Sample records for cardiovascular experimental pharmacology

  1. Advances in Experimental Pharmacological Studies of Effects of Astragalus on Cardiovascular System

    Institute of Scientific and Technical Information of China (English)

    han; ling


    Astragalus (AS), a traditional Chinese tonic medicine, refers to the dry root of perenial herbaceous plants Astragalus membranaceus (Fisch) and Astragalus mongolicus Bge of leguminosae family, which was first recorded in "Shen Nong's Herbal Classic" (神农本草经). The herb is sweet in flavor, slightly warm in nature and acts on the Spleen and Lung channels. It was described that AS possesses the effects of "invigorating Qi to elevate Yang,consolidating superficies to stop sweating, inducing diuresis to remove edema and promoting healing of sore to regenerate tissue". Its chemical components have been discovered to be AS-saponins (ASS), AS-general flavone (AGF), AS-polysaccharides (APS), amino acid and microelements. During the past two decades, the effects of AS, the prescriptions containing AS and its active components on cardiovascular system have been widely studied(1,2). Its effects of positive inotropic action,reducing blood pressure, and in protecting myocardia against injuries caused by ischemia and ischemia/reperfusion or virus infection have been well documented. The underlying mechanisms of the effects have also been deeply studied. This paper summarizes the pharmacological studies on the effects of AS on cardiovascular system conducted in recent years.……

  2. Advances in Experimental Pharmacological Studies of Effects of Astragalus on Cardiovascular System

    Institute of Scientific and Technical Information of China (English)

    韩玲; 陈可冀


    @@Astragalus (AS), a traditional Chinese tonic medicine, refers to the dry root of perenial herbaceous plants Astragalus membranaceus (Fisch) and Astragalus mongolicus Bge of leguminosae family, which was first recorded in "Shen Nong's Herbal Classic" (神农本草经). The herb is sweet in flavor, slightly warm in nature and acts on the Spleen and Lung channels. It was described that AS possesses the effects of "invigorating Qi to elevate Yang,consolidating superficies to stop sweating, inducing diuresis to remove edema and promoting healing of sore to regenerate tissue". Its chemical components have been discovered to be AS-saponins (ASS), AS-general flavone (AGF), AS-polysaccharides (APS), amino acid and microelements. During the past two decades, the effects of AS, the prescriptions containing AS and its active components on cardiovascular system have been widely studied(1,2). Its effects of positive inotropic action,reducing blood pressure, and in protecting myocardia against injuries caused by ischemia and ischemia/reperfusion or virus infection have been well documented. The underlying mechanisms of the effects have also been deeply studied. This paper summarizes the pharmacological studies on the effects of AS on cardiovascular system conducted in recent years.

  3. Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives. (United States)

    Qian, Jia-Qing


    Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihypertensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experimental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacological mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na+,K+ and Ca2+ ion currents. Differing from quinidine and sotalol, which exhibited reverse use-dependent effect, dauricine prolonged APD in a normal use-dependent manner in experimental studies. The antiarrhythmic effect of daurisoline and neferine which is an alkaloid isolated from Nelumbo nucifera Gaertn, and their mechanisms of actions have also been studied. The antiarrhythmic effect of daurisoline is more potent than that of dauricine.

  4. Pharmacology of human experimental anxiety. (United States)

    Graeff, F G; Parente, A; Del-Ben, C M; Guimarães, F S


    This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

  5. Pharmacology of human experimental anxiety

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    F.G. Graeff


    Full Text Available This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

  6. Pharmacological characterisation of cardiovascular histamine receptors in man in vivo. (United States)

    Boyce, M J


    Data from pharmacological studies carried out in healthy subjects using systemic histamine or impromidine and their antagonists are reviewed. Exogenous histamine by rapid injection appears to stimulate only H1-receptors. Chlorpheniramine alone antagonised the responses to histamine. The effects of cardiovascular H2-receptor stimulation are demonstrated best by a sustained and large dose of histamine given by infusion. If it be considered desirable to antagonise all the cardiovascular responses to endogenous histamine, the available pharmacological data in man suggest this would be achieved best by a combination of an H1-and H2-receptor antagonist.

  7. Modelos experimentales de enfermedad cardiovascular Experimental models of cardiovascular disease

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    A. Gil Hernández


    Full Text Available El presente trabajo describe los modelos experimentales de utilidad clínica en el estudio de las enfermedades cardiovasculares y hace énfasis en los modelos usados para determinar los mecanismos fisiopatológicos de la aterosclerosis, así como para evaluar los efectos de productos nutricionales y farmacológicos sobre el desarrollo de este proceso inflamatorio complejo común a muchas enfermedades cardiovasculares. Se revisan los modelos animales en los que se puede inducir aterosclerosis por cambios en la composición de la dieta y los modelos animales en los que la alteración de uno o más genes (animales knock-out y knock-in, o la incorporación de genes foráneos de otras especies, da lugar a la aparición de hiperlipidemia con riesgo asociado de aparición de enfermedad cardiovascular temprana. Por otra parte, se consideran algunas de las líneas celulares más utilizadas en el estudio de los mecanismos moleculares de la aterogénesis y de evaluación de sustancias con interés nutricional o farmacológico.The present work describes clinically useful experimental models for the study of cardiovascular disease and emphasites the models used to determine the pathophysiologic mechanisms of atherosclerosis, as well as to evaluate the effects of nutritional and pharmacological products on the development of this complex inflammatory process present in many cardiovascular diseases. Animal models in which ahterosclerosis may be induced by dietary changes are reviewed, as well as those in which modification in one or more genes (knock-out and knock-in animals, or the incorporation of foreign genes from other species lead to early cardiovascular disease. On the other hand, some of the cell lines most frequently used in studying molecular mechanisms of atherosclerosis and assessment of substances with nutritional or pharmacological interest are considered.

  8. A new season of Chinese cardiovascular pharmacology research

    Institute of Scientific and Technical Information of China (English)

    Alex F CHEN; Ding-feng SU


    @@ In this issue of Acta Pharmacologica Sinica, we are proud to present to our readers and colleagues a series of review articles from several Chinese-American university laboratories in USA[1-6]. These reviews are a collection of the proceedings from the 8th Chinese Cardiovascular Pharmacology Conference held on July 23-26, 2004 in Urumchi,Xinjiang.

  9. [Contribution of animal experimentation to pharmacology]. (United States)

    Sassard, Jean; Hamon, Michel; Galibert, Francis


    Animal experimentation is of considerable importance in pharmacology and cannot yet be avoided when studying complex, highly integrated physiological functions. The use of animals has been drastically reduced in the classical phases of pharmacological research, for example when comparing several compounds belonging to the same pharmacological class. However, animal experiments remain crucial for generating and validating new therapeutic concepts. Three examples of such research, conducted in strict ethical conditions, will be used to illustrate the different ways in which animal experimentation has contributed to human therapeutics.

  10. PPARδ Activity in Cardiovascular Diseases: A Potential Pharmacological Target

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    Angela Tesse


    Full Text Available Activation of peroxisome proliferator-activated receptors (PPARs, and particularly of PPARα and PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARα and PPARγ anti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδ in cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδ selective synthetic agonists were found, improving studies about the physiological and pathophysiological roles of PPARδ activation. Recent reports suggest that the PPARδ activation may play a pivotal role to regulate inflammation, apoptosis, and cell proliferation, suggesting that this transcriptional factor could become an interesting pharmacological target to regulate cardiovascular cell apoptosis, proliferation, inflammation, and metabolism.

  11. Computational pharmacological studies on cardiovascular disease by Qishen Yiqi Diwan

    Institute of Scientific and Technical Information of China (English)

    GU JiangYong; YUAN Gu; ZHU YongHong; XU XiaoJie


    Computational pharmacological methods were used to study the distribution of 1729 compounds contained in a Chinese medicine,Qishen Yiqi Diwan,in chemical space.The results show that most of these compounds have good drug-like properties.Molecular docking was used to study the interactions between 1729 compounds of Qishen Yiqi Diwan and 26 drug targets related to cardiovascular disease and the distribution of 1729 compounds in drug-target space.The results may shed light on the action mechanism and the search for the active compounds in Qishen Yiqi Diwan.

  12. The cardiovascular physiology and pharmacology of endothelin-1. (United States)

    Thorin, Eric; Clozel, Martine


    One year after the discovery in 1980 that the endothelium was obligatory for acetylcholine to relax isolated arteries, it was clearly shown that the endothelium could also promote contraction. In 1988, Dr Yanagisawa's group identified endothelin-1 (ET-1) as the first endothelium-derived contracting factor. The circulating levels of this short (21 amino acids) peptide were quickly determined in humans and it was reported that in most cardiovascular diseases, circulating levels of ET-1 were increased and ET-1 was then recognized as a likely mediator of pathological vasoconstriction in human. The discovery of two receptor subtypes in 1990, ET(A) and ET(B), permitted optimization of bosentan, which entered clinical development in 1993, and was offered to patients with pulmonary arterial hypertension in 2001. In this report, we discuss the physiological and pathophysiological role of endothelium-derived ET-1, the pharmacology of its two receptors, focusing on the regulation of the vascular tone and as much as possible in humans. The coronary bed will be used as a running example, but references to the pulmonary, cerebral, and renal circulation will also be made. Many of the cardiovascular complications associated with aging and cardiovascular risk factors are initially attributable, at least in part, to endothelial dysfunction, particularly dysregulation of the vascular function associated with an imbalance in the close interdependence of NO and ET-1, in which the implication of the ET(B) receptor may be central.

  13. Current status of NADPH oxidase research in cardiovascular pharmacology

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    Rodiño-Janeiro BK


    Full Text Available Bruno K Rodiño-Janeiro,1,2 Beatriz Paradela-Dobarro,1 María Isabel Castiñeiras-Landeira,1 Sergio Raposeiras-Roubín,1,3 José R González-Juanatey,1,3,4 Ezequiel Álvarez1,4 1Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 2European Molecular Biology Laboratory, Grenoble, France; 3Cardiology Department, University Clinic Hospital of Santiago de Compostela, Santiago de Compostela, Spain; 4Medicine Department, University of Santiago de Compostela, Santiago de Compostela, Spain Abstract: The implications of reactive oxygen species in cardiovascular disease have been known for some decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been developed, but the results of clinical trials have not been as good as expected. Therefore, to move forward in the design of new therapeutic strategies for cardiovascular disease based on prevention of production of reactive oxygen species, steps must be taken on two fronts, ie, comprehension of reduction-oxidation signaling pathways and the pathophysiologic roles of reactive oxygen species, and development of new, less toxic, and more selective nicotinamide adenine dinucleotide phosphate (NADPH oxidase inhibitors, to clarify both the role of each NADPH oxidase isoform and their utility in clinical practice. In this review, we analyze the value of NADPH oxidase as a therapeutic target for cardiovascular disease and the old and new pharmacologic agents or strategies to prevent NADPH oxidase activity. Some inhibitors and different direct or indirect approaches are available. Regarding direct NADPH oxidase inhibition, the specificity of NADPH oxidase is the focus of current investigations, whereas the chemical structure-activity relationship studies of known inhibitors have provided pharmacophore models with which to search for new molecules. From a general point of view, small-molecule inhibitors are preferred because of their hydrosolubility

  14. Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine. (United States)

    Zhang, Wenjuan; Tao, Qin; Guo, Zihu; Fu, Yingxue; Chen, Xuetong; Shar, Piar Ali; Shahen, Mohamed; Zhu, Jinglin; Xue, Jun; Bai, Yaofei; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua


    Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases.

  15. Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine (United States)

    Zhang, Wenjuan; Tao, Qin; Guo, Zihu; Fu, Yingxue; Chen, Xuetong; Shar, Piar Ali; Shahen, Mohamed; Zhu, Jinglin; Xue, Jun; Bai, Yaofei; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua


    Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases.

  16. Obesity and cardiovascular physiology: impact of some pharmacological agents. (United States)

    Chaput, Jean-Philippe; Bérubé-Parent, Sonia; Tremblay, Angelo


    The increase in obesity prevalence is problematic as this condition is associated with health complications such as diabetes and cardiovascular diseases, more particularly when the excess body fat is stored in the deep abdominal region. The mainstay of therapy consists of behavior modification related to obesity such as overeating and physical inactivity. When these lifestyle modifying attempts fail, the use of anti-obesity drugs is warranted. Drug treatment is often indicated but is somewhat limited by the minimal number of well tolerated drugs that have proven to have long-term efficacy in maintaining body weight loss. The currently available drugs, sibutramine and orlistat, appear modestly effective in promoting weight loss. Ongoing studies continue to evaluate other drug treatments that may result in body weight reduction through a number of different mechanisms. Thus, the aim of this review is to present an overview of the current drugs available (particularly sibutramine and orlistat) as well as potential future candidates, and the impact of these agents on obesity and cardiovascular physiology. Furthermore, the therapeutic paradox of sibutramine in preventing obesity will be discussed as well as the beneficial impact of physical exercise on cardiac economy.

  17. A Systems Biology Approach to Uncovering Pharmacological Synergy in Herbal Medicines with Applications to Cardiovascular Disease

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    Xia Wang


    Full Text Available Background. Clinical trials reveal that multiherb prescriptions of herbal medicine often exhibit pharmacological and therapeutic superiority in comparison to isolated single constituents. However, the synergistic mechanisms underlying this remain elusive. To address this question, a novel systems biology model integrating oral bioavailability and drug-likeness screening, target identification, and network pharmacology method has been constructed and applied to four clinically widely used herbs Radix Astragali Mongolici, Radix Puerariae Lobatae, Radix Ophiopogonis Japonici, and Radix Salviae Miltiorrhiza which exert synergistic effects of combined treatment of cardiovascular disease (CVD. Results. The results show that the structural properties of molecules in four herbs have substantial differences, and each herb can interact with significant target proteins related to CVD. Moreover, the bioactive ingredients from different herbs potentially act on the same molecular target (multiple-drug-one-target and/or the functionally diverse targets but with potentially clinically relevant associations (multiple-drug-multiple-target-one-disease. From a molecular/systematic level, this explains why the herbs within a concoction could mutually enhance pharmacological synergy on a disease. Conclusions. The present work provides a new strategy not only for the understanding of pharmacological synergy in herbal medicine, but also for the rational discovery of potent drug/herb combinations that are individually subtherapeutic.

  18. Protective Effects of Panax Notoginseng Saponins on Cardiovascular Diseases: A Comprehensive Overview of Experimental Studies

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    Xiaochen Yang


    Full Text Available Panax notoginseng saponins (PNS are one of the most important compounds derived from roots of the herb Panax notoginseng which are traditionally used as a hemostatic medicine to control internal and external bleeding in China for thousands of years. To date, at least twenty saponins were identified and some of them including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were researched frequently in the area of cardiovascular protection. However, the protective effects of PNS on cardiovascular diseases based on experimental studies and its underlying mechanisms have not been reviewed systematically. This paper reviewed the pharmacology of PNS and its monomers Rb1, Rg1, and R1 in the treatment for cardiovascular diseases.

  19. Systems-Pharmacology Dissection of Traditional Chinese Medicine Compound Saffron Formula Reveals Multi-scale Treatment Strategy for Cardiovascular Diseases (United States)

    Liu, Jianling; Mu, Jiexin; Zheng, Chunli; Chen, Xuetong; Guo, Zihu; Huang, Chao; Fu, Yingxue; Tian, Guihua; Shang, Hongcai; Wang, Yonghua


    Cardiovascular diseases (CVDs) have been regarding as “the world’s first killer” of human beings in recent years owing to the striking morbidity and mortality, the involved molecular mechanisms are extremely complex and remain unclear. Traditional Chinese medicine (TCM) adheres to the aim of combating complex diseases from an integrative and holistic point of view, which has shown effectiveness in CVDs therapy. However, system-level understanding of such a mechanism of multi-scale treatment strategy for CVDs is still difficult. Here, we developed a system pharmacology approach with the purpose of revealing the underlying molecular mechanisms exemplified by a famous compound saffron formula (CSF) in treating CVDs. First, by systems ADME analysis combined with drug targeting process, 103 potential active components and their corresponding 219 direct targets were retrieved and some key interactions were further experimentally validated. Based on this, the network relationships among active components, targets and diseases were further built to uncover the pharmacological actions of the drug. Finally, a “CVDs pathway” consisted of several regulatory modules was incorporated to dissect the therapeutic effects of CSF in different pathological features-relevant biological processes. All this demonstrates CSF has multi-scale curative activity in regulating CVD-related biological processes, which provides a new potential way for modern medicine in the treatment of complex diseases. PMID:26813334

  20. Cardiovascular and cerebrovascular pharmacology%心脑血管药理学

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    @@心脑血管药理学 文献标识码:D Cardiovascular and cerebrovascular pharmacology 024 Effect of flavones of Mukdenia rossiikoidz on cardiac infarction in rats   LI Yan1, LUO Ji-Hua2   (1. National Institutes of Pharmaceutical Research and Development, Beijing 102206, China; 2. Medical College, Beihua University, Jilin 132001, China)   AIM: To study the effect of flavones of Mukdenia ross ii koidz on cardiac infarction caused by coronary artery ligation. M ETH ODS: Coronary artery ligation. RESULTS: Flavones of Mukd enia rossiikoidz reduced the area of infarction and attenuated the change in S-T section. CONCLUSION: Flavones of M. rossiikoidz has protective effects against myocardial ischemia.   Key words: Mukdenia rossiikoidz; coronary artery

  1. 双苄基异喹啉类生物碱的心血管药理作用%Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives

    Institute of Scientific and Technical Information of China (English)



    Tetrandrine, dauricine, daurisoline and neferine are bisbenzylisoquinoline alkaloid derivatives isolated from Chinese traditional medicine and herbs. The cardiovascular pharmacological effects and the mechanism of actions of these compounds were reviewed. Tetrandrine isolated from Stephania tetrandra S Moore possesses antihypertensive and antiarrhythmic effects. The antihypertensive effects of tetrandrine have been demonstrated in experimental hypertensive animals and in hypertensive patients. Recent studies showed that in addition to its calcium antagonistic effect, tetrandrine interacted with M receptors. Modulation by M receptor is one of the pharmacological mechanisms of cardiovascular effects of tetrandrine. Dauricine and daurisoloine were isolated from Menispermum dauricum DC. The antiarrhythmic effects of dauricine have been verified in different experimental arrhythmic models and in cardiac arrhythmic patients. Dauricine blocked the cardiac transmembrane Na+,K+ and Ca2+ ion currents. Differing from quinidine and sotalol, which exhibited reverse use-dependent effect, dauricine prolonged APD in a normal use-dependent manner in experimental studies. The antiarrhythmic effect of daurisoline and neferine which is an alkaloid isolated from Nelumbo nucifera Gaertn, and their mechanisms of actions have also been studied. The antiarrhythmic effect of daurisoline is more potent than that of dauricine.

  2. Experimental verification of the feasibility of the cardiovascular impedance simulator. (United States)

    Gwak, Kwan-Woong; Paden, Brad E; Antaki, James F; Ahn, Ihn-Seok


    Mock circulatory systems (MCS) are often used for the development of cardiovascular devices and for the study of the dynamics of blood flow through the cardiovascular system. However, conventional MCS suffer from the repeatability, flexibility, and precision problems because they are typically built up with passive and linear fluidic elements such as compliance chamber, manual valve, and tube. To solve these limitations, we have developed an impedance simulator, comprised of a feedback-controlled positive displacement pump that is capable of generating analogous dynamic characteristics as the conventional fluidic elements would generate, thereby replacing the conventional passive fluidic elements that often cause problems. The impedance simulator is experimentally proven to reproduce the impedance of the various discrete elements, such as resistance and compliance of the cardiovascular system model, as well as the combined impedances of them.

  3. Argentinean Society of Experimental Pharmacology: Brief history and main scientific contributions to the discipline. (United States)

    Sánchez Bruni, Sergio F; Acosta, Gabriela B


    Argentina Biomedical Science has been historically strong. The development of Human and Veterinary Pharmacology in our country as a pivotal discipline has been acknowledged worldwide because of the quality of its contributions. Argentinean Society of Experimental Pharmacology (SAFE) is a non- profit association whose research fields include Experimental and Clinical Pharmacology. SAFE main goals are described as follow (a) To meet active researchers for studying concerns regarding Experimental and Clinical Pharmacology (b) To launch an initiative for development of the discipline in mainly our country and other collaborative countries worldwide (c) To spread the pharmacological know-how obtained from different research teams (d) To strengthen relations between pharmacologists (e) To facilitate the presentation and discussion of scientific papers. This current article shows the SAFE's more important scientific contribution to pharmacology through its former research scientists to the present.

  4. Pharmacologically distinct cardiovascular effects of box jellyfish (Chironex fleckeri) venom and a tentacle-only extract in rats. (United States)

    Ramasamy, Sharmaine; Isbister, Geoffrey K; Seymour, Jamie E; Hodgson, Wayne C


    Using a recently developed technique to extract jellyfish venom from nematocysts, the present study investigated the in vivo cardiovascular effects of Chironex fleckeri venom and tentacle extract (devoid of nematocysts). In anaesthetised rats, venom (10 microg/kg, i.v.) produced a transient pressor response (23+/-4 mmHg) followed, in two of five animals, by cardiovascular collapse. Tentacle extract (100 microg/kg, i.v.) produced a more prolonged hypertensive effect (31+/-3 mmHg) without cardiovascular collapse. Prazosin (50 microg/kg, i.v.) did not have any significant effect on the cardiovascular effects produced by venom. However, prazosin significantly attenuated the pressor response produced by tentacle extract. Ketanserin (1 mg/kg, i.v.) did not have any significant effect on the cardiovascular response of the anaesthetised rat to venom (10 microg/kg, i.v.; 25+/-1 mmHg). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to compare the two jellyfish samples used in the present study. In addition to ensuring reproducibility of future studies and allow comparison with previous research. We show, for the first time, that a pure venom sample extracted from C. fleckeri nematocysts and a tentacle extract have cardiovascular effects in the anaesthetised rat which are different and pharmacologically distinct.

  5. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. (United States)

    Riba, Jordi; Valle, Marta; Urbano, Gloria; Yritia, Mercedes; Morte, Adelaida; Barbanoj, Manel J


    The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

  6. Pharmacological approaches to the treatment of oxidative stress-induced cardiovascular dysfunctions. (United States)

    Zamora, Pedro L; Villamena, Frederick A


    Cardiovascular diseases are a growing major global health problem. Our understanding of the mechanisms of pathophysiology of cardiovascular diseases has been gaining significant advances and a wealth of knowledge implicates oxidative stress as a key causative agent. However, to date, most efforts to treat heart failure using conventional antioxidant therapies have been less than encouraging. With increasing incidences of cardiovascular disease in young as well as in aging populations, and the problem of long-term diminishing efficacy of conventional therapeutics, the need for new treatments has never been greater. In this review, [corrected] a variety of therapeutic targets and compounds applied to treat cardiovascular diseases via inhibition of oxidative stress are presented.

  7. Punishing and cardiovascular effects of intravenous histamine in rats: pharmacological selectivity. (United States)

    Podlesnik, Christopher A; Jimenez-Gomez, Corina


    Although drugs may serve as reinforcers or punishers of operant behavior, the punishing function has received much less experimental attention than the reinforcing function. A sensitive method for studying drug-induced punishment is to assess choice for a punished response over an unpunished response. In these experiments, rats chose between pressing one lever and receiving a sucrose pellet or pressing another lever and receiving a sucrose pellet plus an intravenous injection of histamine. When sucrose was delivered equally frequently for either the punished or the unpunished response, rats selected the unpunished lever consistently, but decreases in the punished response did not differ as a function of intravenous histamine dose (0.1-1 mg/kg/inj). Changing the procedure so that sucrose was delivered on the unpunished lever with p = .5 increased the rats' responding on the punished lever with saline injections. In addition, the same range of histamine doses produced a much larger range of responses on the punished lever that was dose dependent. Using these procedures to assess the receptors mediating histamine's effects, the histamine H1 -receptor antagonists, pyrilamine and ketotifen, antagonized the punishing effect of histamine, but the histamine H2 -receptor antagonist ranitidine did not. However, ranitidine pretreatments reduced histamine-induced heart-rate increases to a greater extent than did the histamine H1 -receptor antagonists when administered at the same doses examined under conditions of histamine punishment. Overall, the present findings extend the general hypothesis that activation of histamine H1 -receptors mediates the punishing effects of histamine. They also introduce methods for rapidly assessing pharmacological mechanisms underlying drug-induced punishment.



    de Souza Grava, André Luiz; Ferrari,Luiz Fernando; Parada, Carlos Amílcar; Defino, Helton Luiz Aparecido


    Objective: To evaluate the effect of anti-inflammatory drugs (dexamethasone, indomethacin, atenolol and indomethacin plus atenolol) and analgesic drugs (morphine) on hyperalgesia experimentally induced by the nucleus pulposus (NP) in contact with the L5 dorsal root ganglion (DRG). Methods: Thirty male Wistar rats of weights ranging from 220 to 250 g were used in the study. Hyperalgesia was induced by means of a fragment of NP removed from the sacrococcygeal region that was placed in contact w...

  9. [Pharmacological properties of phosphorylacetohydrazides in experimental myocardial ischemia]. (United States)

    Balashov, V P; Al'miasheva, M I; Tarasova, R I; Rusina, I F; Kul'kova, N P; Kurmysheva, T V; Voskresenskaia, O V


    It is shown that 2-chloroethoxy-para-N-dimethylphosphorylacetohydrazide and N-acethylhydrazide-para-dimethylaminophenyl-2-chloroethoxyphosphorylacetic acid reliably reduce ischemia-induced depression of inotropic functions of the left ventricle in cats with experimental myocardial infarction model. The effect of both compounds can be explained by the maintenance of viability of the injured myocardium via a delay of the development of acidosis and the support of oxygen recycling in the ischemized zone. Both compounds show pronounced antiradical properties with a non-standard mechanism of action.

  10. Evaluation of the Pharmacological Function of Ulinastatin in Experimental Animals

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    Ling Guo


    Full Text Available Organ protection is a routine therapy in severe injuries. Our aim was to evaluate the beneficial effects of ulinastatin in experimental rats. Rats were randomly divided into a sham control, a model control and an ulinastatin-treated group. Malondialdehyde (MDA and superoxide dismutase (SOD levels were determined. Serum amylase, serum aspartate aminotransaminase (AST, lactate dehydrogenase (LDH and creatine kinase isoenzyme (CKMD activities, interleukin-8 (IL-8, tumor necrosis factor-α (TNF-α, nitric oxide (NO and cardiac troponin I (nTnl levels were examined. Results showed that ulinastatin decreased MDA levels and ameliorated the down-regulation of SOD activity. In addition, ulinastatin pretreatment may decrease serum AST, LDH and CKMD activities, IL-8, TNF-α, and nTnl levels, and enhance NO level. Our results demonstrated that oxidative injury occurred after IR and that ulinastatin exhibits significant protective effects against these effects.

  11. Pharmacological modulation of wound healing in experimental burns. (United States)

    Jurjus, Abdo; Atiyeh, Bishara S; Abdallah, Inaya M; Jurjus, Rosalyne A; Hayek, Shady N; Jaoude, Marlene Abou; Gerges, Alice; Tohme, Rania A


    Factors involved in wound healing and their interdependence are not yet fully understood; nevertheless, new prospects for therapy to favor speedy and optimal healing are emerging. Reports about wound healing modulation by local application of simple and natural agents abound even in the recent literature, however, most are anecdotal and lack solid scientific evidence. We describe the effect of silver sulfadiazine and moist exposed burn ointment (MEBO), a recently described burn ointment of herbal origin, on mast cells and several wound healing cytokines (bFGF, IL-1, TGF-beta, and NGF) in the rabbit experimental burn model. The results demonstrate that various inflammatory cells, growth factors and cytokines present in the wound bed may be modulated by application of local agents with drastic effects on their expression dynamics with characteristic temporal and spatial regulation and changes in the expression pattern. Such data are likely to be important for the development of novel strategies for wound healing since they shed some light on the potential formulations of temporally and combinatory optimized therapeutic regimens.

  12. Student's perception and experience of computer assisted learning as a teaching method in experimental pharmacology

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    Deepika Tikoo


    Conclusion: The study demonstrates the effectiveness of CAL in teaching experimental pharmacology concepts and the students felt that this method helped them in a better understanding of the topic as the effects were clearly visualized on the screen and that such simulations need to be a part of the standard curriculum. [Int J Basic Clin Pharmacol 2015; 4(6.000: 1168-1174

  13. Prevention of cardiovascular disease guided by total risk estimations - challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy.

    LENUS (Irish Health Repository)

    Zannad, Faiez


    This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the \\'treat-to-target\\' paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and \\'real-world\\' populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.

  14. Pharmacology of Casimiroa edulis; II. Cardiovascular effects in the anesthesized dog. (United States)

    Vidrio, H; Magos, G A


    The cardiovascular effects of an aqueous extract of seeds of Casimiroa edulis were assessed in pentobarbital-anesthetized dogs. The extract produced marked hypotension which lasted more than two hours; it was accompanied by moderate and less persistent bradycardia. The histaminergic nature of these effects was investigated in animals pretreated with the specific antagonists diphenhydramine, cimetidine, or a combination of both agents. These experiments showed that both H1- and H2-receptors were involved in the hypotensive response, while the bradycardia was mediated solely through an H1-mechanism. In open-chest dogs instrumented for recording cardiac output (ascending aortic flow), left ventricular contractility (dp/dt), central venous pressure (superior vena cava), systemic blood pressure, heart rate, total peripheral resistance and stroke volume, the extract decreased blood pressure and peripheral resistance and increased cardiac output and stroke volume, without modifying the other parameters. It was concluded that the cardiovascular pattern of Casimiroa edulis in the dog is that of a peripheral arterial vasodilator and that it increases cardiac output by reducing left ventricular afterload.

  15. Friend or foe? Telomerase as a pharmacological target in cancer and cardiovascular disease. (United States)

    Ait-Aissa, Karima; Ebben, Johnathan D; Kadlec, Andrew O; Beyer, Andreas M


    Aging, cancer, and chronic disease have remained at the forefront of basic biological research for decades. Within this context, significant attention has been paid to the role of telomerase, the enzyme responsible for lengthening telomeres, the nucleotide sequences located at the end of chromosomes found in the nucleus. Alterations in telomere length and telomerase activity are a common denominator to the underlying pathology of these diseases. While nuclear-specific, telomere-lengthening effects of telomerase impact cellular/organismal aging and cancer development, non-canonical, extra-nuclear, and non-telomere-lengthening contributions of telomerase have only recently been described and their exact physiological implications are ill defined. Although the mechanism remains unclear, recent reports reveal that the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), regulates levels of mitochondrial-derived reactive oxygen species (mtROS), independent of its established role in the nucleus. Telomerase inhibition has been the target of chemotherapy (directed or indirectly) for over a decade now, yet no telomerase inhibitor is FDA approved and few are currently in late-stage clinical trials, possibly due to underappreciation of the distinct extra-nuclear functions of telomerase. Moreover, evaluation of telomerase-specific therapies is largely limited to the context of chemotherapy, despite reports of the beneficial effects of telomerase activation in the cardiovascular system in relation to such processes as endothelial dysfunction and myocardial infarction. Thus, there is a need for better understanding of telomerase-focused cell and organism physiology, as well as development of telomerase-specific therapies in relation to cancer and extension of these therapies to cardiovascular pathologies. This review will detail findings related to telomerase and evaluate its potential to serve as a therapeutic target.

  16. Long Pentraxin 3: Experimental and Clinical Relevance in Cardiovascular Diseases

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    Fabrizia Bonacina


    Full Text Available Pentraxin 3 (PTX3 is an essential component of the humoral arm of innate immunity and belongs, together with the C-reactive protein (CRP and other acute phase proteins, to the pentraxins' superfamily: soluble, multifunctional, pattern recognition proteins. Pentraxins share a common C-terminal pentraxin domain, which in the case of PTX3 is coupled to an unrelated long N-terminal domain. PTX3 in humans, like CRP, correlates with surrogate markers of atherosclerosis and is independently associated with the risk of developing vascular events. Studies addressing the potential physiopathological role of CRP in the cardiovascular system were so far inconclusive and have been limited by the fact that the sequence and regulation have not been conserved during evolution between mouse and man. On the contrary, the conservation of sequence, gene organization, and regulation of PTX3 supports the translation of animal model findings in humans. While PTX3 deficiency is associated with increased inflammation, cardiac damage, and atherosclerosis, the overexpression limits carotid restenosis after angioplasty. These observations point to a cardiovascular protective effect of PTX3 potentially associated with the ability of tuning inflammation and favor the hypothesis that the increased levels of PTX3 in subjects with cardiovascular diseases may reflect a protective physiological mechanism, which correlates with the immunoinflammatory response observed in several cardiovascular disorders.



    Podlesnik, Christopher A.; Jimenez-Gomez, Corina


    Although drugs may serve as reinforcers or punishers of operant behavior, the punishing function has received much less experimental attention than the reinforcing function. A sensitive method for studying drug-induced punishment is to assess choice for a punished response over an unpunished response. In these experiments, rats chose between pressing one lever and receiving a sucrose pellet or pressing another lever and receiving a sucrose pellet plus an intravenous injection of histamine. Wh...

  18. General Pharmacology of Artesunate, a Commonly used Antimalarial Drug:Effects on Central Nervous, Cardiovascular, and Respiratory System. (United States)

    Lee, Hyang-Ae; Kim, Ki-Suk; Kim, Eun-Joo


    Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR) , and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial) . Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.

  19. Advance in the research of cardiovascular pharmacology of Sophora flavescens%苦参心血管药理作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    董珉翔; 白音夫


    Objective To summarize the chemical composition and pharmacology of Sophora flavescens. And to provide a foundation for the applicaton in the protection of cardiovascular pharmacology. Method The chemical compositions of Sophora favescens. Were summerized by reviewing literatures. Result It is found that matrine and oxymatrine have a lot of cardiovascular functions. They also show the effects of strengthening the heart function, resisting arrhythmia,and dropping the blood pressure. Conclusion By discussing the chemical composition and pharmacology,the mechanism of the cardiovascular pharmacology was revcallcd, which is advatageous to the further research of Sophora flavescens.%目的 对苦参的化学成分和药理作用进行综述,为进一步研究苦参的心血管作用奠定基础.方法 对相关文献进行归纳总结,并对其化学成分的药理作用分类综述.结果 苦参碱和氧化苦参碱有广泛的心血管药理作用,诸如抗心律失常、抗心肌细胞纤维化、对心肌损伤和心肌梗死的保护和降压等作用.结论 通过对苦参的化学成分和药理作用的讨论,揭示了苦参心血管作用的机制,有利于进一步研究.

  20. The rat - Cardiovascular pharmacology


    Sotomayor-Herazo Aristides; Mendoza-Goez Luis


    LA RATA:El Doctor Arístides Sotomayor Herazo, insigneespecialista en Medicina Interna y Cardiólogo, mehizo recordar en muchos de los episodios de estanovela, el signo trágico del que no pudo escaparEdipo. Si hoy existiese Sófocles, seguramente sehubiese impresionado, y tal vez le hubiese gustadocompartir la ocurrencia de la fecunda imaginaciónrealista de Arístides, no del hijo de Lisímaco,estratega militar de la batalla de Maratón de laantigua Grecia en el 409 a. C, sino del “Ari” de hoy,así ...

  1. Role of the dysfunctional ryanodine receptor - Na(+)-Ca(2+)exchanger axis in progression of cardiovascular diseases: What we can learn from pharmacological studies? (United States)

    Acsai, Károly; Ördög, Balázs; Varró, András; Nánási, Péter P


    Abnormal Ca(2+)homeostasis is often associated with chronic cardiovascular diseases, such as hypertension, heart failure or cardiac arrhythmias, and typically contributes to the basic ethiology of the disease. Pharmacological targeting of cardiac Ca(2+)handling has great therapeutic potential offering invaluable options for the prevention, slowing down the progression or suppression of the harmful outcomes like life threatening cardiac arrhythmias. In this review we outline the existing knowledge on the involvement of malfunction of the ryanodine receptor and the Na(+)-Ca(2+)exchanger in disturbances of Ca(2+)homeostasis and discuss important proof of concept pharmacological studies targeting these mechanisms in context of hypertension, heart failure, atrial fibrillation and ventricular arrhythmias. We emphasize the promising results of preclinical studies underpinning the potential benefits of the therapeutic strategies based on ryanodine receptor or Na(+)-Ca(2+)exchanger inhibition.

  2. cardiovasculares

    Directory of Open Access Journals (Sweden)

    Cristina Guerrero


    Full Text Available Uno de los aspectos que más discusión ha suscitado en los últimos tiempos entre quienes nos dedicamos al estudio de la emoción tiene que ver con la eventual asociación entre percepción, valoración y respuesta fisiológica. Esto es, siguiendo la máxima aristotélica, cabría cuestionar si las cosas son como son o son como cada quien las percibe. El objetivo de este experimento ha sido establecer la existencia de una conexión entre percepción de control y responsividad cardiovascular. La muestra estudiada ha estado conformada por estudiantes de la Universidad de Castellón; todos ellos han participado de forma voluntaria. La prueba de estrés ha consistido en un examen real de una asignatura troncal de la titulación que cursaban los participantes. Así pues, utilizando una situación de estrés real, hipotetizamos que las respuestas cardiovasculares (medidas a través de la tasa cardiaca, la presión sanguínea sistólica y la presión sanguínea diastólica dependen de la percepción de control que el individuo tiene, o cree tener, sobre la situación.


    NARCIS (Netherlands)



    In this review, hypotheses are discussed with regard to the role of local, tissue renin-angiotensin systems in the progression of cardiovascular dysfunction. After local renin-anglotensin systems had been described as functionally distinct systems, recent experimental studies have suggested an assoc

  4. The effect of a comprehensive lifestyle intervention on cardiovascular risk factors in pharmacologically treated patients with stable cardiovascular disease compared to usual care: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    IJzelenberg Wilhelmina


    Full Text Available Abstract Background The additional benefit of lifestyle interventions in patients receiving cardioprotective drug treatment to improve cardiovascular risk profile is not fully established. The objective was to evaluate the effectiveness of a target-driven multidisciplinary structured lifestyle intervention programme of 6 months duration aimed at maximum reduction of cardiovascular risk factors in patients with cardiovascular disease (CVD compared with usual care. Methods A single centre, two arm, parallel group randomised controlled trial was performed. Patients with stable established CVD and at least one lifestyle-related risk factor were recruited from the vascular and cardiology outpatient departments of the university hospital. Blocked randomisation was used to allocate patients to the intervention (n = 71 or control group (n = 75 using an on-site computer system combined with allocations in computer-generated tables of random numbers kept in a locked computer file. The intervention group received the comprehensive lifestyle intervention offered in a specialised outpatient clinic in addition to usual care. The control group continued to receive usual care. Outcome measures were the lifestyle-related cardiovascular risk factors: smoking, physical activity, physical fitness, diet, blood pressure, plasma total/HDL/LDL cholesterol concentrations, BMI, waist circumference, and changes in medication. Results The intervention led to increased physical activity/fitness levels and an improved cardiovascular risk factor profile (reduced BMI and waist circumference. In this setting, cardiovascular risk management for blood pressure and lipid levels by prophylactic treatment for CVD in usual care was already close to optimal as reflected in baseline levels. There was no significant improvement in any other risk factor. Conclusions Even in CVD patients receiving good clinical care and using cardioprotective drug treatment, a comprehensive



    Rabbani Syed Arman; Ali Syed Mahtab


    Cardiovascular diseases (CVDs) are the leading cause of death and disability in the world. They have emerged as a major health threat in develop¬ing countries contrary to the prior belief that they were confined primarily to industrialized nations. The global burden of disease due to cardiovascular diseases is escalating, principally due to a sharp rise in the developing countries which are experiencing rapid health transition. An estimated 17.3 million people died from CVDs in 2008 and over ...

  6. The experimental study of the specific pharmacological action of «Artproment» combined gel

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    О. S. Shpychak


    Full Text Available The preclinical experimental research concerning the study of the specific pharmacological action of "ArtpromentÒ" gel has been done. The gel developed contains propolis phenolic hydrophobic drug, articaine hydrochloride, menthol and rosemary oil in its composition. The medicine is planned to application in sports medicine with the purpose of treating traumatic injuries of organs of the locomotor apparatus accompanied with sport traumas (bruises, dislocations, sprains, ruptures of ligaments, tendons, etc.. In this work the pharmacological, physiological, instrumental methods of research and methods of mathematical statistics have been used. The study of the analgesic and local anesthetic action of the gel developed was conducted at the premises of the Central Research Laboratory of NUPh under the supervision of Doctor of Pharmacy, professor L.V.Iakovlieva on the model of tail thermoirritation in white rats weighing 180.0-200.0 g. The analgesic and local anesthetic actions were estimated by the ability of the medicine studied to change the pain threshold (duration of the latent period, sеc. in animals of the test group comparing to the control group in the dose of 25 mg/cm2 and the base in the dose of 30 mg/cm2 after application to the tail. The results of the experiment testify that when studying the influence of the combined gel on the course of the experimental nociceptive response of the central origin the significant analgesic action of "ArtpromentÒ" medicine has been determined; its highest intensity was observed in 2.5 and 3.5 hours after application and is 52 % and 59 %, respectively. Despite the fact that the progress of the pain syndrome in the model of tail thermoirritation is mediated by the central nervous system, it is possible to conclude that the developed gel has an expressed analgesic and local anesthetic action. The medicine shows the significant anti-edema action at the level of the reference medicine "Diclofen-gel" on the

  7. Role of the Renin-Angiotensin-Aldosterone System and Its Pharmacological Inhibitors in Cardiovascular Diseases: Complex and Critical Issues. (United States)

    Borghi, Claudio; Rossi, Francesco


    Hypertension is one of the major risk factor able to promote development and progression of several cardiovascular diseases, including left ventricular hypertrophy and dysfunction, myocardial infarction, stroke, and congestive heart failure. Also, it is one of the major driven of high cardiovascular risk profile in patients with metabolic complications, including obesity, metabolic syndrome and diabetes, as well as in those with renal disease. Thus, effective control of hypertension is a key factor for any preventing strategy aimed at reducing the burden of hypertension-related cardiovascular diseases in the clinical practice. Among various regulatory and contra-regulatory systems involved in the pathogenesis of cardiovascular and renal diseases, renin-angiotensin system (RAS) plays a major role. However, despite the identification of renin and the availability of various assays for measuring its plasma activity, the specific pathophysiological role of RAS has not yet fully characterized. In the last years, however, several notions on the RAS have been improved by the results of large, randomized clinical trials, performed in different clinical settings and in different populations treated with RAS inhibiting drugs, including angiotensin converting enzyme (ACE) inhibitors and antagonists of the AT1 receptor for angiotensin II (ARBs). These findings suggest that the RAS should be considered to have a central role in the pathogenesis of different cardiovascular diseases, for both therapeutic and preventive purposes, without having to measure its level of activation in each patient. The present document will discuss the most critical issues of the pathogenesis of different cardiovascular diseases with a specific focus on RAS blocking agents, including ACE inhibitors and ARBs, in the light of the most recent evidence supporting the use of these drugs in the clinical management of hypertension and hypertension-related cardiovascular diseases.

  8. Does rosmarinic acid underestimate as an experimental cardiovascular drug? Seria o ácido rosmarínico subestimado como droga cardiovascular experimental?

    Directory of Open Access Journals (Sweden)

    Luciana Garros Ferreira


    Full Text Available PURPOSE: The rationale of the present review is to analize the activity of Rosmarinus officinalis in the the cardiovascular system METHODS: A MEDLINE database search (from January 1970 to December 2011 using only rosmarinic acid as searched term. RESULTS: The references search revealed 509 references about rosmarinic acid in 40 years (the first reference is from 1970. There is a powerful prevalence of antioxidant and cancer studies. Other diseases are few cited, as inflammation, brain (Alzheimer and Parkinson disease and, memory; allergy; diabetes; atherosclerosis, and; hypertension. It is necessary to consider the complete absence of studies on coronary artery disease, myocardial ischemia, heart failure or ischemia/reperfusion injury. CONCLUSION: Rosmarinic acid is underestimated as an experimental cardiovascular drug and deserves more attention.OBJETIVO: A justificativa da revisão é analisar a atividade de Rosmarinus officinalis no sistema cardiovascular MÉTODOS: Uma busca de banco de dados MEDLINE (de janeiro de 1970 a dezembro de 2011, utilizando apenas o ácido rosmarínico como termo pesquisado. RESULTADOS: A busca referências revelou 509 referências sobre o ácido rosmarínico em 40 anos (a primeira referência é de 1970. Há uma prevalência poderoso antioxidante e estudos do câncer. Outras doenças são citados alguns, como o cérebro, inflamação (de Alzheimer e doença de Parkinson e, a memória, hipertensão, alergia, diabetes, aterosclerose, e. É necessário ter em conta a ausência completa de estudos sobre a doença de artéria coronária, isquemia do miocárdio, insuficiência cardíaca ou isquemia / lesão de reperfusão. CONCLUSÃO: O ácido rosmarínico é subestimado como uma droga experimental cardiovascular e merece mais atenção.

  9. Pharmacological Preventions of Brain Injury Following Experimental Germinal Matrix Hemorrhage: an Up-to-Date Review. (United States)

    Tang, Jun; Tao, Yihao; Jiang, Bing; Chen, Qianwei; Hua, Feng; Zhang, John; Zhu, Gang; Chen, Zhi


    Germinal matrix hemorrhage (GMH) is defined as the rupture of immature blood vessels in the subependymal zone of premature infants with significant mortality and morbidity. Considering the notable social and ecological stress brought by GMH-induced brain injury and sequelae, safe and efficient pharmacological preventions are badly needed. Currently, several appropriate animal models are available to mimic the clinical outcomes of GMH in human patients. In the long run, hemorrhagic strokes are the research target. Previously, we found that minocycline was efficient to alleviate GMH-induced brain edema and posthemorrhagic hydrocephalus (PHH) in rats, which may be closely related to the activation of cannabinoid receptor 2 (CB2R). However, how the two molecules correlate and the underlined molecular pathway remain unknown. To extensively understand current experimental GMH treatment, this literature review critically evaluates existing therapeutic strategies, potential treatments, and potentially involved molecular mechanisms. Each strategy has its own advantages and disadvantages. Some of the mechanisms are still controversial, requiring an increasing number of animal experiments before the therapeutic strategy would be widely accepted.

  10. Pharmacological benefits of agomelatine and vanillin in experimental model of Huntington's disease. (United States)

    Gupta, Surbhi; Sharma, Bhupesh


    Huntington's disease (HD), a devastating neurodegenerative disorder, is characterized by progressive motor dysfunction, emotional disturbances, dementia, weight loss, depression. Melatonin receptors are widely expressed in the central nervous system. Vanilloids are also valuable as pharmacological tools for investigating neurobiology. This study investigates the utility of agomelatine, a dual agonist of MT₁ and MT₂ melatonin receptor as well as vanillin, a selective agonist of TRPV₁ (vanilloid receptor) in 3-nitropropionic acid (3-NPA) induced experimental HD in rats. Locomotor activity (Actophotometer), motor coordination (Rota rod) and learning-memory (Morris water maze) were assessed. Brain striatum oxidative stress (lipid peroxidation-MDA, glutathione-GSH, superoxide dismutase-SOD and catalase-CAT), nitrosative stress (nitrite/nitrate) and mitochondrial enzyme complexes (I, II and IV) were also assessed. 3-NPA has induced weight loss, impaired locomotion, motor coordination as well as learning and memory. It has induced brain striatum oxidative as well as nitrosative stress, cholinergic dysfunction and impaired mitochondrial enzyme complexes (I, II and IV). Tetrabenazine (TBZ) was used as positive control. Treatment with agomelatine and vanillin and TBZ has significantly attenuated 3-NPA induced weight loss, impaired locomotion, motor coordination and learning-memory as well as biochemical impairments. Thus, agomelatine and vanillin exhibit protective effects against 3-NPA induced HD. It may be concluded that agomelatine and vanillin may provide benefits in HD.

  11. Pharmacological, morphological and behavioral analysis of motor impairment in experimentally vitamin C deficient guinea pigs

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    Oriá Reinaldo Barreto


    Full Text Available The scurvy shows an inflammatory disease and gingival bleeding. Nevertheless, in an animal model for guinea pigs, described by Den Hartog Jager in 1985, scurvy was associated with a motor neuron disease with demyelinization of the pyramidal tract, provoking neurogenic atrophy of muscles. Aiming at searching the protective role of vitamin C in nervous system, a pharmacological, morphological and behavioral study was conducted. Three experimental groups were used: A100, animals receiving 100 mg/ vitamin C/ day; A5.0, animals receiving 5.0 mg/vitamin C/ day; and A0, animals without vitamin C. We analyzed the weight gain, muscular diameter and behavioral tests. In all tests examined, we found significant differences between the supplemented groups in comparison with scorbutic group (p<0.05. Thereafter, the animals were killed for histopathology of gastrocnemius muscle, spinal cord and tooth tissues. In addition, a morphometric study of periodontal thickness and alpha-motor neuron cell body diameter were done. The vitamin C-diet free regimen seemed to induce a disruption in spinal cord morphology, involving the lower motor neuron, as confirmed by a significant reduction in neuron perycaria diameter and muscular atrophy, complicated by increased nutritional deficit.

  12. Comparative effectiveness and molecular pharmacological mechanisms of antiallergic agents on experimental conjunctivitis in mice. (United States)

    Hu, S; Merayo-Lloves, J; Zhao, T; Foster, C S


    The purpose of this study was to determine the effectiveness of antiallergic agents in the treatment of experimental murine ragweed conjunctivitis. SWR/J mice were divided into eight groups: 1; normal controls (unmanipulated); 2, untreated; 3, lodoxamide; 4, cromolyn; 5, livocarbastine; 6, nedocromil; 7, buffer solution (BS); and 8, tetrandine (TDR). Groups 2-8 were exposed to ragweed pollen through topical application to conjunctival and nasal mucosa, followed by conjunctival challenge with the allergen. Allergic conjunctivitis was evaluated by scoring of the clinical signs and histopathology. mRNA gene expression of interleukin 1beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alpha) in conjunctiva was analyzed by reverse transcription polymerase chain reaction techniques. Exposed mice developed allergic conjunctivitis clinically and histologically that was modulated by topical lodoxamide, cromolyn, livocarbastine, or nedocromil eye drops or TDR intraperitoneally injected. Histopathologic analysis demonstrated that the drugs and TDR significantly reduced conjunctival eosinophil infiltration and the number of intact and degranulating mast cells. IL-1beta and TNF-alpha mRNA gene expression in conjunctiva of treated mice was inhibited compared with untreated and BS-treated controls. No IL-6 mRNA expression was observed even on the conjunctiva of the untreated mice. The antiallergic drugs and TDR exerted a similar action on the murine model of allergic conjunctivitis and demonstrated pharmacologic effectiveness on the conjunctival mRNA expression of cytokines IL-1beta and TNF-alpha.

  13. Breathing Maneuvers as a Vasoactive Stimulus for Detecting Inducible Myocardial Ischemia – An Experimental Cardiovascular Magnetic Resonance Study (United States)

    Fischer, Kady; Guensch, Dominik P; Shie, Nancy; Lebel, Julie; Friedrich, Matthias G


    Background Breathing maneuvers can elicit a similar vascular response as vasodilatory agents like adenosine; yet, their potential diagnostic utility in the presence of coronary artery stenosis is unknown. The objective of the study is to investigate if breathing maneuvers can non-invasively detect inducible ischemia in an experimental animal model when the myocardium is imaged with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR). Methods and Findings In 11 anesthetised swine with experimentally induced significant stenosis (fractional flow reserve coronary artery (LAD) and 9 control animals, OS-CMR at 3T was performed during two different breathing maneuvers, a long breath-hold; and a combined maneuver of 60s of hyperventilation followed by a long breath-hold. The resulting change of myocardial oxygenation was compared to the invasive measurements of coronary blood flow, blood gases, and oxygen extraction. In control animals, all breathing maneuvers could significantly alter coronary blood flow as hyperventilation decreased coronary blood flow by 34±23%. A long breath-hold alone led to an increase of 97±88%, while the increase was 346±327% (pcoronary blood flow response was attenuated after both hyperventilation and the following breath-hold. This was matched by the observed oxygenation response as breath-holds following hyperventilation consistently yielded a significant difference in the signal of the MRI images between the perfusion territory of the stenosis LAD and remote myocardium. There was no difference between the coronary territories during the other breathing maneuvers or in the control group at any point. Conclusion In an experimental animal model, the response to a combined breathing maneuver of hyperventilation with subsequent breath-holding is blunted in myocardium subject to significant coronary artery stenosis. This maneuver may allow for detecting severe coronary artery stenosis and have a significant clinical potential as a

  14. Endothelial Small- and Intermediate-Conductance KCa Channels: An Update on Their Pharmacology and Usefulness as Cardiovascular Targets



    Most cardiovascular researchers are familiar with intermediate-conductance KCa3.1 and small-conductance KCa2.3 channels because of their contribution to endothelium-derived hyperpolarization (EDH). However, to immunologists and neuroscientists these channels are primarily known for their role in lymphocyte activation and neuronal excitability. KCa3.1 is involved in the proliferation and migration of T cells, B cell, mast cells, macrophages, fibroblasts and dedifferentiated vascular smooth mus...

  15. Cardiovascular safety pharmacology studies in dogs enabled for a poorly soluble molecule using spray-dried dispersion: Impact on lead selection. (United States)

    Tseng, Yin-Chao; Linehan, Brian; Ng, Khing Jow; Smith, Dustin M; Markert, Michael; Patel, Mita; Guth, Brian; Fryer, Ryan M


    The aim of this study was to identify an adequate formulation for a poorly soluble lead molecule (BI-A) that would achieve sufficiently high plasma concentrations after oral administration in dogs to enable a robust cardiovascular safety pharmacology assessment in telemetry-instrumented conscious dogs during lead optimization in drug discovery. A spray-dried dispersion of BI-A (BI-A-SDD) containing a 1:2 ratio of BI-A and hydroxypropyl methylcellulose acetate succinate-LF was prepared using a Büchi spray dryer B-90 (B-90). Physical form characterization, an in vitro dissolution test and a preliminary pharmacokinetic (PK) study following oral administration of BI-A-SDD were performed. Thereafter, effects on cardiovascular parameters in conscious, chronically-instrumented dogs were investigated for 24h after a single oral dose (5, 10, and 50mg/kg) using a modified Latin square cross-over study design. The BI-A-SDD powder was confirmed to be amorphous and was stable as an aqueous suspension for at least 4h. The BI-A-SDD suspension provided a greater rate and extent of dissolution than the crystalline BI-A suspension and the supersaturation was maintained for at least 4h. In PK studies the Cmax of the BI-A-SDD formulation (25.4μM; 77-fold the projected efficacious Cmax of 0.33μM) was 7.5-fold higher than the Cmax observed using oral administration of a 10% hydroxypropyl-β-cyclodextrin formulation at 100mg/kg in dogs (3.4μM). In conscious, chronically-instrumented dogs, the doses tested and plasma concentrations achieved were sufficient to enable a robust safety pharmacology evaluation. Multiple off-target hemodynamic effects were detected including acute elevations in aortic blood pressure (up to 22% elevation in systolic and diastolic blood pressure) and tachycardia (68% elevation in heart rate), results that were confirmed in other in vivo models. These results led to a deprioritization of BI-A. The study demonstrated that a spray-dried dispersion, prepared

  16. Evaluation of HDL-modulating interventions for cardiovascular risk reduction using a systems pharmacology approach[S (United States)

    Gadkar, Kapil; Lu, James; Sahasranaman, Srikumar; Davis, John; Mazer, Norman A.; Ramanujan, Saroja


    The recent failures of cholesteryl ester transport protein inhibitor drugs to decrease CVD risk, despite raising HDL cholesterol (HDL-C) levels, suggest that pharmacologic increases in HDL-C may not always reflect elevations in reverse cholesterol transport (RCT), the process by which HDL is believed to exert its beneficial effects. HDL-modulating therapies can affect HDL properties beyond total HDL-C, including particle numbers, size, and composition, and may contribute differently to RCT and CVD risk. The lack of validated easily measurable pharmacodynamic markers to link drug effects to RCT, and ultimately to CVD risk, complicates target and compound selection and evaluation. In this work, we use a systems pharmacology model to contextualize the roles of different HDL targets in cholesterol metabolism and provide quantitative links between HDL-related measurements and the associated changes in RCT rate to support target and compound evaluation in drug development. By quantifying the amount of cholesterol removed from the periphery over the short-term, our simulations show the potential for infused HDL to treat acute CVD. For the primary prevention of CVD, our analysis suggests that the induction of ApoA-I synthesis may be a more viable approach, due to the long-term increase in RCT rate. PMID:26522778

  17. What Are We Learning from the FDA-Mandated Cardiovascular Outcome Studies for New Pharmacological Antidiabetic Agents? (United States)

    Lovre, Dragana; Htun, Wynn; Carrion, Carly; Fonseca, Vivian A


    Cardiovascular disease (CVD) is common in patients with diabetes. For these patients, clinicians should seek diabetes treatment that is beneficial rather than harmful in relation to CVD. Until recently, there have been many treatments for hyperglycemia, whose impact on CVD has been controversial. The aims of this review are to evaluate the effectiveness of antihyperglycemic medications on risk factors for CVD and to examine the impact of these drugs on CVD in cardiovascular (CV) outcome trials. In this article, we summarize current knowledge about the impacts of these drugs on various risk factors as well as CV outcomes. We identify the recent emergence of trials with antihyperglycemic agents showing newly discovered CV benefits as well as past trials with antihyperglycemic agents not showing much benefit on CV events. Rather than focusing on treatment strategies, we review the effects of individual drug classes on CV outcomes. We also briefly review goal-driven glycemia reduction and its impact on CVD. We conclude that antihyperglycemic agents are associated with improvement in CV risk factors in patients with diabetes and insulin resistance; in fact, a few drugs reduced CV events in randomized CV outcome trials. Therefore, the use of these drugs is appropriate for reducing glucose and decreasing CV event risk in a select subpopulation.

  18. Laboratory model of the cardiovascular system for experimental demonstration of pulse wave propagation (United States)

    Stojadinović, Bojana; Nestorović, Zorica; Djurić, Biljana; Tenne, Tamar; Zikich, Dragoslav; Žikić, Dejan


    The velocity by which a disturbance moves through the medium is the wave velocity. Pulse wave velocity is among the key parameters in hemodynamics. Investigation of wave propagation through the fluid-filled elastic tube has a great importance for the proper biophysical understanding of the nature of blood flow through the cardiovascular system. Here, we present a laboratory model of the cardiovascular system. We have designed an experimental setup which can help medical and nursing students to properly learn and understand basic fluid hemodynamic principles, pulse wave and the phenomenon of wave propagation in blood vessels. Demonstration of wave propagation allowed a real time observation of the formation of compression and expansion waves by students, thus enabling them to better understand the difference between the two waves, and also to measure the pulse wave velocity for different fluid viscosities. The laboratory model of the cardiovascular system could be useful as an active learning methodology and a complementary tool for understanding basic principles of hemodynamics.


    Directory of Open Access Journals (Sweden)

    Rabbani Syed Arman


    Full Text Available Cardiovascular diseases (CVDs are the leading cause of death and disability in the world. They have emerged as a major health threat in develop¬ing countries contrary to the prior belief that they were confined primarily to industrialized nations. The global burden of disease due to cardiovascular diseases is escalating, principally due to a sharp rise in the developing countries which are experiencing rapid health transition. An estimated 17.3 million people died from CVDs in 2008 and over 80% of CVD deaths take place in low and middle income countries. By 2030, almost 23.6 million people will die from CVDs. Therefore, finding ways to reduce the mortality of cardiovascular disease remains an important public health goal. Traditional Medicines have been an integral part of the healthcare system since time immemorial. WHO reports indicate that around eighty percent of the global population still relies on botanical drugs and several herbal medicines have advanced to clinical use in modern times. Unani occupies an important place in the rich traditional heritage of indigenous systems of medicine in India and contributes significantly to the health care. The core of treatment in Unani System of Medicine is based on drugs of herbal, mineral and animal origin. The ancient classical literature of Unani has mention of numerous drugs possessing cardioprotective and cardiotonic activity, Arjun (Terminalia arjuna and Zafran (Crocus sativus are two of them. The Unani physicians have been using these drugs successfully since ages and this is possible only by inherent quality and safety standards specified in the system.With the advent of new techniques and recent upsurge towards scientific exploration of traditional medicines, empirical data substantiating their safety and efficacy has been generated and had led to better understanding of their role to prevent and cure diseases. The aim of this paper is to review and highlight the work done on Arjun

  20. A novel advanced glycation endproducts breaker restores cardiovascular dysfunctions in experimental diabetic rats

    Institute of Scientific and Technical Information of China (English)

    GangCHENG; Li-liWANG; Hong-yingLIU; HaoCUI; Ying-linCAO; SongLI


    AIM The formation of advanced glycation endproducts (AGEs) on connective tissue and matrix components leads to increases in collagen crosslinkingthat contributes to aortic and myocardial stiffness in normal aging and which occurs at an accelerated rate in diabetes. In this study, we examined the effects of a novel AGEs breaker, C36, on cardiovascular dysfunctions in experimental diabetic rats. METHODS and RESULTS Male Wiatar rats were made diabetic by i.p. injection of 70mg/kg streptozotocin. After 12 weeks of diabetes, the animals were randomly divided into 4 groups (n=8-11),

  1. Cardiovascular Effects of Shock and Trauma in Experimental Models. A Review

    Directory of Open Access Journals (Sweden)

    Mauricio Rocha-e-Silva


    Full Text Available Abstract Experimental models of human pathology are useful guides to new approaches towards improving clinical and surgical treatments. A systematic search through PubMed using the syntax (shock AND (trauma AND (animal model AND (cardiovascular AND ("2010/01/01"[PDat]: "2015/12/31"[PDat] found 88 articles, which were reduced by manual inspection to 43 entries. These were divided into themes and each theme is subsequently narrated and discussed conjointly. Taken together, these articles indicate that valuable information has been developed over the past 5 years concerning endothelial stability, mesenteric lymph, vascular reactivity, traumatic injuries, burn and sepsis. A surviving interest in hypertonic saline resuscitation still exists.

  2. Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals. (United States)

    Ojewole, J A O; Kamadyaapa, D R; Gondwe, M M; Moodley, K; Musabayane, C T


    The cardiovascular effects of Persea americana Mill (Lauraceae) aqueous leaf extract (PAE) have been investigated in some experimental animal paradigms. The effects of PAE on myocardial contractile performance was evaluated on guinea pig isolated atrial muscle strips, while the vasodilatory effects of the plant extract were examined on isolated portal veins and thoracic aortic rings of healthy normal Wistar rats in vitro. The hypotensive (antihypertensive) effect of the plant extract was examined in healthy normotensive and hypertensive Dahl salt-sensitive rats in vivo. P americana aqueous leaf extract (25-800 mg/ml) produced concentration-dependent, significant (p americana leaf could be used as a natural supplementary remedy in essential hypertension and certain cases of cardiac dysfunctions in some rural Africa communities.

  3. Reproduction of continuous flow left ventricular assist device experimental data by means of a hybrid cardiovascular model with baroreflex control. (United States)

    Fresiello, Libera; Zieliński, Krzysztof; Jacobs, Steven; Di Molfetta, Arianna; Pałko, Krzysztof Jakub; Bernini, Fabio; Martin, Michael; Claus, Piet; Ferrari, Gianfranco; Trivella, Maria Giovanna; Górczyńska, Krystyna; Darowski, Marek; Meyns, Bart; Kozarski, Maciej


    Long-term mechanical circulatory assistance opened new problems in ventricular assist device-patient interaction, especially in relation to autonomic controls. Modeling studies, based on adequate models, could be a feasible approach of investigation. The aim of this work is the exploitation of a hybrid (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo experimental data acquired during a continuous flow left ventricular assistance. The hybrid cardiovascular simulator embeds three submodels: a computational cardiovascular submodel, a computational baroreflex submodel, and a hydronumerical interface submodel. The last one comprises two impedance transformers playing the role of physical interfaces able to provide a hydraulic connection with specific cardiovascular sites (in this article, the left atrium and the ascending/descending aorta). The impedance transformers are used to connect a continuous flow pump for partial left ventricular support (Synergy Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular simulator. Data collected from five animals in physiological, pathological, and assisted conditions were reproduced using the hybrid cardiovascular simulator. All parameters useful to characterize and tune the hybrid cardiovascular simulator to a specific hemodynamic condition were extracted from experimental data. Results show that the simulator is able to reproduce animal-specific hemodynamic status both in physiological and pathological conditions, to reproduce cardiovascular left ventricular assist device (LVAD) interaction and the progressive unloading of the left ventricle for different pump speeds, and to investigate the effects of the LVAD on baroreflex activity. Results in chronic heart failure conditions show that an increment of LVAD speed from 20 000 to 22 000 rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3 L/min). Thanks to its flexibility and modular structure, the

  4. The trigonometric responder approach: a new method for detecting responders to pharmacological or experimental challenges. (United States)

    Reuter, M; Siegmund, A; Netter, P


    The paper presents a newly developed response measure that is particularly suitable for the evaluation of pharmacokinetic data. This method is based on trigonometric considerations, defining a hormone response as the difference between the angle of the slope of the curve before and after drug intake. In addition, the size of this difference is compared to the difference obtained in placebo conditions. In this way, the trigonometric response measure overcomes one of the most problematic shortcomings of the 'area under the curve' (AUC) approach, the problem of the initial value. We will present the mathematical background of the trigonometric method and demonstrate its usefulness by evaluating empirical data (a pharmacological challenge test using the dopamine agonist lisuride) and comparing it to classical AUC measures. This has been achieved by contrasting both approaches with responder definitions according to binary time series analysis and the peak value of the curve.

  5. Experimental Benefits of Sex Hormones on Vascular Function and the Outcome of Hormone Therapy in Cardiovascular Disease


    Ross, Reagan L.; Serock, Michelle R; Khalil, Raouf A.


    Cardiovascular disease (CVD) is more common in men and postmenopausal women than premenopausal women, suggesting vascular benefits of female sex hormones. Experimental data have shown beneficial vascular effects of estrogen including stimulation of endothelium-dependent nitric oxide, prostacyclin and hyperpolarizing factor-mediated vascular relaxation. However, the experimental evidence did not translate into vascular benefits of hormone replacement therapy (HRT) in postmenopausal women, and ...

  6. Cardiovascular pharmacology core reviews: aspirin. (United States)

    Gaglia, Michael A; Clavijo, Leonardo


    Acetylsalicylic acid, or aspirin, is perhaps the most well-studied drug in human history, but controversy persists regarding both optimal dose and its use in the primary prevention of atherothrombotic events. This article reviews the following: the effect of aspirin upon the cyclooxygenase pathway; clinical trials of aspirin for both secondary and primary prevention; prospective and retrospective studies of aspirin dose; the potential interaction between aspirin and ticagrelor; and the concept of aspirin resistance. It concludes with a review of major society guidelines regarding aspirin and offers a perspective on the evidence-based use of aspirin in clinical practice.

  7. Advancing pharmacometrics and systems pharmacology. (United States)

    Waldman, S A; Terzic, A


    Pharmacometrics and systems pharmacology are emerging as principal quantitative sciences within drug development and experimental therapeutics. In recognition of the importance of pharmacometrics and systems pharmacology to the discipline of clinical pharmacology, the American Society for Clinical Pharmacology and Therapeutics (ASCPT), in collaboration with Nature Publishing Group and Clinical Pharmacology & Therapeutics, has established CPT: Pharmacometrics & Systems Pharmacology to inform the field and shape the discipline.

  8. Impact of Bisphenol A on the Cardiovascular System — Epidemiological and Experimental Evidence and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Xiaoqian Gao


    Full Text Available Bisphenol A (BPA is a ubiquitous plasticizing agent used in the manufacturing of polycarbonate plastics and epoxy resins. There is well-documented and broad human exposure to BPA. The potential risk that BPA poses to the human health has attracted much attention from regulatory agencies and the general public, and has been extensively studied. An emerging and rapidly growing area in the study of BPA’s toxicity is its impact on the cardiovascular (CV system. Recent epidemiological studies have shown that higher urinary BPA concentration in humans is associated with various types of CV diseases, including angina, hypertension, heart attack and coronary and peripheral arterial disease. Experimental studies have demonstrated that acute BPA exposure promotes the development of arrhythmias in female rodent hearts. Chronic exposure to BPA has been shown to result in cardiac remodeling, atherosclerosis, and altered blood pressure in rodents. The underlying mechanisms may involve alteration of cardiac Ca2+ handling, ion channel inhibition/activation, oxidative stress, and genome/transcriptome modifications. In this review, we discuss these recent findings that point to the potential CV toxicity of BPA, and highlight the knowledge gaps in this growing research area.

  9. Measured outcomes with hypnosis as an experimental tool in a cardiovascular physiology laboratory. (United States)

    Casiglia, Edoardo; Tikhonoff, Valérie; Giordano, Nunzia; Andreatta, Elisa; Regaldo, Giuseppe; Tosello, Maria T; Rossi, Augusto M; Bordin, Daniele; Giacomello, Margherita; Facco, Enrico


    The authors detail their multidisciplinary collaboration of cardiologists, physiologists, neurologists, psychologists, engineers, and statisticians in researching the effects of hypnosis on the cardiovascular system and their additions to that incomplete literature. The article details their results and provides guidelines for researchers interested in replicating their research on hypnosis' effect on the cardiovascular system.

  10. 戒烟药物的心血管不良反应%Cardiovascular adverse reaction of pharmacologic agents for cessation

    Institute of Scientific and Technical Information of China (English)



    Smoking cessation can reduce morbidity and mortality of cardiovascular disease(CVD), which is important in CVD secondary prevention. Smoking is a chronic addiction disease, smoking cessation lead to relapse, often due to withdrawal symptoms. Psychological support and pharmacologic agents for cessation are needed during the smoking cessation process. Multiple randomized, control ed clinical trials demonstrated the benefits of counseling patients with CVD on smoking cessation. In contrast, relatively few clinical trials tested the safety or efficacy of pharmacotherapy for smokers with CVD. Researchers raised concerns about the safety of NRT, champix and sustained-release bupropion in patients with CVD, because both agents can have sympathetic activity and can theoretical y increase myocardial work, and NRT might also aggravate endothelial dysfunction, and reduce the myocardial oxygen supply through coronary vasoconstriction .So more and more doctors has paid attention on the safety of pharmacotherapy in smokers with CVD.%  戒烟可降低心血管疾病发生和死亡风险,是心血管疾病二级预防的重要内容。吸烟是一种慢性成瘾性疾病,戒烟过程中常因戒断症状导致复吸,在戒烟过程中需要心理支持治疗和戒烟药物辅助治疗。许多随机对照临床试验证实,戒烟心理辅导有助于患有心血管疾病吸烟者的戒烟。但很少有临床试验证实戒烟药物在心血管疾病患者应用的安全性及有效性。由于尼古丁替代治疗,以及缓释安非他酮和伐尼克兰均可引起交感神经兴奋,理论上增加心肌作功,提高心肌耗氧量;其中尼古丁替代治疗还可能引起内皮功能障碍,使冠状动脉收缩,心肌供氧量减少,因此,越来越多的研究者开始关注合并心血管疾病吸烟者中戒烟药物应用的安全性。

  11. The matching quality of experimental and control interventions in blinded pharmacological randomised clinical trials

    DEFF Research Database (Denmark)

    Bello, Segun; Wei, Maoling; Hilden, Jørgen


    to systematically identify and analyse studies of matching quality in drug trials. Our primary objective was to assess the proportion of studies that concluded that the matching was inadequate; our secondary objective was to describe mechanisms for inadequate matching. Methods: Systematic review. We searched Pub......Background: Blinding is a pivotal method to avoid bias in randomised clinical trials. In blinded drug trials, experimental and control interventions are often designed to be matched, i.e. to appear indistinguishable. It is unknown how often matching procedures are inadequate, so we decided......Med, Google Scholar and Web of Science Citation Index for studies that assessed whether supposedly indistinguishable interventions (experimental and control) in randomized clinical drug trials could be distinguished based on physical properties (e.g. appearance or smell). Two persons decided on study...

  12. Vitamin E in oxidant stress-related cardiovascular pathologies: focus on experimental studies. (United States)

    Turan, Belma; Vassort, Guy


    The scope of this review is to summarize the important roles of vitamin E family members as protective agents in cardiovascular pathologies of different types of disease states and particularly in diabetes, including some of our research results, to illustrate how this recent knowledge is helping to better understand the roles of the vitamin E family in biology, in animals and humans specifically. Cardiovascular disease, a general name for a wide variety of diseases, disorders and conditions, is caused by disorders of the heart and blood vessels. Cardiovascular disease is the world's largest killer, claiming 17.1 million lives a year. Cardiovascular complications result from multiple parameters including glucotoxicity, lipotoxicity, fibrosis. Obesity and diabetes mellitus are also often linked to cardiovascular disease. In fact, cardiovascular disease is the most life-threatening of the diabetic complications and diabetics are 2- to 4-fold more likely to die of cardiovascular-related causes than non-diabetics. In order to prevent the tendency of cardiovascular disease, primary prevention is needed by modifying risk factors. Several recent studies, besides earlier ones, have reported beneficial effects of therapy with antioxidant agents, including trace elements, vitamins (E and/or C), other antioxidants, against the cardiovascular dysfunction. Hence, the use of peroxisome proliferator activated receptor-α (PPARα) agonists to reduce fatty acid oxidation, of trace elements such as selenium as antioxidant and other antioxidants such as vitamins E and C, contributes to the prevention of these dysfunctions. Moreover, therapy with antioxidants and the above vitamins to prevent or delay the onset and development of cardiovascular complications in diabetic patients and animal models has been investigated although these studies showed inconsistent results.

  13. Possibilities of pharmacologic correction of cognitive disorders in conditions of experimental equivalent of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Nefyodov A.A.


    Full Text Available A comparative analysis of the impact of citicoline, ±-lipoic acid, nicergoline, donepezil and colloidal solution of nano-silver (CSNS on the processes of learning and consolidation of memorable track in the test of the conditional reaction of passive avoidance (CRPA in conditions of experimental allergic encephalomyelitis (EAE was conducted. Testing of passive defensive skill was performed on days 12 and 20 after the induction of EAE. To assess the impact of drugs on the inputted information processes the investigated substances were administered intragastrically (CSNS - intraperitoneally once daily in the definite dose from the second to the day 10 after the induction of EAE (latent phase of the disease, and assessing processes of conditional skill preserving, further administration of drugs by the day 20 of the experiment (average duration of EAE was used. A positive effect of citicoline, ±-lipoic acid, nicergoline and donepezil on the input information processes and the ability to prevent accelerated extinction of acquired contingent skill in the conditions of experimental pathology was established. Drugs statistically significantly increased duration of the latent period of CRPA in comparison with a group of active control by 49%, 43%, 39% and 34%, respectively. Here with preparations were characterized by a high coefficient of antiamnesic activity, by the end of the experiment it was recorded at the level of 95% (citicoline, 81% (±-lipoic acid, 76% (nicergoline and 53% (donepezil. It is shown that the ability to prevent development of cognitive impairment in conditions of experimental equivalent of multiple sclerosis decreases in the number of citicoline (500 mg/kg > ±-lipoic acid (50 mg/kg H nicergoline (10 mg/kg > donepezil (10 mg/kg.

  14. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  15. Pharmacological Effects of Organic Acids in Chinese Herbs and its Application in Cardiovascular Diseases%中药有机酸类成分的药理作用及在心血管疾病的应用

    Institute of Scientific and Technical Information of China (English)

    汤喜兰; 刘建勋; 李磊


    To review the research about the pharmacological effects of organic acids in chinese herbs and its application in cardiovascular diseases. To summarize and analyze related literature about the pharmacological effects of organic acids in chinese herbs and its application in cardiovascular diseases in recent years in China and abroad. Organic Acids in Chinese Herbs has a wide range of pharmacological effects, such as anti-inflammatory response, anti-platelet aggregation, antioxidant and inducing tumor cell apoptosis and so on. The effects of anti-inflammatory response, anti-platelet aggregation and antioxidant may have potential clinical application value for cardiovascular system diseases. We should attach importance to organic acids in chinese herbs and its application in cardiovascular diseases. It is important to clarify the material basis for efficacy of Chinese drugs and provide a new method for preventing and treatment of cardiovascular diseases.%对中药有机酸类成分的药理作用及在心血管疾病的应用进行综述.查阅国内外相关文献并对其进行分析.中药有机酸类成分药理作用广泛,如抗炎症反应,抑制血小板聚集、抗血栓,抗氧化,诱导肿瘤细胞凋亡等,其中抗炎症反应,抑制血小板聚集、抗血栓,抗氧化的药理作用可能对心血管系统疾病具有潜在的临床应用价值.重视中药有机酸类成分在心血管系统疾病中的科学研究,对于中药作用药效物质基础的阐明有重要意义,同时也为心血管疾病的防治提供了新的思路.

  16. Experimental pharmacological investigation of the antiarthrotic effects of the cartilage and bone marrow extract Rumalon

    Energy Technology Data Exchange (ETDEWEB)

    Kalbhen, D.A.


    On the basis of animal experiments, the authors have developed a model of arthrosis which is compatible in its radiological, macroscopic, biochemical, and histological aspects with the pathophysiology of human arthrosis and has been tried in the testing of the antiarthrotic properties of pharmaceuticals. Biochemically induced gonarthroses of experimental animals were used for studies of the effects of a cartilage and bone marrow extract (Rumalon) and a cartilage extract and its high-molecular component DAK-16 on the frequency and progression of degenerative joint diseases. As test parameters, measurements of the articular space, X-ray findings, and macroscopic findings were quantitatively evaluated. The animal experiments show that the inhibitive effects of steroidal and nonsteroidal antirheumatics on the synthesis of the cartilage matrix can be prevented or reduced by simultaneous administration of chondroprotective pharmaceuticals; this may be important on the clinical sector. This antagonism between antiphlogistic agents and Rumalon, which has been observed also in fibroblast cultures and wound healing experiments, is of interest especially for the treatment of activated arthroses.

  17. Neurovascular damage in experimental allergic encephalomyelitis: a target for pharmacological control

    Directory of Open Access Journals (Sweden)

    C. Bolton


    Full Text Available The blood-brain barrier (BBB is composed of a continuous endothelial layer with pericytes and astrocytes in close proximity to offer homeostatic control to the neurovasculature. The human demyelinating disease multiple sclerosis and the animal counterpart experimental allergic encephalomyelitis (EAE are characterized by enhanced permeability of the BBB facilitating oedema formation and recruitment of systemically derived inflammatory-type cells into target tissues to mediate eventual myelin loss and neuronal dysfunction. EAE is considered a useful model for examining the pathology which culminates in loss of BBB integrity and the disease is now proving valuable in assessing compounds for efficacy in limiting damage at neurovascular sites. The precise mechanisms culminating in EAE-induced BBB breakdown are unclear although several potentially disruptive mediators have been implicated and have been previously identified as potent effectors of cerebrovascular damage in non-disease related conditions of the central nervous system. The review considers evidence that common mechanisms may mediate cerebrovascular permeability changes irrespective of the initial insult and discusses therapeutic approaches for the control of BBB leakage in the demyelinating diseases.

  18. Pharmacological modulation of IgE-dependent mast cell degranulation in experimental autoimmune uveoretinitis. (United States)

    de Kozak, Y; Sakai, J; Sainte-Laudy, J; Faure, J P; Benveniste, J


    Immediate hypersensitivity phenomena have been shown previously to occur at the beginning of experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by immunization with purified S-antigen from bovine retina. The onset time and severity of the disease were modified by modulating the mast cell (MC) function. Drugs blocking the release of mediators from MC, disodium cromoglycate and ketotifen, given as eyedrops, slightly delayed the onset and decreased the severity of inflammation. Compound 48/80, a drug effective in depleting MC of their inflammatory mediators, delayed significantly the onset, decreased and sometimes suppressed EAU, when given by the subconjunctival or intraperitoneal routes. No modification of the IgG and the IgE circulating anti-S-antibody level was demonstrated in both types of treatment, whereas in vitro reagin-dependent degranulation of peritoneal MC in the presence of the antigen was decreased in both cases. Identification of MC-bound reagins as IgE was strongly suggested by the blocking effect of anti-IgE antibodies on MC degranulation. These data confirm the link between MC activation and the onset and severity of EAU.

  19. Neuropeptide Y and vasoactive intestinal peptide in experimental subarachnoid hemorrhage; Immunocytochemistry, radioimmunoassay and pharmacology

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    Alafaci, C.; Jansen, I. (Department of Experimental Research, Lund University, Malmoe General Hospital (Sweden)); Uddman, R. (Department of Otorhinolaryngology, Lund University, Malmoe General Hospital (Sweden)); Delgado, T.; Svendgaard, N.A. (Department of Neurosurgery, University Hospital, Lund (Sweden)); Edvinsson, L. (Department of Internal Medicine, University Hospital, Lund (Sweden)); Ekman, R. (Department of Psychiatry and Neurochemistry, University Hospital, Lund (Sweden))


    The involvement of noradrenaline (NA), neuropeptide Y, (NPY), 5-hydroxytryptamine (5-HT), acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) has been examined in the late phase of spasm after an experimental subarachnoid hemorrhage (SAH) in a rat model. Immunocytochemistry and radioimmunoassay of blood vessels from the circle of Willis did not show significant differences in NPY- and VIP-like immunoreactivity 2 days post SAH as compared to control vessels. The postjunctional effects of NA, NPY, 5-HT, Ach and VIP were studied two days after SAH using a sensitive in vitro system. NPY induced contractions were significantly (p<0.01) weaker (lower E{sub max}) in SAH as compared to control rats while the relaxant responses to ACh and VIP were slightly increased after SAH. These observations reveal that in a rat model of SAH, with an approximately 20% in vivo constriction at two days, dynamic changes occur in cerebral artery reactivity without any obvious change in sympathetic or parasympathetic perivascular nerve networks. (author).

  20. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    Full Text Available BACKGROUND: One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death. METHODOLOGY/PRINCIPAL FINDINGS: A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase. CONCLUSIONS

  1. Trait and state positive affect and cardiovascular recovery from experimental academic stress. (United States)

    Papousek, Ilona; Nauschnegg, Karin; Paechter, Manuela; Lackner, Helmut K; Goswami, Nandu; Schulter, Günter


    As compared to negative affect, only a small number of studies have examined influences of positive affect on cardiovascular stress responses, of which only a few were concerned with cardiovascular recovery. In this study, heart rate, low- and high-frequency heart rate variability, blood pressure, and levels of subjectively experienced stress were obtained in 65 students before, during and after exposure to academic stress in an ecologically valid setting. Higher trait positive affect was associated with more complete cardiovascular and subjective post-stress recovery. This effect was independent of negative affect and of affective state during anticipation of the stressor. In contrast, a more positive affective state during anticipation of the challenge was related to poor post-stress recovery. The findings suggest that a temporally stable positive affect disposition may be related to adaptive responses, whereas positive emotional states in the context of stressful events can also contribute to prolonged post-stress recovery.

  2. Space radiation and cardiovascular disease risk

    Institute of Scientific and Technical Information of China (English)

    Marjan Boerma; Gregory A Nelson; Vijayalakshmi Sridharan; Xiao-Wen Mao; Igor Koturbash; Martin Hauer-Jensen


    Future long-distance space missions will be associated with significant exposures to ionizing radiation,and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Groundbased studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses,appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk,and several other studies are ongoing. Moreover,astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation,and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined,the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy.

  3. Space radiation and cardiovascular disease risk. (United States)

    Boerma, Marjan; Nelson, Gregory A; Sridharan, Vijayalakshmi; Mao, Xiao-Wen; Koturbash, Igor; Hauer-Jensen, Martin


    Future long-distance space missions will be associated with significant exposures to ionizing radiation, and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Ground-based studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses, appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk, and several other studies are ongoing. Moreover, astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation, and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined, the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy.

  4. C16, a novel advanced glycation endproduct breaker, restores cardiovascular dysfunction in experimental diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Gang CHENG; Li-li WANG; Wen-sheng QU; Long LONG; Hao CUI; Hong-ying LIU; Ying-lin CAO; Song LI


    Aim: Advanced glycation endproducts (AGE) have been implicated in the pathogenesis of diabetic complications, including diabetic cardiovascular dysfunction.3-[2-(4-Bromo-phenyl)- 1-methyl-2-oxo-ethyl]-4,5,6,7-tetrahydro-benzothiazol-3-ium bromide (C16), a novel AGE breaker, was investigated for its effects on the development of cardiovascular disease in diabetic rats. Methods: Rats that had streptozotocin-induced diabetes for 12 weeks were divided into groups receiving C16 or vehicle by gavage. Results: In hemodynamic studies of the left ventricle,C16 treatment (25 or 50 mg/kg) for 4 weeks resulted in a significant increase in left ventricular systolic pressure, +dp/dtmax, and -dp/dtmax as compared with vehicletreated diabetic rats. Furthermore, in hemodynamic studies of the cardiovascular system, C16 (12.5, 25, or 50 mg/kg) treatment for 4 weeks resulted in a dosedependent and significant increase in cardiac output, a reduction of total peripheral resistance, and an increase in systemic arterial compliance when compared with vehicle-treated diabetic rats. Biochemical studies showed that C16 treatment also resulted in a significant decrease in immunoglobulin G-red blood cell surface crosslink content and an increase in collagen solubility. Morphological and immunohistochemical examinations indicated that C 16 was able to prevent increases of the collagen type Ⅲ/Ⅰ ratio in the aorta and decrease the accumulation of AGE in the aorta. Conclusion: C16 has the ability to reduce AGE accumulation in tissues in vivo, and can restore diabetes-associated cardiovascular disorders in rats. This provides a potential therapeutic approach for cardiovascular disease associated with diabetes and aging in humans.

  5. Cardiovascular benefits of probiotics: a review of experimental and clinical studies. (United States)

    Thushara, Ram Mohan; Gangadaran, Surendiran; Solati, Zahra; Moghadasian, Mohammed H


    The microbiota inhabiting the human gastro-intestinal tract is reported to have a significant impact on the health of an individual. Recent findings suggest that the microbial imbalance of the gut may play a role in pathogenesis of cardiovascular diseases (CVD). Therefore, several studies have delved into the aspect of altering gut microbiota with probiotics as an approach to prevent and/or treat CVD. The World Health Organization defines probiotics as live microorganisms that, when consumed in adequate amounts, have a positive influence on the individual's health. The present review focuses on strategies of human dietary intervention with probiotic strains and their impact on cardiovascular risk factors like hypercholesterolemia, hypertension, obesity and type-2 diabetes. Accumulating evidence shows probiotics to lower low density lipoproteins (LDL)-cholesterol and improve the LDL/high density lipoproteins (HDL) ratio, as well as lower blood pressure, inflammatory mediators, blood glucose levels and body mass index. Thus, probiotics have the scope to be developed as dietary supplements with potential cardiovascular health benefits. However, there is not only ambiguity regarding the exact strains and dosages of the probiotics that will bring about positive health effects, but also factors like immunity and genetics of the individual that might influence the efficacy of probiotics. Therefore, further studies are required not only to understand the mechanisms by which probiotics may beneficially affect the cardiovascular system, but also to rule out any of their probable negative effects on health. The present review aims to critically appraise the complexity of the available data with regard to the cardiovascular benefits of probiotics.

  6. Euterpe oleracea Extract (Açaí) Is a Promising Novel Pharmacological Therapeutic Treatment for Experimental Endometriosis (United States)

    Machado, Daniel Escorsim; Rodrigues-Baptista, Karina Cristina; Alessandra-Perini, Jessica; Soares de Moura, Roberto; dos Santos, Thiago Alves; Pereira, Kariny Gomes; Marinho da Silva, Yasmin; Souza, Pergentino José Cunha; Nasciutti, Luiz Eurico; Perini, Jamila Alessandra


    This study investigated the therapeutic potential of Euterpe oleracea extract (açaí) on the growth and survival of endometriotic lesions using an experimental model. Twenty female Sprague-Dawley rats were randomized into two groups after the implantation and establishment of autologous endometrium onto the peritoneum abdominal wall and treated with 200 mg/kg hydroalcoholic solution extract from açaí stone or vehicle via gastric tube for 30 consecutive days. Body weight, lesion surface areas, histological and immunohistochemistry analyses of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and F4-80 were performed. Levels of VEGF, VEGFR-2, MMP-9 and COX-2 mRNA were measured. Flow cytometry of F4-80 was performed, and ELISA immunoassays measured prostaglandin E2 (PGE2), VEGF and nitric oxide (NO) and concentrations. Macrophage cell line J774.G8 was treated with 10, 20, and 40 μg/mL of açaí for 24, 48 and 72 h, and cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Açaí treatment significantly decreased the implant size, and histological examination indicated atrophy and regression. A reduction in immunostaining and mRNA expression of VEGF, MMP-9 and COX-2 was observed, and F4-80 was lower in the treated group than the control group. The treated group also exhibited lower concentrations of PGE2, VEGF and NO compared to the control group. Macrophages cells treated with 20 and 40 μg/ml of açaí reduced cell viability in about 50% after 24, 48 and 72 h. Our results suggest that açaí effectively suppressed the establishment and growth of endometriotic lesions, and this agent is a promising novel pharmacological therapeutic treatment for endometriosis. PMID:27851787

  7. Injected nanoparticles: the combination of experimental systems to assess cardiovascular adverse effects. (United States)

    Vlasova, Maria A; Tarasova, Olga S; Riikonen, Joakim; Raula, Janne; Lobach, Anatoly S; Borzykh, Anna A; Smirin, Boris V; Kauppinen, Esko I; Eletskii, Alexander V; Herzig, Karl-Heinz; Salonen, Jarno; Tavi, Pasi; Lehto, Vesa-Pekka; Järvinen, Kristiina


    When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.

  8. Blocking 5-HT2 receptor restores cardiovascular disorders in type 1 experimental diabetes (United States)

    García-Pedraza, José-Ángel; Ferreira-Santos, Pedro; Aparicio, Rubén; Montero, María-José; Morán, Asunción


    This study aimed to determine whether the serotonergic modulation, through selective 5-HT2 receptor blockade, restores cardiovascular disturbances in type 1 diabetic rats. Diabetes was induced by alloxan (150 mg/kg, s.c.) and maintained for 4 weeks. 5-HT2 receptor was blocked by sarpogrelate (30 mg/; 14 days; p.o.). Systolic blood pressure (SBP), heart rate (HR), glycaemia and body weight (BW) were monitored periodically. Animals were sacrificed at the end of the study and the heart, right kidney and thoracic aorta were removed; plasma samples were also obtained. Left ventricular hypertrophy index (LVH) and renal hypertrophy index (RH) were determined. Vascular function was studied in aorta rings; additionally, superoxide anion (O2•−) production (by lucigenin-enhanced chemiluminescence) and lipid peroxidation (by thiobarbituric acid reactive substances assay) were measured. Neither alloxan nor sarpogrelate treatments altered HR, LVH or endothelium-independent relaxation. SBP, glycaemia, BW, RH, O2•− production and lipid peroxidation were significantly altered in diabetic animals compared with controls. Sarpogrelate treatment considerably decreased SBP, RH, O2•− production and lipid peroxidation. Endothelium-dependent relaxation was severely reduced in diabetic animal aortas compared to controls; sarpogrelate treatment markedly improved it. Our outcomes show that selectively blocking 5-HT2 receptors has beneficial effects on impaired cardiovascular parameters in diabetes. PMID:27659784

  9. The Mechanisms of Pharmacological Preconditioning of the Brain and the Comparative Efficacy of the Drugs — Direct- and Indirect-Acting Glycogen Synthase Kinase-3β Inhibitors: Experimental Study

    Directory of Open Access Journals (Sweden)

    V. V. Likhvantsev


    Full Text Available Objective: to investigate the activity of sevoflurane, dalargin, and lithium chloride in protecting the rat brain from total ischemia/reperfusion and to define whether the GSK=3^ deposphorylation contributes to the mechanism of pharmacological preconditioning. Materials and methods. Experiments were carried out on 80 male albino rats in which temporary circulatory arrest (CA was simulated by ligating the cardiovascular fascicle for 10 and 20 minutes. The animals were revived by mechanical ventilation external cardiac massage, and the intratracheal injection of adrenaline (epinephrine, Moscow Endocrinology Plant at a dose of 0.1 mg/kg. Animals were divided into 9 groups and sevorane (sevoflurane, Abbott Laboratories, dalargin (Microgen Research-and-Production Association, or lithium chloride (Sigma Chemical Co. were separately given with and without CA. Brain tissue homogenate specimens were obtained from euthanized animals. The concentration of total glycogen synthase kinase-3^ (GSK-3^ was colorimetrically determined using a Hitachi-557 spectrophotometer (Hitachi Ltd., Japan. The content of phosphorylated GSK-3/3 (pGSK-3^ in brain homogenate was estimated by Western blotting. Results. The total level of GSK-3^ in each group was similar (80—90 relative units and remained unchanged throughout each experiment. Twenty-minute ischemia maximally activated GSK-30 through dephosphorylation. Ten-minute ischemia elevated pGSK-3^ levels by more than 5 times as compared to the baseline value revealing the «training» effect. The quantity of pGSK-3^ was unchanged in the ischemia/perfusion group during sevoflurane insufflation and was decreased by 27% during dalargin administration. Conclusion. The experimental model of total ischemia provided evidence that the test drugs had a pharmacological preconditioning effect on brain neurons. According to their increasing effect, the drugs were arranged in the following order: dalargin < sevoflurane < lithium

  10. System analysis of changes in cardiovascular circulatory dynamics in experimental diphtheria in rabbit. (United States)

    Zotov, A K; Frolov, V A; Zotova, T J


    Trivariate correlation analysis of hemodynamic indices of the cardiovascular system in rabbits with diphtheria showed that adaptation of this system to direct action of diphtherin can be visualized by analysis of trivariate correlation tightness for indices of intraventricular pressure in the left and right ventricles and indices of systemic blood pressure. Using empirical production functions for systemic blood pressure indices we found that the contribution of intraventricular pressure in the left and right ventricles on blood pressure values is changed in diphtheria compared to the control. Basing on entropy analysis we established that the regimen of control over values of working intraventricular pressure in both left and right ventricles in diphtheria is changed from quasidetermined to stochastic.

  11. Oligodendroglial alpha-synucleinopathy and MSA-like cardiovascular autonomic failure: experimental evidence. (United States)

    Kuzdas, Daniela; Stemberger, Sylvia; Gaburro, Stefano; Stefanova, Nadia; Singewald, Nicolas; Wenning, Gregor K


    Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with limited symptomatic treatment options. Discrimination of MSA from other degenerative disorders crucially depends on the presence of early and severe cardiovascular autonomic failure (CAF). We have previously shown that neuropathologic lesions in the central autonomic nuclei similar to the human disease are present in transgenic MSA mice generated by targeted oligodendroglial overexpression of α-syn using the PLP promoter. We here explore whether such lesions result in abnormalities of heart rate variability (HRV) and circadian rhythmicity which are typically impaired in MSA patients. HRV analysis was performed in five month old transgenic PLP-α-syn (tg) MSA mice and age-matched wild type controls. Decreased HRV and alterations in the circadian rhythmicity were detected in the tg MSA group. The number of choline-acetyltransferase-immunoreactive neurons in the nucleus ambiguus was significantly decreased in the tg group, whereas the levels of arginine-vasopressin neurons in the suprachiasmatic and paraventricular nucleus were not affected. Our finding of impaired HRV and circadian rhythmicity in tg MSA mice associated with degeneration of the nucleus ambiguus suggests that a cardinal non-motor feature of human MSA can be reproduced in the mouse model strengthening its role as a valuable testbed for studying selective vulnerability and assessing translational therapies.

  12. Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury. (United States)

    Joukar, Siyavash; Bashiri, Hamideh; Dabiri, Shahriar; Ghotbi, Payam; Sarveazad, Arash; Divsalar, Kouros; Joukar, Farzin; Abbaszadeh, Mahsa


    The present study was designed to elucidate the outcome of subchronic co-administration of black tea and nicotine on cardiovascular performance and whether these substances could modulate the isoproterenol-induced cardiac injury. Animal groups were control, black tea, nicotine and black tea plus nicotine. Test groups received nicotine (2 mg/kg s.c.) and black tea brewed (p.o.) each alone and in combination for 4 weeks. On the 28th day, myocardial damage was induced by isoproterenol (50 mg/kg i.p.), and blood samples were taken. On day 29, after hemodynamic parameters recording, hearts were removed for histopathological evaluation. Tea or nicotine consumption had no significant effects on hemodynamic indices of animals without heart damage. When the cardiac injury was induced, tea consumption maintained the maximum dp/dt, and nicotine significantly decreased the pressure-rate product. Moreover, severity of heart lesions was lower in the presence of nicotine or black tea. Concomitant use of these materials did not show extra effects on mentioned parameters more than the effect of each of them alone. The results suggest that subchronic administration of black tea or nicotine for a period of 4 weeks may have a mild cardioprotective effect, while concomitant use of these materials cannot intensify this beneficial effect.

  13. The pharmacology of psilocybin. (United States)

    Passie, Torsten; Seifert, Juergen; Schneider, Udo; Emrich, Hinderk M


    Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.

  14. Hydroxytyrosol ameliorates metabolic, cardiovascular and liver changes in a rat model of diet-induced metabolic syndrome: Pharmacological and metabolism-based investigation. (United States)

    Poudyal, Hemant; Lemonakis, Nikolaos; Efentakis, Panagiotis; Gikas, Evangelos; Halabalaki, Maria; Andreadou, Ioanna; Skaltsounis, Leandros; Brown, Lindsay


    Metabolic syndrome is a clustering of interrelated risk factors for cardiovascular disease and diabetes. The Mediterranean diet has been proposed as an important dietary pattern to confer cardioprotection by attenuating risk factors of metabolic syndrome. Hydroxytyrosol (HT) is present in olive fruit and oil, which are basic constituents of the Mediterranean diet. In this study, we have shown that treatment with HT (20mg/kg/d for 8 weeks) decreased adiposity, improved impaired glucose and insulin tolerance, improved endothelial function with lower systolic blood pressure, decreased left ventricular fibrosis and resultant diastolic stiffness and reduced markers of liver damage in a diet-induced rat model of metabolic syndrome. These results were accompanied by reduced infiltration of monocytes/macrophages into the heart with reduced biomarkers of oxidative stress. Furthermore, in an HRMS-based metabolism study of HT, we have identified 24 HT phase I and II metabolites, six of them being over-produced in high-starch, low-fat diet fed rats treated with HT compared to obese rats on high-carbohydrate, high-fat diet. These results provide direct evidence for cardioprotective effects of hydroxytyrosol by attenuation of metabolic risk factors. The implications of altered metabolism of HT in high-carbohydrate, high-fat diet fed obese rats warrant further investigation.

  15. The pharmacology of Malo maxima jellyfish venom extract in isolated cardiovascular tissues: A probable cause of the Irukandji syndrome in Western Australia. (United States)

    Li, Ran; Wright, Christine E; Winkel, Kenneth D; Gershwin, Lisa-Ann; Angus, James A


    The in vitro cardiac and vascular pharmacology of Malo maxima, a newly described jellyfish suspected of causing Irukandji syndrome in the Broome region of Western Australia, was investigated in rat tissues. In left atria, M. maxima crude venom extract (CVE; 1-100μg/mL) caused concentration-dependent inotropic responses which were unaffected by atropine (1μM), but significantly attenuated by tetrodotoxin (TTX; 0.1μM), propranolol (1μM), Mg(2+) (6mM) or calcitonin gene-related peptide antagonist (CGRP(8-37); 1μM). CVE caused no change in right atrial rate until 100μg/mL, which elicited bradycardia. This was unaffected by atropine, TTX, propranolol or CGRP(8-37). In the presence of Mg(2+), CVE 30-100μg/mL caused tachycardia. In small mesenteric arteries CVE caused concentration-dependent contractions (pEC(50) 1.03±0.07μg/mL) that were unaffected by prazosin (0.3μM), ω-conotoxin GVIA (0.1μM) or Mg(2+) (6mM). There was a 2-fold increase in sensitivity in the presence of CGRP(8-37) (3μM). TTX (0.1μM), box jellyfish Chironex fleckeri antivenom (92.6U/mL) and benextramine (3μM) decreased sensitivity by 2.6, 1.9 and 2.1-fold, respectively. CVE-induced maximum contractions were attenuated by C. fleckeri antivenom (-22%) or benextramine (-49%). M. maxima CVE appears to activate the sympathetic, but not parasympathetic, nervous system and to stimulate sensory nerve CGRP release in left atria and resistance arteries. These effects are consistent with the catecholamine excess thought to cause Irukandji syndrome, with additional actions of CGRP release.

  16. Test of the usefulness of a paradigm to identify potential cardiovascular liabilities of four test articles with varying pharmacological properties in anesthetized guinea pigs. (United States)

    Kijtawornrat, Anusak; Ueyama, Yukie; del Rio, Carlos; Sawangkoon, Suwanakiet; Buranakarl, Chollada; Chaiyabutr, Narongsak; Hamlin, Robert L


    The evaluation of proarrhythmic and hemodynamic liabilities for new compounds remains a major concern of preclinical safety assessment paradigms. Contrastingly, albeit functional liabilities can also translate to clinical morbidity and mortality, lesser preclinical efforts are focused on the evaluation of drug-induced changes in inotrope and lusitrope, particularly in the setting of concomitant hemodynamic/arrhythmic liabilities. This study aimed to establish the feasibility of an anesthetized guinea pig preparation to assess functional liabilities in the setting of simultaneous drug-induced electrocardiographic/hemodynamic changes, by evaluating the effects of various compounds with known cardiovascular properties on direct and indirect indices of left ventricular function. In short, twenty nine male guinea pigs were instrumented to measure electrocardiograms, systemic arterial pressure, and left ventricular pressure-volume relationships. After baseline measurement, all animals were given intravenous infusions of vehicle and two escalating concentrations of either chromanol 293B (n = 8), milrinone (n = 6), metoprolol (n = 7), or nicorandil (n = 8) for 10 minutes each. In all cases, these compounds produced the expected changes. The slope of preload-recruitable stroke work (PRSW), a pressure-volume derived load independent index, was the most sensitive marker of drug-induced changes in inotropy. Among the indirect functional indices studied, only the "contractility index" (dP/dtmax normalized by the pressure at its occurrence) and the static myocardial compliance (ratio of end diastolic volume and pressure) appeared to be adequate predictors of drug-induced changes in inotropy/lusitropy. Overall, the data confirms that both electrophysiological and mechanical liabilities can be accurately assessed in an anesthetized guinea pig preparation.

  17. Pharmacology of Marihuana (Cannabis sativa) (United States)

    Maickel, Roger P.


    A detailed discussion of marihuana (Cannabis sativa) providing the modes of use, history, chemistry, and physiologic properties of the drug. Cites research results relating to the pharmacologic effects of marihuana. These effects are categorized into five areas: behavioral, cardiovascular-respiratory, central nervous system, toxicity-toxicology,…

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

    Directory of Open Access Journals (Sweden)

    D. S. R. Rajkumar


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

  19. A Novel Closed-Chest Porcine Model of Chronic Ischemic Heart Failure Suitable for Experimental Research in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Giuseppe Biondi-Zoccai


    Full Text Available Cardiac pathologies are among the leading causes of mortality and morbidity in industrialized countries, with myocardial infarction (MI representing one of the major conditions leading to heart failure (HF. Hitherto, the development of consistent, stable, and reproducible models of closed-chest MI in large animals, meeting the clinical realism of a patient with HF subsequent to chronic ischemic necrosis, has not been successful. We hereby report the design and ensuing application of a novel porcine experimental model of closed-chest chronic ischemia suitable for biomedical research, mimicking post-MI HF. We also emphasize the key procedural steps involved in replicating this unprecedented model, from femoral artery and vein catheterization to MI induction by permanent occlusion of the left anterior descending coronary artery through superselective deployment of platinum-nylon coils, as well as endomyocardial biopsy sampling for histologic analysis and cell harvesting. Our model could indeed represent a valuable contribution and tool for translational research, providing precious insights to understand and overcome the many hurdles concerning, and currently quenching, the preclinical steps mandatory for the clinical translation of new cardiovascular technologies for personalized HF treatments.

  20. The Directive 2010/63/EU on animal experimentation may skew the conclusions of pharmacological and behavioural studies. (United States)

    Macrì, Simone; Ceci, Chiara; Altabella, Luisa; Canese, Rossella; Laviola, Giovanni


    All laboratory animals shall be provided some form of environmental enrichment (EE) in the nearest future (Directive 2010/63/EU). Displacing standard housing with EE entails the possibility that data obtained under traditional housing may be reconsidered. Specifically, while EE often contrasts the abnormalities of consolidated disease models, it also indirectly demonstrates that their validity depends on housing conditions. We mimicked a situation in which the consequences of a novel pharmacological compound were addressed before and after the adoption of the Directive. We sub-chronically exposed standard- or EE-reared adolescent CD1 mice (postnatal days 23-33) to the synthetic compound JWH-018, and evaluated its short- and long-term potential cannabinoid properties on: weight gain, locomotion, analgesia, motor coordination, body temperature, brain metabolism ((1)H MRI/MRS), anxiety- and depressive-related behaviours. While several parameters are modulated by JWH-018 independently of housing, other effects are environmentally mediated. The transition from standard housing to EE shall be carefully monitored.

  1. Healthspan Pharmacology. (United States)

    Jafari, Mahtab


    The main goal of this paper is to present the case for shifting the focus of research on aging and anti-aging from lifespan pharmacology to what I like to call healthspan pharmacology, in which the desired outcome is the extension of healthy years of life rather than lifespan alone. Lifespan could be influenced by both genetic and epigenetic factors, but a long lifespan may not be a good indicator of an optimal healthspan. Without improving healthspan, prolonging longevity would have enormous negative socioeconomic outcomes for humans. Therefore, the goal of aging and anti-aging research should be to add healthy years to life and not merely to increase the chronological age. This article summarizes and compares two categories of pharmacologically induced lifespan extension studies in animal model systems from the last two decades-those reporting the effects of pharmacological interventions on lifespan extension alone versus others that include their effects on both lifespan and healthspan in the analysis. The conclusion is that the extrapolation of pharmacological results from animal studies to humans is likely to be more relevant when both lifespan and healthspan extension properties of pharmacological intervention are taken into account.

  2. Pharmacological inhibition of FAAH activity in rodents: A promising pharmacological approach for psychological-cardiac comorbidity? (United States)

    Carnevali, Luca; Rivara, Silvia; Nalivaiko, Eugene; Thayer, Julian F; Vacondio, Federica; Mor, Marco; Sgoifo, Andrea


    Numerous studies have documented a link between psychological disorders and cardiac disease. Yet, no systematic attempts have been made to develop pharmacological approaches for mood and anxiety disorders that could also be beneficial for cardiac health. The endocannabinoid system has been implicated in the regulation of stress, emotional behavior and cardiovascular function. General preclinical findings indicate that the endocannabinoid anandamide modulates physiological and behavioral stress responses and may also protect the heart from arrhythmias. Moreover, recent experimental studies suggest that pharmacological enhancement of anandamide signaling via inhibition of its degrading enzyme fatty acid amide hydrolase (FAAH) exerts anxiolytic- and antidepressive-like effects and improves cardiac autonomic function and the electrical stability of the myocardium in rodent models that reproduce aspects of human psychological/cardiac comorbidity. Here we summarize and discuss such experimental findings, which might guide future preclinical studies towards a systematic evaluation of the therapeutic potential of pharmacological approaches that target FAAH activity for the treatment of the comorbidity between psychological disorders and cardiac disease.

  3. Pharmacological characterization of antiepileptic drugs and experimental analgesics on low magnesium-induced hyperexcitability in rat hippocampal slices. (United States)

    Arias, Robert L; Bowlby, Mark R


    Perfusion of acute hippocampal slices with stimulatory buffers has long been known to induce rhythmic, large amplitude, synchronized spontaneous neuronal bursting in areas CA1 and CA3. The characteristics of this model of neuronal hyperexcitability were investigated in this study, particularly with respect to the activity of antiepileptic drugs and compounds representing novel mechanisms of analgesic action. Toward that end, low Mg(2+)/high K(+)-induced spontaneous activity was quantified by a virtual instrument designed for the digitization and analysis of bursting activity. Uninterrupted streams of extracellular field potentials were digitized and analyzed in 10-s sweeps, yielding four quantified parameters of neuronal hyperexcitability. Following characterization of the temporal stability of low Mg(2+)/high K(+)-induced hyperexcitability, compounds representing a diversity of functional mechanisms were tested for their effectiveness in reversing this activity. Of the four antiepileptic drugs tested in this model, only phenytoin proved ineffective, while valproate, gabapentin and carbamazepine varied in their potencies, with only the latter drug proving to be completely efficacious. In addition, three investigational compounds having analgesic potential were examined: ZD-7288, a blocker of HCN channels; EAA-090, an NMDA antagonist; and WAY-132983, a muscarinic agonist. Each of these compounds showed strong efficacy by completely blocking spontaneous bursting activity, along with potency greater than that of the antiepileptic drugs. These data indicate that pharmacological agents with varying mechanisms of action are able to block low Mg(2+)/high K(+)-induced hyperexcitability, and thus this model may represent a useful tool for identifying novel agents and mechanisms involved in epilepsy and neuropathic pain.

  4. Pharmacological evaluation of selective α2c-adrenergic agonists in experimental animal models of nasal congestion. (United States)

    Jia, Yanlin; Mingo, Garfield G; Hunter, John C; Lieber, Gissela B; Palamanda, Jairam R; Mei, Hong; Boyce, Christopher W; Koss, Michael C; Yu, Yongxin; Cicmil, Milenko; Hey, John A; McLeod, Robbie L


    Nasal congestion is one of the most troublesome symptoms of many upper airways diseases. We characterized the effect of selective α2c-adrenergic agonists in animal models of nasal congestion. In porcine mucosa tissue, compound A and compound B contracted nasal veins with only modest effects on arteries. In in vivo experiments, we examined the nasal decongestant dose-response characteristics, pharmacokinetic/pharmacodynamic relationship, duration of action, potential development of tolerance, and topical efficacy of α2c-adrenergic agonists. Acoustic rhinometry was used to determine nasal cavity dimensions following intranasal compound 48/80 (1%, 75 µl). In feline experiments, compound 48/80 decreased nasal cavity volume and minimum cross-sectional areas by 77% and 40%, respectively. Oral administration of compound A (0.1-3.0 mg/kg), compound B (0.3-5.0 mg/kg), and d-pseudoephedrine (0.3 and 1.0 mg/kg) produced dose-dependent decongestion. Unlike d-pseudoephedrine, compounds A and B did not alter systolic blood pressure. The plasma exposure of compound A to produce a robust decongestion (EC(80)) was 500 nM, which related well to the duration of action of approximately 4.0 hours. No tolerance to the decongestant effect of compound A (1.0 mg/kg p.o.) was observed. To study the topical efficacies of compounds A and B, the drugs were given topically 30 minutes after compound 48/80 (a therapeutic paradigm) where both agents reversed nasal congestion. Finally, nasal-decongestive activity was confirmed in the dog. We demonstrate that α2c-adrenergic agonists behave as nasal decongestants without cardiovascular actions in animal models of upper airway congestion.

  5. Isoflurano em emulsão lipídica por via venosa promove estabilidade cardiovascular respiratória em modelo experimental Isoflurano en emulsión lipídica por vía venosa promueve estabilidad cardiovascular respiratoria en modelo experimental Intravenous isoflurane in lipid emulsion promotes cardiovascular and respiratory stability. Experimental model

    Directory of Open Access Journals (Sweden)

    Lígia Andrade da Silva Telles Mathias


    Full Text Available JUSTIFICATIVA E OBJETIVOS: A administração venosa de anestésico inalatório pode causar lesão pulmonar. Halotano em solução lipídica por via venosa promove anestesia com estabilidade hemodinâmica e respiratória. Esta pesquisa procurou estabelecer a dose de indução para emulsão lipídica de isoflurano a 10% e observar as condições cardiovasculares e respiratórias, em anestesia experimental. MÉTODO: Sete porcos machos foram selecionados. Os animais receberam infusão de propofol para as preparações cirúrgicas invasivas: dissecção de artéria femoral e veia jugular, sensor de ecodopplercardiografia no esôfago. Foram registrados freqüência cardíaca (FC, eletrocardiograma (ECG, pressão arterial sistólica (PAS, diastólica (PAD, média (PAM, venosa central (PVC, índice cardíaco (IC, débito cardíaco (DC e índice bispectral (BIS. As frações inspirada e expirada dos gases respiratórios foram analisadas continuamente. Iniciada infusão da emulsão lipídica de isoflurano até o índice bispectral atingir valor de 40 ± 5 (BIS40. Os animais foram mantidos anestesiados e submetidos a laparotomia exploradora para sutura gástrica. RESULTADOS: O volume total infundido para atingir BIS40 foi 25,6 ± 11,2 ml (2,56 ml de isoflurano. O tempo médio para atingir BIS40 foi 15,6 ± 6,9 minutos. Maior velocidade de infusão reduziu o tempo para os animais atingirem BIS40. Condições cardiovasculares e respiratórias mostraram-se estáveis durante a experimentação. A freqüência cardíaca aumentou com a elevação da fração expirada do isoflurano. CONCLUSÕES: A infusão venosa do isoflurano em solução emulsificada promoveu diminuição do índice bispectral, estabilidades hemodinâmica e respiratória e correlação direta com sua fração expirada. O uso do isoflurano em emulsão lipídica pode se constituir em modalidade segura de aplicação deste anestésico.JUSTIFICATIVA Y OBJETIVOS: La administración venosa de anest

  6. General practitioners’ use of absolute risk versus individual risk factors in cardiovascular disease prevention: an experimental study


    Jansen, Jesse; Bonner, Carissa; McKinn, Shannon; Irwig, Les; Glasziou, Paul ,; Doust, Jenny; Teixeira-Pinto, Armando; Hayen, Andrew; Turner, Robin; McCaffery, Kirsten


    Objective To understand general practitioners’ (GPs) use of individual risk factors (blood pressure and cholesterol levels) versus absolute risk in cardiovascular disease (CVD) risk management decision-making. Design Randomised experiment. Absolute risk, systolic blood pressure (SBP), cholesterol ratio (total cholesterol/high-density lipoprotein (TC/HDL)) and age were systematically varied in hypothetical cases. High absolute risk was defined as 5-year risk of a cardiovascular event >15%, hig...

  7. Efeitos da clonidina nas respostas cardiovasculares ao pinçamento aórtico infra-renal: estudo experimental no cão Efectos de la clonidina en las respuestas cardiovasculares al pinzamiento aórtico infra-renal: estudio experimental en el can Effects of clonidine on cardiovascular responses to infrarenal aortic cross-clamping: experimental study in dogs

    Directory of Open Access Journals (Sweden)

    Renato Viccário Achôa


    dogs were submitted to infrarenal aortic cross-clamping during 45 minutes. Hemodynamic parameters were measured at control (C, 10 (Ao10 and 25 (Ao25 minutes after aortic cross-clamping, and 10 (DAo10 and 25 (DAo25 minutes after aortic unclamping. RESULTS: There were significant differences between groups in heart rate, mean blood pressure and cardiac index (G control > G Clon during aortic cross-clamping. After aortic unclamping there were significant differences between groups in heart rate (G Control > G Clon, and right atrium and pulmonary capillary wedge pressures (G Clon > G Control. During aortic cross-clamping both groups have shown significant increase in right atrium pressure, pulmonary capillary wedge pressure, stroke volume index and left ventricular systolic work index, and significant decrease in pulmonary vascular resistance index. There has been significant increase in mean blood pressure, pulmonary artery pressure, cardiac index and right ventricular systolic work index in the G Control. The clonidine group has shown significant heart rate decrease. After aortic unclamping, both groups have shown significant heart rate and mean blood pressure decrease, while right atrium pressure and stroke volume index remained high. Right ventricular systolic work index remained high in the control group, while cardiac index values returned to close to baseline values. In the clonidine group, right atrium pressure, pulmonary wedge pressure and systolic index remained significantly high. CONCLUSIONS: In dogs under our experimental conditions, continuous intravenous clonidine has attenuated cardiovascular responses to infrarenal aortic cross-clamping.

  8. Pharmacological attenuation of blood pressure variability

    Institute of Scientific and Technical Information of China (English)

    Claude JULIEN


    @@ Over the past few years, the research team of Professor Ding-feng SU has reported an impressive quantity of experimental data about the relationships between blood pressure variability (BPV) and end-organ damage, a topic of obvious clinical interest. This research work has been summarized in a paper that appeared in the August issue of the renowned journal Trends in Pharmacological Sciences[1]. The studies by Su et al provide convincing evidence that BPV is an independent cardiovascular risk factor that should be considered as such and, therefore, might become an important target for therapeutic interventions. Besides these exciting perspectives in the prevention and treatment of cardiovasculardiseases, the work by Su et al raises a series of physiological questions.

  9. Overview of safety pharmacology. (United States)

    Goineau, Sonia; Lemaire, Martine; Froget, Guillaume


    Safety pharmacology entails the assessment of the potential risks of novel pharmaceuticals for human use. As detailed in the ICH S7A guidelines, safety pharmacology for drug discovery involves a core battery of studies on three vital systems: central nervous (CNS), cardiovascular (CV), and respiratory. Primary CNS studies are aimed at defining compound effects on general behavior, locomotion, neuromuscular coordination, seizure threshold, and vigilance. The primary CV test battery includes an evaluation of proarrhythmic risk using in vitro tests (hERG channel and Purkinje fiber assays) and in vivo measurements in conscious animals via telemetry. Comprehensive cardiac risk assessment also includes full hemodynamic evaluation in a large, anesthetized animal. Basic respiratory function can be examined in conscious animals using whole-body plethysmography. This allows for an assessment of whether the sensitivity to respiratory-depressant effects can be enhanced by exposure to increased CO2 . Other safety pharmacology topics detailed in this unit are the timing of such studies, ethical and animal welfare issues, and statistical evaluation.

  10. Evaluation of pharmacological activities and assessment of intraocular penetration of an ayurvedic polyherbal eye drop (Itone™ in experimental models

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    Velpandian Thirumurthy


    Full Text Available Abstract Background The polyherbal eye drop (Itone™ is a mixture of aqueous distillates of nineteen traditionally used ingredients that sum up to impart potency to the formulation and make it a useful adjunct in various ocular pathologies. However, as there have been no controlled experimental studies accounting to the above claim, therefore, the present study was designed to evaluate the polyherbal formulation (PHF for antiangiogenic, anti-inflammatory, anticataract, antioxidant and cytotoxicity in addition to the evaluation of intraocular penetration of PHF in rabbit eyes using LC-MS/MS. Materials and methods Antiangiogenic activity of the PHF was evaluated using in ovo chick chorio-allantoic membrane (CAM assay and in vivo cautery induced corneal neovascularization assay in rats. Anticataract potential was evaluated using steroid induced cataract in developing chick embryos, sodium selenite induced cataract in rat pups and galactose induced cataract in rats. The antioxidant activity was evaluated using di-phenyl picryl hydrazyl (DPPH radical scavenging assay. Anti-inflammatory activity was evaluated in vitro using inhibition of LTB4 formation in human WBCs and in vivo using carrageenan induced paw edema assay in rats. The cytotoxicity was evaluated against HeLa cancer cell lines using (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Furthermore evaluation of the intraocular penetration of the PHF was carried out in rabbit eyes via aqueous humor paracentesis and further analysis using LC-MS/MS. Results PHF significantly inhibited VEGF induced proliferation of new blood vessels in CAM assay and inhibited the cautery induced corneal neovascularization in rats. Additionally, PHF showed noticeable delay in the progression of cataract in the selenite and galactose induced cataract models whereby the PHF treated lenses were graded for stages II and III respectively. However, the PHF did not show any anticataract activity in

  11. Cardiovascular complications of cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl


    and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis......Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction....... The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed....

  12. Cardiovascular complications of cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik


    and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis......Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction....... The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed.  ...

  13. Review of existing experimental approaches for the clinical evaluation of the benefits of plant food supplements on cardiovascular function. (United States)

    Meoni, Paolo; Restani, Patrizia; Mancama, Dalu T


    We conducted a survey of the National Centre for Biotechnology Information (NCBI) PubMed database to identify methods most commonly used for the evaluation of the effect of plant food supplements on the cardiovascular system and their relevance to the regulatory status of these products. Particularly, our search strategy was aimed at the selection of studies concerning the clinical evaluation of the beneficial effects of the most commonly studied plant food supplements acting on the cardiovascular system. Following the screening of 3839 papers for inclusion criteria, 48 published reports were retained for this review. Most studies included in this review used a double blind controlled design, and evaluated the effect of plant food supplements on individuals affected by a disease of the cardiovascular system. The majority of the studies were found to be of low methodological quality on the Jadad scale, mainly because of inadequate reporting of adverse events and of patient withdrawals. In comparison, measures used for the evaluation of benefits included mostly cardiovascular risk factors as recommended in international guidelines and in accordance with principles laid down for the evaluation of health claims in food. The risk factors most frequently evaluated belonged to the category of "lipid function and levels", "heart function" and "blood pressure". For the absolute majority of the studies, the study period did not exceed one month. This review highlights critical factors to be considered in the design of studies evaluating the health effects of plant food supplements on the cardiovascular system. Between others, the inclusion of healthy individuals, better reporting and description of the characteristics of the product used could improve the quality and relevance of these studies.

  14. CFTR pharmacology. (United States)

    Zegarra-Moran, Olga; Galietta, Luis J V


    CFTR protein is an ion channel regulated by cAMP-dependent phosphorylation and expressed in many types of epithelial cells. CFTR-mediated chloride and bicarbonate secretion play an important role in the respiratory and gastrointestinal systems. Pharmacological modulators of CFTR represent promising drugs for a variety of diseases. In particular, correctors and potentiators may restore the activity of CFTR in cystic fibrosis patients. Potentiators are also potentially useful to improve mucociliary clearance in patients with chronic obstructive pulmonary disease. On the other hand, CFTR inhibitors may be useful to block fluid and electrolyte loss in secretory diarrhea and slow down the progression of polycystic kidney disease.

  15. Association of dietary sodium intake with atherogenesis in experimental diabetes and with cardiovascular disease in patients with Type 1 diabetes. (United States)

    Tikellis, Chris; Pickering, Raelene J; Tsorotes, Despina; Harjutsalo, Valma; Thorn, Lena; Ahola, Aila; Wadén, Johan; Tolonen, Nina; Saraheimo, Markku; Gordin, Daniel; Forsblom, Carol; Groop, Per-Henrik; Cooper, Mark E; Moran, John; Thomas, Merlin C


    It is recommended that individuals with diabetes restrict their dietary sodium intake. However, although salt intake is correlated with BP (blood pressure), it also partly determines the activation state of the RAAS (renin-angiotensin-aldosterone system), a key mediator of diabetes-associated atherosclerosis. apoE KO (apolipoprotein E knockout) mice were allocated for the induction of diabetes with streptozotocin or citrate buffer (controls) and further randomized to isocaloric diets containing 0.05%, 0.3% or 3.1% sodium with or without the ACEi [ACE (angiotensin-converting enzyme) inhibitor] perindopril. After 6 weeks of study, plaque accumulation was quantified and markers of atherogenesis were assessed using RT-PCR (reverse transcription-PCR) and ELISA. The association of sodium intake and adverse cardiovascular and mortality outcomes were explored in 2648 adults with Type 1 diabetes without prior CVD (cardiovascular disease) from the FinnDiane study. A 0.05% sodium diet was associated with increased plaque accumulation in diabetic apoE KO mice, associated with activation of the RAAS. By contrast, a diet containing 3.1% sodium suppressed atherogenesis associated with suppression of the RAAS, with an efficacy comparable with ACE inhibition. In adults with Type 1 diabetes, low sodium intake was also associated with an increased risk of all-cause mortality and new-onset cardiovascular events. However, high sodium intake was also associated with adverse outcomes, leading to a J-shaped relationship overall. Although BP lowering is an important goal for the management of diabetes, off-target actions to activate the RAAS may contribute to an observed lack of protection from cardiovascular complications in patients with Type 1 diabetes with low sodium intake.

  16. 胡椒醇提物的药理学实验研究%Experimental Study of Alcohol Extract from Pepper on Pharmacology

    Institute of Scientific and Technical Information of China (English)

    邓永坤; 董寿堂; 王银辉; 李辉


    Objective To investigate the pharmacological effect of alcohol extract from pepper on topical application. Methods Two experimental models including xylene - induced ear edema in mice and histamine phosphate induced - foot pruritus in guinea pigs were employed to evaluate topically anti-inflammatory and antipruritic action of 70% alcohol extract from pepper. Internal diameters of auric arterioles and venules in mice were measured initially and then 5,10 and 20min after application of 70% alcohol extract from pepper and again 5,10,15 and 20 min after ip Adrenaline with image analysis system. Simultaneously blood flow state in auric venules was observed. Results Topical administration of 70% alcohol extract from pepper significantly inhibited ear edema induced by xylene, significantly increased threshold quantity of histamine phosphate with which elicited pruritus in guinea pigs, significantly dilated auric arterioles and venules in mice, speeded up blood flow rate of venules. Furthermore, it inhibited adrenaline - induced contraction of arterioles and venules as well as the reduction of blood flow rate of venules. Conclusion 70% alcohol extract of pepper has pharmacological activities of anti-inflammation, alleviating itching and improving micro-circulation.%目的 探讨胡椒醇提物局部外涂的药理作用.方法 分别采用二甲苯致小鼠耳廓肿胀炎症模型和磷酸组胺致豚鼠足部瘙痒模型测试胡椒70%乙醇提取液的局部抗炎止痒作用;利用图像分析系统测定小鼠耳廓局部应用胡椒70%乙醇提取液前与应用后5,10,20 min及腹腔注射肾上腺素后5,10,15,20 min耳廓细动、静脉口径和细静脉血流态,由此评价其对小鼠耳廓正常微循环和肾上腺素引起的微循环障碍的作用.结果 胡椒70%乙醇提取液局部外涂能显著抑制二甲苯所致小鼠耳廓肿胀;显著提高豚鼠足部磷酸组胺致痒阈;显著增加正常小鼠细动、静脉口径及细静脉血流速度,并

  17. Stress, depression and cardiovascular dysregulation: a review of neurobiological mechanisms and the integration of research from preclinical disease models. (United States)

    Grippo, Angela J; Johnson, Alan Kim


    Bidirectional associations between mood disorders and cardiovascular diseases are extensively documented. However, the precise physiological and biochemical mechanisms that underlie such relationships are not well understood. This review focuses on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders. The discussion places an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and the activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction involving the dopamine, norepinephrine and serotonin systems, and (e) behavioral changes including fatigue and physical inactivity. The review also discusses experimental investigations using preclinical disease models to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, (c) a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with an extensive human research literature, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance understanding the association between depression and cardiovascular disease. This will ultimately promote the development of better treatments and interventions for individuals with co-morbid psychological and somatic pathologies.

  18. The nature of the destructive, compensatory and regenerative processes in the brain of rats after experimental moderate traumatic brain injury and the possibility of their pharmacological correction

    Directory of Open Access Journals (Sweden)

    Mamytova E.M.


    analysis showed a reduction in the bulk density of the nucleus is 7, and 21 days of experimental traumatic brain injury in the group without treatment. In Cerebrolysin group on day 14 and 21, the bulk density of the nucleus closer to the control parameters. The same trend was observed in relation to the bulk density of ribosomes and neurofibrillary. In case of injury of moderate severity in the group without a neuroprotectant during the entire study period there is a diffuse lesion of the brain studied departments mostly damaged hemisphere, which appeared resistant dystrophic and destructive changes of the neurons without significant signs of pronounced reparative regeneration in the regenerative posttraumatic period. Conclusion. When using a neuroprotectant cerebrolysin marked increase in intact neurons, which was celebrated not only in the injured, but also in the contralateral hemisphere on the day 21st of the experiment. In this case an increase amount of glial cells was also seen. Citation: Mamytova EM. [The nature of the destructive, compensatory and regenerative processes in the brain of rats after experimental moderate traumatic brain injury and the possibility of their pharmacological correction]. Morphologia. 2016;10(2:18-22. Russian.

  19. Gastrointestinal Pharmacology. (United States)

    Saps, Miguel; Miranda, Adrian


    There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial. A small study found that cyproheptadine was beneficial in the treatment of FAPDs in children. There are conflicting data regarding amitriptyline. While one small study found a significant benefit in quality of life compared with placebo, a large multicenter study found no benefit compared with placebo. The antidepressant, citalopram, failed to meet the primary outcomes in intention-to-treat and per-protocol analysis. Rifaximin has been shown to be efficacious in the treatment of adults with IBS. Those findings differ from studies in children where no benefit was found compared to placebo. To date, there are no placebo-controlled trials published on the use of linaclotide or lubiprostone in children. Alpha 2 delta ligands such as gabapentin and pregabalin are sometimes used in the care of this group of children, but no clinical trials are available in children with FAPDs. Similarly, novel drugs that have been approved for the care of irritable bowel with diarrhea in adults such as eluxadoline have yet to be studied in children.

  20. Mitochondrial cytopathies and cardiovascular disease. (United States)

    Dominic, Elizabeth A; Ramezani, Ali; Anker, Stefan D; Verma, Mukesh; Mehta, Nehal; Rao, Madhumathi


    The global epidemic of cardiovascular disease remains the leading cause of death in the USA and across the world. Functional and structural integrity of mitochondria are essential for the physiological function of the cardiovascular system. The metabolic adaptation observed in normal heart is lost in the failing myocardium, which becomes progressively energy depleted leading to impaired myocardial contraction and relaxation. Uncoupling of electron transfer from ATP synthesis leads to excess generation of reactive species, leading to widespread cellular injury and cardiovascular disease. Accumulation of mitochondrial DNA mutation has been linked to ischaemic heart disease, cardiomyopathy and atherosclerotic vascular disease. Mitochondria are known to regulate apoptotic and autophagic pathways that have been shown to play an important role in the development of cardiomyopathy and atherosclerosis. A number of pharmacological and non-pharmacological treatment options have been explored in the management of mitochondrial diseases with variable success.

  1. Carbon dioxide inhalation as a human experimental model of panic: the relationship between emotions and cardiovascular physiology. (United States)

    Leibold, Nicole K; Viechtbauer, Wolfgang; Goossens, Liesbet; De Cort, Klara; Griez, Eric J; Myin-Germeys, Inez; Steinbusch, Harry W M; van den Hove, Daniël L A; Schruers, Koen R J


    Inhaling carbon dioxide (CO2)-enriched air induces fear and panic symptoms resembling real-life panic attacks, the hallmark of panic disorder. The present study aimed to describe the emotional and cardiovascular effects evoked by inhaling CO2, taking shortcomings of previous studies into account. Healthy volunteers underwent a double inhalation of 0, 9, 17.5, and 35% CO2, according to a randomized, cross-over design. In addition to fear, discomfort, and panic symptom ratings, blood pressure and heart rate were continuously monitored. Results showed a dose-dependent increase in all self-reports. Systolic and diastolic blood pressure rose with increasing CO2 concentration, whereas heart rate results were less consistent. Diastolic blood pressure and heart rate variation correlated with fear and discomfort. Based on this relationship and the observation that the diastolic blood pressure most accurately mimicked the degree of self-reported emotions, it might serve as a putative biomarker to assess the CO2-reactivity in the future.

  2. 西红花的化学成分和心血管药理作用的研究概况%Research on Chemical Constituents of Crocus Sativus and Their Cardiovascular Pharmacological Effects

    Institute of Scientific and Technical Information of China (English)

    楚溪; 刘涛; 韩雪; 张建平


    Cardiovascular diseases are common public health issues. The dried stigma of the plant saffron is used in folk medicine for various purposes. Several lines of evidences suggest that crocin and crocetin are implicated in cardiovascular system. These emerging molecules for the treatment of cardiovascular diseases were studied. Current analysis showed that saffron and its components might be a promising class of compounds for the treatment of the above mentioned cardiovascular diseases.%心血管疾病在临床上是一种非常普遍的疾病。西红花是鸢尾科多年生草本植物番红花的干燥柱头,具有解郁安神、活血化瘀、凉血解毒的功效,可用于产后瘀阻、经闭症瘕、温毒发斑、忧郁痞闷、惊悸发狂等症。目前,也常用于治疗心脑血管疾病。现代药理学研究发现,西红花中的西红花甙与西红花酸对治疗心血管疾病有明显作用。本文系统总结了西红花的化学成分和药理活性,为其深度开发提供参考。

  3. 人参皂苷 Rg1对心血管系统和神经系统药理作用的研究进展%Advances in pharmacological effects ofGensenoside Rg1 on The cardiovascular system and The nervous system

    Institute of Scientific and Technical Information of China (English)

    董艳红; 胡婷婷; 代良萍; 谢晓芳; 彭成


    Gensenoside Rg1 is one of the main active principles in ginseng.Modern pharmacological studies show that Gensenoside Rgh1 as many biological activities on many systems of the body,especially for the influence of the cardiovascular system and nervous system widely.Thisarticle through to retrieve nearly 10 years pharmacological research literature of gensenoside Rg1 ,in the two aspects, Results show that gensenoside Rg1 with protecting the myocardial,anti -myocardial ischemia and promoting the regeneration of blood vessel and anti -myocardial hypoxia injury in the cardiovascular system;Against cerebral ischemia/reperfusion injury in the nervous system,nootropic,antioxidant and anti -aging effects in the nervous system.%人参皂苷 Rg1是人参中的重要成分之一。现代药理学研究显示人参皂苷 Rg1在对人体的很多方面具有很强的药理活性,特别是在心血管系统和神经系统。本文通过检索近10年来人参皂苷 Rg1心血管系统和神经系统药理研究文献,综述人参皂苷 Rg1在此两个方面的药理作用,结果表明人参皂苷 Rg1在心血管系统有保护心肌细胞、抗心肌缺血和促血管再生作用;对神经系统有抗脑缺血再灌注损伤、益智、抗神经细胞氧化损伤的作用,为其药物开发提供依据。

  4. Cardiovascular Deconditioning (United States)

    Charles, John B.; Fritsch-Yelle, Janice M.; Whitson, Peggy A.; Wood, Margie L.; Brown, Troy E.; Fortner, G. William


    Spaceflight causes adaptive changes in cardiovascular function that may deleteriously affect crew health and safety. Over the last three decades, symptoms of cardiovascular changes have ranged from postflight orthostatic tachycardia and decreased exercise capacity to serious cardiac rhythm disturbances during extravehicular activities (EVA). The most documented symptom of cardiovascular dysfunction, postflight orthostatic intolerance, has affected a significant percentage of U.S. Space Shuttle astronauts. Problems of cardiovascular dysfunction associated with spaceflight are a concern to NASA. This has been particularly true during Shuttle flights where the primary concern is the crew's physical health, including the pilot's ability to land the Orbiter, and the crew's ability to quickly egress and move to safety should a dangerous condition arise. The study of astronauts during Shuttle activities is inherently more difficult than most human research. Consequently, sample sizes have been small and results have lacked consistency. Before the Extended Duration Orbiter Medical Project (EDOMP), there was a lack of normative data on changes in cardiovascular parameters during and after spaceflight. The EDOMP for the first time allowed studies on a large enough number of subjects to overcome some of these problems. There were three primary goals of the Cardiovascular EDOMP studies. The first was to establish, through descriptive studies, a normative data base of cardiovascular changes attributable to spaceflight. The second goal was to determine mechanisms of cardiovascular changes resulting from spaceflight (particularly orthostatic hypotension and cardiac rhythm disturbances). The third was to evaluate possible countermeasures. The Cardiovascular EDOMP studies involved parallel descriptive, mechanistic, and countermeasure evaluations.

  5. The Genus Alpinia: A Review of Its Phytochemistry and Pharmacology

    Directory of Open Access Journals (Sweden)

    Wei-Jie Zhang


    Full Text Available Genus Alpinia consists of over 250 species, which are widely distributed in south and southeast Asia. Many plants of genus Alpinia have been used for thousands of years to treat digestive system diseases and as anti-inflammatory drugs. Phytochemical research on this genus has led to the isolation of different kinds of diarylheptanoids, terpenes triterpenoids, phenylbutanoids, lignans, and flavonoids. Experimental evidences revealed that both the crude extracts and pure constituents isolated from the genus Alpinia exhibit a wide range of bioactivities such as anti-cancer, anti-oxidant, anti-bacterial, anti-viral, cardiovascular, and digestive system protective effects. Here, we summarize the phytochemistry and pharmacology investigation of the genus Alpinia, which can provide reference for further research and drug development.

  6. 药理学实验教学中加强实验动物伦理学教育的思考%Consideration on Strengthen the Ethical Education of Laboratory Animal in Pharmacology Experimental Teaching

    Institute of Scientific and Technical Information of China (English)

    马雪; 张慧楠; 贾敏; 周颖; 罗晓星; 孟静茹


    This paper points out the experimental animal ethics education in pharmacology teaching and the im-portance of the experiment,it is good to raises the student good humanity accomplishment and scientific research quality, and promote medical research and life ethics of benign interaction.It also expounds the basic content of ex-perimental animal ethics education,including:animal welfare, the 3R principle, AAALAC accreditation and analy-sis of the experimental animal welfare legislation status, raises questions about animal ethics education problems and thinking in the pharmacology experiment teaching in ourschool.The experimental animal ethics education should become an important part of pharmacology experimental teaching, which enhanced the students′s ethical awareness to better understand and respect for life, and contribute to the sustainable development of medical and pharmaceutical research.%指出了实验动物伦理学教育在药理学教学及实验中的重要性,有培养学生良好的人文素养和科研素质、促进医药研究与生命伦理观的良性互动的作用;阐述了实验动物伦理学教育的基本内容,包括动物福利、“3R”原则、AAALAC认证,并分析了实验动物福利的立法状况;引发了关于我校药理学实验教学中动物伦理学教育的问题与思考:将实验动物伦理教育融入实验教学过程应成为药理学教学的重要内容,既能够增强医药相关专业学生的伦理意识,更好的了解和尊重生命,也有助于促进医药研究的可持续发展。

  7. Cardiovascular System

    Institute of Scientific and Technical Information of China (English)


    2011189 Vulnerable plaque burden post pharmaco-logical and interventional treatments in patients with acute coronary syndrome and borderline lesion: intravascular ultrasound follow up results. YU Danqing (余丹青)

  8. Efeitos do halotano, isoflurano e sevoflurano nas respostas cardiovasculares ao pinçamento aórtico infra-renal: estudo experimental em cães Efectos del halotano, isoflurano y sevoflurano en las respuestas cardiovasculares al pinzamiento aórtico infra-renal: estudio experimental en perros Effects of halothane, isoflurane and sevoflurane on cardiovascular responses to infrarenal aortic cross-clamping: experimental study in dogs

    Directory of Open Access Journals (Sweden)

    Flora Margarida Barra Bisinotto


    OBJECTIVES: Infrarenal aortic cross-clamping is associated to cardiovascular effects. This study aimed at analyzing the effects of halothane, isoflurane and sevoflurane on cardiovascular function of dogs following infrarenal aortic cross-clamping. METHODS: Thirty mongrel dogs were randomly divided in three groups, according to equipotent (0.75 MAC inhaled anesthetic doses: GH (n = 10 - 0.67% halothane; GI (n = 10 - 0.96% isoflurane; and GS (n = 10 - 1.8% sevoflurane. All dogs were submitted to infrarenal aortic cross-clamping for 30 minutes. Hemodynamic parameters were measured at control (C, at 15 (Ao15 and 30 (Ao30 minutes of aortic cross-clamping, and immediately (DAo and 15 (DAo15 minutes after aortic unclamping. RESULTS: In all groups, infrarenal aortic cross-clamping significantly increased mean blood pressure, right atrial pressure, cardiac index, stroke volume index, left ventricular work index and right ventricular work index. Pulmonary artery pressure significantly increased during cross-clamping in GI and GS groups while pulmonary capillary wedge pressure significantly increased in GH and GI groups. After aortic unclamping all hemodynamic parameters have returned to control levels with the exception of cardiac and stroke volume indices which remained high, followed by systemic vascular resistance index decrease. There have been no significant differences among groups in studied attributes, except for heart rate which was always lower in GH group as compared to other groups during and after infrarenal aortic cross-clamping. CONCLUSIONS: In dogs under our experimental conditions, equipotent concentrations (0.75 MAC of inhalational halothane, isoflurane and sevoflurane have not attenuated cardiovascular responses to infrarenal aortic cross-clamping.

  9. The Polypill in the Prevention of Cardiovascular Disease

    NARCIS (Netherlands)

    Lafeber, M.


    Overwhelming data from clinical trials show that pharmacological interventions with aspirin, statins and blood pressure (BP)-lowering agents considerably reduce the risk of cardiovascular events and total mortality. Therefore, current international treatment guidelines recommend to prescribe statins

  10. Methodological innovations expand the safety pharmacology horizon. (United States)

    Pugsley, M K; Curtis, M J


    Almost uniquely in pharmacology, drug safety assessment is driven by the need for elaboration and validation of methods for detecting drug actions. This is the 9th consecutive year that the Journal of Pharmacological and Toxicological Methods (JPTM) has published themed issues arising from the annual meeting of the Safety Pharmacology Society (SPS). The SPS is now past its 10th year as a distinct (from pharmacology to toxicology) discipline that integrates safety pharmacologists from industry with those in academia and the various global regulatory authorities. The themes of the 2011 meeting were (i) the bridging of safety assessment of a new chemical entity (NCE) between all the parties involved, (ii) applied technologies and (iii) translation. This issue of JPTM reflects these themes. The content is informed by the regulatory guidance documents (S7A and S7B) that apply prior to first in human (FIH) studies, which emphasize the importance of seeking model validation. The manuscripts encompass a broad spectrum of safety pharmacology topics including application of state-of-the-art techniques for study conduct and data processing and evaluation. This includes some exciting novel integrated core battery study designs, refinements in hemodynamic assessment, arrhythmia analysis algorithms, and additionally an overview of safety immunopharmacology, and a brief survey discussing similarities and differences in business models that pharmaceutical companies employ in safety pharmacology, together with SPS recommendations on 'best practice' for the conduct of a non-clinical cardiovascular assessment of a NCE.

  11. Experimental Study of Pharmacology of Antineoplastic Pemetrexed%抗肿瘤药培美曲塞的药理实验研究

    Institute of Scientific and Technical Information of China (English)

    宋吉; 姜雨薇; 申莹; 潘本刚


    Objective:To analyze the pharmacological basis of antineoplastic Pei pemetrexed and clinical efficacy of the drug. Methods:Through access to information and conduct pharmacological studies,analysis of the mechanism of antitumor culture of pemetrexed,pharmacodynamics,pharmacokinetics,adverse reactions,tolerance and resistance mechanisms,by clinical reports on the inspection training clinical study of pemetrexed treatment of malignant tumors,analysis of anti-tumor efficacy of the drug.Results:① Mechanism:Pemetrexed through antagonism has folic acid,can inhibit tumor cell replication;②pharmacodynamics:Pemetrexed has a broad-spectrum anti-tumor activity;③Pharmacokinetics:pemetrexed is drug metabolism in line with the multi-chamber models, limited distribution within the organization,the rapid removal of the urine,the mean half-life of 2 ~ 3h;④ adverse reactions:pemetrexed common adverse reactions,including cases of ZTE cells decreased,diarrhea,mucositis,nausea,and vomiting;⑤ tolerance:pemetrexed low severity of adverse reactions,is well tolerated;⑥resistance mechanisms:resistance mechanisms pemetrexed mainly leaf acid polyglutamate synthase.⑦ drug efficacy analysis found that pemetrexed can improve cancer patients disease treatment efficiency,prolong survival.Conclusion:The unique pharmacological effects of pemetrexed has,can effectively reduce the mortality of cancer patients.%分析了抗肿瘤药培美曲塞的药理作用以及该种药物的临床疗效。通过查阅资料以及开展药理研究,分析抗肿瘤药培美曲塞的作用机制、药效学、药代动力学、不良反应、耐受性以及耐药机制,通过查阅临床上报道的关于培美曲塞治疗恶性肿瘤的临床研究,分析该种药物的抗肿瘤功效。通过药理实验,得出以下结果:①作用机制:培美曲塞通所具有的叶酸拮抗作用,能够抑制肿瘤细胞复制;②药效学:培美曲塞具有广谱抗肿瘤活性;③药代动

  12. The pharmacology of Bacopa monniera. A review

    Directory of Open Access Journals (Sweden)

    Ali Esmail Al-Snafi


    Full Text Available Bacopa monniera was distributed in the warmer and wetlands regions of the world. It was widely used in traditional medicine to treat various complains. Bacopa monniera contained alkaloid brahmine , nicotinine, herpestine, bacosides A[3-( α-L-arabinopyranosyl-O-β-D-glucopyranoside-10, 20-dihydroxy-16-keto-dammar-24-ene] , triterpenoid saponins , saponins A, B and C, betulinic acid , D-mannitol , stigmastanol , β-sitosterol , stigmasterol. and pseudojujubogenin glycoside. The pharmacological studies showed that Bacopa monniera possessed many pharmacological effects included central nervous effects ( memory enhancement , antidepressant , anxiolytic , anticonvulsant and antiparkinsonian , antioxidant , gastrointestinal , endocrine , antimicrobial , anti-inflammatory , analgesic , cardiovascular and smooth muscle relaxant effects. The present review focused on the chemical constituents and pharmacological effects of Bacopa monniera.

  13. [Update on the pharmacology of Spirulina (Arthrospira), an unconventional food]. (United States)

    Chamorro, Germán; Salazar, María; Araújo, Katia Gomes de Lima; dos Santos, César Pereira; Ceballos, Guillermo; Castillo, Luis Fabila


    Spirulina (Arthrospira), a filamentous, unicellular alga, is a cyanobacterium grown in certain countries as food for human and animal consumption. It is also used to derive additives in pharmaceuticals and foods. This alga is a rich source of proteins, vitamins, amino acids, minerals, and other nutrients. Its main use, therefore, is as a food supplement. Over the last few years, however, it has been found to have many additional pharmacological properties. Thus, it has been experimentally proven, in vivo and in vitro that it is effective to treat certain allergies, anemia, cancer, hepatotoxicity, viral and cardiovascular diseases, hyperglycemia, hyperlipidemia, immunodeficiency, and inflammatory processes, among others. Several of these activities are attributed to Spirulina itself or to some of its components including fatty acids omega-3 or omega-6, beta-carotene, alpha-tocopherol, phycocyanin, phenol compounds, and a recently isolated complex, Ca-Spirulan (Ca-SP). This paper aims to update and critically review the results published over the last few years with regards to these properties. The conclusion is that even if this cyanobacterium has been one of the most extensively studied from the chemical, pharmacological and toxicological points of view, it is still necessary to expand the research in order to have more consistent data for its possible use in human beings.

  14. SvO(2)-guided resuscitation for experimental septic shock: effects of fluid infusion and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress. (United States)

    Rosário, André Loureiro; Park, Marcelo; Brunialti, Milena Karina; Mendes, Marialice; Rapozo, Marjorie; Fernandes, Denise; Salomão, Reinaldo; Laurindo, Francisco Rafael; Schettino, Guilherme Paula; Azevedo, Luciano Cesar P


    The pathogenetic mechanisms associated to the beneficial effects of mixed venous oxygen saturation (SvO(2))-guided resuscitation during sepsis are unclear. Our purpose was to evaluate the effects of an algorithm of SvO(2)-driven resuscitation including fluids, norepinephrine and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress during a clinically resembling experimental model of septic shock. Eighteen anesthetized and catheterized pigs (35-45 kg) were submitted to peritonitis by fecal inoculation (0.75 g/kg). After hypotension, antibiotics were administered, and the animals were randomized to two groups: control (n = 9), with hemodynamic support aiming central venous pressure 8 to 12 mmHg, urinary output 0.5 mL/kg per hour, and mean arterial pressure greater than 65 mmHg; and SvO(2) (n = 9), with the goals above, plus SvO(2) greater than 65%. The interventions lasted 12 h, and lactated Ringer's and norepinephrine (both groups) and dobutamine (SvO(2) group) were administered. Inflammatory response was evaluated by plasma concentration of cytokines, neutrophil CD14 expression, oxidant generation, and apoptosis. Oxidative stress was evaluated by plasma and myocardial nitrate concentrations, myocardial and vascular NADP(H) oxidase activity, myocardial glutathione content, and nitrotyrosine expression. Mixed venous oxygen saturation-driven resuscitation was associated with improved systolic index, oxygen delivery, and diuresis. Sepsis induced in both groups a significant increase on IL-6 concentrations and plasma nitrate concentrations and a persistent decrease in neutrophil CD14 expression. Apoptosis rate and neutrophil oxidant generation were not different between groups. Treatment strategies did not significantly modify oxidative stress parameters. Thus, an approach aiming SvO(2) during sepsis improves hemodynamics, without any significant effect on inflammatory response and oxidative stress. The beneficial effects associated

  15. Protocol for an experimental investigation of the roles of oxytocin and social support in neuroendocrine, cardiovascular, and subjective responses to stress across age and gender

    Directory of Open Access Journals (Sweden)

    Block Jason


    Full Text Available Abstract Background Substantial empirical evidence has demonstrated that individuals who are socially isolated or have few positive social connections seem to age at a faster rate and have more chronic diseases. Oxytocin is a neurohypophyseal hormone hypothesized to coordinate both the causes and effects of positive social interactions, and may be involved in positive physiological adaptations such as buffering the deleterious effects of stress and promoting resilience. The proposed research will examine whether and how oxytocin influences responses to stress in humans and will consider effects in relation to those of social support. Methods/Design Experimental research will be used to determine whether exogenously administered oxytocin (intranasal influences psychological and physiological outcomes under conditions of stress across gender and age in adulthood. Hypotheses to be tested are: 1 Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress; 2 Oxytocin and social support have similar and additive stress-buffering effects; 3 Oxytocin effects are stronger in women versus men; and 4 Oxytocin effects are similar across a range of adult ages. Hypotheses will be tested with a placebo-controlled, double-blind study using a sample of healthy men and women recruited from the community. Participants are randomly assigned to receive either oxytocin or placebo. They undergo a social stress manipulation with and without social support (randomly assigned, and outcome measures are obtained at multiple times during the procedure. Discussion Understanding the determinants of healthy aging is a major public health priority and identifying effective measures to prevent or delay the onset of chronic diseases is an important goal. Experimental research on oxytocin, social relationships, and health in adulthood will contribute to the scientific knowledge base for maximizing active life and health expectancy. At

  16. Principles of safety pharmacology. (United States)

    Pugsley, M K; Authier, S; Curtis, M J


    Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.).

  17. Cardiovascular pharmacogenetics. (United States)

    Myburgh, Renier; Hochfeld, Warren E; Dodgen, Tyren M; Ker, James; Pepper, Michael S


    Human genetic variation in the form of single nucleotide polymorphisms as well as more complex structural variations such as insertions, deletions and copy number variants, is partially responsible for the clinical variation seen in response to pharmacotherapeutic drugs. This affects the likelihood of experiencing adverse drug reactions and also of achieving therapeutic success. In this paper, we review key studies in cardiovascular pharmacogenetics that reveal genetic variations underlying the outcomes of drug treatment in cardiovascular disease. Examples of genetic associations with drug efficacy and toxicity are described, including the roles of genetic variability in pharmacokinetics (e.g. drug metabolizing enzymes) and pharmacodynamics (e.g. drug targets). These findings have functional implications that could lead to the development of genetic tests aimed at minimizing drug toxicity and optimizing drug efficacy in cardiovascular medicine.

  18. The cardiovascular pharmacology of ICI 170777 ((6RS)-6-methyl-5-(pyrid-4-yl)-3H,6H-1,3,4- thiadiazin-2-one) a novel compound with positive inotropic and vasodilator effects. (United States)

    Collis, M. G.; Keddie, J. R.; Rouse, W.


    1. This paper describes the cardiovascular effects of ICI 170777, a novel compound which enhances cardiac contractility and causes arterial and venous dilatation. 2. The positive inotropic effects of ICI 170777 on the heart were demonstrated by an increase in left ventricular dP/dtmax in the anaesthetized and conscious dog, and by an increase in tension development in isolated papillary muscles from the cat. 3. In the anaesthetized dog, the positive inotropic effects of ICI 170777 and of isoprenaline were attenuated by atenolol (5 mg kg-1, i.v.). Atenolol displaced the dose-response curve to ICI 170777 to the right by 4 fold but displaced the isoprenaline dose-response curve to the right by 247 fold. In vitro, however, atenolol (10 microM) had no significant effect on the positive inotropic response to ICI 170777. In the ganglion-blocked anaesthetized dog, infusion of a low dose of ICI 170777 which had no effect on the basal left ventricular dP/dtmax, selectively potentiated the positive inotropic effects of isoprenaline. These results indicate that ICI 170777 has both a non-adrenoceptor-mediated positive inotropic effect on the heart and also facilitates the beta-adrenoceptor-mediated control of contractility. 4. In the denervated and perfused hind-limb of the dog, ICI 170777 reduced arterial perfusion pressure and increased limb circumference at a constant arterial flow and venous pressure. This indicates that ICI 170777 has direct dilator actions on both arterial and venous vessels. In this preparation, diazoxide exerted an arterial selective vasodilator effect and sodium nitroprusside was a relatively selective venous dilator.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2758224

  19. The protective effects of Schisandra chinensis fruit extract and its lignans against cardiovascular disease: a review of the molecular mechanisms. (United States)

    Chun, Jung Nyeo; Cho, Minsoo; So, Insuk; Jeon, Ju-Hong


    Schisandra chinensis fruit extract (SCE) has traditionally been used as an oriental medicine for the treatment of various human diseases, including cardiovascular disease. Advances in scientific knowledge and analytical technologies provide opportunities for translational research involving S. chinensis; such research may contribute to future drug discovery. To date, emerging experimental evidence supports the therapeutic effects of the SCE or its bioactive lignan ingredients in cardiovascular disease, unraveling the mechanistic basis for their pharmacological actions. In the present review, we highlight SCE and its lignans as promising resources for the development of safe, effective, and multi-targeted agents against cardiovascular disease. Moreover, we offer novel insight into future challenges and perspective on S. chinensis research to future clinical investigations and healthcare strategies.

  20. Cardiovascular benefits of bariatric surgery. (United States)

    Lee, Glenn K; Cha, Yong-Mei


    The prevalence of obesity is increasing in the United States and worldwide, bringing with it an excess of morbidity and premature death. Obesity is strongly associated with both traditional cardiovascular risk factors as well as direct effects on hemodynamics and cardiovascular structure and function. In fact, cardiovascular disease is one of the major causes of morbidity and mortality in obese patients. Often, lifestyle and pharmacological weight-loss interventions are of limited efficacy in severely obese patients. Bariatric surgery has been shown to be a feasible option to achieve substantial and sustained weight loss in this group of patients. It is a safe procedure with low in-hospital and 30-day mortality rates even in groups that are considered higher risk for surgery (e.g., the elderly), especially if performed in high-volume centers. There is observational evidence that bariatric surgery in severely obese patients is associated with both a reduction of traditional cardiovascular risk factors as well as improvement in cardiac structure and function. Marked decreases in the levels of inflammatory and prothrombotic markers, as well as markers of subclinical atherosclerosis and endothelial dysfunction, are seen after bariatric surgery. This article summarizes the existing evidence regarding the cardiovascular benefits in patients following bariatric surgery.

  1. Pharmacology for the Psychotherapist. (United States)

    Goldenberg, Myron Michael

    This book covers those areas of pharmacology that are of importance and interest to the psychotherapist. The 1st chapter introduces the various types of drugs. The 2nd chapter presents an overview of pharmacology and its principles. The 3rd chapter reviews aspects of the human body of importance to understanding the workings of psychotropic drugs.…

  2. Effectiveness of community-based comprehensive healthy lifestyle promotion on cardiovascular disease risk factors in a rural Vietnamese population: a quasi-experimental study

    Directory of Open Access Journals (Sweden)

    Nguyen Quang


    Full Text Available Abstract Background Health promotion is a key component for primary prevention of cardiovascular disease (CVD. This study evaluated the impact of healthy lifestyle promotion campaigns on CVD risk factors (CVDRF in the general population in the context of a community-based programme on hypertension management. Methods A quasi-experimental intervention study was carried out in two rural communes of Vietnam from 2006 to 2009. In the intervention commune, a hypertensive-targeted management programme integrated with a community-targeted health promotion was initiated, while no new programme, apart from conventional healthcare services, was provided in the reference commune. Health promotion campaigns focused on smoking cessation, reducing alcohol consumption, encouraging physical activity and reducing salty diets. Repeated cross-sectional surveys in local adult population aged 25 years and over were undertaken to assess changes in blood pressure (BP and behavioural CVDRFs (smoking, alcohol consumption, physical inactivity and salty diet in both communes before and after the 3-year intervention. Results Overall 4,650 adults above 25 years old were surveyed, in four randomly independent samples covering both communes at baseline and after the 3-year intervention. Although physical inactivity and obesity increased over time in the intervention commune, there was a significant reduction in systolic and diastolic BP (3.3 and 4.7 mmHg in women versus 3.0 and 4.6 mmHg in men respectively in the general population at the intervention commune. Health promotion reduced levels of salty diets but had insignificant impact on the prevalence of daily smoking or heavy alcohol consumption. Conclusion Community-targeted healthy lifestyle promotion can significantly improve some CVDRFs in the general population in a rural area over a relatively short time span. Limited effects on a context-bound CVDRF like smoking suggested that higher intensity of intervention

  3. Integrating pharmacology and clinical pharmacology in universities. (United States)

    Buckingham, Julia C


    Continuing development of safe and effective new medicines is critically important for global health, social prosperity and the economy. The drug discovery-development pipeline depends critically on close partnerships between scientists and clinicians and on educational programmes that ensure that the pharmacological workforce, in its broadest sense, is fit for purpose. Here I consider factors that have influenced the development of basic and clinical pharmacology in UK universities over the past 40 years and discuss ways in which basic pharmacologists, clinical pharmacologists and scientists from different disciplines can work together effectively, while retaining their professional identities and fostering developments in their disciplines. Specifically, I propose the establishment of Institutes of Drug Discovery and Development, whose activities could include development and implementation of a translational pharmacology research strategy, drawing on the collective expertise of the membership and the university as whole; provision of a forum for regular seminars and symposia to promote the discipline, encourage collaboration and develop a cohesive community; provision of a research advisory service, covering, for example, data management, applications for ethics permission, clinical trials design, statistics and regulatory affairs; liaison with potential funders and leadership of major funding bids, including funding for doctoral training; provision of advice on intellectual property protection and the commercialization of research; liaison with corporate partners to facilitate collaboration, knowledge transfer and effective translation; and leadership of undergraduate and postgraduate education in basic and clinical pharmacology and related sciences for medical and science students, including continuing professional development and transferable skills.

  4. Angiotensin-(1-7) : Pharmacological properties and pharmacotherapeutic perspectives

    NARCIS (Netherlands)

    Iusuf, Dilek; Henning, Robert H.; van Gilst, Wiek H.; Roks, Anton J. M.


    Therapeutic modulation of the renin-angiotensin system is not complete without taking into consideration the beneficial effects of angiotensin-(1-7) in cardiovascular pathology. Various pharmacological pathways are already exploited to involve this heptapeptide in therapy as both inhibitors of angio

  5. Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components

    Institute of Scientific and Technical Information of China (English)

    Wen-yu WU; Yi-ping WANG


    Salvia miltiorrhiza,a traditional medical herb known as danshen,has been widely used in China to improve blood circulation,relieve blood stasis,and treat coronary heart disease.S miltiorrhiza depside salt is a novel drug recently developed at the Shanghai Institute of Materia Medica; it contains magnesium lithospermate B (MLB) and its analogs,rosmarinic acid (RA) and lithospermic acid (LA),as active components.The drug has been used in the clinic to improve blood circulation and treat coronary heart disease.The pharmacological effects of the depside salt from S miltiorrhiza and its components have been extensively investigated.Experimental studies have demonstrated that magnesium lithospermate B possesses a variety of biological activities,especially protective effects in the cardiovascular system such as attenuation of atherosclerosis and protection against myocardial ischemia-reperfusion injury.Rosmarinic acid and lithospermic acid also show beneficial effects on the cardiovascular system.This paper reviews the recent findings regarding the mechanisms underlying the pharmacological actions of the active components of S miltiorrhiza depside salt,based on published works and our own observations.

  6. Biochemical and pharmacological assessment of MAP-kinase signaling along pain pathways in experimental rodent models: a potential tool for the discovery of novel antinociceptive therapeutics. (United States)

    Edelmayer, Rebecca M; Brederson, Jill-Desiree; Jarvis, Michael F; Bitner, Robert S


    Injury to the peripheral or central nervous system can induce changes within the nervous tissues that promote a state of sensitization that may underlie conditions of pathological chronic pain. A key biochemical event in the initiation and maintenance of peripheral and central neuronal sensitization associated with chronic pain is the phosphorylation and subsequent activation of mitogen-activated protein kinases (MAPKs) and immediate early gene transcription factors, in particular cAMP-response element binding protein (CREB). In this commentary we review the preclinical data that describe anatomical and mechanistic aspects of nociceptive-induced signaling along nociceptive pathways including peripheral cutaneous axons, the dorsal root ganglia, spinal cord dorsal horn and cerebral cortex. In addition to the regional manifestation of nociceptive signaling, investigations have attempted to elucidate the cellular origin of biochemical nociceptive processing in which communication, i.e. cross-talk between neurons and glia is viewed as an essential component of pathogenic pain development. Here, we outline a research strategy by which nociceptive-induced cellular signaling in experimental pain models, specifically MAPK and CREB phosphorylation can be utilized to provide mechanistic insight into drug-target interaction along the nociceptive pathways. We describe a series of studies using nociceptive inflammatory and neuropathic pain models to investigate the effects of known pain therapeutics on nociceptive-induced biochemical signaling and present this as a complementary research strategy for assessing antinociceptive activity useful in the preclinical development of novel pain therapeutics.

  7. Pharmacology of Periodontal Disease. (United States)


    k 7RD-A157 116 PHARMRCOLOGY’ OF PERIODONTAL DISEASE(U) UNIVERSITY OF i/ I HEALTH SCIENCES/CHICAGO MEDICAL SCHOOL DEPT OF I PHARMACOLOGY S F HOFF 24...Region Bethesda, MD 20814-5044 • .RE: Annual Letter Report , ONR Contract #N00014-84-K-0562 "Pharmacology of Periodontal Disease" Dear Capt. Hancock...Annual Letter Report ONR Contract #N00014-84-K-0562 1,! t "Pharmacology of Periodontal Disease" f Steven F. Hoff, Ph.D. (Principal Investigator) A

  8. Tratamento farmacológico da hiperalgesia experimentalmente induzida pelo núcleo pulposo Pharmacologic treatment of hyperalgesia experimentally induced by nucleus pulposus

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    André Luiz de Souza Grava


    Full Text Available OBJETIVO: Avaliar o efeito de drogas anti-inflamatórias (dexametasona, indometacina, atenolol, indometacina e atenolol e analgésica (morfina sobre a hiperalgesia experimentalmente induzida pelo núcleo pulposo em contato com o gânglio da raiz dorsal de L5. MÉTODOS: Trinta ratos Wistar machos com peso de 220 a 250g foram utilizados no estudo. A indução da hiperalgesia foi realizada por meio do contato de fragmento de núcleo pulposo retirado da região sacrococcígea e colocado sobre o gânglio da raiz dorsal de L5. Os 30 animais foram divididos em grupos experimentais de acordo com a droga utilizada. As drogas foram administradas durante duas semanas a partir da realização do procedimento cirúrgico para a indução da hiperalgesia. A hiperalgesia mecânica e térmica foram avaliadas por meio do teste da pressão constante da pata, von Frey eletrônico e Hargraves por um período de sete semanas. RESULTADOS: A maior redução da hiperalgesia foi observada no grupo de animais tratados pela morfina, seguido pela dexametasona, indometacina e atenolol. A redução da hiperalgesia foi observada após a interrupção da administração das drogas, com exceção do grupo de animais tratados com morfina, nos quais ocorreu aumento da hiperalgesia após a interrupção do tratamento. CONCLUSÕES: A hiperalgesia induzida pelo contato do núcleo pulposo com o gânglio da raiz dorsal pode ser reduzida com a administração de anti-inflamatórios e analgésicos, tendo sido observado a maior redução da hiperalgesia com a administração da morfina e dexametasona.OBJECTIVE: To evaluate the effect of antiinflammatory (dexamethasone, indomethacin, atenolol, indomethacin and atenolol and analgesic drugs (morphine on hyperalgesia experimentally induced by nucleus pulposus (NP contact with the L5- dorsal root ganglion (DRG. METHODS: Thirty male Wistar rats with weights ranging from 220 to 250 g were used in the study. The hyperalgesia was induced by

  9. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich-Christian; Semb, Synne; Nojgaard, Camilla


    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  10. Chiral cardiovascular drugs: an overview. (United States)

    Ranade, Vasant V; Somberg, John C


    Stereochemistry in drug molecules is rapidly becoming an important aspect in drug research, design, and development. Recently, individual stereoisomers of drug molecules with asymmetric centers such as fexofenadine, cetirizine, verapamil, fluoxetine, levalbutarol, and amphetamine, for example, have been separated and developed as individual drugs. These stereoisomers have different therapeutic activity, and each isomer has contributed differently with respect to its formulation's pharmacologic activity, side effects, and toxicity. The present overview discusses chirality among a select group of cardiovascular drugs, their stereochemical synthesis/preparation, isolation techniques using chiral chromatography, methods for confirmation of their enantiomeric purity, pharmacodynamics, and pharmacokinetics. Chirality has been visualized as an important factor in cardiovascular research. It is also becoming evident in other areas of therapeutics.

  11. Pharmacological Effects of Mangiferin

    Institute of Scientific and Technical Information of China (English)

    WEI Zhi-quan; DENG Jia-gang; YAN Li


    Mango leaves have been widely used in the clinical practice for thousands of years in traditional Chinese medicine.Mangiferin,an effective constituent in the mango leaves,has multiple pharmacological actions involved in some basic pathological processes,such as inflammation,oxidative injury,tumor growth,micro-organism infections,metabolic regulations,and immunological regulations.The pharmacological effects of mangiferin from some published data are reviewed in this article.

  12. Genus llex L.: Phytochemistry, Ethnopharmacology, and Pharmacology

    Institute of Scientific and Technical Information of China (English)

    Fan Yi; Xiao-ling Zhao; Yong Peng; Pei-gen Xiao


    The genus llex L. has been used as remedies in traditional Chinese medicine in Aquifoliaceae and beverages for thousands of years due to abundant pharmaceutical bioactivities. There are 600 species in genus llex L. containing various compounds such as terpenoids, saponins, glycosides, etc. Three species, I. cornuta, I. chinensis, and I. rotunda have been admitted in Chinese Pharmacopoeia 2015 to treat dyspepsia, stomatitis, and hyperactivity cough and protect the liver and kidney. Recent studies showed that several species have been daily drunk to promote human health and prevent cardiovascular diseases in the folk. Here we reviewed the genus llex L. in phytochemistry, ethnopharmacology, and pharmacology.

  13. Cardiovascular effects of monoterpenes: a review

    Directory of Open Access Journals (Sweden)

    Márcio R. V. Santos


    Full Text Available The monoterpenes are secondary metabolites of plants. They have various pharmacological properties including antifungal, antibacterial, antioxidant, anticancer, anti-spasmodic, hypotensive, and vasorelaxant. The purpose of this research was to review the cardiovascular effects of monoterpenes. The data in this resarch were collected using the Internet portals Pubmed, Scopus, and ISI Web of Knowledge between the years 1987 and 2010. In the study 33 monoterpenes were included, which were related to each of the thirteen individual words: artery, cardiovascular, heart, myocyte, vasorelaxant, vessel, hypotension, hypotensive, cardiomyocyte, ventricular, vasodilatory, aorta, and aortic. The research utilized 22 articles published mainly in the journals Phytomedicine, Fundamental Clinical Pharmacology, Planta Medica, Life Science, European Journal of Pharmacology, and Brazilian Journal of Medical and Biological Research. Of the 33 monoterpenes studied surveyed, sixteen of them had already been studied for their effects on the cardiovascular system: carvacrol, citronellol, p-cymene, eucalyptol (1,8-cineole, linalool, menthol, myrtenal, myrtenol, α-pinene, rotundifolone (piperitenone oxide, sobrerol, thymol, α-limonene, α-terpinen-4-ol, α-terpineol, and perillyl alcohol. The main effects observed were vasorelaxation, decreased heart rate and blood pressure. This review showed that the monoterpenes may be considered promising agents for prevention or treatment of diseases of the cardiovascular system.

  14. Vitamin D and cardiovascular disease. (United States)

    Norman, P E; Powell, J T


    Vitamin D plays a classical hormonal role in skeletal health by regulating calcium and phosphorus metabolism. Vitamin D metabolites also have physiological functions in nonskeletal tissues, where local synthesis influences regulatory pathways via paracrine and autocrine mechanisms. The active metabolite of vitamin D, 1α,25-dihydroxyvitamin D, binds to the vitamin D receptor that regulates numerous genes involved in fundamental processes of potential relevance to cardiovascular disease, including cell proliferation and differentiation, apoptosis, oxidative stress, membrane transport, matrix homeostasis, and cell adhesion. Vitamin D receptors have been found in all the major cardiovascular cell types including cardiomyocytes, arterial wall cells, and immune cells. Experimental studies have established a role for vitamin D metabolites in pathways that are integral to cardiovascular function and disease, including inflammation, thrombosis, and the renin-angiotensin system. Clinical studies have generally demonstrated an independent association between vitamin D deficiency and various manifestations of degenerative cardiovascular disease including vascular calcification. However, the role of vitamin D supplementation in the management of cardiovascular disease remains to be established. This review summarizes the clinical studies showing associations between vitamin D status and cardiovascular disease and the experimental studies that explore the mechanistic basis for these associations.

  15. Preventive Effects of Catechins on Cardiovascular Disease

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    Xiao-Qiang Chen


    Full Text Available Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the prevention and treatment of cardiovascular disorders, and we review the preventive effects of catechins on cardiovascular disease from the following aspects: Regulating lipid metabolism, regulating blood lipid metabolism, vascular endothelial protection, and reducing blood pressure.

  16. Low prevalence of hypertension with pharmacological treatments and associated factors

    Directory of Open Access Journals (Sweden)

    Helena Gama


    Full Text Available OBJECTIVE: To assess the determinants of the lack of pharmacological treatment for hypertension. METHODS: In 2005, 3,323 Mozambicans aged 25-64 years old were evaluated. Blood pressure, weight, height and smoking status were assessed following the Stepwise Approach to Chronic Disease Risk Factor Surveillance. Hypertensives (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive drug therapy were evaluated for awareness of their condition, pharmacological and non-pharmacological management, as well as use of herbal or traditional remedies. Prevalence ratios (PR were calculated, adjusted for sociodemographic characteristics, cardiovascular risk factors and non-pharmacological treatment. RESULTS: Most of the hypertensive subjects (92.3%, and nearly half of those aware of their condition were not treated pharmacologically. Among the aware, the prevalence of untreated hypertension was higher in men {PR = 1.61; 95% confidence interval (95%CI 1.10;2.36} and was lower in subjects under non-pharmacological treatment (PR = 0.58; 95%CI 0.42;0.79; there was no significant association with traditional treatments (PR = 0.75; 95%CI 0.44;1.26. CONCLUSIONS: The lack of pharmacological treatment for hypertension was more frequent in men, and was not influenced by the presence of other cardiovascular risk factors; it could not be explained by the use of alternative treatments as herbal/traditional medicines or non-pharmacological management. It is important to understand the reasons behind the lack of management of diagnosed hypertension and to implement appropriate corrective actions to reduce the gap in the access to healthcare between developed and developing countries.

  17. Safety Pharmacology Evaluation of Biopharmaceuticals. (United States)

    Amouzadeh, Hamid R; Engwall, Michael J; Vargas, Hugo M


    Biotechnology-derived pharmaceuticals or biopharmaceuticals (BPs) are molecules such as monoclonal antibodies, soluble/decoy receptors, hormones, enzymes, cytokines, and growth factors that are produced in various biological expression systems and are used to diagnose, treat, or prevent various diseases. Safety pharmacology (SP) assessment of BPs has evolved since the approval of the first BP (recombinant human insulin) in 1982. This evolution is ongoing and is informed by various international harmonization guidelines. Based on these guidelines, the potential undesirable effect of every drug candidate (small molecule or BP) on the cardiovascular, central nervous, and respiratory systems, referred to as the "core battery," should be assessed prior to first-in-human administration. However, SP assessment of BPs poses unique challenges such as choice of test species and integration of SP parameters into repeat-dose toxicity studies. This chapter reviews the evolution of SP assessment of BPs using the approval packages of marketed BPs and discusses the past, current, and new and upcoming approach and methods that can be used to generate high-quality data for the assessment of SP of BPs.

  18. Mitochondrial biogenesis: pharmacological approaches. (United States)

    Valero, Teresa


    diseases do not have exclusively a mitochondrial origin but they might have an important mitochondrial component both on their onset and on their development. This is the case of type 2 diabetes or neurodegenerative diseases. Type 2 diabetes is characterized by a peripheral insulin resistance accompanied by an increased secretion of insulin as a compensatory system. Among the explanations about the origin of insulin resistance Mónica Zamora and Josep A. Villena (Department of Experimental and Health Sciences, Universitat Pompeu Fabra / Laboratory of Metabolism and Obesity, Universitat Autònoma de Barcelona, Spain) [5] consider the hypothesis that mitochondrial dysfunction, e.g. impaired (mitochondrial) oxidative capacity of the cell or tissue, is one of the main underlying causes of insulin resistance and type 2 diabetes. Although this hypothesis is not free of controversy due to the uncertainty on the sequence of events during type 2 diabetes onset, e.g. whether mitochondrial dysfunction is the cause or the consequence of insulin resistance, it has been widely observed that improving mitochondrial function also improves insulin sensitivity and prevents type 2 diabetes. Thus restoring oxidative capacity by increasing mitochondrial mass appears as a suitable strategy to treat insulin resistance. The effort made by researchers trying to understand the signaling pathways mediating mitochondrial biogenesis has uncovered new potential pharmacological targets and opens the perspectives for the design of suitable treatments for insulin resistance. In addition some of the current used strategies could be used to treat insulin resistance such as lifestyle interventions (caloric restriction and endurance exercise) and pharmacological interventions (thiazolidinediones and other PPAR agonists, resveratrol and other calorie restriction mimetics, AMPK activators, ERR activators). Mitochondrial biogenesis is of special importance in modern neurochemistry because of the broad spectrum

  19. An in vivo pharmacological evaluation of pardoprunox (SLV308)--a novel combined dopamine D(2)/D(3) receptor partial agonist and 5-HT(1A) receptor agonist with efficacy in experimental models of Parkinson's disease. (United States)

    Jones, C A; Johnston, L C; Jackson, M J; Smith, L A; van Scharrenburg, G; Rose, S; Jenner, P G; McCreary, A C


    Partial D(2/3) dopamine (DA) receptor agonists provide a novel approach to the treatment of the motor symptoms of Parkinson's disease (PD) that may avoid common dopaminergic side-effects, including dyskinesia and psychosis. The present study focussed on the in vivo pharmacological and therapeutic characterisation of the novel D(2/3) receptor partial agonist and full 5-HT(1A) receptor agonist pardoprunox (SLV308; 7-[4-methyl-1-piperazinyl]-2(3H)-benzoxazolone monochloride). Pardoprunox induced contralateral turning behaviour in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra pars compacta (SNpc) (MED=0.03mg/kg; po). In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets, pardoprunox dose-dependently increased locomotor activity (MED=0.03mg/kg; po) and decreased motor disability (MED=0.03mg/kg; po). The effects of pardoprunox were reversed by the D(2) antagonist sulpiride. In contrast pardoprunox attenuated novelty-induced locomotor activity (MED=0.01mg/kg; po), (+)-amphetamine-induced hyperlocomotion (MED=0.3mg/kg; po) and apomorphine-induced climbing (MED=0.6mg/kg; po) in rodents. Pardoprunox also induced 5-HT(1A) receptor-mediated behaviours, including flat body posture and lower lip retraction (MED=0.3mg/kg; po) and these were reversed by the 5-HT(1A) receptor antagonist WAY100635. Collectively, these findings demonstrate that pardoprunox possesses dopamine D2/3 partial agonist effects, 5-HT1A agonist effects and reduces parkinsonism in animal models. functional DA D(2) receptor partial agonist activity and is effective in experimental models predictive of efficacy in PD. The presence of functional 5-HT(1A) agonist activity might confer anti-dyskinetic activity and have effects that control neuropsychiatric components of PD.

  20. Evaluation of the cardiovascular effects of varenicline in rats

    Directory of Open Access Journals (Sweden)

    Selçuk EB


    Full Text Available Engin Burak Selçuk,1 Meltem Sungu,2 Hakan Parlakpinar,3 Necip Ermiş,4 Elif Taslıdere,5 Nigar Vardı,5 Murat Yalçinsoy,6 Mustafa Sagır,3 Alaaddin Polat,7 Mehmet Karatas,8 Burcu Kayhan-Tetik11Department of Family Medicine, 2Inonu University Medical Faculty, Malatya, Turkey; 3Department of Pharmacology, 4Department of Cardiology, 5Department of Histology and Embryology, 6Department of Pulmonary Medicine, 7Department of Physiology, 8Department of Medical Ethics, Inonu University Medical Faculty, Malatya, TurkeyBackground: Cardiovascular disease is an important cause of morbidity and mortality among tobacco users. Varenicline is widely used worldwide to help smoking cessation, but some published studies have reported associated cardiovascular events.Objective: To determine the cardiovascular toxicity induced by varenicline in rats.Materials and methods: We randomly separated 34 rats into two groups: 1 the control group (given only distilled water orally, n=10 and the varenicline group (given 9 µg/kg/day varenicline on days 1–3, 9 µg/kg twice daily on days 4–7, and 18 µg/kg twice daily on days 8–90 [total 83 days], n=24. Each group was then subdivided equally into acute and chronic subgroups, and all rats in these groups were euthanized with anesthesia overdose on days 45 and 90, respectively. Body and heart weights, hemodynamic (mean oxygen saturation, mean blood pressure, and heart rate, electrocardiographic (PR, QRS, and QT intervals biochemical (oxidants and antioxidants, and histopathological analyses (including immunostaining were performed.Results: Acute varenicline exposure resulted in loss of body weight, while chronic varenicline exposure caused heart weight loss and decreased mean blood pressure, induced lipid peroxidation, and reduced antioxidant activity. Both acute and chronic varenicline exposure caused impairment of mean oxygen saturation. QT interval was prolonged in the chronic varenicline group, while PR interval

  1. Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes. (United States)

    Fisman, Enrique Z; Tenenbaum, Alexander


    The traditional oral pharmacological therapy for type 2 diabetes mellitus (T2DM) has been based on the prescription of metformin, a biguanide, as first line antihyperglycemic agent world over. It has been demonstrated that after 3 years of treatment, approximately 50% of diabetic patients could achieve acceptable glucose levels with monotherapy; but by 9 years this had declined to only 25%. Therefore, the implementation of a combined pharmacological therapy acting via different pathways becomes necessary, and its combination with a compound of the sulfonylurea group was along decades the most frequently employed prescription in routine clinical practice. Meglitinides, glitazones and alpha-glucosidase inhibitors were subsequently developed, but the five mentioned groups of oral antihyperglycemic agents are associated with variable degrees of undesirable or even severe cardiovascular events. The gliptins-also called dipeptidyl peptidase 4 (DPP4) inhibitors--are an additional group of antidiabetic compounds with increasing clinical use. We review the status of the gliptins with emphasis on their capabilities to positively or negatively affect the cardiovascular system, and their potential involvement in major adverse cardiovascular events (MACE). Alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin and vildagliptin are the compounds currently in clinical use. Regardless differences in chemical structure and metabolic pathways, gliptins as a group exert favorable changes in experimental models. These changes, as an almost general rule, include improved endothelial function, reduction of inflammatory markers, oxidative stress ischemia/reperfusion injury and atherogenesis. In addition, increased adiponectin levels and modest decreases in lipidemia and blood pressure were reported. In clinical settings, several trials--notably the longer one, employing sitagliptin, with a mean follow-up period of 3 years--did not show an increased risk for ischemic

  2. The Genus Alpinia:A Review of Its Phytochemistry and Pharmacology

    Institute of Scientific and Technical Information of China (English)

    Wei-Jie Zhang; Jian-Guang Luo; Ling-Yi Kong


    Genus Alpinia consists of over 250 species, which are widely distributed in south and southeast Asia. Many plants of genus Alpinia have been used for thousands of years to treat digestive system diseases and as anti-inflammatory drugs. Phytochemical research on this genus has led to the isolation of different kinds of diarylheptanoids, terpenes triterpenoids, phenylbutanoids, lignans, and flavonoids. Experimental evidences revealed that both the crude extracts and pure constituents isolated from the genus Alpinia exhibit a wide range of bioactivities such as anti-cancer, anti-oxidant, anti-bacterial, anti-viral, cardiovascular, and digestive system protective effects. Here, we summarize the phytochemistry and pharmacology investigation of the genus Alpinia, which can provide reference for further research and drug development.

  3. Pharmacological actions and acute toxicity of methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones. (United States)

    Singh, G B; Leach, G D; Atal, C K


    Some pharmacological actions and acute toxicity effects of methyl- and phenyl-3-methoxy-4-hydroxy styryl ketones have been described in experimental animals. The compounds antagonised the contractions evoked by a variety of agonists on several smooth muscle preparations in vitro. They produced inhibitory effects on spontaneously contracting uteri from pregnant rats and relaxant effects on pendular movements of rabbit duodenum and on dog intestinal movements in vivo. The compounds inhibited the castor oil induced diarrhoea in rat and propulsion of charcoal test meal in mice. Phenylbutazone showed similar effect on castor oil diarrhoea. The compounds failed to modify gestation period or parturition in pregnant rats. They antagonised bradykinin-induced bronchospasm in guinea pig. The compounds showed no significant effect on cardiovascular and respiratory systems: CNS and general behaviour were not affected even at high doses. Oral LD50 for both the compounds was greater than 2 g/kg.

  4. Assessing the functional properties of high-density lipoproteins : an emerging concept in cardiovascular research

    NARCIS (Netherlands)

    Triolo, Michela; Annema, Wijtske; Dullaart, Robin P. F.; Tietge, Uwe J. F.


    Although plasma concentrations of high-density lipoprotein (HDL) cholesterol correlate inversely with the incidence of atherosclerotic cardiovascular disease, results from recent epidemiological, genetic and pharmacological intervention studies resulted in a shift of concept. Rather than HDL cholest

  5. Proprotein Convertase Subtilisin/Kexin Type 9: From the Discovery to the Development of New Therapies for Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Nicola Ferri


    Full Text Available The identification of the HMG-CoA reductase inhibitors, statins, has represented a dramatic innovation of the pharmacological modulation of hypercholesterolemia and associated cardiovascular diseases. However, not all patients receiving statins achieve guideline-recommended low density lipoprotein (LDL cholesterol goals, particularly those at high risk. There remains, therefore, an unmet medical need to develop additional well-tolerated and effective agents to lower LDL cholesterol levels. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9, a secretory protein that posttranscriptionally regulates levels of low density lipoprotein receptor (LDLR by inducing its degradation, has opened a new era of pharmacological modulation of cholesterol homeostasis. This paper summarizes the current knowledge of the basic molecular mechanism underlying the regulatory effect of LDLR expression by PCSK9 obtained from in vitro cell-cultured studies and the analysis of the crystal structure of PCSK9. It also describes the epidemiological and experimental evidences of the regulatory effect of PCSK9 on LDL cholesterol levels and cardiovascular diseases and summarizes the different pharmacological approaches under development for inhibiting PCSK9 expression, processing, and the interaction with LDLR.

  6. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing


    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  7. Social Pharmacology: Expanding horizons

    Directory of Open Access Journals (Sweden)

    Rituparna Maiti


    Full Text Available In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinical pharmacology, and deals with different parameters, which are important in creating knowledge on marketed drugs. However, the scope of "social pharmacology" is not covered by the so-called "Phase IV" alone, but it is the science that handles the postmarketing knowledge of drugs. The social pharmacology studies the "life cycle" of any marketed pharmaceutical product in the social terrain, and evaluates the effects of the real environment under circumstances totally different in the drug development process. Therefore, there are far-reaching horizons, plural, and shared predictions among health professionals and other, for beneficial use of a drug, toward maximizing the benefits of therapy, while minimizing negative social consequences.

  8. Social pharmacology: expanding horizons. (United States)

    Maiti, Rituparna; Alloza, José Luis


    In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene) and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinical pharmacology, and deals with different parameters, which are important in creating knowledge on marketed drugs. However, the scope of "social pharmacology" is not covered by the so-called "Phase IV" alone, but it is the science that handles the postmarketing knowledge of drugs. The social pharmacology studies the "life cycle" of any marketed pharmaceutical product in the social terrain, and evaluates the effects of the real environment under circumstances totally different in the drug development process. Therefore, there are far-reaching horizons, plural, and shared predictions among health professionals and other, for beneficial use of a drug, toward maximizing the benefits of therapy, while minimizing negative social consequences.

  9. Pharmacology profiling of chemicals and proteins

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl

    between pharmaceuticals and proteins in vivo potential leads to unwanted adverse effects, toxicity and reduced half-life, but can also lead to novel therapeutic effects of already approved pharmaceuticals. Hence identification of in vivo targets is of importance in discovery, development and repurposing...... of pharmaceuticals, a process referred to as pharmacology profiling. Pharmacology profiling of chemical and protein based pharmaceuticals has been proven valuable in a number studies [2], however missing values in the drug-protein interaction matrix limits the profile for novel or less studied compounds...... as an alternative to experimentally obtained measurements. Here I present several different tools that aid pharmacology profiling of the two main classes of pharmaceuticals; chemicals (small molecules) and proteins (biopharmaceuticals). Biopharmaceuticals have the inherent risks of eliciting an immune response due...

  10. Screening Of Marine Bacteria For Pharmacological Activities

    Directory of Open Access Journals (Sweden)

    S. Vijayalakshmi


    Full Text Available Abstract The symbiotic and associated four marine bacteria BR1 Flavobacterium sp. isolated from Barnacle Balanus amphitriteEM13 Micrococus sp. from Seaweed Enteromorpha compressaPC4 Alcaligenes sp. from Ascidian Polyclinum constellatum and SW12 Bacillus sp. from seawater were cultured and extracted for pharmacological activities. The ethyl acetate extracts of these marine bacterial culture supernatants were screened for pharmacological activities such as Anti inflammatory Analgesic and CNS depressant activities using experimental animal model. In this studySW12 exhibited high activity for both Anti inflammatory and Analgesic. Especially which exhibited highest analgesic activity than standard drug pethidine. Another one PC4 showed highest analgesic activity similar to standard drug. Other two extracts EM13 and BR1 showed high activity in CNS depressant. Based on the result SW12 is a highly potent strain it may produce novel compound for pharmacological drug.

  11. Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia. (United States)

    Kocic, Gordana; Sokolovic, Dusan; Jevtovic, Tatjana; Cvetkovic, Tatjana; Veljkovic, Andrej; Kocic, Hristina; Stojanovic, Svetlana; Jovanovic, Aneta; Jovanovic, Jelena; Zivkovic, Petar


    Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function.

  12. Pharmacological approach to acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ulrich Christian Bang; Synne Semb; Camilla Nφjgaard; Flemming Bendtsen


    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP)based on experimental animal models and clinical trials.Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP). The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi.Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results.Antibodies against tumor necrosis factor-alpha (TNF-α)have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics betalactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.

  13. CD26: a multi-purpose pharmacological target. (United States)

    Vincenzo, Formica; Manfredi, Tesauro; Carmine, Cardillo; Mario, Roselli


    CD26 is a widely expressed transmembrane glycoprotein with peptidase activity in its extracellular domain and which regulates multiple biological processes. It acts mainly as catabolic enzyme for a number of circulating proteins involved in common pathological conditions such as diabetes and cardiovascular disease and may represent a target to modulate bioavailability of crucial substrates. The aim of the present review is to summarize data regarding CD26-based pharmacological interventions. Four main subtopics were identified:1) CD26 as the target of pharmacological inhibitors to increase bioavailability of glucagon-like petide-1 (GLP-1) and hence to enhance GLP-1 glucose-lowering activity in diabetic patients; 2) role of CD26 in the physiology and pathology of the cardiovascular system; 3) the adverse prognostic value of CD26 expression on cancer cells; 4) CD26 down-regulation on lymphocytes as a mechanism of TGF-beta immunomodulation.

  14. Protective Role of the ACE2/Ang-(1–9 Axis in Cardiovascular Remodeling

    Directory of Open Access Journals (Sweden)

    María Paz Ocaranza


    Full Text Available Despite reduction in cardiovascular (CV events and end-organ damage with the current pharmacologic strategies, CV disease remains the primary cause of death in the world. Pharmacological therapies based on the renin angiotensin system (RAS blockade are used extensively for the treatment of hypertension, heart failure, and CV remodeling but in spite of their success the prevalence of end-organ damage and residual risk remain still high. Novel approaches must be discovered for a more effective treatment of residual CV remodeling and risk. The ACE2/Ang-(1–9 axis is a new and important target to counterbalance the vasoconstrictive/proliferative RAS axis. Ang-(1–9 is hydrolyzed slower than Ang-(1–7 and is able to bind the Ang II type 2 receptor. We review here the current experimental evidence suggesting that activation of the ACE2/Ang-(1–9 axis protects the heart and vessels (and possibly the kidney from adverse cardiovascular remodeling in hypertension as well as in heart failure.

  15. Pharmacology and drug distribution

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, L.R.; Weatherall, T.J.


    An overview of the pharmacology of drugs in the treatment of cancer is presented. The discussion begins with the simplest relationship of drugs and particles to one another then proceeds to demonstrate the interrelationship in a biologic system to produce a chemobiodynamic response. The basic principles of pharmacokinetics are reviewed and their correlation with investigational and standard drug therapies is discussed. Voids in the consideration of interactions between chemotherapy and radiotherapy are discussed.

  16. Social pharmacology: expanding horizons


    Rituparna Maiti; José Luis Alloza


    In the current modern and global society, social changes are in constant evolution due to scientific progress (technology, culture, customs, and hygiene) and produce the freedom in individuals to take decisions by themselves or with their doctors toward drug consumption. In the arena of marketed drug products which includes society, individual, administration, and pharmaceutical industry, the young discipline emerged is social pharmacology or sociopharmacology. This science arises from clinic...

  17. Pharmacological interactions of vasoconstrictors. (United States)

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis


    This article is the first of a series on pharmacological interactions involving medicaments commonly prescribed and/or used in odontology: vasoconstrictors in local anaesthetics and anti-inflammatory and anti-microbial analgesics. The necessity for the odontologist to be aware of adverse reactions as a result of the pharmacological interactions is due to the increase in medicament consumption by the general population. There is a demographic change with greater life expectancy and patients have increased chronic health problems and therefore have increased medicament intake. The presence of adrenaline (epinephrine) and other vasoconstrictors in local odontological anaesthetics is beneficial in relation to the duration and depth of anaesthesia and reduces bleeding and systemic toxicity of the local anaesthetic. However, it might produce pharmacological interactions between the injected vasoconstrictors and the local anaesthetic and adrenergic medicament administered exogenically which the odontologist should be aware of, especially because of the risk of consequent adverse reactions. Therefore the importance of conducting a detailed clinical history of the general state of health and include all medicaments, legal as well as illegal, taken by the patient.

  18. Cardiovascular and renal effects of hyperuricaemia and gout

    Directory of Open Access Journals (Sweden)

    R. Pontremoli


    Full Text Available A number of epidemiological studies have reported an association between serum uric acid levels and a wide variety of high-risk conditions including hypertension, insulin resistance, and kidney and cerebro-cardiovascular disease. All things considered, serum uric acid may induce cardiovascular and kidney events both directly and indirectly by promoting other well-known mechanisms of damage. While asymptomatic hyperuricemia is currently not considered to be an indication for urate lowering therapy, there is growing evidence indicating a linear relationship between pharmacological reduction in serum uric acid and incidence of cardiovascular and renal events.

  19. Experimental study and constitutive modelling of the passive mechanical properties of the porcine carotid artery and its relation to histological analysis: Implications in animal cardiovascular device trials. (United States)

    García, A; Peña, E; Laborda, A; Lostalé, F; De Gregorio, M A; Doblaré, M; Martínez, M A


    The present study focusses on the determination, comparison and constitutive modelling of the passive mechanical properties of the swine carotid artery over very long stretches in both proximal and distal regions. Special attention is paid to the histological and mechanical variations of these properties depending on the proximity to the heart. The results can have clinical relevance, especially in the research field of intravascular device design. Before the final clinical trials on humans, research in the vascular area is conducted on animal models, swine being the most common due to the similarities between the human and swine cardiovascular systems as well as the fact that the swine size is suitable for testing devices, in this case endovascular carotid systems. The design of devices usually involves numerical techniques, and an important feature is the appropriate modelling of the mechanical properties of the vessel. Fourteen carotid swine arteries were harvested just after sacrifice and cyclic uniaxial tension tests in longitudinal and circumferential directions were performed for distal and proximal samples. The stress-stretch curves obtained were fitted with a hyperelastic anisotropic model. Stress-free configuration states were also analyzed. Finally, human and swine samples were processed in a histological laboratory and images were used to quantify their microconstituents. The statistical analysis revealed significant differences between the mechanical behavior of proximal and distal locations in the circumferential but not in the longitudinal direction. Circumferential direction samples show clear differences both in residual stretches and tensile curves between the two locations, while the features of longitudinal specimens are independent of the axial position. The statistical analysis provides significant evidence of changes depending on the position of the sample, mainly in elastin and SMC quantification.

  20. Ginseng leaf-stem: bioactive constituents and pharmacological functions

    Directory of Open Access Journals (Sweden)

    Xie Jingtian


    Full Text Available Abstract Ginseng root is used more often than other parts such as leaf stem although extracts from ginseng leaf-stem also contain similar active ingredients with pharmacological functions. Ginseng's leaf-stems are more readily available at a lower cost than its root. This article reviews the pharmacological effects of ginseng leaf-stem on some diseases and adverse effects due to excessive consumption. Ginseng leaf-stem extract contains numerous active ingredients, such as ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils, polyacetylenic alcohols, peptides, amino acids and fatty acids. The extract contains larger amounts of the same active ingredients than the root. These active ingredients produce multifaceted pharmacological effects on the central nervous system, as well as on the cardiovascular, reproductive and metabolic systems. Ginseng leaf-stem extract also has anti-fatigue, anti-hyperglycemic, anti-obesity, anti-cancer, anti-oxidant and anti-aging properties. In normal use, ginseng leaf-stem extract is quite safe; adverse effects occur only when it is over dosed or is of poor quality. Extracts from ginseng root and leaf-stem have similar multifaceted pharmacological activities (for example central nervous and cardiovascular systems. In terms of costs and source availability, however, ginseng leaf-stem has advantages over its root. Further research will facilitate a wider use of ginseng leaf-stem.

  1. Pharmacology exercise for undergraduate: MLNMC model

    Directory of Open Access Journals (Sweden)

    Rakesh C. Chaurasia


    Full Text Available Pharmacology is the backbone of clinical discipline of medical science. In the computer era of advancement, paraclinical teachings become more technical and clinical oriented. Regarding to undergraduate practical’s the animal experimentation and dispensing pharmacy are only exercises. But these are matter of critics due to their non-utility in future. Student’s apathy and non-interest are hidden factor to perform such boring experiments. Meanwhile the old-dated exercises have no potential to tone-up adequate clinical skills in future study instead of wastage of time and money. Killing of innocent animals is crucial and should be socially discouraged. Thus Pharmacology practical are matter of debate in current scenario. Being attachment with past sentiment of traditional dispensing pharmacy and animal experimentations, they are difficult to delete completely. The present article highlights some of our efforts in undergraduate exercises. [Int J Basic Clin Pharmacol 2013; 2(4.000: 495-497

  2. International Conference on Pathophysiology and Drug Therapy of Cardiovascular Disorders

    Institute of Scientific and Technical Information of China (English)


    @@2001 Jan 22-26 Patiala, INDIA Info: Dr Manjeet Singh Professor of Cardiovascular Pharmacology Head, Department of Pharmaceutical Sciences and Drug Research Punjabi University Patiala-147002 Punjab (INDIA) Phn: 91-175-282461/63, ext 6184. Fax: 91-175-283073/282881 E-mail: rnanjeet@pbi. emet. in

  3. Pharmacologic perspectives of functional selectivity by the angiotensin II type 1 receptor

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Hansen, Jakob Lerche


    The angiotensin II type 1 (AT(1)) receptor plays a key role in cardiovascular pathophysiology, and it is a major pharmacologic target in the treatment of many cardiovascular disorders. However, AT(1) receptor activation is also involved in adaptive responses to altered hemodynamic demands...... and to sudden injury occurring in the circulatory system. Hence, current drugs that block all AT(1) receptor actions most likely leave room for improvement. Recent developments show that two major signaling pathways used by the AT(1) receptor may be dissected by pharmacologic means. Key pathologic responses...

  4. Analytical pharmacology: the impact of numbers on pharmacology. (United States)

    Kenakin, Terry; Christopoulos, Arthur


    Analytical pharmacology strives to compare pharmacological data to detailed quantitative models. The most famous tool in this regard is the Black/Leff operational model, which can be used to quantify agonism in a test system and predict it in any other system. Here we give examples of how and where analytical pharmacology has been used to classify drugs and predict mechanism of action in pharmacology. We argue for the importance of analytical pharmacology in drug classification and in prediction of drug mechanisms of action. Although some of the specifics of Black's models have been updated to account for new developments, the principles of analytical pharmacology should shape drug discovery for many years to come.

  5. The pharmacology game. (United States)

    Batscha, Catherine


    This article gives instructions for designing a visually attractive, entertaining, faculty-led computer game for pharmacology review in a nursing education program. The game uses Microsoft PowerPoint, a presentation program that is inexpensive, easy to master, and widely available. Instructions for using Visual Basic for Applications to customize the game are included to allow tracking questions asked and the score of groups playing the game. The game can be easily adapted to material by specific nursing programs with access to PowerPoint.

  6. Pharmacological treatment of schizophrenia. (United States)

    Leucht, S; Heres, S; Kissling, W; Davis, J M


    We present the pharmacological treatment of schizophrenia based on a simple algorithm that starts with the most important decisions starting from the choice of an antipsychotic drug for an acutely ill patient and ends with maintenance treatment. It represents experts opinions, a formal guideline development process was not followed. Concerning acute treatment we present recommendations for the choice of drug in acutely patients, the treatment of agitated patients, persistent depression, negative symptoms and treatment resistance. Concerning maintenance treatment with antipsychotics we discuss indication, choice of drug, continuous versus intermittent treatment, duration of relapse prevention and dose.

  7. Pharmacological Profile of Quinoxalinone

    Directory of Open Access Journals (Sweden)

    Youssef Ramli


    Full Text Available Quinoxalinone and its derivatives are used in organic synthesis for building natural and designed synthetic compounds and they have been frequently utilized as suitable skeletons for the design of biologically active compound. This review covers updated information on the most active quinoxalinone derivatives that have been reported to show considerable pharmacological actions such as antimicrobial, anti-inflammatory, antidiabetic, antiviral, antitumor, and antitubercular activity. It can act as an important tool for chemists to develop newer quinoxalinone derivatives that may prove to be better agents in terms of efficacy and safety.

  8. Repurposing of approved cardiovascular drugs. (United States)

    Ishida, Junichi; Konishi, Masaaki; Ebner, Nicole; Springer, Jochen


    Research and development of new drugs requires both long time and high costs, whereas safety and tolerability profiles make the success rate of approval very low. Drug repurposing, applying known drugs and compounds to new indications, has been noted recently as a cost-effective and time-unconsuming way in developing new drugs, because they have already been proven safe in humans. In this review, we discuss drug repurposing of approved cardiovascular drugs, such as aspirin, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, cardiac glycosides and statins. Regarding anti-tumor activities of these agents, a number of experimental studies have demonstrated promising pleiotropic properties, whereas all clinical trials have not shown expected results. In pathological conditions other than cancer, repurposing of cardiovascular drugs is also expanding. Numerous experimental studies have reported possibilities of drug repurposing in this field and some of them have been tried for new indications ('bench to bedside'), while unexpected results of clinical studies have given hints for drug repurposing and some unknown mechanisms of action have been demonstrated by experimental studies ('bedside to bench'). The future perspective of experimental and clinical studies using cardiovascular drugs are also discussed.

  9. Establishment of pharmacological experimental methods of rat small intestinal crypt cell line%小肠隐窝细胞株药理实验方法的建立

    Institute of Scientific and Technical Information of China (English)

    张子理; 岳双冰; 田欢; 莫婷; 林洪; 张广路; 陈蔚文


    目的:建立小肠隐窝细胞株(IEC-6)药理实验方法。方法:观察细胞接种密度、α-二氟甲基鸟氨酸(DFMO)和胃泌素对IEC-6细胞增殖及细胞鸟氨酸脱羧酶(ODC)的影响。结果:较高接种密度(>0.5×104细胞/孔)组,接种后第2天,细胞生长抑制,尤其是密度增加到4×104细胞/孔时,第2~3天,OD值逐渐增加,第4天明显增加,第5天达高峰,此后OD值开始下降。而低密度(0.2×104细胞/孔)接种后第4天,细胞生长出现抑制,此后其生长与其他密度相似。加入DFMO后1~3天,完全抑制了细胞增殖,此后与空白组一样,细胞逐渐生长。 DFMO还明显抑制IEC-6细胞分化和移行,以及 ODC活性和腐胺含量,与空白组比较具有显著性差异(P<0.01)。IEC-6细胞在胃泌素250μg·L-1作用后第一天,开始增殖,第3天达高峰。胃泌素500μg·L-1作用后第1~2天,细胞开始增殖,第3天以后,细胞增殖下降。胃泌素明显促进细胞分化和移行。与空白组比较,胃泌素250μg·L-1分别使ODC mRNA水平,ODC活性,腐胺含量增加1.09倍(P<0.05),1.71倍(P<0.01)和5.30倍(P<0.01)。同样,胃泌素500μg·L-1可使以上3项指标分别升高1.16倍(P<0.05),1.63倍(P<0.05)和4.41倍(P<0.01)。但胃泌素两个剂量组之间无显著性差异。结论:IEC-6细胞是进行胃肠粘膜修复药理实验的合适细胞模型。%Objective:To established a pharmacological experimental methods of rat small intestinal crypt cell line.Methods:To observed the role of plating densities,alpha-difluoromethylornithine(DFMO)and pentagastrin on the proliferation,differentiation,migration , ODC mRNA level,ODC activity and putrescine content of IEC-6 cells in vitro. Results:Higher plating densities (>0.5×104 cells/well) inhibited the growth of cells on day 2 , especially when a density reach to 4 × 104 cells/well , the OD

  10. Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models

    Directory of Open Access Journals (Sweden)

    Alexander J. Szalai


    Full Text Available Raised blood C-reactive protein (CRP level is a predictor of cardiovascular events, but whether blood CRP is causal in the disease process is unknown. The latter would best be defined by pharmacological inhibition of the protein in the context of a randomized case-control study. However, no CRP specific drug is currently available so such a prospective study cannot be performed. Blood CRP is synthesized primarily in the liver and the liver is an organ where antisense oligonucleotide (ASO drugs accumulate. Taking advantage of this we evaluated the efficacy of CRP specific ASOs in rodents with experimentally induced cardiovascular damage. Treating rats for 4 weeks with a rat CRP-specific ASO achieved >60% reduction of blood CRP. Notably, this effect was associated with improved heart function and pathology following myocardial infarction (induced by ligation of the left anterior descending artery. Likewise in human CRP transgenic mice treated for 2 weeks with a human CRP-specific ASO, blood human CRP was reduced by >70% and carotid artery patency was improved (2 weeks after surgical ligation. CRP specific ASOs might pave the way towards a placebo-controlled trial that could clarify the role of CRP in cardiovascular disease.

  11. Clinical perspectives and fundamental aspects of local cardiovascular and renal renin-angiotensin systems

    Directory of Open Access Journals (Sweden)

    Walmor eDe Mello


    Full Text Available Evidence for the potential role of organ specific cardiovascular renin-angiotensin systems (RAS has been demonstrated experimentally and clinically with respect to certain cardiovascular and renal diseases. These findings have been supported by studies involving pharmacological inhibition during ischemic heart disease, myocardial infarction, cardiac failure; hypertension associated with left ventricular (LV ischemia, myocardial fibrosis and left ventricular hypertrophy (LVH; structural and functional changes of the target organs associated with prolonged dietary salt excess; and intrarenal vascular disease associated with end-stage renal disease (ESRD. Moreover, the severe structural and functional changes induced by these pathological conditions, can be prevented and reversed by agents producing RAS inhibition (even when not necessarily coincident with alterations in arterial pressure.In this review, we discuss specific fundamental and clinical aspects and mechanisms related to the activation or inhibition of local renin angiotensin systems and their implications for cardiovascular and renal diseases. Fundamental aspects involving the role of angiotensins on cardiac and renal functions including the expression of RAS components in the heart and kidney and the controversial role of ACE2 on angiotensin peptide metabolism in humans, were discussed.

  12. [Pharmacological treatment of hyperinflation]. (United States)

    Devillier, P; Roche, N


    Introduction Lung hyperinflation leads to breathlessness, limitation in exercise capacity and tolerance, and impaired quality of life. Thus, it is important to target this key and characteristic feature of COPD. Current knowledge Available pharmacological approaches rely mainly on bronchodilators, in particular beta2 agonists and anticholinergic agents. These treatments act through the reduction of expiratory airflow limitation. However, changes in classical indices of airflow obstruction do not accurately predict effects on hyperinflation and symptoms. The decrease in operating lung volumes (as reflected by inspiratory capacity or functional residual capacity) at rest and during exercise is one of the mechanisms by which these treatments improve quality of life and maybe also decrease the impact of exacerbations. The effect of beta2 agonists on hyperinflation might be amplified by concurrent treatment with inhaled corticosteroids. Perspectives The effect of new treatments targeting airways inflammation on hyperinflation remains to be explored. Conclusions Measuring the reduction in the degree of lung hyperinflation allows a better understanding of the symptomatic effect of COPD pharmacological treatments.

  13. Cardiovascular Disease and Diabetes (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More Cardiovascular Disease & Diabetes Updated:Nov 4,2016 The following statistics speak ... disease. This content was last reviewed August 2015. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...

  14. Cardiovascular manifestations of phaeochromocytoma

    NARCIS (Netherlands)

    Prejbisz, A.; Lenders, J.W.M.; Eisenhofer, G.; Januszewicz, A.


    Clinical expression of phaeochromocytoma may involve numerous cardiovascular manifestations, but usually presents as sustained or paroxysmal hypertension associated with other signs and symptoms of catecholamine excess. Most of the life-threatening cardiovascular manifestations of phaeochromocytoma,

  15. Understanding cardiovascular disease (United States)

    ... page: // Understanding cardiovascular disease To use the sharing features on this page, ... lead to heart attack or stroke. Types of Cardiovascular Disease Coronary heart disease (CHD) is the most common ...

  16. APOE Genotyping, Cardiovascular Disease (United States)

    ... Home Visit Global Sites Search Help? APOE Genotyping, Cardiovascular Disease Share this page: Was this page helpful? Also ... of choice to decrease the risk of developing cardiovascular disease (CVD) . However, there is a wide variability in ...

  17. Molecular pharmacology of G protein-coupled receptors. (United States)

    Summers, R J


    This themed issue of the British Journal of Pharmacology stems from the eighth in the series of meetings on the Molecular Pharmacology of G protein coupled receptors (MPGPCR) held as part of a joint meeting with the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) in Melbourne Australia from 7 to 11 December 2014. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit

  18. Pharmacological Attenuation of Myocardial Reperfusion Injury in a Closed-Chest Porcine Model

    DEFF Research Database (Denmark)

    Ekeløf, Sarah; Rosenberg, Jacob; Jensen, Jan Skov;


    Myocardial ischemia-reperfusion injury is a clinical challenge in interventional cardiology, and at the moment, no pharmacological agent is universally accepted in the prevention. In order to prevent inappropriate clinical trials, a potential pharmacological agent should be proved reproducibly...... effective in clinically relevant experimental studies before initiation of human studies. The closed-chest porcine model is a promising experimental model of ischemia-reperfusion injury. The purpose of this systematic review was to describe the pharmacological treatments evaluated in the closed...

  19. Cardiovascular comorbiditiy in psoriasis


    Gurcharan Singh; Simran Pal Singh Aneja


    The chronic inflammatory nature of psoriasis is also thought to predispose patients to other diseases with an inflammatory component, the most notable being cardiovascular and metabolic (cardiometabolite) disorders. This concept is supported by studies showing that psoriasis is associated with cardiovascular risk factors like diabetes, obesity, hypertension, dyslipidemia, smoking and diseases including MI. Given the increased prevalence of cardiovascular co morbidities in patients, dermatolog...

  20. Experimental study for protective effects of ulinastatin from cardiovascular disease%乌司他丁心血管保护作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    郑翔; 方志成; 周昌娥; 熊鹏; 刘伯毅; 陈黎; 黄云飞


    目的:探讨蛋白酶抑制剂乌司他丁对心肌梗塞后心肌的保护作用及其可能机制.方法:选取3~5月龄日本大耳白兔30只,结扎兔前降支制作心肌梗塞模型,随机均分为对照组(予生理盐水)、常规治疗组(予硝酸甘油等常规治疗)、乌司他丁组(在常规治疗基础上给予乌司他丁治疗).模型制作前、后4周行心脏超声检查,以红四氮唑(TTC)染色评价梗塞面积,流式细胞仪测定细胞凋亡,测定血浆肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6等炎症因子水平.结果:治疗后,乌司他丁组较常规治疗组和对照组左室射血分数明显提高[(56.91±2.04)%:(53.22±2.13)%:(32.49±1.29)%]、梗塞面积显著减小[(21.82±3.12)%:(24.61±1.24)%:(29.73±2.11)%]、细胞凋亡明显减少[(4.98±0.58)%:(6.75±0.51)%:(9.64±0.23)%],P均<0.05;心肌梗塞后1周内TNF-α水平[(331.4±13.6)ng/L:(391.1±16.9)ng/L:(411.5±10.3)ng/L]、IL-6水平[(312.2±25.7)ng/L:(359.4±30.3)ng/L:(409.6±9.1)ng/L]明显降低(P均<0.05),两周后三组炎症因子水平无明显差异(P均>0.05).结论:乌司他丁具有心肌保护作用,机制可能与抑制梗塞面积扩大、细胞凋亡及抗炎作用有关.%Objective: To explore protective effects of proteinase inhibitor-ulinastatin from cardiovascular disease (myo-cardial infarction) and its possible mechanism. Methods: A total of 30 Japanese big-ear rabbits (3~5 months old) were chosen. Anterior descending branch of coronary of rabbit was ligated to make model of myocardial infarction. Then the rabbits were randomly and equally divided into control group (received saline), routine treatment group (received routine treatment as nitroglycerin etc. ) and ulinastatin group (received ulinastatin based on routine treatment) . The patients received echocardiogram examination before and four weeks after treatment. Tetrazolium chloride staining was used to evaluate infarct size, flow cytometry was used to measure apoptosis and

  1. The shifting landscape of safety pharmacology in 2015. (United States)

    Pugsley, Michael K; Authier, Simon; Stonerook, Michael; Curtis, Michael J


    The relative importance of the discipline of safety pharmacology (which integrates physiology, pharmacologyand toxicology) has evolved since the incorporation of the Safety Pharmacology Society (SPS) as an entity on August 10, 2000. Safety pharmacology (SP), as a synthesis of these other fields of knowledge, is concerned with characterizing the safety profile (or potential undesirable pharmacodynamic effects) of new chemical entities (NCEs) and biologicals. Initially focused on the issue of drug-induced QT prolongation it has developed into an important discipline over the past 15years with expertise beyond its initial focus on torsades de pointes (TdP). It has become a repository for interrogation of models for drug safety studies and innovative non-clinical model development, validation and implementation. Thus, while safety pharmacology consists of the triumvirate obligatory cardiovascular, central nervous system (CNS) and respiratory system core battery studies it also involves assessing drug effects on numerous other physiological systems (e.g., ocular, auditory, renal, gastrointestinal, blood, immune) leveraging emerging new technologies in a wide range of non-clinical drug safety testing models. As with previous editorials that preface the themed issue on safety pharmacology methods published in the Journal of Pharmacological and Toxicological Methods (JPTM), we highlight here the content derived from the most recent (2014) SPS meeting held in Washington, DC. The dynamics of the discipline remain fervent and method development, extension and refinement are reflected in the content. This issue of the JPTM continues the tradition of providing a publication summary of articles (reviews, commentaries and methods) with impact on the discipline of safety pharmacology.

  2. Pharmacology of antiplatelet agents. (United States)

    Kalra, Kiran; Franzese, Christopher J; Gesheff, Martin G; Lev, Eli I; Pandya, Shachi; Bliden, Kevin P; Tantry, Udaya S; Gurbel, Paul A


    Pharmacotherapies with agents that inhibit platelet function have proven to be effective in the treatment of acute coronary syndromes, and in the prevention of complications during and after percutaneous coronary intervention. Because of multiple synergetic pathways of platelet activation and their close interplay with coagulation, current treatment strategies are based not only on platelet inhibition, but also on the attenuation of procoagulant activity, inhibition of thrombin generation, and enhancement of clot dissolution. Current strategies can be broadly categorized as anticoagulants, antiplatelet agents, and fibrinolytics. This review focuses on the pharmacology of current antiplatelet therapy primarily targeting the inhibition of the enzyme cyclooxygenase 1, the P2Y12 receptor, the glycoprotein IIb/IIIa receptor, and protease-activated receptor 1.

  3. [Pharmacological treatment of schizophrenia]. (United States)

    Thomas, Pierre


    Decades of practice in psychiatriy and hundreds of clinical trials have demonstrated the efficacy of antipsychotics on symptoms of schizophrenia. Recently, the knowledge acquired from non-interventional studies have supplemented the information needed in daily practice by raising the issue of efficiency by incorporating not only the effectiveness and safety of treatment but also its acceptability by the patient. Adherence to antipsychotic treatment has become the key issue of the prognosis. The pharmacological management of patients with an acute episode of schizophrenia requires rapid therapeutic decisions to treat a patient who is likely to be sometimes unhelpful and agitated. The choice of treatment will have a significant impact on the prevention of psychotic relapses, on the overall prognosis and on the quality of life of the patient. In many countries of the recommendations and treatment algorithms for the management of acute psychosis were distributed, considering factors specific to the patient and his environment, his mental characteristics and local care setting.

  4. Animal Models of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Carlos Zaragoza


    Full Text Available Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.


    Directory of Open Access Journals (Sweden)

    Amita Tomar *, Mridula Mall and Pragya Rai


    Full Text Available This paper reviews the pharmacological importance of citrus fruits. Citrus fruits are used for various pharmacological importance. According to literature the citrus fruit possess anti-cancer, antimicrobial, antioxidant, antiulcer, anti-inflammatory, and hypolipidemic and hepatoprotective properties.

  6. Correlation of left ventricular wall thickness, heart mass, serological parameters and late gadolinium enhancement in cardiovascular magnetic resonance imaging of myocardial inflammation in an experimental animal model of autoimmune myocarditis. (United States)

    Kromen, Wolfgang; Korkusuz, Huedayi; Korkusuz, Yuecel; Esters, Philip; Bauer, Ralf W; Huebner, Frank; Lindemayr, Sebastian; Vogl, Thomas J


    For a definitive diagnosis of myocarditis, different strategies like analysis of late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) up to invasive endomyocardial biopsy have been applied. The objective of the study was to investigate inflammatory changes like left ventricular wall thickening and increase of ventricular mass and to quantitatively analyse their correlation with extent and localisation of myocardial damage in CMR and with subsequent changes of serological markers in an animal model of an experimental autoimmune myocarditis (EAM). In the current study, an EAM was induced in 10 male Lewis rats, 10 rats served as control. On day 21, animals were examined with four CMR protocols to assess the extent of LGE in a 12 segment model of the rat heart. Left myocardial wall thickness and mass and histological grade of inflammation were measured to determine localisation and severity of the induced myocarditis. Depending on the CMR sequence, LGE was mostly found in the left anterior (9.6%) and left lateral (8.7%) myocardial wall segments. Wall thickness correlated with the LGE area in CMR imaging and the histopathological severity of myocarditis for the left lateral myocardial wall segment. In a similar way, the heart mass correlated to the extent of LGE for the left lateral segment. We conclude that in our animal model left ventricular wall thickness and mass reflect the severity of myocardial changes in myocarditis and that the EAM rat model is well suited for further investigations of myocarditis.

  7. Recommendations for safety pharmacology evaluations of oligonucleotide-based therapeutics. (United States)

    Berman, Cindy L; Cannon, Keri; Cui, Yi; Kornbrust, Douglas J; Lagrutta, Armando; Sun, Sunny Z; Tepper, Jeff; Waldron, Gareth; Younis, Husam S


    This document was prepared by the Safety Pharmacology Subcommittee of the Oligonucleotide Safety Working Group (OSWG), a group of industry and regulatory scientists involved in the development and regulation of therapeutic oligonucleotides. The mission of the Subcommittee was to develop scientific recommendations for the industry regarding the appropriate scope and strategies for safety pharmacology evaluations of oligonucleotides (ONs). These recommendations are the consensus opinion of the Subcommittee and do not necessarily reflect the current expectations of regulatory authorities. 1) Safety pharmacology testing, as described in the International Conference on Harmonisation (ICH) S7 guidance, is as applicable to ONs as it is to small molecule drugs and biotherapeutics. 2) Study design considerations for ONs are similar to those for other classes of drugs. In general, as with other therapeutics, studies should evaluate the drug product administered via the clinical route. Species selection should ideally consider relevance of the model with regard to the endpoints of interest, pharmacological responsiveness, and continuity with the nonclinical development program. 3) Evaluation of potential effects in the core battery (cardiovascular, central nervous, and respiratory systems) is recommended. In general: a. In vitro human ether-a-go-go-related gene (hERG) testing does not provide any specific value and is not warranted. b. Emphasis should be placed on in vivo evaluation of cardiovascular function, typically in nonhuman primates (NHPs). c. Due to the low level of concern, neurologic and respiratory function can be assessed concurrently with cardiovascular safety pharmacology evaluation in NHPs, within repeat-dose toxicity studies, or as stand-alone studies. In the latter case, rodents are most commonly used. 4) Other dedicated safety pharmacology studies, beyond the core battery, may have limited value for ONs. Although ONs can accumulate in the kidney and liver

  8. Pharmacological treatment of vertigo. (United States)

    Hain, Timothy C; Uddin, Mohammed


    This review discusses the physiology and pharmacological treatment of vertigo and related disorders. Classes of medications useful in the treatment of vertigo include anticholinergics, antihistamines, benzodiazepines, calcium channel antagonists and dopamine receptor antagonists. These medications often have multiple actions. They may modify the intensity of symptoms (e.g. vestibular suppressants) or they may affect the underlying disease process (e.g. calcium channel antagonists in the case of vestibular migraine). Most of these agents, particularly those that are sedating, also have a potential to modulate the rate of compensation for vestibular damage. This consideration has become more relevant in recent years, as vestibular rehabilitation physical therapy is now often recommended in an attempt to promote compensation. Accordingly, therapy of vertigo is optimised when the prescriber has detailed knowledge of the pharmacology of medications being administered as well as the precise actions being sought. There are four broad causes of vertigo, for which specific regimens of drug therapy can be tailored. Otological vertigo includes disorders of the inner ear such as Ménière's disease, vestibular neuritis, benign paroxysmal positional vertigo (BPPV) and bilateral vestibular paresis. In both Ménière's disease and vestibular neuritis, vestibular suppressants such as anticholinergics and benzodiazepines are used. In Ménière's disease, salt restriction and diuretics are used in an attempt to prevent flare-ups. In vestibular neuritis, only brief use of vestibular suppressants is now recommended. Drug treatments are not presently recommended for BPPV and bilateral vestibular paresis, but physical therapy treatment can be very useful in both. Central vertigo includes entities such as vertigo associated with migraine and certain strokes. Prophylactic agents (L-channel calcium channel antagonists, tricyclic antidepressants, beta-blockers) are the mainstay of treatment

  9. General pharmacology of cis-malonato[4R,5R)-4,5-bis-(aminomethyl)-2-isopropyl-1,3- dioxolane]platinum(II). (United States)

    Kim, D K; Ahn, J S; Ryu, G; Kim, K H; Park, C W; Kim, M S; Chung, M H; Shin, S G; Suh, Y H; Kim, Y S


    The general pharmacological properties of cis-malonato-[(4R,5R)-4,5- bis(aminomethyl)-2-isopropyl-1.3-dioxolane]platinum(II) (SKI 2053R, CAS 146665-77-2), a new potential anticancer agent, were investigated in mice, rats, guinea pigs, rabbits, cats and dogs. Intravenous administration of SKI 2053R had no effect on the central nervous system. SKI 2053R had no effect on the autonomic nervous system and smooth muscles except that it slightly inhibited the spontaneous motility of isolated rabbit ileum at a concentration of 5 x 10(-5) g/ml. SKI 2053R did not adversely affect the respiratory-cardiovascular system, gastrointestinal system, neuromuscular junction, or renal function. SKI 2053R did not significantly alter the levels of serum glucose, serum free fatty acid and plasma lactate, and did not induce hemolysis. SKI 2053R did not affect blood coagulation mechanism and liver function. SKI 2053R did not exhibit anti-inflammatory activity. It was observed that SKI 2053R increased the formation of hemolytic plaque by spleen cells of sensitized mice at high doses (10 mg/kg and 35 mg/kg). Therefore, it is concluded from these general pharmacological studies that SKI 2053R at the doses showing antitumor activity does not induce severe adverse effects on the central nervous, autonomic nervous, respiratory-cardiovascular, gastrointestinal, peripheral nervous, and other systems in experimental animals.

  10. Pharmacological research in neonatology. (United States)

    Dotta, Andrea; Braguglia, Annabella; Salvatori, Guglielmo


    In neonatology unit 40 to 80% of the drugs are used as off-label or unlicensed, particularly in Neonatal Intensive Care Unit (NICU), where it has been described that in a single patient up to 60 parenteral drugs can be administered. The course of a drug inside the organism can be defined in 4 different phases: absorption, distribution, metabolism, elimination; for each of these phases the newborn infant has different characteristics than child and adult. In the last years much more attention has been put in pharmacological research specific for the neonatal age and a good trial design should take into account the following points: (1) to define the pediatric disease in terms of natural history, prevalence, severity, treatment and impact of the new drug; (2) to avoid the "try and error" method based on the adult dose corrected for weight or age; (3) to use adapted methodologies (pharmacokinetics); (4) to avoid small clinical trials (limited number of patients), the use of Randomized Controlled Trials rather than observational studies; (5) to consider ethics providing clear information and reducing pain and stress to the baby and its family.

  11. The pharmacology of salmeterol. (United States)

    Johnson, M


    The pharmacology of salmeterol hydroxynaphthoate (SALM) has been investigated in respiratory tissues in vitro and in animal models in vivo. In guinea pig trachea and human bronchial smooth muscle, SALM was more potent than isoprenaline (ISO), salbutamol (SALB), and clenbuterol (CLEN). The duration of action was greater than 7 h, whereas that for ISO, SALB, and CLEN was 2, 11, and 45 min, respectively. The sustained activity of SALM was reversed by sotalol, but was reestablished when the beta-blocker was removed. SALM was greater than 3000-fold weaker than ISO in cardiac tissues, indicating high beta 2-adrenoceptor selectivity. In the conscious guinea pig, aerosolized SALM, SALB, and CLEN caused dose-related bronchodilatation. The activity of SALM persisted for at least 6 h, compared with less than 2 h for SALB and CLEN. SALM is also a potent inhibitor of mediator release from human lung, this effect being sustained for up to 20 hours. In guinea pig airways in vivo, SALM inhibited histamine-induced plasma protein extravasation for approximately 8 h. Salmeterol is a potent and selective beta 2-adrenoceptor agonist with a unique profile of action. It induces persistent bronchodilatation, sustained suppression of mediator release, and long-lasting inhibition of edema formation. This combination of properties may represent an important new advance in the treatment of bronchial asthma.

  12. [Pharmacological effects of hordenine]. (United States)

    Hapke, H J; Strathmann, W


    Hordenine is an ingredient of some plants which are used as feed for animals, i.e. in sprouting barley. After ingestion of such feed hordenine may be detected in blood or urine of horses which in case of racing horses may be the facts of using prohibited compounds. Results of some experiments in pharmacological models show that hordenine is an indirectly acting adrenergic drug. It liberates norepinephrine from stores. In isolated organs and those structures with reduced epinephrine contents the hordenine-effect is only very poor. Experiments in intact animals (rats, dogs) show that hordenine has a positive inotropic effect upon the heart, increases systolic and diastolic blood pressure, peripheral blood flow volume, inhibits gut movements but has no effect upon the psychomotorical behaviour of mice. All effects are short and only possible after high doses which are not to be expected after ingestion of hordenine containing feed for horses. A measurable increase of the performance of racing horses is quite improbable.

  13. [Pharmacological treatment of obesity]. (United States)

    Gomis Barbará, R


    The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.

  14. Behavior analysis and the growth of behavioral pharmacology. (United States)

    Laties, Victor G


    Psychologists, particularly those influenced by the work of B. F. Skinner, played a major part in the development of behavioral pharmacology in the 1950s and 1960s. Revolutionary changes in pharmacology and psychiatry, including the discovery of powerful therapeutic agents such as chlorpromazine and reserpine, had produced a surge of interest in drug research. Pharmaceutical companies began hiring psychologists with operant conditioning backgrounds so as to compete successfully in the search for new drugs. Psychologists, most of whom were skilled in the behavior-analytic approach, started to assume prominent positions as authors and editors for the Journal of Pharmacology and Experimental Therapeutics as its emphasis on behavior increased. This also proved true with the other publications founded to deal with the popularity of behavioral pharmacology. Especially important were contributions by B. F. Skinner, Peter B. Dews, and Joseph V. Brady.

  15. Adventures in the pharmacological analysis of P2 receptors. (United States)

    Fagura, M S; Jarvis, G E; Dougall, I G; Leff, P


    The pharmacological classification of P2 receptors owes its origin to the pioneering efforts of Geoff Burnstock and those who followed him, research that was conducted primarily in physiological experimental systems. Over recent years, the techniques of molecular biology have been increasingly applied in the study of P2 receptors while, at the same time, advances in their pharmacological analysis have been limited by a lack of potent and selective agonist or antagonist ligands. This has resulted in a classification scheme which is largely structural in nature, with relatively little contribution from pharmacology. Our endeavours in this area have been directed towards the discovery of ligands with which the pharmacological analysis and definition of P2 receptors could be advanced, the ultimate goal being the design of therapeutic agents. This article will describe some of our experiences in this challenging but rewarding area.

  16. The pharmacology of regenerative medicine. (United States)

    Christ, George J; Saul, Justin M; Furth, Mark E; Andersson, Karl-Erik


    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

  17. Cardiovascular Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics for the Clinical Practitioner. (United States)

    Sleder, Anna T; Kalus, James; Lanfear, David E


    Current clinical cardiovascular practice requires a clinician to have a strong foundation in multiple aspects of pharmacology. Modern cardiovascular regimens are complex, and optimal management, application of evolving guidelines, and adoption of new therapies build off a more basic understanding of pharmacokinetics and pharmacodynamics. In addition, it is likely time to add a third pillar into this discussion, the expanding field of pharmacogenomics referring to the genetic influences on drug response. This field has increasing applications in medicine and clearly holds significant promise for cardiovascular disease management. Awareness of pharmacogenomic advances and the fundamentals of pharmacokinetics and pharmacodynamics can help the clinician more easily deliver great care. Here we attempt to briefly summarize and simplify key concepts of pharmacokinetics, pharmacodynamics, and pharmacogenomics relevant to the cardiovascular disease practitioner.

  18. A systematic review on the application of cardiovascular risk prediction models in pharmacoeconomics, with a focus on primary prevention

    NARCIS (Netherlands)

    Stevanovic, Jelena; Postma, Maarten J.; Pechlivanoglou, Petros


    Background: Long-term trials on the effectiveness of pharmacological treatment for primary cardiovascular disease prevention are scant. For that reason risk prediction models are used as a tool to project changes in cardiovascular disease incidence due to changes in risk factor levels observed in sh

  19. The pharmacology of lysergic acid diethylamide: a review. (United States)

    Passie, Torsten; Halpern, John H; Stichtenoth, Dirk O; Emrich, Hinderk M; Hintzen, Annelie


    Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive effects discovered in 1943. It was used during the 1950s and 1960s as an experimental drug in psychiatric research for producing so-called "experimental psychosis" by altering neurotransmitter system and in psychotherapeutic procedures ("psycholytic" and "psychedelic" therapy). From the mid 1960s, it became an illegal drug of abuse with widespread use that continues today. With the entry of new methods of research and better study oversight, scientific interest in LSD has resumed for brain research and experimental treatments. Due to the lack of any comprehensive review since the 1950s and the widely dispersed experimental literature, the present review focuses on all aspects of the pharmacology and psychopharmacology of LSD. A thorough search of the experimental literature regarding the pharmacology of LSD was performed and the extracted results are given in this review. (Psycho-) pharmacological research on LSD was extensive and produced nearly 10,000 scientific papers. The pharmacology of LSD is complex and its mechanisms of action are still not completely understood. LSD is physiologically well tolerated and psychological reactions can be controlled in a medically supervised setting, but complications may easily result from uncontrolled use by layman. Actually there is new interest in LSD as an experimental tool for elucidating neural mechanisms of (states of) consciousness and there are recently discovered treatment options with LSD in cluster headache and with the terminally ill.

  20. The pharmacology of statins. (United States)

    Sirtori, Cesare R


    Statins, inhibitors of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase enzyme, are molecules of fungal origin. By inhibiting a key step in the sterol biosynthetic pathway statins are powerful cholesterol lowering medications and have provided outstanding contributions to the prevention of cardiovascular disease. Their detection in mycetes traces back to close to 40 years ago: there were, originally, widely opposing views on their therapeutic potential. From then on, intensive pharmaceutical development has led to the final availability in the clinic of seven statin molecules, characterized by differences in bioavailability, lipo/hydrophilicity, cytochrome P-450 mediated metabolism and cellular transport mechanisms. These differences are reflected in their relative power (mg LDL-cholesterol reduction per mg dose) and possibly in parenchymal or muscular toxicities. The impact of the antagonism of statins on a crucial step of intermediary metabolism leads, in fact, both to a reduction of cholesterol biosynthesis as well as to additional pharmacodynamic (so called "pleiotropic") effects. In the face of an extraordinary clinical success, the emergence of some side effects, e.g. raised incidence of diabetes and cataracts as well as frequent muscular side effects, have led to increasing concern by physicians. However, also in view of the present relatively low cost of these drugs, their impact on daily therapy of vascular patients is unlikely to change.

  1. Some pharmacological aspects of drug dependence. (United States)

    Chesher, G B


    The self-administration of drugs to achieve altered states of consciousness is recognized as normal human behaviour. Community attitudes towards drug use vary according to the drug and often bear little relationship to the known pharmacological and toxicological effects of the drug. For an objective assessment of the potential dangers associated with drug use, a distinction is made between drug use and drug abuse. It is stressed that the progression from drug use to drug abuse involves social and psychological factors in addition to the pharmacological factors which are outlined in this paper. The sequential development of drug dependency is described under the headings: Induction; continued consumption; compulsive consumption; withdrawal; abstinence; reinduction. Man uses psychotropic drugs because he finds the effects rewarding. Some experimental models to explore the neurophysiological basis of the reward are described. Experiments employing inhibitors of protein synthesis suggest that the phenomena of tolerance and physical dependence involve the synthesis of new protein. It has been suggested that the new protein might be new receptor molecules for the drug or neurotransmitter substances. These new receptors might constitute a "drug memory" and provide a possible explanation for high relapse rate of drug dependent subjects. A pharmacological basis for the methadone maintenance programme of management of narcotic dependent subjects is briefly outlined.

  2. Potassium in hypertension and cardiovascular disease. (United States)

    Castro, Hector; Raij, Leopoldo


    The increased prevalence of hypertension and cardiovascular disease in industrialized societies undoubtedly is associated with the modern high-sodium/low-potassium diet. Extensive experimental and clinical data strongly link potassium intake to cardiovascular outcome. Most studies suggest that the sodium-to-potassium intake ratio is a better predictor of cardiovascular outcome than either nutrient individually. A high-sodium/low-potassium environment results in significant abnormalities in central hemodynamics, leading to potential target organ damage. Altered renal sodium handling, impaired endothelium-dependent vasodilatation, and increased oxidative stress are important mediators of this effect. It remains of paramount importance to reinforce consumption of a low-sodium/high-potassium diet as a critical strategy for prevention and treatment of hypertension and cardiovascular disease.

  3. Citicoline: pharmacological and clinical review, 2010 update. (United States)

    Secades, J J


    This review is based on the previous one published in 2006 -Secades JJ, Lorenzo JL. Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol 2006; 28 (Suppl B): S1-56-, incorporating the new references until now, having all the information available to facilitate the access to the informacion in one document. This review is focused on the main indications of the drug, as acute stroke and its sequelae, including the cognitive impairment, and traumatic brain injury and its sequelae. There are retrieved the most important experimental and clinical data in both indications.

  4. NASA 2010 Pharmacology Evidence Review (United States)

    Steinberg, Susan


    In 2008, the Institute of Medicine reviewed NASA's Human Research Program Evidence in assessing the Pharmacology risk identified in NASA's Human Research Program Requirements Document (PRD). Since this review there was a major reorganization of the Pharmacology discipline within the HRP, as well as a re-evaluation of the Pharmacology evidence. This panel is being asked to review the latest version of the Pharmacology Evidence Report. Specifically, this panel will: (1) Appraise the descriptions of the human health-related risk in the HRP PRD. (2) Assess the relevance and comprehensiveness of the evidence in identifying potential threats to long-term space missions. (3) Assess the associated gaps in knowledge and identify additional areas for research as necessary.

  5. [Pharmacological treatment of chronic pain]. (United States)

    Willimann, Patrick


    The pharmacological treatment of chronic pain differs from acute pain management. In chronic non-cancer pain patients pharmacological treatment is only one element of an interdisciplinary approach. Not pain reduction only but gain in physical and social functioning is mandatory for continuation of therapy. The developpement of a strategy is the most important and difficult step toward an individual and sustained pharmacological pain treatment. Simple practical guidelines can help to find an individual therapeutic straight. Outcome parameters have to be determined. Check-ups for discontinuation of the therapy have to be done periodically. Exact documentation of effect and side effects prevents ungrateful and potential dangerous treatments. The WHO ladder remains the cornerstone of pharmacological pain treatment. Further analgesics as antidepressants and anticonvulsants are important in treatment of neuropathic or mixed pain states. Special considerations have to be done in opioid treatment of non-cancer pain regarding the lack of evidence in long term outcome and possible side effects and risks.

  6. Pharmacological Effects of Rosa Damascena


    Boskabady, Mohammad Hossein; Shafei, Mohammad Naser; Saberi, Zahra; Amini, Somayeh


    Rosa damascena mill L., known as Gole Mohammadi in is one of the most important species of Rosaceae family flowers. R. damascena is an ornamental plant and beside perfuming effect, several pharmacological properties including anti-HIV, antibacterial, antioxidant, antitussive, hypnotic, antidiabetic, and relaxant effect on tracheal chains have been reported for this plant. This article is a comprehensive review on pharmacological effects of R. damascena. Online literature searches were perform...

  7. A review on dronedarone:Pharmacological, pharmacodynamic and pharmacokinetic profile

    Institute of Scientific and Technical Information of China (English)

    Farah Iram; Sadaf Ali; Aftab Ahmad; Shah Alam Khan; Asif Husain


    Dronedarone, a benzofuran containing chemical compound, is a derivative of amiodarone which is classified as a Class III antiarrhythmic agent. It is prescribed to the cardiovas-cular patients who have paroxysmal or persistent atrial fibrillation to lower the chances of hospitalization. Amiodarone, sotalol, procainamide dofetilide, quinidine, ibutilide, fle-cainide, and propafenone are the other useful medicinal products used to treat atrial fibrillation or cardiac arrhythmia. Dronedarone was approved for clinical use in atrial fibrillation by the Food and Drug Administration in 2009. The generic name for drone-darone is Multaq (Sanofi Aventis). This article briefly highlights the important pharma-cological, pharmacodynamic and pharmacokinetic properties of dronedarone.

  8. Neurovascular pharmacology of migraine

    NARCIS (Netherlands)

    MaassenVanDenBrink, Antoinette; Chan, Kayi Y.


    Migraine is a paroxysmal neurovascular disorder, which affects a significant proportion of the population. Since dilation of cranial blood vessels is likely to be responsible for the headache experienced in migraine, many experimental models for the study of migraine have focussed on this feature. T

  9. Lifestyle in Cardiovascular Disease

    NARCIS (Netherlands)

    J.O. Younge (John)


    markdownabstract__Abstract__ Globally, the burden of cardiovascular disease (CVD) is still increasing. However, in recent decades, better treatment modalities have led to less cardiovascular related deaths. After years of research, we now generally accept that lifestyle factors are the most importa

  10. Triglycerides and cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Varbo, Anette


    cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride......-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk...... of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride-lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence...

  11. Cocoa, chocolate, and cardiovascular disease. (United States)

    Galleano, Monica; Oteiza, Patricia I; Fraga, Cesar G


    A significant body of evidence demonstrates that diets rich in fruits and vegetables promote health and attenuate, or delay, the onset of various diseases, including cardiovascular disease, diabetes, certain cancers, and several other age-related degenerative disorders. The concept that moderate chocolate consumption could be part of a healthy diet has gained acceptance in past years based on the health benefits ascribed to selected cocoa components. Specifically, cocoa as a plant and chocolate as food contain a series of chemicals that can interact with cell and tissue components, providing protection against the development and amelioration of pathological conditions. The most relevant effects of cocoa and chocolate have been related to cardiovascular disease. The mechanisms behind these effects are still under investigation. However, the maintenance or restoration of vascular NO production and bioavailability and the antioxidant effects are the mechanisms most consistently supported by experimental data. This review will summarize the most recent research on the cardiovascular effects of cocoa flavanols and related compounds.

  12. Air pollution and cardiovascular disease. (United States)

    Nogueira, J Braz


    Air pollution is associated with increased cardiovascular morbidity and mortality. Recent experimental and epidemiologic studies show that particulate matter (PM) air pollution with PM10 or inhalable (thoracic) particles (mean aerodynamic diameter particles (aerodynamic diameter biological mechanisms responsible for adverse cardiovascular outcomes associated with PM have been described, including the release of pro-oxidative and pro-inflammatory mediators from the lungs into the circulation, autonomic nervous system imbalance, and the direct actions on the heart and vasculature of ultrafine particles translocated into the systemic circulation. The induction of oxidative stress by these particles may be central to all of these putative pathways that trigger coagulation and thrombosis, increased heart rate and reduced heart rate variability, endothelial dysfunction, arterial vasoconstriction, apoptosis, and hypertension. In chronic exposures these alterations favor the development and progression of atherosclerosis and possibly of hypertension in the long term, and in the short term acute exposures contribute to plaque instability, affect various traditional risk factors and trigger acute cardiovascular events (myocardial ischemia and infarction, stroke, heart failure, arrhythmias, and sudden death), particularly in high-risk subjects. There are currently also significant concerns with the risks of engineered nanoparticles.

  13. Pharmacology and clinical pharmacology of methylarginines used as inhibitors of nitric oxide synthases. (United States)

    Kittel, Anja; Maas, Renke


    The methylarginines asymmetric dimethylarginine (ADMA) and monomethylarginine (L-NMMA) are endogenously formed inhibitors of nitric oxide synthases (NOS), which have extensively been investigated as risk markers and used as pharmacological tools to study the L-arginine-nitric oxide (NO) pathway in vitro and in vivo. It is the aim of the present review to summarize the clinical and experimental data on the pharmacological properties that are of relevance when planning and conducting experiments and clinical studies involving methylarginines. Key pharmacodynamic and pharmacokinetic data including IC50 values of ADMA and L-NMMA for NOS isoforms and transport proteins, as well as metabolism by dimethylarginine dimethylaminohydrolases (DDAH1 and DDAH2) and alanine-glyoxylate aminotransferase 2 (AGXT2) are discussed.

  14. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P


    to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt...

  15. Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension

    Directory of Open Access Journals (Sweden)

    Palatini P


    Full Text Available Paolo Palatini1, Edoardo Casiglia1, Jerzy Gąsowski2, Jerzy Głuszek3, Piotr Jankowski4, Krzysztof Narkiewicz5, Francesca Saladini1, Katarzyna Stolarz-Skrzypek4, Valérie Tikhonoff1, Luc Van Bortel6, Wiktoria Wojciechowska4, Kalina Kawecka-Jaszcz41Department of Clinical and Experimental Medicine, University of Padova, Padua, Italy; 2Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Kraków, Poland; 3Department of Arterial Hypertension, University Hospital, Poznan, Poland; 4First Department of Cardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland; 5Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland; 6Heymans Institute of Pharmacology, Ghent University, Ghent, BelgiumAbstract: This review summarizes several scientific contributions at the recent Satellite Symposium of the European Society of Hypertension, held in Milan, Italy. Arterial stiffening and its hemodynamic consequences can be easily and reliably measured using a range of noninvasive techniques. However, like blood pressure (BP measurements, arterial stiffness should be measured carefully under standardized patient conditions. Carotid-femoral pulse wave velocity has been proposed as the gold standard for arterial stiffness measurement and is a well recognized predictor of adverse cardiovascular outcome. Systolic BP and pulse pressure in the ascending aorta may be lower than pressures measured in the upper limb, especially in young individuals. A number of studies suggest closer correlation of end-organ damage with central BP than with peripheral BP, and central BP may provide additional prognostic information regarding cardiovascular risk. Moreover, BP-lowering drugs can have differential effects on central aortic pressures and hemodynamics compared with brachial BP. This may explain the greater beneficial effect provided by newer antihypertensive drugs beyond peripheral BP

  16. Pioneer in Behavioral Pharmacology: A Tribute to Joseph V. Brady (United States)

    Barrett, James E.


    The contributions of Joseph V. Brady to behavioral pharmacology span more than 50 years and range from early studies using the Estes-Skinner ("conditioned emotional response") procedure to examine drug effects and various physiological processes in experimental animals to the implementation of mobile methadone treatment services and to small group…

  17. Pharmacological effect on pyeloureteric dynamics with a clinical perspective

    DEFF Research Database (Denmark)

    Jung, Helene U; Frimodt-Møller, Poul C; Osther, Palle J;


    We searched to review experimental and clinical trials concerning the capabilities of impacting on the ureteric and pelvic activity by means of pharmacological stimulation. Ureteropyeloscopy may cause high renal pelvic pressure. The normal pressure is in the range of 5-15 mmHg whereas pressure...

  18. Introduction: Cardiovascular physics. (United States)

    Wessel, Niels; Kurths, Jürgen; Ditto, William; Bauernschmitt, Robert


    The number of patients suffering from cardiovascular diseases increases unproportionally high with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop high-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Cardiovascular physics-which interconnects medicine, physics, biology, engineering, and mathematics-is based on interdisciplinary collaboration of specialists from the above scientific fields and attempts to gain deeper insights into pathophysiology and treatment options. This paper summarizes advances in cardiovascular physics with emphasis on a workshop held in Bad Honnef, Germany, in May 2005. The meeting attracted an interdisciplinary audience and led to a number of papers covering the main research fields of cardiovascular physics, including data analysis, modeling, and medical application. The variety of problems addressed by this issue underlines the complexity of the cardiovascular system. It could be demonstrated in this Focus Issue, that data analyses and modeling methods from cardiovascular physics have the ability to lead to significant improvements in different medical fields. Consequently, this Focus Issue of Chaos is a status report that may invite all interested readers to join the community and find competent discussion and cooperation partners.

  19. Teaching Cardiovascular Integrations with Computer Laboratories. (United States)

    Peterson, Nils S.; Campbell, Kenneth B.


    Describes a computer-based instructional unit in cardiovascular physiology. The program (which employs simulated laboratory experimental techniques with a problem-solving format is designed to supplement an animal laboratory and to offer students an integrative approach to physiology through use of microcomputers. Also presents an overview of the…

  20. Cardiovascular failure and cardiogenic shock. (United States)

    Patel, Ankitkumar K; Hollenberg, Steven M


    Cardiovascular system failure is commonly faced by the intensivist. Heart failure can occur due to a host of predisposing cardiac disorders or as secondary effects of systemic illness. When the heart is unable to provide an adequate cardiac output to maintain adequate tissue perfusion, cardiogenic shock ensues. Without prompt diagnosis and appropriate management, these patients have significant morbidity and mortality, with in-hospital mortality approaching 60% for all age groups. Accurate and rapid identification of cardiogenic shock as a medical emergency, with expeditious implementation of appropriate therapy, can lead to improved clinical outcomes. In this review, we discuss optimal strategies for diagnosis and monitoring of cardiogenic shock. We discuss the diverse therapeutic strategies employed for cardiogenic shock, including pharmacological (e.g., vasoactive agents, fibrinolytic agents), mechanical (e.g., intraaortic balloon pumps, left ventricular assist devices, percutaneous coronary intervention [PCI]), and surgical approaches such as coronary artery bypass graft (CABG), valvular repair or replacement (e.g., for acute mitral regurgitation, ventricular septal rupture, or free wall rupture).

  1. Cardiovascular comorbiditiy in psoriasis

    Directory of Open Access Journals (Sweden)

    Gurcharan Singh


    Full Text Available The chronic inflammatory nature of psoriasis is also thought to predispose patients to other diseases with an inflammatory component, the most notable being cardiovascular and metabolic (cardiometabolite disorders. This concept is supported by studies showing that psoriasis is associated with cardiovascular risk factors like diabetes, obesity, hypertension, dyslipidemia, smoking and diseases including MI. Given the increased prevalence of cardiovascular co morbidities in patients, dermatologists treating psoriasis need to approach the disease as a potentially multisystem disorder and must alert these patients to the potentially negative effects of their disease.

  2. Urocortin and cardiovascular protection

    Institute of Scientific and Technical Information of China (English)

    Yu HUANG; Xiao-qiang YAO; Chi-wai LAU; Yau-chi CHAN; Suk-ying TSANG; Franky Leung CHAN


    Urocortin and other hypothalamus corticotropin-releasing factor (CRF) polypeptides play biologically diverse roles in the stress, cardiovascular and inflammatory responses by acting on central and peripheral CRF receptors.Urocortin shows a significantly high sequence homology to CRF, and the concurrent expression of type-2 CRF (CRF2) receptors with urocortin in the heart suggests that urocortin may play a physiological role in the cardiac function. Urocortin is thought to be the endogenous agonist producing the cardiovascular actions previously attributed to CRF. This review highlights the current novel findings on the molecular and cellular mechanisms by which urocortin may exert its cardiovascular protective action.

  3. Astaxanthin in cardiovascular health and disease. (United States)

    Fassett, Robert G; Coombes, Jeff S


    Oxidative stress and inflammation are established processes contributing to cardiovascular disease caused by atherosclerosis. However, antioxidant therapies tested in cardiovascular disease such as vitamin E, C and β-carotene have proved unsuccessful at reducing cardiovascular events and mortality. Although these outcomes may reflect limitations in trial design, new, more potent antioxidant therapies are being pursued. Astaxanthin, a carotenoid found in microalgae, fungi, complex plants, seafood, flamingos and quail is one such agent. It has antioxidant and anti-inflammatory effects. Limited, short duration and small sample size studies have assessed the effects of astaxanthin on oxidative stress and inflammation biomarkers and have investigated bioavailability and safety. So far no significant adverse events have been observed and biomarkers of oxidative stress and inflammation are attenuated with astaxanthin supplementation. Experimental investigations in a range of species using a cardiac ischaemia-reperfusion model demonstrated cardiac muscle preservation when astaxanthin is administered either orally or intravenously prior to the induction of ischaemia. Human clinical cardiovascular studies using astaxanthin therapy have not yet been reported. On the basis of the promising results of experimental cardiovascular studies and the physicochemical and antioxidant properties and safety profile of astaxanthin, clinical trials should be undertaken.

  4. TP receptor as a therapeutic target in atherosclerosis and related cardiovascular diseases. (United States)

    Ishizuka, Toshiaki; Higashino, Hideaki


    It had already showed that several thromboxane A(2) receptor (TP receptor) antagonists might be utilized in the treatment of cardiovascular diseases. In addition, recent reports suggested that TP receptor antagonism may be able to restrict vascular inflammation in atherosclerotic vessels. In particular, S18886 has been developed as a non-prostanoid TP receptor antagonist derived from sulotroban that is characterized by a tetrahydronaphthalene ring as a spacer between the 4-cholophenylsulfonamide group and carboxylic acid. Several reports using experimental animal models of atherosclerosis indicated that S18886 caused a regression of advanced atherosclerosis. More recently, several studies and patents showed that new thromboxane modulators combined with another pharmacological activities have been developed. Ohtake et al. discovered TRA-418 (a benzene-condensed heterocyclic derivative) having a TP receptor antagonistic activity and a prostaglandin I(2) receptor agonistic activity. Cesagrande found that 4-methyl-N- (4-trans-nitrooxycyclohexyl)-N-(3-pyridinylmethyl)-1,3- benzenedicarboxamide is endowed with anti-thromboxane and NO-donor actions. Oketani et al. discovered that E3040, a novel benzothiazole derivative, inhibited TXA(2) synthase and 5-LO activities. EK112, a combined angiotensin II and TP receptor antagonist, was developed. These new compounds may be able to restrict further infiltration of inflammatory cells in atherosclerotic vessels, thus stabilizing vulnerable plaques in the related cardiovascular diseases.

  5. The genus Crataegus: chemical and pharmacological perspectives

    Directory of Open Access Journals (Sweden)

    Dinesh Kumar


    Full Text Available Traditional drugs have become a subject of world importance, with both medicinal and economical implications. A regular and widespread use of herbs throughout the world has increased serious concerns over their quality, safety and efficacy. Thus, a proper scientific evidence or assessment has become the criteria for acceptance of traditional health claims. Plants of the genus Crataegus, Rosaceae, are widely distributed and have long been used in folk medicine for the treatment of various ailments such as heart (cardiovascular disorders, central nervous system, immune system, eyes, reproductive system, liver, kidney etc. It also exhibits wide range of cytotoxic, gastroprotective, anti-inflammatory, anti-HIV and antimicrobial activities. Phytochemicals like oligomeric procyanidins, flavonoids, triterpenes, polysaccharides, catecholamines have been identified in the genus and many of these have been evaluated for biological activities. This review presents comprehensive information on the chemistry and pharmacology of the genus together with the traditional uses of many of its plants. In addition, this review discusses the clinical trials and regulatory status of various Crataegus plants along with the scope for future research in this aspect.

  6. Safety pharmacology — Current and emerging concepts

    Energy Technology Data Exchange (ETDEWEB)

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Atkinson, Jeffrey [Lorraine University Pharmacolor Consultants Nancy PCN (France); Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Delaunois, Annie [UCB Pharma (Belgium); Dermody, Ailsa; Govindappa, Karthik [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Guillon, Jean-Michel [Sanofi-aventis (France); Jenkins, Rosalind [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Kenna, Gerry [Astra-Zeneca (United Kingdom); Lemmer, Björn [Ruprecht-Karls-Universität Heidelberg (Germany); Meecham, Ken [Huntingdon Life Sciences (United Kingdom); Olayanju, Adedamola [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Pestel, Sabine [Boehringer-Ingelheim (Germany); Rothfuss, Andreas [Roche (Switzerland); and others


    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests.

  7. Pharmacogenomics in cardiovascular disorders: Steps in approaching personalized medicine in cardiovascular medicine

    Directory of Open Access Journals (Sweden)

    Christopher Barone


    Full Text Available Christopher Barone, Shaymaa S Mousa, Shaker A MousaThe Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USAAbstract: Some of the most commonly prescribed medications are those for cardiovascular maladies. The beneficial effects of these medications have been well documented. However, there can be substantial variation in response to these medications among patients, which may be due to genetic variation. For this reason pharmacogenomic studies are emerging across all aspects of cardiovascular medicine. The goal of pharmacogenomics is to tailor treatment to an individual’s genetic makeup in order to improve the benefit-to-risk ratio. This review examines the potential pharmacogenomic parameters which may lead to a future of personalized medicine. For example, it has been found that patients with CYP2C9 and VKORC1 gene variations have a different response to warfarin. Other studies looking at β-blockers, ACE inhibitors, ARBs, diuretics and statins have shown some results linking genetic variations to pharmacologic response. However these studies have not impacted clinical use yet, unlike warfarin findings, as the small retrospective studies need to be followed up by larger prospective studies for definitive results.Keywords: cardiovascular, pharmacogenomics, genetics, cardiovascular medicine, personalized medicine, polymorphism

  8. Cardiovascular manifestations in hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Vairamani Kandan


    Conclusions: This study shows that cardiovascular manifestations are quite common and varied in hyperthyroidism which are to be looked for in the management. [Int J Res Med Sci 2016; 4(7.000: 3032-3038

  9. Cardiovascular modeling and diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Kangas, L.J.; Keller, P.E.; Hashem, S.; Kouzes, R.T. [Pacific Northwest Lab., Richland, WA (United States)


    In this paper, a novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  10. EVALUACIÓN DE LA OPINIÓN DE ESTUDIANTES DE FARMACIA SOBRE LA IMPLEMENTACIÓN DE ALTERNATIVAS BASADAS EN COMPUTADOR PARA EL PROCESO ENSEÑANZA - APRENDIZAJE DE LA FARMACOLOGÍA EXPERIMENTAL Pharmacy student`s opinion about the implementation of computer based alternatives on experimental pharmacology learning-teaching process

    Directory of Open Access Journals (Sweden)

    María Cristina González Guevara


    relevantes entre los dos recursos de enseñanza.Background. Nowadays the usage of lab animals in education is being eliminated all around the world. Other strategies are looked for to replace it because there is not any evidence that students trained using other alternatives are less qualified. Objective. The purpose of this research work was to contrast the opinion of the pharmacology students of Pharmacy, Universidad Nacional de Colombia, about the implementation of interactive software compared to the isolated tissue technique. Material and methods. This study compared teaching material which uses lab animals to another one based on an interactive software for the isolated tissue of rodent intestine by means of a survey applied to the seven semester students. Results. Student's opinion, in scale 1 to 5, is that there are advantages of the isolated tissue technique over the interactive software (p<0,05 with respect to information contribution (median 5:4 respectively, knowledge integration (median 5:4 and unexpected results interpretation (median 4:3. In relation to obtained information clarity, student's opinion shows that there aren't differences between the two alternatives (median 4. The use of laboratory animal implies an ethical cost (67% that doesn't exist with the use of interactive software (27%. Finally, is high the acceptance of interactive software as an effective tool in pharmacology learning (77% and is noticeable the student's interest about this alternative being used in other courses (79%. Conclusion. Even though some components of the practice can be lost using the interactive software; real assembly knowledge, confrontation to the difficulties of experimentation with alive beings and approximation to life dynamic process. The students think that there are not relevant differences between this two teaching materials.

  11. Experimental Study on Pharmacological Effects of Alcohol Extracts of Aeschynomene indica L.%田皂角醇提取物药理作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    李燕婧; 钟正贤; 陈家源; 卢文杰


    目的观察田皂角醇提取物的药理作用。方法采用试管二倍稀释法、巴豆油致耳郭肿胀法、醋酸扭体法、皮肤过敏试验和急性毒性试验。结果田皂角醇提物对金黄色葡萄球菌、枯草芽孢杆菌有较强抑菌作用,能减轻巴豆油致小鼠耳郭肿胀,减少醋酸致小鼠扭体次数,降低皮肤过敏反应。急性毒性试验表明,田皂角醇提取物的最大给药量为150.7g生药/kg。结论田皂角醇提物具有一定的抑菌、抗炎、镇痛和抗过敏作用,且毒性小。%Objective To observe the pharmacological effects of alcohol extracts of Aeschynomene indica L .. Methods The methods of tube doubling dilution ,the ear swelling induced by the croton oil ,acetic acid twisting as well as the test of skin allergy and acute toxicity test were adopted in the study .Results Alcohol extracts of Ae-schynornene indica L .had strong bacteriostatic effects on staphylococcus aureus and bacillus subtilis ,it inhibited the ear swelling induced by the croton oil , decreased the body twisting times induced by acetic acid , and alleviated skin anaphylaxis in mice .The acute toxicity test showed that the maximum dosage of alcohol extracts of Aeschynomene in -dica L.was 150.7g crude drug/kg.Conclusion Alcohol extracts of Aeschynormene indica L has some bacteriostat-ic,anti-inflammatory,analgesic and antiallergic effects as well as little toxicity .

  12. Pharmacological activation of KCa3.1/KCa2.3 channels produces endothelial hyperpolarization and lowers blood pressure in conscious dogs

    DEFF Research Database (Denmark)

    Damkjaer, Mads; Nielsen, Gorm; Bodendiek, Silke;


    regulation in large mammals which also allow addressing safety issues. We therefore characterized canine endothelial KCa3.1 and KCa2.3 functions and evaluated the effect on blood pressure and heart rate of the KCa3.1/KCa2.3-activator SKA-31 in dogs. Experimental approach.  Canine endothelial KCa3.1/KCa2.......3 functions were studied by patch-clamp electrophysiology and wire-myography in mesenteric arteries. The systemic cardiovascular actions of acute SKA-31 administration were monitored in conscious, unstressed beagle dogs. Key results.  Mesenteric endothelial cells expressed functional KCa3.1 and KCa2......Hg and doubled the magnitude of the response over time. Conclusions and implications.  The present study demonstrates that activation of endothelial KCa3.1 and KCa2.3 lowers arterial blood pressure in dogs by an immediate electrical vasodilator mechanism. The results support the concept that pharmacological...

  13. Phytochemical and Pharmacological Studies on the Genus Psoralea: A Mini Review

    Directory of Open Access Journals (Sweden)

    Cong-Cong Li


    Full Text Available The genus Psoralea, which belongs to the family Fabaceae, comprises ca. 130 species distributed all over the world, and some of the plants are used as folk medicine to treat various diseases. Psoralea corylifolia is a typical example, whose seeds have been widely used in many traditional Chinese medicine formulas for the treatment of various diseases such as leucoderma and other skin diseases, cardiovascular diseases, nephritis, osteoporosis, and cancer. So, the chemical and pharmacological studies on this genus were performed in the past decades. Here, we give a mini review on this genus about its phytochemical and pharmacological studies from 1910 to 2015.

  14. Cardiovascular pharmacogenetics of antihypertensive and lipid- lowering therapies. (United States)

    Vanichakarn, P; Hwa, J; Stitham, J


    Recent changes to the clinical management guidelines for hypertension and hyperlipidemia have placed emphasis on prevention through the pharmacological control and reduction of cardiovascular risk factors. In conjunction with proper diet and lifestyle changes, such risk factor control necessitates the use of safe and effective pharmacotherapy. However, many patients fail to reach or maintain therapeutic goals due to inadequacy and/or variability in response to antihypertensive and lipid-lowering medications. Thus, given the contribution of both hypertension and hyperlipidemia in the development and progression of cardiovascular disease, a personalized approach to pharmacotherapy, as well as disease prevention, seems particularly prudent. With the advancement of cardiovascular pharmacogenetics, the aim is to identify genetic biomarkers of drug-response and disease-susceptibility in order to make informed and individualized decisions, improving patient care through proper drug selection and dosing.

  15. Cardiovascular involvement in patients affected by acromegaly: an appraisal. (United States)

    Mosca, Susanna; Paolillo, Stefania; Colao, Annamaria; Bossone, Eduardo; Cittadini, Antonio; Iudice, Francesco Lo; Parente, Antonio; Conte, Sirio; Rengo, Giuseppe; Leosco, Dario; Trimarco, Bruno; Filardi, Pasquale Perrone


    Cardiovascular complications are frequent in acromegalic patients. Several studies reported increased prevalence of traditional cardiovascular risk factors and early development of endothelial dysfunction and of structural vascular alterations, with subsequent increased risk of coronary artery disease. Furthermore, chronic exposure to high levels of GH and IGF-I leads to the development of the so called "acromegalic cardiomyopathy", characterized by concentric biventricular hypertrophy, diastolic dysfunction and, additionally, by progressive impairment of systolic performance leading to overt heart failure. Cardiac valvulopathies and arrhythmias have also been documented and may concur to the deterioration of cardiac function. Together with strict control of cardiovascular risk factors, early control of GH and IGF-I excess, by surgical or pharmacological therapy, has been reported to ameliorate cardiac and metabolic abnormalities, leading to a significant reduction of left ventricular hypertrophy and to a consistent improvement of cardiac performance.

  16. The impact of mast cells on cardiovascular diseases. (United States)

    Kritikou, Eva; Kuiper, Johan; Kovanen, Petri T; Bot, Ilze


    Mast cells comprise an innate immune cell population, which accumulates in tissues proximal to the outside environment and, upon activation, augments the progression of immunological reactions through the release and diffusion of either pre-formed or newly generated mediators. The released products of mast cells include histamine, proteases, as well as a variety of cytokines, chemokines and growth factors, which act on the surrounding microenvironment thereby shaping the immune responses triggered in various diseased states. Mast cells have also been detected in the arterial wall and are implicated in the onset and progression of numerous cardiovascular diseases. Notably, modulation of distinct mast cell actions using genetic and pharmacological approaches highlights the crucial role of this cell type in cardiovascular syndromes. The acquired evidence renders mast cells and their mediators as potential prognostic markers and therapeutic targets in a broad spectrum of pathophysiological conditions related to cardiovascular diseases.

  17. Blood pressure and cardiovascular risk: what about cocoa and chocolate? (United States)

    Grassi, Davide; Desideri, Giovambattista; Ferri, Claudio


    Cocoa flavonoids are able to reduce cardiovascular risk by improving endothelial function and decreasing blood pressure (BP). Interest in the biological activities of cocoa is daily increasing. A recent meta-analysis shows flavanol-rich cocoa administration decreases mean systolic (-4.5mm Hg; p<0.001) and diastolic (-2.5mm Hg; p<0.001) BP. A 3-mm Hg systolic BP reduction has been estimated to decrease the risk of cardiovascular and all-cause mortality. This paper summarizes new findings concerning cocoa effects on cardiovascular health focusing on putative mechanisms of action and nutritional and "pharmacological" viewpoints. Cocoa consumption could play a pivotal role in human health.

  18. PPAR Genomics and Pharmacogenomics: Implications for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Sharon Cresci


    Full Text Available The peroxisome proliferator-activated receptors (PPARs consist of three related transcription factors that serve to regulate a number of cellular processes that are central to cardiovascular health and disease. Numerous pharmacologic studies have assessed the effects of specific PPAR agonists in clinical trials and have provided insight into the clinical effects of these genes while genetic studies have demonstrated clinical associations between PPAR polymorphisms and abnormal cardiovascular phenotypes. With the abundance of data available from these studies as a background, PPAR pharmacogenetics has become a promising and rapidly advancing field. This review focuses on summarizing the current state of understanding of PPAR genetics and pharmacogenetics and the important implications for the individualization of therapy for patients with cardiovascular diseases.

  19. Cardiovascular Considerations in Antidepressant Therapy: An Evidence-Based Review

    Directory of Open Access Journals (Sweden)

    Habibeh Yekehtaz


    Full Text Available There is a definite correlation between cardiovascular diseases and depressive disorders. Nevertheless, many aspects of this association have yet to be fully elucidated. Up to half of coronary artery disease patients are liable to suffer from some depressive symptoms, with approximately 20% receiving a diagnosis of major depressive disorders. Pharmacotherapy is a key factor in the management of major depression, not least in patients with chronic diseases who are likely to fail to show proper compliance and response to non-pharmacological interventions. Antidepressants are not deemed completely safe. Indeed, numerous side effects have been reported with the administration of antidepressants, among which cardiovascular adverse events are of paramount importance owing to their disabling and life-threatening nature. We aimed to re-examine some of the salient issues in antidepressant therapy vis-à-vis cardiovascular considerations, which should be taken into account when prescribing such medications.

  20. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. (United States)

    Imig, John D


    Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites that importantly contribute to vascular and cardiac physiology. The contribution of EETs to vascular and cardiac function is further influenced by soluble epoxide hydrolase (sEH) that degrades EETs to diols. Vascular actions of EETs include dilation and angiogenesis. EETs also decrease inflammation and platelet aggregation and in general act to maintain vascular homeostasis. Myocyte contraction and increased coronary blood flow are the two primary EET actions in the heart. EET cell signaling mechanisms are tissue and organ specific and provide significant evidence for the existence of EET receptors. Additionally, pharmacological and genetic manipulations of EETs and sEH have demonstrated a contribution for this metabolic pathway to cardiovascular diseases. Given the impact of EETs to cardiovascular physiology, there is emerging evidence that development of EET-based therapeutics will be beneficial for cardiovascular diseases.

  1. Chemotaxonomy and pharmacology of Gentianaceae

    DEFF Research Database (Denmark)

    Jensen, Søren Rosendal; Schripsema, Jan


    the remaining six are members of the Gentianeae. Based on the above results, a tentative list of chemical characteristics for the tribes of the Gentianaceae is presented. Finally, some pharmacologically interesting properties of plant extracts or compounds from taxa within Gentianaceae are listed....

  2. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer. (United States)

    Du, Juan; Cieslak, John A; Welsh, Jessemae L; Sibenaller, Zita A; Allen, Bryan G; Wagner, Brett A; Kalen, Amanda L; Doskey, Claire M; Strother, Robert K; Button, Anna M; Mott, Sarah L; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C; Spitz, Douglas R; Buettner, Garry R; Cullen, Joseph J


    The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

  3. Pharmacologic Agents for Chronic Diarrhea


    Lee, Kwang Jae


    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reductio...

  4. The Pharmacological Potential of Mushrooms

    Directory of Open Access Journals (Sweden)

    Ulrike Lindequist


    Full Text Available This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly.

  5. [Vitamin D and cardiovascular risk]. (United States)

    Mayer, Otto


    The pathogenesis of cardiovascular disease is without any doubt multifactorial, and it is generally accepted, that conventional risk factors determined only about 80% of cardiovascular risk. There is accumulating evidence that vitamin D exerts important pathophysiological effects on cardiovascular system. Low vitamin D was associated with increased cardiovascular risk in several reports. This review summarizes recent epidemiological evidence and possible pathophysiological mechanism for a role of low vitamin D in cardiovascular diseases. Moreover, available data concerning vitamin D supplementation are depicted.

  6. ADMA, cardiovascular disease and diabetes. (United States)

    Krzyzanowska, Katarzyna; Mittermayer, Friedrich; Wolzt, Michael; Schernthaner, Guntram


    The endogenous competitive nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an emerging risk marker for future cardiovascular events. Elevated ADMA concentrations have been described in patients with an adverse cardiovascular risk profile. Recently, various studies investigated the independent role of ADMA as a cardiovascular risk predictor in several patient cohorts. In addition, ADMA might not only be a risk marker but also a causative factor for cardiovascular disease. This review summarizes the literature on the relationship between ADMA, cardiovascular disease and diabetes.

  7. [General pharmacology of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic]. (United States)

    Tone, H; Kiyosaki, T; Nishimori, T; Kobayashi, F; Nishimura, K; Morino, H; Tsuchiyama, M


    General pharmacology of (2"R)-4'-O-tetrahydropyranyladriamycin hydrochloride (THP) was studied in experimental animals. Intravenous administration of THP showed no significant effect on the respiratory and cardiovascular systems, such as blood pressure, heart rate, ECG and respiration in anesthetized rabbits and dogs. But in rats and cats, THP produced a transient decrease in blood pressure resulted from vasodilation. The hypotension was not inhibited by antihistaminics. Contraction of isolated guinea-pig atria was stimulated by THP at high concentrations (10(-4) g/ml). THP inhibited the spontaneous movement of isolated rabbit ileum and rat uterus (virgin and pregnant) at high concentrations (10(-4) g/ml). In some isolated guinea-pig ileum preparations, THP partially (6 approximately 36%) antagonized the contraction inducing by acetylcholine, histamine, serotonin and barium chloride. Urine volume and urinary excretion of electrolytes were increased by intravenous injection of 5.0 mg/kg THP. Vascular permeability was progressed when administered intracutaneously. Hemolytic effect was shown at high concentrations (10(-4) g/ml) but no effect on the coagulation was found. No significant effect of THP was observed on the general behavior and central nervous system, autonomic nervous and peripheral nervous systems. Also, THP had no significant effect on gastrointestinal propulsion in mice, the mucous membranes of the stomach and duodenum of rats, or gastric acid and bile secretion in rats.

  8. Pharmacological and pharmacokinetic aspects of functional gastrointestinal disorders. (United States)

    Camilleri, Michael; Bueno, Lionel; de Ponti, Fabrizio; Fioramonti, Jean; Lydiard, R Bruce; Tack, Jan


    Medications are commonly used for the treatment of patients with functional gastrointestinal disorders. The general goal of this report is to review the pharmacokinetics and pharmacology of medications used in functional gastrointestinal disorders. Methods included literature review, consensus evaluation of the evidence for each topic assigned originally to 1 or 2 authors, and broader review at a harmonization session as part of the Rome III process. This report reviews the animal models that have been validated for the study of effects of pharmacologic agents on sensation and motility; the preclinical pharmacology, pharmacokinetics, and toxicology usually required for introduction of novel therapeutic agents; the biomarkers validated for studies of sensation and motility end points with experimental medications in humans; the pharmacogenomics applied to these medications and disorders; and the pharmacology of agents that are applied or have potential for treatment of functional gastrointestinal disorders, including psychopharmacologic agents. Clinician and basic investigators involved in the treatment or investigation of functional gastrointestinal disorders or disease models need to have a comprehensive understanding of a vast range of medications. It is anticipated that the interaction between investigators of basic science, basic and applied pharmacology, and clinical trials will lead to better treatment of these disorders.

  9. Therapeutic potential of chalcones as cardiovascular agents. (United States)

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar


    Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents.

  10. Quantitative systems pharmacology: a promising approach for translational pharmacology. (United States)

    Gadkar, K; Kirouac, D; Parrott, N; Ramanujan, S

    Biopharmaceutical companies have increasingly been exploring Quantitative Systems Pharmacology (QSP) as a potential avenue to address current challenges in drug development. In this paper, we discuss the application of QSP modeling approaches to address challenges in the translational of preclinical findings to the clinic, a high risk area of drug development. Three cases have been highlighted with QSP models utilized to inform different questions in translational pharmacology. In the first, a mechanism based asthma model is used to evaluate efficacy and inform biomarker strategy for a novel bispecific antibody. In the second case study, a mitogen-activated protein kinase (MAPK) pathway signaling model is used to make translational predictions on clinical response and evaluate novel combination therapies. In the third case study, a physiologically based pharmacokinetic (PBPK) model it used to guide administration of oseltamivir in pediatric patients.

  11. Gender differences in developmental programming of cardiovascular diseases. (United States)

    Dasinger, John Henry; Alexander, Barbara T


    Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr David Barker reporting an inverse relationship between birth weight and blood pressure led to the hypothesis that slow growth during fetal life increased blood pressure and the risk for cardiovascular disease in later life. It is now recognized that growth during infancy and childhood, in addition to exposure to adverse influences during fetal life, contributes to the developmental programming of increased cardiovascular risk. Numerous epidemiological studies support the link between influences during early life and later cardiovascular health; experimental models provide proof of principle and indicate that numerous mechanisms contribute to the developmental origins of chronic disease. Sex has an impact on the severity of cardiovascular risk in experimental models of developmental insult. Yet, few studies examine the influence of sex on blood pressure and cardiovascular health in low-birth weight men and women. Fewer still assess the impact of ageing on sex differences in programmed cardiovascular risk. Thus, the aim of the present review is to highlight current data about sex differences in the developmental programming of blood pressure and cardiovascular disease.

  12. Paradoxical pharmacology: turning our pharmacological models upside down. (United States)

    Page, Clive


    Paradoxical pharmacology is a term first suggested by Richard Bond to refer to intriguing observations that chronic use of some drug types can have the opposite biological effect(s) to those seen following acute administration of the same drug. A good example of 'paradoxical pharmacology' is the research Richard has pioneered showing that whereas acute administration of β-blockers is contraindicated in the treatment of asthma, chronic use of certain β-blockers can have therapeutic benefit. It would appear that those β-blockers that can act as inverse agonists at the β2 receptor particularly show this paradoxical effect and the findings of Richard's research not only challenge the dogma of the treatment of asthma but also challenge many of the pharmacological principles of ligand/receptor interactions established by Sir James Black and others. In this paper, I discuss Richard's efforts to evaluate the chronic effects of β-blockers in the airways and how this research caught the imagination of Sir James Black.

  13. Diabetes Drugs and Cardiovascular Safety

    Directory of Open Access Journals (Sweden)

    Ji Cheol Bae


    Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

  14. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler


    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  15. Animal pharmacodynamics of omeprazole. A survey of its pharmacological properties in vivo. (United States)

    Larsson, H; Mattson, H; Sundell, G; Carlsson, E


    In the present paper, a collection of experimental data is presented describing the pharmacological profile of omeprazole mainly in dogs and rats. Omeprazole potently inhibited gastric acid secretion in different experimental models. In the dog, for instance, omeprazole was 2-7 times more potent than cimetidine, depending on the route of administration, and in the rat the difference was even greater. Omeprazole was equally potent against different types of stimulation, whereas cimetidine was not, indicating differences in their mechanisms of action. In the dog, the duration of the antisecretory effect was long and lasted for 3-4 days after a single maximal dose of omeprazole. The inhibitory effect after repeated, daily administration of submaximal doses therefore gradually increased and attained a steady-state level after five doses. Treatment up to one year with very high oral doses did not affect the duration of effect. During long-term treatment with high doses of omeprazole a 10-fold increase in meal-stimulated plasma gastrin levels was recorded. This was probably due to a nearly complete inhibition of acid secretion over 24 hours during the study. The gastrin values returned to control levels within eight days after the end of the treatment. Omeprazole was rapidly absorbed (peak plasma levels were reached within one hour) and the elimination half-life was approximately one hour. In the dog, the gastric antisecretory effect was related to the total dose and the area under the plasma concentration curve, whereas the peak level or the shape of the curve was of minor importance. Omeprazole, given orally to rats, dose-dependently prevented experimentally induced gastric lesions. Neither inhibition of acid secretion, stimulation of gastric bicarbonate secretion nor interference with the synthesis of endogenous prostaglandins seems to be of any great importance for the gastric protective effect of omeprazole. Omeprazole seems to be very specific in its gastric acid

  16. Experimental Study of Yishou Tiaozhi Tablet(

    Institute of Scientific and Technical Information of China (English)

    ZHONG; Yi


    [1]XU SY. Screening method on lowering lipid drug and inhibiting arteriosclerosis drug. Pharmacological Experimental Methodology. Beijing: The People's Health Publishing House, 1985∶781-783.[2]LI YL. Assay of alkali hydrolytic decomposition method on serum HYP determination. Clinical Journal of Decimology 1988;6(2)∶69-71.[3]LI ZJ, HAN CS, WANG JX. Practical Radioimmunology. Beijing: The Scientific Technological Archive Publishing House, 1989∶198-221.[4]GAO YC. Effect of Yixing decoction on rats' serum lipid level in hyperlipidemia and its mechanism. Academic Journal of Traditional Chinese Medicine 1990;(5)∶53-56.[5]Manninen V, Tenkanen L. Lipid alteration and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA 1988;260∶641-651.[6]HUANG JG, translated. The atherosclerous lipid marker. Fascicle of Cardiovascular Disease in Journal of Foreign Medicine 1987;14(1)∶4-9.[7]YANG RX. Lp(a) and atherosclerosis. Journal of Progression on Cardiovascular Disease 1994;15(4)∶221-223.[8]Colin J, Schwartz MD. A modern view of atherogenesis. Am J Cardio 1993;71∶9B-14B.[9]LIN XQ. Exploration on relationship between HYP and atherosclerosis in hyperlipidemia. Journal of Chinese Circulation 1993;8(3)∶160-163.[10].CHEN SH. Hyperlipidemia and platelet high response. Fascicle of Cardiovascular Disease in Journal of Foreign Medicine 1989;16(5)∶257-262.

  17. Pharmacology teaching and its reform in China

    Institute of Scientific and Technical Information of China (English)

    Wei-dong LI; Yuan ZHANG; Cai-li ZHANG; Xiu-mei ZHANG


    The general situation of pharmacology teaching in China was introduced and the educational reform in China in recent decade is summarized. The aim of the article is to provide those who are interested in teaching of pharmacology to be acquainted with the teaching of pharmacology, including the teaching of both principles and practice, in China.

  18. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W


    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the pharmacok

  19. The Diplomate in Safety Pharmacology (DSP) certification scheme. (United States)

    Authier, Simon; Curtis, Michael J; Soloviev, Maxim; Redfern, Will S; Kallman, Mary Jeanne; Hamlin, Robert L; Leishman, Derek J; Valentin, Jean-Pierre; Koerner, John E; Vargas, Hugo M; Botchway, Alfred; Correll, Krystle; Pugsley, Michael K


    As with other professional disciplines there is a growing need from within industry as well as global regulatory authorities for implementation of a certification process in order to assure that appropriate expertise is developed and quality standards are identified for professionals involved in the practice of Safety Pharmacology (SP). In order to meet this need, the Safety Pharmacology Society (SPS) has developed the Diplomate in Safety Pharmacology (DSP) certification process. There are many benefits to certification including authentication of the discipline within the overall pharmaceutical community and with regulatory authorities. It also encourages participation in SPS activities by other professionals (toxicologists, clinicians, academics) who wish to broaden their professional expertise. It provides an opportunity for candidates to strengthen their fundamental scientific knowledge, and stimulates the sharing of data, methods and model development in the form of publications and presentations on relevant topics in SP. Accreditation in SP occurs after candidates successfully complete a written certification examination conducted at the annual SPS meeting. The DSP exam consists primarily of material pertinent to the conduct of SP vital function core battery studies (i.e., cardiovascular, respiratory and central nervous systems), supplemental SP studies (i.e., renal/urinary, gastrointestinal, immunology, and hematology), Regulatory Guidelines (ICH Guidelines) as well as relevant cross-functional knowledge (e.g., physiology, pharmacology, toxicology, biochemistry, pathology, pharmacokinetics, dosing formulation, analytical methods, and statistics). Maintenance of the DSP certification results from the accrual of credits which are gained from a range of educational and scientific contributions. Eligibility requirements include a combination of at least a bachelor degree in science and two years of relevant professional SP experience and one poster presentation

  20. Pharmacological potential of cerium oxidenanoparticles (United States)

    Celardo, Ivana; Pedersen, Jens Z.; Traversa, Enrico; Ghibelli, Lina


    Nanotechnology promises a revolution in pharmacology to improve or create ex novo therapies. Cerium oxidenanoparticles (nanoceria), well-known as catalysts, possess an astonishing pharmacological potential due to their antioxidant properties, deriving from a fraction of Ce3+ ions present in CeO2. These defects, compensated by oxygen vacancies, are enriched at the surface and therefore in nanosized particles. Reactions involving redox cycles between the Ce3+ and Ce4+oxidation states allow nanoceria to react catalytically with superoxide and hydrogen peroxide, mimicking the behavior of two key antioxidant enzymes, superoxide dismutase and catalase, potentially abating all noxious intracellularreactive oxygen species (ROS) via a self-regenerating mechanism. Hence nanoceria, apparently well tolerated by the organism, might fight chronic inflammation and the pathologies associated with oxidative stress, which include cancer and neurodegeneration. Here we review the biological effects of nanoceria as they emerge from in vitro and in vivo studies, considering biocompatibility and the peculiar antioxidant mechanisms.

  1. Clocks and cardiovascular function (United States)

    McLoughlin, Sarah C.; Haines, Philip; FitzGerald, Garret A.


    Circadian clocks in central and peripheral tissues enable the temporal synchronization and organization of molecular and physiological processes of rhythmic animals, allowing optimum functioning of cells and organisms at the most appropriate time of day. Disruption of circadian rhythms, from external or internal forces, leads to widespread biological disruption and is postulated to underlie many human conditions, such as the incidence and timing of cardiovascular disease. Here, we describe in vivo and in vitro methodology relevant to studying the role of circadian rhythms in cardiovascular function and dysfunction PMID:25707279

  2. Envejecimiento del sistema cardiovascular



    Las principales características del envejecimiento del sistema cardiovascular reflejan cambios anatómicos y estructurales a nivel de la pared de los vasos, la relajación miocárdica, el llenado ventricular y la respuesta a las catecolaminas . Muchos de los cambios funcionales asociados con la edad están relacionados con estos fenómenos. Esta revisión describe los cambios relacionados con el envejecimiento a nivel estructural y funcional del sistema cardiovascular, sus posibles factores etiológ...

  3. Pharmacogenomics and cardiovascular disease

    DEFF Research Database (Denmark)

    Weeke, Peter; Roden, Dan M


    Variability in drug responsiveness is a sine qua non of modern therapeutics, and the contribution of genomic variation is increasingly recognized. Investigating the genomic basis for variable responses to cardiovascular therapies has been a model for pharmacogenomics in general and has established...... resulted in changes to the product labels but also have led to development of initial clinical guidelines that consider how to facilitate incorporating genetic information to the bedside. This review summarizes the state of knowledge in cardiovascular pharmacogenomics and considers how variants described...

  4. Research in cardiovascular care

    DEFF Research Database (Denmark)

    Jaarsma, Tiny; Deaton, Christi; Fitzsimmons, Donna


    To deliver optimal patient care, evidence-based care is advocated and research is needed to support health care staff of all disciplines in deciding which options to use in their daily practice. Due to the increasing complexity of cardiac care across the life span of patients combined...... of the body of knowledge that is needed to further improve cardiovascular care. In this paper, knowledge gaps in current research related to cardiovascular patient care are identified, upcoming challenges are explored and recommendations for future research are given....

  5. Myeloperoxidase and cardiovascular disease. (United States)

    Nicholls, Stephen J; Hazen, Stanley L


    Myeloperoxidase (MPO) is a leukocyte-derived enzyme that catalyzes the formation of a number of reactive oxidant species. In addition to being an integral component of the innate immune response, evidence has emerged that MPO-derived oxidants contribute to tissue damage during inflammation. MPO-catalyzed reactions have been attributed to potentially proatherogenic biological activities throughout the evolution of cardiovascular disease, including during initiation, propagation, and acute complication phases of the atherosclerotic process. As a result, MPO and its downstream inflammatory pathways represent attractive targets for both prognostication and therapeutic intervention in the prophylaxis of atherosclerotic cardiovascular disease.

  6. [Pharmacologic treatment of Asperger syndrome]. (United States)

    Yamada, Satoru


    Asperger syndrome is associated with various dysfunctional and problematic behaviors, in addition to the core features of communication and social skills dysfunction that define these conditions. Although there is currently no pharmacologic cure for the core features of Asperger syndrome. This article discusses the various medications for the behavioral symptoms of Asperger syndrome, which include hyperactivity, aggression, tantrums, self-injury, depression, obsession and so on. Methylphenidate, SSRIs, atypical antipsychotics and mood stabilizer were introduced.

  7. 2011 Annual Meeting of the Safety Pharmacology Society: an overview. (United States)

    Cavero, Icilio


    The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization

  8. Estrogen and estrogen receptors in cardiovascular oxidative stress. (United States)

    Arias-Loza, Paula-Anahi; Muehlfelder, Melanie; Pelzer, Theo


    The cardiovascular system of a premenopausal woman is prepared to adapt to the challenges of increased cardiac output and work load that accompany pregnancy. Thus, it is tempting to speculate whether enhanced adaptability of the female cardiovascular system might be advantageous under conditions that promote cardiovascular disease. In support of this concept, 17β-estradiol as the major female sex hormone has been shown to confer protective cardiovascular effects in experimental studies. Mechanistically, these have been partially linked to the prevention and protection against oxidative stress. Current evidence indicates that estrogens attenuate oxidative stress at two levels: first, by preventing generation of reactive oxygen species (ROS) and, second, by scavenging ROS in the myocardium and in the vasculature. The purpose of this review is to give an overview on current concepts on conditions and mechanisms by which estrogens protect the cardiovascular system against ROS-mediated cellular injury.

  9. Pharmacologic Action of Natamycin for Treatment of Experimental Fungal Keratitis in Rabbits%纳他霉素滴眼剂治疗兔眼真菌性角膜炎的药效研究

    Institute of Scientific and Technical Information of China (English)

    董贤慧; 高维娟; 钱涛; 贺小平; 侯淑敏; 郭银; 韦素春; 杨国兴


    目的:探讨国产纳他霉素滴眼剂对真菌性角膜炎的治疗作用,为其临床应用提供实验基础.方法:成年健康新西兰白兔30只,随机分为6组,真菌性角膜炎(FK)模型组、生理盐水组、纳他霉素滴眼剂赋形剂组、Natacyn组、纳他霉素组和正常对照组,每组10只兔眼.除正常对照组外其余各组角膜基质注射法建立真菌性角膜炎模型.各组动物于造模后第4、10、15和21天于裂隙灯下观察兔眼溃疡情况并评分,第10和21天观察兔眼治愈情况,并记录各组角膜发生新生血管、虹膜炎、前房积脓、斑翳等发生情况.结果:(1)第10、15和21天Natacyn组和纳他霉素组兔眼溃疡评分低于FK模型组(均P< 0.001);纳他霉素组和Natacyn组差别无统计学意义.(2) Natacyn组和纳他霉素组较FK模型组兔眼治愈率升高(均P< 0.001),而前2组治愈率差别无统计学意义.(3)纳他霉素和Natacyn组较FK模型组兔眼真菌性炎症并发症发生率低(均P< 0.001),而前2组真菌性炎症合并症发生率差别无统计学意义(P>0.05).结论:纳他霉素滴眼剂可降低真菌性角膜炎兔眼溃疡评分、提高治愈率、有效预防并发症.%Objective: To evaluate the efficacy of topical natamycin in an experimental rabbit model of fusarium solani, and provide the experimental basis for the clinical safety thereof. Methods:Thirty New Zealand rabbits were randomly divided into 6 groups,fungal keratitis model group(FK) .normal saline eye drop group,vehicle eye drop group,natacyn group,natamycin group and normal control group (10 rabbit eyes in each group). The rabbit model of fungal keratitis was induced by injection in into the central comeal stroma of eyes. After 4 d, 10 d, 15 d, and 21 d of treatment, the eyes of each group were examined clinically by slit lamp with a scoring system. The treatment results of rabbit eyes were observed on the 10 d and 21 d of treatment. The corner vascularisation, iritis

  10. Pharmacogenetics of cardiovascular drugs. (United States)

    Johnson, Julie A; Humma, Larisa M


    Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted.

  11. Cheese and cardiovascular health

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard

    Cardiovascular diseases (CVDs) are the number one cause of mortality worldwide. Low-density lipoprotein (LDL) cholesterol is a well-known risk factor of CVD which increases after the intake of saturated fatty acids (SFA). Cheese is a dietary product commonly consumed in Western countries and known...

  12. Cardiovascular effects of gliptins. (United States)

    Scheen, André J


    Dipeptidyl peptidase 4 (DPP-4) inhibitors (commonly referred to as gliptins) are a novel class of oral antihyperglycaemic agents with demonstrated efficacy in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data and mechanistic studies have indicated a possible beneficial action on blood vessels and the heart, via both glucagon-like peptide 1 (GLP-1)-dependent and GLP-1-independent effects. DPP-4 inhibition increases the concentration of many peptides with potential vasoactive and cardioprotective effects. Clinically, DPP-4 inhibitors improve several risk factors in patients with T2DM. They improve blood glucose control (mainly by reducing postprandial glycaemia), are weight neutral (or even induce modest weight loss), lower blood pressure, improve postprandial lipaemia, reduce inflammatory markers, diminish oxidative stress, and improve endothelial function. Some positive effects on the heart have also been described in patients with ischaemic heart disease or congestive heart failure, although their clinical relevance requires further investigation. Post-hoc analyses of phase II-III, controlled trials suggest a possible cardioprotective effect with a trend for a lower incidence of major cardiovascular events with gliptins than with placebo or active agents. However, the actual relationship between DPP-4 inhibition and cardiovascular outcomes remains to be proven. Major prospective clinical trials with predefined cardiovascular outcomes and involving various DPP-4 inhibitors are now underway in patients with T2DM and a high-risk cardiovascular profile.

  13. Neuropeptides in cardiovascular control. (United States)

    Ganong, W F


    Neuropeptides can affect cardiovascular function in various ways. They can serve as cotransmitters in the autonomic nervous system; for example, vasoactive intestinal peptide (VIP) is released with acetylcholine and neuropeptide Y with norepinephrine from postganglionic neurons. Substance P and, presumably, other peptides can can affect cardiovascular function when released near blood vessels by antidromically conducted impulses in branches of stimulated sensory neurons. In the central nervous system, many different neuropeptides appear to function as transmitters or contransmittes in the neural pathways that regulate the cardiovascular system. In addition neuropeptides such as vasopressin and angiotensin II also circulate as hormones that are involved in cardiovascular control. Large doses of exogenous vasopressin are required to increase blood pressure in normal animals because the increase in total peripheral resistance produced by the hormones is accompanied by a decrease in cardiac output. However, studies with synthetic peptides that selectively antagonize the vasopressor action of vasopressin indicate that circulating vasopressin is important in maintaining blood pressure when animals are hypovolemic due to dehydration, haemorrhage or adrenocortical insufficiency. VIP dilates blood vessels and stimulates renin secretion by a direct action on the juxtaglomerular cells. Renin secretion is stimulated when the concentration of VIP in plasma exceeds 75 pmol/litre, and higher values are seen in a number of conditions. Neostigmine, a drug which increases the secretion of endogenous VIP, also increases renin secretion, and this increase is not blocked by renal denervation or propranolol. Thus, VIP may be a physiologically significant renin stimulating hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Epigenetics and cardiovascular disease (United States)

    Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only...

  15. The Cardiovascular Research Grid (CVRG) (United States)

    U.S. Department of Health & Human Services — The CardioVascular Research Grid (CVRG) project is creating an infrastructure for sharing cardiovascular data and data analysis tools. CVRG tools are developed using...

  16. Aspirin: Pharmacology and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Enma V. Paez Espinosa


    Full Text Available Antiplatelet therapy has been documented to reduce risks of cardiovascular disease after acute myocardial infarction, coronary artery bypass graft, and in chronic atrial fibrillation patients, amongst other risk factors. Conventional management of thrombosis-based disorders includes the use of heparin, oral anticoagulants, and the preferred antiplatelet agent aspirin. Interestingly, aspirin was not intended to be used as an antiplatelet agent; rather, after being repurposed, it has become one of the most widely prescribed antithrombotic drugs. To this end, there have been several milestones in the development of antiplatelet agents in the last few decades, such as adenosine diphosphate receptor inhibitors, phosphodiesterase inhibitors, and GPIIb/IIIa inhibitors. However, given some of the limitations of these therapies, aspirin continues to play a major role in the management of thrombotic and cardiovascular disorders and is expected to do so for years to come.

  17. Pharmacological modulation of arterial stiffness.

    LENUS (Irish Health Repository)

    Boutouyrie, Pierre


    Arterial stiffness has emerged as an important marker of cardiovascular risk in various populations and reflects the cumulative effect of cardiovascular risk factors on large arteries, which in turn is modulated by genetic background. Arterial stiffness is determined by the composition of the arterial wall and the arrangement of these components, and can be studied in humans non-invasively. Age and distending pressure are two major factors influencing large artery stiffness. Change in arterial stiffness with drugs is an important endpoint in clinical trials, although evidence for arterial stiffness as a therapeutic target still needs to be confirmed. Drugs that independently affect arterial stiffness include antihypertensive drugs, mostly blockers of the renin-angiotensin-aldosterone system, hormone replacement therapy and some antidiabetic drugs such as glitazones. While the quest continues for \\'de-stiffening drugs\\

  18. Vitamin D, cardiovascular disease and mortality. (United States)

    Pilz, Stefan; Tomaschitz, Andreas; März, Winfried; Drechsler, Christiane; Ritz, Eberhard; Zittermann, Armin; Cavalier, Etienne; Pieber, Thomas R; Lappe, Joan M; Grant, William B; Holick, Michael F; Dekker, Jacqueline M


    A poor vitamin D status, i.e. low serum levels of 25-hydroxyvitamin D [25(OH)D], is common in the general population. This finding is of concern not only because of the classic vitamin D effects on musculoskeletal outcomes, but also because expression of the vitamin D receptor (VDR) and vitamin D metabolizing enzymes in the heart and blood vessels suggests a role of vitamin D in the cardiovascular system. VDR-knockout mice suffer from cardiovascular disease (CVD), and various experimental studies suggest cardiovascular protection by vitamin D, including antiatherosclerotic, anti-inflammatory and direct cardio-protective actions, beneficial effects on classic cardiovascular risk factors as well as suppression of parathyroid hormone (PTH) levels. In epidemiological studies, low levels of 25(OH)D are associated with increased risk of CVD and mortality. Data from randomized controlled trials (RCTs) are sparse and have partially, but not consistently, shown some beneficial effects of vitamin D supplementation on cardiovascular risk factors (e.g. arterial hypertension). We have insufficient data on vitamin D effects on cardiovascular events, but meta-analyses of RCTs indicate that vitamin D may modestly reduce all-cause mortality. Despite accumulating data suggesting that a sufficient vitamin D status may protect against CVD, we still must wait for results of large-scale RCTs before raising general recommendations for vitamin D in the prevention and treatment of CVD. In current clinical practice, the overall risks and costs of vitamin D supplementation should be weighed against the potential adverse consequences of untreated vitamin D deficiency.

  19. Nonfasting hyperlipidemia and cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, B G; Langsted, A; Freiberg, J J


    , total cholesterol/HDL cholesterol, and apolipoprotein B/apolipoprotein A1 all associate with increased risk of cardiovascular disease. These new data open the possibility that nonfasting rather than fasting lipid profiles can be used for cardiovascular risk prediction. If implemented, this would...... of cardiovascular disease and early death....

  20. Cardiovascular pharmacogenetics in the SNP era. (United States)

    Mooser, V; Waterworth, D M; Isenhour, T; Middleton, L


    In the past pharmacological agents have contributed to a significant reduction in age-adjusted incidence of cardiovascular events. However, not all patients treated with these agents respond favorably, and some individuals may develop side-effects. With aging of the population and the growing prevalence of cardiovascular risk factors worldwide, it is expected that the demand for cardiovascular drugs will increase in the future. Accordingly, there is a growing need to identify the 'good' responders as well as the persons at risk for developing adverse events. Evidence is accumulating to indicate that responses to drugs are at least partly under genetic control. As such, pharmacogenetics - the study of variability in drug responses attributed to hereditary factors in different populations - may significantly assist in providing answers toward meeting this challenge. Pharmacogenetics mostly relies on associations between a specific genetic marker like single nucleotide polymorphisms (SNPs), either alone or arranged in a specific linear order on a certain chromosomal region (haplotypes), and a particular response to drugs. Numerous associations have been reported between selected genotypes and specific responses to cardiovascular drugs. Recently, for instance, associations have been reported between specific alleles of the apoE gene and the lipid-lowering response to statins, or the lipid-elevating effect of isotretinoin. Thus far, these types of studies have been mostly limited to a priori selected candidate genes due to restricted genotyping and analytical capacities. Thanks to the large number of SNPs now available in the public domain through the SNP Consortium and the newly developed technologies (high throughput genotyping, bioinformatics software), it is now possible to interrogate more than 200,000 SNPs distributed over the entire human genome. One pharmacogenetic study using this approach has been launched by GlaxoSmithKline to identify the approximately 4% of

  1. The Cardiovascular Effects of Cocoa Polyphenols—An Overview

    Directory of Open Access Journals (Sweden)

    Ana Clara Aprotosoaie


    Full Text Available Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%–38% of total polyphenols, anthocyanins (4% of total polyphenols and proanthocyanidins (58%–65% of total polyphenols. A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols may reduce the risk of cardiovascular events. Beyond antioxidant properties, cocoa polyphenols exert blood pressure lowering activity, antiplatelet, anti-inflammatory, metabolic and anti-atherosclerotic effects, and also improve endothelial function. This paper reviews the role of cocoa polyphenols in cardiovascular protection, with a special focus on mechanisms of action, clinical relevance and correlation between antioxidant activity and cardiovascular health.

  2. Pharmacology of novel psychoactive substances


    Rickli, Anna


    This PhD work consists of an in vitro and in vivo part. In the in vivo part, we investigated the role of dopamine in the acute clinical effects of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) in healthy human subjects. The role of dopamine in the addictive effects of drug of abuse is well established, but whether it contributes to the acute psychotropic effects of MDMA is unclear. In this pharmacological interaction study, we used the dopamine and weak norepinephrine transporter in...

  3. Non pharmacological treatments in fibromyalgia

    Directory of Open Access Journals (Sweden)

    M. Spath


    Full Text Available To fully answer the complex question of what modes of non pharmacological treatments are useful for fibromyalgia (FM one should ask different layers of questions, and as with peeling layers of onions, be prepared to shed some tears. The first painful question, or layer of the onion, is related to understanding patients’ complaints. Patients who experience recurrent as well as persistent physical symptoms without any objective evidence are too often classified as “psychosomatic disorders” or worse as “non disease” (see Sarzi this issue...

  4. Angiotensin II receptor blockers and cardiovascular protection: Focus on left ventricular hypertrophy regression and atrial fibrillation prevention

    Directory of Open Access Journals (Sweden)

    Cesare Cuspidi


    Full Text Available Cesare Cuspidi1,2, Francesca Negri2, Alberto Zanchetti31Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy; 2Policlinico di Monza; 3Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università di Milano, and Istituto Auxologico Italiano, Milan, ItalyAbstract: Left ventricular hypertrophy (LVH and atrial fibrillation (AF are strong predictors of cardiovascular (CV morbidity and mortality, independently of blood pressure levels and other modifiable and nonmodifiable risk factors. The actions of circulating and tissue angiotensin II, mediated by AT1 receptors, play an important role in the development of a wide spectrum of cardiovascular alterations, including LVH, atrial enlargement and AF. Growing experimental and clinical evidence suggests that antihypertensive drugs may exert different effects on LVH regression and new onset AF in the setting of arterial hypertension. Since a number of large and adequately designed studies have found angiotensin II receptor blockers (ARBs to be more effective in reducing LVH than beta-blockers and data are also available showing their effectiveness in preventing new or recurrent AF, it is reasonable to consider this class of drugs among first line therapies in patients with hypertension and LVH (a very high risk phenotype predisposing to AF and as adjunctive therapy to antiarrhythmic agents in patients undergoing pharmacological or electrical cardioversion of AF.Keywords: angiotensin II receptor blockers, left ventricular hypertrophy, atrial fibrillation

  5. Aldosterone and Its Blockade: A Cardiovascular and Renal Perspective


    Lahera, V.; Cachofeiro, V.; Balfagon, G.; J.L. Rodicio


    Aldosterone not only contributes to salt and water homeostasis, but also exerts direct cardiovascular and renal effects. Numerous experimental and clinical studies indicate that aldosterone participate in cardiac alterations associated with hypertension, heart failure, diabetes and other pathological entities. It is important to mention that dietary salt is a key factor in aldosterone-mediated cardiovascular damage, since damage was moreevident in animals on a high-salt diet than animals on ...

  6. [Multiculturalism and cardiovascular diseases]. (United States)

    Gaudio, Carlo; Corsi, Filippo; Esposito, Cosimo; Di Michele, Sara; Nguyen, Bich Lien; Khatibi, Shahrzad; Sciarretta, Tesir; Franchitto, Silvia; Mirabelli, Francesca; Pannarale, Giuseppe


    Immigration has increased drastically to the point of becoming an ordinary structure of our society. Once in Italy, the immigrant's health is compromised rapidly due to a series of conditions and illnesses that exist in our country: lack of work, inadequate salary, inappropriate residence, lacking family support, climate changes, nutritional differences. Cardiovascular illnesses represent 7.6% of the diseases of the immigrants, and cause 36.6% of deaths. The risk factors that affect the genesis of cardiovascular diseases include: subjective factors (age, ethnic group), environmental, nutritional and pathological (arterial hypertension, AIDS, tuberculosis, alcohol). The challenge for our time is to design a new solidarity model to promote cultural and social integration in order to meet the multiethnical and multiracial needs of western society. This model should permit reconsideration of doctor-patient relationship in order to build a real intercultural society.

  7. Migraine and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Marcelo E. Bigal


    Full Text Available Migraine, especially migraine with aura is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine with and without aura to a broader range of ischemic vascular disorders including angina, myocardial infarction, coronary revascularization, claudication and cardiovascular mortality. The topic is therefore of considerable interest. Accordingly, herein we review the association between migraine and cardiovascular disease. We start by briefly presenting diagnostic criteria for migraine and revising its pathophysiology. We follow by summarizing the evidence on the topic. We then briefly present the results of a recent meta-analysis. We close by highlighting results of a large epidemiological study conducted after the publication of the meta-analysis.

  8. Prodrugs in Cardiovascular Therapy

    Directory of Open Access Journals (Sweden)

    Maryam Tabrizian


    Full Text Available Prodrugs are biologically inactive derivatives of an active drug intended to solve certain problems of the parent drug such as toxicity, instability, minimal solubility and non-targeting capabilities. The majority of drugs for cardiovascular diseases undergo firstpass metabolism, resulting in drug inactivation and generation of toxic metabolites, which makes them appealing targets for prodrug design. Since prodrugs undergo a chemical reaction to form the parent drug once inside the body, this makes them very effective in controlling the release of a variety of compounds to the targeted site. This review will provide the reader with an insight on the latest developments of prodrugs that are available for treating a variety of cardiovascular diseases. In addition, we will focus on several drug delivery methodologies that have merged with the prodrug approach to provide enhanced target specificity and controlled drug release with minimal side effects.

  9. Slow breathing and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Ashish Chaddha


    Full Text Available Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine.

  10. Slow breathing and cardiovascular disease. (United States)

    Chaddha, Ashish


    Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine.

  11. Pharmacologic management of overactive bladder

    Directory of Open Access Journals (Sweden)

    Sum Lam


    Full Text Available Sum Lam1,2, Olga Hilas1,31St. John’s University, College of Pharmacy and Allied Health Professions, Department of Clinical Pharmacy Practice, Queens, New York, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, New York, USA; 3Department of Pharmacy, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York, USAAbstract: Overactive bladder (OAB is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.Keywords: overactive bladder, urinary incontinence, pharmacologic management, antimuscarinic agents, anticholinergics

  12. Cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Graversen, Peter; Abildstrøm, Steen Z; Jespersen, Lasse


    (ECG) abnormalities, heart rate, family history (of ischaemic heart disease), body mass index (BMI), waist-hip ratio, walking duration and pace, leisure time physical activity, forced expiratory volume (FEV)1%pred, household income, education, vital exhaustion, high-density lipoprotein (HDL......AIM: European society of cardiology (ESC) guidelines recommend that cardiovascular disease (CVD) risk stratification in asymptomatic individuals is based on the Systematic Coronary Risk Evaluation (SCORE) algorithm, which estimates individual 10-year risk of death from CVD. We assessed...

  13. Pharmacologic Treatment of Pediatric Hypertension. (United States)

    Dhull, Rachita S; Baracco, Rossana; Jain, Amrish; Mattoo, Tej K


    Prevalence of hypertension is increasing in children and adolescents. Uncontrolled hypertension in children not only causes end organ damage but also increases the risk of adult hypertension and cardiovascular disease. Clinical trials have proven efficacy of antihypertensive medications in children. These medications are well tolerated by children with acceptable safety profile. The choice of agent is usually driven by underlying etiology of hypertension, profile of its side effects, and clinician's preference. This article will review currently available pediatric data on mechanism of action, common adverse effects, pediatric indication, recent clinical trial, and newer drugs in the common classes of antihypertensive medications.

  14. A call for the better utilization of physical activity and exercise training in the defense against cardiovascular disease. (United States)

    Murlasits, Zsolt


    Statins, also known as 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, effectively reduce elevated levels of serum LDL-C concentration and in turn lower cardiovascular morbidity and mortality. Regular exercise and physical activity also have significant preventive effects against cardiovascular diseases by simultaneously reducing multiple risk factors. However, statins also produce a number of adverse events, including muscle pain, which increases dramatically in statin users who also exercise, likely limiting the cardiovascular benefits. Most importantly, reduced physical activity participation due to statin-related side effects can cancel out the benefits of the pharmacological treatment. Although exercise training offers more modest benefits compared to pharmacological therapy against traditional risk factors, considering the total impact of exercise on cardiovascular health, it is now evident that this intervention may offer a greater reduction of risks compared to statin therapy alone. However, primary recommendations regarding cardiovascular therapy still center around pharmacological approaches. Thus a new outlook is called for in clinical practice that provides room for physical activity and exercise training, thus lipid targets can be reached by a combined intervention along with improvements in other cardiovascular parameters, such as endothelial function and low-grade inflammation. Databases such as Pubmed and Google Scholar as well as the reference list of the relevant articles were searched to collect information for this opinion article.

  15. Role of MicroRNAs in Renin-Angiotensin-Aldosterone System-Mediated Cardiovascular Inflammation and Remodeling

    Directory of Open Access Journals (Sweden)

    Maricica Pacurari


    Full Text Available MicroRNAs are endogenous regulators of gene expression either by inhibiting translation or protein degradation. Recent studies indicate that microRNAs play a role in cardiovascular disease and renin-angiotensin-aldosterone system- (RAAS- mediated cardiovascular inflammation, either as mediators or being targeted by RAAS pharmacological inhibitors. The exact role(s of microRNAs in RAAS-mediated cardiovascular inflammation and remodeling is/are still in early stage of investigation. However, few microRNAs have been shown to play a role in RAAS signaling, particularly miR-155, miR-146a/b, miR-132/122, and miR-483-3p. Identification of specific microRNAs and their targets and elucidating microRNA-regulated mechanisms associated RAS-mediated cardiovascular inflammation and remodeling might lead to the development of novel pharmacological strategies to target RAAS-mediated vascular pathologies. This paper reviews microRNAs role in inflammatory factors mediating cardiovascular inflammation and RAAS genes and the effect of RAAS pharmacological inhibition on microRNAs and the resolution of RAAS-mediated cardiovascular inflammation and remodeling. Also, this paper discusses the advances on microRNAs-based therapeutic approaches that may be important in targeting RAAS signaling.

  16. A Pharmacological Primer of Biased Agonism


    Andresen, Bradley T.


    Biased agonism is one of the fastest growing topics in G protein-coupled receptor pharmacology; moreover, biased agonists are used in the clinic today: carvedilol (Coreg®) is a biased agonist of beta-adrenergic receptors. However, there is a general lack of understanding of biased agonism when compared to traditional pharmacological terminology. Therefore, this review is designed to provide a basic introduction to classical pharmacology as well as G protein-coupled receptor signal transductio...

  17. Pharmacologic therapy for nonalcoholic fatty liver disease in adults. (United States)

    Malinowski, Scott S; Byrd, Jennifer S; Bell, Allison M; Wofford, Marion R; Riche, Daniel M


    Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma. NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere. Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH. The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise. There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy. A PubMed search was conducted using the medical subject heading terms "fatty liver" and "steatohepatitis." This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH. Continued investigation of drugs or combinations that improve NAFLD progression is crucial. Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD.

  18. Plectranthus amboinicus (Lour. Spreng: Botanical, Phytochemical, Pharmacological and Nutritional Significance

    Directory of Open Access Journals (Sweden)

    Greetha Arumugam


    Full Text Available Plectranthus amboinicus (Lour. Spreng. is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia and Australia. This herb has therapeutic and nutritional properties attributed to its natural phytochemical compounds which are highly valued in the pharmaceutical industry. Besides, it has horticultural properties due to its aromatic nature and essential oil producing capability. It is widely used in folk medicine to treat conditions like cold, asthma, constipation, headache, cough, fever and skin diseases. The leaves of the plant are often eaten raw or used as flavoring agents, or incorporated as ingredients in the preparation of traditional food. The literature survey revealed the occurrence 76 volatiles and 30 non-volatile compounds belonging to different classes of phytochemicals such as monoterpenoids, diterpenoids, triterpenoids, sesquiterpenoids, phenolics, flavonoids, esters, alcohols and aldehydes. Studies have cited numerous pharmacological properties including antimicrobial, antiinflammatory, antitumor, wound healing, anti-epileptic, larvicidal, antioxidant and analgesic activities. Also, it has been found to be effective against respiratory, cardiovascular, oral, skin, digestive and urinary diseases. Yet, scientific validation of many other traditional uses would be appreciated, mainly to discover and authenticate novel bioactive compounds from this herb. This review article provides comprehensive information on the botany, phytochemistry, pharmacology and nutritional importance of P. amboinicus essential oil and its various solvent extracts. This article allows researchers to further explore the further potential of this multi-utility herb for various biomedical applications.

  19. Plectranthus amboinicus (Lour.) Spreng: Botanical, Phytochemical, Pharmacological and Nutritional Significance. (United States)

    Arumugam, Greetha; Swamy, Mallappa Kumara; Sinniah, Uma Rani


    Plectranthus amboinicus (Lour.) Spreng. is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia and Australia. This herb has therapeutic and nutritional properties attributed to its natural phytochemical compounds which are highly valued in the pharmaceutical industry. Besides, it has horticultural properties due to its aromatic nature and essential oil producing capability. It is widely used in folk medicine to treat conditions like cold, asthma, constipation, headache, cough, fever and skin diseases. The leaves of the plant are often eaten raw or used as flavoring agents, or incorporated as ingredients in the preparation of traditional food. The literature survey revealed the occurrence 76 volatiles and 30 non-volatile compounds belonging to different classes of phytochemicals such as monoterpenoids, diterpenoids, triterpenoids, sesquiterpenoids, phenolics, flavonoids, esters, alcohols and aldehydes. Studies have cited numerous pharmacological properties including antimicrobial, antiinflammatory, antitumor, wound healing, anti-epileptic, larvicidal, antioxidant and analgesic activities. Also, it has been found to be effective against respiratory, cardiovascular, oral, skin, digestive and urinary diseases. Yet, scientific validation of many other traditional uses would be appreciated, mainly to discover and authenticate novel bioactive compounds from this herb. This review article provides comprehensive information on the botany, phytochemistry, pharmacology and nutritional importance of P. amboinicus essential oil and its various solvent extracts. This article allows researchers to further explore the further potential of this multi-utility herb for various biomedical applications.

  20. Management of cardiovascular disease in patients with psoriasis

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Skov, Lone


    INTRODUCTION: Patients with psoriasis have an increased incidence and prevalence of cardiovascular (CV) risk factors, and CV undertreatment in these patients is a well-established problem. The link between psoriasis and CV disease is present on a pathogenic level, as well as due to modifiable...... lifestyle factors such as smoking and alcohol abuse. AREAS COVERED: In this manuscript we describe the evidence associating psoriasis with CV disease, as well as the pharmacological and non-pharmacological treatment of CV risk factors including the CV effects of anti-psoriatic therapy and vice versa. EXPERT...... OPINION: Current guidelines recommend that patients with psoriasis are screened for CV risk factors, and recommend smoking cessation, reduced alcohol consumption, altering of lifestyle to move to a normal-weight body-mass index, exercising 3 times a week for 30 minutes, and monitoring and modifying...

  1. The Mediterranean diet, its components, and cardiovascular disease. (United States)

    Widmer, R Jay; Flammer, Andreas J; Lerman, Lilach O; Lerman, Amir


    One of the best-studied diets for cardiovascular health is the Mediterranean diet. This consists of fish, monounsaturated fats from olive oil, fruits, vegetables, whole grains, legumes/nuts, and moderate alcohol consumption. The Mediterranean diet has been shown to reduce the burden, or even prevent the development, of cardiovascular disease, breast cancer, depression, colorectal cancer, diabetes, obesity, asthma, erectile dysfunction, and cognitive decline. This diet is also known to improve surrogates of cardiovascular disease, such as waist-to-hip ratio, lipids, and markers of inflammation, as well as primary cardiovascular disease outcomes such as death and events in both observational and randomized controlled trial data. These enhancements easily rival those seen with more established tools used to fight cardiovascular disease such as aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and exercise. However, it is unclear if the Mediterranean diet offers cardiovascular disease benefit from its individual constituents or in aggregate. Furthermore, the potential benefit of the Mediterranean diet or its components is not yet validated by concrete cardiovascular disease endpoints in randomized trials or observational studies. This review will focus on the effects of the whole and parts of the Mediterranean diet with regard to both population-based and experimental data highlighting cardiovascular disease morbidity or mortality and cardiovascular disease surrogates when hard outcomes are not available. Our synthesis will highlight the potential for the Mediterranean diet to act as a key player in cardiovascular disease prevention, and attempt to identify certain aspects of the diet that are particularly beneficial for cardioprotection.

  2. Chemistry and pharmacology of Rhaponticum carthamoides: a review. (United States)

    Kokoska, Ladislav; Janovska, Dagmar


    Rhaponticum carthamoides (Willd.) Iljin is a perennial herb, commonly known as a maral root or Russian leuzea, which has been used for centuries in eastern parts of Russia for its marked medicinal properties. This review based on 117 literary sources, with many of them being originally published in non-English languages (mainly in Russian), discusses the current knowledge of traditional uses, chemistry, biological effects and toxicity of this species. Several different classes of compounds were previously isolated from various parts of R. carthamoides of which the main groups are steroids, particularly ecdysteroids, and phenolics (flavonoids and phenolic acids) accompanied with polyacetylenes, sesquiterpene lactones, triterpenoid glycosides and terpenes (essential oil). A comprehensive account of the chemical constituents is given in this review (figures of 120 structures are shown). Various types of preparations, extracts and individual compounds derived from this species have been found to possess a broad spectrum of pharmacological effects on several organs such as the brain, blood, cardiovascular and nervous systems as well as on different biochemical processes and physiological functions including proteosynthesis, work capacity, reproduction, and sexual function. Moreover, the extracts and preparations from the plant, which are hopefully safe, exhibited various additional biological effects e.g. antioxidant, immunomodulatory, anticancerogenic, antimicrobial, antiparasitic and insect antifeedant or repellent activities. The results of data analysis on the chemical, pharmacological and toxicological characteristics of R. carthamoides support the view that this species has beneficial therapeutic properties and indicate its potential as an effective adaptogenic herbal remedy. Finally, some suggestions for further research on chemical and pharmacological properties are given in this review.

  3. Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics. (United States)

    Kolkhof, Peter; Borden, Steffen A


    The blockade of mineralocorticoid receptors (MR) has been shown to be an invaluable therapy in heart failure and hypertension. To date, only two steroidal antimineralocorticoids, spironolactone (and its active metabolite canrenone) and eplerenone, have been approved, whereas novel non-steroidal compounds are in preclinical and early development. The careful investigation of the efficacy and tolerance of spironolactone in essential hypertension initially supported the idea that a more selective second generation of MR antagonists is desired for chronic treatment of cardiovascular diseases. More than 40 years went by between the approval of the first MR antagonist spironolactone and the market introduction of its sole successor, eplerenone. The molecular pharmacology of MR antagonists may be addressed at different levels. Available preclinical and clinical data of the two approved steroidal antimineralocorticoids allow a good comparison of potency and selectivity of MR antagonists and their pharmacokinetic properties. The search for novel generations of MR antagonists with the ultimate goal of a more tissue selective mode of action may require novel compounds that are differentiated with respect to the binding mode to the MR. Other factors that may contribute to tissue selectivity as e.g. the physicochemical properties of a drug and how they influence the resulting pharmacology in the context of tissue selective co-factor expression are even less well understood. In the following we will review these aspects and demonstrate that the molecular pharmacology of current MR antagonists is on the one hand far from well understood and, on the other hand, still offers room for improvements.

  4. Does pharmacotherapy improve cardiovascular outcomes in hemodialysis patients? (United States)

    Mittal, Mayank; Aggarwal, Kul; Littrell, Rachel L; Agrawal, Harsh; Alpert, Martin A


    Cardiovascular disease (CVD) occurs commonly in patients with chronic kidney disease (CKD) including those treated with hemodialysis (HD), and is associated with poor outcomes in this population. Pharmacologic management of hypertension, dyslipidemia, acute and chronic coronary artery disease, and atrial fibrillation in the general population is supported by the results of high-quality, randomized, controlled clinical trials. Pharmacotherapy of these disorders in the general population is effective in improving clinical outcomes. In contrast, information concerning the effect of pharmacotherapy on mortality and cardiovascular outcomes in patients with CKD, and particularly in HD patients, is limited. Available data suggest that, in general, pharmacotherapy of hypertension and dyslipidemia, anti-platelet therapy of CVD, and anticoagulant therapy in patients with atrial fibrillation are less effective in HD patients than in the general population or even in patients with early stage of CKD.

  5. Translational In Vivo Models for Cardiovascular Diseases. (United States)

    Fliegner, Daniela; Gerdes, Christoph; Meding, Jörg; Stasch, Johannes-Peter


    Cardiovascular diseases are still the first leading cause of death and morbidity in developed countries. Experimental cardiology research and preclinical drug development in cardiology call for appropriate and especially clinically relevant in vitro and in vivo studies. The use of animal models has contributed to expand our knowledge and our understanding of the underlying mechanisms and accordingly provided new approaches focused on the improvement of diagnostic and treatment strategies of various cardiac pathologies.Numerous animal models in different species as well as in small and large animals have been developed to address cardiovascular complications, including heart failure, pulmonary hypertension, and thrombotic diseases. However, a perfect model of heart failure or other indications that reproduces every aspect of the natural disease does not exist. The complexity and heterogeneity of cardiac diseases plus the influence of genetic and environmental factors limit to mirror a particular disease with a single experimental model.Thus, drug development in the field of cardiology is not only very challenging but also inspiring; therefore animal models should be selected that reflect as best as possible the disease being investigated. Given the wide range of animal models, reflecting critical features of the human pathophysiology available nowadays increases the likelihood of the translation to the patients. Furthermore, this knowledge and the increase of the predictive value of preclinical models help us to find more efficient and reliable solutions as well as better and innovative treatment strategies for cardiovascular diseases.

  6. Principles of pharmacodynamics and their applications in veterinary pharmacology. (United States)

    Lees, P; Cunningham, F M; Elliott, J


    instance at molecular, cellular and tissue levels in vitro, so that the primary effects can be better understood without interference from the complexities involved in whole animal studies. When a drug, hormone or neurotransmitter combines with a target molecule, it is described as a ligand. Ligands are classified into two groups, agonists (which initiate a chain of reactions leading, usually via the release or formation of secondary messengers, to the response) and antagonists (which fail to initiate the transduction pathways but nevertheless compete with agonists for occupancy of receptor sites and thereby inhibit their actions). The parameters which characterize drug receptor interaction are affinity, efficacy, potency and sensitivity, each of which can be elucidated quantitatively for a particular drug acting on a particular receptor in a particular tissue. The most fundamental objective of PDs is to use the derived numerical values for these parameters to classify and sub-classify receptors and to compare and classify drugs on the basis of their affinity, efficacy, potency and sensitivity. This review introduces and summarizes the principles of PDs and illustrates them with examples drawn from both basic and veterinary pharmacology. Drugs acting on adrenoceptors and cardiovascular, non-steroidal anti-inflammatory and antimicrobial drugs are considered briefly to provide a foundation for subsequent reviews in this issue which deal with pharmacokinetic (PK)-PD modelling and integration of these drug classes. Drug action on receptors has many features in common with enzyme kinetics and gas adsorption onto surfaces, as defined by Michaelis-Menten and Langmuir absorption equations, respectively. These and other derived equations are outlined in this review. There is, however, no single theory which adequately explains all aspects of drug-receptor interaction. The early 'occupation' and 'rate' theories each explain some, but not all, experimental observations. From these

  7. Toxicological evidence in forensic pharmacology. (United States)

    Ferner, R E


    Laboratory evidence of the presence and concentration of a drug in a person who has come to harm is often helpful in forensic pharmacology, and may be crucial. However, its value depends on two critical interpretations by the expert. First, the expert must make a careful analysis of the relationship between the results as measured in the sample and the drug in the patient at the time that harm occurred. That is especially difficult with post-mortem samples. Secondly, the expert must syntheses the laboratory information with the available clinical history and clinical or pathological findings. Even in the most favourable circumstances, when the sample is correctly obtained, identified, and analyzed, it can be hard to say that beyond reasonable doubt a given concentration had a given effect.

  8. Cluster headache: conventional pharmacological management. (United States)

    Becker, Werner J


    Cluster headache pain is very intense, usually increases in intensity very rapidly from onset, and attacks are often frequent. These clinical features result in significant therapeutic challenges. The most effective pharmacological treatment options for acute cluster attack include subcutaneous sumatriptan, 100% oxygen, and intranasal zolmitriptan. Subcutaneous or intramuscular dihydroergotamine and intranasal sumatriptan are additional options. Transitional therapy is applicable mainly for patients with high-frequency (>2 attacks per day) episodic cluster headache, and options include short courses of high-dose oral corticosteroids, dihydroergotamine, and occipital nerve blocks with local anesthetic and steroids. Prophylactic therapy is important both for episodic and chronic cluster headache, and the main options are verapamil and lithium. Verapamil is drug of first choice but may cause cardiac arrhythmias, and periodic electrocardiograms (EKGs) during dose escalation are important. Many other drugs are also in current use, but there is an insufficient evidence base to recommend them.

  9. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran


    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases...... food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids...

  10. Pharmacological activities of Curcuma caesia

    Directory of Open Access Journals (Sweden)

    Satyendra Singh Baghel


    Full Text Available Curcuma caesia Roxb. is a perennial, erect rhizomatous herb with large leaves. Fresh rhizomes are aromatic with intense camphoraceous odour, cultivated for its rhizomes, which are used in traditional medicine. The plant is reported to contain camphor, ar-turmerone, (Z-ocimene, ar-curcumene, 1, 8-cineole, elemene, borneol, bornyl acetate and curcumene as the major constituents. The plant has been reported to have antifungal activity, anti-asthmatic, smooth muscle relaxant, antimicrobial activity, antioxidant activity, analgesic, locomotor depressant, anticonvulsant and muscle relaxant effects, anti-inflammatory properties. It is now considered as a valuable source of unique natural products for development of medicines against various diseases. This review gives a view mainly on the meditional uses, phytochemistry and pharmacological actions of the plant.

  11. Neuropathic pain and pharmacological treatment. (United States)

    Jongen, Joost L M; Hans, Guy; Benzon, Honorio T; Huygen, Frank; Hartrick, Craig T


    Neuropathic pain is a serious chronic condition strongly affecting quality of life, which can be relieved but cannot be cured. Apart from symptomatic management, treatment should focus on the underlying disorder. The estimated prevalence is at least 1% to 5% of the general population. Neuropathic pain is characterized both by spontaneous and evoked pain. A diagnosis of neuropathic pain can usually be established based solely on history and neurological examination. Ancillary investigations may include EMG and computerized tomography/magnetic resonance imaging scans, depending on the localization of the suspected lesion. A limited number of agents, primarily directed at symptom control, are currently approved for use in neuropathic pain. A mechanism-based approach to pharmacological intervention supports the use of polypharmacy in neuropathic pain.

  12. Restructuring the syllabus for MD Pharmacology: Retrospection of bioassay

    Directory of Open Access Journals (Sweden)

    Sarita Mulkalwar


    Full Text Available Introduction: Career prospects in Pharmacology are witnessing a sea change due to fast and unanticipated development in the field of clinical research. Numerous openings exist now in academia, pharmaceutical industry, Clinical Research Organizations (CRO or as regulatory consultants, experimental pharmacologists, etc. In short, there are various options to choose from, depending on one′s interest. It′s high time we ponder now over the training programme for post-graduate students in Pharmacology. It needs to be revised keeping in mind the job prospects & uniqueness of the MD Pharmacology degree. Aim: To take suggestions of experienced pharmacologists on the present syllabus for MD Pharmacology and their opinion on continuation of Bioassay experiment which is currently an important part of it . Materials and Methods: A structured questionnaire was given to 30 experienced pharmacologists to seek their opinion on MD Pharmacology syllabus & continuation of Bioassay as a part of MD practical. Results: Out of 30 participants, 29 (96.6% did not use their knowledge of Bioassay during their 10 years of post MD career, whether in pharmaceutical industry or in academics. Only 5 of them (16.6% feel that experiment on bioassay should be continued in the current state. 76.7% of them wish it to be modified to a Dose Response Curve ( DRC . 6.71% feel that it should be totally scrapped. All the participants feel the need of revising current MD Pharmacology syllabus. Current syllabus is inclined more towards preparing good academicians but it lacks the proper training for creating good clinical research professionals. Medical writing, writing necessary documents for clinical trials including regulatory documents, writing an article for medical journals, marketing communication, product monograph and patient information of a clinical trial could be incorporated. They should be aware of the regulatory requirements for conducting studies on investigational drugs

  13. Therapeutic applications of circadian rhythms for the cardiovascular system

    Directory of Open Access Journals (Sweden)

    Elena V Tsimakouridze


    Full Text Available The cardiovascular system exhibits dramatic time-of-day dependent rhythms, for example the diurnal variation of heart rate, blood pressure, and timing of onset of adverse cardiovascular events such as heart attack and sudden cardiac death. Over the past decade, the circadian clock mechanism has emerged as a crucial factor regulating these daily fluctuations. Most recently, these studies have led to a growing clinical appreciation that targeting circadian biology offers a novel therapeutic approach towards cardiovascular (and other diseases. Here we describe leading-edge therapeutic applications of circadian biology including 1 timing of therapy to maximize efficacy in treating heart disease (chronotherapy; 2 novel biomarkers discovered by testing for genomic, proteomic, metabolomic or other factors at different times of day and night (chronobiomarkers; and 3 novel pharmacologic compounds that target the circadian mechanism with potential clinical applications (new chronobiology drugs. Cardiovascular disease remains a leading cause of death worldwide and new approaches in the management and treatment of heart disease are clearly warranted and can benefit patients clinically.

  14. Primary Prevention of Atherosclerotic Cardiovascular Disease in Women. (United States)

    McKibben, Rebeccah A; Al Rifai, Mahmoud; Mathews, Lena M; Michos, Erin D


    Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality among women. Despite improvements in cardiovascular disease prevention efforts, there remain gaps in cardiovascular disease awareness among women, as well as age and racial disparities in ASCVD outcomes for women. Disparity also exists in the impact the traditional risk factors confer on ASCVD risk between women and men, with smoking and diabetes both resulting in stronger relative risks in women compared to men. Additionally there are risk factors that are unique to women (such as pregnancy-related factors) or that disproportionally affect women (such as auto-immune disease) where preventive efforts should be targeted. Risk assessment and management must also be sex-specific to effectively reduce cardiovascular disease and improve outcomes among women. Evidence supports the use of statin therapy for primary prevention in women at higher ASCVD risk. However, some pause should be given to prescribing aspirin therapy in women without known ASCVD, with most evidence supporting the use of aspirin for women≥65 years not at increased risk for bleeding. This review article will summarize (1) traditional and non-traditional assessments of ASCVD risk and (2) lifestyle and pharmacologic therapies for the primary prevention of ASCVD in women.

  15. Allopurinol as a therapeutic option in cardiovascular disease. (United States)

    Okafor, Osita N; Farrington, K; Gorog, Diana A


    Epidemiological studies indicate that hyperuricaemia is an independent risk factor for cardiovascular disease. Alongside uric acid formation, increased xanthine oxidase activity also results in the formation of oxidative free radicals and superoxide particles. Oxidative stress significantly contributes to the development of cardiovascular disease, including endothelial cell dysfunction, atherosclerosis, vascular calcification and impaired myocardial energetics. Allopurinol, a competitive xanthine oxidase inhibitor, in addition to reducing serum uric acid levels, can act as a free radical scavenger. Although traditionally used for the management of gout, there has been renewed interest in the role of allopurinol in the management of cardiovascular disease. In this review, we summarise the role of the xanthine oxidase pathway in the generation of oxidative stress and evaluate the current body of evidence assessing the clinical effects of allopurinol in patients with cardiovascular disease. A number of small clinical studies have shown a beneficial effect of allopurinol in reducing ischemia-reperfusion injury in the setting of bypass surgery and coronary angioplasty. Additionally, studies in heart failure indicate a potential favourable effect of allopurinol on endothelial dysfunction, LV function and haemodynamic indices, particularly in those with raised serum uric acid levels. Whilst this cheap and readily available pharmacological option may offer a very cost effective therapeutic option, large-scale prospective studies are required to better delineate its role in reducing hard clinical end-points.

  16. Cardiovascular physiology and sleep. (United States)

    Murali, Narayana S; Svatikova, Anna; Somers, Virend K


    Sleep is a natural periodic suspension of consciousness during which processes of rest and restoration occur. The cognitive, reparative and regenerative accompaniments of sleep appear to be essential for maintenance of health and homeostasis. This brief overview will examine the cardiovascular responses to normal and disordered sleep, and their physiologic and pathologic implications. In the past, sleep was believed to be a passive state. The tableau of sleep as it unfolds is anything but a passive process. The brain's activity is as complex as wakefulness, never "resting" during sleep. Following the demise of the 'passive theory of sleep' (the reticular activating system is fatigued during the waking day and hence becomes inactive), there arose the 'active theory of sleep' (sleep is due to an active general inhibition of the brain) (1). Hess demonstrated the active nature of sleep in cats, inducing "physiological sleep" with electrical stimulation of the diencephalon (2). Classical experiments of transection of the cat brainstem (3) at midpontine level inhibited sleep completely, implying that centers below this level were involved in the induction of sleep (1, 4). For the first time, measurement of sleep depth without awakening the sleeper using the electroencephalogram (EEG) was demonstrated in animals by Caton and in humans, by Berger (1). This was soon followed by discovery of the rapid eye movement sleep periods (REM) by Aserinski and Kleitman (5), demonstration of periodical sleep cycles and their association with REM sleep (6, 7). Multiple studies and steady discoveries (4) made polysomnography, with its ability to perform simultaneous whole night recordings of EEG, electromyogram (EMG), and electrooculogram (EOC), a major diagnostic tool in study of sleep disorders. This facility has been of further critical importance in allowing evaluation of the interaction between sleep and changes in hemodynamics and autonomic cardiovascular control. Consequently the

  17. Preventive pharmacological treatment --an evolving new concept in schizophrenia. (United States)

    Sabbag, Rony; Levin, Raz; Edelman, Shany; Heresco-Levy, Uriel


    Treatment for schizophrenia remains one of the major challenges of modern medicine. The development of innovative pharmacological approaches for this disorder can potentially alleviate tremendous human suffering and revolutionize mental health delivery systems. While current treatment guidelines for schizophrenia refer to the post-psychosis onset phase of illness, presently there is a strong resurgent interest in secondary prevention intervention applied during schizophrenia prodrome. This development stems largely from the recognition that neurobiological deficit processes associated with schizophrenia severity and chronicity are already active by the time clinical onset is recognized. Proposed preventive treatments include presently used medications and experimental compounds that hypothetically may influence ongoing pathophysiological processes earlier in their development. The future establishment of the early recognition and intervention concept in schizophrenia is critically dependent on the outcome of ongoing research assessing the feasibility of prodrome diagnosis, the efficacy of specific medications and the alleviation of the risks associated with early pharmacological treatment.

  18. Osteoporosis y enfermedad cardiovascular


    Sarahí Mendoza; Miriam Noa; Rosa Más


    Las enfermedades cardiovasculares (ECV) y la osteoporosis son causas frecuentes de morbilidad en la población adulta, cuya frecuencia aumenta con la edad, por lo que al aumentar la expectativa de vida, constituyen importantes problemas de salud. El riesgo a padecer ambas patologías depende de factores de riesgo, y la prevención consiste en controlar los modificables. Las ECV y la osteoporosis presentan factores etiológicos comunes que involucran la biosíntesis del colesterol y la oxidación li...

  19. Postnatal Cardiovascular Adaptation

    Directory of Open Access Journals (Sweden)

    Ferda Ozlu


    Full Text Available Fetus depends on placental circulation in utero. A successful transition from intrauterin to extrauterine life depends on succesful physiological changes during labor. During delivery, fetus transfers from a liquid environment where oxygen comes via umbilical vein to air environement where oxygenation is supported via air breathing. Endocrinological changes are important for fetus to adapt to extrauterine life. In addition to these, cord clemping plays a crucial role in postnatal adaptation. Establishment of neonatal postnatal life and succesful overcome, the fetal cardiovascular transition period are important to stay on. [Archives Medical Review Journal 2016; 25(2.000: 181-190

  20. Cardiovascular hypertensive emergencies. (United States)

    Papadopoulos, D P; Sanidas, E A; Viniou, N A; Gennimata, V; Chantziara, V; Barbetseas, I; Makris, T K


    Inevitably, a small proportion of patients with systematic hypertension will develop hypertensive crisis at some point. Hypertensive crises can be divided into hypertensive emergency or hypertensive urgency according to the presence or lack of acute target organ damage. In this review, we discuss cardiovascular hypertensive emergencies, including acute coronary syndrome, aortic dissection, congestive heart failure, and sympathomimetic hypertensive crises, including those caused by cocaine use. Each presents in a unique fashion, although some hypertensive emergency patients report nonspecific symptoms. Treatment includes several effective and rapid-acting medications to safely reduce the blood pressure, protect remaining end-organ function, relieve symptoms, minimize the risk of complications, and thereby improve patient outcomes.

  1. Fetal cardiovascular physiology. (United States)

    Rychik, J


    The cardiovascular system of the fetus is physiologically different than the adult, mature system. Unique characteristics of the myocardium and specific channels of blood flow differentitate the physiology of the fetus from the newborn. Conditions of increased preload and afterload in the fetus, such as sacrococcygeal teratoma and twin-twin transfusion syndrome, result in unique and complex pathophysiological states. Echocardiography has improved our understanding of human fetal cadiovasvular physiology in the normal and diseased states, and has expanded our capability to more effectively treat these disease processes.

  2. Antioxidantes y enfermedad cardiovascular


    Vázquez, Clotilde


    La enfermedad cardiovascular se mantiene como la más importante causa de morbi y mortalidad en la mayoría de los países desarrollados, siendo cada vez más frecuente en los países en vías de desarrollo. La orteroesclerosis es un enfermedad crónica de las arterias de mediano y gran calibre, caracterizadas por el endurecimiento y pérdida de elasticidad de su pared, que se acompaña de estrechamiento de su luz. En general, la lesión arteriosclerótica se desarrolla en tres fases: a) inici...

  3. Pharmacogenetics of cardiovascular drug therapy


    Peters, Bas J.M.; Olaf H Klungel; de Boer, Anthonius; Ch Stricker, Bruno H; Maitland-van der Zee, Anke-Hilse


    In developed countries cardiovascular disease is one of the leading causes of death. Cardiovascular drugs such as platelet aggregation inhibitors, oral anticoagulants, antihypertensives and cholesterol lowering drugs are abundantly prescribed to reduce risk of cardiovascular disease. Notable interindividual variation exists in the response to these pharmacotherapeutic interventions, which can be partially explained by factors such as gender, age, diet, concomitant drug use and environmental f...

  4. Oxidative Stress in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Gábor Csányi


    Full Text Available In the special issue “Oxidative Stress in Cardiovascular Disease” authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine.

  5. Complex Pharmacology of Free Fatty Acid Receptors

    DEFF Research Database (Denmark)

    Milligan, Graeme; Shimpukade, Bharat; Ulven, Trond


    G protein-coupled receptors (GPCRs) are historically the most successful family of drug targets. In recent times it has become clear that the pharmacology of these receptors is far more complex than previously imagined. Understanding of the pharmacological regulation of GPCRs now extends beyond...... pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or "free" fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets...... for the treatment of metabolic and inflammatory diseases. Further understanding of the complex pharmacology of these receptors will be critical to unlocking their ultimate therapeutic potential....

  6. The role of oxidative stress and inflammation in cardiovascular aging. (United States)

    Wu, Junzhen; Xia, Shijin; Kalionis, Bill; Wan, Wenbin; Sun, Tao


    Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66(Shc), and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.

  7. Yoga, Anxiety, and Some Cardiovascular Risk Factors in Women

    Directory of Open Access Journals (Sweden)

    Asim CENGIZ


    Full Text Available This study aimed to examine the effects of a yoga program on anxiety, and some cardiovascular risk factors. Forty - six elderly participants aged 40 – 51 years women. The yoga program was based on 3 times/week for 10 weeks a set of yoga techniques, in the form of asana (postures and deep relaxation technique, pranayama (breathing techniques and meditation three for 60 minutes three times a week. The level of anxiety and decreased the risk factors for cardiovascular disease risk factors (CVD. The yoga program reduced the level of anxiety and decreased the risk factors for cardiovascular disease risk factors (CVD in the experimental group. After 8 weeks of the yoga program. SBP, DBP, B MI, HR and WC values were improved. It is likely that the yoga practices of controlling body, mind, and spirit combine to provide useful physiological effects for healthy people and for people compromised by cardiovascular disease.

  8. Echinacea purpurea: Pharmacology, phytochemistry and analysis methods

    Directory of Open Access Journals (Sweden)

    Azadeh Manayi


    Full Text Available Echinacea purpurea (Asteraceae is a perennial medicinal herb with important immunostimulatory and anti-inflammatory properties, especially the alleviation of cold symptoms. The plant also attracted scientists′ attention to assess other aspects of its beneficial effects. For instance, antianxiety, antidepression, cytotoxicity, and antimutagenicity as induced by the plant have been revealed in various studies. The findings of the clinical trials are controversial in terms of side effects. While some studies revealed the beneficial effects of the plant on the patients and no severe adverse effects, some others have reported serious side effects including abdominal pain, angioedema, dyspnea, nausea, pruritus, rash, erythema, and urticaria. Other biological activities of the plant such as antioxidant, antibacterial, antiviral, and larvicidal activities have been reported in previous experimental studies. Different classes of secondary metabolites of the plant such as alkamides, caffeic acid derivatives, polysaccharides, and glycoproteins are believed to be biologically and pharmacologically active. Actually, concurrent determination and single analysis of cichoric acid and alkamides have been successfully developed mainly by using high-performance liquid chromatography (HPLC coupled with different detectors including UV spectrophotometric, coulometric electrochemical, and electrospray ionization mass spectrometric detectors. The results of the studies which were controversial revealed that in spite of major experiments successfully accomplished using E. purpurea, many questions remain unanswered and future investigations may aim for complete recognition of the plant′s mechanism of action using new, complementary methods.

  9. Pharmacological pain management in chronic pancreatitis. (United States)

    Olesen, Søren S; Juel, Jacob; Graversen, Carina; Kolesnikov, Yuri; Wilder-Smith, Oliver H G; Drewes, Asbjørn M


    Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge. Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders. An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established, the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive. Consequently, the management of pain by traditional methods based on nociceptive deafferentation (e.g., surgery and visceral nerve blockade) becomes difficult and often ineffective. This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis. Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source, which should be reserved for special and carefully selected cases. In this review, we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis. In addition, future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.

  10. Cardiovascular benefits of exercise

    Directory of Open Access Journals (Sweden)

    Agarwal SK


    Full Text Available Shashi K AgarwalMedical Director, Agarwal Health Center, NJ, USAAbstract: Regular physical activity during leisure time has been shown to be associated with better health outcomes. The American Heart Association, the Centers for Disease Control and Prevention and the American College of Sports Medicine all recommend regular physical activity of moderate intensity for the prevention and complementary treatment of several diseases. The therapeutic role of exercise in maintaining good health and treating diseases is not new. The benefits of physical activity date back to Susruta, a 600 BC physician in India, who prescribed exercise to patients. Hippocrates (460–377 BC wrote “in order to remain healthy, the entire day should be devoted exclusively to ways and means of increasing one's strength and staying healthy, and the best way to do so is through physical exercise.” Plato (427–347 BC referred to medicine as a sister art to physical exercise while the noted ancient Greek physician Galen (129–217 AD penned several essays on aerobic fitness and strengthening muscles. This article briefly reviews the beneficial effects of physical activity on cardiovascular diseases.Keywords: exercise, cardiovascular disease, lifestyle changes, physical activity, good health

  11. Resveratrol and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Dominique Bonnefont-Rousselot


    Full Text Available The increased incidence of cardiovascular diseases (CVDs has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES, a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS. RES was able to scavenge •OH/O2•− and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH, an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA. Thus, RES could improve •NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…; however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure should compare the results of preclinical studies with those of clinical trials.

  12. Cardiovascular Complications of Pregnancy

    Directory of Open Access Journals (Sweden)

    Maria Carolina Gongora


    Full Text Available Pregnancy causes significant metabolic and hemodynamic changes in a woman’s physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia, gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up.

  13. Cardiovascular Complications of Pregnancy. (United States)

    Gongora, Maria Carolina; Wenger, Nanette K


    Pregnancy causes significant metabolic and hemodynamic changes in a woman's physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia), gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke) and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up.

  14. Roles and mechanisms of ginsenoside in cardiovascular diseases: progress and perspectives. (United States)

    Sun, Yingying; Liu, Yue; Chen, Keji


    Ginseng is among the oldest traditional Chinese medicinal herbs and is widely used in China and Southeast Asia. Over the past 50 years, considerable research has focused on the chemical constituents, pharmacological action, and clinical applications of ginseng. In this review, we examine the current state of research on ginseng, including the main active ingredient ginsenoside, its pharmacological effects on the cardiovascular system, and mechanisms of action. We focus on what is known of the effects of ginseng against atherosclerosis, arrhythmia, myocardial ischemia, and its inhibition of ventricular remodeling, providing a basis for expanding the clinical applications of ginseng.

  15. The impact of long chain polyunsaturated fatty acids on food allergy and cardiovascular disease. Fish and no chips?

    NARCIS (Netherlands)

    van den Elsen, L.W.J.


    This thesis creates more insight into the efficacy and mechanism of action of polyunsaturated fatty acids (PUFA), which act on the interface between pharmacology and nutrition in the prevention of allergic and cardiovascular disease. PUFA are categorized into n-6 and n-3 PUFA. The last decades have

  16. A systematic review on the application of cardiovascular risk prediction models in pharmacoeconomics, with a focus on primary prevention

    NARCIS (Netherlands)

    Stevanovic, J.; Postma, M.J.; Pechlivanoglou, P.


    OBJECTIVES: In the absence of long-term randomized clinical trials (RCTs) on the effectiveness of pharmacological treatment for primary cardiovascular disease (CVD) prevention, risk prediction models are used to project changes in CVD incidence due to changes on risk factor levels observed in short-

  17. Pharmacology of sexually compulsive behavior. (United States)

    Codispoti, Victoria L


    In a meta-analysis on controlled outcomes evaluations of 22,000 sex offenders, Losel and Schmucker found 80 comparisons between treatment and control groups. The recidivism rate averaged 19% in treated groups, and 27% in controls. Most other reviews reported a lower rate of sexual recidivism in treated sexual offenders. Of 2039 citations in this study (including literature in five languages), 60 studies held independent comparisons. Problematic issues included the control groups; various hormonal, surgical, cognitive behavioral, and psychotherapeutic treatments; and sample sizes. In the 80 studies compared after the year 2000, 32% were reported after 2000, 45% originated in the United States, 45% were reported in journals, and 36% were unpublished. Treatment characteristics showed a significant lack of pharmacologic treatment (7.5%), whereas use cognitive and classical behavioral therapy was 64%. In 68% of the studies, no information was available on the integrity of the treatment implementation; 36% of the treatment settings were outpatient only, 31% were prison settings, and 12% were mixed settings (prison, hospital, and outpatient). Integrating research interpretations is complicated by the heterogeneity of sex offenders, with only 56% being adult men and 17.5% adolescents. Offense types reported included 74% child molestation, 48% incest, and 30% exhibitionism. Pedophilia was not singled out. Follow-up periods varied from 12 months to greater than 84 months. The definition of recidivism ran the gamut from arrest (24%), conviction (30%), charges (19%), and no indication (16%). Results were difficult to interpret because of the methodological problems with this type of study. Overall, a positive outcome was noted with sex offender treatment. Cognitive-behavioral and hormonal treatment were the most promising. Voluntary treatment led to a slightly better outcome than mandatory participation. When accounting for a low base rate of sexual recidivism, the reduction


    Directory of Open Access Journals (Sweden)

    A. A. Aleksandrov


    Full Text Available The classic hypoglycemic agents include biguanides, sulfonylurea drugs, meglitinides, glitazones and alpha-glucosidase inhibitors. Modern algorithm of hypoglycemic therapy in the first step considers lifestyle modification and metformin monotherapy, the second step — the combined therapy. However, the effect of combined hypoglycemic therapy on long-term cardiovascular prognosis in patients with type 2 diabetes mellitus is studied insufficiently. Combined therapy with glibenclamide and metformin can result in adverse cardiovascular effects, so that long term therapy should be avoided in patients with coronary heart disease. Adequate pharmacological approaches to hyperglycemia correction should be elaborated.

  19. Physiology and Pharmacology of Ejaculation. (United States)

    Clement, Pierre; Giuliano, François


    Ejaculation is the final stage of coitus in mammalian male and is mandatory for natural procreation. Two synchronized phases, emission and expulsion, form the ejaculatory response and involve specific organs and anatomical structures. The peripheral events leading to ejaculation are commanded by autonomic (sympathetic and parasympathetic) and somatic divisions of the nervous system. The autonomic and somatic motor efferents originate in spinal nuclei located in thoracolumbar and lumbosacral segments. Co-ordinated activation of autonomic and somatic spinal nuclei is orchestrated by a group of lumbar spinal interneurons defined as the spinal generator of ejaculation. The generator of ejaculation together with the autonomic and somatic spinal nuclei constitutes a spinal network that is under the strong influence of stimulating or inhibiting genital sensory and supraspinal inputs. A brain circuitry dedicated to ejaculation has been delineated that is part of a more global network controlling other aspects of the sexual response. This circuitry includes discrete neuronal populations distributed in all divisions of the brain. The corollary to the expanded CNS network is the variety of neurotransmitter systems participating in the ejaculatory process. Among them, serotonin neurotransmission plays a key role and its targeting led to the development of the first registered pharmacological treatment of premature ejaculation in human beings. Critical gaps remain in the understanding of neurophysiopharmacology of ejaculation and management of ejaculatory disorders in human beings needs improvement. Because the ejaculatory response in laboratory animals and in human beings shares many similarities, the use of animal models will certainly provide further advances in the field.

  20. Phage therapy pharmacology phage cocktails. (United States)

    Chan, Benjamin K; Abedon, Stephen T


    Phage therapy is the clinical or veterinary application of bacterial viruses (bacteriophages) as antibacterial "drugs." More generally, phages can be used as biocontrol agents against plant as well as foodborne pathogens. In this chapter, we consider the therapeutic use of phage cocktails, which is the combining of two or more phage types to produce more pharmacologically diverse formulations. The primary motivation for the use of cocktails is their broader spectra of activity in comparison to individual phage isolates: they can impact either more bacterial types or achieve effectiveness under a greater diversity of conditions. The combining of phages can also facilitate better targeting of multiple strains making up individual bacterial species or covering multiple species that might be responsible for similar disease states, in general providing, relative to individual phage isolates, a greater potential for presumptive or empirical treatment. Contrasting the use of phage banks, or even phage isolation against specific etiologies that have been obtained directly from patients under treatment, here we consider the utility as well as potential shortcomings associated with the use of phage cocktails as therapeutic antibacterial agents.

  1. [Pharmacologic treatment of osteoporosis--2011]. (United States)

    Lakatos, Péter


    Osteoporosis affects approximately 9% of the population in Hungary resulting in about 100 000 osteoporotic fractures annually. Thirty-five percent of patients with hip fractures due to osteoporosis will die within 1 year. Direct costs of osteoporosis exceed 25 billion forints per year. Apparently, cost-effective reduction of bone loss and consequent fracture risk will add up to not only financial savings but improvement in quality of life, as well. A number of pharmacological modalities are available for this purpose. The mainstay of the treatment of osteoporosis is the bisphosphonate group that includes effective anti-resorptive compounds mitigating bone loss and fragility. The recently registered denosumab exhibits similar efficacy by neutralizing RANK ligand, however, marked differences can be observed between the two drug classes. Strontium has a unique mechanism of action by rebalancing bone turnover, and thus, providing an efficient treatment option for the not fast bone losers who are at high fracture risk. The purely anabolic teriparatide is available for the extremely severe osteoporotic patients and for those who do not respond to other types of therapy. Older treatment options such as hormone replacement therapy, raloxifene, tibolone or calcitonin may also have a restricted place in the management of osteoporosis.

  2. Cheese and cardiovascular disease risk

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Tholstrup, Tine


    Abstract Currently, the effect of dairy products on cardiovascular risk is a topic with much debate and conflicting results. The purpose of this review is to give an overview of the existing literature regarding the effect of cheese intake and risk of cardiovascular disease (CVD). Studies included...

  3. Vascular endothelial dysfunction and pharmacological treatment

    Institute of Scientific and Technical Information of China (English)

    Jin; Bo; Su


    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smo-king, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide(NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease.

  4. Indian poverty and cardiovascular disease. (United States)

    Ramaraj, Radhakrishnan; Alpert, Joseph Stephen


    Cardiovascular disease is among the world's leading causes of death, and nearly 80% of deaths occur in developing countries. Cardiovascular disease is becoming a major health problem in India, where life expectancy has increased with decreases in infectious disease and childhood mortality. It is well established that this population experiences coronary artery disease at a younger age than other populations. With infectious diseases still endemic, noncommunicable diseases are a lower priority for the governments of developing countries. There is a clear progression to degenerative and lifestyle-related diseases such as cardiovascular disease as a result of current social and economic change. The lack of a public response to the increasing risk for cardiovascular disease thus far is due mostly to a perception among policy makers and the public that cardiovascular disease is largely a problem of the urban rich. In conclusion, this review addresses the imminent threats and ways to tackle the epidemic in India.

  5. Assessment of cardiovascular risk.

    LENUS (Irish Health Repository)

    Cooney, Marie Therese


    Atherosclerotic cardiovascular disease (CVD) is the most common cause of death worldwide. Usually atherosclerosis is caused by the combined effects of multiple risk factors. For this reason, most guidelines on the prevention of CVD stress the assessment of total CVD risk. The most intensive risk factor modification can then be directed towards the individuals who will derive the greatest benefit. To assist the clinician in calculating the effects of these multiple interacting risk factors, a number of risk estimation systems have been developed. This review address several issues regarding total CVD risk assessment: Why should total CVD risk be assessed? What risk estimation systems are available? How well do these systems estimate risk? What are the advantages and disadvantages of the current systems? What are the current limitations of risk estimation systems and how can they be resolved? What new developments have occurred in CVD risk estimation?

  6. Cardiovascular complications in acromegaly. (United States)

    Vitale, G; Pivonello, R; Lombardi, G; Colao, A


    Cardiovascular morbidity and mortality are increased in acromegaly. In fact, GH and IGF-I excess induces a specific cardiomyopathy. The early stage of acromegaly is characterized by the hyperkinetic syndrome (high heart rate and increased systolic output). Frequently, concentric biventricular hypertrophy and diastolic dysfunction occur in acromegaly, leading to an impaired systolic function ending in heart failure if the disease is untreated or unsuccessfully untreated. Besides, abnormalities of cardiac rhythm and of valves have been also described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes, aggravates the acromegalic cardiomyopathy. The suppression of GH/IGF-I following an efficacious therapy could decrease left ventricular mass and improve cardiac function. In conclusion, a careful evaluation of cardiac function, morphology and activity seems to be mandatory in acromegaly.

  7. Cardiovascular diseases and diabetes

    DEFF Research Database (Denmark)

    Green, A.; Sortso, C.; Jensen, Peter Bjødstrup


    We present an investigation of the occurrence of cardiovascular disease in patients with diabetes in Denmark 2000 through 2011. The Diabetes Impact Study 2013 is based on all registrants in the Danish National Diabetes Register as of July 3rd 2013 (n=497,232). Record linkage with the Danish...... of diabetes has been rather constant at higher level in males (around 16-18%) than in females (around 12-14%) during 2000-2011 (incl.). In contrast, the incidence rate of CVD after having diabetes diagnosis has declined from about 4.5 to less than 3 during the same period, with higher declining level...... for males than for females. Efforts to detect diabetes at an earlier stage have not resulted in a reduced occurrence of CVD at the diagnosis of diabetes in Denmark. However, the risk of developing CVD after the diagnosis of diabetes has been declining, possibly reflecting benefits of intensified treatment...

  8. Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations. (United States)

    Low Wang, Cecilia C; Hess, Connie N; Hiatt, William R; Goldfine, Allison B


    Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting.

  9. Cardiovascular Magnetic Resonance Imaging (United States)

    Pelc, Norbert


    Cardiovascular diseases are a major source of morbidity and mortality in the United States. Early detection of disease can often be used to improved outcomes, either through direct interventions (e.g. surgical corrections) or by causing the patient to modify his or her behavior (e.g. smoking cessation or dietary changes). Ideally, the detection process should be noninvasive (i.e. it should not be associated with significant risk). Magnetic Resonance Imaging (MRI) refers to the formation of images by localizing NMR signals, typically from protons in the body. As in other applications of NMR, a homogeneous static magnetic field ( ~0.5 to 4 T) is used to create ``longitudinal" magnetization. A magnetic field rotating at the Larmor frequency (proportional to the static field) excites spins, converting longitudinal magnetization to ``transverse" magnetization and generating a signal. Localization is performed using pulsed gradients in the static field. MRI can produce images of 2-D slices, 3-D volumes, time-resolved images of pseudo-periodic phenomena such as heart function, and even real-time imaging. It is also possible to acquire spatially localized NMR spectra. MRI has a number of advantages, but perhaps the most fundamental is the richness of the contrast mechanisms. Tissues can be differentiated by differences in proton density, NMR properties, and even flow or motion. We also have the ability to introduce substances that alter NMR signals. These contrast agents can be used to enhance vascular structures and measure perfusion. Cardiovascular MRI allows the reliable diagnosis of important conditions. It is possible to image the blood vessel tree, quantitate flow and perfusion, and image cardiac contraction. Fundamentally, the power of MRI as a diagnostic tool stems from the richness of the contrast mechanisms and the flexibility in control of imaging parameters.

  10. The impact of chocolate on cardiovascular health. (United States)

    Fernández-Murga, L; Tarín, J J; García-Perez, M A; Cano, A


    Cardiovascular disease is the leading determinant of mortality and morbidity in women. Functional foods are attracting interest as potential regulators of the susceptibility to disease. Supported by epidemiological evidence, chocolate has emerged as a possible modulator of cardiovascular risk. Chocolate, or cocoa as the natural source, contains flavanols, a subclass of flavonoids. The latter years have witnessed an increasing number of experimental and clinical studies that suggest a protective effect of chocolate against atherogenesis. Oxidative stress, inflammation, and endothelial function define three biological mechanisms that have shown sensitivity to chocolate. Moreover, the consumption of chocolate has been involved in the protective modulation of blood pressure, the lipid profile, the activation of platelets, and the sensitivity to insulin. Dark chocolate seems more protective than milk or white chocolate. Despite this array of benefits, there is a lack of well designed clinical studies demonstrating cardiovascular benefit of chocolate. The high caloric content of chocolate, particularly of some less pure forms, imposes caution before recommending uncontrolled consumption.

  11. [Pharmacological gender-specific medicine]. (United States)

    Ueno, Koichi; Negishi, Etsuko


    In recent years, the concept of Gender-specific Medicine has become more widespread in Japan. We need to understand gender differences in the use patterns of prescription drugs for proper use of medicines. We therefore investigated gender differences in the use of prescription drugs using the data of 9 hospitals in Japan. The data on prescription drugs were extracted from the drug ordering system for a month from March 1 to 31, 2003. We analyzed the data according to sex and age. As a result, we found that the prescription frequency of central nervous system drugs and Kampo medications for females was higher than that for males. There was also the same trend for hormone medicines and vitamins. On the other hand, the prescription frequency of cardiovascular drugs for males was higher than that for females. Moreover, there was the same trend for unclassified metabolic drugs such as arthrifuge. As a result of detailed analysis by age, a correlation between age-specificity of prescription drugs and gender difference of diseases was suggested. Such information has not been investigated in Japan. Since these results are thought to be useful, we will perform a detailed examination and accumulate evidence for their future exploitation in drug therapy.

  12. Sleep duration, cardiovascular disease, and proinflammatory biomarkers

    Directory of Open Access Journals (Sweden)

    Grandner MA


    Full Text Available Michael A Grandner,1,2 Megan R Sands-Lincoln,3 Victoria M Pak,2,4 Sheila N Garland1,5 1Behavioral Sleep Medicine Program, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA; 2Center for Sleep and Circadian Neurobiology, University of Pennsylvania, PA, USA; 3Center for Evidence Based Medicine, Elsevier Inc, Philadelphia, PA, USA; 4Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, PA, USA; 5Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, PA, USA Abstract: Habitual sleep duration has been associated with cardiometabolic disease, via several mechanistic pathways, but few have been thoroughly explored. One hypothesis is that short and/or long sleep duration is associated with a proinflammatory state, which could increase risk for cardiovascular and metabolic diseases. This hypothesis has been largely explored in the context of experimental sleep deprivation studies which have attempted to demonstrate changes in proinflammatory markers following acute sleep loss in the laboratory. Despite the controlled environment available in these studies, samples tend to lack generalization to the population at large and acute sleep deprivation may not be a perfect analog for short sleep. To address these limitations, population based studies have explored associations between proinflammatory markers and habitual sleep duration. This review summarizes what is known from experimental and cross-sectional studies about the association between sleep duration, cardiovascular disease, and proinflammatory biomarkers. First, the association between sleep duration with both morbidity and mortality, with a focus on cardiovascular disease, is reviewed. Then, a brief review of the potential role of proinflammatory markers in cardiovascular disease is presented. The majority of this review details specific findings related to specific

  13. Pharmacology and therapeutics of bronchodilators. (United States)

    Cazzola, Mario; Page, Clive P; Calzetta, Luigino; Matera, M Gabriella


    regimens as much as possible. This review will describe the pharmacology and therapeutics of old, new, and emerging classes of bronchodilator.

  14. Hypericum japonicum Thunb. ex Murray: Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics of an Important Herbal Medicine

    Directory of Open Access Journals (Sweden)

    Lin-Sheng Liu


    Full Text Available Hypericum japonicum Thunb. ex Murray is mainly distributed throughout Asia, Oceania and North America and is used as an important herbal medicine. H. japonicum contains many valuable secondary metabolites, such as flavonoids, phloroglucinols and xanthones and has hepatoprotective, anti-tumor, antibacterial, antiviral, and antioxidant activities and effects on the cardiovascular system and immunity. Coupled with phytochemical and pharmacological research, a series of analytical methods have been developed to evaluate the quality of H. japonicum based on its bioactive components. A pharmacokinetics study involved the absorption of two main flavonoids of H. japonicum in rats. This review aims to present an up-to-date and comprehensive overview of the phytochemistry, pharmacology, quality control and pharmacokinetics of H. japonicum, which should be useful for the greater development of H. japonicum, especially in the development of new drugs and therapeutics for various diseases.

  15. Physical exercise as non-pharmacological treatment of chronic pain: Why and when. (United States)

    Ambrose, Kirsten R; Golightly, Yvonne M


    Chronic pain broadly encompasses both objectively defined conditions and idiopathic conditions that lack physical findings. Despite variance in origin or pathogenesis, these conditions are similarly characterized by chronic pain, poor physical function, mobility limitations, depression, anxiety, and sleep disturbance, and they are treated alone or in combination by pharmacologic and non-pharmacologic approaches, such as physical activity (aerobic conditioning, muscle strengthening, flexibility training, and movement therapies). Physical activity improves general health, disease risk, and progression of chronic illnesses such as cardiovascular disease, type 2 diabetes, and obesity. When applied to chronic pain conditions within appropriate parameters (frequency, duration, and intensity), physical activity significantly improves pain and related symptoms. For chronic pain, strict guidelines for physical activity are lacking, but frequent movement is preferable to sedentary behavior. This gives considerable freedom in prescribing physical activity treatments, which are most successful when tailored individually, progressed slowly, and account for physical limitations, psychosocial needs, and available resources.

  16. Nadroparin calcium: a review of its basic and clinical pharmacology


    Ospina-González, Diego Alexander; Universidad de los Andes; Martínez, Jairo Andrés; Universidad de los Andes; Cifuentes, Luis Fernando; Universidad de los Andes


    Objective: To evaluate critically the evidence on the basic and clinical pharmacology of nadroparin calcium. Data source: We conducted a literature review from October 1985 to September 2010 in the electronic databases: Pubmed, Cochrane, MD Cosult, Medscape, Scielo and Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA).Study selection: Studies published in English, Spanish or French made in humans and animals for experimentation which reviewed the basic and clinical pharmac...

  17. Pharmacologic treatment of migraine. Comparison of guidelines.

    NARCIS (Netherlands)

    Schuurmans, A.; Weel, C. van


    OBJECTIVE: To compare guidelines (not the primary studies) for pharmacologic treatment of migraine as to methods of guideline development; recommendations, particularly on triptans; and quality of supporting evidence (with emphasis on comparative studies of triptans versus ergot alkaloids and nonste

  18. Anti-aging pharmacology: Promises and pitfalls. (United States)

    Vaiserman, Alexander M; Lushchak, Oleh V; Koliada, Alexander K


    Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness. A number of pharmacological agents targeting basic aging pathways (i.e., calorie restriction mimetics, autophagy inducers, senolytics etc.) are now under investigation. This review summarizes the literature related to advances, perspectives and challenges in the field of anti-aging pharmacology.

  19. Neuroimmune pharmacology as a component of pharmacology in medical school curriculum. (United States)

    Chen, Yuh F


    An introduction to the discipline of pharmacology is a standard part of the scientific foundation of medical school curricula. Neuroimmune pharmacology is a new subtopic that integrates fundamental concepts of neuroscience, immunology, infectious disease, and pharmacology. The integration of these areas is important to medical training in view of the growing concern over neurodegenerative diseases and cognitive disorders. This article introduces a submodule and concomitant syllabus for inclusion of neuroimmune pharmacology as a component of a pharmacology curriculum. The introductory lectures of neuroimmune pharmacology will concentrate on the role of the immune system in (1) schizophrenia and major depression; (2) neurodegenerative disorders; and (3) drug addiction. Emphasis will be placed on the competencies of critical thinking, problem solving, learning interest, and effectiveness of medical students. Problem-based learning and case study discussions will also be applied.

  20. Nrf2 and cardiovascular defense. (United States)

    Howden, Reuben


    The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E) 2-related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis). The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

  1. Nrf2 and Cardiovascular Defense

    Directory of Open Access Journals (Sweden)

    Reuben Howden


    Full Text Available The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E 2-related factor 2 (Nrf2, regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis. The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

  2. Urotensin II in cardiovascular regulation

    Directory of Open Access Journals (Sweden)

    Fraser D Russell


    Full Text Available Fraser D RussellSchool of Health and Sport Sciences, Faculty of Science, Health and Education, University of the Sunshine Coast, Sippy Downs, Queensland, AustraliaAbstract: Cardiovascular function is modulated by neuronal transmitters, circulating hormones, and factors that are released locally from tissues. Urotensin II (UII is an 11 amino acid peptide that stimulates its’ obligatory G protein coupled urotensin II receptors (UT to modulate cardiovascular function in humans and in other animal species, and has been implicated in both vasculoprotective and vasculopathic effects. For example, tissue and circulating concentrations of UII have been reported to increase in some studies involving patients with atherosclerosis, heart failure, hypertension, preeclampsia, diabetes, renal disease and liver disease, raising the possibility that the UT receptor system is involved in the development and/or progression of these conditions. Consistent with this hypothesis, administration of UT receptor antagonists to animal models of cardiovascular disease have revealed improvements in cardiovascular remodelling and hemodynamics. However, recent studies have questioned this contributory role of UII in disease, and have instead postulated a protective effect on the cardiovascular system. For example, high concentrations of circulating UII correlated with improved clinical outcomes in patients with renal disease or myocardial infarction. The purpose of this review is to consider the regulation of the cardiovascular system by UII, giving consideration to methodologies for measurement of plasma concentrations, sites of synthesis and triggers for release.Keywords: urotensin II, cardiovascular disease, heart failure, hypertension

  3. Pharmacological treatment of depression in older people


    Curran, Stephen; Byrne, Andrew; Wattis, John


    In the light of recent National Institute for Clinical Excellence (NICE) and Committee for the Safety of Medicines (CSM) guidance we discuss the importance of the diagnosis of depression in old age and review pharmacological interventions. An introductory section is followed by sections on each of the main antidepressant groups. This briefly describes their pharmacology and reviews research done specifically relevant to older people. Finally practical clinical applications are discussed.

  4. Complex pharmacology of free fatty acid receptors


    Milligan, Graeme; Shimpukade, Bharat; Ulven, Trond; Hudson, Brian D.


    G protein-coupled receptors (GPCRs) are historically the most successful family of drug targets. In recent times it has become clear that the pharmacology of these receptors is far more complex than previously imagined. Understanding of the pharmacological regulation of GPCRs now extends beyond simple competitive agonism or antagonism by ligands interacting with the orthosteric binding site of the receptor to incorporate concepts of allosteric agonism, allosteric modulation, signaling bias, c...

  5. Clinical Pharmacology & Therapeutics: Past, Present, and Future. (United States)

    Waldman, S A; Terzic, A


    Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare.

  6. Citicoline: pharmacological and clinical review, 2006 update. (United States)

    Secades, Julio J; Lorenzo, José Luis


    Cytidine 5'-diphosphocholine, CDP-choline, or citicoline is an essential intermediate in the biosynthetic pathway of structural phospholipids in cell membranes, particularly phosphatidylcholine. Following administration by both the oral and parenteral routes, citicoline releases its two main components, cytidine and choline. Absorption by the oral route is virtually complete, and bioavailability by the oral route is therefore approximately the same as by the intravenous route. Once absorbed, citicoline is widely distributed throughout the body, crosses the blood-brain barrier and reaches the central nervous system (CNS), where it is incorporated into the membrane and microsomal phospholipid fraction. Citicoline activates biosynthesis of structural phospholipids of neuronal membranes, increases brain metabolism, and acts upon the levels of different neurotransmitters. Thus, citicoline has been experimentally shown to increase norepinephrine and dopamine levels in the CNS. Owing to these pharmacological mechanisms, citicoline has a neuroprotective effect in hypoxic and ischemic conditions, decreasing the volume of ischemic lesion, and also improves learning and memory performance in animal models of brain aging. In addition, citicoline has been shown to restore the activity of mitochondrial ATPase and membrane Na+/K+ATPase, to inhibit activation of certain phospholipases, and to accelerate reabsorption of cerebral edema in various experimental models. Citicoline has also been shown to be able to inhibit mechanisms of apoptosis associated to cerebral ischemia and in certain neurodegeneration models, and to potentiate neuroplasticity mechanisms. Citicoline is a safe drug, as shown by the toxicological tests conducted, that has no significant systemic cholinergic effects and is a well tolerated product. These pharmacological characteristics and the action mechanisms of citicoline suggest that this product may be indicated for treatment of cerebral vascular disease, head

  7. A Review on the Phytochemistry, Pharmacology, and Pharmacokinetics of Amentoflavone, a Naturally-Occurring Biflavonoid

    Directory of Open Access Journals (Sweden)

    Sheng Yu


    Full Text Available Amentoflavone (C30H18O10 is a well-known biflavonoid occurring in many natural plants. This polyphenolic compound has been discovered to have some important bioactivities, including anti-inflammation, anti-oxidation, anti-diabetes, and anti-senescence effects on many important reactions in the cardiovascular and central nervous system, etc. Over 120 plants have been found to contain this bioactive component, such as Selaginellaceae, Cupressaceae, Euphorbiaceae, Podocarpaceae, and Calophyllaceae plant families. This review paper aims to profile amentoflavone on its plant sources, natural derivatives, pharmacology, and pharmacokinetics, and to highlight some existing issues and perspectives in the future.

  8. Treatment of Pancreatic Cancer with Pharmacological Ascorbate. (United States)

    Cieslak, John A; Cullen, Joseph J


    The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer.

  9. Pharmacological and clinical properties of curcumin

    Directory of Open Access Journals (Sweden)

    Huang S


    Full Text Available Christopher S Beevers¹, Shile Huang²¹Department of Pharmacology, Ross University School of Medicine, Picard-Portsmouth, Commonwealth of Dominica; ²Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USAAbstract: The polyphenol natural product curcumin has been the subject of numerous studies over the past decades, which have identified and characterized the compound's pharmacokinetic, pharmacodynamic, and clinical pharmacological properties. In in vitro and in vivo model systems, curcumin displays potent pharmacological effects, by targeting many critical cellular factors, through a diverse array of mechanisms of action. Despite this tremendous molecular versatility, however, the clinical application of curcumin remains limited due to poor pharmacokinetic characteristics in human beings. The current trend is to develop and utilize unique delivery systems, chemical derivatives, and chemical analogs to circumvent these pharmacological obstacles, in order to optimize the conditions for curcumin as a chemopreventive and chemotherapeutic agent in diseases such as cancer, diabetes, obesity, Alzheimer's disease, and inflammatory disorders. The present work seeks to review recent studies in the basic pharmacological principles and potential clinical applications of curcumin.Keywords: curcumin, pharmacological properties, signal transduction, cellular targets, cancer, inflammation

  10. Characterization and pharmacology of the GHB receptor. (United States)

    Ticku, Maharaj K; Mehta, Ashok K


    Radioligand binding using [(3)H]NCS-382, an antagonist of the GHB receptor, revealed specific binding sites in the rat cerebrocortical and hippocampal membranes. Scatchard analysis of saturation isotherms revealed two different populations of binding sites. NCS-382 was about 10 times more potent than GHB in inhibiting [(3)H]NCS-382 binding. A variety of ligands for other receptors did not affect [(3)H]NCS-382 binding. Quantitative autoradiographic analysis of [(3)H]NCS-382 binding revealed similar characteristics. Thus [(3)H]NCS-382, being more potent and selective, offers advantage over [(3)H]GHB as a radioligand. Unlike GHB, several analogues of GHB such as UMB68 (a tertiary alcohol analogue of GHB), UMB86 (4-hydroxy-4-napthylbutanoic acid, sodium salt), UMB72 [4-(3-phenylpropyloxy)butyric acid, sodium salt], UMB73 (4-benzyloxybutyric acid, sodium salt), UMB66 (3-chloropropanoic acid), gamma-hydroxyvaleric acid (that is, GHV, a 4-methyl-substituted analogue of GHB), 3-HPA (3-hydroxyphenylacetic acid), and ethers of 3-hydroxyphenylacetic acid (UMB108, UMB109, and UMB119) displaced [(3)H]NCS-382 without affecting [(3)H]GABA binding to GABA(B) receptor. Thus these compounds offer an advantage over GHB as an experimental tool. Our study, aimed at exploring the potential involvement of the GHB receptor in the pharmacology of ethanol, indicated that ethanol does not affect [(3)H]NCS-382 binding in the rat brain, thereby suggesting that ethanol does not interact directly with the GHB receptor. Our study, aimed at exploring the involvement of the GHB receptor in the pathology of succinate semialdehyde dehydrogenase deficiency, which is known to cause elevation of GHB levels, revealed no change in the affinity, receptor density or displacement potency as determined by using [(3)H]NCS-382 as a radioligand in Aldh5a1(-/-) vs. Aldh5a1(+/+) mouse brain.

  11. Undergraduates' understanding of cardiovascular phenomena. (United States)

    Michael, Joel A; Wenderoth, Mary Pat; Modell, Harold I; Cliff, William; Horwitz, Barbara; McHale, Philip; Richardson, Daniel; Silverthorn, Dee; Williams, Stephen; Whitescarver, Shirley


    Undergraduates students in 12 courses at 8 different institutions were surveyed to determine the prevalence of 13 different misconceptions (conceptual difficulties) about cardiovascular function. The prevalence of these misconceptions ranged from 20 to 81% and, for each misconception, was consistent across the different student populations. We also obtained explanations for the students' answers either as free responses or with follow-up multiple-choice questions. These results suggest that students have a number of underlying conceptual difficulties about cardiovascular phenomena. One possible source of some misconceptions is the students' inability to apply simple general models to specific cardiovascular phenomena. Some implications of these results for teachers of physiology are discussed.

  12. Fish cardiovascular physiology and disease. (United States)

    Sherrill, Johanna; Weber, E Scott; Marty, Gary D; Hernandez-Divers, Stephen


    Fish patients with cardiovascular disorders present a challenge in terms of diagnostic evaluation and therapeutic options. Veterinarians can approach these cases in fish using methods similar to those employed for other companion animals. Clinicians who evaluate and treat fish in private, aquarium, zoologic, or aquaculture settings need to rely on sound clinical judgment after thorough historical and physical evaluation. Pharmacokinetic data and treatments specific to cardiovascular disease in fish are limited; thus, drug types and dosages used in fish are largely empiric. Fish cardiovascular anatomy, physiology, diagnostic evaluation, monitoring, common diseases, cardiac pathologic conditions, formulary options, and comprehensive references are presented with the goal of providing fish veterinarians with clinically relevant tools.

  13. Vitamin D and cardiovascular disease: is the evidence solid? (United States)

    Al Mheid, Ibhar; Patel, Riyaz S; Tangpricha, Vin; Quyyumi, Arshed A


    Vitamin D deficiency, prevalent in 30-50% of adults in developed countries, is largely due to inadequate cutaneous production that results from decreased exposure to sunlight, and to a lesser degree from low dietary intake of vitamin D. Serum levels of 25-hydroxyvitamin D (25-OH D) vitamin D deficiency and levels >30 ng/mL are considered optimal. While the endocrine functions of vitamin D related to bone metabolism and mineral ion homoeostasis have been extensively studied, robust epidemiological evidence also suggests a close association between vitamin D deficiency and cardiovascular morbidity and mortality. Experimental studies have demonstrated novel actions of vitamin D metabolites on cardiomyocytes, and endothelial and vascular smooth muscle cells. Low 25-OH D levels are associated with left ventricular hypertrophy, vascular dysfunction, and renin-angiotensin system activation. Despite a large body of experimental, cross-sectional, and prospective evidence implicating vitamin D deficiency in the pathogenesis of cardiovascular disease, a causal relationship remains to be established. Moreover, the cardiovascular benefits of normalizing 25-OH D levels in those without renal disease or hyperparathyroidism have not been established, and questions of an epiphenomenon where vitamin D status merely reflects a classic risk burden have been raised. Randomized trials of vitamin D replacement employing cardiovascular endpoints will provide much needed evidence for determining its role in cardiovascular protection.

  14. The pharmacology of topical analgesics. (United States)

    Barkin, Robert L


    Pain management of patients continues to pose challenges to clinicians. Given the multiple dimensions of pain--whether acute or chronic, mild, moderate, or severe, nociceptive or neuropathic--a multimodal approach may be needed. Fortunately, clinicians have an array of nonpharmacologic and pharmacologic treatment choices; however, each modality must be chosen carefully, because some often used oral agents are associated with safety and tolerability issues that restrict their use in certain patients. In particular, orally administered nonsteroidal antiinflammatory drugs, opioids, antidepressants, and anticonvulsants are known to cause systemic adverse effects in some patients. To address this problem, a number of topical therapies in various therapeutic classes have been developed to reduce systemic exposure and minimize the risks of patients developing adverse events. For example, topical nonsteroidal anti-inflammatory drug formulations produce a site-specific effect (ie, cyclo-oxygenase inhibition) while decreasing the systemic exposure that may lead to undesired effects in patients. Similarly, derivatives of acetylsalicylic acid (ie, salicylates) are used in topical analgesic formulations that do not significantly enter the patient's systemic circulation. Salicylates, along with capsaicin, menthol, and camphor, compose the counterirritant class of topical analgesics, which produce analgesia by activating and then desensitizing epidermal nociceptors. Additionally, patches and creams that contain the local anesthetic lidocaine, alone or co-formulated with other local anesthetics, are also used to manage patients with select acute and chronic pain states. Perhaps the most common topical analgesic modality is the cautious application of cutaneous cold and heat. Such treatments may decrease pain not by reaching the target tissue through systemic distribution, but by acting more directly on the affected tissue. Despite the tolerability benefits associated with avoiding

  15. Pharmacological mechanisms in the cardiovascular effects of DCLHb, a hemoglobin based blood substitute

    NARCIS (Netherlands)

    A. Gulati (Anil)


    textabstractThe search for a clinically useful blood substitute has been stimulated by the inherent limitations of the homologous blood transfusion system, particularly its sufficiency, safety and costs. Blood has been described as the "most complicated fluid in animals" (Winslow, 1992). An attempt

  16. Pharmacological potential of Populus nigra extract as antioxidant, anti-inflammatory, cardiovascular and hepatoprotective agent

    Directory of Open Access Journals (Sweden)

    Nadjet Debbache-Benaida


    Conclusions: The extract exerted significant anti-inflammatory, hepatoprotective and vasorelaxant activities, the latter being endothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties, probably related to an inhibition of Ca2+ influx.

  17. Pharmacological potential of Populus nigra extract as antioxidant, anti-inflammatory, cardiovascular and hepatoprotective agent

    Institute of Scientific and Technical Information of China (English)

    Nadjet Debbache-Benaida; Dina Atmani-Kilani; Valrie Barbara Schini-Keirth; Nouredine Djebbli; Djebbar Atmani


    Objective: To evaluate antioxidant, anti-inflammatory, hepatoprotective and vasorelaxant activities of Populus nigra flower buds ethanolic extract. Methods: Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema. Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections. Vasorelaxant effect was estimated in endothelium-intact and-rubbed rings of porcine coronary arteries precontracted with high concentration of U46619. Results:The results showed a moderate antioxidant activity (40%), but potent anti-inflammatory activity (49.9%) on carrageenan-induced mice paw edema, and also as revealed by histopathologic examination, complete protection against AlCl3-induced hepatic toxicity. Relaxant effects of the same extract on vascular preparation from porcine aorta precontracted with high concentration of U46619 were considerable at 10-1 g/L, and comparable (P>0.05) between endothelium-intact (67.74%, IC50=0.04 mg/mL) and-rubbed (72.72%, IC50=0.075 mg/mL) aortic rings. Conclusions: The extract exerted significant anti-inflammatory, hepatoprotective and vasorelaxant activities, the latter being endothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties, probably related to an inhibition of Ca2+influx.

  18. Pattern Recognition of Cardiovascular and Psychomotor Variability in Response to Pharmacological Agents (United States)


    design and analysis ot oattprn recoenition experiments," Bell Sys. Tech. Journal . Vol. 41. 1962. on. 123 - /44. 113J K. Fukunaga. Introduction to...arbitrary relation between probability ot error and measurement subset," Journal ot the American Statistical Association. Vol. /J. No. 369, March 198U...IT I 72p-.. CSEA *1. ~ S mI’t"* L.________3 A4 9VPA1 L Is’ D-AA L5~ 9 smp^ GI c 13 .30 D.D. A.4 ’V RAA L 117 A ~ ~AD.4L L )’v -Mas IF /O U’J r*SAer

  19. Carotenoids and cardiovascular health. (United States)

    Voutilainen, Sari; Nurmi, Tarja; Mursu, Jaakko; Rissanen, Tiina H


    Cardiovascular disease (CVD) is the main cause of death in Western countries. Nutrition has a significant role in the prevention of many chronic diseases such as CVD, cancers, and degenerative brain diseases. The major risk and protective factors in the diet are well recognized, but interesting new candidates continue to appear. It is well known that a greater intake of fruit and vegetables can help prevent heart diseases and mortality. Because fruit, berries, and vegetables are chemically complex foods, it is difficult to pinpoint any single nutrient that contributes the most to the cardioprotective effects. Several potential components that are found in fruit, berries, and vegetables are probably involved in the protective effects against CVD. Potential beneficial substances include antioxidant vitamins, folate, fiber, and potassium. Antioxidant compounds found in fruit and vegetables, such as vitamin C, carotenoids, and flavonoids, may influence the risk of CVD by preventing the oxidation of cholesterol in arteries. In this review, the role of main dietary carotenoids, ie, lycopene, beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, and zeaxanthin, in the prevention of heart diseases is discussed. Although it is clear that a higher intake of fruit and vegetables can help prevent the morbidity and mortality associated with heart diseases, more information is needed to ascertain the association between the intake of single nutrients, such as carotenoids, and the risk of CVD. Currently, the consumption of carotenoids in pharmaceutical forms for the treatment or prevention of heart diseases cannot be recommended.

  20. Novel epigenetic-based therapies useful in cardiovascular medicine

    Institute of Scientific and Technical Information of China (English)

    Claudio Napoli; Vincenzo Grimaldi; Maria Rosaria De Pascale; Linda Sommese; Teresa Infante; Andrea Soricelli


    Epigenetic modifications include DNA methylation, his-tone modifications, and micro RNA. Gene alterations have been found to be associated with cardiovascular diseases, and epigenetic mechanisms are continuously being studied to find new useful strategies for the clinical management of afflicted patients. Numerous cardiovascular disorders are characterized by the abnormal methylation of Cp G islands and so specific drugs that could inhibit DNA methyltransferase directly or by reducing its gene expression(e.g., hydralazine and procainamide) are currently under investigation. The anti-proliferative and anti-inflammatory properties of histone deacetylase inhibitors and their cardio-protective effects have been confirmed in preclinical studies. Furthermore, the regulation of the expression of micro RNA targets through pharmacological tools is still under development. Indeed, large controlled trials are required to establish whether current possible candidate antisense micro RNAs could offer better therapeutic benefits in clinical practice. Here, we updated therapeutic properties, side effects, and feasibility of eme-rging epigenetic-based strategies in cardiovascular diseases by highlighting specific problematic issues that still affect the development of large scale novel therapeutic protocols.

  1. Brain angiotensin AT1 receptors as specific regulators of cardiovascular reactivity to acute psychoemotional stress. (United States)

    Mayorov, Dmitry N


    1. Cardiovascular reactivity, an abrupt rise in blood pressure (BP) and heart rate in response to psychoemotional stress, is a risk factor for heart disease. Pharmacological and molecular genetic studies suggest that brain angiotensin (Ang) II and AT(1) receptors are required for the normal expression of sympathetic cardiovascular responses to various psychological stressors. Moreover, overactivity of the brain AngII system may contribute to enhanced cardiovascular reactivity in hypertension. 2. Conversely, brain AT(1) receptors appear to be less important for the regulation of sympathetic cardiovascular responses to a range of stressors involving an immediate physiological threat (physical stressors) in animal models. 3. Apart from threatening events, appetitive stimuli can induce a distinct, central nervous system-mediated rise in BP. However, evidence indicates that brain AT(1) receptors are not essential for the regulation of cardiovascular arousal associated with positively motivated behaviour, such as anticipation and the consumption of palatable food. The role of central AT(1) receptors in regulating cardiovascular activation elicited by other types of appetitive stimuli remains to be determined. 4. Emerging evidence also indicates that brain AT(1) receptors play a limited role in the regulation of cardiovascular responses to non-emotional natural daily activities, sleep and exercise. 5. Collectively, these findings suggest that, with respect to cardiovascular arousal, central AT(1) receptors may be involved primarily in the regulation of the defence response. Therefore, these receptors could be a potential therapeutic target for selective attenuation of BP hyperreactivity to aversive stressors, without altering physiologically important cardiovascular adjustments to normal daily activities, sleep and exercise.

  2. Evaluation of Antidepressant activity of Simvastatin, Lovastatin and Atorvastatin in Male Swiss Mice - An Experimental Study

    Directory of Open Access Journals (Sweden)

    Gudadappanavar Anupama M


    Full Text Available Context: Depression is the commonest mood disorder, could also be secondary to a number of physical disorders. Pharmacological treatment of such co-morbidities is difficult. If statins show antidepressant activity that could appear to be better lipid-lowering agents as they provide additional benefits in cardiovascular disorders with co-morbidity like depression. Aims: To investigate the effect of simvastatin, lovastatin and atorvastatin for their antidepressant activity using forced swim test and tail suspension test on behavioral models of depression in male swiss mice. Design: Experimental Study Methods and Material: The in vivo antidepressant activity of simvastatin and lovastatin was studied using forced swim test and tail suspension test. The mice received the drug as per their weight and subjected for experimentation. Group mean immobility time was calculated in treated and control groups for comparison. Statistical analysis used: One-way analysis of variance (ANOVA followed by Bonferroni’s multiple comparison test. (P / 0.05 Results: Simvastatin and Lovastatin used in the present study showed significant antidepressant activity in both behavioral models of depression (p<0.05 while atorvastatin failed to show significant antidepressant action. Conclusion: The study suggests that the antidepressant activity of simvastatin and lovastatin, if could be extrapolated to clinical situations, appear to be better lipid-lowering agents as they provide additional benefits in cardiovascular disorders with co-morbidity like depression.

  3. Cardiovascular autonomic neuropathy in diabetes

    DEFF Research Database (Denmark)

    Spallone, Vincenza; Ziegler, Dan; Freeman, Roy


    in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: 1. one abnormal cardio-vagal test identifies possible or early CAN; 2. at least two abnormal cardio-vagal tests....... diagnosis of CAN clinical forms, 2. detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, OH, nondipping, QT interval prolongation), 3. risk stratification for diabetic complications and cardiovascular morbidity and mortality, and 4. modulation of targets of diabetes therapy......Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control...

  4. Cognitive dysfunction after cardiovascular surgery

    DEFF Research Database (Denmark)

    Funder, K S; Steinmetz, J; Rasmussen, L S


    This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive neuropsychol...

  5. Proceedings of the 13. Annual meeting of the Federation of Societies on Experimental Biology; 23. Brazilian congress on biophysics; 30. Brazilian congress on pharmacology and experimental therapeutics; 33. Brazilian congress on physiology; 14. Brazilian congress on clinical research; 22. Brazilian congress on neuroscience and behaviour. Abstracts; Anais do 13. Reuniao anual da Federacao de Sociedades de Biologia Experimental; 23. Congresso brasileiro de biofisica; 30. Congresso brasileiro de farmacologia e terapeutica experimental; 33. Congresso brasileiro de fisiologia; 14. Congresso brasileiro de investigacao clinica; 22. Congresso brasileiro de neurociencias e comportamento. Resumos

    Energy Technology Data Exchange (ETDEWEB)



    Several aspects concerning neuroscience and behavior, compared physiology, endocrinology, pharmacology, molecular immunology and immuno diagnosis, biochemistry, genetic and toxicology of either animals, plants and microorganisms are studied. Topics such as cell membrane structures (including receptors), enzymatic assays, biological pathways, structural chemical analysis, metabolism, biological functions, blood pressure regulation are focused. The use of radiolabelled compounds, e.g. radioassay, radioimmunoassay, radioreceptor assay, are the most applied techniques.

  6. [Subclinical hypothyroidism and cardiovascular risk]. (United States)

    López Rubio, María Antonia; Tárraga López, Pedro Juan; Rodríguez Montes, José Antonio; Frías López, María del Carmen; Solera Albero, Juan; Bermejo López, Pablo


    Objetivos: Valorar si el hipotiroidismo subclínico puede comportarse como un factor de riesgo cardiovascular o un modificador del mismo, identificando variables epidemiológicas y riesgo cardiovascular estimado en una muestra de sujetos diagnosticados en la provincia de Albacete. Método: Estudio observacional, descriptivo y transversal realizado en Albacete durante la primera quincena de enero de 2012 en pacientes de ambos géneros con hipotiroidismo subclínico. Se analizaron las siguientes variables: glucemia basal, colesterol total, colesterol HDL, colesterol LDL, triglicéridos, TSH, T4, peso, talla, I.M.C., tensión arterial, antecedentes de patología cardiovascular, factores de riesgo cardiovascular y riesgo cardiovascular estimado. Resultados: Se obtuvieron 326 pacientes, con predominio femenino (79,2 %), menores de 65 años en el 78% y sin factores de riesgo cardiovascular en el 48,61%. La prevalencia de los factores de riesgo cardiovascular identificados fué: tabaquismo (33,2%), diabetes mellitus (24,9%), hipertensión arterial (23,4%), alteraciones lipídicas (28,9%) y fibrilación auricular (4,9 %). No se encontró asociación entre hipotiroidismo subclínico y la mayoría de los parámetros del perfil lipídico que condicionan un perfil pro-aterogénico, salvo con la hipertrigliceridemia. Asimismo, tampoco se constató asociación con riesgo cardiovascular aumentado. Conclusiones: El perfil del paciente con hipotiroidismo subclínico es una mujer de mediana edad sin factores de riesgo cardiovascular en la mitad de casos. Se ha encontrado relación entre hipotiroidismo subclínico e hipertrigliceridemia, pero no con el resto de parámetros del perfil lipídico, otros factores de riesgo cardiovascular o con aumento de dicho riesgo. Sin embargo, un 25% de diabéticos y un 22% de no diabéticos están en situación de riesgo cardiovascular moderado-alto.

  7. Abstracts of the 10. Annual meeting of the Federation of the Experimental Biological Societies; Resumos da 10. Reuniao anual da Federacao de Sociedades de Biologia Experimental

    Energy Technology Data Exchange (ETDEWEB)



    The meeting was about experimental biology and it was discussed topics related to medicine, pharmacology, cellular biology, biophysics, toxicology, physiology, immunology, radiobiology, photobiology, natural products and environment.

  8. Exercise and the Cardiovascular System


    Saeid Golbidi; Ismail Laher


    There are alarming increases in the incidence of obesity, insulin resistance, type II diabetes, and cardiovascular disease. The risk of these diseases is significantly reduced by appropriate lifestyle modifications such as increased physical activity. However, the exact mechanisms by which exercise influences the development and progression of cardiovascular disease are unclear. In this paper we review some important exercise-induced changes in cardiac, vascular, and blood tissues and discuss...

  9. Stress and atherosclerotic cardiovascular disease. (United States)

    Inoue, Nobutaka


    Recent major advances in medical science have introduced a wide variety of treatments against atherosclerosis-based cardiovascular diseases, which has led to a significant reduction in mortality associated with these diseases. However, atherosclerosis-based cardiovascular disease remains a leading cause of death. Furthermore, progress in medical science has demonstrated the pathogenesis of cardiovascular disease to be complicated, with a wide variety of underlying factors. Among these factors, stress is thought to be pivotal. Several types of stress are involved in the development of cardiovascular disease, including oxidative stress, mental stress, hemodynamic stress and social stress. Accumulating evidence indicates that traditional risk factors for atherosclerosis, including diabetes, hyperlipidemia, hypertension and smoking, induce oxidative stress in the vasculature. Oxidative stress is implicated in the pathogenesis of endothelial dysfunction, atherogenesis, hypertension and remodeling of blood vessels. Meanwhile, mental stress is a well-known major contributor to the development of cardiovascular disease. The cardiovascular system is constantly exposed to hemodynamic stress by the blood flow and/or pulsation, and hemodynamic stress exerts profound effects on the biology of vascular cells and cardiomyocytes. In addition, social stress, such as that due to a lack of social support, poverty or living alone, has a negative impact on the incidence of cardiovascular disease. Furthermore, there are interactions between mental, oxidative and hemodynamic stress. The production of reactive oxygen species is increased under high levels of mental stress in close association with oxidative stress. These stress responses and their interactions play central roles in the pathogenesis of atherosclerosis-based cardiovascular disease. Accordingly, the pathophysiological and clinical implications of stress are discussed in this article.

  10. Vitamin D and Cardiovascular Disease


    Vivian Cristina Garcia; Lígia Araújo Martini


    Vitamin D insufficiency/deficiency has been observed worldwide at all stages of life. It has been characterized as a public health problem, since low concentrations of this vitamin have been linked to the pathogenesis of several chronic diseases. Several studies have suggested that vitamin D is involved in cardiovascular diseases and have provided evidence that it has a role in reducing cardiovascular disease risk. It may be involved in regulation of gene expression through the presence of vi...

  11. Vitamin D and Cardiovascular Disease


    Grübler, Martin R.; Martin Gaksch; Thomas Pieber; Katharina Kienreich; Nicolas Verheyen; Andreas Tomaschitz; Stefan Pilz


    Vitamin D deficiency, as well as cardiovascular diseases (CVD) and related risk factors are highly prevalent worldwide and frequently co-occur. Vitamin D has long been known to be an essential part of bone metabolism, although recent evidence suggests that vitamin D plays a key role in the pathophysiology of other diseases, including CVD, as well. In this review, we aim to summarize the most recent data on the involvement of vitamin D deficiency in the development of major cardiovascular risk...

  12. Adolescent vulnerability to cardiovascular consequences of chronic emotional stress: Review and perspectives for future research. (United States)

    Crestani, Carlos C


    Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. Adolescence has been proposed as a developmental period of vulnerability to stress. This idea has been mainly supported by experimental research in animals demonstrating a higher impact of chronic emotional stress in adolescents compared with adults. Adolescent vulnerability is also based on evidence that stress during this developmental period affects development, so that enduring changes are found in adult animals that experienced stress during adolescence. The purpose of the present review is to discuss experimental research in rodent models that investigated the impact of long-term exposure to stressful events during adolescence on cardiovascular function. The development of cardiovascular function and autonomic activity in rodents is initially reviewed. Then, a discussion of an adolescent vulnerability to cardiovascular effects of chronic stress is presented. From the reviewed literature, perspective for future research is proposed to better elucidate adolescent vulnerability to cardiovascular complications evoked by chronic emotional stress.

  13. [Air pollution and cardiovascular disease]. (United States)

    Haber, Guy; Witberg, Guy; Danenberg, Haim


    Cardiovascular atherothrombosis is the most common cause of death globally, with several well-known risk factors. Air pollution is a byproduct of fuel combustion by motor vehicles, power plants and industrial factories. It is composed of gases, fluids and particulate matter (PM) of different sizes, which include basic carbon, organic carbonic molecules and metals such as vanadium, nickel, zinc and iron. These particles are subdivided by their median size, a major contributing factor for their capability to enter the human body through the respiratory system. Most of the epidemiological studies have shown correlation between acute and long-term exposure to air pollution elements and cardiovascular morbidity in general, and angina pectoris and acute myocardial infarction specifically. Physiological studies have found different arrhythmias as the etiologic cause of cardiovascular morbidity and mortality following exposure to air pollution. A major finding was a decline in heart rate variability, a phenomenon known as endangering for cardiovascular morbidity and mortality, especially in patients after acute myocardial infarction. To date, several pathways have been proposed, including a hypercoagulable state following an inflammatory response, cardiac nervous autonomic disequilibrium, endothelial dysfunction with blood vessel contraction and direct toxic impact on cardiac muscle. Additional research is needed for clarifying the pathophysiological pathways by which air pollution affects the cardiovascular system. That might allow forthcoming with preventive measures and correct treatment, and hence a decrease in cardiovascular morbidity and mortality. Another important target is dose-outcome correlation curves for safety threshold calculation as a basis for air pollution regulations.

  14. Osteoporosis and ischemic cardiovascular disease. (United States)

    Laroche, Michel; Pécourneau, Virginie; Blain, Hubert; Breuil, Véronique; Chapurlat, Roland; Cortet, Bernard; Sutter, Bruno; Degboe, Yannick


    Osteoporosis and cardiovascular disease were long viewed as independent of each other. However, numerous epidemiological studies, which are discussed in the first part of this review, have provided incontrovertible evidence of a link. Thus, the risk of coronary artery disease and stroke is higher in patients with a history of osteoporotic fracture or low bone mineral density than in non-osteoporotic patients. In the other direction, patients with cardiovascular disease are at higher risk for bone loss and osteoporotic fracture. The link between osteoporosis and cardiovascular disease is due in part to shared conventional risk factors such as estrogen deprivation in women, smoking, low physical activity, and diabetes. In addition, atheroma plaque calcification involves cytokines and growth factors that also play a role in bone turnover, including proinflammatory cytokines (IL-6 and TNFα), osteoprotegerin, sclerostin, matrix GLA protein, and FGF-23. Several recent studies have provided support for these pathophysiological hypotheses. Thus, elevation of osteoprotegerin, sclerostin, or FGF-23 levels may explain and predict the occurrence of both osteoporotic fractures and cardiovascular events. The association between osteoporosis and cardiovascular disease found in most epidemiological and pathophysiological studies suggests a need for evaluating potential benefits from routine bone absorptiometry and osteoporotic fracture detection in patients with cardiovascular disease and from exercise testing and arterial Doppler imaging in patients with osteoporosis.

  15. CardioGenBase: A Literature Based Multi-Omics Database for Major Cardiovascular Diseases.

    Directory of Open Access Journals (Sweden)

    Alexandar V

    Full Text Available Cardiovascular diseases (CVDs account for high morbidity and mortality worldwide. Both, genetic and epigenetic factors are involved in the enumeration of various cardiovascular diseases. In recent years, a vast amount of multi-omics data are accumulated in the field of cardiovascular research, yet the understanding of key mechanistic aspects of CVDs remain uncovered. Hence, a comprehensive online resource tool is required to comprehend previous research findings and to draw novel methodology for understanding disease pathophysiology. Here, we have developed a literature-based database, CardioGenBase, collecting gene-disease association from Pubmed and MEDLINE. The database covers major cardiovascular diseases such as cerebrovascular disease, coronary artery disease (CAD, hypertensive heart disease, inflammatory heart disease, ischemic heart disease and rheumatic heart disease. It contains ~1,500 cardiovascular disease genes from ~2,4000 research articles. For each gene, literature evidence, ontology, pathways, single nucleotide polymorphism, protein-protein interaction network, normal gene expression, protein expressions in various body fluids and tissues are provided. In addition, tools like gene-disease association finder and gene expression finder are made available for the users with figures, tables, maps and venn diagram to fit their needs. To our knowledge, CardioGenBase is the only database to provide gene-disease association for above mentioned major cardiovascular diseases in a single portal. CardioGenBase is a vital online resource to support genome-wide analysis, genetic, epigenetic and pharmacological studies.

  16. The role of lipoprotein-associated phospholipase A2 (Lp-PLA₂) in cardiovascular disease. (United States)

    Ikonomidis, Ignatios; Michalakeas, Christos A; Lekakis, John; Parissis, John; Anastasiou-Nana, Maria


    Lipoprotein-associated Phospholipase A2 (Lp-PLA(2)) is an enzyme that belongs to the A2 Phospholipase superfamily and is produced by inflammatory cells that are involved in the process of atherogenesis. Even though there is controversy in current bibliography whether Lp-PLA(2) exerts proatherogenic or anti-atherogenic properties, the weight of evidence suggests a pro-atherogenic role for this protein. Lp-PLA(2) is detected in human atherosclerotic lesions and elevated Lp-PLA(2) levels are associated with an increased risk of cardiovascular events and adverse events in patients with coronary artery disease independently of traditional risk factors and other markers of inflammation. It has been recently shown that direct pharmacological inhibition of Lp-PLA(2) activity exerts beneficiary effects on the atherosclerotic process. This finding is most interesting since it could offer a novel target for therapeutic intervention in patients suffering from cardiovascular disease. The purpose of this review article is to report on the role of Lp-PLA(2) in cardiovascular diseases and to enlighten the putative pathophysiologic mechanisms by which this protein exerts its effect on cardiovascular function. Additionally, the pharmacological interventions that influence Lp-PLA(2) activity and may offer a new approach for the treatment of atherosclerosis will be analyzed.

  17. Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease. (United States)

    Gencel, V B; Benjamin, M M; Bahou, S N; Khalil, R A


    Phytoestrogens are estrogenic compounds of plant origin classified into different groups including isoflavones, lignans, coumestans and stilbenes. Isoflavones such as genistein and daidzein are the most studied and most potent phytoestrogens, and are found mainly in soy based foods. The effects of phytoestrogens are partly mediated via estrogen receptors (ERs): ERα, ERβ and possibly GPER. The interaction of phytoestrogens with ERs is thought to induce both genomic and non-genomic effects in many tissues including the vasculature. Some phytoestrogens such as genistein have additional non-ER-mediated effects involving signaling pathways such as tyrosine kinase. Experimental studies have shown beneficial effects of phytoestrogens on endothelial cells, vascular smooth muscle, and extracellular matrix. Phytoestrogens may also affect other pathophysiologic vascular processes such as lipid profile, angiogenesis, inflammation, tissue damage by reactive oxygen species, and these effects could delay the progression of atherosclerosis. As recent clinical trials showed no vascular benefits or even increased risk of cardiovascular disease (CVD) and CV events with conventional menopausal hormone therapy (MHT), phytoestrogens are being considered as alternatives to pharmacologic MHT. Epidemiological studies in the Far East population suggest that dietary intake of phytoestrogens may contribute to the decreased incidence of postmenopausal CVD and thromboembolic events. Also, the WHO-CARDIAC study supported that consumption of high soybean diet is associated with lower mortalities from coronary artery disease. However, as with estrogen, there has been some discrepancy between the experimental studies demonstrating the vascular benefits of phytoestrogens and the data from clinical trials. This is likely because the phytoestrogens clinical trials have been limited in many aspects including the number of participants enrolled, the clinical end points investigated, and the lack of

  18. Attitude, perception and feedback of second year medical students on teaching-learning methodology and evaluation methods in pharmacology: A questionnaire-based study

    Directory of Open Access Journals (Sweden)

    Uma A Bhosale


    Full Text Available Background: To assess the student′s attitude, perception and feedback on teaching-learning methodology and evaluation methods in pharmacology. Materials and Methods: One hundred and forty second year medical students studying at Smt. Kashibai Navale Medical College, Pune, were selected. They were administered a pre-validated questionnaire containing 22 questions. Suggestions were also asked regarding the qualities of good pharmacology teachers and modification in pharmacology teaching methods. Descriptive statistics were used and results were expressed as percentage. Results: Majority of the students found cardiovascular system (49.25% as the most interesting topic in pharmacology, whereas most of the students opined that cardiovascular system (60.10%, chemotherapy (54.06% and central nervous system (44.15% are going to be the most useful topics in internship. 48.53% students preferred clinical/patient-related pharmacology and 39.13% suggested use of audiovisual-aided lectures. Prescription writing and criticism of prescription were amongst the most useful and interesting in practical pharmacology. Students expressed interest in microteaching and problem-based learning, whereas seminars, demonstrations on manikin and museum studies were mentioned as good adjuvants to routine teaching. Multiple Choice Question (MCQ practice tests and theory viva at the end of a particular system and periodical written tests were mentioned as effective evaluation methods. Students were found to have lot of interest in gathering information on recent advances in pharmacology and suggested to include new drug information along with prototype drugs in a comparative manner. Conclusion: There is a need of conducting few microteaching sessions and more of clinical-oriented problem-based learning with MCQ-based revisions at the end of each class in the pharmacology teaching at undergraduate level.

  19. Non Pharmacological Cognitive Enhancers - Current Perspectives. (United States)

    Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh


    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

  20. PIXE microanalysis in human cells: physiology and pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Moretto, P.; Llabador, Y.; Ortega, R.; Simonoff, M.; Razafindrabe, L. (Centre d' Etudes Nucleaires Bordeaux/Gradignan, 33 - Gradignan (France))


    The micro-PIXE technique has been regularly carried out for more than two years to provide elemental distributions in human cells. Using this technique in the framework of cellular biology, two research axes have been developed: The cellular pharmacology of chemotherapeutic agents and the physiology of ionic cellular exchanges. These studies are based upon in vitro experimental models of human cells, either under the form of isolated cultured cells or as part of well-structured tissues. The aim of this paper is to present the experimental procedures and methodological aspects of cellular and subcellular quantitative mapping. Cell processing, identification of intracellular structures, quantitatives results and beam damage will be discussed and illustrated by examples issuing from the above-mentioned studies. (orig.).

  1. Cardiovascular Risk Factors and Cardiovascular Hyperreactivity in Young Venezuelans

    Directory of Open Access Journals (Sweden)

    Sady Montes Amador


    Full Text Available Background: cardiovascular hyperreactivity in young people has been associated with different risk factors and a family history of hypertension. Objective: to determine the association between a family history of hypertension and cardiovascular risk factors with cardiovascular hyperreactivity. Method: a correlational, cross-sectional study was conducted in a universe of 77 young individuals aged 18 to 40 years from the Churuguara parish of the Falcon State in Venezuela. The variables were: age, sex, skin color, family history of hypertension, medical history of hypertension, diabetes mellitus, alcohol consumption, salt intake, physical activity and body mass index. The diastolic and systolic blood pressure before and after the pressor response elicited by an isometric exercise were determined as hemodynamic variables. Results: thirteen percent of the participants developed vascular reactivity after the hand-held weight test. Cardiovascular hyperreactivity is three times higher in individuals with a family history of hypertension. Sixty percent of those with a body mass index greater than or equal to 27 kg/m2 are hyperreactive. There is a higher cardiovascular response to the hand-held weight test as the consumption of alcohol increases. Thirty three point three percent of the participants who smoke are hyperreactive. Conclusions: there is a significant association between a family history of hypertension, obesity, salt intake, alcohol consumption and vascular hyperreactivity.

  2. A review of the animal pharmacology of roxatidine acetate. (United States)

    Scholtholt, J; Bickel, M; Herling, A W


    Roxatidine acetate (TZU 0460/HOE 760) [N-(3-[3-(1-piperidinylmethyl)-phenoxy]-propyl)acetoxyacetamide hydrochloride] is a specific and competitive H2-receptor antagonist with a chemical structure different from those of cimetidine, ranitidine and famotidine. Roxatidine acetate and its main metabolite roxatidine inhibit histamine-induced gastric acid secretion in vitro with a potency greater than that of cimetidine, and in the range of that produced by ranitidine. Gastric acid secretion following stimulation with dibutyryl cyclic adenosine monophosphate remains unaffected by roxatidine acetate. In vivo experiments in rats and dogs confirm these in vitro findings. Thus, in rats roxatidine acetate inhibits gastric acid secretion with similar values following intraduodenal or intraperitoneal injection, indicating excellent absorption of the drug from the gastrointestinal tract. In all studies it was shown that roxatidine acetate was more potent than cimetidine. In rats single or repeated dosing with roxatidine acetate did not influence drug metabolising enzymes in the liver nor did the drug show antiandrogenic activity in long term animal studies. Extensive general pharmacological studies with roxatidine acetate demonstrate the lack of effects on the central nervous system, on gastrointestinal motility, the autonomic nervous system and the cardiovascular and urogenital systems. Studies on the pharmacokinetics and metabolism of roxatidine acetate demonstrate that there is a presystemic deacetylation producing the main metabolite roxatidine, which is responsible for the in vivo effects of the drug.

  3. Pharmacological management of metabolic syndrome and its lipid complications

    Directory of Open Access Journals (Sweden)

    T Binesh Marvasti


    Full Text Available Obesity epidemic has been spread all over the world in the past few decades and has caused a major public health concern due to its increasing global prevalence. Obese individuals are at higher risks of developing dyslipidemic characteristics resulting in increased triglyceride and LDL-cholesterol content and reduced HDL-cholesterol levels. This disorder has profound implications as afflicted individuals have been demonstrated to be at increased risk of development of hypertension, atherosclerosis, type 2 diabetes and cardiovascular diseases. Today, this phenotype is designated as metabolic syndrome. According to the criteria set by the International Diabetes Federation (IDF, for a patient to be diagnosed with metabolic syndrome, the person must have central obesity plus any two of the following conditions: raised TG, reduced HDL-cholesterol, raised blood pressure, and increased fasting plasma glucose. Current National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III guidelines for the treatment of patients with the metabolic syndrome encourage therapies that lower LDL cholesterol and TG and raise HDL-cholesterol. Primary intervention often involves treatment with statins to improve the lipid profiles of these patients. However, recent studies suggest the potential of newly identified drugs including thiazolidinediones, GLP-1 agonists, and DPP-4 inhibitors that seem to be promising in reducing the level of progression of metabolic syndrome related disorders. This review discusses the current pharmacological treatments of the metabolic syndrome with the above mentioned drugs.

  4. Pharmacological management of metabolic syndrome and its lipid complications. (United States)

    Binesh Marvasti, T; Adeli, Kh


    Obesity epidemic has been spread all over the world in the past few decades and has caused a major public health concern due to its increasing global prevalence. Obese individuals are at higher risks of developing dyslipidemic characteristics resulting in increased triglyceride and LDL-cholesterol content and reduced HDL-cholesterol levels. This disorder has profound implications as afflicted individuals have been demonstrated to be at increased risk of development of hypertension, atherosclerosis, type 2 diabetes and cardiovascular diseases. Today, this phenotype is designated as metabolic syndrome. According to the criteria set by the International Diabetes Federation (IDF), for a patient to be diagnosed with metabolic syndrome, the person must have central obesity plus any two of the following conditions: raised TG, reduced HDL-cholesterol, raised blood pressure, and increased fasting plasma glucose. Current National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines for the treatment of patients with the metabolic syndrome encourage therapies that lower LDL cholesterol and TG and raise HDL-cholesterol. Primary intervention often involves treatment with statins to improve the lipid profiles of these patients. However, recent studies suggest the potential of newly identified drugs including thiazolidinediones, GLP-1 agonists, and DPP-4 inhibitors that seem to be promising in reducing the level of progression of metabolic syndrome related disorders. This review discusses the current pharmacological treatments of the metabolic syndrome with the above mentioned drugs.


    Directory of Open Access Journals (Sweden)

    Jameel Mohd


    Full Text Available The usage of plants, plant extracts or plant-derived pure chemicals for disease management, become a therapeutic modality, which has stood the test of time. In the present review, we focus on pharmacological profile (in tabular form of Tribulus terrestris L., apart from Phytochemistry, Taxonomy and Traditional uses. Data were located, selected and extracted from SCI database, Medline, Pubmed, Highwire and Google Scholar. Fruits and seeds of Tribulus terrestris L., (Zygophyllaceae are of immense importance in oriental medicine because they are used as an aphrodisiac, diuretic and anthelmintic, as well as to treat coughs and kidney failure. Tribulus terrestris L. has reported to have antimicrobial, antihypertension, diuretic, antiacetylcholine, haemolytic activity, spermatogenesis and libido enhancer, antitumor activity and effects on cardiovascular system. Furostanol and spirostanol saponins, flavonoid glycosides, alkaloids, steroidal saponins named terrestrosins A, B, C, D and E, F-gitonis, gitnin and amides have been reported to occur in Tribulus terrestris L. Traditionally T. terrestris is used in folk medicine as a tonic, aphrodisiac, palliative, astringent, stomachic, antihypertensive, diuretic, lithon-triptic, cordial drug and urinary anti-infective. The ash of the whole plant is good for external application in rheumatic-arthritis.

  6. Safety pharmacology and genotoxicity evaluation of AVI-4658. (United States)

    Sazani, Peter; Weller, Doreen L; Shrewsbury, Stephen B


    Duchenne muscular dystrophy (DMD) is caused by dystrophin gene mutations. Restoration of dystrophin by exon skipping was demonstrated with the phosphorodiamidate morpholino oligomers (PMO) class of splice-switching oligomers, in both mouse and dog disease models. The authors report the results of Good Laboratory Practice-compliant safety pharmacology and genotoxicity evaluations of AVI-4658, a PMO under clinical evaluation for DMD. In cynomolgus monkeys, no test article-related effects were seen on cardiovascular, respiratory, global neurological, renal, or liver parameters at the maximum feasible dose (320 mg/kg). Genotoxicity battery showed that AVI-4658 has no genotoxic potential at up to 5000 microg/mL in an in vitro mammalian chromosome aberration test and a bacterial reverse mutation assay. In the mouse bone marrow erythrocyte micronucleus test, a single intravenous injection up to 2000 mg/kg was generally well tolerated and resulted in no mutagenic potential. These results allowed initiation of systemic clinical trials in DMD patients in the United Kingdom.

  7. Importance of cardiovascular disease risk management in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Lorber D


    Full Text Available Daniel Lorber Division of Endocrinology, New York Hospital Queens, Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA Abstract: Type 2 diabetes mellitus (T2DM is commonly accompanied by other cardiovascular disease (CVD risk factors, such as hypertension, obesity, and dyslipidemia. Furthermore, CVD is the most common cause of death in people with T2DM. It is therefore of critical importance to minimize the risk of macrovascular complications by carefully managing modifiable CVD risk factors in patients with T2DM. Therapeutic strategies should include lifestyle and pharmacological interventions targeting hyperglycemia, hypertension, dyslipidemia, obesity, cigarette smoking, physical inactivity, and prothrombotic factors. This article discusses the impact of modifying these CVD risk factors in the context of T2DM; the clinical evidence is summarized, and current guidelines are also discussed. The cardiovascular benefits of smoking cessation, increasing physical activity, and reducing low-density lipoprotein cholesterol and blood pressure are well established. For aspirin therapy, any cardiovascular benefits must be balanced against the associated bleeding risk, with current evidence supporting this strategy only in certain patients who are at increased CVD risk. Although overweight, obesity, and hyperglycemia are clearly associated with increased cardiovascular risk, the effect of their modification on this risk is less well defined by available clinical trial evidence. However, for glucose-lowering drugs, further evidence is expected from several ongoing cardiovascular outcome trials. Taken together, the evidence highlights the value of early intervention and targeting multiple risk factors with both lifestyle and pharmacological strategies to give the best chance of reducing macrovascular complications in the long term. Keywords: cardiovascular risk, hypertension, obesity, dyslipidemia

  8. Optimization of nanoparticles for cardiovascular tissue engineering (United States)

    Izadifar, Mohammad; Kelly, Michael E.; Haddadi, Azita; Chen, Xiongbiao


    Nano-particulate delivery systems have increasingly been playing important roles in cardiovascular tissue engineering. Properties of nanoparticles (e.g. size, polydispersity, loading capacity, zeta potential, morphology) are essential to system functions. Notably, these characteristics are regulated by fabrication variables, but in a complicated manner. This raises a great need to optimize fabrication process variables to ensure the desired nanoparticle characteristics. This paper presents a comprehensive experimental study on this matter, along with a novel method, the so-called Geno-Neural approach, to analyze, predict and optimize fabrication variables for desired nanoparticle characteristics. Specifically, ovalbumin was used as a protein model of growth factors used in cardiovascular tissue regeneration, and six fabrication variables were examined with regard to their influence on the characteristics of nanoparticles made from high molecular weight poly(lactide-co-glycolide). The six-factor five-level central composite rotatable design was applied to the conduction of experiments, and based on the experimental results, a geno-neural model was developed to determine the optimum fabrication conditions. For desired particle sizes of 150, 200, 250 and 300 nm, respectively, the optimum conditions to achieve the low polydispersity index, higher negative zeta potential and higher loading capacity were identified based on the developed geno-neural model and then evaluated experimentally. The experimental results revealed that the polymer and the external aqueous phase concentrations and their interactions with other fabrication variables were the most significant variables to affect the size, polydispersity index, zeta potential, loading capacity and initial burst release of the nanoparticles, while the electron microscopy images of the nanoparticles showed their spherical geometries with no sign of large pores or cracks on their surfaces. The release study revealed

  9. Association between the kinin-forming system and cardiovascular pathophysiology

    Institute of Scientific and Technical Information of China (English)

    Jagdish Narain Sharma


    All the components of the kallikrein-kinin system are located in the cardiac muscle, and its deficiency may lead to cardiac dysfunction. In recent years, numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischaemia, myocardial infarction and left ventricular hypertrophy, have suggested that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular -related diseases. The cardioprotective property of the angiotensin converting enzyme inhibitors is primarily mediated via kinin releasing pathway, which may cause regression of the left ventricular hypertrophy in hypertensive situations. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating hypertension, cardiovascular and renal diseases. In addition, stable kinin agonists may also be available in the future as therapeutic agents for cardiovascular and renal disorders.

  10. Override of spontaneous respiratory pattern generator reduces cardiovascular parasympathetic influence (United States)

    Patwardhan, A. R.; Vallurupalli, S.; Evans, J. M.; Bruce, E. N.; Knapp, C. F.


    We investigated the effects of voluntary control of breathing on autonomic function in cardiovascular regulation. Variability in heart rate was compared between 5 min of spontaneous and controlled breathing. During controlled breathing, for 5 min, subjects voluntarily reproduced their own spontaneous breathing pattern (both rate and volume on a breath-by-breath basis). With the use of this experimental design, we could unmask the effects of voluntary override of the spontaneous respiratory pattern generator on autonomic function in cardiovascular regulation without the confounding effects of altered respiratory pattern. Results from 10 subjects showed that during voluntary control of breathing, mean values of heart rate and blood pressure increased, whereas fractal and spectral powers in heart rate in the respiratory frequency region decreased. End-tidal PCO2 was similar during spontaneous and controlled breathing. These results indicate that the act of voluntary control of breathing decreases the influence of the vagal component, which is the principal parasympathetic influence in cardiovascular regulation.

  11. Recent Research Advances in Ivabradine and Its Cardiovascular Effects

    Institute of Scientific and Technical Information of China (English)

    Zhao GAO


    Elevated heart rate is a major risk factor for cardiovascular diseases. The inhibitor of funny current (Ⅰ (f)), a hyperpolarization-activated cyclic nucleotide-gated channel current, ivabradine is a new agent selectively reduc-ing heart rate devoid of other cardiovascular effects, which has come into the market in Europe for more than 3 years. It has been approved that pure heart rate reduction by ivabradine can improve myocardial ischemia, endothelial function and myocardial contractile function. Long-term administration will not increase all-cause mortality. Its therapeutic value in stable coronary artery disease has been verified in clinical practice, while in other fields of cardiovascular diseases still needs more evidence-based medical research. This article is a review about its recent research advances in experi-mental and clinical studies.

  12. Molecular pharmacology of human NMDA receptors

    DEFF Research Database (Denmark)

    Hedegaard, Maiken; Hansen, Kasper Bø; Andersen, Karen Toftegaard


    current knowledge of the relationship between NMDA receptor structure and function. We summarize studies on the biophysical properties of human NMDA receptors and compare these properties to those of rat orthologs. Finally, we provide a comprehensive pharmacological characterization that allows side......-by-side comparison of agonists, un-competitive antagonists, GluN2B-selective non-competitive antagonists, and GluN2C/D-selective modulators at recombinant human and rat NMDA receptors. The evaluation of biophysical properties and pharmacological probes acting at different sites on the receptor suggest...... that the binding sites and conformational changes leading to channel gating in response to agonist binding are highly conserved between human and rat NMDA receptors. In summary, the results of this study suggest that no major detectable differences exist in the pharmacological and functional properties of human...

  13. Neuroimmune pharmacology from a neuroscience perspective. (United States)

    Northrop, Nicole A; Northrup, Nicole A; Yamamoto, Bryan K


    The focus of this commentary is to describe how neuroscience, immunology, and pharmacology intersect and how interdisciplinary research involving these areas has expanded knowledge in the area of neuroscience, in particular. Examples are presented to illustrate that the brain can react to the peripheral immune system and possesses immune function and that resident immune molecules play a role in normal brain physiology. In addition, evidence is presented that the brain immune system plays an important role in mediating neurodegenerative diseases, the aging process, and neurodevelopment and synaptic plasticity. The identification of these mechanisms has been facilitated by pharmacological studies and has opened new possibilities for pharmacotherapeutic approaches to the treatment of brain disorders. The emerging field of neuroimmune pharmacology exemplifies this interdisciplinary approach and has facilitated the study of basic cellular and molecular events and disease states and opens avenues for novel therapies.

  14. Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications. (United States)

    Mir, Rafia; Karim, Sajjad; Kamal, Mohammad Amjad; Wilson, Cornelia M; Mirza, Zeenat


    Cone snails, also known as marine gastropods, from Conus genus produce in their venom a diverse range of small pharmacologically active structured peptides called conotoxins. The cone snail venoms are widely unexplored arsenal of toxins with therapeutic and pharmacological potential, making them a treasure trove of ligands and peptidic drug leads. Conotoxins are small disulfide bonded peptides, which act as remarkable selective inhibitors and modulators of ion channels (calcium, sodium, potassium), nicotinic acetylcholine receptors, noradrenaline transporters, N-methyl-D-aspartate receptors, and neurotensin receptors. They are highly potent and specific against several neuronal targets making them valuable as research tools, drug leads and even therapeutics. In this review, we discuss their gene superfamily classification, nomenclature, post-translational modification, structural framework, pharmacology and medical applications of the active conopeptides. We aim to give an overview of their structure and therapeutic potential. Understanding these aspects of conopeptides will help in designing more specific peptidic analogues.

  15. Pharmacological action and mechanisms of ginkgolide B

    Institute of Scientific and Technical Information of China (English)

    XIA Shi-hai; FANG Dian-chun


    Objective To review the recent research progress in pharmacological actions and mechanisms of ginkgolide B.Data sources Information included in this article was identified by searching of PUBMED (1987-2006) online resources using the key terms "ginkgolide B", "platelet activating factor", and "pharmacological".Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected.Results The key issues related to the pharmacological actions and mechanisms of ginkgolide B were summarized. The ginkgolide B possesses a number of beneficial effects such as anti-inflammatory, anti-allergic, antioxidant, and neuroprotective effects. Meantime, their mechaniams were discussed.Conclusions The Ginkgolide B is the most potent antagonist of platelet activating factor (PAF) and exhibits therapeutic action in a variety of diseases mainly by the PAF receptor.

  16. The role of food intake regulating peptides in cardiovascular regulation. (United States)

    Mikulášková, B; Maletínská, L; Zicha, J; Kuneš, J


    Obesity is a risk factor that worsens cardiovascular events leading to higher morbidity and mortality. However, the exact mechanisms of relation between obesity and cardiovascular events are unclear. Nevertheless, it has been demonstrated that pharmacological therapy for obesity has great potential to improve some cardiovascular problems. Therefore, it is important to determine the common mechanisms regulating both food intake and blood pressure. Several hormones produced by peripheral tissues work together with neuropeptides involved in the regulation of both food intake and blood pressure. Anorexigenic (food intake lowering) hormones such as leptin, glucagon-like peptide-1 and cholecystokinin cooperate with α-melanocyte-stimulating hormone, cocaine- and amphetamine-regulated peptide as well as prolactin-releasing peptide. Curiously their collective actions result in increased sympathetic activity, especially in the kidney, which could be one of the factors responsible for the blood pressure increases seen in obesity. On the other hand, orexigenic (food intake enhancing) peptides, especially ghrelin released from the stomach and acting in the brain, cooperates with orexins, neuropeptide Y, melanin-concentrating hormone and galanin, which leads to decreased sympathetic activity and blood pressure. This paradox should be intensively studied in the future. Moreover, it is important to know that the hypothalamus together with the brainstem seem to be major structures in the regulation of food intake and blood pressure. Thus, the above mentioned regions might be essential brain components in the transmission of peripheral signals to the central effects. In this short review, we summarize the current information on cardiovascular effects of food intake regulating peptides.

  17. Osteoporosis y enfermedad cardiovascular

    Directory of Open Access Journals (Sweden)

    Sarahí Mendoza


    Full Text Available Las enfermedades cardiovasculares (ECV y la osteoporosis son causas frecuentes de morbilidad en la población adulta, cuya frecuencia aumenta con la edad, por lo que al aumentar la expectativa de vida, constituyen importantes problemas de salud. El riesgo a padecer ambas patologías depende de factores de riesgo, y la prevención consiste en controlar los modificables. Las ECV y la osteoporosis presentan factores etiológicos comunes que involucran la biosíntesis del colesterol y la oxidación lipídica, cuya dilucidación representa una línea priorizada de investigación. El crecimiento y mantenimiento del esqueleto depende del equilibrio entre la formación y la resorción ósea a través de los procesos de modelado y remodelado óseo, controlados por células óseas (osteoblastos -OB-, osteoclastos -OC- y osteocitos, los OB son responsables de la formación ósea, los OC de la resorción ósea y los osteocitos de la red mecano sensorial. Entre los nexos de las ECV y la osteoporosis se encuentra el papel de la vía del mevalonato en la síntesis de colesterol y en la activación de OC, y el papel de los lípidos oxidados en el desarrollo de la aterosclerosis y en la transformación de las células precursoras de OB en adipocitos, disminuyendo la formación de OB activos y favoreciendo la osteoporosis. Ello justifica que sustancias hipolipemiantes y antioxidantes puedan ejercer efectos protectores sobre el hueso, y que la búsqueda de sustancias que actúen sobre ambos blancos sea un aspecto de interés en la prevención o el manejo de estas enfermedades.

  18. New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy

    Directory of Open Access Journals (Sweden)

    Betty Yuen Kwan Law


    Full Text Available Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM. For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri, Hu Zhang (Rhizoma polygoni cuspidati, Donglingcao (Rabdosia rubesens, Hou po (Cortex magnoliae officinalis and Chuan xiong (Rhizoma chuanxiong modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.

  19. Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders. (United States)

    Caliceti, Cristiana; Franco, Placido; Spinozzi, Silvia; Roda, Aldo; Cicero, Arrigo F G


    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids found in such plants as gender Berberis. Berberine is recognised to improve glucose and lipid metabolism disorders and preliminary clinical evidences suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases, suggesting a possible interesting role of berberine and its metabolites in clinical practice. However, its physicochemical properties, pharmacokinetic, and metabolism are not fully elucidated and contradictory data have been reported. This review provides a summary regarding the pharmacological and biological features of berberine, with a focus on berberine as well as their pharmacologically active metabolites and the different mechanisms underlying their activities in order to clarify the correct use of berberine supplementation, alone or in association with other nutraceuticals, for the management of metabolic disorders associated to increased cardiovascular disease risk. A particular attention has also been given to the available clinical trials assessing its short- and middle- term use tolerability, safety and efficacy in various conditions, such as dyslipidaemia, impaired fasting glucose, metabolic syndrome and type 2 diabetes.


    Directory of Open Access Journals (Sweden)

    Das Chandan


    Full Text Available Cassia tora, a popular Indian medicinal plant, has long been used in Ayurvedic system of medicine. The plant has been found to possess diverse number of pharmacological activities. The present paper gives an account of updated information on its phytochemical and pharmacological activities. The review reveals that wide range of phytochemical constituents have been isolated from the plant and it possess important activities like laxative, skin diseases, ringworm, eye diseases, liver complaint, dysentery and anthelmentic. Various other activities like antioxidant, hypoglycemic, hypolipidemic, antinociceptive, antiplasmodial, antifungal & antimicrobial, hyperlipemia & hypotensive have also been reported. These reports are very encouraging and indicate that herb should be studied more extensively for its therapeutic benefits.

  1. The pharmacological treatment of nystagmus: a review. (United States)

    McLean, Rebecca Jane; Gottlob, Irene


    Nystagmus is an involuntary, to-and-fro movement of the eyes that can result in a reduction in visual acuity and oscillopsia. Mechanisms that cause nystagmus are better understood in some forms, such as acquired periodic alternating nystagmus, than in others, for example acquired pendular nystagmus, for which there is limited knowledge. Effective pharmacological treatment exists to reduce nystagmus, particularly in acquired nystagmus and, more recently, infantile nystagmus. However, as there are very few randomized controlled trials in the area, most pharmacological treatment options in nystagmus remain empirical.


    Directory of Open Access Journals (Sweden)

    A. Krishnaveni


    Full Text Available Herbal medicines are the significant and reliable sources for treating various diseases. Argyreia nervosa is traditionally used in wound healing, syphilius,diuretics,rheumatic affections, leucohorrhoea.,cerebral disorders, ulcers, as anti-tumour and to prevent contraception.Phytoconstituents such as flavanoids, steroids, ergoline alkaloids and triterpenoids were identified. Pharmacological studies proved its anticonvulsant, immunomodulatory, hypotensive, anti- inflammatory and nootropic effect.The present form of article highlights the phytochemical and pharmacological studies including traditional practice of Argyreia nervosa have been carried out so far.

  3. Quantum biology and quantum pharmacology: proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Loewdin, P.O.; Oehrn, N.Y.; Sabin, J.R.; Zerner, M.C.


    The 25th Sanibel Symposia, which included the 12th meeting of the Symposium on Quantum Biology and Quantum Pharmacology, was held at the University of Florida Whitney Laboratory at Marineland on the Atlantic Coast of Florida, March 14-23, 1985. The three days (March 14-16) devoted to Quantum Biology and Quantum Pharmacology saw the presentation of more than 50 papers by the 90 participants representing about 20 different nations. These ''Proceedings'' comprise the contributions in both the invited talks and the poster sessions.

  4. The inflammatory protein Pentraxin 3 in cardiovascular disease. (United States)

    Fornai, Francesco; Carrizzo, Albino; Forte, Maurizio; Ambrosio, Mariateresa; Damato, Antonio; Ferrucci, Michela; Biagioni, Francesca; Busceti, Carla; Puca, Annibale A; Vecchione, Carmine


    The acute phase protein Pentraxin 3 (PTX3) plays a non-redundant role as a soluble pattern recognition receptor for selected pathogens and it represents a rapid biomarker for primary local activation of innate immunity and inflammation. Recent evidence indicates that PTX3 exerts an important role in modulating the cardiovascular system in humans and experimental models. In particular, there are conflicting points concerning the effects of PTX3 in cardiovascular diseases (CVD) since several observations indicate a cardiovascular protective effect of PTX3 while others speculate that the increased plasma levels of PTX3 in subjects with CVD correlate with disease severity and with poor prognosis in elderly patients. In the present review, we discuss the multifaceted effects of PTX3 on the cardiovascular system focusing on its involvement in atherosclerosis, endothelial function, hypertension, myocardial infarction and angiogenesis. This may help to explain how the specific modulation of PTX3 such as the use of different dosing, time, and target organs could help to contain different vascular diseases. These opposite actions of PTX3 will be emphasized concerning the modulation of cardiovascular system where potential therapeutic implications of PTX3 in humans are discussed.

  5. Vitamin D and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Martin R. Grübler


    Full Text Available Vitamin D deficiency, as well as cardiovascular diseases (CVD and related risk factors are highly prevalent worldwide and frequently co-occur. Vitamin D has long been known to be an essential part of bone metabolism, although recent evidence suggests that vitamin D plays a key role in the pathophysiology of other diseases, including CVD, as well. In this review, we aim to summarize the most recent data on the involvement of vitamin D deficiency in the development of major cardiovascular risk factors: hypertension, obesity and dyslipidemia, type 2 diabetes, chronic kidney disease and endothelial dysfunction. In addition, we outline the most recent observational, as well as interventional data on the influence of vitamin D on CVD. Since it is still an unresolved issue whether vitamin D deficiency is causally involved in the pathogenesis of CVD, data from randomized controlled trials (RCTs designed to assess the impact of vitamin D supplementation on cardiovascular outcomes are awaited with anticipation. At present, we can only conclude that vitamin D deficiency is an independent cardiovascular risk factor, but whether vitamin D supplementation can significantly improve cardiovascular outcomes is still largely unknown.

  6. [Iodine deficiency in cardiovascular diseases]. (United States)

    Molnár, I; Magyari, M; Stief, L


    The thyroid hormone deficiency on cardiovascular function can be characterized with decreased myocardial contractility and increased peripheral vascular resistance as well as with the changes in lipid metabolism. 42 patients with cardiovascular disease (mean age 65 +/- 13 yr, 16 males) were investigated if iodine insufficiency can play a role as a risk factor for the cardiovascular diseases. The patients were divided in 5 subgroups on the ground of the presence of hypertension, congestive heart failure, cardiomyopathy, coronary disfunction and arrhythmia. Urine iodine concentration (5.29 +/- 4.52 micrograms/dl) was detected with Sandell-Kolthoff colorimetric reaction. The most decreased urine iodine concentration was detected in the subgroups with arrhythmia and congestive heart failure (4.7 +/- 4.94 micrograms/dl and 4.9 +/- 4.81 micrograms/dl, respectively). An elevated TSH level was found by 3 patients (5.3 +/- 1.4 mlU/l). An elevation in lipid metabolism (cholesterol, triglyceride) associated with all subgroups without arrhythmia. In conclusion, the occurrence of iodine deficiency in cardiovascular disease is frequent. Iodine supplementation might prevent the worsing effect of iodine deficiency on cardiovascular disease.

  7. A clinical approach to obstructive sleep apnea as a risk factor for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Maeder MT


    Full Text Available Micha T Maeder,1 Otto D Schoch,2 Hans Rickli1 1Department of Cardiology, 2Department of Respiratory Medicine, Kantonsspital St Gallen, St Gallen, Switzerland Abstract: Obstructive sleep apnea (OSA is associated with cardiovascular risk factors, cardiovascular diseases, and increased mortality. Epidemiological studies have established these associations, and there are now numerous experimental and clinical studies which have provided information on the possible underlying mechanisms. Mechanistic proof-of-concept studies with surrogate endpoints have been performed to demonstrate that treatment of OSA by continuous positive airway pressure (CPAP has the potential to reverse or at least to attenuate not only OSA but also the adverse cardiovascular effects associated with OSA. However, no randomized studies have been performed to demonstrate that treatment of OSA by CPAP improves clinical outcomes in patients with cardiovascular risk factors and/or established cardiovascular disease and concomitant OSA. In the present review, we summarize the current knowledge on the role of OSA as a potential cardiovascular risk factor, the impact of OSA on cardiac function, the role of OSA as a modifier of the course of cardiovascular diseases such as coronary artery disease, atrial fibrillation, and heart failure, and the insights from studies evaluating the impact of CPAP therapy on the cardiovascular features associated with OSA. Keywords: obstructive sleep apnea, cardiovascular, risk, heart failure, atrial fibrillation, hypertension

  8. Alternative Radioligands for Investigating the Molecular Pharmacology of Melatonin Receptors. (United States)

    Legros, Céline; Brasseur, Chantal; Delagrange, Philippe; Ducrot, Pierre; Nosjean, Olivier; Boutin, Jean A


    Melatonin exerts a variety of physiologic activities that are mainly relayed through the melatonin receptors MT1 and MT2 Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[(125)I]-iodomelatonin as a substitute for melatonin. We describe three iodinated ligands: 2-(2-[(2-iodo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) (DIV880) and (2-iodo-N-2-[5-methoxy-2-(naphthalen-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-yl])acetamide (S70254), which are specific ligands at MT2 receptors, and N-[2-(5-methoxy-1H-indol-3-yl)ethyl]iodoacetamide (SD6), an analog of 2-[(125)I]-iodomelatonin with slightly different characteristics. Here, we further characterized these new ligands with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements, and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [(125)I]-S70254 is receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist [43% of melatonin on guanosine 5'-3-O-(thio)triphosphate binding assay], selective for MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissue samples. The molecular pharmacology of both human melatonin receptors MT1 and MT2, using a series of 24 ligands at these receptors and the new radioligands, did not lead to noticeable variations in the profiles. For the first time, we described radiolabeled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit better understanding of the role and implication in physiopathologic processes of the melatonin receptors.

  9. The cardiovascular action of hexarelin

    Institute of Scientific and Technical Information of China (English)

    wYuanjie MAO; Takeshi Tokudome; Ichiro Kishimoto


    Hexarelin, a synthetic growth hormone-releasing peptide, can bind to and activate the growth hormone secretagogue receptor (GHSR) in the brain similar to its natural analog ghrelin. However, the peripheral distribution of GHSR in the heart and blood vessels suggests that hexarelin might have direct cardiovascular actions beyond growth hormone release and neuroendocrine effects. Furthermore, the non-GHSR CD36 had been demonstrated to be a specific cardiac receptor for hexarelin and to mediate its cardioprotective effects. When compared with ghrelin, hexarelin is chemically more stable and functionally more potent. Therefore, it may be a promising therapeutic agent for some car-diovascular conditions. In this concise review, we discuss the current evidence for the cardiovascular action of hexarelin.

  10. Electrocardiographic Predictors of Cardiovascular Mortality

    Directory of Open Access Journals (Sweden)

    Ioana Mozos


    Full Text Available Cardiovascular diseases are the main causes of mortality. Sudden cardiac death may also appear in athletes, due to underlying congenital or inherited cardiac abnormalities. The electrocardiogram is used in clinical practice and clinical trials, as a valid, reliable, accessible, inexpensive method. The aim of the present paper was to review electrocardiographic (ECG signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. The main ECG parameters associated with cardiovascular mortality in the present paper are the P wave (duration, interatrial block, and deep terminal negativity of the P wave in V1, prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, T waves (inverted, T wave axes, spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria.

  11. Cardiovascular risks of antiretroviral therapies. (United States)

    Mondy, Kristin; Tebas, Pablo


    The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.

  12. Social factors and cardiovascular morbidity. (United States)

    Brunner, Eric John


    Recent progress in population health at aggregate level, measured by life expectancy, has been accompanied by lack of progress in reducing the difference in health prospects between groups defined by social status. Cardiovascular disease is an important contributor to this undesirable situation. The stepwise gradient of higher risk with lower status is accounted for partly by social gradients in health behaviors. The psychosocial hypothesis provides a stronger explanation, based on social patterning of living and working environments and psychological assets that individuals develop during childhood. Three decades of research based on Whitehall II and other cohort studies provide evidence for psychosocial pathways leading to cardiovascular morbidity and mortality. Job stress is a useful paradigm because exposure is long term and depends on occupational status. Studies of social-biological translation implicate autonomic and neuroendocrine function among the biological systems that mediate between chronic adverse psychosocial exposures and increased cardiometabolic risk and cardiovascular disease incidence.

  13. [Cardiovascular manifestations of human toxocariasis]. (United States)

    Bolívar-Mejía, Adrián; Rodríguez-Morales, Alfonso J; Paniz-Mondolfi, Alberto E; Delgado, Olinda


    Toxocariasis is a parasitic infection produced by helminths that cannot reach their adult stage in humans. For their etiological species (Toxocara canis and Toxocara cati), man is a paratenic host. Infection by such helminths can produce a variety of clinical manifestations, such as: visceral larvae migrans syndrome, ocular larvae migrans syndrome and covert toxocariasis. In the visceral larvae migrans syndrome, the organs that are mainly involved include liver, lungs, skin, nervous system, muscles, kidneys and the heart. Regarding the latter, the importance of cardiovascular manifestations in toxocariasis, as well as its clinical relevance, has increasingly begun to be recognized. The current article is based on a systematic information search, focused mainly on the clinical and pathological aspects of cardiovascular manifestations in toxocariasis, including its pathophysiology, laboratory findings, diagnosis and therapeutical options, with the objective of highlighting its importance as a zoonosis and its relevance to the fields of cardiovascular medicine in adults and children.

  14. Does caffeine affect cardiovascular responses?

    NARCIS (Netherlands)

    S. Bradamante; L. Barenghi (Livia); S. Versari (Silvia); A. Villa (Alessandro); J.W. de Jong (Jan Willem)


    textabstractCaffeine (1,3,7-trimethylxanthine), a natural alkaloid present in many beverages such as coffee, tea and cola drinks, is the most widely consumed pharmacological compound. Due to its common use and frequent intake in stressful conditions, a great deal of data have been produced by epidem

  15. Therapy of Fabry disease with pharmacological chaperones: from in silico predictions to in vitro tests

    Directory of Open Access Journals (Sweden)

    Cammisa Marco


    Full Text Available Abstract Background Fabry disease is a rare disorder caused by a large variety of mutations in the gene encoding lysosomal alpha-galactosidase. Many of these mutations are unique to individual families. Fabry disease can be treated with enzyme replacement therapy, but a promising novel strategy relies on small molecules, so called "pharmacological chaperones", which can be administered orally. Unfortunately only 42% of genotypes respond to pharmacological chaperones. Results A procedure to predict which genotypes responsive to pharmacological chaperones in Fabry disease has been recently proposed. The method uses a position-specific substitution matrix to score the mutations. Using this method, we have screened public databases for predictable responsive cases and selected nine representative mutations as yet untested with pharmacological chaperones. Mutant lysosomal alpha galactosidases were produced by site directed mutagenesis and expressed in mammalian cells. Seven out of nine mutations responded to pharmacological chaperones. Nineteen other mutations that were tested with pharmacological chaperones, but were not included in the training of the predictive method, were gathered from literature and analyzed in silico. In this set all five mutations predicted to be positive were responsive to pharmacological chaperones, bringing the percentage of responsive mutations among those predicted to be positive and not used to train the classifier to 86% (12/14. This figure differs significantly from the percentage of responsive cases observed among all the Fabry mutants tested so far. Conclusions In this paper we provide experimental support to an "in silico" method designed to predict missense mutations in the gene encoding lysosomal alpha galactosidase responsive to pharmacological chaperones. We demonstrated that responsive mutations can be predicted with a low percentage of false positive cases. Most of the mutations tested to validate the method

  16. Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome.

    Directory of Open Access Journals (Sweden)

    Victoria Campuzano


    Full Text Available A hallmark feature of Williams-Beuren Syndrome (WBS is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH-oxidase (NOX-mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated with elevated angiotensin II (angII, oxidative stress parameters, and Ncf1 expression. Genetic (by crossing with Ncf1 mutant and/or pharmacological (with ang II type 1 receptor blocker, losartan, or NOX inhibitor apocynin reduction of NOX activity controlled hormonal and biochemical parameters in DD mice, resulting in normalized blood pressure and improved cardiovascular histology. We provide strong evidence for implication of the redox system in the pathophysiology of the cardiovascular disease in a mouse model of WBS. The phenotype of these mice can be ameliorated by either genetic or pharmacological intervention reducing NOX activity, likely through reduced angII-mediated oxidative stress. Therefore, anti-NOX therapy merits evaluation to prevent the potentially serious cardiovascular complications of WBS, as well as in other cardiovascular disorders mediated by similar pathogenic mechanism.

  17. Molecular Pharmacology of CXCR4 inhibition

    DEFF Research Database (Denmark)

    Steen, Anne; Rosenkilde, Mette Marie


    pharmacology of well-known CXCR4 antagonists in order to augment the potency and affinity and to increase the specificity of future CXCR4-targeting compounds. In this chapter, binding modes of CXCR4 antagonists that have been shown to mobilize stem cells are discussed. In addition, comparisons between results...

  18. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou


    Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  19. Investigational pharmacology for low back pain

    Directory of Open Access Journals (Sweden)

    Avinash K Bhandary


    Full Text Available Avinash K Bhandary1 , Gary P Chimes2, Gerard A Malanga3 1Department of Physical Medicine and Rehabilitation, 2Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 3New Jersey Sports Medicine Institute; Overlook Hospital; Mountainside Hospital; Rehabilitation Medicine and Electrodiagnosis, St Michael’s Medical Center; Horizon Healthcare Worker’s Compensation Services, Blue Cross and Blue Shield Worker’s Compensation, Summit, NJ, USAStudy design: Review and reinterpretation of existing literature.Objective: This review article summarizes the anatomy and pathogenesis of disease processes that contribute to low back pain, and discusses key issues in existing therapies for chronic low back pain. The article also explains the scientific rationale for investigational pharmacology and highlights emerging compounds in late development.Results/conclusion: While the diverse and complex nature of chronic low back pain continues to challenge clinicians, a growing understanding of chronic low back pain on a cellular level has refined our approach to managing chronic low back pain with pharmacology. Many emerging therapies with improved safety profiles are currently in the research pipeline and will contribute to a multimodal therapeutic algorithm in the near future. With the heterogeneity of the patient population suffering from chronic low back pain, the clinical challenge will be accurately stratifying the optimal pharmacologic approach for each patient.Keywords: low back pain, investigational, pharmacology, drugs

  20. Pharmacological interventions for phantom limb pain

    Institute of Scientific and Technical Information of China (English)

    FANG Jun; LIAN Yan-hong; XIE Kang-jie; CAI Shu-nü


    Objective To review the mechanisms and current clinical application of pharmacological interventions for phantom limb pain.Data sources Both Chinese and English language literatures were searched using MEDLINE (1982-2011),Pubmed (1982-2011) and the Index of Chinese Language Literature (1982-2011).Study selection Data from published articles about pharmacological management of phantom limb pain in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 96 articles which are listed in the reference section of this review.Results By reviewing the mechanisms and current clinical application of pharmacological interventions for phantom limb pain,including anticonvulsants,antidepressants,local anaesthetics,N-methyl-D-aspartate receptor antagonists,non-steroidal anti-inflammatory drugs,tramadol,opioids,calcitonin,capsaicin,beta-adrenergic blockers,clonidine,muscle relaxants,and emerging drugs,we examined the efficacy and safety of these medications,outlined the limitations and future directions.Conclusions Although there is lack of evidence-based consensus guidelines for the pharmacological management of phantom limb pain,we recommend tricyclic antidepressants,gabapentin,tramadol,opioids,local anaesthetics and N-methyl-D-aspartate receptor antagonists as the rational options for the treatment of phantom limb pain.

  1. New approaches to pharmacological treatment of osteoporosis. (United States)

    Akesson, Kristina


    Osteoporosis has been recognized as a major public health problem for less than two decades. The increasing incidence of fragility fractures, such as vertebral, hip, and wrist fractures, first became apparent from epidemiological studies in the early and mid-1980s, when effective treatment was virtually unavailable. Pharmacological therapies that effectively reduce the number of fractures by improving bone mass are now available widely in countries around the world. Most current agents inhibit bone loss by reducing bone resorption, but emerging therapies may increase bone mass by directly promoting bone formation--as is the case with parathyroid hormone. Current treatment alternatives include bisphosphonates, calcitonin, and selective estrogen receptor modulators, but sufficient calcium and vitamin D are a prerequisite. The availability of evidence-based data that show reductions in the incidence of fractures of 30-50% during treatment has been a major step forward in the pharmacological prevention of fractures. With all agents, fracture reduction is most pronounced for vertebral fracture in high-risk individuals; alendronate and risedronate also may protect against hip fracture in the elderly. New approaches to pharmacological treatment will include further development of existing drugs, especially with regard to tolerance and frequency of dosing. New avenues for targeting the condition will emerge as our knowledge of the regulatory mechanisms of bone remodelling increases, although issues of tissue specificity may be difficult to solve. In the long term, information gained through knowledge of bone genetics may be used to adapt pharmacological treatments more precisely to each individual.

  2. The Early Development of Pharmacology in America. (United States)

    Parascandola, John

    Presented is a review of the development of the science of pharmacology, the study of the interaction of chemical agents with living matter. The origins of the field are traced from 17th century Europe to the present, with major emphasis upon the scientists and developments made in the field in the United States. (SL)

  3. Radioreceptor assay: theory and applications to pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Perret, G. (U.E.R. de Medecine, Sante et Biologie Humaine, 93 - Bobigny (France)); Simon, P. (Faculte de Medecine Pitie-Salpetriere, 75 - Paris (France))

    The aim of the first part of this work is to present the theory of the radioreceptor assay and to compare it to the other techniques of radioanalysis (radioimmunoassay, competitive protein binding assays). The technology of the radioreceptor assay is then presented and its components (preparation of the receptors, radioligand, incubation medium) are described. The analytical characteristics of the radioreceptor assay (specificity, sensitivity, reproductibility, accuracy) and the pharmacological significance of the results are discussed. The second part is devoted to the description of the radioreceptor assays of some pharmacological classes (neuroleptics, tricyclic antidepressants, benzodiazepines, ..beta..-blockers, anticholinergic drugs) and to their use in therapeutic drug monitoring. In conclusion, by their nature, radioreceptor assays are highly sensitive, reliable, precise, accurate and simple to perform. Their chief disadvantage relates to specificity, since any substance having an appreciable affinity to the receptor site will displace the specifically bound radioligand. Paradoxically in some cases, this lack of specificity may be advantageous in that it allows for the detection of not only the apparent compound but of active metabolites and endogenous receptor agonists as well and in that radioreceptors assays can be devised for a whole pharmacological class and not only for one drug as it is the case for classical physico-chemical techniques. For all these reasons future of radioreceptor assay in pharmacology appears promising.

  4. Myocardial ATP catabolism and its pharmacological prevention

    NARCIS (Netherlands)

    T. Huizer (Tom)


    textabstractThis thesis deals with high-energy phosphate metabolism during myocardial ischemia. describes the effects of some pharmacological interventions on the energy metabolism of ischemic myocardium. The chapters of this thesis are based on 11 published papers, added as appendices.

  5. Intestinal Microbiota and Metabolic Diseases: Pharmacological Implications. (United States)

    Shen, Liang; Ji, Hong-Fang


    An increasing number of studies show that alterations in intestinal microbiota are linked with metabolic diseases. Here, we propose that intestinal microbiota regulation by polyphenols may be an important mechanism underlying their therapeutic benefits for metabolic diseases. This helps elucidate the intriguing pharmacology of polyphenols and optimize the treatment of metabolic diseases.

  6. New pharmacological strategies in chronic heart failure

    NARCIS (Netherlands)

    van de Wal, RMA; Voors, AA; Plokker, HWM; van Gilst, WH; van Veldhuisen, DJ


    Diuretics, ACE inhibitors and betablockers form the cornerstone of pharmacological treatment of chronic heart failure (CHF), while angiotensin receptor blockers are gaining ground. However, despite optimal treatment CHF remains a syndrome with poor prognosis. For this reason, a large number of new a

  7. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.


    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The major

  8. Pharmacological Treatment Effects on Eye Movement Control (United States)

    Reilly, James L.; Lencer, Rebekka; Bishop, Jeffrey R.; Keedy, Sarah; Sweeney, John A.


    The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to…

  9. Pharmacological management of spasticity in multiple sclerosis

    DEFF Research Database (Denmark)

    Otero-Romero, Susana; Sastre-Garriga, Jaume; Comi, Giancarlo


    BACKGROUND AND OBJECTIVES: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. METHODS...

  10. The role of pharmacology in pediatric oncology

    Energy Technology Data Exchange (ETDEWEB)

    Poplack, D.G.; Massimo, L.; Cornaglia-Ferraris, P


    This book contains 25 chapters. Some of the Titles are: Genetic reasons for pharmacologic treatment failure: gene amplification; New approaches to overcome drug resistance; An overview of adverse late effects of cancer chemotherapy in children; the development of 9-substituted purines as immunomodulators; and High dose cisplatinum: a phase II study.

  11. Systems Pharmacology in Small Molecular Drug Discovery (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge


    Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level. PMID:26901192

  12. History of clinical pharmacy and clinical pharmacology. (United States)

    Miller, R R


    The purpose of the Symposium on Clinical Pharmacy and Clinical Pharmacology is to describe the present and future functional roles of clinical pharmacists and clinical pharmacologists in drug research, professional education, and patient care. Clinical pharmacy is a relatively new professional discipline, being only about 15 years old. This new breed of pharmacists is patient rather than drug product oriented. The discipline arose out of dissatisfaction with old practice norms and the pressing need for a health professional with a comprehensive knowledge of the therapeutic use of drugs. The clinical pharmacy movement began at the University of Michigan in the early 1960s, but much of the pioneering work was done by David Burkholder, Paul Parker, and Charles Walton at the University of Kentucky in the latter part of the 1960s. Clinical pharmacology is a professional discipline that combines basic pharmacology and clinical medicine. Its development began in the early 1950s, primarily as a result of the efforts of Harry Gold. It has had a slower growth than clinical pharmacy but it has made many important contributions to our knowledge of human pharmacology and the rational use of drugs.

  13. 中药血清药理学研究进展%Advances of Serum Pharmacology of Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    黄臣虎; 陆茵; 高骁君; 孙志广; 严令耕


    运用中药血清药理学方法研究中药复方的药效、物质基础及作用机制.通过对中药血清药理方法学中对实验动物、给药剂量和给药方案、采血方案、血清灭活与保存、血清添加量和对照组的设立等的确立,建立最佳的实验方案进行研究.文献检索研究表明,中药复方对神经系统有调节作用,能保护心肌细胞,促进血管内皮细胞增殖,预防哮喘,增强免疫,抗菌抗炎抗病毒.抗纤维化并能延缓糖尿病肾病的发展.中药血清药理学在神经、心血管、呼吸、免疫、消化、生殖、泌尿、骨骼系统以及在抗菌、抗炎、抗肿瘤、抗病毒等方面都有很好的应用,为中药复方药理作用的研究提供了良好的方法.%Use the methods of serum pharmacology of Chinese medicine study the potency, material base,action mechanism of the compound traditional Chinese medicine. Chose the best experimental scheme by the chosen of animals, administration dosage, dosage regimen, blood sampling regime, control group establishment,inactivation, storage and addition quantity of serum. Compound traditional Chinese medicine can regulate nervous system, protect myocardial cells, promote the proliferation of vascular endothelial cells, prevent asthma, enhance immune, antibacterial, anti-inflammatory, antivirus, anti-fibrosis and delay the development of diabetic nephropathy. Serum pharmacology of Chinese medicine have good application in nervous system, cardiovascular system, respiratory system, immune system, digestive system, reproductive system, urinary system, skeletal system, anti-inflammatory, antivirus and anti-fibrosis etc, which can provide a good method for the compound traditional Chinese medicine research.

  14. A Web-based e-learning course: integration of pathophysiology into pharmacology. (United States)

    Tse, Mimi M Y; Lo, Lisa W L


    The Internet is becoming the preferred place to find information. Millions of people go online in search of health and medical information. Likewise, the demand for Web-based courses is growing. This paper presents the development, utilization, and evaluation of a Web-based e-learning course for nursing students, entitled Integration of Pathophysiology into Pharmacology. The pathophysiology component included cardiovascular, respiratory, central nervous and immune system diseases, while the pharmacology component was developed based on 150 commonly used drugs. One hundred and nineteen Year 1 nursing students took part in the course. The Web-based e-learning course materials were uploaded to a WebCT for students' self-directed learning and attempts to pass two scheduled online quizzes. At the end of the semester, students were given a questionnaire to measure the e-learning experience. Their experience in the e-learning course was a positive one. Students stated that they were able to understand rather than memorize the subject content, and develop their problem solving and critical thinking abilities. Online quizzes yielded satisfactory results. In the focus group interview, students indicated that they appreciated the time flexibility and convenience associated with Web-based learning, and also made good suggestions for enhancing Web-based learning. The Web-based approach is promising for teaching and learning pathophysiology and pharmacology for nurses and other healthcare professionals.

  15. [Advances in research of chemical constituents and pharmacological activities of common used spices]. (United States)

    Sun, Chao-nan; Zhu, Yuan; Xu, Xi-ming; Yu, Jiang-nan


    Spices have enjoyed a long history and a worldwide application. Of particular interest is the pharmaceutical value of spices in addition to its basic seasoning function in cooking. Concretely, equipped with complex chemical compositions, spices are of significant importance in pharmacologic actions, like antioxidant, antibacterial, antitumor, as well as therapeutical effects in gastrointestinal disorders and cardiovascular disease. Although increasing evidences in support of its distinct role in the medical field has recently reported, little information is available for substantive, thorough and sophisticated researches on its chemical constituents and pharmacological activities, especially mechanism of these actions. Therefore, in popular wave of studies directed at a single spice, this review presents systematic studies on the chemical constituents and pharmacological activities associated with common used spices, together with current typical individual studies on functional mechanism, in order to pave the way for the exploitation and development of new medicines derived from the chemical compounds of spice (such as, piperine, curcumin, geniposide, cinnamaldehyde, cinnamic acid, linalool, estragole, perillaldehyde, syringic acid, crocin).

  16. Antioxidants from black and green tea: from dietary modulation of oxidative stress to pharmacological mechanisms. (United States)

    Peluso, Ilaria; Serafini, Mauro


    The consumption of tea (Camellia sinensis) has been correlated with a low incidence of chronic pathologies, such as cardiovascular disease and cancer, in which oxidative stress plays a critical role. Tea catechins and theaflavins are, respectively, the bioactive phytochemicals responsible for the antioxidant activity of green tea (GT) and black tea (BT). In addition to their redox properties, tea catechins and theaflavins could have also pharmacological activities, such as the ability to lower glucose, lipid and uric acid (UA) levels. These activities are mediated by pharmacological mechanisms such as enzymatic inhibition and interaction with transporters. Epigallocatechin gallate is the most active compound at inhibiting the enzymes involved in cholesterol and UA metabolism (hydroxy-3-methyl-glutaryl-CoA reductase and xanthine oxidase respectively) and affecting glucose transporters. The structural features of catechins that significantly contribute to their pharmacological effect are the presence/absence of the galloyl moiety and the number and positions of the hydroxyl groups on the rings. Although the inhibitory effects on α-glucosidase, maltase, amylase and lipase, multidrug resistance 1, organic anion transporters and proton-coupled folate transport occur at higher concentrations than those apparent in the circulation, these effects could be relevant in the gut. In conclusion, despite the urgent need for further research in humans, the regular consumption of moderate quantities of GT and BT can effectively modulate their antioxidant capacity, mainly in people subjected to oxidative stress, and could improve the metabolism of glucose, lipid and UA.

  17. Green tea catechins: defensive role in cardiovascular disorders

    Institute of Scientific and Technical Information of China (English)

    Pooja Bhardwaj; Deepa Khanna


    Green tea,Camellia sinensis (Theaeeae),a major source of flavonoids such as catechins,has recently shown multiple cardiovascular health benefits through various experimental and clinical studies.These studies suggest that green tea catechins prevent the incidence of detrimental cardiovascular events,and also lower the cardiovascular mortality rate.Catechins present in green tea have the ability to prevent atherosclerosis,hypertension,endothelial dysfunction,ischemic heart diseases,cardiomyopathy,cardiac hypertrophy and congestive heart failure by decreasing oxidative stress,preventing inflammatory events,reducing platelet aggregation and halting the proliferation of vascular smooth muscle cells.Catechins afford an anti-oxidant effect by inducing anti-oxidant enzymes,inhibiting pro-oxidant enzymes and scavenging free radicals.Catechins present anti-inflammatory activity through the inhibition of transcriptional factor NF-κB-mediated production of cytokines and adhesion molecules.Green tea catechins interfere with vascular growth factors and thus inhibit vascular smooth muscle cell proliferation,and also inhibit thrombogenesis by suppressing platelet adhesion.Additionally,catechins could protect vascular endothelial cells and enhance vascular integrity and regulate blood pressure.In this review various experimental and clinical studies suggesting the role of green tea catechins against the markers of cardiovascular disorders and the underlying mechanisms for these actions are discussed.

  18. The fall and rise of pharmacology--(re-)defining the discipline? (United States)

    Winquist, Raymond J; Mullane, Kevin; Williams, Michael


    Pharmacology is an integrative discipline that originated from activities, now nearly 7000 years old, to identify therapeutics from natural product sources. Research in the 19th Century that focused on the Law of Mass Action (LMA) demonstrated that compound effects were dose-/concentration-dependent eventually leading to the receptor concept, now a century old, that remains the key to understanding disease causality and drug action. As pharmacology evolved in the 20th Century through successive biochemical, molecular and genomic eras, the precision in understanding receptor function at the molecular level increased and while providing important insights, led to an overtly reductionistic emphasis. This resulted in the generation of data lacking physiological context that ignored the LMA and was not integrated at the tissue/whole organism level. As reductionism became a primary focus in biomedical research, it led to the fall of pharmacology. However, concerns regarding the disconnect between basic research efforts and the approval of new drugs to treat 21st Century disease tsunamis, e.g., neurodegeneration, metabolic syndrome, etc. has led to the reemergence of pharmacology, its rise, often in the semantic guise of systems biology. Against a background of limited training in pharmacology, this has resulted in issues in experimental replication with a bioinformatics emphasis that often has a limited relationship to reality. The integration of newer technologies within a pharmacological context where research is driven by testable hypotheses rather than technology, together with renewed efforts in teaching pharmacology, is anticipated to improve the focus and relevance of biomedical research and lead to novel therapeutics that will contain health care costs.

  19. Nitric oxide and cardiovascular system. (United States)

    Cengel, Atiye; Sahinarslan, Asife


    Endothelium has many important functions including the control of blood-tissue permeability and vascular tonus, regulation of vascular surface properties for homeostasis and inflammation. Nitric oxide is the chief molecule in regulation of endothelial functions. Nitric oxide deficiency, which is also known as endothelial dysfunction, is the first step for the occurrence of many disease states in cardiovascular system including heart failure, hypertension, dyslipidemia, insulin resistance, diabetes mellitus, hyperhomocysteinemia and smoking. This review deals with the importance of nitric oxide for cardiovascular system. It also includes the latest improvements in the diagnosis and treatment of endothelial dysfunction.

  20. Nonfasting hyperlipidemia and cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, B G; Langsted, A; Freiberg, J J


    lipoproteins into the arterial intima with subsequent retention leading to atherogenesis, while low HDL cholesterol levels may be an innocent bystander. Finally, nonfasting levels of total cholesterol, non-HDL cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, HDL cholesterol, apolipoprotein A1......, total cholesterol/HDL cholesterol, and apolipoprotein B/apolipoprotein A1 all associate with increased risk of cardiovascular disease. These new data open the possibility that nonfasting rather than fasting lipid profiles can be used for cardiovascular risk prediction. If implemented, this would...

  1. The role of sphingolipids in selected cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Krzysztof Kurek


    Full Text Available Bioactive sphingolipids are engaged with numerous cellular processes such as cell differentiation, proliferation and apoptosis. Sphingolipid metabolism in heart is regulated by physical exercise and PPARs. Ceramide, the main second messenger of sphingomyelin pathway of signal transduction, was found to be involved in development of cardiac dysfunction after ischemia/reperfusion. On the other hand ceramide derivative sphingosine- 1- phosphate has been shown to exert potent cardioprotective action and guards cardiomyocytes against ischemic/reperfusion injury. Pharmacological compounds, which regulate metabolism of sphingolipids can be potentially useful in treatment of selected cardiovascular diseases. The aim of this work is critical review of physiological and pathological role of sphingolipids in circulatory system.

  2. Cardiovascular risk stratification and management in pre-diabetes. (United States)

    Færch, Kristine; Vistisen, Dorte; Johansen, Nanna Borup; Jørgensen, Marit Eika


    Prediabetes, covering individuals with impaired fasting glycemia, impaired glucose tolerance, or high-risk HbA1c levels, is associated with a ∼20 % increased risk of developing cardiovascular disease (CVD) compared with normoglycemic individuals. It is well-known that lifestyle or pharmacologic interventions can prevent diabetes in prediabetic people; however, the evidence is less clear regarding prevention of CVD. Most diabetes prevention trials have failed to show beneficial effects on CVD morbidity and mortality despite significant improvements of CVD risk factors in individuals with prediabetes. Another challenge is how to estimate CVD risk in prediabetic people. In general, prediction models for CVD do not take glucose levels or prediabetes status into account, thereby underestimating CVD risk in these high-risk individuals. More evidence within risk stratification and management of CVD risk in prediabetes is needed in order to recommend useful and effective strategies for early prevention of CVD.

  3. Biofield therapies in cardiovascular disease management: a brief review. (United States)

    Anderson, Joel G; Taylor, Ann Gill


    Though there have been advances over the last 30 years in the therapeutic approaches to cardiovascular disease (CVD), heart disease and stroke remain the leading cause of mortality and morbidity worldwide. Many medical therapies for CVD are associated with a number of side effects, often leading patients to seek non-pharmacological treatments to complement standard care. Referred to as complementary and alternative medicine (CAM), these therapies consist of a heterogeneous group of modalities used in addition to conventional health care. Biofield therapies exist within this CAM domain and involve the direction of healing energy to facilitate general health and well-being by modifying the energy field. What follows is a brief overview of three biofield therapies developed or used within the field of nursing (Therapeutic Touch, Reiki, and Healing Touch), surveying the use of these interventions for individuals with CVD, and outcomes that may impact CVD risk factors and health-related quality of life.

  4. Intensified multifactorial intervention and cardiovascular outcome in type 2 diabetes

    DEFF Research Database (Denmark)

    Pedersen, Oluf; Gaede, Peter


    , and autonomic neuropathy (secondary end points) was diminished by about 60% in the intensively treated group. In conclusion, an intensified and goal-oriented multipronged approach to the treatment of type 2 diabetes reduces cardiovascular events, as well as nephropathy, retinopathy, and autonomic neuropathy......-risk type 2 diabetic patients with microalbuminuria-a strong risk factor of both macrovascular and microvascular complications-aged 55.1 years, who were randomly assigned to a conventional or an intensive, multifactorial intervention for a period of 7.8 years. In the intensive group, a stepwise treatment...... plan was adopted involving both continuous lifestyle education and motivation and an ambitious goal-oriented pharmacological treatment of known modifiable risk factors. The conventional group was treated in accordance with national guidelines for type 2 diabetes with less stringent goals. The specific...

  5. Heterozygous familial hypercholesterolaemia in childhood: cardiovascular risk prevention. (United States)

    van der Graaf, A; Kastelein, J J P; Wiegman, A


    Children with familial hypercholesterolaemia (FH) have severely increased low-density lipoprotein cholesterol (LDL-C) levels that strongly predispose to premature cardiovascular disease (CVD) later in life. Early identification makes it possible to start lipid-lowering therapy at young age to prevent CVD. The atherosclerotic process can be inhibited by potent lipid-lowering therapy. The cornerstone of lipid-lowering therapy is a healthy lifestyle, but most of the time this is insufficient to reach adequate LDL-C goals. Subsequently, pharmacological therapy is initiated with increasing frequency. In the past decade numerous studies have assessed the efficacy and safety of statins in children with FH. Those studies demonstrate that statins are well tolerated, safe and effective. Therefore, these agents have a pivotal role in the treatment of children with FH.

  6. DIETA Y PREVENCIÓN SECUNDARIA DE LA ENFERMEDAD CARDIOVASCULAR Diet and secondary prevention of cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Luis Alberto Ángel Arango


    mortalidad en pacientes con angina y favorecen la recurrencia de arritmias ventriculares (B-III.Background. There is abundant evidence regarding the effects of diet as a strategy for managing cardiovascular risk factors in primary prevention, covering all types of situations and complications including a whole range of studies from cases and controls, retrospective cohorts, prospective studies to controlled random clinical trial. Objectives. Establishing evidence from recent studies and revised and updated clinical practice guidelines about secondary prevention of cardiovascular disease by dietary management. Materials and methods. Databases were electronically searched using the words «secondary prevention» and connectors «heart» and «cardiovascular risk.» Only studies whose main objective had been the reduction of new cardiovascular events were accepted. Results. A Mediterranean-type diet was shown to be associated with lower overall mortality rates, particularly due to cardiac causes. A cholesterol-reducing diet lowered the recurrent heart-attack rate and appearance of angina, as well as recurrent heart-attacks associated with omega 3 fatty acid 18 consumption (recommendations and level of evidence: B-IIa. A fish fat oil rich diet increased the risk of death and sudden death from cardiac causes in subjects suffering from angina and favored the recurrence of ventricular arrhythmias (B-III. Omega-3 fatty acids from fish and vegetables did not reduce greater cardiovascular events in patients with suitable antihypertensive, antithrombotic and dyslipidaemia (BIII pharmacological therapy. Conclusions. Mediterranean-type diets and those reducing cholesterol rich in omega-3 fatty acids probably have a favourable effect on preventing secondary cardiovascular disease (B-IIa. Such effect disappears when associated with pharmacological treatment of cardiovascular risk factors (B-III. Omega-3 fatty acids probably increase mortality in patients suffering from angina and favour

  7. Calcium channel blockers in cardiovascular pharmacotherapy. (United States)

    Godfraind, Theophile


    This paper summarizes the pharmacological properties of calcium channel blockers (CCBs), their established therapeutic uses for cardiovascular disorders and the current improvement of their clinical effects through drug combinations. Their identification resulted from study of small molecules including coronary dilators, which were named calcium antagonists. Further experiments showed that they reduced contraction of arteries by inhibiting calcium entry and by interacting with binding sites identified on voltage-dependent calcium channels. This led to the denomination calcium channel blockers. In short-term studies, by decreasing total peripheral resistance, CCBs lower arterial pressure. By unloading the heart and increasing coronary blood flow, CCBs improve myocardial oxygenation. In long-term treatment, the decrease in blood pressure is more pronounced in hypertensive than in normotensive patients. A controversy on the safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by the National Heart, Lung, and Blood Institute. There are two main types of CCBs: dihydopyridine and non-dihydropyridine; the first type is vascular selective. Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic angina. Non-dihydropyridines have the same indications plus antiarrythmic effects in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order to reach recommended blood pressure goals, there is a recent therapeutic move by combination of CCBs with other antihypertensive agents particularly with inhibitors acting at the level of the renin-angiotensin system. They are also combined with statins. Prevention of dementia has been reported in hypertensive patients treated with nitrendipine, opening a way for further studies on CCBs' beneficial effect in cognitive deterioration associated with aging.

  8. Pharmacology and function of melatonin receptors

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    Dubocovich, M.L.


    The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-(125I)iodomelatonin are identical. It is proposed that 2-(125I)iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-(125I)iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references.

  9. [From Purkinje's pharmacologic observations to molecular drug interactions]. (United States)

    Kvĕtina, J


    The 650th anniversary of the foundation of Charles University (7 April 1348) in Prague has initiated a number of historical surveys of the subjects which has been taught at the University for a longer period of time. The disciplines connected with pharmacotherapy were being developed in an empirical conception at the University from the second half of the 14th century but the beginnings of experimental drug research date as late as the mid-19th century. The present survey of the history of "the sciences of medicaments" therefore attempts to outline in short entries the developmental stages of pharmaceutical and pharmacological investigations in the territory of Bohemia and Moravia in about recent 150 years. The arrangement of data is chronological; in the part covering the second half of the 20th century the research of a predominantly exploratory character (universities and academic institutions and their representatives) and research aimed primarily to innovate medicaments (research institutions of pharmaceutical industry and clinical pharmacology and some of their representatives) are treated separately.

  10. Pharmacological modeling and biostatistical analysis of a new drug

    Directory of Open Access Journals (Sweden)

    Revathi Ananthakrishnan


    Full Text Available Revathi Ananthakrishnan1, Philimon Gona21Cambridge, MA, USA; 2Boston University, Mathematics and Statistics Department, 111 Cummington St, Boston, MA-02215, USAAbstract: Clinical research and clinical trials of experimental drugs to treat human diseases have gained greater importance in recent years. Phase I–IV clinical trials offer patients the opportunity to gain access to a new, more efficacious and safer medication to alleviate or cure their disease. There are potential side effects of every new drug; however, such trials and studies are crucial for drug development and testing in humans. The US Food and Drug Administration (FDA regulated process of evaluating a new drug for treating a particular disease in humans is long, rigorous, and includes the stages starting from preclinical research through the entire human clinical trials process. This review synthesizes results from the above stages and describes the entire mechanism of the clinical study of a new drug for human disease. It emphasizes the associated mathematical modeling and statistical analyses, and bridges pharmacological modeling and biostatistics in clinical research and also provides a basic theoretical overview to biomedical experimentalists. The modern trend in clinical research involves a unified approach among several biomedical subspecialties and it is hoped that even more integrated studies of new drugs will continue to be carried out, leading to novel drugs that are highly effective in curing the associated condition.Keywords: PK/PD pharmacological modeling, biostatistical analyses of clinical trials data, clinical trials, phases of clinical trials, types and designs of clinical trials

  11. Publication trends in Naunyn-Schmiedeberg's Archives of Pharmacology: focus on pharmacology in Egypt. (United States)

    El-Mas, Mahmoud M; El-Gowelli, Hanan M; Michel, Martin C


    In a previous analysis of the country of origin of papers published in Naunyn-Schmiedeberg's Archives of Pharmacology, a major shift toward contributions from emerging market countries, was noticed in comparison of 2010 to 2001 publications. Repeating such analysis for 2012 publications in the journal confirmed this trend. An interesting new trend was the emerging presence of papers from a variety of Islamic countries including Egypt. Based on this trend, we shortly review the history and current structure of pharmacology in Egypt. It appears that the presence of Egyptian pharmacology in international journals including pharmacology journals has sharply been increasing over the last two decades. Challenges for a continuation of this encouraging trend are being discussed.

  12. The contributions of Paul Ehrlich to pharmacology: a tribute on the occasion of the centenary of his Nobel Prize. (United States)

    Bosch, Fèlix; Rosich, Laia


    On the centenary of Paul Ehrlich's Nobel Prize, this German researcher deserves to be remembered as a pioneer in a large number of scientific disciplines. As a result of his enthusiasm and scientific abilities, dedication, and contacts with other scientists of his time, he was able to make countless contributions in fields as diverse as histology, haematology, immunology, oncology, microbiology and pharmacology, among others. Although the Swedish award was meant to recognize the standardization of the manufacture of antidiphtheria serum, it was the discovery of arsphenamine (Salvarsan) for the treatment of syphilis which won him wider international acclaim. From a pharmacological perspective, Ehrlich's outstanding contributions include dissemination of the 'magic bullet' concept for the synthesis of antibacterials, introduction of concepts such as chemoreceptor and chemotherapy, and linking the chemical structure of compounds to their pharmacological activity. These achievements took place within the framework he established for the transition from experimental pharmacology to therapeutic pharmacology. He introduced a modern research system based on the synthesis of multiple chemical structures for pharmacological screening in animal models of disease states. These contributions were undoubtedly decisive in propitiating the wider development of antibiotics decades later. For these reasons, it is fitting to mark the 100th anniversary of the Nobel Prize awarded to this great scientist by commemorating the importance of his contributions to the advance of pharmacology.

  13. Cardiovascular effects of environmental noise exposure. (United States)

    Münzel, Thomas; Gori, Tommaso; Babisch, Wolfgang; Basner, Mathias


    The role of noise as an environmental pollutant and its impact on health are being increasingly recognized. Beyond its effects on the auditory system, noise causes annoyance and disturbs sleep, and it impairs cognitive performance. Furthermore, evidence from epidemiologic studies demonstrates that environmental noise is associated with an increased incidence of arterial hypertension, myocardial infarction, and stroke. Both observational and experimental studies indicate that in particular night-time noise can cause disruptions of sleep structure, vegetative arousals (e.g. increases of blood pressure and heart rate) and increases in stress hormone levels and oxidative stress, which in turn may result in endothelial dysfunction and arterial hypertension. This review focuses on the cardiovascular consequences of environmental noise exposure and stresses the importance of noise mitigation strategies for public health.

  14. High-density lipoproteins: a novel therapeutic target for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    TS Mohamed Saleem


    Full Text Available TS Mohamed Saleem1, PV Sandhya Rani1, K Gauthaman21Department of Pharmacology, Annamacharya College of Pharmacy, New Boyanapalli, Andhrapradesh, India; 2Department of Drug Technology, Faculty of Medical Technology, Derna, LibyaAbstract: Cardiovascular disease has a high rate of mortality in both Western and developing countries. Atherosclerosis and generation of reactive oxygen species through oxidative stress is the major risk factor for cardiovascular disease. Atherothrombosis with low levels of high-density lipoprotein (HDL and high levels of low-density lipoprotein is a major risk factor for atherosclerosis-induced cardiovascular disease. Lipid-lowering drugs like statins, niacin, fibrates, and some newer agents, ie, the apolipoprotein A-I mimetics and the cholesteryl ester transfer protein inhibitors, not only increase HDL levels but are also effective in reducing key atherogenic lipid components, including triglyceride-rich lipoproteins. The aim of this review is to discuss the accumulating evidence suggesting that HDL possesses a diverse range of biological actions, and that increasing HDL levels by drug treatment may be beneficial in the prevention of cardiovascular disease.Keywords: cardiovascular disease, lipoproteins, statins, apolipoprotein, atherosclerosis

  15. [Dyslipidemias: a pending challenge in cardiovascular prevention. Consensus document from CEIPC/SEA Committee]. (United States)

    Royo Bordonada, Miguel Ángel; Lobos Bejarano, José María; Millán Núñez-Cortés, Jesús; Villar Álvarez, Fernando; Brotons Cuixart, Carlos; Camafort Babkowski, Miguel; Guijarro Herráiz, Carlos; de Pablo Zarzosa, Carmen; Pedro-Botet Montoya, Juan; Santiago Nocito, Ana de


    In Spain, where cardiovascular disease (CVD) is the leading cause of death, hypercholesterolemia, one of the most prevalent risk factors in adults, is poorly controlled. Dyslipidemia should not be approached in isolation, but in the context of overall cardiovascular risk (CVR). Measurement of CVR facilitates decision making, but should not be the only tool nor should it take the place of clinical judgment, given the limitations of the available calculation methods. This document, prepared by the Interdisciplinary Spanish Committee on Cardiovascular Prevention, at the proposal of the Spanish Society of Arteriosclerosis, reviews the cardiovascular prevention activities of the regional health authorities, scientific societies and medical professionals. An initiation of a national strategy on cardiovascular prevention is proposed based on lifestyle modification (healthy diet, physical activity and smoking cessation) through actions in different settings. At the population level, regulation of food advertising, elimination of trans fats and reduction of added sugar are feasible and cost-effective interventions to help control dyslipidemias and reduce CVR. In the health setting, it is proposed to facilitate the application of guidelines, improve training for medical professionals, and include CVR assessment among the quality indicators. Scientific societies should collaborate with the health authorities and contribute to the generation and transmission of knowledge. Finally, it is in the hands of professionals to apply the concept of CVR, promote healthy lifestyles, and make efficient use of available pharmacological treatments.

  16. Rho kinases in cardiovascular physiology and pathophysiology: the effect of fasudil. (United States)

    Shi, Jianjian; Wei, Lei


    Rho kinase (ROCK) is a major downstream effector of the small GTPase RhoA. ROCK family, consisting of ROCK1 and ROCK2, plays central roles in the organization of actin cytoskeleton and is involved in a wide range of fundamental cellular functions, such as contraction, adhesion, migration, proliferation, and apoptosis. Due to the discovery of effective inhibitors, such as fasudil and Y27632, the biological roles of ROCK have been extensively explored with particular attention on the cardiovascular system. In many preclinical models of cardiovascular diseases, including vasospasm, arteriosclerosis, hypertension, pulmonary hypertension, stroke, ischemia-reperfusion injury, and heart failure, ROCK inhibitors have shown a remarkable efficacy in reducing vascular smooth muscle cell hypercontraction, endothelial dysfunction, inflammatory cell recruitment, vascular remodeling, and cardiac remodeling. Moreover, fasudil has been used in the clinical trials of several cardiovascular diseases. The continuing utilization of available pharmacological inhibitors and the development of more potent or isoform-selective inhibitors in ROCK signaling research and in treating human diseases are escalating. In this review, we discuss the recent molecular, cellular, animal, and clinical studies with a focus on the current understanding of ROCK signaling in cardiovascular physiology and diseases. We particularly note that emerging evidence suggests that selective targeting ROCK isoform based on the disease pathophysiology may represent a novel therapeutic approach for the disease treatment including cardiovascular diseases.

  17. Endothelial Dysfunction in Experimental Models of Arterial Hypertension: Cause or Consequence?

    Directory of Open Access Journals (Sweden)

    Iveta Bernatova


    Full Text Available Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP. The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (prehypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

  18. Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence? (United States)

    Bernatova, Iveta


    Hypertension is a risk factor for other cardiovascular diseases and endothelial dysfunction was found in humans as well as in various commonly employed animal experimental models of arterial hypertension. Data from the literature indicate that, in general, endothelial dysfunction would not be the cause of experimental hypertension and may rather be secondary, that is, resulting from high blood pressure (BP). The initial mechanism of endothelial dysfunction itself may be associated with a lack of endothelium-derived relaxing factors (mainly nitric oxide) and/or accentuation of various endothelium-derived constricting factors. The involvement and role of endothelium-derived factors in the development of endothelial dysfunction in individual experimental models of hypertension may vary, depending on the triggering stimulus, strain, age, and vascular bed investigated. This brief review was focused on the participation of endothelial dysfunction, individual endothelium-derived factors, and their mechanisms of action in the development of high BP in the most frequently used rodent experimental models of arterial hypertension, including nitric oxide deficient models, spontaneous (pre)hypertension, stress-induced hypertension, and selected pharmacological and diet-induced models.

  19. Laser therapy in cardiovascular disease (United States)

    Rindge, David


    Cardiovascular disease is the number one cause of death worldwide. It is broadly defined to include anything which adversely affects the heart or blood vessels. One-third of Americans have one or more forms of it. By one estimate, average human life expectancy would increase by seven years if it were eliminated. The mainstream medical model seeks mostly to "manage" cardiovascular disease with pharmaceuticals or to surgically bypass or reopen blocked vessels via angioplasty. These methods have proven highly useful and saved countless lives. Yet drug therapy may be costly and ongoing, and it carries the risk of side effects while often doing little or nothing to improve underlying health concerns. Similarly, angioplasty or surgery are invasive methods which entail risk. Laser therapy1 regenerates tissue, stimulates biological function, reduces inflammation and alleviates pain. Its efficacy and safety have been increasingly well documented in cardiovascular disease of many kinds. In this article we will explore the effects of laser therapy in angina, atherosclerosis, coronary artery disease, hypertension, hyperlipidemia, myocardial infarction, stroke and other conditions. The clinical application of various methods of laser therapy, including laserpuncture and transcutaneous, supravascular and intravenous irradiation of blood will be discussed. Implementing laser therapy in the treatment of cardiovascular disease offers the possibility of increasing the health and wellbeing of patients while reducing the costs and enhancing safety of medical care.

  20. Down Syndrome: A Cardiovascular Perspective (United States)

    Vis, J. C.; Duffels, M. G. J.; Winter, M. M.; Weijerman, M. E.; Cobben, J. M.; Huisman, S. A.; Mulder, B. J. M.


    This review focuses on the heart and vascular system in patients with Down syndrome. A clear knowledge on the wide spectrum of various abnormalities associated with this syndrome is essential for skillful management of cardiac problems in patients with Down syndrome. Epidemiology of congenital heart defects, cardiovascular aspects and…