and atorvastatin (20 mg/d); the B group was treated with benazepril (10 mg/d) and atorvastatin (20 mg/d). The treatment period was 24 months. The clinical efficacy and clinical events were observed and the following parameters of each patient were measured before and after treatment: 24h urine protein; creatinine clearance; serum brain natriuretic peptide (BNP); high sensitivity C-reactive protein (hsCRP); blood lipid level; liver function and ejection fraction (EF) value. Compared with the control group, the clinical symptoms of the treatment groups were improved with decreased blood lipid levels, significantly decreased serum BNP and hsCRP levels and significantly increased EF values and creatinine clearance rates (p benazepril effectively improved the cardio-renal functions of early CRS patients. There was no significant difference between the two treatments however, valsartan appeared to be better tolerated by patients.

Profil Disolusi Terbanding, Penetapan Kadar, dan Kualitas Fisik Tablet Atorvastatin Inovator, Generik Bernama Dagang, dan Generik

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Nurul Aini

2015-08-01

Full Text Available Atorvastatin is one of the statins which is used as the first line therapy for hyperlipidemia. The patent of atorvastatin innovator ended in 2011. Besides the innovator brand of atorvastatin, several brand and one generic atorvastatin tablet are currently marketed in Indonesia. In this research, dissolution profiles, assay and physical quality were investigated for three atorvastatin tablet samples consist of one innovator sample, two atorvastatin copy layer products (branded generic atorvastatin sample and atorvastatin generic sample. The dissolution testing were done using FDA (Food and Drug Administration method. The result shows that the innovator and branded generic samples meet all the requirements for physical quality, meanwhile the generic sample failed to meet the disintegration test criteria. The branded generic sample has similar dissolution profile with the innovator, while the generic tablet was not similar. The assay were conducted using High Performance Liquid Chromatography (HPLC method. The assay result of the innovator, branded generic, and generic samples respectively were 97,54%, 106,36% and 97,65% which means that all samples comply with general requirement of active pharmaceutical ingredient in tablet.

Cost effectiveness of atorvastatin in patients with type 2 diabetes mellitus: a pharmacoeconomic analysis of the collaborative atorvastatin diabetes study in the belgian population.

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Annemans, L; Marbaix, S; Webb, K; Van Gaal, L; Scheen, A

2010-01-01

Patients with type 2 diabetes mellitus have a high risk of developing cardiovascular (CV) disease. The clinical benefit of use of statins in patients with type 2 diabetes has been demonstrated in several randomized, controlled trials, including the CARDS clinical trial. Based on the clinical CARDS data, the favourable cost effectiveness of atorvastatin 10 mg in patients with type 2 diabetes has been demonstrated in countries such as the UK and France. This study aimed to estimate the cost effectiveness in the Belgian setting of atorvastatin 10 mg compared with no treatment for the primary prevention of CV events in type 2 diabetes patients without a history of CV disease. A Markov model with 1-year cycles was developed to simulate the CV event and death risk according to the therapeutic approach initiated. The transition probabilities for CV events in the 'no statin treatment' group were derived from the risk equations reported from the large UKPDS. Risk reductions from the CARDS clinical trial were used to adjust these CV event probabilities in the atorvastatin 10 mg treatment group. The characteristics of type 2 diabetes patients without a CV history were derived from the Belgian OCAPI survey. The public healthcare payers' perspective was taken into account for costing. The direct medical costs of CV events were based on the Public Health Authorities' hospital database for acute care costs and on the literature for the follow-up costs. The impact on the reimbursement system of generic entry to the market was considered in the drug cost. Costs were valued as at year 2009; costs and outcomes were discounted at 3% and 1.5%, respectively. Based on a 5-year time horizon, atorvastatin was demonstrated to be cost effective with an incremental cost/quality-adjusted life-year (QALY) of euro 16,681. Over a lifetime horizon (25 years), atorvastatin was demonstrated to be a cost-saving therapeutic intervention. At a threshold of euro 30,000/QALY, atorvastatin had a 98

Technology of making healthy and correction of build of men of the first mature age

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Stroganov S.V.

2010-07-01

Full Text Available Directions of search of ways of making healthy of population of mature age are considered. In an experiment 30 men took part 21-35 years. The men of experimental group conducted training on the basis of 4th of the monthly program of correction and making healthy. There was statistically meaningful divergence in the capacity of men of experimental group by comparison to the men of control group. Also in the subjective estimation of own build, feel for a day, at the end of workweek and after training. Employment on the developed technology induced the men of experimental group a greater measure to give up harmful habits.

The value of atorvastatin over the product life cycle in the United States.

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Grabner, Michael; Johnson, Wallace; Abdulhalim, Abdulla M; Kuznik, Andreas; Mullins, C Daniel

2011-10-01

US health care reform mandates the reduction of wasteful health care spending while maintaining quality of care. Introducing new drugs into crowded therapeutic classes may be viewed as offering "me-too" (new drugs with a similar mechanism of action compared to existing drugs) drugs without incremental benefit. This article presents an analysis of the incremental costs and benefits of atorvastatin, a lipid-lowering agent. This analysis models the cost-effectiveness of atorvastatin over the product life cycle. The yearly cost-effectiveness of atorvastatin compared to simvastatin was modeled from 1997 to 2030 from the point of view of a US third-party payer. Estimates for incremental costs (in US $) and effects (in quality-adjusted life-years [QALYs]) for the primary and secondary prevention of cardiovascular events were taken from previously published literature and adjusted for changes in drug prices over time. Estimates of total statin use were derived using the National Health and Nutrition Examination Survey. Sensitivity analyses were conducted to examine variations in study parameters, including drug prices, indications, and discount rates. Assuming increasing statin use over time (with a mean of 1.07 million new users per year) and a 3% discount rate, the cumulative incremental cost-effectiveness ratio (ICER) of atorvastatin versus simvastatin ranged from cost-savings at release to a maximum of $45,066/QALY after 6 years of generic simvastatin use in 2012. Over the full modeled life cycle (1997-2030), the cumulative ICER of atorvastatin was $20,331/QALY. The incremental value of atorvastatin to US payers (after subtracting costs) was estimated at $44.57 to $194.78 billion, depending on willingness to pay. Findings from the sensitivity analyses were similar. A hypothetical situation in which atorvastatin did not exist was associated with a reduction in total expenditures but also a loss of QALYs gained. The cumulative ICER of atorvastatin varied across the

Solid-state NMR studies of form I of atorvastatin calcium.

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Wang, Wei David; Gao, Xudong; Strohmeier, Mark; Wang, Wei; Bai, Shi; Dybowski, Cecil

2012-03-22

Solid-state (13)C, (19)F, and (15)N magic angle spinning NMR studies of Form I of atorvastatin calcium are reported, including chemical shift tensors of all resolvable carbon sites and fluorine sites. The complete (13)C and (19)F chemical shift assignments are given based on an extensive analysis of (13)C-(1)H HETCOR and (13)C-(19)F HETCOR results. The solid-state NMR data indicate that the asymmetric unit of this material contains two atorvastatin molecules. A possible structure of Form I of atorvastatin calcium (ATC-I), derived from solid-state NMR data and density functional theory calculations of various structures, is proposed for this important active pharmaceutical ingredient (API).

High-Intensity Atorvastatin-Induced Rhabdomyolysis in an Elderly Patient With NSTEMI: A Case Report and Review of the Literature.

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Huynh, Glen A; Lee, Audrey J

2017-12-01

A 91-year-old male was admitted to the hospital for worsening muscle weakness, muscle pain, and unexplained soreness for the past 10 days. Four months prior to his admission, the patient had experienced a myocardial infarction and was initiated on atorvastatin 80 mg daily. Although the provider had instructed the patient to decrease the atorvastatin dose to 40 mg daily 3 months prior to admission, the patient did not adhere to the lower dose regimen until 10 days prior to hospitalization. Upon admission, the patient presented with muscle weakness and pain, a serum creatinine phosphokinase of 18 723 U/L, and a serum creatinine of 1.6 mg/dL. The atorvastatin dose was held and the patient was treated with intravenous fluids. The 2013 American College of Cardiology and American Heart Association Blood Cholesterol Practice Guidelines recommend the use of moderate-intensity statins in patients older than 75 years to prevent myopathy. However, in clinical practice, aggressive statin therapy is often prescribed for significant coronary disease. Prescribing high-intensity statins for patients with advanced age, such as this case, may increase the risk of rhabdomyolysis and other complications. This case report suggests that providers should avoid or be cautious with initiating high-intensity atorvastatin in elderly patients over 75 years to minimize the risk of rhabdomyolysis.

Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol

NARCIS (Netherlands)

Bergheanu, S. C.; van Tol, A.; Dallinga-Thie, G. M.; Liem, A.; Dunselman, P. H. J.; Van Der Bom, J. G.; Jukema, J. W.

Objective: Paraoxonase-1 (PON-1) is a highdensity lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity. Methods: We performed a prespecif ied prospective study in 68

Cigarette smoking weakens exercise habits in healthy men.

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Nagaya, Teruo; Yoshida, Hideyo; Takahashi, Hidekatsu; Kawai, Makoto

2007-10-01

To investigate the longitudinal impact of smoking cessation and relapse on the exercise habits of apparently healthy Japanese men, 750 subjects presenting for a checkup at a metropolitan health center were surveyed annually for 7 years. Exercise was dichotomously classified as none or any. Subjects were grouped in two categories: 98 smokers who ceased smoking during the second year of the study, matched with 196 continuing smokers and 196 men who had never smoked; and 52 relapsed smokers (including 2 new smokers) who did not smoke at baseline or at Year 1 but smoked from Year 2 to final follow-up, matched with 104 continuing smokers and 104 never-smokers. Based on self-reported responses to questionnaires, exercise was consistently less prevalent among smokers who did not quit than among never-smokers throughout the study. Habitual exercise in subjects who had quit smoking increased during the follow-up (any exercise: 42.9% at baseline increased to 51% at final follow-up, p for longitudinal trend = .115). Habitual exercise in matched never-smokers did not change during the study and decreased significantly among persistent smokers (p = .025). Habitual exercise in relapsed smokers decreased during the follow-up (any exercise: 50.0% at baseline declined to 32.7% at final follow-up, p = .007), but habitual exercise in matched persistent smokers and never-smokers did not change. We conclude that smoking and sedentary lifestyle coexist continuously, that smoking cessation is associated with increased habitual exercise among healthy men, and that relapse is associated with reduced habitual exercise, suggesting that cigarette smoking weakens exercise habits.

Relative effects of statin therapy on stroke and cardiovascular events in men and women: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study

DEFF Research Database (Denmark)

Goldstein, L.B.; Amarenco, P.; Lamonte, M.

2008-01-01

BACKGROUND AND PURPOSE: In SPARCL, treatment with atorvastatin 80 mg daily reduced stroke risk in patients with recent stroke or TIA and no known coronary heart disease by 16% versus placebo over 4.9 years of follow-up. The purpose of this secondary analysis was to determine whether men and women.......98 in women; P=0.40). CONCLUSIONS: Stroke and other cardiovascular events are similarly reduced with atorvastatin 80 mg/d in men and women with recent stroke or TIA Udgivelsesdato: 2008/9...

Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole: A Prospective, Randomized, Controlled Trial.

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Zhang, Jian-rong; Wang, Di-qing; Du, Jun; Qu, Guang-su; Du, Jian-lin; Deng, Song-bai; Liu, Ya-jie; Cai, Jin-xi; She, Qiang

2015-12-01

This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole. One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10  mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20  mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30  mg daily, Group B: DAPT + atorvastatin 20  mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30  mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events. A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB2, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05). In patients diagnosed with NSTE-ACS who have had drug-eluting stent implantation

The effect of atorvastatin on survival of rat ischemic flap

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Jian-Xun Chen

2013-04-01

Full Text Available Management of skin avulsion with tissue exposure is a challenge for plastic surgeons. Clinical observations have suggested that longer survival of skin flap prevents further contamination and infection. Less well known is the role of atorvastatin in avulsion skin flap. Therefore, we attempted to determine whether atorvastatin could alleviate avulsion skin flap in a rat model. Twenty male Sprague–Dawley rats were randomized into two groups: the atorvastatin group and the control. Before operation, each rat received an initial blood perfusion scan as baseline data. Then, each rat received an operation of skin flap incision, elevation, and resuturing to the original position under general anesthesia. Another blood perfusion scan was performed on each rat 30 minutes, 4 days, and 7 days postoperatively. On the 7th postoperative day, the necrotic area of skin flap was measured as the skin flap viability. The skin flap tissues at 2.5 and 5 cm distal to the skin flap base were collected for histopathological analysis, as well as measurement of vascular endothelial growth factor (VEGF mRNA expression, and vascular density. Compared with 30 minutes postoperation, there was a significant increase in the ratio of skin flap blood perfusion on the 4th and 7th days postoperation in both control and atorvastatin groups (p<0.05. Compared with the control group, there was a significant decrease in necrotic area, significant increase in ratio of skin flap blood perfusion on postoperation days 4 and 7, and significant increase in vascular density under high field at 2.5 cm distal to the base of skin flap in the atorvastatin group (p<0.05. The VEGF121 and VEGF165 mRNA expression at 2.5 cm distal to the base of skin flap differed significantly between the two groups (p<0.05. Compared with the control group, atorvastatin treatment improved skin flap blood perfusion, vascular density, and necrotic area dependent on VEGF mRNA expression.

Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol

NARCIS (Netherlands)

Bergheanu, S. C.; van Tol, A.; Dallinga-Thie, G. M.; Liem, A.; Dunselman, P. H. J.; van der Bom, J. G.; Jukema, J. W.

2007-01-01

Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity. We performed a prespecified prospective study in 68 patients, part of a

GH administration and discontinuation in healthy elderly men

DEFF Research Database (Denmark)

Lange, K H; Isaksson, F; Rasmussen, M H

2001-01-01

GH administration results in increased lean body mass (LBM), decreased fat mass (FM) and increased energy expenditure (EE). GH therapy may therefore have potential benefits, especially in the elderly, who are known to have decreased function of the GH/IGF-I axis. Several studies have focused...... discontinuation on body composition, resting oxygen uptake (VO2), resting heart rate (HR) and GH related serum markers in healthy elderly men....

Effect of change in body weight on incident diabetes mellitus in patients with stable coronary artery disease treated with atorvastatin (from the treating to new targets study).

Science.gov (United States)

Ong, Kwok-Leung; Waters, David D; Messig, Michael; DeMicco, David A; Rye, Kerry-Anne; Barter, Philip J

2014-05-15

Features of the metabolic syndrome are independent risk factors for new-onset diabetes mellitus (NODM) related to statin therapy. Obesity is the predominant underlying risk factor for the metabolic syndrome and diabetes mellitus. This study investigated whether change in body weight may predict NODM in statin-treated patients. A total of 7,595 patients without prevalent diabetes mellitus at baseline from the Treating to New Targets (TNT) study were included in this analysis. They were randomized to atorvastatin 10 or 80 mg/day and monitored for a median of 4.9 years. NODM developed in 659 patients (8.1% in the 10-mg group and 9.2% in the 80-mg group). There was a significant increase in body weight (0.9 kg, p weight was greater in patients with NODM than those without NODM (1.6 vs 0.9 kg, p weight with NODM risk remained significant after adjusting for confounding factors (hazard ratios 1.33, 1.42, and 1.88 for quartiles 2, 3, and 4 compared with quartile 1, respectively). Similar results were obtained in patients with normal fasting glucose level. In conclusion, 1-year change in body weight is predictive of NODM in patients who underwent statin therapy from the TNT trial. Our study highlights the importance of weight control as a lifestyle measure to prevent statin-related NODM. Copyright © 2014 Elsevier Inc. All rights reserved.

Neutrophil–lymphocyte ratio is associated with low high-density lipoprotein cholesterol in healthy young men

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Duran Tok

2014-04-01

Full Text Available Objective: It has been reported that the neutrophil–lymphocyte ratio is significantly elevated in patients with low high-density lipoprotein cholesterol (<35 mg/dL. But in this study, some patients had hypertension that may have affected the neutrophil–lymphocyte ratio. This study consisted of 1274 asymptomatic healthy young men. In contrast with the previous study, we investigated the neutrophil–lymphocyte ratio in healthy young men with low high-density lipoprotein cholesterol compared with controls. Methods: We studied 1274 asymptomatic young males (military personnel screening who underwent routine health check-up. Of them, 102 subjects had low high-density lipoprotein cholesterol. Results: The neutrophil–lymphocyte ratio was significantly higher among the men with low high-density lipoprotein cholesterol than that of the control group (P < 0.001. Conclusion: We conclude that the neutrophil–lymphocyte ratio is significantly elevated in asymptomatic healthy young men with low high-density lipoprotein cholesterol compared with control participants.

The comparison of the effects of standard 20 mg atorvastatin daily and 20 mg atorvastatin every other day on serum LDL-cholesterol and high sensitive C-reactive protein levels.

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Keleş, Telat; Akar Bayram, Nihal; Kayhan, Tuğba; Canbay, Alper; Sahin, Deniz; Durmaz, Tahir; Ozdemir, Ozcan; Aydoğdu, Sinan; Diker, Erdem

2008-12-01

In this study, we aimed at comparing the effects of standard once daily 20 mg atorvastatin treatment with that of atorvastatin 20 mg administered every other day on serum lipids and high sensitive C-reactive protein (hs-CRP) levels. Sixty-one patients with serum total cholesterol levels of above 200 mg/dl and low density lipoprotein (LDL)--cholesterol levels of above 130 mg/dl were included in this prospective, randomized study. The patients were randomized into daily treatment of 20 mg atorvastatin (standard treatment) and 20 mg atorvastatin every other day (every other day treatment) groups. Before the treatment and at each visit, serum lipids and hs-CRP levels of all the patients were measured. Statistical analyses were performed Chi-square, unpaired t and two-way repeated measurements ANOVA tests. In the every other day treatment group, there was a 36.1% reduction in LDL-cholesterol levels by the end of first month (p0.05). The LDL cholesterol levels of the group receiving 20 mg atorvastatin every day was reduced by %41 by the end of 1 month (pevery other day, there was a 21% decrease in hs-CRP levels compared to the basal measurements at the end of first month (pevery day the decrease in hs-CRP levels at the end of one month was more striking (37%, p0.05). Alternate-day dosing of atorvastatin causes a significant lipid-lowering and antiinflammatory effects similar to that of daily administration and yet may provide some cost savings.

Toxicity of Atorvastatin on Pancreas Mitochondria: A Justification for Increased Risk of Diabetes Mellitus.

Science.gov (United States)

Sadighara, Melina; Amirsheardost, Zahra; Minaiyan, Mohsen; Hajhashemi, Valiollah; Naserzadeh, Parvaneh; Salimi, Ahmad; Seydi, Enayatollah; Pourahmad, Jalal

2017-02-01

Statins (including atorvastatin) are a widely used class of drugs, and like all medications, they have a potential for adverse effects. Recently, it has been shown that statins also exert side effects on the pancreas. In vitro studies have suggested that this class of drugs induced a reduction in insulin secretion. Also, the use of statins is associated with a raised risk of diabetes mellitus (DM), but the mechanisms underlying statin-induced diabetes are poorly known. Literature data indicate that several statins are able to induce apoptosis signalling. This study was designed to examine the mechanism of atorvastatin on mitochondria obtained from rat pancreas. In our study, mitochondria were obtained from the pancreas and then exposed to atorvastatin and vehicle to investigate probable toxic effects. The results showed that atorvastatin (25, 50, 75, 100 and 125 μM) increased reactive oxygen species (ROS) production, mitochondrial swelling, collapse of mitochondrial membrane potential and cytochrome c release, the orchestrating factor for mitochondria-mediated apoptosis signalling. Atorvastatin also reduced the ATP levels. These results propose that the toxicity of atorvastatin on pancreas mitochondria is a key point for drug-induced apoptotic cell loss in the pancreas and therefore a justification for increased risk of DM. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats

OpenAIRE

Nasri, Hamid-Reza; Joukar, Siyavash; Kheradmand, Hamid; Poursalehi, Hamid-Reza; Dabiri, Shahriar

2015-01-01

Objective The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats. Materials and Methods Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 we...

Mechanism of inhibitory effect of atorvastatin on resistin expression induced by tumor necrosis factor-α in macrophages

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Chua Su-Kiat

2009-05-01

Full Text Available Abstract Atorvastatin has been shown to reduce resistin expression in macrophages after pro-inflammatory stimulation. However, the mechanism of reducing resistin expression by atorvastatin is not known. Therefore, we sought to investigate the molecular mechanisms of atorvastatin for reducing resistin expression after proinflammatory cytokine, tumor necrosis factor-α (TNF-α stimulation in cultured macrophages. Cultured macrophages were obtained from human peripheral blood mononuclear cells. TNF-α stimulation increased resistin protein and mRNA expression and atorvastatin inhibited the induction of resistin by TNF-α. Addition of mevalonate induced resistin protein expression similar to TNF-α stimulation. However, atorvastatin did not have effect on resistin protein expression induced by mevalonate. SP600125 and JNK small interfering RNA (siRNA completely attenuated the resistin protein expression induced by TNF-α and mevalonate. TNF-α induced phosphorylation of Rac, while atorvastatin and Rac-1 inhibitor inhibited the phosphorylation of Rac induced by TNF-α. The gel shift and promoter activity assay showed that TNF-α increased AP-1-binding activity and resistin promoter activity, while SP600125 and atorvastatin inhibited the AP-1-binding activity and resistin promoter activity induced by TNF-α. Recombinant resistin and TNF-α significantly reduced glucose uptake in cultured macrophages, while atorvastatin reversed the reduced glucose uptake by TNF-α. In conclusion, JNK and Rac pathway mediates the inhibitory effect of atorvastatin on resistin expression induced by TNF-α.

Atorvastatin and prevention of contrast induced nephropathy following coronary angiography

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Peyman Bidram

2015-01-01

Full Text Available Background: Contrast induced nephropathy (CIN is one of the most common complications after radiographic procedures using intravascular radiocontrast media. The aim of the current study was to assess the effect of atorvastatin on prevention of CIN in patients undergoing coronary angiography. Materials and Methods: In a clinical trial study, 200 patients referred for angiography were randomly divided into two groups of using 80 mg atorvastatin and placebo before the procedure. Furthermore, 100 patients who were under chronic treatment of statins were included as the third group. Serum creatinine (Scr levels before and after the procedure were evaluated and incidence of CIN (post-procedural Scr of >0.5 mg/dl or >25% from baseline was assessed. Results: Mean age of the participants was 60.06 ± 0.69 years and 276 (92% were male. There were no significant differences between group with respect to age and gender. In pre-operation atorvastatin, placebo and long term statin groups, the incidence of CIN was 1%, 2% and 1%, and mean changes of Glomerular filtration rate (GFR was 3.68 ± 1.32, −0.77 ± 1.21 and 1.37 ± 0.86; and mean changes of creatinine (Cr was −0.05 ± 0.02, 0.02 ± 0.02 and −0.01 ± 0.01 respectively. (P = 0.776, 0.026 and 0.041 respectively. In pre-operation atorvastatin group, Cr decreased, and GFR increased significantly (P = 0.019 and 0.007 respectively. Conclusion: pre-operation short term high dose atorvastatin use was associated with a significant decrease in serum Cr level and increase in GFR after angiography.

Atorvastatin reduces lipopolysaccharide-induced expression of cyclooxygenase-2 in human pulmonary epithelial cells

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Chen Ping

2005-04-01

Full Text Available Abstract Objective To explore the effects of atorvastatin on expression of cyclooxygenase-2 (COX-2 in human pulmonary epithelial cells (A549. Methods A549 cells were incubated in DMEM medium containing lipopolysaccharide (LPS in the presence or absence of atorvastatin. After incubation, the medium was collected and the amount of prostaglandin E2 (PGE2 was measured by enzyme-linked immunosorbent assay (ELISA. The cells were harvested, and COX-2 mRNA and protein were analyzed by RT-PCR and western-blot respectively. Results LPS increased the expression of COX-2 mRNA and production of PGE2 in a dose- and time-dependent manner in A549. Induction of COX-2 mRNA and protein by LPS were inhibited by atorvastatin in a dose-dependent manner. Atorvastatin also significantly decreased LPS-induced production of PGE2. There was a positive correlation between reduced of COX-2 mRNA and decreased of PGE2 (r = 0.947, P Conclusion Atorvastatin down-regulates LPS-induced expression of the COX-2 and consequently inhibits production of PGE2 in cultured A549 cells.

Risk factors of osteoporosis in healthy Moroccan men

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Mounach Aziza

2010-07-01

Full Text Available Abstract Background Although not as common as in women, osteoporosis remains a significant health care problem in men. Data concerning risk factors of osteoporosis are lacking for the male Moroccan population. The objective of the study was to identify some determinants associated to low bone mineral density in Moroccan men. Methods a sample of 592 healthy men aged 20-79 years was recruited from the area of Rabat, the capital of Morocco. Measurements were taken at the lumbar spine and proximal femurs using DXA (Lunar Prodigy Vision, GE. Biometrical, clinical, and lifestyle determinants were collected. Univariate, multivariate, and logistic regression analyses were performed. Results the mean (SD age of the patients was 49 (17.2 years old. The prevalence of osteoporosis and osteopenia were 8.7% and 52.8%, respectively. Lumbar spine and hip BMD correlated significantly with age, weight and BMI. When comparing the subjects according to the WHO classification, significant differences were revealed between the three groups of subjects for age, weight and BMI, prevalence of low calcium intake and low physical activity. The multiple regression analysis found that only age, BMI, and high coffee consumption were independently associated to the osteoporotic status. Conclusion ageing and low BMI are the main risk factors associated with osteoporosis in Moroccan men.

Atorvastatin inhibits insulin synthesis by inhibiting the Ras/Raf/ERK/CREB pathway in INS-1 cells

Science.gov (United States)

Sun, Hongxi; Li, Yu; Sun, Bei; Hou, Ningning; Yang, Juhong; Zheng, Miaoyan; Xu, Jie; Wang, Jingyu; Zhang, Yi; Zeng, Xianwei; Shan, Chunyan; Chang, Bai; Chen, Liming; Chang, Baocheng

2016-01-01

Abstract Backround: Type 2 diabetes has become a global epidemic disease. Atorvastatin has become a cornerstone in the prevention and treatment of atherosclerosis. However, increasing evidence showed that statins can dose-dependently increase the risk of diabetes mellitus. The mechanism is not clear. Objective: The Ras complex pathway (Ras/Raf/extracellular signal-regulated kinase [ERK]/cAMP response element-binding protein [CREB]) is the major pathway that regulates the gene transcription. Except for the inhibition of cholesterol synthesis by inhibiting the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-COA) reductase, statins can also downregulate the phosphorylation of a series of downstream substrates including the key proteins of the Ras complex pathway, therefore may inhibit the insulin syntheses in pancreatic beta cells. In our study, we investigated the inhibitory effect and the underlying mechanism of atorvastatin on insulin synthesis in rat islets. Methods: Islets were isolated from Wistar rats and cultured in Roswell Park Memorial Institute (RPMI)-1640 medium. The insulin content in the medium was measured by radioimmunoassay before and after the treatment of 50 μM atorvastatin. Effect of atorvastatin on the expression of insulin message Ribonucleic acid (mRNA) in pancreatic islet beta cells was also detected using quantitative real-time polymerase chain reaction. Western blotting was used to explore the possible role of the Ras complex pathway (Ras/Raf/ERK/CREB) in atorvastatin-inhibited insulin synthesis. The effects of atorvastatin on the binding of nuclear transcription factor p-CREB with CRE in INS-1 cells were examined via chromatin immunoprecipitation assay. Results: Compared with the control group, the insulin level decreased by 27.1% at 24 hours after atorvastatin treatment. Atorvastatin inhibited insulin synthesis by decreasing insulin mRNA expression of pancreatic islet beta cells. The activities of Ras, Raf-1, and p-CREB in the Ras complex

Efficacy of atorvastatin on the prevention of contrast-induced acute kidney injury: a meta-analysis

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Liu L

2018-03-01

Full Text Available Ling-Yun Liu,1 Yang Liu,2 Mei-Yan Wu,2 Yan-Yan Sun,3 Fu-Zhe Ma2 1Department of Andrology, 2Department of Nephrology, the First Hospital of Jilin University, 3Department of Nephrology, the Fourth Hospital of Jilin University, Changchun, China Background: Results of studies on the efficacy of atorvastatin pretreatment on reducing the prevalence of contrast-induced acute kidney injury (CIAKI in patients undergoing coronary angiography (CAG or percutaneous coronary intervention (PCI have been controversial.Objective: We undertook a meta-analysis to evaluate the efficacy of atorvastatin on contrast-induced nephropathy (CIN after CAG or PCI.Materials and methods: We undertook a systematic search of electronic databases (PubMed, Embase, and the Cochrane Library up to June 2017. A meta-analysis was carried out including randomized controlled trials (RCTs that compared atorvastatin pretreatment with pretreatment with a low-dose statin or placebo for CIAKI prevention in patients undergoing CAG. The main endpoint was CIN prevalence.Results: Nine RCTs were included in our meta-analysis. Atorvastatin pretreatment reduced the prevalence of CIN significantly (odds ratio [OR] 0.46; 95% confidence interval [95% CI] 0.27–0.79; p=0.004. The benefit of high-dose atorvastatin pretreatment was consistent when compared with the control group (OR 0.45; 95% CI 0.21–0.95; p=0.04.Conclusion: At high doses, atorvastatin pretreatment was associated with a significant reduction in the prevalence of CIAKI in patients undergoing CAG. Pretreatment with high-dose atorvastatin could be employed to prevent CIAKI. Keywords: atorvastatin, contrast-induced acute kidney injury, coronary angiography, percutaneous coronary intervention, contrast-induced nephropathy, meta-analysis

Studying neuroprotective effect of Atorvastatin as a small molecule drug on high glucose-induced neurotoxicity in undifferentiated PC12 cells: role of NADPH oxidase.

Science.gov (United States)

Rayegan, Samira; Dehpour, Ahmad Reza; Sharifi, Ali Mohammad

2017-02-01

Overproduction of reactive oxygen species (ROS) by NADPH oxidase (NOX) activation has been considered the essential mechanism induced by hyperglycemia in various tissues. However, there is no comprehensive study on the role of NOXs in high glucose (HG)-induced toxic effect in neural tissues. Recently, a therapeutic strategy in oxidative related pathologies has been introduced by blocking the undesirable actions of NOX enzymes by small molecules. The protective roles of Statins in ameliorating oxidative stress by NOX inhibition have been shown in some tissues except neural. We hypothesized then, that different NOXs may have role in HG-induced neural cell injury. Furthermore, we postulate that Atorvastatin as a small molecule may modulate this NOXs activity to protect neural cells. Undifferentiated PC12 cells were treated with HG (140 mM/24 h) in the presence and absence of Atorvastatin (1 μM/96 h). The cell viability was measured by MTT assay and the gene and protein expressions profile of NOX (1-4) were determined by RT-PCR and western blotting, respectively. Levels of ROS and malondialdehyde (MDA) were also evaluated. Gene and protein expression levels of NOX (1-4) and consequently ROS and MDA levels were elevated in HG-treated PC12 cells. Atorvastatin could significantly decrease HG-induced NOXs, ROS and MDA elevation and improve impaired cell viability. It can be concluded that HG could elevate NOXs activity, ROS and MDA levels in neural tissues and Atorvastatin as a small molecule NOX inhibitor drug may prevent and delay diabetic complications, particularly neuropathy.

Effects of music on cardiovascular responses in men with essential hypertension compared with healthy men based on introversion and extraversion.

Science.gov (United States)

Namdar, Hossein; Taban Sadeghi, Mohammadreza; Sabourimoghaddam, Hassan; Sadeghi, Babak; Ezzati, Davoud

2014-01-01

The present research investigated the effects of two different types of music on cardiovascular responses in essential hypertensive men in comparison with healthy men based on introversion and extraversion. One hundred and thirteen hypertensive men referred to Madani Heart Hospital in Tabriz completed the NEO-FFI Questionnaire and after obtaining acceptable scores were classified in four groups: introvert patients, extravert patients, introvert healthy subjects, and extravert healthy subjects (each group with 25 samples with age range 31-50). Baseline blood pressure and heart rate of each subject was recorded without any stimulus. Then subjects were exposed to slow-beat music and blood pressure and heart rate were recorded. After15 minute break, and a little cognitive task for distraction, subjects were exposed to fast-beat music and blood pressure and heart rate were recorded again. Multivariate analysis of covariance (MANCOVA) test showed that extravert patient subjects obtained greater reduction in systolic blood pressure and heart rate after presenting slow-beat music compared with introvert patients (P= 0.035, and P= 0.033 respectively). And extravert healthy subjects obtained greater reduction in heart rate after presenting slow-beat music compared with introvert healthy subjects (P= 0.036). However, there are no significant differences between introvert and extravert groups in systolic and diastolic blood pressure and heart rate after presenting fast-beat music. Based on our results, introvert subjects experience negative emotions more than extravert subjects and negative emotions cause less change in blood pressure in these subjects compared with extravert subjects.

Effects of Music on Cardiovascular Responses in Men with Essential Hypertension Compared with Healthy Men Based on Introversion and Extraversion

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Hossein Namdar

2014-10-01

Full Text Available Introduction: The present research investigated the effects of two different types of music on cardiovascular responses in essential hypertensive men in comparison with healthy men based on introversion and extraversion. Methods: One hundred and thirteen hypertensive men referred to Madani Heart Hospital in Tabriz completed the NEO-FFI Questionnaire and after obtaining acceptable scores were classified in four groups: introvert patients, extravert patients, introvert healthy subjects, and extravert healthy subjects (each group with 25 samples with age range 31-50. Baseline blood pressure and heart rate of each subject was recorded without any stimulus. Then subjects were exposed to slow-beat music and blood pressure and heart rate were recorded. After15 minute break, and a little cognitive task for distraction, subjects were exposed to fast-beat music and blood pressure and heart rate were recorded again. Results: Multivariate analysis of covariance (MANCOVA test showed that extravert patient subjects obtained greater reduction in systolic blood pressure and heart rate after presenting slow-beat music compared with introvert patients (P= 0.035, and P= 0.033 respectively. And extravert healthy subjects obtained greater reduction in heart rate after presenting slow-beat music compared with introvert healthy subjects (P= 0.036. However, there are no significant differences between introvert and extravert groups in systolic and diastolic blood pressure and heart rate after presenting fast-beat music. Conclusion: Based on our results, introvert subjects experience negative emotions more than extravert subjects and negative emotions cause less change in blood pressure in these subjects compared with extravert subjects.

Development and Validation of High Performance Liquid Chromatography Method for Determination Atorvastatin in Tablet

Science.gov (United States)

Yugatama, A.; Rohmani, S.; Dewangga, A.

2018-03-01

Atorvastatin is the primary choice for dyslipidemia treatment. Due to patent expiration of atorvastatin, the pharmaceutical industry makes copy of the drug. Therefore, the development methods for tablet quality tests involving atorvastatin concentration on tablets needs to be performed. The purpose of this research was to develop and validate the simple atorvastatin tablet analytical method by HPLC. HPLC system used in this experiment consisted of column Cosmosil C18 (150 x 4,6 mm, 5 µm) as the stationary reverse phase chomatography, a mixture of methanol-water at pH 3 (80:20 v/v) as the mobile phase, flow rate of 1 mL/min, and UV detector at wavelength of 245 nm. Validation methods were including: selectivity, linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ). The results of this study indicate that the developed method had good validation including selectivity, linearity, accuracy, precision, LOD, and LOQ for analysis of atorvastatin tablet content. LOD and LOQ were 0.2 and 0.7 ng/mL, and the linearity range were 20 - 120 ng/mL.

Comparison of total and compartmental gastric emptying and antral motility between healthy men and women

Energy Technology Data Exchange (ETDEWEB)

Bennink, R.; Van den Maegdenbergh, V.; Roo, M. de; Mortelmans, L. [Department of Nuclear Medicine, UZ KU Leuven (Belgium); Peeters, M.; Geypens, B.; Rutgeerts, P. [Department of Gastroenterology, UZ KU Leuven (Belgium)

1998-09-01

There is increasing evidence of gender-related differences in gastric emptying. The purpose of this study was first, to confirm the difference in gastric emptying for both solid and liquid test meals between healthy men and women, and secondly, to investigate the origin of this difference by studying regional gastric emptying and antral motility. A standard gastric emptying test with additional compartmental (proximal and distal) evaluation and dynamic imaging of the antrum was performed in 20 healthy women studied during the first 10 days of the menstrual cycle, and in 31 healthy age-matched men. In concordance with previous reports, women had a longer half-emptying time for solids as compared to men (86.2{+-}5.1 vs 52.2{+-}2.9 min, P<0.05). In our observations this seemed to be related to a significantly prolonged lag phase and a significant decrease in terminal slope. Dynamical antral scintigraphy did not show a significant difference. The distribution of the test meal within the stomach (proximal vs distal) showed more early proximal retention in women as compared to men. The terminal slope of the distal somach was significantly lower in women. We did not observe a significant difference in gastric emptying of the liquid test meal between men and women. Gastric emptying of solids is significantly slower in healthy women as compared to men. These findings emphasise the importance of using different normal values for clinical and research purposes in gastric emptying scintigraphy in men and women. The difference could not be explained by antral motility alone. Increased proximal retention and a lower terminal emptying rate in women are observations to be further investigated. (orig.) With 5 figs., 2 tabs., 36 refs.

A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia.

Science.gov (United States)

Langslet, Gisle; Breazna, Andrei; Drogari, Euridiki

2016-01-01

The efficacy and safety of atorvastatin in children/adolescents aged 10-17 years with heterozygous familial hypercholesterolemia (HeFH) have been demonstrated in trials of up to 1 year in duration. However, the efficacy/safety of >1 year use of atorvastatin in children/adolescents with HeFH, including children from 6 years of age, has not been assessed. To characterize the efficacy and safety of atorvastatin over 3 years and to assess the impact on growth and development in children aged 6-15 years with HeFH. A total of 272 subjects aged 6-15 years with HeFH and low-density lipoprotein cholesterol (LDL-C) ≥4.0 mmol/L (154 mg/dL) were enrolled in a 3-year study (NCT00827606). Subjects were initiated on atorvastatin (5 mg or 10 mg) with doses increased to up to 80 mg based on LDL-C levels. Mean percentage reductions from baseline in LDL-C at 36 months/early termination were 43.8% for subjects at Tanner stage (TS) 1 and 39.9% for TS ≥2. There was no evidence of variations in the lipid-lowering efficacy of atorvastatin between the TS groups analyzed (1 vs ≥2) or in subjects aged Atorvastatin had a favorable safety and tolerability profile, and only 6 (2.2%) subjects discontinued because of adverse events. Atorvastatin over 3 years was efficacious, had no impact on growth/maturation, and was well tolerated in children and adolescents with HeFH aged 6-15 years. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay

International Nuclear Information System (INIS)

Gajski, Goran; Garaj-Vrhovac, Vera; Orescanin, Visnja

2008-01-01

To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between the results obtained by the comet (Fpg-modified and standard) and micronucleus assay. Overall, the study demonstrated that atorvastatin in its highest dose is capable of producing damage on the level of DNA molecule and cell

Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay

Energy Technology Data Exchange (ETDEWEB)

Gajski, Goran [Institute for Medical Research and Occupational Health, Mutagenesis Unit, 10000 Zagreb (Croatia); Garaj-Vrhovac, Vera [Institute for Medical Research and Occupational Health, Mutagenesis Unit, 10000 Zagreb (Croatia); Orescanin, Visnja [Ruder Boskovic Institute, 10000 Zagreb (Croatia)

2008-08-15

To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between the results obtained by the comet (Fpg-modified and standard) and micronucleus assay. Overall, the study demonstrated that atorvastatin in its highest dose is capable of producing damage on the level of DNA molecule and cell.

Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

International Nuclear Information System (INIS)

Zhao, X.J.; Liu, X.L.; He, G.X.; Xu, H.P.

2014-01-01

The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in

Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

Energy Technology Data Exchange (ETDEWEB)

Zhao, X. J. [Affiliated Hospital of Binzhou Medical University, Department of Cardiology, Binzhou, China, Department of Cardiology, Affiliated Hospital of Binzhou Medical University, Binzhou (China); Liu, X. L. [Qilu Hospital, Shandong University, Department of Cardiology, Jinan, China, Department of Cardiology, Qilu Hospital, Shandong University, Jinan (China); He, G. X. [Third Military Medical University, Southwest Hospital, Department of Cardiology, Chongqing, China, Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing (China); Xu, H. P. [Affiliated Hospital of Binzhou Medical University, Department of Cardiology, Binzhou, China, Department of Cardiology, Affiliated Hospital of Binzhou Medical University, Binzhou (China)

2014-03-03

The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in

Severe rhabdomyolysis as a consequence of the interaction of fusidic acid and atorvastatin.

LENUS (Irish Health Repository)

Magee, Ciara N

2010-11-01

Rhabdomyolysis is a known complication of statin therapy and may be triggered by a pharmacokinetic interaction between a statin and a second medication. Fatal statin-induced rhabdomyolysis has an incidence of 0.15 deaths\\/million prescriptions. We describe 4 cases of severe rhabdomyolysis with the common feature of atorvastatin use and coadministration of fusidic acid. All cases involved long-term therapy with atorvastatin; fusidic acid was introduced for treatment of osteomyelitis or septic arthritis. Three cases occurred in the setting of diabetes mellitus, with 2 in patients with end-stage renal disease, suggesting increased susceptibility to atorvastatin-fusidic acid-induced rhabdomyolysis in these patient populations. Of the 4 patients in this series, 3 died. Fusidic acid is a unique bacteriostatic antimicrobial agent with principal antistaphylococcal activity. There have been isolated reports of rhabdomyolysis attributed to the interaction of statins and fusidic acid, the cause of which is unclear. Fusidic acid does not inhibit the cytochrome P450 3A4 isoenzyme responsible for atorvastatin metabolism; increased atorvastatin levels due to inhibition of the glucuronidation pathway may be responsible. Considering the low frequency of fusidic acid use, the appearance of 4 such cases within a short time and in a small population suggests the probability that development of this potentially fatal complication may be relatively high.

Atorvastatin improves cardiac function and remodeling in chronic non-ischemic heart failure: A clinical and pre-clinical study

Directory of Open Access Journals (Sweden)

Ibrahim Elmadbouh

2015-12-01

Conclusions: Atorvastatin with standard CHF therapy improved cardiac function and remodeling. Cardio-protective “pleiotropic” actions of atorvastatin are anti-inflammatory, anti-fibrotic and anti-oxidative. Thus, atorvastatin has a potential therapeutic value in the management of CHF patients.

Irradiation-Induced Cardiac Connexin-43 and miR-21 Responses Are Hampered by Treatment with Atorvastatin and Aspirin

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Csilla Viczenczova

2018-04-01

Full Text Available Radiation of the chest during cancer therapy is deleterious to the heart, mostly due to oxidative stress and inflammation related injury. A single sub-lethal dose of irradiation has been shown to result in compensatory up-regulation of the myocardial connexin-43 (Cx43, activation of the protein kinase C (PKC signaling along with the decline of microRNA (miR-1 and an increase of miR-21 levels in the left ventricle (LV. We investigated whether drugs with antioxidant, anti-inflammatory or vasodilating properties, such as aspirin, atorvastatin, and sildenafil, may affect myocardial response in the LV and right ventricle (RV following chest irradiation. Adult, male Wistar rats were subjected to a single sub-lethal dose of chest radiation at 25 Gy and treated with aspirin (3 mg/day, atorvastatin (0.25 mg/day, and sildenafil (0.3 mg/day for six weeks. Cx43, PKCε and PKCδ proteins expression and levels of miR-1 as well as miR-21 were determined in the LV and RV. Results showed that the suppression of miR-1 was associated with an increase of total and phosphorylated forms of Cx43 as well as PKCε expression in the LV while having no effect in the RV post-irradiation as compared to the non-irradiated rats. Treatment with aspirin and atorvastatin prevented an increase in the expression of Cx43 and PKCε without change in the miR-1 levels. Furthermore, treatment with aspirin, atorvastatin, and sildenafil completely prevented an increase of miR-21 in the LV while having partial effect in the RV post irradiation. The increase in pro-apoptotic PKCδ was not affected by any of the used treatment. In conclusion, irradiation and drug-induced changes were less pronounced in the RV as compared to the LV. Treatment with aspirin and atorvastatin interfered with irradiation-induced compensatory changes in myocardial Cx43 protein and miR-21 by preventing their elevation, possibly via amelioration of oxidative stress and inflammation.

Blood lactose after dairy product intake in healthy men.

Science.gov (United States)

Pimentel, Grégory; Burton, Kathryn J; Rosikiewicz, Marta; Freiburghaus, Carola; von Ah, Ueli; Münger, Linda H; Pralong, François P; Vionnet, Nathalie; Greub, Gilbert; Badertscher, René; Vergères, Guy

2017-12-01

The absence of a dedicated transport for disaccharides in the intestine implicates that the metabolic use of dietary lactose relies on its prior hydrolysis at the intestinal brush border. Consequently, lactose in blood or urine has mostly been associated with specific cases in which the gastrointestinal barrier is damaged. On the other hand, lactose appears in the blood of lactating women and has been detected in the blood and urine of healthy men, indicating that the presence of lactose in the circulation of healthy subjects is not incompatible with normal physiology. In this cross-over study we have characterised the postprandial kinetics of lactose, and its major constituent, galactose, in the serum of fourteen healthy men who consumed a unique dose of 800 g milk or yogurt. Genetic testing for lactase persistence and microbiota profiling of the subjects were also performed. Data revealed that lactose does appear in serum after dairy intake, although with delayed kinetics compared with galactose. Median serum concentrations of approximately 0·02 mmol/l lactose and approximately 0·2 mmol/l galactose were observed after the ingestion of milk and yogurt respectively. The serum concentrations of lactose were inversely correlated with the concentrations of galactose, and the variability observed between the subjects' responses could not be explained by the presence of the lactase persistence allele. Finally, lactose levels have been associated with the abundance of the Veillonella genus in faecal microbiota. The measurement of systemic lactose following dietary intake could provide information about lactose metabolism and nutrient transport processes under normal or pathological conditions.

Effects of gemfibrozil and atorvastatin on the pharmacokinetics of repaglinide in relation to SLCO1B1 polymorphism.

Science.gov (United States)

Kalliokoski, A; Backman, J T; Kurkinen, K J; Neuvonen, P J; Niemi, M

2008-10-01

In a randomized crossover study, 24 SLCO181-genotyped healthy volunteers were given daily doses of 1,200 mg gemfibrozil, 40 mg atorvastatin, or placebo, followed by 0.25 mg of repaglinide on day 3. The mean increase in the repaglinide area under the plasma concentration-time curve from 0 h to infinity (AUC(0-infinity)) produced by gemfibrozil was larger in individuals with the SLCO1B1 c.521CC genotype (n = 6) than in those with the c.521TC (n = 6) and c.521TT (n = 12) genotypes, by factors of 1.56 (P = 0.004) and 1.54 (P = 0.002), respectively. Gemfibrozil prolonged the repaglinide elimination half-life 1.43 times more in the c.521 CC group than in the c.521TT group (P = 0.047), but no differences were seen in the effects on peak plasma concentration (C(max)). While on gemfibrozil, the minimum blood glucose concentration after repaglinide intake was 19% lower in the c.521CC participants than in the c.521TT participants (P = 0.009). In the c.521TT group, atorvastatin intake had the effect of increasing repaglinide Cmax and AUC(0-infinity) by41% (P = 0.001) and 18% (P = 0.033), respectively. In conclusion, the extent of gemfibrozil-repaglinide interaction depends on SLCO1B1 genotype. Atorvastatin raises plasma repaglinide concentrations, probably by inhibiting organic anion transporting polypeptide 1B1 (OATP1B1).

Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the VYMET study)

DEFF Research Database (Denmark)

Robinson, Jennifer G; Ballantyne, Christie M; Grundy, Scott M

2009-01-01

the lipid-lowering efficacy of ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 or 20 mg, and ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in 1,128 patients with hypercholesterolemia and the metabolic syndrome. The primary end point was the percentage of change from baseline in low......, apolipoprotein B, and lipid/lipoprotein ratios resulted with ezetimibe/simvastatin compared with atorvastatin at all specified dose comparisons (p .../simvastatin than with atorvastatin at all dose comparisons (p atorvastatin 10 mg (p atorvastatin 40 mg (p

Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.

Science.gov (United States)

Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar

2015-08-01

We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Testosterone and sexual desire in healthy women and men.

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van Anders, Sari M

2012-12-01

Sexual desire is typically higher in men than in women, with testosterone (T) thought to account for this difference as well as within-sex variation in desire in both women and men. However, few studies have incorporated both hormonal and social or psychological factors in studies of sexual desire. The present study addressed how three psychological domains (sexual-relational, stress-mood, body-embodiment) were related to links between T and sexual desire in healthy adults and whether dyadic and solitary desire showed associations with T. Participants (n = 196) were recruited as part of the Partnering, Physiology, and Health study, which had 105 men and 91 women who completed questionnaires and provided saliva for cortisol and T assays. T was positively linked to solitary desire in women, with masturbation frequency influencing this link. In contrast, T was negatively correlated with dyadic desire in women, but only when cortisol and perceived social stress were controlled. Replicating past findings, no significant correlations between T and desire in men were apparent, but these analyses showed that the null association remained even when psychological and confound variables were controlled. Men showed higher desire than women, but masturbation frequency rather than T influenced this difference. Results were discussed in terms of challenges to assumptions of clear links between T and desire, gendered approaches to T, and the unitarity of desire.

Acute Effects of Morning Light on Plasma Glucose and Triglycerides in Healthy Men and Men with Type 2 Diabetes

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Versteeg, Ruth I.; Stenvers, Dirk J.; Visintainer, Dana; Linnenbank, Andre; Tanck, Michael W.; Zwanenburg, Gooitzen; Smilde, Age K.; Fliers, Eric; Kalsbeek, Andries; Serlie, Mireille J.; la Fleur, Susanne E.; Bisschop, Peter H.

2017-01-01

Ambient light intensity is signaled directly to hypothalamic areas that regulate energy metabolism. Observational studies have shown associations between ambient light intensity and plasma glucose and lipid levels, but human data on the acute metabolic effects of light are scarce. Since light is the main signal indicating the onset of the diurnal phase of physical activity and food intake in humans, we hypothesized that bright light would affect glucose and lipid metabolism. Therefore, we determined the acute effects of bright light on plasma glucose and lipid concentrations in 2 randomized crossover trials: (1) in 8 healthy lean men and (2) in 8 obese men with type 2 diabetes. From 0730 h, subjects were exposed to either bright light (4000 lux) or dim light (10 lux) for 5 h. After 1 h of light exposure, subjects consumed a 600-kcal mixed meal. Primary endpoints were fasting and postprandial plasma glucose levels. In healthy men, bright light did not affect fasting or postprandial plasma glucose levels. However, bright light increased fasting and postprandial plasma triglycerides. In men with type 2 diabetes, bright light increased fasting and postprandial glucose levels. In men with type 2 diabetes, bright light did not affect fasting triglyceride levels but increased postprandial triglyceride levels. We show that ambient light intensity acutely affects human plasma glucose and triglyceride levels. Our findings warrant further research into the consequences of the metabolic effects of light for the diagnosis and prevention of hyperglycemia and dyslipidemia. PMID:28470119

Effect of atorvastatin combined with Tongxinluo on hemorheology and inflammatory factors in patients with coronary heart disease

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Yu-Huan Ren

2016-10-01

Full Text Available Objective: To analyze the effect of atorvastatin combined with Tongxinluo on hemorheology and inflammatory factors in patients with coronary heart disease. Methods: A total of 42 patients with coronary heart disease treated in our hospital between December 2012 and December 2015 were selected and randomly divided into observation group and control group (n=21, control group received routine therapy, observation group received routine therapy + atorvastatin combined with Tongxinluo therapy, and then cardiac function, blood viscosity as well as serum lipid metabolism indexes and inflammation indexes were compared between the two groups after treatment. Results: After 3 courses of treatment, EF value and E/A ratio of observation group were significantly higher than those of control group, and whole blood high shear viscosity, whole blood low shear viscosity and plasma viscosity were significantly lower than those of control group; serum TC, TG, LDL-C, Leptin, Resistin, Visfatin, IL-18, TNF-C, sTREM-1 and MMP-9 levels of observation group after treatment were significantly lower than those of control group, and IL-4, IL-10, IL-37 and MFG-E8 levels were significantly higher than those of control group. Conclusion: Atorvastatin combined with Tongxinluo can optimize the state of coronary heart disease, and it plays a positive role in optimizing hemorheology, inflammation and other aspects.

Effect of atorvastatin on hyperglycemia-induced brain oxidative stress and neuropathy induced by diabetes

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Nastaran Faghihi

2015-04-01

Conclusion: The findings of the present study reveal that atorvastatin is able to prevent hyperglycemia-induced diabetic neuropathy and inhibit brain oxidative stress during diabetes. It is probable that reduction of urea is one of the reasons for atorvastatin prevention of hyperglycemia-induced neuropathy.

Dietary fat content alters insulin-mediated glucose metabolism in healthy men

NARCIS (Netherlands)

Bisschop, PH; de Metz, J; Ackermans, MT; Endert, E; Pijl, H; Kuipers, F; Meijer, AJ; Sauerwein, HP; Romijn, JA

Background: A high dietary fat intake is involved in the pathogenesis of insulin resistance. Objective: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity. Design: Six healthy men were studied on 3 occasions after consuming for 11 d

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

International Nuclear Information System (INIS)

Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

2010-01-01

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg -1 day -1 or 250 mg kg -1 day -1 for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

Energy Technology Data Exchange (ETDEWEB)

Kumar, Bhowmik Salil [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Young-Joo; Yi, Hong Jae [College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-791 (Korea, Republic of); Chung, Bong Chul [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Jung, Byung Hwa, E-mail: jbhluck@kist.re.kr [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of)

2010-02-19

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg{sup -1} day{sup -1} or 250 mg kg{sup -1} day{sup -1} for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

Antidepressant-like effect of atorvastatin in the forced swimming test in mice: the role of PPAR-gamma receptor and nitric oxide pathway.

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Shahsavarian, Arash; Javadi, Shiva; Jahanabadi, Samane; Khoshnoodi, Mina; Shamsaee, Javad; Shafaroodi, Hamed; Mehr, Shahram Ejtemaei; Dehpour, Ahmadreza

2014-12-15

Atorvastatin is a synthetic and lipophilic statin which has been reported to have a positive role in reducing depression. The potential antidepressant-like effects of atorvastatin and the possible involvement of peroxisome proliferator-activated receptor gamma (PPAR_γ) and nitric oxide system were determined using forced swimming test (FST) in mice was studied. Atorvastatin (0.01, 0.1 and 1 mg/kg, p.o.) was administered 1 h before FST. To assess the involvement of PPAR_γ in the possible antidepressant effect of atorvastatin, pioglitazone, a PPAR_γ agonist (5 mg/kg), and GW-9662, a specific PPAR_γ antagonist (2 mg/kg), was co-administered with atorvastatin (0.01 mg/kg, p.o.) and then FST was performed. The possible role of nitric oxide pathway was determined by using co-administration of a non-specific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.), and a NO precursor, L-arginine (750 mg/kg, i.p.) with sub-effective doses of atorvastatin and pioglitazone. Immobility time was significantly decreased after atorvastatin administration (0.1 and 1 mg/kg, p.o.). Administration of pioglitazone or L-NAME in combination with the sub-effective dose of atorvastatin (0.01 mg/kg, p.o.) reduced the immobility time in the FST compared to drugs alone, showing the participation of these pathways; while co-administration of non-effective doses of atorvastatin and pioglitazone with GW9662 or L-arginine reversed antidepressant-like effect of atorvastatin in FST. Data from concurrent use of GW9662 and atorvastatin also demonstrated that the antidepressant effect of atorvastatin was significantly reversed by GW9662. The antidepressant-like effect of atorvastatin on mice in the FST is mediated at least in part through PPAR_γ receptors and NO pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

Whole-Body Cryostimulation as an Effective Method of Reducing Oxidative Stress in Healthy Men.

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Stanek, Agata; Sieroń-Stołtny, Karolina; Romuk, Ewa; Cholewka, Armand; Wielkoszyński, Tomasz; Cieślar, Grzegorz; Kwiatek, Sebastian; Sieroń, Aleksander; Kawczyk-Krupka, Aleksandra

2016-01-01

Whole-body cryostimulation (WBC) is the therapeutic exposure of the total human body (without underwear) to a very low temperature (below -100°C) for 120-180 s. Currently, WBC is used more frequently not only in the treatment of patients suffering from various diseases, but also by healthy people as a wellness method. The aim of this research is to evaluate the impact of WBC procedures on oxidative stress parameters in healthy men. The study involved 32 healthy male subjects who were randomly divided into 2 groups: 16 men exposed to WBC procedures with subsequent kinesiotherapy (WBC group) and 16 men exposed only to kinesiotherapy procedures (KT group). Depending on the group, the subjects were exposed to 10 daily WBC procedures lasting 3 min, with a subsequent 60-min of kinesiotherapy, or exclusively to kinesiotherapy. In subjects from both groups, a day before the beginning of a cycle of treatment and a day after its completion, the level of selected indicators of oxidative stress and non-enzymatic antioxidants, as well as the activity of antioxidant enzymes in serum, plasma and erythrocyte lysates were determined. In the WBC group subjects, we recorded a statistically significant decrease in the concentrations of most of the parameters of oxidative stress with an accompanying increase in plasma concentrations of non-enzymatic antioxidants (total antioxidant status and uric acid). We recorded no significant changes in the activities of antioxidant enzymes (plasma total superoxide dismutase (SOD) and its isoenzymes SOD-Mn and SOD-ZnCu, erythrocyte catalase, glutathione peroxidase and glutathione reductase). The results we obtained confirmed that WBC decreases oxidative stress in healthy men.

The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

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Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

2016-09-20

Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors.

Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats

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Jingchao Lu

2016-06-01

Full Text Available Background: MMPs/TIMPs system is well known to play important roles in pressure overload-induced cardiac remodeling, and Amlodipine and Atorvastatin have been showed to exert favourable protective effects on cardiovascular disease, however, it is not clear whether Amlodipine and Atorvastatin can improve hypertensive cardiac remodeling and whether the MMPs/TIMPs system is involved. The present study aims to answer these questions. Methods: 36 weeks old male spontaneous hypertension (SHR rats were randomly divided into four groups: 1. SHR control group, 2. Amlodipine alone (10 mg/kg/d group, 3. Atorvastatin alone (10 mg/kg/d group, 4.Combination of Amlodipine and Atorvastatin (10 mg/kg/d for each group. Same gender, weight and age of Wistar-Kyoto (WKY rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The blood pressure and left ventricle mass index were measured. Enzyme activity of MMP-2 and MMP-9 was assessed with Gelatin zymography. MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA and protein expression was studied by RT-PCR and Western blot. Single factor ANOVA and LSD-t test were used in statistical analysis. Results: Treatment with Amlodipine alone or combination with atorvastatin significantly decreased blood pressure, left ventricle mass index in SHR rats (P Conclusion: Amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.

Effect of quadriceps and hamstrings muscle cooling on standing balance in healthy young men.

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Alghadir, A H; Anwer, S; Zafar, H; Al-Eisa, E S

2017-09-01

The present study compared the effect of quadriceps and hamstring muscle cooling on standing balance in healthy young men. Thirty healthy young men (18-30 years) participated in the study. The participants were randomly assigned to three groups (n=10 each): quadriceps cooling (QC), hamstring cooling (HC), or control group (no cooling). Participants in the QC and HC groups received 20 minutes of cooling using a cold pack (gel pack), placed on the anterior thigh (from the apex of the patella to the mid-thigh) and the posterior thigh (from the base of the popliteal fossa to the mid-thigh), respectively. Balance score including unilateral stance was measured at baseline and immediately after the application of the cold pack. No significant difference in the balance score was noted in any group after the application of the cold pack (p⟩0.05). Similarly, no significant differences in post-test balance score were noted among the three groups (p⟩0.05). Cooling of the quadriceps and hamstring muscles has no immediate effect on standing balance in healthy young men. However, longitudinal studies are warranted to investigate the long-term effects of cooling these muscles on standing balance.

High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort.

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Alan T Clarke

Full Text Available Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4-2.6]. High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2-12.7] for HDA, 1.4 [0.9-2.0] for LDA and 1.5 [1.0-2.2] for HDS.The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small.

High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort

Science.gov (United States)

Clarke, Alan T.; Johnson, Paul C. D.; Hall, Gillian C.; Ford, Ian; Mills, Peter R.

2016-01-01

Background & Aims Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment. Methods The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions. Results Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS. Conclusions The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small. PMID:26983033

Combined impact of healthy lifestyle factors on risk of atrial fibrillation: Prospective study in men and women.

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Larsson, Susanna C; Drca, Nikola; Jensen-Urstad, Mats; Wolk, Alicja

2016-01-15

The combined impact of multiple lifestyle factors on risk of atrial fibrillation (AF) remains unclear. We investigated the joint association of four modifiable lifestyle factors on incidence of AF in a prospective study of men and women. The study cohort comprised 39 300 men in the Cohort of Swedish Men and 33 090 women in the Swedish Mammography Cohort who were 45-83 years of age and free from atrial fibrillation at baseline. Healthy lifestyle was defined as body mass index healthy lifestyle factors, the multivariable relative risks (95% confidence interval) of AF were 0.83 (0.65-1.07) for one, 0.74 (0.58-0.94) for two, 0.62 (0.49-0.79) for three, and 0.50 (0.39-0.64) for four healthy lifestyle factors (P for trend healthy lifestyle factors combined were associated with a halving of the risk of AF. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy and safety of fixed dose combination of atorvastatin and hydroxychloroquine: a randomized, double-blind comparison with atorvastatin alone among Indian patients with dyslipidemia.

Science.gov (United States)

Pareek, Anil; Chandurkar, Nitin; Thulaseedharan, N K; Legha, R; Agarwal, Manish; Mathur, S L; Salkar, H R; Pednekar, Sangeeta; Pai, Vikas; Sriram, Usha; Khyalappa, Rajesh; Parmar, Mahendra; Agrawal, Navneet; Dhruv, Urman; Saxena, Subhash

2015-11-01

To evaluate the efficacy and safety of atorvastatin + hydroxychloroquine fixed-dose combination tablets in comparison with atorvastatin alone in treatment of dyslipidemia. This double-blind, randomized, out-patient study was conducted in 328 patients with primary dyslipidemia having low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dL (3.37 mmol/L) to ≤ 250 mg/dL (6.48 mmol/L) and triglycerides ≤ 400 mg/dL (4.52 mmol/L). Eligible patients were randomized to receive either atorvastatin 10 mg (n = 167) or atorvastatin 10 mg + hydroxychloroquine 200 mg (n = 161) for 24 weeks. CTRI/2010/091/006138. To compare percentage change in LDL-C, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to Week 12 and Week 24 between groups. To compare mean change in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), high-sensitivity C-reactive protein (Hs-CRP), and percentage of patients achieving lipid goals at Week 12 and Week 24. At Week 24, percentage reduction in LDL-C (-32.52 [-36.13 to -28.91] vs -39.54 [-43.25 to -35.83]; p = 0.008), TC (-24.41 [-27.10 to -21.72] vs -29.30 [-32.07 to -26.54]; p = 0.013), and non-HDL-C (-30.37 [-33.71 to -27.04] vs -36.76 [-40.18 to -33.33]; p = 0.009) was significantly greater in combination treated patients. Both the treatments showed a significant reduction in triglycerides at Week 24 from baseline, however, this reduction was not statistically significantly different between treatment groups. No significant change in HDL-C was observed in patients from both the treatment groups. At Week 24, change in HbA1c (0.22 [0.07 to 0.37] vs -0.13 [-0.28 to 0.03]; p = 0.002) and FBG was also statistically significant in favor of combination therapy (0.37 [0.07 to 0.67] vs -0.29 [-0.59 to 0.03]; p = 0.003), whereas no statistically significant difference was observed in change in Hs-CRP (p = 0.310). Significantly more patients from the

Safety Measures of L-Carnitine L-Tartrate Supplementation in Healthy Men.

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Rubin, Martyn R.; Volek, Jeff S.; Gomez, Ana L.; Ratamess, Nicholas A.; French, Duncan N.; Sharman, Matthew J.; Kraemer, William J.

2001-01-01

Examined the effects of ingesting the dietary supplement L- CARNIPURE on liver and renal function and blood hematology among healthy men. Analysis of blood samples indicated that there were no statistically significant differences between the L-CARNIPURE and placebo conditions for any variables examined, suggesting there are no safety concerns…

Effects of Atorvastatin calcium combined with Aspirin on serum levels of Hcy, NSE, UA, hs-CRP and inflammatory factors of patients with cerebral infarction

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Shu-Qin Zhang

2017-03-01

Full Text Available Objective: To study the effects of Atorvastatin calcium combined with Aspirin on serum levels of homocysteine (Hcy, neuron-specific enolase (NSE, uric acid (UA, high sensitity C-reactive protein (hs-CRP and inflammatory factors of patients with cerebral infarction. Methods: 100 cases of patients with cerebral infarction from March 2014 to May 2016 were treated in the Department of Neurology of our hospital and affiliated to Huazhong University of Science and Technology of traditional Chinese medicine and Western Medicine. The subjects were divided into the control group (n=50 and the treatment group (n=50 randomly. The control group was treated with Aspirin, the treatment group were treated with Atorvastatin calcium combined with Aspirin. The two groups were treated for 28 d. The serum levels of Hcy, NSE, UA, hs- CRP, interleukin-6 (IL-6, interleukin-8 (IL-8 and tumor necrosis factor-α (TNF-α of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum levels of the Hcy, NSE, UA and hs-CRP of the two groups before treatment (P>0.05. After treatment, the serum levels of the Hcy, NSE, UA and hs-CRP of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group (P0.05. After treatment, the serum levels of the IL-6, IL-8 and TNF-α of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group (P<0.05. Conclusions: Atorvastatin calcium combined with Aspirin can significantly reduce the serum levels of Hcy, NSE, UA, hs-CRP, IL-6, IL-8 and TNF-α of the patients with cerebral infarction.

Influence of ezetimibe in addition to high-dose atorvastatin therapy on plaque composition in patients with ST-segment elevation myocardial infarction assessed by serial Intravascular ultrasound with iMap: the OCTIVUS trial*

DEFF Research Database (Denmark)

Hougaard, Mikkel; Hansen, Henrik Steen; Thayssen, Per

2017-01-01

Background: The aim of this study was to examine the influence of ezetimibe in addition to atorvastatin on plaque composition in patients with first-time ST-segment Elevation Myocardial Infarction treated with primary percutaneous intervention. Methods: Eighty-seven patients were randomized ( 1: 1......) to ezetimibe 10mg or placebo in addition to Atorvastatin 80 mg. Intravascular ultrasound with iMap was performed at baseline and after 12 months in a non-infarctrelated artery. Primary endpoint was change in necrotic core (NC). Secondary endpoints were total atheroma volume (TAV) and percentage atheroma volume.......3 +/- 9.4% to 42.2 +/- 10.7 p - 0.07),p - 0.91 between groups. Conclusions: Ezetimibe in addition to atorvastatin therapy did not influence NC content, but was associated with regression of coronary atherosclerosis. (C) 2016 Elsevier Inc. All rights reserved....

Heat transfer and loss by whole-body hyperthermia during severe lower-body heating are impaired in healthy older men.

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Brazaitis, Marius; Paulauskas, Henrikas; Eimantas, Nerijus; Obelieniene, Diana; Baranauskiene, Neringa; Skurvydas, Albertas

2017-10-01

Most studies demonstrate that aging is associated with a weakened thermoregulation. However, it remains unclear whether heat transfer (for heat loss) from the lower (uncompensable) to the upper (compensable) body during passively-induced severe lower-body heating is delayed or attenuated with aging. Therefore, the main purpose of this study was to investigate heat transfer from uncompensable to compensable body areas in young men and healthy older men during passively-induced whole-body hyperthermia with a demonstrated post-heating change in core body (rectal; T re ) temperature. Nine healthy older men and eleven healthy young men (69±6 vs. 21±1 years old, mean±SD, Pheating in water at approximately 43°C. Despite a similar increment in T re (approximately 2.5°C) in both groups, the heating rate was significantly lower in older men than in young men (1.69±0.12 vs. 2.47±0.29°C/h, respectively; Pheat in the skin and deep muscles than young men, and this was associated with a greater heat-transfer delay and subsequent inertia in the increased core body (T re ) temperature. Copyright © 2017 Elsevier Inc. All rights reserved.

Fitness as a determinant of arterial stiffness in healthy adult men: a cross-sectional study.

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Chung, Jinwook; Kim, Milyang; Jin, Youngsoo; Kim, Yonghwan; Hong, Jeeyoung

2018-01-01

Fitness is known to influence arterial stiffness. This study aimed to assess differences in cardiorespiratory endurance, muscular strength, and flexibility according to arterial stiffness, based on sex and age. We enrolled 1590 healthy adults (men: 1242, women: 348) who were free of metabolic syndrome. We measured cardiorespiratory endurance in an exercise stress test on a treadmill, muscular strength by a grip test, and flexibility by upper body forward-bends from a standing position. The brachial-ankle pulse wave velocity test was performed to measure arterial stiffness before the fitness test. Cluster analysis was performed to divide the patients into groups with low (Cluster 1) and high (Cluster 2) arterial stiffness. According to the k-cluster analysis results, Cluster 1 included 624 men and 180 women, and Cluster 2 included 618 men and 168 women. Men in the middle-aged group with low arterial stiffness demonstrated higher cardiorespiratory endurance, muscular strength, and flexibility than those with high arterial stiffness. Similarly, among men in the old-aged group, the cardiorespiratory endurance and muscular strength, but not flexibility, differed significantly according to arterial stiffness. Women in both clusters showed similar cardiorespiratory endurance, muscular strength, and flexibility regardless of their arterial stiffness. Among healthy adults, arterial stiffness was inversely associated with fitness in men but not in women. Therefore, fitness seems to be a determinant for arterial stiffness in men. Additionally, regular exercise should be recommended for middle-aged men to prevent arterial stiffness.

Comparison of rosuvastatin and atorvastatin for lipid lowering in patients with type 2 diabetes mellitus: results from the URANUS study

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Berne Christian

2005-06-01

Full Text Available Abstract Objective The Use of Rosuvastatin versus Atorvastatin iN type 2 diabetes mellitUS (URANUS study compared rosuvastatin with atorvastatin for the reduction of low-density lipoprotein cholesterol (LDL-C in patients with type 2 diabetes. Methods After a 6-week dietary run-in, patients aged ≥ 18 years with type 2 diabetes and LDL-C ≥ 3.3 mmol/L were randomised to double-blind treatment with rosuvastatin 10 mg (n = 232 or atorvastatin 10 mg (n = 233 for 4 weeks. Doses were then titrated up to a maximum of rosuvastatin 40 mg or atorvastatin 80 mg over 12 weeks to achieve the 1998 European LDL-C goal ( Results Rosuvastatin reduced LDL-C levels significantly more than atorvastatin during the fixed-dose and titration periods (p Conclusion At the start dose and following dose titration, rosuvastatin was significantly more effective than atorvastatin at reducing LDL-C and achieving European LDL-C goals in patients with type 2 diabetes.

Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability

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Ankush Choudhary

2012-08-01

Full Text Available Atorvastatin has low aqueous solubility resulting in low oral bioavailability (12% and thus presents a challenge in formulating a suitable dosage form. To improve the aqueous solubility, a solid dispersion formulation of atorvastatin was prepared by lyophilization utilising skimmed milk as a carrier. Six different formulations were prepared with varying ratios of drug and carrier and the corresponding physical mixtures were also prepared. The formation of a solid dispersion formulation was confirmed by differential scanning calorimetry and X-ray diffraction studies. The optimum drug-to-carrier ratio of 1:9 enhanced solubility nearly 33-fold as compared to pure drug. In vitro drug release studies exhibited a cumulative release of 83.69% as compared to 22.7% for the pure drug. Additionally, scanning electron microscopy studies suggested the conversion of crystalline atorvastatin to an amorphous form. In a Triton-induced hyperlipidemia model, a 3-fold increase in the lipid lowering potential was obtained with the reformulated drug as compared to pure drug. These results suggest that solid dispersion of atorvastatin using skimmed milk as carrier is a promising approach for oral delivery of atorvastatin.

The Effect of Acute Endurance Exercise on Plasma Myostastin in Healthy Elderly Men

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Meysam Gholamali

2015-04-01

Conclusion Plasma Myostatin decreased significantly in the response to endurance exercise, in healthy elderly men. Presumably, according to the results of this study, prescription of endurance exercise may decrease Myostatin and subsequently sarcopenia in elderly people.

Effect of probucol combined with atorvastatin adjuvant therapy on serum indexes of acute cerebral infarction patients during rehabilitation period

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Li Zhang

2016-06-01

Full Text Available Objective: To analyze the effect of probucol combined with atorvastatin adjuvant therapy on serum indexes of acute cerebral infarction patients in rehabilitation period. Methods: A total of 102 patients with acute cerebral infarction were treated in our hospital from August 2011 to June 2015, were confirmed by magnetic resonance imaging and were randomly divided into observation group 51 cases and control group 51 cases according to the order of hospitalization. Control group received atorvastatin treatment alone, observation group received probucol combined with atorvastatin adjuvant therapy, and then differences in levels of serum CXCL16, HMGB1, CD40L and Fibulin-5, P-selectin, NPY, CGRP, visfatin and others, chemokines and inflammation-related factors, vascular endothelial cells and fibrinolytic function, etc were compared between two groups after treatment. Results: Serum CXCL16, HMGB1, CD40L and Fibulin-5 levels of observation group after treatment were lower than those of control group; serum P-selectin, NPY, visfatin, UCH-L1, sVCAM-1 and SAA levels of observation group after treatment were lower than those of control group while CGRP level was higher than that of control group; serum CCL-19, CCL-21, YKL-40, IL-33 and IL- 18 values of observation group after treatment were lower than those of control group; serum vWF, PAI-1 and plasminogen levels of observation group after treatment were lower than those of control group while 6-K-PGF1α and tPA levels were higher than those of control group. Conclusions: Probucol combined with atorvastatin adjuvant therapy for acute cerebral infarction patients in rehabilitation period can effectively optimize patients’ general status and avoid re-infarction in recovery period, and it has positive clinical significance.

Influence of Atorvastatin/Probucol Combination on Blood Lipid and ...

African Journals Online (AJOL)

Changes in carotid intima media thickness (CIMT), plaque area, vulnerability, ... Keywords: Probucol, Atorvastatin, C-reactive protein, Cerebral infarction, Carotid ... artery atherosclerosis formulated by WHO [6]. Clinical symptoms, sign and ...

Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

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Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...

Short term high dose atorvastatin for the prevention of contrast-induced nephropathy in patients undergoing computed tomography angiography

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Hamid Sanei

2014-09-01

Full Text Available BACKGROUND: Statins are shown effective by some studies in preventing contrast-induced nephropathy (CIN. We evaluated the effectiveness of atorvastatin in the prevention of CIN in computed tomography angiography (CTA candidates. METHODS: This study was conducted on patients referring for elective CTA with normal renal function. Patients received atorvastatin (80 mg/day or placebo from 24 h before to 48 h after administration of the contrast material. Serum creatinine was measured before and 48 h after contrast material injection. CIN was defined as an increase in serum creatinine level of ≥ 0.5 mg/dl or ≥ 25% of the baseline creatinine. RESULTS: A total of 236 patients completed the study; 115 atorvastatin, 121 placebo, mean age = 58.40 ± 9.80 year, 68.6% male. Serum creatinine increased after contrast material injection in both the atorvastatin (1.00 ± 0.16-1.02 ± 0.15 mg/dl, P = 0.017 and placebo groups (1.03 ± 0.17-1.08 ± 0.18 mg/dl, P < 0.001. Controlling for age, gender, comorbidities, drug history, and baseline serum creatinine level, patients who received atorvastatin experienced less increase in serum creatinine after contrast material injection (beta = 0.127, P = 0.034. However, there was no difference between the atorvastatin and placebo groups in the incidence of CIN (4.3 vs. 5.0%, P = 0.535. CONCLUSION: In patients undergoing CTA, a short-term treatment with high dose atorvastatin is effective in preventing contrast-induced renal dysfunction, in terms of less increase in serum creatinine level after contrast material injection. Further trials including larger sample of patients and longer follow-ups are warranted.   Keywords: Kidney Diseases, Multidetector Computed Tomography, Contrast Media, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atorvastatin 

Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury.

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Xu, Xin; Gao, Weiwei; Cheng, Shiqi; Yin, Dongpei; Li, Fei; Wu, Yingang; Sun, Dongdong; Zhou, Shuai; Wang, Dong; Zhang, Yongqiang; Jiang, Rongcai; Zhang, Jianning

2017-08-23

Neuroinflammation is an important secondary injury mechanism that has dual beneficial and detrimental roles in the pathophysiology of traumatic brain injury (TBI). Compelling data indicate that statins, a group of lipid-lowering drugs, also have extensive immunomodulatory and anti-inflammatory properties. Among statins, atorvastatin has been demonstrated as a neuroprotective agent in experimental TBI; however, there is a lack of evidence regarding its effects on neuroinflammation during the acute phase of TBI. The current study aimed to evaluate the effects of atorvastatin therapy on modulating the immune reaction, and to explore the possible involvement of peripheral leukocyte invasion and microglia/macrophage polarization in the acute period post-TBI. C57BL/6 mice were subjected to TBI using a controlled cortical impact (CCI) device. Either atorvastatin or vehicle saline was administered orally starting 1 h post-TBI for three consecutive days. Short-term neurological deficits were evaluated using the modified neurological severity score (mNSS) and Rota-rod. Brain-invading leukocyte subpopulations were analyzed by flow cytometry and immunohistochemistry. Pro- and anti-inflammatory cytokines and chemokines were examined using enzyme-linked immunosorbent assay (ELISA). Markers of classically activated (M1) and alternatively activated (M2) microglia/macrophages were then determined by quantitative real-time PCR (qRT-PCR) and flow cytometry. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) staining and immunofluorescence labeling for neuronal nuclei (NeuN). Acute treatment with atorvastatin at doses of 1 mg/kg/day significantly reduced neuronal apoptosis and improved behavioral deficits. Invasions of T cells, neutrophils and natural killer (NK) cells were attenuated profoundly after atorvastatin therapy, as was the production of pro-inflammatory cytokines (IFN-γ and IL-6) and chemokines

Atorvastatin/trimetazidine combination therapy in patients with ...

African Journals Online (AJOL)

Purpose: To explore the outcomes and safety of atorvastatin/trimetazidine combination therapy in patients with chronic cardiac failure. Methods: A total of 144 patients with chronic cardiac failure were divided into test group (n = 72) and control group (n = 72). In addition to conventional anti-heart failure treatment, all patients ...

Muscular exercise can cause highly pathological liver function tests in healthy men.

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Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats

2008-02-01

The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise. Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.

Robust and enduring atorvastatin-mediated memory recovery following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats.

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Zaghi, Gislene Gonçalves Dias; Godinho, Jacqueline; Ferreira, Emilene Dias Fiuza; Ribeiro, Matheus Henrique Dal Molin; Previdelli, Isolde Santos; de Oliveira, Rúbia Maria Weffort; Milani, Humberto

2016-02-04

Chronic cerebral hypoperfusion (CCH) is a common condition associated with the development and/or worsening of age-related dementia.We previously reported persistent memory loss and neurodegeneration after CCH in middle-aged rats. Statin-mediated neuroprotection has been reported after acute cerebral ischemia. Unknown, however, is whether statins can alleviate the outcome of CCH. The present study investigated whether atorvastatin attenuates the cognitive and neurohistological outcome of CCH. Rats (12–15 months old) were trained in a non-food-rewarded radial maze, and then subjected to CCH. Atorvastatin (10 mg/kg, p.o.) was administered for 42 days or 15 days, beginning 5 h after the first occlusion stage. Retrograde memory performance was assessed at 7, 14, 21, 28, and 35 days of CCH, and expressed by “latency,” “number of reference memory errors” and “number of working memory errors.” Neurodegeneration was then examined at the hippocampus and cerebral cortex. Compared to sham, CCH caused profound and persistent memory loss in the vehicle-treated groups, as indicated by increased latency (91.2% to 107.3%) and number of errors (123.5% to 2508.2%), effects from which the animals did not spontaneously recover across time. This CCH-induced retrograde amnesia was completely prevented by atorvastatin (latency: −4.3% to 3.3%; reference/working errors: −2.5% to 45.7%), regardless of the treatment duration. This effect was sustained during the entire behavioral testing period (5 weeks), even after discontinuing treatment. This robust and sustained memory-protective effect of atorvastatin occurred in the absence of neuronal rescue (39.58% to 56.45% cell loss). We suggest that atorvastatin may be promising for the treatment of cognitive sequelae associated with CCH.

Self-reported onset of puberty and subsequent semen quality and reproductive hormones in healthy young men

DEFF Research Database (Denmark)

Jensen, Tina Kold; Finne, Katrine Folmann; Skakkebæk, Niels E

2016-01-01

, at the same time as or later than their peers. Their semen quality (semen volume, sperm concentration, total sperm count and percentages of motile and morphologically normal spermatozoa) and serum concentrations of sex hormones (LH, FSH, total testosterone, SHBG, inhibin B) and testicular size were determined......Study Question Is there an association between pubertal onset and subsequent reproductive health in young men? Summary Answer Self-reported later onset of puberty was associated with reduced semen quality and altered serum levels of reproductive hormones among 1068 healthy, young Danish men. What...... is Known Already The long-term effects of variations in the onset of male puberty on subsequent reproduction remain largely unstudied. Study Design, Size, Duration In a cross-sectional study, young healthy Danish men were approached when they attended a compulsory medical examination to determine...

No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide.

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de la Peña, Amparo; Cui, Xuewei; Geiser, Jeanne; Loghin, Corina

2017-11-01

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of type 2 diabetes mellitus are known to delay gastric emptying (GE). The potential effect of the GLP-1 RA dulaglutide on the pharmacokinetics (PK) of four orally administered drugs and on the pharmacodynamic (PD) effect of warfarin was investigated. In four separate clinical pharmacology studies, digoxin, warfarin, atorvastatin and Ortho-Cyclen ® were orally administered to healthy subjects with and without a subcutaneous dose of dulaglutide 1.5 mg. The effect of dulaglutide coadministration was assessed based on the PK parameters of key analytes. For warfarin PD, the effect of dulaglutide on the international normalized ratio (INR) was evaluated. Areas under the concentration-time curves (AUCs) with and without dulaglutide were similar for all analytes except atorvastatin, where it was reduced by 21%. Maximum concentrations (C max ) were generally lower following coadministration with dulaglutide, with statistically significant reductions (90% confidence intervals of geometric least squares means ratios outside 0.80-1.25) for all analytes except R-warfarin. For all analytes, there was a general trend for the time to C max (t max ) to increase following coadministration with dulaglutide. For warfarin, dulaglutide coadministration had no statistically significant effect on the maximum INR (INR max ); however, a 2% increase in area under the INR curve (AUC INR ) was observed. Dulaglutide did not affect the absorption of the tested medications to a clinically relevant degree. Based on the PK and PD evaluations, no dose adjustments for digoxin, warfarin, atorvastatin and Ortho-Cyclen ® are recommended when coadministered with dulaglutide. NCT01458210, NCT01436201, NCT01432938, and NCT01250834.

Dietary fat intake, circulating and membrane fatty acid composition of healthy Norwegian men and women.

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Min, Y; Blois, A; Geppert, J; Khalil, F; Ghebremeskel, K; Holmsen, H

2014-02-01

The present study aimed to assess the dietary fat intake and blood fatty acid status of healthy Norwegian men and women living in Bergen whose habitual diet is known to be high in long-chain omega-3 fat. Healthy men (n = 41) and women (n = 40) aged 20-50 years who were regular blood donors completed 7-day food diaries and their nutrient intake was analysed by Norwegian food database software, kbs, version 4.9 (kostberegningssystem; University of Oslo, Oslo, Norway). Blood samples were obtained before blood donation and assessed for the fatty acid composition of plasma triglycerides and cholesterol esters, phosphatidylcholine, and red cell phosphatidylcholine and phosphatidylethanolamine. There was no difference in dietary fat intake between men and women. Total and saturated fat intakes exceeded the upper limits of the recommendations of the National Nutrition Council of Norway. Although polyunsaturated fat intake was close to the lower limit of the recommended level, the intake varied greatly among individuals, partly as a result of the use of supplementary fish oil. Moreover, the proportional fatty acid composition of plasma and red cell lipids was similar between men and women. Enrichment of docosahexaenoic acid in red cell phosphatidylethanolamine was found in fish oil users. The results of the present study provide a snapshot of the current nutritional status of healthy Norwegian adults. Moreover, the detailed blood fatty acid composition of men and women whose habitual diet constitutes high long-chain polyunsaturated omega-3 fat as well as saturated fat could be used as reference value for population studies. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin

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Anna Czajkowska-Kośnik

2015-11-01

Full Text Available The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process, attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution—a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin.

Atorvastatin therapy decreases androstenedione and dehydroepiandrosterone sulphate concentrations in patients with polycystic ovary syndrome: randomized controlled study.

Science.gov (United States)

Sathyapalan, Thozhukat; Smith, Karen A; Coady, Anne-Marie; Kilpatrick, Eric S; Atkin, Stephen L

2012-01-01

Hyperandrogenaemia in polycystic ovary syndrome (PCOS) represents a composite of raised serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). In patients with PCOS, testosterone and androstenedione are primarily derived from the ovaries and DHEAS is a metabolite predominantly from the adrenals. It has been shown that atorvastatin reduces testosterone concentrations in patients with PCOS. The objective was to study the effect of atorvastatin on serum androstenedione and DHEAS concentrations in patients with PCOS. A randomized, double-blind, placebo-controlled study was performed. Forty medication-naive patients with PCOs were randomized to either atorvastatin 20mg daily or placebo for three months. Subsequently, a three-month extension study for all patients was undertaken with metformin 1500 mg daily. The main outcome measures were change in androstenedione and DHEAS concentrations. The mean (SD) baseline androstenedione (5.7 [0.8] versus 5.6 [1.3] nmol/L; P = 0.69) and DHEAS (7.1 [1.0] versus 7.2 [1.2] μmol/L; P = 0.72) concentrations were comparable between two groups. There was a significant reduction of androstenedione (5.7 [0.8] versus 4.7 [0.7] nmol/L; P = 0.03) and DHEAS (7.1 [1.0] versus 6.0 [0.9] μmol/L; P = 0.02) with three months of atorvastatin while there were no significant changes with placebo. Three months' treatment with metformin maintained the reduction of androstenedione and DHEAS concentrations with atorvastatin compared with baseline. There were no changes in either DHEAS or androstenedione concentrations in the initial placebo group after 12 weeks of metformin. Twelve weeks of atorvastatin significantly reduced both DHEAS and androstenedione contributing to the total reduction of androgen concentrations and indicating that the reduction of the hyperandrogenaemia could be partly due to the action of atorvastatin at both the ovary and the adrenal gland in PCOS.

Effects of different doses of atorvastatin on NF-κB, inflammatory factors and insulin resistance in elderly patients with early diabetic nephropathy

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Ying Liu

2016-01-01

Full Text Available Objective: To explore the effects of different doses of atorvastatin on NF-κB, inflammatory factors and insulin resistance in elderly patients with early diabetic nephropathy. Methods: A total of 150 cases with elderly early diabetic nephropathy were randomly divided into two groups according to the random number table method. Group A (n=75 was treated with atorvastatin tablets at a dose of 10 mg/d, while group B (n=75 was treated at a dose of 20 mg/d. The NF-κB, inflammatory factors and insulin resistance were detected and compared between the two groups. Results: After treatment, UAER (52.87±7.78 μg/min, SCr (70.43±6.76 μmol/L and BUN (4.04±0.40 mmol/L of group B were significantly decreased compared with before treatment and post-treated group A (P<0.05; phosphorylation level of NF-κB p65 after treatment was (0.80±0.17 μg/min in the peripheral blood of patients from group B, which was significantly reduced compared with before treatment and post-treated group A (P<0.05; inflammatory factors including TNF-α (52.80±7.78 ng/L, IL-6 (70.43±6.76 ng/L and Hs-CRP (4.04±0.40 mg/L of group B after treatment also declined significantly compared with before treatment and post-treated group A (P<0.05; while HbAlc and FBG were not significantly changed after treatment in both groups, and there was no significant difference in each group before and after treatment; FINS (9.88±0.85 mU/L and HOMA-IR (3.36±0.33 of group B after treatment were significantly lowered compared with before treatment and posttreated group A (P<0.05. Conclusions: High dose atorvastatin can inhibit the activity of NF- κB p65 and levels of inflammation, and improve renal function and insulin resistance in elderly patients with early diabetic nephropathy, making it a promising means for clinical application.

Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via down-regulation the Akt signaling pathway.

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Chen, Shuang; Liu, Baoqin; Kong, Dehui; Li, Si; Li, Chao; Wang, Huaqin; Sun, Yingxian

2015-01-01

Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high expression of contractile marker proteins. After injury to the vessel, VSMC shifts from a contractile phenotype to a pathological synthetic phenotype, associated with increased proliferation, migration and matrix secretion. It has been demonstrated that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG-CoA) reductase, exhibits various protective effects against VSMCs. In this study, we investigated the effects of atorvastatin calcium on phenotype modulation of PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways. Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the phenotype modulation and cytoskeleton rearrangements and improved the expression of contractile phenotype marker proteins such as α-SM actin, SM22α and calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion, atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and activation of the Akt signaling pathway, indicating that Akt might play a vital role in the modulation of phenotype.

Protective effects of valsartan and benazepril combined with atorvastatin on cardiorenal syndrome in rats.

Science.gov (United States)

Tang, S-Y; Peng, D-F; Hu, Y-J; Chen, J

2015-01-01

To study the protective effects of valsartan (Val) and benazepril, (Ben) combined with atorvastatin (Ato), on cardiorenal syndrome (CRS) in rats. After establishing cardiorenal syndrome model, the rats were randomly divided into control, Ato, Ben+Ato and Val+Ato groups, which were treated with corresponding drugs. Before and 4 weeks after treatment, the serum creatinine (Scr), blood urea nitrogen (BUN), type-B natriuretic peptide (BNP), aldosterone (ALD), angiotensin (Ang) II, C-reactive protein (CRP), blood lipid and urine protein were determined. The left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) as well as maximum rising and falling rates of left ventricular pressure (±dp/dtmax) were detected. The heart weight index was also determined. 6, 3, 1 and 2 rats control, Ato, Ben+Ato and Val+Ato groups died, respectively. Compared with control group, the serum Cr, BUN, BNP, ALD, CRP and urinary protein levels in treatment groups significantly decreased, and the blood lipid level, LVDP, LVEDP and heart weight index significantly decreased, with increased LVSP. No statistically significant difference was observed among treatment groups. Valsartan and benazepril, combined with atorvastatin, can have significant protective effects on cardiorenal functions of rats with CRS, with no significant difference between these two drugs.

Effect of Ischemic Postconditioning and Atorvastatin in the Prevention of Remote Lung Reperfusion Injury

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Carlos Henrique Marques dos Santos

Full Text Available Abstract Objective: The aim of the present study was to evaluate the ability of ischemic postconditioning, atorvastatin and both associated to prevent or minimize reperfusion injury in the lung of rats subjected to ischemia and reperfusion by abdominal aortic clamping. Methods: We used 41 Wistar norvegic rats, which were distributed into 5 groups: ischemia and reperfusion (I/R, ischemic postcondictioning (IPC, postconditioning + atorvastatin (IPC+A, atorvastatin (A and SHAM. It was performed a medium laparotomy, dissection and isolation of the infra-renal abdominal aorta; except for the SHAM group, all the others were submitted to the aortic clamping for 70 minutes (ischemia and posterior clamp removal (reperfusion, 70 minutes. In the IPC and IPC+A groups, postconditioning was performed between the ischemia and reperfusion phases by four cycles of reperfusion and ischemia lasting 30 seconds each. In the IPC+A and A groups, preceding the surgical procedure, administration of 3.4 mg/day of atorvastatin was performed for seven days by gavage. After the surgical procedure, the right caudal lobe was removed from the lung for histological study, using tissue injury score ranging from grade 1 (normal tissue to grade 4 (intense lesion. Results: The mean lung injury was 3.6 in the I/R group, 1.6 in the IPC group, 1.2 in the IPC+A group, 1.2 in the A group, and 1 in the SHAM group (P<0.01. Conclusion: Ischemic postconditioning and atorvastatin were able to minimize lung reperfusion injury, alone or in combination.

Effects of intensive atorvastatin and rosuvastatin treatment on apolipoprotein B-48 and remnant lipoprotein cholesterol levels

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Atorvastatin and rosuvastatin at maximal doses are both highly effective in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels. Rosuvastatin has been shown to be more effective than atorvastatin in lowering LDL-C, small dense LDL-C and in raising high-density lipoprote...

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

International Nuclear Information System (INIS)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

2014-01-01

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91 st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E max of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

Energy Technology Data Exchange (ETDEWEB)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

2014-10-01

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

Life style and longevity among initially healthy middle-aged men: prospective cohort study.

Science.gov (United States)

Heir, Trond; Erikssen, Jan; Sandvik, Leiv

2013-09-11

Few studies have examined how various lifestyle factors in midlife predict longevity, and none of these studies have examined the impact of physical fitness. The present study aimed to examine longevity in relation to smoking, overweight and physical fitness. We prospectively studied longevity (defined as reaching at least 85 years of age) in relation to smoking status, body mass index and physical fitness in 821 healthy men between 51 and 59 years of age. Of these, 369 were smokers, 320 were overweight, and 31 were obese. The associations were adjusted for age, systolic blood pressure and cholesterol level, using multivariate logistic regression analysis. Deaths were registered until the 31st of December, 2006. Physical fitness was measured as the total work performed in a maximal exercise tolerance bicycle test. 252 men survived to the age of 85 years (30.7%). Smoking status was significantly and independently related to longevity; 37.2% of the non-smokers survived to the age of 85, and 22.8% of the smokers. Among non-smokers, overweight and physical fitness were significantly and independently related to longevity after adjustment for age, blood pressure and cholesterol level, but not among smokers. Among non-smokers with high physical fitness, 48.8% reached the age of 85 years, compared to 27.9% among non-smokers with low physical fitness. Lifestyle variables appear to be strong and independent predictors of longevity in initially healthy middle-aged men. The probability of longevity may be a useful concept when informing the general public about the benefits of a healthy lifestyle.

Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

International Nuclear Information System (INIS)

Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

2014-01-01

Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

Energy Technology Data Exchange (ETDEWEB)

Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

2014-11-01

Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

Acute partial sleep deprivation increases food intake in healthy men.

Science.gov (United States)

Brondel, Laurent; Romer, Michael A; Nougues, Pauline M; Touyarou, Peio; Davenne, Damien

2010-06-01

Acute partial sleep deprivation increases plasma concentrations of ghrelin and decreases those of leptin. The objective was to observe modifications in energy intake and physical activity after acute partial sleep deprivation in healthy men. Twelve men [age: 22 +/- 3 y; body mass index (in kg/m(2)): 22.30 +/- 1.83] completed a randomized 2-condition crossover study. During the first night of each 48-h session, subjects had either approximately 8 h (from midnight to 0800) or approximately 4 h (from 0200 to 0600) of sleep. All foods consumed subsequently (jam on buttered toast for breakfast, buffet for lunch, and a free menu for dinner) were eaten ad libitum. Physical activity was recorded by an actimeter. Feelings of hunger, perceived pleasantness of the foods, desire to eat some foods, and sensation of sleepiness were also evaluated. In comparison with the 8-h sleep session, subjects consumed 559 +/- 617 kcal (ie, 22%) more energy on the day after sleep restriction (P < 0.01), and preprandial hunger was higher before breakfast (P < 0.001) and dinner (P < 0.05). No change in the perceived pleasantness of the foods or in the desire to eat the foods was observed. Physical activity from 1215 to 2015 was higher after sleep restriction than after 8 h of sleep (P < 0.01), even though the sensation of sleepiness was more marked (P < 0.01). One night of reduced sleep subsequently increased food intake and, to a lesser extent, estimated physical activity-related energy expenditure in healthy men. These experimental results, if confirmed by long-term energy balance measurements, suggest that sleep restriction could be a factor that promotes obesity. This trial was registered at clinicaltrials.gov as NCT00986492.

Governing the healthy male citizen: men, masculinity and popular health in Men's Health magazine.

Science.gov (United States)

Crawshaw, Paul

2007-10-01

Recent commentators have noted the potential of newer neo-liberal discourses of health care to position responsibility for the management of well-being with the individual. Often promoted through the inculcation of risk avoidance and management, such discourses are played out in myriad settings, including the popular media. Magazines are one such media site in which diverse exhortations for the achievement of health, well-being and the perfectible body are made, and Bunton [1997. Popular health, advanced liberalism and good housekeeping magazine. In A. Petersen & Bunton R. (Eds.) Foucault, health and medicine (pp. 223-247). London: Routledge] has identified 'magazine medicine' as a significant manifestation of more dedifferentiated models of health care. Recent discussions have placed men's health high on research and policy agendas, with a concomitant interest in more popular realms. The UK magazine Men's Health (MH) is indicative of these trends, and represents a site at which discourses of men, health and masculinity are constructed. Typically reflecting neo-liberal models of health, here men are constructed as active and entrepreneurial citizens able to maintain their own health and well-being through the judicious management of risk in contexts appropriate to dominant discourses of hegemonic masculinity. Data which resulted from a critical discourse analysis of a 2-year sample (21 issues) of MH are considered and findings related to medicalisation, individualisation and risk discussed. It is suggested that magazine texts such as MH reflect newer individualised models of health care and neo-liberal strategies of health governance premised upon constructing a healthy male citizen, willing and able to take responsibility for their own well-being.

Cardiovascular effects of intravenous ghrelin infusion in healthy young men

DEFF Research Database (Denmark)

Vestergaard, Esben Thyssen; Andersen, Niels Holmark; Hansen, Troels Krarup

2007-01-01

Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied the cardio......Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied...... the cardiovascular effects of a constant infusion of human ghrelin at a rate of 5 pmol/kg per minute for 180 min. Fifteen healthy, young (aged 23.2 ± 0.5 yr), normal-weight (23.0 ± 0.4 kg/m2) men volunteered in a randomized double-blind, placebo-controlled crossover study. With the subjects remaining fasting, peak...... myocardial systolic velocity S′, tissue tracking TT, left ventricular ejection fraction EF, and endothelium-dependent flow-mediated vasodilatation were measured. Ghrelin infusion increased S′ 9% (P = 0.002) and TT 10% (P

Effects of cultured shrimp (Litopenaeus vannamei consumption on serum lipoproteins of healthy normolipidemic men

Directory of Open Access Journals (Sweden)

Farzaneh Yousefi

2012-12-01

Full Text Available Background: It has been suggested that moderate shrimp consumption in normolipidemic subjects will not adversely affect the overall lipoprotein profile. Hence, shrimp consumption can be included in “healthy heart" nutritional guidelines. However, the effects of cultured shrimp on serum lipoproteins of normal subjects have not yet investigated. Material and Methods: Twenty-five healthy normolipidemic men who were workers of a shrimp farm in Bushehr province participated in a quasi-experimental study. In a crossover six weeks trial, the effect of three days per week diet (containing 300 g cultured shrimp Litopenaeus vannamei /day on serum lipid profile was compared with a zero-marine baseline diet. Results: After six weeks trial, serum triglyceride and HDL-cholesterol levels were not significantly changed from the baseline levels (p>0.05. However, total cholesterol and LDL-cholesterol levels, total cholesterol to HDL-cholesterol and LDL-cholesterol to HDL-cholesterol ratios were significantly increased (p<0.0001. Conclusion: Moderate cultured shrimp (Litopenaeus vannamei consumption can increase total cholesterol and LDL-cholesterol levels in normolipidemic men. Although a diet containing native shrimp has many benefits for healthy persons, but we do not recommend cultured shrimp in a healthy heart diet for persons with dyslipidemia or cardiovascular diseases.

Effect of Atorvastatin on Serum Levels of Total Cholesterol and High-Sensitivity C-reactive Protein in High-Risk Patients with Atrial Fibrillation in Asia.

Science.gov (United States)

Shi, Ming Yu; Xue, Feng Hua; Teng, Shi Chao; Jiang, Li; Zhu, Jing; Yin, Feng; Gu, Hong Yue

2015-08-01

The aim of this meta-analysis was to investigate the effects of atorvastatin on serum levels of high-sensitivity C-reactive protein (hs-CRP) and total cholesterol in atrial fibrillation (AF) patients in Asia. By searching English and Chinese language-based electronic databases (ie, PubMed, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Wanfang database, China National Knowledge Infrastructure, and VIP database), we identified 13 studies relevant to our topic of interest. Data were collected from the 13 studies and analyzed with Comprehensive Meta-Analysis software (version 2.0, Biostat Inc., Englewood, New Jersey). Initially, our database searches retrieved 356 studies (45 in English, 311 in Chinese). Thirteen studies were selected for the meta-analysis following stringent criteria. The data included 1239 patients with AF, of whom 634 were treated with atorvastatin and included in the treatment group, and 605 patients were treated with conventional treatment and included in the control group. The results of our meta-analysis suggested that the serum levels of hs-CRP (mg/L) and total cholesterol (mmol/L) in the treatment group were significantly lower than those of the control group (hs-CRP: standardized mean difference = 0.962; 95% CI, 0.629-1.295, P < 0.001; total cholesterol: standardized mean difference = 1.400; 95% CI, 0.653-2.146, P < 0.001). The findings of this study suggest that atorvastatin may be very effective in decreasing serum levels of hs-CRP and total cholesterol to prevent cardiovascular events. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Preparation of Candesartan and Atorvastatin Nanoparticles by Solvent Evaporation

Czech Academy of Sciences Publication Activity Database

Vaculíková, E.; Grünwaldová, Veronika; Král, V.; Dohnal, J.; Jampílek, J.

2012-01-01

Roč. 17, č. 11 (2012), s. 13221-13234 ISSN 1420-3049 Institutional support: RVO:61388980 Keywords : candesartan cilexetil * atorvastatin * nanoparticles * solvent evaporation * excipients * dynamic light scattering Subject RIV: CA - Inorganic Chemistry Impact factor: 2.428, year: 2012

Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy

Directory of Open Access Journals (Sweden)

Toth PP

2012-01-01

Full Text Available Peter P Toth1, Kamlesh M Thakker2, Ping Jiang2, Robert J Padley21University of Illinois College of Medicine, Peoria, and CGH Medical Center, Sterling, 2Abbott, Abbott Park, IL, USABackground: The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S versus atorvastatin monotherapy on high-density lipoprotein (HDL particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study.Methods: This was a post hoc analysis of patients (n = 137 who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following ≥4 weeks without lipid-modifying therapy (washout period, the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran–Mantel–Haenszel test.Results: Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (-1.8% versus 4.2%, P = 0.014, and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078 compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001. NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001.Conclusion: Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle

Enhancement of solubility and dissolution rate of atorvastatin ...

African Journals Online (AJOL)

Purpose: To investigate the formation of atorvastatin calcium (AC) co-crystal to improve its solubility and dissolution rate. Method: Co-crystallization of AC in equimolar ratio with isonicotinamide (INA) was carried out by slow solvent evaporation method using methanol. The solid obtained was characterized by powder x-ray ...

Comparison of lipid lowering effect of extra virgin olive oil and atorvastatin in dyslipidemia in type 2 diabetes mellitus

International Nuclear Information System (INIS)

Khan, T.M.

2017-01-01

Extra virgin olive oil (EVOO) is fruit oil with rich source of monounsaturated fats and powerful antioxidants. It acts as hypolipidemic agent and significant decrease of plasma lipids levelwas observed with EVOO use. Atorvastatin is hypolipidemic drug commonly used for treatment of hyperlipidaemia. The purpose of this study was to determine and compare the lipid lowering effect of EVOO with atorvastatin in type 2 diabetic dyslipidaemia which is leading cause of microvascular diseases. Methods: This cross-sectional study was conducted on 60 already diagnosed cases of type 2 diabetes mellitus with dyslipidaemia. All sixty subjects were divided into 2 groups. Atorvastatin 40mg was given to Group One and two tablespoons of extra virgin olive oil orally per day was given to Group Two. Blood was collected for estimation of plasma lipids level at base line, 4th week, and 6th weeks in two groups and was compared statistically. Results: The present study demonstrated 20-40% lipid lowering effect of atorvastatin on plasma lipids level with 9-16% increase in HDL while extra virgin olive oil showed 14 to 25% reduction in plasma lipids with 8-12% increase in HDL-cholesterol level. Conclusion: This study concludes that both atorvastatin and extra virgin olive oil are effective in reducing plasma lipids level in type 2 diabetic dyslipidaemia with more prominent effect of atorvastatin than EVOO. (author)

Comparison Of Lipid Lowering Effect Of Extra Virgin Olive Oil And Atorvastatin In Dyslipidaemia In Type 2 Diabetes Mellitus.

Science.gov (United States)

Khan, Tariq Mahmood; Iqbal, Sohail; Rashid, Muhammad Adnan

2017-01-01

Extra virgin olive oil (EVOO) is fruit oil with rich source of monounsaturated fats and powerful antioxidants. It acts as hypolipidemic agent and significant decrease of plasma lipids level was observed with EVOO use. Atorvastatin is hypolipidemic drug commonly used for treatment of hyperlipidaemia. The purpose of this study was to determine & compare the lipid lowering effect of EVOO with atorvastatin in type 2 diabetic dyslipidaemia which is leading cause of microvascular diseases. This randomised controlled trial was conducted on 60 already diagnosed cases of type 2 diabetes mellitus with dyslipidaemia. All sixty subjects were divided randomly into 2 groups. Atorvastatin 40 mg was given to Group One and two tablespoons of extra virgin olive oil orally per day was given to Group Two. Blood was collected for estimation of plasma lipids level at base line, 4th week, and 6th weeks in two groups and was compared statistically. The present study demonstrated 20-40% lipid lowering effect of atorvastatin on plasma lipids level with 9-16% increase in HDL while extra virgin olive oil showed 14-25% reduction in plasma lipids with 8-12% increase in HDL-cholesterol level. This study concludes that both atorvastatin and extra virgin olive oil are effective in reducing plasma lipids level in type 2 diabetic dyslipidaemia with more prominent effect of atorvastatin than EVOO.

Atorvastatin prevents Aβ oligomer-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting Tau cleavage

Science.gov (United States)

Sui, Hai-juan; Zhang, Ling-ling; Liu, Zhou; Jin, Ying

2015-01-01

Aim: The proteolytic cleavage of Tau is involved in Aβ-induced neuronal dysfunction and cell death. In this study, we investigated whether atorvastatin could prevent Tau cleavage and hence prevent Aβ1–42 oligomer (AβO)-induced neurotoxicity in cultured cortical neurons. Methods: Cultured rat hippocampal neurons were incubated in the presence of AβOs (1.25 μmol/L) with or without atorvastatin pretreatment. ATP content and LDH in the culture medium were measured to assess the neuronal viability. Caspase-3/7 and calpain protease activities were detected. The levels of phospho-Akt, phospho-Erk1/2, phospho-GSK3β, p35 and Tau proteins were measured using Western blotting. Results: Treatment of the neurons with AβO significantly decreased the neuronal viability, induced rapid activation of calpain and caspase-3/7 proteases, accompanied by Tau degradation and relatively stable fragments generated in the neurons. AβO also suppressed Akt and Erk1/2 kinase activity, while increased GSK3β and Cdk5 activity in the neurons. Pretreatment with atorvastatin (0.5, 1, 2.5 μmol/L) dose-dependently inhibited AβO-induced activation of calpain and caspase-3/7 proteases, and effectively diminished the generation of Tau fragments, attenuated synaptic damage and increased neuronal survival. Atorvastatin pretreatment also prevented AβO-induced decreases in Akt and Erk1/2 kinase activity and the increases in GSK3β and Cdk5 kinase activity. Conclusion: Atorvastatin prevents AβO-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting calpain- and caspase-mediated Tau cleavage. PMID:25891085

Elimination of alfentanil delivered by infusion is not altered by the chronic administration of atorvastatin.

LENUS (Irish Health Repository)

McDonnell, C G

2012-02-03

BACKGROUND AND OBJECTIVE: Statins are prescribed for patients with hypercholesterolemia. Atorvastatin is metabolized by cytochrome P4503A4 and inhibits P4503A4 activity in vitro. Alfentanil is a potent opioid used in clinical anaesthetic practice and is also metabolized by P4503A4. This study tested the hypothesis that chronic atorvastatin administration inhibits the metabolism of alfentanil. METHODS: Sixteen patients undergoing elective surgery were studied as matched pairs. One member of each pair was maintained on standard doses of atorvastatin for at least 4 months. Each patient received an alfentanil bolus (80 microg kg(-1)) intravenously (i.v.), followed by an alfentanil infusion (0.67 microg kg(-1) min(-1)) for 90 min. Serial plasma alfentanil concentrations were measured using gas chromatography-nitrogen phosphorous detection. Pharmacokinetic parameters were calculated using two-compartment linear modelling. RESULTS: One patient and the corresponding match were excluded from the analysis. The elimination half-life of alfentanil was similar in the control and atorvastatin groups (98.8 +\\/- 12.4 versus 98.3 +\\/- 11.3 min, respectively). The clearance (Cl), volume of distribution at steady-state (Vdss) and area under the curve (AUC) were similar in the two groups (Cl = 0.20 (+\\/- 0.06) and 0.22 (+\\/- 0.04) L min(-1), Vdss = 0.38 (+\\/- 0.07) and 0.39 (+\\/- 0.07) L kg(-1), AUC = 0.05 (+\\/- 0.02) and 0.04 (+\\/- 0.01) mg min mL(-1)). CONCLUSIONS: Concurrent atorvastatin administration does not alter the pharmacokinetics of alfentanil in patients undergoing elective surgery.

The effect of atorvastatin on pancreatic beta cell requirement in women with polycystic ovary syndrome

Directory of Open Access Journals (Sweden)

Thozhukat Sathyapalan

2017-11-01

Full Text Available Background: There is an increased risk of developing T2DM in women with polycystic ovary syndrome (PCOS, and there is evidence that statins improve metabolic parameters in these patients. However, there are some data to show that statins increase the risk of incipient diabetes. Materials and methods: We have previously shown that 12 weeks of atorvastatin improves insulin resistance when measured using HOMA-IR. This post hoc analysis was designed to look at the effect of atorvastatin on pancreatic β cell function using HOMA-β in the same study. In this randomised, double-blind placebo controlled study, 40 medication-naïve patients with PCOS were randomised to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. Results: There was a significant reduction in HOMA-β (240 ± 3.2 vs 177 ± 2.3; P value <0.01 after 12 weeks of atorvastatin treatment, which was maintained by metformin in the subsequent 12 weeks. There were no changes in HOMA-β after the placebo or after subsequent metformin treatment. There was no linear correlation between reduction in HOMA-β with improvement of free androgen index (FAI (r2 = 0.02; P = 0.72, testosterone (r2 = 0.13; P = 0.49, SHBG (r2 = 0.22; P = 0.48, hsCRP (r2 = 0.19; P = 0.64, triglycerides (r2 = 0.09; P = 0.12, total cholesterol (r2 = 0.11; P = 0.32 or LDL-C (r2 = 0.19; P = 0.38. Conclusion: Treatment with atorvastatin for 12 weeks in women with PCOS significantly reduced HOMA-β. This could be potentially due to fall in β-cell requirement with improvement of insulin resistance rather than a reduction of β-cell function.

Survival Following Radiation and Androgen Suppression Therapy for Prostate Cancer in Healthy Older Men: Implications for Screening Recommendations

International Nuclear Information System (INIS)

Nguyen, Paul L.; Chen, Ming-Hui; Renshaw, Andrew A.; Loffredo, Marian; Kantoff, Philip W.; D'Amico, Anthony V.

2010-01-01

Purpose: The U.S. Preventive Services Task Force has recommended against screening men over 75 for prostate cancer. We examined whether older healthy men could benefit from aggressive prostate cancer treatment. Methods and Materials: 206 men with intermediate to high risk localized prostate cancer randomized to 70 Gy of radiation (RT) or RT plus 6 months of androgen suppression therapy (RT+AST) constituted the study cohort. Within subgroups stratified by Adult Comorbidity Evaluation-27 comorbidity score and age, Cox multivariable analysis was used to determine whether treatment with RT+AST as compared with RT was associated with a decreased risk of death. Results: Among healthy men (i.e., with mild or no comorbidity), 78 were older than the median age of 72.4 years, and in this subgroup, RT+AST was associated with a significantly lower risk of death on multivariable analysis (adjusted hazard ratio = 0.36 (95% CI=0.13-0.98), p = 0.046, with significantly lower 8-year mortality estimates of 16.5% vs. 41.4% (p = 0.011). Conversely, among men with moderate or severe comorbidity, 24 were older than the median age of 73, and in this subgroup, treatment with RT+AST was associated with a higher risk of death (adjusted hazard ratio = 5.2 (1.3-20.2), p = 0.018). Conclusion: In older men with mild or no comorbidity, treatment with RT+AST was associated with improved survival compared with treatment with RT alone, suggesting that healthy older men may derive the same benefits from prostate cancer treatment as younger men. We therefore suggest that prostate cancer screening recommendations should not be based on strict age cutoffs alone but should also take into account comorbidity.

Effects of hydrocortisone on false memory recognition in healthy men and women.

Science.gov (United States)

Duesenberg, Moritz; Weber, Juliane; Schaeuffele, Carmen; Fleischer, Juliane; Hellmann-Regen, Julian; Roepke, Stefan; Moritz, Steffen; Otte, Christian; Wingenfeld, Katja

2016-12-01

Most of the studies focusing on the effect of stress on false memories by using psychosocial and physiological stressors yielded diverse results. In the present study, we systematically tested the effect of exogenous hydrocortisone using a false memory paradigm. In this placebo-controlled study, 37 healthy men and 38 healthy women (mean age 24.59 years) received either 10 mg of hydrocortisone or placebo 75 min before using the false memory, that is, Deese-Roediger-McDermott (DRM), paradigm. We used emotionally charged and neutral DRM-based word lists to look for false recognition rates in comparison to true recognition rates. Overall, we expected an increase in false memory after hydrocortisone compared to placebo. No differences between the cortisol and the placebo group were revealed for false and for true recognition performance. In general, false recognition rates were lower compared to true recognition rates. Furthermore, we found a valence effect (neutral, positive, negative, disgust word stimuli), indicating higher rates of true and false recognition for emotional compared to neutral words. We further found an interaction effect between sex and recognition. Post hoc t tests showed that for true recognition women showed a significantly better memory performance than men, independent of treatment. This study does not support the hypothesis that cortisol decreases the ability to distinguish between old versus novel words in young healthy individuals. However, sex and emotional valence of word stimuli appear to be important moderators. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Hypolipidemic Effect of Fenugreek Seeds and its Comparison with Atorvastatin on Experimentally Induced Hyperlipidemia

Energy Technology Data Exchange (ETDEWEB)

Sharma, M. S. [R.N.T. Medical College, Udaipur (India). Dept. of Physiology; Choudhary, P. R. [C.U. Shah Medical College, Surendranagr (India). Dept. of Physiology

2014-08-15

Objective: To determine the hypolipidemic effect of fenugreek (Methi) seeds and its comparison with atorvastatin on experimentally induced hyperlipidemia in rabbits. Study Design: Experimental interventional study. Place and Duration of Study: Department of Physiology, Dr. S. N. Medical College, Jodhpur, Rajasthan, India, from April 2012 to March 2013. Methodology: Twenty, 1 - 2 years old albino rabbits of European Strains were randomly divided into two groups of 10 rabbits each. All were fed pure cholesterol (0.5 g/kg body weight/day) for 4 weeks to induce hyperlipidemia. Group-I comprised of 10 hyperlipidemic rabbits which were fed normal (regular) diet supplemented with 2 ml aqueous emulsified fenugreek seeds powder (500 mg/kg body weight/day) for 4 weeks. Group-II comprised of 10 hyperlipidemic rabbits, which were fed normal (regular) diet supplemented with 2 ml aqueous emulsion of atorvastatin (0.5 mg/kg body weight/day) for 4 weeks. Fasting blood samples were collected two times during experimental period at weeks (4 and 8) and analyzed for serum total cholesterol and triglycerides, using semi-automated chemistry analyzer. HDL-C was determined by precipitation method and LDL-C and VLDL-C were estimated by Friedewalds formula. LDL/HDL ratio and TG/HDL ratios were also calculated. The significance of difference in mean values of both groups (lipid profile) was assessed by independent student's t-test. Results: Atorvastatin showed a more potent hypolipidemic activity. It reduced serum total cholesterol, TG, LDL and VLDLcholesterol, and the atherogenic index (LDL-C/HDL-C; p < 0.001) highly significantly as compared to fenugreek. There was a significant increase of HDL-C (p < 0.01) in group-I as compared to group-II. Conclusion: Fenugreek and atorvastatin both have hypolipidemic activity in rabbits but atorvastatin is more potent than fenugreek seeds powder. (author)

Hypolipidemic Effect of Fenugreek Seeds and its Comparison with Atorvastatin on Experimentally Induced Hyperlipidemia

International Nuclear Information System (INIS)

Sharma, M. S.; Choudhary, P. R.

2014-01-01

Objective: To determine the hypolipidemic effect of fenugreek (Methi) seeds and its comparison with atorvastatin on experimentally induced hyperlipidemia in rabbits. Study Design: Experimental interventional study. Place and Duration of Study: Department of Physiology, Dr. S. N. Medical College, Jodhpur, Rajasthan, India, from April 2012 to March 2013. Methodology: Twenty, 1 - 2 years old albino rabbits of European Strains were randomly divided into two groups of 10 rabbits each. All were fed pure cholesterol (0.5 g/kg body weight/day) for 4 weeks to induce hyperlipidemia. Group-I comprised of 10 hyperlipidemic rabbits which were fed normal (regular) diet supplemented with 2 ml aqueous emulsified fenugreek seeds powder (500 mg/kg body weight/day) for 4 weeks. Group-II comprised of 10 hyperlipidemic rabbits, which were fed normal (regular) diet supplemented with 2 ml aqueous emulsion of atorvastatin (0.5 mg/kg body weight/day) for 4 weeks. Fasting blood samples were collected two times during experimental period at weeks (4 and 8) and analyzed for serum total cholesterol and triglycerides, using semi-automated chemistry analyzer. HDL-C was determined by precipitation method and LDL-C and VLDL-C were estimated by Friedewalds formula. LDL/HDL ratio and TG/HDL ratios were also calculated. The significance of difference in mean values of both groups (lipid profile) was assessed by independent student's t-test. Results: Atorvastatin showed a more potent hypolipidemic activity. It reduced serum total cholesterol, TG, LDL and VLDLcholesterol, and the atherogenic index (LDL-C/HDL-C; p < 0.001) highly significantly as compared to fenugreek. There was a significant increase of HDL-C (p < 0.01) in group-I as compared to group-II. Conclusion: Fenugreek and atorvastatin both have hypolipidemic activity in rabbits but atorvastatin is more potent than fenugreek seeds powder. (author)

Generic atorvastatin is as effective as the brand-name drug (LIPITOR®) in lowering cholesterol levels: a cross-sectional retrospective cohort study.

Science.gov (United States)

Loch, Alexander; Bewersdorf, Jan Philipp; Kofink, Daniel; Ismail, Dzafir; Abidin, Imran Zainal; Veriah, Ramesh Singh

2017-07-17

In a world of ever increasing health care costs, generic drugs represent a major opportunity to ensure access to essential medicines for people who otherwise would be unable to afford them. However, some clinicians and patients are still questioning the safety and effectiveness of generic formulations compared to the proprietary drugs necessitating further systematic research analyzing the generic drugs' efficacy. Our objective was to compare the lipid lowering effects of generic and branded atorvastatin. This cross-sectional, retrospective cohort study was conducted at the University of Malaya Medical Centre from 1 May 2013 until 30 May 2013. We analyzed the lipid profiles (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) of 629 patients before and at least 3 months after switching them from proprietary atorvastatin (Lipitor ® ) to generic atorvastatin (atorvastatin calcium from Ranbaxy Laboratories, Inc.). We also investigated if there was any difference in the effectiveness of both atorvastatin formulations in various ethnic groups. 266 patients were included in this study. When comparing the median values we found no statistically significant differences (Wilcoxon signed-rank test; p atorvastatin in lowering total cholesterol (4.60 mmol/l pre-transition vs. 4.50 mmol/l post-transition; p = 0.583), LDL-cholesterol (2.42 mmol/l vs. 2.41 mmol/l; p = 0.923) and triglycerides (1.50 mmol/l vs. 1.50 mmol/l; p = 0.513). While there was a statistically significant (p = 0.009) difference in HDL-cholesterol levels favouring proprietary atorvastatin, the extent of this change (1.26 mmol/l vs. 1.25 mmol/l) was deemed not to be clinically relevant. There was no statistically significant difference when analyzing the effects on various ethnic groups. Substituting proprietary atorvastatin for its generic formulation atorvastatin calcium does not result in a less effective management of hyperlipidemia. Our findings lend support to the

Integrated analysis of long noncoding RNA and mRNA profiling ox-LDL-induced endothelial dysfunction after atorvastatin administration.

Science.gov (United States)

Jiang, Ling-Yu; Jiang, Yue-Hua; Qi, Ying-Zi; Shao, Lin-Lin; Yang, Chuan-Hua

2018-06-01

Long noncoding RNAs (lncRNAs) play a key role in the development of endothelial dysfunction. However, few lncRNAs associated with endothelial dysfunction after atorvastatin administration have been reported. In the present study, differentially expressed (DE) genes in ox-LDL versus control and ox-LDL + atorvastatin versus control were detected. Bioinformatics analysis and integrated analysis of mRNAs and lncRNAs were conducted to study the mechanisms of endothelial dysfunction after atorvastatin administration and to explore the regulation functions of lncRNAs. Here, 532 DE mRNAs and 532 DE lncRNAs were identified (among them, 195 mRNAs and 298 lncRNAs were upregulated, 337 mRNAs and 234 lncRNAs were downregulated) after ox-LDL treatment for 24 hours (fold change ≥2.0, P atorvastatin administration, 750 DE mRNAs and 502 DE lncRNAs were identified (among them, 149 mRNAs and 218 lncRNAs were upregulated and 601 mRNAs and 284 lncRNAs were downregulated). After atorvastatin administration, 167 lncRNAs and 262 mRNAs were still DE. Q-PCR validated the results of microarrays. Chronic inflammatory response, nitric oxide biosynthetic process, microtubule cytoskeleton, cell proliferation and cell migration are regulated by lncRNAs, which also participated in the mainly molecular function and biological processes underlying endothelial dysfunction. Atorvastatin partly improved endothelial dysfunction, but the aspects beyond recovery were mainly concentrated in cell cycle, mitosis, and metabolism. Further exploration is required to explicit the mechanism by which lncRNAs participate in endothelial dysfunction.

Atorvastatin Use Associated With Acute Pancreatitis

OpenAIRE

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

2016-01-01

Abstract Few data are present in the literature on the relationship between atorvastatin use and acute pancreatitis. The aim of this study was to explore this issue in Taiwan. Using representative claims data established from the Taiwan National Health Insurance Program, this case?control study consisted of 5810 cases aged 20 to 84 years with a first-time diagnosis of acute pancreatitis during the period 1998 to 2011and 5733 randomly selected controls without acute pancreatitis. Both cases an...

What a man wants: understanding the challenges and motivations to physical activity participation and healthy eating in middle-aged Australian men.

Science.gov (United States)

Caperchione, Cristina M; Vandelanotte, Corneel; Kolt, Gregory S; Duncan, Mitch; Ellison, Marcus; George, Emma; Mummery, W Kerry

2012-11-01

Little attention has been paid to the physical activity (PA) and nutrition behaviors of middle-aged men; thus, the aim of this study was to gather information and gain insight into the PA and nutrition behaviors of these men. Six focus group sessions were undertaken with middle-aged men (N = 30) from regional Australia to explore the challenges and motivations to PA participation and healthy eating. Men had a good understanding of PA and nutrition; however, this was sometimes confounded by inconsistent media messages. Work commitments and family responsibilities were barriers to PA, while poor cooking skills and abilities were barriers to healthy eating. Disease prevention, weight management, and being a good role model were motivators for PA and healthy eating. By understanding what a man wants, PA and nutrition interventions can be designed and delivered to meet the needs of this hard-to-reach population.

Atorvastatin prevents age-related and amyloid-β-induced microglial activation by blocking interferon-γ release from natural killer cells in the brain

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Clarke Rachael

2011-03-01

Full Text Available Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ. IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1 and IFNγ-induced protein 10 kDa (IP-10, expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2 by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by blocking interferon-gamma release from natural killer cells in the brain

LENUS (Irish Health Repository)

Lyons, Anthony

2011-03-31

Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ). IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFNγ-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK) cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2) by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol <130 mg/dL (AIDS Clinical Trials Group Study A5275).

Science.gov (United States)

Nixon, Daniel E; Bosch, Ronald J; Chan, Ellen S; Funderburg, Nicholas T; Hodder, Sally; Lake, Jordan E; Lederman, Michael M; Klingman, Karin L; Aberg, Judith A

Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk. To evaluate atorvastatin as a strategy to reduce cardiovascular risk. A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and atorvastatin treatment. Analyses were as-treated. Ninety-eight participants were enrolled at 31 U S sites and 73 completed study treatment. Atorvastatin treatment did not decrease T-lymphocyte or monocyte activation, circulating biomarker levels (interleukin-6, D-dimer, soluble CD14, soluble CD163, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, high-sensitivity C-reactive protein, CD40L, and P-selectin) or white blood cell Krüppel-like Factor 2/4 messenger RNA levels. Pre-to-post atorvastatin reductions in calculated LDL (-38%), oxidized-LDL (-33%), and lipoprotein-associated phospholipase A2 (-31%) were significant (P atorvastatin did not significantly decrease levels of soluble or cellular biomarkers of immune activation and inflammation but resulted in robust reductions in LDL cholesterol, oxLDL, and lipoprotein-associated phospholipase A 2 , biomarkers associated with cardiovascular risk. Copyright © 2016 National Lipid Association. All rights reserved.

Old and alone: barriers to healthy eating in older men living on their own.

Science.gov (United States)

Hughes, Georgina; Bennett, Kate M; Hetherington, Marion M

2004-12-01

Ageing is associated with reduced energy intake and loss of appetite. Older men tend to have poorer dietary intakes including consumption of fewer fruits and vegetables in comparison to older women. Living and eating alone further diminishes food consumption and dietary quality. The aim of the present study was to explore food choice and energy intake in older men living alone using both quantitative and qualitative methods. 39 older men were interviewed and completed questionnaires on health, food choice, dietary patterns and appetite. Few men managed to consume recommended levels of energy, essential trace elements or vitamins A and D. Age and BMI failed to predict patterns of intake, but men with good cooking skills reported better physical health and higher intake of vegetables. However, cooking skills were negatively correlated with energy intake. Men who managed to consume at least 4 portions of fruits and vegetables each day had significantly higher vitamin C levels, a greater percentage of energy as protein and generally more adequate diets. Interviews revealed that poor cooking skills and low motivation to change eating habits may constitute barriers to improving energy intake, healthy eating and appetite in older men (193).

Effects of atorvastatin and rosuvastatin on blood lipids, platelet ...

African Journals Online (AJOL)

Conclusion: Atorvastatin and rosuvastatin have no significant effect on the antiplatelet .... J20120006; Astra Zeneca UK limited) 10 mg, .... by Johansen et al [29] and Wang et al [30] .... Pan Y, Chen W, Xu Y, Yi X, Han Y, Yang Q, Li X, Huang.

Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia – Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR

Directory of Open Access Journals (Sweden)

García Hugo

2006-12-01

Full Text Available Abstract Background Many patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg and atorvastatin (20 mg in high-risk patients with hypercholesterolemia. Methods A total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and Results Rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p Conclusion In high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated.

Evaluation of the Cytotoxic and Autophagic Effects of Atorvastatin on MCF-7 Breast Cancer Cells

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Tuğba Alarcon Martinez

2018-05-01

Full Text Available Background: Recently, cytotoxic effects of statins on breast cancer cells have been reported. However, the mechanism of anti-proliferative effects is currently unknown. Autophagy is non-apoptotic programmed cell death, which is characterized by degradation of cytoplasmic components and as having a role in cancer pathogenesis. Aims: To investigate the anti-proliferative effects of atorvastatin on MCF-7 human breast adenocarcinoma cells with respect to both autophagy and apoptosis. Study Design: Cell culture study. Methods: Cell viability was analyzed using WST-1 cell proliferation assay. Apoptosis was determined by the TUNEL method, whereas autophagy was assessed by Beclin-1 and LC3B immunofluorescence staining. Ultrastructural analysis of cells was performed by electron microscopy. Results: Atorvastatin reduced MCF-7 cell proliferation in a dose- and time-dependent manner inducing TUNEL-, Beclin-1-, and LC3B-positive cells. Moreover, ultrastructural analysis showed apoptotic, autophagic, and necrotic morphological changes in treatment groups. A statistically significant increase in the apoptotic index was detected with higher concentrations of atorvastatin at 24 h and 48 h (p<0.05. Conclusion: The anti-proliferative effects of atorvastatin on breast cancer cells is mediated by the induction of both apoptosis and autophagy which shows statins as a potential treatment option for breast cancer.

Critical Review on the Analytical Techniques for the Determination of the Oldest Statin-Atorvastatin-in Bulk, Pharmaceutical Formulations and Biological Fluids.

Science.gov (United States)

Kokilambigai, K S; Seetharaman, R; Lakshmi, K S

2017-11-02

Statins are a group of medicines that can help to lower the level of low-density lipoprotein (LDL) cholesterol "bad cholesterol" in the blood. Having a high level of LDL cholesterol is potentially dangerous, as it can lead to a hardening and narrowing of arteries (atherosclerosis) and cardiovascular disease (CVD), atorvastatin is one of the oldest member of the statin family and is used in the treatment of dyslipidemia and the prevention of CVD. Atorvastatin was first made in August 1985 and from 1996 to 2012 under the trade name Lipitor, atorvastatin became the world's best-selling drug. Numerous analytical methodologies are available for the quantification of atorvastatin and its content in pharmaceutical preparations and in biological fluids.

High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs

International Nuclear Information System (INIS)

Podszun, Maren C.; Grebenstein, Nadine; Hofmann, Ute; Frank, Jan

2013-01-01

It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P 450 enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient–drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin–Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV + αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV + αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV + αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4. -- Highlights: ► Vitamin E-atorvastatin interactions were studied in hypercholesterolemic guinea pigs. ► High-dose α-tocopherol did not alter the lipid-lowering efficacy of atorvastatin. ► α-Tocopherol did not change the expression of CYP3A4, CYP4F2, CYP20A or OATP C. ► α-Tocopherol did not affect phase I metabolism of atorvastatin. �

High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Podszun, Maren C.; Grebenstein, Nadine [Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart (Germany); Hofmann, Ute [Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, D-70376 Stuttgart (Germany); Frank, Jan [Institute of Biological Chemistry and Nutrition, University of Hohenheim, D-70599 Stuttgart (Germany); Department of Nutrition and Food Science, University of Bonn, D-53115 Bonn (Germany)

2013-02-01

It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P{sub 450} enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient–drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin–Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV + αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV + αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV + αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4. -- Highlights: ► Vitamin E-atorvastatin interactions were studied in hypercholesterolemic guinea pigs. ► High-dose α-tocopherol did not alter the lipid-lowering efficacy of atorvastatin. ► α-Tocopherol did not change the expression of CYP3A4, CYP4F2, CYP20A or OATP C. ► α-Tocopherol did not affect phase I metabolism of atorvastatin

Can combining different risk interventions into a single formulation contribute to improved cardiovascular disease risk reduction? The single pill of amlodipine/atorvastatin

Directory of Open Access Journals (Sweden)

FD Richard Hobbs

2007-11-01

Full Text Available FD Richard HobbsUniversity of Birmingham, Edgbaston, Birmingham B15 2TT, UK.Abstract: In order to prevent cardiovascular events, it is essential to effectively manage overall risk of cardiovascular disease. However, despite guideline recommendations to this effect, current management of the major, modifiable cardiovascular risk factors such as hypertension and dyslipidemia is disconnected and patient adherence to therapy is poor. This is particularly important for patients with multiple cardiovascular risk factors, who are often prescribed multiple medications. The JEWEL study program investigated the use of single-pill amlodipine/atorvastatin as a strategy to improve management of these patients. The JEWEL program consisted of two 16-week, international, openlabel, multicenter, titration-to-goal studies in patients with hypertension and dyslipidemia. The two studies differed based on country of enrollment and certain tertiary endpoints, but the overall designs were very similar. Patients were enrolled from 255 centers across Canada and 13 European countries. The study was designed to assess the efficacy, safety, and utility of amlodipine/atorvastatin single pill therapy in a real-world setting. Patients were initiated at a dose of amlodipine 5 mg/atorvastatin 10 mg, unless previously treated, and were uptitrated as necessary. The primary efficacy parameter was the percentage of patients, at different levels of cardiovascular risk, achieving country-specific guideline-recommended target levels for blood pressure and lipids. A secondary analysis of efficacy measured attainment of the same single goal for blood pressure across all study participants (JEWEL I and II and the same single goal for LDL-C across all study participants (JEWEL I and II. The program utilized a newly developed questionnaire to gain better understanding of participants’ beliefs and behaviors towards medical treatment of their multiple risk factors. Approximately 2850

Atorvastatin calcium in combination with methylprednisolone for the treatment of multiple sclerosis relapse.

Science.gov (United States)

Li, Xiao-ling; Zhang, Zhen-chang; Zhang, Bo; Jiang, Hua; Yu, Chun-mei; Zhang, Wen-jing; Yan, Xiang; Wang, Man-xia

2014-12-01

This study aimed to investigate the efficacy of combined atorvastatin calcium and methylprednisolone for the treatment of multiple sclerosis relapse. Patients with multiple sclerosis (MS) at the relapse phase were randomized to receive either combined treatment of atorvastatin calcium and methylprednisolone (n = 19) or methylprednisolone alone (n = 19). Expanded Disability Status Scale (EDSS) was administered at baseline, 1 week, 2 weeks, 4 weeks, 3 months, and 6 months after treatment initiation. The number and volume of brain lesions were evaluated using magnetic resonance imaging at baseline and 6 months. The levels of IL-13, IL-35, IFN-γ, and IL-10 in the cerebrospinal fluid were examined using the enzyme-linked immunosorbent assay method. There was no significant difference in EDSS scores at 1, 2, and 4 weeks. At 3 and 6 months, the combined treatment group showed significantly lower EDSS scores than the monotherapy group (P atorvastatin calcium and methylprednisolone can improve the outcomes of MS relapse compared with glucocorticosteroid alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Health-related physical fitness in healthy untrained men

DEFF Research Database (Denmark)

Milanović, Zoran; Pantelić, Saša; Sporiš, Goran

2015-01-01

The purpose of this study was to determine the effects of recreational soccer (SOC) compared to moderate-intensity continuous running (RUN) on all health-related physical fitness components in healthy untrained men. Sixty-nine participants were recruited and randomly assigned to one of three groups...... weeks and consisted of three 60-min sessions per week. All participants were tested for each of the following physical fitness components: maximal aerobic power, minute ventilation, maximal heart rate, squat jump (SJ), countermovement jump with arm swing (CMJ), sit-and-reach flexibility, and body...... improvements in maximal aerobic power after 12 weeks of soccer training and moderate-intensity running, partly due to large decreases in body mass. Additionally soccer training induced pronounced positive effects on jump performance and flexibility, making soccer an effective broad-spectrum fitness training...

Methods for providing intermediates in the synthesis of atorvastatin.

NARCIS (Netherlands)

Dömling, Alexander Stephan Siegfried

2016-01-01

The invention relates to the field of medicinal chemistry, In particular, it relates to methods for providing intermediates in the synthesis of Atorvastatin, a competitive inhibitor of HMG-Co A reductase. Provided is a process for providing a compound having a Formula (I) or a pharmaceutically

Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

Directory of Open Access Journals (Sweden)

Rosario D. C. Hirata

2011-09-01

Full Text Available Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks. They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C and SLCO2B1 (−71T>C gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034. Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05. Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

A Comparison of Secondary Polycythemia in Hypogonadal Men Treated with Clomiphene Citrate versus Testosterone Replacement: A Multi-Institutional Study.

Science.gov (United States)

Wheeler, Karen M; Smith, Ryan P; Kumar, Raj A; Setia, Shaan; Costabile, Raymond A; Kavoussi, Parviz K

2017-04-01

We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Microbiota of lower urine tract and genital organs of healthy men and in infertility].

Science.gov (United States)

Naboka, Iu L; Kogan, M I; Gudima, I A; Ibishev, Kh S; Pasechnik, D G; Logvinov, A K; Ilmdarov, Sh B

2015-01-01

Study microflora of urine, ejaculate, urethra scrape in normal state and infertility. 2 groups of men were examined: I (28)--control, conditionally healthy men (20 - 25 years of age), II (26)--infertile patients (25 - 35 years of age). Middle portion of morning urine, ejaculate, urethra scrape were studied in group I, in II--ejaculate. Bacteriologic study of urine and ejaculate was carried out in an extended kit of nutrient media (HiMedia) for facultative- anaerobic (FAB) and non-clostridia anaerobic bacteria (NAB). Urethra scrape and ejaculate were studied by PCR in group I. In urethra scrape and ejaculate a wide spectrum of FAB and NAB was detected in group I. Corynebacterium spp. and coagulase-negative staphylococci (67.9% each) were the dominant cluster of FAB. Eubacterium spp.--in NAB. Bacteriologic study of ejaculate corresponded in PCR with similar results of dominating bacteria. Among FAB the same clusters dominated during bacteriologic study of ejaculate from group II patients, among NAB--Propionibacterium spp., Peptococcus spp. and Peptostreptococcus spp. Quantitative characteristics of ejaculate of group I and II differed insignificantly. The frequency of detection of certain genera of FAB and NAB was significantly higher in patients with infertility than in conditionally healthy men, however quantitative parameters of the isolated microorganisms practically did not differ between groups.

Synergistic Cardioprotective Effects of Combined Chromium Picolinate and Atorvastatin Treatment in Triton X-100-Induced Hyperlipidemia in Rats: Impact on Some Biochemical Markers.

Science.gov (United States)

Shafik, Noha M; Baalash, Amal; Ebeid, Abla M

2017-12-01

Hyperlipidemia is one of the major risk factors for atherosclerosis and ischemic heart disease. Chromium (Cr) mineral is playing a crucial role in glucose and lipid homeostasis. The aim of this study was to evaluate the protective effects of combined chromium picolinate (CrPic) and atorvastatin treatment against hyperlipidemia-induced cardiac injury. Seventy-five male albino rats were divided into five groups (15 rats each). Hyperlipidemia was induced by intraperitoneal injection of a single dose of Triton X-100 (300 mg/kg body weight (b.w) (group ІІ). Treatment of hyperlipidemic rats was induced by daily administration of CrPic at a dose of 200 μg/kg b.w/day (group ІІІ), atorvastatin at a dose of 10 mg/kg/day (group IV), and combined treatment with both (group V) by gavage for 7 days. At the end of experiment, serum and heart tissues were obtained. Hyperlipidemia was confirmed by histopathology of heart tissues, marked serum dyslipidemia, increased atherogenic indices, and values of ischemia-modified albumin. In addition to increased values of proprotein convertase subtilisin/kexin type 9, activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme and high relative expression levels of pentraxin-3 were observed. However, paraoxonase-1 activity was markedly decreased in the hyperlipidemic group. Significant improvement in all assessed parameters was observed in the rat group treated with both CrPic and atorvastatin. It can be concluded that combined CrPic and atorvastatin treatments had synergistic cardioprotective effects against hyperlipidemia which may be through modulating atherosclerosis as well as cardiac and aortic damage and/or activation of anti-inflammatory and anti-oxidant pathways, thus reversing endothelial dysfunction.

The effect of atorvastatin on pancreatic beta cell requirement in women with polycystic ovary syndrome.

Science.gov (United States)

Sathyapalan, Thozhukat; Coady, Anne-Marie; Kilpatrick, Eric S; Atkin, Stephen L

2017-11-01

There is an increased risk of developing T2DM in women with polycystic ovary syndrome (PCOS), and there is evidence that statins improve metabolic parameters in these patients. However, there are some data to show that statins increase the risk of incipient diabetes. We have previously shown that 12 weeks of atorvastatin improves insulin resistance when measured using HOMA-IR. This post hoc analysis was designed to look at the effect of atorvastatin on pancreatic β cell function using HOMA-β in the same study. In this randomised, double-blind placebo controlled study, 40 medication-naïve patients with PCOS were randomised to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. There was a significant reduction in HOMA-β (240 ± 3.2 vs 177 ± 2.3; P value <0.01) after 12 weeks of atorvastatin treatment, which was maintained by metformin in the subsequent 12 weeks. There were no changes in HOMA-β after the placebo or after subsequent metformin treatment.There was no linear correlation between reduction in HOMA-β with improvement of free androgen index (FAI) ( r 2  = 0.02; P  = 0.72), testosterone ( r 2  = 0.13; P  = 0.49), SHBG ( r 2  = 0.22; P  = 0.48), hsCRP ( r 2  = 0.19; P  = 0.64), triglycerides ( r 2  = 0.09; P  = 0.12), total cholesterol ( r 2  = 0.11; P  = 0.32) or LDL-C ( r 2  = 0.19; P  = 0.38). Treatment with atorvastatin for 12 weeks in women with PCOS significantly reduced HOMA-β. This could be potentially due to fall in β-cell requirement with improvement of insulin resistance rather than a reduction of β-cell function. © 2017 The authors.

PHARMACEUTICAL QUALITY OF GENERIC ATORVASTATIN PRODUCTS COMPARED WITH THE INNOVATOR PRODUCT: A NEED FOR REVISING PRICING POLICY IN PALESTINE.

Science.gov (United States)

Shawahna, Ramzi; Hroub, Abdel Kareem; Abed, Eliama; Jibali, Sondos; Al-Saghir, Ruba; Zaid, Abdel Naser

2016-01-01

Atorvastatin reduces morbidity and mortality due to cardiovascular events. This study was conducted to assess the prices and pharmaceutical quality of innovator atorvastatin 20 mg with its locally available generics in Palestine and to assess the suitability of their interchangeability. The prices of innovator and generic atorvastatin 20 mg were determined and compared. Innovator atorvastatin and four generic products were tested for their pharmaceutical quality. Tablets were tested for their drug contents, weight uniformity, hardness, disintegration and dissolution. Three out of four generics were less expensive than the innovator. Pharmaceutical quality assessments were satisfactory and within limits for all atorvastatin tested products. The average weight ranged from 206.6 ± 8.40 to 330 ± 3.92 mg and the %RSDs were within the permitted limits as per USP. Tablet hardness ranged from 102 ± 1.41 to 197.4 ± 6.88 kg and drug contents ranged from 92.2% to 105.3%. All products disintegrated within permitted time limits and showed very rapid dissolution. Products released more than 85% of their drug contents in less than 15 min. Our results showed that all tested innovator and generic atorvastatin products were of good pharmaceutical quality. Despite the lack of in vivo evaluation, our results indicate that these products are equivalent in vitro. Considering the in vitro release characteristics, these products might be used interchangeably. However, regulatory authorities permit the use of in vitro data in establishing similarity between immediate release oral dosage forms containing biopharmaceutical classification system class I and III drugs only.

Men Who Have Sex With Men in Peru: Acceptability of Medication-Assisted Therapy for Treating Alcohol Use Disorders.

Science.gov (United States)

Brown, Shan-Estelle; Vagenas, Panagiotis; Konda, Kelika A; Clark, Jesse L; Lama, Javier R; Gonzales, Pedro; Sanchez, Jorge; Duerr, Ann C; Altice, Frederick L

2017-07-01

In Peru, the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW). Multiple studies correlate alcohol use disorders (AUDs) with risky sexual behaviors among Peruvian MSM. Qualitative research was used to inform a clinical trial on the acceptability of medication-assisted therapies to assist management of AUDs and improve antiretroviral therapy (ART) adherence among MSM/TGW in Peru. Three focus groups involving HIV-infected or HIV-uninfected MSM/TGW ( n = 26) with AUDs (AUDIT ≥ 8) were transcribed, translated from Spanish into English, and analyzed using thematic content analysis. Despite having an AUD, participants considered themselves "social" drinkers, minimized their drinking behaviors, and differed about whether or not alcohol problems could be treated. Participants expressed skepticism about medication for treating AUDs. Three concepts emerged as necessary components of a treatment program for alcohol problems: cost, family support, and the potential to drink less alcohol without attaining total abstinence. This study reveals important areas of education to increase potential acceptability of a medication for treating AUDs among MSM/TGW. Given the social conditions and knowledge base of the participants, medication-assisted therapies using naltrexone may be a beneficial strategy for MSM with AUDs.

Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways

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Jin, Ying; Sui, Hai-juan; Dong, Yan; Ding, Qi; Qu, Wen-hui; Yu, Sheng-xue; Jin, Ying-xin

2012-01-01

Aim: To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect. Methods: Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05–10 μmol/L) for various lengths of time. For pharmacological experiments, inhibitors were added 30 min prior to addition of atorvastatin. Control cultures received a similar amount of DMSO. Following the treatment period, phase-contrast digital images were taken. Digital images of neurons were analyzed for total neurite branch length (TNBL), neurite number, terminal branch number, and soma area by SPOT Advanced Imaging software. After incubation with atorvastatin for 48 h, the levels of phosphorylated 3-phosphoinoside-dependent protein kinase-1 (PDK1), phospho-Akt, phosphorylated mammalian target of rapamycin (mTOR), phosphorylated 4E-binding protein 1 (4E-BP1), p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK-3β) in the cortical neurons were evaluated using Western blotting analyses. Results: Atorvastatin (0.05–10 μmol/L) resulted in dose-dependent increase in neurite number and length in these neurons. Pretreatment of the cortical neurons with phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 (30 μmol/L) and wortmannin (5 μmol/L), Akt inhibitor tricribine (1 μmol/L) or mTOR inhibitor rapamycin (100 nmol/L) blocked the atorvastatin-induced increase in neurite outgrowth, suggesting that atorvastatin promoted neurite outgrowth via activating the PI3K/Akt/mTOR signaling pathway. Atorvastatin (10 μmol/L) significantly increased the levels of phosphorylated PDK1, Akt and mTOR in the cortical neurons, which were prevented by LY294002 (30 μmol/L). Moreover, atorvastatin (10 μmol/L) stimulated the phosphorylation of 4E-BP1 and p70S6K, the substrates of mTOR, in the cortical neurons. In addition, atorvastatin (10 μmol/L) significantly increased the phosphorylated GSK-3β level in the cortical

The effects of carbohydrate variation in isocaloric diets on glycogenolysis and gluconeogenesis in healthy men

NARCIS (Netherlands)

Bisschop, P. H.; Pereira Arias, A. M.; Ackermans, M. T.; Endert, E.; Pijl, H.; Kuipers, F.; Meijer, A. J.; Sauerwein, H. P.; Romijn, J. A.

2000-01-01

To evaluate the effect of dietary carbohydrate content on postabsorptive glucose metabolism, we quantified gluconeogenesis and glycogenolysis after 11 days of high carbohydrate (85% carbohydrate), control (44% carbohydrate), and very low carbohydrate (2% carbohydrate) diets in six healthy men. Diets

The effects of carbohydrate variation in isocaloric diets on glycogenolysis and gluconeogenesis in healthy men

NARCIS (Netherlands)

Bisschop, PH; Arias, AMP; Ackermans, MT; Endert, E; Pijl, H; Kuipers, F; Meijer, AJ; Sauerwein, HP; Romijn, JA

To evaluate the effect of dietary carbohydrate content on postabsorptive glucose metabolism, we quantified gluconeogenesis and glycogenolysis after 11 days of high carbohydrate (85% carbohydrate), control (44% carbohydrate), and very low carbohydrate (2% carbohydrate) diets in six healthy men. Diets

Effect of Atorvastatin on Orthodontic Tooth Movement in Male Wistar Rats

Science.gov (United States)

MirHashemi, Amir Hossein; Afshari, Maryam; Alaeddini, Mojgan; Etemad-Moghadam, Shahroo; Dehpour, Ahmadreza; Sheikhzade, Sedigheh; Akhoundi, Mohammad Sadegh Ahmad

2013-01-01

Objectives: Statins are used as cholesterol-lowering drugs by many patients and have been recently shown to affect bone metabolism. The aim of this study was to determine the effect of atorvastatinon on orthodontic tooth movement (OTM) in rats. Materials and Methods: Thirty-six adult male Sprague-Dawley rats were randomly divided into three groups of 12 samples each. Group A, served as control with no medication while groups B and C received a daily gavage of carboxymethyl cellulose (CMC) as vehicle and atorvastatin (5 mg/kg) as test substance, respectively. In all three groups, 6mm nickel-titanium closed-coil springs were ligated between the maxillary incisors and first left molars to deliver an initial force of 60g. Tooth movement was measured following sacrifice, 21 days after appliance insertion. Root resorption, PDL width and osteoclast number were histologically evaluated and compared between the groups. Results: The mean amount of tooth movement was 0.62 mm in group A, 0.59 mm in group B and 0.38 mm in group C. OTM reduction following administration of atorvastatin was statistically significant (p0.05). Conclusion: According to the results obtained in the current study, atorvastatin appears to reduce tooth movement in rats; however its effect on osteoclasts, especially osteoclastic function, requires further investigation. PMID:24910664

Comparative study of three modified numerical spectrophotometric methods: An application on pharmaceutical ternary mixture of aspirin, atorvastatin and clopedogrel

Science.gov (United States)

Issa, Mahmoud Mohamed; Nejem, R.'afat Mahmoud; Shanab, Alaa Abu; Hegazy, Nahed Diab; Stefan-van Staden, Raluca-Ioana

2014-07-01

Three novel numerical methods were developed for the spectrophotometric multi-component analysis of capsules and synthetic mixtures of aspirin, atorvastatin and clopedogrel without any chemical separation. The subtraction method is based on the relationship between the difference in absorbance at four wavelengths and corresponding concentration of analyte. In this method, the linear determination ranges were 0.8-40 μg mL-1 aspirin, 0.8-30 μg mL-1 atorvastatin and 0.5-30 μg mL-1 clopedogrel. In the quotient method, 0.8-40 μg mL-1 aspirin, 0.8-30 μg mL-1 atorvastatin and 1.0-30 μg mL-1 clopedogrel were determine from spectral data at the wavelength pairs that show the same ratio of absorbance for other two species. Standard addition method was used for resolving ternary mixture of 1.0-40 μg mL-1 aspirin, 0.8-30 μg mL-1 atorvastatin and 2.0-30 μg mL-1 clopedogrel. The proposed methods were validated. The reproducibility and repeatability were found satisfactory which evidence was by low values of relative standard deviation (atorvastatin and clopedogrel in capsule dosage forms and results were in good concordance with alternative liquid chromatography.

Efficacy of fix dose combination (atorvastatin and amlodipine) in treatment of uncontrolled hypertension and dyslipidemia

International Nuclear Information System (INIS)

Bashir, S.; Sherwani, M.U.K.; Batool, A.

2012-01-01

The fixed-dose combination containing the antihypertensive agent amlodipine and the statin, atorvastatin, is the first combination of its kind designed to treat two risk factors for cardiovascular disease (CVD), i.e., hypertension and dyslipidemia. in this study, blood pressure and lipid lowering effects of combination of amlodipine and atorvastatin were evaluated in uncontrolled hypertensive patients. Methods: Thirty patients both male and female in the age group 35-60 years attending the hypertensive clinic of PMRC FJMC suffering from uncontrolled hypertension were selected. baseline blood pressure was checked after half hour rest in sitting and standing position using mercury sphygmomanometer. Blood sample was collected from all patients after overnight fasting for assessment of serum cholesterol, triglycerides, LDL and HDL cholesterol levels. they were prescribed with fixed dose combination of 5 mg amlodipine and 10 mg atorvastatin. Patients were followed for their blood pressure measurement after every 4 weeks up to 12 weeks. At the end of 12 weeks their fasting blood sample was taken again for determination of serum cholesterol, triglyceride, IDL and HDL cholesterol levels. Results: Systolic blood pressure after 4, 8 and 12 weeks was significantly lower at all intervals from baseline. when systolic blood pressure after 8 and 12 weeks was compared with 4 weeks, the effect was again significant (p=0.024, p=0.002 respectively). There was no significant reduction seen in 8 versus 12 weeks (p=0.493). Diastolic blood pressure at 4, 8 and 12 weeks was significantly lower from baseline. Diastolic blood pressure after 4 and 8 weeks when compared with 8 and 12 weeks was not significantly low (p=0.99 and 0.91 respectively). Lipid profile of the patients was significantly reduced from baseline after twelve weeks of fixed dose combination of treatment (p<0.000). Conclusion: Combination therapy proved to be effective in controlling hypertension and dyslipidemia than single

Efficacy of fix dose combination (atorvastatin and amlodipine) in treatment of uncontrolled hypertension and dyslipidemia

Energy Technology Data Exchange (ETDEWEB)

Bashir, S; Sherwani, M U.K.; Batool, A [Fatima Jinnah Medical College, Lahore (Pakistan)

2012-07-15

The fixed-dose combination containing the antihypertensive agent amlodipine and the statin, atorvastatin, is the first combination of its kind designed to treat two risk factors for cardiovascular disease (CVD), i.e., hypertension and dyslipidemia. in this study, blood pressure and lipid lowering effects of combination of amlodipine and atorvastatin were evaluated in uncontrolled hypertensive patients. Methods: Thirty patients both male and female in the age group 35-60 years attending the hypertensive clinic of PMRC FJMC suffering from uncontrolled hypertension were selected. baseline blood pressure was checked after half hour rest in sitting and standing position using mercury sphygmomanometer. Blood sample was collected from all patients after overnight fasting for assessment of serum cholesterol, triglycerides, LDL and HDL cholesterol levels. they were prescribed with fixed dose combination of 5 mg amlodipine and 10 mg atorvastatin. Patients were followed for their blood pressure measurement after every 4 weeks up to 12 weeks. At the end of 12 weeks their fasting blood sample was taken again for determination of serum cholesterol, triglyceride, IDL and HDL cholesterol levels. Results: Systolic blood pressure after 4, 8 and 12 weeks was significantly lower at all intervals from baseline. when systolic blood pressure after 8 and 12 weeks was compared with 4 weeks, the effect was again significant (p=0.024, p=0.002 respectively). There was no significant reduction seen in 8 versus 12 weeks (p=0.493). Diastolic blood pressure at 4, 8 and 12 weeks was significantly lower from baseline. Diastolic blood pressure after 4 and 8 weeks when compared with 8 and 12 weeks was not significantly low (p=0.99 and 0.91 respectively). Lipid profile of the patients was significantly reduced from baseline after twelve weeks of fixed dose combination of treatment (p<0.000). Conclusion: Combination therapy proved to be effective in controlling hypertension and dyslipidemia than single

The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC-Trial): A randomized controlled first-in-human trial.

Science.gov (United States)

Karamat, Fares A; Horjus, Deborah L; Haan, Yentl C; van der Woude, Lisa; Schaap, Marianne C; Oudman, Inge; van Montfrans, Gert A; Nieuwland, Rienk; Salomons, Gajja S; Clark, Joseph F; Brewster, Lizzy M

2017-12-01

Increasing evidence indicates that the ATP-generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta-guanidinopropionic acid (GPA), a kidney-synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure-lowering agent, we assessed the tolerability of a sub-therapeutic GPA dose in healthy men. In this active and placebo-controlled, triple-blind, single-centre trial, we recruited 24 healthy men (18-50 years old, BMI 18.5-29.9 kg m -2 ) in the Netherlands. Participants were randomized (1:1:1) to one week daily oral administration of GPA 100 mg, creatine 5 g, or matching placebo. The primary outcome was the tolerability of GPA, in an intent-to-treat analysis. Twenty-four randomized participants received the allocated intervention and 23 completed the study. One participant in the placebo arm dropped out for personal reasons. GPA was well tolerated, without serious or severe adverse events. No abnormalities were reported with GPA use in clinical safety parameters, including physical examination, laboratory studies, or 12-Lead ECG. At day 8, mean plasma GPA was 213.88 (SE 0.07) in the GPA arm vs. 32.75 (0.00) nmol l -1 in the placebo arm, a mean difference of 181.13 (95% CI 26.53-335.72). In this first-in-human trial, low-dose GPA was safe and well-tolerated when used during 1 week in healthy men. Subsequent studies should focus on human pharmacokinetic and pharmacodynamic assessments with different doses. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Is salivary cortisol moderating the relationship between salivary testosterone and hand-grip strength in healthy men?

Science.gov (United States)

Crewther, Blair T; Thomas, Andrew G; Stewart-Williams, Steve; Kilduff, Liam P; Cook, Christian J

2017-03-01

This study examined the moderating effect of cortisol (C) on the relationship between testosterone (T) and hand-grip strength (HGS) in healthy young men. Sixty-five males were monitored for salivary T, C and HGS before and 15 min after a short bout (5 × 6-s trials) of sprint cycling exercise. Sprint exercise promoted (p moderating variable. The pre-test combination of high C and low T levels favoured absolute HGS, whereas low pre-test C levels and a smaller T change were linked to larger HGS changes. These associations suggest that, in the current format, T is not necessarily anabolic to muscle strength in healthy young men. Such complexities could also explain some of the inconsistent T relationships with physical performance in lesser trained male populations.

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

Energy Technology Data Exchange (ETDEWEB)

Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); Alegret, Marta; Merlos, Manuel; Roglans, Nuria [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain; Laguna, Juan C., E-mail: jclagunae@ub.edu [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain

2011-02-15

Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

International Nuclear Information System (INIS)

Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S.; Alegret, Marta; Merlos, Manuel; Roglans, Nuria; Laguna, Juan C.

2011-01-01

Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid β-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid β-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights: �

Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats

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Mai A. Zaafan

2013-06-01

Full Text Available Myocardial infarction (MI continues to be a major public health problem in the world. Statins exhibit cardio-protective effects by several mechanisms beyond their lipid lowering activity. Quercetin is a natural flavonoid that possesses significant anti-oxidant and antiinflammatory activities. The present study aimed to investigate the effects of pretreatment with atorvastatin (10 mg/kg and quercetin (50 mg/kg, as well as their combination on isoprenaline-induced MI in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB and serum level of cardiac troponin-I (cTn-I, as well as oxidative stress and inflammatory biomarkers including serum levels of C-reactive protein (CRP, tumor necrosis factor-alpha (TNF-α, and interleukin-10 (IL-10 as well as cardiac contents of lipid peroxides, reduced glutathione (GSH, and nitrite. Furthermore, ECG monitoring and histological examinations of cardiac tissues were done. Isoprenaline increased serum CK-MB activity and cTn-I level as well as inflammatory and oxidative stress biomarkers. In addition, it produced ST-segment elevation and degenerative changes in heart tissues. Pretreatment with atorvastatin suppressed significantly the elevated levels of cTn-I, CRP, TNF-α, and IL-10 in serum coupled with reduction in cardiac lipid peroxides; however, it increased cardiac nitrite content. Quercetin decreased isoprenaline-induced changes in oxidative stress and inflammatory biomarkers with marked improvement in ECG and histopathologic alterations. Combination of quercetin with atorvastatin resulted in similar protective effects. In conclusion, quercetin can be regarded as a promising cardio-protective natural agent in MI alone or combined with atorvastatin.

Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

Science.gov (United States)

Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

2013-01-01

Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

A Randomized Controlled Trial of Atorvastatin in Patients With Bronchiectasis Infected With Pseudomonas Aeruginosa: A Proof of Concept Study.

Science.gov (United States)

Bedi, Pallavi; Chalmers, James D; Graham, Catriona; Clarke, Andrea; Donaldson, Samantha; Doherty, Catherine; Govan, John R W; Davidson, Donald J; Rossi, Adriano G; Hill, Adam T

2017-08-01

There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa. Thirty-two patients chronically infected with P aeruginosa were recruited in this double-blind cross-over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months. Twenty-seven patients completed the study. Atorvastatin did not significantly improve the primary end point of cough as measured by the Leicester Cough Questionnaire (mean difference, 1.92; 95% CI for difference, -0.57-4.41; P = .12). However, atorvastatin treatment resulted in an improved St. Georges Respiratory Questionnaire (-5.62 points; P = .016) and reduced serum levels of CXCL8 (P = .04), tumor necrosis factor (P = .01), and intercellular adhesion molecule 1 (P = .04). There was a trend toward improvement in serum C-reactive protein and serum neutrophil counts (P = .07 and P = .06, respectively). We demonstrated in vitro that atorvastatin 10 μM reduced formyl-methionyl-leucyl phenylalanine-induced upregulation of CD11b expression and changes in calcium flux, reflecting an ability to decrease neutrophil activation. We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with P aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation. ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Simultaneous determination of atorvastatin calcium, ezetimibe, and fenofibrate in a tablet formulation by HPLC.

Science.gov (United States)

Patel, Archita; Macwana, Chhaya; Parmar, Vishal; Patel, Samir

2012-01-01

An accurate, simple, reproducible, and sensitive HPLC method was developed and validated for the simultaneous determination of atorvastatin calcium, ezetimibe, and fenofibrate in a tablet formulation. The analyses were performed on an RP C18 column, 150 x 4.60 mm id, 5 pm particle size. The mobile phase methanol-acetonitrile-water (76 + 13 + 11, v/v/v), was pumped at a constant flow rate of 1 mL/min. UV detection was performed at 253 nm. Retention times of atorvastatin calcium, ezetimibe, and fenofibrate were found to be 2.25, 3.68, and 6.41 min, respectively. The method was validated in terms of linearity, precision, accuracy, LOD, LOQ, and robustness. The response was linear in the range 2-10 microg/mL (r2 = 0.998) for atorvastatin calcium, 2-10 microg/mL (r2 = 0.998) for ezetimibe, and 40-120 microg/mL (r2 = 0.998) for fenofibrate. The developed method can be used for routine quality analysis of the drugs in the tablet formulation.

Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

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William Insull Jr

2010-11-01

Full Text Available William Insull Jr1, Peter P Toth2, H Robert Superko3, Roopal B Thakkar4, Scott Krause4, Ping Jiang4, Rhea A Parreno4, Robert J Padley41Baylor College of Medicine and Methodist Hospital, Houston, Texas; 2University of Illinois College of Medicine, Peoria, Illinois; 3Celera, Alameda, California, Mercer University, Atlanta, Georgia; 4Abbott, Abbott Park, Illinois, USAObjective: To compare the effects of combination niacin extended-release + simvastatin (NER/S versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia.Patients and methods: Patients (n = 137 with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher’s exact test.Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B <80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003. NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022, small LDL (55% versus 45%; P = 0.011, very low-density lipoprotein (VLDL and total chylomicrons (63% versus 39%; P < 0.001, and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007 and VLDL (9.3% versus 0.1%; P < 0.001, compared with atorvastatin.Conclusion: NER/S treatment significantly improved apo A-I levels and the apo

EFFICIENCY AND SAFETY ASSESSMENT OF GENERIC ATORVASTATINE IN PATIENTS WITH HYPERLIPIDEMIA

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J. E. Semyonova

2015-12-01

Full Text Available Aim. To assess in a short-term study efficiency and safety of hypolipidemic therapy with atorvastatine generic, Tulip, in comparison with simvastatine generic, Vasilip, in hyperlipidemic patients.Material and methods. Open, randomized, comparative, cross over study included 87 patients with hyperlipidemia, who didn’t receive hypolipidemic drugs within 6 weeks, or followed hypolipidemic diet for 4 weeks. Each patient received therapy with one of the studied drugs within 6 weeks. Then after 4-week wash-out period the second therapy with the other drug was held. Consequence of courses with each drug was set by randomization. Initial dose of both drugs was 10 mg daily. Dose was adjusted after 3 weeks. The dose was increased to 20 mg daily if cholesterol of low density lipoproteid (CLDL hadn’t reached target level (< 115 mg/dl. of Treatment safety was assessed on the basis of clinical data, hepatic enzymes activity and creatine phosphokinase levels.Results. It is shown, that to reach target figures of plasma lipid spectrum, Vasilip dose was increased significantly more often, than Tulip dose. Average Tulip dose after titration was 14,8 mg daily, Vasilip dose – 15,6 mg daily. Patients with initially higher level of triglycerides (TG > 170 mg/dl after 6 weeks with Tulip treatment showed TG reduction by 38% and with Vasilip treatment – by 20%. Both drugs showed good tolerance, no significant differences in number of side-effects were observed.Conclusion. 6-week treatment with atorvastatine generic Tulip shows significant hypolipidemic effect, which appears in significant reduction of CLDL, total cholesterol, TG compared to the initial levels. Degree of total cholesterol reduction is significantly higher with Tulip treatment compared to Vasilip treatment. Analyses shown that target levels of the assessed figures were reached in more patients, treated with Tulip. Side-effects in Tulip treatment were not severe.

EFFICIENCY AND SAFETY ASSESSMENT OF GENERIC ATORVASTATINE IN PATIENTS WITH HYPERLIPIDEMIA

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J. E. Semyonova

2005-01-01

Full Text Available Aim. To assess in a short-term study efficiency and safety of hypolipidemic therapy with atorvastatine generic, Tulip, in comparison with simvastatine generic, Vasilip, in hyperlipidemic patients.Material and methods. Open, randomized, comparative, cross over study included 87 patients with hyperlipidemia, who didn’t receive hypolipidemic drugs within 6 weeks, or followed hypolipidemic diet for 4 weeks. Each patient received therapy with one of the studied drugs within 6 weeks. Then after 4-week wash-out period the second therapy with the other drug was held. Consequence of courses with each drug was set by randomization. Initial dose of both drugs was 10 mg daily. Dose was adjusted after 3 weeks. The dose was increased to 20 mg daily if cholesterol of low density lipoproteid (CLDL hadn’t reached target level (< 115 mg/dl. of Treatment safety was assessed on the basis of clinical data, hepatic enzymes activity and creatine phosphokinase levels.Results. It is shown, that to reach target figures of plasma lipid spectrum, Vasilip dose was increased significantly more often, than Tulip dose. Average Tulip dose after titration was 14,8 mg daily, Vasilip dose – 15,6 mg daily. Patients with initially higher level of triglycerides (TG > 170 mg/dl after 6 weeks with Tulip treatment showed TG reduction by 38% and with Vasilip treatment – by 20%. Both drugs showed good tolerance, no significant differences in number of side-effects were observed.Conclusion. 6-week treatment with atorvastatine generic Tulip shows significant hypolipidemic effect, which appears in significant reduction of CLDL, total cholesterol, TG compared to the initial levels. Degree of total cholesterol reduction is significantly higher with Tulip treatment compared to Vasilip treatment. Analyses shown that target levels of the assessed figures were reached in more patients, treated with Tulip. Side-effects in Tulip treatment were not severe.

Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis

DEFF Research Database (Denmark)

Christensen, Niels Peter Aae; Van Eerdenbrugh, Bernard; Kwok, Kaho

2013-01-01

To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin.......To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin....

Effects of antioxidant vitamins along with atorvastatin and atorvastatin–niacin combination on diet-induced hypercholesterolemia in rats

OpenAIRE

Solanki, Yogendrasinh B; Bhatt, Rajendra V

2010-01-01

The present study investigated the effects of antioxidant vitamins along with atorvastatin and atorvastatinniacin combination on diet-induced hypercholesterolemia in rats. High cholesterol diet produced a significant increase in the serum total cholesterol, LDL-C, VLDL-C, TG, atherogenic index and decrease in HDL-C and HDL/LDL ratio. The lipid peroxidation and oxidative stress were significantly high in the hyperlipidemic control group. Atorvastatin improved atherogenic index but not the HDL/...

Plasma pre beta-HDL formation is decreased by atorvastatin treatment in type 2 diabetes mellitus : Role of phospholipid transfer protein

NARCIS (Netherlands)

Dallinga-Thie, G. M.; van Tol, A.; Dullaart, R. P. F.

Atorvastatin lowers plasma phospholipid transfer protein (PLTP) activity, which stimulates pre-beta-HDL, generation in vitro. We determined the effect of atorvastatin on pre-beta-HDL formation and its relation with PLTP activity in type 2 diabetes. Methods: Plasma pre-beta-HDL formation as well as

Testosterone levels in healthy men correlate negatively with serotonin 4 receptor binding

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Perfalk, Erik; Cunha-Bang, Sofi da; Holst, Klaus K

2017-01-01

The serotonergic system integrates sex steroid information and plays a central role in mood and stress regulation, cognition, appetite and sleep. This interplay may be critical for likelihood of developing depressive episodes, at least in a subgroup of sensitive individuals. The serotonin 4...... positron emission tomography in a group of 41 healthy men. We estimated global 5-HT4R binding using a latent variable model framework, which models shared correlation between 5-HT4R across multiple brain regions (hippocampus, amygdala, posterior and anterior cingulate, thalamus, pallidostriatum...... and neocortex). We tested whether testosterone and estradiol predict global 5-HT4R, adjusting for age. We found that testosterone, but not estradiol, correlated negatively with global 5-HT4R levels (p=0.02) suggesting that men with high levels of testosterone have higher cerebral serotonergic tonus. Our...

Asymmetric dimethylarginine in somatically healthy schizophrenia patients treated with atypical antipsychotics

DEFF Research Database (Denmark)

Jørgensen, Anders; Knorr, Ulla Benedichte Søsted; Soendergaard, Mia Greisen

2015-01-01

ratio are positively correlated to measures of oxidative stress. METHODS: We included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid chromatography...... in a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L-arginine: ADMA....... Data were related to markers of systemic oxidative stress on DNA, RNA and lipids, as well as measures of medication load, duration of disease and current symptomatology. RESULTS: Plasma ADMA and the L-arginine:ADMA ratio did not differ between schizophrenia patients and controls. Furthermore, ADMA...

Atorvastatin attenuates contrast-induced nephropathy by modulating inflammatory responses through the regulation of JNK/p38/Hsp27 expression

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Xuyu He

2016-05-01

Our study demonstrates that high-dosage atorvastatin treatment attenuates both the inflammatory processes and apoptosis in contrast-induced acute kidney injury, and that the JNK/p38 MAPK pathway participates in the contrast-induced apoptosis of renal tubular cells. Finally, atorvastatin reduces CIN by suppression of apoptosis, which may be through inhibition of JNK/p38 MAPK pathways.

Varicocele among healthy young men in Turkey; prevalence and relationship with body mass index

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Haluk Soylemez

2012-02-01

Full Text Available AIM: Varicocele is characterized by abnormal tortuosity and dilatation of the veins of the pampiniform plexus within the spermatic cord and is one of the causes related to male infertility. This study aimed to investigate the correlation between varicocele and somatometric parameters. We also aimed to determine prevalence and treatment ratio of this disorder among healthy young Turkish men. MATERIALS AND METHODS: A total of 2061 young men aged from 19 to 34 years was enrolled and cross sectionally evaluated for status of varicocele. Body mass index was calculated. Patients were categorized as normal weight, overweight and obese using by National Institutes of Health criteria. Patients underwent physical examinations for the presence and grade of varicocele. If the varicocele was found and previously submitted to different treatment modalities, the age of treatment and outcomes were recorded. RESULTS: Varicocele was present in 498 men (24.2%. The mean age of the participants was 22.7 ± 1.8 years, and the median BMI was 22.8 ± 2.0 kg/m². There were no significant differences in age, height, weight and BMI among the patients with different grades of varicocele (p > 0.05. Although no significant difference was found in varicocele prevalence between normal weight and over-weight participants (p > 0.05, obese participants had significantly lower varicocele prevalence compared with normal or over weight participants (p = 0.006. A total of 49 men had scrotal pain and the treatment ratio was only 2.8%. CONCLUSION: Prevalence of varicocele was found in about 24% of healthy young Turkish population. Participants with varicocele had significantly lower BMI values compared with those without varicocele. Our findings supported the hypothesis that individuals with a greater BMI may have advantages in relieving the varicocele, but further studies are required to clarify this issue. Additionally treatment ratio was low among young men with varicocele.

Simultaneous determination of atorvastatin calcium and ramipril in capsule dosage forms by high-performance liquid chromatography and high-performance thin layer chromatography.

Science.gov (United States)

Panchal, Hiral J; Suhagia, Bhanubhai N

2010-01-01

Two simple and accurate methods to determine atorvastatin calcium and ramipril in capsule dosage forms were developed and validated using HPLC and HPTLC. The HPLC separation was achieved on a Phenomenex Luna C18 column (250 x 4.6 mm id, 5 microm) in the isocratic mode using 0.1% phosphoric acid-acetonitrile (38 + 62, v/v), pH 3.5 +/- 0.05, mobile phase at a flow rate of 1 ml/min. The retention times were 6.42 and 2.86 min for atorvastatin calcium and ramipril, respectively. Quantification was achieved with a photodiode array detector set at 210 nm over the concentration range of 0.5-5 microg/mL for each, with mean recoveries (at three concentration levels) of 100.06 +/- 0.49% and 99.95 +/- 0.63% RSD for atorvastatin calcium and ramipril, respectively. The HPTLC separation was achieved on silica gel 60 F254 HPTLC plates using methanol-benzene-glacial acetic acid (19.6 + 80.0 + 0.4, v/v/v) as the mobile phase. The Rf values were 0.40 and 0.20 for atorvastatin calcium and ramipril, respectively. Quantification was achieved with UV densitometry at 210 nm over the concentration range of 50-500 ng/spot for each, with mean recoveries (at three concentration levels) of 99.98 +/- 0.75% and 99.87 +/- 0.83% RSD for atorvastatin calcium and ramipril, respectively. Both methods were validated according to International Conference on Harmonization guidelines and found to be simple, specific, accurate, precise, and robust. The mean assay percentages for atorvastatin calcium and ramipril were 99.90 and 99.55% for HPLC and 99.91 and 99.47% for HPTLC, respectively. The methods were successfully applied for the determination of atorvastatin calcium and ramipril in capsule dosage forms without any interference from common excipients.

Is Time an Important Problem in Management of Hypertension and Hypercholesterolemia by Using an Amlodipine-Atorvastatin Single Pill Combination?

Science.gov (United States)

Zeng, Rui; Wang, Mian; Zhang, Li

2016-07-26

BACKGROUND Is the timing of dosing for amlodipine and atorvastatin important with regard to therapeutic efficacy? To answer this question, we designed an outpatient, practice-based, case-control study lasting 8 weeks. MATERIAL AND METHODS Two hundred patients were divided into 2 groups: in Group I, patients were provided with a single pill containing amlodipine/atorvastatin (5/20 mg) to be taken each night at 10 pm, and in Group II, patients were taking amlodipine (5 mg) and atorvastatin (20 mg) each morning at 7 am. RESULTS Our results indicated no obvious difference in blood pressure control between the 2 groups. Taking amlodipine at night not only lowered blood pressure, but it also provided better control during the peak blood pressure in the morning. Hypercholesterolemia control in the 2 groups was also not significantly different, taking atorvastatin in the morning was as effective as dosing at night in patients with hypercholesterolemia. While the carotid IMT, hs-CRP, and LVMI were significantly lower after treatment, no differences were found between the 2 groups. Although no obvious difference was found in adverse drug reactions between the 2 groups, compliance was much better in the single-pill group than in patients taking the 2 medications separately. CONCLUSIONS In conclusion, single-pill amlodipine-atorvastatin taken at night can lower blood pressure and reduce the morning peak blood pressure levels the next day. Additionally, this dosing method could improve patient adherence to the therapy.

Effects of Atorvastatin on Ventricular Late Potentials and Repolarization Dispersion in Patients with Hypercholesterolemia

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Chih-Sheng Chu

2007-05-01

Full Text Available Emerging evidence suggests that statins have a favorable impact on the reduction of arrhythmia events and sudden cardiac death in patients with structural heart disease. We aimed to investigate the possibly and directly favorable effects of statins on ventricular late potentials, QT dispersion, and transmural dispersion of repolarization attained by analyzing clinical electrocardiography (ECG risk stratification parameters in patients with hypercholesterolemia without structural heart disease. In total, 82 patients (45 females; mean age, 62 ± 10 years with hypercholesterolemia were enrolled in this prospective study to examine the effects of statin therapy (atorvastatin 10mg/day for 3 months on ECG risk stratification parameters. Surface 12-lead ECG and signal-average ECG (SAECG were recorded before and after statin treatment. The SAECG parameters, QT dispersion, Bazett-corrected QT (QTc dispersion, T wave peak-to-end interval (Tpe, and percentage of Tpe/QT interval were calculated and compared before and after statin therapy. Twelve-lead ambulatory 24-hour ECGs were recorded in 12 patients. The results demonstrated that after statin therapy for 3 months, serum levels of total cholesterol and low-density lipoprotein cholesterol were significantly reduced (both p values < 0.001. However, neither significant changes of each SAECG parameter nor the frequency of late potentials were demonstrated after atorvastatin therapy. In addition, no significant changes in QT dispersion, QTc dispersion, Tpe, or Tpe/QT were found. However, 24-hour ambulatory ECG revealed a flattening effect of circadian variation of QTc dispersion after atorvastatin therapy. In conclusion, the favorable antiarrhythmia effect of atorvastatin (10 mg/day therapy cannot be directly reflected by analyzing these noninvasive ECG risk stratification parameters in low-risk patients with hypercholesterolemia.

Atorvastatin Inhibits Myocardial Apoptosis in a Swine Model of Coronary Microembolization by Regulating PTEN/PI3K/Akt Signaling Pathway

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Jiangyou Wang

2016-01-01

Full Text Available Background/Aims: Phosphatase and tensin homolog deleted on chromosome ten (PTEN has been recognized as a promoter of apoptosis in various tissues, and revealed to be up-regulated in circumstances of coronary microembolization (CME. However, whether this functional protein could be modified by pretreatment of atorvastatin in models of CME has not been disclosed yet. Methods: Swine CME was induced by intra-coronary injection of inertia plastic microspheres (diameter 42 μm into left anterior descending coronary, with or without pretreatment of atorvastatin or PTEN siRNA. Echocardiologic measurements, pathologic examination, TUNEL staining and western blotting were applied to assess their functional, morphological and molecular effects in CME. Results: PTEN were aberrantly up-regulated in cardiomyocytes following CME, with both the mRNA and protein levels increased after CME modeling. Pretreatment with atorvastatin could attenuate the induction of PTEN. Furthermore, down-regulation of PTEN in vivo via siRNA was associated with an improved cardiac function, attenuated myocardial apoptosis, and concomitantly inhibited expressions of key proapoptotic proteins such as Bax, cleaved-caspase-3. Interestingly, atorvastatin could markedly attenuate PTEN expression and therefore partially reverse cardiac dysfunction and attenuate the apoptosis of the myocardium following CME. Conclusion: Modulation of PTEN was probably as a potential mechanism involved in the beneficial effects of pretreatment of atorvastatin to cardiac function and apoptosis in large animal models of CME.

Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin

Science.gov (United States)

Li, Dongye; Wu, Weiheng; Gong, Lei; Li, Yong; Zhang, Qingdui; Zhang, Tao; Zhang, Chao; Zhang, Yu

2015-01-01

Background Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI). Methods Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured. Results DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels. PMID:25973795

Reduced ex Vivo Interleukin-6 Production by Dietary Fish Oil Is Not Modified by Linoleic Acid Intake in Healthy Men

DEFF Research Database (Denmark)

Damsgaard, C. T.; Lauritzen, L.; Calder, P. C.

2009-01-01

production from cultures of whole blood, peripheral blood mononuclear cells (PBMC), and monocytes in healthy men. The study was a double-blinded, controlled, 2 X 2 factorial 8-wk intervention. Sixty-four healthy men were randomized to 5 mL/d FO or olive oil (00) provided in capsules and to spreads and oils......Fish oil (FO) is considered antiinflammatory, but evidence regarding its effect on human cytokine production is conflicting. High linoleic acid (LA) intake may impair any effects of FO. The aim of this study was to investigate how FO combined with high or low LA intake affected ex vivo cytokine...

Short-Term Therapy with High Dose Atorvastatin in Patients with Coronary Artery Disease Can Reduce Inflammatory Process

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Vida Nesar Hossein

2010-08-01

Full Text Available Coronary heart disease is the leading cause of death and disability in adults. The association between acute coronary syndrom (ACS and elevated serum high sensitivity c-reactive protein (hsCRP suggests that chronic inflammation of the coronary arterial wall may play an important role. A number of drugs used in the treatment of cardiovascular disease reduce serum CRP. It* is therefore possible that reduced inflammation contributes to the beneficial effects of these medications. This was a double blind randomized clinical trial on 52 patients were admitted because of ACS at the Mazandaran Heart Center, Iran in 2007. The patients were divided to three randomized groups which received 20, 40, 80* mg Atorvastatin daily for 6 months. At the time of study enrollment and 1, 3 and 6 months after initiation hsCRP were measured. 1 and 3 month after 20mg atorvastatin therapy the median serum concentration of hsCRP did not decrease significantly, but at the end of 6th month it was* significant difference. At 40mg dosage from 3th month to 6th month versus 1st month to 3th month it was significant decrease, at the end of 1th month and 3rd month it was not significant. At 80mg dose at the end of 1th month it was not significant but at the* end of 3th month and end of 6th month it was significant. Intensive lipid-lowering therapy with high-dose atorvastatin therapy relative to moderate lipid-lowering therapy with low-dose atorvastatin reduces hsCRP better. We found that treatment with greater dose of atorvastatin might decrease greater in plasma level of hsCRP.

Application of carbon nanotubes-ionic liquid hybrid in a sensitive atorvastatin ion-selective electrode

International Nuclear Information System (INIS)

Jalali, Fahimeh; Ardeshiri, Moslem

2016-01-01

Atorvastatin (ATR) was determined by a potentiometric method. The ion-pair of ATR and cetyltrimethylammonium bromide (CTAB) was used as a suitable ionophore. A graphite paste electrode was modified with ATR-CTAB ion-pair, multiwalled carbon nanotubes (MWCNTs), and an ionic liquid, 1-butyl-3-mtehyl-imidazolium hexafluorophosphate (BMIMPF 6 ). The amounts of electrode ingredients were optimized (graphite powder: paraffin oil: ATR-CTAB: MWCNTs: BMIMPF 6 (58:26:5:8:3 w/w%). Surface characterization was done by using scanning electron microscopy. The potential measurements were recorded at optimized pH by using acetate buffer solution (0.1 mol L −1 , pH 5.5). At the above experimental conditions, calibration curve (E vs. log [ATR]) was linear (R 2 = 0.9977) in the concentration range of 1.0 × 10 −9 –1.0 × 10 −3 mol L −1 (0.0012–1209 mg L −1 ) of ATR with a Nernstian slope of 58.14 ± 0.2 mV decade −1 , and detection limit of 1.0 × 10 −9 mol L −1 (0.0013 mg L −1 ). After each injection of ATR to the buffer solution, the potential was stabilized in a very short time (average response time ~ 6 s) at 25 °C. The modified graphite paste electrode had a long lifetime (> 4 months). Recovery of the spiked drug to blood serum samples (95.3–98.2%) revealed the reliability of electrode response to ATR. Blood serum samples from consumers were analyzed by the proposed method; the results were comparable with those from HPLC standard method. The potentiometric analysis of ATR tablets by the proposed electrode resulted in a relative error of 0.8% and 1.5% for 20 and 40 mg per tablets, respectively. Finally, the electrode was used in potentiometric titration of ATR (1.0 × 10 −3 mol L −1 ) by CTAB (1.0 × 10 −3 mol L −1 ). Excellent accuracy (≈ 100%) was obtained from the volume of the titrant at the endpoint. - Graphical abstract: Graphite paste was modified with atorvastatin-CTAB (ATR-CTAB), ionic liquid (BMIMPF 6 ) and multiwalled carbon

Acute and chronic effects of dinner with alcoholic beverages on nitric oxide metabolites in healthy men

NARCIS (Netherlands)

Sierksma, A.; Gaag, M.S. van der; Grobbee, D.E.; Hendriks, H.F.J.

2003-01-01

1. The present study investigated the acute and chronic effect of dinner with alcoholic beverages on serum nitric oxide (NO) metabolites, namely nitrate and nitrite (NOx), in 11 healthy, non-smoking middle-aged men. 2. In a randomized, diet-controlled, cross-over trial, subjects consumed dinner with

Low-Grade Inflammation Is Associated with Susceptibility to Infection in Healthy Men

DEFF Research Database (Denmark)

Kaspersen, Kathrine Agergård; Dinh, Khoa Manh; Erikstrup, Lise Tornvig

2016-01-01

Introduction The aim of this study was to examine whether low-grade inflammation (LGI) is associated with a subsequently increased risk of infection. Methods We included 15,754 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. LGI......-years of observation, 571 participants were hospitalized for infection. Similarly, during 26,125 person-years of observation, 7,276 participants filled a prescription of antimicrobials. LGI was associated with increased risk of hospital-based treatment for infection only among men (hazard ratio = 1.60, 95% confidence...

The healthy Nordic diet predicts muscle strength 10 years later in old women, but not old men.

Science.gov (United States)

Perälä, Mia-Maria; von Bonsdorff, Mikaela B; Männistö, Satu; Salonen, Minna K; Simonen, Mika; Kanerva, Noora; Rantanen, Taina; Pohjolainen, Pertti; Eriksson, Johan G

2017-07-01

a number of nutrients have been found to be associated with better muscle strength and mass; however, the role of the whole diet on muscle strength and mass remains still unknown. to examine whether the healthy Nordic diet predicts muscle strength, and mass 10 years later among men and women. about 1,072 participants belong to the Helsinki Birth Cohort Study, born 1934-44. Diet was assessed with a validated food-frequency questionnaire during 2001-04. The Nordic diet score (NDS) was calculated. The score included Nordic fruits, vegetables, cereals, ratio of polyunsaturated to saturated fatty acids, low-fat milk, fish, red meat, total fat and alcohol. Higher scores indicated better adherence to the healthy Nordic diet. Hand grip strength, leg strength (knee extension) and muscle mass were measured during the follow-up, between 2011 and 2013. in women, each 1-unit increase in the NDS was related to 1.83 N greater leg strength (95% confidence interval [CI] 0.14-3.51; P = 0.034), and 1.44 N greater hand grip strength (95% CI: 0.04-2.84; P = 0.044). Women in the highest quartile of the NDS had on average 20.0 N greater knee extension results, and 14.2 N greater hand grip results than those in the lowest quartile. No such associations were observed among men. The NDS was not significantly related to muscle mass either in men or women. adherence to the healthy Nordic diet seems to protect from weaker muscle strength in old women. Therefore, the healthy Nordic diet may help to prevent disability. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men

DEFF Research Database (Denmark)

Asmar, Ali; Asmar, Meena; Simonsen, Lene

2017-01-01

In healthy subjects, we recently demonstrated that during acute administration of GLP-1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP-1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and....../or splanchnic tissues. Nine healthy men were examined twice in random order during a 2-hour infusion of either GLP-1 (1.5 pmol kg(-1) min(-1)) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra-arterial blood pressure. Subcutaneous, abdominal adipose...... and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP-1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP-1 increases cardiac...

Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.

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Katakawa, Mayumi; Fukuda, Noboru; Tsunemi, Akiko; Mori, Mari; Maruyama, Takashi; Matsumoto, Taro; Abe, Masanori; Yamori, Yukio

2016-12-01

Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt-loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases.

PLA-PEG-PLA copolymer-based polymersomes as nanocarriers for delivery of hydrophilic and hydrophobic drugs: preparation and evaluation with atorvastatin and lisinopril.

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Danafar, H; Rostamizadeh, K; Davaran, S; Hamidi, M

2014-10-01

Tri-block poly(lactide)-poly(ethylene glycol)-poly(lactide) (PLA-PEG-PLA) copolymers were synthesized and used to prepare polymersomes loaded separately by the hydrophobic and hydrophilic model drugs, atorvastatin and lisinopril, respectively. The resulting nanostructures were characterized by various techniques such as FTIR, DSC, PCS and AFM. The polymersomes exhibited high encapsulation efficiencies of almost 78% and 70.8% for atorvastatin and lisinopril, respectively. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between atorvastatin and the copolymer. The impact of drug/copolymer ratio and copolymer composition on drug-loading efficiency and drug release behavior were also studied. The results showed that in case of lisinopril, polymersomes exhibited a triphasic drug release, while for atorvastatin a biphasic release profile was obtained. Overall, the results indicated that PLA-PEG-PLA polymersomes can be considered as a promising carrier for both hydrophilic and hydrophobic drugs.

Ursodeoxycholic Acid and Atorvastatin in the Treatment of Nonalcoholic Steatohepatitis

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Murat Kiyici

2003-01-01

Full Text Available BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA in the treatment of NASH.

Effect of atorvastatin on pancreatic Beta-cell function and insulin resistance in type 2 diabetes mellitus patients: a randomized pilot study.

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Goyal, Aman; Singh, Surender; Tandon, Nikhil; Gupta, Nandita; Gupta, Yogendra Kumar

2014-12-01

Statins are commonly used for the management of dyslipidemia in type 2 diabetes mellitus patients. We hypothesized that atorvastatin could modulate the beta-cell function by altering the levels of proapoptotic and antiapoptotic lipoproteins and could also have an effect on insulin resistance. The aim of the present pilot study was to assess the effect of atorvastatin 10 mg on pancreatic beta-cell function and insulin resistance in patients with hyperlipidemia and type 2 diabetes by using the homeostasis model assessment-2 (HOMA2) index. Fifty-one type 2 diabetes patients receiving oral antidiabetes drugs, not taking statins, with baseline low-density lipoprotein cholesterol between 2.6 mmol/L and 4.1 mmol/L were included. Forty-three patients (21 in placebo group and 22 in atorvastatin group) completed the study and were taken up for final analysis. Fasting blood samples were obtained at baseline and at 12 weeks to determine levels of blood glucose, lipid profile, insulin, C-peptide and glycosylated hemoglobin (A1C). Atorvastatin nonsignificantly increased fasting serum insulin (+14.29%, p=0.18), accompanied by marginal nonsignificant increases in fasting plasma glucose and A1C. There was a decrease in HOMA2 percent beta-cell function (-2.9%, p=0.72) and increase in HOMA2 insulin resistance (+14%, p=0.16) in the atorvastatin group as compared with baseline, but the difference was not statistically significant. Atorvastatin in the dose used failed to produce significant change in pancreatic beta-cell function and insulin resistance in type 2 diabetes patients as assessed by the HOMA2 index. The possible explanations include absence of lipotoxicity at prevailing levels of dyslipidemia at baseline or inadequacy of statin dose used in the study. (Clinical Trials Registry-India: CTRI/2008/091/000099). Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Heart rate reserve predicts cardiovascular death among physically unfit but otherwise healthy middle-aged men: a 35-year follow-up study.

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Engeseth, Kristian; Hodnesdal, Christian; Grundvold, Irene; Liestøl, Knut; Gjesdal, Knut; Erikssen, Gunnar; Kjeldsen, Sverre E; Erikssen, Jan E; Bodegard, Johan; Skretteberg, Per Torger

2016-01-01

Heart rate reserve (HRR) has been reported to be inversely associated with cardiovascular (CV) disease and death. The impact of physical fitness (PF) on this relationship has not, however, been described in detail. We investigated how different levels of PF influenced the association between HRR and CV death during a 35-year follow-up. HRR and PF were measured in 2014 apparently healthy, middle-aged men during a symptom-limited bicycle exercise test in 1972-75. The men were divided into tertiles (T1-T3) by age-adjusted HRR. Morbidity and mortality data were registered from hospital charts through 2007 and the Norwegian Cause of Death Registry. Adjusted Cox proportional hazard regression models were used to calculate risks. Incidence of CV death was 528 (26%) during median 30 years of follow-up. Men with the lowest HRR had 41% (HR 1.41 [1.14-1.75]) increased risk of CV death compared with the men with the highest. We found a significant interaction between age-adjusted PF and HRR. After stratifying the men by PF, results were statistically significant only among men with the lowest PF, where the men with lowest HRR had a 70% (HR 1.70 [1.12-2.67]) increased risk of CV death compared with the men with the highest. Low HRR was independently associated with increased risk of CV death in apparently healthy, middle-aged men. The predictive impact of HRR on CV death risk was, however, confined to unfit men. © The European Society of Cardiology 2014.

Eccentric Exercise, Kinesiology Tape, and Balance in Healthy Men.

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Hosp, Simona; Folie, Ramona; Csapo, Robert; Hasler, Michael; Nachbauer, Werner

2017-07-01

  Deficits in balance have been identified as a possible risk factor for knee injuries in athletes. Despite a lack of evidence for its effectiveness, kinesiology tape (KT) is widely used to prevent knee injuries.   To investigate the influence of KT at the knee joint on balance ability in healthy men after eccentric exercise.   Crossover study.   University laboratory.   Twelve young men with no history of lower limb injury volunteered for the study (age = 23.3 ± 2.6 years). All participants were students enrolled in a sports science program.   Participants performed the balance test with and without KT at the knee joint on 2 separate days.   The ability to maintain balance was assessed during a single-legged-stance test using a computerized balance-stability test system. The test was performed before and after 30 minutes of downhill walking on a treadmill.   Eccentric exercise resulted in a deterioration of balance ability, which was attenuated by the use of KT. Further analyses revealed that the effectiveness of KT depended on the participant's balance status, with the preventive effect being greater in participants presenting with poorer baseline balance ability.   Applied to the knee joint, KT counteracted the exercise-related deterioration of balance ability observed when no tape was used. Participants presenting with below-average balance ability received more benefit from KT. By preventing exercise-related impairment of balance ability, KT might help to reduce the risk of sport-associated knee injuries.

Effects of Irbesartan combined Atorvastatin on serum levels of Cys C, Hcy, TNF-α, ET, TGF-b1 in patients with early diabetic nephropathyn

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Abudula.Reziwanguli

2017-10-01

Full Text Available Objective: To observe the effects of Irbesartan combined with Atorvastatin on early diabetic nephropathy patients’ serum Cys C, Hcy, TNF-α, ET and TGF-b1 levels. Methods: A total of 60 early diabetic nephropathy patients were randomly divided into observation group (30 cases and control group (30 cases. Observation group: Irbesartan combined with Atorvastatin; control group: patients were treated only by Irbesartan. Recording and comparing the levels of Cys C, Hcy, TNF-α, ET and TGF-b1 before and after treatment. Results: (1 Before treatment, there was no statistically significant difference in the serum FBG, TG, Scr, BUN levels between the two groups. After treatment, compared with the same group before treatment, the serum TG, Scr, BUN levels of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, the difference between two groups was statistically significant; (2 Before treatment, there was no statistically significant difference in the serum Cys C, Hcy, TNF-α, ET, TGF-b1 levels between the two groups. After treatment, compared with the same group before treatment, the serum Cys C, Hcy, TNF-α, ET, TGF-b1 levels of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, the difference between two groups was statistically significant. Conclusion: Irbesartan combined with Atorvastatin for early diabetic nephropathy patients can reduce the levels of serum Cys C, Hcy, TNF-α, ET, TGF-b1 and be beneficial to protect their nephritic function.

Effect of Atorvastatin vs. Rosuvastatin on cardiac sympathetic nerve activity in non-diabetic patients with dilated cardiomyopathy

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Tsutamoto, Takayoshi; Ibe, Kunihiro [Toyosato Hospital, Toyosato, Shiga (Japan); Sakai, Hiroshi; Yamaji, Masayuki; Kawahara, Chiho; Nakae, Ichiro; Fujii, Masanori; Yamamoto, Takashi; Horie, Minoru [Shiga Univ. of Medical Science, Faculty of Medicine, Otsu, Shiga (Japan)

2011-08-15

Effects of statin therapy on cardiac sympathetic nerve activity in patients with chronic heart failure (CHF) have not previously been evaluated. To compare the effects of lipophilic atorvastatin and hydrophilic rosuvastatin on cardiac sympathetic nerve activity in CHF patients with dilated cardiomyopathy (DCM), 63 stable outpatients with DCM, who were already receiving standard therapy for CHF, were randomized to atorvastatin (n=32) or rosuvastatin (n=31). We evaluated cardiac sympathetic nerve activity by cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and after 6 months of treatment. There were no differences in the baseline characteristics of the 2 groups. In the rosuvastatin group, there were no changes in MIBG parameters, left ventricular ejection fraction or plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 months of treatment. In contrast, the atorvastatin group showed a significant increase in the delayed heart/mediastinum count ratio (2.18{+-}0.4 vs. 2.36{+-}0.4, P<0.0001), and the washout rate was significantly decreased (34.8{+-}5.7 vs. 32.6{+-}6.3%, P=0.0001) after 6 months of treatment compared with the baseline values. The plasma NT-proBNP level was also significantly decreased (729{+-}858 vs. 558{+-}747 pg/ml, P=0.0139). Lipophilic atorvastatin but not hydrophilic rosuvastatin improves cardiac sympathetic nerve activity in CHF patients with DCM. (author)

Cost-effectiveness of rosuvastatin in comparison with generic atorvastatin and simvastatin in a Swedish population at high risk of cardiovascular events

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Gandhi SK

2012-01-01

Full Text Available Sanjay K Gandhi1, Marie M Jensen2, Kathleen M Fox3, Lee Smolen4, Anders G Olsson5, Thomas Paulsson61AstraZeneca LP, Wilmington, DE, USA; 2AstraZeneca, Lund, Sweden; 3Strategic HealthCare Solution, Monkton, MD; 4Medical Decision Modeling Inc, Indianapolis, IN, USA; 5Department of Medical and Health Sciences, Linkoping University, and Stockholm Heart Center, Stockholm; 6AstraZeneca, Sodertalje, SwedenBackground: To assess the long-term cost-effectiveness of rosuvastatin therapy compared with generic simvastatin and generic atorvastatin in reducing the incidence of cardiovascular events and mortality in a Swedish population with Framingham risk ≥20%.Methods: A probabilistic Monte Carlo simulation model based on data from JUPITER (the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin was used to estimate the long-term cost-effectiveness of rosuvastatin 20 mg daily versus simvastatin or atorvastatin 40 mg for the prevention of cardiovascular death and morbidity. The three-stage model included cardiovascular event prevention simulating the 4 years of JUPITER, initial prevention beyond the trial, and subsequent cardiovascular event prevention. A Swedish health care payer perspective (direct costs only was modeled for a lifetime horizon, with 2008/2009 as the costing period. Univariate and probabilistic sensitivity analyses were performed.Results: The incremental cost per quality-adjusted life-year (QALY gained with rosuvastatin 20 mg over simvastatin or atorvastatin 40 mg ranged from SEK88,113 (rosuvastatin 20 mg versus simvastatin 40 mg; Framingham risk ≥30%; net avoidance of 34 events/1000 patients to SEK497,542 (versus atorvastatin 40 mg: Framingham risk ≥20%; net avoidance of 11 events/1000 patients over a lifetime horizon. Probabilistic sensitivity analyses indicated that at a willingness-to-pay threshold of SEK500,000/QALY, rosuvastatin 20 mg would be cost-effective for approximately 75%–85

Application of carbon nanotubes-ionic liquid hybrid in a sensitive atorvastatin ion-selective electrode

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Jalali, Fahimeh, E-mail: fjalali@razi.ac.ir; Ardeshiri, Moslem

2016-12-01

Atorvastatin (ATR) was determined by a potentiometric method. The ion-pair of ATR and cetyltrimethylammonium bromide (CTAB) was used as a suitable ionophore. A graphite paste electrode was modified with ATR-CTAB ion-pair, multiwalled carbon nanotubes (MWCNTs), and an ionic liquid, 1-butyl-3-mtehyl-imidazolium hexafluorophosphate (BMIMPF{sub 6}). The amounts of electrode ingredients were optimized (graphite powder: paraffin oil: ATR-CTAB: MWCNTs: BMIMPF{sub 6} (58:26:5:8:3 w/w%). Surface characterization was done by using scanning electron microscopy. The potential measurements were recorded at optimized pH by using acetate buffer solution (0.1 mol L{sup −1}, pH 5.5). At the above experimental conditions, calibration curve (E vs. log [ATR]) was linear (R{sup 2} = 0.9977) in the concentration range of 1.0 × 10{sup −9}–1.0 × 10{sup −3} mol L{sup −1} (0.0012–1209 mg L{sup −1}) of ATR with a Nernstian slope of 58.14 ± 0.2 mV decade{sup −1}, and detection limit of 1.0 × 10{sup −9} mol L{sup −1} (0.0013 mg L{sup −1}). After each injection of ATR to the buffer solution, the potential was stabilized in a very short time (average response time ~ 6 s) at 25 °C. The modified graphite paste electrode had a long lifetime (> 4 months). Recovery of the spiked drug to blood serum samples (95.3–98.2%) revealed the reliability of electrode response to ATR. Blood serum samples from consumers were analyzed by the proposed method; the results were comparable with those from HPLC standard method. The potentiometric analysis of ATR tablets by the proposed electrode resulted in a relative error of 0.8% and 1.5% for 20 and 40 mg per tablets, respectively. Finally, the electrode was used in potentiometric titration of ATR (1.0 × 10{sup −3} mol L{sup −1}) by CTAB (1.0 × 10{sup −3} mol L{sup −1}). Excellent accuracy (≈ 100%) was obtained from the volume of the titrant at the endpoint. - Graphical abstract: Graphite paste was modified with atorvastatin

Effects of sleep restriction on adiponectin levels in healthy men and women.

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Simpson, Norah S; Banks, Siobhan; Arroyo, Sylmarie; Dinges, David F

2010-12-02

Population studies have consistently found that shorter sleep durations are associated with obesity and cardiovascular disease, particularly among women. Adiponectin is an adipocyte-derived, anti-inflammatory hormone that is related to cardiovascular disease risk. We hypothesized that sleep restriction would reduce adiponectin levels in healthy young adults. 74 healthy adults (57% men, 63% African American, mean age 29.9years) completed 2 nights of baseline sleep at 10h time in bed (TIB) per night followed by 5 nights of sleep restricted to 4h TIB per night. An additional 8 participants were randomized to a control group that received 10h TIB per night throughout the study. Plasma adiponectin levels were measured following the second night of baseline sleep and the fifth night of sleep restriction or control sleep. Sleep restriction resulted in a decrease in plasma adiponectin levels among Caucasian women (Z=-2.19, p=0.028), but an increase among African American women (Z=-2.73, p=0.006). No significant effects of sleep restriction on adiponectin levels were found among men. A 2×2 between-group analysis of covariance on adiponectin change scores controlling for BMI confirmed significant interactions between sleep restriction and race/ethnicity [F(1,66)=13.73, prestriction, race/ethnicity and sex [F(1,66)=4.27, p=0.043)]. Inflammatory responses to sleep loss appear to be moderated by sex and race/ethnicity; observed decreases in adiponectin following sleep restriction may be one avenue by which reduced sleep duration promotes cardiovascular risk in Caucasian women. Copyright © 2010 Elsevier Inc. All rights reserved.

Bioavailability of tryptophan from a single oral dose of a trytophan-enriched peptide mixture in healthy men

NARCIS (Netherlands)

Brink, E.J.; Boelsma, E.; Steijns, J.; Hendriks, H.F.J.

2004-01-01

The aim of the study was to investigate the bioavailability of tryptophan (Trp) from a Trp-enriched peptide mixture in healthy men. A second objective was to investigate the effect of this Trp-enriched protein hydrolysate on potential parameters of serotonergic activity. serum serotonim melatonin

Effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome

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Xiao-Li Zhu

2016-05-01

Full Text Available Objective: To observe the effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome (ACS. Methods: A total of 92 patients with ACS were randomly divided into observation group (47 cases and control group (45 cases. The control group was given Atorvastatin (10mg/d based on the conventional therapy, while the observation group was given Atorvastatin at an intensive dose (40 mg/d based on the conventional therapy. Half a month later, the changes of IL-6, IL-8, hs-CRP, TNF-α, TXB2, GMP-140, PAI-1 and t-PA were observed and compared between the two groups. Results: After treatment, the inflammatory factors (IL-6, IL-8, hs-CRP and TNF-α and the indicators of platelet activity (TXB2, GMP-140 and PAI-1 were obviously decreased, while the indicator of fibrinolytic activity (t-PA was apparently increased in the two groups. Besides, the amplitudes of change referring to these indicators in the observation group were bigger than those in the control group after treatment, and the differences were statistically significant. Conclusion: The intensive therapy with the administration of Atorvastatin at a dose of 40 mg/d was better than the conventional therapy (Atorvastatin: 10 mg/d in aspects of reducing inflammatory factors, inhibiting platelet activity and correcting the high coagulation state of fibrinolytic system.

Atorvastatin effect evaluation based on feature combination of three-dimension ultrasound images

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Luo, Yongkang; Ding, Mingyue

2016-03-01

In the past decades, stroke has become the worldwide common cause of death and disability. It is well known that ischemic stroke is mainly caused by carotid atherosclerosis. As an inexpensive, convenient and fast means of detection, ultrasound technology is applied widely in the prevention and treatment of carotid atherosclerosis. Recently, many studies have focused on how to quantitatively evaluate local arterial effects of medicine treatment for carotid diseases. So the evaluation method based on feature combination was proposed to detect potential changes in the carotid arteries after atorvastatin treatment. And the support vector machine (SVM) and 10-fold cross-validation protocol were utilized on a database of 5533 carotid ultrasound images of 38 patients (17 atorvastatin groups and 21 placebo groups) at baseline and after 3 months of the treatment. With combination optimization of many features (including morphological and texture features), the evaluation results of single feature and different combined features were compared. The experimental results showed that the performance of single feature is poor and the best feature combination have good recognition ability, with the accuracy 92.81%, sensitivity 80.95%, specificity 95.52%, positive predictive value 80.47%, negative predictive value 95.65%, Matthew's correlation coefficient 76.27%, and Youden's index 76.48%. And the receiver operating characteristic (ROC) curve was also performed well with 0.9663 of the area under the ROC curve (AUC), which is better than all the features with 0.9423 of the AUC. Thus, it is proved that this novel method can reliably and accurately evaluate the effect of atorvastatin treatment.

Effect of diet intervention on long-term mortality in healthy middle-aged men with combined hyperlipidaemia.

Science.gov (United States)

Hjerkinn, E M; Sandvik, L; Hjermann, I; Arnesen, H

2004-01-01

The aim was to study the effect of a 5-year diet intervention on 24-year mortality in middle aged men with combined hyperlipidaemia. We studied 104 initially healthy men (in 1972) aged 40-49 years with baseline values of total serum cholesterol >6.45 mmol L-1 and fasting triglycerides >2.55 mmol L-1, within the randomized diet and smoking cessation trial of the Oslo study (n = 1232). The participants were randomized to a 5-year diet intervention or a control group. The diet consisted of a traditional lipid-lowering diet with emphasis on reduction of saturated fat, total caloric intake and body weight. The groups were initially well balanced with regard to traditional risk factors for mortality. Thirty-three subjects died during the 24-year observation period [17 of cardiovascular disease (CVD) and 12 of cancer]. In the diet intervention group, mortality was 51% lower (RR = 0.49, 95% CI 0.22-0.91, P = 0.022) as compared with the control group. This difference remained significant in a Cox regression analysis after adjusting for age and smoking status (RR = 0.47, 95% CI 0.23-0.96, P = 0.038). This study indicates that the investigated 5-year diet intervention significantly reduces late mortality in healthy middle-aged men with combined hyperlipidaemia.

Prevalence of alveolar bone loss in healthy children treated at private pediatric dentistry clinics.

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Guimarães, Maria do Carmo Machado; de Araújo, Valéria Martins; Avena, Márcia Raquel; Duarte, Daniel Rocha da Silva; Freitas, Francisco Valter

2010-01-01

The purpose of this study was to evaluate the prevalence of alveolar bone loss (BL) in healthy children treated at private pediatric dentistry clinics in Brasília, Brazil. The research included 7,436 sites present in 885 radiographs from 450 children. The BL prevalence was estimated by measuring the distance from the cementoenamel junction (CEJ) to alveolar bone crest (ABC). Data were divided in groups: (I) No BL: distance from CEJ to ABC is 2 and 3 mm. Data were treated by the chi-square nonparametric test and Fisher's exact test (pchildren should never be underestimated because BL occurs even in healthy populations, although in a lower frequency.

Polymorphisms in the mitochondrial ribosome recycling factor EF-G2mt/MEF2 compromise cell respiratory function and increase atorvastatin toxicity.

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Sylvie Callegari

Full Text Available Mitochondrial translation, essential for synthesis of the electron transport chain complexes in the mitochondria, is governed by nuclear encoded genes. Polymorphisms within these genes are increasingly being implicated in disease and may also trigger adverse drug reactions. Statins, a class of HMG-CoA reductase inhibitors used to treat hypercholesterolemia, are among the most widely prescribed drugs in the world. However, a significant proportion of users suffer side effects of varying severity that commonly affect skeletal muscle. The mitochondria are one of the molecular targets of statins, and these drugs have been known to uncover otherwise silent mitochondrial mutations. Based on yeast genetic studies, we identify the mitochondrial translation factor MEF2 as a mediator of atorvastatin toxicity. The human ortholog of MEF2 is the Elongation Factor Gene (EF-G 2, which has previously been shown to play a specific role in mitochondrial ribosome recycling. Using small interfering RNA (siRNA silencing of expression in human cell lines, we demonstrate that the EF-G2mt gene is required for cell growth on galactose medium, signifying an essential role for this gene in aerobic respiration. Furthermore, EF-G2mt silenced cell lines have increased susceptibility to cell death in the presence of atorvastatin. Using yeast as a model, conserved amino acid variants, which arise from non-synonymous single nucleotide polymorphisms (SNPs in the EF-G2mt gene, were generated in the yeast MEF2 gene. Although these mutations do not produce an obvious growth phenotype, three mutations reveal an atorvastatin-sensitive phenotype and further analysis uncovers a decreased respiratory capacity. These findings constitute the first reported phenotype associated with SNPs in the EF-G2mt gene and implicate the human EF-G2mt gene as a pharmacogenetic candidate gene for statin toxicity in humans.

Local Progression among Men with Conservatively Treated Localized Prostate Cancer: Results from the Transatlantic Prostate Group

Science.gov (United States)

Eastham, James A.; Kattan, Michael W.; Fearn, Paul; Fisher, Gabrielle; Berney, Daniel M.; Oliver, Tim; Foster, Christopher S.; Møller, Henrik; Reuter, Victor; Cuzick, Jack; Scardino, Peter

2009-01-01

Objectives Men with clinically detected localized prostate cancer treated without curative intent are at risk of complications from local tumor growth. We investigated rates of local progression and need for local therapy among such men. Methods Men diagnosed with prostate cancer during 1990–1996 were identified from cancer registries throughout the United Kingdom. Inclusion criteria were age ≤76 yr at diagnosis, PSA level ≤100 ng/ml, and, within 6 mo after diagnosis, no radiation therapy, radical prostatectomy, evidence of metastatic disease, or death. Local progression was defined as increase in clinical stage from T1/2 to T3/T4 disease, T3 to T4 disease, and/or need for transurethral resection of the prostate (TURP) to relieve symptoms >6 mo after cancer diagnosis. Results The study included 2333 men with median follow-up of 85 mo (range: 6–174). Diagnosis was by TURP in 1255 men (54%), needle biopsy in 1039 (45%), and unspecified in 39 (2%). Only 29% were treated with hormonal therapy within 6 mo of diagnosis. Local progression occurred in 335 men, including 212 undergoing TURP. Factors most predictive of local progression on multivariable analysis were PSA at diagnosis and Gleason score of the diagnostic tissue (detrimental), and early hormonal therapy (protective). We present a nomogram that predicts the likelihood of local progression within 120 mo after diagnosis. Conclusions Men with clinically detected localized prostate cancer managed without curative intent have an approximately 15% risk for local progression within 10 yr of diagnosis. Among those with progression, the need for treatment is common, even among men diagnosed by TURP. When counseling men who are candidates for management without curative intent, the likelihood of symptoms from local progression must be considered. PMID:17544572

Low density lipoprotein subclasses and response to a low-fat diet in healthy men

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Krauss, R.M.; Dreon, D.M. [Lawrence Berkeley Lab., CA (United States). Life Sciences Div.

1994-11-01

Lipid and lipoprotein response to reduced dietary fat intake was investigated in relation to differences in distribution of LDL subclasses among 105 healthy men consuming high-fat (46%) and low-fat (24%) diets in random order for six weeks each. On high-fat, 87 subjects had predominantly large, buoyant LDL as measured by gradient gel electrophoresis and confirmed by analytic ultracentrifugation (pattern A), while the remainder had primarily smaller, denser LDL (pattern B). On low-fat, 36 men changed from pattern A to B. Compared with the 51 men in the stable A group, men in the stable B group (n = 18) had a three-fold greater reduction in LDL cholesterol and significantly greater reductions in plasma apoB and mass of intermediate (LDL II) and small (LDL III) LDL subtractions measured by analytic ultracentrifugation. In both stable A and change groups, reductions in LDL-cholesterol were not accompanied by reduced plasma apoB, consistent with the observation of a shift in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid-depleted (LDL III and IV) subfractions, without significant change in particle number. Genetic and environmental factors influencing LDL subclass distributions thus may also contribute substantially to interindividual variation in response to a low-fat diet.

Physical Activity May Be Associated with Conditioned Pain Modulation in Women but Not Men among Healthy Individuals

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Yukiko Shiro

2017-01-01

Full Text Available Background. Conditioned pain modulation (CPM, a phenomenon also known as diffuse noxious inhibitory control, is thought to be affected by various factors, including sex and level of physical activity. However, the involvement of these factors in CPM remains unclear. Methods. Eighty-six healthy young subjects (M/F, 43/43 participated in this study. Participants were assessed on the basis of their mechanical pressure pain threshold (PPT, CPM response, body mass index (BMI, basal metabolic rate (BMR, and duration of moderate-to-vigorous physical activity (MVPA over a week, using a motion counter. Response to CPM was evaluated as PPT during painful cold stimulation relative to baseline PPT. Results. Men showed significantly higher baseline PPT than women; however, this difference was no longer significant after controlling for confounders. Stepwise multiple linear regression analyses revealed BMR to be a significant contributor towards baseline PPT in the entire study population. In contrast, although there were no significant contributors to CPM response among men and in the overall study group, MVPA was positively associated with CPM response among women (β = 0.397. Conclusions. These results suggest that, among healthy young individuals, CPM response may be associated with moderate-to-vigorous physical activity in women but not in men.

Body composition and circulating estradiol are the main bone density predictors in healthy young and middle-aged men.

Science.gov (United States)

Bilha, S C; Branisteanu, D; Buzduga, C; Constantinescu, D; Cianga, P; Anisie, E; Covic, A; Ungureanu, M C

2018-01-16

Current fracture risk assessment options in men call for improved evaluation strategies. Recent research directed towards non-classic bone mass determinants have often yielded scarce and conflicting results. We aimed at investigating the impact of novel potential bone mass regulators together with classic determinants of bone status in healthy young and middle-aged men. Anthropometric measurements, all-site bone mineral density (BMD) and body composition parameters assessed by dual-energy X-ray absorptiometry and also serum concentrations of (1) the adipokines leptin and resistin, (2) vitamin D and parathormone (PTH), (3) sex hormone binding globulin (SHBG), total testosterone and estradiol (free testosterone was also calculated) and (4) C-terminal telopeptide of type I collagen (CTx) were obtained from 30 apparently healthy male volunteers aged 20-65 years enrolled in this cross-sectional study. Only lean mass (LM) and total estradiol independently predicted BMD in men in multiple regression analysis, together explaining 49% (p ≤ 0.001) of whole-body BMD variance. Hierarchical regression analysis with whole-body BMD as outcome variable demonstrated that the body mass index (BMI) beta coefficient became nonsignificant when LM was added to the model. Adipokines, fat parameters, testosterone (total and free), SHBG, PTH and vitamin D were not independently associated with BMD or CTx. The present study shows that LM and sex hormones-namely estradiol-are the main determinants of bone mass in young and middle-aged men. The effects of BMI upon BMD seem to be largely mediated by LM. Lifestyle interventions should focus on preserving LM in men for improved bone outcomes.

Using drug sales data to evaluate the epidemiology of cardiometabolic risk factors and their inequality: an ecological study on atorvastatin and total cholesterol in Iran.

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Ahmadvand, Alireza; Farzadfar, Farshad; Jamshidi, Hamid Reza; Mohammadi, Naser; Holakouie-Naieni, Kourosh

2015-01-01

Statins have been effective medications in lowering serum total cholesterol (TC) concentrations across populations over time. The aim of this study was to estimate national and provincial trends in atorvastatin sales in Iran, to systematically quantify its relationship with socioeconomic indicators, and changes in TC level. In this retrospective ecological study, conducted in Iran, we examined trends in atorvastatin sales, the wealth index (WI) as a validly-available socio-economic indicator, and TC level between 2004 and 2011. The main outcome variable was mean atorvastatin sold in defined daily dose per 100,000 people per day (DPD). We analyzed the relationship between WI and DPD and between DPD and mean TC across time and space. At national level, both mean WI and mean DPD showed increasing trend over time, while we observed decreasing trend for TC. Mean WI and DPD in 2011 was nearly 5 and 50 time that of their respective figures in 2004, while the mean TC decreased for nearly 10%. Increases in both WI and DPD had happened in every province, but with different patterns. The maximum and minimum changes in DPD versus WI were seen in Gilan and North Khorasan respectively. A striking increase occurred in the sales for atorvastatin in Iran from 2004-2012 in most provinces examined. The wealthier a province became, the more sales were seen for atorvastatin. TC optimistically decreased from 2005 to 2011 and its decrease was positively correlated with increasing sales for atorvastatin.

Psychological gender of men with systolic heart failure: a neglected strategy to cope with the disease?

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Makowska, Agata; Rydlewska, Agnieszka; Krakowiak, Bartosz; Kuczyłska, Alicja; Sorokowski, Piotr; Danel, Dariusz; Pawłowski, Bogusław; Banasiak, Waldemar; Ponikowski, Piotr; Jankowska, Ewa A

2014-05-01

Diminished exercise capacity is a fundamental symptom of heart failure (HF), which is particularly disadvantageous for men for whom exercise capacity contributes significantly to their gender identity, self-esteem, and quality of life. In this study, we aimed to examine whether psychological gender would be different in men with systolic HF as compared with their healthy peers. The authors examined 48 men with systolic HF (age = 64 ± 10 years; body mass index = 28.3 ± 3.4 kg/m(2); NYHA I/II/III [%] = 25/65/10; left ventricular ejection fraction [LVEF] = 32.1 ± 7.8%) and 15 age-matched healthy men. Based on the results of the Polish version of the Bem Sex Role Inventory, the examined men were divided into four types of psychological gender: "masculine" (M), "feminine" (F), "unspecified" (U), and "androgynous" (A). None of the men with HF presented M type of psychological gender, whereas this type was found in 27% of the healthy men (p = .0002). The prevalence of both A (38% vs. 47%) and F (10% vs. 20%, both p > .05) types of psychological gender was similar between men with HF versus without HF. More men with HF fulfilled the criteria of the U type of psychological gender as compared with healthy peers (51% vs. 7%, p = .002). Men with HF and the F type of psychological gender were treated with spironolactone more frequently than those classified with the U and A types (both p masculine" and the overrepresentation of "psychologically unspecified" gender types in the HF group suggests that psychological gender may be affected among men with HF.

Treatment with triple combination of atorvastatin, perindopril, and amlodipine in patients with stable coronary artery disease: A subgroup analysis from the PAPA-CAD study.

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Dézsi, Csaba András

2018-01-01

Background In patients with stable coronary artery disease, aspirin, a statin, and an angiotensin-converting enzyme inhibitor are recommended as first-line agents for secondary prevention. Subgroup analyses of the previously published Hungarian Perindopril plus Amlodipine in PAtients with Coronary Artery Disease (PAPA-CAD) non-interventional trial demonstrated that the addition of the metabolically beneficial, fixed combination of perindopril + amlodipine to atorvastatin further improves the patient's lipid profile. Methods The PAPA-CAD study, a 6-month open-label, prospective, multicenter, observational/non-interventional survey evaluated data accumulated from patients with hypertensive patients with stable coronary artery disease. The herein-reported subgroup analysis was conducted using the findings from those 1130 patients, who were taking atorvastatin in addition to the fixed combination of perindopril + amlodipine at the time of all four study visits (i.e., at baseline and 1, 3, and 6 months later). Results In the subgroup of patients taking atorvastatin as an add-on agent, 82.5% reached the target blood pressure of 140/90 mmHg compared with 78.8% of those not taking a statin. The addition of atorvastatin to the fixed combination of perindopril + amlodipine resulted in further significant improvements of key metabolic parameters. Conclusion This subgroup analysis confirmed that favorable synergism exists among perindopril, amlodipine, and atorvastatin.

Cardiorespiratory Responses and Prediction of Peak Oxygen Uptake during the Shuttle Walking Test in Healthy Sedentary Adult Men

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Neves, Camila D. C.; Lacerda, Ana Cristina Rodrigues; Lage, Vanessa K. S.; Lima, Liliana P.; Fonseca, Sueli F.; de Avelar, Núbia C. P.; Teixeira, Mauro M.; Mendonça, Vanessa A.

2015-01-01

Background The application of the Shuttle Walking Test (SWT) to assess cardiorespiratory fitness and the intensity of this test in healthy participants has rarely been studied. This study aimed to assess and correlate the cardiorespiratory responses of the SWT with the cardiopulmonary exercise testing (CEPT) and to develop a regression equation for the prediction of peak oxygen uptake (VO2 peak) in healthy sedentary adult men. Methods In the first stage of this study, 12 participants underwent the SWT and the CEPT on a treadmill. In the second stage, 53 participants underwent the SWT twice. In both phases, the VO2 peak, respiratory exchange ratio (R), and heart rate (HR) were evaluated. Results Similar results in VO2 peak (P>0.05), R peak (P>0.05) and predicted maximum HR (P>0.05) were obtained between the SWT and CEPT. Both tests showed strong and significant correlations of VO2 peak (r = 0.704, P = 0.01) and R peak (r = 0.737, P0.05) was found. Conclusions The SWT produced maximal cardiorespiratory responses comparable to the CEPT, and the developed equation showed viability for the prediction of VO2 peak in healthy sedentary men. PMID:25659094

Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients

DEFF Research Database (Denmark)

Christensen, Niels Peter Aae; Rantanen, Jukka; Cornett, Claus

2012-01-01

The aim of the present study was to combine vibrational spectroscopy and chemometrics for investigating excipient-induced disproportionation of the calcium salt of atorvastatin into the corresponding free acid form in environments relevant to manufacturing and storage of solid dosage formulations...

Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation.

Science.gov (United States)

Kanate, Abraham S; Hari, Parameswaran N; Pasquini, Marcelo C; Visotcky, Alexis; Ahn, Kwang W; Boyd, Jennifer; Guru Murthy, Guru Subramanian; Rizzo, J Douglas; Saber, Wael; Drobyski, William; Michaelis, Laura; Atallah, Ehab; Carlson, Karen S; D'Souza, Anita; Fenske, Timothy S; Cumpston, Aaron; Bunner, Pamela; Craig, Michael; Horowitz, Mary M; Hamadani, Mehdi

2017-08-01

Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo-HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate. All patients were evaluable for acute GVHD. The cumulative incidences of grade II to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%), respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively. In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression-free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95% CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to 83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95% CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%), and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities attributable to atorvastatin were seen. In conclusion, the addition of atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD allo-HCT appears to be feasible and safe. The preliminary efficacy seen here warrants confirmation in

Calcium Supplements: Do Men Need Them Too?

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... Lifestyle Nutrition and healthy eating Should men take calcium supplements? Answers from Katherine Zeratsky, R.D., L. ... Most healthy men don't need to take calcium supplements. Calcium is important for men for optimal ...

Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin.

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Chunmei Qi

Full Text Available Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA modified ultra-small super paramagnetic iron oxide (USPIO was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI.Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30. Group A with atherosclerosis plaque (n = 10 were controls. VP was established in groups B (n = 10 and C (n = 10 using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured.DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05.After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.

Effects of valsartan combined with atorvastatin on cardiac function, myocardial enzymes and thyroxine levels in patients with chronic heart failure

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Xiao-Gang Wang1

2017-04-01

Full Text Available Objective: To observe the effects of valsartan combined with atorvastatin on cardiac function, myocardial enzymes and thyroxine levels in patients with chronic heart failure (CHF. Methods: 90 cases of CHF cases were divided into observation group and control group according to the order of single and double number, 45 cases each. In the control group, atorvastatin was given on the basis of conventional therapy, and the observation group was given valsartan on the basis of the control group. After 6 months, the differences of cardiac function indexes (LVEF, LVEDD, LVESD, E/A, myocardial enzymes (LDH, AST, CK, CKMB and thyroxine (TT3, TT4, FT3, FT4, TSH in the two groups were observed. Results: After treatment, LVEF and E/A in both groups increased significantly (P0.05, the observation group TT3 and FT3 were respectively (1.37±0.33 mol/L and (2.61±0.69 pmol/L , higher than the control group, the difference was statistically significant (P<0.05. Conclusion: valsartan combined with atorvastatin in the treatment of CHF, can improve cardiac function and myocardial protection effect, and can effectively promote the recovery of thyroid hormone levels, better than the single use of atorvastatin.

Atorvastatin Protects Vascular Smooth Muscle Cells From TGF-β1-Stimulated Calcification by Inducing Autophagy via Suppression of the β-Catenin Pathway

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Demin Liu

2014-01-01

Full Text Available Background: Arterial calcification is a major event in the progression of atherosclerosis. It is reported that statins exhibit various protective effects against vascular smooth muscle cell (VSMC inflammation and proliferation in cardiovascular remodeling. Although statins counteract atherosclerosis, the molecular mechanisms of statins on the calcium release from VSMCs have not been clearly elucidated. Methods: Calcium content of VSMCs was measured using enzyme-linked immunosorbent assay (ELISA. The expression of proteins involved in cellular transdifferentiation was analyzed by western blot. Cell autophagy was measured by fluorescence microscopic analysis for acridine orange staining and transmission electron microscopy analysis. The autophagic inhibitors (3-MA, chloroquine, NH4Cl and bafilomycin A1 and β-catenin inhibitor JW74 were used to assess the effects of atorvastatin on autophagy and the involvement of β-catenin on cell calcification respectively. Furthermore, cell transfection was performed to overexpress β-catenin. Results: In VSMCs, atorvastatin significantly suppressed transforming growth factor-β1 (TGF-β1-stimulated calcification, accompanied by the induction of autophagy. Downregulation of autophagy with autophagic inhibitors significantly suppressed the inhibitory effect of atorvastatin on cell calcification. Moreover, the beneficial effect of atorvastatin on calcification and autophagy was reversed by β-catenin overexpression. Conversely, JW74 supplement enhanced this effect. Conclusion: These data demonstrated that atorvastatin protect VSMC from TGF-β1-stimulated calcification by inducing autophagy through suppression of the β-catenin pathway, identifying autophagy induction might be a therapeutic strategy for use in vascular calcification.

Klotho-related Molecules Upregulated by Smoking Habit in Apparently Healthy Men: A Cross-sectional Study.

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Nakanishi, Kaori; Nishida, Makoto; Harada, Masaya; Ohama, Tohru; Kawada, Noritaka; Murakami, Masaaki; Moriyama, Toshiki; Yamauchi-Takihara, Keiko

2015-09-18

While aging is unavoidable, the aging mechanism is still unclear because of its complexity. Smoking causes premature death and is considered as an environmental aging accelerator. In the present study, we focused on the influence of smoking to the serum concentration of anti-aging protein α-klotho (αKl) and the β-klotho-associated protein fibroblast growth factor (FGF)-21 in men. Subjects consisted of apparently healthy men over 40 years of age who underwent health examination. Physical and biochemical parameters, including the levels of several cytokines and growth factors, were obtained from the subjects. Among middle-aged men (46.1 ± 5.1 years), serum levels of FGF-21, soluble αKl (sαKl), and inflammation-related cytokine interleukin (IL)-6 were significantly higher in smokers than in never-smokers. Serum levels of FGF-21 increased and correlated with alanine transaminase, γ guanosine-5'-triphosphate, and total cholesterol only in smokers, suggesting FGF-21 as a metabolic disorder-related factor in smokers. In aged men (60.3 ± 1.7 years), although the serum levels of sαKl in never-smokers were low, smokers showed highly increased serum levels of sαKl. Serum levels of sαKl was correlated with IL-6 in middle-aged never-smokers, suggesting sαKl regulates IL-6. However, this correlation was disrupted in smokers and aged men.

Men: Eat Right, Stay Healthy

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... sugars helps in overall weight management. Saturated fats. Strong scientific data shows that replacing saturated fats with ... means up to two drinks a day for men up to age 64 and one drink a ...

D-Tagatose increases butyrate production by the colonic microbiota in healthy men and women

OpenAIRE

Venema, Koen; Vermunt, Susanne H.F.; Brink, Elizabeth J.

2011-01-01

D-Tagatose is partly absorbed in the stomach and small intestine. Most of it is fermented by the large intestinal microbiota. The effect of D-tagatose on the composition of the microbiota and production of short chain fatty acids (SCFAs) was studied in vivo and in vitro. Gastrointestinal (GI) complaints were also studied. The in vivo study was performed according to a randomized, placebo-controlled, double-blind, five-way cross-over design in healthy subjects (12 men and 18 women). All subjec...

The effects of diurnal Ramadan fasting on energy expenditure and substrate oxidation in healthy men.

Science.gov (United States)

Alsubheen, Sana'a A; Ismail, Mohammad; Baker, Alicia; Blair, Jason; Adebayo, Adeboye; Kelly, Liam; Chandurkar, Vikram; Cheema, Sukhinder; Joanisse, Denis R; Basset, Fabien A

2017-12-01

The study aimed to examine the effects of diurnal Ramadan fasting (RF) on substrate oxidation, energy production, blood lipids and glucose as well as body composition. Nine healthy Muslim men (fasting (FAST) group) and eight healthy non-practicing men (control (CNT) group) were assessed pre- and post-RF. FAST were additionally assessed at days 10, 20 and 30 of RF in the morning and evening. Body composition was determined by hydrodensitometry, substrate oxidation and energy production by indirect calorimetry, blood metabolic profile by biochemical analyses and energy balance by activity tracker recordings and food log analyses. A significant group×time interaction revealed that chronic RF reduced body mass and adiposity in FAST, without changing lean mass, whereas CNT subjects remained unchanged. In parallel to these findings, a significant main diurnal effect (morning v. evening) of RF on substrate oxidation (a shift towards lipid oxidation) and blood metabolic profile (a decrease in glucose and an increase in total cholesterol and TAG levels, respectively) was observed, which did not vary over the course of the Ramadan. In conclusion, although RF induces diurnal metabolic adjustments (morning v. evening), no carryover effect was observed throughout RF despite the extended daily fasting period (18·0 (sd 0·3) h) and changes in body composition.

Cardiovascular Comorbidity and Mortality in Men With Prostate Cancer Treated With Brachytherapy-Based Radiation With or Without Hormonal Therapy

Energy Technology Data Exchange (ETDEWEB)

Nanda, Akash, E-mail: akash.nanda@orlandohealth.com [Department of Radiation Oncology, MD Anderson Cancer Center Orlando, Orlando, Florida (United States); Chen, Ming-Hui [Department of Statistics, University of Connecticut, Storrs, Connecticut (United States); Moran, Brian J.; Braccioforte, Michelle H. [Prostate Cancer Foundation of Chicago, Westmont, Illinois (United States); D' Amico, Anthony V. [Department of Radiation Oncology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

2013-04-01

Purpose: To assess the impact of coronary artery disease (CAD) risk factors and sequelae on the risk of all-cause mortality (ACM) in men treated for prostate cancer (PC). Methods and Materials: The study cohort comprised 5077 men with PC consecutively treated with curative intent between 1997 and 2006 at the Chicago Prostate Cancer Center. Cox and Fine and Gray's competing risks regression multivariable analyses were performed, assessing whether cardiovascular comorbidity impacted the risk of ACM and PC-specific mortality, respectively, adjusting for CAD risk factors (diabetes mellitus, hypercholesterolemia, or hypertension) and sequelae (congestive heart failure or myocardial infarction), age, year and type of treatment, and known PC prognostic factors. Results: When compared with men with no comorbidity there was a significantly increased risk of ACM in men with congestive heart failure or myocardial infarction (adjusted hazard ratio [AHR] 1.96, P<.001) and in men with diabetes mellitus (AHR 1.60, P=.03) and hypertension (AHR 1.25, P=.04). In contrast, men with hypercholesterolemia had a similar risk of ACM (AHR 0.68, P=.17) when compared with men with no comorbidity. Other factors associated with a significantly increased risk of ACM included age (AHR 1.09, P<.001), prostate-specific antigen level (AHR 1.25, P=.008), and Gleason score 8-10 disease (AHR 1.71, P=.003). Cardiovascular comorbidity did not impact the risk of PC-specific mortality. Conclusions: In addition to age and unfavorable PC prognostic factors, select CAD risk factors and sequelae are associated with an increased risk of ACM in men treated for PC. These comorbidity prognostic factors predict time courses of mortality from competing causes, which may be factored into the decision-making process when considering management options for PC in a given individual.

Cardiovascular Comorbidity and Mortality in Men With Prostate Cancer Treated With Brachytherapy-Based Radiation With or Without Hormonal Therapy

International Nuclear Information System (INIS)

Nanda, Akash; Chen, Ming-Hui; Moran, Brian J.; Braccioforte, Michelle H.; D'Amico, Anthony V.

2013-01-01

Purpose: To assess the impact of coronary artery disease (CAD) risk factors and sequelae on the risk of all-cause mortality (ACM) in men treated for prostate cancer (PC). Methods and Materials: The study cohort comprised 5077 men with PC consecutively treated with curative intent between 1997 and 2006 at the Chicago Prostate Cancer Center. Cox and Fine and Gray's competing risks regression multivariable analyses were performed, assessing whether cardiovascular comorbidity impacted the risk of ACM and PC-specific mortality, respectively, adjusting for CAD risk factors (diabetes mellitus, hypercholesterolemia, or hypertension) and sequelae (congestive heart failure or myocardial infarction), age, year and type of treatment, and known PC prognostic factors. Results: When compared with men with no comorbidity there was a significantly increased risk of ACM in men with congestive heart failure or myocardial infarction (adjusted hazard ratio [AHR] 1.96, P<.001) and in men with diabetes mellitus (AHR 1.60, P=.03) and hypertension (AHR 1.25, P=.04). In contrast, men with hypercholesterolemia had a similar risk of ACM (AHR 0.68, P=.17) when compared with men with no comorbidity. Other factors associated with a significantly increased risk of ACM included age (AHR 1.09, P<.001), prostate-specific antigen level (AHR 1.25, P=.008), and Gleason score 8-10 disease (AHR 1.71, P=.003). Cardiovascular comorbidity did not impact the risk of PC-specific mortality. Conclusions: In addition to age and unfavorable PC prognostic factors, select CAD risk factors and sequelae are associated with an increased risk of ACM in men treated for PC. These comorbidity prognostic factors predict time courses of mortality from competing causes, which may be factored into the decision-making process when considering management options for PC in a given individual

Using focus groups to identify factors affecting healthy weight maintenance in college men.

Science.gov (United States)

Walsh, Jennifer R; White, Adrienne A; Greaney, Mary L

2009-06-01

Healthful eating and physical activity are important for healthy weight maintenance. The hypothesis for this study was that college-aged men would perceive factors affecting eating and physical activity as both contributing to and inhibiting healthy weight maintenance. The overall objective was to explore how men view weight maintenance in the context of these aspects. Subjects (n = 47, mean age = 20.3 +/- 1.7 years) completed an online survey, including the 51-item Three-Factor Eating Questionnaire, and participated in 1 of 6 focus groups. Three face-to-face and 3 online synchronous groups were conducted using a 15-question discussion guide to identify weight maintenance issues around eating, physical activity, and body perceptions. Weight satisfaction decreased with increase in both dietary restraint and disinhibition. Number of attempts to lose weight was positively associated with BMI (r [44] = .465, P = .01) and dietary restraint (r [44] = .515, P = .01). Findings from both focus group formats were similar. Motivators (sports performance/fitness, self-esteem, attractiveness, long-term health) were similar for eating healthfully and being physically active; however, more motivators to be physically active than to eat healthfully emerged. Enablers for eating healthfully included liking the taste, availability of healthful foods, using food rules to guide intake, having a habit of healthful eating, and internal drive/will. Barriers to healthful eating included fat in dairy foods, fruit and vegetable taste, and quick spoilage. Barriers to being physically active included lack of time/time management, obligations, being lazy, and girlfriends. Results may be used to inform future obesity prevention interventions.

Evaluation of efficacy of atorvastatin in prevention of cardiovascular risks in stable chronic obstructive pulmonary disease patients

International Nuclear Information System (INIS)

Rizvi, F.; Alam, R.; Khan, M.; Rizvi, N.

2012-01-01

Objective: To demonstrate the dual cardiopulmonary protective effects of Atorvastatin in COPD patients, which may become the mainstay of therapy in prevention of exacerbation of COPD and cardiovascular events in COPD patients. Study Design: Quasi experimental study. Place and Duration of Study: This study was conducted over a period of 6 months (December 2010 to May 2011) with an individual study period of 3 months (90 days), conducted in the Department of Pharmacology and Therapeutics in collaboration with Chest medicine JPMC Karachi. Subjects and Methods: Thirty five moderate stable COPD with post bronchodilator FEV 3mg/l, were evaluated in a quasi experimental trial. The patients were assigned to give tablet Atorvastatin 20 mg once daily for 12 consecutive weeks. The primary study outcome was to evaluate the reduction in cardiovascular risk by evaluating the improvement in FEV1 and reduction in hsCRP levels. Efficacy was evaluated at days 30, 60 and day 90. Results: Out of 35 patients only 33 (94%) patients completed the study. At baseline hsCRP level was 6.45+-0.30 which decreased to 4.6+-0.19 (p<0.05) at day 90. FEV1 at baseline was 2.16+-0.07 and at day 90 FEV1 increased upto 2.48+-0.06 (p<0.01). This shows that, the Atorvastatin can lead to statistically significant decrease in the hsCRP levels and increase the forced expiratory volume in one second. Conclusion: This study demonstrated that Atorvastatin effectively decreases the cardiovascular risk by decreasing the systemic inflammation which was indicated by decreasing the hsCRP levels and it can also improve the pulmonary functional capacity in COPD patients. (author)

Does a healthy lifestyle behaviour influence the prognosis of low back pain among men and women in a general population? A population-based cohort study.

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Bohman, Tony; Alfredsson, Lars; Jensen, Irene; Hallqvist, Johan; Vingård, Eva; Skillgate, Eva

2014-12-30

To study the influence of healthy lifestyle behaviour on the prognosis of occasional low back pain among men and women in a general population. Cohort study with a 4-year follow-up. General population in Stockholm County, Sweden. The study sample comprised 3938 men and 5056 women aged 18-84 from the Stockholm Public Health Cohort reporting occasional low back pain in the baseline questionnaire 2006. Lifestyle factors and potential confounders were assessed at baseline. The lifestyle factors smoking habits, alcohol consumption, leisure physical activity and consumption of fruit and vegetables were dichotomised using recommendations for a health-enhancing lifestyle and combined to form the exposure variable 'healthy lifestyle behaviour'. The exposure was categorised into five levels according to the number of healthy lifestyle factors met. The follow-up questionnaire in 2010 gave information about the outcome, long duration troublesome low back pain. Crude and adjusted binomial regression models were applied to estimate the association between the exposure and the outcome analysing men and women separately. The risk of developing long duration troublesome low back pain among women with occasional low back pain decreased with increasing healthy lifestyle behaviour (trend test: p=0.006). 21% (28/131) among women with no healthy lifestyle factor (reference) experienced the outcome compared to 9% (36/420) among women with all four factors. Compared to the reference group, the risk was reduced by 35% (RR 0.65, 95% CI 0.44 to 0.96) for women with one healthy lifestyle factor and 52% (RR 0.48, 95% CI 0.31 to 0.77) for women with all four healthy lifestyle factors. There were no clear associations found among men. Healthy lifestyle behaviour seems to decrease the risk of developing long duration troublesome low back pain among women with occasional low back pain and may be recommended to improve the prognosis. Published by the BMJ Publishing Group Limited. For permission to

Healthy lifestyle status, antihypertensive treatment and the risk of heart failure among Finnish men and women.

Science.gov (United States)

Wang, Yujie; Tuomilehto, Jaakko; Jousilahti, Pekka; Antikainen, Riitta; Mähönen, Markku; Katzmarzyk, Peter T; Hu, Gang

2013-11-01

To compare the association between antihypertensive drug treatment and heart failure (HF) risk with the association between engaging in a healthy lifestyle and HF risk. We prospectively investigated the single and joint associations of lifestyle factors and awareness, treatment, blood pressure control status with HF risk among 38 075 Finns, who were 25-74 years old and free of HF at baseline. During a median follow-up of 14.1 years, 638 men and 445 women developed HF. Engaging in a healthy lifestyle was associated with an decreased risk of HF. Compared with normotensive people, hypertensive patients with and without antihypertensive treatment had a higher risk of HF. Hypertensive patients who used antihypertensive drugs but did not engage in a healthy lifestyle had a significantly higher risk of HF [HR 1.75; 95% confidence interval (CI) 1.39-2.21] than hypertensive patients who did not use antihypertensive drugs but engaged in a healthy lifestyle. In addition, compared with hypertensive patients who used antihypertensive drugs and engaged in a healthy lifestyle, hypertensive patients who did not use antihypertensive drug or engage in a healthy lifestyle had a significantly higher risk of HF (HR 1.55; 95% CI 1.24-1.95). The present study demonstrates that HF risk was lower in hypertensive patients who engaged in a healthy lifestyle but higher in hypertensive people using antihypertensive drug treatment.

Atorvastatin effect on values of endotheli-al condition and acute inflammation in patients on program hemodialysis

Directory of Open Access Journals (Sweden)

Barsuk A.L

2013-03-01

Full Text Available Objective: To study the effect of atorvastatin on the values of endothelial condition and acute inflammation in patients on program hemodialysis (PHD. Material and methods: The patients were divided into two groups: 28 PHD patients (main group received atorvastatin, 20 mg once a day for 30 days, and 26 patients (control group had PHD only. Endothelin 1-21 (ET level and von Willebrand factor (vWF activity were determined by enzyme immunoassay, nitric oxide (NO levels — spectrophotometrically, C-reactive protein (CRP — by immunoturbidimetric method, fibrinogen — by Clauss method. Results: After 30 days of observation, control patients were found to have NO and ET increase, as well as the reduced activity of vWF relative to initial data, while fibrinogen and CRP levels scarcely changed. The main group patients had similar changes of endothelial condition values, and their fibrinogen and CRP levels decreased. The correlation between the changes of ET and fibrinogen levels was recorded in the patients of the main group. Conclusion: 30-day administration of atorvastatin, 20 mg per day, lowers CRP and fibrinogen levels in PHD patients. It proves the applicability of statins in this group of patients in case of signs of inflammation.

Atorvastatin in stroke: a review of SPARCL and subgroup analysis

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Branko N Huisa

2010-03-01

Full Text Available Branko N Huisa, Andrew B Stemer, Justin A ZivinDepartment of Neuroscience University of California, San Diego, CA, USAAbstract: Statin therapy in patients with cardiovascular disease is associated with reduced incidence of stroke. The Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL trial showed daily treatment with 80 mg of atorvastatin in patients with a recent stroke or transient ischemic attack (TIA reduced the incidence of fatal or nonfatal stroke by 16%. Several post hoc analyses of different subgroups followed the SPARCL study. They have not revealed any significant differences when patients were sorted by age, sex, presence of carotid disease or type of stroke, with the exception of intracranial hemorrhage as the entry event. Lower low-density lipoprotein cholesterol levels in addition to possible neuroprotective mechanisms due to atorvastatin treatment correlate with improved risk reduction. Although not predefined subgroups and subject to an insufficient power, these post hoc studies have generated new clinical questions. However, clinicians should avoid denying therapy based on such subgroup analysis. At this point, the best evidence powerfully demonstrates stroke and TIA patients should be prescribed high dose statin therapy for secondary stroke prevention.Keywords: statins, intracranial hemorrhage, neuroprotection, outcome, prevention, carotid stenosis, transient ischemic attack

Atorvastatin-Diltiazem Combination Induced Rhabdomyolysis Leading to Diagnosis of Hypothyroidism

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N. D. B. Ehelepola

2017-01-01

Full Text Available Statins and hypothyroidism, independently, can rarely cause rhabdomyolysis. The combination of them especially with concurrent intake of drugs such as diltiazem increases the risk of rhabdomyolysis. Hashimoto’s encephalopathy is a rare condition associated with Hashimoto’s thyroiditis and some patients with that can present with a stroke like picture. An elderly male who has been on atorvastatin for three years and on diltiazem for a week presented with sudden onset inability to walk and confusion. On examination muscle tenderness was noticed and creatine kinase levels indicated rhabdomyolysis which we attributed to atorvastatin. Patient developed a seizure and myoclonus of masseters. Considering this, his confusion and his neutrophilia and high C-reactive protein levels, empirical antibiotics with dexamethasone were started and the patient responded to that. His cerebrospinal fluid and blood culture reports that arrived later did not show sepsis. After going home also his CK (creatine kinase levels remained high; TSH (thyroid-stimulating hormone level test was done and hypothyroidism was diagnosed. His antithyroid peroxidase antibody levels were also very high. We retrospectively think he had Hashimoto’s encephalopathy as well. His lipid profile and TSH and CK values returned to normal in that order after a few months of levothyroxine therapy.

Metabolic Footprinting of Fermented Milk Consumption in Serum of Healthy Men

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Pimentel, Grégory; Burton, Kathryn J; von Ah, Ueli; Bütikofer, Ueli; Pralong, François P; Vionnet, Nathalie; Portmann, Reto; Vergères, Guy

2018-01-01

Abstract Background Fermentation is a widely used method of natural food preservation that has consequences on the nutritional value of the transformed food. Fermented dairy products are increasingly investigated in view of their ability to exert health benefits beyond their nutritional qualities. Objective To explore the mechanisms underpinning the health benefits of fermented dairy intake, the present study followed the effects of milk fermentation, from changes in the product metabolome to consequences on the human serum metabolome after its ingestion. Methods A randomized crossover study design was conducted in 14 healthy men [mean age: 24.6 y; mean body mass index (in kg/m2): 21.8]. At the beginning of each test phase, serum samples were taken 6 h postprandially after the ingestion of 800 g of a nonfermented milk or a probiotic yogurt. During the 2-wk test phases, subjects consumed 400 g of the assigned test product daily (200 g, 2 times/d). Serum samples were taken from fasting participants at the end of each test phase. The serum metabolome was assessed through the use of LC-MS–based untargeted metabolomics. Results Postprandial serum metabolomes after milk or yogurt intake could be differentiated [orthogonal projections to latent structures discriminant analysis (OPLS-DA) Q2 = 0.74]. Yogurt intake was characterized by higher concentrations of 7 free amino acids (including proline, P = 0.03), reduced concentrations of 5 bile acids (including glycocholic acid, P = 0.04), and modulation of 4 indole derivative compounds (including indole lactic acid, P = 0.01). Fasting serum samples after 2 wk of daily intake of milk or yogurt could also be differentiated based on their metabolic profiles (OPLS-DA Q2 = 0.56) and were discussed in light of the postprandial results. Conclusion Metabolic pathways related to amino acids, indole derivatives, and bile acids were modulated in healthy men by the intake of yogurt. Further investigation to explore novel

Endurance exercise per se reduces the cardiovascular risk marker t-PA antigen in healthy, younger, overweight men

DEFF Research Database (Denmark)

Bladbjerg, Else Marie; Skov, Jane; Nordby, Pernille

2017-01-01

This was tested in 60 healthy, younger (20–40 years), overweight (BMI: 25–30 kg/m2) men randomly assigned to 12 weeks of intervention in one of four groups: training (T); energy-reduced diet (D); training and increased diet (T-iD); sedentary lifestyle and unchanged diet (controls, C). Fasting blood samples were...

Paraoxonase (PON1 and PON3 polymorphisms: impact on liver expression and atorvastatin-lactone hydrolysis

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Stephan eRiedmaier

2011-07-01

Full Text Available Atorvastatin δ-lactone, a major, pharmacologically inactive metabolite, has been associated with toxicity. In a previous study we showed that polymorphisms of UGT1A3 influence atorvastatin δ-lactone formation. Here we investigated the reverse reaction, atorvastatin δ-lactone hydrolysis, in a human liver bank. Screening of microarray data revealed paraoxonases PON1 and PON3 among 17 candidate esterases. Microsomal δ-lactone hydrolysis was significantly correlated to PON1 and PON3 protein (rs=0.60; rs=0.62, respectively; P<0.0001. PON1 and PON3 were strongly correlated to each other (rs=0.60 but PON1 was shown to be more extensively glycosylated than PON3. In addition a novel splice variant of PON3 was identified. Genotyping of 40 polymorphisms within the PON-locus identified PON1 promoter polymorphisms (-108T>C, -832G>A, -1741G>A and a tightly linked group of PON3 polymorphisms (-4984A>G, -4105G>A, -1091A>G, -746C>T and F21F to be associated with changes in atorvastatin δ-lactone hydrolysis and expression of PON1 but not PON3. However, carriers of the common PON1 polymorphisms L55M or Q192R showed no difference in δ-lactone hydrolysis or PON expression. Haplotype analysis revealed decreased δ-lactone hydrolysis in carriers of the most common haplotype *1 compared to carriers of haplotypes *2, *3, *4 and *7. Analysis of non-genetic factors showed association of hepatocellular and cholangiocellular carcinoma with decreased PON1 and PON3 expression, respectively. Increased C-reactive protein and γ-glutamyl transferase levels were associated with decreased protein expression of both enzymes, and increased bilirubin levels, cholestasis and pre-surgical exposure to omeprazole or pantoprazole were related to decreased PON3 protein. In conclusion, PON-locus polymorphisms affect PON1 expression whereas non-genetic factors have an effect on PON1 and PON3 expression. This may influence response to therapy or adverse events in statin treatment.

Dyadic Aspects of Sexual Well-Being in Men with Laser-Treated Penile Carcinoma

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Elisabet Skeppner, PhD

2015-06-01

Conclusion: A high level of within-couple agreement concerning sexuality and life satisfaction points to the necessity of including an adequate sexological case history, counseling, and treatment for this group of patients and their partners. Skeppner E and Fugl-Meyer K. Dyadic aspects of sexual well-being in men with laser-treated penile carcinoma. Sex Med 2015;3:67–75.

Cortisol reduces recall of explicit contextual pain memory in healthy young men.

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Schwegler, Kyrill; Ettlin, Dominik; Buser, Iris; Klaghofer, Richard; Goetzmann, Lutz; Buddeberg, Claus; Alon, Eli; Brügger, Mike; de Quervain, Dominique J-F

2010-09-01

Remembering painful incidents has important adaptive value but may also contribute to clinical symptoms of posttraumatic stress disorder and chronic pain states. Because glucocorticoids are known to impair memory retrieval processes, we investigated whether cortisol affects recall of previously experienced pain in healthy young men. In a double-blind, placebo-controlled crossover study, 20 male participants were presented pictures, half of them combined with a heat-pain stimulus. The next day, the same pictures were shown in the absence of pain. Cortisol (20 mg) administered 1h before retention testing reduced recall of explicit contextual pain memory, whereas it did not affect pain threshold or pain tolerance. Copyright 2010 Elsevier Ltd. All rights reserved.

Nutrition for Young Men

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... Healthy Aging Nutrition for Young Men Print Email Nutrition for Young Men Reviewed by Taylor Wolfram, MS, ... 2017 XiXinXing/iStock/Thinkstock For many young men, nutrition isn't always a focus. There are many ...

Promoting fit bodies, healthy eating and physical activity among Indigenous Australian men: a study protocol

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Ricciardelli Lina A

2012-01-01

Full Text Available Abstract Background Overall the physical health of Indigenous men is among the worst in Australia. Research has indicated that modifiable lifestyle factors, such as poor nutrition and physical inactivity, appear to contribute strongly to these poor health conditions. To effectively develop and implement strategies to improve the health of Australia's Indigenous peoples, a greater understanding is needed of how Indigenous men perceive health, and how they view and care for their bodies. Further, a more systematic understanding of how sociocultural factors affect their health attitudes and behaviours is needed. This article presents the study protocol of a community-based investigation into the factors surrounding the health and body image of Indigenous Australian men. Methods and design The study will be conducted in a collaborative manner with Indigenous Australian men using a participatory action research framework. Men will be recruited from three locations around Australia (metropolitan, regional, and rural and interviewed to understand their experiences and perspectives on a number of issues related to health and health behaviour. The information that is collected will be analysed using modified grounded theory and thematic analysis. The results will then be used to develop and implement community events in each location to provide feedback on the findings to the community, promote health enhancing strategies, and determine future action and collaboration. Discussion This study will explore both risk and protective factors that affect the health of Indigenous Australian men. This knowledge will be disseminated to the wider Indigenous community and can be used to inform future health promotion strategies. The expected outcome of this study is therefore an increased understanding of health and health change in Indigenous Australian men, the development of strategies that promote healthy eating and positive patterns of physical activity and, in

Effect of High-Dose Atorvastatin on Renal Function in Subjects With Stroke or Transient Ischemic Attack in the SPARCL Trial

DEFF Research Database (Denmark)

Amarenco, Pierre; Callahan, Alfred, III; Campese, Vito M.

2014-01-01

/L (100-190 mg/dL). METHODS: We explored the effect of randomization to atorvastatin 80 mg/d or placebo on the change in estimated glomerular filtration rate (eGFR; using the 4-component Modification of Diet in Renal Disease Study equation) in SPARCL subjects (n=4731) with (eGFR, ...=3119) and without (eGFR, ≥60 mL/min per 1.73 m2; n=1600) chronic kidney disease overall and by glycemic status at baseline. RESULTS: Mean baseline eGFR was similar between treatment groups (65.5±0.26 versus 65.6±0.26 mL/min per 1.73 m2 atorvastatin versus placebo; 33% versus 34% had chronic kidney...... disease, respectively; P=0.55). After 60 months, eGFR increased 3.46±0.33 mL/min per 1.73 m2 in those randomized to atorvastatin versus 1.42±0.34 mL/min per 1.73 m2 in those randomized to placebo (P

Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care.

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Muñoz, Monica A; Liu, Wei; Delaney, Joseph A C; Brown, Elizabeth; Mugavero, Michael J; Mathews, W Chris; Napravnik, Sonia; Willig, James H; Eron, Joseph J; Hunt, Peter W; Kahn, James O; Saag, Michael S; Kitahata, Mari M; Crane, Heidi M

2013-11-01

The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care. Retrospective observational cohort study. The primary endpoint was absolute change in TG levels measured using the last TG value pretreatment and the first TG value posttreatment. A pre-post quasi-experimental design was used to estimate the change in TG because of initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4⁺ cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures. A total of 493 patients (mean age, 46 years; 95% male) were included (46 patients receiving gemfibrozil; 80, fenofibrate; 291, atorvastatin; and 76, fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG [ΔTG, -45 mg/dL; 95% confidence interval (CI): -80 to -11] in the pre-post study. Compared with fish oil (reference), fibrates were more effective (ΔTG, -66; 95% CI: -120 to -12) in reducing TG levels, whereas atorvastatin was not (ΔTG, -39; 95% CI: -86 to 9). In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering TG values. Fish oil may still represent an attractive alternative for patients with moderately elevated TGs, particularly among patients who may not want or tolerate fibrates.

Diurnal variation of vascular diameter and reactivity in healthy young men

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P.F.D. Bau

2008-06-01

Full Text Available The higher incidence of cardiovascular events in the morning is accompanied by an increased vascular tone. However, there are few published studies designed to evaluate the diurnal variation of vascular and endothelial parameters in healthy subjects. In the present investigation, we evaluated the diurnal variation in brachial artery diameter (BAD, flow-mediated dilation (FMD and endothelium-independent dilation (NFMD in a homogeneous sample of healthy non-smoker young men. Fifty subjects aged 20.8 ± 0.3 years (range: 18 to 25 years were investigated by brachial artery ultrasound. Exclusion criteria were female gender and evidence of clinically significant health problems, including obesity. Volunteers were asked to rest and avoid fat meals as well as alcoholic beverages 48 h before and until completion of the evaluations. BAD, FMD and NFMD were measured at 7 am, 5 pm, and 10 pm and tested by repeated measures ANOVA. BAD was smaller at 7 am (mean ± SEM, 3.8 ± 0.1 mm in comparison with 5 pm (3.9 ± 0.1 and 10 pm (4.0 ± 0.1 mm; P < 0.001. FMD values did not change significantly during the day, while NFMD increased more at 7 am (18.5 ± 1.1%, when compared to 15.5 ± 0.9% at 10 pm and 15.5 ± 0.9% at 5 pm (P = 0.04. The physiological state of vasoconstriction after awakening, with preserved capability to dilate in the morning, should be considered to be part of the healthy cardiovascular adaptation before considering later life risk factors and endothelial dysfunction.

Endurance training of moderate intensity increases testosterone concentration in young, healthy men.

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Grandys, M; Majerczak, J; Duda, K; Zapart-Bukowska, J; Kulpa, J; Zoladz, J A

2009-07-01

The aim of this study was to investigate the effect of short-term, moderate intensity and low volume endurance training on gonadal hormone profile in untrained men. Fifteen young, healthy men performed an endurance training of 5-week duration on a cycle ergometer. Before and after the exercise program all participants completed a maximal incremental test. Concentration of testosterone (T), sex hormone-binding globulin (SHBG) and cortisol (C) as well as blood morphology were determined in venous blood samples at rest both before and after the training. The training program resulted in 3.7% improvement of maximal oxygen uptake (VO(2max)) and 8.2% improvement of power output reached at VO(2max) (PO (max)). This was accompanied by significant increase in T (from 18.84+/-5.73 nmol.l(-1) to 22.03+/-6.61 nmol.l(-1), p = 0.0004) and calculated fT concentration (from 374+/-116 pmol.l(-1) to 470+/-153 pmol.l(-1), p = 0.00005). Moreover, the training caused a significant decrease in SHBG concentration (from 34.45+/-11.26 nmol.l(-1) to 31.95+/-10.40 nmol.l(-1), p = 0.01), whereas no significant changes were found in the cortisol concentration (334+/-138 nmol.l(-1) vs. 367+/-135 nmol.l(-1) for pre- and post-training measures, respectively, p = 0.50) and T/C and fT/C ratios. We have concluded that short-term, moderate intensity and low volume endurance training can significantly increase testosterone concentration in previously untrained men.

Evaluation of efficacy of atorvastatin in prevention of cardiovascular risks in stable chronic obstructive pulmonary disease patients

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Rizvi, F.; Alam, R.; Khan, M. [Jinnah Postgraduate Medical Centre, Karachi (Pakistan); Rizvi, N. [Karachi Univ. (Pakistan)

2012-12-15

Objective: To demonstrate the dual cardiopulmonary protective effects of Atorvastatin in COPD patients, which may become the mainstay of therapy in prevention of exacerbation of COPD and cardiovascular events in COPD patients. Study Design: Quasi experimental study. Place and Duration of Study: This study was conducted over a period of 6 months (December 2010 to May 2011) with an individual study period of 3 months (90 days), conducted in the Department of Pharmacology and Therapeutics in collaboration with Chest medicine JPMC Karachi. Subjects and Methods: Thirty five moderate stable COPD with post bronchodilator FEV <80% and post bronchodilator FEV1/FVC <70%, with hsCRP level >3mg/l, were evaluated in a quasi experimental trial. The patients were assigned to give tablet Atorvastatin 20 mg once daily for 12 consecutive weeks. The primary study outcome was to evaluate the reduction in cardiovascular risk by evaluating the improvement in FEV1 and reduction in hsCRP levels. Efficacy was evaluated at days 30, 60 and day 90. Results: Out of 35 patients only 33 (94%) patients completed the study. At baseline hsCRP level was 6.45+-0.30 which decreased to 4.6+-0.19 (p<0.05) at day 90. FEV1 at baseline was 2.16+-0.07 and at day 90 FEV1 increased upto 2.48+-0.06 (p<0.01). This shows that, the Atorvastatin can lead to statistically significant decrease in the hsCRP levels and increase the forced expiratory volume in one second. Conclusion: This study demonstrated that Atorvastatin effectively decreases the cardiovascular risk by decreasing the systemic inflammation which was indicated by decreasing the hsCRP levels and it can also improve the pulmonary functional capacity in COPD patients. (author)

Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice

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Hoving, Saske [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Heeneman, Sylvia [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Gijbels, Marion J.J. [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (Netherlands); Poele, Johannes A.M. te [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Pol, Jeffrey F.C.; Gabriels, Karen [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Russell, Nicola S [Division of Radiotherapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Daemen, Mat J.A.P. [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Department of Pathology, AMC, Amsterdam (Netherlands); Stewart, Fiona A., E-mail: f.stewart@nki.nl [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands)

2011-10-15

Background and purpose: We previously showed that irradiating the carotid arteries of ApoE{sup -/-} mice accelerated the development of macrophage-rich, inflammatory and thrombotic atherosclerotic lesions. In this study we investigated the potential of anti-inflammatory (atorvastatin, CD40L knockout) and anti-thrombotic (clopidogrel) intervention strategies to inhibit radiation-induced atherosclerosis. Material and methods: ApoE{sup -/-} mice were given 0 or 14 Gy to the neck and the carotid arteries were harvested at 4 or 28 weeks after irradiation. Atorvastatin (15 mg/kg/day) or clopidogrel (20 mg/kg/day) was given in the chow; control groups received regular chow. Clopidogrel inhibited platelet aggregation by 50%. CD40L{sup -/-}/ApoE{sup -/-} and ApoE{sup -/-} littermates were also given 0 or 14 Gy to the neck and the carotid arteries were harvested after 30 weeks. Results: Clopidogrel decreased MCP-1 expression in the carotid artery at 4 weeks after irradiation. Expression of VCAM-1, ICAM-1, thrombomodulin, tissue factor and eNOS was unchanged in atorvastatin and clopidogrel-treated mice. Neither drug inhibited either age-related or radiation-induced atherosclerosis. Furthermore, loss of the inflammatory mediator CD40L did not influence the development of age-related and radiation-induced atherosclerosis. Conclusions: The effects of radiation-induced atherosclerosis could not be circumvented by these specific anti-inflammatory and anti-coagulant therapies. This suggests that more effective drug combinations may be required to overcome the radiation stimulus, or that other underlying mechanistic pathways are involved compared to age-related atherosclerosis.

Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice

International Nuclear Information System (INIS)

Hoving, Saske; Heeneman, Sylvia; Gijbels, Marion J.J.; Poele, Johannes A.M. te; Pol, Jeffrey F.C.; Gabriels, Karen; Russell, Nicola S.; Daemen, Mat J.A.P.; Stewart, Fiona A.

2011-01-01

Background and purpose: We previously showed that irradiating the carotid arteries of ApoE −/− mice accelerated the development of macrophage-rich, inflammatory and thrombotic atherosclerotic lesions. In this study we investigated the potential of anti-inflammatory (atorvastatin, CD40L knockout) and anti-thrombotic (clopidogrel) intervention strategies to inhibit radiation-induced atherosclerosis. Material and methods: ApoE −/− mice were given 0 or 14 Gy to the neck and the carotid arteries were harvested at 4 or 28 weeks after irradiation. Atorvastatin (15 mg/kg/day) or clopidogrel (20 mg/kg/day) was given in the chow; control groups received regular chow. Clopidogrel inhibited platelet aggregation by 50%. CD40L −/− /ApoE −/− and ApoE −/− littermates were also given 0 or 14 Gy to the neck and the carotid arteries were harvested after 30 weeks. Results: Clopidogrel decreased MCP-1 expression in the carotid artery at 4 weeks after irradiation. Expression of VCAM-1, ICAM-1, thrombomodulin, tissue factor and eNOS was unchanged in atorvastatin and clopidogrel-treated mice. Neither drug inhibited either age-related or radiation-induced atherosclerosis. Furthermore, loss of the inflammatory mediator CD40L did not influence the development of age-related and radiation-induced atherosclerosis. Conclusions: The effects of radiation-induced atherosclerosis could not be circumvented by these specific anti-inflammatory and anti-coagulant therapies. This suggests that more effective drug combinations may be required to overcome the radiation stimulus, or that other underlying mechanistic pathways are involved compared to age-related atherosclerosis.

Combined Treatment with Amlodipine and Atorvastatin Calcium Reduces Circulating Levels of Intercellular Adhesion Molecule-1 and Tumor Necrosis Factor-α in Hypertensive Patients with Prediabetes.

Science.gov (United States)

Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

2016-01-01

To assess the effect of amlodipine and atorvastatin on intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α expression, as endothelial function and inflammation indicators, respectively, in hypertensive patients with and without prediabetes. Forty-five consecutive patients with hypertension, diagnosed according to JNC7, were divided into two groups based on the presence (HD group, n = 23) or absence (H group, n = 22) of prediabetes, diagnosed according to 2010 ADA criteria, including impaired glucose tolerance (IGT) and fasting glucose tests. All patients simultaneously underwent 12-week treatment with daily single-pill amlodipine besylate/atorvastatin calcium combination (5/10 mg; Hisun-Pfizer Pharmaceuticals Co. Ltd). Serum isolated before and after treatment from overnight fasting blood samples was analyzed by ELISA. In the HD and H groups after vs. before 12-week amlodipine/atorvastatin treatment, there were significantly (all P atorvastatin improved endothelial function and inflammation, as reflected by lower circulating levels of ICAM-1 and TNF-α, more prominently in hypertensives with than without prediabetes. Starting statin treatment before overt diabetes in hypertensives might thus improve cardiovascular outcomes.

Exercise-induced prostacyclin release positively correlates with VO(2max) in young healthy men.

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Zoladz, J A; Majerczak, J; Duda, K; Chłopicki, S

2009-01-01

In this study we have evaluated the effect of maximal incremental cycling exercise (IE) on the systemic release of prostacyclin (PGI(2)), assessed as plasma 6-keto-PGF(1alpha) concentration in young healthy men. Eleven physically active - untrained men (mean +/- S.D.) aged 22.7 +/- 2.1 years; body mass 76.3 +/- 9.1 kg; BMI 23.30 +/- 2.18 kg . m(-2); maximal oxygen uptake (VO(2max)) 46.5 +/- 3.9 ml . kg(-1) . min(-1), performed an IE test until exhaustion. Plasma concentrations of 6-keto-PGF(1alpha), lactate, and cytokines were measured in venous blood samples taken prior to the exercise and at the exhaustion. The net exercise-induced increase in 6-keto-PGF(1alpha) concentration, expressed as the difference between the end-exercise minus pre-exercise concentration positively correlated with VO(2max) (r=0.78, p=0.004) as well as with the net VO(2) increase at exhaustion (r=0.81, p=0.003), but not with other respiratory, cardiac, metabolic or inflammatory parameters of the exercise (minute ventilation, heart rate, plasma lactate, IL-6 or TNF-alpha concentrations). The exercise-induced increase in 6-keto-PGF(1alpha) concentration?? was significantly higher (p=0.008) in a group of subjects (n=5) with the highest VO(2max) when compared to the group of subjects with the lowest VO(2max), in which no increase in 6-keto-PGF(1alpha) concentration was found. In conclusion, we demonstrated, to our knowledge for the first time, that exercise-induced release of PGI(2) in young healthy men correlates with VO(2max), suggesting that vascular capacity to release PGI(2) in response to physical exercise represents an important factor characterizing exercise tolerance. Moreover, we postulate that the impairment of exercise-induced release of PGI(2) leads to the increased cardiovascular hazard of vigorous exercise.

Effect of mono-unsaturated fatty acids versus complex carbohydrates on high-density lipoproteins in healthy men and women.

NARCIS (Netherlands)

Mensink, R.P.; Katan, M.B.

1987-01-01

The effects of two strictly controlled diets, one rich in complex carbohydrates, the other rich in olive oil, on serum lipids were studied in healthy men and women. Serum cholesterol levels fell on average by 0?44 mmol/l in the carbohydrate group and 0?46 mmol/l in the olive oil group. HDL

Influence of Baseline Psychological Health on Muscle Pain During Atorvastatin Treatment.

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Zaleski, Amanda L; Taylor, Beth A; Pescatello, Linda S; Dornelas, Ellen A; White, Charles Michael; Thompson, Paul D

3-hydroxy-3-methylglutaryl coenzyme A reductase reductase inhibitors (statins) are generally well tolerated, with statin-associated muscle symptoms (SAMS) the most common side effect (~10%) seen in statin users. However, studies and clinical observations indicate that many of the self-reported SAMS appear to be nonspecific (ie, potentially not attributable to statins). Mental health and well-being influence self-perception of pain, so we sought to assess the effect of baseline well-being and depression on the development of muscle pain with 6 months of atorvastatin 80 mg/d (ATORVA) or placebo in healthy, statin-naive adults. The Psychological General Well-being Index (n = 83) and Beck Depression Inventory (n = 55) questionnaires were administered at baseline in participants (aged 59.5 ± 1.2 years) from the effect of Statins on Skeletal Muscle Function and Performance (STOMP) trial (NCT00609063). Muscle pain (Short-Form McGill Pain Questionnaire [SF-MPQ]), pain that interferes with daily life (Brief Pain Inventory [BPI]), and pain severity (BPI) were then measured before, throughout, and after treatment. At baseline, there were no differences in well-being (Psychological General Well-being Index), depression (Beck Depression Inventory), or pain measures (SF-MPQ and BPI) (P values ≥ .05) between the placebo and ATORVA groups. Baseline well-being correlated negatively with baseline BPI pain severity (r = -0.290, P = .008). Baseline depression correlated with baseline pain (SF-MPQ; r = 0.314, P = .020). Baseline well-being and depression did not predict the change in pain severity or interference after 6 months among the total sample or between groups (P values ≥ .05). Baseline well-being and depression were not significant predictors of pain after 6 months of ATORVA (P values ≥ .05). Thus, they do not appear to increase the risk of SAMS in otherwise healthy adults.

Solid State Characterization of Commercial Crystalline and Amorphous Atorvastatin Calcium Samples

OpenAIRE

Shete, Ganesh; Puri, Vibha; Kumar, Lokesh; Bansal, Arvind K.

2010-01-01

Atorvastatin calcium (ATC), an anti-lipid BCS class II drug, is marketed in crystalline and amorphous solid forms. The objective of this study was to perform solid state characterization of commercial crystalline and amorphous ATC drug samples available in the Indian market. Six samples each of crystalline and amorphous ATC were characterized using X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis, Karl Fisher titrimetry, microscopy (hot s...

Physical Activity, Aerobic Capacity, and Total Antioxidant Capacity in Healthy Men and in Men with Coronary Heart Disease

Science.gov (United States)

Gawron-Skarbek, Anna; Kostka, Joanna; Nowak, Dariusz; Drygas, Wojciech; Jegier, Anna; Kostka, Tomasz

2015-01-01

Objective. The purpose of the study was to assess total antioxidant capacity (TAC) of blood serum in relation with habitual leisure time physical activity (LTPA) and aerobic capacity in a group of 90 men with coronary heart disease (CHD) aged 34.8–77.0 years and in 90 age-matched peers without CHD. Methods. Two spectrophotometric methods were applied to assess TAC: Ferric Reducing Ability of Serum (TAC-FRAS) and 2.2-diphenyl-1-picryl-hydrazyl (TAC-DPPH) tests. Aerobic capacity was expressed as physical working capacity at 85% of the maximal heart rate (PWC85%HRmax). Results. CHD patients had higher values of TACFRAS (1.37 ± 0.28 versus 1.27 ± 0.23 mmol FeCl2·L−1; P < 0.05) but there were no group differences for TAC-DPPH and for uric acid (UA). Negative correlation was found between LTPA (also when calculated per kg of body mass) and TAC-DPPH in CHD patients. In CHD patients, TAC-FRAS and UA were lower in subjects with higher aerobic capacity expressed as PWC85%HRmax/kg. Those associations were not found in healthy men. Conclusions. We conclude that TAC of blood serum is moderately adversely related to LTPA and aerobic capacity in patients with CHD. UA, as the main determinant of serum TAC, may be partially responsible for those associations. PMID:26451234

Physical Activity, Aerobic Capacity, and Total Antioxidant Capacity in Healthy Men and in Men with Coronary Heart Disease

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Anna Gawron-Skarbek

2015-01-01

Full Text Available Objective. The purpose of the study was to assess total antioxidant capacity (TAC of blood serum in relation with habitual leisure time physical activity (LTPA and aerobic capacity in a group of 90 men with coronary heart disease (CHD aged 34.8–77.0 years and in 90 age-matched peers without CHD. Methods. Two spectrophotometric methods were applied to assess TAC: Ferric Reducing Ability of Serum (TAC-FRAS and 2.2-diphenyl-1-picryl-hydrazyl (TAC-DPPH tests. Aerobic capacity was expressed as physical working capacity at 85% of the maximal heart rate (PWC85%HRmax. Results. CHD patients had higher values of TACFRAS (1.37±0.28 versus 1.27±0.23 mmol FeCl2·L−1; P<0.05 but there were no group differences for TAC-DPPH and for uric acid (UA. Negative correlation was found between LTPA (also when calculated per kg of body mass and TAC-DPPH in CHD patients. In CHD patients, TAC-FRAS and UA were lower in subjects with higher aerobic capacity expressed as PWC85%HRmax/kg. Those associations were not found in healthy men. Conclusions. We conclude that TAC of blood serum is moderately adversely related to LTPA and aerobic capacity in patients with CHD. UA, as the main determinant of serum TAC, may be partially responsible for those associations.

Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

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Godino, Cosmo; Pavon, Anna Giulia; Mangieri, Antonio; Salerno, Anna; Cera, Michela; Monello, Alberto; Chieffo, Alaide; Magni, Valeria; Cappelletti, Alberto; Margonato, Alberto; Colombo, Antonio

2017-08-01

The acute effects of statin loading dose (LD) on platelet reactivity in patients with chronic stable angina (CSA) are not completely clear. We hypothesized that LDs of atorvastatin and rosuvastatin have different pharmacodynamic acute effects on platelet aggregability in CSA patients with baseline normal platelet reactivity while on dual antiplatelet therapy (DAPT). From September 2011 to February 2014, all consecutive CSA patients on chronic DAPT (aspirin and clopidogrel) were evaluated before elective percutaneous coronary intervention (PCI). An initial assessment of platelet reactivity in response to thrombin receptor agonist, ADP, and ASP (respectively, indicative of the response to clopidogrel and aspirin) was performed with impedance aggregometry. Patients with high platelet reactivity to ADP test (area under the curve >47) were excluded. The remaining patients were randomized into 3 treatment groups: Group A, atorvastatin LD 80 mg; Group B, rosuvastatin LD 40 mg; and Group C, no statin LD (control group). A second assessment of platelet reactivity was performed ≥12 hours after statin LD. 682 patients were screened and 145 were randomized into the 3 groups. At baseline and after statin LD, no significant difference was found in platelet reactivity in response to 3 different agonists between the 3 groups. Subgroup analysis showed that platelet reactivity to ADP test was significantly lower in patients chronically treated with low-dose statins (n = 94) compared with statin-naïve patients (n = 51; 15.32 ± 1.50 vs 18.59 ± 1.30; P = 0.007). Loading dose of atorvastatin (80 mg) or rosuvastatin (40 mg) did not induce significant variation in platelet reactivity in CSA patients with baseline reduced platelet reactivity as in chronic DAPT. Our data confirm that chronic concomitant treatment with low-dose statins and clopidogrel resulted in significantly lower platelet reactivity compared with clopidogrel alone. © 2017 Wiley Periodicals, Inc.

‘BIG, HARD and UP!’ A healthy creed for men to live by?

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Stephan Van der Watt

2016-06-01

Full Text Available The social construction of reality is influenced extensively by the mass media. Commercialised images of masculinity, including discourses to interpret it, are continuously reflected and/or created by sources of mass media, in a myriad of ways. These images are subjectively loaded, but still effectively communicate to us, and even entice and persuade us. It furthermore wields extensive power over men – especially over their self-images, passions, and egos. In this article, dominating images and discourses concerning manhood and male identity – particularly those displayed in men’s health magazines (MHM – were critically examined. This was done through a thematic analysis of 123 issues (spanning more than 10 years of MHM cover pages. The investigation showed that MHM is infused with traditional masculine ideology. Moreover, MHM fails to confront discourses that endorse hegemonic masculinity, for the sake of holistic health. It was suggested that a sober, precautionary, health strategy should challenge men to critically engage with MHM’s reigning creed: ‘big, hard and up’. This creed incites a utilitarian view of sexuality within a culture of performance-driven masculinity, which subsequently fuels anxieties that can lead to unhealthy issues, such as body image dissatisfaction. From a pastoral care perspective, it was asserted that (specifically Christian men need to search for alternative ways to instigate their capacity to experience and facilitate authentic intimacy, in order to work toward the social construction of more balanced and healthy discourses on male identity.   Keywords:Masculinity/Masculinities; Men's Health; Male Sexuality; Embodiment; Pastoral Care Perspective

Atorvastatin inhibits the immediate-early response gene EGR1 and improves the functional profile of CD4+T-lymphocytes in acute coronary syndromes.

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Severino, Anna; Zara, Chiara; Campioni, Mara; Flego, Davide; Angelini, Giulia; Pedicino, Daniela; Giglio, Ada Francesca; Trotta, Francesco; Giubilato, Simona; Pazzano, Vincenzo; Lucci, Claudia; Iaconelli, Antonio; Ruggio, Aureliano; Biasucci, Luigi Marzio; Crea, Filippo; Liuzzo, Giovanna

2017-03-14

Background- Adaptive immune-response is associated with a worse outcome in acute coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment in acute coronary syndromes on CD4+T-cells, and the underlying molecular mechanisms.Approach and results- Blood samples were collected from 50 statin-naïve acute coronary syndrome patients. We assessed CD4+T-cell activation by flow-cytometry, the expression of 84 T-helper transcription-factors and 84 T-cell related genes by RT-qPCR, and protein expression by Western-blot, before and after 24-hours incubation with increasing doses of atorvastatin: 3-10-26 μg/ml (corresponding to blood levels achieved with doses of 10-40-80 mg, respectively). After incubation, we found a significant decrease in interferon-γ-producing CD4+CD28nullT-cells (P = 0.009) and a significant increase in interleukin-10-producing CD4+CD25highT-cells (P 3-fold changes).The in-vivo effects of atorvastatin were analyzed in 10 statin-free acute coronary syndrome patients at baseline, and after 24h and 48h of atorvastatin therapy (80 mg/daily): EGR1-gene expression decreased at 24h (P = 0.01) and 48h (P = 0.005); EGR1-protein levels decreased at 48h (P = 0.03).Conclusions-In acute coronary syndromes, the effects of atorvastatin on immune system might be partially related to the inhibition of the master regulator gene EGR1. Our finding might offer a causal explanation on why statins improve the early outcome in acute coronary syndromes.

Fasting triglycerides predict recurrent ischemic events in patients with acute coronary syndrome treated with statins.

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Schwartz, Gregory G; Abt, Markus; Bao, Weihang; DeMicco, David; Kallend, David; Miller, Michael; Mundl, Hardi; Olsson, Anders G

2015-06-02

Most patients with acute coronary syndrome (ACS) are treated with statins, which reduce atherogenic triglyceride-rich lipoproteins. It is uncertain whether triglycerides predict risk after ACS on a background of statin treatment. This study examined the relationship of fasting triglyceride levels to outcomes after ACS in patients treated with statins. Long-term and short-term relationships of triglycerides to risk after ACS were examined in the dal-OUTCOMES trial and atorvastatin arm of the MIRACL (Myocardial Ischemia Reduction with Acute Cholesterol Lowering) trial, respectively. Analysis of dal-OUTCOMES included 15,817 patients (97% statin-treated) randomly assigned 4 to 12 weeks after ACS to treatment with dalcetrapib (a cholesteryl ester transfer protein inhibitor) or placebo and followed for a median 31 months. Analysis of MIRACL included 1,501 patients treated with atorvastatin 80 mg daily beginning 1 to 4 days after ACS and followed for 16 weeks. Fasting triglycerides at initial random assignment were related to risk of coronary heart disease death, nonfatal myocardial infarction, stroke, and unstable angina in models adjusted for age, sex, hypertension, smoking, diabetes, high-density lipoprotein cholesterol, and body mass index. Fasting triglyceride levels were associated with both long-term and short-term risk after ACS. In dal-OUTCOMES, long-term risk increased across quintiles of baseline triglycerides (p175/≤80 mg/dl) was 1.61 (95% confidence interval: 1.34 to 1.94). There was no interaction of triglycerides and treatment assignment on the primary outcome. In the atorvastatin group of MIRACL, short-term risk increased across tertiles of baseline triglycerides (p=0.03), with a hazard ratio of 1.50 [corrected] (95% confidence interval: 1.05 to 2.15) in highest/lowest tertiles (>195/≤135 mg/dl). The relationship of triglycerides to risk was independent of low-density lipoprotein cholesterol in both studies. Among patients with ACS treated effectively

Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men

DEFF Research Database (Denmark)

Hansen, Mette; Morthorst, Rikke; Larsson, Benny

2005-01-01

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups....... The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters...... change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P

Strong adherence to a healthy dietary pattern is associated with better semen quality, especially in men with poor semen quality.

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Oostingh, Elsje C; Steegers-Theunissen, Régine P M; de Vries, Jeanne H M; Laven, Joop S E; Koster, Maria P H

2017-04-01

To study associations between periconceptional dietary patterns and semen quality parameters. Prospective periconception cohort study. Tertiary hospital. One hundred and twenty-nine male partners of pregnant women who participated in the Rotterdam Periconception Cohort (Predict study). None. Semen quality parameters-ejaculate volume, sperm concentration, total sperm count, progressive motility, immotile sperm, and total motile sperm count (TMSC). Men included in our study were on average 35 (±6 standard deviation) years old and had a body mass index of 26.4 ± 4 kg/m 2 . Two dietary patterns were identified using principle component analysis, which were labeled as "healthy" and "unhealthy." An increase of one factor score (stated as β) represented an increase of 1 standard deviation. Sperm concentration (β = 0.278; 95% CI, 0.112-0.444), total sperm count (β = 1.369; 95% CI, 0.244-2.495), progressive motility (β = 4.305; 95% CI, 0.675-7.936), and TMSC (β = 0.319; 95% CI, 0.113-0.526) were all positively associated with a strong adherence to the healthy dietary pattern. Subgroup analysis showed that these associations were mainly present in men with a TMSC strong adherence to the unhealthy dietary pattern. The positive associations between strong adherence to a healthy dietary pattern and semen parameters in men with poor semen quality support the importance of preconceptional tailored nutritional counseling and coaching of couples who are trying to conceive. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Development and Validation of RP-HPLC Method for Simultaneous Estimation of Ramipril, Aspirin and Atorvastatin in Pharmaceutical Preparations

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Rajesh Sharma

2012-01-01

Full Text Available A simple, sensitive, accurate and rapid reverse phase high performance liquid chromatographic method is developed for the simultaneous estimation of ramipril, aspirin and atorvastatin in pharmaceutical preparations. Chromatography was performed on a 25cm×4.6 mm i.d, 5µm particle, C18 column with Mixture of (A acetonitrile methanol (65:35 and (B 10 mM sodium dihydrogen phosphate monohydrate (NaH2PO4.H2O buffer and mixture of A:B (60:40 v/v adjusted to pH 3.0 with o-phosphoric acid (5%v/v was used as a mobile phase at a flow rate of 1.5 ml min-1. UV detection was performed at 230 nm. Total run time was less then 12 min; retention time for Ramipril, aspirin and Atorvastatin were 3.620, 4.920 min and 11.710 min respectively. The method was validated for accuracy, precision, linearity, specificity and sensitivity in accordance with ICH guidelines. Validation revealed that the method is specific, rapid, accurate, precise, reliable, and reproducible. Calibration plots were linear over the concentration ranges 05-50 µg mL-1 for Ramipril, 05-100 µgmL-1 for aspirin and 02-20 µg mL-1 for atorvastatin. Limits of detection were 0.014, 0.10 and 0.0095 ng mL-1 limits of quantification were 0.043, 0.329 and 0.029 ng mL-1 for ramipril aspirin and atorvastatin respectively. The high recovery and low coefficients of variation confirm the suitability of the method for simultaneous analysis of the all three drugs in the dosage forms. The validated method was successfully used for quantitative analysis of marketed pharmaceutical preparations.

Cost-Effectiveness Analysis of Atorvastatin versus Rosuvastatin in Primary and Secondary Cardiovascular Prevention Populations in Brazil and Columbia.

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Mould-Quevedo, Joaquín F; Gutiérrez-Ardila, Magda Vianey; Ordóñez Molina, Jaime Eduardo; Pinsky, Brett; Vargas Zea, Nicolás

2014-12-01

Latin America has witnessed a marked increase in cardiovascular (CV) disease, the leading cause of death in many countries. The benefits of lipid-lowering therapy to reduce CV-related events are widely accepted. Clinical evidence suggests that rosuvastatin is associated with slightly greater reductions in low-density lipoprotein cholesterol levels than is atorvastatin at comparable doses. Rosuvastatin, however, is often priced at a premium. Our objective was to examine the cost-effectiveness of using atorvastatin versus rosuvastatin in reducing CV events in Brazil and Colombia using real-world prices. A global Markov cohort model of primary and secondary CV prevention was developed and adapted to Brazilian and Colombian settings. The risks and costs of major CV events and efficacy, adherence, and costs of statins were considered. Total gains in life-years, quality-adjusted life-years, major CV events avoided, and costs over the lifetime horizon were estimated. Several dose comparisons were considered. In the Colombian analyses, differences in drug costs between therapies were considerable while outcomes were similar. The incremental cost per quality-adjusted life-year gained for rosuvastatin versus atorvastatin was more than $700,000 and $200,000 in primary and secondary prevention, respectively. Brazilian analyses found lower incremental cost-effectiveness ratios for rosuvastatin at some dose comparisons due to similar pricing between statins. Sensitivity analyses revealed that changes in treatment efficacy and adherence had the largest impact on results. In primary and secondary CV prevention, the efficacy advantage of rosuvastatin was minimal, while its acquisition cost was higher, particularly in Colombia. The incremental cost-effectiveness ratios were, therefore, generally in favor of atorvastatin being the cost-effective option. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights

Effects of maximal atorvastatin and rosuvastatin treatment on markers of glucose homeostasis and inflammation

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Recent studies show that statin therapy, while effective at lowering the risk of cardiovascular disease (CVD), may be associated with an increased risk of diabetes. To test the effects of maximal dosages of rosuvastatin and atorvastatin (80mg/day and 40mg/day, respectively) we obtained frozen serum ...

Moderate-intensity endurance training improves endothelial glycocalyx layer integrity in healthy young men.

Science.gov (United States)

Majerczak, Joanna; Grandys, Marcin; Duda, Krzysztof; Zakrzewska, Agnieszka; Balcerczyk, Aneta; Kolodziejski, Leszek; Szymoniak-Chochol, Dorota; Smolenski, Ryszard T; Bartosz, Grzegorz; Chlopicki, Stefan; Zoladz, Jerzy A

2017-01-01

What is the central question of this study? The main aim of the present study was to determine the effect of prolonged moderate-intensity endurance training on the endothelial glycocalyx layer integrity in relationship to the training-induced changes in oxidative stress and antioxidant defence in humans. What is the main finding and its importance? We have shown, for the first time, a protective effect of prolonged moderate-intensity endurance training on endothelial glycocalyx layer integrity, as judged by significantly lower basal and end-exercise serum concentrations of glycocalyx damage markers, i.e. syndecan-1 and heparan sulfate, accompanied by attenuation of oxidative stress and enhancement of antioxidant defence after training in previously untrained healthy young men. In this study, we evaluated the effect of 20 weeks of moderate-intensity endurance training (ET) on the endothelial glycocalyx layer integrity in relationship to the training-induced changes in antioxidant defence. Eleven healthy young, untrained men performed an incremental cycling exercise bout until exhaustion before and after 20 weeks of ET. Endurance training consisted of 40 min sessions, mainly of moderate intensity (∼50% of maximal oxygen uptake), performed four times per week. Venous blood samples were taken at rest and at the end of the maximal exercise test. Muscle biopsies from vastus lateralis were taken before and after the training. Endurance training resulted in a significant increase in physical capacity (P  0.05). Moderate-intensity ET exerts a pronounced protective effect on endothelial glycocalyx integrity at rest and during exercise, probably through an improvement of antioxidant defence that may represent the vasoprotective mechanisms highly responsive to moderate-intensity endurance training. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Atorvastatin Inhibits the HIF1α-PPAR Axis, Which Is Essential for Maintaining the Function of Human Induced Pluripotent Stem Cells.

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Nakashima, Yoshiki; Miyagi-Shiohira, Chika; Noguchi, Hirofumi; Omasa, Takeshi

2018-06-19

We herein report a novel mechanism of action of statin preparations using a new drug discovery method. Milk fat globule-EGF factor 8 protein (MFG-E8) was identified from the secretory component of mouse embryonic fibroblast (MEF) as a cell adhesion-promoting factor effective for screening active cellular agents of human induced pluripotent stem cells (hiPSCs) in vitro using electrochemical impedance. Our analyses showed that atorvastatin did not cause death in myocardial cells differentiated from hiPSCs but reduced the pluripotent cell survival in vitro when using serum- and albumin-free media, and inhibited the ability to form teratomas in mice. This result could have been already the cytopathic effect of atorvastatin, and complete elimination of hiPSCs was confirmed in the xenotransplantation assay. The administration of atorvastatin to hiPSCs caused the expression of hypoxia inducible factor (HIF)1α mRNA to be unchanged at 6 hr and downregulated at 24 hr. In addition, the inhibition of the survival of hiPSCs was confirmed by HIF1α-peroxisome proliferator-activated receptor (PPAR) axis inhibition. These results suggest that the addition of atorvastatin to hiPSC cultures reduces the survival of pluripotent cells by suppressing the HIF1α-PPAR axis. In summary, the HIF1α-PPAR axis has an important role in maintaining the survival of pluripotent hiPSCs. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Atorvastatin protected from paraquat-induced cytotoxicity in alveolar macrophages via down-regulation of TLR-4

NARCIS (Netherlands)

Alizadeh-Tabrizi, Nazli; Malekinejad, Hassan; Varasteh, Soheil; Cheraghi, Hadi

2017-01-01

The current study designed to clarify the mechanism of paraquat-induced cytotoxicity and protective effects of Atorvastatin on freshly isolated alveolar macrophages (AMs). AMs were collected via bronchoalveolar lavage and exposed to various concentrations of paraquat in the presence and absence of

The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-11C]WAY-100635

International Nuclear Information System (INIS)

Stein, Patrycja; Savli, Markus; Fink, Martin; Spindelegger, Christoph; Moser, Ulrike; Kasper, Siegfried; Lanzenberger, Rupert; Wadsak, Wolfgang; Dudczak, Robert; Kletter, Kurt; Mitterhauser, Markus; Mien, Leonhard-Key

2008-01-01

The higher prevalence rates of depression and anxiety disorders in women compared to men have been associated with sexual dimorphisms in the serotonergic system. The present positron emission tomography (PET) study investigated the influence of sex on the major inhibitory serotonergic receptor subtype, the serotonin-1A (5-HT 1A ) receptor. Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [carbonyl- 11 C]WAY-100635. Effects of age or gonadal hormones were excluded by restricting the inclusion criteria to young adults and by controlling for menstrual cycle phase. The 5-HT 1A receptor BP ND was quantified using (1) the 'gold standard' manual delineation approach with ten regions of interest (ROIs) and (2) a newly developed delineation method using a PET template normalized to the Montreal Neurologic Institute space with 45 ROIs based on automated anatomical labeling. The 5-HT 1A receptor BP ND was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BP ND values in every region investigated, with a borderline significant sex difference in the hypothalamus (p=0.012, uncorrected). There was a high intersubject variability of the 5-HT 1A receptor BP ND within both sexes compared to the small mean differences between men and women. To conclude, when measured in the follicular phase, women do not differ from men in the 5-HT 1A receptor binding. To explain the higher prevalence of affective disorders in women, further studies are needed to evaluate the relationship between hormonal status and the 5-HT 1A receptor expression. (orig.)

Changes in Flow-Mediated Dilatation, Cytokines and Carotid Arterial Stenosis During Aggressive Atorvastatin Treatment in Normocholesterolemic Patients

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Hung-Yi Hsu

2005-02-01

Conclusion: Atorvastatin effectively reduced plasma concentrations of total cholesterol and LDL-cholesterol, and had beneficial effects on endothelial function, in Chinese patients with carotid arterial stenosis and normal LDL-cholesterol levels.

Differences in cortical and pituitary activity in response to hypoglycaemia and cognitive testing in healthy men with different basal activity of the renin-angiotensin system

DEFF Research Database (Denmark)

Bie-Olsen, Lise G; Pedersen-Bjergaard, Ulrik; Kjaer, Troels W

2010-01-01

in cerebral activity during hypoglycaemia and cognitive testing in two groups of healthy men with different basal RAS activity. METHODS: Ten healthy men with high RAS activity and 10 with low activity underwent six oxygen-15-labelled water positron emission tomography scans: twice during normoglycaemia, twice......INTRODUCTION: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differences...... during insulin-induced hypoglycaemia and twice during post-hypoglycaemia. During the scans, the subjects performed a computer-based reaction time test. RESULTS: Occipital areas were consistently more activated in the low RAS group than in the high RAS group throughout all three conditions. During...

Polytetrafluorethylene film-based liquid-three phase micro extraction coupled with differential pulse voltammetry for the determination of atorvastatin calcium.

Science.gov (United States)

Ensafi, Ali A; Khoddami, Elaheh; Rezaei, Behzad

2013-01-01

In this paper, we describe a new combination method based on polytetrafluorethylene (PTFE) film-based liquid three-phase micro extraction coupled with differential pulse voltammetry (DPV) for the micro extraction and quantification of atorvastatin calcium (ATC) at the ultra-trace level. Different factors affecting the liquid-three phases micro extraction of atorvastatin calcium, including organic solvent, pH of the donor and acceptor phases, concentration of salt, extraction time, stirring rate and electrochemical factors, were investigated, and the optimal extraction conditions were established. The final stable signal was achieved after a 50 min extraction time, which was used for analytical applications. An enrichment factor of 21 was achieved, and the relative standard deviation (RSD) of the method was 4.5% (n = 4). Differential pulse voltammetry exhibited two wide linear dynamic ranges of 20.0-1000.0 pmol L(-1) and 0.001-11.0 µmol L(-1) of ATC. The detection limit was found to be 8.1 pmol L(-1) ATC. Finally, the proposed method was used as a new combination method for the determination of atorvastatin calcium in real samples, such as human urine and plasma.

Exogenous cortisol acutely influences motivated decision making in healthy young men.

Science.gov (United States)

Putman, Peter; Antypa, Niki; Crysovergi, Panagiota; van der Does, Willem A J

2010-02-01

The glucocorticoid (GC) hormone cortisol is the end product of the hypothalamic-pituitary-adrenal axis (HPA axis). Acute psychological stress increases HPA activity and GC release. In humans, chronic disturbances in HPA activity have been observed in affective disorders and in addictive behaviour. Recent research indicates that acute effects of GCs may be anxiolytic and increase reward sensitivity. Furthermore, cortisol acutely influences early cognitive processing of emotional stimuli. In order to extend such findings to more complex emotional-cognitive behaviour, the present study tested acute effects of 40 mg cortisol on motivated decision making in 30 healthy young men. Results showed that cortisol indeed increased risky decision making, as predicted. This effect occurred for decisions where making a risky choice could potentially yield a big reward. These results are discussed with respect to currently proposed mechanisms for cortisol's potential anxiolytic effect and GCs' involvement in reward systems.

Protective effect of atorvastatin on d-galactose-induced aging model in mice.

Science.gov (United States)

Kaviani, Elham; Rahmani, Mohammadreza; Kaeidi, Ayat; Shamsizadeh, Ali; Allahtavakoli, Mohamad; Mozafari, Nazanin; Fatemi, Iman

2017-09-15

Atorvastatin (Ator), competitive inhibitors of 3-hydroxymethyl-3-glutaryl-coenzyme-A reductase, is a cholesterol lowering drug. Ator has been shown to have neuroprotective, antioxidant and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. Here we assessed the effect of Ator on the d-galactose (d-gal)-induced aging in mice. For this purpose, Ator (0.1 and 1mg/kg/p.o.), was administrated daily in d-gal-received (500mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behaviors and cognitive functions were evaluated by the elevated plus-maze and novel object recognition tasks, respectively. Physical power was assessed by forced swimming capacity test. Animals brains were analyzed for the superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). We found that Ator decreases the anxiety-like behaviors in d-gal-treated mice. Also, our behavioral tests showed that Ator reverses the d-gal induced learning and memory impairment. Furthermore, we found that Ator increases the physical power of d-gal-treated mice. Our results indicated that the neuroprotective effect of Ator on d-gal induced neurotoxicity is mediated, at least in part, by an increase in the SOD and BDNF levels. The results of present study suggest that Ator could be used as a novel therapeutic strategy for the treatment of age-related conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of heparin on pregnancy associated plasma protein-A concentration in healthy, non-pregnant individuals

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Jespersen, Camilla H B; Vestergaard, Kirstine R.; Schou, Morten

2015-01-01

Objectives: The objective of this study was to determine the differences in pregnancy associated plasma protein-A (PAPP-A) concentrations in heparin naive and heparin treated healthy men and non-pregnant women, to find a possible difference in different age groups, and to determine the response...

Dietary guanidinoacetic acid does not accumulate in the brain of healthy men

DEFF Research Database (Denmark)

Ostojic, Sergej M.; Ostojic, Jelena

2018-01-01

analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations......We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally....... No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used....

Cardiovascular function is better in veteran football players than age-matched untrained elderly healthy men

DEFF Research Database (Denmark)

Schmidt, Jakob Friis; Andersen, Thomas Rostgaard; Andersen, Lars Juel

2015-01-01

The aim of the study was to determine whether lifelong football training may improve cardiovascular function, physical fitness, and body composition. Our subjects were 17 male veteran football players (VPG; 68.1 ± 2.1 years) and 26 healthy age-matched untrained men who served as a control group (CG......, RHI was 21% higher (P training is associated with better LV systolic function, physical fitness......, microvascular function, and a healthier body composition. Overall, VPG have better cardiovascular function compared with CG, which may reduce their cardiovascular morbidity and mortality....

Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load.

Science.gov (United States)

Choudhury, Soumen; Kandasamy, Kannan; Maruti, Bhojane Somnath; Addison, M Pule; Kasa, Jaya Kiran; Darzi, Sazad A; Singh, Thakur Uttam; Parida, Subhashree; Dash, Jeevan Ranjan; Singh, Vishakha; Mishra, Santosh Kumar

2015-10-15

Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1β and TNFα) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

Adiponectin and risk of coronary heart disease in apparently healthy men and women (from the EPIC-Norfolk Prospective Population Study)

NARCIS (Netherlands)

Côté, Mélanie; Cartier, Amélie; Reuwer, Anne Q.; Arsenault, Benoit J.; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J.; Kastelein, John J. P.; Boekholdt, S. Matthijs; Khaw, Kay-Tee

2011-01-01

The objective of the present study was to evaluate the association between adiponectin levels and incidence of coronary heart disease (CHD). We performed a prospective case-control analysis nested in the EPIC-Norfolk cohort. Participants were apparently healthy men and women 45 to 79 years of age

Carbohydrate intake and glycemic index affect substrate oxidation during a controlled weight cycle in healthy men.

Science.gov (United States)

Kahlhöfer, J; Lagerpusch, M; Enderle, J; Eggeling, B; Braun, W; Pape, D; Müller, M J; Bosy-Westphal, A

2014-09-01

Because both, glycemic index (GI) and carbohydrate content of the diet increase insulin levels and could thus impair fat oxidation, we hypothesized that refeeding a low GI, moderate-carbohydrate diet facilitates weight maintenance. Healthy men (n=32, age 26.0±3.9 years; BMI 23.4±2.0 kg/m(2)) followed 1 week of controlled overfeeding, 3 weeks of caloric restriction and 2 weeks of hypercaloric refeeding (+50, -50 and +50% energy requirement) with low vs high GI (41 vs 74) and moderate vs high CHO intake (50% vs 65% energy). We measured adaptation of fasting macronutrient oxidation and the capacity to supress fat oxidation during an oral glucose tolerance test. Changes in fat mass were measured by quantitative magnetic resonance. During overfeeding, participants gained 1.9±1.2 kg body weight, followed by a weight loss of -6.3±0.6 kg and weight regain of 2.8±1.0 kg. Subjects with 65% CHO gained more body weight compared with 50% CHO diet (Pfat oxidation when compared with a low-GI diet (Pfat oxidation was associated with regain in fat mass (r=0.43, Pcarbohydrate content affect substrate oxidation and thus the regain in body weight in healthy men. These results argue in favor of a lower glycemic load diet for weight maintenance after weight loss.

Effects of an outdoor bicycle-based intervention in healthy rural Indian men with normal and low birth weight

DEFF Research Database (Denmark)

Madsen, C; Mogensen, P; Thomas, N

2015-01-01

Physical inactivity and low birth weight (LBW) may lead to an increased risk for developing type 2 diabetes. The extent to which LBW individuals may benefit from physical exercise training when compared with those with normal birth weight (NBW) controls is uncertain. We assessed the impact...... of an outdoor exercise intervention on body composition, insulin secretion and action in young men born with LBW and NBW in rural India. A total of 61 LBW and 56 NBW healthy young men were recruited into the study. The individuals were instructed to perform outdoor bicycle exercise training for 45 min every day...... with LBW in rural India benefit metabolically from exercise training to an extent comparable with NBW controls....

The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers

Energy Technology Data Exchange (ETDEWEB)

Wu, Yen-Wen [National Taiwan University Hospital, Department of Internal Medicine, Taipei (China); National Taiwan University Hospital, Department of Nuclear Medicine, Taipei (China); Kao, Hsian-Li; Chen, Ming-Fong; Lin, Lian-Yu; Wang, Yi-Chih; Lin, Yen-Hung; Lin, Hung-Ju; Huang, Por-Jau [National Taiwan University Hospital, Department of Internal Medicine, Taipei (China); Huang, Chi-Lun [Tao-Yuan General Hospital, Department of Internal Medicine, Tao-Yuan (China); Tzen, Kai-Yuan; Yen, Ruoh-Fang [National Taiwan University Hospital, Department of Nuclear Medicine, Taipei (China); Chi, Yu-Chiao [National Taiwan University, Graduate Institute of Clinical Medicine, College of Medicine, Taipei (China); Yang, Wei-Shiung [National Taiwan University Hospital, Department of Internal Medicine, Taipei (China); National Taiwan University, Graduate Institute of Clinical Medicine, College of Medicine, Taipei (China)

2012-03-15

{sup 18}F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has the potential to track vascular inflammation and monitor therapeutic response. The purpose of this study was to determine the association between arterial inflammation, calcification and serological biomarkers in subjects with atherosclerosis, and to assess their therapeutic response to 12-week atorvastatin treatment. Forty-three statin-naive subjects with atherosclerosis received atorvastatin (40 mg/day) for 12 weeks and underwent {sup 18}F-FDG PET/CT, coronary calcification and abdominal adipose tissue volume measurements. A panel of serological biomarkers was analysed. Arterial inflammation was measured at seven arterial segments and normalized to venous FDG activity to produce target to background ratios (TBR). Thirty-four subjects without cardiovascular disease who repeated PET 1-4 years apart for routine health check-ups were retrospectively evaluated for comparison. The baseline mean TBR values in atherosclerotic patients were positively correlated with age (R = 0.36), body mass index (R = 0.54), abdominal visceral adipose tissue volume (R = 0.65), coronary calcification score (R = 0.40), levels of low-density lipoprotein cholesterol (R = 0.54), matrix metalloproteinase (MMP)-9 (R = 0.46) and fatty acid binding protein 4 (FABP4) (R = 0.67, all p < 0.05). The TBR as well as high-sensitivity C-reactive protein (hsCRP), E-selectin, MMP-9, monocyte chemotactic protein 1, FABP4 and follistatin values were reduced significantly after the 12-week atorvastatin treatment. The TBR reduction marginally correlated with changes in MMP-9 levels (R = 0.56, p = 0.05). The control group, whose median age was younger, by comparison had lower hsCRP and arterial TBR than the subjects with atherosclerosis (all p < 0.05), and moreover had a slight but insignificant increase in mean TBR at their 2.5{+-}0.8 year follow-up. The medium dose of atorvastatin over a 12-week period resulted in a significant

The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers

International Nuclear Information System (INIS)

Wu, Yen-Wen; Kao, Hsian-Li; Chen, Ming-Fong; Lin, Lian-Yu.; Wang, Yi-Chih; Lin, Yen-Hung; Lin, Hung-Ju; Huang, Por-Jau; Huang, Chi-Lun; Tzen, Kai-Yuan; Yen, Ruoh-Fang; Chi, Yu-Chiao; Yang, Wei-Shiung

2012-01-01

18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has the potential to track vascular inflammation and monitor therapeutic response. The purpose of this study was to determine the association between arterial inflammation, calcification and serological biomarkers in subjects with atherosclerosis, and to assess their therapeutic response to 12-week atorvastatin treatment. Forty-three statin-naive subjects with atherosclerosis received atorvastatin (40 mg/day) for 12 weeks and underwent 18 F-FDG PET/CT, coronary calcification and abdominal adipose tissue volume measurements. A panel of serological biomarkers was analysed. Arterial inflammation was measured at seven arterial segments and normalized to venous FDG activity to produce target to background ratios (TBR). Thirty-four subjects without cardiovascular disease who repeated PET 1-4 years apart for routine health check-ups were retrospectively evaluated for comparison. The baseline mean TBR values in atherosclerotic patients were positively correlated with age (R = 0.36), body mass index (R = 0.54), abdominal visceral adipose tissue volume (R = 0.65), coronary calcification score (R = 0.40), levels of low-density lipoprotein cholesterol (R = 0.54), matrix metalloproteinase (MMP)-9 (R = 0.46) and fatty acid binding protein 4 (FABP4) (R = 0.67, all p < 0.05). The TBR as well as high-sensitivity C-reactive protein (hsCRP), E-selectin, MMP-9, monocyte chemotactic protein 1, FABP4 and follistatin values were reduced significantly after the 12-week atorvastatin treatment. The TBR reduction marginally correlated with changes in MMP-9 levels (R = 0.56, p = 0.05). The control group, whose median age was younger, by comparison had lower hsCRP and arterial TBR than the subjects with atherosclerosis (all p < 0.05), and moreover had a slight but insignificant increase in mean TBR at their 2.5±0.8 year follow-up. The medium dose of atorvastatin over a 12-week period resulted in a significant reduction of

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men.

Science.gov (United States)

Veldhuis, Johannes D; Olson, Thomas P; Takahashi, Paul Y; Miles, John M; Joyner, Michael J; Yang, Rebecca J; Wigham, Jean

2015-09-01

Exercise evokes pulsatile GH release followed by autonegative feedback, whereas glucose suppresses GH release followed by rebound-like GH release (feedforward escape). Here we test the hypothesis that age, sex steroids, insulin, body composition and physical power jointly determine these dynamic GH responses. This was a prospectively randomized glucose-blinded study conducted in the Mayo Center for Advancing Translational Sciences in healthy men ages 19-77 years (N=23). Three conditions, fasting/rest/saline, fasting/exercise/saline and fasting/rest/iv glucose infusions, were used to drive GH dynamics during 10-min blood sampling for 6h. Linear correlation analysis was applied to relate peak/nadir GH dynamics to age, sex steroids, insulin, CT-estimated abdominal fat and physical power (work per unit time). Compared with the fasting/rest/saline (control) day, fasting/exercise/saline infusion evoked peak GH within 1h, followed by negative feedback 3-5h later. The dynamic GH excursion was strongly (R(2)=0.634) influenced by (i) insulin negatively (P=0.011), (ii) power positively (P=0.0008), and (iii) E2 positively (P=0.001). Dynamic glucose-modulated GH release was determined by insulin negatively (P=0.0039) and power positively (P=0.0034) (R(2)=0.454). Under rest/saline, power (P=0.031) and total abdominal fat (P=0.012) (R(2)=0.267) were the dominant correlates of GH excursions. In healthy men, dynamic GH perturbations induced by exercise and glucose are strongly related to physical power, insulin, estradiol, and body composition, thus suggesting a network of regulatory pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial.

Science.gov (United States)

Berwanger, Otavio; Santucci, Eliana Vieira; de Barros E Silva, Pedro Gabriel Melo; Jesuíno, Isabella de Andrade; Damiani, Lucas Petri; Barbosa, Lilian Mazza; Santos, Renato Hideo Nakagawa; Laranjeira, Ligia Nasi; Egydio, Flávia de Mattos; Borges de Oliveira, Juliana Aparecida; Dall Orto, Frederico Toledo Campo; Beraldo de Andrade, Pedro; Bienert, Igor Ribeiro de Castro; Bosso, Carlos Eduardo; Mangione, José Armando; Polanczyk, Carisi Anne; Sousa, Amanda Guerra de Moraes Rego; Kalil, Renato Abdala Karam; Santos, Luciano de Moura; Sposito, Andrei Carvalho; Rech, Rafael Luiz; Sousa, Antônio Carlos Sobral; Baldissera, Felipe; Nascimento, Bruno Ramos; Giraldez, Roberto Rocha Corrêa Veiga; Cavalcanti, Alexandre Biasi; Pereira, Sabrina Bernardez; Mattos, Luiz Alberto; Armaganijan, Luciana Vidal; Guimarães, Hélio Penna; Sousa, José Eduardo Moraes Rego; Alexander, John Hunter; Granger, Christopher Bull; Lopes, Renato Delascio

2018-04-03

The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use

Myosin content of single muscle fibers following short-term disuse and active recovery in young and old healthy men

DEFF Research Database (Denmark)

Hvid, Lars G; Brocca, Lorenza; Ørtenblad, Niels

2017-01-01

healthy men. Following disuse, myosin content decreased (p... young and old in both fiber types, with MHC 2a fibers demonstrating an overshooting in young (+31%, pStrong correlations were observed between myosin content and single fiber SF in both young and old, with greater slope steepness in MHC 2a vs 1 fibers indicating an enhanced intrinsic...

Less healthy dietary pattern is associated with smoking in Korean men according to nationally representative data.

Science.gov (United States)

Suh, Sang-Yeon; Lee, Ju Hyun; Park, Sang Shin; Seo, Ah-Ram; Ahn, Hong-Yup; Bae, Woo Kyung; Lee, Yong Joo; Yim, Eunji

2013-06-01

The relationship between smoking and nutrient intake has been widely investigated in several countries. However, Korea presents a population with a smoking rate of approximately 50% and dietary consumption of unique foods. Thus, the aim of this study was to evaluate the association of dietary patterns with smoking in Korean men using a nationally representative sample. The study subjects were comprised of 4,851 Korean men over 19 yr of age who participated in the fourth Korean National Health and Nutrition Examination Survey. Dietary data were assessed by the 24-hr recall method. The smoking group comprised 2,136 men (46.6%). Five dietary patterns were derived using factor analysis: 'sugar & fat', 'vegetables & seafood', 'meat & drinks', 'grains & eggs', and 'potatoes, fruits and dairy products.' Current smokers showed a more significant 'sugar & fat' pattern (P = 0.001) while significantly less of the 'vegetables & seafood' and 'potatoes, fruits and dairy products' patterns (P = 0.011, P Korean male smokers showed less healthy dietary patterns than nonsmokers. Thus, the result of this study underlines the need for health professionals to also provide advice on dietary patterns when counseling patients on smoking cessation.

[Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level].

Science.gov (United States)

Yan, Ling; Ye, Lu; Wang, Kun; Zhou, Jie; Zhu, Chunjia

2016-05-25

Objective: To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels. Methods: One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed. Results: Serum uric acid levels were decreased after treatment in both groups (all P uric acid level ( P uric acid level in patients with hyperuricemia decreased more significantly in the high dose group ( P uric acid levels in two groups ( P >0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels ( P uric acid and 5 had high uric acid ( P uric acid levels and improve reflow after PCI in patients with STEMI.

Simultaneous quantitation of atorvastatin and its two active metabolites in human plasma by liquid chromatography/(– electrospray tandem mass spectrometry

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Pankaj Partani

2014-02-01

Full Text Available A sensitive, accurate and selective liquid chromatography–tandem mass spectrometry method (LC–MS/MS was developed and validated for the simultaneous quantitation of atorvastatin (AT and its equipotent hydroxyl metabolites, 2-hydroxy atorvastatin (2-AT and 4-hydroxy atorvastatin (4-AT, in human plasma. Electrospray ionization (ESI interface in negative ion mode was selected to improve the selectivity and the sensitivity required for this application. Additionally, a solid phase extraction (SPE step was performed to reduce any ion-suppression and/or enhancement effects. The separation of all compounds was achieved in less than 6 min using a C18 reverse-phase fused-core® column and a mobile phase, composed of a mixture of 0.005% formic acid in water:acetonitrile:methanol (35:25:40, v/v/v, in isocratic mode at a flow rate of 0.6 mL/min. The method has lower limit of quantitation (LLOQ of 0.050 ng/mL for all analytes. The method has shown tremendous reproducibility, with intra- and inter-day precision less than 6.6%, and intra- and inter-day accuracy within ±4.3% of nominal values, for all analytes, and has proved to be highly reliable for the analysis of clinical samples. Keywords: Atorvastatin, LC–MS/MS, Solid phase extraction, Pharmacokinetics, Method validation

Physically Targeted Intravenous Polyurethane Nanoparticles for Controlled Release of Atorvastatin Calcium

Science.gov (United States)

Eftekhari, Behnaz Sadat; Karkhaneh, Akbar; Alizadeh, Ali

2017-01-01

Background: Intravenous drug delivery is an advantageous choice for rapid administration, immediate drug effect, and avoidance of first-pass metabolism in oral drug delivery. In this study, the synthesis, formulation, and characterization of atorvastatin-loaded polyurethane (PU) nanoparticles were investigated for intravenous route of administration. Method: First, PU was synthesized and characterized. Second, nanoparticles were prepared in four different ratios of drug to polymer through two different techniques, including emulsion-diffusion and single-emulsion. Finally, particle size and polydispersity index, shape and surface morphology, drug entrapment efficiency (EE), drug loading, and in vitro release were evaluated by dynamics light scattering, scanning electron microscopy, and UV visible spectroscopy, respectively. Results: Within two methods, the prepared nanoparticles had a spherical shape and a smooth surface with a diversity of size ranged from 174.04 nm to 277.24 nm in emulsion-diffusion and from 306.5 nm to 393.12 in the single-emulsion method. The highest EE was 84.76%, for (1:4) sample in the emulsion-diffusion method. It has also been shown that in vitro release of nanoparticles, using the emulsion-diffusion method, was sustained up to eight days by two mechanisms: drug diffusion and polymer relaxation. Conclusion: PU nanoparticles, that were prepared by the emulsion-diffusion method, could be used as effective carriers for the controlled drug delivery of poorly water soluble drugs such as atorvastatin calcium. PMID:28532144

The effect of lipid regulation with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction

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Shu XU

2015-11-01

Full Text Available Objective To analyze the effect of intensive lipid regulation treatment with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction.  Methods Ninety-two patients with atherosclerotic cerebral infarction were randomly divided into two groups: observation group (treated by atorvastatin calcium with the dosage of 20 mg/d, N = 46 and control group (treated by diet without lipid-rich food, N=46. Besides, other drugs given to the patients in two groups were the same. The blood lipid levels and the changes of carotid artery plaques in two groups were analyzed and compared before treatment and 3 months after treatment. Results After treatment, the concentrations of total cholesterol [TC, (4.23 ± 0.92 mmol/L vs (5.24 ± 0.68 mmol/L], triglyceride [TG, (2.46 ± 0.28 mmol/L vs (3.33 ± 0.47 mmol/L], low-density lipoprotein cholesterol [LDL-C, (2.52 ± 0.38 mmol/L vs (4.78 ± 0.86 mmol/L] in the patients of observation group were all decreased and significantly lower than those in the control group (P = 0.000, for all, and the concentration of high-density lipoprotein cholesterol [HDL-C, (1.13 ± 0.41 mmol/L vs (0.85 ± 0.32 mmol/L] in the patients of observation group was increased and significantly than that in the control group (P = 0.003. The carotid artery plaque size [(20.25 ± 0.32 mm2 vs (24.42 ± 10.33 mm2] and thickness [(0.59 ± 0.13 mm vs (1.93 ± 0.23 mm] of carotid artery plaques and intima?media thickness [IMT, (1.32 ± 0.67 mm vs (1.63 ± 0.56 mm] of common carotid artery (CCA in the patients of observation group were all significantly lower than those in patients in the control group (P = 0.000, 0.000, 0.010, respectively. Comparing serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, creatine kinase (CK and creatinine (Cr levels after treatment with before treatment, there was no significant difference between 2 groups (P > 0.05, for all.  Conclusions

Synergistic inhibition of interleukin-6 production in adipose stem cells by tart cherry anthocyanins and atorvastatin

Science.gov (United States)

Studies have shown positive correlations between inflammatory cytokines such as interleukin-6 (IL-6) and the development of chronic diseases including cardiovascular disease by activating C-reactive prorein (CRP). Both atorvastatin calcium (lipitor) as well as flavonoid rich fruit such as tart cherr...

The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men

Science.gov (United States)

Browning, Jeffrey D.; Baxter, Jeannie; Satapati, Santhosh; Burgess, Shawn C.

2012-01-01

Fasting promotes triglyceride (TG) accumulation in lean tissues of some animals, but the effect in humans is unknown. Additionally, fasting lipolysis is sexually dimorphic in humans, suggesting that lean tissue TG accumulation and metabolism may differ between women and men. This study investigated lean tissue TG content and metabolism in women and men during extended fasting. Liver and muscle TG content were measured by magnetic resonance spectroscopy during a 48-h fast in healthy men and women. Whole-body and hepatic carbohydrate, lipid, and energy metabolism were also evaluated using biochemical, calorimetric, and stable isotope tracer techniques. As expected, postabsorptive plasma fatty acids (FAs) were higher in women than in men but increased more rapidly in men with the onset of early starvation. Concurrently, sexual dimorphism was apparent in lean tissue TG accumulation during the fast, occurring in livers of men but in muscles of women. Despite differences in lean tissue TG distribution, men and women had identical fasting responses in whole-body and hepatic glucose and oxidative metabolism. In conclusion, TG accumulated in livers of men but in muscles of women during extended fasting. This sexual dimorphism was related to differential fasting plasma FA concentrations but not to whole body or hepatic utilization of this substrate. PMID:22140269

Diets rich in conjugated linoleic acid and vaccenic acid have no effect on blood pressure and isobaric arterial elasticity in healthy young men

DEFF Research Database (Denmark)

Raff, M.; Tholstrup, T.; Sejrsen, K.

2006-01-01

(VA). Healthy young men (n = 60) with a BMI of 22.5 +/- 2 kg/m(2) (mean +/- SD) participated in this double-blind, randomized, 5-wk, parallel intervention study. The participants substituted 115 g of their daily fat intake with fat from 1 of 3 test diets: 1) CLA-diet rich in CLA (4.7 g/d of c9, t11...... in healthy young men compared with a control diet.......- and t10, c12-CLA isomers in equal amounts); 2) VA-diet rich in VA (3.6 g/d); or 3) C-diet, a control diet with a low content of VA and CLA. All test diets were based on milk fat. BP and AE (measured by an oscillometric method) were measured before and after the intervention period. The effects...

Lack of effect of a high-calorie dextrose or maltodextrin meal on postprandial oxidative stress in healthy young men.

Science.gov (United States)

Fisher-Wellman, Kelsey H; Bloomer, Richard J

2010-10-01

Carbohydrate powder in the form of maltodextrin is widely used by athletes for postexercise glycogen resynthesis. There is some concern that such a practice may be associated with a postprandial rise in reactive oxygen and nitrogen species production and subsequent oxidation of macromolecules. This is largely supported by findings of increased oxidative-stress biomarkers and associated endothelial dysfunction after intake of dextrose. To compare the effects of isocaloric dextrose and maltodextrin meals on blood glucose, triglycerides (TAG), and oxidative-stress biomarkers in a sample of young healthy men. 10 men consumed isocaloric dextrose and maltodextrin powder drinks (2.25 g/kg) in a random-order, crossover design. Blood samples were collected premeal (fasting) and at 1, 2, 4, and 6 hr postmeal and assayed for glucose, TAG, malondialdehyde, hydrogen peroxide, nitrate/nitrite, and Trolox-equivalent antioxidant capacity. Significant meal effects were noted for glucose total area under the curve (p=.004), with values higher for the dextrose meal. No other statistically significant meal effects were noted (p>.05). With respect to the 2 (meal)x5 (time) ANOVA, no significant interaction, time, or meal effects were noted for any variable (p>.05), with the exception of glucose, for which a main effect for both meal (pdextrose or maltodextrin, pose little postprandial oxidative insult to young, healthy men. As such, there should be minimal concern over such feedings, even at high dosages, assuming adequate glucose metabolism.

Working towards Men's Health: Findings from the Sefton Men's Health Project

Science.gov (United States)

Robinson, Mark; Robertson, Steve; McCullagh, Jo; Hacking, Sue

2010-01-01

Objective: To evaluate a health improvement initiative aimed at enhancing the health of men in deprived areas. Design: A healthy lifestyle programme was undertaken with men to increase their health knowledge, and encourage behaviour modification and access to health improvement services. A peer mentoring programme was implemented and a training…

Different Associations of Trunk and Lower-Body Fat Mass Distribution with Cardiometabolic Risk Factors between Healthy Middle-Aged Men and Women

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Bin Wu

2018-01-01

Full Text Available The aim of this study was to assess whether the gender-specific pattern of fat mass (FM distribution is related to gender differences in cardiometabolic risk factors. 207 healthy middle-aged Japanese were included in the study. We measured FM in the total body, trunk, and lower-body with dual-energy X-ray absorptiometry (DXA. The percentage of trunk FM (TFM and lower-body FM (LFM is noted as %TFM and %LFM, respectively. Other measurements included glucose and insulin during oral glucose tolerance test (OGTT, leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1, tumor necrosis factor-α (TNF-α, C-reactive protein (CRP, and systemic oxidative stress marker. Arterial properties were indicated by cardio-ankle vascular index (CAVI and intima-media thickness (IMT of the common carotid artery. The results showed that %TFM is higher whereas %LFM is lower in men than in women and men have a more atherogenic cardiometabolic profile. In both genders, %TFM (%LFM is related to an unfavorable (favorable cardiometabolic profile. In particular, the relation between %LFM and OGTT-derived insulin sensitivity index is stronger in women than in men. These findings suggested that in relatively healthy adults, android and gynoid pattern of FM distribution contributes to gender differences in cardiometabolic risk factors.

Acute psychosocial stress and everyday moral decision-making in young healthy men: The impact of cortisol.

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Singer, Nina; Sommer, Monika; Döhnel, Katrin; Zänkert, Sandra; Wüst, Stefan; Kudielka, Brigitte M

2017-07-01

In everyday life, moral decisions must frequently be made under acute stress. Although there is increasing evidence that both stress and cortisol affect moral judgment and behavior as well as decision-making in various domains unrelated to morality, surprisingly few attempts have been made to explore the effects of stress on everyday moral decision-making. Therefore, in the present study, we exposed 50 young healthy men to the Trier Social Stress Test (TSST) or its non-stressful placebo version (PTSST). We investigated the impact of acute stress exposure and stress-related cortisol levels on decision-making, decision certainty, and emotions in 28 everyday moral conflict situations with altruistic versus egoistic response alternatives. Results showed that the TSST-exposed group made more altruistic decisions than the non-stress control group, while groups did not differ in decision certainty and emotion ratings. Moreover, in correlational as well as regression analyses, additionally controlling for confounding variables, we observed significant positive associations between cortisol levels and altruistic decision-making. Further analyses revealed that altruistic decisions came along with significantly higher decision certainty and significantly more positive emotion ratings than egoistic decisions. Notably, our data also raise the idea that the personality trait agreeableness plays an important role in everyday moral decision-making. In sum, our findings provide initial evidence that both acute stress exposure and cortisol levels have prosocial effects on everyday moral decision-making in young healthy men. Copyright © 2017 Elsevier Inc. All rights reserved.

High Cardiorespiratory Fitness Is Negatively Associated with Daily Cortisol Output in Healthy Aging Men.

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Francesco Lucertini

Full Text Available Physical fitness has salutary psychological and physical effects in older adults by promoting neuroplasticity and adaptation to stress. In aging, however, the effects of fitness on the hypothalamic-pituitary-adrenal (HPA axis are mixed. We investigated the association between cardiorespiratory fitness and HPA activity in healthy elderly men (n = 22, mean age 68 y; smokers, obese subjects, those taking drugs or reporting recent stressful events were excluded, by measuring in saliva: i daily pattern of cortisol secretion (6 samples: 30' post-awakening, and at 12.00, 15.00, 18.00, 21.00, 24.00 h; and ii the cortisol response to a mental challenge. Cardiorespiratory fitness (VO2max was estimated using the Rockport Walking Test and the participants were assigned to high-fit (HF, ≥60°, n = 10 and low-fit (LF, ≤35°, n = 12 groups according to age-specific percentiles of VO2max distribution in the general population. At all daytimes, basal cortisol levels were lower in the HF than the LF group, most notably in the evening and midnight samples, with a significant main effect of physical fitness for cortisol levels overall; the area-under-the-curve for total daily cortisol output was significantly smaller in the HF group. Among the subjects who responded to mental stress (baseline-to-peak increment >1.5 nmol/L; n = 13, 5 LF, 8 HF, the amplitude of cortisol response and the steepness of recovery decline displayed an increasing trend in the HF subjects, although between-group differences failed to reach the threshold for significance. In conclusion, cardiorespiratory fitness in healthy aging men is negatively correlated with daily cortisol output and contributes to buffering the HPA dysregulation that occurs with advancing age, thus possibly playing a beneficial role in contrasting age-related cognitive and physical decline.

Endothelial glycocalyx integrity is preserved in young, healthy men during a single bout of strenuous physical exercise.

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Majerczak, J; Duda, K; Chlopicki, S; Bartosz, G; Zakrzewska, A; Balcerczyk, A; Smoleński, R T; Zoladz, J A

2016-06-20

In the present study we aimed to evaluate whether oxidative stress and inflammation induced by strenuous exercise affect glycocalyx integrity and endothelial function. Twenty one young, untrained healthy men performed a maximal incremental cycling exercise - until exhaustion. Markers of glycocalyx shedding (syndecan-1, heparan sulfate and hyaluronic acid), endothelial status (nitric oxide and prostacyclin metabolites - nitrate, nitrite, 6-keto-prostaglandin F(1alpha)), oxidative stress (8-oxo-2'-deoxyguanosine) and antioxidant capacity (uric acid, non-enzymatic antioxidant capacity) as well as markers of inflammation (sVCAM-1 and sICAM-1) were analyzed in venous blood samples taken at rest and at the end of exercise. The applied strenuous exercise caused a 5-fold increase in plasma lactate and hypoxanthine concentrations (p<0.001), a fall in plasma uric acid concentration and non-enzymatic antioxidant capacity (p<10(-4)), accompanied by an increase (p=0.003) in sVCAM-1 concentration. Plasma 6-keto-prostaglandin F(1alpha) concentration increased (p=0.006) at exhaustion, while nitrate and nitrite concentrations were not affected. Surprisingly, no significant changes in serum syndecan-1 and heparan sulfate concentrations were observed. We have concluded, that a single bout of severe-intensity exercise is well accommodated by endothelium in young, healthy men as it neither results in evident glycocalyx disruption nor in the impairment of nitric oxide and prostacyclin production.

Risk factors for impaired health status differ in women and men treated with percutaneous coronary intervention in the drug-eluting stent era

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Pedersen, Susanne S.; Ong, Andrew T L; Lemos, Pedro A

2006-01-01

In patients treated with percutaneous coronary intervention (PCI) in the drug-eluting stent era, we compared women's and men's health status 6 and 12 months post-PCI and investigated whether predictors of poor health status at 12 months are similar for women and men....

Effect of argan and olive oil consumption on the hormonal profile of androgens among healthy adult Moroccan men.

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Derouiche, Abdelfettah; Jafri, Ali; Driouch, Issam; El Khasmi, Mohammed; Adlouni, Ahmed; Benajiba, Nada; Bamou, Youssef; Saile, Rachid; Benouhoud, Mohammed

2013-01-01

This study aimed to assess the effect of virgin argan oil (VAO) and extra virgin olive oil (EVO) on the hormonal profile of androgens and anthropometric parameters among healthy adult Moroccan men during a controlled nutritional intervention. The study was carried out on 60 young and healthy male volunteers aged between 23 and 40 years old. During a stabilization period of 2 weeks they consumed butter. The group was then randomized into two categories, the first one consuming VAO and the second EVO for 3 weeks. Testosterone (T), luteinizing hormone (LH) and dehydroepiandrosterone (DHEAS) serum concentrations were measured at the beginning of the study and at the end of each period. The Mann-Whitney test was used to compare the two groups (VAO and EVO) during each step of the study. Differences in androgens and anthropometric parameters between the baseline and after 3 weeks of the diet in the VAO and EVO groups were analyzed using the Wilcoxon test. T and LH serum concentrations significantly increased after the intervention period. T levels increased by 19.9% and 17.4% (p consumption of AVO and EVO might be the origin of a positive action on the androgen hormonal profile of men.

Increased nocturnal fat oxidation in young healthy men with low birth weight

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Brøns, Charlotte; Lilleøre, S K; Jensen, C B

2013-01-01

OBJECTIVE: Low birth weight (LBW), a marker of disturbed fetal growth, is associated with adiposity and increased risk of type 2 diabetes (T2D). The aim of the study was to investigate whether LBW is associated with changes in 24-h energy expenditure (EE) and/or substrate utilization rates......, potentially contributing to the development of adiposity and/or T2D compared to matched control subjects. MATERIALS/METHODS: Forty-six young, healthy men were included in the study; 20 with LBW (= 10th percentile) and 26 control subjects with normal birth weight (NBW) (50th-90th percentile). The subjects were...... fed a weight maintenance diet and 24-h energy expenditure (EE), respiratory quotient (RQ), and substrate oxidation were assessed in a respiratory chamber. RESULTS: No differences in 24-h EE, RQ or substrate oxidation were observed between LBW and controls. Interestingly, the LBW group exhibited lower...

The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-{sup 11}C]WAY-100635

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Stein, Patrycja; Savli, Markus; Fink, Martin; Spindelegger, Christoph; Moser, Ulrike; Kasper, Siegfried; Lanzenberger, Rupert [Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna (Austria); Wadsak, Wolfgang; Dudczak, Robert; Kletter, Kurt [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Mitterhauser, Markus; Mien, Leonhard-Key [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); University of Vienna, Department of Pharmaceutical Technology, Vienna (Austria)

2008-12-15

The higher prevalence rates of depression and anxiety disorders in women compared to men have been associated with sexual dimorphisms in the serotonergic system. The present positron emission tomography (PET) study investigated the influence of sex on the major inhibitory serotonergic receptor subtype, the serotonin-1A (5-HT{sub 1A}) receptor. Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [carbonyl-{sup 11}C]WAY-100635. Effects of age or gonadal hormones were excluded by restricting the inclusion criteria to young adults and by controlling for menstrual cycle phase. The 5-HT{sub 1A} receptor BP{sub ND} was quantified using (1) the 'gold standard' manual delineation approach with ten regions of interest (ROIs) and (2) a newly developed delineation method using a PET template normalized to the Montreal Neurologic Institute space with 45 ROIs based on automated anatomical labeling. The 5-HT{sub 1A} receptor BP{sub ND} was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BP{sub ND} values in every region investigated, with a borderline significant sex difference in the hypothalamus (p=0.012, uncorrected). There was a high intersubject variability of the 5-HT{sub 1A} receptor BP{sub ND} within both sexes compared to the small mean differences between men and women. To conclude, when measured in the follicular phase, women do not differ from men in the 5-HT{sub 1A} receptor binding. To explain the higher prevalence of affective disorders in women, further studies are needed to evaluate the relationship between hormonal status and the 5-HT{sub 1A} receptor expression. (orig.)

Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men.

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Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik; Vranes, Milan

2016-09-01

In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P creatine for improved bioenergetics in energy-demanding tissues.

" . . . I Should Maintain a Healthy Life Now and Not Just Live as I Please . . . ": Men's Health and Fatherhood in Rural South Africa.

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Hosegood, Victoria; Richter, Linda; Clarke, Lynda

2016-11-01

This study examines the social context of men's health and health behaviors in rural KwaZulu-Natal, South Africa, particularly in relationship to fathering and fatherhood. Individual interviews and focus groups were conducted with 51 Zulu-speaking men. Three themes related to men's health emerged from the analysis of transcripts: (a) the interweaving of health status and health behaviors in descriptions of "good" and "bad" fathers, (b) the dominance of positive accounts of health and health status in men's own accounts, and (c) fathers' narratives of transformations and positive reinforcement in health behaviors. The study reveals the pervasiveness of an ideal of healthy fathers, one in which the health of men has practical and symbolic importance not only for men themselves but also for others in the family and community. The study also suggests that men hold in esteem fathers who manage to be involved with their biological children who are not coresident or who are playing a fathering role for nonbiological children (social fathers). In South Africa, men's health interventions have predominantly focused on issues related to HIV and sexual health. The new insights obtained from the perspective of men indicate that there is likely to be a positive response to health interventions that incorporate acknowledgment of, and support for, men's aspirations and lived experiences of social and biological fatherhood. Furthermore, the findings indicate the value of data on men's involvement in families for men's health research in sub-Saharan Africa. © The Author(s) 2015.

Comparison Between the Effects of the Alcholic Extract of Mellissia Officinalis and Atorvastatin on Serum Levels of Thyroid Hormones in Hypercholesterolemic Male Rats

Directory of Open Access Journals (Sweden)

Ali Zarei

2013-08-01

Full Text Available Background: Consumption of unsaturated fats reduces the serum level of lipids and leptin. Thyroid hormones and leptin play pivotal roles in metabolism and their amounts are inter-related. This study was done to compare the effects of Mellissia officinalis extract and atorvastatin on the serum levels of thyroid hormones in hypercholesterolemia rats.Materials and Methods: Consumption of unsaturated fats reduces the serum level of lipids and leptin. Thyroid hormones and leptin play pivotal roles in metabolism and their amounts are inter-related. This study was done to compare the effects of Mellissia officinalis extract and atorvastatin on the serum levels of thyroid hormones in hypercholesterolemia rats.Results: The results showed that in experimental groups receiving the plant extract and atorvastatin, the concentration of thyroid hormones increased, whereas the amount of the thyroid-stimulating hormone showed a significant decrease (p<0.05.Conclusion: Mellissia officinalis extract decreases TSH but it increases T3 and T4. Further studies are required for applying this extract to the treatment of hyperthyroidism.

HealthyDads.ca: What Do Men Want in a Website Designed to Promote Emotional Wellness and Healthy Behaviors During the Transition to Parenthood?

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Zelkowitz, Phyllis; Letourneau, Nicole; Howlett, Andrew; Dennis, Cindy-Lee; Russell, Brian; Grover, Steven; Lowensteyn, Ilka; Chan, Peter; Khalifé, Samir

2017-01-01

Background Up to 18% of men experience depression and/or anxiety during the transition to parenthood. Interventions designed specifically to promote the mental health of men during the transition to parenthood are scarce. Internet-delivered interventions may be acceptable and far-reaching in enhancing mental health, parenting knowledge, and healthy behaviors in expectant or new fathers. Objective To guide the development of Healthydads.ca, a website designed to enhance mental health and healthy behaviors in expectant fathers, a needs assessment was conducted to identify fathers’ perspectives of barriers to seeking help for emotional wellness, informational needs, and factors affecting the decision to visit such a website. Methods One hundred and seventy-four men whose partners were expecting, or had recently given birth, in 3 Canadian provinces (Quebec, Ontario, and Alberta) completed a Web-based survey inquiring about information needs related to psychosocial aspects of the transition to parenthood, lifestyle behaviors, parenting, and factors associated with the decision to visit a father-focused website. Results Most men (155/174, 89.1%) reported accessing the Internet to obtain information on pregnancy and spent an average of 6.2 hours online per month. Seeking information about parenting on the Internet was reported by 67.2% (117/174) of men, with a mean of 4.4 hours per month of online searching. Top barriers to seeking help to improve emotional wellness during the perinatal period were: no time to seek help/assistance (130/174, 74.7%), lack of resources available in the health care system (126/174, 72.4%), financial costs associated with services (118/174, 67.8%), and feeling that one should be able to do it alone (113/174, 64.9%). Information needs that were rated highly included: parenting/infant care (52.9-81.6%), supporting (121/174, 69.5%) and improving (124/174, 71.3%) relationship with their partner, work-family balance (120/174, 69.0%), improving

Endogenous plasma estradiol in healthy men is positively correlated with cerebral cortical serotonin 2A receptor binding

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Frokjaer, Vibe G.; Erritzoe, David; Juul, Anders

2010-01-01

the effect of plasma sex hormone levels on neocortical 5-HT2A receptor binding as imaged with [18F]altanserin PET. The effect of endogenous sex-hormone levels was evaluated by multiple linear regression analysis. Results: Mean neocortical 5-HT2A receptor binding was positively correlated with estradiol (p......Background: Sex-hormones influence brain function and are likely to play a role in the gender predisposition to mood and anxiety disorders. Acute fluctuations of sex-hormone levels including hormonal replacement therapy appear to affect serotonergic neurotransmission, but it is unknown if baseline...... levels affect serotonergic neurotransmission. This study was undertaken to examine if baseline levels of endogenous sex hormones are associated with cerebral serotonin 2A (5-HT2A) receptor binding in men. Methods: In a group of 72 healthy men (mean age 37.5 years ±17.4 SD, range 19.6–81.7) we studied...

Reference intervals and variation for urinary epinephrine, norepinephrine and cortisol in healthy men and women in Denmark

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Hansen, Åse Marie; Garde, A H; Christensen, J M

2001-01-01

Reference intervals for urinary epinephrine, norepinephrine and cortisol in 120 healthy individuals performing their routine work were established according to the International Union of Pure and Applied Chemistry (IUPAC) and the International Federation of Clinical Chemistry and Laboratory...... Medicine (IFCC) for use in the risk assessment of exposure to occupational stress. Reference intervals were established for three different times of the day: in morning samples (05.45-07.15) the limit of detection (LOD) was 2.10 micromol epinephrine/mol creatinine (82 women) and 2.86 micromol epinephrine....../mol creatinine (37 men), and the reference interval was 3.6-29.1 micromol norepinephrine/mol creatinine and 2.3-52.8 micromol cortisol/mol creatinine (119 women and men); in afternoon samples (15.30-18.30) the reference interval was 0.64-10.8 micromol epinephrine/mol creatinine (82 women), 1.20-11.2 micromol...

Ageing/Menopausal Status in Healthy Women and Ageing in Healthy Men Differently Affect Cardiometabolic Parameters.

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Campesi, Ilaria; Occhioni, Stefano; Tonolo, Giancarlo; Cherchi, Sara; Basili, Stefania; Carru, Ciriaco; Zinellu, Angelo; Franconi, Flavia

2016-01-01

Gender medicine requires a global analysis of an individual's life. Menopause and ageing induce variations of some cardiometabolic parameters, but, it is unknown if this occurs in a sex-specific manner. Here, some markers of oxidative stress, systemic inflammation, and endothelial dysfunction are analysed in men younger and older than 45 years and in pre- and postmenopausal women. Serum and plasma sample were assayed for TNF-α and IL-6, malondialdehyde and protein carbonyls and for methylated arginines using ELISA kits, colorimetric methods and capillary electrophoresis. Before body weight correction, men overall had higher creatinine, red blood cells and haemoglobin and lower triglycerides than women. Men younger than 45 years had lower levels of TNF-α and malondialdehyde and higher levels of arginine than age-matched women, while postmenopausal women had higher IL-6 concentrations than men, and higher total cholesterol, triglycerides, creatinine and IL-6 levels than younger women. Men younger than 45 years had lower total cholesterol and malondialdehyde than older men. After correction, some differences remained, others were amplified, others disappeared and some new differences emerged. Moreover, some parameters showed a correlation with age, and some of them correlated with each other as functions of ageing and ageing/menopausal status. Ageing/menopausal status increased many more cardiovascular risk factors in women than ageing in men, confirming that postmenopausal women had increased vascular vulnerability and indicating the need of early cardiovascular prevention in women. Sex-gender differences are also influenced by body weight, indicating as a matter of debate whether body weight should be seen as a true confounder or as part of the causal pathway.

Soft-tissue facial characteristics of attractive Chinese men compared to normal men.

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Wu, Feng; Li, Junfang; He, Hong; Huang, Na; Tang, Youchao; Wang, Yuanqing

2015-01-01

To compare the facial characteristics of attractive Chinese men with those of reference men. The three-dimensional coordinates of 50 facial landmarks were collected in 40 healthy reference men and in 40 "attractive" men, soft tissue facial angles, distances, areas, and volumes were computed and compared using analysis of variance. When compared with reference men, attractive men shared several similar facial characteristics: relatively large forehead, reduced mandible, and rounded face. They had a more acute soft tissue profile, an increased upper facial width and middle facial depth, larger mouth, and more voluminous lips than reference men. Attractive men had several facial characteristics suggesting babyness. Nonetheless, each group of men was characterized by a different development of these features. Esthetic reference values can be a useful tool for clinicians, but should always consider the characteristics of individual faces.

Kinematics gait disorder in men with fibromyalgia.

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Heredia-Jimenez, Jose M; Soto-Hermoso, Victor M

2014-01-01

The aim of this study was to assess the kinematics disorder of gait in men with fibromyalgia. We studied 12 male with fibromyalgia and 14 healthy men. Each participant of the study walked five trials along a 18.6-m walkway. Fibromyalgia patients completed a Spanish version of Fibromyalgia Impact Questionnaire. Significant differences between fibromyalgia and control groups were found in velocity, stride length, and cadence. Gait parameters of men affected by fibromyalgia were impaired when compared to those of healthy group due to bradykinesia. According to previous studies to assess gait variables in female patients, the male with fibromyalgia also showed lower values of velocity, cadence, and stride length than healthy group but not reported significant differences in swing, stance, single, or double support phase.

Keeping Active and Healthy Eating for Men

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... training recreational swimming jogging fast-paced sports, like football Tips for Getting Fit Visit the "ChooseMyPlate" website ... men over age 40 and those with a history of coronary heart disease or diabetes, should speak ...

In Healthy Young Men, a Short Exhaustive Exercise Alters the Oxidative Stress Only Slightly, Independent of the Actual Fitness.

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Finkler, Maya; Hochman, Ayala; Pinchuk, Ilya; Lichtenberg, Dov

2016-01-01

The aim of the present study was to evaluate the apparent disagreement regarding the effect of a typical cycling progressive exercise, commonly used to assess VO2max, on the kinetics of ex vivo copper induced peroxidation of serum lipids. Thirty-two (32) healthy young men, aged 24-30 years, who do not smoke and do not take any food supplements, participated in the study. Blood was withdrawn from each participant at three time points (before the exercise and 5 minutes and one hour after exercise). Copper induced peroxidation of sera made of the blood samples was monitored by spectrophotometry. For comparison, we also assayed TBARS concentration and the activity of oxidation-related enzymes. The physical exercise resulted in a slight and reversible increase of TBARS and slight changes in the activities of the studied antioxidant enzymes and the lag preceding peroxidation did not change substantially. Most altered parameters returned to baseline level one hour after exercise. Notably, the exercise-induced changes in OS did not correlate with the physical fitness of the subjects, as evaluated in this study (VO2max = 30-60 mL/min/kg). We conclude that in healthy young fit men a short exhaustive exercise alters only slightly the OS, independent of the actual physical fitness.

The effects of gamma radiation on 2,3-diphosphoglycerate (2,3-DFG) content in healthy men's erythrocytes after submaximal physical exercise

International Nuclear Information System (INIS)

Dudek, I.; Zagorski, T.; Kedziora, J.

1987-01-01

The effects of gamma radiation and submaximal physical exercise on 2,3-DFG content in healthy men erythrocytes were studied. Twelve men aged 20-22 were examined. They were loaded by physical exrecise (at doses of 2 M/kg body weight) for 15 minutes. Erythrocytes were exposed to gamma radiation (500 Gy doses) from a 60 Co source. The concentration of 2,3-DFG in erythrocytes was estimated by Bartlett's method. Gamma radiation was found to decrese 2,3-DFG content in erythrocytes both at rest and after submaximal exercise. Furthermore, submaximal physical exercise was found to decrease 2,3-DFG content in non-irradiated erythrocytes. 20 refs., 1 tab. (author)

Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

International Nuclear Information System (INIS)

Nanda, Akash; Chen, M.-H.; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

2010-01-01

Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score ≥8, or clinical category ≥T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

Effect of short-term intensive atorvastatin treatment on interventional treatment effect and cardiac function of patients with acute coronary syndrome

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Yu Lei

2016-06-01

Full Text Available Objective: To study the effect of short-term intensive atorvastatin treatment on interventional treatment effect and cardiac function of patients with acute coronary syndrome. Methods: A total of 104 cases of patients with acute coronary syndrome who received PCI treatment in Emergency Department of our hospital from May 2014 to November 2015 were retrospectively analyzed and divided into intensive group and routine group according to different atorvastatin treatment methods, and then biochemical indexes, cardiac ultrasound indicators and inflammatory indexes of two groups were compared. Results: Serum TG, TC, LDL-C, hs- CRP, LDH, α-HBDH, CK and CK-MB content of intensive group were significantly lower than those of routine group while HDL-C content was higher than that of routine group; E/ A ratio and LVEF of intensive group were higher than those of routine group while Tei index, systolic index and diastolic index were lower than those of routine group; TLR4 and NF-kB expression levels in peripheral blood as well as TNF-α and IL-6 content in serum of intensive group were significantly lower than those of routine group. Conclusion: Short-term intensive atorvastatin treatment improves the interventional treatment effect of patients with acute coronary syndrome, and can reduce myocardial injury, improve cardiac diastolic and systolic function and inhibit the inflammation mediated by TLR4/NF-kB.

The HAT TRICK programme for improving physical activity, healthy eating and connectedness among overweight, inactive men: study protocol of a pragmatic feasibility trial.

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Caperchione, Cristina M; Bottorff, Joan L; Oliffe, John L; Johnson, Steven T; Hunt, Kate; Sharp, Paul; Fitzpatrick, Kayla M; Price, Ryley; Goldenberg, S Larry

2017-09-06

Physical activity, healthy eating and maintaining a healthy weight are associated with reduced risk of cardiovascular disease, type 2 diabetes and cancer and with improved mental health. Despite these benefits, many men do not meet recommended physical activity guidelines and have poor eating behaviours. Many health promotion programmes hold little appeal to men and consequently fail to influence men's health practices. HAT TRICK was designed as a 12-week face-to-face, gender-sensitised intervention for overweight and inactive men focusing on physical activity, healthy eating and social connectedness and was delivered in collaboration with a major junior Canadian ice hockey team (age range 16-20 years). The programme was implemented and evaluated to assess its feasibility. This article describes the intervention design and study protocol of HAT TRICK. HAT TRICK participants (n=60) were men age 35 years, residing in the Okanagan Region of British Columbia, who accumulate 150 min of moderate to vigorous physical activity a week, with a body mass index of >25 kg/m 2 and a pant waist size of >38'. Each 90 min weekly session included targeted health education and theory-guided behavioural change techniques, as well as a progressive (ie, an increase in duration and intensity) group physical activity component. Outcome measures were collected at baseline, 12 weeks and 9 months and included the following: objectively measured anthropometrics, blood pressure, heart rate, physical activity and sedentary behaviour, as well as self-reported physical activity, sedentary behaviour, diet, smoking, alcohol consumption, sleep habits, risk of depression, health-related quality of life and social connectedness. Programme feasibility data (eg, recruitment, satisfaction, adherence, content delivery) were assessed at 12 weeks via interviews and self-report. Ethical approval was obtained from the University of British Columbia Okanagan Behavioural Research Ethics Board (reference no H

Treating chancroid with enoxacin.

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Naamara, W; Kunimoto, D Y; D'Costa, L J; Ndinya-Achola, J O; Nsanze, H; Ronald, A R; Plummer, F A

1988-01-01

Increasing resistance of Haemophilus ducreyi to antimicrobials necessitates further trials of new antimicrobial agents for treating chancroid. Enoxacin has excellent in vitro activity against H ducreyi, and a randomised clinical trial of three doses of enoxacin 400 mg at intervals of 12 hours compared with a single dose of trimethoprim/sulphametrole (TMP/SMT) 640/3200 mg was therefore conducted. Of 169 men enrolled in the study, 86 received enoxacin and 83 received TMP/SMT. Ulcers were improved or cured in 65/73 men treated with enoxacin and 57/70 men treated with TMP/SMT. This difference was not significant. At 72 hours after treatment, H ducreyi was eradicated from ulcers of 72/77 men treated with enoxacin and of 67/74 of those treated with TMP/SMT. Patients with buboes responded equally well to both treatments. Of 100 H ducreyi strains tested, all were susceptible to both 0.25 mg/l enoxacin and the combination of 0.25 mg/l TMP and 5 mg/l SMT. Although most men treated with either regimen were cured, neither regimen appeared to be the optimum treatment for chancroid. This study shows the efficacy of enoxacin for a soft tissue infection caused by Gram negative organisms. PMID:3044978

Plasma triglycerides and cardiovascular events in the Treating to New Targets and Incremental Decrease in End-Points through Aggressive Lipid Lowering trials of statins in patients with coronary artery disease

DEFF Research Database (Denmark)

Faergeman, Ole; Holme, Ingar; Fayyad, Rana

2009-01-01

We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg...

Effects of atorvastatin and T-786C polymorphism of eNOS gene on plasma metabolic lipid parameters.

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Zago, Vanessa Helena de Souza; Santos, José Eduardo Tanus dos; Danelon, Mirian Regina Gardin; Silva, Roger Marcelo Mesquita da; Panzoldo, Natália Baratella; Parra, Eliane Soler; Alexandre, Fernanda; Virgínio, Vítor Wilson de Moura; Quintão, Eder Carlos Rocha; Faria, Eliana Cotta de

2013-01-01

Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.

HealthyDads.ca: What Do Men Want in a Website Designed to Promote Emotional Wellness and Healthy Behaviors During the Transition to Parenthood?

Science.gov (United States)

Da Costa, Deborah; Zelkowitz, Phyllis; Letourneau, Nicole; Howlett, Andrew; Dennis, Cindy-Lee; Russell, Brian; Grover, Steven; Lowensteyn, Ilka; Chan, Peter; Khalifé, Samir

2017-10-11

Up to 18% of men experience depression and/or anxiety during the transition to parenthood. Interventions designed specifically to promote the mental health of men during the transition to parenthood are scarce. Internet-delivered interventions may be acceptable and far-reaching in enhancing mental health, parenting knowledge, and healthy behaviors in expectant or new fathers. To guide the development of Healthydads.ca, a website designed to enhance mental health and healthy behaviors in expectant fathers, a needs assessment was conducted to identify fathers' perspectives of barriers to seeking help for emotional wellness, informational needs, and factors affecting the decision to visit such a website. One hundred and seventy-four men whose partners were expecting, or had recently given birth, in 3 Canadian provinces (Quebec, Ontario, and Alberta) completed a Web-based survey inquiring about information needs related to psychosocial aspects of the transition to parenthood, lifestyle behaviors, parenting, and factors associated with the decision to visit a father-focused website. Most men (155/174, 89.1%) reported accessing the Internet to obtain information on pregnancy and spent an average of 6.2 hours online per month. Seeking information about parenting on the Internet was reported by 67.2% (117/174) of men, with a mean of 4.4 hours per month of online searching. Top barriers to seeking help to improve emotional wellness during the perinatal period were: no time to seek help/assistance (130/174, 74.7%), lack of resources available in the health care system (126/174, 72.4%), financial costs associated with services (118/174, 67.8%), and feeling that one should be able to do it alone (113/174, 64.9%). Information needs that were rated highly included: parenting/infant care (52.9-81.6%), supporting (121/174, 69.5%) and improving (124/174, 71.3%) relationship with their partner, work-family balance (120/174, 69.0%), improving sleep (100/174, 57.5%), and managing

Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.

OpenAIRE

Seibert Julia; Hysek Cédric M; Penno Carlos A; Schmid Yasmin; Kratschmar Denise V; Liechti Matthias E; Odermatt Alex

2014-01-01

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-h plasma steroid profiles. Sixteen healthy subjects (eight men, eight women) were treated with single doses of M...

Men's re-placement: Social practices in a Men's Shed.

Science.gov (United States)

Anstiss, David; Hodgetts, Darrin; Stolte, Ottilie

2018-05-06

Transitions into retirement can be difficult at the best of times. Many men find themselves having to reflect on who they are and what their lives are about. Their access to social supports and material resources are often disrupted. Men's Sheds offer a space where retired men can actively pursue wellbeing, and respond to disruption and loneliness through emplaced community practices. This paper draws on ethnographic research in a Men's Shed in Auckland, New Zealand in order to explore the social practices through which men create a shared space for themselves in which they can engage in meaningful relationships with each other. We document how participants work in concert to create a space in which they can be together through collective labour. Their emplacement in the shed affords opportunities for supported transitions into retirement and for engaging healthy lives beyond paid employment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Monitoring of macrophage accumulation in statin-treated atherosclerotic mouse model using sodium iodide symporter imaging system

International Nuclear Information System (INIS)

Yoo, Ran Ji; Kim, Min Hwan; Woo, Sang-Keun; Kim, Kwang Il; Lee, Tae Sup; Choi, Yang-Kyu; Kang, Joo Hyun; Lim, Sang Moo; Lee, Yong Jin

2017-01-01

Introduction: Macrophages play a key role in atherosclerotic plaque formation in atherosclerosis, but its detailed understanding has poorly investigated until now. Thus, we sought to demonstrate a noninvasive technique for macrophage tracking to atherosclerotic lesions in apolipoprotein E −/− (ApoE −/− ) mice with an imaging system based on sodium iodide symporter (NIS) gene coupled with 99m Tc-single-photon emission computed tomography (SPECT). Methods and results: Macrophage cells (RAW264.7) were stably transduced with retrovirus expressing NIS gene (RAW-NIS). In RAW-NIS cells, uptake of 125 I was higher than the parental cells. [ 18 F]FDG signals in the aorta at 30 weeks on an ApoE −/− mice with high cholesterol diet were higher (1.7 ± 0.12% injected dose (ID)) than those in control group (0.84 ± 0.06% ID). Through 99m Tc-SPECT/computed tomography (CT), in the RAW-NIS cell injected group, the 99m Tc-pertechnetate uptake in aorta was higher than control groups. However, according to atorvastatin treatment, RAW-NIS cell recruitment reduced to the aorta. Area of 99m Tc-pertechnetate uptake was positively correlated with immunostaining results against macrophage antigen (CD68). Cholesterol and low-density lipoprotein levels of atorvastatin-treated group showed lower than those of atorvastatin-untreated group, but did not reach statistical difference. Conclusions: This novel approach to tracking macrophages to atherosclerotic plaques in vivo can be applied for studies of arterosclerotic vascular disease.

Reduced Oxidative Stress in STEMI Patients Treated by Primary Percutaneous Coronary Intervention and with Antioxidant Therapy

DEFF Research Database (Denmark)

Ekeløf, Sarah; Jensen, Svend Eggert; Rosenberg, Jacob

2014-01-01

performed a systematic search in EMBASE and Pubmed and included eight randomised clinical trials evaluating edaravone, allopurinol, vitamin c, nicorandil, N-acetylcysteine, glucose-insulin-potassium, atorvastatin and deferoxamine. RESULTS: Administration of edaravone, allopurinol, atorvastatin....... CONCLUSIONS: Preliminary studies of edaravone, allopurinol, atorvastatin and nicorandil seems promising though larger clinical trials with a wider range of clinical outcome parameters and trials of higher methodological quality should confirm the clinical benefits before a general recommendation can be given...

Long-term gastrointestinal tolerance of NUTRIOSE FB in healthy men.

Science.gov (United States)

Pasman, W; Wils, D; Saniez, M-H; Kardinaal, A

2006-08-01

To determine the gastrointestinal (GI) tolerance of NUTRIOSE FB in men. A randomized, placebo-controlled, parallel, double-blind study. The metabolic ward of TNO Quality of Life. Forty-eight subjects started the study: 16 men participated in one of the three treatments. SUBJECTS consumed either 22.5 g of pure maltodextrin (Glucidex 6), or 30 or 45 g of the dextrin NUTRIOSE FB daily for 4-5 weeks. Forty-three subjects completed the study (age: 34.7 +/- 8.2 years; BMI 24.9 +/- 3.3 kg m2). Tolerance of NUTRIOSE FB was examined with a GI complaints questionnaire; effectiveness on colonic flora was examined by faecal analysis; fermentation by breath hydrogen excretion measurement. Furthermore, the effect on body weight (BW), energy intake and blood parameters were examined in the study. Both doses of NUTRIOSE FB were very well tolerated and GI complaints hardly differed from the placebo treatment. No diarrhoea was reported due to NUTRIOSE FB supplementation. In the course of the study, some habituation and adaptation of GI symptoms were found. Fermentation and faecal characteristics (pH and enzyme activity) were significantly positively affected with NUTRIOSE FB treatment. Body weight in both NUTRIOSE FB groups remained stable over time, although the placebo-treated group showed a small increase in BW (Deltaday35-1 0.8 +/- 1.0 kg) (P = 0.07). However, total food intake and macronutrient composition of the diet remained the same throughout the study. No significant differences were found between the three treatment groups in hunger and satiety scores and food preferences. Long-term supplementation of 30 or 45 g of the dextrin NUTRIOSE FB per day was well tolerated, and may act as a pre-biotic supplement. TNO Quality of Life was assigned by Roquette Frères to perform the study.

Intraindividual variation of triiodothyronine, thyroxine, thyrotropin and thyroxine-binding globulin in fasting serum from healthy men

International Nuclear Information System (INIS)

Liappis, N.; Hoffmann, U.; Rao, M.L.

1986-01-01

The concentrations of triiodothyronine, thyroxine, thyrotropin and thyroxine-binding globulin were determined in fasting serum from 11 healthy men (age 18-25 years) by radioimmunoassays conducted over a period of 4 weeks on 5 consecutive days per week. The concentrations of thyroxine and thyroxine-binding globulin were very consistent intraindividually, with coefficients of variation of 7.84% and 9.37%, respectively. The triiodothyronine and thyrotropin levels showed significant intraindividual variability with coefficients of variation of 18.38% and 51.85%, respectively. These results point to the type of difficulties encountered in judging serum values, namely intraindividual variations over a given period of time. (orig.) [de

Physical health, self-reliance, and emotional control as moderators of the relationship between locus of control and mental health among men treated for prostate cancer.

Science.gov (United States)

Burns, Shaun Michael; Mahalik, James R

2006-12-01

This investigation examined the moderating effects of physical health and scripts for masculinity (i.e., self-reliance and emotional control) on the relationship between powerful other people locus of control and mental health for 230 men treated for prostate cancer. Regression analyses indicated that physical health and masculine gender scripts moderated the association between powerful other people locus of control and mental health. Specifically, men with poor physical health evinced negative mental health when they endorsed masculine gender scripts and believed powerful other people (i.e., family, friends, or peers) were influential in controlling their cancer. By comparison, men reporting poor physical health, strong beliefs that powerful other people controlled their cancer, and less adherence to masculine scripts experienced positive mental health. The authors discuss future research directions and potential mental health implications for men treated for prostate cancer.

A comparative study of the effect of green tea and sour tea on blood pressure and lipid profile in healthy adult men

Directory of Open Access Journals (Sweden)

Marzieh Kafeshani

2017-06-01

Full Text Available BACKGROUND: Cardiovascular diseases (CVD are a set of metabolic disorders affecting heart and blood vessels. Green tea and sour tea (Hibiscus sabdariffa L. have attracted significant attention recently due to their high popularity, nutrient profile and therapeutic effects. The aim of the present study was to compare the effects of green tea and sour tea supplementation on blood pressure and lipid profile in healthy adult men. METHODS: This randomized, double-blind, placebo-controlled trial included 54 healthy adult men. The participants were randomly assigned to two intervention groups receiving 450 mg green tea or sour tea and one placebo group which consumed 450 mg placebo (maltodextrin for 6 weeks. Blood pressure, lipid profile, dietary intake and physical activity were measured pre- and post-intervention and compared. RESULTS: After 6 weeks of intervention, sour tea supplementation led to a significant decrease in systolic blood pressure (SBP compared with the placebo group. However, we faild to find any significant difference in SBP between green tea and control groups. Also, no significant changes were observed in diastolic blood pressure (DBP and lipid profile between the three groups. In comparison with baseline, there was a significant increase in the mean level of serum high-density lipoprotein cholesterol (HDL-C in green tea and sour tea groups. Also, the interventions resulted in significant decrease in the mean levels of serum total cholesterol (TC and low-density lipoprotein cholesterol (LDL-C and DBP in the sour tea group compared with the pre-intervention value. CONCLUSION: On the basis of our findings, sour tea supplementation led to decreased SBP in healthy men compared with the placebo, but there was no significant difference between their effects on DBP and lipid profile. 

Effect of 8-Week of Selected Aerobic Exercise on Static and Dynamic Balance in Healthy Elderly Inactive Men

OpenAIRE

Masoud Mirmoezzi; Mojtaba Amini; Asghar Khaledan; Davood Khorshidi

2016-01-01

Objectives: Old age refers to years near or passed the middle age and therefore, near to the end of life cycle. Old-aged people have limited reviving capability and are more at risk of catching diseases, syndromes, and ailments. Falling is one of the most common problems in the elderly that occur due to their inability to maintain balance. This study aimed to examine the effect of aerobic exercises on static and dynamic balance in healthy elderly inactive men. Methods &...

Effect of Prior Atorvastatin Treatment on the Frequency of Hospital Acquired Pneumonia and Evolution of Biomarkers in Patients with Acute Ischemic Stroke: A Multicenter Prospective Study

Directory of Open Access Journals (Sweden)

Yuetian Yu

2017-01-01

Full Text Available Objective. To investigate whether prior treatment of atorvastatin reduces the frequency of hospital acquired pneumonia (HAP. Methods. Totally, 492 patients with acute ischemic stroke and Glasgow Coma Scale ≤ 8 were enrolled in this study. Subjects were assigned to prior atorvastatin treatment group (n=268, PG and no prior treatment group (n=224, NG. All the patients were given 20 mg atorvastatin every night during their hospital stay. HAP frequency and 28-day mortality were measured. Levels of inflammatory biomarkers [white blood cell (WBC, procalcitonin (PCT, tumor necrosis factor-alpha (TNF-α, and interleukin-6 (IL-6] were tested. Results. There was no significant difference in the incidence of HAP between PG and NG (25.74% versus. 24.55%, p>0.05 and 28-day mortality (50.72% versus 58.18%, p>0.05. However, prior statin treatment did modify the mortality of ventilator associated pneumonia (VAP (36.54% versus 58.14%, p=0.041 and proved to be a protective factor (HR, 0.564; 95% CI, 0.310~0.825, p=0.038. Concentrations of TNF-α and IL-6 in PG VAP cases were lower than those in NG VAP cases (p<0.01. Conclusions. Prior atorvastatin treatment in patients with ischemic stroke was associated with a lower concentration of IL-6 and TNF-α and improved the outcome of VAP. This clinical study has been registered with ChiCTR-ROC-17010633 in Chinese Clinical Trial Registry.

Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men.

Science.gov (United States)

Van Proeyen, Karen; Ramaekers, Monique; Pischel, Ivo; Hespel, Peter

2012-08-01

The purpose of this study was to investigate the effect of Opuntia ficus-indica (OFI) cladode and fruit-skin extract on blood glucose and plasma insulin increments due to high-dose carbohydrate ingestion, before and after exercise. Healthy, physically active men (n = 6; 21.0 ± 1.6 years, 78.1 ± 6.0 kg) participated in a double-blind placebo-controlled crossover study involving 2 experimental sessions. In each session, the subjects successively underwent an oral glucose tolerance test at rest (OGTT(R)), a 30-min cycling bout at ~75% VO(2max), and another OGTT after exercise (OGTT(EX)). They received capsules containing either 1,000 mg OFI or placebo (PL) 30 min before and immediately after the OGTT(R). Blood samples were collected before (t₀) and at 30-min intervals after ingestion of 75 g glucose for determination of blood glucose and serum insulin. In OGTT(EX) an additional 75-g oral glucose bolus was administered at t₆₀. In OGTT(R), OFI administration reduced the area under the glucose curve (AUC(GLUC)) by 26%, mainly due to lower blood glucose levels at t₃₀ and t₆₀ (p blood glucose at t₆₀ was ~10% lower in OFI than in PL, which resulted in a decreased AUC(GLUC) (-37%, p AUC(INS) were not different between OFI and PL. In conclusion, the current study shows that OFI extract can increase plasma insulin and thereby facilitate the clearance of an oral glucose load from the circulation at rest and after endurance exercise in healthy men.

Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

DEFF Research Database (Denmark)

Sillesen, H.; Amarenco, P.; Hennerici, M.G.

2008-01-01

BACKGROUND AND PURPOSE: The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found that treatment with atorvastatin 80 mg per day reduced the risk of stroke and cardiovascular events in patients with a recent transient ischemic attack (TIA) or stroke. We hypothesized...... this benefit would be greatest in the subgroup of patients with carotid stenosis. METHODS: The SPARCL trial randomized patients with TIA or stroke within 1 to 6 months without known coronary heart disease (CHD) and low-density lipoprotein cholesterol 100 to 190 mg/dL to treatment with atorvastatin 80 mg per...... artery stenosis, treatment with atorvastatin was associated with a 33% reduction in the risk of any stroke (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.47, 0.94; P=0.02), and a 43% reduction in risk of major coronary events (HR 0.57, 95% CI 0.32, 1.00; P=0.05). Later carotid revascularization...

Cystic fibrosis transmembrane conductance regulator is correlated closely with sperm progressive motility and normal morphology in healthy and fertile men with normal sperm parameters.

Science.gov (United States)

Jiang, L-Y; Shan, J-J; Tong, X-M; Zhu, H-Y; Yang, L-Y; Zheng, Q; Luo, Y; Shi, Q-X; Zhang, S-Y

2014-10-01

Cystic fibrosis transmembrane conductance regulator (CFTR) has been demonstrated to be expressed in mature spermatozoa and correlated with sperm quality. Sperm CFTR expression in fertile men is higher than that in infertile men suffering from teratospermia, asthenoteratospermia, asthenospermia and oligospermia, but it is unknown whether CFTR is correlated with sperm parameters when sperm parameters are normal. In this study, 282 healthy and fertile men with normal semen parameters were classified into three age groups, group (I): age group of 20-29 years (98 cases, 27.1 ± 6.2), group (II): age group of 30-39 years (142 cases, 33.7 ± 2.6) and group (III): age group of more than or equal to 40 years (42 cases, 44.1 ± 4.6). Sperm concentration, total count and progressive motility were analysed by computer-assisted sperm analysis. Sperm morphology was analysed by modified Papanicolaou staining. Sperm CFTR expression was conducted by indirect immunofluorescence staining. There was a significant positive correlation (P sperm progressive motility (r = 0.221) and normal morphology (r = 0.202), but there were no correlations between sperm CFTR expression and semen volume, sperm concentration, sperm total count as well as male age (P > 0.05). Our findings show that CFTR expression is associated with sperm progressive motility and normal morphology in healthy and fertile men with normal sperm parameters, but not associated with the number of spermatozoa and male age. © 2013 Blackwell Verlag GmbH.

Phosphorous31 magnetic resonance spectroscopy after total sleep deprivation in healthy adult men.

Science.gov (United States)

Dorsey, Cynthia M; Lukas, Scott E; Moore, Constance M; Tartarini, Wendy L; Parow, Aimee M; Villafuerte, Rosemond A; Renshaw, Perry F

2003-08-01

To investigate chemical changes in the brains of healthy adults after sleep deprivation and recovery sleep, using phosphorous magnetic resonance spectroscopy. Three consecutive nights (baseline, sleep deprivation, recovery) were spent in the laboratory. Objective sleep measures were assessed on the baseline and recovery nights using polysomnography. Phosphorous magnetic resonance spectroscopy scans took place beginning at 7 am to 8 am on the morning after each of the 3 nights. Sleep laboratory in a private psychiatric teaching hospital. Eleven healthy young men. Following a baseline night of sleep, subjects underwent a night of total sleep deprivation, which involved supervision to ensure the absence of sleep but was not polysomnographically monitored. No significant changes in any measure of brain chemistry were observed the morning after a night of total sleep deprivation. However, after the recovery night, significant increases in total and beta-nucleoside triphosphate and decreases in phospholipid catabolism, measured by an increase in the concentration of glycerylphosphorylcholine, were observed. Chemical changes paralleled some changes in objective sleep measures. Significant chemical changes in the brain were observed following recovery sleep after 1 night of total sleep deprivation. The specific process underlying these changes is unclear due to the large brain region sampled in this exploratory study, but changes may reflect sleep inertia or some aspect of the homeostatic sleep mechanism that underlies the depletion and restoration of sleep. Phosphorous magnetic resonance spectroscopy is a technique that may be of value in further exploration of such sleep-wake functions.

Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults.

Science.gov (United States)

Lee, Hoan Jong; Chung, Moon-Hyun; Kim, Woo Joo; Hong, Young Jin; Choi, Kyong Min; Lee, Jina; Oh, Chi Eun; Welsch, Jo Anne; Kim, Kyung-Hyo; Hong, Ki Bae; Dagnew, Alemnew F; Bock, Hans; Dull, Peter M; Odrljin, Tatjana

2014-11-01

This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N=297) or a saline placebo (N=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.

Exposure to gemfibrozil and atorvastatin affects cholesterol metabolism and steroid production in zebrafish (Danio rerio).

Science.gov (United States)

Al-Habsi, Aziz A; Massarsky, Andrey; Moon, Thomas W

2016-09-01

The commonly used lipid-lowering pharmaceuticals gemfibrozil (GEM) and atorvastatin (ATV) are detected in the aquatic environment; however, their potential effects on non-target fish species are yet to be fully understood. This study examined the effects of GEM and/or ATV on female and male adult zebrafish after a 30d dietary exposure. The exposure led to changes in several biochemical parameters, including reduction in cholesterol, triglycerides, cortisol, testosterone, and estradiol. Changes in cholesterol and triglycerides were also associated with changes in transcript levels of key genes involved with cholesterol and lipid regulation, including SREBP2, HMGCR1, PPARα, and SREBP1. We also noted higher CYP3A65 and atrogin1 mRNA levels in drug-treated male fish. Sex differences were apparent in some of the examined parameters at both biochemical and molecular levels. This study supports these drugs affecting cholesterol metabolism and steroid production in adult zebrafish. We conclude that the reduction in cortisol may impair the ability of these fish to mount a suitable stress response, whereas the reduction of sex steroids may negatively affect reproduction. Copyright © 2015 Elsevier Inc. All rights reserved.

In Healthy Young Men, a Short Exhaustive Exercise Alters the Oxidative Stress Only Slightly, Independent of the Actual Fitness

Directory of Open Access Journals (Sweden)

Maya Finkler

2016-01-01

Full Text Available The aim of the present study was to evaluate the apparent disagreement regarding the effect of a typical cycling progressive exercise, commonly used to assess VO2max, on the kinetics of ex vivo copper induced peroxidation of serum lipids. Thirty-two (32 healthy young men, aged 24–30 years, who do not smoke and do not take any food supplements, participated in the study. Blood was withdrawn from each participant at three time points (before the exercise and 5 minutes and one hour after exercise. Copper induced peroxidation of sera made of the blood samples was monitored by spectrophotometry. For comparison, we also assayed TBARS concentration and the activity of oxidation-related enzymes. The physical exercise resulted in a slight and reversible increase of TBARS and slight changes in the activities of the studied antioxidant enzymes and the lag preceding peroxidation did not change substantially. Most altered parameters returned to baseline level one hour after exercise. Notably, the exercise-induced changes in OS did not correlate with the physical fitness of the subjects, as evaluated in this study (VO2max = 30–60 mL/min/kg. We conclude that in healthy young fit men a short exhaustive exercise alters only slightly the OS, independent of the actual physical fitness.

Executive function on the 16-day of bed rest in young healthy men

Science.gov (United States)

Ishizaki, Yuko; Fukuoka, Hideoki; Tanaka, Hidetaka; Ishizaki, Tatsuro; Fujii, Yuri; Hattori-Uchida, Yuko; Nakamura, Minako; Ohkawa, Kaoru; Kobayashi, Hodaka; Taniuchi, Shoichiro; Kaneko, Kazunari

2009-05-01

Microgravity due to prolonged bed rest may cause changes in cerebral circulation, which is related to brain function. We evaluate the effect of simulated microgravity due to a 6° head-down tilt bed rest experiment on executive function among 12 healthy young men. Four kinds of psychoneurological tests—the table tapping test, the trail making test, the pointing test and losing at rock-paper-scissors—were performed on the baseline and on day 16 of the experiment. There was no significant difference in the results between the baseline and day 16 on all tests, which indicated that executive function was not impaired by the 16-day 6° head-down tilting bed rest. However, we cannot conclude that microgravity did not affect executive function because of the possible contribution of the following factors: (1) the timing of tests, (2) the learning effect, or (3) changes in psychophysiology that were too small to affect higher brain function.

BP network for atorvastatin effect evaluation from ultrasound images features classification

Science.gov (United States)

Fang, Mengjie; Yang, Xin; Liu, Yang; Xu, Hongwei; Liang, Huageng; Wang, Yujie; Ding, Mingyue

2013-10-01

Atherosclerotic lesions at the carotid artery are a major cause of emboli or atheromatous debris, resulting in approximately 88% of ischemic strokes in the USA in 2006. Stroke is becoming the most common cause of death worldwide, although patient management and prevention strategies have reduced stroke rate considerably over the past decades. Many research studies have been carried out on how to quantitatively evaluate local arterial effects for potential carotid disease treatments. As an inexpensive, convenient and fast means of detection, ultrasonic medical testing has been widespread in the world, so it is very practical to use ultrasound technology in the prevention and treatment of carotid atherosclerosis. This paper is dedicated to this field. Currently, many ultrasound image characteristics on carotid plaque have been proposed. After screening a large number of features (including 26 morphological and 85 texture features), we have got six shape characteristics and six texture characteristics in the combination. In order to test the validity and accuracy of these combined features, we have established a Back-Propagation (BP) neural network to classify atherosclerosis plaques between atorvastatin group and placebo group. The leave-one-case-out protocol was utilized on a database of 768 carotid ultrasound images of 12 patients (5 subjects of placebo group and 7 subjects of atorvastatin group) for the evaluation. The classification results showed that the combined features and classification have good recognition ability, with the overall accuracy 83.93%, sensitivity 82.14%, specificity 85.20%, positive predictive value 79.86%, negative predictive value 86.98%, Matthew's correlation coefficient 67.08%, and Youden's index 67.34%. And the receiver operating characteristic (ROC) curve in our test also performed well.

Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women

International Nuclear Information System (INIS)

Biegon, Anat; Fowler, Joanna S.; Alexoff, David L.; Kim, Sung Won; Logan, Jean; Pareto, Deborah; Schlyer, David; Wang, Gene-Jack

2015-01-01

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with (11)C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: (11)C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, including brain and torso or pelvis scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned following pretreatment with a clinical dose of the aromatase inhibitor letrozole.Time activity curves were obtained and standard uptake values (SUV) calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole body radiation exposures were calculated using Olinda software. Results: Liver uptake was higher than all other organs, but was not blocked by pretreatment with letrozole. Mean SUVs in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (ranging from 0.48±0.05 in lungs to 1.5±0.13 in kidneys). Mean ovarian SUVs (3.08±0.7) were comparable to brain levels and higher than all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced (11)C-vorozole uptake. Conclusions: PET with (11)C-vorozole is useful for assessing physiological changes in estrogen synthesis capacity in the human body. Baseline levels in

Spirometry of healthy adult South African men

African Journals Online (AJOL)

1996-07-07

Jul 7, 1996 ... radiographic screening process was used to identify a healthy population ... significantly lower values than the Autolink for FVC measurements despite .... t Medical Instrumentation. ATS '" American ... Quality control. Biological ...

Long-term gastrointestinal tolerance of NUTRIOSE®FB in healthy men

NARCIS (Netherlands)

Pasman, W.; Wils, D.; Saniez, M.H.; Kardinaal, A.

2006-01-01

Objective: To determine the gastrointestinal (GI) tolerance of NUTRIOSE®FB in men. Design: A randomized, placebo-contro lled, parallel, double-blind study. Setting: The metabolic ward of TNO Quality of Life. Subjects: Forty-eight subjects started the study: 16 men participated in one of the three

The studies of PLGA nanoparticles loading atorvastatin calcium for oral administration in vitro and in vivo

Directory of Open Access Journals (Sweden)

Zhenbao Li

2017-05-01

Full Text Available A biodegradable poly(lactic-co-glycolic acid loading atorvastatin calcium (AC nanoparticles (AC-PLGA-NPs were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGA-NPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.

Comparative effects of cholesteryl ester transfer protein inhibition, statin or ezetimibe on lipid factors: The ACCENTUATE trial.

Science.gov (United States)

Nicholls, Stephen J; Ray, Kausik K; Ballantyne, Christie M; Beacham, Lauren A; Miller, Debra L; Ruotolo, Giacomo; Nissen, Steven E; Riesmeyer, Jeffrey S

2017-06-01

The optimal approaches to management of patients treated with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study aimed to compare the effects of adding the cholesteryl ester transfer protein inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin-treated high-vascular risk patients on lipid parameters. 366 patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40 mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the United States. Lipid parameters, safety and tolerability were measured. Addition of evacetrapib significantly reduced LDL-C (-33%) compared with ezetimibe (-27%, p=0.045), increasing statin dose (-6%) and statin alone (0%, pstatin dose (pstatin dose, and p=0.004 vs. statin alone). Addition of evacetrapib to atorvastatin produced an increase in hsCRP compared with ezetimibe (p=0.02). While evacetrapib improved traditional atherogenic and putative protective lipid measures compared with ezetimibe and increasing statin dose in patients with ASCVD and/or diabetes, it also adversely affected novel atherogenic risk factors. These findings may contribute to the lack of clinical benefit observed in the ACCELERATE trial. Copyright © 2017 Elsevier B.V. All rights reserved.

Rosuvastatin and atorvastatin: comparative effects on glucose metabolism in non-diabetic patients with dyslipidaemia.

Science.gov (United States)

Abbas, Ahmed; Milles, John; Ramachandran, Sudarshan

2012-01-01

The ever increasing interventional CVD outcome studies have resulted in statins being an essential factor of cardiovascular prevention strategies. The JUPITER study in 2008, despite reducing CVD and overall mortality, highlighted an increase in new onset diabetes in the rosuvastatin treated arm. Since then there have been many meta-analyses of the RCTs and the largest carried out by Sattar et al showed a significant increase in the incidence of diabetes during the trials. The findings from the individual studies when comparing the different statins were less clear. A higher statin dosage and risk factors associated with diabetes appeared to predict this phenomenon. There have been many studies investigating the effects of statins on glycaemic control, but again no clear conclusion is apparent. Despite the increase in new onset diabetes observed, the risk is clearly out-weighed by the CVD benefits observed in nearly all the statin trials. Thus, no change is required to any of the prevention guidelines regarding statins. However, it may be prudent to monitor glycaemic control after commencing statin therapy. This review will focus on atorvastatin which is the most widely used statin worldwide and rosuvastatin which is the most efficacious. This will be against a background of the effects of other statins on glucose metabolism in non-diabetic patients.

Lower Urinary Tract Symptoms, Erectile Dysfunction, and Quality of Life in Poststroke Men

DEFF Research Database (Denmark)

Tibaek, Sigrid; Gard, Gunvor; Dehlendorff, Christian

2017-01-01

The aim of the current study was to compare lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and quality of life (QoL) in poststroke and healthy men. Thirty poststroke men with stroke-related LUTS, and as controls, 96 healthy men participated in this controlled, cross-sectional study...

Pemphigus erythematosus relapse associated with atorvastatin intake

Directory of Open Access Journals (Sweden)

Lo Schiavo A

2014-09-01

Full Text Available Ada Lo Schiavo,1 Rosa Valentina Puca,1 Francesca Romano,1 Roberto Cozzi2 1Department of Dermatology, Second University of Naples, Naples, Italy; 2Department of Dermatology, AORN "A Cardarelli", Naples, Italy Abstract: Statins, also known as 3-hydroxy-3-methylglutaril-CoA reductase inhibitors, are well-tolerated drugs used for prevention of atherosclerosis and cardiovascular events. Although they are generally considered safe, some serious adverse effects, such as myositis, myopathy, and rhabdomyolysis can rarely occur. Furthermore, recent data from long-term follow-up on patients who have been taking statins for a long period of time suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reactions is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. Herein we report the case of a 70 year-old man who developed a relapse of pemphigus erythematosus, a syndrome with features of both lupus erythematosus and pemphigus, after atorvastatin intake. Keywords: pemphigus erythematosus, autoimmune disease, treatment, pathogenesis, statins

Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population

OpenAIRE

Herrera-González, Sarahí; Martínez-Treviño, Denisse Aideé; Aguirre-Garza, Marcelino; Gómez-Silva, Magdalena; Barrera-Saldaña, Hugo Alberto; León-Cachón, Rafael Baltazar Reyes

2017-01-01

Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiote...

Effect of Chlorella Ingestion on Oxidative Stress and Fatigue Symptoms in Healthy Men.

Science.gov (United States)

Okada, Hirotaka; Yoshida, Noriko; Kakuma, Tatsuyuki; Toyomasu, Kouji

2018-05-21

We examined the effects of dietary chlorella ingestion on oxidative stress and fatigue symptoms in healthy men under resting and fatigue conditions. We conducted a double-blind, parallel-arm controlled study. Twenty-seven healthy male volunteers (mean age, 35.4±10.4 years) were randomly divided into the chlorella and placebo groups, and received chlorella (6 g/day) and lactose as placebo (7.2 g/day), respectively, for 4 weeks. To simulate mild fatigue, subjects underwent exercise (40% of the heart rate reserve) for 30 minutes. Fatigue was measured using the visual analog scale of fatigue (F-VAS) pre- and post-exercise. Serum antioxidant capacity (AC), malondialdehyde levels, and other indices of oxidative stress were measured pre- and post-exercise. All measurements were repeated after the intervention period and the results were compared with baseline measurements. Under resting conditions, AC significantly increased after the intervention period in the chlorella group, but not in the placebo group. Malondialdehyde levels after the intervention period were significantly lower in the chlorella group than in the placebo group. There were no significant differences in any of the oxidative-stress indices measured pre- and post-exercise, either before or after intervention, in either group. F-VAS significantly increased after exercise at all measurement time-points in both groups, except after the intervention period in the chlorella group. Under fatigue conditions, there were no significant differences in oxidative stress indices between the groups. Our results suggest that chlorella ingestion has the potential to relieve oxidative stress and enhance tolerance for fatigue under resting conditions.

The Effect of Occasional Alcohol Drinking on Semen Quality and Sperm Morphology among Young and Healthy Polish Men

Directory of Open Access Journals (Sweden)

Felicja Lwow

2017-10-01

Full Text Available ABSTRACT Background: Ethanol (EtOH is an agent that seems to exert an especially harmful effect on male fertility. The impact of high EtOH intake on fertility was demonstrated in numerous researches, with data suggesting that this effect may have been due to decreased semen quality; however, similar negative effects were not identified among occasional EtOH drinkers. There are currently no recommendations for alcohol consumption for men who plan to have a child other than avoiding high EtOH intake. Thus, studies on the effect of moderate and occasional EtOH drinking on semen quality are needed to develop appropriate recommendations for men planning to have a child in the future. The aim of this study was to determine whether changes in semen quality parameters and sperm morphology occur in healthy young men who occasionally exceed the WHO-recommended weekly dose of EtOH but are not alcohol dependent and do not frequently consume high amounts of EtOH. Methods: The study sample consisted of 172 young men residing in urban areas. The semen quality and morphology of men who consumed more than 140 g of ethanol (high-risk group, HR, n=44 weekly was compared with that of low-risk group members (LR, n=128 who reported lower alcohol consumption. Results: The only between-group difference in semen characteristics was the identification of a higher percentage of macrocephalic sperm in the HR group (P=0.011. Alcohol intake was the sole factor influencing the percentage of macrocephalic sperm (b=0.171, P=0.025, multiple linear regression. Conclusions: We concluded that occasional alcohol consumption did not alter fertility but caused the accumulation of macrocephalic sperm potentially containing damaged DNA. Therefore, we recommend that men who plan to father children stop drinking alcohol at least 3 months before engaging in sexual intercourse that may lead to pregnancy.

Probiotic yogurt and acidified milk similarly reduce postprandial inflammation and both alter the gut microbiota of healthy, young men.

Science.gov (United States)

Burton, Kathryn J; Rosikiewicz, Marta; Pimentel, Grégory; Bütikofer, Ueli; von Ah, Ueli; Voirol, Marie-Jeanne; Croxatto, Antony; Aeby, Sébastien; Drai, Jocelyne; McTernan, Philip G; Greub, Gilbert; Pralong, François P; Vergères, Guy; Vionnet, Nathalie

2017-05-01

Probiotic yogurt and milk supplemented with probiotics have been investigated for their role in 'low-grade' inflammation but evidence for their efficacy is inconclusive. This study explores the impact of probiotic yogurt on metabolic and inflammatory biomarkers, with a parallel study of gut microbiota dynamics. The randomised cross-over study was conducted in fourteen healthy, young men to test probiotic yogurt compared with milk acidified with 2 % d-(+)-glucono-δ-lactone during a 2-week intervention (400 g/d). Fasting assessments, a high-fat meal test (HFM) and microbiota analyses were used to assess the intervention effects. Baseline assessments for the HFM were carried out after a run-in during which normal milk was provided. No significant differences in the inflammatory response to the HFM were observed after probiotic yogurt compared with acidified milk intake; however, both products were associated with significant reductions in the inflammatory response to the HFM compared with the baseline tests (assessed by IL6, TNFα and chemokine ligand 5) (Pyogurt intake (FC=-1·3, P adj=0·03), increased abundance of Bifidobacterium species after acidified milk intake (FC=1·4, P adj=0·04) and detection of Lactobacillus delbrueckii spp. bulgaricus (FC=7·0, P adjyogurt intake. Probiotic yogurt and acidified milk similarly reduce postprandial inflammation that is associated with a HFM while inducing distinct changes in the gut microbiota of healthy men. These observations could be relevant for dietary treatments that target 'low-grade' inflammation.

Outcomes in men with large prostates ({>=}60 cm{sup 3}) treated with definitive proton therapy for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Mcgee, Lisa; Mendenhall, William M. [Dept. of Radiation Oncology, Univ. of Florida Coll. of Medicine, Gainesville (United States); Mendenhall, Nancy P.; Morris, Christopher G.; Marcus, Robert J. Jr. [Dept. of Radiation Oncology, Univ. of Florida Coll. of Medicine, Gainesville (United States); Univ. of Florida Proton Therapy Inst., Jacksonville (United States); Henderson, Randal H.; Nichols, Romaine C. Jr.; Li, Zuofeng; Williams, Christopher R.; Hoppe, Bradford S. [Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: bhoppe@floridaproton.org

2013-04-15

Background: Large prostate size is associated with higher rates of genitourinary and gastrointestinal toxicities after definitive treatment for prostate cancer, and because of this many men will undergo cytoreduction with androgen deprivation therapy (ADT) before definitive therapy, which results in its own unique toxicities and worsens quality of life. This series investigates genitourinary and gastrointestinal toxicity in men with large prostates (> 60 cm{sup 3}) undergoing definitive proton therapy (PT) for prostate cancer. Material and methods: From 2006 to 2010, 186 men with prostates {>=}60 cm{sup 3} were treated with definitive PT (median dose, 78 CGE) for low- (47%), intermediate- (37%) and high-risk (16%) prostate cancer. Median prostate size was 76 cm{sup 3} (range, 60-143 cm{sup 3}) and pretreatment IPSS was > 15 in 27%. At baseline, 51% were managed for obstructive symptoms with transurethral resection of the prostate (TURP) (9.7%) or medical management with {alpha} blockers (32%), 5 {alpha}-reductase inhibitors (15%), and/or saw palmetto (11%). Fourteen men received ADT for cytoreduction. Results: Median follow-up was two years. Grade 3 genitourinary toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). Multivariate analysis demonstrated pretreatment medical management (p = 0.0065) and pretreatment TURP (p 0.0002) were significantly associated with grade 3 genitourinary toxicity. One man experienced grade 3 gastrointestinal toxicity and 15 men had grade 2 gastrointestinal toxicities. On multivariate analysis, dose > 78 CGE was associated with increased grade 2 + gastrointestinal toxicity (p = 0.0142). Conclusion: Definitive management of men with large prostates without ADT was associated with low rates of genitourinary and gastrointestinal toxicity.

Outcomes in men with large prostates (≥60 cm3) treated with definitive proton therapy for prostate cancer

International Nuclear Information System (INIS)

Mcgee, Lisa; Mendenhall, William M.; Mendenhall, Nancy P.; Morris, Christopher G.; Marcus, Robert J. Jr.; Henderson, Randal H.; Nichols, Romaine C. Jr.; Li, Zuofeng; Williams, Christopher R.; Hoppe, Bradford S.

2013-01-01

Background: Large prostate size is associated with higher rates of genitourinary and gastrointestinal toxicities after definitive treatment for prostate cancer, and because of this many men will undergo cytoreduction with androgen deprivation therapy (ADT) before definitive therapy, which results in its own unique toxicities and worsens quality of life. This series investigates genitourinary and gastrointestinal toxicity in men with large prostates (> 60 cm 3 ) undergoing definitive proton therapy (PT) for prostate cancer. Material and methods: From 2006 to 2010, 186 men with prostates ≥60 cm 3 were treated with definitive PT (median dose, 78 CGE) for low- (47%), intermediate- (37%) and high-risk (16%) prostate cancer. Median prostate size was 76 cm 3 (range, 60-143 cm 3 ) and pretreatment IPSS was > 15 in 27%. At baseline, 51% were managed for obstructive symptoms with transurethral resection of the prostate (TURP) (9.7%) or medical management with α blockers (32%), 5 α-reductase inhibitors (15%), and/or saw palmetto (11%). Fourteen men received ADT for cytoreduction. Results: Median follow-up was two years. Grade 3 genitourinary toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). Multivariate analysis demonstrated pretreatment medical management (p = 0.0065) and pretreatment TURP (p 0.0002) were significantly associated with grade 3 genitourinary toxicity. One man experienced grade 3 gastrointestinal toxicity and 15 men had grade 2 gastrointestinal toxicities. On multivariate analysis, dose > 78 CGE was associated with increased grade 2 + gastrointestinal toxicity (p = 0.0142). Conclusion: Definitive management of men with large prostates without ADT was associated with low rates of genitourinary and gastrointestinal toxicity

The rate of intestinal glucose absorption is correlated with plasma glucose-dependent insulinotropic polypeptide concentrations in healthy men

DEFF Research Database (Denmark)

Wachters-Hagedoorn, Renate E; Priebe, Marion G; Heimweg, Janneke A J

2006-01-01

and slowly available glucose. In a crossover study, glucose, insulin, GLP-1, and GIP concentrations were monitored for 6 h after consumption of glucose, uncooked cornstarch (UCCS) or corn pasta in 7 healthy men. All test meals were naturally labeled with 13C. Using a primed, continuous D-[6,6-2H2]glucose...... in the early postprandial phase (15-90 min) occurred after consumption of glucose. There was a strong positive within-subject correlation between RaEx and GIP concentrations (r = 0.73, P meals. Rapidly and slowly digestible carbohydrates differ considerably in their ability to stimulate...

Male sexual function can be maintained without aromatization: randomized placebo-controlled trial of dihydrotestosterone (DHT) in healthy, older men for 24 months.

Science.gov (United States)

Sartorius, Gideon A; Ly, Lam P; Handelsman, David J

2014-10-01

Male sexual function is highly androgen dependent but whether aromatization of testosterone (T) to estradiol is required remains contentious. This study aims to investigate the effects of selective estrogen deficiency induced by a nonaromatizable androgen, dihydrotestosterone (DHT), on sexual function of healthy middle-aged and older men. Randomized clinical trial of daily transdermal DHT (70 mg) or placebo gel treatment in 114 healthy middle-aged and older (>50 years, mean 60.5 years) men without known prostate disease maintaining selective estrogen deficiency for 24 months. The end points were responses to a psychosexual and mood questionnaire completed before, at 3 months, then at 6 monthly intervals during and 3 months after study. Data were analyzed by mixed model analysis of variance for repeated measures using age and body mass index (BMI) as covariates and including interactions of treatment with age and time-on-study. DHT treatment increased serum DHT with complete suppression of serum T, luteinizing hormone, follicle stimulating hormone, and estradiol throughout the 24-month study resulting in reduced spinal bone density. There were no spontaneous complaints, or discontinuations for, adverse effects on sexual function during the study. DHT administration had no effects on any of 33 measures of sexual function and mood, apart from a mild, but significant decrease in overall sexual desire, which was reversible after cessation of treatment. Increasing age and less often increasing BMI were associated with significant decreases in most aspects of sexual function. We conclude that aromatization plays only a minimal role in maintenance of sexual function in healthy eugonadal middle-aged or older men, but age and obesity are significantly associated with decreases in most aspects of self-reported sexual function and satisfaction. The dependence of male sexual function on aromatization may be conditional on age and obesity and can be overcome by a

Metabolically Healthy Obesity and Ischemic Heart Disease

DEFF Research Database (Denmark)

Hansen, Louise; Netterstrom, Marie K.; Johansen, Nanna B.

2017-01-01

Context: Recent studies have suggested that a subgroup of obese individuals is not at increased risk of obesity-related complications. This subgroup has been referred to as metabolically healthy obese. Objective: To investigate whether obesity is a risk factor for development of ischemic heart...... risk factors (low high-density lipoprotein cholesterol, elevated blood pressure, triglycerides, and fasting plasma glucose). Metabolically healthy individuals were defined as having no metabolic risk factors, and metabolically unhealthy individuals were defined as having a minimum of one. Main Outcome...... Measures: IHD. Results: During follow-up, 323 participants developed IHD. Metabolically healthy obese men had increased risk of IHD compared with metabolically healthy normal-weight men [hazard ratio (HR), 3.1; 95% confidence interval (CI), 1.1 to 8.2)]. The corresponding results for women were less...

Tricky Treats

Centers for Disease Control (CDC) Podcasts

The Eagle Books are a series of four books that are brought to life by wise animal characters - Mr. Eagle, Miss Rabbit, and Coyote - who engage Rain That Dances and his young friends in the joy of physical activity, eating healthy foods, and learning from their elders about health and diabetes prevention. Tricky Treats shows children the difference between healthy snacks and sweet treats.

Dysfunctional sexual beliefs: a comparative study of heterosexual men and women, gay men, and lesbian women with and without sexual problems.

Science.gov (United States)

Peixoto, Maria Manuela; Nobre, Pedro

2014-11-01

Conservative and dysfunctional sexual beliefs are commonly associated with sexual problems among heterosexual men and women. However, little is known about the role of sexual beliefs in sexual problems in gay men and lesbians. The present study aimed at analyzing the role of sexual beliefs in sexual dysfunction in a sample of heterosexual and homosexual men and women. Participants answered questions about self-perceived sexual problems and completed the Sexual Dysfunctional Beliefs Questionnaire. Two hundred twelve men (106 gay) and 192 women (96 lesbian) completed a Web survey. Findings indicated that men with sexual dysfunction (regardless of sexual orientation) reported significantly more conservative beliefs and more erroneous beliefs related to partner's sexual satisfaction compared with sexually healthy men. Also, gay men with sexual dysfunction (but not heterosexual men) scored higher on belief in sex as an abuse of men's power compared with healthy controls. In addition, heterosexual men scored higher on "macho" beliefs, beliefs regarding partner's sexual satisfaction, and partner's power, compared with gay men. For women, a main effect was found for sexual orientation, with lesbian women scoring higher on sexual desire as a sin, age-related beliefs, and affection primacy and lower on beliefs related to motherhood primacy. Overall, findings suggest that dysfunctional sexual beliefs may play a role as vulnerability factors for sexual dysfunction regardless of sexual orientation, particularly in men. © 2014 International Society for Sexual Medicine.

The Effect of Statins on Skeletal Muscle Function

Science.gov (United States)

Parker, Beth A.; Capizzi, Jeffrey A.; Grimaldi, Adam S.; Clarkson, Priscilla M.; Cole, Stephanie M.; Keadle, Justin; Chipkin, Stuart; Pescatello, Linda S.; Simpson, Kathleen; White, C. Michael; Thompson, Paul D.

2015-01-01

Background Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials and the effect of statins on muscle performance has not been carefully studied. Methods and Results The Effect of STatins On Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase (CK), exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo were administered for 6 months to 420 healthy, statin-naive subjects. No individual CK value exceeded 10 times normal, but average CK increased 20.8 ± 141.1 U/L (pmuscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 vs 10; p = 0.05). Myalgic subjects on atorvastatin or placebo decreased muscle strength in 5 of 14 and 4 of 14 variables respectively (p = 0.69). Conclusions These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average CK suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in CK should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. Clinical Trial Registration Information: www.clinicaltrials.gov; Identifier: NCT00609063. PMID:23183941

Effect of statins on skeletal muscle function.

Science.gov (United States)

Parker, Beth A; Capizzi, Jeffrey A; Grimaldi, Adam S; Clarkson, Priscilla M; Cole, Stephanie M; Keadle, Justin; Chipkin, Stuart; Pescatello, Linda S; Simpson, Kathleen; White, C Michael; Thompson, Paul D

2013-01-01

Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (Pmuscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice

NARCIS (Netherlands)

Delsing, D.J.; Jukema, J.W.; van de Wiel, M.A.; Emeis, J.; van der Laarse, A.; Havekes, L.M.; Princen, H.M.G.

2003-01-01

This study was designed to investigate the potential antiatherosclerotic effects of the calcium antagonist amlodipine as compared with the HMG-CoA reductase inhibitor atorvastatin and the combination of both in ApoE*3-Leiden transgenic mice. Four groups of 15 ApoE*3-Leiden mice were put on a

Features of gas exchange of healthy people of working age

OpenAIRE

Noreiko S.B.

2011-01-01

The purpose of this study was to improve the accuracy of determining the basal metabolism of healthy people. Comparative studies of basal metabolism of healthy men and women on probation and respiratory physical factors are considered. Surveyed 30 healthy men and women aged 21-56 years. Determination of the volume of absorbed oxygen and produces carbon dioxide carried by the gas analyzer "Spirolit-2" were defined. Calculate the actual respiratory rate. It is established that the actual value ...

Aromatase imaging with [N-methyl-11C]vorozole PET in healthy men and women.

Science.gov (United States)

Biegon, Anat; Alexoff, David L; Kim, Sung Won; Logan, Jean; Pareto, Deborah; Schlyer, David; Wang, Gene-Jack; Fowler, Joanna S

2015-04-01

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with (11)C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aimed to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathologic situations can be studied. (11)C-vorozole (111-296 MBq/subject) was injected intravenously in 13 men and 20 women (age range, 23-67 y). PET data were acquired over a 90-min period. Each subject had 4 scans, 2 per day separated by 2-6 wk, including brain and torso or pelvis scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned after pretreatment with a clinical dose of the aromatase inhibitor letrozole. Time-activity curves were obtained, and standardized uptake values (SUV) were calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone, and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole-body radiation exposures were calculated using OLINDA software. Liver uptake was higher than uptake in any other organ but was not blocked by pretreatment with letrozole. Mean SUVs were higher in men than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than SUVs in any other organ (ranging from 0.48 ± 0.05 in lungs to 1.5 ± 0.13 in kidneys). Mean ovarian SUVs (3.08 ± 0.7) were comparable to brain levels and higher than in any other organ. Furthermore, ovarian SUVs in young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, whereas aging and cigarette smoking reduced (11)C-vorozole uptake. PET with (11)C-vorozole is useful for assessing physiologic changes in estrogen synthesis capacity in the human body. Baseline levels

Intercorrelations of lipoprotein subfractions and their covariation with lifestyle factors in healthy men

DEFF Research Database (Denmark)

Parlesak, Alexandr; Eckoldt, Joachim; Winkler, Karl

2014-01-01

So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration of triglyceri......So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration...... of triglycerides, cholesterol, phospholipids, and apolipoproteins (ApoA1, ApoA2 and ApoB) in subfractions of LDL and HDL in 265 healthy working men. Concentrations of cholesterol, phospholipids, and ApoB in small, dense atherogenic LDL particles (sdLDL) correlated negatively (p..., phospholipids, and ApoA1 in HDL2, respectively. Age correlated positively with sdLDL while increasing BMI correlated with an atherogenic shift of cholesterol, phospholipids, and ApoB from large, buoyant LDL (lbLDL) to sdLDL and decreasing concentrations of HDL2 constituents. Physical activity and alcohol intake...

The assessment of serum levels of malondialdehyde and total antioxidant capacity after the use of atorvastatin in patients with coronary artery stenosis

Directory of Open Access Journals (Sweden)

Gholamreza Shahsavari

2015-02-01

significant reduction of plasma MDA levels as well as a significant enhancement of TAC in coronary artery stenosis patients with long time receiving atorvastatin contribute to the lowering oxidative stress in this patients.

Maximal exercise testing of men with prostate cancer being treated with androgen deprivation therapy.

Science.gov (United States)

Wall, Bradley A; Galvão, Daniel A; Fatehee, Naeem; Taaffe, Dennis R; Spry, Nigel; Joseph, David; Newton, Robert U

2014-12-01

Exercise is being increasingly established as a key adjuvant therapy in clinical oncology. As research has demonstrated the beneficial effect of exercise for cancer management, a growing number of patients with cancer are undertaking structured exercise programs. This study aimed to determine the safety and feasibility of formal exercise testing in clinical settings as it is becoming increasingly used as a screening tool and for exercise prescription purposes. One hundred and twelve patients with prostate cancer undergoing androgen deprivation therapy (ADT) took part in a physician-supervised multistage maximal stress test (Bruce protocol). Sixty patients had been on ADT for 3 months (chronic). Of these men, 85% were able to meet the criteria for the attainment of V˙O2max, whereas three positive tests (3.2%) were observed. The three participants who recorded a positive stress test underwent further medical examination and were subsequently cleared of clinically significant cardiovascular disease. Apart from the relatively low V˙O2max (24.7 ± 6.0 mL·kg·min, 10th-15th percentile), compared with normative data in healthy age-matched controls, the cardiovascular response to exercise was similar in this cancer population. Moreover, treatment duration did not seem to influence cardiovascular responses to exercise. This early evidence suggests that risk of adverse events during maximal exercise testing is relatively low in this population and certainly no higher than that in ages-matched, apparently healthy individuals. Maximal exercise testing was demonstrated to be feasible and safe, providing a direct assessment of V˙O2max. The relatively low number of positive tests in this study suggests that the risk of adverse events is relatively low in this population and certainly no higher than that in age-matched, apparently healthy individuals.

Mortality in women treated with assisted reproductive technology treatment - addressing the healthy patient effect

DEFF Research Database (Denmark)

Vassard, Ditte; Schmidt, Lone; Pinborg, Anja

2018-01-01

Previous studies have reported reduced mortality among women undergoing assisted reproductive technology (ART) treatment, possibly related to selection of healthy women into ART treatment. The aim of this study was to explore the impact of relevant selection factors on the association between ART...... treatment and mortality and explore effect modification by parity. Women treated with ART in fertility clinics in Denmark during 1994-2009 (n = 42,897) were age-matched with untreated women from the background population (n = 204,514) and followed until ultimo 2010. With adjustment for relevant confounders...

Congenital color blindness in young Turkish men.

Science.gov (United States)

Citirik, Mehmet; Acaroglu, Golge; Batman, Cosar; Zilelioglu, Orhan

2005-04-01

We investigated a healthy population of men from different regions of Turkey for the presence of congenital red-green color blindness. Using Ishihara pseudoisochromatic plates, 941 healthy men from the Turkish army were tested for congenital red-green color blindness. The prevalence of red-green color blindness was 7.33 +/- 0.98% (5.10% protans and 2.23% deutans). These ratios were higher than other reported samples from Mediterranean Europe. Higher percentages of color blindness were found in regions with a lower education level and more consanguineous marriages.

Endurance exercise per se reduces the cardiovascular risk marker t-PA antigen in healthy, younger, overweight men

DEFF Research Database (Denmark)

Bladbjerg, Else Marie; Skov, Jane; Nordby, Pernille

2017-01-01

This was tested in 60 healthy, younger (20–40 years), overweight (BMI: 25–30 kg/m2) men randomly assigned to 12 weeks of intervention in one of four groups: training (T); energy-reduced diet (D); training and increased diet (T-iD); sedentary lifestyle and unchanged diet (controls, C). Fasting blood samples were...... obtained before and after 12 weeks of intervention and analyzed for plasma t-PA:Ag.  Results Body weight was reduced in groups T and D. We observed a decrease in t-PA:Ag from baseline to 12 weeks in all three exercise and diet intervention groups, and no change in the control group. A between...