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Sample records for adenosine triphosphate-based chemotherapy

  1. Visual and Plasmon Resonance Absorption Sensor for Adenosine Triphosphate Based on the High Affinity between Phosphate and Zr(IV).

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    Qi, Wenjing; Liu, Zhongyuan; Zhang, Wei; Halawa, Mohamed Ibrahim; Xu, Guobao

    2016-10-12

    Zr(IV) can form phosphate and Zr(IV) (-PO₃(2-)-Zr(4+)-) complex owing to the high affinity between Zr(IV) with phosphate. Zr(IV) can induce the aggregation of gold nanoparticles (AuNPs), while adenosine triphosphate(ATP) can prevent Zr(IV)-induced aggregation of AuNPs. Herein, a visual and plasmon resonance absorption (PRA)sensor for ATP have been developed using AuNPs based on the high affinity between Zr(IV)with ATP. AuNPs get aggregated in the presence of certain concentrations of Zr(IV). After the addition of ATP, ATP reacts with Zr(IV) and prevents AuNPs from aggregation, enabling the detection of ATP. Because of the fast interaction of ATP with Zr(IV), ATP can be detected with a detection limit of 0.5 μM within 2 min by the naked eye. Moreover, ATP can be detected by the PRA technique with higher sensitivity. The A520nm/A650nm values in PRA spectra increase linearly with the concentrations of ATP from 0.1 μM to 15 μM (r = 0.9945) with a detection limit of 28 nM. The proposed visual and PRA sensor exhibit good selectivity against adenosine, adenosine monophosphate, guanosine triphosphate, cytidine triphosphate and uridine triphosphate. The recoveries for the analysis of ATP in synthetic samples range from 95.3% to 102.0%. Therefore, the proposed novel sensor for ATP is promising for real-time or on-site detection of ATP.

  2. Visual and Plasmon Resonance Absorption Sensor for Adenosine Triphosphate Based on the High Affinity between Phosphate and Zr(IV)

    Science.gov (United States)

    Qi, Wenjing; Liu, Zhongyuan; Zhang, Wei; Halawa, Mohamed Ibrahim; Xu, Guobao

    2016-01-01

    Zr(IV) can form phosphate and Zr(IV) (–PO32−–Zr4+–) complex owing to the high affinity between Zr(IV) with phosphate. Zr(IV) can induce the aggregation of gold nanoparticles (AuNPs), while adenosine triphosphate(ATP) can prevent Zr(IV)-induced aggregation of AuNPs. Herein, a visual and plasmon resonance absorption (PRA)sensor for ATP have been developed using AuNPs based on the high affinity between Zr(IV)with ATP. AuNPs get aggregated in the presence of certain concentrations of Zr(IV). After the addition of ATP, ATP reacts with Zr(IV) and prevents AuNPs from aggregation, enabling the detection of ATP. Because of the fast interaction of ATP with Zr(IV), ATP can be detected with a detection limit of 0.5 μM within 2 min by the naked eye. Moreover, ATP can be detected by the PRA technique with higher sensitivity. The A520nm/A650nm values in PRA spectra increase linearly with the concentrations of ATP from 0.1 μM to 15 μM (r = 0.9945) with a detection limit of 28 nM. The proposed visual and PRA sensor exhibit good selectivity against adenosine, adenosine monophosphate, guanosine triphosphate, cytidine triphosphate and uridine triphosphate. The recoveries for the analysis of ATP in synthetic samples range from 95.3% to 102.0%. Therefore, the proposed novel sensor for ATP is promising for real-time or on-site detection of ATP. PMID:27754349

  3. Visual and Plasmon Resonance Absorption Sensor for Adenosine Triphosphate Based on the High Affinity between Phosphate and Zr(IV

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    Wenjing Qi

    2016-10-01

    Full Text Available Zr(IV can form phosphate and Zr(IV (–PO32−–Zr4+– complex owing to the high affinity between Zr(IV with phosphate. Zr(IV can induce the aggregation of gold nanoparticles (AuNPs, while adenosine triphosphate(ATP can prevent Zr(IV-induced aggregation of AuNPs. Herein, a visual and plasmon resonance absorption (PRAsensor for ATP have been developed using AuNPs based on the high affinity between Zr(IVwith ATP. AuNPs get aggregated in the presence of certain concentrations of Zr(IV. After the addition of ATP, ATP reacts with Zr(IV and prevents AuNPs from aggregation, enabling the detection of ATP. Because of the fast interaction of ATP with Zr(IV, ATP can be detected with a detection limit of 0.5 μM within 2 min by the naked eye. Moreover, ATP can be detected by the PRA technique with higher sensitivity. The A520nm/A650nm values in PRA spectra increase linearly with the concentrations of ATP from 0.1 μM to 15 μM (r = 0.9945 with a detection limit of 28 nM. The proposed visual and PRA sensor exhibit good selectivity against adenosine, adenosine monophosphate, guanosine triphosphate, cytidine triphosphate and uridine triphosphate. The recoveries for the analysis of ATP in synthetic samples range from 95.3% to 102.0%. Therefore, the proposed novel sensor for ATP is promising for real-time or on-site detection of ATP.

  4. A sensitive aptasensor for colorimetric detection of adenosine triphosphate based on the protective effect of ATP-aptamer complexes on unmodified gold nanoparticles.

    Science.gov (United States)

    Huo, Yuan; Qi, Liang; Lv, Xiao-Jun; Lai, Ting; Zhang, Jing; Zhang, Zhi-Qi

    2016-04-15

    Adenosine triphosphate (ATP) is the most direct source of energy in organisms. This study is the first to demonstrate that ATP-aptamer complexes provide greater protection for unmodified gold nanoparticles (AuNPs) against salt-induced aggregation than either aptamer or ATP alone. This protective effect was confirmed using transmission electron microscopy, dynamic light scattering, Zeta potential measurement, and fluorescence polarization techniques. Utilizing controlled particle aggregation/dispersion as a gauge, a sensitive and selective aptasensor for colorimetric detection of ATP was developed using ATP-binding aptamers as the identification element and unmodified AuNPs as the probe. This aptasensor exhibited a good linear relationship between the absorbance and the logarithm concentration of ATP within a 50-1000 nM range. ATP analogs such as guanosine triphosphate, uridine triphosphate and cytidine triphosphate resulted in little or no interference in the determination of ATP.

  5. [Adenosine deaminase in experimental trypanosomiasis: future implications].

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    Pérez-Aguilar, Mary Carmen; Rondón-Mercado, Rocío

    2015-09-01

    The adenosine deaminase represents a control point in the regulation of extracellular adenosine levels, thus playing a critical role in the modulation of purinergic responses to certain pathophysiological events. Several studies have shown that serum and plasma enzyme levels are elevated in some diseases caused by microorganisms, which may represent a compensatory mechanism due to the elevated levels of adenosine and the release of inflammatory mediators. Recent research indicates that adenosine deaminase activity decreases and affects hematological parameters of infected animals with Trypanosoma evansi, so that such alterations could have implications in the pathogenesis of the disease. In addition, the enzyme has been detected in this parasite; allowing the inference that it could be associated with the vital functions of the same, similar to what occurs in mammals. This knowledge may be useful in the association of chemotherapy with specific inhibitors of the enzyme in future studies.

  6. Adenosine and adenosine receptors: Newer therapeutic perspective

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    Manjunath S

    2009-01-01

    Full Text Available Adenosine, a purine nucleoside has been described as a ′retaliatory metabolite′ by virtue of its ability to function in an autocrine manner and to modify the activity of a range of cell types, following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by binding of adenosine to any of the four adenosine receptor subtypes namely A1, A2a, A2b, A3, which have been cloned in humans, and are expressed in most of the organs. Each is encoded by a separate gene and has different functions, although overlapping. For instance, both A1 and A2a receptors play a role in regulating myocardial oxygen consumption and coronary blood flow. It is a proven fact that adenosine plays pivotal role in different physiological functions, such as induction of sleep, neuroprotection and protection against oxidative stress. Until now adenosine was used for certain conditions like paroxysmal supraventricular tachycardia (PSVT and Wolff Parkinson White (WPW syndrome. Now there is a growing evidence that adenosine receptors could be promising therapeutic targets in a wide range of conditions including cardiac, pulmonary, immunological and inflammatory disorders. After more than three decades of research in medicinal chemistry, a number of selective agonists and antagonists of adenosine receptors have been discovered and some have been clinically evaluated, although none has yet received regulatory approval. So this review focuses mainly on the newer potential role of adenosine and its receptors in different clinical conditions.

  7. Understanding Chemotherapy

    Science.gov (United States)

    N ational C ancer I nstitute Understanding Chemotherapy What is chemotherapy? Chemotherapy is a cancer treatment that uses drugs to destroy cancer cells. It is also called “chemo.” Today, there are ...

  8. Adenosine receptor neurobiology: overview.

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    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases.

  9. Adenosine and sleep

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    Yanik, G.M. Jr.

    1987-01-01

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A/sub 1/ receptors, /sup 3/H-L-PIA binding was measured. The Bmax values for /sup 3/H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in /sup 3/H-L-PIA binding resulted from REM sleep deprivation and not from stress.

  10. Cancer Chemotherapy

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    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  11. Role of A3 adenosine receptor in diabetic neuropathy.

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    Yan, Heng; Zhang, Enshui; Feng, Chang; Zhao, Xin

    2016-10-01

    Neuropathy is the most common diabetic complication. Although the A1 and A2A adenosine receptors are important pharmacological targets in alleviating diabetic neuropathy, the role of the A3 adenosine receptor remains unknown. Because the A3 adenosine receptor regulates pain induced by chronic constriction injury or chemotherapy, its stimulation might also attenuate diabetic neuropathy. This study examines the effects of systemic treatment with the A3 adenosine receptor agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-β-d-ribofuranuronamide (IB-MECA) on diabetic neuropathy and explores the putative mechanisms underlying its pharmacological effects. We show that IB-MECA alleviated mechanical hyperalgesia and thermal hypoalgesia in mice 2 weeks but not 4 weeks after streptozocin (STZ) treatment. Furthermore, IB-MECA prevented the reduction in sciatic motor nerve conduction velocity and sensory nerve conduction velocity in diabetic mice 2 weeks but not 4 weeks after STZ treatment. Similarly, IB-MECA inhibited the activation of nuclear factor-κB and decreased the generation of tumor necrosis factor-α in the spinal cord of mice 2 weeks but not 4 weeks after STZ treatment. These phenomena were associated with reduction of A3 adenosine receptor expression in the spinal cord after long-term diabetes. Our results suggest that the A3 adenosine receptor plays a critical role in regulating diabetic neuropathy and that reduction in A3 adenosine receptor expression/function might contribute to the progression of diabetic neuropathy. © 2016 Wiley Periodicals, Inc.

  12. Adenosine improves cardiomyocyte respiratory efficiency.

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    Babsky, A M; Doliba, M M; Doliba, N M; Osbakken, M D

    1998-01-01

    The role of adenosine on the regulation of mitochondrial function has been studied. In order to evaluate this the following experiments were done in isolated rat cardiomyocites and mitochondria using polarographic techniques. Cardiomyocyte oxygen consumption (MVO2) and mitochondrial respiratory function (State 3 and State 4, respiratory control index, and ADP/O ratio) were evaluated after exposure to adenosine. Cardiomyocyte MVO2 was significantly lower in cells previously exposed to adenosine (10 microM, 15 min or 30 min cell incubation) than in cells not exposed to adenosine (control). Addition of dipyridamole (10 microM) or 8-(p-Sulfophenyl) theophylline (50 microM) to cardiomyocytes before adenosine incubation prevented the adenosine-induced changes in MVO2. Mitochondria obtained from isolated perfused beating heart previously perfused with adenosine (10 microM, 30 min heart perfusion) also resulted in significant increases in ADP/O and respiratory control index compared to matching control. Mitochondria isolated from cardiomyocytes previously exposed to adenosine (10 microM, 15 min or 30 min cell incubation) resulted in a significant increase in mitochondrial ADP/O ratio compared to control. Adenosine-induced decrease in cardiomyocyte MVO2 may be related to an increase in efficiency of mitochondrial oxidative phosphorylation, and more economical use of oxygen, which is necessary for survival under ischemic stress.

  13. Effects of adenosine on lymphangiogenesis.

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    Bénédicte Lenoir

    Full Text Available BACKGROUND: The lymphatic system controls tissue homeostasis by draining protein-rich lymph to the vascular system. Lymphangiogenesis, the formation of lymphatic vessels, is a normal event in childhood but promotes tumor spread and metastasis during adulthood. Blocking lymphangiogenesis may therefore be of therapeutic interest. Production of adenosine is enhanced in the tumor environment and contributes to tumor progression through stimulation of angiogenesis. In this study, we determined whether adenosine affects lymphangiogenesis. METHODS: Lymphatic endothelial cells (HMVEC-dLy were cultured in presence of adenosine and their proliferation, migration and tube formation was assessed. Gelatin sponges embedded with the stable analogue of adenosine 2-chloro adenosine were implanted in mice ear and lymphangiogenesis was quantified. Mice were intravenously injected with adenoviruses containing expression vector for 5'-endonucleotidase, which plays a major role in the formation of adenosine. RESULTS: In vitro, we observed that adenosine decreased the proliferation of lymphatic endothelial cells, their migration and tube formation. However, in vivo, gelatin sponges containing 2-chloro adenosine and implanted in mice ear displayed an elevated level of lymphangiogenesis (2.5-fold, p<0.001. Adenovirus-mediated over-expression of cytosolic 5'-nucleotidase IA stimulated lymphangiogenesis and the recruitment of macrophages in mouse liver. Proliferation of lymphatic endothelial cells was enhanced (2-fold, p<0.001 when incubated in the presence of conditioned medium from murine macrophages. CONCLUSION: We have shown that adenosine stimulates lymphangiogenesis in vivo, presumably through a macrophage-mediated mechanism. This observation suggests that blockade of adenosine receptors may help in anti-cancer therapies.

  14. Imaging Adenosine Triphosphate (ATP).

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    Rajendran, Megha; Dane, Eric; Conley, Jason; Tantama, Mathew

    2016-08-01

    Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provide valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities.

  15. Some neural effects of adenosin.

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    Haulică, I; Brănişteanu, D D; Petrescu, G H

    1978-01-01

    The possible neural effects of adenosine were investigated by using electrophysiological techniques at the level of some central and peripheral synapses. The evoked potentials in the somatosensorial cerebral cortex are influenced according to both the type of administration and the level of the electrical stimulation. While the local application does not induce significant alterations, the intrathalamic injections and the perfusion of the IIIrd cerebral ventricle do change the distribution of activated units at the level of different cortical layers especially during the peripheral stimulation. The frequency of spontaneous miniature discharges intracellularly recorded in the neuromuscular junction (mepp) is significantly depressed by adenosine. This effect is calcium- and dose-dependent. The end plate potentials (EPP) were also depressed. The statistical binomial analysis of the phenomenon indicated that adenosine induces a decrease if the presynaptic pool of the available transmitter. The data obtained demonstrate a presynaptic inhibitory action of adenosine beside its known vascular and metaholic effects.

  16. Regulation of adenosine levels during cerebral ischemia

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    Stephanie CHU; Wei XIONG; Dali ZHANG; Hanifi SOYLU; Chao SUN; Benedict C ALBENSI; Fiona E PARKINSON

    2013-01-01

    Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events,and attenuates the excitotoxic neuronal injury.Adenosine is produced both intracellularly and extracellularly,and nucleoside transport proteins transfer adenosine across plasma membranes.Adenosine levels and receptor-mediated effects of adenosine are regulated by intracellular ATP consumption,cellular release of ATP,metabolism of extracellular ATP (and other adenine nucleotides),adenosine influx,adenosine efflux and adenosine metabolism.Recent studies have used genetically modified mice to investigate the relative contributions of intra-and extracellular pathways for adenosine formation.The importance of cortical or hippocampal neurons as a source or a sink of adenosine under basal and hypoxic/ischemic conditions was addressed through the use of transgenic mice expressing human equilibrative nucleoside transporter 1 (hENT1) under the control of a promoter for neuron-specific enolase.From these studies,we conclude that ATP consumption within neurons is the primary source of adenosine in neuronal cultures,but not in hippocampal slices or in vivo mice exposed to ischemic conditions.

  17. Novel aspects of extracellular adenosine dynamics revealed by adenosine sensor cells

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    Kunihiko Yamashiro

    2017-01-01

    Full Text Available Adenosine modulates diverse physiological and pathological processes in the brain, including neuronal activities, blood flow, and inflammation. However, the mechanisms underlying the dynamics of extracellular adenosine are not fully understood. We have recently developed a novel biosensor, called an adenosine sensor cell, and we have characterized the neuronal and astrocytic pathways for elevating extracellular adenosine. In this review, the physiological implications and therapeutic potential of the pathways revealed by the adenosine sensor cells are discussed. We propose that the multiple pathways regulating extracellular adenosine allow for the diverse functions of this neuromodulator, and their malfunctions cause various neurological and psychiatric disorders.

  18. Types of chemotherapy

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    ... medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor ...

  19. Chemotherapy for Thyroid Cancer

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    ... Type and Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  20. Chemotherapy for Testicular Cancer

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    ... Type and Stage Testicular Cancer Treating Testicular Cancer Chemotherapy for Testicular Cancer Chemotherapy (chemo) is the use of drugs to treat ... that is only in the testicle. Doctors give chemotherapy in cycles, with each period of treatment followed ...

  1. Side Effects of Chemotherapy

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    ... Jacket Fashion Show Contact Us Side Effects of Chemotherapy Each of the chemotherapy drugs available today works in a slightly different ... few rules of thumb when it comes to chemotherapy that should always be kept in mind. Ignore ...

  2. Chemotherapy and Your Mouth

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    ... Treatment and Oral Health > Chemotherapy and Your Mouth Chemotherapy and Your Mouth Main Content Are You Being ... Problems Too? Remember Are You Being Treated With Chemotherapy for Cancer? If so, this booklet can help ...

  3. Pathologic overproduction: the bad side of adenosine.

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    Borea, Pier Andrea; Gessi, Stefania; Merighi, Stefania; Vincenzi, Fabrizio; Varani, Katia

    2017-03-02

    Adenosine is an endogenous ubiquitous purine nucleoside, increased by hypoxia, ischemia and tissue damage that mediates a number of physiopathological effects by interacting with four G-protein-coupled receptors, identified as A1 , A2A , A2B , and A3 . Physiological and acutely-increased adenosine is associated with beneficial effects mostly including vasodilation and decrease of inflammation. In contrast chronic overproduction of adenosine occurs in important pathological states, where long lasting increases in the nucleoside levels are responsible for the bad side of adenosine associated with chronic inflammation, fibrosis and organ damage. In this review we describe and critically discuss the pathologic overproduction of adenosine analysing when, where and how adenosine exerts its detrimental effects through the body.

  4. chemotherapy patients

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    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  5. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  6. Adenosine, Energy Metabolism, and Sleep

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    Tarja Porkka-Heiskanen

    2003-01-01

    Full Text Available While the exact function of sleep remains unknown, it is evident that sleep was developed early in phylogenesis and represents an ancient and vital strategy for survival. Several pieces of evidence suggest that the function of sleep is associated with energy metabolism, saving of energy, and replenishment of energy stores. Prolonged wakefulness induces signs of energy depletion in the brain, while experimentally induced, local energy depletion induces increase in sleep, similarly as would a period of prolonged wakefulness. The key molecule in the induction of sleep appears to be adenosine, which induces sleep locally in the basal forebrain.

  7. Homeostatic control of synaptic activity by endogenous adenosine is mediated by adenosine kinase.

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    Diógenes, Maria José; Neves-Tomé, Raquel; Fucile, Sergio; Martinello, Katiuscia; Scianni, Maria; Theofilas, Panos; Lopatár, Jan; Ribeiro, Joaquim A; Maggi, Laura; Frenguelli, Bruno G; Limatola, Cristina; Boison, Detlev; Sebastião, Ana M

    2014-01-01

    Extracellular adenosine, a key regulator of neuronal excitability, is metabolized by astrocyte-based enzyme adenosine kinase (ADK). We hypothesized that ADK might be an upstream regulator of adenosine-based homeostatic brain functions by simultaneously affecting several downstream pathways. We therefore studied the relationship between ADK expression, levels of extracellular adenosine, synaptic transmission, intrinsic excitability, and brain-derived neurotrophic factor (BDNF)-dependent synaptic actions in transgenic mice underexpressing or overexpressing ADK. We demonstrate that ADK: 1) Critically influences the basal tone of adenosine, evaluated by microelectrode adenosine biosensors, and its release following stimulation; 2) determines the degree of tonic adenosine-dependent synaptic inhibition, which correlates with differential plasticity at hippocampal synapses with low release probability; 3) modulates the age-dependent effects of BDNF on hippocampal synaptic transmission, an action dependent upon co-activation of adenosine A2A receptors; and 4) influences GABAA receptor-mediated currents in CA3 pyramidal neurons. We conclude that ADK provides important upstream regulation of adenosine-based homeostatic function of the brain and that this mechanism is necessary and permissive to synaptic actions of adenosine acting on multiple pathways. These mechanistic studies support previous therapeutic studies and implicate ADK as a promising therapeutic target for upstream control of multiple neuronal signaling pathways crucial for a variety of neurological disorders.

  8. Pleural effusion during acute myeloid leukemia induction chemotherapy: A perplexing case

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    Chandran K Nair

    2013-01-01

    Full Text Available We are reporting a case of pneumonia associated with pleural effusion during the neutropenic phase of induction chemotherapy. In spite of being Adenosine deaminase negative, the pleural effusion responded only to empiric therapy with antitubercular agents. The diagnosis was confirmed with positive PCR testing for mycobacterium tuberculosis.

  9. Repeated administration of adenosine increases its cardiovascular effects in rats.

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    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  10. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation

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    Noam eRudich

    2012-06-01

    Full Text Available Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease (COPD patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells, as an attractive drug candidate. Four subtypes (A1, A2a, A2b and A3 of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R in mediating hyper responsiveness to adenosine in mast cells, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human mast cells. The relevance of mouse studies to the human is discussed.

  11. Chemotherapy (For Parents)

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    ... Getting Involved Teaching Kids to Be Smart About Social Media Chemotherapy KidsHealth ... and Where Chemo Is Given Common Side Effects of Chemotherapy Common Side Effects (continued) Common Side ...

  12. Chemotherapy | Smokefree.gov

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    Chemotherapy works by killing cancer cells, but healthy cells get attacked too. Damage to healthy cells can cause uncomfortable side effects. Use this action deck to get information on common chemotherapy side effects and learn how to manage them.

  13. Adenosine Deaminase Activities in Hyperlipidaemic Patients ...

    African Journals Online (AJOL)

    Journal of Health and Visual Sciences ... Abstract. Adenosine Deaminase Activities, markers of cellular-mediated immunity ... were statistically significantly higher (P<0.001) in the test groups than in the control groups (10.7+3iu/1) respectively.

  14. Uterine/Endometrial Cancer: Chemotherapy

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    ... Types of Gynecologic Cancers Uterine/Endometrial Cancer Chemotherapy Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for endometrial cancer is usually given intravenously (injected ...

  15. [History of cancer and chemotherapy before chemotherapy].

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    Bonnichon, Philippe; Berger, J P; Bonni, N; Fontaine, M; Pion-Graff, J

    2014-01-01

    Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates the use of arsphenamine by infusion. So, he is considered as the father of chemotherapy. In fact, the first to have thought through chemotherapy was Sir Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the first edition of his book and several others were printed until 1753. In this book, he describes the first intravenous treatment, it sets the first indications, dosages and different products which can be used. However this method has been forgotten until the late 19th century.

  16. Adenosine modulation of [Ca2+]i in cerebellar granular cells: multiple adenosine receptors involved.

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    Vacas, Javier; Fernández, Mercedes; Ros, Manuel; Blanco, Pablo

    2003-12-01

    Elimination of adenosine by addition of adenosine deaminase (ADA) to the media leads to alterations in intracellular free calcium concentration ([Ca(2+)](i)) in cerebellar granular cells. Adenosine deaminase brings about increases or decreases in [Ca(2+)](i) depending on the previous activation state of the cell. These effects are dependent on the catalytic activity of adenosine deaminase, since its previous catalytic inactivation with Hg(2+) prevents the above-mentioned changes in intracellular calcium. Extracellular calcium is required for the increase in [Ca(2+)](i) promoted by ADA. This rise is insensitive to thapsigargin, but sensitive to micromolar concentrations of Ni(2+). Toxins specific for L, N and P/Q calcium channels do not overtly reduce this effect. N(6)-Cyclopentyl adenosine (CPA), an A(1) receptor agonist, produces a partial reversion of ADA effects, while CGS21680, A(2A)/A(2B) receptor agonist, slightly enhances them. Expression of A(1), A(2A), A(2B) and A(3) adenosine receptor mRNAs was detected in cerebellar granular cell cultures. These results suggest that adenosine modulate [Ca(2+)](i) in cerebellar granule cells through different adenosine receptor subtypes which, at least in part, seem to act through R-type calcium channels.

  17. Adenosine stress protocols for myocardial perfusion imaging

    Directory of Open Access Journals (Sweden)

    Baškot Branislav

    2008-01-01

    Full Text Available Background/Aim. Treadmill test combined with myocardial perfusion scintigraphy (MPS is a commonly used technique in the assessment of coronary artery disease. There are many patients, however, who may not be able to undergo treadmill test. Such patients would benefit from pharmacological stress procedures combined with MPS. The most commonly used pharmacological agents for cardiac stress are coronary vasodilatators (adenosine, dipyridamol and catecholamines. Concomitant low-level treadmill exercise with adenosine pharmacologic stress (AdenoEX during MPS has become commonly used in recent years. A number of studies have demonstrated a beneficial impact of AdenoEX protocol. The aim of the study was, besides introducing into practice the two types of protocols of pharmatological stress test with adenosine, as a preparation for MPS, to compare and monitor the frequency of their side effects to quality, acquisition, as well as to standardize the onset time of acquisition (diagnostic imaging for both protocols. Methods. A total of 130 patients underwent pharmacological stress test with adenosine (vasodilatator. In 108 of the patients we performed concomitant exercise (AdenoEX of low level (50W by a bicycle ergometar. In 28 of the patients we performed Adenosine abbreviated protocol (AdenoSCAN. Side effects of adenosine were followed and compared between the two kinds of protocols AdenoEX and AdenoSCAN. Also compared were image quality and suggested time of acquisition after the stress test. Results. Numerous side effects were found, but being short-lived they did not require any active interventions. The benefit of AdenoEX versus AdenoSCAN included decreased side effects (62% vs 87%, improved safety and patients tolerance, improved target-to-background ratios because of less subdiaphragmatic activity, earlier acquisition, and improved sensitivity. Conclusion. The safety and efficacy of adenosine pharmacological stress is even better with concomitant

  18. The expression of copper-transporting P-type adenosine triphosphatase in ovarian cancer and its correlation with chemotherapy resistance%P型铜转运ATP酶在卵巢癌中的表达及其与化疗耐药的关系

    Institute of Scientific and Technical Information of China (English)

    李侠; 吴绪峰; 陈惠祯

    2008-01-01

    目的:探讨P型铜转运ATP酶(copper-transporting P-type adenosine triphosphatase,ATP 7B)在卵巢癌组织中的表达及其与临床病理参数、化疗耐药的关系.方法:用半定量RT-PCR技术检测ATP 7B在36例卵巢癌组织,10例良性卵巢肿瘤组织,10例正常卵巢组织中的表达水平.结果:ATP7B在卵巢癌组织中的阳性表达率为38.9%,显著高于在良性卵巢肿瘤(0%)及正常卵巢组织中(0%)的表达(P<0.01).ATP7B的表达与肿瘤分化程度有关,ATP7B在低分化组织中的表达明显高于高、中分化组(P<0.05).ATP7B在术前化疗组中的表达高于术前未化疗组,差异有统计学意义(P<0.05).ATP7B表达阳性的卵巢癌患者对化疗的反应率(28.6%)明显低于表达为阴性的患者(72.7%)(P<0.05).结论:ATP 7B可能在卵巢癌对铂类抗肿瘤药的耐药过程中发挥了重要作用.

  19. Adenosine receptor targeting in health and disease.

    Science.gov (United States)

    Gessi, Stefania; Merighi, Stefania; Fazzi, Debora; Stefanelli, Angela; Varani, Katia; Borea, Pier Andrea

    2011-12-01

    The adenosine receptors A(1), A(2A), A(2B) and A(3) are important and ubiquitous mediators of cellular signaling that play vital roles in protecting tissues and organs from damage. In particular, adenosine triggers tissue protection and repair by different receptor-mediated mechanisms, including increasing the oxygen supply:demand ratio, pre-conditioning, anti-inflammatory effects and the stimulation of angiogenesis. The state of the art of the role of adenosine receptors which have been proposed as targets for drug design and discovery, in health and disease, and an overview of the ligands for these receptors in clinical development. Selective ligands of A(1), A(2A), A(2B) and A(3) adenosine receptors are likely to find applications in the treatment of pain, ischemic conditions, glaucoma, asthma, arthritis, cancer and other disorders in which inflammation is a feature. The aim of this review is to provide an overview of the present knowledge regarding the role of these adenosine receptors in health and disease.

  20. Modulation and metamodulation of synapses by adenosine.

    Science.gov (United States)

    Ribeiro, J A; Sebastião, A M

    2010-06-01

    The presence of adenosine in all nervous system cells (neurones and glia) together with its intensive release following insults makes adenosine as a sort of 'regulator' of synaptic communication, leading to the homeostatic coordination of brain function. Besides the direct actions of adenosine on the neurosecretory mechanisms, to tune neurotransmitter release, adenosine receptors interact with other receptors as well as with transporters as part of its attempt to fine-tune synaptic transmission. This review will focus on examples of the different ways adenosine can use to modulate or metamodulate synapses, in other words, to trigger or brake the action of some neurotransmitters and neuromodulators, to cross-talk with other G protein-coupled receptors, with ionotropic receptors and with receptor kinases as well as with transporters. Most of these interactions occur through A2A receptors, which in spite of their low density in some brain areas, such as the hippocampus, may function as amplifiers of the signalling of other mediators at synapses.

  1. The role of adenosine receptors and endogenous adenosine in citalopram-induced cardiovascular toxicity

    Directory of Open Access Journals (Sweden)

    Kubilay Oransay

    2014-01-01

    Full Text Available Aim: We investigated the role of adenosine in citalopram-induced cardiotoxicity. Materials and Methods: Protocol 1: Rats were randomized into four groups. Sodium cromoglycate was administered to rats. Citalopram was infused after the 5% dextrose, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; A 1 receptor antagonist, 8-(-3-chlorostyryl-caffeine (CSC; A 2a receptor antagonist, or dimethyl sulfoxide (DMSO administrations. Protocol 2: First group received 5% dextrose intraperitoneally 1 hour prior to citalopram. Other rats were pretreated with erythro-9-(2-hydroxy-3-nonyl adenine (EHNA; inhibitor of adenosine deaminase and S-(4-Nitrobenzyl-6-thioinosine (NBTI; inhibitor of facilitated adenosine transport. After pretreatment, group 2 received 5% dextrose and group 3 received citalopram. Adenosine concentrations, mean arterial pressure (MAP, heart rate (HR,  QRS duration and QT interval were evaluated. Results: In the dextrose group, citalopram infusion caused a significant decrease in MAP and HR and caused a significant prolongation in QRS and QT. DPCPX infusion significantly prevented the prolongation of the QT interval when compared to control. In the second protocol, citalopram infusion did not cause a significant change in plasma adenosine concentrations, but a significant increase observed in EHNA/NBTI groups. In EHNA/NBTI groups, citalopram-induced MAP and HR reductions, QRS and QT prolongations were more significant than the dextrose group. Conclusions: Citalopram may lead to QT prolongation by stimulating adenosine A 1 receptors without affecting the release of adenosine.

  2. Extravasation of chemotherapy

    DEFF Research Database (Denmark)

    Langer, Seppo W

    2010-01-01

    Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led...

  3. Chemotherapy for Soft Tissue Sarcomas

    Science.gov (United States)

    ... Stage Soft Tissue Sarcoma Treating Soft Tissue Sarcomas Chemotherapy for Soft Tissue Sarcomas Chemotherapy (chemo) is the use of drugs given into ... Depending on the type and stage of sarcoma, chemotherapy may be given as the main treatment or ...

  4. The role of adenosine in Alzheimer's disease.

    Science.gov (United States)

    Rahman, Anisur

    2009-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system manifested by cognitive and memory deterioration, a variety of neuropsychiatric symptoms, behavioral disturbances, and progressive impairment of daily life activities. Current pharmacotherapies are restricted to symptomatic interventions but do not prevent progressive neuronal degeneration. Therefore, new therapeutic strategies are needed to intervene with these progressive pathological processes. In the past several years adenosine, a ubiquitously released purine ribonucleoside, has become important for its neuromodulating capability and its emerging positive experimental effects in neurodegenerative diseases. Recent research suggests that adenosine receptors play important roles in the modulation of cognitive function. The present paper attempts to review published reports and data from different studies showing the evidence of a relationship between adenosinergic function and AD-related cognitive deficits. Epidemiological studies have found an association between coffee (a nonselective adenosine receptor antagonist) consumption and improved cognitive function in AD patients and in the elderly. Long-term administration of caffeine in transgenic animal models showed a reduced amyloid burden in brain with better cognitive performance. Antagonists of adenosine A2A receptors mimic these beneficial effects of caffeine on cognitive function. Neuronal cell cultures with amyloid beta in the presence of an A2A receptor antagonist completely prevented amyloid beta-induced neurotoxicity. These findings suggest that the adenosinergic system constitutes a new therapeutic target for AD, and caffeine and A2A receptor antagonists may have promise to manage cognitive dysfunction in AD.

  5. AMP is an adenosine A1 receptor agonist.

    Science.gov (United States)

    Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J

    2012-02-17

    Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

  6. Adenosine: An immune modulator of inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Jeff Huaqing Ye; Vazhaikkurichi M Rajendran

    2009-01-01

    Inflammatory bowel disease (IBD) is a common and lifelong disabling gastrointestinal disease. Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response. Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models. High extracellular adenosine suppresses and resolves chronic inflammation in IBD models. High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis. Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells, respectively. Increased extracellular adenosine levels activate the A2a receptor, which would reduce cytokines responsible for chronic inflammation.

  7. Neurotoxicity of cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Miyoung Yang; Changjong Moon

    2013-01-01

    There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causal mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.

  8. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

    Aims of this project - The aim of this study was to design and synthesise novel 2-aminopyrimidine derivatives as potential adenosine A1 and A2A receptor antagonists. Background and rationale - Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease) and is characterised by the selective death of the dopaminergic neurons of the nigro-striatal pathway. Distinctive motor symptoms include bradykinesia, muscle rigidity and tremor, while non-m...

  9. Chemotherapy for Melanoma.

    Science.gov (United States)

    Wilson, Melissa A; Schuchter, Lynn M

    2016-01-01

    Prior to the recent therapeutic advances, chemotherapy was the mainstay of treatment options for advanced-stage melanoma. A number of studies have investigated various chemotherapy combinations in order to expand on the clinical responses achieved with single-agent dacarbazine, but these have not demonstrated an improvement in overall survival. Similar objective responses were observed with the combination of carboplatin and paclitaxel as were seen with single-agent dacarbazine. The combination of chemotherapy and immunotherapy, known as biochemo-therapy, has shown high clinical responses; however, biochemo-therapy has not been shown to improve overall survival and resulted in increased toxicities. In contrast, palliation and long-term responses have been observed with localized treatment with isolated limb perfusion or infusion in limb-isolated disease. Although new, improved therapeutic options exist for first-line management of advanced-stage melanoma, chemotherapy may still be important in the palliative treatment of refractory, progressive, and relapsed melanoma. We review the various chemotherapy options available for use in the treatment and palliation of advanced-stage melanoma, discuss the important clinical trials supporting the treatment recommendations, and focus on the clinical circumstances in which treatment with chemotherapy is useful.

  10. Selective deletion of the A1 adenosine receptor abolishes heart-rate slowing effects of intravascular adenosine in vivo.

    Directory of Open Access Journals (Sweden)

    Michael Koeppen

    Full Text Available OBJECTIVE: Intravenous adenosine induces temporary bradycardia. This is due to the activation of extracellular adenosine receptors (ARs. While adenosine can signal through any of four ARs (A1AR, A2AAR, A2BAR, A3AR, previous ex vivo studies implicated the A1AR in the heart-rate slowing effects. Here, we used comparative genetic in vivo studies to address the contribution of individual ARs to the heart-rate slowing effects of intravascular adenosine. METHODS AND RESULTS: We studied gene-targeted mice for individual ARs to define their in vivo contribution to the heart-rate slowing effects of adenosine. Anesthetized mice were treated with a bolus of intravascular adenosine, followed by measurements of heart-rate and blood pressure via a carotid artery catheter. These studies demonstrated dose-dependent slowing of the heart rate with adenosine treatment in wild-type, A2AAR(-/-, A2BAR(-/-, or A3AR(-/- mice. In contrast, adenosine-dependent slowing of the heart-rate was completely abolished in A1AR(-/- mice. Moreover, pre-treatment with a specific A1AR antagonist (DPCPX attenuated the heart-rate slowing effects of adenosine in wild-type, A2AAR(-/-, or A2BAR(-/- mice, but did not alter hemodynamic responses of A1AR(-/- mice. CONCLUSIONS: The present studies combine pharmacological and genetic in vivo evidence for a selective role of the A1AR in slowing the heart rate during adenosine bolus injection.

  11. [The involvement of adenosine and adenosine deaminase in experimental myocardial infarct].

    Science.gov (United States)

    Stratone, A; Busuioc, A; Roşca, V; Bazgan, L; Popa, M; Hăulică, I

    1989-01-01

    By the ligature of the left coronary artery in the rat anesthetized with nembutal (10 mg/100 i.p.) a significant increase of the 5'-nucleotidase activity (Wooton method) was noticed 10 minutes after the left ventricle infarction (from an average value of 1038.5 +/- 187 mU/g tissue to 1537 +/- 225 mU/g fresh tissue). The adenosine desaminase levels spectrophotometrically determined by Denstedt technique, do not appear significantly modified 10 or 30 minutes after the left ventricle infarction. The chromatographically determined adenosine levels, by HPLC technique, decrease from the average value of 11.63 +/- 1.4 micrograms/mg PT to 8.60 +/- 1.0 micrograms/mg PT 30 minutes after infarction. The observed changes are explained by the conditions of hypoxia in the infarcted ventricle which lead to the raise in adenosine levels by activating the 5'-nucleotidase and their depression by a very fast metabolism of the same substance.

  12. Effects of adenosine agonist R-phenylisopropyl-adenosine on halothane anesthesia and antinociception in rats

    Institute of Scientific and Technical Information of China (English)

    Hai-chun MA; Yan-fen WANG; Chun-sheng FENG; Hua ZHAO; Shuji DOHI

    2005-01-01

    Aim: To investigate the antinociceptive effect of adenosine agonist Rphenylisopropyl-adenosine (R-PIA) given to conscious rats by intracerebroventricular (ICV) and intrathecal (IT), and identify the effect of R-PIA on minimum alveolar concentration (MAC) of halothane with pretreatment of A1 receptor an tagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or K+ channel blocker 4-aminopyridine (4-AP). Methods: Sprague-Dawley rats were implanted with 24 gauge stainless steel guide cannula using stereotaxic apparatus and ICV method, and an IT catheter (PE-10, 8.5 cm) was inserted into the lumbar subarachnoid space, while the rats were under pentobarbital anesthesia. After one week of recovery from surgery, rats were randomly assigned to one of the following protocols: MAC of halothane, or tail-flick latency. All measurements were performed after R-PIA (0.8-2.0 μg) microinjection into ICV and IT with or without pretreatment of DPCPX or 4-AP. Results: Microinjection of adenosine agonist R PIA in doses of 0.8-2.0 μg into ICV and IT produced a significant dose- and time dependent antinociceptive action as reflected by increasing latency times and ICV administration of adenosine agonist R-PIA (0.8 μg) reducing halothane anes thetic requirements (by 29%). The antinociception and reducing halothane requirements effected by adenosine agonist R-PIA was abolished by DPCPX and 4-AP. Conclusion: ICV and IT administration of adenosine agonist R-PIA produced an antinociceptive effect in a dose-dependent manner and decreased hal othane MAC with painful stimulation through activation of A1 receptor subtype, and the underlying mechanism involves K+ channel activation.

  13. N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors

    Science.gov (United States)

    Fang, Ming; Chai, Yiqiu; Chen, Guanjv; Wang, Huidong; Huang, Bo

    2016-01-01

    The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32–35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR. PMID:27668428

  14. N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors.

    Science.gov (United States)

    Fang, Ming; Chai, Yiqiu; Chen, Guanjv; Wang, Huidong; Huang, Bo

    The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32-35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR.

  15. The Role of Adenosine Signaling in Headache: A Review

    Directory of Open Access Journals (Sweden)

    Nathan T. Fried

    2017-03-01

    Full Text Available Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments. In this review, we highlight evidence that supports the involvement of adenosine signaling in different forms of headache, headache triggers, and basic headache physiology. This evidence supports adenosine A2A receptors as a critical adenosine receptor subtype involved in headache pain. Adenosine A2A receptor signaling may contribute to headache via the modulation of intracellular Cyclic adenosine monophosphate (cAMP production or 5' AMP-activated protein kinase (AMPK activity in neurons and glia to affect glutamatergic synaptic transmission within the brainstem. This evidence supports the further study of adenosine signaling in headache and potentially illuminates it as a novel therapeutic target for migraine.

  16. Primary adenosine monophosphate (AMP) deaminase deficiency in a hypotonic infant.

    Science.gov (United States)

    Castro-Gago, Manuel; Gómez-Lado, Carmen; Pérez-Gay, Laura; Eirís-Puñal, Jesús; Martínez, Elena Pintos; García-Consuegra, Inés; Martín, Miguel Angel

    2011-06-01

    The spectrum of the adenosine monophosphate (AMP) deaminase deficiency ranges from asymptomatic carriers to patients who manifest exercise-induced muscle pain, occasionally rhabdomyolysis, and idiopathic hyperCKemia. However, previous to the introduction of molecular techniques, rare cases with congenital weakness and hypotonia have also been reported. We report a 6-month-old girl with the association of congenital muscle weakness and hypotonia, muscle deficiency of adenosine monophosphate deaminase, and the homozygous C to T mutation at nucleotide 34 of the adenosine monophosphate deaminase-1 gene. This observation indicates the possible existence of a primary adenosine monophosphate deaminase deficiency manifested by congenital muscle weakness and hypotonia.

  17. Pretreatment with adenosine and adenosine A1 receptor agonist protects against intestinal ischemia-reperfusion injury in rat

    Institute of Scientific and Technical Information of China (English)

    V Haktan Ozacmak; Hale Sayan

    2007-01-01

    AIM: To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury.METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N6-cyclopentyladenosine, A1 receptor agonist or 8-cyclopentyl-1,3-dipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase,malondialdehyde, and reduced glutathione levels were measured.RESULTS: Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist.CONCLUSION: The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.

  18. Combination Chemotherapy for Influenza

    Directory of Open Access Journals (Sweden)

    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  19. Mechanism of protection of adenosine from sulphate radical anion and repair of adenosine radicals by caffeic acid in aqueous solution

    Indian Academy of Sciences (India)

    M Sudha Swaraga; L Charitha; M Adinarayana

    2005-07-01

    The photooxidation of adenosine in presence of peroxydisulphate (PDS) has been studied by spectrophotometrically measuring the absorbance of adenosine at 260 nm. The rates of oxidation of adenosine by sulphate radical anion have been determined in the presence of different concentrations of caffeic acid. Increase in [caffeic acid] is found to decrease the rate of oxidation of adenosine suggesting that caffeic acid acts as an efficient scavenger of $SO_{4}^{\\bullet-}$ and protects adenosine from it. Sulphate radical anion competes for adenosine as well as for caffeic acid. The quantum yields of photooxidation of adenosine have been calculated from the rates of oxidation of adenosine and the light intensity absorbed by PDS at 254 nm, the wavelength at which PDS is activated to sulphate radical anion. From the results of experimentally determined quantum yields (exptl) and the quantum yields calculated (cal) assuming caffeic acid acting only as a scavenger of $SO_{4}^{\\bullet-}$ show that exptl values are lower than cal values. The ' values, which are experimentally found quantum yield values at each caffeic acid concentration and corrected for $SO_{4}^{\\bullet-}$ scavenging by caffeic acid, are also found to be greater than exptl values. These observations suggest that the transient adenosine radicals are repaired by caffeic acid in addition to scavenging of sulphate radical anions.

  20. Electroacupuncture improves neuropathic pain Adenosine,adenosine 5'-triphosphate disodium and their receptors perhaps change simultaneously

    Institute of Scientific and Technical Information of China (English)

    Wen Ren; Wenzhan Tu; Songhe Jiang; Ruidong Cheng; Yaping Du

    2012-01-01

    Applying a stimulating current to acupoints through acupuncture needles-known as electroacupuncture-has the potential to produce analgesic effects in human subjects and experimental animals.When acupuncture was applied in a rat model,adenosine 5'-triphosphate disodium in the extracellular space was broken down into adenosine,which in turn inhibited pain transmission by means of an adenosine A1 receptor-dependent process.Direct injection of an adenosine A1 receptor agonist enhanced the analgesic effect of acupuncture.The analgesic effect of acupuncture appears to be mediated by activation of A1 receptors located on ascending nerves.In neuropathic pain,there is upregulation of P2X purinoceptor 3(P2X3)receptor expression in dorsal root ganglion neurons.Conversely,the onset of mechanical hyperalgesia was diminished and established hyperalgesia was significantly reversed when P2X3 receptor expression was downregulated.The pathways upon which electroacupuncture appear to act are interwoven with pain pathways,and electroacupuncture stimuli converge with impulses originating from painful areas.Electroacupuncture may act via purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on neuropathic pain.

  1. Serum adenosine deaminase activity in cutaneous anthrax.

    Science.gov (United States)

    Sunnetcioglu, Mahmut; Karadas, Sevdegul; Aslan, Mehmet; Ceylan, Mehmet Resat; Demir, Halit; Oncu, Mehmet Resit; Karahocagil, Mustafa Kasım; Sunnetcioglu, Aysel; Aypak, Cenk

    2014-07-06

    Adenosine deaminase (ADA) activity has been discovered in several inflammatory conditions; however, there are no data associated with cutaneous anthrax. The aim of this study was to investigate serum ADA activity in patients with cutaneous anthrax. Sixteen patients with cutaneous anthrax and 17 healthy controls were enrolled. We measured ADA activity; peripheral blood leukocyte, lymphocyte, neutrophil, and monocyte counts; erythrocyte sedimentation rate; and C reactive protein levels. Serum ADA activity was significantly higher in patients with cutaneous anthrax than in the controls (panthrax.

  2. Chemotherapy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Javier Sastre; Jose Angel García-Saenz; Eduardo Díaz-Rubio

    2006-01-01

    Metastatic gastric cancer remains a non-curative disease.Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase Ⅱ and Ⅲ studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed.Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considered as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase Ⅲ trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116study, postoperative chemoradiation has been Accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease.Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase Ⅱstudies are showing promising results. Phase Ⅲ trials are needed.

  3. Chemotherapy of herpesvirus infections.

    Science.gov (United States)

    Jawetz, E

    1975-07-01

    Herpesviruses commonly produce lesions that come to the attention of physicians. Many different chemicals are known to suppress the growth of herpesviruses in vitro, but only a few of these have found application in clinical practice. A critical assessment of the place of some of these forms of chemotherapy was briefly presented.

  4. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  5. Comorbidities in Neurology: Is Adenosine the Common Link?

    Science.gov (United States)

    Boison, Detlev; Aronica, Eleonora

    2015-01-01

    Comorbidities in Neurology represent a major conceptual and therapeutic challenge. For example, temporal lobe epilepsy (TLE) is a syndrome comprised of epileptic seizures and comorbid symptoms including memory and psychiatric impairment, depression, and sleep dysfunction. Similarly, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are accompanied by various degrees of memory dysfunction. Patients with AD have an increased likelihood for seizures, whereas all four conditions share certain aspects of psychosis, depression, and sleep dysfunction. This remarkable overlap suggests common pathophysiological mechanisms, which include synaptic dysfunction and synaptotoxicity, as well as glial activation and astrogliosis. Astrogliosis is linked to synapse function via the tripartite synapse, but astrocytes also control the availability of gliotransmitters and adenosine. Here we will specifically focus on the ‘adenosine hypothesis of comorbidities’ implying that astrocyte activation, via overexpression of adenosine kinase (ADK), induces a deficiency in the homeostatic tone of adenosine. We present evidence from patient-derived samples showing astrogliosis and overexpression of ADK as common pathological hallmark of epilepsy, AD, PD, and ALS. We discuss a transgenic ‘comorbidity model’, in which brain-wide overexpression of ADK and resulting adenosine deficiency produces a comorbid spectrum of seizures, altered dopaminergic function, attentional impairment, and deficits in cognitive domains and sleep regulation. We conclude that dysfunction of adenosine signaling is common in neurological conditions, that adenosine dysfunction can explain comorbid phenotypes, and that therapeutic adenosine augmentation might be effective for the treatment of comorbid symptoms in multiple neurological conditions. PMID:25979489

  6. Endogenous adenosine curtails lipopolysaccharide-stimulated tumour necrosis factor synthesis

    NARCIS (Netherlands)

    Eigler, A; Greten, T F; Sinha, B; Haslberger, C; Sullivan, G W; Endres, S

    1997-01-01

    Recent studies have demonstrated the inhibitory effect of exogenous adenosine on TNF production. During inflammation endogenous adenosine levels are elevated and may be one of several anti-inflammatory mediators that reduce TNF synthesis. In the present study the authors investigated this role of ad

  7. Adenosine receptor modulation: potential implications in veterinary medicine.

    Science.gov (United States)

    Dip, Ramiro G

    2009-01-01

    Adenosine is a purine nucleoside whose concentration increases during inflammation and hypoxia and the many roles of this molecule are becoming better understood. Increased reactivity to adenosine of the airways of asthmatic but not of normal subjects underlines the role of adenosine in airway inflammation. The identification and pharmacological characterisation of different adenosine receptors have stimulated the search for subtype-specific ligands able to modulate the effects of this molecule in a directed way. Several compounds of different chemical classes have been identified as having potential drawbacks, including side effects resulting from the broad distribution of the receptors across the organism, have prevented clinical application. In this article, the effects of adenosine's different receptors and the intracellular signalling pathways are reviewed. The potential of adenosine receptor modulation as a therapeutic target for chronic airway inflammation is considered, taking equine recurrent airway disease and feline asthma as examples of naturally occurring airway obstructive diseases. Other potential applications for adenosine receptor modulation are also discussed. As the intrinsic molecular events of adenosine's mechanism of action become uncovered, new concrete therapeutic approaches will become available for the treatment of various conditions in veterinary medicine.

  8. Extending the Clinical Phenotype of Adenosine Deaminase 2 Deficiency.

    Science.gov (United States)

    Ben-Ami, Tal; Revel-Vilk, Shoshana; Brooks, Rebecca; Shaag, Avraham; Hershfield, Michael S; Kelly, Susan J; Ganson, Nancy J; Kfir-Erenfeld, Shlomit; Weintraub, Michael; Elpeleg, Orly; Berkun, Yackov; Stepensky, Polina

    2016-10-01

    Adenosine deaminase 2 deficiency is an autoinflammatory disease, characterized by various forms of vasculitis. We describe 5 patients with adenosine deaminase 2 deficiency with various hematologic manifestations, including pure red cell aplasia, with no evidence for vasculitis. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Adenosine Receptors: Expression, Function and Regulation

    Directory of Open Access Journals (Sweden)

    Sandeep Sheth

    2014-01-01

    Full Text Available Adenosine receptors (ARs comprise a group of G protein-coupled receptors (GPCR which mediate the physiological actions of adenosine. To date, four AR subtypes have been cloned and identified in different tissues. These receptors have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. This review will describe the biochemical characteristics and signaling cascade associated with each receptor and provide insight into how these receptors are regulated in response to agonists. A key property of some of these receptors is their ability to serve as sensors of cellular oxidative stress, which is transmitted by transcription factors, such as nuclear factor (NF-κB, to regulate the expression of ARs. Recent observations of oligomerization of these receptors into homo- and heterodimers will be discussed. In addition, the importance of these receptors in the regulation of normal and pathological processes such as sleep, the development of cancers and in protection against hearing loss will be examined.

  10. A High-Affinity Adenosine Kinase from Anopheles Gambiae

    Energy Technology Data Exchange (ETDEWEB)

    M Cassera; M Ho; E Merino; E Burgos; A Rinaldo-Matthis; S Almo; V Schramm

    2011-12-31

    Genome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (K{sub m} = 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site, but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with a bound bisubstrate analogue Ap{sub 4}A (2.0 {angstrom} resolution) reveals interactions for adenosine and ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg{sup 2+} ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layer {alpha}/{beta}/{alpha} sandwich, and a small cap domain in contact with adenosine. The specificity and tight binding for adenosine arise from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168, and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64, and Asn68 and the ribosyl 2'- and 3'-hydroxyl groups. The structure is more similar to that of human adenosine kinase (48% identical) than to that of AK from Toxoplasma gondii (31% identical). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to AMP at near the diffusion limit, suggesting an important role for this enzyme in the maintenance of the adenine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects.

  11. Prevent Infections During Chemotherapy

    Centers for Disease Control (CDC) Podcasts

    2011-10-24

    This podcast discusses the importance of preventing infections in cancer patients who are undergoing chemotherapy. Dr. Lisa Richardson, CDC oncologist, talks about a new Web site for cancer patients and their caregivers.  Created: 10/24/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 10/24/2011.

  12. Chemotherapy of Leishmaniasis.

    Science.gov (United States)

    1978-12-01

    NOTES 1S. KEY WORDS (Continue on reverse side linscoeawy and identiIIy by block number) LEISHMANIA LEISHMANIASIS CHEMOTHERAPY ANTILEISHMANIAL PENTOSTAM...number of compounds was supplied by WRAIR for testing on four strains of Leishmania in December 1977. Preliminary data were supplied to WRAIR by the...j_ = L. tropica major (Strain LV39 from USSR) and the New World cutaneous leishmaniasis by L. mexicana amazonensis (Strain LV78 from Brazil). The test

  13. Vasoconstrictor and vasodilator effects of adenosine in the kidney

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Schnermann, Jurgen

    2003-01-01

    Adenosine is an ATP breakdown product that in most vessels causes vasodilatation and that contributes to the metabolic control of organ perfusion, i.e., to the match between oxygen demand and oxygen delivery. In the renal vasculature, in contrast, adenosine can produce vasoconstriction, a respons...... activation from changes in vascular adenosine concentration, a characteristic that is ideally suited for the role of renal adenosine as a paracrine factor in the control of glomerular function.......Adenosine is an ATP breakdown product that in most vessels causes vasodilatation and that contributes to the metabolic control of organ perfusion, i.e., to the match between oxygen demand and oxygen delivery. In the renal vasculature, in contrast, adenosine can produce vasoconstriction, a response...... that has been suggested to be an organ-specific version of metabolic control designed to restrict organ perfusion when transport work increases. However, the vasoconstriction elicited by an intravenous infusion of adenosine is only short lasting, being replaced within 1-2 min by vasodilatation. It appears...

  14. Temporal variations of adenosine metabolism in human blood.

    Science.gov (United States)

    Chagoya de Sánchez, V; Hernández-Muñoz, R; Suárez, J; Vidrio, S; Yáñez, L; Aguilar-Roblero, R; Oksenberg, A; Vega-González, A; Villalobos, L; Rosenthal, L; Fernández-Cancino, F; Drucker-Colín, R; Díaz-Muñoz, M

    1996-08-01

    Eight diurnally active (06:00-23:00 h) subjects were adapted for 2 days to the room conditions where the experiments were performed. Blood sampling for adenosine metabolites and metabolizing enzymes was done hourly during the activity span and every 30 min during sleep. The results showed that adenosine and its catabolites (inosine, hypoxanthine, and uric acid), adenosine synthesizing (S-adenosylhomocysteine hydrolase and 5'-nucleotidase), degrading (adenosine deaminase) and nucleotide-forming (adenosine kinase) enzymes as well as adenine nucleotides (AMP, ADP, and ATP) undergo statistically significant fluctuations (ANOVA) during the 24 h. However, energy charge was invariable. Glucose and lactate chronograms were determined as metabolic indicators. The same data analyzed by the chi-square periodogram and Fourier series indicated ultradian oscillatory periods for all the metabolites and enzymatic activities determined, and 24-h oscillatory components for inosine, hypoxanthine, adenine nucleotides, glucose, and the activities of SAH-hydrolase, 5'-nucleotidase, and adenosine kinase. The single cosinor method showed significant oscillatory components exclusively for lactate. As a whole, these results suggest that adenosine metabolism may play a role as a biological oscillator coordinating and/or modulating the energy homeostasis and physiological status of erythrocytes in vivo and could be an important factor in the distribution of purine rings for the rest of the organism.

  15. Increased Cortical Extracellular Adenosine Correlates with Seizure Termination

    Science.gov (United States)

    Van Gompel, Jamie J.; Bower, Mark R.; Worrell, Gregory A.; Stead, Matt; Chang, Su-Youne; Goerss, Stephan J.; Kim, Inyong; Bennet, Kevin E.; Meyer, Fredric B.; Marsh, W. Richard; Blaha, Charles D.; Lee, Kendall H.

    2014-01-01

    Objective Seizures are currently defined by their electrographic features. However, neuronal networks are intrinsically dependent upon neurotransmitters of which little is known regarding their peri-ictal dynamics. Evidence supports adenosine as having a prominent role in seizure termination, as its administration can terminate and reduce seizures in animal models. Further, microdialysis studies in humans suggest adenosine is elevated peri-ictally, but the relationship to the seizure is obscured by its temporal measurement limitations. Because electrochemical techniques can provide vastly superior temporal resolution, we test the hypothesis that extracellular adenosine concentrations rise during seizure termination in an animal model and humans using electrochemistry. Methods White farm swine (n=45) were used in an acute cortical model of epilepsy and 10 human epilepsy patients were studied during intraoperative electrocorticography (Ecog). Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) based fast scan cyclic voltametry (FSCV) and fixed potential amperometry were obtained utilizing an adenosine specific triangular waveform or biosensors respectively. Results Simultaneous Ecog and electrochemistry demonstrated an average adenosine rise of 260% compared to baseline at 7.5 ± 16.9 seconds with amperometry (n=75 events) and 2.6 ± 11.2 seconds with FSCV (n=15 events) prior to electrographic seizure termination. In agreement with these animal data, adenosine elevation prior to seizure termination in a human patient utilizing FSCV was also seen. Significance Simultaneous Ecog and electrochemical recording supports the hypothesis that adenosine rises prior to seizure termination, suggesting that adenosine itself may be responsible for seizure termination. Future work using intraoperative WINCS based FSCV recording may help to elucidate the precise relationship between adenosine and seizure termination. PMID:24483230

  16. Adenosine and Preexcitation Variants: Reappraisal of Electrocardiographic Changes.

    Science.gov (United States)

    Ali, Hussam; Lupo, Pierpaolo; Foresti, Sara; De Ambroggi, Guido; Epicoco, Gianluca; Fundaliotis, Angelica; Cappato, Riccardo

    2016-07-01

    Intravenous adenosine is a short-acting blocker of the atrioventricular node that has been used to unmask subtle or latent preexcitation, and also to enable catheter ablation in selected patients with absent or intermittent preexcitation. Depending on the accessory pathway characteristics, intravenous adenosine may produce specific electrocardiographic changes highly suggestive of the preexcitation variant. Herein, we view different ECG responses to this pharmacological test in various preexcitation patterns that were confirmed by electrophysiological studies. Careful analysis of electrocardiographic changes during adenosine test, with emphasis on P-delta interval, preexcitation degree, and atrioventricular block, can be helpful to diagnose the preexcitation variant/pattern.

  17. Possible mechanism of adenosine protection in carbon tetrachloride acute hepatotoxicity. Role of adenosine by-products and glutathione peroxidase.

    Science.gov (United States)

    Chagoya de Sánchez, V; Hernández-Muñoz, R; Yáñez, L; Vidrio, S; Díaz-Muñoz, M

    1995-02-01

    Adenosine proved to be an effective hepatoprotector increasing the survival rate of rats receiving lethal doses of CCl4. Searching for the mechanism of action, we found that adenosine transiently prevents the necrotic liver damage associated to an acute CCl4 treatment. The antilipoperoxidative action of the nucleoside was evidenced by a decrease of TBA-reactive products and the diene conjugates elicited by the hepatotoxin. Adenosine's protective effect was demonstrated by reverting the decrease of cytochrome P-450 while preserved intact the activity of the microsomal enzyme glucose-6-phosphatase. CCl4 promoted an increase in the oxidant stress through an enhancement in oxidized glutathione levels. This action was also completely counteracted by the nucleoside. Adenosine was unable to prevent CCl4 activation and, even, increased .CCl3 formation in the presence of PBN in vivo. However, in the presence of the nucleoside, irreversible binding of 14CCl4 to the microsomal lipid fraction of the treated animals was decreased. These results suggest that adenosine protective action might be exerted at the level of the propagation reaction following CCl4 activation. Two possible mechanisms were associated to the nucleoside protection: (1) the peroxide-metabolyzed enzymes, GSH-per, showed a marked increase after 30 minutes of adenosine treatment, which was potentiated by the hepatotoxin, suggesting an important role of this enzyme in the nucleoside's action; (2) the adenosine catabolism induced an increase in uric acid level, and allopurinol, a purine metabolism inhibitor, prevented such elevation as well as the antilipoperoxidative action of adenosine and the increase of GSH-per associated with the nucleoside treatment. These facts strongly suggest that the protective effect elicited by adenosine is not a direct one, but rather is related to its catabolic products, such as uric acid, which has been recognized as a free radical scavenger.

  18. Rosuvastatin increases extracellular adenosine formation in humans in vivo: a new perspective on cardiovascular protection.

    OpenAIRE

    Meijer, P; Oyen, W.J.G.; Dekker, D.; Broek, P.H.H. van den; Wouters, C.W.; Boerman, O.C.; Scheffer, G. J.; Smits, P; Rongen, G.A.P.J.M.

    2009-01-01

    OBJECTIVE: Statins may increase extracellular adenosine formation from adenosine monophosphate by enhancing ecto-5'-nucleotidase activity. This theory was tested in humans using dipyridamole-induced vasodilation as a read-out for local adenosine formation. Dipyridamole inhibits the transport of extracellular adenosine into the cytosol resulting in increased extracellular adenosine and subsequent vasodilation. In addition, we studied the effect of statin therapy in a forearm model of ischemia-...

  19. Adenosine Deaminase Activity in Diabetic and Obese Patients ...

    African Journals Online (AJOL)

    Journal of Health and Visual Sciences ... Abstract. Adenosine deaminase (ADA) commonly associated with severe combined ... The results (mean±) show that the mean values in the test groups were significantly higher than the controls ...

  20. Inhibition of uptake of adenosine into human blood platelets

    NARCIS (Netherlands)

    Lips, J.P.M.; Sixma, J.J.; Trieschnigg, A.C.

    1980-01-01

    Adenosine transport into human blood platelets is mediated by two independent systems with different affinities. Both systems transport only purine nucleosides and no pyrimidine nucleosides. In experiments with differently substituted purine nucleosides, purines and analogues, differences in carrier

  1. Adenosine Deaminase Deficiency – More Than Just an Immunodeficiency

    OpenAIRE

    Kathryn Victoria Whitmore; Hubert Bobby Gaspar

    2016-01-01

    Adenosine deaminase (ADA) deficiency is best known as a form of severe combined immunodeficiency (SCID) which results from mutations in the gene encoding adenosine deaminase. Affected patients present with clinical and immunological manifestations typical of a severe combined immunodeficiency. Therapies are currently available that can that target these immunological disturbances and treated patients show varying degrees of clinical improvement. However, there is now a growing body of evidenc...

  2. Low-dose adenosine stress echocardiography: Detection of myocardial viability

    Science.gov (United States)

    Djordjevic-Dikic, Ana; Ostojic, Miodrag; Beleslin, Branko; Nedeljkovic, Ivana; Stepanovic, Jelena; Stojkovic, Sinisa; Petrasinovic, Zorica; Nedeljkovic, Milan; Saponjski, Jovica; Giga, Vojislav

    2003-01-01

    Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months) were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments with baseline dyssynergy, adenosine echocardiography identified 122 segments as positive for viability, and 135 as necrotic since no improvement of systolic thickening was observed. Follow-up wall motion score index was 1.31 ± 0.30 (p < 0.001 vs. rest). The sensitivity of adenosine echo test for identification of viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%. Positive and negative predictive values were 97% and 80%, respectively. Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability. PMID:12812523

  3. The A3 adenosine receptor: history and perspectives.

    Science.gov (United States)

    Borea, Pier Andrea; Varani, Katia; Vincenzi, Fabrizio; Baraldi, Pier Giovanni; Tabrizi, Mojgan Aghazadeh; Merighi, Stefania; Gessi, Stefania

    2015-01-01

    By general consensus, the omnipresent purine nucleoside adenosine is considered a major regulator of local tissue function, especially when energy supply fails to meet cellular energy demand. Adenosine mediation involves activation of a family of four G protein-coupled adenosine receptors (ARs): A(1), A(2)A, A(2)B, and A(3). The A(3) adenosine receptor (A(3)AR) is the only adenosine subtype to be overexpressed in inflammatory and cancer cells, thus making it a potential target for therapy. Originally isolated as an orphan receptor, A(3)AR presented a twofold nature under different pathophysiologic conditions: it appeared to be protective/harmful under ischemic conditions, pro/anti-inflammatory, and pro/antitumoral depending on the systems investigated. Until recently, the greatest and most intriguing challenge has been to understand whether, and in which cases, selective A(3) agonists or antagonists would be the best choice. Today, the choice has been made and A(3)AR agonists are now under clinical development for some disorders including rheumatoid arthritis, psoriasis, glaucoma, and hepatocellular carcinoma. More specifically, the interest and relevance of these new agents derives from clinical data demonstrating that A(3)AR agonists are both effective and safe. Thus, it will become apparent in the present review that purine scientists do seem to be getting closer to their goal: the incorporation of adenosine ligands into drugs with the ability to save lives and improve human health.

  4. Low-dose adenosine stress echocardiography: Detection of myocardial viability

    Directory of Open Access Journals (Sweden)

    Nedeljkovic Milan

    2003-06-01

    Full Text Available Abstract Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability.

  5. Why chemotherapy can fail?

    Science.gov (United States)

    Król, M; Pawłowski, K M; Majchrzak, K; Szyszko, K; Motyl, T

    2010-01-01

    There are many reasons that lead to failure of cancer chemotherapy. Cancer has the ability to become resistant to many different types of drugs. Increased efflux of drug, enhanced repair/increased tolerance to DNA damage, high antiapoptotic potential, decreased permeability and enzymatic deactivation allow cancer cell survive the chemotherapy. Treatment can lead to the death of most tumor cells (drug-sensitive), but some of them (drug-resistant) survive and grow again. These tumor cells may arise from stem cells. There are many studies describing human experiments with multidrug resistance, especially in breast cancer. Unfortunately, studies of canine or feline ABC super family members are not as extensive as in human or mice and they are limited to several papers describing PGP in mammary cancer, cutaneous mast cell tumors and lymphoma. Multidrug resistance is one of the most significant problems in oncology today. The involvement of many different, not fully recognized, mechanisms in multidrug resistance of cancer cells makes the development of effective methods of therapy very difficult. Understanding the mechanisms of drug resistance in cancer cells may improve the results of treatment. This review article provides a synopsis of all aspects that refer to cancer cell resistance to antitumor drugs.

  6. 1-(beta-D-Erythrofuranosyl)adenosine.

    Science.gov (United States)

    Kline, Paul C; Zhao, Hongqiu; Noll, Bruce C; Oliver, Allen G; Serianni, Anthony S

    2010-04-01

    The title compound, also known as beta-erythroadenosine, C(9)H(11)N(5)O(3), (I), a derivative of beta-adenosine, (II), that lacks the C5' exocyclic hydroxymethyl (-CH(2)OH) substituent, crystallizes from hot ethanol with two independent molecules having different conformations, denoted (IA) and (IB). In (IA), the furanose conformation is (O)T(1)-E(1) (C1'-exo, east), with pseudorotational parameters P and tau(m) of 114.4 and 42 degrees, respectively. In contrast, the P and tau(m) values are 170.1 and 46 degrees, respectively, in (IB), consistent with a (2)E-(2)T(3) (C2'-endo, south) conformation. The N-glycoside conformation is syn (+sc) in (IA) and anti (-ac) in (IB). The crystal structure, determined to a resolution of 2.0 A, of a cocrystal of (I) bound to the enzyme 5'-fluorodeoxyadenosine synthase from Streptomyces cattleya shows the furanose ring in a near-ideal (O)E (east) conformation (P = 90 degrees and tau(m) = 42 degrees) and the base in an anti (-ac) conformation.

  7. Different efficacy of adenosine and NECA derivatives at the human A3 adenosine receptor: insight into the receptor activation switch.

    Science.gov (United States)

    Dal Ben, Diego; Buccioni, Michela; Lambertucci, Catia; Kachler, Sonja; Falgner, Nico; Marucci, Gabriella; Thomas, Ajiroghene; Cristalli, Gloria; Volpini, Rosaria; Klotz, Karl-Norbert

    2014-01-15

    A3 Adenosine receptors are promising drug targets for a number of diseases and intense efforts are dedicated to develop selective agonists and antagonists of these receptors. A series of adenosine derivatives with 2-(ar)-alkynyl chains, with high affinity and different degrees of selectivity for human A3 adenosine receptors was tested for the ability to inhibit forskolin-stimulated adenylyl cyclase. All these derivatives are partial agonists at A3 adenosine receptors; their efficacy is not significantly modified by the introduction of small alkyl substituents in the N(6)-position. In contrast, the adenosine-5'-N-ethyluronamide (NECA) analogs of 2-(ar)-alkynyladenosine derivatives are full A3 agonists. Molecular modeling analyses were performed considering both the conformational behavior of the ligands and the impact of 2- and 5'-substituents on ligand-target interaction. The results suggest an explanation for the different agonistic behavior of adenosine and NECA derivatives, respectively. A sub-pocket of the binding site was analyzed as a crucial interaction domain for receptor activation.

  8. Palliative chemotherapy: oxymoron or misunderstanding?

    Science.gov (United States)

    Roeland, E J; LeBlanc, T W

    2016-03-21

    Oncologists routinely prescribe chemotherapy for patients with advanced cancer. This practice is sometimes misunderstood by palliative care clinicians, yet data clearly show that chemotherapy can be a powerful palliative intervention when applied appropriately. Clarity regarding the term "palliative chemotherapy" is needed: it is chemotherapy given in the non-curative setting to optimize symptom control, improve quality of life, and sometimes to improve survival. Unfortunately, oncologists lack adequate tools to predict which patients will benefit. In a study recently published in BMC Palliative Care, Creutzfeldt et al. presented an innovative approach to advancing the science in this area: using patient reported outcomes to predict responses to palliative chemotherapy. With further research, investigators may be able to develop predictive models for use at the bedside to inform clinical decision-making about the risks and benefits of treatment. In the meantime, oncologists and palliative care clinicians must work together to reduce the use of "end-of-life chemotherapy"-chemotherapy given close to death, which does not improve longevity or symptom control-while optimizing the use of chemotherapy that has true palliative benefits for patients.

  9. Chemotherapy for children with medulloblastoma

    NARCIS (Netherlands)

    Michiels, E.M.; Schouten-van Meeteren, A.Y.; Doz, F.; Janssens, G.O.R.J.; Dalen, E.C. van

    2015-01-01

    BACKGROUND: Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by delet

  10. A history of cancer chemotherapy.

    Science.gov (United States)

    DeVita, Vincent T; Chu, Edward

    2008-11-01

    The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents. It was, however, four World War II-related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.

  11. Interstitial pneumonitis following intrapleural chemotherapy

    Directory of Open Access Journals (Sweden)

    Humphries Gary N

    2009-02-01

    Full Text Available Abstract Background Mucinous neoplasms within the abdomen may disseminate by direct extension through the diaphragm to involve the pleural space. Treatment of this condition is by parietal and visceral pleurectomy followed by hyperthermic intrapleural chemotherapy. Case presentation In this case report a patient developed persistent right upper lobe interstitial pneumonitis and progressive parenchymal fibrosis following intrapleural chemotherapy treatment with mitomycin C and doxrubicin. The condition persisted until death 28 months later. Death was from progressive intraabdominal disease with intestinal obstruction and sepsis associated with progressive pulmonary parenchymal disease. The right pleural space disease did not recur. Conclusion This manuscript is the first case report describing interstitial pneumonitis and lung fibrosis following intrapleural chemotherapy. Since pulmonary toxicity from chemotherapy is a dose-dependent phenomenon, dose reduction of intrapleural as compared to intraperitoneal hyperthermic chemotherapy may be necessary.

  12. Intracoronary adenosine improves myocardial perfusion in late reperfused myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Myocardial perfusion associates with clinical syndromes and prognosis.Adenosine could improve myocardial perfusion of acute myocardial infarction within 6 hours,but few data are available on late perfusion of myocardial infarction (MI).This study aimed at quantitatively evaluating the value of intracoronary adenosine improving myocardial perfusion in late reperfused MI with myocardial contrast echocardiography(MCE).Methods Twenty-six patients with anterior wall infarcts were divided randomly into 2 groups:adenosine group(n=12) and normal saline group(n=14).Their history of myocardial infarction was about 3-12 weeks.Adenosine or normalsaline was given when the guiding wire crossed the lesion through percutaneous coronary intervention(PCI),then the balloon was dilated and stent(Cypher/Cypher select)was implanted at the lesion.Contrast pulse sequencing MCE with Sonovue contrast via the coronary route was done before PCI and 30 minutes after PCI.Video densitometry and contrast filled-blank area were calculated with the CUSQ off-line software.Heart function and cardiac events were followed up within 30 days.Results Perfusion in the segments of the criminal occlusive coronary artery in the adenosine group was better than that in the saline group(5.71±0.29 vs 4.95±1.22,P<0.05).Ischemic myocardial segment was deminished significantly afterPCI,but the meliorated area was bigger in the adenosine group than in the saline group((1.56±0.60)cm2 vs(1.02±0.56) cm2,P<0.05).The video densitometry in critical segments was also improved significantly in the adenosine group (5.53±0.36 vs 5.26±0.35,P<0.05).Left ventricular ejection fraction(LVEF)was improved in all patients after PCI,but EF was not significant between the two groups((67±6)% vs(62±7)%,P>0.05).There was no in-hospital or 30-day major adverse cardiac event(MACE)in the adenosine group but 3 MACE in the saline group in 30 days after PCI.Conclusions Adenosine could improve myocardial microvascular

  13. Differential adenosine sensitivity of diaphragm and skeletal muscle arterioles.

    Science.gov (United States)

    Aaker, Aaron; Laughlin, M H

    2002-09-01

    The hyperemic response in exercising skeletal muscle is dependent on muscle fiber-type composition and fiber recruitment patterns, but the vascular control mechanisms producing exercise hyperemia in skeletal muscle remain poorly understood. The purpose of this study was to test the hypothesis that arterioles from white, low-oxidative skeletal muscle are less responsive to adenosine-induced dilation than are arterioles from diaphragm (Dia) and red, high-oxidative skeletal muscle. Second-order arterioles (2As) were isolated from the white portion of gastrocnemius muscle (WG; low-oxidative, fast-twitch muscle tissue) and two types of high-oxidative skeletal muscle [Dia and red portion of gastrocnemius muscle (RG)] of rats. Results reveal that 2As from all three types of muscle dilated in response to the endothelium-dependent dilator acetylcholine (WG: 48 +/- 3%, Dia: 51 +/- 3%, RG: 74 +/- 3%). In contrast, adenosine dilated only 2As from WG (48 +/- 4%) and Dia (46 +/- 5%) but not those from RG (5 +/- 5%). Thus adenosine-induced dilator responses differed among 2As of these different types of muscle tissue. However, the results do not support our hypothesis because 2As from Dia and WG dilated in response to adenosine, whereas 2As from RG did not. We conclude that the adenosine responsiveness of 2As from rat skeletal muscle cannot be predicted only by the fiber-type composition or oxidative capacity of the skeletal muscle tissue wherein the arteriole lies.

  14. Correlation between blood adenosine metabolism and sleep in humans.

    Science.gov (United States)

    Díaz-Muñoz, M; Hernández-Muñoz, R; Suárez, J; Vidrio, S; Yááñez, L; Aguilar-Roblero, R; Rosenthal, L; Villalobos, L; Fernández-Cancino, F; Drucker-Colín, R; Chagoya De Sanchez, V

    1999-01-01

    Blood adenosine metabolism, including metabolites and metabolizing enzymes, was studied during the sleep period in human volunteers. Searching for significant correlations among biochemical parameters found: adenosine with state 1 of slow-wave sleep (SWS); activity of 5'-nucleotidase with state 2 of SWS; inosine and AMP with state 3-4 of SWS; and activity of 5'-nucleotidase and lactate with REM sleep. The correlations were detected in all of the subjects that presented normal hypnograms, but not in those who had fragmented sleep the night of the experiment. The data demonstrate that it is possible to obtain information of complex brain operations such as sleep by measuring biochemical parameters in blood. The results strengthen the notion of a role played by adenosine, its metabolites and metabolizing enzymes, during each of the stages that constitute the sleep process in humans.

  15. Metronomic chemotherapy regimens in oncology

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Metronomic chemotherapy implies the regular use of cytotoxic agents in doses much smaller than the maximum tolerable doses for a long time. Preclinical experiments show that this treatment option has a many-sided (antiangiogenic, immunostimulating, and direct cytotoxic effect on tumor. Moreover, this approach has gained the widest acceptance in treating patients with metastatic breast cancer in clinical practice. By taking into account the high activity of angiogenesis in colon cancer progression, it is interesting to study the impact of metronomic chemotherapy regimens for this nosological entity as well. This literature review considers not only the history of metronomic chemotherapy, the mechanisms of action, and a range of drugs having an antitumor effect in the metronomic regimens, but also analyzes clinical trials of metronomic chemotherapy regimens in patients with metastatic colon cancer.

  16. Acute emesis: moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

    2011-01-01

    This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

  17. Managing Chemotherapy Side Effects: Constipation

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods such as: ● ● Whole-grain breads and cereals ● ● Fruits and vegetables ● ● Nuts and seeds ...

  18. Tween 20-stabilized gold nanoparticles combined with adenosine triphosphate-BODIPY conjugates for the fluorescence detection of adenosine with more than 1000-fold selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Szu-Ying; Shih, Ya-Chen [Department of Chemistry, National Sun Yat-sen University, Taiwan (China); Tseng, Wei-Lung, E-mail: tsengwl@mail.nsysu.edu.tw [Department of Chemistry, National Sun Yat-sen University, Taiwan (China); School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Taiwan (China); Center for Nanoscience and Nanotechnology, National Sun Yat-sen University, Taiwan (China); Center for Stem Cell Research, Kaohsiung Medical University, Taiwan (China)

    2015-02-01

    Graphical abstract: A simple, enzyme-free, label-free, sensitive and selective system was developed for detecting adenosine based on the use of Tween 20-stabilized gold nanoparticles as an efficient quencher for boron dipyrromethene-conjugated adenosine 5′-triphosphate and as a recognition element for adenosine. - Highlights: • The proposed method can detect adenosine with more than 1000-fold selectivity. • The analysis of adenosine is rapid (∼6 min) using the proposed method. • This method provided better sensitivity for adenosine as compared to aptamer-based sensors. • This method can be applied for the determination of adenosine in urine. - Abstract: This study describes the development of a simple, enzyme-free, label-free, sensitive, and selective system for detecting adenosine based on the use of Tween 20-stabilized gold nanoparticles (Tween 20-AuNPs) as an efficient fluorescence quencher for boron dipyrromethene-conjugated adenosine 5′-triphosphate (BODIPY-ATP) and as a recognition element for adenosine. BODIPY-ATP can interact with Tween 20-AuNPs through the coordination between the adenine group of BODIPY-ATP and Au atoms on the NP surface, thereby causing the fluorescence quenching of BODIPY-ATP through the nanometal surface energy transfer (NSET) effect. When adenosine attaches to the NP surface, the attached adenosine exhibits additional electrostatic attraction to BODIPY-ATP. As a result, the presence of adenosine enhances the efficiency of AuNPs in fluorescence quenching of BODIPY-ATP. The AuNP-induced fluorescence quenching of BODIPY-ATP progressively increased with an increase in the concentration of adenosine; the detection limit at a signal-to-noise ratio of 3 for adenosine was determined to be 60 nM. The selectivity of the proposed system was more than 1000-fold for adenosine over any adenosine analogs and other nucleotides. The proposed system combined with a phenylboronic acid-containing column was successfully applied to the

  19. The Use of Adenosine Agonists to Treat Nerve Agent-Induced Seizure and Neuropathology

    Science.gov (United States)

    2016-09-01

    kainate, adenosine and neuropeptide Y receptors. Neurochemical Research. 28: 1501-1515. 23. Bjorness, T. E. & R. W. Greene. 2009. Adenosine and sleep ...al. 2004. Adenosine and sleep -wake regulation. Progress in Neurobiology. 73: 379-396. 31. Schubert, P., et al. 1997. Protective mechanisms of...effects of adenosine by caffeine or 8-(p-sulfophenyl)theophylline. The Journal of Pharmacology and Experimental Therapeutics. 240: 428-432. 44

  20. Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ?

    OpenAIRE

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

    2016-01-01

    Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoim...

  1. Development of coronary vasospasm during adenosine-stress myocardial perfusion CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Jeong Gu; Choi, Seong Hoon; Kang, Byeong Seong; Bang, Min Aeo; Kwon, Woon Jeong [Dept. of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of)

    2015-06-15

    Adenosine is a short-acting coronary vasodilator, and it is widely used during pharmacological stress myocardial perfusion imaging. It has a well-established safety profile, and most of its side effects are known to be mild and transient. Until now, coronary vasospasm has been rarely reported as a side effect of adenosine during or after adenosine stress test. This study reports a case of coronary vasospasm which was documented on stress myocardial perfusion CT imaging during adenosine stress test.

  2. Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

    Science.gov (United States)

    Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

    2017-07-01

    Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

  3. Adenosine A(3) receptor-induced CCL2 synthesis in cultured mouse astrocytes

    NARCIS (Netherlands)

    Wittendorp, MC; Boddeke, HWGM; Biber, K

    2004-01-01

    During neuropathological conditions, high concentrations of adenosine are released, stimulating adenosine receptors in neurons and glial cells. It has recently been shown that stimulation of adenosine receptors in glial cells induces the release of neuroprotective substances such as NGF, S-100beta,

  4. DMPD: Shaping of monocyte and macrophage function by adenosine receptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17056121 Shaping of monocyte and macrophage function by adenosine receptors. Hasko ...tml) (.csml) Show Shaping of monocyte and macrophage function by adenosine receptors. PubmedID 17056121 Titl...e Shaping of monocyte and macrophage function by adenosine receptors. Authors Has

  5. The role of glial adenosine receptors in neural resilience and the neurobiology of mood disorders

    NARCIS (Netherlands)

    Calker, D; Biber, K

    2005-01-01

    Adenosine receptors were classified into A(1)- and A(2)-receptors in the laboratory of Bernd Hamprecht more than 25 years ago. Adenosine receptors are instrumental to the neurotrophic effects of glia cells. Both microglia and astrocytes release after stimulation via adenosine receptors factors that

  6. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy.

    Science.gov (United States)

    Ma, Yan; Chapman, Julia; Levine, Mark; Polireddy, Kishore; Drisko, Jeanne; Chen, Qi

    2014-02-05

    Ascorbate (vitamin C) was an early, unorthodox therapy for cancer, with an outstanding safety profile and anecdotal clinical benefit. Because oral ascorbate was ineffective in two cancer clinical trials, ascorbate was abandoned by conventional oncology but continued to be used in complementary and alternative medicine. Recent studies provide rationale for reexamining ascorbate treatment. Because of marked pharmacokinetic differences, intravenous, but not oral, ascorbate produces millimolar concentrations both in blood and in tissues, killing cancer cells without harming normal tissues. In the interstitial fluid surrounding tumor cells, millimolar concentrations of ascorbate exert local pro-oxidant effects by mediating hydrogen peroxide (H(2)O(2)) formation, which kills cancer cells. We investigated downstream mechanisms of ascorbate-induced cell death. Data show that millimolar ascorbate, acting as a pro-oxidant, induced DNA damage and depleted cellular adenosine triphosphate (ATP), activated the ataxia telangiectasia mutated (ATM)/adenosine monophosphate-activated protein kinase (AMPK) pathway, and resulted in mammalian target of rapamycin (mTOR) inhibition and death in ovarian cancer cells. The combination of parenteral ascorbate with the conventional chemotherapeutic agents carboplatin and paclitaxel synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer. On the basis of its potential benefit and minimal toxicity, examination of intravenous ascorbate in combination with standard chemotherapy is justified in larger clinical trials.

  7. Contributory role of adenosine deaminase in metabolic syndrome

    African Journals Online (AJOL)

    olayemitoyin

    Summary: Adenosine deaminase (ADA) is an enzyme of purine metabolism ... as obesity, insulin resistance, fasting hyperglycaemia, lipid abnormalities and ... Body mass index (BMI), fasting blood glucose (FBG), Glycated ... regulation of intracellular and extra cellular ... studies have indicated that defective signalling from.

  8. No role of interstitial adenosine in insulin-mediated vasodilation

    DEFF Research Database (Denmark)

    Dela, F; Stallknecht, B

    1999-01-01

    The mechanisms behind the vasodilatory effect of insulin are not fully understood, but nitric oxide plays an important role. We have investigated the possibility that insulin mediates vasodilatation in the human skeletal muscle via an increase in extracellular adenosine concentrations. In eight h...

  9. Adenosine receptor blockade reduces splanchnic hyperemia in cirrhotic rats.

    Science.gov (United States)

    Lee, S S; Chilton, E L; Pak, J M

    1992-06-01

    To explore a possible role for adenosine in the pathogenesis of the splanchnic hyperemia of cirrhosis, we administered 8-phenyltheophylline, a specific adenosine receptor antagonist, to rats with biliary cirrhosis caused by bile duct ligation and to control sham-operated rats. Micro-Doppler flow studies showed that a 10-mumol/kg dose of 8-phenyltheophylline completely abolished the superior mesenteric hyperemic response to infusions of exogenous adenosine in both cirrhotic and control rats. Analysis of regional blood flows by radioactive microspheres demonstrated that this dose of 8-phenyltheophylline in cirrhotic rats significantly increased portal tributary vascular resistance by 60% and decreased portal tributary blood flow by 26%. This decrease was entirely the result of a 42% reduction in the intestinal blood flow. 8-phenyltheophylline did not affect cardiac output, arterial pressure or any other extrasplanchnic hemodynamic variables in cirrhotic rats. No detectable effect of 8-phenyltheophylline was seen in sham-operated rats. These results suggest that adenosine may be involved in the genesis of splanchnic hyperemia in cirrhotic rats.

  10. Adenosine receptor modulation of seizure susceptibility in rats

    Energy Technology Data Exchange (ETDEWEB)

    Szot, P.

    1987-01-01

    Adenosine is considered to be a neuromodulator or cotransmitter in the periphery and CNS. This neuromodulatory action of adenosine may be observed as an anticonvulsant effect. Dose-response curves for R-phenylisopropyladenosine (PIA), cycohexyladenosine (CHA), 2-chloroadenosine (2-ClAdo), N-ethylcarboxamidoadenosine (NECA) and S-PIA were generated against PTZ seizure thresholds in the rat. The rank order of potency for adenosine agonists to elevate PTZ seizure threshold was R-PIA > 2-ClAdo > NECA > CHA > S-PIA. R-PIA was approximately 80-fold more potent than S-PIA. This 80-fold difference in potency between the diasteriomers of PIA was consistent with an A{sub 1} adenoise receptor-mediated response. The anticonvulsant action of 2-ClAdo was reversed by pretreatment with theoplylline. Chronic administration of theophylline significantly increased the specific binding of {sup 3}H-cyclohexyladenosine in membranes of the cerebral cortex and cerebellum of the rat. Chronic exposure to theophylline produced a significant increase in the densities of both the high- and low-affinity forms of A{sub 1} adenosine receptors in the cerebral cortex.

  11. Searching Inhibitors of Adenosine Kinase by Simulation Methods

    Institute of Scientific and Technical Information of China (English)

    ZHU Rui-Xin; ZHANG Xing-Long; DONG Xi-Cheng; CHEN Min-Bo

    2006-01-01

    Searching new inhibitors of adenosine kinase (AK) is still drawing attention of experimental scientists. A better and solid model is here proposed by means of simulation methods from different ways, the direct analysis of receptor itself, the conventional 3D-QSAR methods and the integration of docking method and the conventional QSAR analysis.

  12. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Science.gov (United States)

    2010-04-01

    ... device that measures the release of adenosine triphosphate (ATP) from platelets following aggregation. This measurement is made on platelet-rich plasma using a photometer and a luminescent firefly extract. Simultaneous measurements of platelet aggregation and ATP release are used to evaluate platelet...

  13. CD39/adenosine pathway is involved in AIDS progression.

    Directory of Open Access Journals (Sweden)

    Maria Nikolova

    2011-07-01

    Full Text Available HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25(high FoxP3+CD127(low T cells (Treg play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS.

  14. Adenosine Receptor Heteromers and their Integrative Role in Striatal Function

    Directory of Open Access Journals (Sweden)

    Sergi Ferré

    2007-01-01

    Full Text Available By analyzing the functional role of adenosine receptor heteromers, we review a series of new concepts that should modify our classical views of neurotransmission in the central nervous system (CNS. Neurotransmitter receptors cannot be considered as single functional units anymore. Heteromerization of neurotransmitter receptors confers functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Some of these characteristics can be used as a “biochemical fingerprint” to identify neurotransmitter receptor heteromers in the CNS. This is exemplified by changes in binding characteristics that are dependent on coactivation of the receptor units of different adenosine receptor heteromers. Neurotransmitter receptor heteromers can act as “processors” of computations that modulate cell signaling, sometimes critically involved in the control of pre- and postsynaptic neurotransmission. For instance, the adenosine A1-A2A receptor heteromer acts as a concentration-dependent switch that controls striatal glutamatergic neurotransmission. Neurotransmitter receptor heteromers play a particularly important integrative role in the “local module” (the minimal portion of one or more neurons and/or one or more glial cells that operates as an independent integrative unit, where they act as processors mediating computations that convey information from diverse volume-transmitted signals. For instance, the adenosine A2A-dopamine D2 receptor heteromers work as integrators of two different neurotransmitters in the striatal spine module.

  15. Striatal adenosine-cannabinoid receptor interactions in rats over-expressing adenosine A2A receptors.

    Science.gov (United States)

    Chiodi, Valentina; Ferrante, Antonella; Ferraro, Luca; Potenza, Rosa Luisa; Armida, Monica; Beggiato, Sarah; Pèzzola, Antonella; Bader, Michael; Fuxe, Kjell; Popoli, Patrizia; Domenici, Maria Rosaria

    2016-03-01

    Adenosine A2A receptors (A2 A Rs) and cannabinoid CB1 receptors (CB1 Rs) are highly expressed in the striatum, where they functionally interact and form A2A /CB1 heteroreceptor complexes. We investigated the effects of CB1 R stimulation in a transgenic rat strain over-expressing A2 A Rs under the control of the neural-specific enolase promoter (NSEA2A rats) and in age-matched wild-type (WT) animals. The effects of the CB1 R agonist WIN 55,212-2 (WIN) were significantly lower in NSEA2A rats than in WT animals, as demonstrated by i) electrophysiological recordings of synaptic transmission in corticostriatal slices; ii) the measurement of glutamate outflow from striatal synaptosomes and iii) in vivo experiments on locomotor activity. Moreover, while the effects of WIN were modulated by both A2 A R agonist (CGS 21680) and antagonists (ZM 241385, KW-6002 and SCH-442416) in WT animals, the A2 A R antagonists failed to influence WIN-mediated effects in NSEA2A rats. The present results demonstrate that in rats with genetic neuronal over-expression of A2 A Rs, the effects mediated by CB1 R activation in the striatum are significantly reduced, suggesting a change in the stoichiometry of A2A and CB1 receptors and providing a strategy to dissect the involvement of A2 A R forming or not forming heteromers in the modulation of striatal functions. These findings add additional evidence for the existence of an interaction between striatal A2 A Rs and CB1 Rs, playing a fundamental role in the regulation of striatal functions. We studied A2A -CB1 receptor interaction in transgenic rats over-expressing adenosine A2A receptors under the control of the neuron-specific enolase promoter (NSEA2A ). In these rats, we demonstrated a reduced effect of the CB1 receptor agonist WIN 55,212-2 in the modulation of corticostriatal synaptic transmission and locomotor activity, while CB1 receptor expression level did not change with respect to WT rats. A reduction in the expression of A2A -CB1

  16. Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Friis, Ulla Glenert; Uhrenholt, Torben Rene

    2007-01-01

    AIMS: Adenosine causes vasoconstriction of afferent arterioles of the mouse kidney through activation of adenosine A(1) receptors and Gi-mediated stimulation of phospholipase C. In the present study, we further explored the signalling pathways by which adenosine causes arteriolar vasoconstriction....... METHODS AND RESULTS: Adenosine (10(-7) M) significantly increased the intracellular calcium concentration in mouse isolated afferent arterioles measured by fura-2 fluorescence. Pre-treatment with thapsigargin (2 microM) blocked the vasoconstrictor action of adenosine (10(-7) M) indicating that release...

  17. Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

    Directory of Open Access Journals (Sweden)

    Cátia Vieira

    2014-01-01

    Full Text Available Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis lacks adenosine neuromodulation, which may contribute to acceleration of gastrointestinal transit. The loss of adenosine neuromodulation results from deficient accumulation of the nucleoside at the myenteric synapse despite the fact that the increases in ATP release were observed. Disparity between ATP outflow and adenosine deficit in postinflammatory ileitis is ascribed to feed-forward inhibition of ecto-5′-nucleotidase/CD73 by high extracellular ATP and/or ADP. Redistribution of NTPDase2, but not of NTPDase3, from ganglion cell bodies to myenteric nerve terminals leads to preferential ADP accumulation from released ATP, thus contributing to the prolonged inhibition of muscle-bound ecto-5′-nucleotidase/CD73 and to the delay of adenosine formation at the inflamed neuromuscular synapse. On the other hand, depression of endogenous adenosine accumulation may also occur due to enhancement of adenosine deaminase activity. Both membrane-bound and soluble forms of ecto-5′-nucleotidase/CD73 and adenosine deaminase were detected in the inflamed myenteric plexus. These findings provide novel therapeutic targets for inflammatory gut motility disorders.

  18. The Rickettsia prowazekii invasion gene homolog (invA) encodes a Nudix hydrolase active on adenosine (5')-pentaphospho-(5')-adenosine.

    Science.gov (United States)

    Gaywee, Jariyanart; Xu, WenLian; Radulovic, Suzana; Bessman, Maurice J; Azad, Abdu F

    2002-03-01

    The genomic sequence of Rickettsia prowazekii, the obligate intracellular bacterium responsible for epidemic typhus, reveals an uncharacterized invasion gene homolog (invA). The deduced protein of 18,752 Da contains a Nudix signature, the specific motif found in the Nudix hydrolase family. To characterize the function of InvA, the gene was cloned and overexpressed in Escherichia coli. The expressed protein was purified to near homogeneity and subsequently tested for its enzymatic activity against a series of nucleoside diphosphate derivatives. The purified InvA exhibits hydrolytic activity toward dinucleoside oligophosphates (Np(n)N; n > or = 5), a group of cellular signaling molecules. At optimal pH 8.5, the enzyme actively degrades adenosine (5')-pentaphospho-(5')-adenosine into ATP and ADP with a K(m) of 0.1 mM and k(cat) of 1.9 s(-1). Guanosine (5')-pentaphospho-(5')-guanosine and adenosine-(5')-hexaphospho (5')-adenosine are also substrates. Similar to other Nudix hydrolases, InvA requires a divalent metal cation, Mg(2+) or Zn(2+), for optimal activity. These data suggest that the rickettsial invasion protein likely plays a role in controlling the concentration of stress-induced dinucleoside oligophosphates following bacterial invasion.

  19. Small-Animal PET Study of Adenosine A(1) Receptors in Rat Brain : Blocking Receptors and Raising Extracellular Adenosine

    NARCIS (Netherlands)

    Paul, Soumen; Khanapur, Shivashankar; Rybczynska, Anna A.; Kwizera, Chantal; Sijbesma, Jurgen W. A.; Ishiwata, Kiichi; Willemsen, Antoon T. M.; Elsinga, Philip H.; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2011-01-01

    Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-C-11-methyl-3-propyl-xanthine (C-11-MPDX) and PET. This study aims to test whether C-11-MPDX

  20. Small-Animal PET Study of Adenosine A(1) Receptors in Rat Brain : Blocking Receptors and Raising Extracellular Adenosine

    NARCIS (Netherlands)

    Paul, Soumen; Khanapur, Shivashankar; Rybczynska, Anna A.; Kwizera, Chantal; Sijbesma, Jurgen W. A.; Ishiwata, Kiichi; Willemsen, Antoon T. M.; Elsinga, Philip H.; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2011-01-01

    Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-C-11-methyl-3-propyl-xanthine (C-11-MPDX) and PET. This study aims to test whether C-11-MPDX c

  1. Fast-scan Cyclic Voltammetry for the Characterization of Rapid Adenosine Release.

    Science.gov (United States)

    Nguyen, Michael D; Venton, B Jill

    2015-01-01

    Adenosine is a signaling molecule and downstream product of ATP that acts as a neuromodulator. Adenosine regulates physiological processes, such as neurotransmission and blood flow, on a time scale of minutes to hours. Recent developments in electrochemical techniques, including fast-scan cyclic voltammetry (FSCV), have allowed direct detection of adenosine with sub-second temporal resolution. FSCV studies have revealed a novel mode of rapid signaling that lasts only a few seconds. This rapid release of adenosine can be evoked by electrical or mechanical stimulations or it can be observed spontaneously without stimulation. Adenosine signaling on this time scale is activity dependent; however, the mode of release is not fully understood. Rapid adenosine release modulates oxygen levels and evoked dopamine release, indicating that adenosine may have a rapid modulatory role. In this review, we outline how FSCV can be used to detect adenosine release, compare FSCV with other techniques used to measure adenosine, and present an overview of adenosine signaling that has been characterized using FSCV. These studies point to a rapid mode of adenosine modulation, whose mechanism and function will continue to be characterized in the future.

  2. Intracerebral adenosine infusion improves neurological outcome after transient focal ischemia in rats.

    Science.gov (United States)

    Kitagawa, Hisashi; Mori, Atsushi; Shimada, Jun; Mitsumoto, Yasuhide; Kikuchi, Tetsuro

    2002-04-01

    Second Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan In order to elucidate the role of adenosine in brain ischemia, the possible protective effects of adenosine on ischemic brain injury were investigated in a rat model of brain ischemia both in vitro and in vivo. Exogenous adenosine dose-dependently rescued cortical neuronal cells from injury after glucose deprivation in vitro. Adenosine (1 mM) also significantly reduced hypoglycemia/hypoxia-induced glutamate release from the hippocampal slice. In a rat model of transient middle cerebral artery occlusion (MCAO), extracellular adenosine concentration was increased immediately after occlusion, and then returned to the baseline by 30 min after reperfusion. Adenosine infusion through a microdialysis probe into the ipsilateral striatum (1 mM adenosine, 2 microl min(-1), total 4.5 h from the occlusion to 3 h after reperfusion) showed a significant improvement in the neurological outcome, and about 25% reduction of infarct volume, although the effect did not reach statistical significance, compared with the vehicle-treated group at 20 h after 90 min of MCAO. These results demonstrated the neuroprotective effect of adenosine against ischemic brain injury both in vitro and in vivo, suggesting the possible therapeutic application of adenosine regulating agents, which inhibit adenosine uptake or metabolism to enhance or maintain extracellular endogenous adenosine levels, for stroke treatment.

  3. Adenosine transiently modulates stimulated dopamine release in the caudate-putamen via A1 receptors.

    Science.gov (United States)

    Ross, Ashley E; Venton, B Jill

    2015-01-01

    Adenosine modulates dopamine in the brain via A1 and A2A receptors, but that modulation has only been characterized on a slow time scale. Recent studies have characterized a rapid signaling mode of adenosine that suggests a possible rapid modulatory role. Here, fast-scan cyclic voltammetry was used to characterize the extent to which transient adenosine changes modulate stimulated dopamine release (5 pulses at 60 Hz) in rat caudate-putamen brain slices. Exogenous adenosine was applied and dopamine concentration monitored. Adenosine only modulated dopamine when it was applied 2 or 5 s before stimulation. Longer time intervals and bath application of 5 μM adenosine did not decrease dopamine release. Mechanical stimulation of endogenous adenosine 2 s before dopamine stimulation also decreased stimulated dopamine release by 41 ± 7%, similar to the 54 ± 6% decrease in dopamine after exogenous adenosine application. Dopamine inhibition by transient adenosine was recovered within 10 min. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the dopamine modulation, whereas dopamine modulation was unaffected by the A2A receptor antagonist SCH 442416. Thus, transient adenosine changes can transiently modulate phasic dopamine release via A1 receptors. These data demonstrate that adenosine has a rapid, but transient, modulatory role in the brain. Here, transient adenosine was shown to modulate phasic dopamine release on the order of seconds by acting at the A1 receptor. However, sustained increases in adenosine did not regulate phasic dopamine release. This study demonstrates for the first time a transient, neuromodulatory function of rapid adenosine to regulate rapid neurotransmitter release.

  4. Adenosine receptor control of cognition in normal and disease.

    Science.gov (United States)

    Chen, Jiang-Fan

    2014-01-01

    Adenosine and adenosine receptors (ARs) are increasingly recognized as important therapeutic targets for controlling cognition under normal and disease conditions for its dual roles of neuromodulation as well as of homeostatic function in the brain. This chapter first presents the unique ability of adenosine, by acting on the inhibitory A1 and facilitating A2A receptor, to integrate dopamine, glutamate, and BNDF signaling and to modulate synaptic plasticity (e.g., long-term potentiation and long-term depression) in brain regions relevant to learning and memory, providing the molecular and cellular bases for adenosine receptor (AR) control of cognition. This led to the demonstration of AR modulation of social recognition memory, working memory, reference memory, reversal learning, goal-directed behavior/habit formation, Pavlovian fear conditioning, and effort-related behavior. Furthermore, human and animal studies support that AR activity can also, through cognitive enhancement and neuroprotection, reverse cognitive impairments in animal models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and schizophrenia. Lastly, epidemiological evidence indicates that regular human consumption of caffeine, the most widely used psychoactive drug and nonselective AR antagonists, is associated with the reduced cognitive decline in aging and AD patients, and with the reduced risk in developing PD. Thus, there is a convergence of the molecular studies revealing AR as molecular targets for integrating neurotransmitter signaling and controlling synaptic plasticity, with animal studies demonstrating the strong procognitive impact upon AR antagonism in normal and disease brains and with epidemiological and clinical evidences in support of caffeine and AR drugs for therapeutic modulation of cognition. Since some of adenosine A2A receptor antagonists are already in phase III clinical trials for motor benefits in PD patients with remarkable safety profiles

  5. Breast Cancer Chemotherapy and Your Heart

    Science.gov (United States)

    ... American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , Sara ... cancer treatments. Breast cancer treatments include the following: Chemotherapy involves drugs that are intended to kill the ...

  6. Fertility preservation after chemotherapy for Hodgkin lymphoma

    NARCIS (Netherlands)

    van der Kaaij, Marleen A. E.; van Echten-Arends, Jannie; Simons, Arnold H. M.; Kluin-Nelemans, Hanneke C.

    2010-01-01

    Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause pro

  7. Congenital sacrococcygeal PNET and chemotherapy

    Directory of Open Access Journals (Sweden)

    Colin Patrick Hawkes

    2012-01-01

    Full Text Available We present the case of a congenital localised sacrococcygeal primitive neuroectodermal tumor treated aggressively with surgical resection and modified age-appropriate adjuvant chemotherapy. The conventional combination chemotherapy of vincristine, adriamycin, cyclophosphamide, ifosfamide and etoposide was modified to a regimen including vincristine, adriamicin, cyclophosphamide and actinomycin in order to minimise the predicted toxicity in this age group. Adjuvant "induction" chemotherapy commenced at 4 weeks of age and consisted of four cycles of vincristine, adriamycin and cyclophosphamide at 50%, 75%, 75% and 100% of recommended doses (vincristine 0.05 mg/kg, adriamycin 0.83 mg/kg daily × 2, cyclophosphamide 40 mg/kg at 3-weekly intervals. This was followed by four cycles of "maintenance" chemotherapy with vincristine (0.025 mg/kg, actinomycin (0.025 mg/kg and cyclophosphamide (36 mg/kg at full recommended doses. Cardioxane at a dose of 16.6 mg/kg was infused immediately prior to the adriamycin. Our patient is thriving at 19 months out from end of treatment.

  8. Chemotherapy of human african trypanosomiasis.

    Science.gov (United States)

    Bacchi, Cyrus J

    2009-01-01

    Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.

  9. Chemotherapy of Human African Trypanosomiasis

    Directory of Open Access Journals (Sweden)

    Cyrus J. Bacchi

    2009-01-01

    Full Text Available Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.

  10. Managing Chemotherapy Side Effects: Diarrhea

    Science.gov (United States)

    ... such as Pedialyte ® ••Tea (without caffeine) ••Water ••Applesauce ••Bananas ••Crackers ••Cream of wheat or rice cereal ••Eggs •• ... has a series of 18 Chemotherapy Side Effects Sheets at: www.cancer.gov/chemo-side-effects

  11. Chemotherapy-associated recurrent pneumothoraces in lymphangioleiomyomatosis.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2012-02-01

    Lymphangioleiomyomatosis is a rare cause of pneumothorax in women. We present the case of a 48-year-old woman with lymphangioleiomyomatosis, who had never had a pneumothorax prior to commencing chemotherapy for breast cancer. During chemotherapy she developed 3 pneumothoraces and 2 episodes of pneumomediastinum. We suggest that the pneumothoraces were caused by the chemotherapy. To our knowledge, this is the first reported case of chemotherapy triggering pneumothoraces in a woman with lymphangioleiomyomatosis.

  12. Chemotherapy and You: Support for People with Cancer

    Science.gov (United States)

    ... Terms Blogs and Newsletters Health Communications Publications Reports Chemotherapy and You: Support for People With Cancer Chemotherapy ... ePub This booklet covers: Questions and answers about chemotherapy. Answers common questions, such as what chemotherapy is ...

  13. Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses

    Science.gov (United States)

    Moore, Kimberly A.; Nicoll, Roger A.; Schmitz, Dietmar

    2003-11-01

    The release properties of synapses in the central nervous system vary greatly, not only across anatomically distinct types of synapses but also among the same class of synapse. This variation manifests itself in large part by differences in the probability of transmitter release, which affects such activity-dependent presynaptic forms of plasticity as paired-pulse facilitation and frequency facilitation. This heterogeneity in presynaptic function reflects differences in the intrinsic properties of the synaptic terminal and the activation of presynaptic neurotransmitter receptors. Here we show that the unique presynaptic properties of the hippocampal mossy fiber synapse are largely imparted onto the synapse by the continuous local action of extracellular adenosine at presynaptic A1 adenosine receptors, which maintains a low basal probability of transmitter release.

  14. Expression of human adenosine deaminase in murine hematopoietic cells.

    Science.gov (United States)

    Belmont, J W; MacGregor, G R; Wager-Smith, K; Fletcher, F A; Moore, K A; Hawkins, D; Villalon, D; Chang, S M; Caskey, C T

    1988-01-01

    Multiple replication-defective retrovirus vectors were tested for their ability to transfer and express human adenosine deaminase in vitro and in vivo in a mouse bone marrow transplantation model. High-titer virus production was obtained from vectors by using both a retrovirus long terminal repeat promoter and internal transcriptional units with human c-fos and herpes virus thymidine kinase promoters. After infection of primary murine bone marrow with one of these vectors, human adenosine deaminase was detected in 60 to 85% of spleen colony-forming units and in the blood of 14 of 14 syngeneic marrow transplant recipients. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells. Images PMID:3072474

  15. Plasma Adenosine Deaminase Enzyme Reduces with Treatment of ...

    African Journals Online (AJOL)

    olayemitoyin

    Plasma ADA in DSTB patients before and 6 months of chemotherapy were not significantly different compared MDR TB patients. ... Also, ADA deficiency has a direct effect on the lungs, .... showed that the patients were sputum smear negative.

  16. Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice.

    Science.gov (United States)

    Witts, Emily C; Nascimento, Filipe; Miles, Gareth B

    2015-10-01

    Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925-1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output.

  17. Evidence for an A1-adenosine receptor in the guinea-pig atrium.

    Science.gov (United States)

    Collis, M. G.

    1983-01-01

    1 The purpose of this study was to determine whether the adenosine receptor that mediates a decrease in the force of contraction of the guinea-pig atrium is of the A1- or A2-sub-type. 2 Concentration-response curves to adenosine and a number of 5'- and N6-substituted analogues were constructed and the order of potency of the purines was: 5'-N-cyclopropylcarboxamide adenosine (NCPCA) = 5'-N-ethylcarboxamide adenosine (NECA) greater than N6cyclohexyladenosine (CHA) greater than L-N6-phenylisopropyl adenosine (L-PIA) = 2-chloroadenosine- greater than adenosine greater than D-N6-phenylisopropyl adenosine (D-PIA). 3 The difference in potency between the stereoisomers D- and L-PIA was over 100 fold. 4 The adenosine transport inhibitor, dipyridamole, potentiated submaximal responses to adenosine but had no significant effect on those evoked by the other purines. 5 Theophylline antagonized responses evoked by all purines, and with D-PIA revealed a positive inotropic effect that was abolished by atenolol. 6 The results indicate the existence of an adenosine A1-receptor in the guinea-pig atrium. PMID:6297647

  18. Arterial occlusion precipitated by cisplatinbased chemotherapy

    OpenAIRE

    2010-01-01

    Cisplatin-based therapy is curative in testicular cancer. Adverse effects of cisplatin-based chemotherapy include dose-dependent myelosuppression, nephrotoxicity, neurotoxicity, and ototoxicity. By contrast, chemotherapy-associated vascular complications are unpredictable. Few incidents of digital gangrene with cisplatin have been reported. Here, we present a patient who developed arterial occlusion leading to gangrene of the toe after cisplatinbased chemotherapy.

  19. Adenosine receptors and stress : Studies using methylmercury, caffeine and hypoxia

    OpenAIRE

    Björklund, Olga

    2008-01-01

    Brain development is a precisely organized process that can be disturbed by various stress factors present in the diet (e.g. exposure to xenobiotics) as well as insults such as decreased oxygen supply. The consequent adverse changes in nervous system function may not necessarily be apparent until a critical age when neurodevelopmental defects may be unmasked by a subsequent challenge. Adenosine and its receptors (AR) (A1, A2A, A2B and A3) which participate in the brain stres...

  20. Synthesis of novel chromene scaffolds for adenosine receptors.

    Science.gov (United States)

    Costa, Marta; Areias, Filipe; Castro, Marian; Brea, Jose; Loza, María I; Proença, Fernanda

    2011-06-07

    A one-pot procedure was developed for the synthesis of novel 3-[amino(methoxy)methylene]-2-oxo-3,4-dihydro-2H-chromen-4-yl)-3-cyanoacetamides and chromeno[3,4-c]pyridine-1-carbonitriles from the reaction of 2-oxo-2H-chromene-3-carbonitriles and cyanoacetamides. These chromene derivatives were identified as new scaffolds for adenosine receptors and the hits 3a, 3c, 5a, and 5b were found.

  1. Severe combined immunodeficiency due to adenosine deaminase deficiency.

    Science.gov (United States)

    Hussain, Waqar; Batool, Asma; Ahmed, Tahir Aziz; Bashir, Muhammad Mukarram

    2012-03-01

    Severe Combined Immunodeficiency is the term applied to a group of rare genetic disorders characterised by defective or absent T and B cell functions. Patients usually present in first 6 months of life with respiratory/gastrointestinal tract infections and failure to thrive. Among the various types of severe combined immunodeficiency, enzyme deficiencies are relatively less common. We report the case of a 6 years old girl having severe combined immunodeficiency due to adenosine deaminase deficiency.

  2. Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

    Science.gov (United States)

    Ho, Ming-Fen; Low, Leanne M.; Rose’Meyer, Roselyn B.

    2016-01-01

    Background Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID:26907173

  3. Adenosine receptors in post-mortem human brain.

    Science.gov (United States)

    James, S; Xuereb, J H; Askalan, R; Richardson, P J

    1992-01-01

    1. Adenosine A2-like binding sites were characterized in post-mortem human brain membranes by examining several compounds for their ability to displace [3H]-CGS 21680 (2[p-(2 carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine) binding. 2. Two A2-like binding sites were identified in the striatum. 3. The more abundant striatal site was similar to the A2a receptor previously described in rat striatum, both in its pharmacological profile and striatal localization. 4. The less abundant striatal site had a pharmacological profile similar to that of the binding site characterized in the other brain regions examined. This was intermediate in character between A1 and A2 and may represent another adenosine receptor subtype. 5. The co-purification of [3H]-CGS 21680 binding during immunoisolation of human striatal cholinergic membranes was used to assess the possible cholinergic localization of A2-like binding sites in the human striatum. Only the more abundant striatal site co-purified with cholinergic membranes. This suggests that this A2a-like site is present on cholinergic neurones in the human striatum.

  4. Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Ansong, Charles; Ortega, Corrie; Payne, Samuel H.; Haft, Daniel H.; Chauvigne-Hines, Lacie M.; Lewis, Michael P.; Ollodart, Anja R.; Purvine, Samuel O.; Shukla, Anil K.; Fortuin, Suereta; Smith, Richard D.; Adkins, Joshua N.; Grundner, Christoph; Wright, Aaron T.

    2013-01-24

    The annotation of protein function is almost completely performed by in silico approaches. However, computational prediction of protein function is frequently incomplete and error prone. In Mycobacterium tuberculosis (Mtb), ~25% of all genes have no predicted function and are annotated as hypothetical proteins. This lack of functional information severely limits our understanding of Mtb pathogenicity. Current tools for experimental functional annotation are limited and often do not scale to entire protein families. Here, we report a generally applicable chemical biology platform to functionally annotate bacterial proteins by combining activity-based protein profiling (ABPP) and quantitative LC-MS-based proteomics. As an example of this approach for high-throughput protein functional validation and discovery, we experimentally annotate the families of ATP-binding proteins in Mtb. Our data experimentally validate prior in silico predictions of >250 ATPases and adenosine nucleotide-binding proteins, and reveal 73 hypothetical proteins as novel ATP-binding proteins. We identify adenosine cofactor interactions with many hypothetical proteins containing a diversity of unrelated sequences, providing a new and expanded view of adenosine nucleotide binding in Mtb. Furthermore, many of these hypothetical proteins are both unique to Mycobacteria and essential for infection, suggesting specialized functions in mycobacterial physiology and pathogenicity. Thus, we provide a generally applicable approach for high throughput protein function discovery and validation, and highlight several ways in which application of activity-based proteomics data can improve the quality of functional annotations to facilitate novel biological insights.

  5. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review th...

  6. Chemotherapy e-prescribing: opportunities and challenges

    Directory of Open Access Journals (Sweden)

    Elsaid KA

    2015-05-01

    Full Text Available Khaled A Elsaid,1,2 Steven Garguilo,1 Christine M Collins2 1Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, Boston, MA, 2Pharmacy Services, Rhode Island Hospital, Providence, RI, USA Abstract: Chemotherapy drugs are characterized by low therapeutic indices and significant toxicities at clinically prescribed doses, raising serious issues of drug safety. The safety of the chemotherapy medication use process is further challenged by regimen complexity and need to tailor treatment to patient status. Errors that occur during chemotherapy prescribing are associated with serious and life-threatening outcomes. Computerized provider order entry (CPOE systems were shown to reduce overall medication errors in ambulatory and inpatient settings. The adoption of chemotherapy CPOE is lagging due to financial cost and cultural and technological challenges. Institutions that adopted infusional or oral chemotherapy electronic prescribing modified existing CPOE systems to allow chemotherapy prescribing, implemented chemotherapy-specific CPOE systems, or developed home-grown chemotherapy electronic prescribing programs. Implementation of chemotherapy electronic prescribing was associated with a significant reduction in the risk of prescribing errors, most significantly dose calculation and adjustment errors. In certain cases, implementation of chemotherapy CPOE was shown to improve the chemotherapy use process. The implementation of chemotherapy CPOE may increase the risk of new types of errors, especially if processes are not redesigned and adapted to CPOE. Organizations aiming to implement chemotherapy CPOE should pursue a multidisciplinary approach engaging all stakeholders to guide system selection and implementation. Following implementation, organizations should develop and use a risk assessment process to identify and evaluate unanticipated consequences and CPOE-generated errors. The results of these analyses should serve to

  7. Treatment of Nausea and Vomiting During Chemotherapy.

    Science.gov (United States)

    Mustian, Karen M; Devine, Katie; Ryan, Julie L; Janelsins, Michelle C; Sprod, Lisa K; Peppone, Luke J; Candelario, Grace D; Mohile, Supriya G; Morrow, Gary R

    2011-01-01

    Nausea and vomiting are two of the most troubling side effects patients experience during chemotherapy. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still a major problem for patients receiving chemotherapy. Many cancer patients will delay or refuse future chemotherapy treatments and contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting. The purpose of this article is to provide an overview of the patho-psychophysiology of chemotherapy-induced nausea and vomiting and the recommended guidelines for treatment.

  8. Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5’-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway

    Science.gov (United States)

    Torini, Juliana Roberta; Brandão-Neto, José; DeMarco, Ricardo; Pereira, Humberto D'Muniz

    2016-01-01

    Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S. mansoni and could be a promising target for anti-schistosoma therapies. Here, we present 13 SmMTAP structures from the wild type (WT), including three single and one double mutant, and generate a solid structural framework for structure description. These crystal structures of SmMTAP reveal that the active site contains three substitutions within and near the active site when compared to it mammalian counterpart, thus opening up the possibility of developing specific inhibitors to the parasite MTAP. The structural and kinetic data for 5 substrates reveal the structural basis for this interaction, providing substract for inteligent design of new compounds for block this enzyme activity. PMID:27935959

  9. Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5'-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway.

    Science.gov (United States)

    Torini, Juliana Roberta; Brandão-Neto, José; DeMarco, Ricardo; Pereira, Humberto D'Muniz

    2016-12-01

    Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S. mansoni and could be a promising target for anti-schistosoma therapies. Here, we present 13 SmMTAP structures from the wild type (WT), including three single and one double mutant, and generate a solid structural framework for structure description. These crystal structures of SmMTAP reveal that the active site contains three substitutions within and near the active site when compared to it mammalian counterpart, thus opening up the possibility of developing specific inhibitors to the parasite MTAP. The structural and kinetic data for 5 substrates reveal the structural basis for this interaction, providing substract for inteligent design of new compounds for block this enzyme activity.

  10. [Effects of dopamine and adenosine on regulation of water-electrolyte exchange in Amoeba proteus].

    Science.gov (United States)

    Bagrov, Ia Iu; Manusova, N B

    2014-01-01

    Dopamine and adenosine both regulate transport of sodium chloride in the renal tubules in mammals. We have studied the effect of dopamine and adenosine on spontaneous activity of contractile vacuole of Amoeba proteous. Both substances stimulated contractile vacuole. The effect of dopamine was suppressed by D2 receptor antagonist, haloperidol, but not by D1 antagonist, SCH 39166. Adenylate cyclase inhibitor, 2.5-dideoxyadenosine, suppressed the effect of dopamine, but not of adenosine. Inhibitor of protein kinase C, staurosporine, in contrast, blocked the effect of adenosine, but not dopamine. Notably, dopamine opposed effect of adenosine and vice versa. These results suggest that similar effects of dopamine and adenosine could be mediated by different intracellulare mechanisms.

  11. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

    2015-01-01

    Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP......) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18...

  12. Contraction induced secretion of VEGF from skeletal muscle cells is mediated by adenosine

    DEFF Research Database (Denmark)

    Høier, Birgitte; Olsen, Karina; Nyberg, Michael Permin

    2010-01-01

    The role of adenosine and contraction for secretion of VEGF in skeletal muscle was investigated in human subjects and rat primary skeletal muscle cells. Microdialysis probes were inserted into the thigh muscle of seven male subjects and dialysate was collected at rest, during infusion of adenosine...... and contraction caused secretion of VEGF (pcontraction induced secretion of VEGF protein was abolished by the A(2B) antagonist enprofyllin and markedly reduced by inhibition of PKA or MAPK. The results demonstrate that adenosine causes secretion of VEGF from human skeletal muscle cells...... and that the contraction induced secretion of VEGF is partially mediated via adenosine acting on A(2B) adenosine receptors. Moreover, the contraction induced secretion of VEGF protein from muscle is dependent on both PKA and MAPK activation, but only the MAPK pathway appears to be adenosine dependent....

  13. Adenosine contributes to blood flow regulation in the exercising human leg by increasing prostaglandin and nitric oxide formation

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Nyberg, Michael; Thaning, Pia

    2009-01-01

    /min); (2) whether adenosine-induced vasodilation is mediated via formation of prostaglandins and/or NO; and (3) the femoral arterial and venous plasma adenosine concentrations during leg exercise with the microdialysis technique in a total of 24 healthy, male subjects. Inhibition of adenosine receptors......+/-8%, and 66+/-8%, respectively (Pplasma adenosine concentrations were similar at rest and during exercise. These results suggest that adenosine contributes to the regulation of skeletal muscle blood flow by stimulating prostaglandin and NO synthesis.......Adenosine can induce vasodilation in skeletal muscle, but to what extent adenosine exerts its effect via formation of other vasodilators and whether there is redundancy between adenosine and other vasodilators remain unclear. We tested the hypothesis that adenosine, prostaglandins, and NO act...

  14. Endogenous adenosine and hemorrhagic shock: effects of caffeine administration or caffeine withdrawal.

    OpenAIRE

    Conlay, L A; Evoniuk, G; Wurtman, R J

    1988-01-01

    Plasma adenosine concentrations doubled when rats were subjected to 90 min of profound hemorrhagic shock. Administration of caffeine (20 mg per kg of body weight), an adenosine-receptor antagonist, attenuated the hemorrhage-induced decrease in blood pressure. In contrast, chronic caffeine consumption (0.1% in drinking water), followed by a brief period of caffeine withdrawal, amplified the hypotensive response to hemorrhage. These data suggest that endogenous adenosine participates in the hyp...

  15. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia.

    OpenAIRE

    Felicita Pedata; Anna Maria Pugliese; Elisabetta Coppi; Ilaria Dettori; Giovanna Maraula; Lucrezia Cellai; Alessia Melani

    2014-01-01

    The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes). Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by ...

  16. Interaction between Intrathecal Gabapentin and Adenosine in the Formalin Test of Rats

    OpenAIRE

    Yoon, Myung Ha; Choi, Jeong Il; Park, Heon Chang; Bae, Hong Beom

    2004-01-01

    Spinal gabapentin and adenosine have been known to display an antinociceptive effect. We evaluated the nature of the interaction between gabapentin and adenosine in formalin-induced nociception at the spinal level. Male Sprague-Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, 50 µL) into the hindpaw. After examination of the effects of gabapentin and adenosine, the resulting interaction was investigated with isobolographic and f...

  17. Endogenous adenosine and hemorrhagic shock: effects of caffeine administration or caffeine withdrawal.

    OpenAIRE

    Conlay, L A; Evoniuk, G; Wurtman, R.J.

    1988-01-01

    Plasma adenosine concentrations doubled when rats were subjected to 90 min of profound hemorrhagic shock. Administration of caffeine (20 mg per kg of body weight), an adenosine-receptor antagonist, attenuated the hemorrhage-induced decrease in blood pressure. In contrast, chronic caffeine consumption (0.1% in drinking water), followed by a brief period of caffeine withdrawal, amplified the hypotensive response to hemorrhage. These data suggest that endogenous adenosine participates in the hyp...

  18. Pulmonary blastoma: remission with chemotherapy

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Jacobsen, M; Vindeløv, L

    1984-01-01

    A 59-year-old man with pulmonary blastoma, who had undergone right-sided pneumonectomy, had a relapse of the tumour 7 months later. Light-microscopic and ultrastructural studies were consistent with recurrence from the primary tumour. Cell kinetic studies revealed a high fraction of tumour cells ...... in the S-phase. Complete remission of the recurrence was obtained within 16 days after initiation of combination chemotherapy consisting of CCNU, vincristine, VP-16 and cyclophosphamide....

  19. Topical adenosine increases the proportion of thick hair in Caucasian men with androgenetic alopecia.

    Science.gov (United States)

    Iwabuchi, Tokuro; Ideta, Ritsuro; Ehama, Ritsuko; Yamanishi, Haruyo; Iino, Masato; Nakazawa, Yosuke; Kobayashi, Takashi; Ohyama, Manabu; Kishimoto, Jiro

    2016-05-01

    Adenosine is an effective treatment for androgenetic alopecia (AGA) in Japanese men and women. Adenosine exerts its effects by significantly increasing the proportion of thick hair. In this study, we assessed the clinical outcome of adenosine treatment for 6 months in 38 Caucasian men. The change in proportion of thick hair (≥60 μm) compared with baseline in the adenosine group was significantly higher than that in the placebo group (P thick hair in Caucasian men with AGA as well as in Japanese men and women.

  20. Adenosine Modulates the Oocyte Developmental Competence by Exposing Stages and Synthetic Blocking during In Vitro Maturation.

    Science.gov (United States)

    Cheon, Yong-Pil

    2016-06-01

    Purine metabolism is known factor for nuclear maturation of oocytes through both follicle cells and oocyte itself. However, it is largely unknown the roles of purine metabolism in the oocyte competence for fertilization and early development. In this study, the effects of adenosine in oocyte competence for development were examined using adenosine and its synthetic inhibitors. Adenosine treatment from GV intact stage for 18 hr (fGV) caused of decrease the fertilization rate but of increase the cleavage rate compared from the other stage treatment groups. Hadacidin did not effect on fertilization rate but increased cleavage rate without stage specificity. Adenosine did not block the effects of hadacidin with the exception of fGV group. By the inhibition of purine synthetic pathways the fertilization rate was decreased in the fGV and fGVB groups but increased in the fMII group. Exogenous adenosine caused of decrease fertilization rate in the fGVB group but increase in the fMII group. Cleavage rate was dramatically increased in the adenosine treatment with synthetic inhibitors. It means that the metabolism of purine has stage specific effects on fertilization and cleavage. Exogenous adenosine had only can improve oocyte developmental competence when it treated at GV intact stage. On the other hand, endogenous synthesis in all maturation stage caused of increase the cleavage rate without effects on fertilization. These data suggest that adenosine at GV stage as a paracrine fashion and inhibitions of endogenous adenosine in all stage improve oocyte developmental competence..

  1. Symptoms in Children After Chemotherapy

    Directory of Open Access Journals (Sweden)

    Sevcan Atay Turan

    2016-08-01

    Full Text Available Introduction: Identification of symptoms resulted from chemotherapy in children. Materials and Methods: In this study 46 children and adolescents who had chemotherapy in a pediatric oncology clinic of an oncology hospital were included. Sociodemographic questionnaire and Memorial Symptom Assessment Scale (10-18 years were used as data collection tool. Results: In this survey the mean age of children with cancer was 13.47±2.14 years and the majority of them (41.3% were monitored with non-Hodgkin’s lymphoma diagnosis. The most common symptoms in children who had chemotherapy in hospital were fatigue (76.1%, feeling nervous (69.6%, alopecia (65.2%, nausea (60.9% and feeling sad (60.9%, while the least common symptoms were swelling in the arms/legs (8.7% and problems in urination (6.5%. The most troublesome symptoms were dizziness (66.6%, difficulty in swallowing (64.3%, pain (47.8% and hair loss (43.4%. Conclusions: It was seen that the children still experience high prevalence of post-treatment symptoms, they had more intense psychological symptoms and physical symptoms caused more discomfort.

  2. Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via Adenosine Receptors

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2017-04-01

    Full Text Available IntroductionMany antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells.MethodsCultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS in the presence of dead and dying cells, their supernatants (SNs, or purified agonists and antagonists were used to evaluate the stimulation of proliferation. Viable cell quantification was performed by either flow cytometry of harvested cells or by crystal violet staining of adherent cells. High-performance liquid chromatography and liquid chromatography coupled with mass spectrometry of cell SNs were deployed to identify the nature of growth-promoting factors. Coimplantation of living cells in the presence of SNs collected from dead and dying cells and specific agonists was used to evaluate tumor growth in vivo.ResultsThe stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanoma cells, mouse fibroblasts, and primary FLS. We found that small soluble molecules present in the protein-free fraction of SNs of dead and dying cells were responsible for the promotion of proliferation. The nucleoside inosine released by dead and dying cells acting via adenosine receptors was identified as putative inducer of proliferation of surviving tumor cells after irradiation and heat treatment.ConclusionInosine released by dead and dying cells mediates tumor cell proliferation via purinergic receptors. Therapeutic strategies surmounting this pathway may help to reduce the rate of recurrence after radio- and chemotherapy.

  3. Adenosine conjugated lipidic nanoparticles for enhanced tumor targeting.

    Science.gov (United States)

    Swami, Rajan; Singh, Indu; Jeengar, Manish Kumar; Naidu, V G M; Khan, Wahid; Sistla, Ramakrishna

    2015-01-01

    Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol-sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41 μg/ml for native DTX, 0.30 μg/ml for unconjugated SLN formulation, and 0.09 μg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN-SLN as compared to DTX. IC50 was found to be 0.44 μg/ml for free DTX, 0.39 μg/ml for unconjugated SLN and 0.22 μg/ml for ADN-SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic

  4. Adenosine triphosphate (ATP) as a possible indicator of extraterrestrial biology

    Science.gov (United States)

    Chappelle, E. W.; Picciolo, G. L.

    1974-01-01

    The ubiquity of adenosine triphosphate (ATP) in terrestrial organisms provides the basis for proposing the assay of this vital metabolic intermediate for detecting extraterrestrial biological activity. If an organic carbon chemistry is present on the planets, the occurrence of ATP is possible either from biosynthetic or purely chemical reactions. However, ATP's relative complexity minimizes the probability of abiogenic synthesis. A sensitive technique for the quantitative detection of ATP was developed using the firefly bioluminescent reaction. The procedure was used successfully for the determination of the ATP content of soil and bacteria. This technique is also being investigated from the standpoint of its application in clinical medicine.

  5. Ribosome-inactivating lectins with polynucleotide:adenosine glycosidase activity.

    Science.gov (United States)

    Battelli, M G; Barbieri, L; Bolognesi, A; Buonamici, L; Valbonesi, P; Polito, L; Van Damme, E J; Peumans, W J; Stirpe, F

    1997-05-26

    Lectins from Aegopodium podagraria (APA), Bryonia dioica (BDA), Galanthus nivalis (GNA), Iris hybrid (IRA) and Sambucus nigra (SNAI), and a new lectin-related protein from Sambucus nigra (SNLRP) were studied to ascertain whether they had the properties of ribosome-inactivating proteins (RIP). IRA and SNLRP inhibited protein synthesis by a cell-free system and, at much higher concentrations, by cells and had polynucleotide:adenosine glycosidase activity, thus behaving like non-toxic type 2 (two chain) RIP. APA and SNAI had much less activity, and BDA and GNA did not inhibit protein synthesis.

  6. Characterization of spontaneous, transient adenosine release in the caudate-putamen and prefrontal cortex.

    Science.gov (United States)

    Nguyen, Michael D; Lee, Scott T; Ross, Ashley E; Ryals, Matthew; Choudhry, Vishesh I; Venton, B Jill

    2014-01-01

    Adenosine is a neuroprotective agent that inhibits neuronal activity and modulates neurotransmission. Previous research has shown adenosine gradually accumulates during pathologies such as stroke and regulates neurotransmission on the minute-to-hour time scale. Our lab developed a method using carbon-fiber microelectrodes to directly measure adenosine changes on a sub-second time scale with fast-scan cyclic voltammetry (FSCV). Recently, adenosine release lasting a couple of seconds has been found in murine spinal cord slices. In this study, we characterized spontaneous, transient adenosine release in vivo, in the caudate-putamen and prefrontal cortex of anesthetized rats. The average concentration of adenosine release was 0.17±0.01 µM in the caudate and 0.19±0.01 µM in the prefrontal cortex, although the range was large, from 0.04 to 3.2 µM. The average duration of spontaneous adenosine release was 2.9±0.1 seconds and 2.8±0.1 seconds in the caudate and prefrontal cortex, respectively. The concentration and number of transients detected do not change over a four hour period, suggesting spontaneous events are not caused by electrode implantation. The frequency of adenosine transients was higher in the prefrontal cortex than the caudate-putamen and was modulated by A1 receptors. The A1 antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine, 6 mg/kg i.p.) increased the frequency of spontaneous adenosine release, while the A1 agonist CPA (N(6)-cyclopentyladenosine, 1 mg/kg i.p.) decreased the frequency. These findings are a paradigm shift for understanding the time course of adenosine signaling, demonstrating that there is a rapid mode of adenosine signaling that could cause transient, local neuromodulation.

  7. Adenosine Inhibits the Excitatory Synaptic Inputs to Basal Forebrain Cholinergic, GABAergic and Parvalbumin Neurons in mice

    Directory of Open Access Journals (Sweden)

    Chun eYang

    2013-06-01

    Full Text Available Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal forebrain (BF region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV neurons to determine the effect of adenosine. Whole-cell recordings were made BF cholinergic neurons and from BF GABAergic & PV neurons with the size (>20 µm and intrinsic membrane properties (prominent H-currents corresponding to cortically projecting neurons. A brief (2 min bath application of adenosine (100 μM decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents in all groups of BF cholinergic, GABAergic and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1 μM. Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1-receptor mediated inhibition of glutamatergic inputs to cortically-projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required for

  8. Effect of phentolamine on the hyperemic response to adenosine in patients with microvascular disease.

    Science.gov (United States)

    Aarnoudse, Wilbert; Geven, Maartje; Barbato, Emanuele; Botman, Kees-joost; De Bruyne, Bernard; Pijls, Nico H J

    2005-12-15

    For accurate measurement of the fractional flow reserve (FFR) of the myocardium, the presence of maximum hyperemia is of paramount importance. It has been suggested that the hyperemic effect of the conventionally used hyperemic stimulus, adenosine, could be submaximal in patients who have microvascular dysfunction and that adding alpha-blocking agents could augment the hyperemic response in these patients. We studied the effect of the nonselective alpha-blocking agent phentolamine, which was administered in addition to adenosine after achieving hyperemia, in patients who had microvascular disease and those who did not. Thirty patients who were referred for percutaneous coronary intervention were selected. Of these 30 patients, 15 had strong indications for microvascular disease and 15 did not. FFR was measured using intracoronary adenosine, intravenous adenosine, and intracoronary papaverine before and after intracoronary administration of the nonselective alpha blocker phentolamine. In patients who did not have microvascular disease, no differences in hyperemic response to adenosine were noted, whether or not alpha blockade was given before adenosine administration; FFR levels before and after phentolamine were 0.76 and 0.75, respectively, using intracoronary adenosine (p = 0.10) and 0.75 and 0.74, respectively, using intravenous adenosine (p = 0.20). In contrast, in patients who had microvascular disease, some increase in hyperemic response was observed after administration of phentolamine; FFR levels decreased from 0.74 to 0.70 using intracoronary adenosine (p = 0.003) and from 0.75 to 0.72 using intravenous adenosine (p = 0.04). Although statistically significant, the observed further decrease in microvascular resistance after addition of phentolamine was small and did not affect clinical decision making in any patient. In conclusion, when measuring FFR, routinely adding an alpha-blocking agent to adenosine does not affect clinical decision making.

  9. Evidence for an A2/Ra adenosine receptor in the guinea-pig trachea

    Science.gov (United States)

    Brown, C.M.; Collis, M.G.

    1982-01-01

    1 An attempt was made to determine whether the extracellular adenosine receptor that mediates relaxation in the guinea-pig trachea is of the A1/Ri or A2/Ra subtype. 2 Dose-response curves to adenosine and a number of 5′- and N6-substituted analogues were constructed for the isolated guinea-pig trachea, contracted with carbachol. 3 The 5′-substituted analogues of adenosine were the most potent compounds tested, the order of potency being 5′-N-cyclopropylcarboxamide adenosine (NCPCA) > 5′-N-ethylcarboxamide adenosine (NECA) > 2-chloroadenosine > L-N6-phenylisopropyladenosine (L-PIA) > adenosine > D-N6-phenylisopropyladenosine (D-PIA). 4 The difference in potency between the stereoisomers D- and L-PIA on the isolated trachea was at the most five fold. 5 Responses to low doses of adenosine and its analogues were attenuated after treatment with either theophylline or 8-phenyltheophylline. The responses to 2-chloroadenosine were affected to a lesser extent than were those to the other purines. 6 Adenosine transport inhibitors, dipyridamole and dilazep, potentiated responses to adenosine, did not affect those to NCPCA, NECA, L-PIA and D-PIA but significantly reduced the responses to high doses of 2-chloroadenosine. 7 Relaxations evoked by 9-β-D-xylofuranosyladenosine which can activate intracellular but not extracellular adenosine receptors, were attenuated by dipyridamole but unaffected by 8-phenyltheophylline. 8 The results support the existence of an extracellular A2/Ra subtype of adenosine receptor and an intracellular purine-sensitive site, both of which mediate relaxation. PMID:6286021

  10. The Effect of Neoadjuvant Chemotherapy Compared to Adjuvant Chemotherapy in Healing after Nipple-Sparing Mastectomy.

    Science.gov (United States)

    Frey, Jordan D; Choi, Mihye; Karp, Nolan S

    2017-01-01

    Nipple-sparing mastectomy is the latest advancement in the treatment of breast cancer. The authors aimed to investigate the effects of neoadjuvant and adjuvant chemotherapy in nipple-sparing mastectomy. Patients undergoing nipple-sparing mastectomy from 2006 to June of 2015 were identified. Results were stratified by presence of neoadjuvant or adjuvant chemotherapy. A total of 840 nipple-sparing mastectomies were performed. Twenty-eight were in those who received neoadjuvant chemotherapy and 93 were in patients receiving adjuvant chemotherapy. Patients receiving both neoadjuvant and adjuvant chemotherapy were included in the neoadjuvant group. Nipple-sparing mastectomies that received neoadjuvant (with or without adjuvant) chemotherapy were compared to those in patients who received adjuvant chemotherapy. Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have explantation (p = 0.0239) and complete nipple-areola complex necrosis (p = 0.0021). Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have implant explantation (p = 0.0015) and complete nipple-areola complex necrosis (p = 0.0004) compared to those with no chemotherapy. Compared to nipple-sparing mastectomies in patients with no chemotherapy, those with adjuvant chemotherapy were more likely to have a hematoma (p = 0.0021). Those that received both neoadjuvant and adjuvant chemotherapy were more likely to have complete nipple-areola complex necrosis compared with both the neoadjuvant chemotherapy-only and adjuvant chemotherapy-only groups (p < 0.0001). Nipple-sparing mastectomy is safe to perform in the setting of neoadjuvant and adjuvant chemotherapy. As a whole, neoadjuvant (with or without adjuvant) chemotherapy increases risk of complications. Therapeutic, III.

  11. Chemotherapy

    Directory of Open Access Journals (Sweden)

    Ofer Merimsky

    2000-01-01

    Full Text Available Subjects and Methods: Seven patients with progressive localized or metastatic chemo-resistant osteosarcoma were treated by gemcitabine.The protocol included gemcitabine 1000 mg/m2/w for 7 consecutive weeks, followed by 1 week rest. If no progression was observed,maintenance by gemcitabine 1000 mg/m2/w for 3 weeks every 28 days was given until failure was clinically or radiologically evident.

  12. Chemotherapy

    Science.gov (United States)

    ... tumor cells. Mitotic inhibitors—These agents are usually plant-based, natural substances that interfere with the production ... drugs Infertility Seizures Weakness Balance or coordination problems Memory or cognitive problems Brain swelling Damage to internal ...

  13. Chemotherapie-induzierte Neuropathien (CIN

    Directory of Open Access Journals (Sweden)

    Vass A

    2009-01-01

    Full Text Available Durch Chemotherapie induzierte Neuropathien manifestieren sich meist als überwiegend sensorische Neuropathien, die zu Koordinationsstörungen und neuropathischen Schmerzen führen. Da es keine kausale Therapie gibt, stellen sie eine dosislimitierende Nebenwirkung der Tumortherapie dar. Hervorgerufen werden sie durch fünf Substanzgruppen: Platinderivate, Taxane, Vinca-Alkaloide sowie Bortezomib und Thalidomid. In dieser Übersicht wird auf die kumulativen Dosen dieser Substanzen und die jeweilige Symptomatik und Häufigkeit der dadurch entstehenden Neuropathien eingegangen.

  14. Immunological aspects of cancer chemotherapy.

    Science.gov (United States)

    Zitvogel, Laurence; Apetoh, Lionel; Ghiringhelli, François; Kroemer, Guido

    2008-01-01

    Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.

  15. [Adjuvant chemotherapy for patients with rectal cancer].

    Science.gov (United States)

    Qvortrup, Camilla; Mortensen, John Pløen; Pfeiffer, Per

    2013-09-09

    A new Cochrane meta-analysis evaluated adjuvant chemotherapy (5-fluorouracil (5FU)-based, not modern combination chemotherapy) in almost 10,000 patients with rectal cancer and showed a 17% reduction in mortality corresponding well to the efficacy observed in recent studies, which reported a reduction in mortality just about 20%. The authors recommend adjuvant chemotherapy which is in accordance with the Danish national guidelines where 5-FU-based chemotherapy is recommended for stage III and high-risk stage II rectal cancer.

  16. [Oral complications of chemotherapy of malignant neoplasms].

    Science.gov (United States)

    Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

    1999-01-01

    Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

  17. Different Modulating Effects of Adenosine on Neonatal and Adult Polymorphonuclear Leukocytes

    Directory of Open Access Journals (Sweden)

    Pei-Chen Hou

    2012-01-01

    Full Text Available Polymorphonuclear leukocytes (PMNs are the major leukocytes in the circulation and play an important role in host defense. Intact PMN functions include adhesion, migration, phagocytosis, and reactive oxygen species (ROS release. It has been known for a long time that adenosine can function as a modulator of adult PMN functions. Neonatal plasma has a higher adenosine level than that of adults; however, little is known about the modulating effects of adenosine on neonatal PMNs. The aim of this study was to investigate the effects of adenosine on neonatal PMN functions. We found that neonatal PMNs had impaired adhesion, chemotaxis, and ROS production abilities, but not phagocytosis compared to adult PMNs. As with adult PMNs, adenosine could suppress the CD11b expressions of neonatal PMNs, but had no significant suppressive effect on phagocytosis. In contrast to adult PMNs, adenosine did not significantly suppress chemotaxis and ROS production of neonatal PMNs. This may be due to impaired phagocyte reactions and a poor neonatal PMN response to adenosine. Adenosine may not be a good strategy for the treatment of neonatal sepsis because of impaired phagocyte reactions and poor response.

  18. The effect of circulating adenosine on cerebral haemodynamics and headache generation in healthy subjects

    DEFF Research Database (Denmark)

    Birk, S; Petersen, K.A.; Kruuse, Christina Rostrup

    2005-01-01

    been investigated in man and reports regarding the effect of intravenous adenosine on cerebral blood flow are conflicting. Twelve healthy participants received adenosine 80, 120 microg kg(-1) min(-1) and placebo intravenously for 20 min, in a double-blind, three-way, crossover, randomized design...

  19. Genetically Controlled Upregulation of Adenosine A(1) Receptor Expression Enhances the Survival of Primary Cortical Neurons

    NARCIS (Netherlands)

    Serchov, Tsvetan; Atas, Hasan-Cem; Normann, Claus; van Calker, Dietrich; Biber, Knut

    2012-01-01

    Adenosine has a key endogenous neuroprotective role in the brain, predominantly mediated by the adenosine A(1) receptor (A(1)R). This has been mainly explored using pharmacological tools and/or receptor knockout mice strains. It has long been suggested that the neuroprotective effects of A(1)R are i

  20. Extracellular ATP and adenosine : The Yin and Yang in immune responses?

    NARCIS (Netherlands)

    Faas, M. M.; Saez, T.; de Vos, P.

    Extracellular adenosine 50-triphosphate (ATP) and adenosine molecules are intimately involved in immune responses. ATP is mostly a pro-inflammatory molecule and is released during hypoxic condition and by necrotic cells, as well as by activated immune cells and endothelial cells. However, under

  1. Nafion-CNT coated carbon-fiber microelectrodes for enhanced detection of adenosine.

    Science.gov (United States)

    Ross, Ashley E; Venton, B Jill

    2012-07-07

    Adenosine is a neuromodulator that regulates neurotransmission. Adenosine can be monitored using fast-scan cyclic voltammetry at carbon-fiber microelectrodes and ATP is a possible interferent in vivo because the electroactive moiety, adenine, is the same for both molecules. In this study, we investigated carbon-fiber microelectrodes coated with Nafion and carbon nanotubes (CNTs) to enhance the sensitivity of adenosine and decrease interference by ATP. Electrodes coated in 0.05 mg mL(-1) CNTs in Nafion had a 4.2 ± 0.2 fold increase in current for adenosine, twice as large as for Nafion alone. Nafion-CNT electrodes were 6 times more sensitive to adenosine than ATP. The Nafion-CNT coating did not slow the temporal response of the electrode. Comparing different purine bases shows that the presence of an amine group enhances sensitivity and that purines with carbonyl groups, such as guanine and hypoxanthine, do not have as great an enhancement after Nafion-CNT coating. The ribose group provides additional sensitivity enhancement for adenosine over adenine. The Nafion-CNT modified electrodes exhibited significantly more current for adenosine than ATP in brain slices. Therefore, Nafion-CNT modified electrodes are useful for sensitive, selective detection of adenosine in biological samples.

  2. Treatment of paroxysmal supraventricular tachycardia with intravenous injection of adenosine triphosphate.

    OpenAIRE

    Saito, D.; Ueeda, M; Abe, Y.; Tani, H; Nakatsu, T.; Yoshida, H.; Haraoka, S; Nagashima, H

    1986-01-01

    Intravenous adenosine triphosphate rapidly terminated all 11 episodes of paroxysmal supraventricular tachycardia in 10 patients. Eight patients reported side effects but these resolved within 20 seconds and did not require treatment. Adenosine triphosphate is a suitable agent for the rapid termination of paroxysmal supraventricular tachycardia.

  3. Photomodulation of G protein-coupled adenosine receptors by a novel light-switchable ligand.

    Science.gov (United States)

    Bahamonde, María Isabel; Taura, Jaume; Paoletta, Silvia; Gakh, Andrei A; Chakraborty, Saibal; Hernando, Jordi; Fernández-Dueñas, Víctor; Jacobson, Kenneth A; Gorostiza, Pau; Ciruela, Francisco

    2014-10-15

    The adenosinergic system operates through G protein-coupled adenosine receptors, which have become promising therapeutic targets for a wide range of pathological conditions. However, the ubiquity of adenosine receptors and the eventual lack of selectivity of adenosine-based drugs have frequently diminished their therapeutic potential. Accordingly, here we aimed to develop a new generation of light-switchable adenosine receptor ligands that change their intrinsic activity upon irradiation, thus allowing the spatiotemporal control of receptor functioning (i.e., receptor activation/inactivation dependent on location and timing). Therefore, we synthesized an orthosteric, photoisomerizable, and nonselective adenosine receptor agonist, nucleoside derivative MRS5543 containing an aryl diazo linkage on the N(6) substituent, which in the dark (relaxed isomer) behaved as a full adenosine A3 receptor (A3R) and partial adenosine A2A receptor (A2AR) agonist. Conversely, upon photoisomerization with blue light (460 nm), it remained a full A3R agonist but became an A2AR antagonist. Interestingly, molecular modeling suggested that structural differences encountered within the third extracellular loop of each receptor could modulate the intrinsic, receptor subtype-dependent, activity. Overall, the development of adenosine receptor ligands with photoswitchable activity expands the pharmacological toolbox in support of research and possibly opens new pharmacotherapeutic opportunities.

  4. Adenosine testing after cryoballoon pulmonary vein isolation improves long-term clinical outcome

    NARCIS (Netherlands)

    Y. van Belle (Yves); P. Janse (Petter); N. de Groot (Natasja); W. Anné (Wim); D.A.M.J. Theuns (Dominic); L.J.L.M. Jordaens (Luc)

    2012-01-01

    textabstractBackground Adenosine infusion after pulmonary vein isolation (PVI) with radiofrequency energy reveals dormant muscular sleeves and predicts atrial fibrillation (AF) recurrence. The aim of our study was to determine whether adenosine could reveal dormant PV sleeves after cryoballoon isola

  5. The ischemic preconditioning effect of adenosine in patients with ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Berglund Margareta

    2009-11-01

    Full Text Available Abstract Introduction In vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans. Aims We hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV systolic function. Materials and methods We studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of Results PSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (P = 0.0001 and low-dose adenosine infusion (P = 0.0009. However, in the ischemic walls, PSV increased only during low-dose adenosine infusion (P = 0.001, while no changes in PSV occurred during placebo infusion (P = NS. Conclusion Low-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans.

  6. Adenosine Amine Congener as a Cochlear Rescue Agent

    Directory of Open Access Journals (Sweden)

    Srdjan M. Vlajkovic

    2014-01-01

    Full Text Available We have previously shown that adenosine amine congener (ADAC, a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg was administered intraperitoneally to Wistar rats (8–10 weeks old at intervals (6–72 hours after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours. Hearing sensitivity was assessed using auditory brainstem responses (ABR before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz. Pharmacokinetic studies demonstrated a short (5 min half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment.

  7. Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation.

    Directory of Open Access Journals (Sweden)

    Peter A Keyel

    Full Text Available Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA, which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1β production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation.

  8. Adenosine signaling and the energetic costs of induced immunity.

    Directory of Open Access Journals (Sweden)

    Brian P Lazzaro

    2015-04-01

    Full Text Available Life history theory predicts that trait evolution should be constrained by competing physiological demands on an organism. Immune defense provides a classic example in which immune responses are presumed to be costly and therefore come at the expense of other traits related to fitness. One strategy for mitigating the costs of expensive traits is to render them inducible, such that the cost is paid only when the trait is utilized. In the current issue of PLOS Biology, Bajgar and colleagues elegantly demonstrate the energetic and life history cost of the immune response that Drosophila melanogaster larvae induce after infection by the parasitoid wasp Leptopilina boulardi. These authors show that infection-induced proliferation of defensive blood cells commands a diversion of dietary carbon away from somatic growth and development, with simple sugars instead being shunted to the hematopoetic organ for rapid conversion into the raw energy required for cell proliferation. This metabolic shift results in a 15% delay in the development of the infected larva and is mediated by adenosine signaling between the hematopoietic organ and the central metabolic control organ of the host fly. The adenosine signal thus allows D. melanogaster to rapidly marshal the energy needed for effective defense and to pay the cost of immunity only when infected.

  9. Adenosine Deaminase Deficiency - More Than Just an Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Kathryn Victoria Whitmore

    2016-08-01

    Full Text Available Adenosine deaminase (ADA deficiency is best known as a form of severe combined immunodeficiency (SCID which results from mutations in the gene encoding adenosine deaminase. Affected patients present with clinical and immunological manifestations typical of a severe combined immunodeficiency. Therapies are currently available that can that target these immunological disturbances and treated patients show varying degrees of clinical improvement. However, there is now a growing body of evidence that deficiency of ADA has significant impact on non-immunological organ systems. This review will outline the impact of ADA deficiency on various organ systems, starting with the well understood immunological abnormalities. We will discuss possible pathogenic mechanisms and also highlight ways in which current treatments could be improved. In doing so, we aim to present ADA deficiency as more than an immunodeficiency and suggest that it should be recognized as a systemic metabolic disorder that affects multiple organ systems. Only by fully understanding ADA deficiency and its manifestations in all organ systems can we aim to deliver therapies that will correct all the clinical consequences.

  10. Novel trypanocidal analogs of 5'-(methylthio)-adenosine.

    Science.gov (United States)

    Sufrin, Janice R; Spiess, Arthur J; Marasco, Canio J; Rattendi, Donna; Bacchi, Cyrus J

    2008-01-01

    The purine nucleoside 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) is an analog of the polyamine pathway metabolite 5'-deoxy-5'-(methylthio)-adenosine (MTA). HETA is a lead structure for the ongoing development of selectively targeted trypanocidal agents. Thirteen novel HETA analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of Trypanosoma brucei brucei LAB 110 EATRO and at least one drug-resistant Trypanosoma brucei rhodesiense clinical isolate. New compounds were also assessed in a cell-free assay for their activities as substrates of trypanosome MTA phosphorylase. The most potent analog in this group was 5'-deoxy-5'-(hydroxyethylthio)-tubercidin, whose in vitro cytotoxicity (50% inhibitory concentration [IC50], 10 nM) is 45 times greater than that of HETA (IC50, 450 nM) against pentamidine-resistant clinical isolate KETRI 269. Structure-activity analyses indicate that the enzymatic cleavage of HETA analogs by trypanosome MTA phosphorylase is not an absolute requirement for trypanocidal activity. This suggests that additional biochemical mechanisms are associated with the trypanocidal effects of HETA and its analogs.

  11. Comparison of exogenous adenosine and voluntary exercise on human skeletal muscle perfusion and perfusion heterogeneity

    DEFF Research Database (Denmark)

    Heinonen, Ilkka H.A.; Kemppainen, Jukka; Kaskinoro, Kimmo;

    2010-01-01

    femoral artery infusion of adenosine (1 mg * min(-1) * litre thigh volume(-1)), which has previously been shown to induce maximal whole thigh blood flow of ~8 L/min. This response was compared to the blood flow induced by moderate-high intensity one-leg dynamic knee extension exercise. Adenosine increased...... muscle. Additionally, it remains to be determined what proportion of adenosine-induced flow elevation is specifically directed to muscle only. In the present study we measured thigh muscle capillary nutritive blood flow in nine healthy young men using positron emission tomography at rest and during...... muscle blood flow on average to 40 +/- 7 ml. min(-1) per 100g(-1) of muscle and an aggregate value of 2.3 +/- 0.6 L * min(-1) for the whole thigh musculature. Adenosine also induced a substantial change in blood flow distribution within individuals. Muscle blood flow during adenosine infusion...

  12. Interstitial and plasma adenosine stimulate nitric oxide and prostacyclin formation in human skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Thaning, Pia;

    2010-01-01

    One major unresolved issue in muscle blood flow regulation is that of the role of circulating versus interstitial vasodilatory compounds. The present study determined adenosine-induced formation of NO and prostacyclin in the human muscle interstitium versus in femoral venous plasma to elucidate....... In young healthy humans, microdialysate was collected at rest, during arterial infusion of adenosine, and during interstitial infusion of adenosine through microdialysis probes inserted into musculus vastus lateralis. Muscle interstitial NO and prostacyclin increased with arterial and interstitial infusion...... levels. These findings provide novel insight into the role of adenosine in skeletal muscle blood flow regulation and vascular function by revealing that both interstitial and plasma adenosine have a stimulatory effect on NO and prostacyclin formation. In addition, both skeletal muscle and microvascular...

  13. New chromene scaffolds for adenosine A(2A) receptors: synthesis, pharmacology and structure-activity relationships.

    Science.gov (United States)

    Areias, Filipe; Costa, Marta; Castro, Marián; Brea, José; Gregori-Puigjané, Elisabet; Proença, M Fernanda; Mestres, Jordi; Loza, María I

    2012-08-01

    In silico screening of a collection of 1584 academic compounds identified a small molecule hit for the human adenosine A(2A) receptor (pK(i) = 6.2) containing a novel chromene scaffold (3a). To explore the structure-activity relationships of this new chemical series for adenosine receptors, a focused library of 43 2H-chromene-3-carboxamide derivatives was synthesized and tested in radioligand binding assays at human adenosine A(1), A(2A), A(2B) and A(3) receptors. The series was found to be enriched with bioactive compounds for adenosine receptors, with 14 molecules showing submicromolar affinity (pK(i) ≥ 6.0) for at least one adenosine receptor subtype. These results provide evidence that the chromene scaffold, a core structure present in natural products from a wide variety of plants, vegetables, and fruits, constitutes a valuable source for novel therapeutic agents. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors

    DEFF Research Database (Denmark)

    Gnad, Thorsten; Scheibler, Saskia; von Kügelgen, Ivar

    2014-01-01

    hamster or rat. However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A2A...... of A2A receptors or injection of lentiviral vectors expressing the A2A receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A2A agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate...... that adenosine-A2A signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies....

  15. Reconstruction of the adenosine system by bone marrow-derived mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Huicong Kang; Qi Hu; Xiaoyan Liu; Yinhe Liu; Feng Xu; Xiang Li; Suiqiang Zhu

    2012-01-01

    In the present study, we transplanted bone marrow-derived mesenchymal stem cells into the CA3 area of the hippocampus of chronic epilepsy rats kindled by lithium chloride-pilocarpine. Immunofluorescence and western blotting revealed an increase in adenosine A1 receptor expression and a decrease in adenosine A2a receptor expression in the brain tissues of epileptic rats 3 months after transplantation. Moreover, the imbalance in the A1 adenosine receptor/A2a adenosine receptor ratio was improved. Electroencephalograms showed that frequency and amplitude of spikes in the hippocampus and frontal lobe were reduced. These results suggested that mesenchymal stem cell transplantation can reconstruct the normal function of the adenosine system in the brain and greatly improve epileptiform discharges.

  16. Autophagy occurs within an hour of adenosine triphosphate treatment after nerve cell damage:the neuroprotective effects of adenosine triphosphate against apoptosis

    Institute of Scientific and Technical Information of China (English)

    Na Lu; Baoying Wang; Xiaohui Deng; Honggang Zhao; Yong Wang; Dongliang Li

    2014-01-01

    After hypoxia, ischemia, or inlfammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, lfow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations (2, 4, 6, 8, 10 mmol/L) over time (1, 2, 3, and 6 hours) on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SY5Y cells. The enhanced autophagy ifrst appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury.

  17. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    Science.gov (United States)

    Konno, Takashi; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-08-22

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production.

  18. Involvement of adenosine A2a receptor in intraocular pressure decrease induced by 2-(1-octyn-1-yl)adenosine or 2-(6-cyano-1-hexyn-1-yl)adenosine.

    Science.gov (United States)

    Konno, Takashi; Murakami, Akira; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-04-01

    The aim of the present study is to clarify the mechanism for the decrease in intraocular pressure by 2-alkynyladenosine derivatives in rabbits. The receptor binding analysis revealed that 2-(1-octyn-1-yl)adenosine (2-O-Ado) and 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) selectively bound to the A(2a) receptor with a high affinity. Ocular hypotensive responses to 2-O-Ado and 2-CN-Ado were inhibited by the adenosine A(2a)-receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), but not by the adenosine A(1)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or the adenosine A(2b)-receptor antagonist alloxazine. In addition, 2-O-Ado and 2-CN-Ado caused an increase in outflow facility, which was inhibited by CSC, but not by DPCPX or alloxazine. Moreover, 2-O-Ado and 2-CN-Ado increased cAMP in the aqueous humor, and the 2-O-Ado-induced an increase in cAMP was inhibited by CSC. These results suggest that 2-O-Ado and 2-CN-Ado reduced intraocular pressure via an increase in outflow facility. The ocular hypotension may be mainly mediated through the activation of adenosine A(2a) receptor, although a possible involvement of adenosine A(1) receptor cannot be completely ruled out. 2-O-Ado and 2-CN-Ado are useful lead compounds for the treatment of glaucoma.

  19. Chemotherapy and Dietary Phytochemical Agents

    Directory of Open Access Journals (Sweden)

    Katrin Sak

    2012-01-01

    Full Text Available Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way.

  20. Inhibition by adenosine of histamine and leukotriene release from human basophils.

    Science.gov (United States)

    Peachell, P T; Lichtenstein, L M; Schleimer, R P

    1989-06-01

    Adenosine inhibited the release of histamine and leukotriene C4 (LTC4) from immunologically-activated basophils in a dose-dependent manner. Structural congeners of adenosine also attenuated the elaboration of these two mediators from stimulated basophils and a rank order of potency for the inhibition was observed following the sequence 2-chloroadenosine greater than or equal to N-ethylcarboxamidoadenosine (NECA) greater than adenosine greater than or equal to R-phenylisopropyladenosine (R-PIA) greater than or equal to S-PIA. These same nucleosides modulated the generation of LTC4 more potently than the release of histamine. A number of methylxanthines, which are antagonists of cell surface adenosine receptors, reversed the inhibition by adenosine and its congeners of the release of both histamine and LTC4 to varying extents. Dipyridamole and nitrobenzylthioinosine (NBTI), agents that block the intracellular uptake of adenosine, antagonized the inhibition of histamine release by adenosine (and 2-chloroadenosine) but failed to reverse the attenuation of LTC4 generation by the nucleoside. These same uptake blockers were unable to antagonize the inhibitory effects of NECA on either histamine or LTC4 release. In purified basophils, NECA and R-PIA, and in that order of decreasing reactivity, increased total cell cyclic adenosine monophosphate (cAMP) levels and inhibited the stimulated release of mediators. In total, these results suggest that the basophil possesses a cell surface adenosine receptor which, on the basis of both pharmacological and biochemical criteria, most closely conforms to an A2/Ra-like receptor. However, in addition to an interaction at the cell surface, studies with agents that block the intracellular uptake of adenosine suggest that the nucleoside may also exert intracellular effects when countering the release of histamine (but not LTC4).

  1. Sawhorse waveform voltammetry for selective detection of adenosine, ATP, and hydrogen peroxide.

    Science.gov (United States)

    Ross, Ashley E; Venton, B Jill

    2014-08-05

    Fast-scan cyclic voltammetry (FSCV) is an electrochemistry technique which allows subsecond detection of neurotransmitters in vivo. Adenosine detection using FSCV has become increasingly popular but can be difficult because of interfering agents which oxidize at or near the same potential as adenosine. Triangle shaped waveforms are traditionally used for FSCV, but modified waveforms have been introduced to maximize analyte sensitivity and provide stability at high scan rates. Here, a modified sawhorse waveform was used to maximize the time for adenosine oxidation and to manipulate the shapes of cyclic voltammograms (CVs) of analytes which oxidize at the switching potential. The optimized waveform consists of scanning at 400 V/s from -0.4 to 1.35 V and holding briefly for 1.0 ms followed by a ramp back down to -0.4 V. This waveform allows the use of a lower switching potential for adenosine detection. Hydrogen peroxide and ATP also oxidize at the switching potential and can interfere with adenosine measurements in vivo; however, their CVs were altered with the sawhorse waveform and they could be distinguished from adenosine. Principal component analysis (PCA) was used to determine that the sawhorse waveform was better than the triangle waveform at discriminating between adenosine, hydrogen peroxide, and ATP. In slices, mechanically evoked adenosine was identified with PCA and changes in the ratio of ATP to adenosine were observed after manipulation of ATP metabolism by POM-1. The sawhorse waveform is useful for adenosine, hydrogen peroxide, and ATP discrimination and will facilitate more confident measurements of these analytes in vivo.

  2. The Regulation of Skeletal Muscle Active Hyperemia: The Differential Role of Adenosine in Muscles of Varied Fiber Types

    Science.gov (United States)

    1986-04-21

    response. Proctor (1984) found theophylline, a competitiv~ antagonist of adenosine, attenuated the response in the low-oxidative hamster cremaster ...exogenously applied adenosine in hamster cremaster muscle but did not affect the vascular response to muscle stimulation. Differences in the exact drugs...found that the addition of adenosine deaminase to the suffusion solution adjacent to the arterioles of the transilluminated hamster cremaster muscle

  3. 75 FR 8981 - Prospective Grant of Exclusive License: Treatment of Glaucoma by Administration of Adenosine A3...

    Science.gov (United States)

    2010-02-26

    ... Glaucoma by Administration of Adenosine A3 Antagonists AGENCY: National Institutes of Health, Public Health.../092,292, entitled ``A3 Adenosine Receptor Antagonists,'' filed July 10, 1998 , PCT Application PCT/US99/ 15562, entitled''A3 Adenosine Receptor Antagonists,'' filed July 2, 1999 , U.S. Patent...

  4. Chemotherapy and Sex: Is Sexual Activity OK during Treatment?

    Science.gov (United States)

    ... and Procedures Chemotherapy Is it safe to have sex with my husband while undergoing chemotherapy? Answers from ... best to discuss any concerns about chemotherapy and sex with your doctor, who's familiar with your individual ...

  5. Chemotherapy and Hair Loss: What to Expect during Treatment

    Science.gov (United States)

    Tests and Procedures Chemotherapy Find out what to expect when it comes to chemotherapy and hair loss. Plan to use your energy staying ... you have cancer and are about to undergo chemotherapy, the chance of hair loss is very real. ...

  6. [Chemotherapy-induced stomatitis and diarrhea].

    Science.gov (United States)

    Kadowaki, Shigenori; Yamaguchi, Kensei

    2011-11-01

    Chemotherapy-induced mucositis is a clinically important and sometimes dose-limiting toxicity of cancer treatment, including standard-dose chemotherapy, high-dose chemotherapy and chemoradiotherapy. Consequently, dose reductions or treatment delays resulting from mucositis may impair treatment effectiveness. Symptoms are oral mucositis, dysphagia, abdominal pain and diarrhea, depending on the affected site. Although the underlying pathobiology of oral mucositis has been considerably elucidated over the past decade, there are few interventions for the prevention or treatment validated by randomized trials. The most commonly accepted intervention is basic oral care. Diarrhea is most common in patients treated with irinotecan and in some cases, life-threatening. No definitive interventions for the prevention of diarrhea exist, but there is evidence that loperamide and octreotide are effective for chemotherapy-induced diarrhea. In future, there is a need for well designed trials, preferably including a placebo or no treatment control, validating more effective interventions for managing chemotherapy- induced mucositis.

  7. Chemotherapy of metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Colorectal cancer is one of the leading causes of cancer incidence and mortality. In 2008 inRussian Federation55 719 new cases of colorectal cancer were diagnosed and 37 911 patients died of this disease. A significant progress was achieved in metastatic colorectal cancer treatment during the last decades. A lot of treatment options became available: from 5-fluoruracil monotherapy to combined treatment treatment schemes including surgery. A group of patients with isolated liver metastases was distinguished, who can achieve 5-year survival rate of 40 % after systemic treatment and surgery. Today, based on clinical data and molecular analysis, we come close to individualized treatment of this patient group. In this literature review results of metastatic colorectal cancer chemotherapy are being analyzed and rational treatment tactic is proposed based on therapy goals. 

  8. History of chemotherapy of leprosy.

    Science.gov (United States)

    Noordeen, Shaik K

    2016-01-01

    Chemotherapy of leprosy over the past 70 years has passed through several phases, from sulfones, to clofazimine, and to highly bactericidal drugs like rifampicin. The use particularly of the more potent drugs in effective combinations and the development of standard multidrug therapy regimens have made a huge difference in the successful treatment of leprosy as well as in reducing tremendously the prevalence of leprosy globally. A major contributing factor to development of better drugs and drug combinations has been the introduction of the mouse footpad model to evaluate the in vivo activity of drugs against Mycobacterium leprae. The World Health Organization has recommended multidrug therapy, which has been used to treat more than 15 million patients in the last 30 years and has set an excellent record with regard to its very high rate of cure, very low occurrence of relapse, and very rare occurrence of drug resistance.

  9. Adenosine-5'-phosphosulfate kinase is essential for Arabidopsis viability.

    Science.gov (United States)

    Mugford, Sarah G; Matthewman, Colette A; Hill, Lionel; Kopriva, Stanislav

    2010-01-04

    In Arabidopsis thaliana, adenosine-5'-phosphosulfate kinase (APK) provides activated sulfate for sulfation of secondary metabolites, including the glucosinolates. We have successfully isolated three of the four possible triple homozygous mutant combinations of this family. The APK1 isoform alone was sufficient to maintain WT levels of growth and development. Analysis of apk1 apk2 apk3 and apk1 apk3 apk4 mutants suggests that APK3 and APK4 are functionally redundant, despite being located in cytosol and plastids, respectively. We were, however, unable to isolate apk1 apk3 apk4 mutants, most probably because the apk1 apk3 apk4 triple mutant combination is pollen lethal. Therefore, we conclude that APS kinase is essential for plant reproduction and viability.

  10. Adenosine Monophosphate-Based Detection of Bacterial Spores

    Science.gov (United States)

    Kern, Roger G.; Chen, Fei; Venkateswaran, Kasthuri; Hattori, Nori; Suzuki, Shigeya

    2009-01-01

    A method of rapid detection of bacterial spores is based on the discovery that a heat shock consisting of exposure to a temperature of 100 C for 10 minutes causes the complete release of adenosine monophosphate (AMP) from the spores. This method could be an alternative to the method described in the immediately preceding article. Unlike that method and related prior methods, the present method does not involve germination and cultivation; this feature is an important advantage because in cases in which the spores are those of pathogens, delays involved in germination and cultivation could increase risks of infection. Also, in comparison with other prior methods that do not involve germination, the present method affords greater sensitivity. At present, the method is embodied in a laboratory procedure, though it would be desirable to implement the method by means of a miniaturized apparatus in order to make it convenient and economical enough to encourage widespread use.

  11. Late-onset adenosine deaminase deficiency presenting with Heck's disease.

    Science.gov (United States)

    Artac, Hasibe; Göktürk, Bahar; Bozdemir, Sefika Elmas; Toy, Hatice; van der Burg, Mirjam; Santisteban, Ines; Hershfield, Michael; Reisli, Ismail

    2010-08-01

    Focal epithelial hyperplasia, also known as Heck's disease, is a rare but distinctive entity of viral etiology with characteristic clinical and histopathological features. It is a benign, asymptomatic disease of the oral mucosa caused by human papilloma viruses (HPV). Previous studies postulated an association between these lesions and immunodeficiency. Genetic deficiency of adenosine deaminase (ADA) results in varying degrees of immunodeficiency, including neonatal onset severe combined immunodeficiency (ADA-SCID), and milder, later onset immunodeficiency. We report a 12-year-old girl with the late onset-ADA deficiency presenting with Heck's disease. Our case report should draw attention to the possibility of immunodeficiency in patients with HPV-induced focal epithelial hyperplasia.

  12. Adenosine for postoperative analgesia: A systematic review and meta-analysis

    Science.gov (United States)

    2017-01-01

    Purpose Perioperative infusion of adenosine has been suggested to reduce the requirement for inhalation anesthetics, without causing serious adverse effects in humans. We conducted a meta-analysis of randomized controlled trials evaluating the effect of adenosine on postoperative analgesia. Methods We retrieved articles in computerized searches of Scopus, Web of Science, PubMed, EMBASE, and Cochrane Library databases, up to July 2016. We used adenosine, postoperative analgesia, and postoperative pain(s) as key words, with humans, RCT, and CCT as filters. Data of eligible studies were extracted, which included pain scores, cumulative opioid consumption, adverse reactions, and vital signs. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed-effects or random-effects models, depending on the heterogeneity of the included trials. Results In total, 757 patients from 9 studies were included. The overall effect of adenosine on postoperative VAS/VRS scores and postoperative opioid consumption was not significantly different from that of controls (P >0.1). The occurrence of PONV and pruritus was not statistically significantly different between an adenosine and nonremifentanil subgroup (P >0.1), but the rate of PONV occurrence was greater in the remifentanil subgroup (P 0.1). Conclusion Adenosine has no analgesic effect or prophylactic effect against PONV, but reduce systolic blood pressure and heart rates. Adenosine may benefit patients with hypertension, ischemic heart disease, and tachyarrhythmia, thereby improving cardiac function. PMID:28333936

  13. The Role of Adenosine in Pulmonary Vein Isolation: A Critical Review

    Directory of Open Access Journals (Sweden)

    Paolo D. Dallaglio

    2016-01-01

    Full Text Available The cornerstone of atrial fibrillation (AF ablation is pulmonary vein isolation (PVI, which can be achieved in more than 95% of patients at the end of the procedure. However, AF recurrence rates remain high and are related to recovery of PV conduction. Adenosine testing is used to unmask dormant pulmonary vein conduction (DC. The aim of this study is to review the available literature addressing the role of adenosine testing and determine the impact of ablation at sites of PV reconnection on freedom from AF. Adenosine infusion, by restoring the excitability threshold, unmasks reversible injury that could lead to recovery of PV conduction. The studies included in this review suggest that adenosine is useful to unmask nontransmural lesions at risk of reconnection and that further ablation at sites of DC is associated with improvement in freedom from AF. Nevertheless it has been demonstrated that adenosine is not able to predict all veins at risk of later reconnection, which means that veins without DC are not necessarily at low risk. The role of the waiting period in the setting of adenosine testing has also been analyzed, suggesting that in the acute phase adenosine use should be accompanied by enough waiting time.

  14. The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells.

    Science.gov (United States)

    Wilson, Jeffrey M; Ross, William G; Agbai, Oma N; Frazier, Renea; Figler, Robert A; Rieger, Jayson; Linden, Joel; Ernst, Peter B

    2009-04-15

    The endogenous purine nucleoside adenosine is an important antiinflammatory mediator that contributes to the control of CD4(+) T cell responses. While adenosine clearly has direct effects on CD4(+) T cells, it remains to be determined whether actions on APC such as dendritic cells (DC) are also important. In this report we characterize DC maturation and function in BMDC stimulated with LPS in the presence or absence of the nonselective adenosine receptor agonist NECA (5'-N-ethylcarboxamidoadenosine). We found that NECA inhibited TNF-alpha and IL-12 in a concentration-dependent manner, whereas IL-10 production was increased. NECA-treated BMDC also expressed reduced levels of MHC class II and CD86 and were less effective at stimulating CD4(+) T cell proliferation and IL-2 production compared with BMDC exposed to vehicle control. Based on real-time RT-PCR, the A(2A) adenosine receptor (A(2A)AR) and A(2B)AR were the predominant adenosine receptors expressed in BMDC. Using adenosine receptor subtype selective antagonists and BMDC derived from A(2A)AR(-/-) and A(2B)AR(-/-)mice, it was shown that NECA modulates TNF-alpha, IL-12, IL-10, and CD86 responses predominantly via A(2B)AR. These data indicate that engagement of A(2B)AR modifies murine BMDC maturation and suggest that adenosine regulates CD4(+) T cell responses by selecting for DC with impaired immunogencity.

  15. Evidence for evoked release of adenosine and glutamate from cultured cerebellar granule cells

    Energy Technology Data Exchange (ETDEWEB)

    Schousboe, A.; Frandsen, A.; Drejer, J. (Univ. of Copenhagen (Denmark))

    1989-09-01

    Evoked release of ({sup 3}H)-D-aspartate which labels the neurotransmitter glutamate pool in cultured cerebellar granule cells was compared with evoked release of adenosine from similar cultures. It was found that both adenosine and (3H)-D-aspartate could be released from the neurons in a calcium dependent manner after depolarization of the cells with either 10-100 microM glutamate or 50 mM KCl. Cultures of cerebellar granule cells treated with 50 microM kainate to eliminate GABAergic neurons behaved in the same way. This together with the observation that cultured astrocytes did not exhibit a calcium dependent, potassium stimulated adenosine release strongly suggest that cerebellar granule cells release adenosine in a neurotransmitter-like fashion together with glutamate which is the classical neurotransmitter of these neurons. Studies of the metabolism of adenosine showed that in the granule cells adenosine is rapidly metabolized to ATP, ADP, and AMP, but in spite of this, adenosine was found to be released preferential to ATP.

  16. Role of adenosine signalling and metabolism in β-cell regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Olov, E-mail: olov.andersson@ki.se

    2014-02-01

    Glucose homeostasis, which is controlled by the endocrine cells of the pancreas, is disrupted in both type I and type II diabetes. Deficiency in the number of insulin-producing β cells – a primary cause of type I diabetes and a secondary contributor of type II diabetes – leads to hyperglycemia and hence an increase in the need for insulin. Although diabetes can be controlled with insulin injections, a curative approach is needed. A potential approach to curing diabetes involves regenerating the β-cell mass, e.g. by increasing β-cell proliferation, survival, neogenesis or transdifferentiation. The nucleoside adenosine and its cognate nucleotide ATP have long been known to affect insulin secretion, but have more recently been shown to increase β-cell proliferation during homeostatic control and regeneration of the β-cell mass. Adenosine is also known to have anti-inflammatory properties, and agonism of adenosine receptors can promote the survival of β-cells in an inflammatory microenvironment. In this review, both intracellular and extracellular mechanisms of adenosine and ATP are discussed in terms of their established and putative effects on β-cell regeneration. - Highlights: • A potential way to cure diabetes is to regenerate the β-cell mass by promoting cell survival, proliferation or neogenesis. • Adenosine may promote β-cell regeneration through several cellular mechanisms. • Adenosine and its cognate nucleotide ATP can each promote β-cell proliferation. • Do adenosine and ATP interact in promoting β-cell proliferation?.

  17. Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Nakazawa, Taisuke; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-02-01

    Adenosine is a potent vasodilator of retinal blood vessels and is implicated to be a major regulator of retinal blood flow during metabolic stress, but little is known about the impact of diabetes on the role of adenosine in regulation of retinal hemodynamics. Therefore, we examined how diabetes affects adenosine-induced vasodilation of retinal arterioles. Male Wistar rats were treated with streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6-8 weeks later. Rats were treated with tetrodotoxin (50 microg/kg, intravenously [i.v.]) to eliminate any nerve activity and prevent movement of the eye and infused with methoxamine continuously to maintain adequate systemic circulation. Fundus images were captured with a digital camera that was equipped with a special objective lens, and diameters of retinal arterioles were measured. Adenosine increased diameters of retinal arterioles and decreased systemic blood pressure. These responses were significantly attenuated by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.) and the adenosine triphosphate-dependent K+ (K(ATP)) channel blocker glibenclamide (20 mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats, whereas diabetes did not alter vasodilation of retinal arterioles to adenosine. In contrast, both depressor response and vasodilation of retinal arteriole to acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to adenosine and acetylcholine observed in diabetic rats were diminished by N(G)-nitro-L-arginine methyl ester. There were no differences in the responses to pinacidil, a K(ATP) channel opener, between the diabetic and nondiabetic rats. These results suggest that both the activation of nitric oxide synthase and opening of K(ATP) channels contribute to the vasodilator effects of adenosine in rats in vivo. However, diabetes has no significant impact on the vasodilation mediated by these mechanisms in

  18. Smoke Extract Impairs Adenosine Wound Healing. Implications of Smoke-Generated Reactive Oxygen Species

    Science.gov (United States)

    Zimmerman, Matthew C.; Zhang, Hui; Castellanos, Glenda; O’Malley, Jennifer K.; Alvarez-Ramirez, Horacio; Kharbanda, Kusum; Sisson, Joseph H.; Wyatt, Todd A.

    2013-01-01

    Adenosine concentrations are elevated in the lungs of patients with asthma and chronic obstructive pulmonary disease, where it balances between tissue repair and excessive airway remodeling. We previously demonstrated that the activation of the adenosine A2A receptor promotes epithelial wound closure. However, the mechanism by which adenosine-mediated wound healing occurs after cigarette smoke exposure has not been investigated. The present study investigates whether cigarette smoke exposure alters adenosine-mediated reparative properties via its ability to induce a shift in the oxidant/antioxidant balance. Using an in vitro wounding model, bronchial epithelial cells were exposed to 5% cigarette smoke extract, were wounded, and were then stimulated with either 10 μM adenosine or the specific A2A receptor agonist, 5′-(N-cyclopropyl)–carboxamido–adenosine (CPCA; 10 μM), and assessed for wound closure. In a subset of experiments, bronchial epithelial cells were infected with adenovirus vectors encoding human superoxide dismutase and/or catalase or control vector. In the presence of 5% smoke extract, significant delay was evident in both adenosine-mediated and CPCA-mediated wound closure. However, cells pretreated with N-acetylcysteine (NAC), a nonspecific antioxidant, reversed smoke extract–mediated inhibition. We found that cells overexpressing mitochondrial catalase repealed the smoke extract inhibition of CPCA-stimulated wound closure, whereas superoxide dismutase overexpression exerted no effect. Kinase experiments revealed that smoke extract significantly reduced the A2A-mediated activation of cyclic adenosine monophosphate–dependent protein kinase. However, pretreatment with NAC reversed this effect. In conclusion, our data suggest that cigarette smoke exposure impairs A2A-stimulated wound repair via a reactive oxygen species–dependent mechanism, thereby providing a better understanding of adenosine signaling that may direct the development of

  19. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    Science.gov (United States)

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists.

  20. Adenine arabinoside inhibition of adenovirus replication enhanced by an adenosine deaminase inhibitor.

    Science.gov (United States)

    Wigand, R

    1979-01-01

    The inhibition of adenovirus multiplication by adenine arabinoside was determined by yield reduction in one-step multiplication cycle. Inhibition was greatly enhanced by an adenosine deaminase inhibitor (2-deoxycoformycin) in concentrations down to 10 ng/ml. Adenovirus types from four subgroups showed similar results. However, the enhancing effect of adenosine deaminase inhibitor was great in HeLa cells, moderate in human fibroblasts, and negligible in Vero cells. This difference could be explained by different concentrations of adenosine deaminase found in cell homogenates.

  1. Role of adenosine A2b receptor overexpression in tumor progression.

    Science.gov (United States)

    Sepúlveda, Cesar; Palomo, Iván; Fuentes, Eduardo

    2016-12-01

    The adenosine A2b receptor is a G-protein coupled receptor. Its activation occurs with high extracellular adenosine concentration, for example in inflammation or hypoxia. These conditions are generated in the tumor environment. Studies show that A2b receptor is overexpressed in various tumor lines and biopsies from patients with different cancers. This suggests that A2b receptor can be used by tumor cells to promote progression. Thus A2b participates in different events, such as angiogenesis and metastasis, besides exerting immunomodulatory effects that protect tumor cells. Therefore, adenosine A2b receptor appears as an interesting therapeutic target for cancer treatment.

  2. An STS in the human adenosine deaminase gene (located 20q12-q13. 11)

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, B.C.; States, J.C. (Wayne State Univ., Detroit, MI (United States))

    1991-09-25

    The human adenosine deaminase gene has been characterized in detail. The adenosine gene product, as part of the purine catabolic pathway, catalyzes the irreversible deamination of adenosine and deoxyadenosine. Deficiency of this activity in humans is associated with an autosomal recessive form of severe combined immunodeficiency disease. Recently, this genetic deficiency disease has been targeted for the first attempts at gene therapy in humans. Using the polymerase chain reaction (PCR), a fragment of the expected size (160 bp) was amplified from human genomic DNA.

  3. Adenosine A2A receptor binding profile of two antagonists, ST1535 and KW6002: consideration on the presence of atypical adenosine A2A binding sites

    Directory of Open Access Journals (Sweden)

    Teresa Riccioni

    2010-08-01

    Full Text Available Adenosine A2A receptors seem to exist in typical (more in striatum and atypical (more in hippocampus and cortex subtypes. In the present study, we investigated the affinity of two adenosine A2A receptor antagonists, ST1535 [2 butyl -9-methyl-8-(2H-1,2,3-triazol 2-yl-9H-purin-6-xylamine] and KW6002 [(E-1,3-diethyl-8-(3,4-dimethoxystyryl-7-methyl-3,7-dihydro-1H-purine-2,6,dione] to the “typical” and “atypical” A2A binding sites. Affinity was determined by radioligand competition experiments in membranes from rat striatum and hippocampus. Displacement of the adenosine analog [3H]CGS21680 [2-p-(2-carboxyethylphenethyl-amino-5’-N-ethylcarbox-amidoadenosine] was evaluated in the absence or in the presence of either CSC [8-(3-chlorostyryl-caffeine], an adenosine A2A antagonist that pharmacologically isolates atypical binding sites, or DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor antagonist that pharmacologically isolates typical binding site. ZM241385 [84-(2-[7-amino-2-(2-furyl [1,2,4]-triazol[2,3-a][1,3,5]triazin-5-yl amino]ethyl phenol] and SCH58261 [(5-amino-7-(β-phenylethyl-2-(8-furylpyrazolo(4,3-e-1,2,4-triazolo(1,5-c pyrimidine], two other adenosine A2A receptor antagonists, which were reported to differently bind to atypical and typical A2A receptors, were used as reference compounds. ST1535, KW6002, ZM241385 and SCH58261 displaced [3H]CGS21680 with higher affinity in striatum than in hippocampus. In hippocampus, no typical adenosine A2A binding was detected, and ST1535 was the only compound that occupied atypical A2A adenosine receptors. Present data are explained in terms of heteromeric association among adenosine A2A, A2B and A1 receptors, rather than with the presence of atypical A2A receptor subtype.

  4. The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells

    DEFF Research Database (Denmark)

    Hayashi, M.; Inagaki, A.; Novak, Ivana;

    2016-01-01

    Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl− chann...

  5. The role of muscarinic receptors in the beneficial effects of adenosine against myocardial reperfusion injury in rats.

    Directory of Open Access Journals (Sweden)

    Lei Sun

    Full Text Available Adenosine, a catabolite of ATP, displays a wide variety of effects in the heart including regulation of cardiac response to myocardial ischemia and reperfusion injury. Nonetheless, the precise mechanism of adenosine-induced cardioprotection is still elusive. Isolated Sprague-Dawley rat hearts underwent 30 min global ischemia and 120 min reperfusion using a Langendorff apparatus. Both adenosine and acetylcholine treatment recovered the post-reperfusion cardiac function associated with adenosine and muscarinic receptors activation. Simultaneous administration of adenosine and acetylcholine failed to exert any additive protective effect, suggesting a shared mechanism between the two. Our data further revealed a cross-talk between the adenosine and acetylcholine receptor signaling in reperfused rat hearts. Interestingly, the selective M(2 muscarinic acetylcholine receptor antagonist methoctramine significantly attenuated the cardioprotective effect of adenosine. In addition, treatment with adenosine upregulated the expression and the maximal binding capacity of muscarinic acetylcholine receptor, which were inhibited by the selective A(1 adenosine receptor antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX and the nitric oxide synthase inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME. These data suggested a possible functional coupling between the adenosine and muscarinic receptors behind the observed cardioprotection. Furthermore, nitric oxide was found involved in triggering the response to each of the two receptor agonist. In summary, there may be a cross-talk between the adenosine and muscarinic receptors in ischemic/reperfused myocardium with nitric oxide synthase might serve as the distal converging point. In addition, adenosine contributes to the invigorating effect of adenosine on muscarinic receptor thereby prompting to regulation of cardiac function. These findings argue for a potentially novel mechanism behind the adenosine

  6. Safe chemotherapy in the home environment.

    Science.gov (United States)

    Chavis-Parker, Paula

    2015-05-01

    The Oncology Nursing Society and the American Society of Clinical Oncology have established guidelines for the safe and effective use of chemotherapeutic medications in the acute and outpatient care settings. A review of literature was performed to determine the safe and effective administration of chemotherapy in the home environment. The administration of oral and intravenous chemotherapy in the home has become a common intervention for patients being treated for cancer based on patient preference, cost-effectiveness of healthcare delivery, and increasing demand for oncology services. Home healthcare nurses can greatly impact the management of adverse effects of chemotherapy in the home, increasing the quality of life and improving patient outcomes.

  7. Overview, prevention and management of chemotherapy extravasation.

    Science.gov (United States)

    Kreidieh, Firas Y; Moukadem, Hiba A; El Saghir, Nagi S

    2016-02-10

    Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.

  8. Chemotherapy-Induced Nausea and Vomiting.

    Science.gov (United States)

    Mustian, Karen M; Darling, Tom V; Janelsins, Michelle C; Jean-Pierre, Pascal; Roscoe, Joseph A; Morrow, Gary R

    2008-01-01

    Despite treatment advances, nausea and vomiting, especially anticipatory nausea and vomiting, delayed nausea and vomiting and nausea alone, are still the most common, expected and feared side effects among patients receiving chemotherapy. Of the 70 to 80% of cancer patients who experience chemotherapy-induced nausea and vomiting many will delay or refuse future chemotherapy treatments and contemplate stopping all treatments because of fear of further nausea and vomiting. The purpose of this chapter is to provide an overview of the patho-psychophysiology of CINV, the recommended guidelines for standard treatment, and highlight newer targeted treatment approaches.

  9. Hemodynamic significance of coronary stenosis by vessel attenuation measurement on CT compared with adenosine perfusion MRI

    NARCIS (Netherlands)

    den Dekker, Martijn A. M.; Pelgrim, Gert Jan; Pundziute, Gabija; van den Heuvel, Edwin R.; Oudkerk, Matthijs; Vliegenthart, Rozemarijn

    Purpose: We assessed the association between corrected contrast opacification (CCO) based on coronary computed tomography angiography (cCTA) and inducible ischemia by adenosine perfusion magnetic resonance imaging (APMR). Methods: Sixty cardiac asymptomatic patients with extra-cardiac arterial

  10. Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Nesterov, Sergey V; Kemppainen, Jukka;

    2007-01-01

    ) muscles during exercise, measured using positron emission tomography. In six healthy young women, BF was measured at rest and then during three incremental low and moderate intermittent isometric one-legged knee-extension exercise intensities without and with theophylline-induced nonselective adenosine...... exercise intensity in the QF muscle group. Adenosine seems to play a role in muscle BF heterogeneity even in the absence of changes in bulk BF at low and moderate one-leg intermittent isometric exercise intensities.......Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF...

  11. Laboratory procedures manual for the firefly luciferase assay for adenosine triphosphate (ATP)

    Science.gov (United States)

    Chappelle, E. W.; Picciolo, G. L.; Curtis, C. A.; Knust, E. A.; Nibley, D. A.; Vance, R. B.

    1975-01-01

    A manual on the procedures and instruments developed for the adenosine triphosphate (ATP) luciferase assay is presented. Data cover, laboratory maintenance, maintenance of bacterial cultures, bacteria measurement, reagents, luciferase procedures, and determination of microbal susceptibility to antibiotics.

  12. Targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax

    OpenAIRE

    Popov, Serguei G.; Popova, Taissia G.; Kashanchi, Fatah; Bailey, Charles

    2011-01-01

    AIM: To establish whether activation of adenosine type-3 receptors (A3Rs) and inhibition of interleukin-1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores.

  13. Influence of the adenosine A1 receptor on blood pressure regulation and renin release

    DEFF Research Database (Denmark)

    Brown, Russell D.; Thorén, Peter; Steege, Andreas

    2006-01-01

    The present study was performed to investigate the role of adenosine A1 receptors in regulating blood pressure in conscious mice. Adenosine A1-receptor knockout (A1R-/-) mice and their wild-type (A1R+/+) littermates were placed on standardized normal-salt (NS), high-salt (HS), or salt-deficient (SD......) diets for a minimum of 10 days before telemetric blood pressure and urinary excretion measurements in metabolic cages. On the NS diet, daytime and nighttime mean arterial blood pressure (MAP) was 7-10 mmHg higher in A1R-/- than in A1R+/+ mice. HS diet did not affect the MAP in A1R-/- mice....... The elevated plasma renin concentrations found in the A1R-/- mice could also result in increased blood pressure. Our results confirm that adenosine, acting through the adenosine A1 receptor, plays an important role in regulating blood pressure, renin release, and sodium excretion....

  14. ALLERGEN-INDUCED CHANGES IN ADENOSINE 5'-MONOPHOSPHATE BRONCHIAL RESPONSIVENESS - EFFECT OF NEDOCROMIL SODIUM

    NARCIS (Netherlands)

    AALBERS, R; KAUFMAN, HF; GROEN, H; KOETER, GH; DEMONCHY, JGR

    1992-01-01

    Bronchial hyperresponsiveness to adenosine 5'-monophosphate (AMP) was studied after allergen challenge in allergic asthmatic patients. Measurements were made with and without nedocromil sodium pretreatment. Nedocromil sodium inhibited both the early and late asthmatic reactions (P <.01). After aller

  15. Evidence that the positive inotropic effects of the alkylxanthines are not due to adenosine receptor blockade.

    Science.gov (United States)

    Collis, M. G.; Keddie, J. R.; Torr, S. R.

    1984-01-01

    We investigated the possibility that the positive inotropic effects of the alkylxanthines are due to adenosine receptor blockade. The potency of 8-phenyltheophylline, theophylline and enprofylline as adenosine antagonists was assessed in vitro, using the guinea-pig isolated atrium, and in vivo, using the anaesthetized dog. The order of potency of the alkylxanthines as antagonists of the negative inotropic response to 2-chloroadenosine in vitro, and of the hypotensive response to adenosine in vivo was 8-phenyltheophylline greater than theophylline greater than enprofylline. The order of potency of the alkylxanthines as positive inotropic and chronotropic agents in the anaesthetized dog was enprofylline greater than theophylline greater than 8-phenyltheophylline. The results of this study indicate that the inotropic effects of the alkylxanthines in the anaesthetized dog are not due to adenosine receptor blockade. PMID:6322898

  16. ALLERGEN-INDUCED CHANGES IN ADENOSINE 5'-MONOPHOSPHATE BRONCHIAL RESPONSIVENESS - EFFECT OF NEDOCROMIL SODIUM

    NARCIS (Netherlands)

    AALBERS, R; KAUFMAN, HF; GROEN, H; KOETER, GH; DEMONCHY, JGR

    1992-01-01

    Bronchial hyperresponsiveness to adenosine 5'-monophosphate (AMP) was studied after allergen challenge in allergic asthmatic patients. Measurements were made with and without nedocromil sodium pretreatment. Nedocromil sodium inhibited both the early and late asthmatic reactions (P <.01). After

  17. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed Ahmed; Skoetz, Nicole

    2011-01-01

    BACKGROUND: Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been...... questioned recently and some clinical study groups advocate chemotherapy only for this indication. OBJECTIVES: We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) comparing chemotherapy alone with CMT in patients with early stage Hodgkin lymphoma with respect...

  18. Chemotherapy-induced sclerosing cholangitis

    Energy Technology Data Exchange (ETDEWEB)

    Sandrasegaran, K.; Alazmi, W.M.; Tann, M.; Fogel, E.L.; McHenry, L.; Lehman, G.A

    2006-08-15

    Aim: To review the computed tomography (CT), magnetic resonance imaging (MRI) and cholangiographic findings of chemotherapy-induced sclerosing cholangitis (CISC). Methods: Between January 1995 and December 2004, 11 patients in the endoscopic retrograde cholangiography database were identified with CISC. Twelve CT, four MRI, 69 endoscopic and nine antegrade cholangiographic studies in these patients were reviewed. Serial change in appearance and response to endoscopic treatment were recorded. Results: CISC showed segmental irregular biliary dilatation with strictures of proximal extrahepatic bile ducts. The distal 5 cm of common bile duct was not affected in any patient. CT and MRI findings included altered vascular perfusion of one or more liver segments, liver metastases or peritoneal carcinomatosis. Biliary strictures needed repeated stenting in 10 patients (mean: every 4.7 months). Cirrhosis (n = 1) or confluent fibrosis (n = 0) were uncommon findings. Conclusion: CISC shares similar cholangiographic appearances to primary sclerosing cholangitis (PSC). Unlike PSC, biliary disease primarily involved ducts at the hepatic porta rather than intrahepatic ducts. Multiphasic contrast-enhanced CT or MRI may show evidence of perfusion abnormalities, cavitary liver lesions, or metastatic disease.

  19. Patient expectancy and post-chemotherapy nausea

    DEFF Research Database (Denmark)

    Colagiuri, Ben; Zachariae, Robert

    2010-01-01

    , specifically controlling for a history of nausea, and involving breast cancer patients, none of the moderators assessed were statistically significant. CONCLUSIONS: These findings suggest that patient expectancies may contribute to post-chemotherapy nausea and that expectancy-based manipulations may provide......BACKGROUND: Post-chemotherapy nausea remains a significant burden to cancer patients. While some studies indicate that expecting nausea is predictive of experiencing nausea, there are a number of conflicting findings. PURPOSE: The purpose of this study was to conduct a meta-analytic review......, there was a robust positive association between expectancy and post-chemotherapy nausea (ESr = 0.18, equivalent to Cohen's d = 0.35), suggesting that patients with stronger expectancies experience more chemotherapy-induced nausea. Although weaker associations were found in studies employing multivariate analysis...

  20. Managing Chemotherapy Side Effects: Memory Changes

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Memory Changes What is causing these changes? Your doctor will work to find out what is causing these problems. They may be caused by ...

  1. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Science.gov (United States)

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  2. Adjuvant chemotherapy in early breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent

    2016-01-01

    % of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast...... are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials...... adjuvant trials demonstrated that patients with either TOP2A or centromere 17 aberrations, but not with HER2 amplification, benefit from anthracycline-containing adjuvant chemotherapy. Anthracyclins have additional distinct biological mechanisms; and results from the DBCG 89D suggested that tumours...

  3. Adverse Effects of Radiation and Chemotherapy

    OpenAIRE

    1991-01-01

    The long-term consequences of radiation and chemotherapy on intellectual and endocrine function in children with brain tumors is reviewed from the Departments of Neurology and Pediatrics, State University of New York, Buffalo, NY.

  4. A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways.

    Science.gov (United States)

    Janes, Kali; Esposito, Emanuela; Doyle, Timothy; Cuzzocrea, Salvatore; Tosh, Dillip K; Jacobson, Kenneth A; Salvemini, Daniela

    2014-12-01

    Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. We recently reported that activation of the Gi/Gq-coupled A3 adenosine receptor (A3AR) with selective A3AR agonists (ie, IB-MECA) blocked the development of chemotherapy induced-neuropathic pain evoked by distinct agents, including paclitaxel, without interfering with anticancer effects. The mechanism or mechanisms of action underlying these beneficial effects has yet to be explored. We now demonstrate that IB-MECA attenuates the development of paclitaxel-induced neuropathic pain by inhibiting the activation of spinal NADPH oxidase and two downstream redox-dependent systems. The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy. Copyright © 2014

  5. Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices.

    Science.gov (United States)

    Greene, R W; Haas, H L

    1985-09-01

    Intracellular recordings with a bridge amplifier of CA1 pyramidal neurones in vitro were employed to study the mechanisms of action of exogenously applied adenosine in the hippocampal slice preparation of the rat. Adenosine enhanced the calcium-dependent, long-duration after-hyperpolarization (a.h.p.) at least in part by a reduction in the rate of decay of the a.h.p. Both the reduced rate of decay and that of the control can be described with a single exponential. Antagonism of the calcium-dependent potassium current (and as a result, the a.h.p.) by bath application of CdCl2 or intracellular injection of EGTA (ethyleneglycolbis-(beta-aminoethyl ether)N,N'-tetraacetic acid) did not reduce the adenosine-evoked hyperpolarization or decrease in input resistance. Similarly, TEA (tetraethylammonium), which antagonizes both the voltage- and calcium-sensitive, delayed, outward rectification, had no effect on the adenosine-evoked changes in resting membrane properties. Adenosine did not affect the early, transient, outward rectification. During exposure to 4-aminopyridine (4-AP) in concentrations sufficient to antagonize this early rectification, the changes in resting membrane properties evoked by adenosine were unaffected. We conclude that the enhancement of the a.h.p. and accommodation by adenosine may be mediated by a change in the regulation of intracellular calcium. However, the mechanism responsible for the hyperpolarization and decrease in input resistance evoked by adenosine is both calcium and voltage insensitive. Thus, it appears distinct from that mediating the enhancement of the a.h.p. and accommodation.

  6. Role of adenosine A1 and A2A receptors in the alcohol withdrawal syndrome.

    Science.gov (United States)

    Kaplan, G B; Bharmal, N H; Leite-Morris, K A; Adams, W R

    1999-10-01

    The role of adenosine receptor-mediated signaling was examined in the alcohol withdrawal syndrome. CD-1 mice received a liquid diet containing ethanol (6.7%, v/v) or a control liquid diet that were abruptly discontinued after 14 days of treatment. Mice consuming ethanol showed a progressive increase in signs of intoxication throughout the drinking period. Following abrupt discontinuation of ethanol diet, mice demonstrated reversible signs of handling-induced hyperexcitability that were maximal between 5-8 h. Withdrawing mice received treatment with adenosine receptor agonists at the onset of peak withdrawal (5.5 h) and withdrawal signs were blindly rated (during withdrawal hours 6 and 7). Adenosine A1-receptor agonist R-N6(phenylisopropyl)adenosine (0.15 and 0.3 mg/ kg) reduced withdrawal signs 0.5 and 1.5 h after drug administration in a dose-dependent fashion. Adenosine A2A-selective agonist 2-p-(2-carboxyethyl)phenylethyl-amino-5'-N-ethylcarboxamidoadenosine (0.3 mg/kg) reduced withdrawal signs at both time points. In ethanol-withdrawing mice, there were significant decreases in adenosine transporter sites in striatum without changes in cortex or cerebellum. In ethanol-withdrawing mice, there were no changes in adenosine A1 and A2A receptor concentrations in cortex, striatum, or cerebellum. There appears to be a role for adenosine A1 and A2A receptors in the treatment of the ethanol withdrawal syndrome. Published by Elsevier Science Inc.

  7. Sitagliptin attenuates sympathetic innervation via modulating reactive oxygen species and interstitial adenosine in infarcted rat hearts.

    Science.gov (United States)

    Lee, Tsung-Ming; Chen, Wei-Ting; Yang, Chen-Chia; Lin, Shinn-Zong; Chang, Nen-Chung

    2015-02-01

    We investigated whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression in post-infarcted normoglycemic rats, focusing on adenosine and reactive oxygen species production. DPP-4 bound adenosine deaminase has been shown to catalyse extracellular adenosine to inosine. DPP-4 inhibitors increased adenosine levels by inhibiting the complex formation. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline or sitagliptin in in vivo and ex vivo studies. Post-infarction was associated with increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine and dihydroethidium fluorescent staining. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham. Compared with vehicle, infarcted rats treated with sitagliptin significantly increased interstitial adenosine levels and attenuated oxidative stress. Sympathetic hyperinnervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Ex vivo studies showed a similar effect of erythro-9-(2-hydroxy-3-nonyl) adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated levels of superoxide and NGF. Furthermore, the beneficial effects of sitagliptin on superoxide anion production and NGF levels can be reversed by 8-cyclopentyl-1,3-dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation via adenosine A1 receptor and xanthine oxidase-dependent pathways, which converge through the attenuated formation of superoxide in the non-diabetic infarcted rats.

  8. Adenosine concentrations in the interstitium of resting and contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Maclean, D.; Rådegran, G.

    1998-01-01

    effect remain unanswered. METHODS AND RESULTS: The interstitial adenosine concentration was determined in the vastus lateralis muscle of healthy humans via dialysis probes inserted in the muscle. The probes were perfused with buffer, and the dialysate samples were collected at rest and during graded knee...... and demonstrates that adenosine and its precursors increase in the exercising muscle interstitium, at a rate associated with intensity of muscle contraction and the magnitude of muscle blood flow....

  9. Effect of insulin and glucose on adenosine metabolizing enzymes in human B lymphocytes.

    Science.gov (United States)

    Kocbuch, Katarzyna; Sakowicz-Burkiewicz, Monika; Grden, Marzena; Szutowicz, Andrzej; Pawelczyk, Tadeusz

    2009-01-01

    In diabetes several aspects of immunity are altered, including the immunomodulatory action of adenosine. Our study was undertaken to investigate the effect of different glucose and insulin concentrations on activities of adenosine metabolizing enzymes in human B lymphocytes line SKW 6.4. The activity of adenosine deaminase in the cytosolic fraction was very low and was not affected by different glucose concentration, but in the membrane fraction of cells cultured with 25 mM glucose it was decreased by about 35% comparing to the activity in cells maintained in 5 mM glucose, irrespective of insulin concentration. The activities of 5'-nucleotidase (5'-NT) and ecto-5'-NT in SKW 6.4 cells depended on insulin concentration, but not on glucose. Cells cultured with 10(-8) M insulin displayed an about 60% lower activity of cytosolic 5'-NT comparing to cells maintained at 10(-11) M insulin. The activity of ecto-5'-NT was decreased by about 70% in cells cultured with 10(-8) M insulin comparing to cells grown in 10(-11) M insulin. Neither insulin nor glucose had an effect on adenosine kinase (AK) activity in SKW 6.4 cells or in human B cells isolated from peripheral blood. The extracellular level of adenosine and inosine during accelerated catabolism of cellular ATP depended on glucose, but not on insulin concentration. Concluding, our study demonstrates that glucose and insulin differentially affect the activities of adenosine metabolizing enzymes in human B lymphocytes, but changes in those activities do not correlate with the adenosine level in cell media during accelerated ATP catabolism, implying that nucleoside transport is the primary factor determining the extracellular level of adenosine.

  10. Combined chemotherapy including platinum derivatives for medulloblastoma. The usefulness as maintenance chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hikaru; Otani, Mitsuhiro; Yoshida, Kazunari; Kagami, Hiroshi; Shimazaki, Kenji; Toya, Shigeo; Kawase, Takeshi [Keio Univ., Tokyo (Japan). School of Medicine

    1997-02-01

    The authors reviewed 24 cerebellar medulloblastoma patients treated at Keio University to determine usefulness of combined chemotherapy including platinum derivatives (cisplatin, carboplatin) as the induction and maintenance treatment. All patients underwent radical surgery and craniospinal irradiation. Ten received adjuvant chemotherapy other than platinum derivatives (mainly with nitrosourea compounds), five were treated by induction and maintenance chemotherapy including platinum derivatives, and nine patients did not undergo chemotherapy. The progression-free survival rate of patients treated with platinum derivatives was better than that of patients treated with other modes of chemotherapy and also that of patients who did not receive chemotherapy. The results were especially good in the case of four patients treated with maintenance chemotherapy consisting of carboplatin and etoposide, two of whom had been free from relapse beyond the risk period of Collins. The occurrences of toxicity in maintenance chemotherapy with carboplatin and etoposide were limited to transient leucopenia. The present study indicates combined chemotherapy including platinum derivatives benefits patients with medulloblastoma, and could be useful, especially as maintenance treatment. (author)

  11. Cardiac endothelial transport and metabolism of adenosine and inosine

    Science.gov (United States)

    Schwartz, Lisa M.; Bukowski, Thomas R.; Revkin, James H.; Bassingthwaighte, James B.

    2010-01-01

    The influence of transmembrane flux limitations on cellular metabolism of purine nucleosides was assessed in whole organ studies. Transcapillary transport of the purine nucleosides adenosine (Ado) and inosine (Ino) via paracellular diffusion through interendothelial clefts in parallel with carrier-mediated transendothelial fluxes was studied in isolated, Krebs-Henseleit-perfused rabbit and guinea pig hearts. After injection into coronary inflow, multiple-indicator dilution curves were obtained from coronary outflow for 90 s for 131I-labeled albumin (intravascular reference tracer), [3H]arabinofuranosyl hypoxanthine (AraH; extracellular reference tracer and nonreactive adenosine analog), and either [14C]Ado or [14C]Ino. Ado or Ino was separated from their degradative products, hypoxanthine, xanthine, and uric acid, in each outflow sample by HPLC and radioisotope counting. Ado and Ino, but not AraH, permeate the luminal membrane of endothelial cells via a saturable transporter with permeability-surface area product PSecl and also diffuse passively through interendothelial clefts with the same conductance (PSg) as AraH. These parallel conductances were estimated via fitting with an axially distributed, multi-pathway, four-region blood-tissue exchange model. PSg for AraH were ~4 and 2.5 ml · g−1 · min−1 in rabbits and guinea pigs, respectively. In contrast, transplasmalemmal conductances (endothelial PSecl) were ~0.2 ml · g−1 · min−1 for both Ado and Ino in rabbit hearts but ~2 ml · g−1 · min−1 in guinea pig hearts, an order of magnitude different. Purine nucleoside metabolism also differs between guinea pig and rabbit cardiac endothelium. In guinea pig heart, 50% of the tracer Ado bolus was retained, 35% was washed out as Ado, and 15% was lost as effluent metabolites; 25% of Ino was retained, 50% washed out, and 25% was lost as metabolites. In rabbit heart, 45% of Ado was retained and 5% lost as metabolites, and 7% of Ino was retained and 3% lost as

  12. Online cleanup of accelerated solvent extractions for determination of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP) in royal jelly using high-performance liquid chromatography.

    Science.gov (United States)

    Xue, Xiaofeng; Wang, Feng; Zhou, Jinhui; Chen, Fang; Li, Yi; Zhao, Jing

    2009-06-10

    Determination of the levels of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP) in royal jelly is important for the study of its pharmacological activities, health benefits, and adenosine phosphate degradation. In this study was developed a novel method to determine ATP, ADP, and AMP levels in royal jelly using accelerated solvent extraction (ASE) followed by online cleanup and high-performance liquid chromatography (HPLC) with diode array detection (DAD). The optimum extraction conditions were obtained using an 11 mL ASE cell, ethanol/water (5:5 v/v) as the extraction solvent, 1500 psi, 80 degrees C, a 5 min static time, and a 60% flush volume. Optimum separation of the three compounds was achieved in AMP levels in 15 samples of royal jelly of different origins was performed. Sample results indicated that the AMP concentration was 24.2-2214.4 mg kg(-1), whereas ATP and ADP were not detectable or present only at low levels.

  13. Mechanisms of chemotherapy-induced behavioral toxicities.

    Science.gov (United States)

    Vichaya, Elisabeth G; Chiu, Gabriel S; Krukowski, Karen; Lacourt, Tamara E; Kavelaars, Annemieke; Dantzer, Robert; Heijnen, Cobi J; Walker, Adam K

    2015-01-01

    While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence, neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs) activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  14. Mechanisms of chemotherapy-induced behavioral toxicities

    Directory of Open Access Journals (Sweden)

    Elisabeth G Vichaya

    2015-04-01

    Full Text Available While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms of chemotherapy include (i cognitive deficiencies such as problems with attention, memory and executive functioning; (ii fatigue and motivational deficit; and (iii neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  15. [Combined radio- and chemotherapy of anal cancer].

    Science.gov (United States)

    Dobrowsky, W

    1986-05-30

    The treatment regime in anal carcinoma is changing from being a mainly surgical problem. Combined radio-chemotherapy is of increasing interest as treatment of choice. The new treatment modality, including chemotherapy with Mitomycin C and 5-fluorouracil combined with percutaneous and interstitial radiotherapy is presented. The treatment regimes performed at the University Department for Radiotherapy and Radiobiology Vienna is discussed with regard to tolerance, side effects and local control.

  16. Striatal adenosine signaling regulates EAAT2 and astrocytic AQP4 expression and alcohol drinking in mice.

    Science.gov (United States)

    Lee, Moonnoh R; Ruby, Christina L; Hinton, David J; Choi, Sun; Adams, Chelsea A; Young Kang, Na; Choi, Doo-Sup

    2013-02-01

    Adenosine signaling is implicated in several neuropsychiatric disorders, including alcoholism. Among its diverse functions in the brain, adenosine regulates glutamate release and has an essential role in ethanol sensitivity and preference. However, the molecular mechanisms underlying adenosine-mediated glutamate signaling in neuroglial interaction remain elusive. We have previously shown that mice lacking the ethanol-sensitive adenosine transporter, type 1 equilibrative nucleoside transporter (ENT1), drink more ethanol compared with wild-type mice and have elevated striatal glutamate levels. In addition, ENT1 inhibition or knockdown reduces glutamate transporter expression in cultured astrocytes. Here, we examined how adenosine signaling in astrocytes contributes to ethanol drinking. Inhibition or deletion of ENT1 reduced the expression of type 2 excitatory amino-acid transporter (EAAT2) and the astrocyte-specific water channel, aquaporin 4 (AQP4). EAAT2 and AQP4 colocalization was also reduced in the striatum of ENT1 null mice. Ceftriaxone, an antibiotic compound known to increase EAAT2 expression and function, elevated not only EAAT2 but also AQP4 expression in the striatum. Furthermore, ceftriaxone reduced ethanol drinking, suggesting that ENT1-mediated downregulation of EAAT2 and AQP4 expression contributes to excessive ethanol consumption in our mouse model. Overall, our findings indicate that adenosine signaling regulates EAAT2 and astrocytic AQP4 expressions, which control ethanol drinking in mice.

  17. Functional proteomics of adenosine triphosphatase system in the rat striatum during aging

    Institute of Scientific and Technical Information of China (English)

    Roberto Federico Villa; Federica Ferrari; Antonella Gorini

    2012-01-01

    The maximum rates of adenosine triphosphatase (ATPase) systems related to energy consumption were systematically evaluated in synaptic plasma membranes isolated from the striata of male Wistar rats aged 2, 6, 12, 18, and 24 months, because of their key role in presynaptic nerve ending homeostasis. The following enzyme activities were evaluated: sodium-potassium-magnesium adenosine triphosphatase (Na+, K+, Mg2+-ATPase); ouabain-insensitive magnesium adenosine triphosphatase (Mg2+-ATPase); sodium-potassium adenosine triphosphatase (Na+, K+-ATPase); direct magnesium adenosine triphosphatase (Mg2+-ATPase); calcium-magnesium adenosine triphosphatase (Ca2+, Mg2+-ATPase); and acetylcholinesterase. The results showed that Na+, K+-ATPase decreased at 18 and 24 months, Ca2+, Mg2+-ATPase and acetylcholinesterase decreased from 6 months, while Mg2+-ATPase was unmodified. Therefore, ATPases vary independently during aging, suggesting that the ATPase enzyme systems are of neuropathological and pharmacological importance. This could be considered as an experimental model to study regeneration processes, because of the age-dependent modifications of specific synaptic plasma membranes. ATPases cause selective changes in some cerebral functions, especially bioenergetic systems. This could be of physiopathological significance, particularly in many central nervous system diseases, where, during regenerative processes, energy availability is essential.

  18. Localization of Adenosine Triphosphatase Activity on the Chloroplast Envelope in Tendrils of Pisum sativum1

    Science.gov (United States)

    Sabnis, Dinkar D.; Gordon, Mildred; Galston, Arthur W.

    1970-01-01

    When samples of pea tendril tissue were incubated in the Wachstein-Meisel medium for the demonstration of adenosine triphosphatases, deposits of lead reaction product were localized between the membranes of the chloroplast envelope. The presence of Mg2+ was necessary for adenosine triphosphatase activity, and Ca2+ could not substitute for this requirement. Varying the pH of incubation to 5.5 or 9.4 inhibited enzyme activity, as did the addition of p-chloromercuribenzoic acid or N-ethylmaleimide. The adenosine triphosphatase was apparently inactivated or degraded when the plants were grown in the dark for 24 hours prior to incubation. The enzyme was substrate-specific for adenosine triphosphate; no reaction was obtained with adenosine diphosphate, uridine triphosphate, inosine triphosphate, p-nitrophenyl phosphate, and sodium β-glycerophosphate. Sites of nonspecific depositions of lead are described. The adenosine triphosphatase on the chloroplast envelope may be involved in the light-induced contraction of this organelle. Images PMID:4245003

  19. Purine molecules as hypnogenic factors role of adenosine, ATP, and caffeine.

    Science.gov (United States)

    Díaz-Muñoz, M; Salín-Pascual, R

    2010-12-01

    Purines are ubiquitous molecules with important roles in the regulation of metabolic networks and signal transduction events. In the central nervous system, adenosine and ATP modulate the sleep-wake cycle, acting as ligands of specific transmembrane receptors and as allosteric effectors of key intracellular enzymes for brain energy expenditure. Two types of adenosine receptors seem to be relevant to the sleep function, A1 and A2A. Caffeine, an antagonist of adenosine receptors, has been used as a tool in some of the studies reviewed in the present chapter. Possible changes in adenosine functioning due to the aging process have been observed in animal models and abnormalities in the adenosine system could also explain primary insomnia or the reduced amount of delta sleep and increased sensitivity to caffeine in some subjects with sleep deficits. Caffeine is a methylated-derivate of xanthine with profound effects on the onset and quality of sleep episodes. This purine acts principally as an antagonist of the A2A receptors. Adenosine and ATP in the nervous system are the bridge between metabolic activity, recovery function, and purinergic transmission that underlies the daily wake-sleep cycle in mammals. Modulators of purine actions have the potential to alleviate insomnia and other sleep disorders based on their physiopathological role during the sleep process.

  20. In vivo effects of adenosine 5´-triphosphate on rat preneoplastic liver

    Directory of Open Access Journals (Sweden)

    Ana V. Frontini

    2011-04-01

    Full Text Available The utilization of adenosine 5´-triphosphate (ATP infusions to inhibit the growth of some human and animals tumors was based on the anticancer activity observed in in vitro and in vivo experiments, but contradictory results make the use of ATP in clinical practice rather controversial. Moreover, there is no literature regarding the use of ATP infusions to treat hepatocarcinomas. The purpose of this study was to investigate whether ATP prevents in vivo oncogenesis in very-early-stage cancer cells in a well characterized two-stage model of hepatocarcinogenesis in the rat. As we could not preclude the possible effect due to the intrinsic properties of adenosine, a known tumorigenic product of ATP hydrolysis, the effect of the administration of adenosine was also studied. Animals were divided in groups: rats submitted to the two stage preneoplasia initiation/promotion model of hepatocarcinogenesis, rats treated with intraperitoneal ATP or adenosine during the two phases of the model and appropriate control groups. The number and volume of preneoplastic foci per liver identified by the expression of glutathione S-transferase placental type and the number of proliferating nuclear antigen positive cells significantly increased in ATP and adenosine treated groups. Taken together, these results indicate that in this preneoplastic liver model, ATP as well as adenosine disturb the balance between apoptosis and proliferation contributing to malignant transformation.

  1. Decreased intravesical adenosine triphosphate in patients with refractory detrusor overactivity and bacteriuria.

    Science.gov (United States)

    Walsh, Colin A; Cheng, Ying; Mansfield, Kylie J; Parkin, Katrina; Mukerjee, Chinmoy; Moore, Kate H

    2013-04-01

    Although several studies have examined the relationship between adenosine triphosphate release from the urothelium and bladder sensations including painful filling and urgency, the association between bacteriuria and urothelial adenosine triphosphate release has not been well studied. We evaluated women with refractory detrusor overactivity who were experiencing an acute exacerbation of detrusor overactivity symptoms including frequency, urgency and nocturia (and/or urge incontinence). We measured changes in intravesical adenosine triphosphate levels in these women with and without bacteriuria. In this prospective cohort study women with refractory detrusor overactivity were invited to our unit during acute symptomatic exacerbation. On presentation a catheter urine specimen was collected and 50 ml normal saline instilled into the bladder to evoke gentle stretch, with removal after 5 minutes. Adenosine triphosphate concentrations were determined on fresh washings using a bioluminescence assay. The incidence of bacteriuria 10(3) cfu/ml or greater was 27% (15 of 56 specimens) during the 16-month study period. Adenosine triphosphate concentrations were lower during episodes of bacteriuria in the overall cohort (p = 0.0013) and paired samples from individual patients (p = 0.031) compared to episodes of sterile urine. In the first study on the subject to our knowledge, we demonstrated a striking difference between adenosine triphosphate levels measured in the presence and absence of bacteriuria in this patient group. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.

    Science.gov (United States)

    Densmore, John C; Schaid, Terry R; Jeziorczak, Paul M; Medhora, Meetha; Audi, Said; Nayak, Shraddha; Auchampach, John; Dwinell, Melinda R; Geurts, Aron M; Jacobs, Elizabeth R

    2017-02-01

    Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury.

  3. Serum adenosine deaminase as oxidative stress marker in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Shashikala Magadi Dasegowda

    2015-05-01

    Results: The study observed an increased level of serum adenosine deaminase, malondialdehyde and decreased levels of total antioxidant capacity in type 2 diabetes mellitus compared to controls. Serum adenosine deaminase levels in type 2 diabetics were 50.77 +/- 6.95 and in controls was 17.86 +/- 4.04. Serum Malondialdehyde levels in type 2 diabetics was 512.13 +/- 70.15 and in controls was 239.32 +/- 23.97. Serum total antioxidant levels in type 2 diabetics was 0.39+/-0.15 and in controls was 1.66+/-0.25. Positive correlation was seen between serum adenosine deaminase and malondialdehyde and it was statistically significant. Statistically significant negative correlation was seen between serum adenosine deaminase and total antioxidant capacity. Conclusion: Adenosine deaminase can be used as oxidative stress marker. Their increased levels indicate oxidative stress in type 2 diabetes mellitus. Therefore, estimation of serum adenosine deaminase levels help in early prediction and prevention of long term complications occurring due to oxidative stress in diabetics, thereby decreasing the mortality and morbidity in them. [Int J Res Med Sci 2015; 3(5.000: 1195-1198

  4. Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.

    Directory of Open Access Journals (Sweden)

    Sammeta V Raju

    Full Text Available Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR, a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B adenosine receptor (A(2BAR, largely abolished the adenosine-stimulated chloride transport, suggesting that A(2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.

  5. Chemotherapy induced nausea AND vomiting (CINV

    Directory of Open Access Journals (Sweden)

    Bannur R. Nandeesh

    2012-06-01

    Full Text Available Chemotherapy is the first line treatment in management of many cancers, both for cure and palliation; hence it’s crucial to minimize the unpleasant side effects of chemotherapy to increase tolerability to chemotherapy. Most of the conventional anti cancer drugs are emetogenic. Patients receiving chemotherapy experience different degrees of nausea and vomiting depending on the emetogenic potential of the anti cancer drugs given and the patient characteristics. With a better understanding of the pathophysiology, distinct phases of chemotherapy-induced nausea and vomiting (CINV i.e., acute emesis, delayed emesis and anticipatory emesis have been identified. Identification of various mediators has led to the development of different drugs acting through different mechanisms which are useful in the prevention and treatment of CINV. Serotonin receptor three (5-HT3 antagonists, corticosteroids and neurokinin type one receptor (NK-1 antagonists are of proven usefulness and have wide therapeutic indexes in the prevention of CINV. Other drugs like dopamine receptor antagonists & benzodiazepines are not routinely used because of their narrow therapeutic index. Practice guidelines for prevention of CINV will not only improve patient’s tolerability to chemotherapy & wellbeing, but also decrease hospital stay and overall cost of treatment of the patient. [Int J Basic Clin Pharmacol 2012; 1(3.000: 125-131

  6. Fasting and differential chemotherapy protection in patients.

    Science.gov (United States)

    Raffaghello, Lizzia; Safdie, Fernando; Bianchi, Giovanna; Dorff, Tanya; Fontana, Luigi; Longo, Valter D

    2010-11-15

    Chronic calorie restriction has been known for decades to prevent or retard cancer growth, but its weight-loss effect and the potential problems associated with combining it with chemotherapy have prevented its clinical application. Based on the discovery in model organisms that short term starvation (STS or fasting) causes a rapid switch of cells to a protected mode, we described a fasting-based intervention that causes remarkable changes in the levels of glucose, IGF-I and many other proteins and molecules and is capable of protecting mammalian cells and mice from various toxins, including chemotherapy. Because oncogenes prevent the cellular switch to this stress resistance mode, starvation for 48 hours or longer protects normal yeast and mammalian cells and mice but not cancer cells from chemotherapy, an effect we termed Differential Stress Resistance (DSR). In a recent article, 10 patients who fasted in combination with chemotherapy, reported that fasting was not only feasible and safe but caused a reduction in a wide range of side effects accompanied by an apparently normal and possibly augmented chemotherapy efficacy. Together with the remarkable results observed in animals, these data provide preliminary evidence in support of the human application of this fundamental biogerontology finding, particularly for terminal patients receiving chemotherapy. Here we briefly discuss the basic, pre-clinical, and clinical studies on fasting and cancer therapy.

  7. Cyclic adenosine monophosphate signal pathway in targeted therapy of lymphoma

    Institute of Scientific and Technical Information of China (English)

    DOU Ai-xia; WANG Xin

    2010-01-01

    Objective To review the role of cyclic adenosine monophosphate (cAMP) signal pathway in the pathogenesis oflymphoma and explore a potential lymphoma therapy targeted on this signaling pathway.Data sources The data cited in this review were mainly obtained from the articles listed in Medline and PubMed,published from January 1995 to June 2009. The search terms were "cAMP" and "lymphoma".Study selection Articles regarding the role of the cAMP pathway in apoptosis of lymphoma and associated cells and itspotential role in targeted therapy of lymphoma.Results In the transformation of lymphocytic malignancies, several signal pathways are involved. Among of them, thecAMP pathway has attracted increasing attention because of its apoptosis-inducing role in several lymphoma cells. cAMPpathway impairment is found to influence the prognosis of lymphoma. Targeted therapy to the cAMP pathway seems tobe a new direction for lymphoma treatment, aiming at restoring the cAMP function.Conclusions cAMP signal pathway has different effects on various lymphoma cells. cAMP analogues andphosphodiesterase 4B (PDE4B) inhibitors have potential clinical significance. However, many challenges remain inunderstanding the various roles of such agents.

  8. Adenosine diphosphate sugar pyrophosphatase prevents glycogen biosynthesis in Escherichia coli

    Science.gov (United States)

    Moreno-Bruna, Beatriz; Baroja-Fernández, Edurne; Muñoz, Francisco José; Bastarrica-Berasategui, Ainara; Zandueta-Criado, Aitor; Rodríguez-López, Milagros; Lasa, Iñigo; Akazawa, Takashi; Pozueta-Romero, Javier

    2001-01-01

    An adenosine diphosphate sugar pyrophosphatase (ASPPase, EC 3.6.1.21) has been characterized by using Escherichia coli. This enzyme, whose activities in the cell are inversely correlated with the intracellular glycogen content and the glucose concentration in the culture medium, hydrolyzes ADP-glucose, the precursor molecule of glycogen biosynthesis. ASPPase was purified to apparent homogeneity (over 3,000-fold), and sequence analyses revealed that it is a member of the ubiquitously distributed group of nucleotide pyrophosphatases designated as “nudix” hydrolases. Insertional mutagenesis experiments leading to the inactivation of the ASPPase encoding gene, aspP, produced cells with marginally low enzymatic activities and higher glycogen content than wild-type bacteria. aspP was cloned into an expression vector and introduced into E. coli. Transformed cells were shown to contain a dramatically reduced amount of glycogen, as compared with the untransformed bacteria. No pleiotropic changes in the bacterial growth occurred in both the aspP-overexpressing and aspP-deficient strains. The overall results pinpoint the reaction catalyzed by ASPPase as a potential step of regulating glycogen biosynthesis in E. coli. PMID:11416161

  9. Role of adenosine in tubuloglomerular feedback and acute renal failure.

    Science.gov (United States)

    Osswald, H; Vallon, V; Mühlbauer, B

    1996-12-01

    1. Adenosine (ADO) can induce renal vasoconstriction and a fall in glomerular filtration rate. When the rate of ATP hydrolysis prevails over the rate of ATP synthesis the kidney generates ADO at an enhanced rate. 2. Tubuloglomerular feedback (TGF) is the vascular response to changes of the NaCl concentration in the tubular fluid at the macula densa segment, which is the result of transepithelial electrolyte reabsorption by the proximal tubule and the loop of Henle. 3. TGF can be inhibited by ADO-A1 receptor antagonists and is potentiated by substances that can elevate extracellular ADO concentrations. These observations led to the hypothesis that ADO is an element of the signal transmission processes in the juxtaglomerular apparatus. 4. Renal ischaemia and nephrotoxic substances can induce acute renal failure (ARF). ADO receptor antagonists have been shown to ameliorate renal function in several different models of ARF in laboratory animals and humans. 5. A number of factors, such as extracellular volume contraction, low NaCl diet, angiotensin II and cyclooxygenase inhibitors enhance to a similar extent: (a) the renal vascular response to endogenous and exogenous ADO; (b) the TGF response of the nephron; and (c) the severity of ARF. All three phenomena are susceptible to antagonism by ADO receptor antagonists. 6. Therefore, we conclude that ADO plays a significant role in normal and pathological states of kidney function.

  10. Intracellular Adenosine Triphosphate Deprivation through Lanthanide-Doped Nanoparticles.

    Science.gov (United States)

    Tian, Jing; Zeng, Xiao; Xie, Xiaoji; Han, Sanyang; Liew, Oi-Wah; Chen, Yei-Tsung; Wang, Lianhui; Liu, Xiaogang

    2015-05-27

    Growing interest in lanthanide-doped nanoparticles for biological and medical uses has brought particular attention to their safety concerns. However, the intrinsic toxicity of this new class of optical nanomaterials in biological systems has not been fully evaluated. In this work, we systematically evaluate the long-term cytotoxicity of lanthanide-doped nanoparticles (NaGdF4 and NaYF4) to HeLa cells by monitoring cell viability (mitochondrial activity), adenosine triphosphate (ATP) level, and cell membrane integrity (lactate dehydrogenase release), respectively. Importantly, we find that ligand-free lanthanide-doped nanoparticles induce intracellular ATP deprivation of HeLa cells, resulting in a significant decrease in cell viability after exposure for 7 days. We attribute the particle-induced cell death to two distinct cell death pathways, autophagy and apoptosis, which are primarily mediated via the interaction between the nanoparticle and the phosphate group of cellular ATP. The understanding gained from the investigation of cytotoxicity associated with lanthanide-doped nanoparticles provides keen insights into the safe use of these nanoparticles in biological systems.

  11. In Vitro Functional Study of Rice Adenosine 5'-Phosphosulfate Kinase

    Institute of Scientific and Technical Information of China (English)

    WANG De-zhen; CHEN Guo-guo; LU Lu-jia; JIANG Zhao-jun; RAO Yu-chun; SUN Mei-hao

    2016-01-01

    Sulfate can be activated by ATP sulfurylase and adenosine 5'-phosphosulfate kinase (APSK)in vivo. Recent studies suggested that APSK inArabidopsis thaliana regulated the partition between APS reduction and phosphorylation and its activity can be modulated by cellular redox status. In order to study regulation of APSK in rice (OsAPSK),OsAPSK1 gene was cloned and its activity was analyzed. OsAPSK1 C36 and C69 were found to be the conserved counterparts of C86 and C119, which involved in disulfide formation in AtAPSK.C36A/C69A OsAPSK1 double mutation was made by site directed mutagenesis. OsAPSK1 and its mutant were prokaryotically over-expressed and purified, and then assayed for APS phosphorylation activity. OsAPSK1 activity was depressed by oxidized glutathione, while the activity of its mutantwas not. Further studies in the case that oxidative stress will fluctuatein vivo3'-phosphoadenosine-5'-phosphosulfate content, and all APSK isoenzymes have similar regulation patterns are necessary to be performed.

  12. Diagnostic value of adenosine deaminase to differentiate exudates and transudates.

    Science.gov (United States)

    Jadhav, Ashish Anantrao; Bardapurkar, Jayashree Suhas

    2007-01-01

    The differentiation of pleural effusions as exudates or transudates is the first step in the diagnosis of pleural effusions. The aim of this study was to evaluate the value of adenosine deaminase (ADA) concentration in the pleural effusions for differentiating exudates from transudates. Sixty indoor patients, admitted to our hospital, having pleural effusions and suffering from varying etiologies were included in this study. According to the final diagnosis, these 60 patients were divided into two groups: exudates (50) and transudates (10). The mean pleural ADA, serum ADA and pleural fluid/serum ADA ratio were significantly (P exudates as compared to transudates. Using a cut-off point of 22 IU/L, the sensitivity and specificity of pleural ADA in the diagnosis of exudates was computed to be 90% and 90% respectively. At a cut-off point 1.28, pleural fluid/serum ADA ratio was found to have sensitivity 84% and specificity 90%, respectively. From this study it is concluded that, ADA is a useful biochemical marker to suggest exudative effusions.

  13. Feasibility and safety of high-dose adenosine perfusion cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Holloway Cameron J

    2010-11-01

    Full Text Available Abstract Introduction Adenosine is the most widely used vasodilator stress agent for Cardiovascular Magnetic Resonance (CMR perfusion studies. With the standard dose of 140 mcg/kg/min some patients fail to demonstrate characteristic haemodynamic changes: a significant increase in heart rate (HR and mild decrease in systolic blood pressure (SBP. Whether an increase in the rate of adenosine infusion would improve peripheral and, likely, coronary vasodilatation in those patients is unknown. The aim of the present study was to assess the tolerance and safety of a high-dose adenosine protocol in patients with inadequate haemodynamic response to the standard adenosine protocol when undergoing CMR perfusion imaging. Methods 98 consecutive patients with known or suspected coronary artery disease (CAD underwent CMR perfusion imaging at 1.5 Tesla. Subjects were screened for contraindications to adenosine, and an electrocardiogram was performed prior to the scan. All patients initially received the standard adenosine protocol (140 mcg/kg/min for at least 3 minutes. If the haemodynamic response was inadequate (HR increase Results All patients successfully completed the CMR scan. Of a total of 98 patients, 18 (18% did not demonstrate evidence of a significant increase in HR or decrease in SBP under the standard adenosine infusion rate. Following the increase in the rate of infusion, 16 out of those 18 patients showed an adequate haemodynamic response. One patient of the standard infusion group and two patients of the high-dose group developed transient advanced AV block. Significantly more patients complained of chest pain in the high-dose group (61% vs. 29%, p = 0.009. On multivariate analysis, age > 65 years and ejection fraction Conclusions A substantial number of patients do not show adequate peripheral haemodynamic response to standard-dose adenosine stress during perfusion CMR imaging. Age and reduced ejection fraction are predictors of inadequate

  14. Adenosine Deaminase Inhibition Prevents Clostridium difficile Toxin A-Induced Enteritis in Mice ▿

    Science.gov (United States)

    de Araújo Junqueira, Ana Flávia Torquato; Dias, Adriana Abalen Martins; Vale, Mariana Lima; Spilborghs, Graziela Machado Gruner Turco; Bossa, Aline Siqueira; Lima, Bruno Bezerra; Carvalho, Alex Fiorini; Guerrant, Richard Littleton; Ribeiro, Ronaldo Albuquerque; Brito, Gerly Anne

    2011-01-01

    Toxin A (TxA) is able to induce most of the classical features of Clostridium difficile-associated disease in animal models. The objective of this study was to determine the effect of an inhibitor of adenosine deaminase, EHNA [erythro-9-(2-hydroxy-3-nonyl)-adenine], on TxA-induced enteritis in C57BL6 mice and on the gene expression of adenosine receptors. EHNA (90 μmol/kg) or phosphate-buffered saline (PBS) was injected intraperitoneally (i.p.) 30 min prior to TxA (50 μg) or PBS injection into the ileal loop. A2A adenosine receptor agonist (ATL313; 5 nM) was injected in the ileal loop immediately before TxA (50 μg) in mice pretreated with EHNA. The animals were euthanized 3 h later. The changes in the tissue were assessed by the evaluation of ileal loop weight/length and secretion volume/length ratios, histological analysis, myeloperoxidase assay (MPO), the local expression of inducible nitric oxide synthase (NOS2), pentraxin 3 (PTX3), NF-κB, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) by immunohistochemistry and/or quantitative reverse transcription-PCR (qRT-PCR). The gene expression profiles of A1, A2A, A2B, and A3 adenosine receptors also were evaluated by qRT-PCR. Adenosine deaminase inhibition, by EHNA, reduced tissue injury, neutrophil infiltration, and the levels of proinflammatory cytokines (TNF-α and IL-1β) as well as the expression of NOS2, NF-κB, and PTX3 in the ileum of mice injected with TxA. ATL313 had no additional effect on EHNA action. TxA increased the gene expression of A1 and A2A adenosine receptors. Our findings show that the inhibition of adenosine deaminase by EHNA can prevent Clostridium difficile TxA-induced damage and inflammation possibly through the A2A adenosine receptor, suggesting that the modulation of adenosine/adenosine deaminase represents an important tool in the management of C. difficile-induced disease. PMID:21115723

  15. [Adapting immunisation schedules for children undergoing chemotherapy].

    Science.gov (United States)

    Fernández-Prada, María; Rodríguez-Martínez, María; García-García, Rebeca; García-Corte, María Dolores; Martínez-Ortega, Carmen

    2016-10-20

    Children undergoing chemotherapy for cancer have special vaccination needs after completion of the treatment. The aim of this study was to evaluate the adaptation of post-chemotherapy vaccination schedules. An observational study was performed on a retrospective cohort that included all children aged from 0 to 14 years, who completed chemotherapy in a tertiary hospital between 2009 and 2015. Inclusion and exclusion criteria were applied. Immunisation was administered in accordance with the guidelines of the Vaccine Advisory Committee of the Spanish Association of Paediatrics. Primary Care immunisation and clinical records of the Preventive Medicine and Public Health Department were reviewed. Of the 99 children who had received chemotherapy, 51 (70.6% males) were included in the study. As regards the type of tumour, 54.9% had a solid organ tumour, and 45.1% had a haematological tumour. Post-chemotherapy immunisation was administered to 70.6%. The most common vaccines received were: diphtheria-tetanus-pertussis or diphtheria-tetanus (54.9%), meningococcus C (41.2%), and seasonal influenza (39.2%). The rate of adaptation of the immunisation schedule after chemotherapy was 9.8%. The pneumococcal conjugate vaccine against 7v or 13v was administered to 21.6% of study subjects. However, only 17.6% received polysaccharide 23v. None received vaccination against hepatitis A. No statistically significant differences were observed between adherence to immunisation schedules and type of tumour (P=.066), gender (P=.304), or age (P=.342). Post-chemotherapy immunisation of children with cancer is poor. The participation of health professionals in training programs and referral of paediatric cancer patients to Vaccine Units could improve the rate of schedule adaptation and proper immunisation of this population. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Chemotherapy, cognitive impairment and hippocampal toxicity.

    Science.gov (United States)

    Dietrich, J; Prust, M; Kaiser, J

    2015-11-19

    Cancer therapies can be associated with significant central nervous system (CNS) toxicity. While radiation-induced brain damage has been long recognized both in pediatric and adult cancer patients, CNS toxicity from chemotherapy has only recently been acknowledged. Clinical studies suggest that the most frequent neurotoxic adverse effects associated with chemotherapy include memory and learning deficits, alterations of attention, concentration, processing speed and executive function. Preclinical studies have started to shed light on how chemotherapy targets the CNS both on cellular and molecular levels to disrupt neural function and brain plasticity. Potential mechanisms include direct cellular toxicity, alterations in cellular metabolism, oxidative stress, and induction of pro-inflammatory processes with subsequent disruption of normal cellular and neurological function. Damage to neural progenitor cell populations within germinal zones of the adult CNS has been identified as one of the key mechanisms by which chemotherapy might exert long-lasting and progressive neurotoxic effects. Based on the important role of the hippocampus for maintenance of brain plasticity throughout life, several experimental studies have focused on the study of chemotherapy effects on hippocampal neurogenesis and associated learning and memory. An increasing body of literature from both animal studies and neuroimaging studies in cancer patients suggests a possible relationship between chemotherapy induced hippocampal damage and the spectrum of neurocognitive deficits and mood alterations observed in cancer patients. This review aims to briefly summarize current preclinical and neuroimaging studies that are providing a potential link between the neurotoxic effects of chemotherapy and hippocampal dysfunction, highlighting challenges and future directions in this field of investigation.

  17. Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Blank, Oliver; von Tresckow, Bastian; Monsef, Ina

    2017-01-01

    in a sensitivity analysis, the results showed that the combination of chemotherapy and radiotherapy improved OS compared to chemotherapy alone (HR 0.31; 95% CI 0.19 to 0.52; P evidence). In contrast to chemotherapy alone the use of chemotherapy and radiotherapy improved PFS (HR 0.42; 95.......94; 95% CI 0.31 to 27.55; P = 0.35;low- quality evidence), there is no evidence for a difference between the use of chemotherapy alone and chemotherapy plus radiotherapy. For complete response rate (CRR) (RR 1.08; 95% CI 0.93 to 1.25; P = 0.33; low- quality evidence), there is also no evidence...... improve OS compared to chemotherapy plus radiotherapy (HR 2.12; 95% CI 1.03 to 4.37; P = 0.04; low- quality evidence). This trial also had a potential other high risk of bias due to a high number of patients not receiving planned therapy. There is no evidence for a difference between chemotherapy alone...

  18. Adenosine elicits an eNOS-independent reduction in arterial blood pressure in conscious mice that involves adenosine A(2A) receptors

    DEFF Research Database (Denmark)

    Andersen, Henrik; Jaff, Mohammad G; Høgh, Ditte;

    2011-01-01

    Aims:  Adenosine plays an important role in the regulation of heart rate and vascular reactivity. However, the mechanisms underlying the acute effect of adenosine on arterial blood pressure in conscious mice are unclear. Therefore, the present study investigated the effect of the nucleoside on mean...... arterial blood pressure (MAP) and heart rate (HR) in conscious mice. Methods:  Chronic indwelling catheters were placed in C57Bl/6J (WT) and endothelial nitric oxide synthase knock-out (eNOS(-/-) ) mice for continuous measurements of MAP and HR. Using PCR and myograph analysis involment of adenosine...... receptors was investigated in human and mouse renal blood vessels Results:  Bolus infusion of 0.5 mg/kg adenosine elicited significant transient decreases in MAP (99.3±2.3 to 70.4±4.5 mmHg) and HR (603.2±18.3 to 364.3±49.2 min(-1) ) which were inhibited by the A(2A) receptor antagonist ZM 241385. Activation...

  19. Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

    DEFF Research Database (Denmark)

    Langberg, H; Bjørn, C; Boushel, Robert Christopher

    2002-01-01

    increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P muscular activity increases the interstitial concentrations...... of bradykinin and adenosine in both skeletal muscle and the connective tissue around its adjacent tendon. These findings support a role for bradykinin and adenosine in exercise-induced hyperaemia in skeletal muscle and suggest that bradykinin and adenosine are potential regulators of blood flow in peritendinous...

  20. Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents: an in vitro study.

    Directory of Open Access Journals (Sweden)

    Robert Edward Sims

    Full Text Available Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K(+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state.

  1. In vivo adenosine A(2B) receptor desensitization in guinea-pig airway smooth muscle: implications for asthma.

    Science.gov (United States)

    Breschi, Maria Cristina; Blandizzi, Corrado; Fogli, Stefano; Martinelli, Cinzia; Adinolfi, Barbara; Calderone, Vincenzo; Camici, Marcella; Martinotti, Enrica; Nieri, Paola

    2007-12-01

    This study was aimed at characterizing the role of adenosine receptor subtypes in the contractility modulation of guinea-pig airway smooth muscle in normal and pathological settings. In vitro and in vivo experiments were performed by testing selective agonists and antagonists on isolated tracheal smooth muscle preparations and pulmonary inflation pressure, respectively, under normal conditions or following ovalbumin-induced allergic sensitization. In normal and sensitized animals, the adenosine A(2A)/A(2B) receptor agonist, NECA, evoked relaxing responses of isolated tracheal preparations precontracted with histamine, and such an effect was reversed by the adenosine A(2B) antagonist, MRS 1706, in the presence or in the absence of epithelium. The expression of mRNA coding for adenosine A(2B) receptors was demonstrated in tracheal specimens. In vitro desensitization with 100 microM NECA markedly reduced the relaxing effect of the agonist. In vivo NECA or adenosine administration to normal animals inhibited histamine-mediated bronchoconstriction, while these inhibitory effects no longer occurred in sensitized guinea-pigs. Adenosine plasma levels were significantly higher in sensitized than normal animals. In conclusion, our data demonstrate that: (i) adenosine A(2B) receptors are responsible for the relaxing effects of adenosine on guinea-pig airways; (ii) these receptors can undergo rapid adaptive changes that may affect airway smooth muscle responsiveness to adenosine; (iii) ovalbumin-induced sensitization promotes a reversible inactivation of adenosine A(2B) receptors which can be ascribed to homologous desensitization. These findings can be relevant to better understand adenosine functions in airways as well as mechanisms of action of asthma therapies targeting the adenosine system.

  2. Adenosine enhances sweet taste through A2B receptors in the taste bud.

    Science.gov (United States)

    Dando, Robin; Dvoryanchikov, Gennady; Pereira, Elizabeth; Chaudhari, Nirupa; Roper, Stephen D

    2012-01-01

    Mammalian taste buds use ATP as a neurotransmitter. Taste Receptor (type II) cells secrete ATP via gap junction hemichannels into the narrow extracellular spaces within a taste bud. This ATP excites primary sensory afferent fibers and also stimulates neighboring taste bud cells. Here we show that extracellular ATP is enzymatically degraded to adenosine within mouse vallate taste buds and that this nucleoside acts as an autocrine neuromodulator to selectively enhance sweet taste. In Receptor cells in a lingual slice preparation, Ca(2+) mobilization evoked by focally applied artificial sweeteners was significantly enhanced by adenosine (50 μM). Adenosine had no effect on bitter or umami taste responses, and the nucleoside did not affect Presynaptic (type III) taste cells. We also used biosensor cells to measure transmitter release from isolated taste buds. Adenosine (5 μM) enhanced ATP release evoked by sweet but not bitter taste stimuli. Using single-cell reverse transcriptase (RT)-PCR on isolated vallate taste cells, we show that many Receptor cells express the adenosine receptor, Adora2b, while Presynaptic (type III) and Glial-like (type I) cells seldom do. Furthermore, Adora2b receptors are significantly associated with expression of the sweet taste receptor subunit, Tas1r2. Adenosine is generated during taste stimulation mainly by the action of the ecto-5'-nucleotidase, NT5E, and to a lesser extent, prostatic acid phosphatase. Both these ecto-nucleotidases are expressed by Presynaptic cells, as shown by single-cell RT-PCR, enzyme histochemistry, and immunofluorescence. Our findings suggest that ATP released during taste reception is degraded to adenosine to exert positive modulation particularly on sweet taste.

  3. Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Gérard Jean-Louis

    2010-07-01

    Full Text Available Abstract Background Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. Methods We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz. After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyltheophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean ± standard deviation between the groups by a variance analysis and post hoc test. Results Desflurane 6% (84 ± 6% of baseline enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 ± 8% of baseline, P N-mercaptopropionylglycine (54 ± 3% of baseline, 8-(p-Sulfophenyltheophylline (62 ± 9% of baseline, HOE140 (58 ± 6% of baseline abolished desflurane-induced postconditioning. Adenosine (80 ± 9% of baseline and bradykinin (83 ± 4% of baseline induced postconditioning (P vs control, N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 ± 8 and 58 ± 5% of baseline, respectively. Conclusions In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin

  4. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  5. Ameliorative effect of adenosine on hypoxia-reoxygenation injury in LLC-PK1, a porcine kidney cell line.

    Science.gov (United States)

    Yonehana, T; Gemba, M

    1999-06-01

    We studied the effects of adenosine on injury caused by hypoxia and reoxygenation in LLC-PK1 cells. Lactate dehydrogenase and gamma-glutamyltranspeptidase were released from cells exposed to hypoxia for 6 hr and then reoxygenation for 1 hr. The addition of adenosine at 100 microM to the medium before hypoxia began significantly decreased enzyme leakage into medium during both hypoxia and reoxygenation. The adenosine A1-receptor agonist, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), at the concentration of 100 microM, did not affect enzyme release, but the adenosine A2-receptor agonist 2-p-[2-car-boxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-adenosi ne hydrochloride (CGS 21680) at the concentration of 100 nM, suppressed the injury caused by hypoxia and reoxygenation. There were decreases in cAMP contents and ATP levels in LLC-PK1 cells injured by hypoxia and reoxygenation. Adenosine (100 microM) restored ATP levels in the cells during reoxygenation. With adenosine, the intracellular cAMP level was increased prominently during reoxygenation. These results suggest that adenosine protects LLC-PK1 cells from injury caused by hypoxia and reoxygenation by increasing the intracellular cAMP level via adenosine A2 receptor.

  6. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    MILA TREMENTOSA GARCIA

    Full Text Available SUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  7. Preoperative Arterial Interventional Chemotherapy on Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Hui; LING HU-Hua; TANG Liang-dan; ZHANG Xing-hua

    2008-01-01

    Objective:To discuss the therapeutic effect of preoperative interventional chemotherapy on cervical cancer.Methods:Preoperative interventional chemotherapy by femoral intubation was performed in 25 patients with bulky cervical cancer.The patients received bleomycin 45 mg and cisplatin or oxaliplatin 80 mg/m2.Results:25 cases(including 8 cases with stage Ⅰ and 17 cases with stage Ⅱ)received one or two courses of preoperative interventional chemotherapy.The size of the focal lesions was decreased greatly and radical hysterectomy and lymphadenectomy were performed successfully in all the patients.All of the specimens were sent for pathological examination.Lymphocyte infiltration was found more obvious in the cancer tissues as compared with their counterpart before treatment.As a result,relevant vaginal bleeding was stopped completely shortly after the treatment.Conclusion:Arterial interventional chemotherapy was proved to reduce the local size of cervical cancer and thus control the hemorrhage efficiently.The patients with cervical cancer can receive radical hysterectomy therapy after the interventional chemotherapy.

  8. [Chemotherapy of chiasmal gliomas in children].

    Science.gov (United States)

    Helcl, F

    1995-04-01

    Chiasmal gliomas are rare tumors occurring predominantly in childhood. Their optimal treatment is still controversial. In the past only neurosurgeons (performing partial or subtotal removal of the tumor, biopsy or shunting procedure in hydrocephalus) and radiotherapeutists participated in their treatment. In the middle of the eighties there was only a single article dealing with chemotherapy of these tumors (Rosenstock, 1985). Since that time there was an increased number of articles about harmful effects of radiotherapy on the developing child's brain. Neurosurgeons are aware that they will not solve this problem alone. During the past 7 years we have observed gradual retreat from radiotherapy and an inclination to combined chemotherapy of the chiasmal gliomas in children. The author has been engaged in the research of this clinical entity for more than 10 years and he offers to readers a summary of the contemporary knowledge about chemotherapy of chiasmal gliomas in children. Despite the fact that there is lacking experience with long-term survivors after chemotherapy, which is extremely important especially in this disease, the preliminary short-term results of combined chemotherapy of chiasmal gliomas in children are promising. Rapid development of chemistry and pharmacology in the last few years is promising for the discovery of further, more effective anti-tumor drugs. Their new combinations could improve present non-satisfactory results of treatment of chiasmal gliomas in children. (Ref. 25.)

  9. Treatment of triple-negative breast cancer using anti-EGFR-directed radioimmunotherapy combined with radiosensitizing chemotherapy and PARP inhibitor.

    Science.gov (United States)

    Al-Ejeh, Fares; Shi, Wei; Miranda, Mariska; Simpson, Peter T; Vargas, Ana Cristina; Song, Sarah; Wiegmans, Adrian P; Swarbrick, Alex; Welm, Alana L; Brown, Michael P; Chenevix-Trench, Georgia; Lakhani, Sunil R; Khanna, Kum Kum

    2013-06-01

    Triple-negative breast cancer (TNBC) is associated with poor survival. Chemotherapy is the only standard treatment for TNBC. The prevalence of BRCA1 inactivation in TNBC has rationalized clinical trials of poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors. Similarly, the overexpression of epidermal growth factor receptor (EGFR) rationalized anti-EGFR therapies in this disease. However, clinical trials using these 2 strategies have not reached their promise. In this study, we used EGFR as a target for radioimmunotherapy and hypothesized that EGFR-directed radioimmunotherapy can deliver a continuous lethal radiation dose to residual tumors that are radiosensitized by PARP inhibitors and chemotherapy. We analyzed EGFR messenger RNA in published gene expression array studies and investigated EGFR protein expression by immunohistochemistry in a cohort of breast cancer patients to confirm EGFR as a target in TNBC. Preclinically, using orthotopic and metastatic xenograft models of EGFR-positive TNBC, we investigated the effect of the novel combination of (177)Lu-labeled anti-EGFR monoclonal antibody, chemotherapy, and PARP inhibitors on cell death and the survival of breast cancer stem cells. In this first preclinical study of anti-EGFR radioimmunotherapy in breast cancer, we found that anti-EGFR radioimmunotherapy is safe and that TNBC orthotopic tumors and established metastases were eradicated in mice treated with anti-EGFR radioimmunotherapy combined with chemotherapy and PARP inhibitors. We showed that the superior response to this triple-agent combination therapy was associated with apoptosis and eradication of putative breast cancer stem cells. Our data support further preclinical investigations toward the development of combination therapies using systemic anti-EGFR radioimmunotherapy for the treatment of recurrent and metastatic TNBC.

  10. CSF ADENOSINE DEAMINASE (ADA ACTIVITY IN PATIENTS WITH MENINGITIS

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    Justin

    2016-05-01

    Full Text Available Meningitis is inflammation of the meninges (pia, arachnoid and dura mater covering the brain and the spinal cord. ADA is an enzyme in the purine salvage pathway which is found in abundance in active T-lymphocytes. Hence, an attempt was made to estimate the CSF ADA level in patients with suspected meningitis and throw light on its use in differentiating the various types of meningitis. AIMS AND OBJECTIVES To estimate the level of CSF adenosine deaminase level in different types of meningitis. To assess its usefulness in differentiating the various types (bacterial, viral and tuberculous of meningitis. MATERIALS AND METHODS The study was conducted at the medical wards of Govt. Rajaji Hospital, Madurai, a prospective analytical study from a period of April 2012 to September 2012. OBSERVATION AND RESULTS Tuberculous meningitis occurred more in the age group of 21–40 years. Bacterial meningitis was seen mainly in patients < 20 years of age. Viral meningitis was seen in all age groups. CSF ADA level was highest in tuberculous meningitis, the mean value being 24.5 U/L. The mean value of ADA in bacterial meningitis was 4.54 U/L and viral meningitis patients had lowest mean ADA value of 2.65 U/L. CONCLUSION In our study, 50 patients with meningitis admitted in Government Rajaji Hospital from April 2012 to September 2012 were evaluated. Meningitis predominantly affected people in the age group of 20-40 years in our study with a male: female ratio of 1.9:1. Cases of tuberculous meningitis constituted 48% of the study group and bacterial and viral meningitis were 26% each. CSF protein values were higher and sugar values lower in patients with tuberculous and bacterial meningitis. CSF cell counts were higher in patients with bacterial meningitis.

  11. Equilibrium and kinetic selectivity profiling on the human adenosine receptors.

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    Guo, Dong; Dijksteel, Gabrielle S; van Duijl, Tirsa; Heezen, Maxime; Heitman, Laura H; IJzerman, Adriaan P

    2016-04-01

    Classical evaluation of target selectivity is usually undertaken by measuring the binding affinity of lead compounds against a number of potential targets under equilibrium conditions, without considering the kinetics of the ligand-receptor interaction. In the present study we propose a combined strategy including both equilibrium- and kinetics-based selectivity profiling. The adenosine receptor (AR) was chosen as a prototypical drug target. Six in-house AR antagonists were evaluated in a radioligand displacement assay for their affinity and in a competition association assay for their binding kinetics on three AR subtypes. One of the compounds with a promising kinetic selectivity profile was also examined in a [(35)S]-GTPγS binding assay for functional activity. We found that XAC and LUF5964 were kinetically more selective for the A1R and A3R, respectively, although they are non-selective in terms of their affinity. In comparison, LUF5967 displayed a strong equilibrium-based selectivity for the A1R over the A2AR, yet its kinetic selectivity thereon was less pronounced. In a GTPγS assay, LUF5964 exhibited insurmountable antagonism on the A3R while having a surmountable effect on the A1R, consistent with its kinetic selectivity profile. This study provides evidence that equilibrium and kinetic selectivity profiling can both be important in the early phases of the drug discovery process. Our proposed combinational strategy could be considered for future medicinal chemistry efforts and aid the design and discovery of different or even better leads for clinical applications.

  12. Behavior and stability of adenosine triphosphate (ATP) during chlorine disinfection.

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    Nescerecka, Alina; Juhna, Talis; Hammes, Frederik

    2016-09-15

    Adenosine triphosphate (ATP) analysis is a cultivation-independent alternative method for the determination of bacterial viability in both chlorinated and non-chlorinated water. Here we investigated the behavior and stability of ATP during chlorination in detail. Different sodium hypochlorite doses (0-22.4 mg-Cl2 L(-1); 5 min exposure) were applied to an Escherichia coli pure culture suspended in filtered river water. We observed decreasing intracellular ATP with increasing chlorine concentrations, but extracellular ATP concentrations only increased when the chlorine dose exceeded 0.35 mg L(-1). The release of ATP from chlorine-damaged bacteria coincided with severe membrane damage detected with flow cytometry (FCM). The stability of extracellular ATP was subsequently studied in different water matrixes, and we found that extracellular ATP was stable in sterile deionized water and also in chlorinated water until extremely high chlorine doses (≤11.2 mg-Cl2 L(-1); 5 min exposure). In contrast, ATP decreased relatively slowly (k = 0.145 h(-1)) in 0.1 μm filtered river water, presumably due to degradation by either extracellular enzymes or the fraction of bacteria that were able to pass through the filter. Extracellular ATP decreased considerably faster (k = 0.368 h(-1)) during batch growth of a river water bacterial community. A series of growth potential tests showed that extracellular ATP molecules were utilized as a phosphorus source during bacteria proliferation. From the combined data we conclude that ATP released from bacteria at high chlorine doses could promote bacteria regrowth, contributing to biological instability in drinking water distribution systems.

  13. Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland.

    Science.gov (United States)

    Souza-Teodoro, Luis Henrique; Dargenio-Garcia, Letícia; Petrilli-Lapa, Camila Lopes; Souza, Ewerton da Silva; Fernandes, Pedro A C M; Markus, Regina P; Ferreira, Zulma S

    2016-03-01

    Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by β-adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y1 receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects.

  14. Novel treatment strategies in triple-negative breast cancer: specific role of poly(adenosine diphosphate-ribose polymerase inhibition

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    Audeh MW

    2014-10-01

    Full Text Available M William Audeh Division of Medical Oncology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Inhibitors of the poly(adenosine triphosphate-ribose polymerase (PARP-1 enzyme induce synthetic lethality in cancers with ineffective DNA (DNA repair or homologous repair deficiency, and have shown promising clinical activity in cancers deficient in DNA repair due to germ-line mutation in BRCA1 and BRCA2. The majority of breast cancers arising in carriers of BRCA1 germ-line mutations, as well as half of those in BRCA2 carriers, are classified as triple-negative breast cancer (TNBC. TNBC is a biologically heterogeneous group of breast cancers characterized by the lack of immunohistochemical expression of the ER, PR, or HER2 proteins, and for which the current standard of care in systemic therapy is cytotoxic chemotherapy. Many “sporadic” cases of TNBC appear to have indicators of DNA repair dysfunction similar to those in BRCA-mutation carriers, suggesting the possible utility of PARP inhibitors in a subset of TNBC. Significant genetic heterogeneity has been observed within the TNBC cohort, creating challenges for interpretation of prior clinical trial data, and for the design of future clinical trials. Several PARP inhibitors are currently in clinical development in BRCA-mutated breast cancer. The use of PARP inhibitors in TNBC without BRCA mutation will require biomarkers that identify cancers with homologous repair deficiency in order to select patients likely to respond. Beyond mutations in the BRCA genes, dysfunction in other genes that interact with the homologous repair pathway may offer opportunities to induce synthetic lethality when combined with PARP inhibition. Keywords: PARP, triple negative breast cancer, PARP inhibitors

  15. Chemotherapy in Ewing′s sarcoma

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    Jain Sandeep

    2010-01-01

    Full Text Available Ewing′s sarcoma constitutes three per cent of all pediatric malignancies. Ewing′s sarcoma has generally been more responsive to chemotherapy than adult-type sarcomas, and chemotherapy is now recommended for all patients with this disease. It is essential to integrate local control measures in the form of surgery and/or radiotherapy at the appropriate time, along with chemotherapy to eradicate the disease. This approach has improved the survival substantially to the tune of 70% in localized disease, although outcome for metastatic disease remains dismal. Newer therapeutic approaches are required to improve outcome for metastatic and recurrent or refractory Ewing′s sarcoma in organized co-operative group trials.

  16. Role of chemotherapy in Hodgkin's lymphoma.

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    Seam, Pamela; Janik, John E; Longo, Dan L; Devita, Vincent T

    2009-01-01

    The development of curative chemotherapy regimens for the treatment of Hodgkin's lymphoma (HL) is one of the true success stories in oncology. Most patients diagnosed with HL today can be cured. The major task remaining before us is curing as many patients as possible with their initial therapeutic approach while minimizing the acute toxicities and limiting the lifetime risks of important secondary events such as cardiovascular complications and secondary malignancies. In the 40 years since DeVita et al. developed the mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy regimen, we have learned a great deal about risk stratification to minimize treatment-related toxicity. Positron emission tomography may further assist us in reducing radiation treatment without compromising cures. This review will discuss the development of the chemotherapy regimens used in the management of early and advanced stage HL and the advantages and disadvantages of their use in combination with radiation therapy.

  17. Reducing psychological distress in patients undergoing chemotherapy.

    Science.gov (United States)

    Milanti, Ariesta; Metsälä, Eija; Hannula, Leena

    Psychological distress is a common problem among patients with cancer, yet it mostly goes unreported and untreated. This study examined the association of a psycho-educational intervention with the psychological distress levels of breast cancer and cervical cancer patients undergoing chemotherapy. The design of the study was quasi-experimental, pretest-posttest design with a comparison group. One hundred patients at a cancer hospital in Jakarta, Indonesia, completed Distress Thermometer screening before and after chemotherapy. Fifty patients in the intervention group were given a psycho-educational video with positive reappraisal, education and relaxation contents, while receiving chemotherapy. Patients who received the psycho-educational intervention had significantly lower distress levels compared with those in the control group. Routine distress screening, followed by distress management and outcome assessment, is needed to improve the wellbeing of cancer patients.

  18. Role of nitric oxide and adenosine in the onset of vasodilation during dynamic forearm exercise.

    Science.gov (United States)

    Casey, Darren P; Mohamed, Essa A; Joyner, Michael J

    2013-02-01

    We tested the hypothesis that nitric oxide (NO) and adenosine contribute to the onset of vasodilation during dynamic forearm exercise. Twenty-two subjects performed rhythmic forearm exercise (20 % of maximum) during control and NO synthase (NOS) inhibition (N (G)-monomethyl-L-arginine; L-NMMA) trials. A subset of subjects performed a third trial of forearm exercise during combined inhibition of NOS and adenosine (aminophylline; n = 9). Additionally, a separate group of subjects (n = 7) performed rhythmic forearm exercise during control, inhibition of adenosine alone and combined inhibition of adenosine and NOS. Forearm vascular conductance (FVC; ml min(-1) · 100 mmHg(-1)) was calculated from blood flow and mean arterial pressure (mmHg). The onset of vasodilation was assessed by calculating the slope of the FVC response for every duty cycle between baseline and steady state, and the number of duty cycles (1-s contraction/2-s relaxation) to reach steady state. NOS inhibition blunted vasodilation at the onset of exercise (11.1 ± 0.8 vs. 8.5 ± 0.6 FVC units/duty cycle; P Vasodilation was blunted further with combined inhibition of NOS and adenosine (7.5 ± 0.6 vs. 6.2 ± 0.8 FVC units/duty cycle; P vasodilation during dynamic forearm exercise.

  19. Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury

    Science.gov (United States)

    Gaudin, Alice; Yemisci, Müge; Eroglu, Hakan; Lepetre-Mouelhi, Sinda; Turkoglu, Omer Faruk; Dönmez-Demir, Buket; Caban, Seçil; Sargon, Mustafa Fevzi; Garcia-Argote, Sébastien; Pieters, Grégory; Loreau, Olivier; Rousseau, Bernard; Tagit, Oya; Hildebrandt, Niko; Le Dantec, Yannick; Mougin, Julie; Valetti, Sabrina; Chacun, Hélène; Nicolas, Valérie; Desmaële, Didier; Andrieux, Karine; Capan, Yilmaz; Dalkara, Turgay; Couvreur, Patrick

    2014-12-01

    There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.

  20. Pulmonary Vascular Capacitance as a Predictor of Vasoreactivity in Idiopathic Pulmonary Arterial Hypertension Tested by Adenosine

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    Shafie

    2015-09-01

    Full Text Available Background Acute pulmonary vasoreactivity testing has been recommended in the diagnostic work-up of patients with idiopathic pulmonary arterial hypertension (IPAH. Pulmonary arteriolar capacitance (Cp approximated by stroke volume divided by pulmonary pulse pressure (SV/PP is considered as an independent predictor of mortality in patients with IPAH. Objectives We sought to evaluate any differences in baseline and adenosine Cp between vasoreactive and non-vasoreactive IPAH patients tested with adenosine. Patients and Methods Fourteen patients with IPAH and a vasoreactive adenosine vasoreactivity testing according to the ESC guidelines were compared with 24 IPAH patients with nonreactive adenosine test results. Results There were no statistical significant differences between the two groups regarding NYHA class, body surface area, heart rate, and systemic blood pressure during right heart catheterization. Hemodynamic study showed no statistical significant differences in cardiac output/Index, mean pulmonary artery pressure, pulmonary vascular resistance, and baseline Cp between the two groups. There was a statistical significant but weak increase in adenosine Cp in vasoreactive group compared to non-reactive group (P = 0.04. Multivariable analysis showed an association between Cp and vasoreactivity (Beta = 2, P = 0.04, OR = 0.05 (95%CI = 0.003 - 0.9. Conclusions Cp could be considered as an index for the prediction of vasoreactivity in patients with IPAH. Prediction of long-term response to calcium channel blockers in patients with IPAH and a positive vasoreactive test by this index should be addressed in further studies.

  1. Aberrant bone density in aging mice lacking the adenosine transporter ENT1.

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    David J Hinton

    Full Text Available Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1 is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP, an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density.

  2. Circadian variations of adenosine level in blood and liver and its possible physiological significance.

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    Chagoya de Sánchez, V; Hernández-Muñoz, R; Díaz-Muñoz, M; Villalobos, R; Glender, W; Vidrio, S; Suárez, J; Yañez, L

    1983-09-12

    The role of adenosine as a possible physiological modulator was explored by measuring its concentration in different tissues during a 24-hour period. Initially the circadian variations of adenosine and other purine compounds such as inosine, hypoxanthine, uric acid and adenine nucleotides were studied in the rat blood. A daily cyclic response was observed, with low levels of adenosine from 08.00 - 20.00 h, followed by an increase from this time on. Inosine and hypoxanthine levels were elevated during the day and low at night. The uric acid changes observed indicate that the decrease in purine catabolism coincides with a decrease in inosine and hypoxanthine levels and an increase in adenosine. The blood adenine nucleotides, energy charge and phosphorylation potential remained constant during the day and showed oscillatory changes during the night. Similar studies were made in the liver, a primary source of circulating purines. Liver adenosine was high during the night while inosine and hypoxanthine remained low along the 24 hours. The results suggest that liver purine metabolism might participate in the maintenance and renewal of the blood purine pool and in the energy state of erythrocytes in vivo.

  3. Adenosine A2A receptor hyperexpression in patients with severe SIRS after cardiopulmonary bypass.

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    Kerbaul, François; Bénard, Frédéric; Giorgi, Roch; Youlet, By; Carrega, Louis; Zouher, Ibrahim; Mercier, Laurence; Gérolami, Victoria; Bénas, Vincent; Blayac, Dorothée; Gariboldi, Vlad; Collart, Frédéric; Guieu, Régis

    2008-08-01

    Adenosine (ADO) is an endogenous nucleoside, which has been involved in blood pressure failure during severe systemic inflammatory response syndrome (severe SIRS) after cardiac surgery with cardiopulmonary bypass (CPB). Adenosine acts via its receptor subtypes, namely A1, A2A, A2B, or A3. Because A2A receptors are implicated in vascular tone, their expression might contribute to severe SIRS. We compared adenosine plasma levels (APLs) and A2A ADO receptor expression (ie, B, K, and mRNA amount) in patients with or without postoperative SIRS. : This was a prospective comparative observational study. Forty-four patients who underwent cardiac surgery involving CPB. Ten healthy subjects served as controls. Among the patients, 11 presented operative vasoplegia and postoperative SIRS (named complicated patients) and 33 were without vasoplegia or SIRS (named uncomplicated patients). Adenosine plasma levels, K, B, and mRNA amount (mean +/- SD) were measured on peripheral blood mononuclear cells. Adenosine plasma levels, B, and K were significantly higher in complicated patients than in uncomplicated patients (APLs: 2.7 +/- 1.0 vs 1.0 +/- 0.5 micromol l, P SIRS after CPB.

  4. Oculomotor Deficits after Chemotherapy in Childhood.

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    Einar-Jón Einarsson

    Full Text Available Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years. Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy was markedly poorer (p<0.001 and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence (p = 0.004, whereas smooth pursuit and saccade onset times were shorter (p = 0.004 in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%, unsteadiness, light-headedness and that things around them were spinning or moving (87%. Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of

  5. Systemic chemotherapy for metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yannan Zhao; Biyun Wang

    2015-01-01

    Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer (MBC). Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metastasis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combination agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel-bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and cetuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall survival with maintenance chemotherapy according to a Korean phase Ⅲ clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy (X-based X) appears favorable based on a series of domestic studies.

  6. Weight changes during chemotherapy for breast cancer

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    Luciano José Megale Costa

    Full Text Available CONTEXT: Patients receiving adjuvant chemotherapy for breast cancer have a tendency to gain weight. This tendency has determining factors not completely defined and an unknown prognostic impact. OBJECTIVE: To evaluate weight change during chemotherapy for breast cancer in a defined population and to identify its predisposing factors and possible prognostic significance. DESIGN: Observational, retrospective cohort study. SETTING: Private clinical oncology service. PARTICIPANTS: 106 consecutive patients with breast cancer treated between June 1994 and April 2000, who received neoadjuvant (n = 8, adjuvant (n = 74 or palliative (n = 24 chemotherapy. INTERVETION: Review of medical records and gathering of clinical information, including patients’ body weights before treatment and at follow-up reviews. MAIN MEASUREMENTS: Body weight change, expressed as percentage of body weight per month in treatment; role of clinical data in weight change; and influence of weight change in overall survival and disease-free survival. RESULTS: There was a mean increase of 0.50 ± 1.42% (p = 0.21 of body weight per month of treatment. We noted a negative correlation between metastatic disease and weight gain (r = -0.447, p < 0.0001. In the adjuvant and neoadjuvant therapy groups there was a mean weight gain of 0.91 ± 1.19 % (p < 0.00001 per month, whereas in the metastatic (palliative group, we observed a mean loss of 0.52 ± 1.21% (p = 0.11 of body weight per month during the treatment. We did not observe any statistically significant correlation between weight changes and disease-free survival or overall survival. CONCLUSIONS: Women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy gain weight, whereas metastatic cancer patients will probably lose weight during palliative chemotherapy. Further studies are needed in order to evaluate the prognostic significance of weight changes during chemotherapy.

  7. Vesicant chemotherapy extravasation antidotes and treatments.

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    Schulmeister, Lisa

    2009-08-01

    Oncology nurses and pharmacists often are given the responsibility of developing or updating institutional policies to manage vesicant chemotherapy extravasations. Antidote and treatment recommendations of vesicant chemotherapy manufacturers, antidotes and treatments approved by the U.S. Food and Drug Administration (FDA), and guidelines and recommendations made by professional oncology organizations are useful resources in this process. This article describes manufacturers' recommendations, lists antidotes and treatments approved by the FDA, and reviews published guidelines and recommendations. Available antidote and treatment formulations and their preparation and administration also are discussed.

  8. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    Science.gov (United States)

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  9. Intrathecal chemotherapy. Selection of cytostatic agents.

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    Hayakawa, T; Yamada, R; Kanai, N; Kuroda, R; Ushio, Y; Higashi, H; Mogami, H

    1970-09-01

    Selection of cytostatic agents for intrathecal administration is the subject of this paper.Both the toxic side effects-destruction of blood-brain barrier and change of body weight-and the cytostatic effects on intracranially transplanted Yoshida ascites sarcoma were investigated of intrathecal administration of various cytostatic agents. As a result, it may be concluded that Methotrexate and Endoxan and lower dose of mitomycin C are suitable drugs for intrathecal chemotherapy.Based on these findings, clinical cases of malignant brain tumours were treated with intrathecal chemotherapy.Grateful acknowledgement is made to Professor Dennosuke Jinnai for his constant interest and guidance in this investigation.

  10. Retinoblastoma: Achieving new standards with methods of chemotherapy

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    Swathi Kaliki

    2015-01-01

    Full Text Available The management of retinoblastoma (RB has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms "RB," and "treatment," "chemotherapy," "systemic chemotherapy," "IVC," "IAC," "periocular chemotherapy," or "intravitreal chemotherapy." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  11. Change of SPARC expression after chemotherapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yong-Yin Gao; Xin-Yuan Zhang; Yi Ba; Ding-Zhi Huang; Ru-Bing Han; Xia Wang; Shao-Hua Ge; Hong-Li Li; Ting Deng; Rui Liu; Ming Bai; Li-Kun Zhou

    2015-01-01

    Objective:The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine (SPARC) expression changes atfer chemotherapy in gastric cancer (GC) is unclear. hTis study investigated the inlfuence of chemotherapy on SPARC expression in GC. Methods:Immunohistochemistry was used to analyze SPARC expression in 132 GC cases (including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy). SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the inlfuence of chemotherapy on SPARC expression. Results:SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPARC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy, gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression atfer chemotherapy were independent prognostic factors. Conclusion:SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC atfer chemotherapy.

  12. Intracellular adenosine formation and release by freshly-isolated vascular endothelial cells from rat skeletal muscle: effects of hypoxia and/or acidosis.

    Science.gov (United States)

    Le, G Y; Essackjee, H C; Ballard, H J

    2014-07-18

    Previous studies suggested indirectly that vascular endothelial cells (VECs) might be able to release intracellularly-formed adenosine. We isolated VECs from the rat soleus muscle using collagenase digestion and magnetic-activated cell sorting (MACS). The VEC preparation had >90% purity based on cell morphology, fluorescence immunostaining, and RT-PCR of endothelial markers. The kinetic properties of endothelial cytosolic 5'-nucleotidase suggested it was the AMP-preferring N-I isoform: its catalytic activity was 4 times higher than ecto-5'nucleotidase. Adenosine kinase had 50 times greater catalytic activity than adenosine deaminase, suggesting that adenosine removal in VECs is mainly through incorporation into adenine nucleotides. The maximal activities of cytosolic 5'-nucleotidase and adenosine kinase were similar. Adenosine and ATP accumulated in the medium surrounding VECs in primary culture. Hypoxia doubled the adenosine, but ATP was unchanged; AOPCP did not alter medium adenosine, suggesting that hypoxic VECs had released intracellularly-formed adenosine. Acidosis increased medium ATP, but extracellular conversion of ATP to AMP was inhibited, and adenosine remained unchanged. Acidosis in the buffer-perfused rat gracilis muscle elevated AMP and adenosine in the venous effluent, but AOPCP abolished the increase in adenosine, suggesting that adenosine is formed extracellularly by non-endothelial tissues during acidosis in vivo. Hypoxia plus acidosis increased medium ATP by a similar amount to acidosis alone and adenosine 6-fold; AOPCP returned the medium adenosine to the level seen with hypoxia alone. These data suggest that VECs release intracellularly formed adenosine in hypoxia, ATP during acidosis, and both under simulated ischaemic conditions, with further extracellular conversion of ATP to adenosine. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Predictors and Diagnostic Significance of the Adenosine Related Side Effects on Myocardial Perfusion SPECT/CT Imaging

    Directory of Open Access Journals (Sweden)

    Nilüfer Yıldırım Poyraz

    2014-10-01

    Full Text Available Objective: The aim of this study was to investigate the relationship between patient characteristics and adenosine-related side-effects during stress myocard perfusion imaging (MPI. The effect of presence of adenosine-related side-effects on the diagnostic value of MPI with integrated SPECT/CT system for coronary artery disease (CAD, was also assessed in this study. Methods: Total of 281 patients (109 M, 172 F; mean age:62.6±10 who underwent standard adenosine stress protocol for MPI, were included in this study. All symptoms during adenosine infusion were scored according to the severity and duration. For the estimation of diagnostic value of adenosine MPI with integrated SPECT/CT system, coronary angiography (CAG or clinical follow-up were used as gold standard. Results: Total of 173 patients (61.6% experienced adenosine-related side-effects (group 1; flushing, dyspnea, and chest pain were the most common. Other 108 patients completed pharmacologic stress (PS test without any side-effects (group 2. Test tolerability were similar in the patients with cardiovascular or airway disease to others, however dyspnea were observed significantly more common in patients with mild airway disease. Body mass index (BMI ≥30 kg/m2 and age ≤45 years were independent predictors of side-effects. The diagnostic value of MPI was similar in both groups. Sensitivity of adenosine MPI SPECT/CT was calculated to be 86%, specificity was 94% and diagnostic accuracy was 92% for diagnosis of CAD. Conclusion: Adenosine MPI is a feasible and well tolerated method in patients who are not suitable for exercise stress test as well as patients with cardiopulmonary disease. However age ≤45 years and BMI ≥30 kg/m2 are the positive predictors of adenosine-related side-effects, the diagnostic value of adenosine MPI SPECT/CT is not affected by the presence of adenosine related side-effects.

  14. Autoradiographic localization of adenosine receptors in rat brain using (/sup 3/H)cyclohexyladenosine

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, R.R.; Synder, S.H.

    1982-09-01

    Adenosine (A1) receptor binding sites have been localized in rat brain by an in vitro light microscopic autoradiographic method. The binding of (/sup 3/H)N6-cyclohexyladenosine to slide-mounted rat brain tissue sections has the characteristics of A1 receptors. It is saturable with high affinity and has appropriate pharmacology and stereospecificity. The highest densities of adenosine receptors occur in the molecular layer of the cerebellum, the molecular and polymorphic layers of the hippocampus and dentate gyrus, the medial geniculate body, certain thalamic nuclei, and the lateral septum. High densities also are observed in certain layers of the cerebral cortex, the piriform cortex, the caudate-putamen, the nucleus accumbens, and the granule cell layer of the cerebellum. Most white matter areas, as well as certain gray matter areas, such as the hypothalamus, have negligible receptor concentrations. These localizations suggest possible central nervous system sites of action of adenosine.

  15. Downregulation of adenosine and P2X receptor-mediated cardiovascular responses in heart failure rats

    DEFF Research Database (Denmark)

    Zhao, Xin; Sun, X Y; Erlinge, D;

    2000-01-01

    Neurohormonal changes in congestive heart failure (CHF) include an enhanced peripheral sympathetic nerve activity which results in increased release of noradrenaline, neuropeptide Y and ATP. To examine if such changes in CHF would modulate peripheral pre- and postsynaptic receptors of ATP and its...... effects mediated by the endothelial P2Y receptors are unaffected in CHF. Moreover, the adenosine-mediated inhibitory effects on heart rate and blood pressure were also attenuated in the CHF rats. The most important changes in adenosine and P2-receptor function induced by ischaemic CHF were the reduced...... pressor effect mediated by the P2X receptor and the increased heart rate due to an attenuated inhibitory effect of adenosine....

  16. Role of adenosine in the antiepileptic effects of deep brain stimulation

    Science.gov (United States)

    Miranda, Maisa F.; Hamani, Clement; de Almeida, Antônio-Carlos G.; Amorim, Beatriz O.; Macedo, Carlos E.; Fernandes, Maria José S.; Nobrega, José N.; Aarão, Mayra C.; Madureira, Ana Paula; Rodrigues, Antônio M.; Andersen, Monica L.; Tufik, Sergio; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine. PMID:25324724

  17. Adenosine A3 receptor activation is neuroprotective against retinal neurodegeneration.

    Science.gov (United States)

    Galvao, Joana; Elvas, Filipe; Martins, Tiago; Cordeiro, M Francesca; Ambrósio, António Francisco; Santiago, Ana Raquel

    2015-11-01

    Death of retinal neural cells, namely retinal ganglion cells (RGCs), is a characteristic of several retinal neurodegenerative diseases. Although the role of adenosine A3 receptor (A3R) in neuroprotection is controversial, A3R activation has been reported to afford protection against several brain insults, with few studies in the retina. In vitro models (retinal neural and organotypic cultures) and animal models [ischemia-reperfusion (I-R) and partial optic nerve transection (pONT)] were used to study the neuroprotective properties of A3R activation against retinal neurodegeneration. The A3R selective agonist (2-Cl-IB-MECA, 1 μM) prevented apoptosis (TUNEL(+)-cells) induced by kainate and cyclothiazide (KA + CTZ) in retinal neural cultures (86.5 ± 7.4 and 37.2 ± 6.1 TUNEL(+)-cells/field, in KA + CTZ and KA + CTZ + 2-Cl-IB-MECA, respectively). In retinal organotypic cultures, 2-Cl-IB-MECA attenuated NMDA-induced cell death, assessed by TUNEL (17.3 ± 2.3 and 8.3 ± 1.2 TUNEL(+)-cells/mm(2) in NMDA and NMDA+2-Cl-IB-MECA, respectively) and PI incorporation (ratio DIV4/DIV2 3.3 ± 0.3 and 1.3 ± 0.1 in NMDA and NMDA+2-Cl-IB-MECA, respectively) assays. Intravitreal 2-Cl-IB-MECA administration afforded protection against I-R injury decreasing the number of TUNEL(+) cells by 72%, and increased RGC survival by 57%. Also, intravitreal administration of 2-Cl-IB-MECA inhibited apoptosis (from 449.4 ± 37.8 to 207.6 ± 48.9 annexin-V(+)-cells) and RGC loss (from 1.2 ± 0.6 to 8.1 ± 1.7 cells/mm) induced by pONT. This study demonstrates that 2-Cl-IB-MECA is neuroprotective to the retina, both in vitro and in vivo. Activation of A3R may have great potential in the management of retinal neurodegenerative diseases characterized by RGC death, as glaucoma and diabetic retinopathy, and ischemic diseases.

  18. Metallic taste in cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Ijpma, I.; Renken, R. J.; ter Horst, G. J.; Reyners, A. K. L.

    Background: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic

  19. Managing Chemotherapy Side Effects: Sexual and Fertility Changes in Women

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Sexual and Fertility Changes in Women “Talk with your doctor before you start treatment. Ask how chemotherapy could affect your ability to have children. ” Ask what ...

  20. Management of chemotherapy-induced nausea and vomiting.

    LENUS (Irish Health Repository)

    Zubairi, Ishtiaq H

    2006-08-01

    Chemotherapy-induced nausea and vomiting are symptoms that cause major concern to oncology patients. This article explores the types of nausea and vomiting in the context of chemotherapy, and discusses their pathogenesis and management.

  1. Chemotherapy Side Effects: A Cause of Heart Disease?

    Science.gov (United States)

    ... Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including weakening of the heart muscle (cardiomyopathy) and ...

  2. Metallic taste in cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Ijpma, I.; Renken, R. J.; ter Horst, G. J.; Reyners, A. K. L.

    2015-01-01

    Background: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic

  3. Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651.

    Science.gov (United States)

    Goorin, Allen M; Schwartzentruber, Douglas J; Devidas, Meenakshi; Gebhardt, Mark C; Ayala, Alberto G; Harris, Michael B; Helman, Lee J; Grier, Holcombe E; Link, Michael P

    2003-04-15

    Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously. Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS +/- SE is 65% +/- 6% (69% +/- 8% for immediate surgery and 61% +/- 8% for presurgical chemotherapy; P =.8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy). Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy.

  4. Magnetically assisted fluorescence ratiometric assays for adenosine deaminase using water-soluble conjusated polymers

    Institute of Scientific and Technical Information of China (English)

    HE Fang; YU MingHui; WANG Shu

    2009-01-01

    A magnetically assisted fluorescence ratiometric technique has been developed for adenosine deami-nase assays with high sensitivity using water-soluble cationic conjugated polymers (CCPs).The assay contains three elements:a biotin-labeled aptamer of adenosine (biotin-aptamer),a signaling probe single-stranded DNA-tagged fiuorescein at terminus (ssDNA-FI) and a CCP.The specific binding of adenosine to biotin-aptamer makes biotin-aptamer and ssDNA-FI unhybridized,and the ssDNA-FI is washed out after streptavidin-coated magnetic beads are added and separated from the assay solution under magnetic field.In this case,after the addition of CCP to the magnetic beads solution,the fluo-rescence resonance energy transfer (FRET) from CCP to fluorescein is inefficient.Upon adding adenosine deaminase,the adenosine is converted into inosine,and the biotin-aptamer is hybridized with ssDNA-FI to form doubled stranded DNA (biotin-dsDNA-FI).The ssONA-FI is attached to the mag-netic beads at the separation step,and the addition of CCP to the magnetic beads solution leads to efficient FRET from CCP to fluorescein.Thus the adenosine deaminase activity can be monitored by fluorescence spectra in view of the intensity decrease of CCP emission or the increase of fluorescein emission in aqueous solutions.The assay integrates surface-functionalized magnetic particles with significant amplification of detection signal of water-soluble cationic conjugated polymers.

  5. Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors

    Science.gov (United States)

    Roseti, Cristina; Martinello, Katiuscia; Fucile, Sergio; Piccari, Vanessa; Mascia, Addolorata; Di Gennaro, Giancarlo; Quarato, Pier Paolo; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Arcella, Antonella; Simonato, Michele; Fredholm, Bertil B.; Limatola, Cristina; Miledi, Ricardo; Eusebi, Fabrizio

    2008-01-01

    We examined how the endogenous anticonvulsant adenosine might influence γ-aminobutyric acid type A (GABAA) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 μM), GABAA receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABAA-current (IGABA) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced IGABA run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated IGABA run-down in ≈40% and ≈20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 μM) potentiated IGABA run-down but only in ≈20% of tested oocytes. CGS15943 administration again decreased IGABA run-down in patch-clamped neurons from either human or rat neocortex slices. IGABA run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABAA-receptor stability is tonically influenced by A2A but not by A1 receptors. IGABA run-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2–A3 receptors alter the stability of GABAA receptors, which could offer therapeutic opportunities. PMID:18809912

  6. 2'-O methylation of internal adenosine by flavivirus NS5 methyltransferase.

    Directory of Open Access Journals (Sweden)

    Hongping Dong

    Full Text Available RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 2'-O methyltransferase activities that are required for the formation of 5' type I cap (m(7GpppAm of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and Dengue virus (serotype 4; DENV-4 specifically methylates polyA, but not polyG, polyC, or polyU, indicating that the methylation occurs at adenosine residue. RNAs with internal adenosines substituted with 2'-O-methyladenosines are not active substrates for internal methylation, whereas RNAs with adenosines substituted with N⁶-methyladenosines can be efficiently methylated, suggesting that the internal methylation occurs at the 2'-OH position of adenosine. Mass spectroscopic analysis further demonstrated that the internal methylation product is 2'-O-methyladenosine. Importantly, genomic RNA purified from DENV virion contains 2'-O-methyladenosine. The 2'-O methylation of internal adenosine does not require specific RNA sequence since recombinant methyltransferase of DENV-4 can efficiently methylate RNAs spanning different regions of viral genome, host ribosomal RNAs, and polyA. Structure-based mutagenesis results indicate that K61-D146-K181-E217 tetrad of DENV-4 methyltransferase forms the active site of internal methylation activity; in addition, distinct residues within the methyl donor (S-adenosyl-L-methionine pocket, GTP pocket, and RNA-binding site are critical for the internal methylation activity. Functional analysis using flavivirus replicon and genome-length RNAs showed that internal methylation attenuated viral RNA translation and replication. Polymerase assay revealed that internal 2'-O-methyladenosine reduces the efficiency of RNA elongation. Collectively, our results demonstrate that flavivirus NS5 performs 2'-O methylation of internal adenosine of

  7. Adenosine transport systems on dissociated brain cells from mouse, guinea-pig, and rat

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, M.E.; Geiger, J.D. (Univ. of Manitoba, Winnipeg (Canada))

    1990-09-01

    The kinetics and sodium dependence of adenosine transport were determined using an inhibitor-stop method on dissociated cell body preparations obtained from mouse, guinea-pig and rat brain. Transport affinity (KT) values for the high affinity adenosine transport systems KT(H) were significantly different between these three species; mean +/- SEM values were 0.34 +/- 0.1 in mouse, 0.9 +/- 0.2 in rat, and 1.5 +/- 0.5 microM in guinea-pig. The KT values for the low affinity transport system KT(L) were not different between the three species. Brain cells from rat displayed a significantly greater maximal capacity to accumulate (3H)adenosine (Vmax) than did mouse or guinea-pig for the high affinity system, or than did mouse for the low affinity system. When sodium chloride was replaced in the transport medium with choline chloride, the KT(H) values for guinea-pig and rat were both increased by approximately 100%; only in rat did the change reach statistical significance. The sodium-dependence of adenosine transport in mouse brain was clearly absent. The differences between KT(H) values in mouse and those in guinea-pig or rat were accentuated in the absence of sodium. The differences in kinetic values, ionic requirements, and pharmacological characteristics between adenosine transporters in CNS tissues of mouse, guinea-pig and rat may help account for some of the variability noted among species in terms of their physiological responses to adenosine.

  8. Genetic factors influencing pyrimidine-antagonist chemotherapy

    NARCIS (Netherlands)

    Maring, JG; Groen, HJM; Wachters, FM; Uges, DRA; de Vries, EGE

    2005-01-01

    Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of

  9. Diarree en koorts bij chemotherapie door listeriose

    NARCIS (Netherlands)

    Quak, E.; Laarhoven, H.W.M. van; Bos, H.; Bouwhuis, J.W.; Herpen, C.M.L. van; Graaf, W.T.A. van der

    2010-01-01

    We present two patients with colorectal carcinoma who were admitted with fever and diarrhoea during treatment with chemotherapy. Blood cultures taken from both patients revealed an infection with Listeria monocytogenes. A contaminated ice cream was probably the source of infection in one patient. Th

  10. Chemotherapy for metastatic seminoma in elderly patients

    NARCIS (Netherlands)

    Rentinck, MEM; Nieboer, P; Sleijfer, DT; Gietema, JA; Van der Graaf, WTA

    2003-01-01

    Testicular germ cell tumours are rarely diagnosed in the elderly. In view of the high cure rate of these tumours, even in elderly patients treatment with chemotherapy and/or radiotherapy should be considered. In this report we describe two older patients with metastatic testicular seminoma. Both

  11. Aspects of enteral nutrition in cancer chemotherapy

    NARCIS (Netherlands)

    Smit, Jitske Martha

    1985-01-01

    This thesis deals with several aspects of the influences of intensive cancer chemotherapy on the nutritional status, the metabolism, and the gastrointestinal tract of the host and describes whether these results can be influenced by enteral hyperalimentation, We studied these aspects in patients

  12. Aspects of enteral nutrition in cancer chemotherapy

    NARCIS (Netherlands)

    Smit, Jitske Martha

    1985-01-01

    This thesis deals with several aspects of the influences of intensive cancer chemotherapy on the nutritional status, the metabolism, and the gastrointestinal tract of the host and describes whether these results can be influenced by enteral hyperalimentation, We studied these aspects in patients wit

  13. Sarcopenia and chemotherapy-mediated toxicity

    Science.gov (United States)

    Vega, Maria Cecília Monteiro Dela; Laviano, Alessandro; Pimentel, Gustavo Duarte

    2016-01-01

    ABSTRACT This narrative review focuses on the role of sarcopenia and chemotherapy-induced toxicity in cancer patients. Consistent evidence shows that sarcopenia in cancer patients leads to decreased overall survival by influencing treatment discontinuation and dose reduction. Therefore, sarcopenia should be considered a robust prognostic factor of negative outcome as well as a determinant of increased healthcare costs. PMID:28076611

  14. Chemotherapy of ovarian cancer in elderly patients

    Institute of Scientific and Technical Information of China (English)

    Tiffany A. Troso-Sandoval; Stuart M. Lichtman

    2015-01-01

    Epithelial ovarian cancer is primarily a disease of older women. Advanced age is risk factor for decreased survival. Optimal surgery and the safe and effective administration of chemotherapy are essential for prolonged progression-free and overall survival (OS). In this article, the available regimens in both the primary treatment and relapsed setting are reviewed.

  15. Sarcopenia and chemotherapy-mediated toxicity

    OpenAIRE

    Vega,Maria Cecília Monteiro Dela; Laviano, Alessandro; Pimentel, Gustavo Duarte

    2016-01-01

    ABSTRACT This narrative review focuses on the role of sarcopenia and chemotherapy-induced toxicity in cancer patients. Consistent evidence shows that sarcopenia in cancer patients leads to decreased overall survival by influencing treatment discontinuation and dose reduction. Therefore, sarcopenia should be considered a robust prognostic factor of negative outcome as well as a determinant of increased healthcare costs.

  16. Neoadjuvant chemotherapy in locally advanced colon cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

    2015-01-01

    BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...

  17. Efflux Pump‑Mediated Resistance in Chemotherapy

    African Journals Online (AJOL)

    Annals of Medical and Health Sciences Research | July 2012 | Vol 2 | Issue 2 | ... of antimicrobial drug resistance, which contributes to treatment failure, high medical ... websites, as well as standard textbooks on chemotherapy, provided the needed information ..... Most reports on bacterial efflux pump inhibitors are based on.

  18. Managing Chemotherapy Side Effects: Nausea and Vomiting

    Science.gov (United States)

    ... boiled, without the skin ••White rice ••White toast ••Bananas ••Canned fruit such as applesauce, peaches, and pears •• ... has a series of 18 Chemotherapy Side Effects Sheets at: www.cancer.gov/chemo-side-effects

  19. STUDIES ON CHEMOTHERAPY AND SERODIAGNOSIS FOR CLONORCHIS SINENSIS INFECTION.

    Science.gov (United States)

    CHEMOTHERAPEUTIC AGENTS, *SERODIAGNOSIS, PARASITIC DISEASES , CHEMOTHERAPY, PARASITIC DISEASES , DOSAGE, TOXICITY, BODY WEIGHT, PATHOLOGY, MORTALITY RATE, HEMATOLOGY, SODIUM COMPOUNDS, BIOASSAY, JAPAN.

  20. Plasma concentrations of the cyclic nucleotides, adenosine 3',5'-monophosphate and guanosine 3'.5'-monophosphate, in healthy adults treated with theophylline

    DEFF Research Database (Denmark)

    Fenger, M; Eriksen, P B; Andersen, O;

    1982-01-01

    Plasma concentrations of cyclic adenosine monophosphate and cyclic guanosine monophosphate were measured in 10 health adults before, during and after periods of theophylline administration. Cyclic adenosine monophosphate concentrations did not change significantly, but cyclic guanosine monophosph...

  1. Adenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation.

    LENUS (Irish Health Repository)

    Wakai, A

    2012-02-03

    The effects of adenosine on neutrophil (polymorphonuclear neutrophils; PMN)-directed changes in vascular permeability are poorly characterized. This study investigated whether adenosine modulates activated PMN vascular endothelial growth factor (vascular permeability factor; VEGF) release and transendothelial migration. PMN activated with tumour necrosis factor-alpha (TNF-alpha, 10 ng\\/mL) were incubated with adenosine and its receptor-specific analogues. Culture supernatants were assayed for VEGF. PMN transendothelial migration across human umbilical vein endothelial cell (HUVEC) monolayers was assessed in vitro. Adhesion molecule receptor expression was assessed flow cytometrically. Adenosine and some of its receptor-specific analogues dose-dependently inhibited activated PMN VEGF release. The rank order of potency was consistent with the affinity profile of human A2B receptors. The inhibitory effect of adenosine was reversed by 3,7-dimethyl-1-propargylxanthine, an A2 receptor antagonist. Adenosine (100 microM) or the A2B receptor agonist 5\\'-N-ethylcarboxamidoadenosine (NECA, 100 microM) significantly reduced PMN transendothelial migration. However, expression of activated PMN beta2 integrins and HUVEC ICAM-1 were not significantly altered by adenosine or NECA. Adenosine attenuates human PMN VEGF release and transendothelial migration via the A2B receptor. This provides a novel target for the modulation of PMN-directed vascular hyperpermeability in conditions such as the capillary leak syndrome.

  2. Performance of adenosine "stress-only" perfusion MRI in patients without a history of myocardial infarction : a clinical outcome study

    NARCIS (Netherlands)

    Lubbers, Daniel D.; Rijlaarsdam-Hermsen, Dorine; Kuijpers, Dirkjan; Kerkhof, Marjan; Sijens, Paul E.; van Dijkman, Paul R. M.; Oudkerk, Matthijs

    To assess the diagnostic value of adenosine "stress-only" myocardial perfusion MR for ischemia detection as an indicator for coronary angiography in patients without a prior myocardial infarction and a necessity to exclude ischemia. Adenosine perfusion MRI was performed at 1.5 T in 139 patients with

  3. Real time adenosine fluctuations detected with fast-scan cyclic voltammetry in the rat striatum and motor cortex.

    Science.gov (United States)

    Adamah-Biassi, Ekue B; Almonte, Antoine G; Blagovechtchenski, Evgeny; Grinevich, Valentina P; Weiner, Jeff L; Bonin, Keith D; Budygin, Evgeny A

    2015-12-30

    Adenosine serves many functions within the CNS, including inhibitory and excitatory control of neurotransmission. The understanding of adenosine dynamics in the brain is of fundamental importance. The goal of the present study was to explore subsecond adenosine fluctuations in the rat brain in vivo. Long Evans rats were anesthetized and a carbon fiber electrode was positioned in the motor cortex or dorsal striatum. Real time electrochemical recordings were made at the carbon fiber electrodes every 100ms by applying a triangular waveform (-0.4 to +1.5V, 400V/s). Adenosine spikes were identified by the background-subtracted cyclic voltammogram. The frequency of detected adenosine spikes was relatively stable in both tested regions, and the time intervals between spikes were regular and lasted from 1 to 5s within an animal. Spike frequency ranged from 0.5 to 1.5Hz in both the motor cortex and the dorsal striatum. Average spike amplitudes were 85±11 and 66±7nM for the motor cortex and the dorsal striatum, respectively. The current study established that adenosine signaling can operate on a fast time scale (within seconds) to modulate brain functions. This finding suggests that spontaneous adenosine release may play a fast, dynamic role in regulating an organism's response to external events. Therefore, adenosine transmission in the brain may have characteristics similar to those of classical neurotransmitters, such as dopamine and norepinephrine. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Caffeine intake inverts the effect of adenosine on myocardial perfusion during stress as measured by T1 mapping

    NARCIS (Netherlands)

    Kuijpers, Dirkjan; Prakken, Niek H.; Vliegenthart, Rozemarijn; van Dijkman, Paul R. M.; van der Harst, Pim; Oudkerk, Matthijs

    2016-01-01

    Caffeine intake before adenosine stress myocardial perfusion imaging may cause false negative findings. We hypothesized that the antagonistic effect of caffeine can be measured by T1 relaxation times in rest and adenosine stress cardiac magnetic resonance imaging (CMR), as T1 mapping techniques are

  5. Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Zhe ZHANG; Hui-cai GUO; Li-nan ZHANG; Yong-li WANG

    2009-01-01

    Aim: The present study investigated the effect of adenosine on Na+-K+ pumps in acutely isolated guinea pig (C, avia sp.) ven-tricular myocytes.Methods: The whole-cell, patch-damp technique was used to record the Na+-K+ pump current (Ip) in acutely isolated guinea pig ventricular myocytes.Results: Adenosine inhibited the high DHO-affinity pump current (Ih) in a concentration-dependent manner, which was blocked by the selective adenosine A1 receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists stau-rosporine, GF 109203X or the specific δ isoform antagonist rottlerin. In addition, the inhibitory action of adenosine was mimicked by a selective A1 receptor agonist CCPA and a specific activator peptide of PKC-δ, PP114. In contrast, the selec-tive A2A receptor agonist CGS21680 and A3 receptor agonist Cl-IB-MECA did not affect lb. Application of the selective A2A receptor antagonist SCH58261 and A3 receptor antagonist MRS1191 also failed to block the effect of adenosine. Further-more, H89, a selective protein kinase A (PKA) antagonist, did not exert any effect on adenosine-induced Ih inhibition.Conclusion: The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of Ih via adenosine A1 receptors and the PKC-δ isoform.

  6. Separation of effects of adenosine on energy metabolism from those on cyclic AMP in rat thymic lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nordeen, S.K.; Young, D.A.

    1977-08-10

    In rat thymic lymphocytes incubated for 2 h without exogenous energy-providing substrate, adenosine may be substituted for glucose as a means of maximally restoring energy metabolism and those cellular functions whose rates are sensitive to small changes in the energy balance, such as protein synthesis and uridine utilization for RNA synthesis. Since effects of adenosine in thymocytes and other cells have frequently been attributed to changes in cyclic AMP, this report investigates its possible involvement in these glucose-like restorative actions of adenosine. Although the same range of doses of adenosine effective at raising cyclic AMP also elicit roughly parallel stimulations of protein synthesis and uridine utilization, further results dissociate the restorative actions from those on cyclic AMP. (a) Other purine nucleosides mimic the glucose-like actions of adenosine without increasing cyclic AMP; (b) conversely, prostaglandin E/sub 1/ mimics the cyclic AMP response without restoring energy metabolism or energy-dependent functions; and (c) potentiation of the cyclic AMP response, either by inhibiting phosphodiesterase or adenosine deaminase, does not enhance the restorative response to a range of doses of adenosine. Finally, cyclic AMP-mediated glycogenolysis cannot account for the glucose-like effects since addition of adenosine increases, not decreases, levels of glycogen.

  7. NTS adenosine A2a receptors inhibit the cardiopulmonary chemoreflex control of regional sympathetic outputs via a GABAergic mechanism.

    Science.gov (United States)

    Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J

    2015-07-01

    Adenosine is a powerful central neuromodulator acting via opposing A1 (inhibitor) and A2a (activator) receptors. However, in the nucleus of the solitary tract (NTS), both adenosine receptor subtypes attenuate cardiopulmonary chemoreflex (CCR) sympathoinhibition of renal, adrenal, and lumbar sympathetic nerve activity and attenuate reflex decreases in arterial pressure and heart rate. Adenosine A1 receptors inhibit glutamatergic transmission in the CCR pathway, whereas adenosine A2a receptors most likely facilitate release of an unknown inhibitory neurotransmitter, which, in turn, inhibits the CCR. We hypothesized that adenosine A2a receptors inhibit the CCR via facilitation of GABA release in the NTS. In urethane-chloralose-anesthetized rats (n = 51), we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of the 5-HT3 receptor agonist phenylbiguanide (1-8 μg/kg) before and after selective stimulation of NTS adenosine A2a receptors [microinjections into the NTS of CGS-21680 (20 pmol/50 nl)] preceded by blockade of GABAA or GABAB receptors in the NTS [bicuculline (10 pmol/100 nl) or SCH-50911 (1 nmol/100 nl)]. Blockade of GABAA receptors virtually abolished adenosine A2a receptor-mediated inhibition of the CCR. GABAB receptors had much weaker but significant effects. These effects were similar for the different sympathetic outputs. We conclude that stimulation of NTS adenosine A2a receptors inhibits CCR-evoked hemodynamic and regional sympathetic reflex responses via a GABA-ergic mechanism.

  8. Extracellular adenosine regulates colitis through effects on lymphoid and nonlymphoid cells

    OpenAIRE

    Kurtz, Courtney C.; Drygiannakis, Ioannis; Naganuma, Makoto; Feldman, Sanford; Bekiaris, Vasileios; Linden, Joel; Ware, Carl F.; Ernst, Peter B.

    2014-01-01

    Adenosine is a purine metabolite that can mediate anti-inflammatory responses in the digestive tract through the A2A adenosine receptor (A2AAR). We examined the role of this receptor in the control of inflammation in the adoptive transfer model of colitis. Infection of A2AAR−/− mice with Helicobacter hepaticus increased colonic inflammation scores compared with uninfected A2AAR controls. Comparison of T cell subsets in wild-type and A2AAR−/− mice revealed differences in markers associated wit...

  9. Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

    Directory of Open Access Journals (Sweden)

    ROBERTO PAES-DE-CARVALHO

    2002-09-01

    Full Text Available The nucleoside adenosine plays an important role as a neurotransmitter or neuromodulator in the central nervous system, including the retina. In the present paper we review compelling evidence showing that adenosine is a signaling molecule in the developing retina. In the chick retina, adenosine transporters are present since early stages of development before the appearance of adenosine A1 receptors modulating dopamine-dependent adenylate cyclase activity or A2 receptors that directly activate the enzyme. Experiments using retinal cell cultures revealed that adenosine is taken up by specific cell populations that when stimulated by depolarization or neurotransmitters such as dopamine or glutamate, release the nucleoside through calcium-dependent transporter-mediated mechanisms. The presence of adenosine in the extracellular medium and the long-term activation of adenosine receptors is able to regulate the survival of retinal neurons and blocks glutamate excitoxicity. Thus, adenosine besides working as a neurotransmitter or neuromodulator in the mature retina, is considered as an important signaling molecule during retinal development having important functions such as regulation of neuronal survival and differentiation.O nucleosídeo adenosina apresenta um importante papel como neurotransmissor ou neuromodulador no sistema nervoso central, inclusive na retina. Neste artigo apresentamos uma revisão das evidências que mostram que a adenosina é uma molécula sinalizadora na retina em desenvolvimento. Na retina de pinto, transportadores de adenosina estão presentes desde estágios precoces do desenvolvimento, antes do aparecimento dos receptores A1 que modulam a atividade adenilato ciclase dependente de dopamina ou dos receptores A2 que ativam diretamente a enzima. Experimentos usando culturas de células de retina revelaram que a adenosina é captada por populações celulares específicas que, quando estimuladas por despolarização ou por

  10. Investigation of the Interaction between Adenosine and Human Serum Albumin by Fluorescent Spectroscopy and Molecular Modeling

    Institute of Scientific and Technical Information of China (English)

    CUI Feng-Ling; WANG Jun-Li; LI Fang; FAN Jing; QU Gui-Rong; YAO Xiao-Jun; LEI Bei-Lei

    2008-01-01

    The binding interaction of adenosine with human serum albumin (HSA) was investigated under simulative physiological conditions by fluorescence spectroscopy in combination with a molecular modeling method. A strong fluorescence quenching reaction of adenosine to HSA was observed and the quenching mechanism was suggested as static quenching according to the Stern-Volmer equation. The binding constants (K) at different temperatures as well as thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS), were calculated according to relevant fluorescent data and Vant'Hoff equation. The hydrophobic interaction was a predominant intermolecular force in order to stabilize the complex, which was in agreement with the results of molecular modeling study.

  11. Dielectric spectra broadening as a signature for dipole-matrix interaction. III. Water in adenosine monophosphate/adenosine-5'-triphosphate solutions.

    Science.gov (United States)

    Puzenko, Alexander; Levy, Evgeniya; Shendrik, Andrey; Talary, Mark S; Caduff, Andreas; Feldman, Yuri

    2012-11-21

    In this, the third part of our series on the dielectric spectrum symmetrical broadening of water, we consider the nucleotide aqueous solutions. Where in Parts I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)] and II [E. Levy et al., J. Chem. Phys. 136, 114503 (2012)], the dipole-dipole or ion-dipole interaction had a dominant feature, now the interplay between these two types of dipole-matrix interactions will be considered. We present the results of high frequency dielectric measurements of different concentrations of adenosine monophosphate/adenosine-5'-triphosphate aqueous solutions. We observed the Cole-Cole broadening of the main relaxation peak of the solvent in the solutions. Moreover, depending on the nucleotide concentration, we observed both types of dipole-matrix interaction. The 3D trajectory approach (described in detail in Part I) is applied in order to highlight the differences between the two types of interaction.

  12. The effect of chemotherapy on rat brain PET: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Kim, Il Han; Yu, A Ram; Park, Ji Ae; Woo, Sang Keun; Kim, Jong Guk; Cheon, Gi Jeong; Kim, Byeong Il; Choi, Chang Woon; Lim, Sang Moo; Kim, Hee Joung; Kim, Kyeong Min [Korea Institute Radiological and Medical Science, Seoul (Korea, Republic of)

    2010-10-15

    Chemotherapy was widely used for the therapy of cancer patients. When chemotherapy was performed, transient cognitive memory problem was occurred. This cognitive problem in brain was called as chemobrain. In this study, we have developed rat model for chemobrain. Cerebral glucose metabolism after chemotherapy was assessed using animal PET and voxel based statistical analysis method

  13. A Primary Hepatic Lymphoma Treated with Liver Resection and Chemotherapy

    Directory of Open Access Journals (Sweden)

    Konstantinos Bouliaris

    2014-01-01

    Full Text Available Primary hepatic lymphoma (PHL is a rare malignancy, which is frequently misdiagnosed. Although chemotherapy is the treatment of choice there are reports that a combination of surgery and adjuvant chemotherapy can offer better results. Herein we present an interesting case of a large primary non-Hodgkin lymphoma originating from liver was treated with a liver which resection and chemotherapy.

  14. Side Effects of Chemotherapy and Radiation (For Parents)

    Science.gov (United States)

    ... 1- to 2-Year-Old Side Effects of Chemotherapy and Radiation KidsHealth > For Parents > Side Effects of Chemotherapy and Radiation Print A A A What's in ... and can no longer do their jobs efficiently. Chemotherapy (or "chemo") and radiation , the two most common ...

  15. Repetitive systemic morphine alters activity-dependent plasticity of Schaffer-collateral-CA1 pyramidal cell synapses: involvement of adenosine A1 receptors and adenosine deaminase.

    Science.gov (United States)

    Sadegh, Mehdi; Fathollahi, Yaghoub

    2014-10-01

    The effectiveness of O-pulse stimulation (TPS) for the reversal of O-pattern primed bursts (PB)-induced long-term potentiation (LTP) were examined at the Schaffer-collateral-CA1 pyramidal cell synapses of hippocampal slices derived from rats chronically treated with morphine (M-T). The results showed that slices derived from both control and M-T rats had normal field excitatory postsynaptic potential (fEPSP)-LTP, whereas PS-LTP in slices from M-T rats was significantly greater than that from control slices. When morphine was applied in vitro to slices derived from rats chronically treated with morphine, the augmentation of PS-LTP was not seen. TPS given 30 min after LTP induction failed to reverse the fEPSP- or PS-LTP in both groups of slices. However, TPS delivered in the presence of long-term in vitro morphine caused the PS-LTP reversal. This effect was blocked by the adenosine A1 receptor (A1R) antagonist CPX (200 nM) and furthermore was enhanced by the adenosine deaminase (ADA) inhibitor EHNA (10 μM). Interestingly, TPS given 30 min after LTP induction in the presence of EHNA (10 μM) can reverse LTP in morphine-exposed control slices in vitro. These results suggest adaptive changes in the hippocampus area CA1 in particular in adenosine system following repetitive systemic morphine. Chronic in vivo morphine increases A1R and reduces ADA activity in the hippocampus. Consequently, adenosine can accumulate because of a stimulus train-induced activity pattern in CA1 area and takes the opportunity to work as an inhibitory neuromodulator and also to enable CA1 to cope with chronic morphine. In addition, adaptive mechanisms are differentially working in the dendrite layer rather than the somatic layer of hippocampal CA1.

  16. Maintenance Chemotherapy of Stage Ⅲ Epithelial Ovarian Carcinoma-Focusing on Individualized Maintenance Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Zhao; Yi Zhang; Qiao Zhang

    2005-01-01

    OBJECTIVE To investigate the role of maintenance chemotherapy on stage Ⅲ ovarian carcinoma.METHODS A retrospective analysis was conducted of 47 stage Ⅲ ovarian carcinoma patients with clinical complete remission after first-line chemotherapy. Among these patients, 21 cases were treated with maintenance chemotherapy, while the other 26 cases were free of treatment until progression. The 2 groups were compared with respect to progression-free survival (PFS) and overall survival(OS).RESULTS The median PFS and OS were not significantly different between the 2 groups. For those patients, in a subgroup of suboptimal surgery (residual disease >2 cm), the median PFS was 110 weeks and 56 weeks and the median OS was 223 weeks and 157 weeks for the maintenance and non-treated respectively. Both PFS and OS values favoured the maintenance group, P=0.004 and P=0.015 respectively. In a subgroup of optimal surgery (residual disease ≤2 cm), the differences were not significant.CONCLUSION Patients with stage Ⅲ ovarian carcinoma with clinical complete remission may benefit from maintenance chemotherapy, if the residual disease is >2 cm. To those with a residual disease ≤2 cm, the maintenance chemotherapy maybe of no value. So "individualized maintenance chemotherapy" should be conducted in the clinical setting.

  17. G-quadruplex based Exo III-assisted signal amplification aptasensor for the colorimetric detection of adenosine.

    Science.gov (United States)

    Xu, Lei; Shen, Xin; Li, Bingzhi; Zhu, Chunhong; Zhou, Xuemin

    2017-08-08

    Adenosine is an endogenous nucleotide pivotally involved in nucleic acid and energy metabolism. Its excessive existence may indicate tumorigenesis, typically lung cancer. Encouraged by its significance as the clinical biomarker, sensitive assay methods towards adenosine have been popularized, with high cost and tedious procedures as the inevitable defects. Herein, we report a label-free aptamer-based exonuclease III (Exo III) amplification colorimetric aptasensor for the highly sensitive and cost-effective detection of adenosine. The strategy employed two unlabeled hairpin DNA oligonucleotides (HP1 and HP2), where HP1 contained the aptamer towards adenosine and HP2 embedded the guanine-rich sequence (GRS). In the presence of adenosine, hairpin HP1 could form specific binding with adenosine and trigger the unfolding of HP1's hairpin structure. The resulting adenosine-HP1 complex could hybridize with HP2, generating the Exo III recognition site. After Exo III-assisted degradation, the GRS was released from HP2, and the adenosine-HP1 was released back to the solution to combine another HP2, inducing the cycling amplification. After multiple circulations, the released ample GRSs were induced to form G-quadruplex, further catalyzing the oxidation of TMB, yielding a color change which was finally mirrored in the absorbance change. On the contrary, the absence of adenosine failed to unfold HP1, remaining color unchanged eventually. Thanks to the amplification strategy, the limit of detection was lowered to 17 nM with a broad linear range from 50 nM to 6 μM. The proposed method was successfully applied to the detection of adenosine in biological samples and satisfying recoveries were acquired. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The Safety of an Adenosine A(1)-Receptor Antagonist, Rolofylline, in Patients with Acute Heart Failure and Renal Impairment Findings from PROTECT

    NARCIS (Netherlands)

    Teerlink, John R.; Iragui, Vicente J.; Mohr, Jay P.; Carson, Peter E.; Hauptman, Paul J.; Lovett, David H.; Miller, Alan B.; Pina, Ileana L.; Thomson, Scott; Varosy, Paul D.; Zile, Michael R.; Cleland, John G. F.; Givertz, Michael M.; Metra, Marco; Ponikowski, Piotr; Voors, Adriaan A.; Davison, Beth A.; Cotter, Gad; Wolko, Denise; DeLucca, Paul; Salerno, Christina M.; Mansoor, George A.; Dittrich, Howard; O'Connor, Christopher M.; Massi, Barry M.

    2012-01-01

    Background: Adenosine exerts actions in multiple organ systems, and adenosine receptors are a therapeutic target in many development programmes. Objective: The aim of this analysis was to evaluate the safety of rolofylline, an adenosine A(1)-receptor antagonist, in patients with acute heart failure.

  19. Adenosine A(1) Receptors in the Central Nervous System : Their Functions in Health and Disease, and Possible Elucidation by PET Imaging

    NARCIS (Netherlands)

    Paul, S.; Elsinga, P. H.; Ishiwata, K.; Dierckx, R. A. J. O.; van Waarde, A.

    2011-01-01

    Adenosine is a neuromodulator with several functions in the central nervous system (CNS), such as inhibition of neuronal activity in many signaling pathways. Most of the sedating, anxiolytic, seizure-inhibiting and protective actions of adenosine are mediated by adenosine A(1) receptors (A(1)R) on t

  20. Effect of TRA-8 anti-death receptor 5 antibody in combination with chemotherapy in an ex vivo human ovarian cancer model.

    Science.gov (United States)

    Frederick, Peter J; Kendrick, James E; Straughn, J Michael; Della Manna, Debbie L; Oliver, Patsy G; Lin, Hui-Yi; Grizzle, William E; Stockard, Cecil R; Alvarez, Ronald D; Zhou, Tong; LoBuglio, Albert F; Buchsbaum, Donald J

    2009-07-01

    To investigate the cytotoxicity of TRA-8, an antibody that specifically binds death receptor 5, alone and in combination with chemotherapy, using an ex vivo human ovarian cancer model. Twenty-six ovarian cancer specimens were obtained during ovarian cancer debulking, and tumor slices were prepared with the Krumdieck tissue slicer. The tumor slices were exposed to varying concentrations of TRA-8, carboplatin/paclitaxel, or the combination of TRA-8 and chemotherapy. Using nonlinear modeling, dose-response curves and IC50 values were generated for specimens treated with TRA-8. The additive and synergistic cytotoxic effects of chemotherapy combination with TRA-8 were evaluated in specimens. In addition to adenosine triphosphate viability assays, the treated and untreated slices were assessed by immunohistochemistry to confirm apoptosis induction. Specimens from 13 patients yielded TRA-8-induced IC50 values. Of these specimens, 15% were found to be sensitive to TRA-8-induced cytotoxicity at IC50 doses less than 500 ng/mL. Specimens from 13 patients underwent combination treatment with TRA-8 and carboplatin/paclitaxel. Of these specimens, 77% exhibited additive cytotoxicity in comparison with those treated with either agent alone, whereas 15% exhibited synergistic cytotoxicity. Immunohistochemical analysis of terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling and cleaved caspase 3 staining demonstrated a dose-dependent increase in apoptosis with the combination treatment. This study demonstrates the efficacy of the death receptor monoclonal antibody TRA-8 in combination with conventional chemotherapy in an ex vivo human ovarian cancer model. This model can be used to assess cytotoxicity of novel agents in combination with chemotherapy in ovarian cancer.

  1. Adjuvant chemotherapy for advanced endometrial cancer.

    Science.gov (United States)

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  2. Role of chemotherapy in stage llb nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xin-Bin Pan; Xiao-Dong Zhu

    2012-01-01

    The efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy on stage lib nasopharyngeal carcinoma(NPC) remains unclear.Conventional two-dimensional radiotherapy combined with concurrent chemotherapy can improve the overall survival,progression-free survival,recurrence-free survival,and distant metastasis-free survival of patients with stage lib NPC.Intensity-modulated radiotherapy without concurrent chemotherapy also provides good outcomes for patients with stage lib NPC.This article summarizes the features of stage lib NPC and reviews the role of chemotherapy in this subgroup of NPC.

  3. CF101, An Agonist to the A3 Adenosine Receptor, Enhances the Chemotherapeutic Effect of 5-Fluorouracil in a Colon Carcinoma Murine Model

    Directory of Open Access Journals (Sweden)

    Sara Bar-Yehuda

    2005-01-01

    Full Text Available NF-κB and the upstream kinase PKB/Akt are highly expressed in chemoresistance tumor cells and may hamper the apoptotic pathway. CF101, a specific agonist to the A3 adenosine receptor, inhibits the development of colon carcinoma growth in cell cultures and xenograft murine models. Because CF101 has been shown to downregulate PKB/Akt and NF-κB protein expression level, we presumed that its combination with chemotherapy will enhance the antitumor effect of the cytotoxic drug. In this study, we utilized 3-[4,5Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT and colony formation assays and a colon carcinoma xenograft model. It has been shown that a combined treatment of CF101 and 5-fluorouracil (5-FU enhanced the cytotoxic effect of the latter on HCT-116 human colon carcinoma growth. Downregulation of PKB/Akt, NF-κB, and cyclin D1, and upregulation of caspase-3 protein expression level were observed in cells and tumor lesions on treatment with a combination of CF101 and 5-FU. Moreover, in mice treated with the combined therapy, myelotoxicity was prevented as was evidenced by normal white blood cell and neutrophil counts. These results show that CF101 potentiates the cytotoxic effect of 5-FU, thus preventing drug resistance. The myeloprotective effect of CF101 suggests its development as an add-on treatment to 5-FU.

  4. Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction.

    Science.gov (United States)

    Gaspar, H Bobby; Cooray, Samantha; Gilmour, Kimberly C; Parsley, Kathryn L; Zhang, Fang; Adams, Stuart; Bjorkegren, Emma; Bayford, Jinhua; Brown, Lucinda; Davies, E Graham; Veys, Paul; Fairbanks, Lynette; Bordon, Victoria; Petropoulou, Theoni; Petropolou, Theoni; Kinnon, Christine; Thrasher, Adrian J

    2011-08-24

    Genetic defects in the purine salvage enzyme adenosine deaminase (ADA) lead to severe combined immunodeficiency (SCID) with profound depletion of T, B, and natural killer cell lineages. Human leukocyte antigen-matched allogeneic hematopoietic stem cell transplantation (HSCT) offers a successful treatment option. However, individuals who lack a matched donor must receive mismatched transplants, which are associated with considerable morbidity and mortality. Enzyme replacement therapy (ERT) for ADA-SCID is available, but the associated suboptimal correction of immunological defects leaves patients susceptible to infection. Here, six children were treated with autologous CD34-positive hematopoietic bone marrow stem and progenitor cells transduced with a conventional gammaretroviral vector encoding the human ADA gene. All patients stopped ERT and received mild chemotherapy before infusion of gene-modified cells. All patients survived, with a median follow-up of 43 months (range, 24 to 84 months). Four of the six patients recovered immune function as a result of engraftment of gene-corrected cells. In two patients, treatment failed because of disease-specific and technical reasons: Both restarted ERT and remain well. Of the four reconstituted patients, three remained off enzyme replacement. Moreover, three of these four patients discontinued immunoglobulin replacement, and all showed effective metabolic detoxification. All patients remained free of infection, and two cleared problematic persistent cytomegalovirus infection. There were no adverse leukemic side effects. Thus, gene therapy for ADA-SCID is safe, with effective immunological and metabolic correction, and may offer a viable alternative to conventional unrelated donor HSCT.

  5. Determination of Adenosine Triphosphate on Marine Particulates:Synthesis of Methods for Use on OTEC Samples

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Anthony T.; Hartwig, Eric O.

    1982-08-01

    Adenosine triphosphate (ATP) is an indicator of living biomass in marine particulates. This report details the method used by Lawrence Berkeley Laboratory to analyze particulate ATP in samples taken from oligotrophic, tropical ocean waters. It represents a synthesis of previously published methods.

  6. Determination of adenosine triphosphate on marine particulates: synthesis of methods for use on OTEC samples

    Energy Technology Data Exchange (ETDEWEB)

    Jones, A.T.; Hartwig, E.O.

    1982-08-01

    Adenosine triphosphate (ATP) is an indicator of living biomass in marine particulates. This report details the method used by Lawrence Berkeley Laboratory to analyze particulate ATP in samples taken from oligotrophic, tropical ocean waters. It represents a synthesis of previously published methods.

  7. Unexpected Discovery of Dichloroacetate Derived Adenosine Triphosphate Competitors Targeting Pyruvate Dehydrogenase Kinase To Inhibit Cancer Proliferation.

    Science.gov (United States)

    Zhang, Shao-Lin; Hu, Xiaohui; Zhang, Wen; Tam, Kin Yip

    2016-04-14

    Pyruvate dehydrogenase kinases (PDKs) have recently emerged as an attractive target for cancer therapy. Herein, we prepared a series of compounds derived from dichloroacetate (DCA) which inhibited cancer cells proliferation. For the first time, we have successfully developed DCA derived inhibitors that preferentially bind to the adenosine triphosphate (ATP) pocket of PDK isoform 1 (PDK1).

  8. SIGNIFICANCE OF ADENOSINE DEAMINASE SERUM CONCENTRATIONS IN THE DIAGNOSIS OF EXTRA-PULMONARY TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    Stevanovic G,

    2011-06-01

    Full Text Available Extra pulmonary tuberculosis (EPTB is a growing problem worldwide. Due to the nature of the disease, the diversity of clinical pictures as well as its minor epidemiological importance, the diagnosis is difficult and often late.In addition to standard TB diagnostic techniques use of new biochemical (surrogate markers are increased. With this work we wanted to examine the usefulness of serum adenosine deaminase levels as a diagnostic parameter for EPTB.The work included 116 patients with fever of unknown origin in which tuberculosis or infectious mononucleosis was not proven and 51 person who had proven EPTB. Correlated adenosine deaminase levels between these two groups we obtained significantly higher values ​​in patients with EPTB. The calculated sensitivity was 0.56, specificity 0.89, positive predictive value 0.80 and negative predictive value 0.72. Certain reducing of the values observed during anti TB therapy. In previous studies the diagnostic importance of adenosine deaminase in the diagnosis of tuberculosis serosityes was demonstrated. The significance of serum levels in diagnosis is rarely evaluated during EPTB. Our findings are similar to the results of authors who have conducted such testing in the pediatric population.Increased concentrations of serum adenosine deaminase have shown the potential of usable screening test and can be used as an indicative EPTB parameter. To fully assess its diagnostic significance require future clinical research.

  9. Therapeutic efficacy of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) against organophosphate intoxication

    NARCIS (Netherlands)

    Bueters, T.J.H.; Groen, B.; Danhof, M.; IJzerman, A.P.; Helden, H.P.M. van

    2002-01-01

    The objective of the present study was to investigate whether reduction of central acetylcholine (ACh) accumulation by adenosine receptor agonists could serve as a generic treatment against organophosphate (OP) poisoning. The OPs studied were tabun (O-ethyl-N-dimethylphosphoramidocyanidate), sarin (

  10. Allosteric modulators affect the internalization of human adenosine A1 receptors.

    NARCIS (Netherlands)

    Klaasse, E.C.; Hout, G. van den; Roerink, S.F.; Grip, W.J. de; IJzerman, A.P.; Beukers, M.W.

    2005-01-01

    To study the effect of allosteric modulators on the internalization of human adenosine A(1) receptors, the receptor was equipped with a C-terminal yellow fluorescent protein tag. The introduction of this tag did not affect the radioligand binding properties of the receptor. CHO cells stably expressi

  11. REPRODUCTIVE CONDITION, GLOMERULAR ADENOSINE DIPHOSPHATASE ACTIVITY, AND PLATELET-AGGREGATION IN THE RAT - EFFECT OF ENDOTOXIN

    NARCIS (Netherlands)

    VISSCHER, CA; FAAS, MM; BAKKER, WW; SCHUILING, GA

    1993-01-01

    In experiment A, the activity of the glomerular antithrombotic enzyme adenosine diphosphatase (ADPase) and the sensitivity of this enzyme for endotoxin (1.0 mug/kg BW) in various reproductive conditions of female rats were studied through use of enzyme histochemical methods. In experiment B, the eff

  12. REDUCTION OF ADENOSINE-A1-RECEPTORS IN THE PERFORANT PATHWAY TERMINAL ZONE IN ALZHEIMER HIPPOCAMPUS

    NARCIS (Netherlands)

    JAARSMA, D; SEBENS, JB; KORF, J

    1991-01-01

    The cells of origin of the perforant pathway are destroyed in Alzheimer's disease (AD). In rat the adenosine A1-receptors are specifically localized on the perforant path terminals in the molecular layer of the dentate gyrus. In the present study the density of A1-receptors in the hippocampus of Alz

  13. Presynaptic inhibition by kainate receptors converges mechanistically with presynaptic inhibition by adenosine and GABAB receptors.

    Science.gov (United States)

    Partovi, Dara; Frerking, Matthew

    2006-11-01

    Kainate receptors are widely reported to regulate the release of neurotransmitter in the CNS, but the mechanisms involved remain controversial. Previous studies have found that the kainate receptor agonist ATPA, which selectively activates Glu(K5)-containing kainate receptors, depresses glutamate release at Schaffer-collateral synapses in the hippocampus. In the present study, we provide pharmacological evidence that this depressant effect is mediated by Glu(K5)-containing heteromers, but is distinct from a similar depressant effect engaged by the kainate receptor agonist domoate. The depressant effect of ATPA is insensitive to antagonists for GABA(A), GABA(B), and adenosine receptors, and is also unaffected by lowering the release probability by reducing extracellular calcium. However, the effect of ATPA is partly occluded by prior activation of GABA(B) receptors and completely occluded by prior activation of adenosine receptors, suggesting a mechanistic convergence of heteromeric Glu(K5) kainate receptor signaling with GABA(B) receptors and adenosine receptors. The effects of domoate are partially occluded by both adenosine and GABA(B) receptor agonists, indicating at least a partial convergence of Glu(K5)-lacking kainate receptor signaling with these other pathways. The depressant effect of ATPA is not blocked by inhibition of serine/threonine protein kinases. These results suggest that ATPA and domoate inhibit glutamate release through mechanisms that converge with those of classical metabotropic receptor agonists, although they do so through different receptors.

  14. Indicator cell lines for the detection of hidden mycoplasma contamination, using an adenosine phosphorylase screening test

    NARCIS (Netherlands)

    Spierenburg, G.T.; Polak-Vogelzang, A.A.; Bast, B.J.E. G.

    Mycoplasmas are a major cause of cell culture contamination and are especially troublesome during HAT selection. The enzyme adenosine phosphorylase (adoP) is present in all common mycoplasma species but is considered to have a low activity in mammalian cells. However, using an adoP screening test,

  15. REDUCTION OF ADENOSINE-A1-RECEPTORS IN THE PERFORANT PATHWAY TERMINAL ZONE IN ALZHEIMER HIPPOCAMPUS

    NARCIS (Netherlands)

    JAARSMA, D; SEBENS, JB; KORF, J

    1991-01-01

    The cells of origin of the perforant pathway are destroyed in Alzheimer's disease (AD). In rat the adenosine A1-receptors are specifically localized on the perforant path terminals in the molecular layer of the dentate gyrus. In the present study the density of A1-receptors in the hippocampus of Alz

  16. Abnormal adenosine and dopamine receptor expression in lymphocytes of Lesch-Nyhan patients.

    Science.gov (United States)

    García, M G; Puig, J G; Torres, R J

    2009-11-01

    Self-injurious behavior is the most outstanding feature of Lesch-Nyhan syndrome and has recently been ascribed to an obsessive-compulsive behavior. Lesch-Nyhan syndrome results from the complete enzyme deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) but the link between abnormal purine metabolism and its neurological and behavioral manifestations remains largely unknown. Previous studies led us to hypothesize that adenosine and dopamine receptor expression could be altered in HPRT-deficient cells. To test this hypothesis, we examined mRNA expressions of adenosine (ADORA2A and ADORA2B) and dopamine receptors (DRD1 and DRD2 like), and dopamine transporter (DAT1) in peripheral blood lymphocytes (PBLs) from Lesch-Nyhan patients. We also examined the influence of hypoxanthine in these expressions. As compared to normal PBLs, both ADORA2A and DRD5 expression were abnormal in PBLs from Lesch-Nyhan patients. In contrast, DAT1 expression was similar to control values in HPRT deficient PBLs. These results indicate an abnormal adenosine and dopamine receptor expression in HPRT-deficient cells and suggest disrupted adenosine and dopamine neurotransmission may have a significant role in the pathogenesis of the neurological manifestations of Lesch-Nyhan syndrome.

  17. Production of adenosine from extracellular ATP at the striatal cholinergic synapse.

    Science.gov (United States)

    James, S; Richardson, P J

    1993-01-01

    The components of the ectonucleotidase pathway at the immunoaffinity-purified striatal cholinergic synapse have been studied. The ecto-ATPase (EC 3.6.1.15) had a Km of 131 microM, whereas the ecto-ADPase (EC 3.6.1.6) had a Km of 58 microM, was Ca(2+)-dependent, and was inhibited by the ATP analogue 5'-adenylylimidodiphosphate (AMPPNP). The ecto-5'-nucleotidase (EC 3.1.3.5) had a Km of 21 microM, was inhibited by AMPPNP and alpha,beta-methylene ADP, and by a specific antiserum. The Vmax values of the ATPase, ADPase, and 5'-nucleotidase enzymes present at this synapse were in a ratio of 30:14:1. Very little ecto-adenylate kinase activity was detected on these purified synapses. The intraterminal 5'-nucleotidase enzyme, which amounted to 40% of the total 5'-nucleotidase activity, was inhibited by AMPPNP, alpha,beta-methylene ADP, and the antiserum, and also had the same kinetic properties as the ectoenzyme. The time course of ATP degradation to adenosine outside the nerve terminals showed a delay, followed by a period of sustained adenosine production. The delay in adenosine production was proportional to the initial ATP concentration, was a consequence of feedforward inhibition of the ADPase and 5'-nucleotidase, and was inversely proportional to the ecto-5'-nucleotidase activity. The function and characteristics of this pathway and the central role of 5'-nucleotidase in the regulation of extraterminal adenosine concentrations are discussed.

  18. Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships

    Directory of Open Access Journals (Sweden)

    Siew Lee Cheong

    2011-01-01

    Full Text Available In the past few decades, medicinal chemistry research towards potent and selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3 has been evolving rapidly. These antagonists are deemed therapeutically beneficial in several pathological conditions including neurological and renal disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of compounds have been successfully synthesized and identified as potent human adenosine receptor antagonists. In this paper, an overview of the structure-activity relationship (SAR profiles of promising nonxanthine pyrazolo derivatives is reported and discussed. We have emphasized the SAR for some representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3-d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This overview not only clarifies the structural requirements deemed essential for affinity towards individual adenosine receptor subtypes, but it also sheds light on the rational design and optimization of existing structural templates to allow us to conceive new, more potent adenosine receptor antagonists.

  19. Identification of A3 adenosine receptor agonists as novel non-narcotic analgesics.

    Science.gov (United States)

    Janes, K; Symons-Liguori, A M; Jacobson, K A; Salvemini, D

    2016-04-01

    Chronic pain negatively impacts the quality of life in a variety of patient populations. The current therapeutic repertoire is inadequate in managing patient pain and warrants the development of new therapeutics. Adenosine and its four cognate receptors (A1 , A2A , A2B and A3 ) have important roles in physiological and pathophysiological states, including chronic pain. Preclinical and clinical studies have revealed that while adenosine and agonists of the A1 and A2A receptors have antinociceptive properties, their therapeutic utility is limited by adverse cardiovascular side effects. In contrast, our understanding of the A3 receptor is only in its infancy, but exciting preclinical observations of A3 receptor antinociception, which have been bolstered by clinical trials of A3 receptor agonists in other disease states, suggest pain relief without cardiovascular side effects and with sufficient tolerability. Our goal herein is to briefly discuss adenosine and its receptors in the context of pathological pain and to consider the current data regarding A3 receptor-mediated antinociception. We will highlight recent findings regarding the impact of the A3 receptor on pain pathways and examine the current state of selective A3 receptor agonists used for these studies. The adenosine-to-A3 receptor pathway represents an important endogenous system that can be targeted to provide safe, effective pain relief from chronic pain.

  20. A3 Adenosine receptors mediate oligodendrocyte death and ischemic damage to optic nerve.

    Science.gov (United States)

    González-Fernández, Estíbaliz; Sánchez-Gómez, María Victoria; Pérez-Samartín, Alberto; Arellano, Rogelio O; Matute, Carlos

    2014-02-01

    Adenosine receptor activation is involved in myelination and in apoptotic pathways linked to neurodegenerative diseases. In this study, we investigated the effects of adenosine receptor activation in the viability of oligodendrocytes of the rat optic nerve. Selective activation of A3 receptors in pure cultures of oligodendrocytes caused concentration-dependent apoptotic and necrotic death which was preceded by oxidative stress and mitochondrial membrane depolarization. Oligodendrocyte apoptosis induced by A3 receptor activation was caspase-dependent and caspase-independent. In addition to dissociated cultures, incubation of optic nerves ex vivo with adenosine and the A3 receptor agonist 2-CI-IB-MECA(1-[2-Chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-b-D-ribofuranuronamide)-induced caspase-3 activation, oligodendrocyte damage, and myelin loss, effects which were prevented by the presence of caffeine and the A3 receptor antagonist MRS 1220 (N-[9-Chloro-2-(2-furanyl)[1,2,4]-triazolo [1,5-c]quinazolin-5-yl]benzene acetamide). Finally, ischemia-induced injury and functional loss to the optic nerve was attenuated by blocking A3 receptors. Together, these results indicate that adenosine may trigger oligodendrocyte death via activation of A3 receptors and suggest that this mechanism contributes to optic nerve and white matter ischemic damage.

  1. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

    NARCIS (Netherlands)

    Hassan, Amel; Booth, Claire; Brightwell, Alex; Allwood, Zoe; Veys, Paul; Rao, Kanchan; Hoenig, Manfred; Friedrich, Wilhelm; Gennery, Andrew; Slatter, Mary; Bredius, Robbert; Finocchi, Andrea; Cancrini, Caterina; Aiuti, Alessandro; Porta, Fulvio; Lanfranchi, Arnalda; Ridella, Michela; Steward, Colin; Filipovich, Alexandra; Marsh, Rebecca; Bordon, Victoria; Al-Muhsen, Saleh; Al-Mousa, Hamoud; Alsum, Zobaida; Al-Dhekri, Hasan; Al Ghonaium, Abdulaziz; Speckmann, Carsten; Fischer, Alain; Mahlaoui, Nizar; Nichols, Kim E.; Grunebaum, Eyal; Al Zahrani, Daifulah; Roifman, Chaim M.; Boelens, Jaap; Davies, E. Graham; Cavazzana-Calvo, Marina; Notarangelo, Luigi; Gaspar, H. Bobby

    2012-01-01

    Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed o

  2. Ischemic nucleotide breakdown increases during cardiac development due to drop in adenosine anabolism/catabolism ratio

    NARCIS (Netherlands)

    J.W. de Jong (Jan Willem); E. Keijzer (Elisabeth); T. Huizer (Tom); B. Schoutsen

    1990-01-01

    markdownabstractAbstract Our earlier work on reperfusion showed that adult rat hearts released almost twice as much purine nucleosides and oxypurines as newborn hearts did [Am J Physiol 254 (1988) H1091]. A change in the ratio anabolism/catabolism of adenosine could be responsible for this effect.

  3. Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis.

    Science.gov (United States)

    Liddicoat, Brian J; Hartner, Jochen C; Piskol, Robert; Ramaswami, Gokul; Chalk, Alistair M; Kingsley, Paul D; Sankaran, Vijay G; Wall, Meaghan; Purton, Louise E; Seeburg, Peter H; Palis, James; Orkin, Stuart H; Lu, Jun; Li, Jin Billy; Walkley, Carl R

    2016-10-01

    Adenosine deaminases that act on RNA (ADARs) convert adenosine residues to inosine in double-stranded RNA. In vivo, ADAR1 is essential for the maintenance of hematopoietic stem/progenitors. Whether other hematopoietic cell types also require ADAR1 has not been assessed. Using erythroid- and myeloid-restricted deletion of Adar1, we demonstrate that ADAR1 is dispensable for myelopoiesis but is essential for normal erythropoiesis. Adar1-deficient erythroid cells display a profound activation of innate immune signaling and high levels of cell death. No changes in microRNA levels were found in ADAR1-deficient erythroid cells. Using an editing-deficient allele, we demonstrate that RNA editing is the essential function of ADAR1 during erythropoiesis. Mapping of adenosine-to-inosine editing in purified erythroid cells identified clusters of hyperedited adenosines located in long 3'-untranslated regions of erythroid-specific transcripts and these are ADAR1-specific editing events. ADAR1-mediated RNA editing is essential for normal erythropoiesis. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  4. Extracellular Adenosine Triphosphate Affects Systemic and Kidney Immune Cell Populations in Pregnant Rats

    NARCIS (Netherlands)

    Spaans, Floor; Melgert, Barbro N.; Borghuis, Theo; Klok, Pieter A.; de Vos, Paul; Bakker, Winston W.; van Goor, Harry; Faas, Marijke

    PROBLEM: Changes in the systemic immune response are found in preeclampsia. This may be related to high extracellular adenosine triphosphate (ATP) levels. The question arose whether ATP could affect immune responses in pregnancy. Previously, we investigated whether ATP affected monocyte activation

  5. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    Directory of Open Access Journals (Sweden)

    Felicita Pedata

    2014-01-01

    Full Text Available The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes. Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.

  6. The effect of ticlopidine administration to humans on the binding of adenosine diphosphate to blood platelets

    NARCIS (Netherlands)

    Lips, J.P.M.; Sixma, J.J.; Schiphorst, M.E.

    1980-01-01

    Administration of Ticlopidine to human volunteers resulted in a prolonged bleeding time and decreased or absent aggregation of platelets with collagen and epinephrine. Adenosine diphosphate (ADP) induced platelet aggregation was initiated by a normal shape change, but the rate of the first wave of a

  7. Therapeutic efficacy of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) against organophosphate intoxication

    NARCIS (Netherlands)

    Bueters, T.J.H.; Groen, B.; Danhof, M.; IJzerman, A.P.; Helden, H.P.M. van

    2002-01-01

    The objective of the present study was to investigate whether reduction of central acetylcholine (ACh) accumulation by adenosine receptor agonists could serve as a generic treatment against organophosphate (OP) poisoning. The OPs studied were tabun (O-ethyl-N-dimethylphosphoramidocyanidate), sarin (

  8. DISSIMILARITY IN METHACHOLINE AND ADENOSINE 5'-MONOPHOSPHATE RESPONSIVENESS 3-H AND 24-H AFTER ALLERGEN CHALLENGE

    NARCIS (Netherlands)

    AALBERS, R; KAUFFMAN, HF; KOETER, GH; POSTMA, DS; DEVRIES, K; DEMONCHY, JGR

    1991-01-01

    Bronchial hyperresponsiveness (BHR) to methacholine and adenosine 5'-monophosphate (AMP) was studied in 15 allergic asthmatic patients before and 3 and 24 h after allergen challenge with hose dust mite (HDM). Subjects attended the clinic on 3 consecutive days. On the first day a control solution was

  9. Dynamic Regulation of the Adenosine Kinase Gene during Early Postnatal Brain Development and Maturation

    Science.gov (United States)

    Kiese, Katharina; Jablonski, Janos; Boison, Detlev; Kobow, Katja

    2016-01-01

    The ubiquitous metabolic intermediary and nucleoside adenosine is a “master regulator” in all living systems. Under baseline conditions adenosine kinase (ADK) is the primary enzyme for the metabolic clearance of adenosine. By regulating the availability of adenosine, ADK is a critical upstream regulator of complex homeostatic and metabolic networks. Not surprisingly, ADK dysfunction is involved in several pathologies, including diabetes, epilepsy, and cancer. ADK protein exists in the two isoforms nuclear ADK-L, and cytoplasmic ADK-S, which are subject to dynamic expression changes during brain development and in response to brain injury; however, gene expression changes of the Adk gene as well as regulatory mechanisms that direct the cell-type and isoform specific expression of ADK have never been investigated. Here we analyzed potential gene regulatory mechanisms that may influence Adk expression including DNA promoter methylation, histone modifications and transcription factor binding. Our data suggest binding of transcription factor SP1 to the Adk promoter influences the regulation of Adk expression. PMID:27812320

  10. REPRODUCTIVE CONDITION, GLOMERULAR ADENOSINE DIPHOSPHATASE ACTIVITY, AND PLATELET-AGGREGATION IN THE RAT - EFFECT OF ENDOTOXIN

    NARCIS (Netherlands)

    VISSCHER, CA; FAAS, MM; BAKKER, WW; SCHUILING, GA

    1993-01-01

    In experiment A, the activity of the glomerular antithrombotic enzyme adenosine diphosphatase (ADPase) and the sensitivity of this enzyme for endotoxin (1.0 mug/kg BW) in various reproductive conditions of female rats were studied through use of enzyme histochemical methods. In experiment B, the

  11. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds.

    Directory of Open Access Journals (Sweden)

    Shinji Kataoka

    Full Text Available In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3 on taste nerves as well as metabotropic (P2Y purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate, but not anterior (fungiform, palate taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields.

  12. Adenosine Monophosphate (AMP)-Activated Protein Kinase: A New Target for Nutraceutical Compounds.

    Science.gov (United States)

    Marín-Aguilar, Fabiola; Pavillard, Luis E; Giampieri, Francesca; Bullón, Pedro; Cordero, Mario D

    2017-01-29

    Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor which is activated by increases in adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio and/or adenosine diphosphate (ADP)/ATP ratio, and increases different metabolic pathways such as fatty acid oxidation, glucose transport and mitochondrial biogenesis. In this sense, AMPK maintains cellular energy homeostasis by induction of catabolism and inhibition of ATP-consuming biosynthetic pathways to preserve ATP levels. Several studies indicate a reduction of AMPK sensitivity to cellular stress during aging and this could impair the downstream signaling and the maintenance of the cellular energy balance and the stress resistance. However, several diseases have been related with an AMPK dysfunction. Alterations in AMPK signaling decrease mitochondrial biogenesis, increase cellular stress and induce inflammation, which are typical events of the aging process and have been associated to several pathological processes. In this sense, in the last few years AMPK has been identified as a very interesting target and different nutraceutical compounds are being studied for an interesting potential effect on AMPK induction. In this review, we will evaluate the interaction of the different nutraceutical compounds to induce the AMPK phosphorylation and the applications in diseases such as cancer, type II diabetes, neurodegenerative diseases or cardiovascular diseases.

  13. Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ‡

    Science.gov (United States)

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

    2016-01-01

    Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1–20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8–14 days post-immunization, shortly before EAU expression, but ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses and this effect was γδ T cell-dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help improve the design of ADA- and AR-targeted therapies. PMID:26856700

  14. High fetal plasma adenosine concentration: a role for the fetus in preeclampsia?

    LENUS (Irish Health Repository)

    Espinoza, Jimmy

    2012-02-01

    OBJECTIVE: Clinical observations suggest a role for the fetus in the maternal manifestations of preeclampsia, but the possible signaling mechanisms remain unclear. This study compares the fetal plasma concentrations of adenosine from normal pregnancies with those from preeclampsia. STUDY DESIGN: This secondary data analysis included normal pregnancies (n = 27) and patients with preeclampsia (n = 39). Patients with preeclampsia were subclassified into patients with (n = 25) and without (n = 14) abnormal uterine artery Doppler velocimetry (UADV). RESULTS: Fetal plasma concentrations of adenosine were significantly higher in patients with preeclampsia (1.35 +\\/- 0.09 mumol\\/L) than in normal pregnancies (0.52 +\\/- 0.06 mumol\\/L; P < .0001). Fetal plasma concentrations of adenosine in patients with preeclampsia with abnormal UADV (1.78 +\\/- 0.15 mumol\\/L), but not with normal UADV (0.58 +\\/- 0.14 mumol\\/L), were significantly higher than in normal pregnancies (P < .0001). CONCLUSION: Patients with preeclampsia with sonographic evidence of chronic uteroplacental ischemia have high fetal plasma concentrations of adenosine.

  15. Transient Delivery of Adenosine as a Novel Therapy to Prevent Epileptogenesis

    Science.gov (United States)

    2015-10-01

    10q11-q24 in the human and on chromosome 14 A2-B in the mouse (Klobutcher et al., 1976; Samuelson and Farber, 1985). Although the size of the gene that...adenosine ki- nase in streptozotocin-induced diabetes mellitus rats. Mol Cell Biochem 236: 163–171. Samuelson LC and Farber RA (1985) Cytological

  16. Altered purinergic signaling in uridine adenosine tetraphosphate-induced coronary relaxation in swine with metabolic derangement

    NARCIS (Netherlands)

    Z. Zhou (Zhichao); O. Sorop (Oana); V.J. de Beer (Vincent Jacob); I. Heinonen (Ilkka); C. Cheng (Caroline); A.H.J. Danser (Jan); D.J.G.M. Duncker (Dirk); D. Merkus (Daphne)

    2017-01-01

    textabstractWe previously demonstrated that uridine adenosine tetraphosphate (Up4A) induces potent and partially endothelium-dependent relaxation in the healthy porcine coronary microvasculature. We subsequently showed that Up4A-induced porcine coronary relaxation was impaired via downregulation of

  17. B-cell development and functions and therapeutic options in adenosine deaminase-deficient patients

    NARCIS (Netherlands)

    I. Brigida (Immacolata); A.V. Sauer (Aisha); F. Ferrua (Francesca); S. Giannelli (Stefania); S. Scaramuzza (Samantha); V. Pistoia (Valentina); M.C. Castiello (Maria Carmina); B.H. Barendregt (Barbara); M.P. Cicalese (Maria Pia); F. Casiraghi (Federica); C. Brombin (Chiara); J. Puck (Jennifer); K. Muller (Karin); L.D. Notarangelo (Luigi Daniele); D. Montin (Davide); J.M. van Montfrans (Joris); M.G. Roncarolo (Maria Grazia); E. Traggiai (Elisabetta); J.J.M. van Dongen (Jacques); M. van der Burg (Mirjam); A. Aiuti (Alessandro)

    2014-01-01

    textabstractBackground Adenosine deaminase (ADA) deficiency causes severe cellular and humoral immune defects and dysregulation because of metabolic toxicity. Alterations in B-cell development and function have been poorly studied. Enzyme replacement therapy (ERT) and hematopoietic stem cell (HSC) g

  18. Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent

    Science.gov (United States)

    Song, Anren; Zhang, Yujin; Han, Leng; Yegutkin, Gennady G.; Liu, Hong; Sun, Kaiqi; D'Alessandro, Angelo; Li, Jessica; Karmouty-Quintana, Harry; Iriyama, Takayuki; Weng, Tingting; Zhao, Shushan; Wang, Wei; Wu, Hongyu; Nemkov, Travis; Subudhi, Andrew W.; Jameson-Van Houten, Sonja; Julian, Colleen G.; Lovering, Andrew T.; Hansen, Kirk C.; Zhang, Hong; Bogdanov, Mikhail; Dowhan, William; Jin, Jianping; Kellems, Rodney E.; Eltzschig, Holger K.; Blackburn, Michael; Roach, Robert C.; Xia, Yang

    2017-01-01

    Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response is unknown. We report that in healthy lowlanders, plasma adenosine levels are rapidly induced by initial ascent to high altitude and achieved even higher levels upon re-ascent, a feature that is positively associated with quicker acclimatization. Erythrocyte equilibrative nucleoside transporter 1 (eENT1) levels are reduced in humans at high altitude and in mice under hypoxia. eENT1 deletion allows rapid accumulation of plasma adenosine to counteract hypoxic tissue damage in mice. Adenosine signalling via erythrocyte ADORA2B induces PKA phosphorylation, ubiquitination and proteasomal degradation of eENT1. Reduced eENT1 resulting from initial hypoxia is maintained upon re-ascent in humans or re-exposure to hypoxia in mice and accounts for erythrocyte hypoxic memory and faster acclimatization. Our findings suggest that targeting identified purinergic-signalling network would enhance the hypoxia adenosine response to counteract hypoxia-induced maladaptation. PMID:28169986

  19. Inhibition of adenosine deaminase attenuates endotoxin-induced release of cytokines in vivo in rats.

    Science.gov (United States)

    Tofovic, S P; Zacharia, L; Carcillo, J A; Jackson, E K

    2001-09-01

    The purpose of this study was to investigate in vivo the effects of modulating the adenosine system on endotoxin-induced release of cytokines and changes in heart performance and neurohumoral status in early, profound endotoxemia in rats. Time/pressure variables of heart performance and blood pressure were recorded continuously, and plasma levels of tumor necrosis factor alpha (TNFalpha), interleukin 1-beta (IL-1beta), plasma renin activity (PRA), and catecholamines were determined before and 90 min after administration of endotoxin (30 mg/kg of lipopolysaccharide, i.v.). Erythro-9[2-hydroxyl-3-nonyl] adenine (EHNA; an adenosine deaminase inhibitor) had no effects on measured time-pressure variables of heart performance under baseline conditions and during endotoxemia, yet significantly attenuated endotoxin-induced release of cytokines and PRA. Pretreatment with the non-selective adenosine receptor antagonist DPSPX not only prevented the effects of EHNA but also increased the basal release of cytokines and augmented PRA. At baseline, caffeine (a non-selective adenosine receptor antagonist) increased HR, +dP/dtmax, heart rate x ventricular pressure product (HR x VPSP) and +dP/dtmax normalized by pressure (+dP/dtmax/VPSP), and these changes persisted during endotoxemia. Caffeine attenuated endotoxin-induced release of cytokines and augmented endotoxin-induced increases in plasma catecholamines and PRA. Pretreatment with propranolol abolished the effects of caffeine on heart performance and neurohumoral activation during the early phase of endotoxemia. 6N-cyclopentyladenosine (CPA; selective A1 adenosine receptor agonist) induced bradicardia and negative inotropic effects, reduced work load (i.e., decreased HR, VPSP, +dP/dtmax, +dP/dtmax/VPSP and HR x VPSP) and inhibited endotoxin-induced tachycardia and renin release. CGS 21680 (selective A2A adenosine receptor agonist) decreased blood pressure under basal condition but did not potentiate decreases in blood pressure

  20. Progress in Personalizing Chemotherapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    James S. Chang

    2012-01-01

    Full Text Available Platinum-based chemotherapy is commonly used for the treatment of locally advanced and metastatic bladder cancer. However, there are currently no methods to predict chemotherapy response in this disease setting. A better understanding of the biology of bladder cancer has led to developments of molecular biomarkers that may help guide clinical decision making. These biomarkers, while promising, have not yet been validated in prospective trials and are not ready for clinical applications. As alkylating agents, platinum drugs kill cancer cells mainly through induction of DNA damage. A microdosing approach is currently being tested to determine if chemoresistance can be identified by measuring platinum-induced DNA damage using highly sensitive accelerator mass spectrometry technology. The hope is that these emerging strategies will help pave the road towards personalized therapy in advanced bladder cancer.

  1. Side effects of chemotherapy in musculoskeletal oncology.

    Science.gov (United States)

    Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Romantini, Matteo; Angelini, Andrea; Ruggieri, Pietro

    2010-01-01

    With recent advances in medical and orthopedic oncology, radiation therapy and single- or multiple-agent perioperative chemotherapy are currently applied as an essential part of the multidisciplinary treatment to improve disease-free and overall survival of patients with primary and metastatic bone and soft tissue tumors. However, these treatments have led to unwanted complications. A better understanding of the effects of various antineoplastic agents on bone, soft tissue, and organs may provide the basis for the more efficacious use of antiproliferative drugs when fracture healing or allograft incorporation is required. This knowledge may also provide a rationale for concurrent treatment with drugs that protect against or compensate for adverse effects in osseous repair resulting from chemotherapy.

  2. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik

    2012-01-01

    INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval...... debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study...... is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p

  3. Intestinal response to myeloablative chemotherapy in piglets

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko; Shen, René Liang; Petersen, Bodil L

    2014-01-01

    Chemotherapy-induced myeloablation prior to allogeneic hematopoietic stem cell transplantation (HSCT) may be associated with severe toxicity. The current understanding of the pathophysiology of oral and gastrointestinal (GI) toxicity is largely derived from studies in rodents and very little...... is known from humans, especially children. We hypothesized that milk-fed piglets can be used as a clinically relevant model of GI-toxicity related to a standard conditioning chemotherapy (intravenous busulfan, Bu plus cyclophosphamide, Cy) used prior to HSCT. In study 1, dose-response relationships were....../kg) and bone marrow was collected on day 11. Histology of bone marrow samples showed total aplasia after treatment A. Using this treatment in study 2, Bu-Cy pigs showed lowered spleen and intestinal weights and variable clinical signs of dehydration, sepsis, and pneumonia at tissue collection. Oral mucositis...

  4. Neoadjuvant chemotherapy for invasive bladder cancer.

    Science.gov (United States)

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

    Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents.

  5. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik;

    2012-01-01

    INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval...... debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study...... is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p

  6. [Effectiveness of scalp cooling in chemotherapy].

    Science.gov (United States)

    Poder, Thomas G; He, Jie; Lemieux, Renald

    2011-10-01

    The main objectives of this literature review are to determine if scalp cooling is efficient and safe, if there are side effects and if the patients' quality of life improves. In terms of effectiveness, scalp cooling seems to get good performance in its aim to prevent hair loss in patients receiving chemotherapy. The weighted average results of all identified studies indicate that this technology allows for 63.5% of patients to have a good preservation of their hair. In studies with a group of control, the weighted rates of good preservation of the hair are 50.6% with scalp cooling and 16.3% without. From the standpoint of safety technology, the main risk is that of scalp metastases. However, no study has successfully demonstrated a statistically significant difference between groups of patients receiving chemotherapy with or without scalp cooling.

  7. Using Epigenetic Therapy to Overcome Chemotherapy Resistance.

    Science.gov (United States)

    Strauss, Julius; Figg, William D

    2016-01-01

    It has been known for decades that as cancer progresses, tumors develop genetic alterations, making them highly prone to developing resistance to therapies. Classically, it has been thought that these acquired genetic changes are fixed. This has led to the paradigm of moving from one cancer therapy to the next while avoiding past therapies. However, emerging data on epigenetic changes during tumor progression and use of epigenetic therapies have shown that epigenetic modifications leading to chemotherapy resistance have the potential to be reversible with epigenetic therapy. In fact, promising clinical data exist that treatment with epigenetic agents can diminish chemotherapy resistance in a number of tumor types including chronic myelogenous leukemia, colorectal, ovarian, lung and breast cancer. The potential for epigenetic-modifying drugs to allow for treatment of resistant disease is exciting and clinical trials have just begun to evaluate this area.

  8. Value of adenosine infusion for infarct size determination using real-time myocardial contrast echocardiography

    Directory of Open Access Journals (Sweden)

    da Luz Protásio

    2006-02-01

    Full Text Available Abstract Background Myocardial contrast echocardiography has been used for determination of infarct size (IS in experimental models. However, with intermittent harmonic imaging, IS seems to be underestimated immediately after reperfusion due to areas with preserved, yet dysfunctional, microvasculature. The use of exogenous vasodilators showed to be useful to unmask these infarcted areas with depressed coronary flow reserve. This study was undertaken to assess the value of adenosine for IS determination in an open-chest canine model of coronary occlusion and reperfusion, using real-time myocardial contrast echocardiography (RTMCE. Methods Nine dogs underwent 180 minutes of coronary occlusion followed by reperfusion. PESDA (Perfluorocarbon-Exposed Sonicated Dextrose Albumin was used as contrast agent. IS was determined by RTMCE before and during adenosine infusion at a rate of 140 mcg·Kg-1·min-1. Post-mortem necrotic area was determined by triphenyl-tetrazolium chloride (TTC staining. Results IS determined by RTMCE was 1.98 ± 1.30 cm2 and increased to 2.58 ± 1.53 cm2 during adenosine infusion (p = 0.004, with good correlation between measurements (r = 0.91; p 2 and showed no significant difference with IS determined by RTMCE before or during hyperemia. A slight better correlation between RTMCE and TTC measurements was observed during adenosine (r = 0.99; p Conclusion RTMCE can accurately determine IS in immediate period after acute myocardial infarction. Adenosine infusion results in a slight better detection of actual size of myocardial damage.

  9. Regulatory effects of adenosine A2A receptors on psychomotor ability and mood behavior of mice

    Directory of Open Access Journals (Sweden)

    Li JIANG

    2011-07-01

    Full Text Available Objective To explore the effects of gene knock-out,agonist or inhibitor of adenosine A2A receptor on the locomotor activity,and anxiety-or depression-like behavior of mice.Methods Male C57BL/6 mice,comprising those underwent gene knock-out of adenosine A2A receptor(A2AKO and their wild-type(WT littermates,were assigned into A2AKO group and WT group.Another batch of male C57BL/6,specific-pathogen-free(SPF mice,were assigned into SCH58261 group,CGS21680 group and control group.Mice of aforesaid 3 groups were transperitoneally administered with SCH58261,a specific inhibitor of adenosine A2A receptor at a dose of 2mg/kg,CGS21680,a specific agonist of adenosine A2A receptor at a dose of 0.5mg/kg,and vehicle(0.25ml,comprising DMSO and saline,respectively.Ten minutes after injection,mice of the 3 groups underwent open-field test,elevated plus-maze test and forced swimming test to detect their locomotor activity,anxiety-and depression-like behavior.Results a Compared with WT group,the total movement distance decreased(P 0.05.b Compared with control group,the total movement distance decreased and the stay time in the peripheral area increased significantly in the open field test(P 0.05.Conclusions The agonist of adenosine A2A receptor may depress the spontaneous motility and exploratory behavior,and exacerbate the anxiety and depression,and it simulates the effect induced by knock-out of A2A receptor gene,but it is opposite to the effect induced by A2A receptor inhibitor.

  10. Cloning of two adenosine receptor subtypes from mouse bone marrow-derived mast cells.

    Science.gov (United States)

    Marquardt, D L; Walker, L L; Heinemann, S

    1994-05-01

    Adenosine potentiates the stimulated release of mast cell mediators. Pharmacologic studies suggest the presence of two adenosine receptors, one positively coupled to adenylate cyclase and the other coupled to phospholipase C activation. To identify mast cell adenosine receptor subtypes, cDNAs for the A1 and A2a adenosine receptors were obtained by screening a mouse brain cDNA library with the use of PCR-derived probes. Mouse bone marrow-derived mast cell cDNA libraries were constructed and screened with the use of A1 and A2a cDNA probes, which revealed the presence of A2a, but not A1, receptor clones. A putative A2b receptor was identified by using low stringency mast cell library screening. Northern blotting of mast cell poly(A)+ RNA with the use of receptor subtype probes labeled single mRNA bands of 2.4 kb and 1.8 kb for the A2a and A2b receptors, respectively. In situ cells. An A2a receptor-specific agonist failed to enhance mast cell mediator release, which suggests that the secretory process is modulated through the A2b and/or another receptor subtype. By using RNase protection assays, we found that mast cells that had been cultured in the presence of N-ethylcarboxamidoadenosine for 24 h exhibited a decrease in both A2a and A2b receptor RNA levels. Cells that had been cultured for 1 to 2 days in the presence of dexamethasone demonstrated increased amounts of A2a receptor mRNA, but no identifiable change in A2b receptor mRNA. Mast cells possess at least two adenosine receptor subtypes that may be differentially regulated.

  11. The role of plasma adenosine deaminase in chemoattractant-stimulated oxygen radical production in neutrophils.

    Science.gov (United States)

    Kälvegren, Hanna; Fridfeldt, Jonna; Bengtsson, Torbjörn

    2010-06-01

    Adenosine deaminase (ADA) has a role in many immunity mediated disorders, such as asthma, tuberculosis and coronary artery disease. This study aims to investigate the ability of plasma ADA to modulate reactive oxygen species (ROS) production in neutrophils, and examine the involvement of adenosine and the cyclic AMP signaling pathway in this process. Neutrophils were stimulated, in the absence or presence of plasma, with the chemotactic peptide fMLP (formyl-methionyl-leucyl-phenylalanine), and the ROS production was determined with luminol-enhanced chemiluminescence. Activity of ADA was measured spectrophotometrically. Plasma dose-dependently amplified the ROS generation in fMLP-stimulated neutrophils. In parallel, incubation of neutrophils in plasma elevated the total ADA-activity approximately 10 times from 1.3 U/ml to 12 U/ml. Inhibition of ADA, or type IV phosphodiesterases, significantly lowered the plasma-mediated ROS production. Furthermore, the high-affinity adenosine A(1) receptor antagonists DPCPX and 8-phenyltheophylline markedly inhibited the plasma-induced respiratory burst in neutrophils, suggesting an A(1) receptor-mediated mechanism. This study suggests that plasma ADA amplifies the release of toxic oxygen radicals from neutrophils through a downregulation of the inhibitory adenosine/cAMP-system and an enhanced activation of the stimulatory adenosine A(1)-receptor. This mechanism has probably a crucial role in regulating neutrophil function and in the defence against microbial infections. However, a sustained neutrophil activation could also contribute to inflammatory disorders such as atherosclerosis. 2010 Elsevier GmbH. All rights reserved.

  12. Adenosine, caffeine, and performance: from cognitive neuroscience of sleep to sleep pharmacogenetics.

    Science.gov (United States)

    Urry, Emily; Landolt, Hans-Peter

    2015-01-01

    An intricate interplay between circadian and sleep-wake homeostatic processes regulate cognitive performance on specific tasks, and individual differences in circadian preference and sleep pressure may contribute to individual differences in distinct neurocognitive functions. Attentional performance appears to be particularly sensitive to time of day modulations and the effects of sleep deprivation. Consistent with the notion that the neuromodulator, adenosine , plays an important role in regulating sleep pressure, pharmacologic and genetic data in animals and humans demonstrate that differences in adenosinergic tone affect sleepiness, arousal and vigilant attention in rested and sleep-deprived states. Caffeine--the most often consumed stimulant in the world--blocks adenosine receptors and normally attenuates the consequences of sleep deprivation on arousal, vigilance, and attention. Nevertheless, caffeine cannot substitute for sleep, and is virtually ineffective in mitigating the impact of severe sleep loss on higher-order cognitive functions. Thus, the available evidence suggests that adenosinergic mechanisms, in particular adenosine A2A receptor-mediated signal transduction, contribute to waking-induced impairments of attentional processes, whereas additional mechanisms must be involved in higher-order cognitive consequences of sleep deprivation. Future investigations should further clarify the exact types of cognitive processes affected by inappropriate sleep. This research will aid in the quest to better understand the role of different brain systems (e.g., adenosine and adenosine receptors) in regulating sleep, and sleep-related subjective state, and cognitive processes. Furthermore, it will provide more detail on the underlying mechanisms of the detrimental effects of extended wakefulness, as well as lead to the development of effective, evidence-based countermeasures against the health consequences of circadian misalignment and chronic sleep restriction.

  13. Modulatory effect of adenosine receptors on the ascending and descending neural reflex responses of rat ileum

    Directory of Open Access Journals (Sweden)

    Schusdziarra Volker

    2002-12-01

    Full Text Available Abstract Background Adenosine is known to act as a neuromodulator by suppressing synaptic transmission in the central and peripheral nervous system. Both the release of adenosine within the small intestine and the presence of adenosine receptors on enteric neurons have been demonstrated. The aim of the present study was to characterize a possible involvement of adenosine receptors in the modulation of the myenteric reflex. The experiments were carried out on ileum segments 10 cm in length incubated in an single chambered organ bath, and the reflex response was initiated by electrical stimulation (ES. Results ES caused an ascending contraction and a descending relaxation followed by a contraction. All motility responses to ES were completely blocked by tetrodotoxin, indicating that they are mediated by neural mechanisms. Atropine blocked the contractile effects, whereas the descending relaxation was significantly increased. The A1 receptor agonist N6-cyclopentyladenosine increased the ascending contraction, whereas the ascending contraction was reduced by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. Activation of the A1 receptor further reduced the descending relaxation and the latency of the peristaltic reflex. The A2B receptor antagonist alloxazine increased ascending contraction, whereas descending relaxation remained unchanged. For A2A and A3 receptors, we found contradictory effects of the agonists and antagonists, thus there is no clear physiological role for these receptors at this time. Conclusions This study suggests that the myenteric ascending and descending reflex response of the rat small intestine is modulated by release of endogenous adenosine via A1 receptors.

  14. Role of adenosine and the orexinergic perifornical hypothalamus in sleep-promoting effects of ethanol.

    Science.gov (United States)

    Sharma, Rishi; Sahota, Pradeep; Thakkar, Mahesh M

    2014-03-01

    Strong clinical and preclinical evidence suggests that acute ethanol promotes sleep. However, very little is known about how and where ethanol acts to promote sleep. We hypothesized that ethanol may induce sleep by increasing extracellular levels of adenosine and inhibiting orexin neurons in the perifornical hypothalamus. Experiments 1 and 2: Within-Subject Design; Experiment 3: Between-Subject Design. N/A. N/A. N/A. Using adult male Sprague-Dawley rats as our animal model, we performed three experiments to test our hypothesis. Our first experiment examined the effect of A1 receptor blockade in the orexinergic perifornical hypothalamus on sleep- promoting effects of ethanol. Bilateral microinjection of the selective A1 receptor antagonist 1,3-dipropyl-8-phenylxanthine (500 μM; 250 nL/side) into orexinergic perifornical hypothalamus significantly reduced nonrapid eye movement sleep with a concomitant increase in wakefulness, suggesting that blockade of adenosine A1 receptor attenuates ethanol-induced sleep promotion. Our second experiment examined adenosine release in the orexinergic perifornical hypothalamus during local ethanol infusion. Local infusion of pharmacologically relevant doses of ethanol significantly and dose-dependently increased adenosine release. Our final experiment used c-Fos immunohistochemistry to examine the effects of ethanol on the activation of orexin neurons. Acute ethanol exposure significantly reduced the number of orexin neurons containing c-Fos, suggesting an inhibition of orexin neurons after ethanol intake. Based on our results, we believe that ethanol promotes sleep by increasing adenosine in the orexinergic perifornical hypothalamus, resulting in A1 receptor-mediated inhibition of orexin neurons.

  15. Mechanisms of chemotherapy-induced behavioral toxicities

    OpenAIRE

    Vichaya, Elisabeth G.; Chiu, Gabriel S.; Karen eKrukowski; Lacourt, Tamara E.; Annemieke eKavelaars; Robert eDantzer; Cobi J Heijnen; Adam K. Walker

    2015-01-01

    While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during tre...

  16. Paul Ehrlich: From magic bullets to chemotherapy

    Directory of Open Access Journals (Sweden)

    Juan Fernando Cediel

    2008-09-01

    Full Text Available Paul Ehrlich is one of the most notable figures in the world of science. Considered by many as the father of chemotherapy, he was awarded the Nobel Prize in Physiology and Medicine in 1908 for his contributions to immunology. This document outlines some of his most important findings, including those who led him to create his famous «magic bullets», precursors of current chemotherapeutic agents.

  17. Role of adenosine-guided pulmonary vein isolation in patients undergoing catheter ablation for atrial fibrillation: a meta-analysis.

    Science.gov (United States)

    Chen, Yi-He; Lin, Hui; Xie, Cheng-Long; Hou, Jian-Wen; Li, Yi-Gang

    2017-04-01

    Adenosine had been reported to unmask dormant conduction and thus identify pulmonary vein at risk of reconnection. However, the role of adjunctive adenosine infusion after pulmonary vein isolation (PVI) on long-term arrhythmia-free survival was still contentious. The purpose of the present meta-analysis was to assess the association of adenosine testing with long-term ablation success in patients with atrial fibrillation (AF) (i.e. freedom from AF recurrence). We systematically searched the electronic databases and finally included 10 studies, with 1771 patients undergoing adenosine-guided PVI and 1787 patients undergoing conventional PVI. In comparison to conventional PVI alone, adenosine-guided PVI improved the arrhythmia-free survival by 17% during a median follow-up of 12 months [relative risk (RR): 1.17; 95% confidence interval (CI): 1.07 to 1.27; P = 0.014]. Patients undergoing adenosine-guided PVI had similar fluoroscopy time to those who undergoing conventional PVI [weighted mean difference (WMD): 1.76; 95% CI: -5.66 to 9.17; P = 0.64], despite longer procedure time (WMD: 20.6; 95% CI: 0.70 to 40.50; P = 0.042). From the available data of clinical studies, adenosine-guided PVI was associated with an increased arrhythmia-free survival when compared with conventional PVI in patients undergoing catheter ablation for AF.

  18. Recombinant human thrombopoietin in myelosuppressive chemotherapy.

    Science.gov (United States)

    Vadhan-Raj, S

    2001-07-01

    Recombinant human thrombopoietin (rhTPO) is a full-length glycosylated molecule that has been under evaluation in the setting of chemotherapy-induced myelosuppression. It has been shown to be a potent stimulator of platelet production in cancer patients when administered prior to chemotherapy. The peak platelet response to a single dose of rhTPO is observed around day 12, and is accompanied by a significant increase in the number of mature megakaryocytes in bone marrow. Consistent with this biologic effect, rhTPO administered postchemotherapy has been shown to be effective in attenuating severe thrombocytopenia induced by carboplatin, which produces a late platelet nadir. Early clinical experience with a regimen that produces an early nadir, however, such as AI (doxorubicin [Adriamycin] and ifosfamide [Ifex]), suggests that administration of rhTPO both prior to and following chemotherapy might be important to reduce thrombocytopenia severity. Treatment with rhTPO in these clinical trials has been well tolerated with a favorable safety profile. Randomized clinical trials have been initiated to determine further the importance of schedule in the prevention and treatment of severe thrombocytopenia in cancer patients.

  19. [Buccal manifestations in patients submitted to chemotherapy].

    Science.gov (United States)

    Hespanhol, Fernando Luiz; Tinoco, Eduardo Muniz Barretto; Teixeira, Henrique Guilherme de Castro; Falabella, Márcio Eduardo Vieira; Assis, Neuza Maria de Souza Picorelli

    2010-06-01

    Several changes in the oral cavity due to chemotherapy can be observed and can lead to important systemic complications, increasing the time of the patient in hospital and the costs of the treatment as well as affect the quality of life of the patients. The aim of this study was to assess the oral manifestation in patients treated with chemotherapy according to sex, age and tumor type. Data was collected in an oncology hospital in Juiz de Fora, Minas Gerais State, from patients' records that were submitted to oncologic treatment. It was possible to verify that mucositis, associated or not to other type of lesions, was the most common lesion in both sex of all ages (15.5%). Xerostomia and other lesions, such as Candida infection and aphthous lesions, were also present. It is possible to improve the quality of life of the patient during and after anti-neoplastic therapies through a protocol of odontological assistance that includes changes of the oral environment previous to chemotherapy such as profilaxis, caries removal, treatment of periodontal and periapical lesions, oral hygiene instructions, diet orientation and laser therapy. It is very important the insertion of the dentist in the oncologic medical team for the early diagnosis of the oral manifestation and follow-up during treatment time.

  20. [Experimental study on chemotherapy of acute glanders].

    Science.gov (United States)

    Iliukhin, V I; Rotov, K A; Senina, T V; Snatenkov, E A; Tikhonov, S N; Plekhanova, N G; Kulikova, A S; Shubnikova, E V; Korol', E V; Nekhezina, M O

    2012-01-01

    Glanders is a zoonotic infection inducing acute forms of the disease (pneumonia, sepsis) in humans and animals under certain conditions, which even with the use of modern chemotherapy have unfavourable prognosis. Insufficient of efficacy of antibiotics with in vitro low MIC for planktonic bacterial suspension of Burkholderia mallei in chemotherapy of acute forms of glanders was due to the capacity of the pathogen for intracellular survival and formation of biofilms. Under such conditions the susceptibility of B. mallei to antibiotics lowered by several orders of magnitude. Chemotherapy of the glanders acute forms in animals usually provided only an increase of the lifespan, while among the survivors there was recorded a high relapse rate. More favourable outcomes were observed with the use of in vitro effective antibiotics in the form of clathrate compounds or especially liposomal forms. In the experiments with golden hamsters the survival rate reached 100% in 1000 Dlm infection even with the treatment onset by meropenem liposomal form 48 hours after the infection. Chemotherapeutics in the liposomal form significantly lowered resistance of B. mallei in both the experiments with a suspension of planktonic organisms and the use of bacteria interned in eukaryotic cells (Tetrahymena pyriformis).

  1. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E

    2014-01-01

    BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not rece......BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have...... not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression...... at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; Pchemotherapy (hazard ratio, 0.35), the time until the first...

  2. Chemotherapy resistance mechanisms in advanced skin cancer

    Directory of Open Access Journals (Sweden)

    Bhuvanesh Sukhlal Kalal

    2017-03-01

    Full Text Available Melanoma is a most dangerous and deadly type of skin cancer, and considered intrinsically resistant to both radiotherapy and chemotherapy. It has become a major public health concern as the incidence of melanoma has been rising steadily over recent decades with a 5-year survival remaining less than 5%. Detection of the disease in early stage may be curable, but late stage metastatic disease that has spread to other organs has an extremely poor prognosis with a median survival of less than 10 months. Since metastatic melanoma is unresponsive to therapy that is currently available, research is now focused on different treatment strategies such as combinations of surgery, chemotherapy and radiotherapy. The molecular basis of resistance to chemotherapy seen in melanoma is multifactorial; defective drug transport system, altered apoptotic pathway, deregulation of apoptosis and/or changes in enzymatic systems that mediate cellular metabolic machinery. Understanding of alterations in molecular processes involved in drug resistance may help in developing new therapeutic approaches to treatment of malignant melanoma.

  3. Adenosine stimulates the migration of human endothelial progenitor cells. Role of CXCR4 and microRNA-150.

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    Magali Rolland-Turner

    Full Text Available BACKGROUND: Administration of endothelial progenitor cells (EPC represents a promising option to regenerate the heart after myocardial infarction, but is limited because of low recruitment and engraftment in the myocardium. Mobilization and migration of EPC are mainly controlled by stromal cell-derived factor 1α (SDF-1α and its receptor CXCR4. We hypothesized that adenosine, a cardioprotective molecule, may improve the recruitment of EPC to the heart. METHODS: EPC were obtained from peripheral blood mononuclear cells of healthy volunteers. Expression of chemokines and their receptors was evaluated using microarrays, quantitative PCR, and flow cytometry. A Boyden chamber assay was used to assess chemotaxis. Recruitment of EPC to the infarcted heart was evaluated in rats after permanent occlusion of the left anterior descending coronary artery. RESULTS: Microarray analysis revealed that adenosine modulates the expression of several members of the chemokine family in EPC. Among these, CXCR4 was up-regulated by adenosine, and this result was confirmed by quantitative PCR (3-fold increase, P<0.001. CXCR4 expression at the cell surface was also increased. This effect involved the A(2B receptor. Pretreatment of EPC with adenosine amplified their migration towards recombinant SDF-1α or conditioned medium from cardiac fibroblasts. Both effects were abolished by CXCR4 blocking antibodies. Adenosine also increased CXCR4 under ischemic conditions, and decreased miR-150 expression. Binding of miR-150 to the 3' untranslated region of CXCR4 was verified by luciferase assay. Addition of pre-miR-150 blunted the effect of adenosine on CXCR4. Administration of adenosine to rats after induction of myocardial infarction stimulated EPC recruitment to the heart and enhanced angiogenesis. CONCLUSION: Adenosine increases the migration of EPC. The mechanism involves A(2B receptor activation, decreased expression of miR-150 and increased expression of CXCR4. These

  4. [Influence of cancer chemotherapy on conjunctival epithelium and goblet cells].

    Science.gov (United States)

    Wojciechowska, Katarzyna; Jesionek-Kupnicka, Dorota; Jurowski, Piotr

    2013-01-01

    Evaluation of different types of chemotherapy schemes administered in lung, breast and bowel cancer on conjunctival epithelium and goblet cells morphology. 36 patients (72 eyes) were enrolled to the study. Patients were divided into three groups depending on type of cancer and chemotherapy: group I - patients diagnosed with non- small cells lung cancer treated with PE schema (cisplatin, etoposide), group II - with breast cancer treated with FAC schema (fluorouracil, doxorubicin, cyclophosphamide), group Ill - bowel cancer treated with FU/LV schema (fluorouracil, leucovorin). Examinations were performed before chemotherapy and after Il'th, IV'th, VI'th chemotherapy cycle. Conjuntival specimen were obtained with exfoliative cytology, stained with PAS and hematoxyline. Statistically significant deterioration of conjunctival epithelium and goblet cells in all the groups in each time of examination (p<0.001) was observed. Alterations were aggravated with duration of chemotherapy. Before chemotherapy all the patients had normal epithelium and goblet cells (grade 0 or 1 according to the Nelson's scale). Conjunctival cells status gradually deteriorated and altered from the normal glandular epithelium to the squamous cells epithelium through the process of squamous metaplasia. In further chemotherapy cycles each patient (1,0 fraction) had abnormal morphology of epithelium and goblet cells (grade 2 or 3 of Nelson's scale). Chemotherapy induces squamous metaplasia of epithelium and the reduction of number of conjunctival goblet cells. This abnormalities were time dependent and increased with duration of chemotherapy and were not depended on type of chemotherapy scheme.

  5. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development.

  6. Growth inhibitory effect and apoptosis induced by extracellular ATP and adenosine on human gastric carcinoma cells: involvement of intracellular uptake of adenosine

    Institute of Scientific and Technical Information of China (English)

    Ming-xia WANG; Lei-ming REN

    2006-01-01

    Aim: To study the growth inhibitory and apoptotic effects of adenosine triphosphate (ATP) and adenosine (ADO) on human gastric carcinoma (HGC)-27 cells in vitro and the mechanisms related to the actions of ATP and ADO. Methods: MTT assay was used to determine the reduction of cell viability. The morphological changes of HGC-27 cells induced by ATP or ADO were observed under fluorescence light microscope by acridine orange/ethidium bromide double-stained cells. The internucleosomal fragmentation of genomic DNA was detected by agarose gel electrophoresis. The apoptotic rate and cell-cycle analysis after treatment with ATP or ADO was determined by flow cytometry. Results: ATP, ADO and the intermediate metabolites, ADP and AMP, and the agonist of purinergic receptors, reduced cell viability of HGC-27 cells at doses of 0.3 and 1.0 mmol·L-1. The distribution of cell cycle phase and proliferation index (PI) value of HGC-27 cells changed when exposed to ATP or ADO at the concentrations of 0.1,0.3 and 1 mmol/L for 48 h. ATP and ADO both altered the distribution of cell cycle phase via Go/G1-phase arrest and significantly decreased PI value. Under light microscope, the tumor cells exposed to 0.3 mmol·L-1 ATP or ADO displayed morphological changes of apoptosis; a ladder-like pattern of DNA fragmentation obtained from HGC-27 cells treated with 0.1-1 mmol·L-1 ATP or ADO appeared in agarose gel electrophoresis; ATP and ADO induced the apoptosis of HGC-27 cells in a dose-dependent manner at concentrations between 0.03-1 mmol·L-1. The maximum apoptotic rate of HGC-27 cells exposed to ATP or ADO for 48 h was 13.53% or 15.9%, respectively. HGC-27 cell death induced by ATP or ADO was significantly inhibited by dipy-ridamole (10 mmol·L-1), an inhibitor of adenosine transporter, but was not affected by aminophylline, a broad inhibitor of PI receptors and pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetrasodium salt (30 nmol·L-1), a non-selective antagonist of P2

  7. Coronary microembolization does not induce acute preconditioning against infarction in pigs-the role of adenosine.

    Science.gov (United States)

    Skyschally, Andreas; Schulz, Rainer; Gres, Petra; Konietzka, Ina; Martin, Claus; Haude, Michael; Erbel, Raimund; Heusch, Gerd

    2004-08-01

    After coronary microembolization (ME) adenosine is released from ischemic areas of the microembolized myocardium. This adenosine dilates vessels in adjacent nonembolized myocardium and increases coronary blood flow. For ischemic preconditioning (IP) to protect the myocardium against infarction, an increase in the interstitial adenosine concentration (iADO) prior to the subsequent ischemia/reperfusion is necessary. We hypothesized that the adenosine release after ME is sufficient to increase iADO and protect the myocardium against infarction from subsequent ischemia/reperfusion. We have therefore compared myocardial protection by either coronary microembolization or ischemic preconditioning prior to ischemia/reperfusion. In anesthetized pigs, the left anterior descending (LAD) was cannulated and perfused from an extracorporeal circuit. In 11 pigs, sustained ischemia was induced by 85% inflow reduction for 90 min (controls). Two other groups of pigs were subjected either to IP (n = 8; 10-min ischemia/15-min reperfusion) or coronary ME (n = 9; i.c. microspheres; 42 microm Ø; 3000 x ml(-1) x min inflow) prior to sustained ischemia. Coronary venous adenosine concentration (vADO) and iADO (microdialysis) were measured. Infarct size was determined after 2-h reperfusion by triphenyl tetrazolium chloride staining. In pigs subjected to IP, infarct size was reduced to 2.6 +/- 1.1% (mean +/- S.E.M.) vs. 17.0 +/- 3.2% in controls. iADO was increased from 2.4 +/- 1.3 to 13.1 +/- 5.8 micromol x l(-1) during the reperfusion following IP. In pigs subjected to ME, at 10 min after ME, coronary blood flow (38.6 +/- 3.6 to 53.6 +/- 4.3 ml x min(-1)) and vADO (0.25 +/- 0.04 to 0.48 +/- 0.07 micromol x l(-1)) were increased. However, iADO (2.0 +/- 0.5 at baseline vs. 2.3 +/- 0.6 micromol x l(-1) at 10 min after ME) did not increase. Infarct size induced by sustained ischemia following ME (22.5 +/- 5.2%) was above that of controls for any given subendocardial blood flow. ME released

  8. Chemotherapy-Induced Peripheral Neuropathy: Current Status and Progress

    OpenAIRE

    Brewer, Jamie R; Morrison, Gladys; Dolan, M Eileen; Gini F Fleming

    2015-01-01

    As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, wit...

  9. Neoadjuvant chemotherapy or chemoradiotherapy for locally advanced esophageal cancer.

    Science.gov (United States)

    Smithers, B Mark; Thomson, Iain

    2013-11-01

    In patients with operable esophageal cancer, there is evidence supporting the use of preoperative chemotherapy or preoperative chemoradiation. The addition of radiotherapy to chemotherapy seems more relevant for the more locally advanced cancers. There is a need to examine in trials more modern chemotherapy combinations with and without concurrent radiation and for research into assessing methods for predicting outcomes from neoadjuvant therapy as part of the paradigm of therapy for this disease.

  10. Regulation of adenosine triphosphate-sensitive potassium channels suppresses the toxic effects of amyloid-beta peptide (25-35)

    Institute of Scientific and Technical Information of China (English)

    Min Kong; Maowen Ba; Hui Liang; Peng Shao; Tianxia Yu; Ying Wang

    2013-01-01

    In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nω-nitro-L-arginine, also protected PC12 cells from intracellular reactive oxygen species levels. However, the H2O2-degrading enzyme catalase could that the increases in both mitochondrial membrane potential and reactive oxygen species levels adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β

  11. Protective effects of inhibition of adenosine monophosphate activated protein kinase activity against cerebral ischemia-reperfusion injury in mice

    Institute of Scientific and Technical Information of China (English)

    补娟

    2013-01-01

    Objective To observe the effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on shape,function and inflammatory factor of microglia for mice after cerebral ischemia-reperfusion

  12. Comparison of adenosine stress and dobutamine stress by real-time myocardial contrast echocardiography in detecting myocardium ischemia in dogs

    Institute of Scientific and Technical Information of China (English)

    XING Yan-qiu; HOU Bo-wen; ZHANG Yun; LIU Xiang-qun; GAO Hai-qing

    2009-01-01

    spectively. Conclusions Even small distal infarcts can be detected by RTPI; peri-infarct ischemia can be accurately recognized by RTPI during stress; adenosine and dobutamine stress appear equally reliable in the RTPI evaluation of peri-infarct ischemia.

  13. Gastric carcinoma: curative resection and adjuvant chemotherapy.

    Science.gov (United States)

    Carrillo Hernández, J F; Ernesto de Obaldía Castillo, G; Ramírez Ortega, C; Frías Mendivil, M; Pardo, M

    1994-01-01

    A retrospective study of gastric adenocarcinoma treated with surgery as curative attempt was performed at the Oncology Service, in the Hospital Regional 20 de Noviembre, ISSSTE. Morbidity and mortality of the surgical procedures were evaluated, the significance of several risk factors and the survival impact of adjuvant chemotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC). In the period from 1975 to 1991 a total of 483 new cases were seen. In only 54 patients (11.2%) was it possible to undertake a curative resection. The patients were assigned to three groups of treatment: surgery alone (14 cases), surgery + 5-FU (19 cases), and surgery + 5-FU+MMC (21 cases). Three different types of surgical techniques are regularly performed in our service for gastric cancer treatment: Billroth II distal gastrectomy, total gastrectomy with Roux-En-Y reconstruction, and esophagogastrectomy with esophagogastrostomy. Surgical morbidity and mortality was low, with 9% of duodenal stump fistulas and 27% with partial stenosis of esophagojejunostomy; the operative mortality was zero. Chemotherapy toxicity was transient and low, no related deaths were recorded. The prognostic factors associated significantly with survival were lymph node status and tumor penetration. The histologic differentiation as well as the tumor location and type of surgery had no significance. The estimated 5-year survival of the patients treated with surgery alone was 62%, while that of the patients treated with surgery plus chemotherapy was 38%. These groups were not comparable, however, because of important differences in their prognostic factors. The groups treated with 5-FU alone or in combination with MMC had no survival difference between them.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Pain in chemotherapy-induced peripheral neurotoxicity.

    Science.gov (United States)

    Marmiroli, Paola; Scuteri, Arianna; Cornblath, David R; Cavaletti, Guido

    2017-09-01

    Chemotherapy-induced peripheral neurotoxicity (CIPN) is a potentially dose-limiting side effect of the treatment of several cancers. CIPN is predominantly or exclusively sensory, and it is frequently associated with unpleasant symptoms, overall referred to as "pain." However, given the markedly different clinical presentation and course of CIPN depending on the antineoplastic drug used, the broad term "pain" in the specific context of CIPN needs to be reconsidered and refined. In fact, a precise identification of the features of CIPN has relevant implication in the design of rational-based clinical trials and in the selection of possible active drugs. © 2017 Peripheral Nerve Society.

  15. Anaphylaxis to chemotherapy and monoclonal antibodies.

    Science.gov (United States)

    Castells, Mariana C

    2015-05-01

    Hypersensitivity reactions are increasingly prevalent, although underrecognized and underreported. Platins induce immunoglobulin E-mediated sensitization; taxenes and some monoclonal antibodies can induce reactions at first exposure. Severe hypersensitivity can preclude first-line therapy. Tryptase level at the time of a reaction is a useful diagnostic tool. Skin testing provides a specific diagnosis. Newer tests are promising diagnostic tools to help identify patients at risk before first exposure. Safe management includes rapid drug desensitization. This review provides information regarding the scope of hypersensitivity and anaphylactic reactions induced by chemotherapy and biological drugs, as well as diagnosis, management, and treatment options.

  16. Anti-tumor immunity, autophagy and chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Gy(o)rgyi Müzes; Ferenc Sipos

    2012-01-01

    Autophagy or self-digestion of cells is activated upon various stressful stimuli and has been found to be a survival and drug resistance pathway in cancer.However,genetic studies support that autophagy can act as a tumor suppressor.Furthermore,defective autophagy is implicated in tumorigenesis,as well.The precise impact of autophagy on malignant transformation has not yet been clarified,but recent data suggest that this complex process is mainly directed by cell types,phases,genetic background and microenvironment.Relation of autophagy to anticancer immune responses may indicate a novel aspect in cancer chemotherapy.

  17. Timing of chemotherapy and surgery in a murine osteosarcoma model.

    Science.gov (United States)

    Bell, R S; Roth, Y F; Gebhardt, M C; Bell, D F; Rosenberg, A E; Mankin, H J; Suit, H D

    1988-10-01

    The sequential use of chemotherapy and surgery in the treatment of osteosarcoma developed in an empirical fashion without the benefit of investigations in animal models. The MGH-OGS murine osteosarcoma is a transplantable tumor that resembles the human disease with respect to histology, local invasiveness, metastatic characteristics, tumor ploidy, and its response to chemotherapy. We have used this tumor model to investigate the efficacy of preoperative, perioperative, and postoperative chemotherapy on the development of pulmonary metastases in three different experimental protocols. In each experimental design, perioperative chemotherapy demonstrated a significant advantage in preventing systemic relapse.

  18. Ischemic preconditioning protects post-ischemic renal function in anesthetized dogs: role of adenosine and adenine nucleotides

    Institute of Scientific and Technical Information of China (English)

    Fan-zhu LI; Shoji KIMURA; Akira NISHIYAMA; Matlubur RAHMAN; Guo-xing ZHANG; Youichi ABE

    2005-01-01

    Aim: To investigate the effects of renal ischemic preconditioning (IPC) on both renal hemodynamics and the renal interstitial concentrations of adenosine and adenine nucleotides induced by ischemia-reperfusion injury.Methods: Renal hemodynamics responses to ischemia-reperfusion injury in mongrel dog models were determined with or without multiple brief renal ischemic preconditioning treatments, as well as the adenosine A1 receptor antagonist (KW-3902),respectively.The renal interstitial concentrations of adenosine and adenine nucleotides in response to ischemia-reperfusion injury, either following 1-3 cycles of IPC or not, were measured simultaneously using microdialysis sampling technology.Results: One 10-min IPC, adenosine A1 receptor antagonist (KW3902) also shortened the recovery time of renal blood flow (RBF) and urine flow (UF), as well as mean blood pressure (BP).Advanced renal IPC attenuated the increment of adenosine and adenine nucleotides, as well as recovery time during the 60-min reperfusion which followed the 60-min renal ischemia.All of these recovery times were dependent on the cycles of 10-min IPC.The renal interstitial concentrations of adenosine and adenine nucleotides increased and decreased during renal ischemia and reperfusion, respectively.Conclusion: A significant relativity in dog models exists between the cycles of 10-min renal IPC and the recovery time of BP, UF, and RBF during the 60-min renal reperfusion following 60-min renal ischemia, respectively.Renal IPC can protect against ischemiareperfusion injury and the predominant effect of endogenous adenosine induced by prolonged renal ischemia; renal adenosine A1 receptor activation during the renal ischemia-reperfusion injury is detrimental to renal function.

  19. Activation of NTS A(1) adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex.

    Science.gov (United States)

    Ichinose, Tomoko K; Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2012-09-01

    Previously we have shown that adenosine operating via the A(1) receptor subtype may inhibit glutamatergic transmission in the baroreflex arc within the nucleus of the solitary tract (NTS) and differentially increase renal (RSNA), preganglionic adrenal (pre-ASNA), and lumbar (LSNA) sympathetic nerve activity (ASNA>RSNA≥LSNA). Since the cardiopulmonary chemoreflex and the arterial baroreflex are mediated via similar medullary pathways, and glutamate is a primary transmitter in both pathways, it is likely that adenosine operating via A(1) receptors in the NTS may differentially inhibit regional sympathetic responses evoked by activation of cardiopulmonary chemoreceptors. Therefore, in urethane-chloralose-anesthetized rats (n = 37) we compared regional sympathoinhibition evoked by the cardiopulmonary chemoreflex (activated with right atrial injections of serotonin 5HT(3) receptor agonist phenylbiguanide, PBG, 1-8 μg/kg) before and after selective stimulation of NTS A(1) adenosine receptors [microinjections of N(6)-cyclopentyl adenosine (CPA), 0.033-330 pmol/50 nl]. Activation of cardiopulmonary chemoreceptors evoked differential, dose-dependent sympathoinhibition (RSNA>ASNA>LSNA), and decreases in arterial pressure and heart rate. These differential sympathetic responses were uniformly attenuated in dose-dependent manner by microinjections of CPA into the NTS. Volume control (n = 11) and blockade of adenosine receptor subtypes in the NTS via 8-(p-sulfophenyl)theophylline (8-SPT, 1 nmol in 100 nl) (n = 9) did not affect the reflex responses. We conclude that activation of NTS A(1) adenosine receptors uniformly inhibits neural and cardiovascular cardiopulmonary chemoreflex responses. A(1) adenosine receptors have no tonic modulatory effect on this reflex under normal conditions. However, when adenosine is released into the NTS (i.e., during stress or severe hypotension/ischemia), it may serve as negative feedback regulator for depressor and sympathoinhibitory reflexes

  20. Sleep-Wake Regulation and Its Impact on Working Memory Performance: The Role of Adenosine

    Directory of Open Access Journals (Sweden)

    Carolin Franziska Reichert

    2016-02-01

    Full Text Available The sleep-wake cycle is regulated by a fine-tuned interplay between sleep-homeostatic and circadian mechanisms. Compelling evidence suggests that adenosine plays an important role in mediating the increase of homeostatic sleep pressure during time spent awake and its decrease during sleep. Here, we summarize evidence that adenosinergic mechanisms regulate not only the dynamic of sleep pressure, but are also implicated in the interaction of homeostatic and circadian processes. We review how this interaction becomes evident at several levels, including electrophysiological data, neuroimaging studies and behavioral observations. Regarding complex human behavior, we particularly focus on sleep-wake regulatory influences on working memory performance and underlying brain activity, with a specific emphasis on the role of adenosine in this interplay. We conclude that a change in adenosinergic mechanisms, whether exogenous or endogenous, does not only impact on sleep-homeostatic processes, but also interferes with the circadian timing system.

  1. Adenosine A2B receptor: from cell biology to human diseases

    Science.gov (United States)

    Sun, Ying; Huang, Pingbo

    2016-08-01

    Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide array of biological processes. Recently, significant advances have been made in our understanding of A2B adenosine receptor (A2BAR). In this review, we first summarize some of the general characteristics of A2BAR, and then we describe the multiple binding partners of the receptor, such as newly identified α-actinin-1 and p105, and discuss how these associated proteins could modulate A2BAR’s functions, including certain seemingly paradoxical functions of the receptor. Growing evidence indicates a critical role of A2BAR in cancer, renal disease, and diabetes, in addition to its importance in the regulation of vascular diseases and lung disease. Here, we also discuss the role of A2BAR in cancer, renal disease, and diabetes and the potential of the receptor as a target for treating these three diseases.

  2. Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report

    Science.gov (United States)

    Shakiba, Marjan; Mahjoub, Fatemeh; Fazilaty, Hassan; Rezagholizadeh, Fereshteh; Shakiba, Arghavan; Ziadlou, Maryam; Gahl, William A.; Behnam, Babak

    2016-01-01

    Hypermethioninemia may be benign, present as a nonspecific sign of nongenetic conditions such as liver failure and prematurity, or a severe, progressive inborn error of metabolism. Genetic causes of hypermethioninemia include mitochondrial depletion syndromes caused by mutations in the MPV17 and DGUOK genes and deficiencies of cystathionine β-synthase, methionine adenosyltransferase types I and III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase, citrin, fumarylacetoacetate hydrolase, and adenosine kinase. Here we present a 3-year old girl with a history of poor feeding, irritability, respiratory infections, cholestasis, congenital heart disease, neurodevelopmental delay, hypotonia, sparse hair, facial dysmorphisms, liver dysfunction, severe hypermethioninemia and mild homocystinemia. Genetic analysis of the adenosine kinase (ADK) gene revealed a previously unreported variant (c.479–480 GA>TG) resulting in a stop codon (p.E160X) in ADK. A methionine-restricted diet normalized the liver function test results and improved her hypotonia. PMID:27500280

  3. A Case of Hypogammaglobulinemia with Enteroviral Meningoencephalitis, Associated with Increased Adenosine Deaminase in Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Alborizi Abdolvahab

    2009-06-01

    Full Text Available We describe the development of enterovirus meningoencephalitis associated with increased adenosine deaminase in cerebrospinal fluid of a 12-year-old boy, a known case of hypogamaglobulinemia despite monthly replacement of IVIg.The patient was referred to our center with fever, headache and vomiting for 10 days. CSF analysis was compatible with aseptic meningoencephalitis but high CSF protein (>200mg/dl and high level of adenosine deaminase in CSF (30IU/L were against the diagnosis of simple viral meningoencephalitis. Nested PCR of CSF for entrovirus was positive. Treatment with daily high-dose IVIg was commenced, with significant clinical improvement. For patients with increased ADA and lymphocytic pleocytosis in CSF, differential diagnoses should include enteroviral meningitis. Antibodies, although crucial, cannot on their own prevent enteroviral infection in some hypogamaglbulinemic patients.

  4. CD73-Generated Adenosine: Orchestrating the Tumor-Stroma Interplay to Promote Cancer Growth

    Directory of Open Access Journals (Sweden)

    Bertrand Allard

    2012-01-01

    Full Text Available Despite the coming of age of cancer immunotherapy, clinical benefits are still modest. An important barrier to successful cancer immunotherapy is that tumors employ a number of mechanisms to facilitate immune escape, including the production of anti-inflammatory cytokines, the recruitment of regulatory immune subsets, and the production of immunosuppressive metabolites. Significant therapeutic opportunity exists in targeting these immunosuppressive pathways. One such immunosuppressive pathway is the production of extracellular adenosine by CD73, an ectonucleotidase overexpressed in various types of cancer. We hereafter review the biology of CD73 and its role in cancer progression and metastasis. We describe the role of extracellular adenosine in promoting tumor growth through paracrine and autocrine action on tumor cells, endothelial cells, and immune cells.

  5. Synthesis and Pharmacological Evaluation of Modified Adenosines Joined to Mono-Functional Platinum Moieties

    Directory of Open Access Journals (Sweden)

    Stefano D'Errico

    2014-07-01

    Full Text Available The synthesis of four novel platinum complexes, bearing N6-(6-amino-hexyladenosine or a 1,6-di(adenosin-N6-yl-hexane respectively, as ligands of mono-functional cisplatin or monochloro(ethylendiamineplatinum(II, is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of the adenosine base system and a primary amine of an alkyl chain installed on the C6 position of the purine. The cytotoxic behaviour of the synthesized complexes has been studied in A549 adenocarcinomic human alveolar basal epithelial and MCF7 human breast adenocarcinomic cancer cell lines, in order to investigate their effects on cell viability and proliferation.

  6. Interaction of Divalent Metal Ions with the Adenosine Triphosphate Measured Using Nuclear Magnetic Resonance

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The interaction of adenosine triphosphate with divalent metal ions is important in biochemical functions. The effects of pH and metal ions Mg2+, Ca2+, Zn2+, Mn2+, and Co2+ on the chemical shift of the phosphate group of ATP have been studied using Nuclear Magnetic Resonance. The chemical shift of the β-phosphate of ATP is the most sensitive to pH. Ca2+ and Mg2+ bind with the α- and β-phosphate groups of ATP. Zn2+ binds to the adenosine ring hydrogen as well as to phosphate. The paramagnetic ions Mn2+ and Co2+ do not cause chemical shifts of the phosphate or proton peak. Mn2+ and Co2+ broaden the resonance peak only.

  7. Delayed emesis: moderately emetogenic chemotherapy (single-day chemotherapy regimens only)

    DEFF Research Database (Denmark)

    Roila, Fausto; Warr, David; Aapro, Matti

    2011-01-01

    An update of the recommendations for the prophylaxis of delayed emesis induced by moderately emetogenic chemotherapy discussed during the third Perugia Consensus Conference (June 2009) sponsored by MASCC-ESMO was presented. The review considered new studies published since the second consensus co...

  8. Differential effects of the adenosine A1 receptor agonist adenosine amine congener on renal, femoral and carotid vascular conductance in preterm fetal sheep.

    Science.gov (United States)

    Booth, Lindsea C; Tummers, Leonie; Jensen, Ellen C; Barrett, Carolyn J; Malpas, Simon C; Gunn, Alistair J; Bennet, Laura

    2008-11-01

    1. Adenosine A(1) receptor activation is critical for endogenous neuroprotection from hypoxia-ischaemia, raising the possibility that treatment with A(1) receptor agonists may be an effective physiological protection strategy for vulnerable preterm infants. However, the A(1) receptor can mediate unwanted systemic effects, including vasoconstriction of the afferent glomerular arteriole. There is limited information on whether this occurs at doses that improve cerebral perfusion in the immature brain. 2. Therefore, in the present study, we examined whether infusion of the selective A(1) receptor agonist adenosine amine congener (ADAC) is associated with reduced renal perfusion in chronically instrumented preterm (0.7 gestation) fetal sheep. In the present study, ADAC was given in successive doses of 2.5, 5.0 and 15.0 microg, 45 min apart. 3. Treatment with ADAC was associated with a marked reduction in renal vascular conductance (and blood flow), whereas carotid conductance was increased and there was no significant effect on femoral conductance. In contrast with the stable effects of increasing ADAC dose on vascular conductance, there was a significant dose-related fall in fetal heart rate and blood pressure. 4. In conclusion, these short-term data support the concern that A(1) receptor agonist infusion can selectively impair renal perfusion, even at low doses.

  9. Efficient retrovirus-mediated transfer and expression of a human adenosine deaminase gene in diploid skin fibroblasts from an adenosine deaminase-deficient human

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, T.D.; Hock, R.A.; Osborne, W.R.A.; Miller, A.D.

    1987-02-01

    Skin fibroblasts might be considered suitable recipients for therapeutic genes to cure several human genetic diseases; however, these cells are resistant to gene transfer by most methods. The authors studied the ability of retroviral vectors to transfer genes into normal human diploid skin fibroblasts. Retroviruses carrying genes for neomycin or hygromycin B resistance conferred drug resistance to greater than 50% of the human fibroblasts after a single exposure to virus-containing medium. This represents at least a 500-fold increase in efficiency over other methods. Transfer was achieved in the absence of helper virus by using amphotropic retrovirus-packaging cells. A retrovirus vector containing a human adenosine deaminase (ADA) cDNA was constructed and used to infect ADA/sup -/ fibroblasts from a patient with ADA deficiency. The infected cells produced 12-fold more ADA enzyme than fibroblasts from normal individuals and were able to rapidly metabolize exogenous deoxyadenosine and adenosine, metabolites that accumulate in plasma in ADA-deficient patients and are responsible for the severe combined immunodeficiency in these patients. These experiments indicate the potential of retrovirus-mediated gene transfer into human fibroblasts for gene therapy.

  10. Adenosine kinase inhibition protects against cranial radiation-induced cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Munjal M Acharya

    2016-06-01

    Full Text Available Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting, however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK. Adult rats exposed to cranial irradiation (10 Gy showed significant declines in performance of hippocampal-dependent cognitive function tasks (novel place recognition, novel object recognition, and contextual fear conditioning 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the fear conditioning task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP. Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection also against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS

  11. Microcontroller-assisted compensation of adenosine triphosphate levels: instrument and method development.

    Science.gov (United States)

    Hu, Jie-Bi; Chen, Ting-Ru; Chen, Yu-Chie; Urban, Pawel L

    2015-01-30

    In order to ascertain optimum conditions for biocatalytic processes carried out in vitro, we have designed a bio-opto-electronic system which ensures real-time compensation for depletion of adenosine triphosphate (ATP) in reactions involving transfer of phosphate groups. The system covers ATP concentration range of 2-48 μM. The report demonstrates feasibility of the device operation using apyrase as the ATP-depleting enzyme.

  12. Adenosine Preconditioning versus Ischemic Preconditioning in Patients undergoing Off-Pump Coronary Artery Bypass (OPCAB

    Directory of Open Access Journals (Sweden)

    SeyedKhalil Forouzannia

    2015-10-01

    Full Text Available Background: During off-pump coronary artery bypass (OPCAB, the heart is subjected to ischemic and reperfusion injury. Preconditioning is a mechanism that permits the heart to tolerate myocardial ischemia. The aim of this study was to compare the effects of Adenosine preconditioning with ischemic preconditioning on the global ejection fraction (EF in patients undergoing OPCAB.Methods: In this single-blind, randomized controlled trial, sixty patients undergoing OPCAB were allocated into three equally-numbered groups through simple randomization: Adenosine group, ischemic group, and control group. The patients in the Adenosine group received an infusion of Adenosine. In the ischemic group, ischemic preconditioning was induced by the temporary occlusion of the left anterior descending coronary artery twice for a 2-minute period, followed by 3-minute reperfusion before bypass grafting of the first coronary vessel. The control group received an intravenous infusion of 0.9% saline. Blood samples at different times were sent for the measurement of creatine kinase isoenzyme MB (CK-MB and cardiac troponin I (cTnI. We also recorded electrocardiographic indices and clinical parameters, including postoperative use of inotropic drugs and preoperative and postoperative EF.Results: History of myocardial infarction, hyperlipidemia, diabetes mellitus, kidney disease, preoperative arrhythmias, and utilization of postoperative inotrope was the same between the three groups. The incidence of postoperative arrhythmias was not significant between the three groups. Also, there were no significant differences in preoperative and postoperative EF and the serum levels of enzymes (cTnI and CK-MB between the groups.Conclusion: Based on the findings of this study, there was no significant difference in the postoperative EF between the groups. Although the incidence of arrhythmias was higher in the ischemic preconditioning group than in the other groups, the difference

  13. Synthesis and characterization of chemically anchored adenosine with PHEMA grafted gold nanoparticles

    Science.gov (United States)

    Bach, Long Giang; Islam, Md. Rafiqul; Jeong, Yeon Tae; Gal, Yeong Soon; Lim, Kwon Taek

    2012-01-01

    The synthesis of chemically anchored adenosine with biocompatible poly(2-hydroxylethyl methacrylate) grafted gold nanoparticles (Ado-i-PHEMA-g-AuNPs) was realized by employing a simple strategy. Disulfide-containing poly(2-hydroxylethyl methacrylate) (DT-PHEMA) was initially synthesized by atom transfer radical polymerization (ATRP). The formation of DT-PHEMA was confirmed by 1H-NMR and FT-IR. The molecular weight and molecular weight distribution were found to be 9.6 kg/mol and 1.40 from GPC analysis. DT-PHEMA was subsequently used for the synthesis of PHEMA-g-AuNPs by a grafting to protocol. The grafting of DT-PHEMA on the surface of AuNPs was confirmed by FT-IR, TGA, XPS, and EDX analyses. The particle size of the PHEMA-g-AuNPs was found to be ca. 5.0 nm from HR-TEM analysis. Boronic acid was used for functionalization of PHEMA-g-AuNPs, which was then subjected for covalent immobilization with adenosine via strong interaction between free hydroxyl groups of adenosine and boronic acid. Characterization and properties of the Ado-i-PHEMA-g-AuNPs were investigated by taking advantage from FT-IR, XPS, EDX, and UV-visible spectroscopy. The Ado-i-PHEMA-g-AuNPs nanocomposite exhibits a surface plasmon resonance peak at 586 nm which is red shifted from AuNPs (521 nm), indicating significant changes of surface property upon PHEMA-adenosine immobilization onto the surface of AuNPs.

  14. Anticonvulsant activity of B2, an adenosine analog, on chemical convulsant-induced seizures.

    Directory of Open Access Journals (Sweden)

    Min Li

    Full Text Available Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6-(3-methoxyl-4-hydroxybenzyl adenine riboside (B2 is a N(6-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP, pentylenetetrazol (PTZ, picrotoxin, kainite acid (KA, or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A1 and A2A receptors. Furthermore, DPCPX, a selective A1 receptor antagonist, but not SCH58261, a selective A2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A1 receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy.

  15. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency.

    OpenAIRE

    Montiel-Equihua, C. A.; Thrasher, A. J.; Gaspar, H B

    2009-01-01

    The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID) and especially adenosine deaminase (ADA)-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. P...

  16. Expression of Drosophila adenosine deaminase in immune cells during inflammatory response.

    Science.gov (United States)

    Novakova, Milena; Dolezal, Tomas

    2011-03-11

    Extra-cellular adenosine is an important regulator of inflammatory responses. It is generated from released ATP by a cascade of ectoenzymes and degraded by adenosine deaminase (ADA). There are two types of enzymes with ADA activity: ADA1 and ADGF/ADA2. ADA2 activity originates from macrophages and dendritic cells and is associated with inflammatory responses in humans and rats. Drosophila possesses a family of six ADGF proteins with ADGF-A being the main regulator of extra-cellular adenosine during larval stages. Herein we present the generation of a GFP reporter for ADGF-A expression by a precise replacement of the ADGF-A coding sequence with GFP using homologous recombination. We show that the reporter is specifically expressed in aggregating hemocytes (Drosophila immune cells) forming melanotic capsules; a characteristic of inflammatory response. Our vital reporter thus confirms ADA expression in sites of inflammation in vivo and demonstrates that the requirement for ADA activity during inflammatory response is evolutionary conserved from insects to vertebrates. Our results also suggest that ADA activity is achieved specifically within sites of inflammation by an uncharacterized post-transcriptional regulation based mechanism. Utilizing various mutants that induce melanotic capsule formation and also a real immune challenge provided by parasitic wasps, we show that the acute expression of the ADGF-A protein is not driven by one specific signaling cascade but is rather associated with the behavior of immune cells during the general inflammatory response. Connecting the exclusive expression of ADGF-A within sites of inflammation, as presented here, with the release of energy stores when the ADGF-A activity is absent, suggests that extra-cellular adenosine may function as a signal for energy allocation during immune response and that ADGF-A/ADA2 expression in such sites of inflammation may regulate this role.

  17. Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction.

    Science.gov (United States)

    Acharya, Munjal M; Baulch, Janet E; Lusardi, Theresa A; Allen, Barrett D; Chmielewski, Nicole N; Baddour, Al Anoud D; Limoli, Charles L; Boison, Detlev

    2016-01-01

    Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal-dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered

  18. P2X receptors regulate adenosine diphosphate release from hepatic cells.

    Science.gov (United States)

    Chatterjee, Cynthia; Sparks, Daniel L

    2014-12-01

    Extracellular nucleotides act as paracrine regulators of cellular signaling and metabolic pathways. Adenosine polyphosphate (adenosine triphosphate (ATP) and adenosine diphosphate (ADP)) release and metabolism by human hepatic carcinoma cells was therefore evaluated. Hepatic cells maintain static nanomolar concentrations of extracellular ATP and ADP levels until stress or nutrient deprivation stimulates a rapid burst of nucleotide release. Reducing the levels of media serum or glucose has no effect on ATP levels, but stimulates ADP release by up to 10-fold. Extracellular ADP is then metabolized or degraded and media ADP levels fall to basal levels within 2-4 h. Nucleotide release from hepatic cells is stimulated by the Ca(2+) ionophore, ionomycin, and by the P2 receptor agonist, 2'3'-O-(4-benzoyl-benzoyl)-adenosine 5'-triphosphate (BzATP). Ionomycin (10 μM) has a minimal effect on ATP release, but doubles media ADP levels at 5 min. In contrast, BzATP (10-100 μM) increases both ATP and ADP levels by over 100-fold at 5 min. Ion channel purinergic receptor P2X7 and P2X4 gene silencing with small interference RNA (siRNA) and treatment with the P2X inhibitor, A438079 (100 μM), decrease ADP release from hepatic cells, but have no effect on ATP. P2X inhibitors and siRNA have no effect on BzATP-stimulated nucleotide release. ADP release from human hepatic carcinoma cells is therefore regulated by P2X receptors and intracellular Ca(2+) levels. Extracellular ADP levels increase as a consequence of a cellular stress response resulting from serum or glucose deprivation.

  19. Gene therapy for severe combined immunodeficiency due to adenosine deaminase deficiency.

    Science.gov (United States)

    Montiel-Equihua, Claudia A; Thrasher, Adrian J; Gaspar, H Bobby

    2012-02-01

    The severe combined immunodeficiency caused by the absence of adenosine deaminase (SCID-ADA) was the first monogenic disorder for which gene therapy was developed. Over 30 patients have been treated worldwide using the current protocols, and most of them have experienced clinical benefit; importantly, in the absence of any vector-related complications. In this document, we review the progress made so far in the development and establishment of gene therapy as an alternative form of treatment for ADA-SCID patients.

  20. Effects of an induced adenosine deaminase deficiency on T-cell differentiation in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Barton, R.W.

    1985-10-15

    Inherited deficiency of the enzyme adenosine deaminase (ADA) has been found in a significant proportion of patients with severe combined immunodeficiency disease and inherited defect generally characterized by a deficiency of both B and T cells. Two questions are central to understanding the pathophysiology of this disease: (1) at what stage or stages in lymphocyte development are the effects of the enzyme deficiency manifested; (2) what are the biochemical mechanisms responsible for the selective pathogenicity of the lymphoid system. We have examined the stage or stages of rat T-cell development in vivo which are affected by an induced adenosine deaminase deficiency using the ADA inhibitors, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and 2'-deoxycoformycin (DCF). In normal rats given daily administration of an ADA inhibitor, cortical thymocytes were markedly depleted; peripheral lymphocytes and pluripotent hemopoietic stem cells (CFU-S) all were relatively unaffected. Since a deficiency of ADA affects lymphocyte development, the regeneration of cortical and medullary thymocytes and their precursors after sublethal irradiation was used as a model of lymphoid development. By Day 5 after irradiation the thymus was reduced to 0.10-0.5% of its normal size; whereas at Days 9 and 14 the thymus was 20-40% and 60-80% regenerated, respectively. When irradiated rats were given daily parenteral injections of the ADA inhibitor plus adenosine or deoxyadenosine, thymus regeneration at Days 9 and 14 was markedly inhibited, whereas the regeneration of thymocyte precursors was essentially unaffected. Thymus regeneration was at least 40-fold lower than in rats given adenosine or deoxyadenosine alone. Virtually identical results were obtained with both ADA inhibitors, EHNA and DCF.

  1. A3 Adenosine Receptors Modulate Hypoxia-inducible Factor-1a Expression in Human A375 Melanoma Cells

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    Stefania Merighi

    2005-10-01

    Full Text Available Hypoxia-inducible factor-1 (HIF-1 is a key regulator of genes crucial to many aspects of cancer biology. The purine nucleoside, adenosine, accumulates within many tissues under hypoxic conditions, including that of tumors. Because the levels of both HIF-1 and adenosine are elevated within the hypoxic environment of solid tumors, we investigated whether adenosine may regulate HIF-1. Here we show that, under hypoxic conditions (< 2% 02, adenosine upregulates HIF-1α protein expression in a dose-dependent and timedependent manner, exclusively through the A3 receptor subtype. The response to adenosine was generated at the cell surface because the inhibition of A3 receptor expression, by using small interfering RNA, abolished nucleoside effects. A3 receptor stimulation in hypoxia also increases angiopoietin-2 (Ang-2 protein accumulation through the induction of HIF-1α. In particular, we found that A3 receptor stimulation activates p44/p42 and p38 mitogen-activated protein kinases, which are required for A3-induced increase of HIF-1a and Ang-2. Collectively, these results suggest a cooperation between hypoxic and adenosine signals that ultimately may lead to the increase in HIF-1-mediated effects in cancer cells.

  2. Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on ocular blood flow in rabbits.

    Science.gov (United States)

    Konno, Takashi; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2007-02-27

    Previously, we reported that a relatively selective adenosine A(2A) receptor agonist 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) elicited ocular hypotension in rabbits (Journal of Pharmacological Sciences 2005;97:501-509). In the present study, we investigated the effect of 2-CN-Ado on ocular blood flow in rabbit eyes. An intravitreal injection of 2-CN-Ado increased ocular blood flow, measured by a non-contact laser flowmeter. 2-CN-Ado-induced increase in ocular blood flow was accompanied with the retinal vasodilation. The increase in ocular blood flow was inhibited by an adenosine A(2A) receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, but not by an adenosine A(2B) receptor antagonist alloxazine or an adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. The repetitive applications of topical 2-CN-Ado twice a day for 7 days produced a persistent increase in ocular blood flow with ocular hypotension. These results suggest that 2-CN-Ado increases the ocular blood flow mainly via adenosine A(2A) receptor, and that the topical application of 2-CN-Ado for several days not only increases the ocular blood flow but also prolong ocular hypotension, indicating that 2-CN-Ado may be a useful lead compound for the treatment of ischemic retinal diseases such as glaucoma.

  3. Value of the adenosine test for diagnosis of dual AV nodal physiology in patients with AV nodal reentrant tachycardia

    Institute of Scientific and Technical Information of China (English)

    周斌全; 胡申江; 鲁端; 王建安

    2002-01-01

    Objectives: This study was aimed at assessing the value of the adenosine test for noninvasive diagnosis of dual AV nodal physiology(DAVNP) in patients with AV nodal reentrant tachycardia (AVNRT). Methods: 53 patients with paroxysmal supraventricular tachycardia (PSVT) were given incremental doses of adenosine intravenously during sinus rhythm before electrophysiological study. The adenosine test was repeated on a subset of 18 patients with AVNRT after radiofrequency catheter ablation. Results: Sudden increments of PR interval of more than 60 msec between two consecutive beats were observed in 26(83.9%) of 31 patients with typical AVNRT and 2 (9.1%) of 22 patients with AVRT and AT (P<0.01). The maximal PR increment between 2 consecutive beats in the AVNRT group(105±45ms) was significantly greater than that in the AVRT and AT group (20±13ms) (P<0.01).In postablation adenosine test, DAVNP was eliminated in all 8 patients who underwent slow pathway abolition that EPS showed the slow pathway disappeared and 4 of 10 patients who underwent slow pathway modification that EPS showed the slow pathway persisted. Six of 10 patients who exhibited persistent duality showed a marked reduction in the number of beats conducted in the slow pathway after adenosine injection(P<0.01).Conclusions: Administration of adenosine during sinus rhythm may be a useful bedside test for diagnosis of DAVNP in high percentage of patients with typical AVNRT and additionally for evaluating the effects of radiofrequency ablation.

  4. An enzyme-free strategy for ultrasensitive detection of adenosine using a multipurpose aptamer probe and malachite green.

    Science.gov (United States)

    Zhao, Hui; Wang, Yong-Sheng; Tang, Xian; Zhou, Bin; Xue, Jin-Hua; Liu, Hui; Liu, Shan-Du; Cao, Jin-Xiu; Li, Ming-Hui; Chen, Si-Han

    2015-08-01

    We report on an enzyme-free and label-free strategy for the ultrasensitive determination of adenosine. A novel multipurpose adenosine aptamer (MAAP) is designed, which serves as an effective target recognition probe and a capture probe for malachite green. In the presence of adenosine, the conformation of the MAAP is converted from a hairpin structure to a G-quadruplex. Upon addition of malachite green into this solution, a noticeable enhancement of resonance light scattering was observed. The signal response is directly proportional to the concentration of adenosine ranging from 75 pM to 2.2 nM with a detection limit of 23 pM, which was 100-10,000 folds lower than those obtained by previous reported methods. Moreover, this strategy has been applied successfully for detecting adenosine in human urine and blood samples, further proving its reliability. The mechanism of adenosine inducing MAAP to form a G-quadruplex was demonstrated by a series of control experiments. Such a MAAP probe can also be used to other strategies such as fluorescence or spectrophotometric ones. We suppose that this strategy can be expanded to develop a universal analytical platform for various target molecules in the biomedical field and clinical diagnosis.

  5. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

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    Ji-feng FENG

    2015-06-01

    Full Text Available Objective: To explore the clinical efficacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL. Methods: A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efficacy and related adverse reactions of 2 groups were observed. Results: The rate of complete remission (CR in observational group was significantly higher than in control group (χ2=4.6589, P=0.0309. However, there was no significant difference in objective remission rate (ORR between 2 groups (P=0.3651. The rates of 3-year overall survival (OS, progression-free survival (PFS and disease-free survival (DFS were 80.30% (53/66, 69.70% (46/66 and 59.09% (39/66 in observational group, and 61.29% (19/31, 58.06% (18/31 and 58.06% (18/31 in control group, respectively. The OS in observational group was significantly longer than in control group (P=0.035. However, there was no significant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089; P=0.438; χ2=0.1562, P=0.6927. Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the first-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  6. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    FENG Ji-feng

    2015-01-01

    Objective:To explore the clinical efifcacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL). Methods:A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efifcacy and related adverse reactions of 2 groups were observed. Results:The rate of complete remission (CR) in observational group was signiifcantly higher than in control group (χ2=4.6589,P=0.0309). However, there was no signiifcant difference in objective remission rate (ORR) between 2 groups (P=0.3651). The rates of 3-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were 80.30% (53/66), 69.70% (46/66) and 59.09% (39/66) in observational group, and 61.29% (19/31), 58.06% (18/31) and 58.06% (18/31) in control group, respectively. The OS in observational group was signiifcantly longer than in control group (P=0.035). However, there was no signiifcant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089;P=0.438;χ2=0.1562,P=0.6927). Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the ifrst-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  7. Role of nitric oxide in adenosine-induced vasodilation in humans

    Science.gov (United States)

    Costa, F.; Biaggioni, I.; Robertson, D. (Principal Investigator)

    1998-01-01

    Vasodilation is one of the most prominent effects of adenosine and one of the first to be recognized, but its mechanism of action is not completely understood. In particular, there is conflicting information about the potential contribution of endothelial factors. The purpose of this study was to explore the role of nitric oxide in the vasodilatory effect of adenosine. Forearm blood flow responses to intrabrachial adenosine infusion (125 microg/min) were assessed with venous occlusion plethysmography during intrabrachial infusion of saline or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (12.5 mg/min). Intrabrachial infusions of acetylcholine (50 microg/min) and nitroprusside (3 microg/min) were used as a positive and negative control, respectively. These doses were chosen to produce comparable levels of vasodilation. In a separate study, a second saline infusion was administered instead of L-NMMA to rule out time-related effects. As expected, pretreatment with L-NMMA reduced acetylcholine-induced vasodilation; 50 microg/min acetylcholine increased forearm blood flow by 150+/-43% and 51+/-12% during saline and L-NMMA infusion, respectively (Pvasodilation is not mediated by nitric oxide in the human forearm.

  8. Electrophysiologic effects of adenosine triphosphate on rabbit sinoatrial node pace maker cells via P1 receptors

    Institute of Scientific and Technical Information of China (English)

    RENLei-Ming; LIJun-Xia; SHIChen-Xia; ZHAODing

    2003-01-01

    AIM: To study the electrophysiologic effects of adenosine triphosphate (ATP) on rabbit sinoatrial node pacemakercells and the receptors related with the action of ATP. METHODS: Intracellular microelectrode method was usedto record the parameters of action potential (AP) in the rabbit sinoatrial nodes. RESULTS: ATP (0.1-3 mmol/L)decreased the rate of pacemaker firing (RPF) by 16 %-43 % and velocity of diastolic depolarization (VDD) by 33 %-67 %, increased the amplitude of AP (APA) by 6 %-9 % and maximal rate of depolarization (Vmax) by 30 %-76 %,shortened APD50 by 7 %-12 % and APD90 by 6.3 %-9 %, concentration-dependently. The effects of ATP, adenos-ine (Ado), and adenosine diphosphate at the same concentration on AP were not different from each other significantly.Neither uridine triphosphate nor, α,β-methylene ATP had significant electrophysiologic effects on the sinoatrialnode of rabbits. Both the electrophysiologic effects of ATP and Ado on pacemaker cells were inhibited by P1receptor antagonist aminophylline 0.1 mmol/L (P0.05). CONCLUSION: There are nofunctional P2X1 and P2Y2 receptors on pacemaker cells of the rabbit sinoatrial nodes, and the electrophysiologiceffects of ATP in the rabbit sinoatrial node pacemaker cells are mediated via P1 receptors by Ado degraded fromATP.

  9. Identification and function of adenosine A3 receptor in afferent arterioles.

    Science.gov (United States)

    Lu, Yan; Zhang, Rui; Ge, Ying; Carlstrom, Mattias; Wang, Shaohui; Fu, Yiling; Cheng, Liang; Wei, Jin; Roman, Richard J; Wang, Lei; Gao, Xichun; Liu, Ruisheng

    2015-05-01

    Adenosine plays an important role in regulation of renal microcirculation. All receptors of adenosine, A1, A2A, A2B, and A3, have been found in the kidney. However, little is known about the location and function of the A3 receptor in the kidney. The present study determined the expression and role of A3 receptors in mediating the afferent arteriole (Af-Art) response and studied the interaction of A3 receptors with angiotensin II (ANG II), A1 and A2 receptors on the Af-Art. We found that the A3 receptor expressed in microdissected isolated Af-Art and the mRNA levels of A3 receptor were 59% of A1. In the isolated microperfused Af-Art, A3 receptor agonist IB-MECA did not have a constrictive effect. Activation of A3 receptor dilated the preconstricted Af-Art by norepinephrine and blunted the vasoconstrictive effect of both adenosine A1 receptor activation and ANG II on the Af-Art, respectively. Selective A2 receptor antagonist (both A2A and A2B) had no effect on A3 receptor agonist-induced vasodilation, indicating that the dilatory effect of A3 receptor activation is not mediated by activation of A2 receptor. We conclude that the A3 receptor is expressed in the Af-Art, and activation of the A3 receptor dilates the Af-Art.

  10. Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney

    Directory of Open Access Journals (Sweden)

    Ayodele Jacob Akinyemi

    2017-04-01

    Full Text Available In this study, the effect of enzymes involved in degradation of renal adenosine and l-arginine was investigated in rats exposed to cadmium (Cd and treated with curcumin, the principal active phytochemical in turmeric rhizome. Animals were divided into six groups (n = 6: saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. The results of this study revealed that the activities of renal adenosine deaminase and arginase were significantly increased in Cd-treated rats when compared with the control (p < 0.05. However, co-treatment with curcumin inhibits the activities of these enzymes compared with Cd-treated rats. Furthermore, Cd intoxication increased the levels of some renal biomarkers (serum urea, creatinine, and electrolytes and malondialdehyde level with a concomitant decrease in functional sulfhydryl group and nitric oxide (NO. However, co-treatment with curcumin at 12.5 mg/kg and 25 mg/kg, respectively, increases the nonenzymatic antioxidant status and NO in the kidney, with a concomitant decrease in the levels of malondialdehyde and renal biomarkers. Therefore, our results reinforce the importance of adenosine deaminase and arginase activities in Cd poisoning conditions and suggest some possible mechanisms of action by which curcumin prevent Cd-induced renal toxicity in rats.

  11. Effect of caffeine and adenosine on G2 repair: mitotic delay and chromosome damage.

    Science.gov (United States)

    González-Fernández, A; Hernández, P; López-Sáez, J F

    1985-04-01

    Proliferating plant cells treated during the late S period with 5-aminouracil (AU), give the typical response that DNA-damaging agents induce, characterized by: an important mitotic delay, and a potentiation of the chromosome damage by caffeine post-treatment. The study of labelled prophases, after a tritiated thymidine pulse, allowed evaluation of the mitotic delay induced by AU as well as its reversion by caffeine, while chromosome damage was estimated by the percentage of anaphases and telophases showing chromosomal aberrations. Post-treatment with adenosine alone has shown no effect on mitotic delay or chromosomal damage. However, when cells after AU were incubated in caffeine plus adenosine, the chromosome damage potentiation was abolished without affecting the caffeine action on mitotic delay. As a consequence, we postulate that caffeine could have two effects on G2 cells with damaged DNA: the first, to cancel their mitotic delay and the second to inhibit some DNA-repair pathway(s). Only this last effect could be reversed by adenosine.

  12. Carbohydrate management, anaerobic metabolism, and adenosine levels in the armoured catfish, Liposarcus pardalis (castelnau), during hypoxia.

    Science.gov (United States)

    Maccormack, Tyson James; Lewis, Johanne Mari; Almeida-Val, Vera Maria Fonseca; Val, Adalberto Luis; Driedzic, William Robert

    2006-04-01

    The armoured catfish, Liposarcus pardalis, tolerates severe hypoxia at high temperatures. Although this species can breathe air, it also has a strong anaerobic metabolism. We assessed tissue to plasma glucose ratios and glycogen and lactate in a number of tissues under "natural" pond hypoxia, and severe aquarium hypoxia without aerial respiration. Armour lactate content and adenosine in brain and heart were also investigated. During normoxia, tissue to plasma glucose ratios in gill, brain, and heart were close to one. Hypoxia increased plasma glucose and decreased tissue to plasma ratios to less than one, suggesting glucose phosphorylation is activated more than uptake. High normoxic white muscle glucose relative to plasma suggests gluconeogenesis or active glucose uptake. Excess muscle glucose may serve as a metabolic reserve since hypoxia decreased muscle to plasma glucose ratios. Mild pond hypoxia changed glucose management in the absence of lactate accumulation. Lactate was elevated in all tissues except armour following aquarium hypoxia; however, confinement in aquaria increased armour lactate, even under normoxia. A stress-associated acidosis may contribute to armour lactate sequestration. High plasma lactate levels were associated with brain adenosine accumulation. An increase in heart adenosine was triggered by confinement in aquaria, although not by hypoxia alone.

  13. N-ethyl-carboxamide adenosine inhibits perioral dyskinesias induced by sulpiride + SKF 38393 in rabbits.

    Science.gov (United States)

    Caporali, M G; Scotti de Carolis, A; Popoli, P

    1992-11-13

    A pattern of perioral dyskinesia was induced in adult male rabbits by concomitant stimulation of dopamine D1 receptors (SKF 38393) and blockade of dopamine D2 receptors (sulpiride). Rabbits treated with sulpiride (6 and 12.5 mg/kg i.v.) then, 90 min thereafter, with SKF 38393 (0.1, 1 and 10 mg/kg i.v.) showed a pattern of perioral dyskinesia characterized by compulsive and repetitive sniffing, licking and vacuous chewing. These effects were completely prevented by the administration of N-ethylcarboxamide adenosine (NECA), an A2 > A1 adenosine receptor agonist. The present results confirm that perioral dyskinesia is dependent on the activation of dopamine D1 receptors. They also show that, in order to induce perioral dyskinesia in rabbits, a concomitant blockade of dopamine D2 receptors is required. Finally, the antagonistic effect of NECA on the appearance of perioral movements confirms that adenosine receptors play a key role in the control of dopamine-mediated effects.

  14. Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats

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    Zhenzhen Hu

    2013-01-01

    Full Text Available Cordycepin (3′-deoxyadenosine is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs, like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs. Sleep was recorded using electroencephalogram (EEG for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM sleep. Interestingly, cordycepin increased θ (theta waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.

  15. Drug Cocktail Optimization in Chemotherapy of Cancer

    Science.gov (United States)

    Preissner, Saskia; Dunkel, Mathias; Hoffmann, Michael F.; Preissner, Sarah C.; Genov, Nikolai; Rong, Wen Wei; Preissner, Robert; Seeger, Karlheinz

    2012-01-01

    Background In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP). Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. Objective The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. Data sources and methods Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. Results We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy. PMID:23236419

  16. Drug cocktail optimization in chemotherapy of cancer.

    Directory of Open Access Journals (Sweden)

    Saskia Preissner

    Full Text Available BACKGROUND: In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP. Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. OBJECTIVE: The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. DATA SOURCES AND METHODS: Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. RESULTS: We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy.

  17. The role of intravitreal chemotherapy for retinoblastoma

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    Fairooz P Manjandavida

    2015-01-01

    Full Text Available Targeted therapy in retinoblastoma (RB is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC, retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

  18. Sensitivity of Interstitial combined Chemotherapy against Glioma

    Institute of Scientific and Technical Information of China (English)

    WANG Ming-sheng; LIN Jian-ying; ZHOU Guo-sheng; ZHANG Xin-zhong

    2006-01-01

    Objective To investigate the inhibitory effects of combination chemotherapy of Carboplatin(CBP) ,Teniposide (Vm-26) ,Methasquin(MTX),and Nimodipine(NIM) on glioma,and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells,and to compare the sensitivity of glioma cells to administration of CBP,Vm-26, MTX, and NIM with that of the administration of CBP + NIM, Vm-26 + NIM, MTX + NIM, CBP + Vm-26 + MTX, or CBP + Vm-26 + MTX + NIM respectively. Results The inhibition rate of CBP + Vm-26 + MTX + NIM combination administration against glioma cells was 96.64%,which was higher than that of CBP + NIM (69.03%), Vm-26 + NIM (71.53%), MTX + NIM (52. 75% ), CBP + Vm-26 + MTX(78.59%)(P<0.01),and the dosage of CBP,Vm-26,and MTX was declined to 1/10 ~ 1/100 that of respective use of CBP,Vm-26,and MTX. Conclusions The curative effects of combination administration of CBP,Vm-26, MTX, and NIM was much better than that of respective administration,suggesting a higher inhibition rate and a lower dosage use.

  19. Induction of cancer cell stemness by chemotherapy.

    Science.gov (United States)

    Hu, Xingwang; Ghisolfi, Laura; Keates, Andrew C; Zhang, Jian; Xiang, Shuanglin; Lee, Dong-ki; Li, Chiang J

    2012-07-15

    Recent studies indicate that cancer stem cells (CSCs) exist in most hematological and solid tumors. CSCs are characterized by their ability to self-renew and their capacity to differentiate into the multitude of cells that comprise the tumor mass. Moreover, these cells have been shown to be intrinsically resistant to conventional anticancer therapies. Despite their fundamental role in cancer pathogenesis, the cellular origin of CSCs remains highly controversial. The aim of this study was to examine whether heterogeneous cancer cells can acquire stem cell-like properties in response to chemotherapy. We demonstrate that carboplatin can induce the self-renewal (spherogenesis) and pluripotency (Sox2 and Oct3/4 expression) of hepatocellular carcinoma (HCC) cells grown under stem cell culture conditions. Moreover, we show that non-CSC cells, obtained by side population flow cytometric sorting using Hoechst 33342, can acquire stem-like properties after exposure to carboplatin. Finally, we show that knockdown of Sox2 and Oct3/4 gene expression in HCC cells can reduce carboplatin-mediated increases in sphere formation and increase cellular sensitivity to chemotherapy. Taken together, our data indicate that bulk cancer cells may be an important source of CSCs during tumor development, and that targeting Sox2 and/or Oct3/4 may be a promising approach for targeting CSCs in clinical cancer treatment.

  20. Cancer chemotherapy and cardiac arrhythmias: a review.

    Science.gov (United States)

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2015-02-01

    Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC) that increases the morbidity and mortality of cancer patients. Cardiac arrhythmias have been reported as an adverse effect of many chemotherapeutic drugs, including novel targeted therapies. The relationship between chemotherapy and arrhythmias has not been well-established and the proarrhythmogenic mechanisms remain uncertain as they can be the result of a direct electrophysiological effect or of changes in cardiac structure and function, including myocardial ischaemia and heart failure, which create an arrhythmogenic substrate. In this review we summarise available evidence of proarrhythmia induced by CC, discuss the possible mechanisms involved in this adverse effect and emphasise the importance of cardiac monitoring for the early diagnosis, intervention and surveillance of those patients more susceptible to develop proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists should be fully aware of proarrhythmia and the close collaboration between cardiologists and oncologists would result in a better cardiovascular assessment, risk stratification, cardiac monitoring and treatment during CC and during the follow-up. The final objective is to understand the mechanisms of proarrhythmia and evaluate its real incidence and clinical relevance so as to select the safest and most effective treatment for cancer patients.

  1. Thermotherapy, chemotherapy, and meristem culture in banana.

    Science.gov (United States)

    Lassois, Ludivine; Lepoivre, Philippe; Swennen, Rony; van den Houwe, Ines; Panis, Bart

    2013-01-01

    Bananas that provide a staple food to the millions of people are adversely affected by several viruses such as Banana bunchy Top Virus (BBTV), Banana Streak Virus (BSV), and Cucumber Mosaic Virus (CMV). These viruses are known to have a devastating effect on crop production and constraint to the international exchange and conservation of banana germplasm-a cornerstone for breeding new cultivars. The viruses are particularly problematic in vegetative propagated crops, like bananas, because of their transmission in the planting material. Different virus eradication techniques have been developed, such as thermotherapy, chemotherapy, and meristem culture for providing virus-free planting material. Meristem culture proved to be the most effective procedure to eradicate phloem-associated viruses. This method requires isolation of meristematic dome of plant under the aseptic conditions and culture in an appropriate nutrient medium to develop new virus-free plants. Thermotherapy is another widely used virus eradication technique, which is initially carried out on in vivo or in vitro plants and eventually combined with meristem culture technique. The plantlets are initially grown at 28°C day temperature and increase it by 2°C per day until reaches 40°C and the night temperature at 28°C; maintain plants at 40°C for 4 weeks; excise meristem and culture onto the regeneration medium. In chemotherapy technique, antiviral chemical compound Virazole(®) is applied on meristem culture. Combination of these techniques is also applied to improve the eradication rate.

  2. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, J; Deasy, J O [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2014-06-15

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.

  3. Effective chemotherapy induce apoptosis in vivo in patients with leukemia

    Institute of Scientific and Technical Information of China (English)

    岑溪南; 朱平; 虞积仁; 石永进; 马明信

    2003-01-01

    Objective To investigate apoptosis in vivo in patients with leukemia at different stages of the first cycle of chemotherapy.Methods We detected apoptosis of HL-60 cells and peripheral blood leukemia cells in 17 patients at different stages, using in situ terminal deoxynucleotidyl transferase (TdT) fluorescence measurement and DNA electrophoresis. Results When HL-60 cells were incubated with 0.02 mg/L harringtonine for 0 to 48 hours, agarose gel electrophoresis showed that DNA ladder patterns became evident only at 12 hour into the treatment. In situ TdT assay showed that apoptotic cells occurred after one hour of the treatment. Apoptotic cells were few (0-3.3%) before chemotherapy, but increased substantially (11.4%-87.5%) during chemotherapy in patients with complete remission (CR) or partial remission (PR). Apoptotic cells were few (0-6.1%) during chemotherapy in ten patients with no remission (NR). DNA ladder cannot be detected by agarose gel electrophoresis either before, during or after chemotherapy. Wilcoxon signed rank test shows: P=0.0012<0.01, apoptotic cells during chemotherapy were present in greater quantity than prior to chemotherapy. Wilcoxon rank sum test shows: P=0.0011<0.01, with the median of apoptotic cells during chemotherapy in patients with CR or PR more than with NR.Conclusions TdT assay can be used to detect apoptotic cells earlier and more sensitively than DNA agarose gel electrophoresis. In situ TdT assay is useful to detect apoptosis in vivo in the initial phase of chemotherapy for immediate modification of the chemotherapy regimen, whereas electrophoretic analysis is not sensitive enough to detect apoptotic cell in vivo. Where the median of apoptotic cells during chemotherapy in patients with CR or PR were greater than with NR, only effective drug therapy could induce apoptosis.

  4. The effect on survival of continuing chemotherapy to near death

    Directory of Open Access Journals (Sweden)

    Ayanian John Z

    2011-09-01

    Full Text Available Abstract Background Overuse of anti-cancer therapy is an important quality-of-care issue. An aggressive approach to treatment can have negative effects on quality of life and cost, but its effect on survival is not well-defined. Methods Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 7,879 Medicare-enrolled patients aged 65 or older who died after having survived at least 3 months after diagnosis of advanced non-small cell lung cancer (NSCLC between 1991 and 1999. We used Cox proportional hazards regression analysis, propensity scores, and instrumental variable analysis (IVA to compare survival among patients who never received chemotherapy (n = 4,345, those who received standard chemotherapy but not within two weeks prior to death (n = 3,235, and those who were still receiving chemotherapy within 14 days of death (n = 299. Geographic variation in the application of chemotherapy was used as the instrument for IVA. Results Receipt of chemotherapy was associated with a 2-month improvement in overall survival. However, based on three different statistical approaches, no additional survival benefit was evident from continuing chemotherapy within 14 days of death. Moreover, patients receiving chemotherapy near the end of life were much less likely to enter hospice (81% versus 51% with no chemotherapy and 52% with standard chemotherapy, P Conclusions Continuing chemotherapy for advanced NSCLC until very near death is associated with a decreased likelihood of receiving hospice care but not prolonged survival. Oncologists should strive to discontinue chemotherapy as death approaches and encourage patients to enroll in hospice for better end-of-life palliative care.

  5. Assessment of quality of life during chemotherapy.

    Science.gov (United States)

    Gunnars, B; Nygren, P; Glimelius, B

    2001-01-01

    Increasingly more aggressive chemotherapy together with expected small differences between treatments with respect to objective endpoints has heightened awareness about the importance of addressing how patients experience and value the impact that treatment has had on their overall life situation. Assessment of a patient's quality of life (QoL) is now conceptually viewed as an important complement to traditional objective evaluation measures. It was therefore considered important to review the basis for the assessment of this endpoint when The Swedish Council of Technology Assessment in Health Care (SBU) performed a systematic overview of chemotherapy effects in several tumour types. The group came to the following conclusions: QoL assessments, mostly by patient self-reporting in questionnaires, have come increasingly into use during the past decade. A number of general, cancer-specific and cancer diagnosis-specific instruments have been developed. There is at present little need for development of new cancer instruments, although specific treatment modalities and tumour types may need new additional modules. A predefined hypothesis should determine the instrument to be used. Since the selection of a QoL instrument in a specific study influences both the results and the conclusions, it is essential to carefully select the instrument or instruments that have the greatest likelihood of identifying relevant differences between treatment alternatives. Interpretation of QoL data is more difficult than interpretation of objective endpoints such as survival time, objective response rates or toxicity. Despite these difficulties, QoL analyses have provided new insights into the advantages and disadvantages of various treatments not provided by traditional end-points. Some palliative treatments seemingly increase patients' QoL despite side-effects or the lack of, or marginal, increases in survival. When using potentially curative chemotherapy, it is not a matter of when the

  6. Role of adipokinetic hormone and adenosine in the anti-stress response in Drosophila melanogaster.

    Science.gov (United States)

    Zemanová, Milada; Stašková, Tereza; Kodrík, Dalibor

    2016-01-01

    The role of adipokinetic hormone (AKH) and adenosine in the anti-stress response was studied in Drosophila melanogaster larvae and adults carrying a mutation in the Akh gene (Akh(1)), the adenosine receptor gene (AdoR(1)), or in both of these genes (Akh(1) AdoR(1) double mutant). Stress was induced by starvation or by the addition of an oxidative stressor paraquat (PQ) to food. Mortality tests revealed that the Akh(1) mutant was the most resistant to starvation, while the AdoR(1) mutant was the most sensitive. Conversely, the Akh(1) AdoR(1) double mutant was more sensitive to PQ toxicity than either of the single mutants. Administration of PQ significantly increased the Drome-AKH level in w(1118) and AdoR(1) larvae; however, this was not accompanied by a simultaneous increase in Akh gene expression. In contrast, PQ significantly increased the expression of the glutathione S-transferase D1 (GstD1) gene. The presence of both a functional adenosine receptor and AKH seem to be important for the proper control of GstD1 gene expression under oxidative stress, however, the latter appears to play more dominant role. On the other hand, differences in glutathione S-transferase (GST) activity among the strains, and between untreated and PQ-treated groups were minimal. In addition, the glutathione level was significantly lower in all untreated AKH- or AdoR-deficient mutant flies as compared with the untreated control w(1118) flies and further declined following treatment with PQ. All oxidative stress characteristics modified by mutations in Akh gene were restored or even improved by 'rescue' mutation in flies which ectopically express Akh. Thus, the results of the present study demonstrate the important roles of AKH and adenosine in the anti-stress response elicited by PQ in a D. melanogaster model, and provide the first evidence for the involvement of adenosine in the anti-oxidative stress response in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Caffeine acts via A1 adenosine receptors to disrupt embryonic cardiac function.

    Directory of Open Access Journals (Sweden)

    Daniela L Buscariollo

    Full Text Available BACKGROUND: Evidence suggests that adenosine acts via cardiac A1 adenosine receptors (A1ARs to protect embryos against hypoxia. During embryogenesis, A1ARs are the dominant regulator of heart rate, and A1AR activation reduces heart rate. Adenosine action is inhibited by caffeine, which is widely consumed during pregnancy. In this study, we tested the hypothesis that caffeine influences developing embryos by altering cardiac function. METHODOLOGY/PRINCIPAL FINDINGS: Effects of caffeine and adenosine receptor-selective antagonists on heart rate were studied in vitro using whole murine embryos at E9.5 and isolated hearts at E12.5. Embryos were examined in room air (21% O(2 or hypoxic (2% O(2 conditions. Hypoxia decreased heart rates of E9.5 embryos by 15.8% and in E12.5 isolated hearts by 27.1%. In room air, caffeine (200 µM had no effect on E9.5 heart rates; however, caffeine increased heart rates at E12.5 by 37.7%. Caffeine abolished hypoxia-mediated bradycardia at E9.5 and blunted hypoxia-mediated bradycardia at E12.5. Real-time PCR analysis of RNA from isolated E9.5 and E12.5 hearts showed that A1AR and A2aAR genes were expressed at both ages. Treatment with adenosine receptor-selective antagonists revealed that SCH-58261 (A2aAR-specific antagonist had no affects on heart function, whereas DPCPX (A1AR-specific antagonist had effects similar to caffeine treatment at E9.5 and E12.5. At E12.5, embryonic hearts lacking A1AR expression (A1AR-/- had elevated heart rates compared to A1AR+/- littermates, A1AR-/- heart rates failed to decrease to levels comparable to those of controls. Caffeine did not significantly affect heart rates of A1AR-/- embryos. CONCLUSIONS/SIGNIFICANCE: These data show that caffeine alters embryonic cardiac function and disrupts the normal cardiac response to hypoxia through blockade of A1AR action. Our results raise concern for caffeine exposure during embryogenesis, particularly in pregnancies with increased risk of

  8. The tyranny of adenosine recognition among RNA aptamers to coenzyme A

    Directory of Open Access Journals (Sweden)

    Frank Joseph

    2003-12-01

    Full Text Available Abstract Background Understanding the diversity of interactions between RNA aptamers and nucleotide cofactors promises both to facilitate the design of new RNA enzymes that utilize these cofactors and to constrain models of RNA World evolution. In previous work, we isolated six pools of high affinity RNA aptamers to coenzyme A (CoA, the principle cofactor in biological acyltransfer reactions. Interpretation of the evolutionary significance of those results was made difficult by the fact that the affinity resin attachment strongly influenced the outcome of those selections. Here we describe the selection of four new pools isolated on a disulfide-linked CoA affinity matrix to minimize context-dependent recognition imposed by the attachment to the solid support. Results The four new aptamer libraries show no sequence or structural relation to a previously dominant CoA-binding species, even though they were isolated from the same initial random libraries. Recognition appears to be limited to the adenosine portion of the CoA – in particular the Höogsteen edge – for most isolates surveyed, even when a counter selection was employed to remove such RNAs. Two of the recovered isolates are eluted with intact CoA more efficiently than with AMP alone suggesting a possible pantotheine interaction. However, a detailed examination of recognition specificity revealed that the 3' phosphate of CoA, and not the pantotheine arm, determined recognition by these two isolates. Conclusion Most aptamers that have been targeted towards cofactors containing adenosine recognize only the adenosine portion of the cofactor. They do not distinguish substituents on the 5' carbon, even when those substituents have offered hydrogen bonding opportunities and the selection conditions discouraged adenosine recognition. Beyond hydrogen bonding, additional factors that guide the selection towards adenosine recognition include aromatic stacking interactions and relatively few

  9. Chemotherapie bij gebruik van clozapine; een verhoogde kans op agranulocytose?

    NARCIS (Netherlands)

    Van Gool, A.R.; Van Der Velden, M.T.; Oosten, A.W.; Van Meerten, E.; Verhoeven, W.M.A.; Loonen, A.J.M.

    2008-01-01

    In a 37-year-old female, a combined treatment consisting of chemotherapy and radiation was considered for cervical cancer. However, she was using clozapine for the treatment of schizophrenia. As both clozapine and chemotherapy can induce decrease of white blood cell counts, we had to decide if cloza

  10. Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-12-01

    Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic.

  11. Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas

    NARCIS (Netherlands)

    Triebels, V H J M; Taphoorn, M J B; Brandes, A A; Menten, J; Frenay, M; Tosoni, A; Kros, J M; Stege, E Biemond-ter; Enting, R H; Allgeier, A; van Heuvel, I; van den Bent, M J

    2004-01-01

    The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma. The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the

  12. Third-line chemotherapy for small cell lung cancer

    NARCIS (Netherlands)

    de Jong, WK; ten Hacken, NHT; Groen, HJM

    2006-01-01

    Efficacy of third-line chemotherapy treatment for small cell lung cancer (SCLC) is unknown. We present our experience with third-tine chemotherapy for recurrent SCLC. Between January 1996 and July 2004 all. consecutive patients treated for SCLC were retrospectively studied. We recorded patient chara

  13. [Prevention and management of appetite loss during cancer chemotherapy].

    Science.gov (United States)

    Tsujimura, Hideki; Yamada, Mitsugi; Asako, Eri; Kodama, Yukako; Sato, Tsuneo; Nabeya, Yoshihiro

    2014-10-01

    Appetite loss during cancer chemotherapy may lead to malnutrition and a decreased quality of life. To overcome this problem, evidence-based guidelines have been established for chemotherapy-induced emesis and mucositis. However, unsolved issues such as taste alimentation remain. Since the clinical picture of appetite loss is complex, individual management strategies depending on the type of the disease and treatment are required.

  14. The effect of chemotherapy on the growing skeleton

    NARCIS (Netherlands)

    van Leeuwen, BL; Kamps, WA; Jansen, HWB; Hoekstra, HJ

    2000-01-01

    With the increasing use of high dose (poly)chemotherapy schedules in the treatment of childhood cancer it is particularly important to know the adverse effects of these treatments. Growth is a complex mechanism affected not only by chemotherapy but also by the malignancy itself as well as nutritiona

  15. Chemotherapy-induced alopecia: advice and support for hair loss.

    Science.gov (United States)

    Roe, Helen

    This article provides insight into the growth cycle of a hair follicle and the potential impact chemotherapy agents can have on this process, which often results in hair loss (alopecia). It explores the psychological consequences of chemotherapy-induced alopecia for an individual as a result of the perceptions of others as well as an individual's perception of his or her self-image. Despite the development of various forms of scalp cooling, chemotherapy-induced alopecia remains a major side effect for patients receiving chemotherapy; however, there have been improvements in wig provision and changing public opinion relating to baldness. Although chemotherapy-induced alopecia affects both males and females and all age groups, this article focuses on the potential impact for patients receiving chemotherapy as a form of treatment for breast cancer. As professionals we need to understand the social significance of hair in relation to a person's outward presentation and social interactions, along with the possible psychological implications of a person losing his or her bodily hair, and not just the head hair. We must aim to minimize the distress alopecia can cause by: ensuring we provide patients with up-to-date verbal and written information to enable them to prepare for losing their hair; helping them to preserve their self-image and minimize the psychological consequences of hair loss while receiving chemotherapy; and preparing them for their hair re-growth following completion of chemotherapy.

  16. Abiraterone in metastatic prostate cancer without previous chemotherapy

    NARCIS (Netherlands)

    Ryan, C.J.; Smith, M.R.; Bono, J. De; Molina, A.; Logothetis, C.J.; Souza, P. de; Fizazi, K.; Mainwaring, P.; Piulats, J.M.; Ng, S.; Carles, J.; Mulders, P.F.A.; Basch, E.; Small, E.J.; Saad, F.; Schrijvers, D.; Poppel, H. van; Mukherjee, S.D.; Suttmann, H.; Gerritsen, W.R.; Flaig, T.W.; George, D.J.; Yu, E.Y.; Efstathiou, E.; Pantuck, A.; Winquist, E.; Higano, C.S.; Taplin, M.E.; Park, Y.; Kheoh, T.; Griffin, T.; Scher, H.I.; Rathkopf, D.E.

    2013-01-01

    BACKGROUND: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. METHODS: In this double-blind study, we

  17. IS CHEMOTHERAPY ASSOCIATED WITH DEVELOPMENT OF BARRETT-ESOPHAGUS

    NARCIS (Netherlands)

    PETERS, FTM; SLEIJFER, DT; VANIMHOFF, GW; KLEIBEUKER, JH

    1993-01-01

    Columnar-lined or Barrett's esophagus is a premalignant condition. It is almost unvariably due to chronic gastroesophageal reflux. Since there are some reports that Barrett's esophagus can be induced by chemotherapy, we investigated 20 male patients, treated with chemotherapy for testicular cancer,

  18. [Intraperitoneal chemotherapy in the treatment of advanced ovarian cancer].

    Science.gov (United States)

    Classe, J-M; Muller, M; Frenel, J-S; Berton Rigaud, D; Ferron, G; Jaffré, I; Gladieff, L

    2010-05-01

    The standard treatment for advanced ovarian cancer consist in complete surgical debulking and intravenous platin and taxane based chemotherapy. Despite research efforts, a lot of patients still die from peritoneal carcinomatosis. The aim of our work was to present the state of art about intraperitoneal chemotherapy. Intraperitoneal chemotherapy (IPC): three multi-institutional randomised trials showed that platin based IPC gave better results in term of overall and disease free survival when compared to standard intravenous treatment. Even so, IPC is not yet becoming a new international standard of treatment because a high rate of morbidity. Hyperthermic Intraperitoneal chemotherapy (HIPEC) represents an innovative alternative to IPC. HIPEC is based on a complete surgical debulking without any visible mass and an intraperitoneal chemotherapy with synergy of hyperthermia. Phase II trails have shown its feasibility. Randomised trials are needed to assess its efficiency in improving survival. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  19. Liver Injury Induced by Anticancer Chemotherapy and Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Y. Maor

    2013-01-01

    Full Text Available Cytotoxic chemotherapy prolongs survival of patients with advanced and metastatic tumors. This is, however, a double-edged sword with many adverse effects. Since the liver has a rich blood supply and plays an active role in the metabolism of medications, it is not surprising that there can be hepatic injury related to chemotherapy. In addition, radioembolization may affect the parenchyma of normal and cirrhotic livers. We review chemotherapy-associated liver injury in patients with colorectal liver metastases, including downsizing chemotherapy and neoadjuvant chemotherapy. We discuss the mechanism of the hepatic injury, secondary to reactive oxygen species, and the spectrum of hepatic injury including, steatosis, steatohepatitis, hepatic sinusoidal injury and highlight the pharmacogenomics of such liver insults. Methods for reducing and treating the hepatotoxicity are discussed for specific agents including tamxifen and the newly introduced targeted antibodies.

  20. Dietetic management in gastrointestinal complications from antimalignant chemotherapy.

    Science.gov (United States)

    Calixto-Lima, L; Martins de Andrade, E; Gomes, A P; Geller, M; Siqueira-Batista, R

    2012-01-01

    Antineoplastic chemotherapy (CT) represents the systemic treatment of malignant tumors. It can be used alone or combined with surgery and / or radiotherapy. The cytotoxic agents used in chemotherapy work on both cancerous cells and noncancerous cells of the body, generally resulting in high toxicity. The biological aggressiveness of chemotherapy particularly affects rapidly replicating cells, such as those of the digestive tract, resulting in adverse effects that impair food intake, leading to compromised nutritional status and which may lead to cachexia. The main toxic effects of chemotherapy in the gastrointestinal tract include nausea, vomiting -these are the most frequent- constipation, diarrhea, xerostomia, mucositis, dysphagia and anorexia. Given the high frequency of such effects, nutritional intervention should be an integral part of cancer treatment, to maintain and/or improve the patient's nutritional status and reduce or minimize the side effects caused by treatment. Accordingly, the goal of this study is to review dietetic conduct in the process of caring for patients undergoing cancer chemotherapy.