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Sample records for adenosine ketogenic diet

  1. Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity.

    Masino, S A; Kawamura, M; Wasser, C D; Wasser, C A; Pomeroy, L T; Ruskin, D N

    2009-09-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  2. Ketogenic Diets and Pain

    Masino, Susan A.; Ruskin, David N.

    2013-01-01

    Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain.

  3. Purines and neuronal excitability: links to the ketogenic diet.

    Masino, S A; Kawamura, M; Ruskin, D N; Geiger, J D; Boison, D

    2012-07-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A(1)Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms. PMID:21880467

  4. Nonfasting Versus Initial Fasting Ketogenic Diet

    J Gordon Millichap

    2005-02-01

    Full Text Available A retrospective evaluation of the ketogenic diet (KD was conducted comparing efficacy and tolerability of the diet with or without initial fasting and fluid restriction and involving university centers in Seoul, Korea.

  5. Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet.

    Rogawski, Michael A; Löscher, Wolfgang; Rho, Jong M

    2016-01-01

    Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement of γ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, such as adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures. PMID:26801895

  6. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

    Villeneuve, Nathalie; Pinton, Florence; Bahi-Buisson, Nadia; Dulac, Olivier; Chiron, Catherine; Nabbout, Rima

    2009-01-01

    Aim: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method: From the 70 patients who received the ketogenic diet during a 3-year period at…

  7. Carnitine Level Changes with the Ketogenic Diet

    J Gordon Millichap

    2002-01-01

    The effects of the ketogenic diet (KD) on carnitine levels were determined in 38 consecutive patients with epilepsy treated at Rush-Presbyterian-St Luke’s Medical Center, Chicago, IL Carnitine levels were determined at 0, 1, 6, 12, and 24 months of diet treatment.

  8. Ketogenic diets, mitochondria, and neurological diseases

    Gano, Lindsey B.; Patel, Manisha; Rho, Jong M

    2014-01-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad...

  9. Childhood Absence Epilepsy Successfully Treated with the Paleolithic Ketogenic Diet

    Clemens, Zsófia; Kelemen, Anna; Fogarasi, András; Tóth, Csaba

    2013-01-01

    Introduction Childhood absence epilepsy is an epilepsy syndrome responding relatively well to the ketogenic diet with one-third of patients becoming seizure-free. Less restrictive variants of the classical ketogenic diet, however, have been shown to confer similar benefits. Beneficial effects of high fat, low-carbohydrate diets are often explained in evolutionary terms. However, the paleolithic diet itself which advocates a return to the human evolutionary diet has not yet been studied in epi...

  10. Ketogenic Diet for Obesity: Friend or Foe?

    Antonio Paoli

    2014-02-01

    Full Text Available Obesity is reaching epidemic proportions and is a strong risk factor for a number of cardiovascular and metabolic disorders such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, and also certain types of cancers. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Genetic predisposition in combination with inactive lifestyles and high caloric intake leads to excessive weight gain. Even though there may be agreement about the concept that lifestyle changes affecting dietary habits and physical activity are essential to promote weight loss and weight control, the ideal amount and type of exercise and also the ideal diet are still under debate. For many years, nutritional intervention studies have been focused on reducing dietary fat with little positive results over the long-term. One of the most studied strategies in the recent years for weight loss is the ketogenic diet. Many studies have shown that this kind of nutritional approach has a solid physiological and biochemical basis and is able to induce effective weight loss along with improvement in several cardiovascular risk parameters. This review discusses the physiological basis of ketogenic diets and the rationale for their use in obesity, discussing the strengths and the weaknesses of these diets together with cautions that should be used in obese patients.

  11. Effects of a ketogenic diet on brain metabolism in epilepsy

    Korsholm, Kirsten; Law, Ian

    2013-01-01

    For a subpopulation of drug-resistant epilepsies, a ketogenic diet constitutes the treatment of choice. A ketogenic diet is a high-fat, low-protein, and low-carbohydrate diet, which induces ketosis. Despite the use in treatment of epilepsy since 1924, the clinical efficacy was not demonstrated in a...... controlled, randomized trial until 2008, showing its capability of reducing seizure frequency with more than 50%. However, the exact mechanism of this form of treatment is still unknown. We report here a patient with drug-resistant epilepsy on a ketogenic diet, where a brain 18F-FDG PET examination...

  12. Ketogenic diets and physical performance

    Phinney SD

    2004-08-01

    Full Text Available Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15-25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.

  13. Ketogenic diets and physical performance

    Phinney Stephen D

    2004-08-01

    Full Text Available Abstract Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.

  14. Glut1 deficiency syndrome and novel ketogenic diets.

    Klepper, Joerg; Leiendecker, Baerbel

    2013-08-01

    The classical ketogenic diet has been used for refractory childhood epilepsy for decades. It is also the treatment of choice for disorders of brain energy metabolism, such as Glut1 deficiency syndrome. Novel ketogenic diets such as the modified Atkins diet and the low glycemic index treatment have significantly improved the therapeutic options for dietary treatment. Benefits of these novel diets are increased palatability, practicability, and thus compliance-at the expense of lower ketosis. As high ketones appear essential to meet the brain energy deficit caused by Glut1 deficiency syndrome, the use of novel ketogenic diets in this entity may be limited. This article discusses the current data on novel ketogenic diets and the implications on the use of these diets in regard to Glut1 deficiency syndrome. PMID:23666044

  15. The Ketogenic Diet 2011: How It Works

    Keren Politi

    2011-01-01

    Full Text Available Although the ketogenic diet (KD has been widely accepted as a legitimate and successful therapy for epilepsy and other neurological disorders, its mechanism of action remains an enigma. The use of the KD causes major metabolic changes. The most significant of them seems to be the situation of chronic ketosis, but there are others as well, for instance, high level of polyunsaturated fatty acids (PUFAs. These “primary” influences lead to “secondary”, in part adaptive, effects, for instance changes in mitochondrial density and gene expression. Clinically, the influences of the diet are considered as anticonvulsive and neuroprotective, although neuroprotection can also lead to prevention of seizures. Potential clinical implications of these mechanisms are discussed.

  16. Mitochondrial Profiles and the Anticonvulsant Effect of the Ketogenic Diet

    J Gordon Millichap

    2006-09-01

    Full Text Available A study of the anticonvulsant effect of the ketogenic diet (KD in adolescent rats, at Emory University and other centers, found that the hippocampus responds by inducing mitochondrial biogenesis, enhancing metabolic gene expression, and increasing energy reserves.

  17. Ketogenic Diet for Epilepsy with Type 1 Diabetes

    J Gordon Millichap

    2010-01-01

    Researchers at Medical University Vienna, Austria, report the efficacy and safety of the ketogenic diet (KD) in treatment of epilepsy in a 3-year 6 month-old girl with diabetes type 1 followed for 15 months.

  18. Ketogenic diets, mitochondria, and neurological diseases.

    Gano, Lindsey B; Patel, Manisha; Rho, Jong M

    2014-11-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate "classic KD", as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

  19. Ketogenic diet and astrocyte/neuron metabolic interactions

    Vamecq Joseph

    2007-05-01

    Full Text Available The ketogenic diet is an anticonvulsant diet enriched in fat. It provides the body with a minimal protein requirement and a restricted carbohydrate supply, the vast majority of calories (more than 80-90% being given by fat. Though anticonvulsant activity of ketogenic diet has been well documented by a large number of experimental and clinical studies, underlying mechanisms still remain partially unclear. Astrocyte-neuron interactions, among which metabolic shuttles, may influence synaptic activity and hence anticonvulsant protection. The astrocyte-neuron metabolic shuttles may be themselves influenced by the availability in energetic substrates such as hydrates of carbon and fats. Historically, ketogenic diet had been designed to mimic changes such as ketosis occurring upon starvation, a physiological state already known to exhibit anticonvulsant protection and sometimes referred to as “water diet”. For this reason, a special attention should be paid to metabolic features shared in common by ketogenic diet and starvation and especially those features that might result in anticonvulsant protection. Compared to feeding by usual mixed diet, starvation and ketogenic diet are both characterised by increased fat, lowered glucose and aminoacid supplies to cells. The resulting impact of these changes in energetic substrates on astrocyte/neuron metabolic shuttles might have anticonvulsant and/or neuroprotective properties. This is the aim of this communication to review some important astrocyte/neuron metabolic interactions (astrocyte/neuron lactate shuttle, glutamateinduced astrocytic glycolysis activation, glutamate/glutamine cycle along with the neurovascular coupling and the extent to which the way of their alteration by starvation and/or ketogenic diet might result in seizure and/or brain protection.

  20. Ketogenic diet and epilepsy: an up-date review

    Alberto VERROTTI

    2009-12-01

    Full Text Available Background and Aims: Ketogenic diet is currently a therapeutic option for the treatment of epilepsy other than anticonvulsant drugs, for which there is a growing interest in Europe and worldwide, mainly due to the persisting number of refractory patients and the adverse side effects of antiepileptic old and new drugs. Aim of the present article is to review literature data regarding the use of the diet in the different types of epilepsies and epilepsy syndromes, trying to better understand the main evidence-based indications for its use.Material and Methods: A literature search was based on a Medline search of published retrospective, not-controlled prospective and randomized controlled trials on the use of the ketogenic diet for the treatment of epilepsies and antiepileptic encephalopathies. In some instances, case reports were also included. A search on standard textbooks and review articles on the use of the ketogenic diet was considered as well. A summary and a critical appraisal of what emerged from the literature for each epileptic syndrome will be discussed in this review.Conclusions: Ketogenic diet is considered as the primary treatment of GLUT-1 deficiency syndrome and pyruvate-dehydrogenase deficiency. It is so far included as secondary option for the so called “catastrophic epileptic encephalopaties of childhood”, and should be a potential treatment against a wide variety of other seizure types and epilepsy syndromes as well as many symptomatic localization-related epilepsies. The best evidence of its efficacy regards refractory infantile spasms, Dravet syndrome and myoclonic-astatic epilepsy as well as epileptic encephalopathies due to cortical migration disorders. There is also a growing interest for dietary treatments for epilepsy other than ketogenic diet, such as the modified Atkins diet and the low glicemic index diet , both providing a daily amount of fat less than the ketogenic diet. Presently, some authors prefer to use

  1. CSF Amino Acids, Pterins and Mechanism of the Ketogenic Diet

    J. Gordon Millichap

    2015-11-01

    Full Text Available Investigators from Hospital Sant Joan de Deu, Barcelona, Spain, studied the relationship between the etiology of refractory childhood epilepsy, CSF neurotransmitters, pterins, and amino acids, and response to a ketogenic diet in 60 patients with refractory epilepsy, 83% focal and 52% idiopathic.

  2. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets

    GiuseppeBiagini

    2014-04-01

    Full Text Available Various ketogenic diet (KD therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs. In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the

  3. The ketogenic diet and other dietary treatments for refractory epilepsy in children

    Suvasini Sharma

    2014-01-01

    Full Text Available The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed.

  4. The ketogenic diet and other dietary treatments for refractory epilepsy in children.

    Sharma, Suvasini; Jain, Puneet

    2014-07-01

    The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed. PMID:25221391

  5. Ketogenic diet and epilepsy: an up-date review

    Verrotti, Alberto; Pascotto, Antonio; Operto, Francesca; FORTUNATO, Delia; Rita Della CORTE; Coppola, Giangennaro; Alfredo D'Aniello

    2009-01-01

    Background and Aims: Ketogenic diet is currently a therapeutic option for the treatment of epilepsy other than anticonvulsant drugs, for which there is a growing interest in Europe and worldwide, mainly due to the persisting number of refractory patients and the adverse side effects of antiepileptic old and new drugs. Aim of the present article is to review literature data regarding the use of the diet in the different types of epilepsies and epilepsy syndromes, trying to better understand th...

  6. Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets

    GiuseppeBiagini; MaddalenaMarchiò; ElenaTimofeeva

    2014-01-01

    Various ketogenic diet (KD) therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonv...

  7. Ketogenic Diets: Evidence for Short and Long-term Efficacy

    Kossoff, Eric H.; Rho, Jong M

    2009-01-01

    The use of dietary treatments for epilepsy (ketogenic, modified Atkins, and low glycemic index diets) has been in continuous use since 1921. These treatments have been well-studied in the short-term, with approximately 50% of children having at least a 50% reduction in seizures after 6 months. Approximately one-third will have >90% reduction in their seizures as well. Animal studies confirm these findings, with broad evidence demonstrating the diet's acute anticonvulsant effects. In addition,...

  8. The ketogenic diet for type II bipolar disorder.

    Phelps, James R; Siemers, Susan V; El-Mallakh, Rif S

    2013-01-01

    Successful mood stabilizing treatments reduce intracellular sodium in an activity-dependent manner. This can also be achieved with acidification of the blood, as is the case with the ketogenic diet. Two women with type II bipolar disorder were able to maintain ketosis for prolonged periods of time (2 and 3 years, respectively). Both experienced mood stabilization that exceeded that achieved with medication; experienced a significant subjective improvement that was distinctly related to ketosis; and tolerated the diet well. There were no significant adverse effects in either case. These cases demonstrate that the ketogenic diet is a potentially sustainable option for mood stabilization in type II bipolar illness. They also support the hypothesis that acidic plasma may stabilize mood, perhaps by reducing intracellular sodium and calcium. PMID:23030231

  9. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets.

    Giordano, Carmela; Marchiò, Maddalena; Timofeeva, Elena; Biagini, Giuseppe

    2014-01-01

    Various ketogenic diet (KD) therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine) and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin, and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs). In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the neurohormonal

  10. Ketogenic diet in 3 cases of childhood refractory status epilepticus

    Sort, Rune; Born, Alfred P; Pedersen, Karen N.;

    2013-01-01

    Refractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus in...... several cases. We have listed these and reviewed all cases of KD used in RSE at our centre. KD was given as 4:1 fat:carbohydrate-protein solution....

  11. Medium-chain Triglyceride Ketogenic Diet, An Effective Treatment for Drug-resistant Epilepsy and A Comparison with Other Ketogenic Diets

    Yeou-mei Christiana Liu; Huei-Shyong Wang

    2013-01-01

    The ketogenic diet (KD) is one of the most effective therapies for drug-resistant epilepsy. The efficacy of the medium-chain triglyceride KD (MCTKD) is as excellent as the classic KD (CKD), which has been documented in several subsequent retrospective, prospective, and randomized studies. MCT oil is more ketogenic than long-chain triglycerides. Therefore, the MCTKD allows more carbohydrate and protein food, which makes the diet more palatable than the CKD. The MCTKD is not based on diet ratio...

  12. The ketogenic diet and other dietary treatments for refractory epilepsy in children

    Suvasini Sharma; Puneet Jain

    2014-01-01

    The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use o...

  13. Will seizure control improve by switching from the modified Atkins diet to the traditional ketogenic diet?

    Kossoff, Eric H; Bosarge, Jennifer L; Miranda, Maria J;

    2010-01-01

    It has been reported that children can maintain seizure control when the ketogenic diet (KD) is transitioned to the less-restrictive modified Atkins diet (MAD). What is unknown, however, is the likelihood of additional seizure control from a switch from the MAD to the KD. Retrospective information...

  14. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

    De Paoli, A; Rubini, A.; Volek, J S; Grimaldi, K A

    2013-01-01

    Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases...

  15. Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss

    Alonso-Moraga Ángeles

    2008-10-01

    Full Text Available Abstract Background Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine. Methods A prospective study was carried out in 31 obese subjects (22 male and 19 female with the inclusion criteria whose body mass index and age was 36.46 ± 2.22 and 38.48 ± 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD due to the incorporation of virgin olive oil as the principal source of fat (≥30 ml/day, moderate red wine intake (200–400 ml/day, green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12 were analyzed by paired Student's t test. Results There was an extremely significant (p 2→31.76 kg/m2, systolic blood pressure (125.71 mmHg→109.05 mmHg, diastolic blood pressure (84.52 mmHg→ 75.24 mmHg, total cholesterol (208.24 mg/dl→186.62 mg/dl, triacylglicerols (218.67 mg/dl→113.90 mg/dl and glucose (109.81 mg/dl→ 93.33 mg/dl. There was a significant (p = 0.0167 reduction in LDLc (114.52 mg/dl→105.95 mg/dl and an extremely significant increase in HDLc (50.10 mg/dl→54.57 mg/dl. The most affected parameter was the triacylglicerols (47.91% of reduction. Conclusion The SKMD is safe, an effective way of losing weight, promoting non

  16. Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis

    Ye, Fang; Li, Xiao-Jia; Jiang, Wan-Lin; Sun, Hong-Bin; Liu, Jie

    2015-01-01

    Background and Purpose Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice. Methods Electronic searc...

  17. Alternative diets to the classical ketogenic diet-Can we be more liberal?

    Miranda, Maria J; Turner, Zahava; Magrath, Gwyneth

    2012-01-01

    )-KD, modified Atkins diet (MAD) and low glycaemic index treatment (LGIT), compared to the classical KD. The clinical evidence to date suggests that the more liberal versions of the classical KD such as MCT KD, MAD and LGIT have an efficacy close to the classical KD; however, no RCT data are available for MAD......The ketogenic diet (KD), a high-fat, adequate protein, low-carbohydrate diet has been used since 1921 for the treatment of severe medically refractory epilepsy. In the past 15 years, the use of the KD has expanded enormously and a huge amount of clinical evidence of its efficacy is available. The...... classical KD is however restrictive and therefore alternative more liberal varieties of the classical KD have been developed within the last 8 years. The purpose of this report is to summarise the principles and evidence of effectiveness of the alternative ketogenic diets: Medium Chain Triglyceride (MCT...

  18. Will seizure control improve by switching from the Modified Atkins Diet to the traditional Ketogenic Diet?

    Kossoff, Eric H.; Dorward, Jennifer L.; Miranda, Maria J.; Wiemer-Kruel, Adelheid; Kang, Hoon Chul; Kim, Heung Dong

    2010-01-01

    It has been reported that children can maintain seizure control when the ketogenic diet (KD) is transitioned to the less restrictive modified Atkins diet (MAD). What is unknown, however, is the likelihood of additional seizure control from a switch from the MAD to the KD. Retrospective information was obtained from 27 patients who made this dietary change from 4 different institutions. Ten (37%) had ≥10% additional seizure reduction with the KD above the MAD, of which 5 became seizure-free. T...

  19. Renal Stone Associated with the Ketogenic Diet in a 5-Year Old Girl with Intractable Epilepsy

    Choi, Ji Na; Song, Ji Eun; Shin, Jae Il; Kim, Heung Dong; Kim, Myung Joon; Lee, Jae Seung

    2010-01-01

    In this paper, we report on a 5-year-old girl who developed a renal stone while following the ketogenic diet to treat refractory seizure disorder. Three months after initiating the ketogenic diet, she developed severe abdominal pain and vomiting. The spot urine calcium-to-creatinine (Ca/Cr) ratio and 24-hour urine evaluation showed hypercalciuria. Computed tomography (CT) imaging revealed a stone in the right ureteropelvic junction, resulting in hydronephrosis of the right kidney. The renal s...

  20. EFFICACY OF THE KETOGENIC DIET AS A THERAPY FOR INTRACTABLE EPILEPSY IN CHILDREN

    MIRJAVADI Seyed Alireza; TONEKABONI, Seyed Hassan; GHAZAVI, Mohammadreza; Azargashb, Eznollah; ABDOLLAH GORJI, Fatemeh; Mohammad GHOFRANI

    2010-01-01

    ObjectiveTo determine the role of ketogenic diet in the treatment of intractable epilepsy in children.Materials & MethodsSixty six consecutive children (1-16 years old) with intractable epilepsy whose seizure were not neurodegenerative nor febrile in origin were recruited. They received the ketogenic diet and we evaluated its effect on seizure frequency for 3 months. All these children had more than five seizures per week despite adequate therapy with at least 3-4 anticonvulsant medications. ...

  1. Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

    Milene L Brownlow

    Full Text Available Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs, widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition and Tg4510 (a model of tau deposition mice were offered either a ketogenic or a control (NIH-31 diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition.

  2. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report

    Servadei Franco

    2010-04-01

    Full Text Available Abstract Background Management of glioblastoma multiforme (GBM has been difficult using standard therapy (radiation with temozolomide chemotherapy. The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI. Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter. Methods Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET. Results After two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy. Conclusion This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed

  3. Substantial and sustained seizure reduction with ketogenic diet in a patient with Ohtahara syndrome

    Adithya Sivaraju

    2015-01-01

    Full Text Available Ketogenic diet has been shown to be efficacious in some epileptic encephalopathies but rarely reported as being useful in children with Ohtahara syndrome. This could possibly be attributed to the rarity of the disease and associated short survival period. We report on a 5-year-old child with Ohtahara syndrome, whose seizures failed to improve with all known medications, continued to show persistent suppression-burst pattern on the electroencephalography (EEG and had substantial reduction in seizure frequency for one year post-initiation of ketogenic diet. He has not had a single visit to the emergency room because of seizures in the last one year, and more importantly, there has been a clear improvement noted in his level of interaction and temperament. Patients with Ohtahara syndrome invariably have medically intractable seizures and catastrophic neurodevelopmental outcome. Ketogenic diet is a treatment modality that might be worth considering even in this group of patients.

  4. The Ketogenic and Atkins Diets Effect on Intractable Epilepsy: A Comparison

    Ahad GHAZAVI

    2014-07-01

    Full Text Available How to Cite This Article: Ghazavi A, Tonekaboni SH, Karimzadeh P, Nikibakhsh AA, Khajeh A, Fayyazi A. The Ketogenic and Atkins Diets Effect on Intractable Epilepsy: A Comparison. Iran J Child Neurol. 2014 Summer;8(3: 12-17.AbstractObjectiveIntractable epilepsy is a major difficulty in child neurology, because the numbers of drugs that are available for treatment are limited and new treatments such as diets must be tried. Now there are some diets available for treating patients with intractable epilepsy. The oldest diet is the classic ketogenic diet and one of thenewest diets is the modified Atkins diet. Patients have a harder time accepting the classic ketogenic diet than the Atkins diet, which is easier to accept because the food tastes better. This study compares the efficacy of the ketogenic diet and the Atkins diet for intractable epilepsy in children.Materials & MethodsThis study is a clinical trial survey with sample size of 40 children with refractory epilepsy who were patients at Mofid hospital in Tehran, Iran. Initially, from Jan 2005–Oct 2007, 20 children were treated with the Atkins diet, and then from Oct 2007–March 2010, the other group was treated with the classic ketogenic diet and the results were compared. ResultsIn this study, response to treatment was greater than a 50% reduction in seizures and at the end of first, second, and third months for the ketogenic diet were 55%, 30%, and 70% and for the Atkins diet were 50%, 65%, and 70%, respectively.ConclusionThe results of this study show that there is no significant difference between the classic Ketogenic diet and the Atkins diet at the end of first, second, and third months and both had similar responses to the treatments.References Camfield CS, Canfield PR, Gordon K, Wirrell E, Dooley JM. Incidence of epilepsy in childhood and adolescents in Nova Scotia. Epilepsia, 1996 Jan;37(1:19-23.Gessner U, Sagmeister M, Horisberger B. The cost of Epilepsy in

  5. Ketogenic diet does not affect strength performance in elite artistic gymnasts

    Paoli Antonio; Grimaldi Keith; D’Agostino Dominic; Cenci Lorenzo; Moro Tatiana; Bianco Antonino; Palma Antonio

    2012-01-01

    Abstract Background Despite the increasing use of very low carbohydrate ketogenic diets (VLCKD) in weight control and management of the metabolic syndrome there is a paucity of research about effects of VLCKD on sport performance. Ketogenic diets may be useful in sports that include weight class divisions and the aim of our study was to investigate the influence of VLCKD on explosive strength performance. Methods 8 athletes, elite artistic gymnasts (age 20.9 ± 5.5 yrs) were recruited. We anal...

  6. Ketogenic diet for adults in super-refractory status epilepticus

    Thakur, Kiran T.; Probasco, John C.; Hocker, Sara E.; Roehl, Kelly; Henry, Bobbie; Kossoff, Eric H.; Kaplan, Peter W.; Geocadin, Romergryko G.; Hartman, Adam L.; Venkatesan, Arun

    2014-01-01

    Objective: To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). Methods: We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. Results: Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. Conclusion: We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. Classification of evidence: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE. PMID:24453083

  7. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets.

    Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A

    2013-08-01

    Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand. PMID:23801097

  8. Medium-chain Triglyceride Ketogenic Diet, An Effective Treatment for Drug-resistant Epilepsy and A Comparison with Other Ketogenic Diets

    Yeou-mei Christiana Liu

    2013-02-01

    Full Text Available The ketogenic diet (KD is one of the most effective therapies for drug-resistant epilepsy. The efficacy of the medium-chain triglyceride KD (MCTKD is as excellent as the classic KD (CKD, which has been documented in several subsequent retrospective, prospective, and randomized studies. MCT oil is more ketogenic than long-chain triglycerides. Therefore, the MCTKD allows more carbohydrate and protein food, which makes the diet more palatable than the CKD. The MCTKD is not based on diet ratios as is the CKD, but uses a percentage of calories from MCT oil to create ketones. There has also been literature which documents the associated gastrointestinal side effects from the MCTKD, such as diarrhea, vomiting, bloating, and cramps. Therefore, the MCTKD has been an underutilized diet therapy for intractable epilepsy among children.The author has used up to >70% MCTKD diet to maximize seizure control with gastrointestinal side effects optimally controlled. As long as health care professionals carefully manage MCTKD, many more patients with epilepsy who are not appropriate for CKD or modified Atkins diet or low glycemic index treatment will benefit from this treatment. A comparison between the MCTKD and other KDs is also discussed.

  9. Excellent Response to a Ketogenic Diet in a Patient with Alternating Hemiplegia of Childhood

    Roubergue, Anne; Philibert, Bertrand; Gautier, Agnès; Kuster, Alice; Markowicz, Karine; Billette De Villemeur, Thierry; Vuillaumier-Barrot, Sandrine; Nicole, Sophie; Roze, Emmanuel; Doummar, Diane

    2014-01-01

    Alternating hemiplegia of childhood (AHC) is a rare disorder caused by heterozygous mutations in ATP1A3. AHC is associated with early-onset plegic and tonic/dystonic attacks and permanent neurologic deficits. Attacks tend to persist through life. Flunarizine therapy occasionally reduces the severity, duration and frequency of attacks. A ketogenic diet/modified Atkins diet (KD/MAD) can attenuate paroxysmal movement disorders associated with GLUT1 deficiency syndrome (GLUT1DS), but there are no...

  10. THE EFFECT OF THE KETOGENIC DIET ON THE GROWTH AND BIOCHEMICAL PARAMETERS OF THE CHILDREN WITH RESISTANT EPILEPSY

    Mohammadreza ALAEI

    2010-04-01

    Full Text Available ObjectiveThe aim of this study was to evaluate the effect of the ketogenic diet on the growth parameters of the children with resistant epilepsy.Materials & MethodsA total of 36 children with resistant epilepsy who were 2 to 7 year old were put on the ketogenic diet. Their growth and biochemical parameters were studied at the beginning of the study and after 3 months.ResultsWeight decreased in all patients. Serum levels of hemoglobin, calcium, and blood sugar decreased significantly but remained in the normal range. Creatinine did not change, but BUN showed a significant increase.ConclusionWe can lower the complications of ketogenic diets by using more unsaturated fat, more water, and more minerals.Keywords: ketogenic diet, epilepsy, growth parameters, biochemicalparameters, children

  11. The Ketogenic and Atkins Diets Effect on Intractable Epilepsy: A Comparison

    GHAZAVI, Ahad; Seyed Hassan TONEKABONI; Karimzadeh, Parvaneh; Ahmad Ali NIKIBAKHSH; Ali KHAJEH; FAYYAZI, Afshin

    2014-01-01

    How to Cite This Article: Ghazavi A, Tonekaboni SH, Karimzadeh P, Nikibakhsh AA, Khajeh A, Fayyazi A. The Ketogenic and Atkins Diets Effect on Intractable Epilepsy: A Comparison. Iran J Child Neurol. 2014 Summer;8(3): 12-17.AbstractObjectiveIntractable epilepsy is a major difficulty in child neurology, because the numbers of drugs that are available for treatment are limited and new treatments such as diets must be tried. Now there are some diets available for treating patients with intractab...

  12. Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet

    Lussier, Danielle M.; Woolf, Eric C.; Johnson, John L.; Brooks, Kenneth S.; Blattman, Joseph N.; Scheck, Adrienne C.

    2016-01-01

    Background Glioblastoma multiforme is a highly aggressive brain tumor with a poor prognosis, and advances in treatment have led to only marginal increases in overall survival. We and others have shown previously that the therapeutic ketogenic diet (KD) prolongs survival in mouse models of glioma, explained by both direct tumor growth inhibition and suppression of pro-inflammatory microenvironment conditions. The aim of this study is to assess the effects of the KD on the glioma reactive immun...

  13. Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

    Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

    2016-06-01

    Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI. PMID:26785903

  14. Ketogenic Diet, but Not Polyunsaturated Fatty Acid Diet, Reduces Spontaneous Seizures in Juvenile Rats with Kainic Acid-induced Epilepsy

    Dustin, Simone M.; Stafstrom, Carl E

    2016-01-01

    Background and Purpose: The high-fat, low-carbohydrate ketogenic diet (KD) is effective in many cases of drug-resistant epilepsy, particularly in children. In the classic KD, fats consist primarily of long-chain saturated triglycerides. Polyunsaturated fatty acids (PUFAs), especially the n-3 type, decrease neuronal excitability and provide neuroprotection; pilot human studies have raised the possibility of using PUFAs to control seizures in patients. Methods: To determine the relative roles o...

  15. Ketogenic Diet for Children with Epilepsy: A Practical Meal Plan in a Hospital.

    Lee, Eunjoo; Kang, Hoon-Chul; Kim, Heung Dong

    2016-01-01

    A ketogenic diet (KD) is a dietary approach to treat intractable epilepsy. The KD begins with hospitalization and the child and their parents can adapt to the KD for 1-2 weeks. Recently, various type of dietary intervention such as the modified Atkins diet (MAD) and the low glycemic index treatment (LGIT) have been performed. Since 2010, we carried out the KD, MAD, and LGIT for total of 802 patients; 489 patients (61%) for the KD, 147 patients (18.3%) with the MAD, and 166 patients (20.7%) for the LGIT. In this report, application of these dietary practices in Severance Hospital is shared. PMID:26839878

  16. Ketogenic Diet for Children with Epilepsy: A Practical Meal Plan in a Hospital

    Lee, Eunjoo; Kang, Hoon-Chul; Kim, Heung Dong

    2016-01-01

    A ketogenic diet (KD) is a dietary approach to treat intractable epilepsy. The KD begins with hospitalization and the child and their parents can adapt to the KD for 1-2 weeks. Recently, various type of dietary intervention such as the modified Atkins diet (MAD) and the low glycemic index treatment (LGIT) have been performed. Since 2010, we carried out the KD, MAD, and LGIT for total of 802 patients; 489 patients (61%) for the KD, 147 patients (18.3%) with the MAD, and 166 patients (20.7%) fo...

  17. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2014-01-01

    Introduction The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would ...

  18. An unfortunate challenge: Ketogenic diet for the treatment of Lennox-Gastaut syndrome in tyrosinemia type 1.

    De Lucia, Silvana; Pichard, Samia; Ilea, Adina; Greneche, Marie-Odile; François, Laurent; Delanoë, Catherine; Schiff, Manuel; Auvin, Stéphane

    2016-07-01

    The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed. PMID:27052529

  19. THE EFFECT OF THE KETOGENIC DIET ON THE GROWTH AND BIOCHEMICAL PARAMETERS OF THE CHILDREN WITH RESISTANT EPILEPSY

    Mohammadreza ALAEI

    2010-03-01

    Full Text Available ObjectiveThe aim of this study was to evaluate the effect of the ketogenic diet on the growth parameters of the children with resistant epilepsy.Materials & MethodsA total of 36 children with resistant epilepsy who were 2 to 7 year old were put on the ketogenic diet. Their growth and biochemical parameters were studied at the beginning of the study and after 3 months.ResultsWeight decreased in all patients. Serum levels of hemoglobin, calcium, and blood sugar decreased significantly but remained in the normal range. Creatinine did not change, but BUN showed a significant increase.ConclusionWe can lower the complications of ketogenic diets by using more unsaturated fat, more water, and more minerals.

  20. Occurrence of GLUT1 deficiency syndrome in patients treated with ketogenic diet.

    Ramm-Pettersen, Anette; Nakken, Karl O; Haavardsholm, Kathrine Cammermeyer; Selmer, Kaja Kristine

    2014-03-01

    Glucose transporter 1 deficiency syndrome (GLUT1-DS) is a treatable metabolic encephalopathy caused by a mutation in the SLC2A1 gene. This mutation causes a compromised transport of glucose across the blood-brain barrier. The treatment of choice is ketogenic diet, with which most patients become seizure-free. At the National Centre for Epilepsy, we have, since 2005, offered treatment with ketogenic diet (KD) and modified Atkins diet (MAD) to children with difficult-to-treat epilepsy. As we believe many children with GLUT1-DS are unrecognized, the aim of this study was to search for patients with GLUT1-DS among those who had been responders (>50% reduction in seizure frequency) to KD or MAD. Of the 130 children included, 58 (44%) were defined as responders. Among these, 11 were already diagnosed with GLUT1-DS. No mutations in the SLC2A1 gene were detected in the remaining patients. However, the clinical features of these patients differed considerably from the patients diagnosed with GLUT1-DS. While 9 out of 10 patients with GLUT1-DS became seizure-free with dietary treatment, only 3 out of the 33 remaining patients were seizure-free with KD or MAD treatment. We therefore conclude that a seizure reduction of >50% following dietary treatment is not a suitable criterion for identifying patients with GLUT1-DS, as these patients generally achieve complete seizure freedom shortly after diet initiation. PMID:24508593

  1. Danish study of a Modified Atkins diet for medically intractable epilepsy in children: Can we achieve the same results as with the classical ketogenic diet?

    Miranda, M. J.; Mortensen, M.; Povlsen, J. H.;

    2011-01-01

    Modified Atkins diet (MAD) is a less restrictive variety of the classical ketogenic diet (KD), used for treating patients with medically resistant epilepsy. There are only few reports comparing the two types of diets in terms of seizure reduction and tolerability. We compared the effect of a MAD ...

  2. Long Term Successful Weight Loss with a Combination Biphasic Ketogenic Mediterranean Diet and Mediterranean Diet Maintenance Protocol

    Antonio Paoli

    2013-12-01

    Full Text Available Weight loss protocols can only be considered successful if they deliver consistent results over the long term—a goal which is often elusive, so much so that the term “yo-yo” is used to describe the perennial weight loss/weight regain battle common in obesity. We hypothesized that a ketogenic Mediterranean diet with phytoextracts (KEMEPHY combined with the acknowledged health benefits of traditional Mediterranean nutrition may favor long term weight loss. We analysed 89 male and female obese subjects, aged between 25 and 65 years who were overall healthy apart from being overweight. The subjects followed a staged diet protocol over a period of 12 months: 20 day of KEMEPHY; 20 days low carb-non ketogenic; 4 months Mediterranean normocaloric nutrition; a second 20 day ketogenic phase followed by 6 months of Mediterranean normocaloric nutrition. For the majority of subjects (88.25% there was significant loss of weight (from 100.7 ± 16.54 to 84.59 ± 9.71 kg; BMI from 35.42 ± 4.11 to 30.27 ± 3.58 and body fat (form 43.44% ± 6.34% to 33.63% ± 7.6% during both ketogenic phases followed by successful maintenance, without weight regain, during the 6 month stabilization phase with only 8 subjects failing to comply. There were also significant and stable decreases in total cholesterol, LDLc, triglycerides and glucose levels over the 12 month study period. HDLc showed small increases after the ketogenic phases but over the full 12 months there was no significant change. No significant changes were observed in ALT, AST, Creatinine or BUN. The combination of a biphasic KEMEPHY diet separated by longer periods of maintenance nutrition, based on the traditional Mediterranean diet, led to successful long term weight loss and improvements in health risk factors in a majority of subjects; compliance was very high which was a key determinant of the results seen.

  3. A Ketogenic Diet Increases Brown Adipose Tissue Mitochondrial Proteins and UCP1 Levels in Mice

    Srivastava, Shireesh; Baxa, Ulrich; Niu, Gang; Chen, Xiaoyuan; Veech, Richard L.

    2012-01-01

    We evaluated the effects of feeding a ketogenic diet (KD) for a month on general physiology with emphasis on brown adipose tissue (BAT) in mice. KD did not reduce the caloric intake, or weight or lipid content of BAT. Relative epididymal fat pads were 40% greater in the mice fed the KD (P = 0.06) while leptin was lower (P < 0.05). Blood glucose levels were 30% lower while D-β-hydroxybutyrate levels were about 3.5-fold higher in the KD group. Plasma insulin and leptin levels in the KD group we...

  4. The Effects of a Ketogenic Diet on Exercise Metabolism and Physical Performance in Off-Road Cyclists

    Adam Zajac

    2014-06-01

    Full Text Available The main objective of this research was to determine the effects of a long-term ketogenic diet, rich in polyunsaturated fatty acids, on aerobic performance and exercise metabolism in off-road cyclists. Additionally, the effects of this diet on body mass and body composition were evaluated, as well as those that occurred in the lipid and lipoprotein profiles due to the dietary intervention. The research material included eight male subjects, aged 28.3 ± 3.9 years, with at least five years of training experience that competed in off-road cycling. Each cyclist performed a continuous exercise protocol on a cycloergometer with varied intensity, after a mixed and ketogenic diet in a crossover design. The ketogenic diet stimulated favorable changes in body mass and body composition, as well as in the lipid and lipoprotein profiles. Important findings of the present study include a significant increase in the relative values of maximal oxygen uptake (VO2max and oxygen uptake at lactate threshold (VO2 LT after the ketogenic diet, which can be explained by reductions in body mass and fat mass and/or the greater oxygen uptake necessary to obtain the same energy yield as on a mixed diet, due to increased fat oxidation or by enhanced sympathetic activation. The max work load and the work load at lactate threshold were significantly higher after the mixed diet. The values of the respiratory exchange ratio (RER were significantly lower at rest and during particular stages of the exercise protocol following the ketogenic diet. The heart rate (HR and oxygen uptake were significantly higher at rest and during the first three stages of exercise after the ketogenic diet, while the reverse was true during the last stage of the exercise protocol conducted with maximal intensity. Creatine kinase (CK and lactate dehydrogenase (LDH activity were significantly lower at rest and during particular stages of the 105-min exercise protocol following the low carbohydrate

  5. Ketogenic diet does not affect strength performance in elite artistic gymnasts

    Paoli Antonio

    2012-07-01

    Full Text Available Abstract Background Despite the increasing use of very low carbohydrate ketogenic diets (VLCKD in weight control and management of the metabolic syndrome there is a paucity of research about effects of VLCKD on sport performance. Ketogenic diets may be useful in sports that include weight class divisions and the aim of our study was to investigate the influence of VLCKD on explosive strength performance. Methods 8 athletes, elite artistic gymnasts (age 20.9 ± 5.5 yrs were recruited. We analyzed body composition and various performance aspects (hanging straight leg raise, ground push up, parallel bar dips, pull up, squat jump, countermovement jump, 30 sec continuous jumps before and after 30 days of a modified ketogenic diet. The diet was based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrates, but which mimicked their taste, with the addition of some herbal extracts. During the VLCKD the athletes performed the normal training program. After three months the same protocol, tests were performed before and after 30 days of the athletes’ usual diet (a typically western diet, WD. A one-way Anova for repeated measurements was used. Results No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p  Conclusions Despite concerns of coaches and doctors about the possible detrimental effects of low carbohydrate diets on athletic performance and the well known importance of carbohydrates there are no data about VLCKD and strength performance. The undeniable and sudden effect of VLCKD on fat loss may be useful for those athletes who compete in sports based on weight class. We have demonstrated that using VLCKD for a

  6. Environmental Enrichment Mitigates Detrimental Cognitive Effects of Ketogenic Diet in Weanling Rats.

    Scichilone, John M; Yarraguntla, Kalyan; Charalambides, Ana; Harney, Jacob P; Butler, David

    2016-09-01

    For decades, the ketogenic diet has been an effective treatment of intractable epilepsy in children. Childhood epilepsy is pharmacoresistant in 25-40 % of patients taking the current prescribed medications. Chronic seizure activity has been linked to deficits in cognitive function and behavioral problems which negatively affect the learning abilities of the child. Recent studies suggest the ketogenic diet (KD), a high fat with low carbohydrate and protein diet, has adverse effects on cognition in weanling rats. The diet reduces circulating glucose levels to where energy metabolism is converted from glycolysis to burning fat and generating ketone bodies which has been suggested as a highly efficient source of energy for the brain. In contrast, when weanling rats are placed in an enriched environment, they exhibit increased spatial learning, memory, and neurogenesis. Thus, this study was done to determine if weanling rats being administered a KD in an environmental enrichment (EE) would still exhibit the negative cognitive effects of the diet previously observed. The present study suggests that an altered environment is capable of reducing the cognitive deficits in weanling rats administered a KD. Learning was improved with an EE. The effect of diet and environment on anxiety and depression suggests a significant reduction in anxiety with enrichment rearing. Interestingly, circulating energy substrate levels were increased in the EE groups along with brain-derived neurotrophic factor despite the least changes in weight gain. In light of numerous studies using KDs that seemingly have adverse effects on cognition, KD-induced reductions in excitotoxic events would not necessarily eliminate that negative aspect of seizures. PMID:27112438

  7. Adenosine: front and center in linking nutrition and metabolism to neuronal activity

    Greene, Robert W

    2011-01-01

    Many individuals with epilepsy benefit from consuming a ketogenic diet, which is similar to the more commonly known Atkins diet. The underlying molecular reason for this has not been determined. However, in this issue of the JCI, Masino et al. have elucidated the mechanism responsible for the antiepileptic effects of the ketogenic diet in mice. The diet is shown to decrease expression of the enzyme adenosine kinase (Adk), which is responsible for clearing the endogenous antiepileptic agent ad...

  8. MED23-associated refractory epilepsy successfully treated with the ketogenic diet.

    Lionel, Anath C; Monfared, Nasim; Scherer, Stephen W; Marshall, Christian R; Mercimek-Mahmutoglu, Saadet

    2016-09-01

    We report a new patient with refractory epilepsy associated with a novel pathogenic homozygous MED23 variant. This 7.5-year-old boy from consanguineous parents had infantile onset global developmental delay and refractory epilepsy. He was treated with the ketogenic diet at 2.5 years of age and became seizure free on the first day. He had microcephaly and truncal hypotonia. His brain MRI showed delayed myelination and thin corpus callosum. He was enrolled in a whole exome sequencing research study, which identified a novel, homozygous, likely pathogenic (c.1937A>G; p.Gln646Arg) variant in MED23. MED23 is a regulator of energy homeostasis and glucose production. Liver-specific Med23-knockout mice showed reduced liver gluconeogenesis and lower blood glucose levels compared to control mice. This is the first patient with documented refractory epilepsy caused by a novel homozygous pathogenic variant in MED23 expanding the phenotypic spectrum. Identification of the underlying genetic defect in MED23 sheds light on the possible mechanism of complete response to the ketogenic diet in this child. © 2016 Wiley Periodicals, Inc. PMID:27311965

  9. Lipoid pneumonia--a case of refractory pneumonia in a child treated with ketogenic diet.

    Buda, Piotr; Wieteska-Klimczak, Anna; Własienko, Anna; Mazur, Agnieszka; Ziołkowski, Jerzy; Jaworska, Joanna; Kościesza, Andrzej; Dunin-Wąsowicz, Dorota; Książyk, Janusz

    2013-01-01

    Lipoid pneumonia (LP) is a chronic inflammation of the lung parenchyma with interstitial involvement due to the accumulation of endogenous or exogenous lipids. Exogenous LP (ELP) is associated with the aspiration or inhalation of oil present in food, oil-based medications or radiographic contrast media. The clinical manifestations of LP range from asymptomatic cases to severe pulmonary involvement, with respiratory failure and death, according to the quantity and duration of the aspiration. The diagnosis of exogenous lipoid pneumonia is based on a history of exposure to oil and the presence of lipid-laden macrophages on sputum or bronchoalveolar lavage (BAL) analysis. High-resolution computed tomography (HRCT) is the imaging technique of choice for evaluation of patients with suspected LP. The best therapeutic strategy is to remove the oil as early as possible through bronchoscopy with multiple BALs and interruption in the use of mineral oil. Steroid therapy remains controversial, and should be reserved for severe cases. We describe a case of LP due to oil aspiration in 3-year-old girl with intractable epilepsy on ketogenic diet. Diagnostic problems were due to non-specific symptoms that were mimicking serious infectious pneumonia. A high index of suspicion and precise medical history is required in cases of refractory pneumonia and fever unresponsive to conventional therapy. Gastroesophageal reflux and a risk of aspiration may be regarded as relative contraindications to the ketogenic diet. Conservative treatment, based on the use of oral steroids, proved to be an efficient therapeutic approach in this case. PMID:23996884

  10. Effectiveness of the ketogenic diet used to treat resistant childhood epilepsy in Scandinavia

    Hallböök, Tove; Sjölander, Arvid; Åmark, Per;

    2015-01-01

    in the majority of patients. Long-term efficacy of KD was comparable or even better than reported in newer AEDs. Addition of potassium citrate reduced risk of kidney-stones. Our data indicate that the response might be predicted by seizure-frequency before initiation of the diet but not by age...... three and six months. Side-effects were noted in 29 subjects; most could be treated and only two stopped due to hyperlipidaemia and two due to kidney-stones. In 167 patients treated with potassium-citrate, one developed kidney-stones, compared with six of 123 without potassium-citrate treatment......BACKGROUND: This Scandinavian collaborative retrospective study of children treated with ketogenic diet (KD) highlights indications and effectiveness over two years follow-up. METHODS: Five centres specialised in KD collected data retrospectively on 315 patients started on KD from 1999 to 2009...

  11. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways

  12. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    Mueller-Klieser Wolfgang

    2011-07-01

    Full Text Available Abstract Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2, 3-oxoacid-CoA transferase 1 (OXCT1 and acetyl-CoA acetyltransferase 1 (ACAT1 were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic

  13. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot train

    Schmidt, Melanie; Pfetzer, Nadja; Schwab, Micheal; Strauss, Ingrid; Kaemmerer, Ulrike

    2012-01-01

    Background: Tumor patients exhibit an increased peripheral demand of fatty acids and protein. Contrarily, tumors utilize glucose as their main source of energy supply. Thus, a diet supplying the cancer patient with sufficient fat and protein for his demands while restricting the carbohydrates (CHO) tumors thrive on, could be a helpful strategy in improving the patients’ situation. A ketogenic diet (KD) fulfills these requirements. Therefore, we performed a pilot study to investigate the feasi...

  14. Beneficial effect of feeding a ketogenic diet to mothers on brain development in their progeny with a murine model of pyruvate dehydrogenase complex deficiency

    Lioudmila Pliss

    2016-06-01

    Conclusion: The findings provide for the first time experimental support for beneficial effects of a ketogenic diet during the prenatal and early postnatal periods on the brain development of PDC-deficient mammalian progeny.

  15. Ketogenic Diet: An Early Option for Epilepsy Treatment, Instead of A Last Choice Only

    Huei-Shyong Wang

    2012-02-01

    Full Text Available Ketogenic diet (KD was usually tried as a last resort in the treatment of intractable epilepsy after failure of many antiepileptics and even epilepsy surgery. Glucose transporter-1 deficiency and pyruvate dehydrogenase deficiency must be treated with KD as the first choice because of inborn errors of glucose metabolism. Infantile spasms, tuberous sclerosis complex, Rett syndrome, Doose syndrome, Dravet syndrome, etc., appear to respond to KD, and it has been suggested by the international consensus statement to use KD early. We believe that all patients with epilepsy, except those with contraindicated situations such as pyruvate carboxylase deficiency, porphyria, β-oxidation defects, primary carnitine deficiency, etc., may try KD before trying other regimens.

  16. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

    Zhou Weihua

    2007-02-01

    Full Text Available Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A and a human malignant glioma (U87-MG. Methods Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal® was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal® on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet. Results KetoCal® administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal® diet reduced plasma glucose levels while elevating plasma ketone body (β-hydroxybutyrate levels. Tumor microvessel density was less in the calorically restricted KetoCal® groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, β-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid Co

  17. Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet

    Mukherjee Purna

    2008-11-01

    Full Text Available Abstract Background Astrocytomas are largely dependent on glycolysis to satisfy their bioenergetic requirements for growth and survival. Therapies that target glycolysis can potentially manage astrocytoma growth and progression. Dietary restriction of the high fat/low carbohydrate ketogenic diet (KD-R reduces glycolysis and is effective in managing experimental mouse and human astrocytomas. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG, is a potent glycolytic inhibitor that can mimic effects of energy restriction both in vitro and in vivo, but can also produce adverse effects when administered at doses greater than 200 mg/kg. The goal here was to determine if low doses of 2-DG could act synergistically with the KD-R to better manage growth of the CT-2A malignant mouse astrocytoma. Methods The therapeutic effect of a KD-R supplemented with a low dose of 2-DG (25 mg/kg was examined in adult C57BL/6J mice bearing the syngeneic CT-2A malignant astrocytoma grown orthotopically. Mice were fed the standard unrestricted diet for the first 3 days after tumor implantation prior to their separation into one of four diet groups fed either a standard rodent diet in unrestricted amounts (SD-UR or a KD-R with or without 2-DG for 10 days. The KD-R was restricted to reduce body weight by about 20%. 2-DG was initiated 6 days after tumor implantation and was continued for 7 days. Brain tumors were excised and weighed. Results Energy intake, body weights, and CT-2A tumor weights were similar in the SD-UR and the SD-UR+2-2DG mouse groups over the dietary treatment period (days 3–13. Tumor weights were about 48% and 80% lower in the KD-R and in the KD-R+2-DG groups, respectively, than in the SD-UR group. Mouse health and vitality was better in the KD-R group than in the KD-R+2-DG group. Conclusion Astrocytoma growth was reduced more in the KD-R mouse group supplemented with 2-DG than in the mouse groups receiving either dietary restriction or 2-DG

  18. A pilot study of the Spanish Ketogenic Mediterranean Diet: an effective therapy for the metabolic syndrome.

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés

    2011-01-01

    The "Spanish Ketogenic Mediterranean Diet" (SKMD) has been shown to promote potential therapeutic properties for the metabolic syndrome. The purpose of this study was to evaluate the potential therapeutic properties under free-living conditions of the SKMD in patients with metabolic syndrome (following the International Diabetes Federation consensus guidelines) over a 12-week period. A prospective study was carried out in 22 obese subjects with metabolic syndrome (12 men and 10 women) with the inclusion criteria whose body mass index of 36.58 ± 0.54 kg/m² and age was 41.18 ± 2.28 years. Statistical differences between the parameters studied before and after the administration of the SKMD (week 0 and 12, respectively) were analyzed by paired Student's t test. There was an extremely significant (P fasting plasma glucose (from 118.81 mg/dL to 91.86 mg/dL), triacylglycerols (from 224.86 mg/dL to 109.59 mg/dL), high-density lipoprotein cholesterol (from 44.44 to 57.95 mg/dL), systolic blood pressure (from 141.59 mm Hg to 123.64 mm Hg), and diastolic blood pressure (from 89.09 mm Hg to 76.36 mm Hg). The most affected parameter was the triacylglycerols (51.26% reduction). After the diet all the subjects were free of metabolic syndrome according to the International Diabetes Federation definition, and 100% of them had normal triacylglycerols and high-density lipoprotein cholesterol levels, in spite of the fact that 77.27% of them still had a body mass index of > 30 kg/m². We conclude that the SKMD could be an effective and safe way to cure patients suffering from metabolic syndrome. Future research should include a larger sample size, a longer-term use, and a comparison with other ketogenic diets. PMID:21612461

  19. Protective effect of the ketogenic diet in Scn1a mutant mice

    Dutton, Stacey B. B.; Sawyer, Nikki T.; Kalume, Franck; Jumbo-Lucioni, Patricia; Borges, Karin; Catterall, William A.; Escayg, Andrew

    2011-01-01

    Summary Purpose We evaluated the ability of the ketogenic diet (KD) to improve thresholds to flurothyl-induced seizures in two mouse lines with Scn1a mutations: one that models Dravet syndrome (DS) and another that models genetic (generalized) epilepsy with febrile seizures plus (GEFS+). Methods At postnatal day 21, mouse models of DS and GEFS+ were fasted for 12–14 hours and then placed on either a 6:1 KD or a standard diet (SD) for two weeks. At the end of the two-week period, we measured thresholds to seizures induced by the chemiconvulsant flurothyl. Body weight, β-hydroxybutyrate (BHB) levels, and glucose levels were also recorded every two days over a two-week period in separate cohorts of mutant and wild-type mice that were either on the KD or the SD. Key Findings Mice on the KD gained less weight and exhibited significantly higher BHB levels compared to mice on the SD. Importantly, thresholds to flurothyl-induced seizures were restored to more normal levels in both mouse lines after two weeks on the KD. Significance These results indicate that the KD may be an effective treatment for refractory patients with SCN1A mutations. The availability of mouse models of DS and GEFS+ also provides an opportunity to better understand the mechanism of action of the KD, which may facilitate the development of improved treatments. PMID:21801172

  20. Ketogenic diet attenuates spatial and item memory impairment in pentylenetetrazol-kindled rats.

    Jiang, Yan; Lu, Yuqiang; Jia, Mengmeng; Wang, Xiaohang; Zhang, Zhengxiang; Hou, Qun; Wang, Baohui

    2016-09-01

    The ketogenic diet (KD) controls seizure and improves cognition in patients with drug refractory epilepsy. However, few experimental models have shown this neuroprotective effect on cognition. In this study, we investigated the cognitive protective effects of KD in pentylenetetrazol (PTZ)-kindled rats. We used two relatively low-stress behavioral assessment methods, the novel object recognition (NOR) task and the novel placement recognition (NPR) task, to reveal impairment in item and spatial memory, respectively. We used the Morris water maze (MWM) test for comparisons amongst memory assessment methods. The KD group had a slower body weight gain and shorter bregma-lambda length than the control normal diet (ND) group. KD did not increase anxiety or decrease motor activities in an open-field test. KD attenuated the decrease in exploration ratio both in NOR and NPR tasks in kindled rats. Compared to the kindled ND rats, kindled KD rats stayed longer in target quarter during the probe trial testing of MWM. However, there were no differences in memory acquisition based on the MWM test results. In conclusion, KD attenuated the spatial and item memory impairment in PTZ-induced seizures. PMID:27343950

  1. False-positive breath-alcohol test after a ketogenic diet.

    Jones, A W; Rössner, S

    2007-03-01

    A 59-year-old man undergoing weight loss with very low calorie diets (VLCD) attempted to drive a car, which was fitted with an alcohol ignition interlock device, but the vehicle failed to start. Because the man was a teetotaller, he was surprised and upset by this result. VLCD treatment leads to ketonemia with high concentrations of acetone, acetoacetate and beta-hydroxybutyrate in the blood. The interlock device determines alcohol (ethanol) in breath by electrochemical oxidation, but acetone does not undergo oxidation with this detector. However, under certain circumstances acetone is reduced in the body to isopropanol by hepatic alcohol dehydrogenase (ADH). The ignition interlock device responds to other alcohols (e.g. methanol, n-propanol and isopropanol), which therefore explains the false-positive result. This 'side effect' of ketogenic diets needs further discussion by authorities when people engaged in safety-sensitive work (e.g. bus drivers and airline pilots) submit to random breath-alcohol tests. PMID:16894360

  2. An observational study of sequential protein-sparing, very low-calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean-like diet for the treatment of obesity.

    Castaldo, Giuseppe; Monaco, Luigi; Castaldo, Laura; Galdo, Giovanna; Cereda, Emanuele

    2016-09-01

    The impact of a rehabilitative multi-step dietary program consisting in different diets has been scantily investigated. In an open-label study, 73 obese patients underwent a two-phase weight loss (WL) program: a 3-week protein-sparing, very low-calorie, ketogenic diet (<500 kcal/day; Oloproteic(®) Diet) and a 6-week hypocaloric (25-30 kcal/kg of ideal body weight/day), low glycemic index, Mediterranean-like diet (hypo-MD). Both phases improved visceral adiposity, liver enzymes, GH levels, blood pressure and glucose and lipid metabolism. However, the hypo-MD was responsible for a re-increase in blood lipids and glucose tolerance parameters. Changes in visceral adiposity and glucose control-related variables were more consistent in patients with metabolic syndrome. However, in these patients the hypo-MD did not result in a consistent re-increase in glucose control-related variables. A dietary program consisting in a ketogenic regimen followed by a balanced MD appeared to be feasible and efficacious in reducing cardiovascular risk, particularly in patients with metabolic syndrome. PMID:27193396

  3. PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPARγ activation in the liver

    Research highlights: → PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression. → Hepatic expressions of PPARγ and PCG-1α are induced by a ketogenic diet. → PPARγ antagonist attenuates a ketogenic diet-induced PAI-1 expression. → Ketogenic diet advances the phase of circadian clock in a PPARα-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor α (PPARα) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPARα-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPARα-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPARα target genes such as Cyp4A10 and FGF21 was damped in PPARα-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPARα-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPARα activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPARγ and its coactivator PCG-1α were more effectively induced in PPARα-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPARγ antagonist, in both WT and PPARα-null mice. PPARγ activation seems to be involved in KD-induced hypofibrinolysis by augmenting PAI-1 gene expression

  4. Ketogenic diet improves forelimb motor function after spinal cord injury in rodents.

    Femke Streijger

    Full Text Available High fat, low carbohydrate ketogenic diets (KD are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1 expression. Pharmacological inhibition of MCTs with 4-CIN (α-cyano-4-hydroxycinnamate prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited.

  5. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis

    Humala Nelson

    2006-04-01

    Full Text Available Abstract Background The cause of neuronal death in amyotrophic lateral sclerosis (ALS is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization. Results SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-β-3 hydroxybutyrate (DBH, has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047. In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030. DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH. Conclusion This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.

  6. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet.

    Vanderperre, Benoît; Herzig, Sébastien; Krznar, Petra; Hörl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

    2016-05-01

    Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic profiles, and both defects could be restored by reexpression of MPC1. Labeling experiments using 13C-labeled glucose and glutamine demonstrated that MPC deficiency causes increased glutaminolysis and reduced contribution of glucose-derived pyruvate to the TCA cycle. Morphological defects were observed in mutant embryonic brains, together with major alterations of their metabolome including lactic acidosis, diminished TCA cycle intermediates, energy deficit and a perturbed balance of neurotransmitters. Strikingly, these changes were reversed when the pregnant dams were fed a ketogenic diet, which provides acetyl-CoA directly to the TCA cycle and bypasses the need for a functional MPC. This allowed the normal gestation and development of MPC deficient pups, even though they all died within a few minutes post-delivery. This study establishes the MPC as a key player in regulating the metabolic state necessary for embryonic development, neurotransmitter balance and post-natal survival. PMID:27176894

  7. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet

    Krznar, Petra; Hörl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

    2016-01-01

    Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic profiles, and both defects could be restored by reexpression of MPC1. Labeling experiments using 13C-labeled glucose and glutamine demonstrated that MPC deficiency causes increased glutaminolysis and reduced contribution of glucose-derived pyruvate to the TCA cycle. Morphological defects were observed in mutant embryonic brains, together with major alterations of their metabolome including lactic acidosis, diminished TCA cycle intermediates, energy deficit and a perturbed balance of neurotransmitters. Strikingly, these changes were reversed when the pregnant dams were fed a ketogenic diet, which provides acetyl-CoA directly to the TCA cycle and bypasses the need for a functional MPC. This allowed the normal gestation and development of MPC deficient pups, even though they all died within a few minutes post-delivery. This study establishes the MPC as a key player in regulating the metabolic state necessary for embryonic development, neurotransmitter balance and post-natal survival. PMID:27176894

  8. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet

    Seyfried B

    2009-09-01

    Full Text Available Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect, malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  9. Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis

    Klement, Rainer J.; Champ, Colin E.; Otto, Christoph; Kämmerer, Ulrike

    2016-01-01

    Background Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice. Methods We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]). Conclusions There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors. PMID:27159218

  10. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    Angela M Poff

    Full Text Available INTRODUCTION: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. METHODS: We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week. Tumor growth was monitored by in vivo bioluminescent imaging. RESULTS: KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. CONCLUSIONS: KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  11. The effects of a ketogenic diet on ATP concentrations and the number of hippocampal mitochondria in Aldh5a1−/− mice

    Nylen, Kirk; Velazquez, Jose Luis Perez; Sayed, Venus; Gibson, K. Michael; Burnham, W.M.; Snead, O. Carter

    2009-01-01

    Summary BACKGROUND Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inborn error of GABA metabolism characterized clinically by ataxia, psychomotor retardation and seizures. A mouse model of SSADH deficiency, the Aldh5a1−/− mouse, has been used to study the pathophysiology and treatment of this disorder. Recent work from our group has shown that the ketogenic diet (KD) is effective in normalizing the Aldh5a1−/− phenotype, although the mechanism of the effect remains unclear. METHODS Here, we examine the effects of a KD on the number of hippocampal mitochondria as well as on ATP levels in hippocampus. Electron microscopy was performed to determine the number of mitochondria in the hippocampus of Aldh5a1−/− mice. Adenosine triphosphate (ATP) levels were measured in hippocampal extracts. RESULTS Our results show that the KD increases the number of mitochondria in Aldh5a1−/− mice. We also show that Aldh5a1−/− mice have significant reductions in hippocampal ATP levels as compared to controls, and that the KD restores ATP in mutant mice to normal levels. CONCLUSIONS & GENERAL SIGNIFICANCE Taken together, our data suggest that the KD’s actions on brain mitochondria may play a role in the diet’s ability to treat murine SSADH deficiency. PMID:19168117

  12. The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study.

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés

    2011-01-01

    The "Spanish Ketogenic Mediterranean Diet" (SKMD) has been shown to be an effective and safe way to cure patients suffering from metabolic syndrome (MS). Keeping in mind that nonalcoholic fatty liver disease (NAFLD) is closely associated with MS, the purpose of this study was to evaluate the potential therapeutic properties under free living conditions of the SKMD in patients with MS (following the International Diabetes Federation [IDF] consensus guidelines) and NAFLD (suspected by using a cutoff value of alanine aminotransferase [ALT] levels of >40 U/L and confirmed by abdominal ultrasonography) over a 12-week period. A prospective study was carried out in 14 obese men meeting the inclusion criteria and whose body mass index (BMI) and age were 36.58±0.54 kg/m² and 41.18±2.28 years, respectively. Statistical differences between the parameters studied before and after administration of the SKMD (week 0 and 12) were analyzed by paired Student's t test (continuous variables) and the χ² test (discontinuous variables). Pfasting plasma glucose (from 118.57 mg/dL to 90.14 mg/dL), triacylglycerols (from 232.64 mg/dL to 111.21 mg/dL), high-density lipoprotein-cholesterol (HDLc) (from 42.81 mg/dL to 58.71 mg/dL), systolic blood pressure (from 142.86 mm Hg to 125.36 mm Hg), and diastolic blood pressure (from 89.64 mm Hg to 77.86 mm Hg). After the diet all the subjects were free of MS according to the IDF definition, and 100% of them had normal triacylglycerols and HDLc levels, in spite of the fact that 100% of them still had a BMI of >30 kg/m². We conclude that the SKMD could be an effective and safe way to treat patients suffering from MS and the associated NAFLD. PMID:21688989

  13. Do Glut1 (glucose transporter type 1) defects exist in epilepsy patients responding to a ketogenic diet?

    Becker, Felicitas; Schubert, Julian; Weckhuysen, Sarah; Suls, Arvid; Grüninger, Steffen; Korn-Merker, Elisabeth; Hofmann-Peters, Anne; Sperner, Jürgen; Cross, Helen; Hallmann, Kerstin; Elger, Christian E; Kunz, Wolfram S; Madeleyen, René; Lerche, Holger; Weber, Yvonne G

    2015-08-01

    In the recent years, several neurological syndromes related to defects of the glucose transporter type 1 (Glut1) have been descried. They include the glucose transporter deficiency syndrome (Glut1-DS) as the most severe form, the paroxysmal exertion-induced dyskinesia (PED), a form of spastic paraparesis (CSE) as well as the childhood (CAE) and the early-onset absence epilepsy (EOAE). Glut1, encoded by the gene SLC2A1, is the most relevant glucose transporter in the brain. All Glut1 syndromes respond well to a ketogenic diet (KD) and most of the patients show a rapid seizure control. Ketogenic Diet developed to an established treatment for other forms of pharmaco-resistant epilepsies. Since we were interested in the question if those patients might have an underlying Glut1 defect, we sequenced SLC2A1 in a cohort of 28 patients with different forms of pharmaco-resistant epilepsies responding well to a KD. Unfortunately, we could not detect any mutations in SLC2A1. The exact action mechanisms of KD in pharmaco-resistant epilepsy are not well understood, but bypassing the Glut1 transporter seems not to play an important role. PMID:26088884

  14. Revealing the molecular relationship between type 2 diabetes and the metabolic changes induced by a very-low-carbohydrate low-fat ketogenic diet

    Naval Jordi

    2010-12-01

    Full Text Available Abstract Background The prevalence of type 2 diabetes is increasing worldwide, accounting for 85-95% of all diagnosed cases of diabetes. Clinical trials provide evidence of benefits of low-carbohydrate ketogenic diets in terms of clinical outcomes on type 2 diabetes patients. However, the molecular events responsible for these improvements still remain unclear in spite of the high amount of knowledge on the primary mechanisms of both the diabetes and the metabolic state of ketosis. Molecular network analysis of conditions, diseases and treatments might provide new insights and help build a better understanding of clinical, metabolic and molecular relationships among physiological conditions. Accordingly, our aim is to reveal such a relationship between a ketogenic diet and type 2 diabetes through systems biology approaches. Methods Our systemic approach is based on the creation and analyses of the cell networks representing the metabolic state in a very-low-carbohydrate low-fat ketogenic diet. This global view might help identify unnoticed relationships often overlooked in molecule or process-centered studies. Results A strong relationship between the insulin resistance pathway and the ketosis main pathway was identified, providing a possible explanation for the improvement observed in clinical trials. Moreover, the map analyses permit the formulation of some hypothesis on functional relationships between the molecules involved in type 2 diabetes and induced ketosis, suggesting, for instance, a direct implication of glucose transporters or inflammatory processes. The molecular network analysis performed in the ketogenic-diet map, from the diabetes perspective, has provided insights on the potential mechanism of action, but also has opened new possibilities to study the applications of the ketogenic diet in other situations such as CNS or other metabolic dysfunctions.

  15. Dieta cetogênica no tratamento de epilepsias farmacorresistentes The ketogenic diet on the treatment of drug resistant epilepsies

    Carla Barbosa Nonino-Borges

    2004-12-01

    Full Text Available A epilepsia é uma condição clínica crônica correspondente a um grupo de doenças que tem em comum crises epilépticas; ela atinge de 0,5% a 1,0% da população dos países desenvolvidos, podendo esta prevalência ser maior nos países em desenvolvimento. Aproximadamente um terço dos pacientes evolui com crises epilépticas intratáveis com medicamentos; em alguns casos, é possível o tratamento cirúrgico. Nos pacientes em que cirurgia não é possível, a dieta cetogênica passa a ser uma opção terapêutica, principalmente em crianças. Espera-se que esta terapia seja eficaz para, pelo menos, um terço dos pacientes, resultando em redução ou controle das crises. No presente trabalho, apresentamos métodos para o preparo e uso a dieta cetogênica. O planejamento da dieta é individualizado, seguindo-se recomendações para o consumo energético e proporções de gorduras, proteínas e carboidratos específicos. Sempre que introduzida a dieta, o paciente deve ser monitorizado, devido à possibilidade de efeitos adversos. A orientação dos pais ou responsáveis sobre a dieta cetogênica, e como ela funciona, proporciona maior aceitação e aderência a esta forma de tratamento da epilepsia.Epilepsy is a chronic condition that affects 0.5% to 1.0% of the population in developed countries. This prevalence may be higher in developing countries. A significant proportion of the patients, nearly one third of them will have their condition evolved into a stage of uncontrolled crises, in some cases, surgical procedure may be indicated. However, for several patients, surgery is not possible. In these cases, ketogenic diet is a therapeutic option, especially for children. It is supposed that nearly one third of the patients that use the ketogenic diet, experience seizure control or reduction in the number of seizures. The current study presents methods of preparing and using ketogenic diet. The diet must be individualized, considering the

  16. Research into the (Cost- effectiveness of the ketogenic diet among children and adolescents with intractable epilepsy: design of a randomized controlled trial

    Hendriksen Jos GM

    2011-01-01

    Full Text Available Abstract Background Epilepsy is a neurological disorder, characterized by recurrent unprovoked seizures which have a high impact on the individual as well as on society as a whole. In addition to the economic burden, epilepsy imposes a substantial burden on the patients and their surroundings. Patients with uncontrolled epilepsy depend heavily on informal care and on health care professionals. About 30% of patients suffer from drug-resistant epilepsy. The ketogenic diet can be a treatment of last resort, especially for children. The beneficial effect of the ketogenic diet has been proven, but information is lacking about its cost-effectiveness. In the current study we will evaluate the (cost- effectiveness of the ketogenic diet in children and adolescents with intractable epilepsy. Methods/Design In a RCT we will compare the ketogenic diet with usual care. Embedded in this RCT will be a trial-based and model-based economic evaluation, looking from a societal perspective at the cost-effectiveness and cost-utility of the ketogenic diet versus usual care. Fifty children and adolescents (aged 1-18 with intractable epilepsy will be screened for eligibility before randomization into the intervention or the usual care group. The primary outcome measure is the proportion of children with a 50% or more reduction in seizure frequency. Secondary outcomes include seizure severity, side effects/complaints, neurocognitive, socio-emotional functioning, and quality of life. Costs and productivity losses will be assessed continuously by a prospective diary and a retrospective questionnaire. Measurements will take place during consults at baseline, at 6 weeks and at 4 months after the baseline period, and 3, 6, 9 and 12 months follow-up after the 4 months consult. Discussion The proposed research project will be the first study to provide data about the cost-effectiveness of the ketogenic diet for children and adolescents with intractable epilepsy, in comparison

  17. Treatment of glycogenosys type V (McArdle disease) with creatine and ketogenic diet with clinical scores and with 31P-MRS on working leg muscle

    Vorgerd, M; Zange, J

    2007-01-01

    McArdle’s disease is caused by genetic defects of the musclespecific isozyme of glycogen phosphorylase, which block ATP formation from glycogen in skeletal muscle. Creatine supplementation and ketogenic diet have been tested as potential supplements for muscle energy metabolism which may improve muscle symptomatic. Outcome measures were clinical scores describing muscle symptomatic and parameters derived from 31P-MRS examinations on working muscle. In two placebo controlled cross-over studies...

  18. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis.

    Mengmeng Lv

    Full Text Available The role of dietary restriction regimens such as caloric restriction, ketogenic diet and intermittent fasting in development of cancers has been detected via abundant preclinical experiments. However, the conclusions are controversial. We aim to review the relevant animal studies systematically and provide assistance for further clinical studies.Literatures on associations between dietary restriction and cancer published in PubMed in recent twenty years were comprehensively searched. Animal model, tumor type, feeding regimen, study length, sample size, major outcome, conclusion, quality assessment score and the interferential step of cancer were extracted from each eligible study. We analyzed the tumor incidence rates from 21 studies about caloric restriction.Fifty-nine studies were involved in our system review. The involved studies explored roles of dietary restriction during initiation, progression and metastasis of cancer. About 90.9% of the relevant studies showed that caloric restriction plays an anti-cancer role, with the pooled OR (95%CI of 0.20 (0.12, 0.34 relative to controls. Ketogenic diet was also positively associated with cancer, which was indicated by eight of the nine studies. However, 37.5% of the related studies obtained a negative conclusion that intermittent fasting was not significantly preventive against cancer.Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated.

  19. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus

    Mavropoulos John C

    2008-12-01

    Full Text Available Abstract Objective Dietary carbohydrate is the major determinant of postprandial glucose levels, and several clinical studies have shown that low-carbohydrate diets improve glycemic control. In this study, we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus. Research design and methods Eighty-four community volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate, ketogenic diet (1c. Results Forty-nine (58.3% participants completed the study. Both interventions led to improvements in hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group had greater improvements in hemoglobin A1c (-1.5% vs. -0.5%, p = 0.03, body weight (-11.1 kg vs. -6.9 kg, p = 0.008, and high density lipoprotein cholesterol (+5.6 mg/dL vs. 0 mg/dL, p Conclusion Dietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes. The diet lower in carbohydrate led to greater improvements in glycemic control, and more frequent medication reduction/elimination than the low glycemic index diet. Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes.

  20. The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study

    Hepburn Juanita

    2005-12-01

    Full Text Available Abstract Background Polycystic ovary syndrome (PCOS is the most common endocrine disorder affecting women of reproductive age and is associated with obesity, hyperinsulinemia, and insulin resistance. Because low carbohydrate diets have been shown to reduce insulin resistance, this pilot study investigated the six-month metabolic and endocrine effects of a low-carbohydrate, ketogenic diet (LCKD on overweight and obese women with PCOS. Results Eleven women with a body mass index >27 kg/m2 and a clinical diagnosis of PCOS were recruited from the community. They were instructed to limit their carbohydrate intake to 20 grams or less per day for 24 weeks. Participants returned every two weeks to an outpatient research clinic for measurements and reinforcement of dietary instruction. In the 5 women who completed the study, there were significant reductions from baseline to 24 weeks in body weight (-12%, percent free testosterone (-22%, LH/FSH ratio (-36%, and fasting insulin (-54%. There were non-significant decreases in insulin, glucose, testosterone, HgbA1c, triglyceride, and perceived body hair. Two women became pregnant despite previous infertility problems. Conclusion In this pilot study, a LCKD led to significant improvement in weight, percent free testosterone, LH/FSH ratio, and fasting insulin in women with obesity and PCOS over a 24 week period.

  1. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    Oishi, Katsutaka, E-mail: k-ooishi@aist.go.jp [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Uchida, Daisuke [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki (Japan); Ohkura, Naoki [Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa (Japan); Horie, Shuichi [Department of Clinical Biochemistry, Kagawa Nutrition University, Sakado, Saitama (Japan)

    2010-10-15

    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR

  2. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    Voelker Hans

    2008-04-01

    Full Text Available Abstract Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT. Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12 or a standard diet (SD group; n = 12 ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume. Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT

  3. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further

  4. Ketogenic diet exposure during the juvenile period increases social behaviors and forebrain neural activation in adult Engrailed 2 null mice.

    Verpeut, Jessica L; DiCicco-Bloom, Emanuel; Bello, Nicholas T

    2016-07-01

    Prolonged consumption of ketogenic diets (KD) has reported neuroprotective benefits. Several studies suggest KD interventions could be useful in the management of neurological and developmental disorders. Alterations in the Engrailed (En) genes, specifically Engrailed 2 (En2), have neurodevelopmental consequences and produce autism-related behaviors. The following studies used En2 knockout (KO; En2(-/-)), and wild-type (WT; En2(+/+)), male mice fed either KD (80% fat, 0.1% carbohydrates) or control diet (CD; 10% fat, 70% carbohydrates). The objective was to determine whether a KD fed from weaning at postnatal day (PND) 21 to adulthood (PND 60) would alter brain monoamines concentrations, previously found dysregulated, and improve social outcomes. In WT animals, there was an increase in hypothalamic norepinephrine content in the KD-fed group. However, regional monoamines were not altered in KO mice in KD-fed compared with CD-fed group. In order to determine the effects of juvenile exposure to KD in mice with normal blood ketone levels, separate experiments were conducted in mice removed from the KD or CD and fed standard chow for 2days (PND 62). In a three-chamber social test with a novel mouse, KO mice previously exposed to the KD displayed similar social and self-grooming behaviors compared with the WT group. Groups previously exposed to a KD, regardless of genotype, had more c-Fos-positive cells in the cingulate cortex, lateral septal nuclei, and anterior bed nucleus of the stria terminalis. In the novel object condition, KO mice previously exposed to KD had similar behavioral responses and pattern of c-Fos immunoreactivity compared with the WT group. Thus, juvenile exposure to KD resulted in short-term consequences of improving social interactions and appropriate exploratory behaviors in a mouse model that displays autism-related behaviors. Such findings further our understanding of metabolic-based therapies for neurological and developmental disorders. PMID

  5. The efficacy of the ketogenic diet on motor functions in Parkinson’s disease: A rat model

    Shaafi, Sheida; Najmi, Safa; Aliasgharpour, Hamed; Mahmoudi, Javad; Sadigh-Etemad, Saeed; Farhoudi, Mahdi; Baniasadi, Negar

    2016-01-01

    Background: The ketogenic diet (KD), high in fat and low in carbohydrate and protein, provides sufficient protein but insufficient carbohydrates for all the metabolic needs of the body. KD has been known as a therapeutic manner intractable epilepsy. In recent years, the effectiveness of KD drew attention to the treatment of some other disorders such as Parkinson’s disease (PD). This study has evaluated the efficacy of KD on motor function in Parkinsonian model of rat and compared it with pramipexole. Methods: A total of 56 male Wistar rats weighing 200-240 g between 12 and 14 weeks of age were randomized in seven 8-rat groups as follows: Control group; sham-operated group; KD group; Parkinsonian control group; KD-Parkinsonian group; pramipexole-Parkinsonian group; and KD-pramipexole-Parkinsonian group. The results of bar test, beam traversal task test, and cylinder task test were compared between the groups. Results: The mean number of ketone bodies had increased significantly in the rats blood after KD. Regarding the results of the triad tests, no statistically significant difference was found between the controls and the sham-operated group. Among the Parkinsonian rats, better results were found in KD groups compared to the non-KD group. The KD enhanced the effect of pramipexole for motor function but did not reach a statistically significant level. Conclusion: The KD reinforced the motor function in Parkinsonian rats in our study. When the diet was combined with pramipexole, the effectiveness of the drug increased in enhancing motor function. PMID:27326359

  6. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model.

    Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d'Amati, Giulia; Tiranti, Valeria

    2014-01-01

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2(-/-)) mouse model did not recapitulate the human disease but showed azoospermia and mitochondrial dysfunctions. We challenged this mouse model with a low glucose and high lipid content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta-oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a general impairment of bioenergetic metabolism. Only Pank2(-/-) mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. These mice also showed structural alteration of muscle morphology, which was comparable with that observed in a patient with pantothenate kinase-associated neurodegeneration. We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration. PMID:24316510

  7. 生酮饮食在儿童孤独症治疗中的研究进展%Progress of children with autism treatment of ketogenic diet

    李玲; 王纪文

    2014-01-01

    生酮饮食是一种高脂肪、适量蛋白质和低碳水化合物的饮食,主要用于治疗儿童难治性癫(痫).儿童孤独症是广泛性发育障碍中最常见的亚型,以社会交往障碍、语言发育障碍和刻板行为等为主要表现,尚无特效药物治疗,早期康复和教育训练是其主要的治疗方法.现对生酮饮食在治疗儿童孤独症的临床应用和可能机制进行综述.%The ketogenic diet is a high-fat,low-carbohydrate diet that imitates ketone bodies from hunger produce,is a kind of treatment for children with refractory epilepsy.Autism is a subtype of pervasive developmental disorder characterized by impaired social interaction,language barriers and stereotyped behavior.Some children may be associated with epilepsy.Early rehabilitation education and training are the main method of treatment.This review summarized ketogenic diet clinical applications for the treatment of children with autism and potential mechanisms.

  8. 生酮饮食抑制脑胶质瘤作用的研究进展%Recent advance in ketogenic diet inhibiting brain glioma

    宣自学; 袁守军

    2016-01-01

    Metabolism has been a focus of cancer research in the last few years,and researchers have found that many pathways associated with tumor growth were related to metabolic pathways.The ketogenic diet (high fat,low carbohydrate and protein) caused metabolic changes,such as a reduction in blood glucose and an increase in blood ketones.Findings indicated that ketogenic diet could reduce the energy for cancer cells and inhibit tumor growth;furthermore,it did not significantly affect the energy metabolism and physiology of body.To date,ketogenic diet is considered as an anti-angiogenic,anti-metastatic and pro-apoptotic metabolic therapy,and the metabolic therapy has the potential to improve the outcome of patients with glioblastoma multiforme and other malignant brain cancers.In this review,we discuss the research progresses about anti-brain tumor effect ofketogenic diet and its related mechanism.%新陈代谢一直是癌症研究的焦点,研究者们发现许多肿瘤生长相关的信号通路与肿瘤细胞代谢途径息息相关.生酮饮食(高脂肪、低碳水化合物和蛋白质)能够引起代谢方式的变化,例如降低血糖和增加血酮体.研究发现生酮饮食可以断绝肿瘤细胞能量供给,抑制肿瘤细胞生长,而对机体能量代谢和生理状况无明显影响.到目前为止,生酮饮食已经被认为是一种通过抗血管新生、抗肿瘤侵袭转移和促凋亡的代谢治疗策略,且该治疗策略可能会提高多形性胶质母细胞瘤和其他恶性脑瘤的治疗效果.本文将综述生酮饮食的抗恶性脑瘤的作用及其机制研究进展.

  9. Does ketogenic diet improve cognitive function in patients with GLUT1-DS? A 6- to 17-month follow-up study.

    Ramm-Pettersen, Anette; Stabell, Kirsten Engberg; Nakken, Karl O; Selmer, Kaja Kristine

    2014-10-01

    The aim of this study was to investigate the effects of ketogenic diet (KD) on cognitive function in patients with glucose transporter protein 1 deficiency syndrome (GLUT1-DS). Six patients with GLUT1-DS who were referred to the National Centre for Epilepsy in Norway during the period of November 2011-September 2013 were included. They were diagnosed with GLUT1-DS on the basis of early-onset seizures and developmental delay (with or without movement disorders or microcephaly) in addition to CSF-to-blood glucose ratio below 0.5. They were all treated with either classical KD or modified Atkins diet (MAD). The effect of the diet with >90% reduction in the seizure frequency was, in retrospect, considered as a support for the diagnosis. The patients underwent standardized neuropsychological assessment before the diet was initiated, and they were reassessed after a minimum of six months on the diet. The neuropsychological tests were individually selected for each patient in order to match their cognitive level. The main finding was a considerable improvement in several aspects of neuropsychological functioning after 6-17 months of dietary treatment in all the six patients. The greatest progress was seen in the youngest children. Our findings suggest that early diagnosis and dietary treatment are important in order to prevent developmental delay. However, also adults with GLUT1-DS may profit from dietary treatment by improving alertness, setting the stage for enhanced learning capacity, as well as physical endurance and quality of life. PMID:25240122

  10. Impact of ketogenic diet on emotional and social behavior in children with intractable epilepsy%生酮饮食对难治性癫痫患儿情绪和社会行为的影响

    徐文成; 陶玺宬; 周自云; 吴德; 唐久来

    2015-01-01

    目的:了解生酮饮食( ketogenic diet,KD)对难治性癫痫患儿情绪和社会行为的影响。方法采用前瞻性病例对照研究,对66例难治性癫痫患儿,在告知相关生酮治疗疗效和不良反应后由家长选择入组,加用生酮饮食治疗的35例为生酮组,继续单用抗癫痫药物治疗的31例为对照组。研究启动前对两组患儿进行情绪和社会行为评估,生酮饮食治疗启动后,分别在第3、6、12个月再进行情绪和社会行为的评估,将评分结果转化成T分进行分析,比较生酮组和对照组之间,以及生酮组自身治疗前后患儿情绪和社会行为的改变情况。结果生酮组生酮饮食治疗后第3、6、12个月,患儿的问题维度(忧郁、焦虑、冲动性、攻击性)较对照组明显下降(P<0.05);能力维度(注意力、依从性、模仿)较对照组有明显提高(P<0.05),其中在治疗初3个月改善最为明显。结论生酮饮食能明显改善难治性癫痫患儿的情绪和社会行为,较为安全。%Objective To understand the impact of the ketogenic diet ( ketogenic diet, KD) on the emotional and social behavior in children with refractory epilepsy. Methods A prospective case-control study was performed in 66 cases of children with intractable epilepsy from June 2011 to December 2014 treated in the hospital. After the relevant ketogenic diet efficacy and adverse reactions were informed, the groups were selected by the parents(35 cases in the patient group received completely fasting ketogenic diet treatment regimen, and 31 cases in the control group continued to receive the antiepileptic drug treatment) . Before the onset of study, the motional and social behavior of two groups of children was assessed, and after the ketogenic diet treatment, the emotional and social behavior in the following 3, 6, 12 months was assessed again, then the results of the assessment were transformed into T points scoring and compared, and the changes in the

  11. Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

    Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

    2016-08-01

    We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P rats (P rats (P rats (P rats (P rats compared with KD rats (P rats (P rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. PMID:27357802

  12. Effect of ketogenic diet on hippocampus mossy fiber sprouting and GluR5 expression in kainic acid induced rat model

    XU Xiang-ping; SUN Ruo-peng; JIN Rui-feng

    2006-01-01

    @@ Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown.1Mossy fiber sprouting in the inner molecular layer of the dentate gyrus causes the synaptic reorganization in the hippocampus, which is an important cause of temporal lobe epilepsy in animals and humans.1,2 It is also essential to the genesis and development of epilepsy. As the predominant excitatory neurotransmitter in the central nervous system, glutamate plays a role in synaptic reorganization and development of epilepsy. In recent years, the role of glutamate receptor 5 (GluR5) in the genesis of seizures has attracted more and more attention of researchers and this receptor has become a candidate target of new antiepileptic drugs.3,4 In this study, we investigated the possible antiepileptic mechanism of KD in terms of synaptic reorganization and GluR5 expression, attempting to provide a theoretical basis for the development of new antiepileptic drugs.

  13. Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies

    Mantis John G

    2004-10-01

    Full Text Available Abstract Background The high fat, low carbohydrate ketogenic diet (KD was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted (SD-UR or restricted (SD-R, and either a KD unrestricted (KD-UR or restricted (KD-R. All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once/week over a nine-week treatment period. Results Body weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p Conclusions The results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone bodies for energy is predicted to manage EL epileptic seizures through multiple integrated changes of inhibitory and excitatory neural systems.

  14. The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up.

    Lambrechts, Danielle A J E; de Kinderen, Reina J A; Vles, Hans S H; de Louw, Anton J; Aldenkamp, Albert P; Majoie, Marian J M

    2015-10-01

    The present study assessed the long-term (i.e., 24months) efficacy of the ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy, with focus on seizure frequency, seizure severity, and tolerability. Most patients were treated with the MCT-diet. At one and two years, 33% and 23%, respectively, of the 48 included patients were still on the KD. After three months, one year, and two years of treatment, 16.7% of the patients were responders. The highest responder rate (i.e., 22.9%) was seen at six and nine months of treatment. Of the fifteen patients with seizure clusters during baseline, 60% were responders after three months when looking at cluster reduction and most of them were not responders for the total seizure frequency. From three months of treatment onwards, most of the patients had a relevant decrease in seizure severity which was mainly related to the most severe seizure type. Gastrointestinal dysfunction was often reported, especially in the first six weeks of treatment. Growth deceleration was present in 30% of the patients, and weight reduction in 15%. Improved arousal was mentioned in 30% of patients. No patients developed ECG abnormalities or kidney stones. Increase in lipid profile was rare. The KD is an effective therapy for children with therapy-resistant epilepsy. Effectiveness is reflected in the reduction of seizure frequency as well as in the reduction of seizure severity. After 6months of treatment, it is obvious which patients are responders and tolerate the treatment well. Most of these patients will continue to benefit from the KD for a longer time. Long-term use of the diet was well tolerated. PMID:26301622

  15. Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder.

    Smith, Jacklyn; Rho, Jong M; Teskey, G Campbell

    2016-05-01

    Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder characterized by deficits in sociability and communication, and restricted and/or repetitive motor behaviors. Amongst the diverse hypotheses regarding the pathophysiology of ASD, one possibility is that there is increased neuronal excitation, leading to alterations in sensory processing, functional integration and behavior. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD), traditionally used in the treatment of medically intractable epilepsy, has already been shown to reduce autistic behaviors in both humans and in rodent models of ASD. While the mechanisms underlying these effects remain unclear, we hypothesized that this dietary approach might shift the balance of excitation and inhibition towards more normal levels of inhibition. Using high-resolution intracortical microstimulation, we investigated basal sensorimotor excitation/inhibition in the BTBR T+Itpr(tf)/J (BTBR) mouse model of ASD and tested whether the KD restores the balance of excitation/inhibition. We found that BTBR mice had lower movement thresholds and larger motor maps indicative of higher excitation/inhibition compared to C57BL/6J (B6) controls, and that the KD reversed both these abnormalities. Collectively, our results afford a greater understanding of cortical excitation/inhibition balance in ASD and may help expedite the development of therapeutic approaches aimed at improving functional outcomes in this disorder. PMID:26876011

  16. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

    Poff, A M; Ward, N; Seyfried, T N; Arnold, P; D'Agostino, D P

    2015-01-01

    The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control), low glucose (LG), ketone supplementation (βHB), hyperbaric oxygen (HBOT), or combination therapy (LG+βHB+HBOT) on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers. PMID:26061868

  17. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

    A M Poff

    Full Text Available The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control, low glucose (LG, ketone supplementation (βHB, hyperbaric oxygen (HBOT, or combination therapy (LG+βHB+HBOT on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers.

  18. Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus

    Hansen, Suzanne L; Nielsen, Ane H; Knudsen, Katrine E; Artmann, Andreas; Kristiansen, Uffe; Hansen, Steen Honore'; Hansen, Harald S; Petersen, Gitte

    activity or type of diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines were significantly decreased by the KD, but were unaffected by seizure activity. The study shows that the KD had clear antiepileptogenic properties in the pentylenetetrazole kindling model and does not...... support a role of endocannabinoids in this model. The significance of the decreased hippocampal level of oleoylethanolamide awaits further studies....

  19. Diastolic Dysfunction Induced by a High-Fat Diet Is Associated with Mitochondrial Abnormality and Adenosine Triphosphate Levels in Rats

    Kang, Ki-Woon; Kim, Ok-Soon; Chin, Jung Yeon; Kim, Won Ho; Park, Sang Hyun; Choi, Yu Jeong; Shin, Jong Ho; Jung, Kyung Tae; Lim, Do-Seon; Lee, Seong-Kyu

    2015-01-01

    Background Obesity is well-known as a risk factor for heart failure, including diastolic dysfunction. However, this mechanism in high-fat diet (HFD)-induced obese rats remain controversial. The purpose of this study was to investigate whether cardiac dysfunction develops when rats are fed with a HFD for 10 weeks; additionally, we sought to investigate the association between mitochondrial abnormalities, adenosine triphosphate (ATP) levels and cardiac dysfunction. Methods We examined myocardia...

  20. Dieta cetogênica no tratamento das epilepsias graves da infância: percepção das mães Ketogenic diet in the treatment of intractable epilepsy in children: mothers view

    Alexsandra Tomé

    2003-06-01

    Full Text Available Este estudo teve como propósito perceber os sentimentos e dificuldades de mães de crianças com epilepsia resistente ao tratamento medicamentoso em relação à adoção e ao seguimento da dieta cetogênica, bem como auxiliar a influência dessa dietoterapia na rotina familiar. A metodologia utilizada foi a da pesquisa qualitativa, tendo como técnica de coleta de dados a entrevista semi-estruturada, realizada com três mães atendidas pelo Centro de Neuropediatria do Hospital de Clínicas da Universidade Federal do Paraná. Em virtude das características da dieta cetogênica, os resultados mostram que o período inicial, o da sua adoção, é bastante difícil, tanto para a criança como para toda a sua família. Entretanto, com a diminuição das crises epilépticas e a adaptação ao tratamento, uma mudança de sentimentos é observada. O estudo revela também a importância da atuação de profissionais, não apenas com competência técnica mas também com sensibilidade e empatia, no apoio às famílias das crianças em tratamento.The purpose of this study was to identify the feelings and difficulties experienced by mothers of children with drug-resistant epilepsy concerning the adoption of the ketogenic diet and its follow-up, as well as to evaluate the influence of this dietotherapy on the family routine. The qualitative research methodology was used, and data were collected through semi-structured interview, carried out with three mothers who attended the Neuropediatrics Center of the Clinical Hospital of the Federal University of Paraná, Brazil. Because of the characteristics of the ketogenic diet, the results show that the initial period, corresponding to the phase of adoption, is very difficult, for both the child and all the family. However, with the decrease in the epileptic crises and the adaptation to the treatment, a change in the feelings is observed. The study also reveals the importance of the performance of the

  1. Effect of ketogenic diet on growth of human colon cancer cells in nude mice%生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响

    郝光伟; 王海玉; 何德明; 陈榆升; 吴国豪; 张波

    2014-01-01

    Objective:To observe the effect of ketogenic diet on the growth of human colon cancer cells in nude mice and to de-termine its possible mechanisms. Methods:A total of 24 male BALB/C nude mice were injected subcutaneously with the tumor cells of the colon cancer cell line HCT116. These animals were randomized into two feeding groups. One group was fed with a ketogenic diet (KD group;n=12), and the other group was given a standard diet (SD group;n=12) ad libitum. Experiments were completed upon at-taining a target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on body weight, serum glucose, ketone body, insulin, tumor growth, and survival time, which is the interval between tumor cell injection and attainment of target tumor vol-ume. Results:The tumor growth was significantly more delayed in the KD group than in the SD group. Tumors in the KD and SD groups reached the target tumor volume at 33.8 ± 6.7 days and 24.8 ± 3.1 days, respectively. The ketone body in the KD group was ele-vated with a slight reduction in serum insulin, and the difference in serum glucose in the two groups was insignificant. Importantly, the KD group had significantly larger necrotic areas and less vessel density than the SD group. Conclusion:The application of an unre-stricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and its effect on other tumor-relevant functions, such as invasive growth and metastasis.%目的:观察生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响;探讨生酮饮食可能的作用机制。方法:24只雄性BALB/C裸鼠皮下注射人结肠癌HCT116细胞系后随机分成2组,分别给予正常饮食(standard diet,SD)及生酮饮食(ketogenic diet,KD),两组饮食均不限制总量。当肿瘤体积达到600~700 mm3时实验终止,并将接种当日至肿瘤达到目标体积的时间定义为肿瘤生长期

  2. Presentación de un caso de aplicación de la dieta cetogénica en la epilepsia refractaria Presentation of a case of ketogenic diet application to refractory epilepsy

    Ligia M Marcos Plasencia

    2007-12-01

    Full Text Available Se presenta el caso de un paciente del sexo masculino, de 2 años de edad, que padece síndrome de West y que ha recibido tratamiento con múltiples drogas antiepilépticas sin obtener resultados alentadores ni en las crisis ni en su desarrollo psicomotor, seriamente afectado. Se establece el régimen de alimentación cetogénico de instalación progresiva, sin período de ayuno inicial, y se observa un cambio clínico en el paciente a partir de que se logran niveles de cetosis, constatados por la aparición de cuerpos cetónicos en la orina. Los cambios clínicos consisten en la disminución del número de crisis diarias y de su intensidad, en la posibilidad de suspender una de las drogas antiepilépticas que usaba, y en el aumento del nivel de vigilia del paciente. Se concluye que no se debe renunciar a esta alternativa de tratamiento en los casos de epilepsia refractaria.The case of a 2-year-old male patient suffering from West syndrome that had been treated with multiple antiepileptic drugs without encouraging results, neither in the seizures, nor in his psychomotor development, which was seriously affected, was reported. A progressive ketogenic diet was established without initial fasting, and it was observed a clinical change in the patient, since ketosis levels were attained and confirmed by the appearance of ketone bodies in urine. The clinical changes consisted in the reduction of the number of daily seizures and their intensity, in the possibility of stopping the use of one of the antiepileptic drugs, and in the increase of the level of sleeplessness of the patient. It was concluded that this treatment alternative should not be rejected in the cases of refractory epilepsy.

  3. Ketogenic dietary therapy for epilepsy and other disorders: current perspectives

    Neal EG

    2014-01-01

    Elizabeth G Neal 1Matthew's Friends Clinics, Lingfield, UK, 2UCL Institute of Child Health, London, UK Abstract: The ketogenic diet (KD) is a high-fat, restricted-carbohydrate regime, originally designed to mimic metabolic responses to fasting and has been used since the 1920s as a treatment for epilepsy. Modified variants of the KD include the addition of medium-chain triglyceride and less-restrictive modified Atkins and low glycemic index protocols. Scientifically proven as treatment f...

  4. Ketogenic dietary therapy for epilepsy and other disorders: current perspectives

    Neal, Elizabeth

    2014-01-01

    Elizabeth G Neal 1Matthew's Friends Clinics, Lingfield, UK, 2UCL Institute of Child Health, London, UK Abstract: The ketogenic diet (KD) is a high-fat, restricted-carbohydrate regime, originally designed to mimic metabolic responses to fasting and has been used since the 1920s as a treatment for epilepsy. Modified variants of the KD include the addition of medium-chain triglyceride and less-restrictive modified Atkins and low glycemic index protocols. Scientifically proven as treatme...

  5. Avaliação do perfil metabólico, nutricional e efeitos adversos de crianças com epilepsia refratária em uso da dieta cetogênica Assessment of serum biochemistry, nutritional status and adverse effects of children with refractory epilepsy using the ketogenic diet

    Sueli Rizzutti

    2006-10-01

    Full Text Available OBJETIVO: Avaliar os efeitos adversos, o perfil metabólico e o crescimento pôndero-estatural de crianças com crises epilépticas de difícil controle, as quais foram submetidas a dieta cetogênica. MÉTODOS: Selecionaram-se 23 pacientes na faixa etária de 2 até 17 anos com epilepsia de difícil controle medicamentoso, sendo 43,5% (n=10 do sexo masculino e 56,5% (n=13 do sexo feminino, provenientes do Setor de Neuropediatria da Disciplina de Neurologia da Universidade Federal de São Paulo. Foram submetidos a dieta cetogênica e acompanhados por um período mínimo de um ano. Dois pacientes não conseguiram manter a cetose por falta de adesão dos pais à dieta. RESULTADOS: Os efeitos adversos encontrados foram reversíveis, incluindo hiperlipidemia, obstipação (17,4%, náuseas e vômitos (43,4%, sonolência (47,8%, infecções intercorrentes (3,0%, recusa da dieta (13,0% e epistaxe (4,3%. O crescimento pôndero-estatural não foi afetado, tendo o peso e a estatura seguido o percentil adequado. CONCLUSÃO: A dieta cetogênica pode constituir-se em uma alternativa segura e efetiva para o tratamento de crianças com epilepsia refratária.OBJECTIVE: The purpose of this research was to evaluate adverse events, serum biochemistry, growth and nutritional status of children with difficult-to-control seizures who were submitted to ketogenic diet. METHODS: Twenty-three patients aging from 2 to 17 years with refractory epilepsies, where 43.5% (n=10 were males and 56.5% (n=13 females from the Sector of Neuropediatrics, Discipline of Neurology of the Universidade Federal de São Paulo, were treated with the ketogenic diet and followed up for at least 1 year. Two patients were not able to achieve persistent ketosis either because they rejected the diets or their parents did not comply. RESULTS: Adverse events were all reversible and included hyperlipidemia, constipation (17.4%, nausea and vomiting (43.4%, drowsiness (47.8%, intercurrent infections (3

  6. Prospective multicenter study on long-term ketogenic diet therapy for intractable childhood epilepsy%长期生酮饮食治疗儿童难治性癫(癎)的前瞻性多中心研究

    中华医学会儿科学分会神经学组生酮饮食疗法协作组

    2013-01-01

    Objective To evaluate the efficacy and safety of long-term ketogenic diet (KD) on the children with intractable epilepsy.Method This was a prospective,open-label study of intractable epilepsy patients treated with the classic KD with a lipid-to-nonlipid ratio 4:1 between October 2004 and July 2011 at five Chinese epilepsy centers.A total of 299 patients were enrolled.The patients were divided into different groups according to age (including the below-l-year-old group,1-to-3-year-old group,3-to-6-year-old group,6-to-10-year-old group,and over-10-year-old group),etiology (cryptogenic epilepsy,symptomatic epilepsy,and idiopathic epilepsy),and the seizure types (included infantile spasm,Lennox-Gastaut syndrome,Ohtahara syndrome,tuberous sclerosis,Dravet syndrome,generalized epilepsy,and partial epilepsy).Parents were assigned to write seizure diaries which recorded the seizure presentations,tolerability,and complications associated with the KD.Patients' weight and height were measured every week.Blood β-hydroxybutyric acid,blood sugar,and urinary ketone bodies were monitored closely.Patients were followed up through telephone calls hy the nutritionists every month and regular outpatient visits or hospitalizations were recommended at all time-points which included the third,sixth and twelfth month after initiation.Efficacy was measured through seizure frequency.The variables related to the efficacy were also analyzed.SPSS 17.0 was used for all statistical analysis.Result At 3,6,and 12 months after initiation,65.9%,44.8%,and 26.4% patients remained on the diet,and 37.4%,26.1%,and 20.4% had a >50% reduction in their seizure frequency,including 21.7%,10.7%,and l l.0% who became seizure free,respectively.At 24 months after initiation,29 patients remained on the diet,and 28 patients had a >90% seizure reduction,including five became seizure free.At 36 months after initiation,7 patients remained on the diet,and all of them had a > 90% seizure

  7. 生酮饮食添加治疗难治性癫(癇)36例%Clinical observation of ketogenic diet adding for refractory epilepsy in 36 cases of children

    朱登纳; 谢蒙蒙; 王军; 王俊辉; 王明梅; 张广宇; 马德有; 熊华春; 孙莉

    2014-01-01

    Objective To observe the clinical efficacy,retention rates,adverse reactions of the ketogenic diet (KD) and their effects on cognitive function in children with refractory epilepsy,and to compare the clinical efficacy and retention rates of in-patient group and out-patient group.Methods This study enrolled 36 patients with refractory epilepsy who received KD therapy in Rehabilitation Center for Children with Cerebral Palsy in Henan Province of the Third Affiliated Hospital of Zhengzhou University from May 2012 to Oct.2013.They were divided into in-patient group and out-patient group.The in-patient group received classic KD therapy which started with fasting,the ratio of lipid to non-lipid was 4 ∶ 1 ;while the out-patient group was not asked for fasting,and lipid to non-lipid ratio gradually increased to 4 ∶ 1.Seizure frequency before treatment was set as the baseline,the clinical efficiency was evaluated,changes in seizure frequency,type,degree and the duration of each episode were recorded during KD therapy,and Gesell Developmental Scale assessment was respectively performed prior to KD therapy,3,6,12 months after KD therapy.Results The total effective rates in the in-patient group were 60.0%,45.0%,40.0%,respectively after 3,6,12 months of therapy,the retention rates were 80.0%,55.0%,and 40.0%,respectively,and the complete control rate was 30% ;while the total effective rates in out-patient group were 37.5%,25.0%,and 18.8%,respectively after 3,6,12 months of treatment,the retention rates were 62.5 %,37.5 %,18.8%,respectively,and the complete control rate was 12.5 % ;the in-patient group showed a significant difference compared with the out-patient group in the clinical efficacy (P < 0.05),two groups had no significant difference in retention rate (P > 0.05),short-time adverse effects in the in-patient group were mainly gastrointestinal reactions and long-term adverse effects were mainly kidney stones,adverse effects in

  8. Diets

    Your diet is made up of what you eat. A healthy diet May include fruits, vegetables, whole grains, and fat- ... added sugars There are many different types of diets. Some, like a vegetarian diet, don't include ...

  9. Ketogenic dietary therapy for epilepsy and other disorders: current perspectives

    Neal EG

    2014-04-01

    Full Text Available Elizabeth G Neal 1Matthew's Friends Clinics, Lingfield, UK, 2UCL Institute of Child Health, London, UK Abstract: The ketogenic diet (KD is a high-fat, restricted-carbohydrate regime, originally designed to mimic metabolic responses to fasting and has been used since the 1920s as a treatment for epilepsy. Modified variants of the KD include the addition of medium-chain triglyceride and less-restrictive modified Atkins and low glycemic index protocols. Scientifically proven as treatment for intractable seizures in children, these ketone-generating diets are increasingly also being used in adults. They are the treatment of choice in glucose transporter type 1 deficiency syndrome and pyruvate dehydrogenase deficiency. Evidence for the potential of KD therapy to be included within the treatment options for cancer and neurodegenerative disorders is more limited, albeit an exciting area of research with future clinical potential. This review discusses the key aspects of KD therapy, including the efficacy of treatments and clinical implementation. The importance of appropriate initiation, adequate clinical supervision, regular monitoring, and assessment of nutritional needs is highlighted. Keywords: diet, seizures, ketosis

  10. The Modified Atkins Diet in Refractory Epilepsy

    Suvasini Sharma; Puneet Jain

    2014-01-01

    The modified Atkins diet is a less restrictive variation of the ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Recent studies have shown good efficacy and tolerability of this diet in refractory epilepsy. In this review, we discuss the use of the modified Atkins diet in refractory epilepsy.

  11. The modified atkins diet in refractory epilepsy.

    Sharma, Suvasini; Jain, Puneet

    2014-01-01

    The modified Atkins diet is a less restrictive variation of the ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Recent studies have shown good efficacy and tolerability of this diet in refractory epilepsy. In this review, we discuss the use of the modified Atkins diet in refractory epilepsy. PMID:24627806

  12. Low-carbohydrate diets cause obesity, low-carbohydrate diets reverse obesity: a metabolic mechanism resolving the paradox

    Mobbs, Charles V.; Mastaitis, Jason; Yen, Kelvin; Schwartz, Joseph; Mohan, Vinuta; Poplawski, Michal; Isoda, Fumiko

    2006-01-01

    High-fat diets produce obesity in part because, per calorie, glucose produces greater post-prandial thermogenesis than lipids, an effect probably mediated by glucose-sensing neurons. A very low carbohydrate/high-fat/high-protein Atkins-type diet produces obesity but is marginally ketogenic in mice. In contrast, high-sucrose/low-fat diets, and very low carbohydrate/high-fat/low-protein (anti-epileptic) ketogenic diets reverse diet-induced obesity independent of caloric intake. We propose that ...

  13. Diets

    ... many different types of diets. Some, like a vegetarian diet, don't include meats. Others, like the Mediterranean diet, describe a traditional way of eating of a specific region. And there are diets for people with certain health problems, such as diabetes and high blood pressure. ...

  14. 21 CFR 862.1385 - 17-Hydroxycorticosteroids (17-ketogenic steroids) test system.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 17-Hydroxycorticosteroids (17-ketogenic steroids... Clinical Chemistry Test Systems § 862.1385 17-Hydroxycorticosteroids (17-ketogenic steroids) test system. (a) Identification. A 17-hydroxycorticosteroids (17-ketogenic steroids) test system is a...

  15. [Not Quite] The Ketogenic Diet in a Pill

    Andrew J Kim

    2015-04-01

    Full Text Available Researchers at Okayama University, Japan showed lactate dehydrogenase (LDH inhibition suppresses neuronal excitation in vitro, reduces EEG discharges and seizures in rodent models, and may provide a novel mechanism for anticonvulsant medications in human patients.

  16. What Constitutes a Relevant Animal Model of the Ketogenic Diet?

    Gregory L Holmes

    2008-01-01

    Animal models of human disease have been enormously important in improving our understanding of the pathophysiological basis and the development of novel therapies. In epilepsy, modeling using both in vivo and in vitro preparations has provided insight into fundamental neuronal mechanisms. Indeed, much of our understanding of seizure mechanisms comes from animal studies. The conceptual advances in understanding basic mechanisms of epilepsies have been largely validated in humans, attesting to...

  17. Effects of glucogenic and ketogenic feeding strategies on splanchnic glucose and amino acid metabolism in postpartum transition Holstein cows

    Larsen, Mogens; Kristensen, Niels Bastian

    2012-01-01

    assigned to 1 of 3 feeding strategies: a glucogenic diet (GLCG) based on sodium hydroxide treated wheat grain (56.5% of diet dry matter); a ketogenic diet (KETO) based on fodder beets (40.5% of diet dry matter); or an alfalfa-glucogenic strategy (ALF-GLCG) supplying 100% alfalfa (Medicago sativa L...... lactation progressed with ALF-GLCG and GLCG, but not with KETO. The high alfalfa haylage allowance at 4 DIM with the ALF-GLCG treatment induced the lowest net release of nutrients from the splanchnic tissues at 4 DIM. The hepatic removal of lactate as percent of total influx (mean ± SEM) increased from 27...... increasing small intestinal glucose absorption was observed. In conclusion, the glucogenic feeding strategy induced the highest glucogenic status among the tested feeding strategies due to greater release of glucose from splanchnic tissues. In contrast, the immediate postpartum high allowance of alfalfa...

  18. Adenosine in exercise adaptation.

    Simpson, R E; Phillis, J. W.

    1992-01-01

    By influencing the regulation of the mechanisms of angiogenesis, erythropoietin production, blood flow, myocardial glucose uptake, glycogenolysis, systolic blood pressure, respiration, plasma norepinephrine and epinephrine levels, adenosine may exert a significant effect on the body's adaptation response to exercise. However, adenosine's possible influence over the vasodilatory response to exercise in skeletal muscle is controversial and more research is required to resolve this issue. Variou...

  19. Breath acetone concentration; biological variability and the influence of diet

    Španěl, Patrik; Dryahina, Kseniya; Rejšková, A.; Chippendale, T. W. E.; Smith, D.

    2011-01-01

    Roč. 32, č. 8 (2011), N23-N31. ISSN 0967-3334 R&D Projects: GA ČR GP203/09/P172 Institutional research plan: CEZ:AV0Z40400503 Keywords : acetone * breath * ketogenic diet Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.677, year: 2011

  20. Adenosine Receptors and Asthma

    Wilson, Constance N; Nadeem, Ahmed; Spina, Domenico; Brown, Rachel; Page, Clive P.; Jamal Mustafa, S.

    2009-01-01

    The pathophysiological processes underlying respiratory diseases like asthma are complex, resulting in an overwhelming choice of potential targets for the novel treatment of this disease. Despite this complexity, asthmatic subjects are uniquely sensitive to a range of substances like adenosine, thought to act indirectly to evoke changes in respiratory mechanics and in the underlying pathology, and thereby to offer novel insights into the pathophysiology of this disease. Adenosine is of partic...

  1. Lower fat and better quality diet therapy for children with pharmacoresistant epilepsy

    Yoon, Jung-Rim; Kim, Heung Dong; Kang, Hoon-Chul

    2013-01-01

    The ketogenic diet (KD) is an established, effective, nonpharmacologic treatment for children with pharmacoresistant epilepsy. Although the KD is the most well-established dietary therapy for epilepsy, it is too restrictive and is associated with serious complications; therefore, alternative lower-fat diets, including a modified Atkins diet and low-glycemic index diet, have been developed. Recent ongoing clinical evidence suggests that other dietary therapies have an efficacy almost comparabl...

  2. Impact of ketogenic diet on follicular helper T cells in children with intractable epilepsy%生酮饮食治疗对难治性癫(痫)患儿滤泡辅助性T淋巴细胞的影响

    周厚福; 李成荣; 廖建湘; 王国兵; 林素芳; 陈黎

    2015-01-01

    胞数量及功能,抑制B淋巴细胞分化,这可能是少数患儿长期KD治疗导致低丙种球蛋白血症的原因之一.%Objective To explore the impact of ketogenic diet (KD) on follicular helper T cells(TFH) in children with intractable epilepsy.Methods Thirty-three cases with intractable epilepsy were selected between Jul.2013 and Jan.2014 in Shenzhen Children's Hospital,19 boys and 14 girls; average age was 39.6 months,and seventeen age-matched healthy children who took a physical examination in the same hospital were assigned as the healthy control group.Blood samples were collected from the children with refractory epilepsy before and after 1 week of KD treatment.The proportions of the various stages of B cells and TFH cells were detected by flow cytometry.The plasma concentration of interleukin-21 (IL-21) was determined by enzyme-linked immunosorbent assay(ELISA),and realtime quantitative PCR(RT-PCR) was performed to detect the levels of peroxisome proliferator-activated receptor gamma (PPAR-γ),B-lymphocyte-induced maturation protein-1 (Blimp-1),B-cell lymphoma 6 (Bcl6) and IL-21 mRNA expression in CD4 + T cells.Results (1) The number of TFH cells in children with intractable epilepsy [(3.57 ± 0.58) %] was remarkably decreased after KD treatment(P < 0.01),while there were no difference between after KD treatment and healthy control group[(4.93 ±0.70)% vs (5.03 ±0.63)%,P >0.05].(2) The levels of transcription factor Bcl6 expression after treatment were significantly decreased,while inhibitory factor Blimp-1 expression increased (P < 0.05).(3)The plasma concentration of IL-21 had a trend to decrease (P > 0.05),while there were no difference before and after KD treatment,and levels of IL-21 mRNA expressions in CD4 +T cells were significantly decreased after the treatment (8.28 × 10-3 ± 1.19 × 10-3 vs 1.72 × 10-2 ± 0.81 × 10-2,t =3.08,P < 0.05).(4) There was no significant difference in CD27-IgD + B cells before and after KD

  3. Adenosine and sleep

    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 A1 receptors, 3H-L-PIA binding was measured. The Bmax values for 3H-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 3H-L-PIA binding resulted from REM sleep deprivation and not from stress

  4. Adenosine and sleep

    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.

  5. A decade of the modified Atkins diet (2003–2013): Results, insights, and future directions.

    Kossoff, Eric H; Cervenka, Mackenzie C; Henry, Bobbie J; Haney, Courtney A; Turner, Zahava

    2013-12-01

    The modified Atkins diet has been used since 2003 for the treatment of children and adults with refractory epilepsy.This “alternative” ketogenic diet is started in clinic, without fasting, hospitalization, and restriction of protein,calories, or fluid intake. Now after 10 years of continued use, approximately 400 patients have been reported in over 30 studies of the modified Atkins diet as treatment for intractable seizures, with results demonstrating similar efficacy to the ketogenic diet and improved tolerability. The modified Atkins diet is being increasingly used in the adult population. Clinical trials have provided insight into the mechanisms of action of dietary therapies overall. This review will discuss the past decade of experience with the modified Atkins diet as well as predictions for its role in the treatment of epilepsy a decade from now. PMID:24386671

  6. Ketogene Diät zur Behandlung von pharmakoresistenten Epilepsien und Stoffwechseldefekten im Kindesalter

    Liebhaber, Gisela Maria

    2005-01-01

    Die Ketogene Diät ist eine streng bilanzierte, sehr fettreiche, an Kohlenhydraten stark reduzierte Ernährungsform mit ausreichendem Eiweiß- und Energiegehalt. Sie wurde in den 1920er-Jahren entwickelt und hat ihre Indikationen in der Behandlung des Glucose-Transporter-Defekts, des Pyruvat-Dehydrogenase-Mangels und bei pharmakoresistenten Epilepsien. Da nur sehr wenig deutschsprachige Literatur über die Ketogene Diät vorliegt, wird im ersten Teil der Arbeit ein Überblick über die Ketogene Diät...

  7. Adenosine and Sleep

    Bjorness, Theresa E.; Greene, Robert W.

    2009-01-01

    Over the last several decades the idea that adenosine (Ado) plays a role in sleep control was postulated due in large part to pharmacological studies that showed the ability of Ado agonists to induce sleep and Ado antagonists to decrease sleep. A second wave of research involving in vitro cellular analytic approaches and subsequently, the use of neurochemical tools such as microdialysis, identified a population of cells within the brainstem and basal forebrain arousal centers, with activity t...

  8. Weight loss and body composition changes following three sequential cycles of ketogenic enteral nutrition

    Gianfranco Cappello

    2012-01-01

    Full Text Available Background: Ketogenic enteral nutrition (KEN is a modification of the protein sparing modified fast in which a protein solution is introduced with a continuous infusion through a nasogastric tube over 10-days cycles. The aim of the study was to perform a retrospective analysis of the safety, compliance, weight loss and body composition changes after 3 sequential 10-days cycles of KEN therapy. Materials and Methods: From a large number of patients who underwent KEN therapy in our department over a 5-year period, we selected 188 patients who participated in 3 KEN cycles with 10-13 days of break between them. Before and after the treatment cycles, body composition was analyzed by bioelectric impedance; a final assessment was made 10 days after the end of last cycle. During each rest period all the patients were on a low-carbohydrate, normal caloric diet. Results: Most patients (97% successfully tolerated the nasogastric treatment and lost an average of 14.4 kg of body weight, 10.6 kg of fat mass and 3.4 kg of body cell mass. Adverse effects were recorded as mild gastric hypersecretion (2% and constipation (5%. Patients continued to lose fat during the 10-day follow up period after the end of each KEN Cycle. This effect may be explained by abnormality of water distribution during the rapid weight loss inducing the observed change in fat mass. Conclusion: Ten-days KEN treatment cycles can induce rapid weight loss and reduction of fat mass in obese patients. Furthermore, preservation of lean mass can be achieved by infusing 1.9 g of protein/kg of BCM.

  9. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    de Mello Maria; Ventrucci Gislaine; Gomes-Marcondes Maria

    2002-01-01

    Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rat...

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

    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...

  11. Adenosine-Associated Delivery Systems

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

    2016-01-01

    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

  12. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy

    Law, Tsz Hong; Davies, Emma S. S.; Pan, Yuanlong; Zanghi, Brian; Want, Elizabeth; Volk, Holger A.

    2015-01-01

    Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dog...

  13. MODIFIED ATKINS DIET FOR INTRACTABLE CHILDHOOD EPILEPSY

    Mohammad BARZEGAR

    2010-12-01

    Full Text Available ObjectiveThe aim of the present study was to evaluate the efficacy and tolerability of a modified Atkins diet for intractable childhood epilepsy.Materials & MethodsTwenty one children with medically intractable epilepsy were enrolled in the study. Inclusion criteria were at least four seizures per month and a trial of at least three anticonvulsants without becoming seizure-free. The subjects received the diet over a 6-month period.ResultsThree months after diet initiation, 15 patients (71.4% remained on the diet and 12 (57.1% had >50% seizure reduction. Eleven patients (52.4% completed the 6-month study and 8 (38.1% chose to remain on the diet afterward. At 6 months, 9 patients (42.8% had >50% seizure reduction. The diet was more effective in cryptogenic epilepsy (p=0.032. Most complications were transient and successfully managed by careful follow-up and conservative strategies.ConclusionThe modified Atkins diet is an effective and well- tolerated therapy for intractable childhood epilepsy.Keywords:Atkins diet, ketogenic diet,intractable epilepsy, children

  14. Lower fat and better quality diet therapy for children with pharmacoresistant epilepsy.

    Yoon, Jung-Rim; Kim, Heung Dong; Kang, Hoon-Chul

    2013-08-01

    The ketogenic diet (KD) is an established, effective, nonpharmacologic treatment for children with pharmacoresistant epilepsy. Although the KD is the most well-established dietary therapy for epilepsy, it is too restrictive and is associated with serious complications; therefore, alternative lower-fat diets, including a modified Atkins diet and low-glycemic index diet, have been developed. Recent ongoing clinical evidence suggests that other dietary therapies have an efficacy almost comparable to that of the KD. In addition, a diet rich in polyunsaturated fatty acids appears to increase the efficacy of diet therapy and reduce the complications of a high-fat diet. Here, we review the systematic information about lower-fat diets and better-quality dietary therapies and the current clinical status of each of these dietary approaches. PMID:24019842

  15. Impact of weight loss achieved through a very-low calorie diet on compensatory mechanisms activated during weight reduction in obese individuals

    Torgersen, Linn-Christin Haugland

    2014-01-01

    Background: Diet-induced weight loss is accompanied by compensatory mechanisms, with increased drive to eat, and reduced energy expenditure, which try to restore energy balance. Ketosis has been shown to modulate some of these compensatory mechanisms, particularly at the level of appetite, but few studies have been done in this field. Purpose: Evaluate the impact of losing weight with a ketogenic very low calorie diet (VLCD) on subjective feelings of appetite, resting metabo...

  16. Adenosine-induced activation of esophageal nociceptors.

    Ru, F; Surdenikova, L; Brozmanova, M; Kollarik, M

    2011-03-01

    Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors. Whole cell perforated patch-clamp recordings and single-cell RT-PCR analysis were performed on the primary afferent neurons retrogradely labeled from the esophagus in the guinea pig. Extracellular recordings were made from the isolated innervated esophagus. In patch-clamp studies, adenosine evoked activation (inward current) in a majority of putative nociceptive (capsaicin-sensitive) vagal nodose, vagal jugular, and spinal dorsal root ganglia (DRG) neurons innervating the esophagus. Single-cell RT-PCR analysis indicated that the majority of the putative nociceptive (transient receptor potential V1-positive) neurons innervating the esophagus express the adenosine receptors. The neural crest-derived (spinal DRG and vagal jugular) esophageal nociceptors expressed predominantly the adenosine A(1) receptor while the placodes-derived vagal nodose nociceptors expressed the adenosine A(1) and/or A(2A) receptors. Consistent with the studies in the cell bodies, adenosine evoked activation (overt action potential discharge) in esophageal nociceptive nerve terminals. Furthermore, the neural crest-derived jugular nociceptors were activated by the selective A(1) receptor agonist CCPA, and the placodes-derived nodose nociceptors were activated by CCPA and/or the selective adenosine A(2A) receptor CGS-21680. In contrast to esophageal nociceptors, adenosine failed to stimulate the vagal esophageal low-threshold (tension) mechanosensors. We conclude that adenosine selectively activates esophageal nociceptors. Our data indicate that the esophageal neural crest-derived nociceptors can be activated via the adenosine A(1) receptor while the placodes

  17. Adenosine in inflammatory joint diseases

    Chan, E. S. L.; Fernandez, P.; Cronstein, B. N.

    2007-01-01

    Inflammatory joint diseases are a group of heterogeneous disorders with a variety of different etiologies and disease manifestations. However, there are features that are common to all of them: first, the recruitment of various inflammatory cell types that are attracted to involved tissues over the course of the disease process. Second, the treatments used in many of these diseases are commonly medications that suppress or alter immune function. The demonstration that adenosine has endogenous...

  18. Role of extracellular adenosine in Drosophila

    FENCKOVÁ, Michaela

    2011-01-01

    This thesis describes several aspects of the role for extracellular adenosine in Drosophila. Reverse genetic, molecular and microscopic methods together with the most forefront Drosophila research techniques have been applied to elucidate the role of adenosine signaling in the regulation of development, physiology and metabolism of Drosophila larvae. The thesis helps to establish the model for extracellular adenosine as a stress-signal for the release of energy stores. It also describes the e...

  19. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

    Bielohuby, Maximilian; Sisley, Stephanie; Sandoval, Darleen; Herbach, Nadja; Zengin, Ayse; Fischereder, Michael; Menhofer, Dominik; Stoehr, Barbara J M; Stemmer, Kerstin; Wanke, Rüdiger; Tschöp, Matthias H; Seeley, Randy J; Bidlingmaier, Martin

    2013-11-01

    Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects. PMID:23982154

  20. Glucose transporter type 1 deficiency syndrome effectively treated with modified Atkins diet.

    Haberlandt, Edda; Karall, Daniela; Jud, Veronika; Baumgartner, Sara Sigl; Zotter, Sibylle; Rostasy, Kevin; Baumann, Matthias; Scholl-Buergi, Sabine

    2014-04-01

    This is a report on the successful treatment of a 6-year-old girl with genetically proven glucose transporter type 1 deficiency syndrome (GLUT1-DS) with modified Atkins diet (MAD). GLUT1-DS is an inborn disorder of glucose transport across the blood-brain barrier, which leads to energy deficiency of the brain with a broad spectrum of neurological symptoms including therapy-resistant epilepsy. Usually classical ketogenic diet (KD) is the standard treatment for patients with GLUT1-DS. Treatment with MAD, a variant of KD, for an observation period of 17 months resulted in improvement of seizures, alertness, cognitive abilities, and electroencephalography in this patient. PMID:23888468

  1. Effect of adenosine and adenosine analogs on [14C]aminopyrine accumulation by rabbit parietal cells

    Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on [14C]aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. [14C]Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated [14C]aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on [14C]aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased [14C]aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion

  2. Optical Aptasensors for Adenosine Triphosphate

    Ng, Stella; Lim, Hui Si; Ma, Qian; Gao, Zhiqiang

    2016-01-01

    Nucleic acids are among the most researched and applied biomolecules. Their diverse two- and three-dimensional structures in conjunction with their robust chemistry and ease of manipulation provide a rare opportunity for sensor applications. Moreover, their high biocompatibility has seen them being used in the construction of in vivo assays. Various nucleic acid-based devices have been extensively studied as either the principal element in discrete molecule-like sensors or as the main component in the fabrication of sensing devices. The use of aptamers in sensors - aptasensors, in particular, has led to improvements in sensitivity, selectivity, and multiplexing capacity for a wide verity of analytes like proteins, nucleic acids, as well as small biomolecules such as glucose and adenosine triphosphate (ATP). This article reviews the progress in the use of aptamers as the principal component in sensors for optical detection of ATP with an emphasis on sensing mechanism, performance, and applications with some discussion on challenges and perspectives. PMID:27446501

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

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

    2014-01-01

    Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies. Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of β-adrenergic receptors. Because BAT...... 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....

  4. Adenosine regulation of alveolar fluid clearance

    Factor, Phillip; Mutlu, Göskhan M.; Chen, Lan; Mohameed, Jameel; Akhmedov, Alexander T.; Meng, Fan Jing; Jilling, Tamas; Lewis, Erin Rachel; Johnson, Meshell D.; Xu, Anna; Kass, Daniel; Martino, Janice M.; Bellmeyer, Amy; Albazi, John S.; Emala, Charles

    2007-01-01

    Adenosine is a purine nucleoside that regulates cell function through G protein-coupled receptors that activate or inhibit adenylyl cyclase. Based on the understanding that cAMP regulates alveolar epithelial active Na+ transport, we hypothesized that adenosine and its receptors have the potential to regulate alveolar ion transport and airspace fluid content. Herein, we report that type 1 (A1R), 2a (A2aR), 2b (A2bR), and 3 (A3R) adenosine receptors are present in rat and mouse lungs and alveol...

  5. Adenosine triphosphate inhibition of yeast trehalase.

    Panek, A D

    1969-09-01

    Yeast trehalase has been found to be inhibited non-competitively by adenosine triphosphate. Such a biological control could explain the accumulation of trehalose during the stationary phase of the growth curve. PMID:5370287

  6. Role of adenosine receptors in caffeine tolerance

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity

  7. Electrocardiographic profile of adenosine pharmacological stress testing

    Sun, Hao; TIAN, YUEQIN; ZHENG, LIHUI; Pan, Qingrong; XIE, BOQIA

    2015-01-01

    Adenosine stress testing in conjunction with radionuclide myocardial perfusion imaging has become a common approach for the detection of coronary artery diseases in patients who are unable to perform adequate levels of exercise. However, specific electrocardiographic alterations during the test have been rarely described. Using a Chinese population, the aim of the present study was to provide a detailed electrocardiographic profile of adenosine stress testing. The study population included 1,...

  8. Adenosine stress protocols for myocardial perfusion imaging

    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

  9. Internalization and desensitization of adenosine receptors

    Klaasse, Elisabeth C.; IJzerman, Adriaan P.; de Grip, Willem J.; Beukers, Margot W.

    2007-01-01

    Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A1, A2A, A2B and A3 receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body and involved in a variety of physiological processes and diseases, there is great interest in understanding how the different subtypes are re...

  10. Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report

    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

  11. Paleolithic diet

    Malus, Katja

    2014-01-01

    The paleolithic diet is a diet which imitates the nutrition eaten by various species of hominoids living in the paleolithic era by using foodstuffs available today. The objectives of our thesis were to research the nutrition of human ancestors, to describe a modern paleolithic diet and compare it to healthy dietary guidelines and present experience of individuals who were experimentally eating a paleolithic diet. The aim was to determine whether consuming a paleolithic diet could have benefic...

  12. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adenosine triphosphate release assay. 864.7040 Section 864.7040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Adenosine triphosphate release assay. (a) Identification. An adenosine triphosphate release assay is...

  13. Study of Ectonucleotidases and Adenosine Deaminases in Drosophila

    PREUER, Kristina

    2013-01-01

    Extracellular adenosine triphosphate and extracellular adenosine are important regulatory molecules in the human immune system. The concentrations of these molecules are in turn regulated by ectonucleotidases and adenosine deaminases. In this thesis I attempt to test the gene silencing efficiency of RNA interference for three different genes coding for such enzymes in the model organism Drosophila melanogaster.

  14. Internalization and desensitization of adenosine receptors.

    Klaasse, E.C.; IJzerman, A.P.; Grip, W.J. de; Beukers, M.W.

    2008-01-01

    Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A(1), A(2A), A(2B) and A(3) receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein clas

  15. Effects of adenosine infusion into renal interstitium on renal hemodynamics

    This study was designed to investigate the hemodynamic effects of exogenous adenosine in the interstitium of the rat kidney. Adenosine or its analogues were infused into the renal interstitium by means of chronically implanted capsules. In fusion of adenosine decreased glomerular filtration rate (GFR) from 0.81 +/- 0.06 to 0.37 +/- 0.06 ml/min while having no effect on renal blood flow (RBF). The metabolically stable analogue, 2-chloradenosine (2-ClAdo), decreased GFR from 0.73 +/- 0.07 to 021 +/- 0.06 ml/min. Interstitial infusion of theophylline, an adenosine receptor antagonist, completely abolished the effects of adenosine and 2-ClAdo on GFR. The distribution of adenosine, when infused into the renal interstitium, was determined using radiolabeled 5'-(N-ethyl)-carboxamidoadenosine (NECA), a metabolically stable adenosine agonist. After continuous infusion, [3H]NECA was distributed throughout the kidney. The effects of NECA to reduce GFR were similar to those of adenosine and 2-ClAdo. They conclude that increased levels of adenosine in the renal interstitium markedly decrease GFR without affecting RBF in steady-state conditions. The marked effects of adenosine agonists during their infusion into the renal interstitium and the complete blockade of these effects by theophylline suggest an extracellular action of adenosine

  16. Adenosine: An immune modulator of inflammatory bowel diseases

    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.

  17. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy.

    Law, Tsz Hong; Davies, Emma S S; Pan, Yuanlong; Zanghi, Brian; Want, Elizabeth; Volk, Holger A

    2015-11-14

    Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0-9·89/month) in comparison with the placebo diet (2·67/month, 0·33-22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall MCTD (1·63/month, 0-7·58/month) in comparison with the placebo diet (1·69/month, 0·33-13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·041 (sd 0·004) v. 0·031 (sd 0·016) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment. PMID:26337751

  18. Vegetarian Diet

    A vegetarian diet focuses on plants for food. These include fruits, vegetables, dried beans and peas, grains, seeds and nuts. There is no single type of vegetarian diet. Instead, vegetarian eating patterns usually fall into the ...

  19. Vegetarian Diet

    A vegetarian diet focuses on plants for food. These include fruits, vegetables, dried beans and peas, grains, seeds and nuts. There is no single type of vegetarian diet. Instead, vegetarian eating patterns usually fall into ...

  20. Polyunsaturated fatty acid-enriched diet therapy for a child with epilepsy.

    Yoon, Jung-Rim; Lee, Eun Joo; Kim, Heung Dong; Lee, Jae Hwan; Kang, Hoon-Chul

    2014-02-01

    The ketogenic diet (KD) is a high-fat, low-carbohydrate diet with an established efficacy for treating medically refractory epilepsy in children. Fatty acids are the most important constituent of the KD in all aspects of efficacy and complications. Among fatty acids, polyunsaturated fatty acids (PUFAs) increase anticonvulsant properties and reduce the complications associated with the high-fat diet. Here, we report a 7-year-old boy with Lennox-Gastaut syndrome combined with mitochondrial respiratory chain complex I deficiency, whose medically intractable seizures have been successfully controlled with a PUFA-enriched modified Atkins diet without any significant adverse events. The diet consists of canola oil and diverse menu items like fish and nuts instead of olive oil and has an ideal 1:2.8 ratio of omega-3 to omega-6. In addition, fractionation of this boy's plasma showed normal levels of fatty acids, including omega-3 (alpha-linoleic acid, eicosapentaenoic acid) and omega-6 (linoleic acid, arachidonic acid) as well as monounsaturated fatty acids (oleic acid). Plasma docosahexanoic acid remained low after PUFA-enriched diet therapy. PUFA-enriched diet therapy is likely to increase the efficacy of diet therapy and reduce complications of a high-fat diet in children with refractory epilepsy. PMID:23465587

  1. Adenosine receptors and asthma in humans

    Wilson, C N

    2008-01-01

    According to an executive summary of the GINA dissemination committee report, it is now estimated that approximately 300 million people (5% of the global population or 1 in 20 persons) have asthma. Despite the scientific progress made over the past several decades toward improving our understanding of the pathophysiology of asthma, there is still a great need for improved therapies, particularly oral therapies that enhance patient compliance and that target new mechanisms of action. Adenosine...

  2. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    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...

  3. Role of adenosine in oligodendrocyte precursor maturation

    Elisabetta Coppi

    2015-04-01

    Full Text Available Differentiation and maturation of oligodendroglial cells are postnatal processes involving specific morphological changes correlated with the expression of stage-specific surface antigens and functional voltage-gated ion channels. A small fraction of oligodendrocyte progenitor cells (OPCs generated during development are maintained in an immature and slowly proliferative or quiescent state in the adult central nervous system (CNS representing an endogenous reservoir of immature cells. Adenosine receptors are expressed by OPCs and a key role of adenosine in oligodendrocyte maturation has been recently recognised. As evaluated on OPC cultures, adenosine by stimulating A1 receptors, promotes oligodendrocyte maturation and inhibits their proliferation; on the contrary by stimulating A2A receptors, it inhibits oligodendrocyte maturation. A1 and A2A receptor-mediated effects are related to opposite modifications of outward delayed rectifying membrane K+ currents (IK that are involved in regulation of oligodendrocyte differentiation. Brain A1 and A2A receptors might represent new molecular targets for drugs useful in demyelinating pathologies, such as multiple sclerosis (MS, stroke and brain trauma.

  4. Effect of adenosine and adenosine analogs on ( sup 14 C)aminopyrine accumulation by rabbit parietal cells

    Ota, S.; Hiraishi, H.; Terano, A.; Mutoh, H.; Kurachi, Y.; Shimada, T.; Ivey, K.J.; Sugimoto, T. (Univ. of Tokyo (Japan))

    1989-12-01

    Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on (14C)aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. (14C)Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated (14C)aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on (14C)aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased (14C)aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.

  5. Turnover of adenosine in plasma of human and dog blood

    To determine half-life and turnover of plasma adenosine, heparinized blood from healthy volunteers was incubated with radiolabeled adenosine in the physiological concentration range of 0.1-1 microM. Plasma levels of adenosine in vitro were 82 +/- 14 nM and were similar to those determined immediately after blood collection with a ''stopping solution.'' Dipyridamole (83 microM) and erythro-9(2-hydroxynon-3yl)-adenine (EHNA) (8 microM) did not measurably alter basal adenosine levels but completely blocked the uptake of added adenosine. Inhibition of ecto-5'-nucleotidase with 100 microM alpha, beta-methyleneadenosine 5'-diphosphate (AOPCP) reduced plasma adenosine to 22 +/- 6 nM. For the determination of adenosine turnover, the decrease in specific radioactivity of added [3H]adenosine was measured using a dipyridamole-containing stopping solution. Without altering basal adenosine levels, the half-life was estimated to be 0.6 s. Similar experiments were carried out with washed erythrocytes or in the presence of AOPCP, yielding half-lives of 0.7 and 0.9 s, respectively. When the initial adenosine concentration was 1 microM, its specific activity decreased by only 11% within 5 s, whereas total plasma adenosine exponentially decreased with a half-life of 1.5 s. Venous plasma concentrations were measured after relief of a 3-min forearm ischemia. Changes in plasma adenosine did not correlate well with changes in blood flow but were augmented in the presence of dipyridamole

  6. Silk Fibroin Encapsulated Powder Reservoirs for Sustained Release of Adenosine

    Pritchard, Eleanor M.; Szybala, Cory; Boison, Detlev; Kaplan, David L.

    2010-01-01

    Due to its unique properties, silk fibroin was studied as a biodegradable polymer vehicle for sustained, local delivery of the anticonvulsant adenosine from encapsulated reservoirs. Silk is a biologically derived protein polymer that is biocompatible, mechanically strong and degrades to non-toxic products in vivo. To achieve local, sustained, controlled adenosine release from fully degradable implants, solid adenosine powder reservoirs were coated with silk fibroin. Material properties of the...

  7. Breath acetone concentration; biological variability and the influence of diet

    Previous measurements of acetone concentrations in the exhaled breath of healthy individuals and the small amount of comparable data for individuals suffering from diabetes are briefly reviewed as a prelude to the presentation of new data on the sporadic and wide variations of breath acetone that occur in ostensibly healthy individuals. Data are also presented which show that following a ketogenic diet taken by eight healthy individuals their breath acetone concentrations increased up to five times over the subsequent 6 h. Similarly, the breath acetone increased six and nine times when a low carbohydrate diet was taken by two volunteers and remained high for the several days for which the diet was continued. These new data, together with the previous data, clearly indicate that diet and natural intra-individual biological and diurnal variability result in wide variations in breath acetone concentration. This places an uncertainty in the use of breath acetone alone to monitor blood glucose and glycaemic control, except and unless the individual acts as their own control and is cognizant of the need for dietary control. (note)

  8. A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment

    Ohta, Akio

    2016-01-01

    Within tumors, some areas are less oxygenated than others. Since their home ground is under chronic hypoxia, tumor cells adapt to this condition by activating aerobic glycolysis; however, this hypoxic environment is very harsh for incoming immune cells. Deprivation of oxygen limits availability of energy sources and induces accumulation of extracellular adenosine in tumors. Extracellular adenosine, upon binding with adenosine receptors on the surface of various immune cells, suppresses pro-inflammatory activities. In addition, signaling through adenosine receptors upregulates a number of anti-inflammatory molecules and immunoregulatory cells, leading to the establishment of a long-lasting immunosuppressive environment. Thus, due to hypoxia and adenosine, tumors can discourage antitumor immune responses no matter how the response was induced, whether it was spontaneous or artificially introduced with a therapeutic intention. Preclinical studies have shown the significance of adenosine in tumor survival strategy by demonstrating tumor regression after inactivation of adenosine receptors, inhibition of adenosine-producing enzymes, or reversal of tissue hypoxia. These promising results indicate a potential use of the inhibitors of the hypoxia–adenosine pathway for cancer immunotherapy. PMID:27066002

  9. Adenosine A1 receptor agonists inhibit trigeminovascular nociceptive transmission

    Goadsby, P J; Hoskin, K L; Storer, R J;

    2002-01-01

    There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg/kg, intraperit......There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg...

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

    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.

  11. Intravenous adenosine and radiopharmaceutical injection in the same line was feasible in adenosine stress myocardial perfusion imaging

    Adenosine stress myocardial perfusion imaging was performed with an intravenous adenosine and radiopharmaceutical injection in the same line. A syringe containing 720 μ/kg of adenosine in 40 ml of saline was prepared and injected at the constant infusion rate of 400 ml/h. Adenosine was temporarily stopped by the stopcock when 1.5 ml of thallium was injected for 0.5 second from the three-way stopcock with two ways opened. Thereafter, the stopcock was returned to the original position in 0.5 second, and adenosine flow returned to the constant flow rate again. In this method, 0.75% of adenosine total dose was injected at a rate of 3.0 ml/s and adenosine was stopped for 3.6 second. There were no significant differences in either effects and adverse events of adenosine between this method and two intravenous injection line methods. Adenosine stress in one venous line method would be an easy method maintaining the dose effect and safety. (author)

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

    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.

  13. Characterization of adenosine binding proteins in human placental membranes

    We have characterized two adenosine binding proteins in human placenta. In membranes, one site is detected with [3H] -N-ethylcarboxamidoadenosine ([3H]NECA). This site is similar to the adenosine A2 receptor. We call this site the adenosine A2-like binding site. In detergent extracts, the second site is detected and has the characteristics of an adenosine A1 receptor. The soluble adenosine A2-like binding site cannot be detected without a rapid assay. Binding to the adenosine A1 receptor with [3H]-2-chloroadenosine and [3H]NECA is time dependent, saturable, and reversible. Equilibrium displacement analysis with adenosine agonists reveals an A1 specificity: 2-chloroadenosine > R-phenylisopropyladenosine > 5'-N-ethylcarboxamidoadenosine. The antagonist potency order is 1,3-diethyl-8-phenylxanthine > isobutylmethylxanthine > theophylline. Competition analysis of membranes with the A,-selective ligands [3H]-cyclohexyladenosine [3H] cylopentylxanthine revealed adenosine A1 agonist and antagonist potency orders. We have purified the adenosine A2-like binding site. The adenosine A2-like binding site is an ubiquitous major cellular protein. It is glycosylated, highly asymmetric, and acidic. The native protein is an homodimer with a subunit molecular mass of 98 kDa. The sedimentation coefficient and partial specific volume of the binding complex are 6.9 s and 0.698 ml/g, respectively. The Stokes' radius is 70 Angstrom. The native molecular mass of the detergent-protein complex is 230 kDa. The adenosine A2-like binding site has an agonist potency order of 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine >> R-phenylisopropyladenosine and an antagonist potency order of isobutylmethylxanthine > theophylline >> 1,3-diethyl-8-phenylxanthine

  14. Characterization of adenosine binding proteins in human placental membranes

    Hutchison, K.A.

    1989-01-01

    We have characterized two adenosine binding proteins in human placenta. In membranes, one site is detected with ({sup 3}H) -N-ethylcarboxamidoadenosine (({sup 3}H)NECA). This site is similar to the adenosine A{sub 2} receptor. We call this site the adenosine A{sub 2}-like binding site. In detergent extracts, the second site is detected and has the characteristics of an adenosine A{sub 1} receptor. The soluble adenosine A{sub 2}-like binding site cannot be detected without a rapid assay. Binding to the adenosine A{sub 1} receptor with ({sup 3}H)-2-chloroadenosine and ({sup 3}H)NECA is time dependent, saturable, and reversible. Equilibrium displacement analysis with adenosine agonists reveals an A{sub 1} specificity: 2-chloroadenosine > R-phenylisopropyladenosine > 5{prime}-N-ethylcarboxamidoadenosine. The antagonist potency order is 1,3-diethyl-8-phenylxanthine > isobutylmethylxanthine > theophylline. Competition analysis of membranes with the A,-selective ligands ({sup 3}H)-cyclohexyladenosine ({sup 3}H) cylopentylxanthine revealed adenosine A{sub 1} agonist and antagonist potency orders. We have purified the adenosine A{sub 2}-like binding site. The adenosine A{sub 2}-like binding site is an ubiquitous major cellular protein. It is glycosylated, highly asymmetric, and acidic. The native protein is an homodimer with a subunit molecular mass of 98 kDa. The sedimentation coefficient and partial specific volume of the binding complex are 6.9 s and 0.698 ml/g, respectively. The Stokes' radius is 70 {Angstrom}. The native molecular mass of the detergent-protein complex is 230 kDa. The adenosine A{sub 2}-like binding site has an agonist potency order of 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine >> R-phenylisopropyladenosine and an antagonist potency order of isobutylmethylxanthine > theophylline >> 1,3-diethyl-8-phenylxanthine.

  15. High-dose adenosine overcomes the attenuation of myocardial perfusion reserve caused by caffeine.

    Reyes, E.; Loong, C Y; Harbinson, Mark; Donovan, J; Anagnostopoulos, C.; Underwood, S. R.

    2008-01-01

    Objectives:We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation.Background:Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose.Methods:Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (bas...

  16. Diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms

    Choi, In Young; Piccio, Laura; Childress, Patra; Bollman, Bryan; Ghosh, Arko; Brandhorst, Sebastian; Suarez, Jorge; Michalsen, Andreas; Cross, Anne H.; Morgan, Todd E.; Wei, Min; Paul, Friedemann; Bock, Markus; Longo, Valter D.

    2016-01-01

    Summary Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here we show that periodic 3 day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice, and completely reversed symptoms in 20% of the animals. These improvements were associated with increased corticosterone levels and Treg cell number, reduced levels of pro-inflammatory cytokines, TH1 and TH17 cells, and antigen presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in response to both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that a FMD or a chronic ketogenic diet are safe, feasible and potentially effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients (NCT01538355). PMID:27239035

  17. Adenosine and its receptors as therapeutic targets: An overview

    Sachdeva, Sakshi; Gupta, Monika

    2012-01-01

    The main goal of the authors is to present an overview of adenosine and its receptors, which are G-protein coupled receptors. The four known adenosine receptor subtypes are discussed along with the therapeutic potential indicating that these receptors can serve as targets for various dreadful diseases.

  18. Effect of theophylline on adenosine production in the canine myocardium

    Adenosine is thought to participate in local regulation of coronary blood flow. However, competitive antagonists of adenosine fail to block myocardial active hyperemia. The authors examined the effect of locally administered theophylline on active hyperemia and myocardial adenosine production during intracoronary isoproterenol infusion in the dog heart. Isoproterenol decreased coronary resistance and increased myocardial adenosine production. Infusion of theophylline at a rate that attenuated the vasodilator response to exogenously administered adenosine failed to attenuate the increase in coronary blood flow produced by isoproterenol. However, theophylline plus isoproterenol production greater increases in myocardial adensine production than isoproterenol alone. The curves relating resistance and adenosine in the presence of theophylline fell to the right of those in the absence of theophylline. These findings suggest that the failure of theophylline to attenuate isoproterenol hyperemia in the dog heart results at least in part from an increase in adenosine concentration at the arteriole to a level beyond that blocked by this competitive antagonist and that adenosine may in fact play a role in isoproterenol-induced active hyperemia

  19. A High-Affinity Adenosine Kinase from Anopheles Gambiae

    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.

  20. Extracellular formation and uptake of adenosine during skeletal muscle contraction in the rat: role of adenosine transporters.

    Lynge, J; Juel, C; Hellsten, Y

    2001-12-01

    1. The existence of adenosine transporters in plasma membrane giant vesicles from rat skeletal muscles and in primary skeletal muscle cell cultures was investigated. In addition, the contribution of intracellularly or extracellularly formed adenosine to the overall extracellular adenosine concentration during muscle contraction was determined in primary skeletal muscle cell cultures. 2. In plasma membrane giant vesicles, the carrier-mediated adenosine transport demonstrated saturation kinetics with Km = 177 +/- 36 microM and Vmax = 1.9 +/- 0.2 nmol x ml(-1) x s(-1) (0.7 nmol (mg protein)(-1) x s(-1)). The existence of an adenosine transporter was further evidenced by the inhibition of the carrier-mediated adenosine transport in the presence of NBMPR (nitrobenzylthioinosine; 72% inhibition) or dipyridamol (64% inhibition; P electro-stimulation of skeletal muscle is due to production of adenosine in the extracellular space of skeletal muscle and that adenosine is taken up rather than released by the skeletal muscle cells during contraction. PMID:11731589

  1. IBS Diet

    ... often conflicting advice is available, especially on the Internet. Much of it is associated with a considerable cost. Video with Peter Whorwell, MD Diet, Eating and IBS Symptoms There are a variety of ...

  2. Mediterranean Diet

    ... Restaurant Deciphering the Menu Ordering Your Meal Eating Fast Food Dining Out Tips by Cuisine Physical Activity Fitness ... the average American diet. In fact, saturated fat consumption is well within our dietary guidelines. More than ...

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

    Kubilay Oransay; Nil Hocaoglu; Mujgan Buyukdeligoz; Yesim Tuncok; Sule Kalkan

    2014-01-01

    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...

  4. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2015-01-01

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse ...

  5. Modulation of bladder function by luminal adenosine turnover and A1 receptor activation

    Prakasam, H. Sandeep; Herrington, Heather; Roppolo, James R.; Jackson, Edwin K.; Apodaca, Gerard

    2012-01-01

    The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed ...

  6. Distribution of adenosine receptors in human sclera fibroblasts

    Cui, Dongmei; Trier, Klaus; Chen, Xiang; Zeng, Junwen; Yang, Xiao; Hu, Jianmin; Ge, Jian

    2008-01-01

    Purpose Systemic treatment with adenosine receptor antagonists has been reported to affect the biochemistry and ultrastructure of rabbit sclera. This study was conducted to determine whether adenosine receptors (ADORs) are present in human scleral fibroblasts (HSF). Methods Primary HSF were cultured in vitro and identified with anti-vimentin, anti-keratin, anti-desmin, and anti-S-100 antibodies. Confocal fluorescence microscopy was used to study the distribution of ADORs in the HSF cell lines...

  7. Proton transfer in oxidized adenosine self-aggregates.

    Capobianco, Amedeo; Caruso, Tonino; Celentano, Maurizio; La Rocca, Mario Vincenzo; Peluso, Andrea

    2013-10-14

    The UV-vis and the IR spectra of derivativized adenosine in dichloromethane have been recorded during potentiostatic oxidation at an optically transparent thin layer electrode. Oxidized adenosine shows a broad Zundel like absorption extending from 2800 up to 3600 cm(-1), indicating that a proton transfer process is occurring. Theoretical computations predict that proton transfer is indeed favored in oxidized 1:1 self-association complexes and allow to assign all the observed transient spectroscopic signals. PMID:24116647

  8. Diet and Spondylitis

    ... Spondylitis Info For Teens Message Boards & Forums Donate Diet & Spondylitis Learn About Spondyloarthritis / Diet & Spondylitis Overview For ... Diet Blood Work and Spondylitis Spondylitis Awareness Month Diet's Effect On Spondylitis Symptoms In recent years many ...

  9. Nutrition and Diet

    ... Thai HbH:Vietnamese Relevant links Living with Thalassemia NUTRITION ▶ Nutrition and DietDiet for the Non-transfused ... booklet ▶ 3 Simple Suggestions for a Healthy Diet Nutrition and Diet Nutritional deficiencies are common in thalassemia, ...

  10. Diet and Nutrition

    ... Resources > Diet and Nutrition Go Back Diet and Nutrition Email Print + Share Diet and nutrition concerns of ... you. NEW!! Test your knowledge of diet and nutrition by taking this self-assessment for an opportunity ...

  11. Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis.

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

    2016-03-15

    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 showed that adenosine receptor agonists can be anti- or proinflammatory. 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 d postimmunization, shortly before EAU expression; however, 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 to improve the design of ADA- and adenosine receptor-targeted therapies. PMID:26856700

  12. Antagonism by theophylline of respiratory inhibition induced by adenosine.

    Eldridge, F L; Millhorn, D E; Kiley, J P

    1985-11-01

    The effects on respiration of an analogue of adenosine, L-2-N6-(phenylisopropyl)adenosine (PIA), and of the methylxanthine, theophylline, were determined in 19 vagotomized glomectomized cats whose end-tidal PCO2 was kept constant by means of a servo-controlled ventilator. Integrated phrenic nerve activity was used to represent respiratory output. Our results show that PIA, whether given systemically or into the third cerebral ventricle, depressed respiration. Systemically administered theophylline stimulated respiration. Theophylline given intravenously, or into the third ventricle not only reversed the depressive effects of previously administered PIA but caused further increases of respiration above the control level. Prior systemic administration of theophylline blocked both respiratory and hypotensive effects of subsequently administered PIA. Effects of either agent on medullary extracellular fluid pH did not explain the results. We conclude that the adenosine analogue PIA, acts to inhibit neurons in the brain that are involved in the control of respiration and that its effects are blocked by theophylline. We suggest that adenosine acts as a tonic modulator of respiration and that theophylline stimulates breathing by competitive antagonism of adenosine at neuronal receptor sites. PMID:4066573

  13. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial

    Garvin Fiona

    2009-08-01

    Full Text Available Abstract Background Alzheimer's disease (AD is characterized by early and region-specific declines in cerebral glucose metabolism. Ketone bodies are produced by the body during glucose deprivation and are metabolized by the brain. An oral ketogenic compound, AC-1202, was tested in subjects with probable AD to examine if ketosis could improve cognitive performance. Methods Daily administration of AC-1202 was evaluated in 152 subjects diagnosed with mild to moderate AD in a US-based, 90-day, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were on a normal diet and continued taking approved AD medications. Primary cognitive end points were mean change from Baseline in the AD Assessment Scale-Cognitive subscale (ADAS-Cog, and global scores in the AD Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC. AC-1202 was compared to Placebo in several population groups, including: intention-to-treat (ITT, per protocol, and dosage compliant groups. Results were also stratified by APOE4 carriage status (a predefined analysis based on the epsilon 4 (E4 variant of the apolipoprotein E gene. This trial was registered with ClinicalTrials.gov, registry number NCT00142805, information available at http://clinicaltrials.gov/ct2/show/NCT00142805 Results AC-1202 significantly elevated a serum ketone body (β-hydroxybutyrate 2 hours after administration when compared to Placebo. In each of the population groups, a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45: 1.9 point difference, p = 0.0235 in ITT; 2.53 point difference, p = 0.0324 in per protocol; 2.6 point difference, p = 0.0215 in dosage compliant. Among participants who did not carry the APOE4 allele (E4(-, a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45 and Day 90. In the ITT population, E4(- participants (N = 55

  14. Modification of survival of gamma irradiated mice by adenosine nucleotides

    The administration prior to irradiation of adenosine triphosphate (ATP) or other adenosine nucleotides, singly or in combination, increased the radioresistance of mice. Post-irradiation treatment with the adenosine nucleotides had no effect on the survival of the irradiated mice. Dose reduction factors of 2.32 could be obtained by pretreatment of mice with the following combination of protective agents: S-2(4-aminobutylamino)ethyl phosphorothioic aced (WR 2822), cysteamine (MEA) and ATP. Since cyclic AMP levels were unchanged in the spleen or gut by administration of cysteamine and other protectors it is unlikely that the increase in protection was due to changes in cyclic AMP levels. The calcium salt of ATP provided a higher level of protection than the ATP alone, indicating that the protective mechanism of ATP is probably not related to anoxia. (orig.)

  15. Thallium-201 scintigraphy of the myocardium in connection with adenosine

    It is shown that thallium-201 SPECT studies of the myocardium performed subsequent to intravenous infusion of adenosine provide results at least as valuable as those from exercise thallium-201 scintigraphy in the diagnosis of coronary artery disease. The infusion of adenosine offers great advantages over exercise studies in that it is a standardized procedure uninfluenced by a patient's physical fitness, which can thus be used in all cases. There are quite a number of clinically tolerable untoward reactions that may be associated with discomfort but do not warrant discontinuation of the procedure. Serious, verifiable side-effects are rare and disappear immediately on termination of the infusion. The most recent research in this field has shown that newly developed compounds of 99mTc are also suitable for radionuclide studies of the myocardium with adenosine vasodilation. (orig.)

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

    Full Text Available 17056121 Shaping of monocyte and macrophage function by adenosine receptors. Hasko G, Pacher...e Shaping of monocyte and macrophage function by adenosine receptors. Authors Hasko G, Pacher

  17. Investigating real-time activation of adenosine receptors by bioluminescence resonance energy transfer technique

    Huang, Yimei; Yang, Hongqin; Zheng, Liqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen

    2013-02-01

    Adenosine receptors play important roles in many physiological and pathological processes, for example regulating myocardial oxygen consumption and the release of neurotransmitters. The activations of adenosine receptors have been studied by some kinds of techniques, such as western blot, immunohistochemistry, etc. However, these techniques cannot reveal the dynamical response of adenosine receptors under stimulation. In this paper, bioluminescence resonance energy transfer technique was introduced to study the real-time activation of adenosine receptors by monitoring the dynamics of cyclic adenosine monophosphate (cAMP) level. The results showed that there were significant differences between adenosine receptors on real-time responses under stimulation. Moreover, the dynamics of cAMP level demonstrated that competition between adenosine receptors existed. Taken together, our study indicates that monitoring the dynamics of cAMP level using bioluminescence resonance energy transfer technique could be one potential approach to investigate the mechanism of competitions between adenosine receptors.

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

    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. No role of interstitial adenosine in insulin-mediated vasodilation

    Dela, F; Stallknecht, B

    1999-01-01

    healthy subjects (H) and in four subjects with a complete, high (C5-C6/7) spinal cord injury (SCI) a hyperinsulinaemic (480 mU min-1 kg-1), isoglycaemic clamp was performed. SCI subjects were included as it has been proposed that adenosine and adenine nucleotides may be released from nerve endings in the...... skeletal muscle. Adenosine concentrations in the extracellular fluid (ECF) of skeletal muscle in the thigh were measured by means of the microdialysis technique. Leg blood flow (LBF) was measured by termodilution. In response to insulin infusion, LBF always increased (P < 0.05) (from 228 +/- 25 and 318...

  20. Why do premature newborn infants display elevated blood adenosine levels?

    Panfoli, Isabella; Cassanello, Michela; Bruschettini, Matteo; Colella, Marina; Cerone, Roberto; Ravera, Silvia; Calzia, Daniela; Candiano, Giovanni; Ramenghi, Luca

    2016-05-01

    Our preliminary data show high levels of adenosine in the blood of very low birth weight (VLBW) infants, positively correlating to their prematurity (i.e. body weight class). This prompted us to look for a mechanism promoting such impressive adenosine increase. We hypothesized a correlation with oxygen challenge. In fact, it is recognized that either oxygen lack or its excess contribute to the pathogenesis of the injuries of prematurity, such as retinopathy (ROP) and periventricular white matter lesions (PWMI). The optimal concentration of oxygen for resuscitation of VLBW infants is currently under revision. We propose that the elevated adenosine blood concentrations of VLBW infants recognizes two sources. The first could be its activity-dependent release from unmyelinated brain axons. Adenosine in this respect would be an end-product of the hypometabolic VLBW newborn unmyelinated axon intensely firing in response to the environmental stimuli consequent to premature birth. Adenosine would be eventually found in the blood due to blood-brain barrier immaturity. In fact, adenosine is the primary activity-dependent signal promoting differentiation of premyelinating oligodendrocyte progenitor cells (OPC) into myelinating cells in the Central Nervous System, while inhibiting their proliferation and inhibiting synaptic function. The second, would be the ecto-cellular ATP synthesized by the endothelial cell plasmalemma exposed to ambient oxygen concentrations due to premature breathing, especially in lung. ATP would be rapidly transformed into adenosine by the ectonucleotidase activities such as NTPDase I (CD39), and NT5E (CD73). An ectopic extra-mitochondrial aerobic ATP synthetic ability was reported in many cell plasma-membranes, among which endothelial cells. The potential implications of the cited hypotheses for the neonatology area would be great. The amount of oxygen administration for reviving of newborns would find a molecular basis for its assessment. VLBW

  1. Cyclic adenosine monophosphate phosphodiesterase in brain: effect on anxiety.

    Beer, B; Chasin, M; Clody, D E; Vogel, J R

    1972-04-28

    Drugs that reduce anxiety may be mediated by cyclic adenosine monophosphate in the brain because (i) potent anxiety-reducing drugs are also potent inhibitors of brain phosphodiesterase activity; (ii) dibutyryl cyclic adenosine monophosphate has the ability to reduce anxiety; (iii) the methylxanthines show significant anxiety-reducing effects; (iv) theophylline and chlordiazepoxide produce additive anxiety-reducing activity; and (v) there is a significant correlation between the anxiety-reducing property of drugs and their ability to inhibit phosphodiesterase activity in the brain. PMID:4402069

  2. Cytotoxic purine nucleoside analogues bind to A1, A2A and A3 adenosine receptors

    Jensen, Kyle; Johnson, L’Aurelle A.; Jacobson, Pamala A.; Kachler, Sonja; Kirstein, Mark N.; Lamba, Jatinder; Klotz, Karl-Norbert

    2012-01-01

    Fludarabine, clofarabine and cladribine are anti-cancer agents which are analogues of the purine nucleoside adenosine. These agents have been associated with cardiac and neurological toxicities. Because these agents are analogues of adenosine, they may act through adenosine receptors to elicit their toxic effects. The objective of this study was to evaluate the ability of cytotoxic nucleoside analogues to bind and activate adenosine receptor subtypes (A1, A2A, A2B, and A3). Radioligand bindin...

  3. Adenosine and a selective A2a receptor agonist regadenoson used in myocardial stress test

    Adenosine pharmacological myocardial stress test has been widely used in clinic. However, the side effects related with adenosine administration has been an issue of controversy. Current Phase Ⅲ study of regadenoson, a selective A2a receptor agonist, reveals its potential to substitute adenosine as a new agent for pharmacological myocardial stress test. This review briefs adenosine and regadenoson and their clinical utilities in myocardial stress test. (authors)

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

    ROBERTO PAES-DE-CARVALHO

    2002-01-01

    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 activa...

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

    Ross, Ashley E.; Venton, B. Jill

    2014-01-01

    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 dop...

  6. The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias.

    Welihinda, Ajith A; Kaur, Manmeet; Greene, Kelly; Zhai, Yongjiao; Amento, Edward P

    2016-06-01

    Inosine is an endogenous purine nucleoside that is produced by catabolism of adenosine. Adenosine has a short half-life (approximately 10s) and is rapidly deaminated to inosine, a stable metabolite with a half-life of approximately 15h. Resembling adenosine, inosine acting through adenosine receptors (ARs) exerts a wide range of anti-inflammatory and immunomodulatory effects in vivo. The immunomodulatory effects of inosine in vivo, at least in part, are mediated via the adenosine A2A receptor (A2AR), an observation that cannot be explained fully by in vitro pharmacological characterization of inosine at the A2AR. It is unclear whether the in vivo effects of inosine are due to inosine or a metabolite of inosine engaging the A2AR. Here, utilizing a combination of label-free, cell-based, and membrane-based functional assays in conjunction with an equilibrium agonist-binding assay we provide evidence for inosine engagement at the A2AR and subsequent activation of downstream signaling events. Inosine-mediated A2AR activation leads to cAMP production with an EC50 of 300.7μM and to extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation with an EC50 of 89.38μM. Our data demonstrate that inosine produces ERK1/2-biased signaling whereas adenosine produces cAMP-biased signaling at the A2AR, highlighting pharmacological differences between these two agonists. Given the in vivo stability of inosine, our data suggest an additional, previously unrecognized, mechanism that utilizes inosine to functionally amplify and prolong A2AR activation in vivo. PMID:26903141

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

    Høier, Birgitte; Olsen, Karina; Nyberg, Michael Permin; Bangsbo, Jens; Hellsten, Ylva

    2010-01-01

    and during knee extensor exercise. The dialysate was analyzed for content of VEGF protein and adenosine. The mechanism of VEGF secretion from muscle cells in culture was examined in resting and electro stimulated cells, and in response to the adenosine analogue NECA, and the adenosine A(2A) receptor...

  8. A prospective study of the modified Atkins diet for adults with idiopathic generalized epilepsy.

    Kverneland, Magnhild; Selmer, Kaja K; Nakken, Karl O; Iversen, Per O; Taubøll, Erik

    2015-12-01

    For children with pharmacoresistant epilepsy, the ketogenic diet is an established treatment option worldwide. However, for adults, this treatment is less frequently offered, and its efficacy less well-documented. The aim of this study was to examine efficacy and tolerability of such a diet as an adjuvant therapy to antiepileptic drugs for adult patients with pharmacoresistant generalized epilepsy. Thirteen patients (12 women) aged 16-57 years were included prospectively. They were treated with a modified Atkins diet for 12 weeks. Nine of the 13 participants had juvenile myoclonic epilepsy (JME), two had childhood absence epilepsy, one had Jeavons syndrome, and one had generalized epilepsy of unknown type. Six participants, all with JME, completed the 12-week study period. Among these six, four had >50% seizure reduction. Their seizure severity, using the revised Liverpool Seizure Severity Scale, was reduced by 1, 5, 57.5, and 70 points, respectively (scale: 1-100 points). In three of these four responders, quality of life, assessed by QOLIE-89, increased more than 20 points (scale: 0-100 points). Mean reduction of body weight after 12 weeks on diet was 6.5 (range: 4.3-8.1) kg. Lack of motivation, poor compliance, and seizure aggravation were the main reasons for premature termination of the diet. Apart from one patient who developed gallstones when ending the treatment after 10 months, no adverse effects were noted. In conclusion, using a modified Atkins diet for 12 weeks led to a clinically relevant reduction of seizure frequency in four of thirteen adult patients with pharmacoresistant generalized epilepsy. All responders were diagnosed with JME. In three of the four, the benefits of diet were so considerable that they chose to continue the treatment. PMID:26588588

  9. Iodine in diet

    Diet - iodine ... Many months of iodine deficiency in a person's diet may cause goiter or hypothyroidism . Without enough iodine, ... and older children. Getting enough iodine in the diet may prevent a form of physical and intellectual ...

  10. Caffeine in the diet

    Diet - caffeine ... for caffeine. It can be avoided in the diet. Caffeine stimulates, or excites, the brain and nervous ... medications such as pain relievers , over-the-counter diet pills, and cold medicines. Caffeine has no flavor. ...

  11. Searching Inhibitors of Adenosine Kinase by Simulation Methods

    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. Adenosine receptor modulation of seizure susceptibility in rats

    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 A1 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 3H-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 A1 adenosine receptors in the cerebral cortex

  13. Dietary effects of adenosine monophosphate to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream, Pagrus major.

    Hossain, Md Sakhawat; Koshio, Shunsuke; Ishikawa, Manabu; Yokoyama, Saichiro; Sony, Nadia Mahjabin

    2016-09-01

    Our study explored the dietary effects of adenosine monophosphate (AMP) to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream. A semi-purified basal diet supplemented with 0% (Control), 0.1% (AMP-0.1), 0.2% (AMP-0.2), 0.4% (AMP-0.4) and 0.8% (AMP-0.8) purified AMP to formulate five experimental diets. Each diet was randomly allocated to triplicate groups of fish (mean initial weight 3.4 g) for 56 days. The results indicated that dietary AMP supplements tended to improve growth performances. One of the best ones was found in diet group AMP-0.2, followed by diet groups AMP-0.1, AMP-0.4 and AMP-0.8. The Apparent digestibility coefficients (dry matter, protein and lipid) also improved by AMP supplementation and the significantly highest dry matter digestibility was observed in diet group AMP-0.2. Fish fed diet groups AMP-0.2 and AMP-0.4 had significantly higher peroxidase and bactericidal activities than fish fed the control diet. Nitro-blue-tetrazolium (NBT) activity was found to be significantly (P  0.05) by dietary supplementation. In contrast, catalase activity decreased with AMP supplementation. Moreover, the fish fed AMP supplemented diets had better improvement (P stress resistances. Interestingly, the fish fed diet groups AMP-0.2 and AMP-0.4 showed the least oxidative stress condition. Finally it is concluded that, dietary AMP supplementation enhanced the growth, digestibility, immune response and stress resistance of red sea bream. The regression analysis revealed that a dietary AMP supplementation between 0.2 and 0.4% supported weight gain and lysozyme activity as a marker of immune functions for red sea bream, which is also inline with the most of the growth and health performance parameters of fish under present experimental conditions. PMID:27514786

  14. Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling

    Lohse, M.J.; Klotz, K.N.; Schwabe, U.

    1991-04-01

    It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine ((R)-AHPIA) into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling.

  15. Metabolic changes of cultured DRG neurons induced by adenosine using confocal microscopy imaging

    Zheng, Liqin; Huang, Yimei; Chen, Jiangxu; Wang, Yuhua; Yang, Hongqin; Zhang, Yanding; Xie, Shusen

    2012-12-01

    Adenosine exerts multiple effects on pain transmission in the peripheral nervous system. This study was performed to use confocal microscopy to evaluate whether adenosine could affect dorsal root ganglia (DRG) neurons in vitro and test which adenosine receptor mediates the effect of adenosine on DRG neurons. After adding adenosine with different concentration, we compared the metabolic changes by the real time imaging of calcium and mitochondria membrane potential using confocal microscopy. The results showed that the effect of 500 μM adenosine on the metabolic changes of DRG neurons was more significant than others. Furthermore, four different adenosine receptor antagonists were used to study which receptor mediated the influences of adenosine on the cultured DRG neurons. All adenosine receptor antagonists especially A1 receptor antagonist (DPCPX) had effect on the Ca2+ and mitochondria membrane potential dynamics of DRG neurons. The above studies demonstrated that the effect of adenosine which may be involved in the signal transmission on the sensory neurons was dose-dependent, and all the four adenosine receptors especially the A1R may mediate the transmission.

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

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

    2009-01-01

    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 in...

  17. Low-salt diet

    ... harmful to you, a salt substitute is a good way to lower the amount of sodium in your diet. Alternate Names Low-sodium diet; Salt restriction Images Low sodium diet References American Heart Association Nutrition Committee; Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, et al. Diet and ...

  18. Lifestyle and diet

    Opie, Lionel H

    2014-01-01

    Abstract Currently, there is widespread interest in many different diets. The best-known diets include the New Atkins diet in the USA, the Dukan diet in France, and in South Africa the Noakes diet. Two different approaches have emerged, one focusing on a life-long healthy lifestyle and the other emphasising weight loss. These are in fact complementary aims, as will be reviewed and reconciled. Furthermore, besides the dietary approach, there is a valid case for added drug therapy for selected ...

  19. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

    Brunetti, D.; Dusi, S.; C. Giordano; Lamperti, C; Morbin, M; Fugnanesi, V.; Marchet, S.; Fagiolari, G.; Sibon, O.; Moggio, M.; d'Amati, G.; TIRANTI, V.

    2013-01-01

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2−/− ) mouse model did not recapitulate the human disease but showed azo...

  20. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

    Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d'Amati, Giulia; Tiranti, Valeria

    2014-01-01

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2,

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

    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. PMID:26311185

  2. Abiotic regioselective phosphorylation of adenosine with borate in formamide.

    Furukawa, Yoshihiro; Kim, Hyo-Joong; Hutter, Daniel; Benner, Steven A

    2015-04-01

    Nearly 40 years ago, Schoffstall and his coworkers used formamide as a solvent to permit the phosphorylation of nucleosides by inorganic phosphate to give nucleoside phosphates, which (due to their thermodynamic instability with respect to hydrolysis) cannot be easily created in water by an analogous phosphorylation (the "water problem" in prebiotic chemistry). More recently, we showed that borate could stabilize certain carbohydrates against degradation (the "asphalt problem"). Here, we combine the two concepts to show that borate can work in formamide to guide the reactivity of nucleosides under conditions where they are phosphorylated. Specifically, reaction of adenosine in formamide with inorganic phosphate and pyrophosphate in the presence of borate gives adenosine-5'-phosphate as the only detectable phosphorylated product, with formylation (as opposed to hydrolysis) being the competing reaction. PMID:25826074

  3. Effects of adenosine metabolism in astrocytes on central nervous system oxygen toxicity.

    Chen, Yu-liang; Zhang, Ya-nan; Wang, Zhong-zhuang; Xu, Wei-gang; Li, Run-ping; Zhang, Jun-dong

    2016-03-15

    Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central nervous system oxygen toxicity (CNS-OT), which greatly limits HBO's application. The regulation of astrocytes to the metabolism of adenosine is involved in epilepsy. In our study, we aimed to observe the effects of HBO exposure on the metabolism of adenosine in the brain. Furthermore, we aimed to confirm the possible mechanism underlying adenosine's mediation of the CNS-OT. Firstly, anesthetized rats exposed to 5 atm absolute HBO for 80 min. The concentrations of extracellular adenosine, ATP, ADP, and AMP were detected. Secondly, free-moving rats were exposed to HBO at the same pressure for 20 min, and the activities of 5'-nucleotidase and ADK in brain tissues were measured. For the mechanism studies, we observed the effects of a series of different doses of drugs related to adenosine metabolism on the latency of CNS-OT. Results showed HBO exposure could increase adenosine content by inhibiting ADK activity and improving 5'-nucleotidase activity. And adenosine metabolism during HBO exposure may be a protective response against HBO-induced CNS-OT. Moreover, the improvement of adenosine concentration, activation of adenosine A1R, or suppression of ADK and adenosine A2AR, which are involved in the prevention of HBO-induced CNS-OT. This is the first study to demonstrate HBO exposure regulated adenosine metabolism in the brain. Adenosine metabolism and adenosine receptors are related to HBO-induced CNS-OT development. These results will provide new potential targets for the termination or the attenuation of CNS-OT. PMID:26806404

  4. The emerging role of adenosine deaminases in insects

    Doleželová, Eva; Žurovec, Michal; Doležal, T.; Šimek, Petr; Bryant, P. J.

    2005-01-01

    Roč. 35, č. 5 (2005), s. 381-389. ISSN 0965-1748 R&D Projects: GA ČR(CZ) GA204/04/1205; GA AV ČR(CZ) IAA5007107 Grant ostatní: United States National Science Foundation(US) 440860-21565 Institutional research plan: CEZ:AV0Z50070508 Keywords : adenosine deaminase * ADA * growth factor Subject RIV: ED - Physiology Impact factor: 2.733, year: 2005

  5. Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

    Nam, Hyung Wook; Bruner, Robert C.; Choi, Doo-Sup

    2013-01-01

    Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, ...

  6. Myocardial energy metabolism in ischemic preconditioning, role of adenosine catabolism

    Kavianipour, Mohammad

    2002-01-01

    Brief episodes of ischemia and reperfusion render the myocardium more resistant to necrosis from a subsequent, otherwise lethal ischemic insult. This phenomenon is called ischemic preconditioning(IP). Today, much is known about the signalling pathways involved in IP; however, the details of the final steps leading to cardioprotection, remain elusive. Adenosine (a catabolite of ATP) plays a major role in the signalling pathways of IP. Following IP there is an unexplained discrepancy between an...

  7. Adenosine signaling in striatal circuits and alcohol use disorders.

    Nam, Hyung Wook; Bruner, Robert C; Choi, Doo-Sup

    2013-09-01

    Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction. PMID:23912595

  8. Anxiolytic activity of adenosine receptor activation in mice.

    Jain, N; Kemp, N; Adeyemo, O; Buchanan, P; Stone, T W

    1995-10-01

    1. Purine analogues have been examined for anxiolytic- and anxiogenic-like activity in mice, by use of the elevated plus-maze. 2. The selective A1 receptor agonist, N6-cyclopentyladenosine (CPA) had marked anxiolytic-like activity at 10 and 50 microg kg(-1), with no effect on locomotor performance at these doses. 3. The A1 selective adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (CPX) had no significant effect on anxiety-related measures or locomotor behaviour, but blocked the anxiolytic-like activity of CPA. The hydrophilic xanthine, 8-(p-sulphophenyl) theophylline did not prevent anxiolysis by CPA. 4. Caffeine had anxiogenic-like activity at 30 mg kg(-1) which was prevented by CPA at 50 micro kg(-1). 5. The A2 receptor agonist, N6-[2-(3,5-dimethoxyphenyl)-2(2-methylphenyl)-ethyl]adenosine (DPMA) had no effect on anxiety behaviour but depressed locomotor activity at the highest dose tested of 1 mg kg(-1). The A2 receptor antagonist, 1,3-dimethyl-l-propargylxanthine (DMPX) had no effect on anxiety-related measures or locomotion and did not modify the anxiolytic-like activity of CPA. 6. Administration of DPMA in combination with anxiolytic doses of CPA prevented the anxiolytic-like activity of the latter. 7. The results suggest that the selective activation of central A1 adenosine receptors induces anxiolytic-like behaviour, while the activation of A2 sites causes locomotor depression and reduces the effects of A1 receptor activation. The absence of any effect of CPX alone suggests that the receptors involved in modulating behaviour in the elevated plus-maze in mice are not activated tonically by endogenous adenosine. PMID:8640355

  9. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    de Mello Maria

    2002-04-01

    Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

  10. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

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

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

    2007-01-01

    calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP(3), is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 microM) blocked the adenosine-induced constriction whereas the...... protein kinase C inhibitor calphostin C had no effect. The calcium-activated chloride channel inhibitor IAA-94 (30 microM) inhibited the adenosine-mediated constriction. Patch clamp experiments showed that adenosine treatment induced a depolarizing current in preglomerular smooth muscle cells which was....... 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 of...

  12. Adenosine A1 Receptor Antagonist Versus Montelukast on Airway Reactivity and Inflammation

    Nadeem, Ahmed; Obiefuna, Peter C.M.; Wilson, Constance N.; Mustafa, S. Jamal

    2006-01-01

    Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans by activating adenosine A1 receptors. Previously, it is reported that a high dose of L-97-1, a water-soluble, small molecule adenosine A1 receptor antagonist, blocks early and late allergic responses, and bronchial hyper-responsiveness to histamine in a hyper-responsive rabbit model of allergic asthma. Effects of a lower dose of L-97-1 are compared to montelukast, a cysteinyl leukotriene-1 receptor antagonist on ...

  13. Traditional Acupuncture Triggers a Local Increase in Adenosine in Human Subjects

    Takano, Takahiro; Chen, Xiaolin; Luo, Fang; Fujita, Takumi; Ren, Zeguang; Goldman, Nanna; Zhao, Yuanli; Markman, John D.; Nedergaard, Maiken

    2012-01-01

    Acupuncture is a form of Eastern medicine that has been practiced for centuries. Despite its long history and worldwide application, the biological mechanisms of acupuncture in relieving pain have been poorly defined. Recent studies in mice, however, demonstrate that acupuncture triggers increases in interstitial adenosine, which reduces the severity of chronic pain through adenosine A1 receptors, suggesting that adenosine-mediated antinociception contributes to the clinical benefits of acupu...

  14. Respiratory stimulant effects of adenosine in man after caffeine and enprofylline.

    Smits, P; Schouten, J; Thien, T.

    1987-01-01

    In a double-blind and randomized study the respiratory stimulant effect of continuous intravenous adenosine infusion was studied after previous administration of caffeine, placebo and enprofylline in 10 healthy young volunteers. After placebo, adenosine induced an increase of minute ventilation (from 6.3 to 12.5 l min-1), tidal volume (from 0.60 to 0.96 l), and breathing rate (from 11.0 to 14.8 min-1). Venous pCO2 fell and pH rose after adenosine. Caffeine significantly reduced the adenosine-...

  15. Caffeine in the diet

    Diet - caffeine ... Caffeine is absorbed and passes quickly into the brain. It does not collect in the bloodstream or ... been consumed. There is no nutritional need for caffeine. It can be avoided in the diet. Caffeine ...

  16. Diet and Nutrition

    ... need to know about Wilson Disease Diet and Nutrition Food . . . . Adherence to a low copper diet is ... and arthritis; cardiomyopathy, dysrhythmias; pancreatitis; hypoparathyroidism; menstrual irregularities: infertility, repeated miscarriages From: A Diagnostic Tool for Physicians ( ...

  17. Diet and Exercise

    ... Financing Living Donation Home / After The Transplant / Staying Healthy / Diet And Exercise Medications Post-Transplant Medications Types of ... be aware of the important role of a healthy diet and exercise plan in healing. Prior to your ...

  18. Diets that Work

    ... Brussel Sprouts Green Salad Tangerines A Vegetarian or Vegan Diet A vegetarian diet generally excludes animal products. ... Steamed Green Beans with Pine Nuts Fruit Salad Vegan Roasted Vegetables with Whole Wheat Pasta Green Salad ...

  19. Diet and Your Liver

    ... the scarring and hardening of the liver. Diet Recommendations: • Limit salt and foods that contain a lot of salt • Talk to your doctor about how much protein to have in your diet Fatty Liver Disease ...

  20. Diet and Exercise Tips

    ... Health News & Publications Annual Meeting Calendar Diet and Exercise Tips Diet and Exercise Tips News media interested ... caffeine content (tea, sodas, chocolate drinks) and caffeinated coffee to two cups per day. Minimize alcohol to ...

  1. Effects of adenosine and adenosine A2A receptor agonist on motor nerve conduction velocity and nerve blood flow in experimental diabetic neuropathy.

    Kumar, Sokindra; Arun, K H S; Kaul, Chaman L; Sharma, Shyam S

    2005-01-01

    This study examined the effects of chronic administration of adenosine and CGS 21680 hydrochloride (adenosine A(2A) receptor agonist) on motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and histology of sciatic nerve in animal model of diabetic neuropathy. Adenosinergic agents were administered for 2 weeks after 6 weeks of streptozotocin-induced (50 mg/kg i.p.) diabetes in male Sprague-Dawley rats. Significant reduction in sciatic MNCV and NBF were observed after 8 weeks in diabetic animals in comparison with control (non diabetic) rats. Adenosine (10 mg/kg, i.p.) significantly improved sciatic MNCV and NBF in diabetic rats. The protective effect of adenosine on MNCV and NBF was completely reversed by theophylline (50 mg/kg, i.p.), a non-selective adenosine receptor antagonist, suggesting that the adenosine effect was mediated via adenosinergic receptors. CGS 21680 (0.1 mg/kg, i.p.) significantly improved NBF; however, MNCV was not significantly improved in diabetic rats. At a dose of 1 mg/kg, neither MNCV nor NBF was improved by CGS 21680 in diabetic rats. ZM 241385 (adenosine A(2A) receptor antagonist) prevented the effect of CGS 21680 (0.1 mg/kg, i.p.). Histological changes observed in sciatic nerve were partially improved by the adenosinergic agents in diabetic rats. Results of the present study, suggest the potential of adenosinergic agents in the therapy of diabetic neuropathy. PMID:15829161

  2. Diet quality assessment indexes

    Kênia Mara Baiocchi de Carvalho; Eliane Said Dutra; Nathalia Pizato; Nádia Dias Gruezo; Marina Kiyomi Ito

    2014-01-01

    Various indices and scores based on admittedly healthy dietary patterns or food guides for the general population, or aiming at the prevention of diet-related diseases have been developed to assess diet quality. The four indices preferred by most studies are: the Diet Quality Index; the Healthy Eating Index; the Mediterranean Diet Score; and the Overall Nutritional Quality Index. Other instruments based on these indices have been developed and the words 'adapted', 'revised', or 'new version I...

  3. Diet induced thermogenesis

    Westerterp KR

    2004-01-01

    Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Resu...

  4. The New Nordic Diet

    Salomo, Louise; Poulsen, Sanne Kellebjerg; Rix, Marianne;

    2016-01-01

    PURPOSE: High phosphorus content in the diet may have adverse effect on cardiovascular health. We investigated whether the New Nordic Diet (NND), based mainly on local, organic and less processed food and large amounts of fruit, vegetables, wholegrain and fish, versus an Average Danish Diet (ADD...

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

    Michael D Nguyen

    Full Text Available 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.

  6. Lifestyle and diet.

    Opie, Lionel H

    2014-01-01

    Currently, there is widespread interest in many different diets. The best-known diets include the New Atkins diet in the USA, the Dukan diet in France, and in South Africa the Noakes diet. Two different approaches have emerged, one focusing on a life-long healthy lifestyle and the other emphasising weight loss. These are in fact complementary aims, as will be reviewed and reconciled. Furthermore, besides the dietary approach, there is a valid case for added drug therapy for selected lipid disorders with the use statins. In addition, new drugs are emerging that in the future might eventually considerably reduce the negative health impact of coronary artery disease. PMID:25629717

  7. Modern diets and youth

    Kos, Špela

    2011-01-01

    The purpose of this thesis is to analyse the attitude that young people (aged between 18 and 30) have to modern diets. 209 young people were included in the survey. In the research entitled “Modern diets and youth” I tried to find out what effects education level and orientation have on: their opinion on fashionable diets, knowledge of different diets, personal experience. I was interested in the sources from which they acquire information on fashionable diets, who or what encourages them to ...

  8. Is adenosine a modulator of peripheral vasoconstrictor responses?

    Dayan, Lior; Brill, Silviu; Hochberg, Uri; Jacob, Giris

    2016-01-01

    Background Local vasoconstrictor reflexes, the vascular myogenic response (VMR) and the veno-arterial reflex (VAR) are necessary for the maintenance of regional blood flow and systemic arterial blood pressure during orthostatic stress. Their molecular mechanism is unknown. We postulated that adenosine is involved in the activation of these local reflexes. Methods This hypothesis was tested in 10 healthy male volunteers (age 29 ± 3 years, BMI 24 ± 1 kg/m2). We used veno-occlusive plethysmograp...

  9. Differential response of Drosophila cell lines to extracellular adenosine

    Fleischmannová, J.; Kučerová, Lucie; Šandová, Kateřina; Steinbauerová, Veronika; Brož, Václav; Šimek, Petr; Žurovec, Michal

    2012-01-01

    Roč. 42, č. 5 (2012), s. 321-331. ISSN 0965-1748 R&D Projects: GA MŠk(CZ) LC06077 Grant ostatní: AV ČR(CZ) KJB501410801; European Community´s Seventh Framwork Programme (FP7/2007-2013)(CZ) 229518 Institutional research plan: CEZ:AV0Z50070508 Institutional support: RVO:60077344 Keywords : adenosine recycling * nucleoside transport * Mbn2 Subject RIV: CE - Biochemistry Impact factor: 3.234, year: 2012 http://www.sciencedirect.com/science/article/pii/S0965174812000033

  10. Anxiolytic activity of adenosine receptor activation in mice.

    Jain, N; Kemp, N; Adeyemo, O; Buchanan, P.; Stone, T W

    1995-01-01

    1. Purine analogues have been examined for anxiolytic- and anxiogenic-like activity in mice, by use of the elevated plus-maze. 2. The selective A1 receptor agonist, N6-cyclopentyladenosine (CPA) had marked anxiolytic-like activity at 10 and 50 microg kg(-1), with no effect on locomotor performance at these doses. 3. The A1 selective adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (CPX) had no significant effect on anxiety-related measures or locomotor behaviour, but blocked ...

  11. Diet induced thermogenesis

    Westerterp KR

    2004-08-01

    Full Text Available Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Results Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.

  12. Stimulation of adenosine receptors: approach to enhancement of hematopoiesis suppressed by chemoradiotherapy

    Elevated extracellular adenosine has been found to stimulate hematopoiesis in experimental mice exposed to radiotherapy (gamma-rays), chemotherapy (5-fluorouracil), or combined action of both these modalities (gamma-rays + carboplatin). These findings have been obtained after treatment of the animals with the combination of dipyridamole (DP), preventing the cellular uptake of adenosine, and adenosine monophosphate (AMP), acting as adenosine prodrug. Increased cycling of hematopoietic progenitor cells following the administration of DP + AMP has been shown to represent an important mechanism of acceleration of regeneration of suppressed hematopoiesis. In recent experiments, non-degradable synthetic adenosine receptor agonists, more or less specific for individual subtypes of adenosine receptors (A1, A2A, A2B, and A3 subtypes) have been studied. These studies have included 5'-(N-ethylcarboxamido)adenosine (NECA, rather non-selective agonist with relatively high affinity to A2B receptor subtype), N6-cyclopentyladenosine (CPA, agonist specific for A1 receptor subtype), 2-p-(carboxyethyl)phene thylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680, agonist specific for A2A receptor subtype), and 1-deoxy-1-([((3- iodophenyl)methyl)-amino]-9H-purin-9-yl)-N-methyl-beta-D-ribofuranoamide (IB-MECA, agonist specific for A3 receptor subtype). Results from these studies have stressed the potential significance of stimulation of various adenosine receptor subtypes for modulation of functional status of hematopoietic progenitor cells. These findings may find important practical implications in the treatment of side effects of chemoradiotherapy

  13. Role of adenosine in the sympathetic activation produced by isometric exercise in humans.

    Costa, F.; Biaggioni, I

    1994-01-01

    Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of...

  14. Lack of adenosine A(3) receptors causes defects in mouse peripheral blood parameters

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

    2014-01-01

    Roč. 10, č. 3 (2014), s. 509-514. ISSN 1573-9538 R&D Projects: GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : Adenosine A(3) receptor * Adenosine A(3) receptor knockout mice * Hematopoiesis Subject RIV: BO - Biophysics Impact factor: 3.886, year: 2014

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

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

    2010-01-01

    Adenosine is a widely used pharmacological agent to induce a 'high flow' control condition to study the mechanisms of exercise hyperemia, but it is not known how well adenosine infusion depicts exercise-induced hyperemia especially in terms of blood flow distribution at the capillary level in hum...

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

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

    2007-01-01

    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...

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

    Cátia Vieira; Maria Teresa Magalhães-Cardoso; Fátima Ferreirinha; Isabel Silva; Ana Sofia Dias; Julie Pelletier; Jean Sévigny; Paulo Correia-de-Sá

    2014-01-01

    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 ...

  18. Adenosine Amine Congener as a Cochlear Rescue Agent

    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.

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

    Lazzaro, Brian P

    2015-04-01

    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. PMID:25915419

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

    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.

  1. Distribution of adenosine receptors in human sclera fibroblasts

    Cui, Dongmei; Trier, Klaus; Chen, Xiang; Zeng, Junwen; Yang, Xiao; Hu, Jianmin

    2008-01-01

    Purpose Systemic treatment with adenosine receptor antagonists has been reported to affect the biochemistry and ultrastructure of rabbit sclera. This study was conducted to determine whether adenosine receptors (ADORs) are present in human scleral fibroblasts (HSF). Methods Primary HSF were cultured in vitro and identified with anti-vimentin, anti-keratin, anti-desmin, and anti-S-100 antibodies. Confocal fluorescence microscopy was used to study the distribution of ADORs in the HSF cell lines and in the frozen human scleral sections. ADOR protein expression in HSF and human sclera was confirmed by western blot analysis of cell lysates. Results ADORs were expressed in both HSF and human sclera. This was confirmed by western blot. ADORA1 expression was concentrated in the nucleus. ADORA2A was concentrated mainly in one side of the cytoplasm, and ADORA2B was found both in the nucleus and the cytoplasm. ADORA3 was expressed weakly in the cytoplasm. Conclusions All four subtypes of ADOR were found in HSF and may play a role in scleral remodeling. PMID:18385786

  2. Cloning, expression and pharmacological characterization of rabbit adenosine A1 and A3 receptors.

    Hill, R J; Oleynek, J J; Hoth, C F; Kiron, M A; Weng, W; Wester, R T; Tracey, W R; Knight, D R; Buchholz, R A; Kennedy, S P

    1997-01-01

    The role of adenosine A1 and A3 receptors in mediating cardioprotection has been studied predominantly in rabbits, yet the pharmacological characteristics of rabbit adenosine A1 and A3 receptor subtypes are unknown. Thus, the rabbit adenosine A3 receptor was cloned and expressed, and its pharmacology was compared with that of cloned adenosine A1 receptors. Stable transfection of rabbit A1 or A3 cDNAs in Chinese hamster ovary-K1 cells resulted in high levels of expression of each of the receptors, as demonstrated by high-affinity binding of the A1/A3 adenosine receptor agonist N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA). For both receptors, binding of 125I-ABA was inhibited by the GTP analog 5'-guanylimidodiphosphate, and forskolin-stimulated cyclic AMP accumulation was inhibited by the adenosine receptor agonist (R)-phenylisopropyladenosine. The rank orders of potency of adenosine receptor agonists for inhibition of 125I-ABA binding were as follows: rabbit A1, N6-cyclopentyladenosine = (R)-phenylisopropyladenosine > N-ethylcarboxamidoadenosine > or = I-ABA > or = N6-2-(4-aminophenyl) ethyladenosine > > N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide > N6-(4-amino-3-benzyl)adenosine; rabbit A3, N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide > or = I-ABA > > N-ethylcarboxamidoadenosine > N6-2-(4-aminophenyl) ethyladenosine = N6-cyclopentyladenosine = (R)-phenylisopropyladenosine > N6-(4-amino-3-benzyl)adenosine. The adenosine receptor antagonist rank orders were as follow: rabbit A1, 8-cyclopentyl-1,3-dipropylxanthine > 1,3- dipropyl-8-(4-acrylate)phenylxanthine > or = xanthine amine congener > > 8-(p-sulfophenyl)theophylline; rabbit A3, xanthine amine congener > 1,3-dipropyl-8-(4-acrylate)phenylxanthine > or = 8-cyclopentyl-1,3-dipropylxanthine > > 8-(p-sulfophenyl)theophylline. These observations confirm the identity of the expressed proteins as A1 and A3 receptors. The results will facilitate further in-depth studies of the roles of A1 and A3 receptors in

  3. Quantitative analysis of adenosine using Liquid Chromatography/Atmospheric Pressure Chemical Ionization - tandem Mass Spectrometry (LC/APCI-MS/MS)

    Van Dycke, Annelies; Verstraete, Alain; Pil, Kristof; Raedt, Robrecht; Vonck, Kristl; Boison, Detlev; Boon, Paul

    2010-01-01

    Adenosine-secreting cellular brain implants constitute a promising therapeutic approach for the treatment of epilepsy. To engineer neural stem cells for therapeutic adenosine delivery, a reliable and fast analytical method is necessary to quantify cell-based adenosine release. Here we describe the development, optimization and validation of adenosine measurement using liquid chromatography – atmospheric pressure chemical ionization – tandem mass spectrometry (LC-APCI-MS/MS). LC-MS/MS in posit...

  4. Distinct Roles for the A2B Adenosine Receptor in Acute and Chronic Stages of Bleomycin-Induced Lung Injury

    Yang ZHOU; Schneider, Daniel J.; Morschl, Eva; Song, Ling; Pedroza, Mesias; Karmouty-Quintana, Harry; Le, Thuy.; Sun, Chun-Xiao; Blackburn, Michael R.

    2010-01-01

    Adenosine is an extracellular signaling molecule that is generated in response to cell injury where it orchestrates tissue protection and repair. Whereas adenosine is best known for promoting anti-inflammatory activities during acute injury responses, prolonged elevations can enhance destructive tissue remodeling processes associated with chronic disease states. The generation of adenosine and the subsequent activation of the adenosine 2B receptor (A2BR) is an important processes in the regul...

  5. Interaction of porphyrins with adenine and adenosine complexes. Effect of a metal nature

    Reactions of complex formation of 5,10,15,20-tetraphenylporphine (H2TPP) and tetra-tert-butylphthalocyanine (H2(t-Bu)4Pc) with adenine and adenosine complexes of d-metals (M=Cd, Co, Cu, Hg, Zn) in DMSO and ethanol are studied. It was found that H2TPP reacts with Cu(II) and Hg(II) adeninates and adenosinates in DMSO, but does not react with Zn(II), Co(II), and Cd(II) adeninates and adenosinates (with both bridging and monodentate type of the ligand coordination). H2(t-Bu)4Pc enters the complex formation reaction with adeninates and adenosinates of all studied metals in DMSO at almost equal rates. The states of adenine and adenosine complexes of different d-metals in DMSO and ethanol are proposed on the basis of kinetic data obtained

  6. Adenosine stimulates DNA fragmentation in human thymocytes by Ca(2+)-mediated mechanisms.

    Szondy, Z

    1994-12-15

    Incubation of human thymocytes with an optimum concentration of adenosine and its receptor site agonist, 2-chloroadenosine, induced increases in intracellular cyclic AMP (cAMP) (from a resting 0.6 +/- 0.1 to 4.1 +/- 0.2 pmol/10(7) cells within 5 min) and Ca2+ (from the resting 85 +/- 7 nM to a peak of 210 +/- 25 nM) levels and resulted in internucleosomal DNA fragmentation and cell death (apoptosis). Other adenosine analogues were also effective at inducing DNA fragmentation, the order of potency being 2-p-(carboxyethylphenylethylamino)-5'-carboxyamidoadenosine 13399-13402], at 60 ng/ml concentration also prevented adenosine-induced DNA fragmentation when added prior to adenosine. This suggested a complex cross-talk between the adenosine-triggered signal transduction cascade and the activation state of protein kinase C in regulating apoptosis of human thymocytes. PMID:7818494

  7. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    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. PMID:16023100

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

    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.

  9. 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.

    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. PMID:15821340

  10. Real-time monitoring of extracellular adenosine using enzyme-linked microelectrode arrays.

    Hinzman, Jason M; Gibson, Justin L; Tackla, Ryan D; Costello, Mark S; Burmeister, Jason J; Quintero, Jorge E; Gerhardt, Greg A; Hartings, Jed A

    2015-12-15

    Throughout the central nervous system extracellular adenosine serves important neuroprotective and neuromodulatory functions. However, current understanding of the in vivo regulation and effects of adenosine is limited by the spatial and temporal resolution of available measurement techniques. Here, we describe an enzyme-linked microelectrode array (MEA) with high spatial (7500 µm(2)) and temporal (4 Hz) resolution that can selectively measure extracellular adenosine through the use of self-referenced coating scheme that accounts for interfering substances and the enzymatic breakdown products of adenosine. In vitro, the MEAs selectively measured adenosine in a linear fashion (r(2)=0.98±0.01, concentration range=0-15 µM, limit of detection =0.96±0.5 µM). In vivo the limit of detection was 0.04±0.02 µM, which permitted real-time monitoring of the basal extracellular concentration in rat cerebral cortex (4.3±1.5 µM). Local cortical injection of adenosine through a micropipette produced dose-dependent transient increases in the measured extracellular concentration (200 nL: 6.8±1.8 µM; 400 nL: 19.4±5.3 µM) [P<0.001]. Lastly, local injection of dipyridamole, which inhibits transport of adenosine through equilibrative nucleoside transporter, raised the measured extracellular concentration of adenosine by 120% (5.6→12.3 µM) [P<0.001]. These studies demonstrate that MEAs can selectively measure adenosine on temporal and spatial scales relevant to adenosine signaling and regulation in normal and pathologic states. PMID:26183072

  11. Specificity of synergistic coronary flow enhancement by adenosine and pulsatile perfusion in the dog.

    Pagliaro, P; Senzaki, H; Paolocci, N; Isoda, T; Sunagawa, G; Recchia, F A; Kass, D A

    1999-10-01

    1. Coronary flow elevation from enhanced perfusion pulsatility is synergistically amplified by adenosine. This study determined the specificity of this interaction and its potential mechanisms. 2. Mean and phasic coronary flow responses to increasing pulsatile perfusion were assessed in anaesthetized dogs, with the anterior descending coronary artery servoperfused to regulate real-time physiological flow pulsatility at constant mean pressure. Pulsatility was varied between 40 and 100 mmHg. Hearts ejected into the native aorta whilst maintaining stable loading. 3. Increasing pulsatility elevated mean coronary flow +11.5 +/- 1.7 % under basal conditions. Co-infusion of adenosine sufficient to raise baseline flow 66 % markedly amplified this pulsatile perfusion response (+82. 6 +/- 14.3 % increase in mean flow above adenosine baseline), due to a leftward shift of the adenosine-coronary flow response curve at higher pulsatility. Flow augmentation with pulsatility was not linked to higher regional oxygen consumption, supporting direct rather than metabolically driven mechanisms. 4. Neither bradykinin, acetylcholine nor verapamil reproduced the synergistic amplification of mean flow by adenosine and higher pulsatility, despite being administered at doses matching basal flow change with adenosine. 5. ATP-sensitive potassium (KATP) activation (pinacidil) amplified the pulse-flow response 3-fold, although this remained significantly less than with adenosine. Co-administration of the phospholipase A2 inhibitor quinacrine virtually eliminated adenosine-induced vasodilatation, yet synergistic interaction between adenosine and pulse perfusion persisted, albeit at a reduced level. 6. Thus, adenosine and perfusion pulsatility specifically interact to enhance coronary flow. This synergy is partially explained by KATP agonist action and additional non-flow-dependent mechanisms, and may be important for modulating flow reserve during exercise or other high output states where

  12. Overexpression, purification and crystallographic analysis of a unique adenosine kinase from Mycobacterium tuberculosis

    Adenosine kinase from M. tuberculosis has been overexpressed, purified and crystallized in the presence of adenosine. Structure determination using molecular replacement with diffraction data collected at 2.2 Å reveals a dimeric structure. Adenosine kinase from Mycobacterium tuberculosis is the only prokaryotic adenosine kinase that has been isolated and characterized. The enzyme catalyzes the phosphorylation of adenosine to adenosine monophosphate and is involved in the activation of 2-methyladenosine, a compound that has demonstrated selective activity against M. tuberculosis. The mechanism of action of 2-methyladenosine is likely to be different from those of current tuberculosis treatments and this compound (or other adenosine analogs) may prove to be a novel therapeutic intervention for this disease. The M. tuberculosis adenosine kinase was overexpressed in Escherichia coli and the enzyme was purified with activity comparable to that reported previously. The protein was crystallized in the presence of adenosine using the vapour-diffusion method. The crystals diffracted X-rays to high resolution and a complete data set was collected to 2.2 Å using synchrotron radiation. The crystal belonged to space group P3121, with unit-cell parameters a = 70.2, c = 111.6 Å, and contained a single protein molecule in the asymmetric unit. An initial structural model of the protein was obtained by the molecular-replacement method, which revealed a dimeric structure. The monomers of the dimer were related by twofold crystallographic symmetry. An understanding of how the M. tuberculosis adenosine kinase differs from the human homolog should aid in the design of more potent and selective antimycobacterial agents that are selectively activated by this enzyme

  13. Attractants in purified diets

    Pascual, Felicitas P.

    1980-01-01

    Juvenile Penaeus monodon were reared on purified diets containing different attractants used to gelatinize the cornstarch: plain water, shrimp, mussel, squid or trash fish extract. The highest survival rate was observed in the group given the shrimp attractant, followed by mussel, fish and squid. However growth appeared best in the diet containing mussel extract. Mussel extract apparently can be used to enhance the attractability of purified diets.

  14. 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.

    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 extraction procedures developed here were compared with the classical adenosine phosphate extraction procedures (perchloric acid). The results indicate that the two techniques are similar in terms of recovery and reproducibility, but when other factors such as extraction time, environmental protection, and worker's health are considered, ASE is preferable to the classical extraction method. With this ASE-HPLC method, a minisurvey of ATP, ADP, and 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. PMID:19435312

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

    Dallaglio, Paolo D.; Betts, Timothy R.; Ginks, Matthew; Bashir, Yaver; Anguera, Ignasi; Rajappan, Kim

    2016-01-01

    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. PMID:26981309

  16. Susceptibility to seizure-induced sudden death in DBA/2 mice is altered by adenosine.

    Faingold, Carl L; Randall, Marc; Kommajosyula, Srinivasa P

    2016-08-01

    Sudden unexpected death in epilepsy (SUDEP) is rare but is an important public health burden due to the number of patient years lost. Respiratory dysfunction following generalized convulsive seizure is a common sequence of events in witnessed SUDEP cases. The DBA/2 mouse model of SUDEP exhibits generalized convulsive audiogenic seizures (AGSz), which result in seizure-induced respiratory arrest (S-IRA) in ∼75% of these animals, while the remaining DBA/2 mice exhibit AGSz without S-IRA. SUDEP induction may involve actions of adenosine, which is released during generalized seizures in animals and patients and is known to depress respiration. This study examined the effects of systemic administration of agents that alter the actions of adenosine on the incidence of S-IRA in DBA/2 mice. DBA/2 mice that consistently exhibited AGSz without S-IRA showed a significantly increased incidence of S-IRA following treatment with 5-iodotubercidin, which blocks adenosine metabolism. Treatment of DBA/2 mice that consistently exhibited AGSz followed by S-IRA with a non-selective adenosine antagonist, caffeine, or an A2A adenosine receptor subtype-selective antagonist (SCH 442416) significantly reduced S-IRA incidence. By contrast, an A1 adenosine receptor antagonist (DPCPX) was not effective in reducing S-IRA incidence. These findings suggest that preventative approaches for SUDEP should consider agents that reduce the actions of adenosine. PMID:27259068

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

    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?.

  18. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production.

    Clayton, Aled; Al-Taei, Saly; Webber, Jason; Mason, Malcolm D; Tabi, Zsuzsanna

    2011-07-15

    Extracellular adenosine is elevated in cancer tissue, and it negatively regulates local immune responses. Adenosine production from extracellular ATP has attracted attention as a mechanism of regulatory T cell-mediated immune regulation. In this study, we examined whether small vesicles secreted by cancer cells, called exosomes, contribute to extracellular adenosine production and hence modulate immune effector cells indirectly. We found exosomes from diverse cancer cell types exhibit potent ATP- and 5'AMP-phosphohydrolytic activity, partly attributed to exosomally expressed CD39 and CD73, respectively. Comparable levels of activity were seen with exosomes from pleural effusions of mesothelioma patients. In such fluids, exosomes accounted for 20% of the total ATP-hydrolytic activity. Exosomes can perform both hydrolytic steps sequentially to form adenosine from ATP. This exosome-generated adenosine can trigger a cAMP response in adenosine A(2A) receptor-positive but not A(2A) receptor-negative cells. Similarly, significantly elevated cAMP was also triggered in Jurkat cells by adding exosomes with ATP but not by adding exosomes or ATP alone. A proportion of healthy donor T cells constitutively express CD39 and/or CD73. Activation of T cells by CD3/CD28 cross-linking could be inhibited by exogenously added 5'AMP in a CD73-dependent manner. However, 5'AMP converted to adenosine by exosomes inhibits T cell activation independently of T cell CD73 expression. This T cell inhibition was mediated through the adenosine A(2A) receptor. In summary, the data highlight exosome enzymic activity in the production of extracellular adenosine, and this may play a contributory role in negative modulation of T cells in the tumor environment. PMID:21677139

  19. The Adverse Events and Hemodynamic Effects of Adenosine-Based Cardiac MRI

    We wanted to prospectively assess the adverse events and hemodynamic effects associated with an intravenous adenosine infusion in patients with suspected or known coronary artery disease and who were undergoing cardiac MRI. One hundred and sixty-eight patients (64 ± 9 years) received adenosine (140 μg/kg/min) during cardiac MRI. Before and during the administration, the heart rate, systemic blood pressure, and oxygen saturation were monitored using a MRI-compatible system. We documented any signs and symptoms of potential adverse events. In total, 47 out of 168 patients (28%) experienced adverse effects, which were mostly mild or moderate. In 13 patients (8%), the adenosine infusion was discontinued due to intolerable dyspnea or chest pain. No high grade atrioventricular block, bronchospasm or other life-threatening adverse events occurred. The hemodynamic measurements showed a significant increase in the heart rate during adenosine infusion (69.3 ± 11.7 versus 82.4 ± 13.0 beats/min, respectively; p < 0.001). A significant but clinically irrelevant increase in oxygen saturation occurred during adenosine infusion (96 ± 1.9% versus 97 ± 1.3%, respectively; p < 0.001). The blood pressure did not significantly change during adenosine infusion (systolic: 142.8 ± 24.0 versus 140.9 ± 25.7 mmHg; diastolic: 80.2 ± 12.5 mmHg versus 78.9 ± 15.6, respectively). This study confirms the safety of adenosine infusion during cardiac MRI. A considerable proportion of all patients will experience minor adverse effects and some patients will not tolerate adenosine infusion. However, all adverse events can be successfully managed by a radiologist. The increased heart rate during adenosine infusion highlights the need to individually adjust the settings according to the patient, e.g., the number of slices of myocardial perfusion imaging.

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

    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. PMID:25063794

  1. Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats.

    Scaramuzzi, R J; Baker, D J

    2003-10-01

    Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co-factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re-cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine-potentiating drugs in the treatment of age-related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age. PMID:14633184

  2. Adenosine derived from Staphylococcus aureus-engulfed macrophages functions as a potent stimulant for the induction of inflammatory cytokines in mast cells

    Ma, Ying Jie; Kim, Chan-Hee; Ryu, Kyoung-Hwa; Kim, Min-Su; So, Young-In; Lee, Kong-Joo; Garred, Peter; Lee, Bok-Luel

    2011-01-01

    adenosine receptor blocker, verified that purified adenosine can induce interleukin-8 production via adenosine receptors on mast cells. Moreover, adenosine was purified from S. aureusengulfed RAW264.7 cells, a murine macrophage cell line, used to induce phagocytosis of S. aureus. These results show a novel...

  3. Intravenous infusion of adenosine but not inosine stimulates respiration in man.

    Reid, P G; Watt, A H; Routledge, P A; Smith, A P

    1987-01-01

    The effects on respiration of intravenous infusions of the endogenous nucleoside adenosine and its deaminated metabolite, inosine, administered in random order, single-blind, were compared in six healthy volunteers. The infusion rate of each nucleoside was initially 3.1 mg min-1 and was increased stepwise every 2 min, as tolerated, up to a possible maximum of 23.4 mg ml-1. The maximum dose rates received by all subjects were 8.5 mg min-1 for adenosine and 16.8 mg min-1 for inosine. Adenosine ...

  4. Receptor crosstalk: haloperidol treatment enhances A2A adenosine receptor functioning in a transfected cell model

    Trincavelli, Maria Letizia; Cuboni, Serena; Catena Dell’Osso, Mario; Maggio, Roberto; Klotz, Karl-Norbert; Novi, Francesca; Panighini, Anna; Daniele, Simona; Martini, Claudia

    2010-01-01

    A2A adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A2A adenosine receptors are regulated by D2 dopamine receptor ligands. These two receptors are co-expressed at the level of the basal ganglia and interact to form functional heterodimers. In this context, possible changes in A2A adenosine receptor functional responses caused by the chronic blockade/activation of D2 dop...

  5. Dopamine/adenosine interactions involved in effort-related aspects of food motivation

    Salamone, John D.; Correa, Merce

    2009-01-01

    Nucleus accumbens dopamine (DA) is involved in effort-related aspects of food motivation. Accumbens DA depletions reduce the tendency of rats to work for food, and alter effort-related choice, but leave other aspects of food motivation and appetite intact. DA and adenosine receptors interact to regulate effort-related processes. Adenosine A2A antagonists can reverse the effects of DA D2 antagonists on effort-related choice, and intra-accumbens injections of a adenosine A2A agonist produce eff...

  6. Adenosine-induced hyperpolarization of the membrane voltage in rat mesangial cells in primary culture.

    Pavenstädt, H. (Hermann); Ruh, J; Greger, R; Schollmeyer, P.

    1994-01-01

    1. The effect of adenosine on membrane voltage and ion currents was studied in rat mesangial cells in primary culture. Membrane voltage was measured with the patch clamp technique in the slow- or fast whole cell configuration. The resting membrane voltage of mesangial cells was -48 +/- 0.5 mV. Adenosine (10(-8)-10(-3) M) induced a sustained and concentration-dependent hyperpolarization of membrane voltage (ED50 approximately 6 x 10(-7) M). Adenosine (10(-5) M) hyperpolarized the membrane volt...

  7. The role of adenosine A2A receptors on neuromuscular transmission upon ageing

    Pousinha, Paula Isabel Antunes, 1978-

    2012-01-01

    Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2012 Adenosine is a neuromodulator with important actions in the nervous system. The activation of adenosine A2A receptors has been shown to modulate the action of other receptors. Considering that it was observed an interaction between adenosine A2A receptors and TrkB receptors in hippocampus, I hypothesized that the activation of A2A receptors could also facilitate BDNF actions on ne...

  8. Role of endogenous adenosine in the expression of opiate withdrawal in rats.

    Salem, A; Hope, W

    1999-03-12

    Samples of extracellular fluid from striatum and nucleus accumbens of anaesthetised rats undergoing opiate withdrawal were collected using microdialysis and then analysed for adenosine and its metabolites using high performance liquid chromatography (HPLC) and ultraviolet (UV) detection. Although the amount of adenosine present in the dialysate from either brain region was below the limit of detection by 90 min after probe placement, the metabolites could still be detected. Samples of dialysates collected from the nucleus accumbens contained significantly higher concentrations of hypoxanthine and inosine following naloxone challenge. The data are compatible with the hypothesis that endogenous adenosine might be involved in the expression of the opiate abstinence syndrome. PMID:10204679

  9. Anti-Inflammatory and Immunosuppressive Effects of the A2A Adenosine Receptor

    Gillian R. Milne; Palmer, Timothy M.

    2011-01-01

    The production of adenosine represents a critical endogenous mechanism for regulating immune and inflammatory responses during conditions of stress, injury, or infection. Adenosine exerts predominantly protective effects through activation of four 7-transmembrane receptor subtypes termed A1, A2A, A2B, and A3, of which the A2A adenosine receptor (A2AAR) is recognised as a major mediator of anti-inflammatory responses. The A2AAR is widely expressed on cells of the immune system and numerous in ...

  10. DIET at the nanoscale

    Dujardin, G.; Boer-Duchemin, E.; Le Moal, E.; Mayne, A. J.; Riedel, D.

    2016-01-01

    We review the long evolution of DIET (Dynamics at surfaces Induced by Electronic Transitions) that began in the 1960s when Menzel, Gomer and Redhead proposed their famous stimulated desorption model. DIET entered the "nanoscale" in the 1990s when researchers at Bell Labs and IBM realized that the Scanning Tunneling Microscope (STM) could be used as an atomic size source of electrons to electronically excite individual atoms and molecules on surfaces. Resonant and radiant Inelastic Electron Tunneling (IET) using the STM have considerably enlarged the range of applications of DIET. Nowadays, "DIET at the nanoscale" covers a broad range of phenomena at the atomic-scale. This includes molecular dynamics (dissociation, desorption, isomerization, displacement, chemical reactions), vibrational spectroscopy and dynamics, spin spectroscopy and manipulation, luminescence spectroscopy, Raman spectroscopy and plasmonics. Future trends of DIET at the nanoscale offer exciting prospects for new methods to control light and matter at the nanoscale.

  11. Diet Choices to Prevent Cancer

    ... colors of vegetables and fruits each day. A healthy diet also includes whole grains and is low in ... can I do to improve my diet? A healthy diet includes a variety of fruits, vegetables, whole grains, ...

  12. Diet and Nutrition in Porphyria

    ... You are here Home About Porphyria Diet and Nutrition A proper diet is important to all individuals, ... alter food intake. Therefore, attention to diet and nutrition is important in almost any disease. Porphyrias are ...

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

    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.

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

    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

  15. Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

    Hellsten, Ylva; Frandsen, Ulrik

    1997-01-01

    1. The present study examined the capacity for adenosine formation, uptake and metabolism in contracting primary rat muscle cells and in microvascular endothelial cells in culture. 2. Strong and moderate electrical simulation of skeletal muscle cells led to a significantly greater increase in the...... extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P < 0.05) compared with non-stimulated muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P < 0.05) in the intensely contracted, but not in the moderately contracted muscle cells....... 3. Addition of microvascular endothelial cells to the cultured skeletal muscle cells enhanced the contraction-induced accumulation of extracellular adenosine (P < 0.05), whereas endothelial cells in culture alone did not cause extracellular accumulation of adenosine. 4. Skeletal muscle cells were...

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

    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.

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

    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...... 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...... µM in brain slices. In vivo recordings showed a tendency towards increased adenosine levels in rats with hyperammonemia and systemic inflammation compared to a control group (3.7 ± 0.7 vs. 0.8 ± 0.2 µM, P = 0.06). This was associated with a significant increase in ICP and CBF. Intervention with the...

  18. [Breastfeeding and vegan diet].

    Wagnon, J; Cagnard, B; Bridoux-Henno, L; Tourtelier, Y; Grall, J-Y; Dabadie, A

    2005-10-01

    Vegan diet in lactating women can induce vitamin B12 deficiency for their children with risk of an impaired neurological development. A 9.5-month-old girl presented with impaired growth and severe hypotonia. She had a macrocytic anemia secondary to vitamin B12 deficiency. MRI showed cerebral atrophy. She was exclusively breastfed. Her mother was also vitamin B12 deficient, secondary to a vegan diet. She had a macrocytic anemia when discharged from the maternity. Vegan diet is a totally inadequate regimen for pregnant and lactating women, especially for their children. Prevention is based on screening, information and vitamin supplementation. PMID:16208206

  19. Actinides and rare earths complexation with adenosine phosphate nucleotides

    Organophosphorus compounds are important molecules in both nuclear industry and living systems fields. Indeed, several extractants of organophosphorus compounds (such as TBP, HDEHP) are used in the nuclear fuel cycle reprocessing and in the biological field. For instance, the nucleotides are organophosphates which play a very important role in various metabolic processes. Although the literature on the interactions of actinides with inorganic phosphate is abundant, published studies with organophosphate compounds are generally limited to macroscopic and / or physiological approaches. The objective of this thesis is to study the structure of several organophosphorus compounds with actinides to reach a better understanding and develop new specific buildings blocks. The family of the chosen molecules for this procedure consists of three adenine nucleotides mono, bi and triphosphate (AMP, adenosine monophosphate - ADP, adenosine diphosphate - ATP, adenosine triphosphate) and an amino-alkylphosphate (AEP O-phosphoryl-ethanolamine). Complexes synthesis was conducted in aqueous and weakly acidic medium (2.8-4) for several lanthanides (III) (Lu, Yb, Eu) and actinides (U (VI), Th (IV) and Am (III)). Several analytical and spectroscopic techniques have been used to describe the organization of the synthesized complexes: spectrometric analysis performed by FTIR and NMR were used to identify the functional groups involved in the complexation, analysis by ESI-MS and pH-metric titration were used to determine the solution speciation and EXAFS analyzes were performed on Mars beamline of the SOLEIL synchrotron, have described the local cation environment, for both solution and solid compounds. Some theoretical approaches of DFT were conducted to identify stable structures in purpose of completing the experimental studies. All solid complexes (AMP, ADP, ATP and AEP) have polynuclear structures, while soluble ATP complexes are mononuclear. For all synthesized complexes, it has been

  20. Adenosine, Caffeine, and Performance: From Cognitive Neuroscience of Sleep to Sleep Pharmacogenetics

    Urry, Emily; Landolt, Hans-Peter

    2014-01-01

    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 adenosine , plays an important r...

  1. Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

    Aliagas, Elisabet; Villar-Menéndez, Izaskun; Sévigny, Jean; Roca, Mercedes; Romeu, Miriam; Ferrer, Isidre; Martín-Satué, Mireia; Barrachina, Marta

    2013-01-01

    Schizophrenia (SZ) is a major chronic neuropsychiatric disorder characterized by a hyperdopaminergic state. The hypoadenosinergic hypothesis proposes that reduced extracellular adenosine levels contribute to dopamine D2 receptor hyperactivity. ATP, through the action of ecto-nucleotidases, constitutes a main source of extracellular adenosine. In the present study, we examined the activity of ecto-nucleotidases (NTPDases, ecto-5′-nucleotidase, and alkaline phosphatase) in the postmortem putame...

  2. Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats

    Zhenzhen Hu; Chung-Il Lee; Vikash Kumar Shah; Eun-Hye Oh; Jin-Yi Han; Jae-Ryong Bae; Kinam Lee; Myong-Soo Chong; Jin Tae Hong; Ki-Wan Oh

    2013-01-01

    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 ...

  3. Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

    Jaiswal Pundrik; Soldati Thierry; Thewes Sascha; Baskar Ramamurthy

    2012-01-01

    Abstract Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factor...

  4. Local adenosine receptor blockade accentuates the sympathetic responses to fatiguing exercise

    Cui, Jian; Leuenberger, Urs A.; Blaha, Cheryl; Yoder, Jonathan; Gao, Zhaohui; Sinoway, Lawrence I.

    2010-01-01

    The role adenosine plays in evoking the exercise pressor reflex in humans remains controversial. We hypothesized that localized forearm adenosine receptor blockade would attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing handgrip exercise in humans. Blood pressure (Finometer), heart rate, and MSNA from the peroneal nerve were assessed in 11 healthy young volunteers during fatiguing isometric handgrip, postexercise circulatory occlusion (PECO), and passive muscle stretch...

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

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

    2014-01-01

    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 th...

  6. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells.

    Cronstein, B. N.; Eberle, M A; Gruber, H E; Levin, R I

    1991-01-01

    Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, we determined whether a 48-hr pretreatment with methotrexate affected adenosine release from [14C]adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts from 4 +/- 1% t...

  7. Radio-chromatographic determination of plasmatic adenosine deaminase (A.D.)

    We were able, by using a radio-chromatographic method, to measure an adenosine deaminase activity in normal human heparinized platelet-poor plasma, which can degrade 0.016 μM adenosine. This activity suppressed by heating 56 C for 30 minutes is inhibited by high concentrations of urea and is proportional to the amount of plasma, source of enzyme, in the systems. (authors)

  8. Aptamer-based Electrochemical Biosensors for Highly Selective and Quantitative Detection of Adenosine

    ZHENG Fan; WU Zai-sheng; ZHANG Song-bai; GUO Meng-meng; CHEN Chen-rui; SHEN Guo-li; YU Ru-qin

    2008-01-01

    A new adenosine biosensor based on aptamer probe is introduced in this article.An amino-labeled aptamer probe was immobilized on the gold electrode modified with an o-phenylenediamine electropolymerized film.When adenosine is bound specifically to the aptamer probe,the interface of the biosensor is changed,resulting in the decrement of the peak current.The response current is proportional to the amount of adenosine in sample.The used electrode can be easily regenerated in hot water.The proposed biosensor represents a linear response to adenosine over a concentration range of 1.0×10-7-1.0×10-4 mol/L with a detection limit of 1.0×10-8 mol/L.The presented biosensor exhibits a nice specificity towards adenosine.It offers a promising approach for adenosine assay due to its excellent electrochemical properties that are believed to be very attractive for electrochemical studies and electroanalytical applications.

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

    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

  10. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells

    Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, the authors determined whether a 48-hr pretreatment with methotrexate affected adenosine release from [14C]adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts. The effect of methotrexate on adenosine release was not due to cytotoxicity since cells treated with maximal concentrations of methotrexate took up [14C]adenine and released 14C-labeled purine (a measure of cell injury) in a manner identical to control cells. Methotrexate treatment of fibroblasts dramatically inhibited adherence to fibroblasts by both unstimulated neutrophils and stimulated neutrophils. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, methotrexate induces the accumulation of AICAR, the nucleoside precursor of which has previously been shown to cause adenosine release from ischemic cardiac tissue. The observation that the antiinflammatory actions of methotrexate are due to the capacity of methotrexate to induce adenosine release may form the basis for the development of an additional class of antiinflammatory drugs

  11. Intravenous adenosine (adenoscan) versus exercise in the noninvasive assessment of coronary artery disease by SPECT

    LaManna, M.M.; Mohama, R.; Slavich, I.L. 3d.; Lumia, F.J.; Cha, S.D.; Rambaran, N.; Maranhao, V. (Deborah Heart and Lung Center, Browns Mills, NJ (USA))

    1990-11-01

    Fifteen patients at a mean age of 58 underwent adenosine and maximal exercise thallium SPECT imaging. All scans were performed 1 week apart and within 4 weeks of cardiac catheterization. SPECT imaging was performed after the infusion of 140 micrograms/kg/min of adenosine for 6 minutes. Mean heart rate increment during adenosine administration was 67 +/- 3.7 to 77 +/- 4.1. Mean blood pressure was 136 +/- 7.2 to 135 +/- 6.2 systolic and 78 +/- 1.8 to 68 +/- 2.6 diastolic. No adverse hemodynamic effects were observed. There were no changes in PR or QRS in intervals. Five stress ECGs were ischemic. No ST changes were observed with adenosine. Although 68% of the patients had symptoms of flushing, light-headedness, and dizziness during adenosine infusion, symptoms resolved within 1 minute of dosage adjustment or termination of the infusion in all but one patient, who required theophylline. Sensitivity for coronary artery detection was 77% and specificity 100%. Concordance between adenoscans and exercise thallium scintigraphy was high (13/15 = 87%). In two patients, there were minor scintigraphic differences. The authors conclude that adenosine is a sensitive, specific, and safe alternative to exercise testing in patients referred for thallium imaging and may be preferable to dipyridamole.

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

    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.

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

    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.

  14. Interstitial Cystitis and Diet

    ... Toolkit Donate Monthly Giving Corporate Giving Planned Gifts & Estate Planning Donor Stock Transfer Instructions IC Charity in ... questionnaire on IC and diet. Revised Tuesday, April 5th, 2016 Home About IC What is Interstitial Cystitis ( ...

  15. Understanding the DASH diet

    ... diabetes Improve cholesterol levels Reduce the chance of kidney stones The National Heart, Blood, and Lung Institute helped develop the DASH diet. It is also recommended by: The American Heart ...

  16. Diet and cancer

    Fiber and cancer; Cancer and fiber; Nitrates and cancer; Cancer and nitrates ... DIET AND BREAST CANCER The link between nutrition and breast cancer has been well studied. To reduce risk of breast cancer the American ...

  17. Iron in diet

    Diet - iron; Ferric acid; Ferrous acid; Ferritin ... The human body needs iron to make the oxygen-carrying proteins hemoglobin and myoglobin. Hemoglobin is found in red blood cells and myoglobin is found ...

  18. Diet - chronic kidney disease

    ... this special diet to limit the buildup of waste products in the body. Limiting fluids between dialysis ... up when the kidneys no longer function well. Dangerous heart rhythms may result, which can lead to ...

  19. Diet for Ataxia

    ... discuss these guidelines with a physical therapist and nutritionist familiar with movement disorders. Ataxia is a complex ... fiber to your diet with your physician or nutritionist, ask them if you might also benefit by ...

  20. Are Detox Diets Safe?

    ... addiction that leads to health problems, including serious eating disorders, heart problems, and even death. Detox supplements can have side effects. Many of the supplements used during detox diets ...

  1. Sea Lion Diet Data

    National Oceanic and Atmospheric Administration, Department of Commerce — California sea lions pup and breed at four of the nine Channel Islands in southern California. Since 1981, SWFSC MMTD has been conducting a diet study of sea lions...

  2. Magnesium in diet

    Diet - magnesium ... Magnesium is needed for more than 300 biochemical reactions in the body. It helps to maintain normal ... There is ongoing research into the role of magnesium in preventing and managing disorders such as high ...

  3. Calcium in diet

    Diet - calcium ... Calcium is one of the most important minerals for the human body. It helps form and maintain healthy teeth and bones. A proper level of calcium in the body over a lifetime can help ...

  4. Diet and breast cancer

    Isabelle Romieu

    2011-01-01

    Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability ...

  5. Vegan Diets and Hypothyroidism

    Serena Tonstad; Edward Nathan; Keiji Oda; Gary Fraser

    2013-01-01

    Diets eliminating animal products have rarely been associated with hypothyroidism but may protect against autoimmune disease. Thus, we investigated whether risk of hypothyroidism was associated with vegetarian compared to omnivorous dietary patterns. The Adventist Health Study-2 was conducted among church members in North America who provided data in a self-administered questionnaire. Hypothyroidism was queried at baseline in 2002 and at follow-up to 2008. Diet was examined as a determinant o...

  6. A high-fat diet negatively affects rat sperm mitochondrial respiration.

    Ferramosca, A; Conte, A; Moscatelli, N; Zara, V

    2016-05-01

    Recent evidences have linked abdominal obesity, insulin resistance, and dyslipidemia to male infertility. Since a defective energy metabolism may play an important role in the impairment of sperm quality, the aim of this study is to investigate the sperm energetic metabolism in rats fed with a high-fat diet, an animal model associated with metabolic syndrome development. Sexually mature male Sprague-Dawley rats were divided into two groups and fed for 4 weeks a standard diet (control group) or a diet enriched in 35% of fat (high fat group). Liver and adipose tissue weight, plasma glucose, insulin, and lipid concentrations were determined. Activities of enzymes involved in sperm energetic metabolism were evaluated by spectrophotometric assays. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption. The administration of a high-fat diet caused a significant increase in body weight of rats and provoked hyperglycemia, hyperinsulinemia, and dyslipidemia. In these animals, we also observed a reduction in sperm concentration and motility. The investigation of sperm energetic metabolism in animals fed a high-fat diet revealed an impairment in the activity of pyruvate and lactate dehydrogenase, citrate synthase, and respiratory chain complexes. A parallel reduction in the cellular levels of adenosine triphosphate (ATP) and an increase in oxidative damage were also observed. A defective energy metabolism may play an important role in the impairment of sperm quality in the high-fat diet fed rats. PMID:27062222

  7. Adenosine concentration in the porcine coronary artery wall and A2A receptor involvement in hypoxia-induced vasodilatation

    Frøbert, Ole; Haink, Gesine; Simonsen, Ulf; Gravholt, Claus H; Levin, Max; Deussen, Andreas

    2006-01-01

    We tested whether hypoxia-induced coronary artery dilatation could be mediated by an increase in adenosine concentration within the coronary artery wall or by an increase in adenosine sensitivity. Porcine left anterior descendent coronary arteries, precontracted with prostaglandin F2α (10−5m), were mounted in a pressure myograph and microdialysis catheters were inserted into the tunica media. Dialysate adenosine concentrations were analysed by HPLC. Glucose, lactate and pyruvate were measured by an automated spectrophotometric kinetic enzymatic analyser. The exchange fraction of [14C]adenosine over the microdialysis membrane increased from 0.32 ± 0.02 to 0.46 ± 0.02 (n = 4, P < 0.01) during the study period. At baseline, interstitial adenosine was in the region of 10 nm which is significantly less than previously found myocardial concentrations. Hypoxia (PO2 30 mmHg for 60 min, n = 5) increased coronary diameters by 20.0 ± 2.6% (versus continuous oxygenation −3.1 ± 2.4%, n = 6, P < 0.001) but interstitial adenosine concentration fell. Blockade of adenosine deaminase (with erythro-9-(2-hydroxy-3-nonyl-)-adenine, 5 μm), adenosine kinase (with iodotubericidine, 10 μm) and adenosine transport (with n-nitrobenzylthioinosine, 1 μm) increased interstitial adenosine but the increase was unrelated to hypoxia or diameter. A coronary dilatation similar to that during hypoxia could be obtained with 30 μm of adenosine in the organ bath and the resulting interstitial adenosine concentrations (n = 5) were 20 times higher than the adenosine concentration measured during hypoxia. Adenosine concentration–response experiments showed vasodilatation to be more pronounced during hypoxia (n = 9) than during normoxia (n = 9, P < 0.001) and the A2A receptor antagonist ZM241385 (20 nm, n = 5), attenuated hypoxia-induced vasodilatation while the selective A2B receptor antagonist MRS1754 (20 nm, n = 4), had no effect. The lactate/pyruvate ratio was significantly increased in

  8. Adenosine to Inosine editing frequency controlled by splicing efficiency.

    Licht, Konstantin; Kapoor, Utkarsh; Mayrhofer, Elisa; Jantsch, Michael F

    2016-07-27

    Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon-intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates. We demonstrate for the first time that the extent of editing is controlled by splicing kinetics when editing is guided by intronic elements. In contrast, editing sites that are exclusively defined by exonic structures are almost unaffected by the splicing efficiency of nearby introns. In addition, we show that editing levels in pre- and mature mRNAs do not match. This phenomenon can in part be explained by the editing state of an RNA influencing its splicing rate but also by the binding of the editing enzyme ADAR that interferes with splicing. PMID:27112566

  9. Adenosine, type 1 receptors: role in proximal tubule Na+ reabsorption.

    Welch, W J

    2015-01-01

    Adenosine type 1 receptor (A1 -AR) antagonists induce diuresis and natriuresis in experimental animals and humans. Much of this effect is due to inhibition of A1 -ARs in the proximal tubule, which is responsible for 60-70% of the reabsorption of filtered Na(+) and fluid. Intratubular application of receptor antagonists indicates that A1 -AR mediates a portion of Na(+) uptake in PT and PT cells, via multiple transport systems, including Na(+) /H(+) exchanger-3 (NHE3), Na(+) /PO4(-) co-transporter and Na(+) -dependent glucose transporter, SGLT. Renal microperfusion and recollection studies have shown that fluid reabsorption is reduced by A1 -AR antagonists and is lower in A1 -AR KO mice, compared to WT mice. Absolute proximal reabsorption (APR) measured by free-flow micropuncture is equivocal, with studies that show either lower APR or similar APR in A1 -AR KO mice, compared to WT mice. Inhibition of A1 -ARs lowers elevated blood pressure in models of salt-sensitive hypertension, partially due to their effects in the proximal tubule. PMID:25345761

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

    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.

  11. Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase

    Serracino-Inglott, Ferdinand; Virlos, Ioannis T; Habib, Nagy A; Williamson, Robin CN; Mathie, Robert T

    2002-01-01

    Background Previous work has suggested that in the liver, adenosine preconditioning is mediated by nitric oxide. Whether the endothelial isoform of nitric oxide synthase plays a part in this mechanism has however not yet been investigated. Methods Wistar rats were used (6 in each group) – Groups: (1) sham, (2) ischemia-reperfusion, (3) adenosine + ischemia-reperfusion, (4) endothelial isoform inhibitor + adenosine + ischemia-reperfusion. Results Using immunohistochemistry, this study has revealed a decrease in the expression of endothelial nitric oxide synthase following hepatic ischemia-reperfusion. This was prevented by adenosine pre-treatment. When an inhibitor of endothelial nitric oxide synthase was administered prior to adenosine pre-treatment, pre-conditioning did not occur despite normal expression of endothelial nitric oxide synthase. Conclusions These findings suggest that adenosine attenuates hepatic injury by preventing the downregulation of endothelial nitric oxide synthase that occurs during ischemia-reperfusion. PMID:12241560

  12. Radio-chromatographic determination of plasmatic adenosine deaminase (A.D.); Determination radiochromatographique de l'adenosine deaminase (A.D.)

    Chivot, J.J.; Depernet, D.; Caen, J. [Commissariat a l' Energie Atomique, Bruyeres-le-Chatel (France). Centre d' Etudes

    1970-07-01

    We were able, by using a radio-chromatographic method, to measure an adenosine deaminase activity in normal human heparinized platelet-poor plasma, which can degrade 0.016 {mu}M adenosine. This activity suppressed by heating 56 C for 30 minutes is inhibited by high concentrations of urea and is proportional to the amount of plasma, source of enzyme, in the systems. (authors) [French] Nous avons pu, en utilisant une methode radiochromatographique, mesurer une activite adenosine deaminasique dans le plasma humain pauvre en plaquettes heparine qui peut degrader 0,016 {mu}M d'adenosine. Cette activite qui est supprimee par chauffage a 56 degres pendant 30 minutes, est reduite par conservation a -20 C pendant une semaine, est inhibee par d'importantes concentrations d'uree et ne l'est pas, ni par le dipyridamol, ni par le pHMB. Cette activite est proportionnelle a la quantite de plasma, source d'enzyme, mise dans les differents systemes reactifs. (auteur)

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

    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...

  14. Comparative study of adenosine deaminase activity, insulin resistance and lipoprotein(a) among smokers and healthy non-smokers

    Ramesh Ramasamy; Sathish Babu Murugaiyan; Arulkumaran U.; Sathiya R.; Kuzhandai Velu V.; Niranjan Gopal

    2016-01-01

    Background: Adenosine deaminase also known as adenosine aminohydrolase involved in purine metabolism. Its primary function is development and maintenance of immune system. The main objective of the study was to estimate adenosine deaminase (ADA) enzyme and find its correlation with lipoprotein(a) and insulin resistance among smokers and healthy non-smokers. Methods: Fifty smokers and fifty healthy non-smokers were selected based on WHO definition. ADA, lipid profile and glucose was estimat...

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

    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.

  16. A2A adenosine receptor-mediated increase in coronary flow in hyperlipidemic APOE–knockout mice

    Teng, Bunyen

    2011-01-01

    Bunyen Teng, S Jamal MustafaDepartment of Physiology and Pharmacology and Center for Cardiovascular and Respiratory Sciences, West Virginia University, Morgantown, WV, USAAbstract: Adenosine-induced coronary vasodilation is predominantly A2A adenosine receptor (AR)-mediated, whereas A1 AR is known to negatively modulate the coronary flow (CF). However, the coronary responses to adenosine in hyperlipidemia and atherosclerosis are not well understood. Using hyperlipidemic/atherosclerotic apolip...

  17. Modulation of adenosine A(2A) receptor function by interacting proteins. New targets for Huntington’s disease

    Bakešová, Jana

    2012-01-01

    [eng] In this dissertation we studied the pharmacological and functional consequences of adenosine A2A receptor interaction with other proteins, as other neurotransmitter receptores localized in the human brain and an important enzyme regulating the extracellular concentration of adenosine, the ecto-ADA (adenosine desaminase). The first aim of this thesis was to study the molecular and functional interaction of A(2A)Rwith ADA. We found out that A(2A)Racted as a membrane anchoring protein of A...

  18. Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1.

    Naval-Macabuhay, Isaac; Casanova, Víctor; Navarro, Gemma; García, Felipe; León, Agathe; Miralles, Laia; Rovira, Cristina; Martinez-Navio, José M; Gallart, Teresa; Mallol, Josefa; Gatell, José M; Lluís, Carme; Franco, Rafael; McCormick, Peter J; Climent, Núria

    2016-02-01

    Regulatory T cells have an important role in immune suppression during HIV-1 infection. As regulatory T cells produce the immunomodulatory molecule adenosine, our aim here was to assess the potential of adenosine removal to revert the suppression of anti-HIV responses exerted by regulatory T cells. The experimental setup consisted of ex vivo cocultures of T and dendritic cells, to which adenosine deaminase, an enzyme that hydrolyzes adenosine, was added. In cells from healthy individuals, adenosine hydrolysis decreased CD4(+)CD25(hi) regulatory T cells. Addition of 5'-N-ethylcarboxamidoadenosine, an adenosine receptor agonist, significantly decreased CD4(+)CD25(lo) cells, confirming a modulatory role of adenosine acting via adenosine receptors. In autologous cocultures of T cells with HIV-1-pulsed dendritic cells, addition of adenosine deaminase led to a significant decrease of HIV-1-induced CD4(+)CD25(hi) forkhead box p3(+) cells and to a significant enhancement of the HIV-1-specific CD4(+) responder T cells. An increase in the effector response was confirmed by the enhanced production of CD4(+) and CD8(+) CD25(-)CD45RO(+) memory cell generation and secretion of Th1 cytokines, including IFN-γ and IL-15 and chemokines MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5. These ex vivo results show, in a physiologically relevant model, that adenosine deaminase is able to enhance HIV-1 effector responses markedly. The possibility to revert regulatory T cell-mediated inhibition of immune responses by use of adenosine deaminase, an enzyme that hydrolyzes adenosine, merits attention for restoring T lymphocyte function in HIV-1 infection. PMID:26310829

  19. Chronic hypoxia enhances adenosine release in rat PC12 cells by altering adenosine metabolism and membrane transport.

    Kobayashi, S; Zimmermann, H; Millhorn, D E

    2000-02-01

    Acute exposure to hypoxia causes a release of adenosine (ADO) that is inversely related to the O2 levels in oxygen-sensitive pheochromocytoma (PC12) cells. In the current study, chronic exposure (48 h) of PC12 cells to moderate hypoxia (5% O2) significantly enhanced the release of ADO during severe, acute hypoxia (1% O2). Investigation into the intra- and extracellular mechanisms underpinning the secretion of ADO in PC12 cells chronically exposed to hypoxia revealed changes in gene expression and activities of several key enzymes associated with ADO production and metabolism, as well as the down-regulation of a nucleoside transporter. Decreases in the enzymatic activities of ADO kinase and ADO deaminase accompanied by an increase in those of cytoplasmic and ecto-5'-nucleotidases bring about an increased capacity to produce intra- and extracellular ADO. This increased potential to generate ADO and decreased capacity to metabolize ADO indicate that PC12 cells shift toward an ADO producer phenotype during hypoxia. The reduced function of the rat equilibrative nucleoside transporter rENT1 also plays a role in controlling extracellular ADO levels. The hypoxia-induced alterations in the ADO metabolic enzymes and the rENT1 transporter seem to increase the extracellular concentration of ADO. The biological significance of this regulation is unclear but is likely to be associated with modulating cellular activity during hypoxia. PMID:10646513

  20. Angina pectoris-like pain provoked by intravenous adenosine in healthy volunteers.

    Sylvén, C; Beermann, B; Jonzon, B; Brandt, R

    1986-07-26

    In a study to characterise the chest pain induced by adenosine this agent was given as a bolus into a peripheral vein to six healthy volunteers (five men) aged 30-44. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (one third, two thirds, and the full maximum tolerable dose) and three doses of saline were given single blind in randomised order. Thereafter aminophylline 5 mg/kg was given and the procedure repeated in a different randomised order. On the third day between two thirds and the full maximum tolerable dose was given followed by 10 mg dipyridamole intravenously and a second injection of the same dose of adenosine. Heart rate and atrioventricular blocks were recorded by electrocardiography. One minute after each dose of adenosine the chest pain was scored. The maximum tolerable dose of adenosine ranged from 10.6 to 37.1 mg. All subjects experienced uneasy central chest pain provoking anxiety. The pain radiated to the shoulders, ulnar aspect of the arms, epigastric area, back, and into the throat. The pain began about 20 seconds after the injection and lasted 10-15 seconds. Increasing the dose of adenosine increased the intensity of the pain. Administration of aminophylline reduced the pain significantly. Second degree heart block was recorded in five of the six subjects during the time that the pain was experienced. After aminophylline no block was observed. Dipyridamole increased the intensity of pain. The duration of second degree heart block increased in four of the subjects, and in two of these third degree heart block occurred. These findings suggest that adenosine released from the myocardium during ischaemia induces angina pectoris by stimulating theophylline sensitive receptors. PMID:3089465

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

    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

  2. Three minute versus six minute adenosine infusion in myocardial perfusion scintigraphy

    Pharmacological stress imaging techniques are used widely in clinical nuclear cardiology for evaluation of ischemic heart disease. Adenosine is often used but is expensive and causes significant side effects .The aim of this retrospective review was to study the tolerance and efficacy, of adenosine infusion of a 3 minute (min) versus the conventional 6 min stress protocol and to assess the cost efficiency of the 3 min protocol. Three hundred thirty one patients had myocardial scintigraphy using adenosine as a stressing agent. Blood pressure, heart rate and ECG were recorded at baseline and during the test. Symptoms (flushing, headache, chest pain, dyspnoea, neck pain) were recorded throughout the adenosine infusion. All the patients had had either 6 min or 3 min adenosine infusion at 140 mg/kg per minute. 169 of them had side effects. Flushing (32% at 3 min vs 50 % at 6 min, p<0.05), headache (11.5% at 3 min vs 7 % at 6 min p-not significant-ns), chest pain (8% at 3 min vs 13 % at 6 min, ns), dyspnoea (7% at 3 min vs %10 at 6 min, ns), ECG changes (10% at 3 min vs 28% at 6 min, p<0.05), neck pain (4.5% at 3 min vs 9% at 6 min, ns), abdominal discomfort (3% at 3 min vs 3% at 6 min, ns) and fall in blood pressure (6% at 3 min vs 8.5% at 6 min, ns). The change in heart rate was not significant with either protocol. The 6 min and 3 min infusions of adenosine had similar accuracy (73% vs 70%) for the detection of coronary artery disease. The patients tolerated the 3 min protocol better with only 40% of the patients having minimal side effects compared with 60% for the 6 mon protocol. The 3 min protocol is also cost effective as it uses less adenosine and therefore reduces total costs by 40 US$ per patient. (author)

  3. Structural basis of the substrate specificity of Bacillus cereus adenosine phosphorylase

    Dessanti, Paola [Cornell University, Ithaca, NY 14853-1301 (United States); Università di Sassari, (Italy); Zhang, Yang [Cornell University, Ithaca, NY 14853-1301 (United States); Allegrini, Simone [Università di Sassari, (Italy); Tozzi, Maria Grazia [Università di Pisa, (Italy); Sgarrella, Francesco [Università di Sassari, (Italy); Ealick, Steven E., E-mail: see3@cornell.edu [Cornell University, Ithaca, NY 14853-1301 (United States)

    2012-03-01

    Adenosine phosphorylase from B. cereus shows a strong preference for adenosine over other 6-oxopurine nucleosides. Mutation of Asp204 to asparagine reduces the efficiency of adenosine cleavage but does not affect inosine cleavage, effectively reversing the substrate specificity. The structures of D204N complexes explain these observations. Purine nucleoside phosphorylases catalyze the phosphorolytic cleavage of the glycosidic bond of purine (2′-deoxy)nucleosides, generating the corresponding free base and (2′-deoxy)ribose 1-phosphate. Two classes of PNPs have been identified: homotrimers specific for 6-oxopurines and homohexamers that accept both 6-oxopurines and 6-aminopurines. Bacillus cereus adenosine phosphorylase (AdoP) is a hexameric PNP; however, it is highly specific for 6-aminopurines. To investigate the structural basis for the unique substrate specificity of AdoP, the active-site mutant D204N was prepared and kinetically characterized and the structures of the wild-type protein and the D204N mutant complexed with adenosine and sulfate or with inosine and sulfate were determined at high resolution (1.2–1.4 Å). AdoP interacts directly with the preferred substrate through a hydrogen-bond donation from the catalytically important residue Asp204 to N7 of the purine base. Comparison with Escherichia coli PNP revealed a more optimal orientation of Asp204 towards N7 of adenosine and a more closed active site. When inosine is bound, two water molecules are interposed between Asp204 and the N7 and O6 atoms of the nucleoside, thus allowing the enzyme to find alternative but less efficient ways to stabilize the transition state. The mutation of Asp204 to asparagine led to a significant decrease in catalytic efficiency for adenosine without affecting the efficiency of inosine cleavage.

  4. Structural basis of the substrate specificity of Bacillus cereus adenosine phosphorylase

    Adenosine phosphorylase from B. cereus shows a strong preference for adenosine over other 6-oxopurine nucleosides. Mutation of Asp204 to asparagine reduces the efficiency of adenosine cleavage but does not affect inosine cleavage, effectively reversing the substrate specificity. The structures of D204N complexes explain these observations. Purine nucleoside phosphorylases catalyze the phosphorolytic cleavage of the glycosidic bond of purine (2′-deoxy)nucleosides, generating the corresponding free base and (2′-deoxy)ribose 1-phosphate. Two classes of PNPs have been identified: homotrimers specific for 6-oxopurines and homohexamers that accept both 6-oxopurines and 6-aminopurines. Bacillus cereus adenosine phosphorylase (AdoP) is a hexameric PNP; however, it is highly specific for 6-aminopurines. To investigate the structural basis for the unique substrate specificity of AdoP, the active-site mutant D204N was prepared and kinetically characterized and the structures of the wild-type protein and the D204N mutant complexed with adenosine and sulfate or with inosine and sulfate were determined at high resolution (1.2–1.4 Å). AdoP interacts directly with the preferred substrate through a hydrogen-bond donation from the catalytically important residue Asp204 to N7 of the purine base. Comparison with Escherichia coli PNP revealed a more optimal orientation of Asp204 towards N7 of adenosine and a more closed active site. When inosine is bound, two water molecules are interposed between Asp204 and the N7 and O6 atoms of the nucleoside, thus allowing the enzyme to find alternative but less efficient ways to stabilize the transition state. The mutation of Asp204 to asparagine led to a significant decrease in catalytic efficiency for adenosine without affecting the efficiency of inosine cleavage

  5. Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder.

    Silva-Ramos, M; Silva, I; Faria, M; Magalhães-Cardoso, M T; Correia, J; Ferreirinha, F; Correia-de-Sá, P

    2015-12-01

    This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [(3)H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n = 31) and control organ donors (n = 23). The neurogenic release of ATP and [(3)H]ACh was higher (P bladders. Relaxation of detrusor contractions induced by acetylcholine required 30-fold higher concentrations of adenosine. Despite VAChT-positive cholinergic nerves exhibiting higher A(1) immunoreactivity in BPH bladders, the endogenous adenosine tonus revealed by adenosine deaminase is missing. Restoration of A1 inhibition was achieved by favoring (1) ATP hydrolysis with apyrase (2 U mL(-1)) or (2) extracellular adenosine accumulation with dipyridamole or EHNA, as these drugs inhibit adenosine uptake and deamination, respectively. In conclusion, reduced ATP hydrolysis leads to deficient adenosine formation and A(1) receptor-mediated inhibition of cholinergic nerve activity in the obstructed human bladder. Thus, we propose that pharmacological manipulation of endogenous adenosine levels and/or A(1) receptor activation might be useful to control bladder overactivity in BPH patients. PMID:26521170

  6. New Nordic diet versus average Danish diet

    Khakimov, Bekzod; Poulsen, Sanne Kellebjerg; Savorani, Francesco;

    2016-01-01

    and 3-hydroxybutanoic acid were related to a higher weight loss, while higher concentrations of salicylic, lactic and N-aspartic acids, and 1,5-anhydro-D-sorbitol were related to a lower weight loss. Specific gender- and seasonal differences were also observed. The study strongly indicates that healthy...... metabolites reflecting specific differences in the diets, especially intake of plant foods and seafood, and in energy metabolism related to ketone bodies and gluconeogenesis, formed the predominant metabolite pattern discriminating the intervention groups. Among NND subjects higher levels of vaccenic acid...

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

    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. PMID:26732366

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

    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. PMID:27295623

  9. Diet affects spawning in zebrafish.

    Markovich, Michelle L; Rizzuto, Noel V; Brown, Paul B

    2007-01-01

    Seven-month-old zebrafish (Danio rerio) were fed four different diets to test the hypothesis that diet affects spawning success and resulting characteristics of eggs and offspring. The diets were: the recommended feeding regime for zebrafish (a mixture of Artemia, flake feed, and liver paste); Artemia; a flake feed; and a commercially available trout diet. The number of eggs laid and average egg diameter were significantly different as functions of male, female, and individual matings. Fish fed the flake diet produced significantly fewer eggs (mean, 116) than fish fed all other diets (means, 166-187). However, the percent hatch of eggs from fish fed the flake diet (62.5%) was significantly higher than from fish fed the trout diet (19.5%). The percentages of hatched eggs from fish fed the control diet (36.2%) or Artemia (35.6%) were not significantly different from each other or from fish fed the other two diets. Wet weight and diameter of eggs were not significantly affected by diet. Larval length was significantly higher from parents fed the flake diet (14.5 mm) compared to larvae from parents fed Artemia (13.7 mm). Length of larvae from fish fed the control or trout diets was intermediate and not significantly different from fish fed the flake diet or Artemia. Larval weight was not significantly affected by dietary treatment, but offspring from fish fed the flake diet were heavier than larvae from adults fed any of the other diets. Feeding adult zebrafish the flake diet alone resulted in more viable offspring and larger larvae and is a simpler feeding regime than the current recommendation. The authors recommend feeding adult zebrafish flake diets to satiation three times daily for maximum production of viable offspring. PMID:18041944

  10. Diet and lung cancer

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews and...... large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation with...... vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects are...

  11. Diet and lung cancer

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects...

  12. Vegan Diets and Hypothyroidism

    Serena Tonstad

    2013-11-01

    Full Text Available Diets eliminating animal products have rarely been associated with hypothyroidism but may protect against autoimmune disease. Thus, we investigated whether risk of hypothyroidism was associated with vegetarian compared to omnivorous dietary patterns. The Adventist Health Study-2 was conducted among church members in North America who provided data in a self-administered questionnaire. Hypothyroidism was queried at baseline in 2002 and at follow-up to 2008. Diet was examined as a determinant of prevalent (n = 4237 of 65,981 [6.4%] and incident cases (1184 of 41,212 [2.9%] in multivariate logistic regression models, controlled for demographics and salt use. In the prevalence study, in addition to demographic characterstics, overweight and obesity increased the odds (OR 1.32, 95% CI: 1.22–1.42 and 1.78, 95% CI: 1.64–1.93, respectively. Vegan versus omnivorous diets tended to be associated with reduced risk (OR 0.89, 95% CI: 0.78–1.01, not statistically significant while a lacto-ovo diet was associated with increased risk (OR 1.09, 95% CI: 1.01–1.18. In the incidence study, female gender, white ethnicity, higher education and BMI were predictors of hypothyroidism. Following a vegan diet tended to be protective (OR 0.78, 95% CI: 0.59–1.03, not statistically significant. In conclusion, a vegan diet tended to be associated with lower, not higher, risk of hypothyroid disease.

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

    Hayashi, M; Inagaki, A; Novak, I; Matsuda, H

    2016-07-01

    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(-) channels important for anion secretion, we herein performed experiments on Capan-1, a human pancreatic duct cell line, using open-circuit Ussing chamber and gramicidin-perforated patch-clamp techniques. The luminal addition of adenosine increased the negative transepithelial potential difference (V te) in Capan-1 monolayers with a half-maximal effective concentration value of approximately 10 μM, which corresponded to the value obtained on whole-cell Cl(-) currents in Capan-1 single cells. The effects of adenosine on V te, an equivalent short-circuit current (I sc), and whole-cell Cl(-) currents were inhibited by CFTRinh-172, a cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel inhibitor. The adenosine A2B receptor agonist, BAY 60-6583, increased I sc and whole-cell Cl(-) currents through CFTR Cl(-) channels, whereas the A2A receptor agonist, CGS 21680, had negligible effects. The A2B receptor antagonist, PSB 603, inhibited the response of I sc to adenosine. Immunohistochemical analysis showed that the A2A and A2B receptors colocalized with Ezrin in the luminal membranes of Capan-1 monolayers and in rat pancreatic ducts. Adenosine elicited the whole-cell Cl(-) currents in guinea pig duct cells. These results demonstrate that luminal adenosine regulates anion secretion by activating CFTR Cl(-) channels via adenosine A2B receptors on the luminal membranes of Capan-1 cells. The present study endorses that purinergic signaling is important in the regulation of pancreatic secretion. PMID:26965147

  14. [Acne and diet].

    Melnik, B C

    2013-04-01

    In industrialized countries acne presents as an epidemic disease of civilization affecting sebaceous follicles of adolescents and young adults, associated with increased body mass index and insulin resistance. "Western style" diet, characterized by high glycaemic load and increased consumption of insulinotropic milk proteins, plays an important role in acne pathogenesis. On the cellular level, nutrient-derived metabolic signals are sensed by the metabolic transcription factor FoxO1 and integrated by the regulatory kinase mTORC1. mTORC1, the central hub of protein- and lipid biosynthesis, cell growth and proliferation, is activated by insulin, IGF-1 and branched-chain essential amino acids, especially leucine. The understanding of Western diet-mediated nutrient signalling with over-activated mTORC1 offers a reasonable approach for dietary intervention in acne by lowering glycaemic load and consumption of milk and milk products. A suitable diet attenuating increased mTORC1 activity is a Palaeolithic-like diet with reduced intake of sugar, hyperglycaemic grains, milk and milk products but enriched consumption of vegetables and fish. PMID:23529682

  15. The rock diet

    Fordyce, Fiona; Johnson, Chris

    2002-01-01

    You may think there is little connection between rocks and our diet, indeed a serving of rocks may sound very unappetising! But rocks are a vital source of the essential elements and minerals we need to keep us healthy, such as calcium for healthy teeth and bones.

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

    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...... extensor exercise. At rest, the interstitial concentration of adenosine was 220+/-100 nmol/L and femoral arterial blood flow (FaBF) was 0.19+/-0.02 L/min. When the subjects exercised lightly, at a work rate of 10 W, there was a markedly higher (1140+/-540 nmol/L; P... 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....

  17. Circadian rhythm in adenosine A1 receptor of mouse cerebral cortex

    In order to investigate diurnal variation in adenosine A1 receptors binding parameters, Bmax and Kd values of specifically bound N6-cyclohexyl-[3H]adenosine were determined in the cerebral cortex of mice that had been housed under controlled light-dark cycles for 4 weeks. Significant differences were found for Bmax values measured at 3-hr intervals across a 24-h period, with low Bmax values during the light period and high Bmax values during the dark period. The amplitude between 03.00 and 18.00 hr was 33%. No substantial rhythm was found in the Kd values. It is suggested that the changes in the density of A1 receptors could reflect a physiologically-relevant mechanism by which adenosine exerts its modulatory role in the central nervous system

  18. The Three Possible 2-(Pyrenylethynyl) Adenosines: Rotameric Energy Barriers Govern the Photodynamics of These Structural Isomers.

    Reuss, Andreas J; Grünewald, Christian; Braun, Markus; Engels, Joachim W; Wachtveitl, Josef

    2016-05-01

    This article presents a comprehensive study of the photophysics of 2-(2-pyrenylethynyl) adenosine and 2-(4-pyrenylethynyl) adenosine, which are structural isomers of the well-established fluorescent RNA label 2-(1-pyrenylethynyl) adenosine. We performed steady-state and ultrafast transient absorption spectroscopy studies along with time-resolved fluorescence emission experiments in different solvents to work out the interplay of locally excited and charge-transfer states. We found the ultrafast photodynamics to be crucial for the fluorescence decay behavior, which extends up to tens of nanoseconds and is partially multi-exponential. These features in the ultrafast dynamics are indicative of the rotational energy barriers in the first excited state. PMID:26635201

  19. High blood pressure and diet

    ... this page: //medlineplus.gov/ency/article/007483.htm High blood pressure and diet To use the sharing features on ... diet is a proven way to help control high blood pressure . These changes can also help you lose weight ...

  20. Diet and Inflammatory Bowel Disease.

    Knight-Sepulveda, Karina; Kais, Susan; Santaolalla, Rebeca; Abreu, Maria T

    2015-08-01

    Patients with inflammatory bowel disease (IBD) are increasingly becoming interested in nonpharmacologic approaches to managing their disease. One of the most frequently asked questions of IBD patients is what they should eat. The role of diet has become very important in the prevention and treatment of IBD. Although there is a general lack of rigorous scientific evidence that demonstrates which diet is best for certain patients, several diets-such as the low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; the specific carbohydrate diet; the anti-inflammatory diet; and the Paleolithic diet-have become popular. This article discusses the diets commonly recommended to IBD patients and reviews the supporting data. PMID:27118948

  1. Diet History Questionnaire: Suggested Citations

    Use of the Diet History Questionnaire and Diet*Calc Analysis Software for publication purposes should contain a citation which includes version information for the software, questionnaire, and nutrient database.

  2. Is Dieting OK for Kids?

    ... Dictionary of Medical Words En Español What Other Kids Are Reading Movie: Digestive System Winter Sports: Sledding, ... Crushes What's a Booger? Is Dieting OK for Kids? KidsHealth > For Kids > Is Dieting OK for Kids? ...

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

    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.

  4. Increase of adenosine plasma levels after oral trimetazidine: a pharmacological preconditioning?

    Blardi, Patrizia; de Lalla, Arianna; Volpi, Luciana; Auteri, Alberto; Di Perri, Tullio

    2002-01-01

    Trimetazidine (1-[2,3,4-trimethoxybenzyl] piperazine) (TMZ) is a cellular anti-ischemic agent able to prevent intracellular ATP decrease, limit intracellular acidosis, protect against oxygen-free radical-induced toxicity and inhibit neutrophil infiltration. However, its definitive mechanism of action had not been identified. Recent studies showed the existence of an endogenous mechanism of cellular protection against ischemia, defined as 'ischemic preconditioning'. This mechanism was related mainly to cellular liberation of adenosine, a nucleoside with protective effects in myocardial ischemia. Since TMZ acts by increasing cell tolerance to ischemia and adenosine is the mediator of ischemic preconditioning, in this study we investigated a possible interaction between TMZ and adenosine. Two groups of patients affected by angina pectoris, were admitted to the study. They received a single oral dose of TMZ. One group was treated, during different sessions, with TMZ 10 and 20 mg, the other group with TMZ 40 and 80 mg. After a 3 day wash-out from drug administration, each group received a placebo. Blood samples were collected at baseline (time 0) and 1, 2, 3, 4, 6, 8 h after drug administration, in order to detect plasma levels of adenosine by a high-performance liquid chromatography method. We observed that the administration of TMZ at doses of 10, 20, 40 and 80 mg induced an increase of adenosine plasma levels of 19, 50, 62 and 62%, respectively. We hypothesized that the activity of TMZ could depend, at least in part, on adenosine mediation and this interaction opens a new interpretation of the drug antischemic effect. PMID:11820865

  5. 2'-O methylation of internal adenosine by flavivirus NS5 methyltransferase.

    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

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

    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

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

    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. Lack of effect of adenosine on the function of rodent osteoblasts and osteoclasts in vitro.

    Hajjawi, Mark O R; Patel, Jessal J; Corcelli, Michelangelo; Arnett, Timothy R; Orriss, Isabel R

    2016-06-01

    Extracellular ATP, signalling through P2 receptors, exerts well-documented effects on bone cells, inhibiting mineral deposition by osteoblasts and stimulating the formation and resorptive activity of osteoclasts. The aims of this study were to determine the potential osteotropic effects of adenosine, the hydrolysis product of ATP, on primary bone cells in vitro. We determined the effect of exogenous adenosine on (1) the growth, alkaline phosphatase (TNAP) activity and bone-forming ability of osteoblasts derived from the calvariae of neonatal rats and mice and the marrow of juvenile rats and (2) the formation and resorptive activity of osteoclasts from juvenile mouse marrow. Reverse transcription polymerase chain reaction (RT-PCR) analysis showed marked differences in the expression of P1 receptors in osteoblasts from different sources. Whilst mRNA for the A1 and A2B receptors was expressed by all primary osteoblasts, A2A receptor expression was limited to rat bone marrow and mouse calvarial osteoblasts and the A3 receptor to rat bone marrow osteoblasts. We found that adenosine had no detectable effects on cell growth, TNAP activity or bone formation by rodent osteoblasts in vitro. The analogue 2-chloroadenosine, which is hydrolysed more slowly than adenosine, had no effects on rat or mouse calvarial osteoblasts but increased TNAP activity and bone formation by rat bone marrow osteoblasts by 30-50 % at a concentration of 1 μM. Osteoclasts were found to express the A2A, A2B and A3 receptors; however, neither adenosine (≤100 μM) nor 2-chloroadenosine (≤10 μM) had any effect on the formation or resorptive activity of mouse osteoclasts in vitro. These results suggest that adenosine, unlike ATP, is not a major signalling molecule in the bone. PMID:26861849

  9. Interleukin-6-type cytokines in neuroprotection and neuromodulation: Oncostatin M, but not leukemia inhibitory factor, requires neuronal Adenosine A1 receptor function

    Moidunny, S.; Dias, R.; Van Calker, D.; Boddeke, H.; Sebastiao, A.; Biber, K.

    2010-01-01

    Objective: Adenosine is a neuromodulator in the central nervous system exhibiting anticonvulsive, neuroprotective and sedating/sleep regulating properties. A pathophysiological importance of adenosine in various neuropsychiatric diseases (e.g. epilepsy, neurodegenerative disorders, apoplexia and moo

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

    Fenger, M; Eriksen, P B; Andersen, O; Nielsen, M K; Knudsen, P J

    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...

  11. Molecular expression of adenosine receptors in OVCAR-3, Caov-4 and SKOV-3 human ovarian cancer cell lines.

    Hajiahmadi, S; Panjehpour, M; Aghaei, M; Mousavi, S

    2015-01-01

    Adenosine receptors (A1, A2a, A2b and A3) have several physiological and pathological roles in cancer cell lines. The present study was carried out to evaluate the mRNA and protein expression profile and functional role of adenosine receptors in OVCAR-3, Caov-4 and SKOV-3 ovarian cancer cell lines. The levels of mRNA and protein expression of A1, A2a, A2b and A3 adenosine receptors in the ovarian cancer cell lines were measured by Real-time PCR and western blotting. The functional roles of adenosine receptors were investigated through measurement of cAMP levels after agonist treatment. The mRNA and protein of all adenosine receptors subtypes were expressed in the ovarian cancer cell lines. Our findings demonstrated that A2b and A3 had the most mRNA and protein expression. Moreover, cAMP assay confirmed the functional role of A2b and A3 adenosine receptors. This findings demonstrated that A2b and A3 subtypes are most important adenosine receptors in humn ovarian cancer cell lines. This information provide a strong possibility into the relationship of A2b and A3 adenosine receptor and ovarian cancer. PMID:26430456

  12. Molecular expression of adenosine receptors in OVCAR-3, Caov-4 and SKOV-3 human ovarian cancer cell lines

    Hajiahmadi, S.; Panjehpour, M.; Aghaei, M.; Mousavi, S.

    2015-01-01

    Adenosine receptors (A1, A2a, A2b and A3) have several physiological and pathological roles in cancer cell lines. The present study was carried out to evaluate the mRNA and protein expression profile and functional role of adenosine receptors in OVCAR-3, Caov-4 and SKOV-3 ovarian cancer cell lines. The levels of mRNA and protein expression of A1, A2a, A2b and A3 adenosine receptors in the ovarian cancer cell lines were measured by Real-time PCR and western blotting. The functional roles of adenosine receptors were investigated through measurement of cAMP levels after agonist treatment. The mRNA and protein of all adenosine receptors subtypes were expressed in the ovarian cancer cell lines. Our findings demonstrated that A2b and A3 had the most mRNA and protein expression. Moreover, cAMP assay confirmed the functional role of A2b and A3 adenosine receptors. This findings demonstrated that A2b and A3 subtypes are most important adenosine receptors in humn ovarian cancer cell lines. This information provide a strong possibility into the relationship of A2b and A3 adenosine receptor and ovarian cancer. PMID:26430456

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

    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.

  14. Comparison of adenosine and treadmill exercise thallium-201 stress tests for the detection of coronary artery disease.

    Abe, S; Takeishi, Y; Chiba, J; Ikeda, K; Tomoike, H

    1993-12-01

    To determine the clinical usefulness of adenosine Tl-201 imaging for the evaluation of coronary artery disease, 22 patients with suspected coronary artery disease who underwent adenosine and exercise Tl-201 single photon emission computed tomography (SPECT) were studied. The peak levels of heart rate (83 vs 123 bpm, p pressure products (10220 vs 20410 bpm x mmHg, p < 0.001) were markedly smaller during adenosine infusion than during exercise. Segmental agreements between adenosine and exercise tests were 90% (218 of 242 segments) regarding the presence of perfusion defects and 89% (215 of 242 segments) regarding the presence of redistribution. Regional Tl-201 uptake (r = 0.85, p < 0.001) and the extent (r = 0.75, p < 0.001) and intensity (r = 0.83, p < 0.001) of Tl-201 defects during adenosine testing were closely correlated with those of exercise testing. Adenosine and exercise tests showed similar sensitivities for the identification of individual coronary stenosis (85% vs 78%). However, in patients who were unable to perform adequate exercise (maximal heart rate < 120 bpm), the sensitivity of adenosine imaging tended to be higher than that of exercise imaging (92% vs 69%, p = 0.07). Adenosine Tl-201 imaging is an alternative to the exercise test for assessing the severity and loci of coronary artery disease, especially in patients who are unable to perform adequate physical exercise. PMID:8283603

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

    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. PMID:25910812

  16. Association between Total Diet Cost and Diet Quality Is Limited

    Carlson, Andrea; Dong, Diansheng; Lino, Mark

    2014-01-01

    There is a common perception that it costs more to eat a healthy diet than a less healthy one. We derive a panel data model that accounts for unobserved specific individual effects to estimate the relationship between diet quality and total daily food expenditure. Since total daily diet cost and diet quality are both calculated from the foods chosen in our data, we account for the fact that there is an endogenous relationship between diet quality and cost. We find that while total daily food ...

  17. Regulation of photoreceptor gap junction phosphorylation by adenosine in zebrafish retina.

    Li, Hongyan; Chuang, Alice Z; O'Brien, John

    2014-05-01

    Electrical coupling of photoreceptors through gap junctions suppresses voltage noise, routes rod signals into cone pathways, expands the dynamic range of rod photoreceptors in high scotopic and mesopic illumination, and improves detection of contrast and small stimuli. In essentially all vertebrates, connexin 35/36 (gene homologs Cx36 in mammals, Cx35 in other vertebrates) is the major gap junction protein observed in photoreceptors, mediating rod-cone, cone-cone, and possibly rod-rod communication. Photoreceptor coupling is dynamically controlled by the day/night cycle and light/dark adaptation, and is directly correlated with phosphorylation of Cx35/36 at two sites, serine110 and serine 276/293 (homologous sites in teleost fish and mammals, respectively). Activity of protein kinase A (PKA) plays a key role during this process. Previous studies have shown that activation of dopamine D4 receptors on photoreceptors inhibits adenylyl cyclase, down-regulates cAMP and PKA activity, and leads to photoreceptor uncoupling, imposing the daytime/light condition. In this study, we explored the role of adenosine, a nighttime signal with a high extracellular concentration at night and a low concentration in the day, in regulating photoreceptor coupling by examining photoreceptor Cx35 phosphorylation in zebrafish retina. Adenosine enhanced photoreceptor Cx35 phosphorylation in daytime, but with a complex dose-response curve. Selective pharmacological manipulations revealed that adenosine A2a receptors provide a potent positive drive to phosphorylate photoreceptor Cx35 under the influence of endogenous adenosine at night. A2a receptors can be activated in the daytime as well by micromolar exogenous adenosine. However, the higher affinity adenosine A1 receptors are also present and have an antagonistic though less potent effect. Thus, the nighttime/darkness signal adenosine provides a net positive drive on Cx35 phosphorylation at night, working in opposition to dopamine to

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

    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

  19. Pharmacological Characterization of Novel A3 Adenosine Receptor-selective Antagonists

    Jacobson, Kenneth A.; Park, Kyung-Sun; JIANG, JI-LONG; KIM, YONG-CHUL; Olah, Mark E.; Stiles, Gary L.; Ji, Xiao-duo

    1997-01-01

    The effects of putative A3 adenosine receptor antagonists of three diverse chemical classes (the flavonoid MRS 1067, the 6-phenyl-1,4-dihydropyridines MRS 1097 and MRS 1191, and the triazoloquinazo-line MRS 1220) were characterized in receptor binding and functional assays. MRS1067, MRS 1191 and MRS 1220 were found to be competitive in saturation binding studies using the agonist radioligand [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide) at cloned human brain A3 recep...

  20. Wound Healing Is Accelerated by Agonists of Adenosine A2 (Gα s-linked) Receptors

    Montesinos, M. Carmen; Gadangi, Pratap; Longaker, Michael; Sung, Joanne; Levine, Jamie; Nilsen, Diana; Reibman, Joan; Min LI; Jiang, Chuan-Kui; Hirschhorn, Rochelle; Recht, Phoebe A.; Ostad, Edward; Levin, Richard I.; Cronstein, Bruce N.

    1997-01-01

    The complete healing of wounds is the final step in a highly regulated response to injury. Although many of the molecular mediators and cellular events of healing are known, their manipulation for the enhancement and acceleration of wound closure has not proven practical as yet. We and others have established that adenosine is a potent regulator of the inflammatory response, which is a component of wound healing. We now report that ligation of the Gαs-linked adenosine receptors on the cells o...

  1. Adenosine A1 Receptor Mediates Delayed Cardioprotective Effect of Sildenafil in Mouse

    Salloum, Fadi N.; Das, Anindita; Thomas, Christopher S; Yin, Chang; Kukreja, Rakesh C.

    2007-01-01

    Sildenafil induces powerful cardioprotection against ischemia/reperfusion (I/R) injury. Since adenosine is known to be major trigger of ischemic preconditioning, we hypothesized that A1 adenosine receptor (A1AR) activation plays a role in sildenafil-induced cardioprotective signaling. Adult male C57BL-wild type (WT) mice or their corresponding A1AR knockout (A1AR-KO) mice were treated intraperitoneally (i.p.) with either sildenafil (0.71 mg/kg, equivalent to 50 mg dose for a 70 kg patient) or...

  2. Adenosine and the adenosine A2A receptor agonist, CGS21680, upregulate CD39 and CD73 expression through E2F-1 and CREB in regulatory T cells isolated from septic mice.

    Bao, Rui; Shui, Xianqi; Hou, Jiong; Li, Jinbao; Deng, Xiaoming; Zhu, Xiaoyan; Yang, Tao

    2016-09-01

    The number of regulatory T cells (Treg cells) and the expression of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1; also known as CD39) and 5'-ectonucleotidase (NT5E; also known as CD73) on the Treg cell surface are increased during sepsis. In this study, to determine the factors leading to the high expression of CD39 and CD73, and the regulation of the CD39/CD73/adenosine pathway in Treg cells under septic conditions, we constructed a mouse model of sepsis and separated the Treg cells using a flow cytometer. The Treg cells isolated from the peritoneal lavage and splenocytes of the mice were treated with adenosine or the specific adenosine A2A receptor agonist, CGS21680, and were transfected with specific siRNA targeting E2F transcription factor 1 (E2F-1) or cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), which are predicted transcription regulatory factors of CD39 or CD73. The regulatory relationships among these factors were then determined by western blot analysis and dual-luciferase reporter assay. In addition, changes in adenosine metabolism were measured in the treated cells. The results revealed that adenosine and CGS21680 significantly upregulated CD39 and CD73 expression (PTreg cell surface during sepsis. Adenosine and its A2A receptor agonist served as the signal transducer factors of the CD39/CD73/adenosine pathway, accelerating adenosine generation. Our study may benefit further research on adenosine metabolism for the treatment of sepsis. PMID:27430240

  3. Adenosine modulates hypoxia-induced responses in rat PC12 cells via the A2A receptor.

    Kobayashi, S; Conforti, L; Pun, R Y; Millhorn, D E

    1998-04-01

    1. The present study was undertaken to determine the role of adenosine in mediating the cellular responses to hypoxia in rat phaeochromocytoma (PC12) cells, an oxygen-sensitive clonal cell line. 2. Reverse transcriptase polymerase chain reaction studies revealed that PC12 cells express adenosine deaminase (the first catalysing enzyme of adenosine degradation) and the A2A and A2B adenosine receptors, but not the A1 or A3 adenosine receptors. 3. Whole-cell current- and voltage-clamp experiments showed that adenosine attenuated the hypoxia-induced membrane depolarization. The hypoxia-induced suppression of the voltage-sensitive potassium current (IK(V)) was markedly reduced by adenosine. Furthermore, extracellularly applied adenosine increased the peak amplitudes of IK(V) in a concentration-dependent manner. This increase was blocked by pretreatment not only with a non-specific adenosine receptor antagonist, 8-phenyltheophylline (8-PT), but also with a selective A2A receptor antagonist, ZM241385. 4. Ca2+ imaging studies using fura-2 acetoxymethyl ester (fura-2 AM) revealed that the increase in intracellular free Ca2+ during hypoxic exposure was attenuated significantly by adenosine. Voltage-clamp studies showed that adenosine inhibited the voltage-dependent Ca2+ currents (ICa) in a concentration-dependent fashion. This inhibition was also abolished by both 8-PT and ZM241385. 5. The modulation of both IK(V) and ICa by adenosine was prevented by intracellular application of an inhibitor of protein kinase A (PKA), PKA inhibitor fragment (6-22) amide. In addition, the effect of adenosine on either IK(V) or ICa was absent in PKA-deficient PC12 cells. 6. These results indicate that the modulatory effects of adenosine on the hypoxia-induced membrane responses of PC12 cells are likely to be mediated via activation of the A2A receptor, and that the PKA pathway is required for these modulatory actions. We propose that this modulation serves to regulate membrane excitability in

  4. Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

    Mingote, Susana; Pereira, Mariana; Farrar, Andrew M.; McLaughlin, Peter J.; Salamone, John D.

    2008-01-01

    Adenosine A2A receptors are involved in the regulation of several behavioral functions. Adenosine A2A antagonists exert antiparkinsonian effects in animal models, and adenosine A2A agonists suppress locomotion and impair various aspects of motor control. The present experiments were conducted to study the effects of low doses of the adenosine A2A agonist CGS 21680 on lever pressing, specific parameters of food intake, and sedation. In the first experiment, the effects of CGS 21680 on fixed ra...

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

    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. PMID:23181321

  6. Is a healthy diet an environmentally sustainable diet?

    Macdiarmid, Jennie I

    2013-02-01

    The concept of a healthy and environmentally sustainable diet is not new, but with increasing concern about future global food security and climate change there is a renewed interest in this topic. Dietary intakes in UK accounts for approximately 20-30% of total annual greenhouse gas emissions (GHGE), with the greatest contributions coming from high intakes of meat and dairy products. Dietary proposals to help mitigate climate change (i.e. reduce GHGE) have focused on reducing consumption of meat and dairy products, but this must be considered in the context of the whole diet, alongside any possible nutritional consequences for health. Bringing together health and environmental impact of the diet raises the question of whether a healthy diet can also be an environmentally sustainable diet. While recent research showed that it is possible to achieve a realistic diet that meets dietary requirement for health and has lower GHGE, it cannot be assumed that a healthy diet will always have lower GHGE. With different combinations of food it is possible to consume a diet that meets dietary requirements for health, but has high GHGE. It is important to understand what constitutes a sustainable diet, but this then needs to be communicated effectively to try and change well-established dietary intakes of the population. Studies show that understanding of sustainable diets is poor and there are many misconceptions (e.g. the overestimation of the protein requirements for a healthy diet), which could contribute to the barriers towards changing dietary intakes. PMID:23186839

  7. Adenosine induces vasoconstriction through Gi-dependent activation of phospholipase C in isolated perfused afferent arterioles of mice

    Hansen, Pernille B; Castrop, Hayo; Briggs, Josie; Schnermann, Jurgen

    2003-01-01

    Adenosine induces vasoconstriction of renal afferent arterioles through activation of A1 adenosine receptors (A1AR). A1AR are directly coupled to Gi/Go, resulting in inhibition of adenylate cyclase, but the contribution of this signaling pathway to smooth muscle cell activation is unclear. In......-induced vasoconstriction was stable for up to 30 min and was most pronounced in the most distal part of the afferent arterioles. Adenosine did not cause vasoconstriction in arterioles from A1AR-/- mice. Pretreatment with pertussis toxin (PTX) (400 ng/ml) for 2 h blocked the vasoconstricting action of adenosine or N(6......) blocked the constriction responses to both adenosine and angiotensin II. In contrast, the adenylate cyclase inhibitor SQ22536 (10 micro M) and the protein kinase A antagonist KT5720 (0.1 and 1 micro M) did not induce significant vasoconstriction of afferent arterioles. It is concluded that the...

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

    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

  9. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women

    Volek JS

    2004-01-01

    Full Text Available Objective To compare the effects of isocaloric, energy-restricted very low-carbohydrate ketogenic (VLCK and low-fat (LF diets on weight loss, body composition, trunk fat mass, and resting energy expenditure (REE in overweight/obese men and women. Design Randomized, balanced, two diet period clinical intervention study. Subjects were prescribed two energy-restricted (-500 kcal/day diets: a VLCK diet with a goal to decrease carbohydrate levels below 10% of energy and induce ketosis and a LF diet with a goal similar to national recommendations (%carbohydrate:fat:protein = ~60:25:15%. Subjects: 15 healthy, overweight/obese men (mean s.e.m.: age 33.2 2.9 y, body mass 109.1 4.6 kg, body mass index 34.1 1.1 kg/m2 and 13 premenopausal women (age 34.0 2.4 y, body mass 76.3 3.6 kg, body mass index 29.6 1.1 kg/m2. Measurements: Weight loss, body composition, trunk fat (by dual-energy X-ray absorptiometry, and resting energy expenditure (REE were determined at baseline and after each diet intervention. Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person. Results Actual nutrient intakes from food records during the VLCK (%carbohydrate:fat:protein = ~9:63:28% and the LF (~58:22:20% were significantly different. Dietary energy was restricted, but was slightly higher during the VLCK (1855 kcal/day compared to the LF (1562 kcal/day diet for men. Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss, total fat loss, and trunk fat loss for men (despite significantly greater energy intake. The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss. The greater reduction in trunk fat was not merely due to the greater total fat loss, because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women

  10. Diet and psychological health.

    Miller, M

    1996-09-01

    This article reviews research that suggests a relationship between diet and psychological symptoms. Mind-body dualism (as it relates to clinical practice) and the limited role of nutrition in mainstream biomedical training and treatment are discussed as background issues. Two areas of inquiry that have generated relevant research findings in this area are reviewed: (1) orthomolecular theory and vitamin deficiencies, and (2) clinical ecology/environmental medicine theory and the impact of "food allergies." Although clinical case reports and promising research findings have been reported, the impact of diet on psychological health is neither widely accepted nor integrated into mental health treatment methods. Ongoing research findings in brain biochemistry and psychoneuroimmunology point to communication pathways that can provide a clearer understanding of the links between nutritional intake, central nervous system and immune function, and psychological health status. These findings may lead to greater acceptance of dietary treatment approaches among health practitioners addressing psychological disorders. PMID:8795935

  11. Protein and vegetarian diets.

    Marsh, Kate A; Munn, Elizabeth A; Baines, Surinder K

    2013-08-19

    A vegetarian diet can easily meet human dietary protein requirements as long as energy needs are met and a variety of foods are eaten. Vegetarians should obtain protein from a variety of plant sources, including legumes, soy products, grains, nuts and seeds. Eggs and dairy products also provide protein for those following a lacto-ovo-vegetarian diet. There is no need to consciously combine different plant proteins at each meal as long as a variety of foods are eaten from day to day, because the human body maintains a pool of amino acids which can be used to complement dietary protein. The consumption of plant proteins rather than animal proteins by vegetarians may contribute to their reduced risk of chronic diseases such as diabetes and heart disease. PMID:25369930

  12. Protection of Aboriginal diet

    One aspect of public concern about uranium mining in Australia has centred on possible harm to humans, particularly Aboriginal people arising from the release of radionuclides into the environment. A dose assessment model was developed based on the dispersion of radionuclides in water, their bioaccumulation in aquatic and terrestrial animals and the diet of the critical group. Of the diet components, the consumption of freshwater mussels, fish and water lilies gives rise to greater than 90% of the total exposure. On the bases of modelling dose estimates, showing which variables are more significant in the estimation of radiation exposure resulting from release of water from Ranger, limits have been deducted from the maximum annual quantity of radionuclides that can be added to Magela Creek waters without causing members of this community to be exposed to significant amounts of radiations. 2 figs., ills

  13. Depression, diet and exercise.

    Jacka, Felice N; Berk, Michael

    2013-09-16

    Unhealthy lifestyle behaviour is driving an increase in the burden of chronic non-communicable diseases worldwide. Recent evidence suggests that poor diet and a lack of exercise contribute to the genesis and course of depression. While studies examining dietary improvement as a treatment strategy in depression are lacking, epidemiological evidence clearly points to diet quality being of importance to the risk of depression. Exercise has been shown to be an effective treatment strategy for depression, but this is not reflected in treatment guidelines, and increased physical activity is not routinely encouraged when managing depression in clinical practice. Recommendations regarding dietary improvement, increases in physical activity and smoking cessation should be routinely given to patients with depression. Specialised and detailed advice may not be necessary. Recommendations should focus on following national guidelines for healthy eating and physical activity. PMID:25370279

  14. My New Diet

    2012-01-01

    正I liked eat fast food before.But it was not healthy,so I changed my diet.Now let me tell you something about my new diet.At 6:30 a.m.,I have breakfast at home.For breakfast,I often eat an egg,some bread and a glass of milk.At 11:30 a.m.,I have lunch at school.I usually have a bowl of rice,some meat and vegetables,sometimes I eat some fish.I with my family often have supper at home in the evening.I usually eat porridge and some vegetables.Sometimes I eat noodles for supper.After supper,I usually have some fruit.Because I usually eat healthy food now,so I am much healthier than before.

  15. Diet and Longevity

    He Bingxian

    2000-01-01

    @@In 1985 the International Natural Medicine Society declared the Hoten area, Xinjiang (a province of China) as one of the areas of most pronounced longevity in the world. Why are there more elderly people in Hoten? There are many factors. On the basis of our many years of research, our claim is that diet is the most important factor. Now I will discuss the following factors to illustrate.

  16. Diet-Regulated Anxiety

    Michelle Murphy; Mercer, Julian G.

    2013-01-01

    A substantial proportion of noncommunicable disease originates in habitual overconsumption of calories, which can lead to weight gain and obesity and attendant comorbidities. At the other end of the spectrum, the consequences of undernutrition in early life and at different stages of adult life can also have major impact on wellbeing and quality of life. To help address some of these issues, greater understanding is required of interactions with food and contemporary diets throughout the life...

  17. Diet and gastric cancer

    Šipetić Sandra B.; Tomić-Kundaković Slađana; Vlajinac Hristina D.; Janković Slavenka M.; Marinković Jelena M.; Maksimović Jadranka M.

    2003-01-01

    The aim of this case-control study, conducted in Serbia during the period 1998-2000, was to investigate whether diet was associated with the development of gastric cancer. The case group consisted of 131 patients with histologically confirmed gastric cancer, and the control group of 131 patients with orthopedics diseases and injuries. Cases and controls were individually matched by age (±± 2 years), gender, and place of residence. On the basis of multivariate logistic regression analysis, fol...

  18. [Diet and migraine].

    Leira, R; Rodríguez, R

    1996-05-01

    Some foods in our diet can spark off migraine attacks in susceptible individuals. Some foods can bring an attack on through an allergic reaction. A certain number such as citrus fruits, tea, coffee, pork, chocolate, milk, nuts, vegetables and cola drinks have been cited as possible allergens associated with migraine. This mechanism has however been criticized: an improvement in symptoms by eliminating some food(s) from our diet does not necessarily mean an immunologically based allergic reaction. The high IgE incidence rate is not greater in such patients than in the population at large. Other allergic reactions unrelated to diet may also be associated with migraine attacks. On the other hand substances in food may be the cause of modifications in vascular tone and bring migraine on in those so prone. Among such substances are tyramine, phenylalanine, phenolic flavonoids, alcohol, food additives (sodium nitrate, monosodium glutamate, aspartame) and caffeine. Another recognized trigger for migraine is hypoglycemia. Such foods as chocolate, cheese, citrus fruits, bananas, nuts, 'cured' meats, dairy products, cereals, beans, hot dogs, pizza, food additives (sodium nitrate, monosodium glutamate in Chinese restaurant food, aspartame as a sweetener), coffee, tea, cola drinks, alcoholic drinks such as red wine, beer or whisky distilled in copper stills, all may bring on a migraine attack. For every patient we have to assess which foodstuffs are involved in the attack (not necessarily produced by consuming the product concerned) in order to try to avoid their consumptions as a means of prophylaxis for migraine. PMID:8681169

  19. Recent developments in A2B adenosine receptor ligands.

    Kalla, Rao V; Zablocki, Jeff; Tabrizi, Mojgan Aghazadeh; Baraldi, Pier Giovanni

    2009-01-01

    A selective, high-affinity A(2B) adenosine receptor (AR) antagonist will be useful as a pharmacological tool to help determine the role of the A(2B)AR in inflammatory diseases and angiogenic diseases. Based on early A(2B)AR-selective ligands with nonoptimal pharmaceutical properties, such as 15 (MRS 1754: K(i)(hA(2B)) = 2 nM; K(i)(hA(1)) = 403 nM; K(i)(hA(2A)) = 503 NM, and K(i)(hA(3)) = 570 nM), several groups have discovered second-generation A(2B)AR ligands that are suitable for development. Scientists at CV Therapeutics have discovered the selective, high-affinity A(2B)AR antagonist 22, a 8-(4-pyrazolyl)-xanthine derivative, (CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM). Compound 22 has demonstrated favorable pharmacokinetic (PK) properties (T(1/2) = 4 h and F > 35% rat), and it is a functional antagonist at the A(2B)AR(K (B) = 6 nM). In a mouse model of asthma, compound 22 demonstrated a dose-dependent efficacy supporting the role of the A(2B)AR in asthma. In two Phase I clinical trails, 22 (CVT-6883) was found to be safe, well tolerated, and suitable for once-daily dosing. Baraldi et al. have independently discovered a selective, high-affinity A(2B)AR antagonist, 30 (MRE2029F20), 8-(5-pyrazolyl)-xanthine (K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) = 200 nM; K(i)(hA(2A), A(3)) > 1,000, that has been selected for development in conjunction with King Pharmaceuticals. Compound 30 has been demonstrated to be a functional antagonist of the A(2B)AR, and it has been radiolabeled for use in pharmacological studies. A third compound, 58 (LAS-38096), is a 2-aminopyrimidine derivative (discovered by the Almirall group) that has high A(2B)AR affinity and selectivity (K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM), and 58 has been moved into preclinical safety testing. A fourth selective, high-affinity A(2B)AR antagonist, 54 (OSIP339391 K(i))(hA(2B)) = 0.5 nM; K(i))(hA(1

  20. High fetal plasma adenosine concentration: a role for the fetus in preeclampsia?

    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.

  1. Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

    Galagudza M

    2012-04-01

    Full Text Available Michael Galagudza1, Dmitry Korolev1, Viktor Postnov2, Elena Naumisheva2, Yulia Grigorova3, Ivan Uskov1, Eugene Shlyakhto11Institute of Experimental Medicine, VA Almazov Federal Heart, Blood and Endocrinology Center, 2Chemical Faculty, St Petersburg State University, 3Department of Pathophysiology, IP Pavlov State Medical University, St Petersburg, Russian FederationAbstract: Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery.Keywords: silica nanoparticles, targeted drug delivery, myocardium, ischemia, reperfusion

  2. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

    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

  3. Brain stem adenosine receptors modulate centrally mediated hypotensive responses in conscious rats: A review

    Noha N. Nassar

    2015-05-01

    Full Text Available Adenosine is implicated in the modulation of cardiovascular responses either at the peripheral or at central level in experimental animals. However, there are no dedicated reviews on the involvement of adenosine in mediating the hypotensive response of centrally administered clonidine in general and specifically in aortically barodenervated rats (ABD. The conscious ABD rat model exhibits surgically induced baroreflex dysfunction and exaggerated hypotensive response, compared with conscious sham-operated (SO rats. The current review focuses on, the role of adenosine receptors in blood pressure (BP regulation and their possible crosstalk with other receptors e.g. imidazoline (I1 and alpha (α2A adrenergic receptor (AR. The former receptor is a molecular target for clonidine, whose hypotensive effect is enhanced approx. 3-fold in conscious ABD rats. We also discussed how the balance between the brain stem adenosine A1 and A2A receptors is regulated by baroreceptors and how such balance influences the centrally mediated hypotensive responses. The use of the ABD rat model yielded insight into the downstream signaling cascades following clonidine-evoked hypotension in a surgical model of baroreflex dysfunction.

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

    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.

  5. Adenosine triphosphatase, acetylcholinesterase and sulfhydryl groups of rat skin at local x-ray irradiation

    The activity of acetylcholinesterase (ACE), adenosine triphosphatase (ATPase), and sulfhydryl groups(SH-groups) in different structural elements of skin in the course of radiation epidermitis was studied. The posterior extremities of Wistar rats were exposed to single x-ray irradiation at a dose of 30 Gy

  6. Efficacy of Adenosine for Acute Treatment of Supraventricular Tachycardia in Infants and Children

    Seyed Mohammad Dalili

    2008-10-01

    Full Text Available Background: This study was done to assess the efficacy and adverse effects of the different doses of adenosine in the pediatric age group with respect to multiple patient variables. Methods: Over a period of 1 year, 86 occasions of supraventricular tachycardia (SVT were treated with adenosine in 81 infants and children aged between 18 days and 12 years (median of 1.3 years, SD=3. Adenosine efficacy was evaluated in terms of the patients’ demographics, SVT rate, electrocardiogram characteristics, and route of drug administration.Results: The dose of 50μg/kg was effective only in 24% of the SVT cases, and the additional doses of 100μg/kg, 150μg/kg, and 200μg/kg were effective in another 29% of the cases. The drug efficacy was higher in the infants than that in the older children. There were no predictors other than age for the estimation of the efficacy of the drug. Conclusion: Our findings showed that the current recommended doses of adenosine are ineffective in the vast majority of children and infants with SVT. No patient-related factor other than age seems to affect the efficacy of the drug

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

    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.

  8. Hematopoiesis in 5-Fluorouracil-Treated Adenosine A(3) Receptor Knock-Out Mice

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

    2015-01-01

    Roč. 64, č. 2 (2015), s. 255-262. ISSN 0862-8408 Institutional support: RVO:68081707 Keywords : Adenosine A(3) receptor knock-out mice * Hematopoiesis * 5-fluorouracil-induced hematotoxicity Subject RIV: BO - Biophysics Impact factor: 1.293, year: 2014

  9. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds.

    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.

  10. Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor.

    Johansson, B; Halldner, L; Dunwiddie, T V; Masino, S A; Poelchen, W; Giménez-Llort, L; Escorihuela, R M; Fernández-Teruel, A; Wiesenfeld-Hallin, Z; Xu, X J; Hårdemark, A; Betsholtz, C; Herlenius, E; Fredholm, B B

    2001-07-31

    Caffeine is believed to act by blocking adenosine A(1) and A(2A) receptors (A(1)R, A(2A)R), indicating that some A(1) receptors are tonically activated. We generated mice with a targeted disruption of the second coding exon of the A(1)R (A(1)R(-/-)). These animals bred and gained weight normally and had a normal heart rate, blood pressure, and body temperature. In most behavioral tests they were similar to A(1)R(+/+) mice, but A(1)R(-/-) mice showed signs of increased anxiety. Electrophysiological recordings from hippocampal slices revealed that both adenosine-mediated inhibition and theophylline-mediated augmentation of excitatory glutamatergic neurotransmission were abolished in A(1)R(-/-) mice. In A(1)R(+/-) mice the potency of adenosine was halved, as was the number of A(1)R. In A(1)R(-/-) mice, the analgesic effect of intrathecal adenosine was lost, and thermal hyperalgesia was observed, but the analgesic effect of morphine was intact. The decrease in neuronal activity upon hypoxia was reduced both in hippocampal slices and in brainstem, and functional recovery after hypoxia was attenuated. Thus A(1)Rs do not play an essential role during development, and although they significantly influence synaptic activity, they play a nonessential role in normal physiology. However, under pathophysiological conditions, including noxious stimulation and oxygen deficiency, they are important. PMID:11470917

  11. Erythropoiesis- and Thrombopoiesis-Characterizing Parameters in Adenosine A(3) Receptor Knock-Out Mice

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Weiterová, Lenka

    2013-01-01

    Roč. 62, č. 3 (2013), s. 305-311. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : ELEVATING EXTRACELLULAR ADENOSINE * COLONY-STIMULATING FACTOR * HEMATOPOIETIC PROGENITOR CELLS Subject RIV: BO - Biophysics Impact factor: 1.487, year: 2013

  12. Structural basis of the substrate specificity of Bacillus cereus adenosine phosphorylase

    Dessanti, Paola; Zhang, Yang; Allegrini, Simone; Tozzi, Maria Grazia; Sgarrella, Francesco; Ealick, Steven E. (Cornell); (Sassari); (Pisa)

    2012-10-08

    Purine nucleoside phosphorylases catalyze the phosphorolytic cleavage of the glycosidic bond of purine (2{prime}-deoxy)nucleosides, generating the corresponding free base and (2{prime}-deoxy)ribose 1-phosphate. Two classes of PNPs have been identified: homotrimers specific for 6-oxopurines and homohexamers that accept both 6-oxopurines and 6-aminopurines. Bacillus cereus adenosine phosphorylase (AdoP) is a hexameric PNP; however, it is highly specific for 6-aminopurines. To investigate the structural basis for the unique substrate specificity of AdoP, the active-site mutant D204N was prepared and kinetically characterized and the structures of the wild-type protein and the D204N mutant complexed with adenosine and sulfate or with inosine and sulfate were determined at high resolution (1.2-1.4 {angstrom}). AdoP interacts directly with the preferred substrate through a hydrogen-bond donation from the catalytically important residue Asp204 to N7 of the purine base. Comparison with Escherichia coli PNP revealed a more optimal orientation of Asp204 towards N7 of adenosine and a more closed active site. When inosine is bound, two water molecules are interposed between Asp204 and the N7 and O6 atoms of the nucleoside, thus allowing the enzyme to find alternative but less efficient ways to stabilize the transition state. The mutation of Asp204 to asparagine led to a significant decrease in catalytic efficiency for adenosine without affecting the efficiency of inosine cleavage.

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

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

    2000-01-01

    degradation product adenosine, experiments were performed in a rat model of ischaemic CHF. In this model, ischaemia was induced in rats by ligation of the left coronary artery. Our results demonstrate that there is a selective downregulation of P2X receptor-mediated pressor effects, while the hypotensive...

  14. Stimulation of Glia Reveals Modulation of Mammalian Spinal Motor Networks by Adenosine.

    David Acton

    Full Text Available Despite considerable evidence that glia can release modulators to influence the excitability of neighbouring neurons, the importance of gliotransmission for the operation of neural networks and in shaping behaviour remains controversial. Here we characterise the contribution of glia to the modulation of the mammalian spinal central pattern generator for locomotion, the output of which is directly relatable to a defined behaviour. Glia were stimulated by specific activation of protease-activated receptor-1 (PAR1, an endogenous G-protein coupled receptor preferentially expressed by spinal glia during ongoing activity of the spinal central pattern generator for locomotion. Selective activation of PAR1 by the agonist TFLLR resulted in a reversible reduction in the frequency of locomotor-related bursting recorded from ventral roots of spinal cord preparations isolated from neonatal mice. In the presence of the gliotoxins methionine sulfoximine or fluoroacetate, TFLLR had no effect, confirming the specificity of PAR1 activation to glia. The modulation of burst frequency upon PAR1 activation was blocked by the non-selective adenosine-receptor antagonist theophylline and by the A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, but not by the A2A-receptor antagonist SCH5826, indicating production of extracellular adenosine upon glial stimulation, followed by A1-receptor mediated inhibition of neuronal activity. Modulation of network output following glial stimulation was also blocked by the ectonucleotidase inhibitor ARL67156, indicating glial release of ATP and its subsequent degradation to adenosine rather than direct release of adenosine. Glial stimulation had no effect on rhythmic activity recorded following blockade of inhibitory transmission, suggesting that glial cell-derived adenosine acts via inhibitory circuit components to modulate locomotor-related output. Finally, the modulation of network output by endogenous adenosine was found to

  15. Adenosine stress myocardial perfusion scintigraphy in pediatric patients after arterial switch operation

    Arterial switch operation (ASO) has become the established treatment for correction of transposition of great arteries (TGA). Despite the immediate correction of abnormal hemodynamics, acute and delayed complications related to the coronaries may cause morbidity and mortality. We evaluated the incidence of perfusion abnormalities and safety of adenosine by stress–rest myocardial perfusion single-photon emission computed tomography (SPECT) [myocardial perfusion scintigraphy (MPS)] using Tc-99m Sestamibi (MIBI) in asymptomatic children post-ASO. Prospective study. We conducted a prospective, single-institutional study where stress–rest MPS was performed on 10 children of age between 1.25 and 6 years. Two of the patients had additional ventricular septal defect, one patient had left ventricular outflow tract obstruction, and another had Taussig–Bing anomaly. All the patients underwent corrective surgery as a single-stage procedure at the age of 176 ± 212 days (range 9-560 days). Adenosine was administered at a rate of 140 μg/kg/min intravenously as continuous infusion for duration of 6 min. All the continuous variables were summarized as mean ± standard deviation, or range and median. Mann–Whitney test for unpaired data and Wilcoxon Rank test for paired samples were used. The average increase in heart rate over the basal heart rate after adenosine stress was 59.7 ± 17.0%. No acute or remote complications were observed in any case. None of the patients demonstrated myocardial perfusion defects, either at rest or after adenosine stress. MPS post-adenosine induced vasodilatation is safe and feasible in patients of ASO for transposition of great arteries. One-stage repair, implantation of excised coronary buttons within neo-aortic sinus, and minimal or no mobilization of proximal coronaries may eliminate the occurrence of perfusion defects in patients of corrected TGA

  16. Role of nitric oxide in adenosine-induced vasodilation in humans

    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 (P<.01, n=6). In contrast, L-NMMA did not affect the increase in forearm blood flow produced by 3 microg/min nitroprusside (165+/-30% and 248+/-41% during saline and L-NMMA, respectively) or adenosine (173+/-48% and 270+/-75% during saline and L-NMMA, respectively). On the basis of our observations, we conclude that adenosine-induced vasodilation is not mediated by nitric oxide in the human forearm.

  17. Mechanisms of the adenosine A2A receptor-induced sensitization of esophageal C fibers.

    Brozmanova, M; Mazurova, L; Ru, F; Tatar, M; Hu, Y; Yu, S; Kollarik, M

    2016-02-01

    Clinical studies indicate that adenosine contributes to esophageal mechanical hypersensitivity in some patients with pain originating in the esophagus. We have previously reported that the esophageal vagal nodose C fibers express the adenosine A2A receptor. Here we addressed the hypothesis that stimulation of the adenosine A2A receptor induces mechanical sensitization of esophageal C fibers by a mechanism involving transient receptor potential A1 (TRPA1). Extracellular single fiber recordings of activity originating in C-fiber terminals were made in the ex vivo vagally innervated guinea pig esophagus. The adenosine A2A receptor-selective agonist CGS21680 induced robust, reversible sensitization of the response to esophageal distention (10-60 mmHg) in a concentration-dependent fashion (1-100 nM). At the half-maximally effective concentration (EC50: ≈3 nM), CGS21680 induced an approximately twofold increase in the mechanical response without causing an overt activation. This sensitization was abolished by the selective A2A antagonist SCH58261. The adenylyl cyclase activator forskolin mimicked while the nonselective protein kinase inhibitor H89 inhibited mechanical sensitization by CGS21680. CGS21680 did not enhance the response to the purinergic P2X receptor agonist α,β-methylene-ATP, indicating that CGS21680 does not nonspecifically sensitize to all stimuli. Mechanical sensitization by CGS21680 was abolished by pretreatment with two structurally different TRPA1 antagonists AP18 and HC030031. Single cell RT-PCR and whole cell patch-clamp studies in isolated esophagus-specific nodose neurons revealed the expression of TRPA1 in A2A-positive C-fiber neurons and demonstrated that CGS21682 potentiated TRPA1 currents evoked by allylisothiocyanate. We conclude that stimulation of the adenosine A2A receptor induces mechanical sensitization of nodose C fibers by a mechanism sensitive to TRPA1 antagonists indicating the involvement of TRPA1. PMID:26564719

  18. Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs.

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

    2014-02-01

    Previously we have shown that stimulation of inhibitory A1 adenosine receptors located in the nucleus tractus solitarii (NTS) attenuates cardiopulmonary chemoreflex (CCR) evoked inhibition of renal, adrenal and lumbar sympathetic nerve activity and reflex decreases in arterial pressure and heart rate. Activation of facilitatory A2a adenosine receptors, which dominate over A1 receptors in the NTS, contrastingly alters baseline activity of regional sympathetic outputs: it decreases renal, increases adrenal and does not change lumbar nerve activity. Considering that NTS A2a receptors may facilitate release of inhibitory transmitters we hypothesized that A2a receptors will act in concert with A1 receptors differentially inhibiting regional sympathetic CCR responses (adrenal>lumbar>renal). In urethane/chloralose anesthetized rats (n=38) we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of serotonin 5HT3 receptor agonist, phenylbiguanide, (1-8μg/kg) before and after selective stimulation, blockade or combined blockade and stimulation of NTS A2a adenosine receptors (microinjections into the NTS of CGS-21680 0.2-20pmol/50nl, ZM-241385 40pmol/100nl or ZM-241385+CGS-21680, respectively). We found that stimulation of A2a adenosine receptors uniformly inhibited the regional sympathetic and hemodynamic reflex responses and this effect was abolished by the selective blockade of NTS A2a receptors. This indicates that A2a receptor triggered inhibition of CCR responses and the contrasting shifts in baseline sympathetic activity are mediated via different mechanisms. These data implicate that stimulation of NTS A2a receptors triggers unknown inhibitory mechanism(s) which in turn inhibit transmission in the CCR pathway when adenosine is released into the NTS during severe hypotension. PMID:24216055

  19. Value of adenosine infusion for infarct size determination using real-time myocardial contrast echocardiography

    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.

  20. Electrochemical aptasensor for the detection of adenosine by using PdCu@MWCNTs-supported bienzymes as labels.

    Wu, Dan; Ren, Xiang; Hu, Lihua; Fan, Dawei; Zheng, Yang; Wei, Qin

    2015-12-15

    A highly sensitive electrochemical adenosine aptasensor was fabricated by covalently immobilizing 3'-NH2-terminated capture probe (SSDNA1) and thionine (TH) on Au-GS modified glassy carbon electrode. 3'-SH-terminated adenosine aptamer (SSDNA2) was adsorbed onto palladium/copper alloyed supported on MWCNTs (PdCu@MWCNTs)-conjugated multiple bienzymes, glucose oxidase (GOx), and horseradish peroxidase (HRP) (SSDNA2/PdCu@MWCNTs/HRP/GOx). Then, it was immobilized onto the electrode surface through the hybridization between the adenosine aptamer and the capture probe. The signal was amplified based on the gradual electrocatalytic reduction of GOx-generated hydrogen peroxide by the multiple HRP through the mediating ability of the loaded multiple TH. However, the peak current of TH decreased in the presence of adenosine because the interaction between adenosine and its aptamer made SSDNA2/PdCu@MWCNTs/HRP/GOx release from the modified electrode. Various experimental parameters have been optimized for the detection of adenosine and tests for selectivity, reproducibility and stability have also been performed. Under the optimal condition, the proposed aptasensor displayed a wide linear range (10-400 nM) with the low detection limit (2.5 nM), which has been applied in human serum samples with satisfactory results. Thus, the combination of Au-GS as a sensor platform and PdCu@MWCNTs/HRP/GOx as labels can be a promising amplification strategy for highly sensitive adenosine detection. PMID:26164010

  1. Activation of adenosine receptors and inhibition of cyclooxygenases: two recent pharmacological approaches to modulation of radiation suppressed hematopoiesis

    Searching for drugs conforming to requirements for protection and/or treatment of radiation-induced damage belongs to the most important tasks of current radiobiology. In the Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic, Brno, Czech Republic, two original approaches for stimulation of radiation-suppressed hematopoiesis have been tested in recent years, namely activation of adenosine receptors and inhibition of cyclooxygenases. Non-selective activation of adenosine receptors, induced by combined administration of dipyridamole, a drug preventing adenosine uptake and supporting thus its extracellular receptor-mediated action, and adenosine monophosphate, an adenosine prodrug, has been found to stimulate hematopoiesis when the drugs were given either pre- or post-irradiation. When synthetic adenosine receptor agonists selective for individual adenosine receptor subtypes were tested, stimulatory effects in myelosuppressed mice have been found after administration of IB-MECA, a selective adenosine A3 receptor agonist. Non-selective cyclooxygenase inhibitors, inhibiting both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), indomethacin, diclofenac, or flurbiprofen, have been observed to act positively on radiation-perturbed hematopoiesis in sublethally irradiated mice. However, their undesirable gastrointestinal side effects have been found to negatively influence survival of lethally irradiated animals. Recently tested selective COX-2 inhibitor meloxicam, preserving protective action of COX-1-synthesized prostaglandins in the gastrointestinal tissues, has been observed to retain the hematopoiesis-stimulating effects of non-selective cyclooxygenase inhibitors and to improve the survival of animals exposed to lethal radiation doses. These findings bear evidence for the possibility to use selective adenosine A3 receptor agonists and selective COX-2 inhibitors in human practice for treatment of

  2. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction.

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R; Rattan, Ramandeep

    2015-05-10

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent. PMID:25895126

  3. Chronic Consptipation and Diet

    Mehmet Ince

    2011-02-01

    Full Text Available Constipation presented a lof of sign-symptoms is not a single disease and a disorder that affect colonic and anorectal function. Constipation is defined as decreased of defecation number by physicians and all of problems relation with defecation by patients. But a accurate and correct defitinition giving base on patophyslogically by Rome III criteria. As patophyslogically, constipation is improved by decreased material that will be reached cecum, decreased motility of colon and multiple results improving defecation disorders. Constipation can be divided irratable bowel syndrome with constipation (normal transit, slow transit constipation and defecation disorders but there is no accurate border in this classification. Neurotransmitters, stress, medical therapies, sleep and meals are association with etiology of constipation. A high fiber diet can reach easily to cecum and prevent constipation. Therefore aim of this review is to stress effect of fiber diet in the first and second type of constipation. Slow transit constipation in 13-15% patients and irratable bowel sendrom with constipation (normal transit in 59% patients has being diagnosed. Seconder causes of constipation can be found with a good history taking from patients. Accurate diagnosis can be find with colon transit time followed by abdominal and pelvic examinitian. Treatment should be begin after correction of seconder causes. It should be recommendation to patients a high fiber diet, exercise, appropriate fluid with medical therapy. Lubiprostone and Tegaserod are used to begin for treatment of slow transit constipation. Laparoscopic surgery is recommened to patients not recoveried by medical therapy. [TAF Prev Med Bull 2011; 10(1.000: 71-76

  4. Interfacial molecular recognition of adenine, adenosine and ATP by a C60-uracil adduct via complementary base pairing

    Marczak, Renata; Hoang, Vu T.; Noworyta, Krzysztof; Zandler, Melvin E.; Kutner, Wlodzimierz; D'Souza, Francis

    2002-10-01

    A new C60-uracil adduct was demonstrated to recognize adenine, adenosine, or adenosine 5'-triphosphate (ATP) via complementary base pairing which led to complex formation. The base-pairing mechanism was modeled by ab initio B3LYP/3-21G(*) calculations which revealed the Watson-Crick (A-T) interactions. Stable "expanded liquid" Langmuir films of the complexes were prepared with the limiting area per molecule increasing for different subphase composition in the order: water < adenine < adenosine < ATP solution. Comparison of experimental and calculated areas per molecule and dipole moments suggest both prevailing horizontal orientation of the complexes in films.

  5. Diet in dermatology: Revisited

    Kaimal Sowmya; Thappa Devinder

    2010-01-01

    Diet has an important role to play in many skin disorders, and dermatologists are frequently faced with the difficulty of separating myth from fact when it comes to dietary advice for their patients. Patients in India are often anxious about what foods to consume, and what to avoid, in the hope that, no matter how impractical or difficult this may be, following this dictum will cure their disease. There are certain disorders where one or more components in food are central to the pathogenesis...

  6. Defying birth defects through diet?

    Crider, Krista S.; Lynn B. Bailey

    2011-01-01

    The risk of certain birth defects can be modified by maternal diet. A high-fat maternal mouse diet has recently been reported to substantially increase the penetrance of birth defects known to be associated with a deficiency of transcription factor Cited2 as well as induce cleft palate. These effects were associated with a more than twofold reduction in embryonic expression of Pitx2c. This investigation suggests the need to further explore this provocative gene-diet interaction in human studies.

  7. 腺苷和睡眠觉醒调节%Adenosine and Sleep-Wake Regulation

    曲卫敏; 孙宇; 许奇; 黄志力

    2011-01-01

    腺苷作为神经调质,调节多种神经生物学功能.随觉醒时间延长,动物脑内腺苷水平逐渐增高,在睡眠期显著降低.因此,腺苷被认为是调节睡眠的内稳态因子之一.腺苷受体(receptor,R)有A1R、A2AR、A2BR和A3R四种亚型,其中A1R和A2AR与诱导睡眠相关.激活A1R可抑制促觉醒神经元诱导睡眠,也可抑制促眠神经元导致觉醒,其作用存在脑区依赖性.A2AR介导内源性前列素D:的促眠作用,A2AR激动剂具有最强的促眠效应,阻断A2AR引起觉醒,在睡眠觉醒调节中扮演重要角色.本文综述腺苷调节睡眠和觉醒的研究进展,讨论腺苷受体激动剂和拮抗剂在睡眠疾病治疗中的潜在价值及存在问题.%Adenosine may function as a neuromodulator in the central nervous system. The extracellular concentration of adenosine increases in the brain during prolonged wakefulness and decreases during the sleep recovery penod. Therefore, adenosine is proposed to act as one of homeostatic regulators of sleep.There are four adenosine receptor subtypes, adenosine A1 receptor (A1R), A2AR, A2BR and A3R. Both the adenosine A1R and A2AR are demonstrated to be involved in sleep induction. Inhibition of wake-promoting neurons via the A1R mediates the sleep-inducing effects of adenosine, whereas activation of A1R in sleep-promoting neurons induces wakefulness, suggesting that A1R regulates the sleep-wake cycle in a site-dependent manner. On the other hand, the A2AR mediates the somnogenic effects of endogenous PGD2.A2AR agonist induces the most potent sleep similar to physiological sleep among somnogens reported so far,whereas blockade of A2AR induces wakefulness. Among adenosine receptors responsible for sleep induction,the role of A2AR is predominant. This paper presents an overview of the current knowledge about the role of adenosine in the sleep-wake regulation and briefly discusses the potential therapeutic applications of agonists and antagonists of these

  8. Diet, nutrition, and cancer

    Palmer, S.

    1985-01-01

    Evidence pertaining to the role of dietary factors in carcinogenesis comes from both epidemiological studies and laboratory experiments. In 1982, the Committee on Diet, Nutrition, and Cancer of the National Research Council conducted a comprehensive evaluation of this evidence. That assessment as well as recent epidemiological and laboratory investigations suggest that a high fat diet is associated with increased susceptibility to cancer of different sites, particularly the breast and colon, and to a lesser extent, the prostate. Current data permit no definitive conclusions about other dietary macroconstituents including cholesterol, total caloric intake, protein, carbohydrates and total dietary fiber. Specific components of fiber, however, may have a protective effect against colon cancer. In epidemiological studies, frequent consumption of certain fruits and vegetables, especially citrus fruits and carotene-rich and cruciferous vegetables, is associated with a lower incidence of cancers at various sites. The specific components responsible for these effects are not clearly identified, although the epidemiological evidence appears to be most consistent for a protective effect of carotene on lung cancer and less so for vitamins A and C and various cancer sites. The laboratory evidence is most consistent for vitamin A deficiency and enhanced tumorigenesis, and for the ability of various nonnutritive components in cruciferous vegetables to block in-vivo carcinogenesis. The data for minerals and carcinogenesis are extremely limited, although preliminary evidence from both epidemiological and laboratory studies suggests that selenium may protect against overall cancer risk. 402 references.

  9. Diet and dementia.

    Whalley, Lawrence J; Starr, John M; Deary, Ian J

    2004-09-01

    The ageing brain adapts to the accumulation of damage caused by oxidative stress and inflammation. Adaptive processes include neuroprotective and neurorestorative mechanisms. Individual differences in susceptibility to dementia arise when these mechanisms are impaired or are overwhelmed by the molecular pathology of Alzheimer's disease. Neuroprotection relies upon extrinsic and intrinsic defences. An adequate intake of antioxidant micronutrients (eg, vitamin C and vitamin E) and anti-inflammatory macronutrients (eg, omega-3 polyunsaturated fatty acids) forms an essential component of extrinsic defences against brain ageing. There are many epidemiological data to support an association between an inadequate intake of antioxidants and/or fish oils (an important source of omega-3 polyunsaturated fatty acids) and a greater than expected incidence of late onset dementia. These associations are confounded by established links between poverty, poor diet and failing health, especially in old age. Such links may be sufficient to explain some of the effects of an inadequate diet on the retention of cognitive function and increased risk of dementia in old age. More compelling is the association between increased plasma homocysteine concentration and later increased risk of dementia. This association is possibly caused by an inadequate intake of vitamin B(12)/folate. PMID:15494103

  10. Diet and breast cancer

    Isabelle Romieu

    2011-10-01

    Full Text Available Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability of food intake is wider,is beginning to show interesting results.Tanto la dieta como la nutrición han sido estudiadas en relación con el riesgo de cáncer de mama, dada la gran variación de incidencia de cáncer entre países, y la posibilidad de explicarla a través de la respuesta inflamatoria o inmune, así como ingesta de antioxidantes,entre otros.Hasta la fecha, ninguna asociación clara con la dieta ha sido encontrada, excepto para el consumo de alcohol, más allá del sobrepeso y del incremento de peso. Sin embargo, los estudios que se están realizando en países de mediano a bajo nivel de ingresos, con mayor variabilidad de ingesta de alimentos, comienzan a mostrar resultados interesantes.

  11. Diet in dermatology: Revisited

    Kaimal Sowmya

    2010-01-01

    Full Text Available Diet has an important role to play in many skin disorders, and dermatologists are frequently faced with the difficulty of separating myth from fact when it comes to dietary advice for their patients. Patients in India are often anxious about what foods to consume, and what to avoid, in the hope that, no matter how impractical or difficult this may be, following this dictum will cure their disease. There are certain disorders where one or more components in food are central to the pathogenesis, e.g. dermatitis herpetiformis, wherein dietary restrictions constitute the cornerstone of treatment. A brief list, although not comprehensive, of other disorders where diet may have a role to play includes atopic dermatitis, acne vulgaris, psoriasis vulgaris, pemphigus, urticaria, pruritus, allergic contact dermatitis, fish odor syndrome, toxic oil syndrome, fixed drug eruption, genetic and metabolic disorders (phenylketonuria, tyrosinemia, homocystinuria, galactosemia, Refsum′s disease, G6PD deficiency, xanthomas, gout and porphyria, nutritional deficiency disorders (kwashiorkar, marasmus, phrynoderma, pellagra, scurvy, acrodermatitis enteropathica, carotenemia and lycopenemia and miscellaneous disorders such as vitiligo, aphthous ulcers, cutaneous vasculitis and telogen effluvium. From a practical point of view, it will be useful for the dermatologist to keep some dietary information handy to deal with the occasional patient who does not seem to respond in spite of the best, scientific and evidence-based therapy.

  12. [Sustainable diet: history lessons].

    Fatati, Giuseppe

    2015-11-01

    Global dietary patterns changed dramatically in the past 50 years, presenting both a boom and a threat to the health and well-being of populations everywhere. We need sustainable diets, with low-input, local and seasonal agro-ecological food productions as well as short distance production-consumption nets for fair trade. The development of a global food system able to guarantee everyone a balanced food intake requires health professionals an awareness and a commitment to increasingly complex education. Dietary changes such as the adherence of to the Mediterranean Dietary Pattern can reduce the environmental footprint and thus the use of natural resources. Increased focus on improving the utilization of freshwater fishes and the correct use of the waters of rivers and lakes should also be encouraged. Cultural heritage, food quality and culinary skills are other key aspects determining sustainable dietary patterns and food security. The Mediterranean street food (Mediterraneità), for intrinsic characteristics, can represent valid model to address the main issues concerning the sustainable food system. The issues of sustainability offer a great opportunity to nutritional science and scientists to play a more central role in the political analysis of future food systems. We are confident that preserve the past helps us understand the present and build for the future, the Mediterranean lifestyle is much more than the Mediterranean diet and, finally, the rivers and the lakes may be our future. PMID:26668038

  13. Dieting Habits of Men.

    Vining, Virginia L; Cotugna, Nancy; Fang, Chengshun; Sue Snider, O

    2016-08-01

    There is little research involving the US male population regarding weight control and behavior that may affect weight status. Gender-specific weight-control programs for men aren't the standard. Our study objectives were to survey dieting and health habits of an adult male employee population and to determine if the population would be interested in gender-specific programming. Demographics, weight-control practices and interest in gender-specific weight-control programs were examined cross sectionally. A 50-question web-based survey was posted via email from October 2-30, 2014 to male employees at a Mid-Atlantic university. Statistical analyses included frequencies, means and percentages. Chi square and t tests were conducted. The 254 participants were ages 18-65+ years, predominantly white, college educated with annual incomes above $50,000. Sources of nutrition knowledge ranged from a high of web sites (65 %) to a low of registered dietitians (9 %). Macronutrient restrictions reported for dieting were carbohydrates 77 %, fats 40 % and protein 19 %. The >30 age group was more likely to have: decreased amount of food intake P = .001), reducing overall calories (P = .047), skipping meals (P = .006) or trying commercial programs (P = .011). There was nothing of significance for those motivation for males to lose and maintain weight loss. PMID:26758439

  14. Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

    Jaiswal Pundrik

    2012-01-01

    Full Text Available Abstract Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factors affecting aggregate size are modulated by adenosine and caffeine. Result Adenosine and caffeine induced the formation of large and small aggregates respectively, in evolutionarily distinct slime molds known to use diverse chemoattractants for their aggregation. Due to its genetic tractability, we chose D. discoideum to further investigate the factors affecting aggregate size. The changes in aggregate size are caused by the effect of the compounds on several parameters such as cell number and size, cell-cell adhesion, cAMP signal relay and cell counting mechanisms. While some of the effects of these two compounds are opposite to each other, interestingly, both compounds increase the intracellular glucose level and strengthen cell-cell adhesion. These compounds also inhibit the synthesis of cAMP phosphodiesterase (PdsA, weakening the relay of extracellular cAMP signal. Adenosine as well as caffeine rescue mutants impaired in stream formation (pde4- and pdiA- and colony size (smlA- and ctnA- and restore their parental aggregate size. Conclusion Adenosine increased the cell division timings thereby making large number of cells available for aggregation and also it marginally increased the cell size contributing to large aggregate size. Reduced cell division rates and decreased cell size in the presence of caffeine makes the aggregates smaller than controls. Both the compounds altered the speed of the chemotactic amoebae causing a variation in aggregate size

  15. Characterization of the binding of a novel nonxanthine adenosine antagonist radioligand, ( sup 3 H)CGS 15943, to multiple affinity states of the adenosine A1 receptor in the rat cortex

    Jarvis, M.F.; Williams, M.; Do, U.H.; Sills, M.A. (CIBA-GEIGY Corp., Summit, NJ (USA))

    1991-01-01

    The triazoloquinazoline CGS 15943 is the first reported nonxanthine adenosine antagonist that has high affinity for brain adenosine receptors. In the present study, the binding of (3H) CGS 15943 to recognition sites in rat cortical membranes was characterized. Saturation experiments revealed that (3H)CGS 15943 labeled a single class of recognition sites with high affinity and limited capacity. Competition studies revealed that the binding of (3H)CGS 15943 was consistent with the labeling of brain adenosine A1 receptors. Adenosine agonists inhibited 1 nM (3H)CGS 15943 binding with the following order of activity N6-cyclopentyladenosine (IC50 = 15 nM) greater than 2-chloroadenosine greater than (R)-N6-phenylisopropyladenosine greater than 5'-N6-ethylcarboxamidoadenosine greater than (S)N6-phenylisopropyladenosine greater than CGS 21680 greater than CV 1808 (IC50 greater than 10,000 nM). The potency order for adenosine antagonists was CGS 15943 (IC50 = 5 nM) greater than 8-phenyltheophylline greater than 1,3-dipropyl-8-(4-amino-2-chloro)phenylxanthine greater than 1,3-diethyl-8-phenylxanthine greater than theophylline = caffeine (IC50 greater than 10,000 nM). Antagonist inhibition curves were steep and best described by a one-site binding model. In contrast, adenosine A1 agonist competition curves were shallow, as indicated by Hill coefficients less than unity. Computer analysis revealed that these inhibition curves were best described by a two-site binding model. Agonist competition curves generated in the presence of 1 mM GTP resulted in a rightward shift and steepening of the inhibition-concentration curves, whereas antagonist binding was not altered in the presence of GTP. The complex binding interactions found with adenosine agonists indicate that (3H)CGS 15943 labels both high and low affinity components of the adenosine A1 receptor in the rat cortex.

  16. Regulation of adenosine triphosphate-sensitive potassium channels suppresses the toxic effects of amyloid-beta peptide (25-35)

    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

  17. Protective effects of inhibition of adenosine monophosphate activated protein kinase activity against cerebral ischemia-reperfusion injury in mice

    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

  18. Cyclic adenosine monophosphate-dependent phosphorylation of mammalian mitochondrial proteins: enzyme and substrate characterization and functional role

    Dobrová, Zuzana; Sardanelli, A. M.; Speranza, F.; Scacco, S.; Signorile, A.; Lorusso, V.; Papa, S.

    2001-01-01

    Roč. 40, - (2001), s. 13941-13947. ISSN 0006-2960 Institutional research plan: CEZ:AV0Z5020903 Keywords : cAMP * cyclic adenosine monophosphate Subject RIV: CE - Biochemistry Impact factor: 4.114, year: 2001

  19. Diet Quality and Academic Performance

    Florence, Michelle D.; Asbridge, Mark; Veugelers, Paul J.

    2008-01-01

    Background: Although the effects of nutrition on health and school performance are often cited, few research studies have examined the effect of diet quality on the academic performance of children. This study examines the association between overall diet quality and academic performance. Methods: In 2003, 5200 grade 5 students in Nova Scotia,…

  20. DO HEALTHIER DIETS COST MORE?

    Ranney, Christine K.; McNamara, Paul E.

    2002-01-01

    Do healthier diets cost more? We estimate a hedonic regression model of the U.S. diet. Given food expenditures and information on dietary intake we infer the marginal cost of improved quality. Meeting the Pyramid recommendations implies decreased expenditures from two of the seven food groups.

  1. Cystic Fibrosis: Diet and Nutrition

    ... a Friend Who Cuts? Cystic Fibrosis: Diet and Nutrition KidsHealth > For Teens > Cystic Fibrosis: Diet and Nutrition Print A A A Text Size What's in ... or the flu. With the right balance of nutrition, extra fat and calories , and prescribed supplements, though, ...

  2. Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder

    Silva-Ramos, M.; Silva, I; Faria, M.; Magalhães-Cardoso, M. T.; Correia, J.; Ferreirinha, F; Correia-de-Sá, P.

    2015-01-01

    This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [3H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n...

  3. Efficient, low-cost protein factories: expression of human adenosine deaminase in baculovirus-infected insect larvae.

    Medin, J A; Hunt, L; Gathy, K; Evans, R K; Coleman, M S

    1990-01-01

    Human adenosine deaminase (EC 3.5.4.4), a key purine salvage enzyme essential for immune competence, has been overproduced in Spodoptera frugiperda cells and in Trichoplusia ni (cabbage looper) larvae infected with recombinant baculovirus. The coding sequence of human adenosine deaminase was recombined into a baculovirus immediately downstream from the strong polyhedrin gene promoter. Approximately 60 hr after infection of insect cells with the recombinant virus, maximal levels of intracellul...

  4. Differential modulation of ATP-induced calcium signalling by A1 and A2 adenosine receptors in cultured cortical astrocytes

    Alloisio, Susanna; Cugnoli, Carlo; Ferroni, Stefano; Nobile, Mario

    2004-01-01

    Despite the accumulating evidence that under various pathological conditions the extracellular elevation of adenine-based nucleotides and nucleosides plays a key role in the control of astroglial reactivity, how these signalling molecules interact in the regulation of astrocyte function is still largely elusive.The action of the nucleoside adenosine in the modulation of the intracellular calcium signalling ([Ca2+]i) elicited by adenosine 5′-triphosphate (ATP)-induced activation of P2 purinoce...

  5. Nucleoside-Derived Antagonists to A3 Adenosine Receptors Lower Mouse Intraocular Pressure and Act across Species

    Wang, Zhao; Do, Chi Wai; Avila, Marcel Y.; Peterson-Yantorno, Kim; Stone, Richard A.; Gao, Zhan-Guo; Joshi, Bhalchandra; Besada, Pedro; Jeong, Lak Shin; Jacobson, Kenneth A.; Civan, Mortimer M.

    2009-01-01

    The purpose of the study was to determine whether novel, selective antagonists of human A3 adenosine receptors (ARs) derived from the A3-selective agonist Cl-IB-MECA lower intraocular pressure (IOP) and act across species. IOP was measured invasively with a micropipette by the Servo-Null Micropipette System (SNMS) and by non-invasive pneumotonometry during topical drug application. Antagonist efficacy was also assayed by measuring inhibition of adenosine-triggered shrinkage of native bovine n...

  6. Adenosine inhibitory effect on enhanced growth of aortic smooth muscle cells from streptozotocin-induced diabetic rats.

    Parés-Herbuté, N.; Hillaire-Buys, D.; Etienne, P.; Gross, R.; Loubatières-Mariani, M. M.; MONNIER, L.

    1996-01-01

    1. There is evidence to suggest that adenosine may regulate arterial smooth muscle cell (SMC) growth and proliferation, which is a key event in atherogenesis. This regulation may be mediated via adenylate cyclase. As diabetes is a known risk factor for atherosclerosis, we investigated the growth of aortic SMC from diabetic rats in primary culture and their sensitivity to adenosine and to adenylate cyclase activity. 2. Diabetes was induced with streptozotocin (STZ, 66 mg kg-1, i.p.) Aortic SMC...

  7. Sleep-Wake Regulation and Its Impact on Working Memory Performance: The Role of Adenosine

    Reichert, Carolin Franziska; Maire, Micheline; Schmidt, Christina; Cajochen, Christian

    2016-01-01

    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. PMID:26861410

  8. Alteration of membrane phospholipid methylation by adenosine analogs does not affect T lymphocyte activation

    Membrane phospholipid methylation has been described during activation of various immune cells. Moreover recent data indicated modulation of immune cells functions by adenosine. As S-adenosyl-methionine and S-adenosyl-homocysteine are adenosine analogs and modulators of transmethylation reactions, the effects of SAH and SAM were investigated on membrane phospholipid methylation and lymphocyte activation. SAM was shown to induce the membrane phospholipid methylation as assessed by the 3Hmethyl-incorporation in membrane extract. This effect was inhibited by SAH. In contrast SAM and SAH did not affect the phytohemagglutinin-induced proliferative response of peripheral blood mononuclear cells. SAH neither modified the early internalization of membrane CD3 antigens nor did it prevent the late expression of HLA-DR antigens on lymphocytes activated by phytohemagglutinin. These results indicate that in vitro alteration of phospholipid methylation does not affect subsequent steps of human T lymphocyte activation and proliferation

  9. Platelet aggregation and serum adenosine deaminase (ADA) activity in pregnancy associated with diabetes, hypertension and HIV.

    Leal, Claudio A M; Leal, Daniela B R; Adefegha, Stephen A; Morsch, Vera M; da Silva, José E P; Rezer, João F P; Schrekker, Clarissa M L; Abdalla, Faida H; Schetinger, Maria R C

    2016-07-01

    Platelet aggregation and adenosine deaminase (ADA) activity were evaluated in pregnant women living with some disease conditions including hypertension, diabetes mellitus and human immunodeficiency virus infection. The subject population is consisted of 15 non-pregnant healthy women [control group (CG)], 15 women with normal pregnancy (NP), 7 women with hypertensive pregnancy (HP), 10 women with gestational diabetes mellitus (GDM) and 12 women with human immunodeficiency virus-infected pregnancy (HIP) groups. The aggregation of platelets was checked using an optical aggregometer, and serum ADA activity was determined using the colorimetric method. After the addition of 5 µM of agonist adenosine diphosphate, the percentage of platelet aggregation was significantly (p pregnancy and pregnancy-associated diseases suggest that platelet aggregation and ADA activity could serve as peripheral markers for the development of effective therapy in the maintenance of homeostasis and some inflammatory process in these pathophysiological conditions. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27273565

  10. Synthesis and Pharmacological Evaluation of Modified Adenosines Joined to Mono-Functional Platinum Moieties

    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.

  11. Tumour necrosis factor-α and adenosine in endotoxin shockleading related cardiovascular symptoms

    S. Sipka

    1995-01-01

    Full Text Available We have observed uncontrollable cardiogenic shock as a cardiovascular manifestation of systemic inflammatory response syndrome (SIRS leading to death in a 62-year-old woman. The diagnosis of SIRS was based on the demonstration of endotoxinaemia, and highly elevated plasma levels of tumour necrosis factor (TNF-α, and interleukin (IL-10. We suggest that these cytokines may contribute to the terminal SIRS-related arrythmias, impaired myocardial contractility, as well as increased vascular permeability. In addition, the increased production of adenosine, a counter-regulatory mediator of inflammation, may also play a role in cardiodepression. We suggest a relationship between the action of TNF-α , IL-10 and adenosine in the pathogenesis of circulatory symptoms described above.

  12. Interaction of Divalent Metal Ions with the Adenosine Triphosphate Measured Using Nuclear Magnetic Resonance

    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.

  13. Thermodynamic studies on protonation constant of adenosine and guanosine at different temperatures and ionic strengths

    Highlights: • Protonation constants of adenosine and guanosine were determined. • The dependence of temperature and ionic strength were characterized. • Potentiometric and spectrophotometric methods were used. - Abstract: Stepwise protonation constants of two purine nucleosides (adenosine and guanosine) were determined at different temperatures (293.15 to 308.15) and various ionic strengths (0.101 to 3.503 mol · kg−1 NaClO4) using a combination of potentiometric and spectrophotometric method. The thermodynamic parameters (i.e. enthalpy change, ΔH, and entropy change, ΔS) of the protonations were calculated at different temperatures using van’t Hoff and virial equations. The dependence of the protonation constant on ionic strength is modeled by a Debye–Hückel type equation and discussed. Finally, the protonation constants of the nucleosides and the enthalpy change of protonations were determined at zero ionic strength

  14. Diets could prevent many diseases.

    Lands, William E M

    2003-04-01

    The 2002 ISSFAL Meeting arranged a special evening discussion with professional dietitians about diet-tissue-disease relationships involving essential fatty acids and eicosanoids. The balance of eicosanoid precursors in human tissues differs widely, reflecting voluntary dietary choices among different groups worldwide. An empirical quantitative diet-tissue relationship fits these diverse values as well as other research reports on essential fatty acid metabolism. Information for dietitians and nutritionists about essential fatty acids and eicosanoids is also given in two distance learning web sites, http://ods.od.nih.gov/eicosanoids/ and http:// efaeducation.nih.gov/, which facilitate dietitian education and diet counseling. These sites also have an innovative, interactive diet planning software program with the empirical equation embedded in it to help evaluate personal food choices in the context of the diet-tissue-disease relationship and other widely recommended dietary advice. PMID:12848276

  15. Health effects of vegan diets.

    Craig, Winston J

    2009-05-01

    Recently, vegetarian diets have experienced an increase in popularity. A vegetarian diet is associated with many health benefits because of its higher content of fiber, folic acid, vitamins C and E, potassium, magnesium, and many phytochemicals and a fat content that is more unsaturated. Compared with other vegetarian diets, vegan diets tend to contain less saturated fat and cholesterol and more dietary fiber. Vegans tend to be thinner, have lower serum cholesterol, and lower blood pressure, reducing their risk of heart disease. However, eliminating all animal products from the diet increases the risk of certain nutritional deficiencies. Micronutrients of special concern for the vegan include vitamins B-12 and D, calcium, and long-chain n-3 (omega-3) fatty acids. Unless vegans regularly consume foods that are fortified with these nutrients, appropriate supplements should be consumed. In some cases, iron and zinc status of vegans may also be of concern because of the limited bioavailability of these minerals. PMID:19279075

  16. Cassava For Space Diet

    Katayama, Naomi; Yamashita, Masamichi; Njemanze, Philip; Nweke, Felix; Mitsuhashi, Jun; Hachiya, Natumi; Miyashita, Sachiko; Hotta, Atuko

    Space agriculture is an advanced life support enginnering concept based on biological and ecological system ot drive the materials recycle loop and create pleasant life environment on distant planetary bodies. Choice of space diet is one of primary decision required ot be made at designing space agriculture. We propose cassava, Manihot esculenta and, for one major composition of space food materials, and evaluate its value and feasibility of farming and processing it for space diet. Criteria to select space crop species could be stated as follows. 1) Fill th enutritional requirements. There is no perfect food material to meet this requirements without making a combination with others. A set of food materials which are adopted inthe space recipe shall fit to the nutritional requirement. 2) Space food is not just for maintaining physiological activities of human, but an element of human culture. We shall consider joy of dining in space life. In this context, space foos or recipe should be accepted by future astronauts. Food culture is diverse in the world, and has close relatioship to each cultural background. Cassava root tuber is a material to supply mainly energy in the form of carbohydrate, same as cereals and other tuber crops. Cassava leaf is rich in protein high as 5.1 percents about ten times higher content than its tuber. In the food culture in Africa, cassava is a major component. Cassava root tuber in most of its strain contains cyanide, it should be removed during preparation for cooking. However certain strain are less in this cyanogenic compound, and genetically modified cassava can also aboid this problem safely.

  17. Diagnostic value of domestic made adenosine in 99Tcm-MIBI myocardial perfusion SPECT for detecting coronary artery disease

    Objective: To evaluate the accuracy and safety of domestic made adenosine in 99Tcm- methoxyisobutylisonitrile (MIBI) myocardial perfusion SPECT during adenosine stress for the diagnosis of coronary ischemia. Methods: One hundred and two patients [73 men, 29 women, mean age (57 ± 10.4) years] with suspected coronary artery disease underwent adenosine stress and rest myocardial perfusion imaging. Adenosine was infused intravenously at a constant rate of 0.14 mg·kg-1·main-1 for 6 min. At the end of 3 min, 925 MBq of 99Tcm-MIBI was injected. In 70 patients coronary angiography was also performed within one week. Results: Thirty-nine patients had significant coronary artery stenosis and 31 patients had normal result. Adenosine stress myocardial perfusion scintigraphy was abnormal in 32 out of the 39 patients in coronary artery stenosis (sensitivity, 82.05%), and normal in 26 out of the 31 patients with normal angiography (specificity 83.87%). The positive and negative predictive values were 86.49% and 78.79% respectively. The frequency of side-effects was slight and transient with the incidence of 85.29%. Conclusion: The domestic made adenosine in stress myocardial perfusion imaging is safe and sensitive for detecting myocardial ischemia. (authors)

  18. Cellular mechanisms for the treatment of chronic heart failure: the nitric oxide- and adenosine-dependent pathways.

    Minamino, Tetsuo; Kitakaze, Masafumi

    2002-05-01

    Accumulated evidence suggests that several drugs proven to improve survival in patients with chronic heart failure (CHF) enhance endogenous nitric oxide (NO)- and/or adenosine-dependent pathways. Indeed, we and others have demonstrated that: i) antagonists of either renin-angiotensin-aldosterone or beta-adrenergic systems enhance NO-dependent pathways; ii) although carvedilol and amlodipine belong to different drug classes, both of them can increase cardiac adenosine levels; iii) increased adenosine levels by dipyridamole are associated with the improvement of CHF. Interestingly, both NO and adenosine have multifactorial beneficial actions in cardiovascular systems. First of all, both of them induce vasodilation and decrease myocardial hypercontractility, which may contribute to a reduction in the severity of myocardial ischaemia. Both adenosine and NO are also involved in cardioprotection attributable to acute and late phases of ischaemic preconditioning, respectively. Secondly, they can modulate the neurohormonal systems that contribute to the progression of CHF. Thus, we propose that enhancement of endogenous NO and/or adenosine as potential therapeutic targets in a new strategy for the treatment for CHF. PMID:15989539

  19. [Thallium-201 myocardial perfusion imaging during adenosine-induced coronary vasodilation in patients with ischemic heart disease].

    Takeishi, Y; Chiba, J; Abe, S; Ikeda, K; Tonooka, I; Komatani, A; Takahashi, K; Nakagawa, Y; Shiraishi, T; Tomoike, H

    1992-09-01

    201Tl myocardial perfusion imaging during adenosine infusion was performed in consecutive 55 patients with suspected coronary artery disease. Adenosine was infused intravenously at a rate of 0.14 mg/kg/min for 6 minutes and a dose of 111 MBq of 201Tl was administered in a separate vein at the end of third minute of infusion. Myocardial SPECT imaging was begun 5 minutes and 3 hours after the end of adenosine infusion. For evaluating the presence of perfusion defects, 2 short axis images at the basal and apical levels and a vertical long axis image at the mid left ventricle were used. The regions with decreased 201Tl uptake were assessed semi-quantitatively. Adenosine infusion caused a slight reduction in systolic blood pressure and an increase in heart rate. The rate pressure products increased slightly (9314 +/- 2377 vs. 10360 +/- 2148, p < 0.001). Chest pain (24%) and headache (13%) were the frequent side effects. The second-degree atrioventricular block was developed in 11 of 55 (20%) patients. All symptoms and hemodynamic changes were well tolerated and disappeared within 1 or 2 minutes after discontinuing adenosine infusion. The sensitivity and specificity for the detection of patients with coronary artery disease were 100% (31/31) and 88% (7/8), respectively. 201Tl myocardial imaging during adenosine infusion was considered to be safe and useful for evaluating the patients with ischemic heart disease. PMID:1453559

  20. Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on ocular blood flow in rabbits.

    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. PMID:17239401

  1. Comparison of adenosine and exercise stress 201Tl myocardial perfusion imaging for diagnosing coronary heart disease in women

    Objective: To compare the diagnostic value of adenosine and exercise stress myocardial perfusion imaging (MPI) for detecting coronary heart disease (CHD) in women. Methods: One hundred and thirty-eight patients with CHD were randomly divided into two groups: adenosine stress group (n=69)and exercise stress group (n=69). All patients underwent myocardial SPECT evaluation. Coronary angiography (CAG), referred as 'gold standard' , was performed in each patient within 1 week before or after MPI. The diagnostic value of the two stress MPI was compared with χ2 test or Fisher's exact test. Results: In adenosine stress group, the sensitivity, negative predictive value and accuracy were 88.2% (45/51), 72.7% (16/22), 88.4% (61/69), respectively, which were not significantly different from those of the exercise stress group (91.7% (44/48), 66.7% (8/12), 81.2% (52/64); χ2 =0.571, 0.714, 0.249, P>0.05). However, the false positive rate of adenosine stress (11.1%, 2/18) was significantly lower than that of exercise stress (50.0%, 8/16), P=0.023. Conclusions: Adenosine and exercise stress MPI have similar value for CHD diagnosis in women, however, adenosine stress MPI may have an advantage of low false positive rate. (authors)

  2. Evaluation of myocardial blood supply using adenosine stress myocardial perfusion imaging

    Objective: To retrospectively evaluate the value and accuracy of adenosine stress and rest SPECT myocardial perfusion imaging. Methods: A total of 1858 patients who were suspected or known for coronary artery disease (CAD) underwent 99Tcm-methoxyisobutylisonitrile (MIBI) myocardial perfusion SPECT with adenosine infusion using the standard 2-day protocol. Images were interpreted by two or more experienced nuclear medicine physicians. Coronary angiography was carried out in all patients within one month. Kappa test was used to analyze the correlation between the two imaging studies. Results: By coronary angiography, there were 957 patients diagnosed of CAD (one-, two-, three-vessel disease: 506, 256, 195, respectively) and 901 normal. Stenosis was found in 1603 vessels, including left anterior descending coronary artery (LAD): 765, left circumflex coronary artery (LCX): 399 and right coronary artery (RCA): 439. By adenosine induced stress myocardial perfusion imaging, 876 patients were diagnosed of myocardial ischemia (sensitivity: 876/957, 91.54%) and 651 patients had negative findings (specificity: 651/901,72.25 %). The positive and negative predictive values were 77.80% (876/1126) and 88.93% (651/732), respectively. The correlation coefficient between the two imaging studies was 0.641. The vessel-based sensitivity was 81.31% (622/765) for LAD, 56.64% (226/399) for LCX and 70.62% (310/439) for RCA, respectively. The sensitivity for detection of one-, two-, three-vessel stenosis was 87.55% (443/506), 94.92% (243/256) and 97.44% (190/195), respectively. The side-effects was mild and transient with an incidence rate of 84.12% (1563/1858), without major cardiac events. Conclusion: Stress myocardial perfusion imaging induced by adenosine is reliable for the evaluation of myocardial blood supply in CAD patients. (authors)

  3. Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

    Gass, Natalia

    2010-01-01

    Background: Adenosine is a potent sleep-promoting substance, and one of its targets is the basal forebrain. Fairly little is known about its mechanism of action in the basal forebrain and about the receptor subtype mediating its regulating effects on sleep homeostasis. Homeostatic deficiency might be one of the causes of the profoundly disturbed sleep pattern in major depressive disorder, which could explain the reduced amounts of delta-activity-rich stages 3 and 4. Since major depression has...

  4. Adenosine receptors in the immature brain : with special reference to their role in hypoxic ischemia

    Ådén, Ulrika

    2001-01-01

    Although the newborn brain tolerates a much longer period of oxygen deprivation and ischemia than does the adult brain, perinatal hypoxic ischemia probably is an important cause of neurological dysfunction, cerebral palsy and epilepsy later in life. Hence it is important to investigate the mechanisms that modulate the extent of perinatal ischernic brain damage. There is good evidence that endogenous adenosine acts as a neuroprotective agent in models of ischemia in the m...

  5. Adenosine kinase inhibition protects against cranial radiation-induced cognitive dysfunction

    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

  6. A Review of Tandem Mass Spectrometry Characterization of Adenosine Diphosphate-Ribosylated Peptides

    Hengel, Shawna M.; Goodlett, David R.

    2011-01-01

    The use of tandem mass spectrometry to identify and characterize sites of protein adenosine diphosphate (ADP) ribosylation will be reviewed. Specifically, we will focus on data acquisition schemes and fragmentation techniques that provide peptide sequence and modification site information. Also discussed are uses of synthetic standards to aid characterization, and an enzymatic method that converts ADP-ribosylated peptides into ribosyl mono phosphorylated peptides making identification amenabl...

  7. Adenosine Preconditioning versus Ischemic Preconditioning in Patients undergoing Off-Pump Coronary Artery Bypass (OPCAB

    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

  8. Autoimmune dysregulation and purine metabolism in adenosine deaminase (ADA)-deficiency

    Aisha Vanessa Sauer; Immacolata eBrigida; Nicola eCarriglio; Alessandro eAiuti

    2012-01-01

    Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA) or hematopoietic stem cell gene therapy (HSC-GT). Although ...

  9. Role of adenosine receptor agonists in pharmacological modulation of myelosuppression induced by ionizing radiation

    Hofer, Michal; Pospíšil, Milan; Holá, Jiřina; Vacek, Antonín; Štreitová, Denisa

    Buenos Aires, 2008. s. 1-7. [IRPA 12 - 12th International Congress of the International Radiation Protection Association - Strengthening Radiation Protection Worldwide. 19.10.2008-24.10.2008, Buenos Aires] R&D Projects: GA ČR(CZ) GA305/06/0015; GA ČR(CZ) GA305/08/0158 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : adenosine receptors * hematopoiesis * radiation-induced myelosuppression Subject RIV: BO - Biophysics

  10. Cordyceps pruinosa produces cordycepin and N6-(2-hydroxyethyl)-adenosine in culture

    Meng Zebin; Wen Tingchi; Kang Jichuan; Lei Bangxing; Hyde Kevin D.

    2014-01-01

    Cordyceps species are entomophagous pathogens with medicinal properties, mostly linked to cordycepin and N6- (2-hydroxyethyl)-adenosine (HEA). An isolate of Cordyceps pruinosa (GZUCC 8552) was obtained from a fruiting body formed on the cocoon a Limacodidae insect collected in Guizhou Province, China. Morphological and molecular analysis (combined 5.8S ITS, RPB1 and 18S RNA) confirmed the species to be Cordyceps pruinosa. Metabolites of the isolate grown in...

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

    Shashikala Magadi Dasegowda; Ashok Kumar Jeppu; Sushith; Kavitha Ashok Kumar

    2015-01-01

    Background: Oxidative stress markers are increased in type 2 diabetes mellitus and its estimation helps in predicting the long term complications. In present study comparison and correlation of the levels of serum adenosine deaminase, serum malondialdehyde, and serum total antioxidant capacity in type 2 diabetes mellitus and in age and sex matched healthy controls. Methods: Study group consisted of 100 individuals between the age group of 35-65 years of age. Of which 50 individuals with t...

  12. Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism.

    Ledent, C; Dumont, J E; Vassart, G.; Parmentier, M

    1992-01-01

    Cyclic AMP (cAMP) is the major intracellular second messenger of thyrotropin (TSH) action on thyroid cells. It stimulates growth as well as the function and differentiation of cultured thyrocytes. The adenosine A2 receptor, which activates adenylyl cyclase via coupling to the stimulating G protein (Gs), has been shown to promote constitutive activation of the cAMP cascade when transfected into various cell types. In order to test whether the A2 receptor was able to function similarly in vivo ...

  13. Contribution of adenosine to compensatory dilation in hypoperfused contracting human muscles is independent of nitric oxide

    Casey, Darren P.; Joyner, Michael J.

    2011-01-01

    We previously demonstrated that nitric oxide (NO) contributes to compensatory vasodilation in the contracting human forearm subjected to acute hypoperfusion. We examined the potential role of an adenosine-NO interaction to this response in 17 male subjects (25 ± 2 yr). In separate protocols subjects performed rhythmic forearm exercise (20% of maximum) while hypoperfusion was evoked by balloon inflation in the brachial artery above the elbow. Each trial included exercise before inflation, exer...

  14. Respiratory activity in medulla oblongata and its modulation by adenosine and opioids

    Herlenius, Eric

    1998-01-01

    From the moment of birth the complex neuronal networks generating breathing has to function continuously and adapt to the new postnatal environmental demands. This thesis aims at studying the perinatal development of respiratory control and its modulation by adenosine and opioids. Respiratory activity was studied in vitro using brainstem spinal cord preparations and in vivo with a barometric plethysmograph. In vitro whole-cell patch clamp recordings of respiratory related ne...

  15. Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression

    Bopp, Tobias; Becker, Christian; Klein, Matthias; Klein-Heßling, Stefan; Palmetshofer, Alois; Serfling, Edgar; Heib, Valeska; Becker, Marc; Kubach, Jan; Schmitt, Steffen; Stoll, Sabine; Schild, Hansjörg; Staege, Martin S.; Stassen, Michael; Jonuleit, Helmut

    2007-01-01

    Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact–dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferati...

  16. Impairment of skeletal muscle adenosine triphosphate–sensitive K+ channels in patients with hypokalemic periodic paralysis

    Tricarico, Domenico; Servidei, Serenella; Tonali, Pietro; Jurkat-Rott, Karin; Camerino, Diana Conte

    1999-01-01

    The adenosine triphosphate (ATP)–sensitive K+ (KATP) channel is the most abundant K+ channel active in the skeletal muscle fibers of humans and animals. In the present work, we demonstrate the involvement of the muscular KATP channel in a skeletal muscle disorder known as hypokalemic periodic paralysis (HOPP), which is caused by mutations of the dihydropyridine receptor of the Ca2+ channel. Muscle biopsies excised from three patients with HOPP carrying the R528H mutation of the dihydropyridin...

  17. Photophysical processes of the spectroscopic RNA probe 2-(1-ethynylpyrene-adenosine (PyA

    Engels J.

    2013-03-01

    Full Text Available We examine the photoinduced excited state dynamics of pyrene modified adenosine, a versatile probe for folding and hybridization of ribonucleic acids. Measurements in different solvents revealed complex ultrafast dynamics, but high robustness since the overall fluorescence quantum yield (Φf is hardly affected. The result is a strong fluorescent RNA-probe whose spectral properties change in a defined way upon environmental changes.

  18. Possible regulation of the Salmonella typhimurium histidine operon by adenosine triphosphate phosphoribosyltransferase: large metabolic effects.

    Goitein, R K; Parsons, S. M.

    1980-01-01

    An effort to find growth conditions leading to conditional regulation of the histidine operon of Salmonella typhimurium by the allosteric first enzyme of the pathway, adenosine triphosphate phosphoribosyltransferase (EC 2.4.2.17), is reported. A strain deleting the enzyme, TR3343, behaved simply and predictably under all growth conditions, whereas histidine auxotrophs containing active enzyme behaved in complicated ways dependent upon the location of the histidine pathway lesion. hisE strains...

  19. Inhibition of adenosine deaminase (ADA)-mediated metabolism of cordycepin by natural substances

    Li, Gen; Nakagome, Izumi; Hirono, Shuichi; Itoh, Tomoo; Fujiwara, Ryoichi

    2015-01-01

    Cordycepin, which is an analogue of a nucleoside adenosine, exhibits a wide variety of pharmacological activities including anticancer effects. In this study, ADA1- and ADA2-expressing HEK293 cells were established to determine the major ADA isoform responsible for the deamination of cordycepin. While the metabolic rate of cordycepin deamination was similar between ADA2-expressing and Mock cells, extensive metabolism of cordycepin was observed in the ADA1-expressing cells with K m and V max v...

  20. The effects of adenosine on plasma homocysteine levels and some other biochemical parameters

    Turgut, Günfer; Rota, Simin; Aybek, Hülya; Turgut, Sebahat; Sert, Seelahattin; Genç, Osman

    2009-01-01

    Süleyman Demirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 2007 Aralık; 14(4) The effects of adenosine on plasma homocysteine levels and some other biochemical parameters Günfer Turgut*, Simin Rota**, Hülya Aybek**, Sebahat Turgut*, Selahattin Sert**, Osman Genç* *Pamukkale University Faculty of Medicine Departments of Physiology, Denizli, Turkey **Pamukkale University,Faculty of Medicine, Departments of Biochemistry Denizl...