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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.

    Science.gov (United States)

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

    Science.gov (United States)

    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

  3. Ketogenic Diet in Epileptic Encephalopathies

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    Suvasini Sharma

    2013-01-01

    Full Text Available The ketogenic diet is a medically supervised high-fat, low-carbohydrate diet that has been found useful in patients with refractory epilepsy. It has been shown to be effective in treating multiple seizure types and epilepsy syndromes. In this paper, we review the use of the ketogenic diet in epileptic encephalopathies such as Ohtahara syndrome, West syndrome, Dravet syndrome, epilepsy with myoclonic atonic seizures, and Lennox-Gastaut syndrome.

  4. Nonfasting Versus Initial Fasting Ketogenic Diet

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    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. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

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    Antonio Paoli

    2014-01-01

    Full Text Available An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson’s disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review.

  6. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

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    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. Childhood Absence Epilepsy Successfully Treated with the Paleolithic Ketogenic Diet

    OpenAIRE

    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...

  8. Ketogenic Diet for Obesity: Friend or Foe?

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    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.

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

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Law, Ian

    2013-01-01

    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......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...

  10. Ketogenic diets and physical performance

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    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.

  11. Ketogenic diets and physical performance

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    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.

  12. The Ketogenic Diet 2011: How It Works

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    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.

  13. Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet.

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    Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich

    2016-04-01

    High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone. PMID:26902182

  14. Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy

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    Patricia Azevedo de Lima

    2014-12-01

    Full Text Available A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed.

  15. Ketogenic Diet for Epilepsy with Type 1 Diabetes

    OpenAIRE

    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.

  16. Ketogenic diet and astrocyte/neuron metabolic interactions

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    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.

  17. Mitochondria: The ketogenic diet--A metabolism-based therapy.

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    Vidali, Silvia; Aminzadeh, Sepideh; Lambert, Bridget; Rutherford, Tricia; Sperl, Wolfgang; Kofler, Barbara; Feichtinger, René G

    2015-06-01

    Mitochondria are the energy-producing organelles of the cell, generating ATP via oxidative phosphorylation mainly by using pyruvate derived from glycolytic processing of glucose. Ketone bodies generated by fatty acid oxidation can serve as alternative metabolites for aerobic energy production. The ketogenic diet, which is high in fat and low in carbohydrates, mimics the metabolic state of starvation, forcing the body to utilize fat as its primary source of energy. The ketogenic diet is used therapeutically for pharmacoresistant epilepsy and for "rare diseases" of glucose metabolism (glucose transporter type 1 and pyruvate dehydrogenase deficiency). As metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells; there is increasing evidence that the ketogenic diet may also be beneficial as an adjuvant cancer therapy by potentiating the antitumor effect of chemotherapy and radiation treatment. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.

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

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    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

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

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    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.

  20. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets

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    Carmela eGiordano

    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

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

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    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.

  2. INTRACTABLE SEIZURE DISORDERS: EFFICACY OF THE CLASSIC KETOGENIC DIET

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    P. Karimzadeh

    2009-01-01

    Full Text Available ObjectiveThe ketogenic diet is a high-fat, low carbohydrate, adequate protein diet,developed in the 1920s for the management of intractable seizure disorders in children. To evaluate efficacy and tolerability of the classic ketogenic diet, we analyzed records of the children started on the diet from 1999 to 2006 at the Mofid children's hospital.Materials & MethodsThe subjects were 87 children, mean age 55 months. Before initiation of the diet, 55% of the patients had seizures, at least 1-4 times per day, 36% - 5 or more per day and 9% - 2 to 4 times per week. Mean number of Anti Epileptic Drugs (AEDs tried for them was 8 and 67% were receiving three or more drugs.ResultsThe ketogenic diet showed drastic improvement, with at least 50% reduction in seizure frequency in 87% of our patients, 39% of whom showed complete seizure control in the third month. After one year, in 80% of the patients who returned, improvement continued, with 26% of them being seizure free; besides, 23% had one AED decreased, 36% had two or three AEDs decreased, and 25% (one child had all AEDs discontinued. Of the 30 improved cases, 20%, at the end of the first year, had improved behavior as well, and 23% of them had become more alert. The median diet duration of the improved group was 15 months.ConclusionThe improvement in our patients, low side effects, and the duration of diet by families reveal that the ketogenic diet can still be a very useful alternative therapy in certain epileptic children.

  3. The ketogenic diet for type II bipolar disorder.

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    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

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

    DEFF Research Database (Denmark)

    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....

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

    OpenAIRE

    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...

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

    DEFF Research Database (Denmark)

    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...

  7. The effects of ketogenic diet on oxidative stress and antioxidative capacity markers of Taekwondo athletes.

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    Rhyu, Hyun-Seung; Cho, Su-Youn; Roh, Hee-Tae

    2014-12-01

    The purpose of this study was to investigate the effects of the ketogenic diet through 3 weeks on oxidative stress and antioxidative capacity markers in Taekwondo athletes. The participants selected for this research were 18 high school taekwondo contestants aged 15-18 who had at least 5 yr of career as contestant. The subjects were randomly assigned to the ketogenic diet (KD) group and the Non ketogenic diet (NDK) group. Body composition and oxidative stress and antioxidative capacity markers (LDH, MDA, ROS, HDL, and SOD) were analysed before and after 3 weeks of ketogenic diet. No significant difference was found between the groups in body composition, ROS and SOD level. The KD group showed an elevated HDL level and NKD group showed an elevated LDH and MDA level after ketogenic diet by 3 weeks. This result suggests that weight loss by 3 weeks of calorie restriction and exercise can cause oxidative stress, and that ketogenic diet can be effective for preventing it. It could also be inferred that ketogenic diet can be effective for increasing blood antioxidative capacity.

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

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    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...

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

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    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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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......)-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 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...

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

    OpenAIRE

    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. ...

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

    OpenAIRE

    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...

  13. The ketogenic diet for the treatment of myoclonic astatic epilepsy in a child with type 1 diabetes mellitus.

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    Aylward, Nicole M; Shah, Namrata; Sellers, Elizabeth A

    2014-08-01

    Initiation of the ketogenic diet in a child with epilepsy and type 1 diabetes mellitus presents a challenge because the distinction between diet-induced ketosis and diabetic ketoacidosis is difficult to discern. We report the successful use of the ketogenic diet in a child with myoclonic astatic epilepsy and type 1 diabetes.

  14. Timing of ketogenic diet initiation in an experimental epilepsy model.

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    Su, S W; Cilio, M R; Sogawa, Y; Silveira, D C; Holmes, G L; Stafstrom, C E; Silveira, D

    2000-12-29

    Following kainic acid (KA)-induced status epilepticus (SE), the ketogenic diet (KD) retards the development of epileptogenesis, with fewer spontaneous recurrent seizures (SRS) and less mossy fiber sprouting than rats on a normal diet. In this study, we investigated whether there is a critical period for initiation of the KD, in terms of the diet's effectiveness in reducing SRS. In addition, we investigated whether early treatment with the KD prevents the deficits in spatial learning and memory that ordinarily follow KA-induced SE. Young rats (P30) underwent KA-induced SE, followed by assignment to one of three treatment groups: control diet ('KA'), KD begun 2 days after SE ('KD2'), and KD begun fourteen days after SE ('KD14'). For 12 weeks following SE, rats were monitored by closed circuit video recording (12 h/wk) to detect SRS. KD2 rats had significantly fewer SRS than rats in the control or KD14 groups. On water maze testing to assess spatial learning and memory, KD2 rats had significantly poorer acquisition of place learning than control (KA alone) or KD14 rats. KD2 rats also failed to gain weight well. There was no difference between groups on routine histologic examination of the hippocampus. In summary, P30 rats placed on the KD 2 days after SE were relatively protected from recurrent seizures, but showed behavioral and physical impairment. Rats placed on the KD 14 days after KA-induced SE did not differ from controls with regard to spontaneous seizure rate.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  2. Prospective study of the modified atkins diet in combination with a ketogenic liquid supplement during the initial month.

    Science.gov (United States)

    Kossoff, Eric H; Dorward, Jennifer L; Turner, Zahava; Pyzik, Paula L

    2011-02-01

    The modified Atkins diet is a high-fat, low-carbohydrate treatment for intractable childhood epilepsy. As data suggest that a stricter diet onset can be more effective, we added a ketogenic supplement to the modified Atkins diet during its initial month. Thirty children with intractable epilepsy were prospectively started on the modified Atkins diet in combination with a daily 400-calorie KetoCal shake. At 1 month, 24 (80%) children had >50% seizure reduction, of which 11 (37%) had >90% seizure reduction. There was no significant loss of efficacy during the second month after KetoCal was discontinued. The use of this ketogenic supplement increased daily fat intake and thus the ketogenic ratio (1.8:1 versus 1.0:1 in the modified Atkins diet alone, P = .0002), but did not change urinary or serum ketosis. The addition of a ketogenic supplement to the modified Atkins diet during its initial month appears to be beneficial.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2010-12-01

    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 four different institutions. Ten (37%) patients had ≥10% additional seizure reduction with the KD over the MAD, of which five became seizure-free. The five children who did not improve on the MAD failed to improve when transitioned to the KD. A higher incidence of improvement with the KD occurred for those with myoclonic-astatic epilepsy (70% vs. 12% for all other etiologies, p = 0.004), including all who became seizure-free. These results suggest that the KD probably represents a "higher dose" of dietary therapy than the MAD, which may particularly benefit those with myoclonic-astatic epilepsy.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Diet and identity: being a good parent in the face of contradictions presented by the ketogenic diet.

    Science.gov (United States)

    Webster, Michelle; Gabe, Jonathan

    2016-01-01

    The ketogenic diet is a high-fat diet used to treat drug-resistant childhood epilepsy. Given that negative meanings tend to be attached to fatty foods and children's food consumption is seen to be the responsibility of parents, the ketogenic diet may be problematic for parenting identity. This article draws upon in-depth semi-structured interviews with 12 parents from 10 families that have a child whose epilepsy is being treated with the ketogenic diet. The main focus of the article is the meanings these parents attached to foods and how they were drawn upon or altered to overcome some of the contradictions presented by the diet. It will be argued that the diet was medicalised and parents came to view food as medicine. When viewing food in this way, negative associations with fat were reversed. Furthermore, parents also used food as a symbol of inclusion and prioritised portion size or the child's enjoyment of food in order to use food as a symbol of love. In turn this enabled parents to feel they were being good parents. Overall, it seems that diet can be medicalised and the identity of the good parent maintained if dietary treatment is successful.

  7. Long term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol.

    Science.gov (United States)

    Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A; Lodi, Alessandra; Bosco, Gerardo

    2013-12-01

    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. PMID:24352095

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

    Science.gov (United States)

    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

  9. 生酮饮食与肿瘤治疗%Ketogenic diet and cancer treatment

    Institute of Scientific and Technical Information of China (English)

    鲁运新; 石汉平

    2015-01-01

    目的总结生酮饮食种类及其在肿瘤治疗中的研究进展,归纳其抗肿瘤作用机制及临床应用前景。方法以“生酮饮食、肿瘤”作为关键词检索pubmed数据库获得相关文献。结果肿瘤细胞比正常细胞更加依赖葡萄糖的供给,生酮饮食限制碳水化合物的摄入,抑制肿瘤相关信号通路的传导,发挥抗肿瘤作用。结论生酮饮食单用或联合放化疗可以抑制动物模型的肿瘤生长,但临床应用尚需大规模前瞻性临床试验的结果。%Objective To summarize the various types of ketogenic diet and its research progress in cancer treatment. Methods Related articles were retrieved by searching the pubmed database with the key words “ketogenic diet” and “cancer”. Results The malignant transformed cells were more dependent on glucose supply than their normal counterparts. Ketogenic diet, low in carbohydrate, exerts anti-neoplastic character by inhibiting the tumor-related signal transduction. Conclusions Ketogenic diet, alone or combined with chemo-radio-therapy could hammer tumor growth in rodents, whereas its clinical application warrants large-scale prospective clinical trials.

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

    OpenAIRE

    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 ...

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    OpenAIRE

    Antonio Paoli; Antonino Bianco; Grimaldi, Keith A; Alessandra Lodi; Gerardo Bosco

    2013-01-01

    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 ...

  14. Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy

    Science.gov (United States)

    GROLEAU, VERONIQUE; SCHALL, JOAN I; STALLINGS, VIRGINIA A; BERGQVIST, CHRISTINA A

    2014-01-01

    AIM The long-term effects of the ketogenic diet, a high fat diet for treating intractable epilepsy, on resting energy expenditure (REE) are unknown. The aim of this study was to evaluate the impact of 15 months of ketogenic diet treatment on growth and REE in children with intractable epilepsy. METHOD Growth, body composition and REE were assessed at baseline, 3 and 15 months in 24 children (14 males, 10 females; mean age 5y 6mo (SD 26mo), range 7mo–6y 5mo), 10 with cerebral palsy [CP]). Fifteen were identified as ketogenic diet responders at 3 months and continued on the ketogenic diet until 15 months. These were compared to 75 healthy children (43 males, 32 females; mean age 6y 3mo [SD 21mo] age range 2–9y). REE was expressed as percentage predicted, growth as height (HAz) and weight (WAz) z-scores, and body composition as fat and fat free mass (FFM). RESULTS HAz declined −0.2 and −0.6 from baseline to 3 and 15 months, respectively (p=0.001), while WAz was unchanged. In ketogenic diet responders, FFM, age and CP diagnosis predicted REE (overall R2=0.76, p<0.001) and REE did not change. REE adjusted for FFM was lower (p<0.01) in children with CP at baseline (mean [standard error], −143[51] kcals/d) and 15 months (−198[53] kcals/d) compared to the healthy children. INTERPRETATION After 15 months of the ketogenic diet, linear growth status declined while weight status and REE were unchanged. REE remained reduced in children with CP. PMID:24749520

  15. The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

    Science.gov (United States)

    Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

    2015-02-01

    Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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?

    DEFF Research Database (Denmark)

    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...

  20. Ketogenic Diet Decreases Emergency Room Visits and Hospitalizations Related to Epilepsy

    Directory of Open Access Journals (Sweden)

    Husam R. Kayyali

    2016-01-01

    Full Text Available Background. Approximately, one-third of patients with epilepsy are refractory to pharmacological treatment which mandates extensive medical care and imposes significant economic burden on patients and their societies. This study intends to assess the impact of the treatment with ketogenic diet (KD on reducing seizure-related emergency room visits and hospitalizations in children with refractory epilepsy. Methods. This is a retrospective review of children treated with the KD in one tertiary center. We compared a 12 months’ period prior to KD with 12 months after the diet was started in regard to the number of emergency department (ED visits, hospitalizations, and hospital days as well as their associated charges. Results. 37 patients (57% males were included. Their ages at time of KD initiation were (4.0±2.78 years. Twelve months after the KD initiation, the total number of ED visits was reduced by 36% with a significant decrease of associated charges (p=0.038. The number of hospital admissions was reduced by 40% and the number of hospital days was reduced by 39%. The cumulative charges showed net cost savings after 9 months when compared to the prediet baseline. Conclusion. In children with refractory epilepsy, treatment with the ketogenic diet reduces the number of ED visits and hospitalizations and their corresponding costs.

  1. Should we routinely use modified Atkins diet instead of regular ketogenic diet to treat children with epilepsy?

    Science.gov (United States)

    Auvin, Stéphane

    2012-05-01

    The modified Atkins diet (MAD) consists of a nearly balanced diet without any age-dependent restriction of recommended daily calorie intake. Recently, there has been a marked increase in the use of the MAD in the treatment of epilepsy. Over the last 8 years, evidence suggesting that the MAD may exhibit similar anticonvulsant properties as the traditional ketogenic diet (KD) has been accumulating. KD is now an 'evidence-based' treatment for refractory epilepsy. Although there are currently no direct comparisons data from the literature suggest that the KD is more efficacious than the MAD. However, the MAD is easier to administer and has better tolerability. This review discusses when to consider each diet. The MAD may be the first diet of choice. In case of insufficient efficacy under the MAD, a switch from the MAD to the KD should be considered.

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

    Directory of Open Access Journals (Sweden)

    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

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

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    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

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

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    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

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

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    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

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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....... Twenty-five patients who stopped the diet within four weeks because of compliance-problems and minor side-effects were excluded. Seizure-type(s), seizure-frequency, anti-epileptic drugs and other treatments, mental retardation, autism-spectrum disorder and motor-dysfunction were identified and treatment...... 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 (relative risk = 8...

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

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    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

  9. Effects of ketogenic diets on the occurrence of pilocarpine-induced status epilepticus of rats.

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    Gama, Iclea Rocha; Trindade-Filho, Euclides Marinho; Oliveira, Suzana Lima; Bueno, Nassib Bezerra; Melo, Isabelle Tenório; Cabral-Junior, Cyro Rego; Barros, Elenita M; Galvão, Jaqueline A; Pereira, Wanessa S; Ferreira, Raphaela C; Domingos, Bruna R; da Rocha Ataide, Terezinha

    2015-02-01

    Two sources of medium-chain triglycerides--triheptanoin with anaplerotic properties and coconut oil with antioxidant features--have emerged as promising therapeutic options for the management of pharmacoresistant epilepsy. We investigated the effects of ketogenic diets (KDs) containing coconut oil, triheptanoin, or soybean oil on pilocarpine-induced status epilepticus (SE) in rats. Twenty-four adult male Wistar rats were divided into 4 groups and fed a control diet (7% lipids) or a KD containing soybean oil, coconut oil, or triheptanoin (69.8% lipids). The ketogenic and control diets had a lipid:carbohydrate + protein ratio of 1:11.8 and 3.5:1, respectively. SE was induced in all rats 20 days after initiation of the dietary treatment, through the administration of pilocarpine (340 mg/kg; i.p.). The latency, frequency, duration, and severity of seizures before and during SE were observed with a camcorder. SE was aborted after 3 h with the application of diazepam (5 mg/kg; i.p.). The rats in the triheptanoin-based KD group needed to undergo a higher number of seizures to develop SE, as compared to the control group (P < 0.05). Total weight gain, intake, energy intake, and feed efficiency coefficient, prior to induction of SE, differed between groups (P < 0.05), where the triheptanoin-based KD group showed less weight gain than all other groups, less energy intake than the Control group and intermediate values of feed efficiency coefficient between Control and other KDs groups. Triheptanoin-based KD may have a neuroprotective effect on the establishment of SE in Wistar rats.

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

    OpenAIRE

    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...

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

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    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.

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

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    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.

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

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    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

  14. Low carbohydrate ketogenic diet prevents the induction of diabetes using streptozotocin in rats.

    Science.gov (United States)

    Al-Khalifa, A; Mathew, T C; Al-Zaid, N S; Mathew, E; Dashti, H

    2011-11-01

    Diabetes continues to be an overwhelmingly prevalent endocrine disorder that leads to several micro- and macrocomplications. It has been widely accepted that changes in dietary habits could induce or prevent the onset of diabetes. It is shown that low carbohydrate ketogenic diet (LCKD) is effective in the amelioration of many of the deleterious consequences of diabetes. However, its role in preventing the onset of diabetes is not understood. Therefore, this study is focused on the effect of LCKD in preventing the induction of diabetes using streptozotocin (STZ) in rats by biochemical and histological methods. Forty-two Wistar rats weighing 150-250 g were used in this study. The animals were divided into three groups: normal diet (ND), low carbohydrate ketogenic diet (LCKD), and high carbohydrate diet (HCD). Specific diets ad libitum were given to each group of animals for a period of 8 weeks. Each group was further subdivided into normal control, sham control and diabetic groups. Animals in the diabetic group were given a single intraperitoneal injection of STZ (55 mg/kg). All the animals were sacrificed 4 weeks after the injection of STZ. Daily measurements of food and water intake as well as weekly measurement of body weight were taken during the whole 12 weeks of the experiment. After injecting with STZ, the blood glucose level of all the groups increased significantly except for the group fed on LCKD (p value<0.01). Also, food intake, water intake and urine output were significantly increased in all groups except for the LCKD group (p value<0.01). There was also a significant decrease in the weight gain of the animals that were fed on a LCKD as compared to other groups (p value<0.05). Although, substantial decrease in the number of β cells was noticed in diabetic rats, there were no change in the number of β cells in the LCKD treated diabetic animals as compared to LCKD control group. The results presented in this study, therefore, suggests that LCKD prevents

  15. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease

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    Van Leuven Fred

    2005-10-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-β (Aβ deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD. Results Starting at three months of age, two groups of female transgenic mice carrying the "London" APP mutation (APP/V717I were fed either, a standard diet (SD composed of high carbohydrate/low fat chow, or a ketogenic diet (KD composed of very low carbohydrate/high saturated fat chow for 43 days. Animals fed the KD exhibited greatly elevated serum ketone body levels, as measured by β-hydroxybutyrate (3.85 ± 2.6 mM, compared to SD fed animals (0.29 ± 0.06 mM. In addition, animals fed the KD lost body weight (SD 22.2 ± 0.6 g vs. KD 17.5 ± 1.4 g, p = 0.0067. In contrast to earlier studies, the brief KD feeding regime significantly reduced total brain Aβ levels by approximately 25%. Despite changes in ketone levels, body weight, and Aβ levels, the KD diet did not alter behavioral measures. Conclusion Previous studies have suggested that diets rich in cholesterol and saturated fats increased the deposition of Aβ and the risk of developing AD. Here we demonstrate that a diet rich in saturated fats and low in carbohydrates can actually reduce levels of Aβ. Therefore, dietary strategies aimed at reducing Aβ levels should take into account interactions of dietary components and the metabolic outcomes, in particular, levels of carbohydrates, total calories, and presence of ketone bodies should be considered.

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

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    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

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

    Science.gov (United States)

    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

  18. Nonpharmacologic care for patients with Lennox-Gastaut syndrome: ketogenic diets and vagus nerve stimulation.

    Science.gov (United States)

    Kossoff, Eric H W; Shields, W Donald

    2014-09-01

    Individuals with Lennox-Gastaut syndrome (LGS) often do not respond to or become resistant to pharmacologic treatments. Ketogenic diets (KDs) and vagus nerve stimulation (VNS) are nonpharmacologic treatment options for these intractable patients. The classic KD, a high-fat, low-carbohydrate diet with 90% of calories derived from fat, has been used in the treatment of seizures for >90 years. About half of patients with LGS respond to the KD with a >50% reduction in seizures and some patients may achieve a >90% reduction. Vagus nerve stimulation therapy involves a surgically implanted generator that delivers intermittent electrical stimuli to the brain via an electrode wrapped around the left vagus nerve. It is utilized as adjunctive therapy for patients with drug-resistant epilepsy (including patients with LGS) who are not suitable candidates for resective surgery. Similar to the KD, about half of LGS patients respond to VNS therapy, with a >50% reduction in seizures, and the response may improve over time. Both the KD and VNS are options for patients with LGS.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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 (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

  2. Ketogenic diet protects against epileptogenesis as well as neuronal loss in amygdaloid-kindling seizures.

    Science.gov (United States)

    Jiang, Yan; Yang, Yi; Wang, Shuang; Ding, Yao; Guo, Yi; Zhang, Man-Man; Wen, Shu-Qun; Ding, Mei-Ping

    2012-02-01

    Ketogenic diets (KD) have shown beneficial effects in terms of anticonvulsant and anti-epileptogenic properties in several experimental models. However, few studies have investigated the consequences of KD with regards to the anti-epileptogenic and neuroprotective effects in kindling-induced seizures. Here, postnatal day 28 male Sprague-Dawley rats received one of two experimental diets for 4 weeks: (a) a 'classic' 4:1 KD; and (b) a normal regular rodent chow diet (ND). Fully-kindled seizures were achieved by daily electrical stimulation in the amygdala. Seizure stage and after-discharge duration (ADD) were assessed daily. The after-discharge threshold (ADT) was measured every 5 days. The effects of the two diets on neuronal loss were observed before kindling and 20 days after stimulation by Nissl staining. We found that the progression of seizure stage and ADD was delayed by KD. KD prevented the ADT decrease on day 5. The incidence of generalized seizures was lower in the KD group compared to the ND group. The neuronal density was decreased in the ipsilateral hilus of the dentate gyrus (DG) and CA1 area, as well as the contralateral CA1 area before kindling in the KD group. However, KD prevented neuronal loss in the ipsilateral CA1 area 20 days after stimulation. Our data suggest that KD can protect against epileptogenesis by preventing both after-discharge generation and propagation in kindling seizures. In addition, KD also possesses a neuroprotective function during kindling although it changes hippocampal development in early life.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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

    Science.gov (United States)

    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

  6. Is the interaction between fatty acids and tryptophan responsible for the efficacy of a ketogenic diet in epilepsy? The new hypothesis of action.

    Science.gov (United States)

    Maciejak, P; Szyndler, J; Turzyńska, D; Sobolewska, A; Kołosowska, K; Krząścik, P; Płaźnik, A

    2016-01-28

    The effects of a ketogenic diet in controlling seizure activity have been proven in many studies, although its mechanism of action remains elusive in many regards. We hypothesize that the ketogenic diet may exert its antiepileptic effects by influencing tryptophan (TRP) metabolism. The aim of this study was to investigate the influence of octanoic and decanoic fatty acids (FAs), the main components in the MCT diet (medium-chain triglyceride diet, a subtype of the ketogenic diet), on the metabolism of TRP, the activity of the kynurenic pathway and the concentrations of monoamines and amino acids, including branched-chain amino acids (BCAA) and aromatic amino acids (AAA) in rats. The acute effects of FA on the sedation index and hippocampal electrical after-discharge threshold were also assessed. We observed that intragastric administration of FA increased the brain levels of TRP and the central and peripheral concentrations of kynurenic acid (KYNA), as well as caused significant changes in the brain and plasma concentrations of BCAA and AAA. We found that the administration of FA clearly increased the seizure threshold and induced sedation. Furthermore, we have demonstrated that blocking TRP passage into the brain abolished these effects of FA but had no similar effect on the formation of ketone bodies. Given that FAs are major components of a ketogenic diet, it is suggested that the anticonvulsant effects of a ketogenic diet may be at least partly dependent on changes in TRP metabolism. We also propose a more general hypothesis concerning the intracellular mechanism of the ketogenic diet. PMID:26601775

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

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    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.

  8. THE KETOGENIC DIET AS A TREATMENT PARADIGM FOR DIVERSE NEUROLOGICAL DISORDERS

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    Jong Min Rho

    2012-04-01

    Full Text Available Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more natural treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

  9. What are the minimum requirements for ketogenic diet services in resource-limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy.

    Science.gov (United States)

    Kossoff, Eric H; Al-Macki, Nabil; Cervenka, Mackenzie C; Kim, Heung D; Liao, Jianxiang; Megaw, Katherine; Nathan, Janak K; Raimann, Ximena; Rivera, Rocio; Wiemer-Kruel, Adelheid; Williams, Emma; Zupec-Kania, Beth A

    2015-09-01

    Despite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow-up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost-effective recommendations for new ketogenic diet centers in resource-limited regions of the world.

  10. The effect of weight loss by ketogenic diet on the body composition, performance-related physical fitness factors and cytokines of Taekwondo athletes.

    Science.gov (United States)

    Rhyu, Hyun-Seung; Cho, Su-Youn

    2014-10-01

    The purpose of this study was to investigate the effects of the weight loss through 3 weeks of ketogenic diet on performance-related physical fitness and inflammatory cytokines in Taekwondo athletes. The subjects selected for this research were 20 Taekwondo athletes of the high schools who participated in a summer camp training program. The subjects were randomly assigned to 2 groups, 10 subjects to each group: the ketogenic diet (KD) group and the non-ketogenic diet (NKD) group. Body composition, performance-related physical fitness factors (2,000 m sprint, Wingate test, grip force, back muscle strength, sit-up, 100 m sprint, standing broad jump, single leg standing) and cytokines (Iinterleukin-6, Interferon-γ, tumor necrosis factor-α) were analyzed before and after 3weeks of ketogenic diet. No difference between the KD and NKD groups in weight, %body fat, BMI and fat free mass. However, the KD group, compared to the NKD group, finished 2,000 m sprint in less time after weight loss, and also felt less fatigue as measured by the Wingate test and showed less increase in tumor necrosis factor-α. This result suggests that KD diet can be helpful for weight category athletes, such as Taekwondo athletes, by improving aerobic capacity and fatigue resistance capacity, and also by exerting positive effect on inflammatory response.

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

    Science.gov (United States)

    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

  12. Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet.

    Science.gov (United States)

    Porta, Natacha; Vallée, Louis; Boutry, Elisabeth; Fontaine, Monique; Dessein, Anne-Frédérique; Joriot, Sylvie; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; Auvin, Stéphane

    2009-06-01

    The ketogenic diet (KD) and the modified Atkins diet are effective therapies for intractable epilepsy. We compared retrospectively the KD and modified Atkins diet in 27 children and also assessed serum long chain fatty acid profiles. After 3 months, using an intent-to-treat analysis, the KD was more successful, with >50% seizure reduction in 11/17 (65%) vs. 2/10 (20%) with the modified Atkins diet, p=0.03. After 6 months, however, the difference was no longer significant: 7/17 (41%) vs. 2/10 (20%) (p=0.24). We observed a preventive effect of both diets on the occurrence of status epilepticus. After 1 and 3 months of either diet, responders experienced a significant decrease in serum arachidonic acid concentration compared to non-responders. The KD and modified Atkins diet led to seizure reduction in this small pilot series, with slightly better results after 3 months with the KD, but not after 6 months. The decrease of serum arachidonic acid levels might be involved in the anticonvulsive effects of KD or modified Atkins diet.

  13. Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

    NARCIS (Netherlands)

    Ellenbroek, Johanne H; van Dijck, Laura; Töns, Hendrica A; Rabelink, Ton J; Carlotti, Françoise; Ballieux, Bart E P B; de Koning, Eelco J P

    2014-01-01

    High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term ef

  14. Progress of ketogenic diet in cancer treatment%生酮饮食抗肿瘤治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    汪柳旭

    2015-01-01

    越来越多研究表明,生酮饮食已开始用于癫痫以外的神经疾病的治疗.肿瘤细胞线粒体的缺损导致其不能利用酮体作为主要能量来源,生酮饮食能增加氧化应激作用,抑制信号通路传导,发挥抗肿瘤作用.此外,生酮饮食也能增加放化疗药物的抗肿瘤效应.生酮饮食在肿瘤模型和临床试验中表现出一定的治疗效果.%Recently, more and more studies have indicated that the ketogenic diet began to be used for neurological conditions other than epilepsy.Because of mitochondrial defectiong, tumor cells are unable to use ketone bodies as a primary energy source.The ketogenic diet exerts anti-tumor effect by increasing oxidatetivesress and inhibiting the signal transduction.Besides, ketogenic diet may also enhance the anti-tumor effect of radiation therapy and chemotherapies.The ketogenic diets in tumor models and clinical trials have shown therapeutic effect.

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

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    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.

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

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    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

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

    DEFF Research Database (Denmark)

    Hansen, Suzanne L; Nielsen, Ane H; Knudsen, Katrine E;

    2009-01-01

    The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure...... activity may mediate neuroprotection as may several N-acylethanolamines. It is unknown how the KD interfere with the endocannabinoid system. We investigated the antiepileptogenic potential of the KD in the pentylenetetrazole kindling model in young mice and measured the hippocampal levels of CB(1)-R...... by Western blot and of endocannabinoids and N-acylethanolamines by mass spectrometry. The KD significantly decreased incidence and severity of seizures, and significantly increased the latency to clonic convulsions. There were no changes in levels of endocannabinoids or CB(1)-R expression by either seizure...

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

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    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

  19. Ketogenic diet in pediatric intractable epilepsy%生酮饮食疗法在儿童难治性癫(痫)治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    俞宏真

    2014-01-01

    生酮饮食是一种高脂肪、低碳水化合物和适量蛋白质的饮食.生酮饮食治疗难治性癫(痫),疗效确切,但作用机制仍未完全明了.该文对生酮饮食疗法在儿童难治性癫痫应用的疗效及该饮食疗法控制癫(痫)发作的作用机制研究进展作一综述.%Ketogenic diet is a kind of diet with high fat,low carbohydrate and protein.Ketogenic diet has an curative effect on intractable epilepsy,but the mechanism is still not fully understood.In this paper,the curative effect of the ketogenic diet therapy in pediatric refractory epilepsy and the research progress of the mechanism of action to control seizures are reviewed.

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

    OpenAIRE

    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...

  1. 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.

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    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.

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

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    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.

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

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    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  5. 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

    Directory of Open Access Journals (Sweden)

    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

  6. 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

    International Nuclear Information System (INIS)

    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

  7. 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?

    Science.gov (United States)

    Miranda, Maria J; Mortensen, Mette; Povlsen, Jane H; Nielsen, Helle; Beniczky, Sándor

    2011-03-01

    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 evaluated prospectively on 33 consecutive children with medically resistant epilepsy, with a group of 50 patients, previously treated with KD. Patients who had >50% seizure reduction were considered responders. After 3 months on the MAD, 17 patients (52%) were responders, including 14 (42%) who had >90% seizure reduction. After 6 months, 13 patients (39%) were responders. Seventeen patients (52%) remained on the MAD at least 12 months with excellent overall tolerance and compliance, including 9 patients (27%) who were responders, 4 of them (12%) having >90% seizure reduction. Although there was a trend for higher incidence of responders in the KD group, this failed to reach the level of significance: after 6 months 39% on MAD and 60% on KD were responders. However, this trend was not observed when the two groups were adjusted for difference in age (patients in the MAD group were older than the KD group). In conclusion, our experience suggests that the MAD is similarly effective as the KD in reducing seizure frequency in children with medically resistant epilepsy.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  10. Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms.

    Science.gov (United States)

    Wang, Shan; Ding, Yao; Ding, Xiao-Yan; Liu, Zhi-Rong; Shen, Chun-Hong; Jin, Bo; Guo, Yi; Wang, Shuang; Ding, Mei-Ping

    2016-02-12

    The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K(+)-Cl(-) co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression.

  11. Progress of the antiepileptic mechanisms of ketogenic diet%生酮饮食抗癫(疒间)机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    姬辛娜; 秦炯

    2010-01-01

    生酮饮食(ketogenic diet,KD)是一种高脂低糖低蛋白饮食,直接引发酮体、脂肪酸升高以及糖酵解抑制等全身性变化.癫疒间发病机制主要与离子通道、神经递质和神经细胞损伤等相关.该文着重从癫(疒间)发生的角度阐述KD所引发的全身性变化,通过调控离子通道的开放和关闭,调节兴奋性和抑制性神经递质的平衡,增加能量代谢、减少氧自由基的生成和促进神经细胞再生等方式发挥抗癫疒间作用.%Ketogenic diet (KD) is a high-fat,low-protein,low-carbohydrate diet that results in series of adaptive changes such as ketosis,fatty acid increasing and glycolysis depression.The mechanisms of the epilepsy correlated with the iron channel,neurotransmitter and neurocyte injury.The novel stresses the antiepileptic effects of above general changes in controlling the iron channels open or close,balancing the excitable and inhibitive neurotransmitters,increasing energy reserve,inhibiting free radical production and promoting neurocyte regeneration.

  12. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  13. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  14. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Bueno, Nassib Bezerra; de Melo, Ingrid Sofia Vieira; de Oliveira, Suzana Lima; da Rocha Ataide, Terezinha

    2013-10-01

    The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.

  15. 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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Science.gov (United States)

    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

  17. Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver.

    Science.gov (United States)

    Genzer, Yoni; Dadon, Maayan; Burg, Chen; Chapnik, Nava; Froy, Oren

    2015-12-01

    Ketogenic diet (KD) is used for weight loss or to treat epilepsy. KD leads to liver AMP-activated protein kinase (AMPK) activation, which would be expected to inhibit gluconeogenesis. However, KD leads to increased hepatic glucose output. As AMPK and its active phosphorylated form (pAMPK) show circadian oscillation, this discrepancy could stem from wrong-time-of-day sampling. The effect of KD was tested on mouse clock gene expression, AMPK, mTOR, SIRT1 and locomotor activity for 2 months and compared to low-fat diet (LFD). KD led to 1.5-fold increased levels of blood glucose and insulin. Brain pAMPK/AMPK ratio was 40% higher under KD, whereas that in liver was not affected. KD led to 40% and 20% down-regulation of the ratio of pP70S6K/P70S6K, the downstream target of mTOR, in the brain and liver, respectively. SIRT1 levels were 40% higher in the brain, but 40% lower in the liver of KD-fed mice. Clock genes showed delayed rhythms under KD. In the brain of KD-fed mice, amplitudes of clock genes were down-regulated, whereas 6-fold up-regulation was found in the liver. The metabolic state under KD indicates reduced satiety in the brain and reduced anabolism alongside increased gluconeogenesis in the liver.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus

    Science.gov (United States)

    Goday, A; Bellido, D; Sajoux, I; Crujeiras, A B; Burguera, B; García-Luna, P P; Oleaga, A; Moreno, B; Casanueva, F F

    2016-01-01

    Brackground: The safety and tolerability of very low-calorie-ketogenic (VLCK) diets are a current concern in the treatment of obese type 2 diabetes mellitus (T2DM) patients. Objective: Evaluating the short-term safety and tolerability of a VLCK diet (<50 g of carbohydrate daily) in an interventional weight loss program including lifestyle and behavioral modification support (Diaprokal Method) in subjects with T2DM. Methods: Eighty-nine men and women, aged between 30 and 65 years, with T2DM and body mass index between 30 and 35 kg m−2 participated in this prospective, open-label, multi-centric randomized clinical trial with a duration of 4 months. Forty-five subjects were randomly assigned to the interventional weight loss (VLCK diet), and 44 to the standard low-calorie diet. Results: No significant differences in the laboratory safety parameters were found between the two study groups. Changes in the urine albumin-to-creatinine ratio in VLCK diet were not significant and were comparable to control group. Creatinine and blood urea nitrogen did not change significantly relative to baseline nor between groups. Weight loss and reduction in waist circumference in the VLCK diet group were significantly larger than in control subjects (both P<0.001). The decline in HbA1c and glycemic control was larger in the VLCK diet group (P<0.05). No serious adverse events were reported and mild AE in the VLCK diet group declined at last follow-up. Conclusions: The interventional weight loss program based on a VLCK diet is most effective in reducing body weight and improvement of glycemic control than a standard hypocaloric diet with safety and good tolerance for T2DM patients. PMID:27643725

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Update on ketogenic diet therapies in epilepsy%生酮饮食疗法治疗癫(癎)新进展

    Institute of Scientific and Technical Information of China (English)

    廖建湘; 陈瑞东

    2015-01-01

    生酮饮食(KD)最早用于治疗癫(癎),近年来对难治性癫(癎)的治疗取得较好效果,特别是在Dravet综合征、Doose综合征、婴儿痉挛症、发热性感染相关癫(癎)综合征(FIRES)、结节性硬化症和局灶性皮质发育不良等顽固性、结构性癫(癎)等的治疗方面,有了更多的临床证据,尤其是KD能够改善认知、言语和行为问题,值得重视.%Although the ketogenic diet(KD) has originally been used to treat epilepsies,plenty of evidence about the efficacy to intractable epilepsy has not accumulated until recently.These epilepsy or epilepsy syndrome include:Dravet syndrome,Doose syndrome,infantile spasms,Angelman syndrome with epilepsy,tuberous sclerosis complex and focal cerebral dysplasia or other structural epilepsy.It is worth paying more attention to the efficacy of KD on cognition,language development and behavior problems.

  5. 生酮饮食治疗儿童难治性癫痫的进展%Progress of ketogenic diet treatment of intractable epilepsy in Children

    Institute of Scientific and Technical Information of China (English)

    王明梅; 谢蒙蒙(综述); 朱登纳(审校)

    2015-01-01

    Refractory childhood epilepsy refers to those cases with dififcult control of epileptic attacks after at least two formal anticonvulsants treatment. Recently, ketogenic diet (KD), a high-fat, low-carbohydrate and adequate-protein diet, becomes an important method for the treatment of refractory epilepsy in children. Before employing KD, children should be checked to exclude known metabolic diseases. Although the mechanism of KD treatment is not entirely clear, it has a certain clinical curative effect. Many factors inlfuence the curative effect of KD. Most of the adverse effects of KD treatment are transient and can be recovered through active prevention and handling, which gives a generally good prognosis.%儿童难治性癫痫是指经2种以上抗癫痫药物的正规治疗,发作仍不能完全控制的癫痫。而生酮饮食(KD)作为一种特殊饮食(高脂肪、低碳水化合物、适量蛋白质的饮食),是治疗儿童难治性癫痫的重要方法。实施KD前,需排除某些代谢性疾病。虽然KD的治疗机制尚未完全明确,但已取得一定的临床疗效。多种因素影响KD的疗效。KD治疗中的不良反应大多为一过性,经积极预防和处理,一般预后良好。

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

    OpenAIRE

    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...

  7. The clinical efifcacy and adverse reactions of ketogenic diet therapy in children with refractory epilepsy Reviewer%生酮饮食治疗儿童难治性癫痫的疗效和不良反应

    Institute of Scientific and Technical Information of China (English)

    拜世英; 马艳红(综述)

    2015-01-01

    生酮饮食系一种高脂肪、低碳水化合物和适量蛋白质的特殊饮食,生酮饮食疗法是近年来治疗儿童难治性癫痫安全有效的重要措施,不但疗效确切,而且不良反应较少且多为一过性,一般预后良好。文章综述了生酮饮食治疗儿童难治性癫痫的有效率、依从性和不良反应及其产生原因。%The ketogenic diet (KD) is a special diet with high-fat, low-carbohydrate and moderate amount of protein. The KD therapy is a safe, potentially effective and important treatment of refractory childhood epilepsy in recent years. It has con-ifrmed clinical efifcacy and a generally good prognosis. The adverse reactions of KD treatment are normally less and transient. In this paper, the effective rate, patient compliance, adverse reactions and their causes of KD in treating children with refractory epilepsy were reviewed.

  8. Adaptation of Myocardial Substrate Metabolism to a Ketogenic Nutrient Environment*

    Science.gov (United States)

    Wentz, Anna E.; d'Avignon, D. André; Weber, Mary L.; Cotter, David G.; Doherty, Jason M.; Kerns, Robnet; Nagarajan, Rakesh; Reddy, Naveen; Sambandam, Nandakumar; Crawford, Peter A.

    2010-01-01

    Heart muscle is metabolically versatile, converting energy stored in fatty acids, glucose, lactate, amino acids, and ketone bodies. Here, we use mouse models in ketotic nutritional states (24 h of fasting and a very low carbohydrate ketogenic diet) to demonstrate that heart muscle engages a metabolic response that limits ketone body utilization. Pathway reconstruction from microarray data sets, gene expression analysis, protein immunoblotting, and immunohistochemical analysis of myocardial tissue from nutritionally modified mouse models reveal that ketotic states promote transcriptional suppression of the key ketolytic enzyme, succinyl-CoA:3-oxoacid CoA transferase (SCOT; encoded by Oxct1), as well as peroxisome proliferator-activated receptor α-dependent induction of the key ketogenic enzyme HMGCS2. Consistent with reduction of SCOT, NMR profiling demonstrates that maintenance on a ketogenic diet causes a 25% reduction of myocardial 13C enrichment of glutamate when 13C-labeled ketone bodies are delivered in vivo or ex vivo, indicating reduced procession of ketones through oxidative metabolism. Accordingly, unmetabolized substrate concentrations are higher within the hearts of ketogenic diet-fed mice challenged with ketones compared with those of chow-fed controls. Furthermore, reduced ketone body oxidation correlates with failure of ketone bodies to inhibit fatty acid oxidation. These results indicate that ketotic nutrient environments engage mechanisms that curtail ketolytic capacity, controlling the utilization of ketone bodies in ketotic states. PMID:20529848

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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

    Institute of Scientific and Technical Information of China (English)

    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

  11. 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

    Directory of Open Access Journals (Sweden)

    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

  12. A calculator for the classic and non-classic ketogenic diet based on Chinese food composition therapy on refractory epilepsy%应用计算机软件提高经典及非经典生酮饮食治疗难治性癫(癎)的操作性

    Institute of Scientific and Technical Information of China (English)

    邓宇虹

    2014-01-01

    Objective To simplify the manipulation of ketogenic diet recipes through software design.Methods Based on a Chinese food composition database,the software included 3 separate modules for the calculation of recipes for the classic ketogenic diet,modified Atkins diet and low glycemic index diet.It was applied in 10 refractory epilepsy patients,including 8 children and 2 adults,aged from 1 to 34 years,who took an average of 2.7 kinds of medication.Eight patients had daily seizures ;the other 2 cases had seizures 4-15 times per month.Two patients used the classic 4 ∶ 1 ketogenic diet module;4 patients started with the classic 4 ∶ 1 ketogenic diet and then shifted to 1 ∶ 1 to 4 ∶1 modified Atkins diet module after 2 to 5 months;4 patients used the 1 ∶ 1 to 4 ∶ 1 modified Atkins diet module.The software could automatically display the daily recommended intake value of total energy,fat,carbohydrate and protein according to the input of age,height,weight,activity level and the proportion of fat/(carbohydrate and protein),then patients or dietitians were allowed to select a different modules for recipe design.Results Forty percents(4/10 cases) of the patients had seizure reduced to 50%-90%,20% (2/10 cases) of the patients had seizure reduced to 90% 99%,and 20% (2/10 cases) of the patients became seizure free.Half-year retention rate reached 70% (7/10 cases).Conclusions This specially designed software for Chinese epilepsy patients can help simplify the operation of the ketogenic diet and modified Atkins diet and improve retention rates.It can be used in classic and non-classical ketogenic diets.%目的 通过计算机辅助设计食谱简化生酮饮食的操作.方法 设计一款基于中国食物成分数据库的软件,使用3个模块分别计算经典生酮饮食、改良阿特金斯饮食、低血糖生成指数饮食,用于指导药物无效且无法手术的10例难治性癫痫患者添加经典及非经典生酮饮食.其中儿童患者8

  13. 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

    Institute of Scientific and Technical Information of China (English)

    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

  14. Randomized control study on two different protocols of ketogenic diet for refractory epilepsy in children%两种生酮饮食方案治疗儿童难治性癫(癎)的随机对照研究

    Institute of Scientific and Technical Information of China (English)

    胡雁; 路新国; 文家伦; 王春; 陈黎; 陈彦; 廖建湘

    2012-01-01

    目的 评估按需和按时服用生酮饮食(ketogenic diet,KD)两种方案的疗效和安全性.方法 采用随机数字表法将60例难治性癫(癎)患儿随机分成按需服用KD组和按时服用KD组,每组30例.全量服用KD后连续72 h每6小时监测血酮、血糖和尿酮,比较两组患儿酮症状态的稳定性.记录发作频率并确定起效时间,分别在治疗后4周、12周、24周、48周评估两组患儿的疗效及安全性.结果 治疗4周后,按需服用KD组与按时服用KD组发作完全缓解率分别为33.3% (10/30)与30.0% (9/30),两组疗效相当(P>0.05).按需服用KD组治疗有效病例平均起效时间为(6.18±2.42)d,而按时服用KD组有效病例平均起效时间为(8.63±2.63)d,两组比较差异有统计学意义(P<0.05).治疗后12周、24周和48周,按需服用KD组发作完全缓解率分别为30.0%(9/30)、34.8%(8/23)和36.8% (7/19);按时服用KD组发作完全缓解率分别为33.3% (10/30)、30.4% (7/23)和44.4% (8/18),两组比较差异无统计学意义(P>0.05).1年后,按需服用KD组和按时服用KD组治疗保留率分别为63.3% (19/30)与60.0% (18/30),两组比较差异无统计学意义(P>0.05).治疗过程中,按需服用KD组与按时服用KD组的不良反应主要为可治疗的胃肠道反应和代谢紊乱.结论 按需服用KD和按时服用KD两种治疗方案均基本安全有效,按需服用方案更易达到酮症状态,起效更迅速,较易被患儿接受.因此在临床实施过程中可根据患儿的饮食习惯,灵活安排进食时间以提高治疗的依从性.%Objective To assess the efficacy and safety of two different protocols of ketogenic diet (KD)-eating on demand or eating at regular intervals for refractory epilepsy in children.Methods Sixty children with refractory epilepsy were randomly divided into eating on demand group (n =30) and eating at regular intervals group (n =30) by random number table method.After taking the whole amount of

  15. [National consensus on the ketogenic diet].

    Science.gov (United States)

    Armeno, Marisa; Caraballo, Roberto; Vaccarezza, María; Alberti, M Julia; Ríos, Viviana; Galicchio, Santiago; de Grandis, Elizabeth S; Mestre, Graciela; Escobal, Nidia; Matarrese, Pablo; Viollaz, Rocío; Agostinho, Ariela; Díez, Cecilia; Cresta, Araceli; Cabrera, Analía; Blanco, Virginia; Ferrero, Hilario; Gambarini, Victoria; Sosa, Patricia; Bouquet, Cecilia; Caramuta, Luciana; Guisande, Silvina; Gamboni, Beatriz; Hassan, Amal; Pesce, Laura; Argumedo, Laura; Dlugoszewski, Corina; DeMartini, Martha G; Panico, Luis

    2014-09-01

    Introduccion. La epilepsia es una enfermedad cronica que afecta al 0,5-1% de la poblacion, mayormente de inicio durante la infancia. Un tercio de los pacientes evoluciona hacia una forma refractaria al tratamiento con farmacos antiepilepticos, lo que plantea al equipo de salud un desafio terapeutico. La dieta cetogenica (DC) es un tratamiento no farmacologico efectivo utilizado como un metodo alternativo para el tratamiento de la epilepsia refractaria. Objetivos. Es necesario establecer directrices para utilizar la DC adecuadamente y asi expandir su conocimiento y utilizacion en paises hispanoparlantes. El Comite Nacional de Dieta Cetogenica, dependiente de la Sociedad Argentina de Neurologia Infantil, elaboro este consenso para estandarizar el uso de la DC basandose en la bibliografia publicada y la experiencia clinica. El grupo esta formado por neuropediatras, medicos nutricionistas y licenciadas en nutricion de cinco provincias de Argentina pertenecientes a 10 centros que aplican la DC como tratamiento de la epilepsia refractaria. Desarrollo. Se exponen temas tales como la seleccion del paciente, el asesoramiento a la familia antes del tratamiento, las interacciones de la DC con la medicacion anticonvulsionante, los suplementos, el control de efectos adversos y la retirada de dicha dieta. Conclusiones. La DC es un tratamiento util para los pacientes pediatricos con epilepsia intratable. Es fundamental la educacion y colaboracion del paciente y la familia. El tratamiento debe llevarlo a cabo un equipo interdisciplinar experimentado, siguiendo un protocolo. La formacion de un grupo nacional interdisciplinar, y la publicacion de este consenso, ofrece la posibilidad de orientar a nuevos centros en su implantacion.

  16. A high isoflavone diet decreases 5' adenosine monophosphate-activated protein kinase activation and does not correct selenium-induced elevations in fasting blood glucose in mice.

    Science.gov (United States)

    Stallings, Michael T; Cardon, Brandon R; Hardman, Jeremy M; Bliss, Tyler A; Brunson, Scott E; Hart, Chris M; Swiss, Maria D; Hepworth, Squire D; Christensen, Merrill J; Hancock, Chad R

    2014-04-01

    Selenium (Se) has been implicated as a micronutrient that decreases adenosine monophosphate-activated protein kinase (AMPK) signaling and may increase diabetes risk by reducing insulin sensitivity. Soy isoflavones (IF) are estrogen-like compounds that have been shown to attenuate insulin resistance, hyperglycemia, adiposity, and increased AMPK activation. We hypothesized that a high IF (HIF) diet would prevent the poor metabolic profile associated with high Se intake. The purpose of this study was to examine changes in basal glucose metabolism and AMPK signaling in response to an HIF diet and/or supplemental Se in a mouse model. Male FVB mice were divided into groups receiving either a control diet with minimal IF (low IF) or an HIF diet. Each dietary group was further subdivided into groups receiving either water or Se at a dose of 3 mg Se/kg body weight daily, as Se-methylselenocysteine (SMSC). After 5 months, mice receiving SMSC had elevated fasting glucose (P < .05) and a tendency for glucose intolerance (P = .08). The increase in dietary IF did not result in improved fasting blood glucose. Interestingly, after 6 months, HIF-fed mice had decreased basal AMPK activation in liver and skeletal muscle tissue (P < .05). Basal glucose metabolism was changed by SMSC supplementation as evidenced by increased fasting blood glucose and glucose intolerance. High dietary IF levels did not protect against aberrant blood glucose. In FVB mice, decreased basal AMPK activation is not the mechanism through which Se exerts its effect. These results suggest that more research must be done to elucidate the role of Se and IF in glucose metabolism.

  17. 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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  19. Ablation of adenosine monophosphate-activated protein kinaseα1 in vascular smooth muscle cells promotes diet-induced atherosclerotic calcification in vivo

    Institute of Scientific and Technical Information of China (English)

    CAI Zhe-jun; DING Ye; ZHANG Miao; LU Qiu-lun; WU Sheng-nan; ZHU Huai-ping; SONG Ping; ZOU Ming-hui

    2016-01-01

    AIM:Atherosclerotic calcification is highly linked with plaque instability and cardiovascular events .Adenosine monophosphate-activated protein kinase ( AMPK) has been involved in the pathogenesis of various cardiovascular disease .The contributions of AMPKαsubunits to the development of atherosclerotic calcification in vivo remained unknown .We hypothesized that AMPKαsubunits may play a role in the development of atherosclerotic calcification .METHODS: Atherosclerotic calcification was generated by 24-week fed of western diet in ApoE-/-background mice .Calcification was evaluated in aortic roots and innominate arteries of ApoE-/-mice or in mice with dual deficiencies of ApoE and AMPKαsubunits globally ( AMPKα1 and AMPKα2 ) , or vascular smooth muscle cell ( VSMC)-specific or macrophage-specific knockout of AMPKα1 with atherosclerotic calcification pone diet . The mechanism of AMPKα1 in regulating Runx2 was further explored in human aortic VSMC .RESULTS: Ablation of AMPKα1 but not AMPKα2 in ApoE-/-background promoted atherosclerotic calcification with increased Runt -related transcription factor ( Runx2 ) expression in VSMC compared with ApoE-/-mice.Conversely, chronic administration of metformin, which activated AMPK, markedly reduced ath-erosclerotic calcification and Runx2 expression in ApoE-/-mice but had less effects in ApoE-/-/AMPKα1 -/-mice.Furthermore, VSMC-but not macrophage-specific deficiency of AMPKα1 in ApoE-/-background promoted atherosclerotic calcification in vivo com-pared with the controls .AMPKα1 silencing in human aortic VSMC prevented Runx 2 from proteasome degradation to trigger osteoblastic differentiation of VSMC .Conversely , activation of AMPK led to Runx 2 instability by inducing its small ubiquitin-like modifier modifi-cation (SUMOylation).Protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, was directly phosphorylated by AMPKα1 at serine 510, to enhance its SUMO E3-ligase activity.Ablation of PIAS1

  20. The modified atkins diet in refractory epilepsy.

    Science.gov (United States)

    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.

  1. The Modified Atkins Diet in Refractory Epilepsy

    Directory of Open Access Journals (Sweden)

    Suvasini Sharma

    2014-01-01

    Full Text Available 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.

  2. 添加生酮饮食治疗难治性癫痫的长期保留率和不良反应%Long-term retention rate and side effects of ketogenic diet in Chinese patients with refraetory epilepsy

    Institute of Scientific and Technical Information of China (English)

    邓宇虹; 周锦华; 黎冰梅; 刘晓蓉; 廖卫平

    2012-01-01

    目的:评价添加生酮饮食(KD)治疗难治性癫痫的长期保留率和不良反应.方法:将28例难治性癫痫病人在1年半内陆续入组.病人住院期间以脂肪/(蛋白质+糖类)重量比=4:1饮食开始,出院继续4:1或适当减低比例.随访3、6和12个月的保留率,统计疗效和不良反应的发生率.结果:3、6和12个月的保留率分别为68%(19/28)、43%(10/23)和28%(5/18).3个月时68%(19/28)病人减少>50%的发作,43%(12/28)病人减少>90%的发作,无发作率为11%(3/28).启动期主要不良反应为胃肠道不适、酮症酸中毒、低血糖;维持期主要不良反应为便秘、高脂血症和低蛋白血症,仅有1例因不良反应而退出.结论:添加生酮饮食治疗难治性癫痫病人疗效较高,但保留率不高.不良反应不是治疗失败的主要原因,如何根据中国人的生活习惯来提高操作性是努力的方向.%Objective: To evaluate the effect and long-term retention of ketogenic diet (KD) in add-on therapy for refractory epilepsy patients with Chinese eating habits. Methods: 28 Chinese patients with refractory epilepsy were recruited in one and half a year. In the first three months, there were no changes of the anti-epilepsy drug. All patients were hospitalized and started with fat/(protein + carbohydrates) = 4∶1 diet,then maintained the 4∶1 diet after discharged. According to the recruiting day, the follow-up period persisted from 3 months to 12 months. The retention rate, the efficacy and the incidence of side effects were observed. Results: On the third month,68% of patients reduced 〉50% seizures, 43% (12/28) of patients reduced 〉90% seizures, 11 % were seizure-free. The retention rate was 68% ( 19/28 ) at the third month, while it was 43 % ( 10/23 ) at the sixth month and 28%(5/18) at one year. The major side effects in the first two weeks were gastrointestinal reactions, ketoacidosis and low glucose. The major side effects in the persistence

  3. 21 CFR 862.1385 - 17-Hydroxycorticosteroids (17-ketogenic steroids) test system.

    Science.gov (United States)

    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...

  4. Adenosine and adenosine receptors: Newer therapeutic perspective

    Directory of Open Access Journals (Sweden)

    Manjunath S

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. [Autism spectrum disorder and epilepsy: the role of ketogenic diet].

    Science.gov (United States)

    Garcia-Penas, J J

    2016-01-01

    Introduccion. Un 5-40% de los pacientes autistas desarrolla epilepsia. Aunque generalmente se controlan bien con medicacion, hasta un 20-30% de estas epilepsias son refractarias al tratamiento farmacologico. En esta poblacion, la dieta cetogenica (DC) puede ser una terapia alternativa altamente eficaz y debe considerarse seriamente. Objetivo. Revisar el papel de la DC en el tratamiento de la epilepsia infantil refractaria y en los pacientes que asocian autismo y epilepsia. Desarrollo. La DC es un tratamiento eficaz y bien tolerado para las epilepsias infantiles refractarias, incluyendo los pacientes que asocian autismo y epilepsia. Es fundamental caracterizar de forma precisa el sindrome epileptico para conocer cuales son los mejores candidatos para tratar con DC. Por otra parte, el efecto positivo de la DC sobre las alteraciones del metabolismo oxidativo mitocondrial y la evidencia experimental obtenida con DC en animales autistas sugieren que pueda ser una alternativa eficaz en los pacientes con autismo. Conclusiones. Basandose en la utilidad demostrada de la DC en el tratamiento de pacientes con epilepsia y autismo, esta terapia se ha usado en los ultimos años como una terapia alternativa para los pacientes autistas, aunque se desconoce cual es su eficacia real. Es necesario realizar un estudio aleatorizado y controlado para definir el perfil de eficacia y seguridad en esta poblacion.

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

    OpenAIRE

    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...

  8. Diets

    Science.gov (United States)

    ... prevent weight-related diseases, such as heart disease, diabetes, arthritis and some cancers. A healthy diet is an important part of a weight-loss ... you to lose weight. NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  9. Diet Redux: Outcomes from Reattempting Dietary Therapy for Epilepsy.

    Science.gov (United States)

    Kossoff, Eric H; Doerrer, Sarah C; Winesett, Steven P; Turner, Zahava; Henry, Bobbie J; Bessone, Stacey; Stanfield, Anthony; Cervenka, Mackenzie C

    2016-07-01

    The outcome for patients attempting dietary therapy for epilepsy a second time is unknown. Twenty-six subjects treated with the ketogenic diet as children who then began either the ketogenic diet or a Modified Atkins Diet (MAD) at least 6 months later were evaluated. The mean age at the first diet trial was 5.6 years and at the second diet trial was 11.5 years. Most restarted dietary therapy because of persistent seizures (65%) or recurrence after seizure freedom (19%). Overall, 77% had a ≥50% seizure reduction with the first diet, and 50% with the second diet, P = .04. Individual subject responses were largely similar, with 14 (54%) having identical seizure reduction both times, 9 worse (35%) with the second attempt, and 3 (16%) improved. The second diet trial was more likely to lead to >50% seizure reduction if the first trial was started at a later age (7.4 vs 3.9 years, P = .04).

  10. Modified Atkins diet therapy for a case with glucose transporter type 1 deficiency syndrome.

    Science.gov (United States)

    Ito, Susumu; Oguni, Hirokazu; Ito, Yasushi; Ishigaki, Keiko; Ohinata, Junko; Osawa, Makiko

    2008-03-01

    Glucose transporter type 1 deficiency syndrome (GLUT-1 DS), giving rise to impaired glucose transport across the blood-brain barrier, is characterized by infantile seizures, complex motor disorders, global developmental delay, acquired microcephaly, and hypoglycorrhachia. GLUT-1 DS can be treated effectively with a ketogenic diet because it can provide an alternative fuel for brain metabolism; however, the excessive restriction of food intake involved frequently makes it difficult for patients to initiate or continue the diet. Recently, the modified Atkins diet, which is much less restrictive in terms of the total calorie and protein intake than the classical ketogenic diet, has been shown to be effective and well tolerated in children with intractable epilepsy. We successfully introduced the modified Atkins diet to a 7-year-old boy with GLUT-1 DS, whose caregivers refused ketogenic diet treatment because of strong concerns over restricting the diet. The modified Atkins diet should be considered for patients with GLUT-1 DS as an alternative to the traditional ketogenic diet.

  11. Adenosine Receptors and Asthma

    OpenAIRE

    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...

  12. Movement disorders in GLUT1 deficiency syndrome respond to the modified Atkins diet

    NARCIS (Netherlands)

    Leen, W.G.; Mewasingh, L.; Verbeek, M.M.; Kamsteeg, E.J.; Warrenburg, B.P.C. van de; Willemsen, M.A.A.P.

    2013-01-01

    BACKGROUND: Movement disorders are a prominent feature of glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1DS). First-choice treatment is a ketogenic diet, but compliance is poor. We have investigated the effect of the modified Atkins diet as an alternative treatment for movement disorders in

  13. 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

    Institute of Scientific and Technical Information of China (English)

    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

  14. Adenosine and sleep

    International Nuclear Information System (INIS)

    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

  15. Adenosine and sleep

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  17. Adenosine and Sleep

    OpenAIRE

    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...

  18. [Modified Atkins diet brought back the joy of life to a developmentally severely disabled youth].

    Science.gov (United States)

    Arvio, Maria; Kuisma, Liisa; Pöntinen, Mervi

    2010-01-01

    Ketogenic diet is worth considering for persons with refractory epilepsy who cannot be helped with conventional means, for instance patients receiving gavage feeding are an ideal target group but patients eating normally have to adapt themselves to an unbalanced and fat-rich diet. We describe a developmentally severely disabled man, whose epilepsy settled, autistic features were alleviated, behavioral problems disappeared and whose weight and blood lipid and glucose values have remained normal for one year during a modified Atkins diet.

  19. Efficacy of the Atkins diet as therapy for intractable epilepsy.

    Science.gov (United States)

    Kossoff, Eric H; Krauss, Gregory L; McGrogan, Jane R; Freeman, John M

    2003-12-23

    The ketogenic diet is effective for treating seizures in children with epilepsy. The Atkins diet can also induce a ketotic state, but has fewer protein and caloric restrictions, and has been used safely by millions of people worldwide for weight reduction. Six patients, aged 7 to 52 years, were started on the Atkins diet for the treatment of intractable focal and multifocal epilepsy. Five patients maintained moderate to large ketosis for periods of 6 weeks to 24 months; three patients had seizure reduction and were able to reduce antiepileptic medications. This provides preliminary evidence that the Atkins diet may have a role as therapy for patients with medically resistant epilepsy.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Imaging Adenosine Triphosphate (ATP).

    Science.gov (United States)

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

    2016-08-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    The present study was performed to investigate the role of adenosine A1 receptors in regulating blood pressure in conscious mice. Adenosine A1-receptor knockout (A1R-/-) mice and their wild-type (A1R+/+) littermates were placed on standardized normal-salt (NS), high-salt (HS), or salt-deficient (SD...... in sodium excretion between the two genotypes on the HS diet. Even on the SD diet, A1R-/- mice had an increased sodium excretion compared with A1R+/+ mice. An abolished tubuloglomerular feedback response and reduced tubular reabsorption can account for the elevated salt excretion found in A1R-/- animals....... The elevated plasma renin concentrations found in the A1R-/- mice could also result in increased blood pressure. Our results confirm that adenosine, acting through the adenosine A1 receptor, plays an important role in regulating blood pressure, renin release, and sodium excretion....

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

    OpenAIRE

    Björklund, Olga

    2008-01-01

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

  4. A pilot study of the modified Atkins diet for Sturge-Weber syndrome.

    Science.gov (United States)

    Kossoff, Eric H; Borsage, Jennifer L; Comi, Anne M

    2010-12-01

    The modified Atkins diet (MAD) is a dietary treatment for epilepsy which does not restrict fluids or calories. This theoretically makes the MAD safer than the ketogenic diet for children with Sturge-Weber syndrome (SWS). Five children aged 4-18 years with SWS and at least monthly intractable seizures were started prospectively on the MAD for 6 months. All children had urinary ketosis and seizure improvement, including 3 with > 50% seizure reduction.

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  7. Regulation of adenosine levels during cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  8. Blood ketones are directly related to fatigue and perceived effort during exercise in overweight adults adhering to low-carbohydrate diets for weight loss: a pilot study.

    Science.gov (United States)

    White, Andrea M; Johnston, Carol S; Swan, Pamela D; Tjonn, Sherrie L; Sears, Barry

    2007-10-01

    Ketogenic diets have been associated with reductions in free-living physical activity, a response that can be counterproductive in individuals trying to lose weight. To explore whether popular low-carbohydrate diets might impact the desire to exercise by raising blood ketone concentrations, fatigue and perceived effort during exercise were compared in untrained, overweight adults adhering to a ketogenic low-carbohydrate diet or to a control diet low in carbohydrate, but not ketogenic (5%, 65%, and 30% or 40%, 30%, and 30% of energy from carbohydrate, fat, and protein, respectively). In this prospective, randomized, 2-week pilot study, all meals and snacks were provided to subjects, and energy intake was strictly controlled to provide approximately 70% of that needed for weight maintenance. At baseline and at the end of week 2, exercise testing was conducted in fasting participants. Weight loss and the reductions in fat mass did not differ by group during the trial. At week 2, blood beta-hydroxybutyrate concentrations were 3.6-fold greater for the ketogenic vs nonketogenic group (P=0.018) and correlated significantly with perceived exercise effort (r2=0.22, P=0.049). Blood beta-hydroxybutyrate was also significantly correlated to feelings of "fatigue" (r=0.458, P=0.049) and to "total mood disturbance" (r=0.551, P=0.015) while exercising. These pilot data indicate that ketogenic, low-carbohydrate diets enhance fatigability and can reduce the desire to exercise in free-living individuals. PMID:17904939

  9. MODIFIED ATKINS DIET FOR INTRACTABLE CHILDHOOD EPILEPSY

    Directory of Open Access Journals (Sweden)

    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

  10. The modified Atkins diet.

    Science.gov (United States)

    Kossoff, Eric H; Dorward, Jennifer L

    2008-11-01

    In 2003, a case series was published describing the benefits of a less restrictive ketogenic diet (KD) started as an outpatient without a fast and without any restrictions on calories, fluids, or protein. This "Modified Atkins Diet" (MAD) restricts carbohydrates to 10 g/day (15 g/day in adults) while encouraging high fat foods. Now 5 years later, there have been eight prospective and retrospective studies published on this alternative dietary therapy, both in children as well as adults. In these reports, 45 (45%) have had 50-90% seizure reduction, and 28 (28%) >90% seizure reduction, which is remarkably similar to the traditional KD. This review will discuss basics and tips to best provide the MAD, evidence for its efficacy, suggestions about the role of ketosis in dietary treatment efficacy, and its side effect profile. Lastly, the possible future benefits of this treatment for new-onset seizures, adults, neurologic conditions other than epilepsy, and developing countries of the world will be discussed.

  11. [The use of the ketogenic diet as treatment for refractory epilepsy in the paediatric age].

    Science.gov (United States)

    Pablos-Sánchez, Tamara; Oliveros-Leal, Liliana; Núñez-Enamorado, Noemí; Camacho-Salas, Ana; Moreno-Villares, José Manuel; Simón-De las Heras, Rogelio

    2014-01-16

    Introduccion. El 23-25% de los niños epilepticos son refractarios a farmacos antiepilepticos. El interes por la dieta cetogenica como tratamiento en estos pacientes no candidatos a otras opciones terapeuticas ha resurgido ultimamente. Objetivo. Valorar la eficacia y seguridad del tratamiento con dieta cetogenica en un importante numero de pacientes pediatricos con epilepsia refractaria en nuestro centro y determinar si los resultados obtenidos corroboran otros de publicacion reciente. Pacientes y metodos. Se revisaron retrospectivamente las historias clinicas de 41 niños con epilepsia refractaria que fueron tratados con dieta cetogenica entre 1998 y 2011, la mayoria con dieta tipo Radcliffe II. La mediana de edad al inicio de la dieta fue de 3,92 años. Resultados. A los seis meses del inicio de la dieta se redujeron las crisis en al menos un 50% en un 36,84% de la muestra (el 10,53% de los niños alcanzo mas de un 90% de reduccion y un 5,26% quedo sin crisis). Aproximadamente un 50% por grupo de edad en los mas pequeños respondio de manera positiva. Un 58,54% de los pacientes presento algun efecto secundario, tolerable y transitorio, principalmente elevacion de los niveles de colesterol y estreñimiento, sin observarse variacion en los parametros antropometricos. Conclusiones. La dieta cetogenica supone una buena alternativa terapeutica en los casos de epilepsia refractaria en la edad pediatrica, con mayor probabilidad de beneficio cuanto menor sea la edad del niño al inicio de la dieta. En general, es bien tolerada. Son de gran importancia en estos pacientes las revisiones periodicas con control nutricional.

  12. HEPATIC FATTY ACID PROFILE OF RATS FED A TRIHEPTANOIN-BASED KETOGENIC DIET.

    Science.gov (United States)

    Vieira de Melo, Ingrid Sofia; Da Rocha Ataide, Terezinha; Lima de Oliveira, Suzana; Bezerra Bueno, Nassib; Duarte de Freitas, Johnnatan; Goulart Sant'Ana, Antônio Euzébio

    2015-07-01

    Objetivo: el objetivo de este estudio fue evaluar la influencia del consumo de una dieta cetogénica complementada con triheptanoína, un triacilglicerol de cadena media y anaplerótico, en el perfil de ácidos grasos del hígado de ratones Wistar. Métodos: tres grupos de ratones Wistar machos (n = 10) fueron sometidos durante 60 días a una dieta AIN-93 de control, una dieta cetogénica basada en triheptanoína o una dieta cetogénica a base de aceite de soja. Los hígados fueron escindidos y sometidos a extracción de lípidos y metilación para obtener los ésteres metílicos de ácidos grasos, que se sometieron a cromatografía de gas-espectrometría de masa. Resultados y discusión: en comparación con los ratones alimentados con la dieta de control, los de ambas dietas cetogénicas mostraron una reducción significativa en las concentraciones de los ácidos grasos 9-hexadecenoico y 9-octadecenoico, mientras que los alimentados con triheptanoína mostraron niveles de ácido octadecenoico aumentados. Conclusión: los cambios en los perfiles de ácidos grasos del hígado de los ratones alimentados con dietas cetogénicas no están relacionados con la fuente de grasa de la dieta (triheptanoína o aceite de soja), sino más bien con la concentración total de lípidos.

  13. [Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review].

    Science.gov (United States)

    Araya-Quintanilla, F; Celis-Rosati, A; Rodriguez-Leiva, C; Silva-Navarro, C; Silva-Pinto, Y; Toro-Jeria, B

    2016-05-16

    Introduccion. La epilepsia es una patologia cerebral que afecta tanto a niños como a adultos. Desde los años veinte, la dieta cetogenica ha ganado prestigio como otra opcion de tratamiento en pacientes con epilepsia refractaria. Sujetos y metodos. Se realiza una sintesis de la evidencia a traves de una revision sistematica de ensayos clinicos aleatorizados que hayan comparado una dieta cetogenica sola con otros tipos de dieta para el tratamiento de estos pacientes. Objetivo. Determinar la efectividad de la dieta cetogenica en la disminucion de los episodios de convulsiones en pacientes con epilepsia refractaria. La estrategia de busqueda incluyo ensayos clinicos aleatorizados y ensayos clinicos controlados. Las bases de datos usadas fueron: Medline, LILACS, Central y CINAHL. Resultados. Se obtuvieron seis articulos que cumplian con los criterios de elegibilidad. Conclusiones. Existe evidencia limitada de que la dieta cetogenica en comparacion con la dieta de trigliceridos de cadena media es mas efectiva en disminuir la frecuencia de las convulsiones. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta gradual (2,5:1 y 3:1) es mas efectiva para disminuir las crisis epilepticas. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta Atkins es mas efectiva para disminuir la frecuencia de convulsiones en tres meses. La decision de aplicar este tipo de dietas tambien debe basarse en costes, preferencias y seguridad del tratamiento. Ademas, debe considerarse la probabilidad de que algunos estudios, por problemas de indizacion, hayan quedado fuera de la revision.

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

    OpenAIRE

    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...

  15. Adenosine, Energy Metabolism, and Sleep

    Directory of Open Access Journals (Sweden)

    Tarja Porkka-Heiskanen

    2003-01-01

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

  16. Long-term follow-up of children treated with the modified Atkins diet.

    Science.gov (United States)

    Chen, Wendy; Kossoff, Eric H

    2012-06-01

    The modified Atkins diet has been studied in mostly short-term clinical trials and case series. No studies have systematically examined the long-term benefits and side effects. The modified Atkins diet was started without prior ketogenic diet use in 87 children at the Johns Hopkins Hospital since 2002, of which 54 continued for more than 6 months. Children who had not been seen within the past 2 years were contacted by phone and email. At their most recent point during the modified Atkins diet (mean 19.9 months), 30 of 54 (55%) children with diet durations of more than 6 months achieved >50% improvement; 19 (35%) were seizure-free. Using an intent-to-treat analysis, at 12 months, 33 of 87 (38%) had >50% seizure reduction; 16 (18%) were seizure-free. These results are similar to published data for short-term modified Atkins diet and long-term ketogenic diet use. Side effects were predominantly elevations in lipid profile and gastrointestinal upset.

  17. Optical Aptasensors for Adenosine Triphosphate

    Science.gov (United States)

    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

  18. Bland diet

    Science.gov (United States)

    Heartburn - bland diet; Nausea - bland diet; Diarrhea - bland diet; Peptic ulcer - bland diet ... A bland diet can be used alongside lifestyle changes to help treat ulcers, heartburn, nausea, vomiting, diarrhea, and gas. You may ...

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

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2012-01-01

    Nine periparturient Holstein cows catheterized in major splanchnic vessels were used in a complete randomized design with repeated measurements to investigate effects of glucogenic and ketogenic feeding strategies on splanchnic metabolism of glucose and amino acids. At parturition, cows were...... incremental increase in hepatic glucose release rather than hepatic catabolism of amino acids....

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Noam eRudich

    2012-06-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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....

  3. Adenosine triphosphate inhibition of yeast trehalase.

    Science.gov (United States)

    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

  4. Electrocardiographic profile of adenosine pharmacological stress testing

    OpenAIRE

    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,...

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

    Science.gov (United States)

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

    2003-12-01

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

  6. Adenosine stress protocols for myocardial perfusion imaging

    Directory of Open Access Journals (Sweden)

    Baškot Branislav

    2008-01-01

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

  7. Determination of adenosine effects and adenosine receptors in murine corpus cavernosum.

    Science.gov (United States)

    Tostes, Rita C; Giachini, Fernanda R C; Carneiro, Fernando S; Leite, Romulo; Inscho, Edward W; Webb, R Clinton

    2007-08-01

    This study tested the hypothesis that adenosine, in murine corpora cavernosa, produces direct relaxation of smooth muscle cells and inhibition of contractile responses mediated by sympathetic nerve stimulation. Penes were excised from anesthetized male C57BL/6 mice, dissected, and cavernosal strips were mounted to record isometric force. Adenosine, 2-chloroadenosine (stable analog of adenosine), and 2-phenylaminoadenosine (CV1808) (A2(A)/A2(B) agonist) produced concentration-dependent relaxations of phenylephrine-contracted tissues. Relaxation to 2-chloroadenosine was inhibited, in a concentration-dependent manner, by 2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261; A2(A) antagonist; 10(-9)-10(-6) M) and N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamida (MRS1706; A2(B) antagonist; 10(-8)-10(-6) M). The combination of both antagonists abrogated 2-chloroadenosine-induced relaxation. Electrical field stimulation (EFS; 1-32 Hz) of adrenergic nerves produced frequency-dependent contractions that were inhibited by compounds that increase adenosine levels, such as 5'-iodotubercidin (adenosine kinase inhibitor), erythro-9-(2-hydroxy-3-nonyl)adenine (adenosine deaminase inhibitor), and dipyridamole (inhibitor of adenosine transport). The adenosine A1 receptor agonist N(6)-cyclopentyladenosine (C8031) right-shifted contractile responses to EFS, with a significant inhibitory effect at 10(-6) M. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine (C101) (10(-7) M) enhanced contractile responses to EFS and eliminated the inhibitory effects of 5'-iodotubercidin. Dipyridamole and 5'-iodotubercidin had no effect on adenosine-mediated relaxation. In summary, adenosine directly relaxes cavernosal smooth muscle cells, by the activation of A2(A)/A2(B) receptor subtypes. In addition, adenosine negatively modulates sympathetic neurotransmission, by A1 receptor

  8. A randomized, crossover comparison of daily carbohydrate limits using the modified Atkins diet.

    Science.gov (United States)

    Kossoff, Eric H; Turner, Zahava; Bluml, Renee M; Pyzik, Paula L; Vining, Eileen P G

    2007-05-01

    The modified Atkins diet is a dietary therapy for intractable epilepsy that mimics the ketogenic diet, yet does not restrict protein, calories, and fluids. The ideal starting carbohydrate limit is unknown. Twenty children with intractable epilepsy were randomized to either 10 or 20 g of carbohydrates per day for the initial 3 months of the modified Atkins diet, and then crossed over to the opposite amount. A significantly higher likelihood of >50% seizure reduction was noted for children started on 10 g of carbohydrate per day at 3 months: 60% versus 10% (P=0.03). Most parents reported no change in seizure frequency or ketosis between groups, but improved tolerability with 20 g per day. A starting carbohydrate limit of 10 g per day for children starting the modified Atkins diet may be ideal, with a planned increase to a more tolerable 20 g per day after 3 months.

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

    Science.gov (United States)

    Shakiba, Marjan; Mahjoub, Fatemeh; Fazilaty, Hassan; Rezagholizadeh, Fereshteh; Shakiba, Arghavan; Ziadlou, Maryam; Gahl, William A.; Behnam, Babak

    2016-01-01

    Hypermethioninemia may be benign, present as a nonspecific sign of nongenetic conditions such as liver failure and prematurity, or a severe, progressive inborn error of metabolism. Genetic causes of hypermethioninemia include mitochondrial depletion syndromes caused by mutations in the MPV17 and DGUOK genes and deficiencies of cystathionine β-synthase, methionine adenosyltransferase types I and III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase, citrin, fumarylacetoacetate hydrolase, and adenosine kinase. Here we present a 3-year old girl with a history of poor feeding, irritability, respiratory infections, cholestasis, congenital heart disease, neurodevelopmental delay, hypotonia, sparse hair, facial dysmorphisms, liver dysfunction, severe hypermethioninemia and mild homocystinemia. Genetic analysis of the adenosine kinase (ADK) gene revealed a previously unreported variant (c.479–480 GA>TG) resulting in a stop codon (p.E160X) in ADK. A methionine-restricted diet normalized the liver function test results and improved her hypotonia. PMID:27500280

  10. Internalization and desensitization of adenosine receptors.

    NARCIS (Netherlands)

    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

  11. Adenosine: An immune modulator of inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Jeff Huaqing Ye; Vazhaikkurichi M Rajendran

    2009-01-01

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

  12. Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy

    Science.gov (United States)

    Schoeler, Natasha E.; Leu, Costin; White, Jon; Plagnol, Vincent; Ellard, Sian; Matarin, Mar; Yellen, Gary; Thiele, Elizabeth A.; Mackay, Mark; McMahon, Jacinta M.; Scheffer, Ingrid E.; Sander, Josemir W.; Cross, J. Helen; Sisodiya, Sanjay M.

    2015-01-01

    In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF) > 0.01, using PLINK. Response to KDT in individuals with variants with MAF  0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAF 0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes. PMID:26590798

  13. High-Fat Diet Changes Hippocampal Apolipoprotein E (ApoE) in a Genotype- and Carbohydrate-Dependent Manner in Mice.

    Science.gov (United States)

    Lane-Donovan, Courtney; Herz, Joachim

    2016-01-01

    Alzheimer's disease is a currently incurable neurodegenerative disease affecting millions of individuals worldwide. Risk factors for Alzheimer's disease include genetic risk factors, such as possession of ε4 allele of apolipoprotein E (ApoE4) over the risk-neutral ApoE3 allele, and lifestyle risk factors, such as diet and exercise. The intersection of these two sources of disease risk is not well understood. We investigated the impact of diet on ApoE levels by feeding wildtype, ApoE3, and ApoE4 targeted replacement (TR) mice with chow, high-fat, or ketogenic (high-fat, very-low-carbohydrate) diets. We found that high-fat diet affected both plasma and hippocampal levels of ApoE in an isoform-dependent manner, with high-fat diet causing a surprising reduction of hippocampal ApoE levels in ApoE3 TR mice. Conversely, the ketogenic diet had no effect on hippocampal ApoE. Our findings suggest that the use of dietary interventions to slow the progression AD should take ApoE genotype into consideration.

  14. High-Fat Diet Changes Hippocampal Apolipoprotein E (ApoE in a Genotype- and Carbohydrate-Dependent Manner in Mice.

    Directory of Open Access Journals (Sweden)

    Courtney Lane-Donovan

    Full Text Available Alzheimer's disease is a currently incurable neurodegenerative disease affecting millions of individuals worldwide. Risk factors for Alzheimer's disease include genetic risk factors, such as possession of ε4 allele of apolipoprotein E (ApoE4 over the risk-neutral ApoE3 allele, and lifestyle risk factors, such as diet and exercise. The intersection of these two sources of disease risk is not well understood. We investigated the impact of diet on ApoE levels by feeding wildtype, ApoE3, and ApoE4 targeted replacement (TR mice with chow, high-fat, or ketogenic (high-fat, very-low-carbohydrate diets. We found that high-fat diet affected both plasma and hippocampal levels of ApoE in an isoform-dependent manner, with high-fat diet causing a surprising reduction of hippocampal ApoE levels in ApoE3 TR mice. Conversely, the ketogenic diet had no effect on hippocampal ApoE. Our findings suggest that the use of dietary interventions to slow the progression AD should take ApoE genotype into consideration.

  15. Paleolithic diet

    OpenAIRE

    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...

  16. Empirical prediction of net splanchnic release of ketogenic nutrients, acetate, butyrate and β-hydroxybutyrate in ruminants: a meta-analysis.

    Science.gov (United States)

    Loncke, C; Nozière, P; Bahloul, L; Vernet, J; Lapierre, H; Sauvant, D; Ortigues-Marty, I

    2015-03-01

    For energy feeding systems for ruminants to evolve towards a nutrient-based system, dietary energy supply has to be determined in terms of amount and nature of nutrients. The objective of this study was to establish response equations of the net hepatic flux and net splanchnic release of acetate, butyrate and β-hydroxybutyrate to changes in diet and animal profiles. A meta-analysis was applied on published data compiled from the FLuxes of nutrients across Organs and tissues in Ruminant Animals database, which pools the results from international publications on net splanchnic nutrient fluxes measured in multi-catheterized ruminants. Prediction variables were identified from current knowledge on digestion, hepatic and other tissue metabolism. Subsequently, physiological and other, more integrative, predictors were obtained. Models were established for intakes up to 41 g dry matter per kg BW per day and diets containing up to 70 g concentrate per 100 g dry matter. Models predicted the net hepatic fluxes or net splanchnic release of each nutrient from its net portal appearance and the animal profile. Corrections were applied to account for incomplete hepatic recovery of the blood flow marker, para-aminohippuric acid. Changes in net splanchnic release (mmol/kg BW per hour) could then be predicted by combining the previously published net portal appearance models and the present net hepatic fluxes models. The net splanchnic release of acetate and butyrate were thus predicted from the intake of ruminally fermented organic matter (RfOM) and the nature of RfOM (acetate: residual mean square error (RMSE)=0.18; butyrate: RMSE=0.01). The net splanchnic release of β-hydroxybutyrate was predicted from RfOM intake and the energy balance of the animals (RMSE=0.035), or from the net portal appearance of butyrate and the energy balance of the animals (RMSE=0.050). Models obtained were independent of ruminant species, and presented low interfering factors on the residuals, least

  17. Adenosine receptors and asthma in humans

    OpenAIRE

    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...

  18. Chemoelectrical energy conversion of adenosine triphosphate

    Science.gov (United States)

    Sundaresan, Vishnu Baba; Sarles, Stephen Andrew; Leo, Donald J.

    2007-04-01

    Plant and animal cell membranes transport charged species, neutral molecules and water through ion pumps and channels. The energy required for moving species against established concentration and charge gradients is provided by the biological fuel - adenosine triphosphate (ATP) -synthesized within the cell. The adenosine triphosphatase (ATPases) in a plant cell membrane hydrolyze ATP in the cell cytoplasm to pump protons across the cell membrane. This establishes a proton gradient across the membrane from the cell exterior into the cell cytoplasm. This proton motive force stimulates ion channels that transport nutrients and other species into the cell. This article discusses a device that converts the chemical energy stored in adenosine triphosphate into electrical power using a transporter protein, ATPase. The V-type ATPase proteins used in our prototype are extracted from red beet(Beta vulgaris) tonoplast membranes and reconstituted in a bilayer lipid membrane or BLM formed from POPC and POPS lipids. A pH7 medium that can support ATP hydrolysis is provided on both sides of the membrane and ATP is dissolved in the pH7 buffer on one side of the membrane. Hydrolysis of ATP results in the formation of a phosphate ion and adenosine diphosphate. The energy from the reaction activates ATPase in the BLM and moves a proton across the membrane. The charge gradient established across the BLM due to the reaction and ion transport is converted into electrical current by half-cell reference electrodes. The prototype ATPase cell with an effective BLM area of 4.15 mm2 carrying 15 μl of ATPase proteins was observed to develop a steady state peak power output of 70 nW, which corresponds to a specific power of 1.69 μW/cm2 and a current density of 43.4 μA/cm2 of membrane area.

  19. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    1989-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  4. A metabolic immune checkpoint: adenosine in tumor microenvironment

    Directory of Open Access Journals (Sweden)

    Akio eOhta

    2016-03-01

    Full Text Available 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 anti-tumor 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.

  5. Vegetarian Diet

    Science.gov (United States)

    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 ...

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

    Institute of Scientific and Technical Information of China (English)

    V Haktan Ozacmak; Hale Sayan

    2007-01-01

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

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

    Indian Academy of Sciences (India)

    M Sudha Swaraga; L Charitha; M Adinarayana

    2005-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    OpenAIRE

    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...

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

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

    Boison, Detlev; Aronica, Eleonora

    2015-01-01

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

  12. A High-Affinity Adenosine Kinase from Anopheles Gambiae

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-31

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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    OpenAIRE

    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 ...

  16. Inhibition of uptake of adenosine into human blood platelets

    NARCIS (Netherlands)

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

    1980-01-01

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

  17. Distribution of adenosine receptors in human sclera fibroblasts

    OpenAIRE

    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...

  18. IBS Diet

    Science.gov (United States)

    ... 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 ...

  19. Mediterranean Diet

    Science.gov (United States)

    ... 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 ...

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

    OpenAIRE

    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 ...

  1. Role of A3 adenosine receptor in diabetic neuropathy.

    Science.gov (United States)

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

    2016-10-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  5. Adenosine A1 receptor agonists inhibit trigeminovascular nociceptive transmission

    DEFF Research Database (Denmark)

    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...... from the external jugular vein to determine levels of calcitonin gene-related peptide (CGRP) release before and after drug administration. Intravenous administration of the highly selective adenosine A1 receptor agonist, GR79236 (3-100 microg/kg) had a dose-dependent inhibitory effect on SSS...... 33 +/- 2 pmol/l (n = 6) to 64 +/- 3 pmol/l, an effect substantially reduced by pre-treatment with GR79236 (30 microg/kg; P agonist, GR190178 (30-1000 microg/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion...

  6. The effects of methylmercury on motor activity are sex- and age-dependent, and modulated by genetic deletion of adenosine receptors and caffeine administration.

    Science.gov (United States)

    Björklund, Olga; Kahlström, Johan; Salmi, Peter; Ogren, Sven Ove; Vahter, Marie; Chen, Jiang-Fan; Fredholm, Bertil B; Daré, Elisabetta

    2007-11-30

    Adenosine and its receptors are, as part of the brain stress response, potential targets for neuroprotective drugs. We have investigated if the adenosine receptor system affects the developmental neurotoxicity caused by the fish pollutant methylmercury (MeHg). Behavioral outcomes of low dose perinatal MeHg exposure were studied in mice where the A(1) and A(2A) adenosine receptors were either partially blocked by caffeine treatment or eliminated by genetic modification (A(1)R and A(2A)R knock-out mice). From gestational day 7 to day 7 of lactation dams were administered doses that mimic human intake via normal diet, i.e. 1microM MeHg and/or 0.3g/l caffeine in the drinking water. This exposure to MeHg resulted in a doubling of brain Hg levels in wild type females and males at postnatal day 21 (PND21). Open field analysis was performed at PND21 and 2 months of age. MeHg caused time-dependent behavioral alterations preferentially in male mice. A decreased response to amphetamine in 2-month-old males pointed to disturbances in dopaminergic functions. Maternal caffeine intake induced long-lasting changes in the offspring evidenced by an increased motor activity and a modified response to psychostimulants in adult age, irrespectively of sex. Similar alterations were observed in A(1)R knock-out mice, suggesting that adenosine A(1) receptors are involved in the alterations triggered by caffeine exposure during development. Perinatal caffeine treatment and, to some extent, genetic elimination of adenosine A(1) receptors, attenuated the behavioral consequences of MeHg in males. Importantly, also deletion of the A(2A) adenosine receptor reduced the vulnerability to MeHg, consistent with the neuroprotective effects of adenosine A(2A) receptor inactivation observed in hypoxia and Parkinson's disease. Thus, the consequences of MeHg toxicity during gestation and lactation can be reduced by adenosine A(1) and A(2A) receptor inactivation, either via their genetic deletion or by

  7. Modulating effect of adenosine deaminase on function of adenosine A1receptors

    Institute of Scientific and Technical Information of China (English)

    Wan-chun SUN; Yan CAO; Lei JIN; Li-zhen WANG; Fan MENG; Xing-zu ZHU

    2005-01-01

    Aim: To study the modulating effect of adenosine deaminase (ADA) on yhe adenosine A1 receptor (A1R) in HEK293 cells stably expressing the human A1R.Methods: cDNA was amplified by RT-PCR using total RNA from human embryo brain tissue as the template. The PCR products were subcloned into the plasmid pcDNA3 and cloned into the plasmid pcDNA3.1. The cloned A1R cDNA was sequenced and stably expressed in HEK293 cells. The modulating effect of adenosine deaminase on A1R was studied by using [3H]DPCPX binding assay and an intracellular calcium assay. Results: HEK293 cells stably expressing human A1R were obtained. Saturation studies showed that the KD value and Bmax value of [3H]DPCPX were 1.6±0.2 nmol/L and 1.819±0.215 nmol/g of protein respectively, in the absence of ecto-ADA respectively, and 1.3±0.2 nmol/L and 1.992±0.130 nmol/g of protein in the presence of ecto-ADA respectively, suggesting that the KD value and Bmax value of [3H]DPCPX were unaffected by ecto-ADA. In the case of [3H]DPCPX competition curves obtained from intact cells or membranes, A1R agonist CCPA/[3H]DPCPX competition curve could be fitted well to a one-site model in the absence of ecto-ADA and a two-site model in the presence of ecto ADA with a KH value of 0.74 (0.11-4.8) nmol/L (intact cells) or 1.8 (0.25-10) nmol/L (membrane) and a KL value of 0.94 (0.62-1.41) μmol/L (intact cells) or 0.77 (0.29-0.99) μmol/L (membrane). The KL value is not significantly different from the IC50 value of 0.84(0.57-1.23) μmol/L (intact cells) or 0.84 (0.63-1.12) μmol/L (membrane) obtained in the absence of ecto-ADA. Similar results were obtained from the CPA/[3H]DPCPX competition curve in the absence or presence of ecto-ADA on intact cells or membranes. Intracellular calcium assay demonstrated that the EC50 value of CPA were 10 (5-29) nmol/L and 94 (38-229) nmol/L in the presence or absence of ecto-ADA, respectively. Conclusion: A1R stably expressed in the HEK293 cells display a low affinity for agonists in

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

    International Nuclear Information System (INIS)

    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.)

  9. Role of adenosine as adjunctive therapy in acute myocardial infarction.

    Science.gov (United States)

    Forman, Mervyn B; Stone, Gregg W; Jackson, Edwin K

    2006-01-01

    Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus "myocardial reperfusion injury" may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high-risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil-mediated microvascular injury resulting in a progressive decrease in blood flow ("no-reflow" phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well-characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio-protective effects of adenosine are supported by its role as a mediator of pre- and post-conditioning. In experimental models, administration of adenosine in the peri-reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3-h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55-65%). Post hoc analysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk-patients undergoing reperfusion therapy. PMID:16961725

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

    Science.gov (United States)

    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.

  11. Phosphorylation of adenosine with trimetaphosphate under simulated prebiotic conditions.

    Science.gov (United States)

    Cheng, Changmei; Fan, Chang; Wan, Rong; Tong, Chunyuan; Miao, Zhiwei; Chen, Jing; Zhao, Yufen

    2002-06-01

    The phosphorylation of adenosine with trimetaphosphate in solution, in solid phase and using wet-dry cycles was carried out and it was found that wet-dry cycles were the most efficient. The catalytic effects of some metal ions on the phosphorylation were also studied and it was discovered that Ni(II) is the most effective. The combination of wet-dry cycles (4 cycles) and catalysis by Ni(II) led to an unprecedented high conversion of adenosine to phosphorylated products (30%) near neutral pH. The main phosphorylated products were 2',3'-cyclic AMP (10.4%) and 5'-ATP (13.0%). PMID:12227426

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-01

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

  15. Diet after gastric banding

    Science.gov (United States)

    Gastric banding surgery - your diet; Obesity - diet after banding; Weight loss - diet after banding ... about any problems you are having with your diet, or about other issues related to your surgery ...

  16. Nutrition and Diet

    Science.gov (United States)

    ... 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, ...

  17. Diet and Nutrition

    Science.gov (United States)

    ... 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 ...

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

    OpenAIRE

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

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

    Science.gov (United States)

    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

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

    Lifescience Database Archive (English)

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

  2. Searching Inhibitors of Adenosine Kinase by Simulation Methods

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  3. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Science.gov (United States)

    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... disorders. (b) Classification. Class I (general controls)....

  4. Vasoconstrictor and vasodilator effects of adenosine in the kidney

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Schnermann, Jurgen

    2003-01-01

    that the steady-state response to the increase of plasma adenosine levels above normal resulting from the infusion is global renal vasorelaxation that is the result of A2AR activation in most parts of the renal vasculature, including larger renal arteries, juxtamedullary afferent arterioles, efferent arterioles...

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

    Directory of Open Access Journals (Sweden)

    Cátia Vieira

    2014-01-01

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

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

    Science.gov (United States)

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

    2002-03-01

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

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

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

    Science.gov (United States)

    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

  10. Fluoride in diet

    Science.gov (United States)

    Diet - fluoride ... bones and teeth. Too much fluoride in the diet is very rare. Rarely, infants who get too ... of essential vitamins is to eat a balanced diet that contains a variety of foods from the ...

  11. Iodine in diet

    Science.gov (United States)

    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 ...

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

    Science.gov (United States)

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

    2015-10-01

    Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925-1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output. PMID:26311185

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

    OpenAIRE

    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...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    OpenAIRE

    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...

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

    NARCIS (Netherlands)

    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,

  17. The modified Atkins diet for intractable epilepsy may be associated with late-onset egg-induced anaphylactic reaction: a case report.

    Science.gov (United States)

    Levy, Yael; Peleg-Weiss, Lilach; Goldberg-Stern, Hadassa

    2011-03-01

    The modified Atkins diet is a therapeutic option for children with intractable epilepsy. It is less restrictive than the traditional ketogenic diet, with ≈60% of calories from fat sources. We describe a 6-y-old boy with intractable epilepsy treated with the modified Atkins diet who presented to the emergency department with first-time anaphylactic reaction to egg. Symptoms of urticaria and angioedema, shortness of breath, wheezing, and cyanosis developed several minutes after he ate a hard-boiled egg. His history was remarkable for asthma, but no food allergies were documented. The anaphylactic reaction appeared after 6 mo of treatment with the modified Atkins diet (including 10-15 eggs daily), which ameliorated his seizures, and was preceded by streptococcal pharyngitis. Laboratory workup revealed specific immunoglobulin E antibodies to egg. This is the first report of new-onset egg allergy in a child, probably triggered by the high egg content of the modified Atkins diet. The risk of egg allergy should be kept in mind when treating epileptic children with the modified Atkins diet, especially those with comorbid asthma.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...

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

    Science.gov (United States)

    Bagrov, Ia Iu; Manusova, N B

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  2. Evaluation of Serum Adenosine Deaminase and Retinol in patients with Laryngeal Cancer

    Directory of Open Access Journals (Sweden)

    R.B Metgudmath

    2013-12-01

    Full Text Available Laryngeal cancers account for 4% of all head and neck cancers in India. The disease process has better prognosis if it is diagnosed early. In view of this the objective of the study was to assess the reliability of serum enzyme marker adenosine deaminase and non-enzymatic anti-oxidant retinol in laryngeal cancer patients as supportive parameters for diagnostic purpose. Materials and methods:-25 clinically and histopathologically confirmed patients of laryngeal cancer in age group of 45-65 years were included in the study and 25 healthy subjects with in the same age group served as controls. Results:-The level of serum ADA was significantly elevated in laryngeal cancer patients in comparison to controls whereas retinol levels were significantly decreased. Conclusion: - Lipid per-oxidation as a result of cancer leads to membrane damage and an increase in cytoplasmic ADA. It is also associated with a decrease in levels of non-enzymatic antioxidant retinol. These biochemical parameters may be used as supportive parameters for diagnostic purpose and may add further for prognostic information. Further studies are required on a larger sample size to explore strategies by which normal levels of anti-oxidant can be maintained by a retinol rich diet which may play a role in reducing the morbidity and mortality due to cancer.

  3. The New Nordic Diet

    DEFF Research Database (Denmark)

    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...... modifications of the diet are needed in order to make this food concept beneficial regarding phosphorus absorption....

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

    Science.gov (United States)

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

    2016-05-01

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

  5. Comparison of the novel vasodilator uridine triphosphate and adenosine for the measurement of fractional flow reserve

    DEFF Research Database (Denmark)

    Sivertsen, Jacob; Jensen, Jan Skov; Galatius, Søren;

    2014-01-01

    AIM: Examination of the fractional flow reserve (FFR) responses of intravenous (IV) adenosine with increasing doses of intracoronary (IC) adenosine versus IC uridine triphosphate (UTP) in patients with coronary artery disease. METHODS AND RESULTS: We measured FFR in 25 patients during continuous IV...... and IC infusion (using a microcatheter in the coronary ostium). Standard IV adenosine infusion (140 μg/kg/min) was compared to 8 equimolar incremental doses of IC UTP and IC adenosine (20, 40, 60, 80, 160, 240, 320 and 640 μg/min) in a randomized order. Across all doses, ΔFFR[IC UTP - IC adenosine......] was -0.038 ± 0.008, Pdose of IC UTP, FFR was significantly lower (FFR[IC UTP] = 0.62 ± 0.04) than during IV adenosine (FFR[IV adenosine] = 0.72 ± 0.05; P=.02) and IC adenosine (FFR[IC adenosine] = 0.68 ± 0.05; P=.03). Furthermore, UTP had significantly fewer side effects compared...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  9. Activation of A(2) adenosine receptors dilates cortical efferent arterioles in mouse

    DEFF Research Database (Denmark)

    Al-Mashhadi, Rozh H; Skøtt, Ole; Vanhoutte, Paul M;

    2009-01-01

    that the adenosine-induced vasodilatation was inhibited by the A(2)-specific receptor blocker 3,7-dimethyl-1-propargylxanthine. In the presence of this inhibitor, adenosine failed to alter the basal vessel diameter of quiescent efferent arterioles. Using primer-specific polymerase chain reaction we found...

  10. Adenosine receptors in COPD and asymptomatic smokers : effects of smoking cessation

    NARCIS (Netherlands)

    Versluis, Mieke; ten Hacken, Nick; Postma, Dirkje; Barroso, Begona; Rutgers, Bea; Geerlings, Marie; Willemse, Brigitte; Timens, Wim; Hylkema, Machteld

    2009-01-01

    Our group has shown that 1-year smoking cessation persisted or increased airway inflammation in chronic obstructive pulmonary disease (COPD). We compared adenosine and adenosine receptor (AR) expression in COPD and asymptomatic smokers (AS) before and after 1-year smoking cessation. Sputum cytospins

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

    OpenAIRE

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

    1986-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Brian P Lazzaro

    2015-04-01

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

  14. Adenosine Amine Congener as a Cochlear Rescue Agent

    Directory of Open Access Journals (Sweden)

    Srdjan M. Vlajkovic

    2014-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  16. Distribution of adenosine receptors in human sclera fibroblasts

    Science.gov (United States)

    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

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

    OpenAIRE

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    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 human...... muscle. Additionally, it remains to be determined what proportion of adenosine-induced flow elevation is specifically directed to muscle only. In the present study we measured thigh muscle capillary nutritive blood flow in nine healthy young men using positron emission tomography at rest and during...... femoral artery infusion of adenosine (1 mg * min(-1) * litre thigh volume(-1)), which has previously been shown to induce maximal whole thigh blood flow of ~8 L/min. This response was compared to the blood flow induced by moderate-high intensity one-leg dynamic knee extension exercise. Adenosine increased...

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik

    1997-01-01

    in the extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P muscle cells...... found to have ecto-forms of several enzymes involved in nucleotide metabolism, including ATPases capable of converting extracellular ATP to ADP and AMP. 5. Adenosine added to the cell medium was taken up by muscle cells and incorporated into the adenine nucleotide pool so that after 30 min of incubation......, over 95% of the adenosine label was present in ATP, ADP and AMP. A similar extent of incorporation of adenosine into the nucleotide pool was evident in the endothelial cells. 6. The present data suggest that contracting muscle cells induce an elevation in the extracellular adenosine concentration...

  4. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    Science.gov (United States)

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

    2005-08-22

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  6. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    Science.gov (United States)

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

    2005-08-22

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production. PMID:16023100

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

    Science.gov (United States)

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

    2005-04-01

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

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

    Science.gov (United States)

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

    2005-04-01

    The aim of the present study is to clarify the mechanism for the decrease in intraocular pressure by 2-alkynyladenosine derivatives in rabbits. The receptor binding analysis revealed that 2-(1-octyn-1-yl)adenosine (2-O-Ado) and 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) selectively bound to the A(2a) receptor with a high affinity. Ocular hypotensive responses to 2-O-Ado and 2-CN-Ado were inhibited by the adenosine A(2a)-receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), but not by the adenosine A(1)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or the adenosine A(2b)-receptor antagonist alloxazine. In addition, 2-O-Ado and 2-CN-Ado caused an increase in outflow facility, which was inhibited by CSC, but not by DPCPX or alloxazine. Moreover, 2-O-Ado and 2-CN-Ado increased cAMP in the aqueous humor, and the 2-O-Ado-induced an increase in cAMP was inhibited by CSC. These results suggest that 2-O-Ado and 2-CN-Ado reduced intraocular pressure via an increase in outflow facility. The ocular hypotension may be mainly mediated through the activation of adenosine A(2a) receptor, although a possible involvement of adenosine A(1) receptor cannot be completely ruled out. 2-O-Ado and 2-CN-Ado are useful lead compounds for the treatment of glaucoma. PMID:15821340

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    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

  12. Heart disease and diet

    Science.gov (United States)

    Diet - heart disease ... diet and lifestyle can reduce your risk of: Heart disease, heart attacks, and stroke Conditions that lead to heart disease, including high cholesterol , high blood pressure, and obesity ...

  13. Diets that Work

    Science.gov (United States)

    ... 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 ...

  14. Diet and Nutrition

    Science.gov (United States)

    ... 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 ( ...

  15. Diet and Exercise

    Science.gov (United States)

    ... 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 ...

  16. Diet and Exercise Tips

    Science.gov (United States)

    ... 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 ...

  17. Diet and Your Liver

    Science.gov (United States)

    ... 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 ...

  18. Caffeine in the diet

    Science.gov (United States)

    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 ...

  19. Effect of adenosine and adenosine receptor antagonist on Müller cell potassium channel in Rat chronic ocular hypertension models.

    Science.gov (United States)

    Yang, Zijian; Huang, Ping; Liu, Xiaohong; Huang, Shouyue; Deng, Lianfu; Jin, Zhe; Xu, Shuo; Shen, Xi; Luo, Xunda; Zhong, Yisheng

    2015-01-01

    Müller cells are principal glial cells in rat retina and have attracted much attention in glaucoma studies. However, it is not clear whether adenosine and adenosine receptor (AR) antagonists play any roles in the regulation of potassium channels in Müller cells and subsequently in the promotion of glutamine synthetase (GS) and L-Glutamate/L-Aspartate Transporter (GLAST) functions. We found that chronic ocular hypertension (COH) in rat down-regulated Müller cells Kir2.1, Kir4.1, TASK-1, GS and GLAST expressions and attenuated the peak of inward potassium current. Retinal ganglion cells (RGC) count was lower in the COH rats than that in the sham operation animals. Intravitreal injection of selective A2A AR antagonist SCH442416 up-regulated Müller cell Kir4.1, TASK-1, GS and GLAST expressions and enhanced inward potassium currents compared with those in the COH rats with vehicle control. Meanwhile, the RGC count was higher following intravitreal injection of SCH442416 in the COH rats than that after vehicle injection. The fact that PKA inhibitor H-89 blocked these SCH442416 effects suggested that the PKA signaling pathway was involved in the observed ocular responses following the intravitreal SCH442416 injection. PMID:26063641

  20. Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?

    Science.gov (United States)

    Brown, Andrew J

    2007-01-01

    Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-being and mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which can replace glucose as an energy source for the brain. One of these ketone bodies, beta-hydroxybutyrate (BHB), is an isomer of the notorious drug of abuse, GHB (gamma-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatment for alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoria often noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain. Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABA(B) receptors. I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells, perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans. These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood are timely and warranted, especially when considering their structural similarities and the popularity of ketogenic diets and GHB as a drug of abuse. PMID:17011713

  1. Diet quality assessment indexes

    OpenAIRE

    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...

  2. Vegetarian diets and children.

    Science.gov (United States)

    Sanders, T A; Reddy, S

    1994-05-01

    The diets and growth of children reared on vegetarian diets are reviewed. Excessive bulk combined with low energy density can be a problem for children aged vegetarian diets. It is suggested that vegans and vegetarians should use oils with a low ratio of linoleic to linolenic acid in view of the recently recognized role of docosahexaenoic acid in visual functioning. If known pitfalls are avoided, the growth and development of children reared on both vegan and vegetarian diets appears normal.

  3. Diet induced thermogenesis

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-01

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

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

    Science.gov (United States)

    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

  6. Diet quality assessment indexes

    Directory of Open Access Journals (Sweden)

    Kênia Mara Baiocchi de Carvalho

    2014-10-01

    Full Text Available 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, II or III' added to their names. Even validated indices usually find only modest associations between diet and risk of disease or death, raising questions about their limitations and the complexity associated with measuring the causal relationship between diet and health parameters. The objective of this review is to describe the main instruments used for assessing diet quality, and the applications and limitations related to their use and interpretation.

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

    Science.gov (United States)

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

    2008-02-01

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

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

    Science.gov (United States)

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

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists. PMID:25063794

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

    Science.gov (United States)

    Cheon, Yong-Pil

    2016-06-01

    Purine metabolism is known factor for nuclear maturation of oocytes through both follicle cells and oocyte itself. However, it is largely unknown the roles of purine metabolism in the oocyte competence for fertilization and early development. In this study, the effects of adenosine in oocyte competence for development were examined using adenosine and its synthetic inhibitors. Adenosine treatment from GV intact stage for 18 hr (fGV) caused of decrease the fertilization rate but of increase the cleavage rate compared from the other stage treatment groups. Hadacidin did not effect on fertilization rate but increased cleavage rate without stage specificity. Adenosine did not block the effects of hadacidin with the exception of fGV group. By the inhibition of purine synthetic pathways the fertilization rate was decreased in the fGV and fGVB groups but increased in the fMII group. Exogenous adenosine caused of decrease fertilization rate in the fGVB group but increase in the fMII group. Cleavage rate was dramatically increased in the adenosine treatment with synthetic inhibitors. It means that the metabolism of purine has stage specific effects on fertilization and cleavage. Exogenous adenosine had only can improve oocyte developmental competence when it treated at GV intact stage. On the other hand, endogenous synthesis in all maturation stage caused of increase the cleavage rate without effects on fertilization. These data suggest that adenosine at GV stage as a paracrine fashion and inhibitions of endogenous adenosine in all stage improve oocyte developmental competence.. PMID:27660830

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

    Science.gov (United States)

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

    2014-09-15

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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    BACKGROUND: Adenosine has been proposed to be a locally produced regulator of blood flow in skeletal muscle. However, the fundamental questions of to what extent adenosine is formed in skeletal muscle tissue of humans, whether it is present in the interstitium, and where it exerts its vasodilatory...... 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...... concentration and a higher FaBF (2.22+/-0.18 L/min; PATP, ADP, and AMP increased from...

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

    OpenAIRE

    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...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Teresa Riccioni

    2010-08-01

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

  17. The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Rongen, G.A.P.J.M.; Karemaker, J.M.; Wieling, W.; Marres, H.A.M.; Lenders, J.W.M.

    2004-01-01

    The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemorecepto

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    Adenosine is an endogenous neurotransmitter that is released from the brain during hypoxia and relaxes isolated human cerebral arteries. Many cerebral artery dilators cause migraine attacks. However, the effect of intravenous adenosine on headache and cerebral artery diameter has not previously...... been investigated in man and reports regarding the effect of intravenous adenosine on cerebral blood flow are conflicting. Twelve healthy participants received adenosine 80, 120 microg kg(-1) min(-1) and placebo intravenously for 20 min, in a double-blind, three-way, crossover, randomized design....... Headache was rated on a verbal scale (0-10). Regional cerebral blood flow (rCBF) with 133Xe inhalation and single-photon emission computed tomography (SPECT) and MCA flow velocity (V(MCA)) with transcranial Doppler, were measured in direct sequence. Six participants developed headache during 80 microg kg...

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

    Science.gov (United States)

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

    1975-01-01

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

  20. Actinides and rare earths complexation with adenosine phosphate nucleotides

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

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

    OpenAIRE

    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...

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

    Science.gov (United States)

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

    2009-01-01

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

  4. Cyclization of the phosphate side chain of adenosine triphosphate: formation of monoadenosine 5'-trimetaphosphate.

    Science.gov (United States)

    Glonek, T; Kleps, R A; Myers, T C

    1974-07-26

    Monoadenosine 5'-trimetaphosphate has been prepared from adeno-sine 5'-triphosphate by a carbodiimide-mediated condensation. The molecule was characterized by (3l)P nuclear magnetic resonance, and its (31)P spectrum was simulated through the assumption of a three-phosphorus spin system. The molecule is highly reactive and is rapidly converted to adenosine triphosphate upon contact with water. PMID:4834364

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Label-Free Sensing of Adenosine Based on Force Variations Induced by Molecular Recognition

    Directory of Open Access Journals (Sweden)

    Jingfeng Li

    2015-03-01

    Full Text Available We demonstrate a simple force-based label-free strategy for the highly sensitive sensing of adenosine. An adenosine ssDNA aptamer was bound onto an atomic force microscopy (AFM probe by covalent modification, and the molecular-interface adsorption force between the aptamer and a flat graphite surface was measured by single-molecule force spectroscopy (SMFS. In the presence of adenosine, the molecular recognition between adenosine and the aptamer resulted in the formation of a folded, hairpin-like DNA structure and hence caused a variation of the adsorption force at the graphite/water interface. The sensitive force response to molecular recognition provided an adenosine detection limit in the range of 0.1 to 1 nM. The addition of guanosine, cytidine, and uridine had no significant interference with the sensing of adenosine, indicating a strong selectivity of this sensor architecture. In addition, operational parameters that may affect the sensor, such as loading rate and solution ionic strength, were investigated.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Shashikala Magadi Dasegowda

    2015-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Sammeta V Raju

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

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

    Institute of Scientific and Technical Information of China (English)

    Roberto Federico Villa; Federica Ferrari; Antonella Gorini

    2012-01-01

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

  13. Adenosine Deaminase Activity in Chronic Lymphocytic Leukemia and Healthy Subjects

    Science.gov (United States)

    Ghaderi, Bayazid; Amini, Sabrieh; Maroofi, Farzad; Jalali, Chiya; Javanmardi, Mitra; Roshani, Daem; Abdi, Mohammad

    2016-01-01

    Background B cell chronic lymphocytic leukemia is one of the most frequent hematologic malignancies in the world. Cellular surface CD markers and serum Beta-2-microglobulin may be used as a prognostic tool in CLL patients. Objectives In the present study we introduce serum adenosine deaminase as a diagnostic marker in CLL. Materials and Methods Blood samples were collected from B-CLL and healthy subjects. White blood cell, red blood cell and platelet count and blood Erythrocyte sedimentation rate was recorded and serum Beta-2-microglobulin, Lactate dehydrogenase and total ADA enzyme activity were determined. Results Serum ADA activity was significantly higher in patients group than that of controls. ADA had a significant and direct correlation with B2M, WBC, LDH and ESR. However, there was not any relation between ADA and the stages of disease. Diagnostic cut-off, sensitivity and specificity of the serum ADA test were 27.97 U/L, 91% and 94%, respectively. Conclusions A higher ADA activity in patients group and its correlation with CLL markers were seen in our study. High diagnostic value of serum ADA in our study suggests that it might be considered as a useful screening tool among the other markers in CLL.

  14. An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation.

    Science.gov (United States)

    Shang, Luqing; Wang, Yaxin; Qing, Jie; Shu, Bo; Cao, Lin; Lou, Zhiyong; Gong, Peng; Sun, Yuna; Yin, Zheng

    2014-12-01

    Enterovirus 71 (EV71), one of the major causative agents of Hand-Foot-Mouth Disease (HFMD), causes severe pandemics and hundreds of deaths in the Asia-Pacific region annually and is an enormous public health threat. However, effective therapeutic antiviral drugs against EV71 are rare. Nucleoside analogues have been successfully used in the clinic for the treatment of various viral infections. We evaluated a total of 27 nucleoside analogues and discovered that an adenosine nucleoside analogue NITD008, which has been reported to be an antiviral reagent that specifically inhibits flaviviruses, effectively suppressed the propagation of different strains of EV71 in RD, 293T and Vero cells with a relatively high selectivity index. Triphosphorylated NITD008 (ppp-NITD008) functions as a chain terminator to directly inhibit the RNA-dependent RNA polymerase activity of EV71, and it does not affect the EV71 VPg uridylylation process. A significant synergistic anti-EV71 effect of NITD008 with rupintrivir (AG7088) (a protease inhibitor) was documented, supporting the potential combination therapy of NITD008 with other inhibitors for the treatment of EV71 infections.

  15. Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma.

    Science.gov (United States)

    ten Kate, J; van den Ingh, H F; Khan, P M; Bosman, F T

    1986-04-15

    Immunoreactive adenosine deaminase complexing protein (ADCP) was studied in 91 human colorectal adenocarcinomas. The expression of ADCP was correlated with that of secretory component (SC) and carcinoembryonic antigen (CEA), with the histological grade and the Dukes' stage of the carcinomas. The histological grade was scored semi-quantitatively according to 5 structural and 4 cytological variables. ADCP expression was observed in 3 different staining patterns, namely: (1) diffuse cytoplasmic (77% of the carcinomas); (2) granular cytoplasmic (13%); and (3) membrane-associated (66%). These patterns were observed alone or in combination. Eleven percent of the carcinomas exhibited no ADCP immunoreactivity. Linear regression analysis showed that the expression of ADCP correlates with that of SC and CEA. However, no significant correlation emerged between the histological parameters or the Dukes' stage and any of the immunohistological parameters. Comparison of the histological characteristics of carcinomas exhibiting little or no ADCP immunoreactivity with those showing extensive immunoreactivity, showed that membranous ADCP immunoreactivity occurs more frequently in well-differentiated carcinomas. Structural parameters showed a better correlation with membranous ADCP expression than the cytological variables. It is concluded that membranous expression of ADCP and CEA are indicators of a high level of differentiation as reflected primarily in the structural characteristics of the tumor. PMID:3957458

  16. Distribution of adenosine deaminase complexing protein (ADCP) in human tissues.

    Science.gov (United States)

    Dinjens, W N; ten Kate, J; van der Linden, E P; Wijnen, J T; Khan, P M; Bosman, F T

    1989-12-01

    The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process. PMID:2573631

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    DOU Ai-xia; WANG Xin

    2010-01-01

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

  1. DIET at the nanoscale

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Holloway Cameron J

    2010-11-01

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

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

    Science.gov (United States)

    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

  4. Diet Choices to Prevent Cancer

    Science.gov (United States)

    ... 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, ...

  5. Diet and Nutrition in Porphyria

    Science.gov (United States)

    ... 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 ...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    Robert Edward Sims

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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    Science.gov (United States)

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

    2007-12-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

    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

  16. Rapid tolerance against focal cerebral ischemia induced by isoflurane anesthesia is attenuated by adenosine A1 receptor antagonist in rats

    Institute of Scientific and Technical Information of China (English)

    刘艳红; 熊利泽

    2003-01-01

    The brief anesthesia with isoflurane induces rapid tolerance against focal cerebral ischemia in rats and adenosine A1 receptor antagonist, DPCPX, attenuates the beneficial effect of isoflurane preconditioning.

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

    Science.gov (United States)

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

    2016-03-01

    Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by β-adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y1 receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects. PMID:26732366

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

    Directory of Open Access Journals (Sweden)

    Justin

    2016-05-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  1. Promising Medicated Diet

    Institute of Scientific and Technical Information of China (English)

    Yang Wei

    2009-01-01

    @@ The founding conference of World Federation of Chinese Medicine Societies-Special Committee of Medicated Diet & Dietotherapy(WFCMS-SCMDAD).and the first world medicated diet and life nurturing academic seminar was held in the Great Hall of the People.Beijing,China,on August 11.A total of 400 experts and professors on medicated diet and life nurturing from 17 countries and regions including Japan,ROK,U.S.,Canada,U.K.,ect.Honorary President Professor Cai Guangxian delivered a welcoming speech to declare the organization's found.

  2. [Breastfeeding and vegan diet].

    Science.gov (United States)

    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.

  3. Biochemistry of an olfactory purinergic system: dephosphorylation of excitatory nucleotides and uptake of adenosine

    Energy Technology Data Exchange (ETDEWEB)

    Trapido-Rosenthal, H.G.; Carr, W.E.; Gleeson, R.A.

    1987-10-01

    The olfactory organ of the spiny lobster, Panulirus argus, is composed of chemosensory sensilla containing the dendrites of primary chemosensory neurons. Receptors on these dendrites are activated by the nucleotides AMP, ADP, and ATP but not by the nucleoside adenosine. It is shown here that the lobster chemosensory sensilla contain enzymes that dephosphorylate excitatory nucleotides and an uptake system that internalizes the nonexcitatory dephosphorylated product adenosine. The uptake of (/sup 3/H)-adenosine is saturable with increasing concentration, linear with time for up to 3 h, sodium dependent, insensitive to moderate pH changes and has a Km of 7.1 microM and a Vmax of 5.2 fmol/sensillum/min (573 fmol/micrograms of protein/min). Double-label experiments show that sensilla dephosphorylate nucleotides extracellularly; /sup 3/H from adenine-labeled AMP or ATP is internalized, whereas 32P from phosphate-labeled nucleotides is not. The dephosphorylation of AMP is very rapid; /sup 3/H from AMP is internalized at the same rate as /sup 3/H from adenosine. Sensillar 5'-ectonucleotidase activity is inhibited by ADP and the ADP analog alpha, beta-methylene ADP. Collectively, these results indicate that the enzymes and the uptake system whereby chemosensory sensilla of the lobster inactivate excitatory nucleotides and clear adenosine from extracellular spaces are very similar to those present in the internal tissues of vertebrates, where nucleotides have many neuroactive effects.

  4. Comparative transcriptome analysis of Bacillus subtilis responding to dissolved oxygen in adenosine fermentation.

    Directory of Open Access Journals (Sweden)

    Wen-Bang Yu

    Full Text Available Dissolved oxygen (DO is an important factor for adenosine fermentation. Our previous experiments have shown that low oxygen supply in the growth period was optimal for high adenosine yield. Herein, to better understand the link between oxygen supply and adenosine productivity in B. subtilis (ATCC21616, we sought to systematically explore the effect of DO on genetic regulation and metabolism through transcriptome analysis. The microarrays representing 4,106 genes were used to study temporal transcript profiles of B. subtilis fermentation in response to high oxygen supply (agitation 700 r/min and low oxygen supply (agitation 450 r/min. The transcriptome data analysis revealed that low oxygen supply has three major effects on metabolism: enhance carbon metabolism (glucose metabolism, pyruvate metabolism and carbon overflow, inhibit degradation of nitrogen sources (glutamate family amino acids and xanthine and purine synthesis. Inhibition of xanthine degradation was the reason that low oxygen supply enhanced adenosine production. These provide us with potential targets, which can be modified to achieve higher adenosine yield. Expression of genes involved in energy, cell type differentiation, protein synthesis was also influenced by oxygen supply. These results provided new insights into the relationship between oxygen supply and metabolism.

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

    Directory of Open Access Journals (Sweden)

    David J Hinton

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

  6. Diet for Ataxia

    Science.gov (United States)

    ... 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 ...

  7. Sea Lion Diet Data

    Data.gov (United States)

    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...

  8. Magnesium in diet

    Science.gov (United States)

    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 ...

  9. Diet - chronic kidney disease

    Science.gov (United States)

    ... Tips to keep from becoming thirsty include: Avoid salty foods Freeze some juice in an ice cube ... diet. Look for these words on food labels: Low-sodium No salt added Sodium-free Sodium-reduced Unsalted ...

  10. Diet - chronic kidney disease

    Science.gov (United States)

    ... 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 ...

  11. Interstitial Cystitis and Diet

    Science.gov (United States)

    ... 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 ( ...

  12. Are Detox Diets Safe?

    Science.gov (United States)

    ... 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 ...

  13. Diet and cancer

    Science.gov (United States)

    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 ...

  14. Vegan Diets and Hypothyroidism

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

  16. Vegan diets and hypothyroidism.

    Science.gov (United States)

    Tonstad, Serena; Nathan, Edward; Oda, Keiji; Fraser, Gary

    2013-11-20

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport

    DEFF Research Database (Denmark)

    Novak, Ivana; Hede, Susanne; Hansen, Mette

    2007-01-01

    Previously, we have shown that pancreatic acini release adenosine triphosphate (ATP) and ATP-handling enzymes, and pancreatic ducts express various purinergic P2 receptors. The aim of the present study was to establish whether pancreatic ducts also express adenosine receptors and whether...... these could be involved in secretory processes, which involve cystic fibrosis transmembrane regulator (CFTR) Cl(-) channels or Ca(2+)-activated Cl(-) channels and [Formula: see text] transporters. Reverse transcriptase polymerase chain reaction analysis on rat pancreatic ducts and human duct cell......) for duct cell lines. Whole-cell patch-clamp recordings on rat pancreatic ducts showed that, in about half of the recordings, adenosine depolarized the membrane voltage, and this was because of the opening of Cl(-) channels. Using a Cl(-)-sensitive fluorophore and single-cell imaging on duct cell lines...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    HE Fang; YU MingHui; WANG Shu

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hongping Dong

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

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

    Science.gov (United States)

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

    2008-01-01

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

  4. Caffeine's Attenuation of Cocaine-Induced Dopamine Release by Inhibition of Adenosine.

    Science.gov (United States)

    Malave, Lauren B; Broderick, Patricia A

    2014-06-01

    Background: It is well known that the reinforcing properties of cocaine addiction are caused by the sharp increase of dopamine (DA) in the reward areas of the brain. However, other mechanisms have been speculated to contribute to the increase. Adenosine is one system that is associated with the sleep-wake cycle and is most important in regulating neuronal activity. Thus, more and more evidence is pointing to its involvement in regulating DA release. The current study set out to examine the role of adenosine in cocaine-induced DA release. Methods: Increasing doses of cocaine, caffeine, and their combination, as well as, 8-cyclopentyltheophylline (CPT), an adenosine A1 antagonist (alone and in combination with cocaine) were used to denote a response curve. A novel biosensor, the BRODERICK PROBE(®) was implanted in the nucleus accumbens to image the drug-induced surge of DA release in vivo, in the freely moving animal in real time. Results: Combinations of cocaine and caffeine were observed to block the increased release of DA moderately after administration of the low dose (2.5 mg/kg cocaine and 12.5 mg/kg caffeine) and dramatically after administration of the high dose (10 mg/kg cocaine and 50 mg/kg caffeine), suggesting neuroprotection. Similarly, CPT and cocaine showed a decreased DA surge when administered in combination. Thus, the low and high dose of a nonselective adenosine antagonist, caffeine, and a moderate dose of a selective adenosine antagonist, CPT, protected against the cocaine-induced DA release. Conclusions: These results show a significant interaction between adenosine and DA release and suggest therapeutic options for cocaine addiction and disorders associated with DA dysfunction. PMID:25054079

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

    DEFF Research Database (Denmark)

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

    1982-01-01

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

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

    NARCIS (Netherlands)

    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

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

    LENUS (Irish Health Repository)

    Wakai, A

    2012-02-03

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

  8. Chronic hypoxia increases arterial blood pressure and reduces adenosine and ATP induced vasodilatation in skeletal muscle in healthy humans

    DEFF Research Database (Denmark)

    Calbet, J A L; Boushel, Robert Christopher; Robach, P;

    2014-01-01

    AIMS: To determine the role played by adenosine, ATP and chemoreflex activation on the regulation of vascular conductance in chronic hypoxia. METHODS: The vascular conductance response to low and high doses of adenosine and ATP was assessed in ten healthy men. Vasodilators were infused into the f...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-08-10

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

  10. Determination of the onset of beta-methyl-digoxin action by potentiation of the adenosine response in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Fukuda,Tamotsu

    1985-06-01

    Full Text Available The onset of beta-methyl-digoxin action was investigated by the potentiation of the adenosine response in guinea pigs and rats, and compared with that of digoxin and dipyridamole. A number of i.v. infusions of adenosine were given to determine the mean control adenosine response and its 95% confidence limits. After oral administration of the drugs, successive infusions of adenosine were continued until a drug-induced potentiation of the adenosine response was observed. The time of appearance of the potentiated adenosine response was marked as the onset of action of the drugs. The onset of action in guinea pigs was 9 to 12 min for 0.2 to 0.4 mg/kg of beta-methyl-digoxin, 90 to 100 min for 0.2 mg/kg of digoxin and 25 min for 5 mg/kg of dipyridamole. The maximal potentiation was 48.8 to 53.8% at 18 to 21 min for beta-methyl-digoxin, 74.5% at 130 min for digoxin and 74.8% at 80 min for dipyridamole. Adenosine infused i.v. into rats produced heart block, as in guinea pigs. However, in rats, the adenosine response was not potentiated by beta-methyl-digoxin and digoxin. Dipyridamole at a dose as high as 200 mg/kg produced 25.8% potentiation at 36 min after oral administration to rats.

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

    Science.gov (United States)

    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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-07-01

    Adenosine is a powerful central neuromodulator acting via opposing A1 (inhibitor) and A2a (activator) receptors. However, in the nucleus of the solitary tract (NTS), both adenosine receptor subtypes attenuate cardiopulmonary chemoreflex (CCR) sympathoinhibition of renal, adrenal, and lumbar sympathetic nerve activity and attenuate reflex decreases in arterial pressure and heart rate. Adenosine A1 receptors inhibit glutamatergic transmission in the CCR pathway, whereas adenosine A2a receptors most likely facilitate release of an unknown inhibitory neurotransmitter, which, in turn, inhibits the CCR. We hypothesized that adenosine A2a receptors inhibit the CCR via facilitation of GABA release in the NTS. In urethane-chloralose-anesthetized rats (n = 51), we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of the 5-HT3 receptor agonist phenylbiguanide (1-8 μg/kg) before and after selective stimulation of NTS adenosine A2a receptors [microinjections into the NTS of CGS-21680 (20 pmol/50 nl)] preceded by blockade of GABAA or GABAB receptors in the NTS [bicuculline (10 pmol/100 nl) or SCH-50911 (1 nmol/100 nl)]. Blockade of GABAA receptors virtually abolished adenosine A2a receptor-mediated inhibition of the CCR. GABAB receptors had much weaker but significant effects. These effects were similar for the different sympathetic outputs. We conclude that stimulation of NTS adenosine A2a receptors inhibits CCR-evoked hemodynamic and regional sympathetic reflex responses via a GABA-ergic mechanism. PMID:25910812

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    ROBERTO PAES-DE-CARVALHO

    2002-09-01

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

  19. 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.

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2012-11-21

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

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

    Science.gov (United States)

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

    2012-11-21

    In this, the third part of our series on the dielectric spectrum symmetrical broadening of water, we consider the nucleotide aqueous solutions. Where in Parts I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)] and II [E. Levy et al., J. Chem. Phys. 136, 114503 (2012)], the dipole-dipole or ion-dipole interaction had a dominant feature, now the interplay between these two types of dipole-matrix interactions will be considered. We present the results of high frequency dielectric measurements of different concentrations of adenosine monophosphate/adenosine-5'-triphosphate aqueous solutions. We observed the Cole-Cole broadening of the main relaxation peak of the solvent in the solutions. Moreover, depending on the nucleotide concentration, we observed both types of dipole-matrix interaction. The 3D trajectory approach (described in detail in Part I) is applied in order to highlight the differences between the two types of interaction. PMID:23181321

  2. Adenosine modulates hypoxia-induced responses in rat PC12 cells via the A2A receptor.

    Science.gov (United States)

    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

  3. New Nordic diet versus average Danish diet

    DEFF Research Database (Denmark)

    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...

  4. Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

    OpenAIRE

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  7. Diet and lung cancer

    DEFF Research Database (Denmark)

    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...

  8. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    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......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...... 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...

  9. Vegetarian diets and children.

    Science.gov (United States)

    Sanders, T A

    1995-08-01

    Although the general health and development of vegan and vegetarian children seem to be normal, there may be subtle differences compared with omnivores. They are at increased risk of iron deficiency, and impaired psychomotor development associated with iron deficiency has been reported in macrobiotic infants. Fortunately, this impairment is not permanent, and follow-up studies have reported higher-than-average intelligence quotients among older macrobiotic children. Several other hazards of vegetarian diets have been identified, including vitamin B12 deficiency, rickets, and a bulky diet that can restrict energy intake in the first few years of life; however, these pitfalls can be avoided easily, and children can be successfully reared on vegetarian diets.

  10. Vegan Diets and Hypothyroidism

    Directory of Open Access Journals (Sweden)

    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.

  11. Recent developments in A2B adenosine receptor ligands.

    Science.gov (United States)

    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

  12. REPRODUCTIVE CONDITION, GLOMERULAR ADENOSINE DIPHOSPHATASE ACTIVITY, AND PLATELET-AGGREGATION IN THE RAT - EFFECT OF ENDOTOXIN

    NARCIS (Netherlands)

    VISSCHER, CA; FAAS, MM; BAKKER, WW; SCHUILING, GA

    1993-01-01

    In experiment A, the activity of the glomerular antithrombotic enzyme adenosine diphosphatase (ADPase) and the sensitivity of this enzyme for endotoxin (1.0 mug/kg BW) in various reproductive conditions of female rats were studied through use of enzyme histochemical methods. In experiment B, the eff

  13. High fetal plasma adenosine concentration: a role for the fetus in preeclampsia?

    LENUS (Irish Health Repository)

    Espinoza, Jimmy

    2012-02-01

    OBJECTIVE: Clinical observations suggest a role for the fetus in the maternal manifestations of preeclampsia, but the possible signaling mechanisms remain unclear. This study compares the fetal plasma concentrations of adenosine from normal pregnancies with those from preeclampsia. STUDY DESIGN: This secondary data analysis included normal pregnancies (n = 27) and patients with preeclampsia (n = 39). Patients with preeclampsia were subclassified into patients with (n = 25) and without (n = 14) abnormal uterine artery Doppler velocimetry (UADV). RESULTS: Fetal plasma concentrations of adenosine were significantly higher in patients with preeclampsia (1.35 +\\/- 0.09 mumol\\/L) than in normal pregnancies (0.52 +\\/- 0.06 mumol\\/L; P < .0001). Fetal plasma concentrations of adenosine in patients with preeclampsia with abnormal UADV (1.78 +\\/- 0.15 mumol\\/L), but not with normal UADV (0.58 +\\/- 0.14 mumol\\/L), were significantly higher than in normal pregnancies (P < .0001). CONCLUSION: Patients with preeclampsia with sonographic evidence of chronic uteroplacental ischemia have high fetal plasma concentrations of adenosine.

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

    Science.gov (United States)

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

    2016-04-14

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

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

    Directory of Open Access Journals (Sweden)

    Felicita Pedata

    2014-01-01

    Full Text Available The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes. Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.

  16. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

    NARCIS (Netherlands)

    Hassan, Amel; Booth, Claire; Brightwell, Alex; Allwood, Zoe; Veys, Paul; Rao, Kanchan; Hoenig, Manfred; Friedrich, Wilhelm; Gennery, Andrew; Slatter, Mary; Bredius, Robbert; Finocchi, Andrea; Cancrini, Caterina; Aiuti, Alessandro; Porta, Fulvio; Lanfranchi, Arnalda; Ridella, Michela; Steward, Colin; Filipovich, Alexandra; Marsh, Rebecca; Bordon, Victoria; Al-Muhsen, Saleh; Al-Mousa, Hamoud; Alsum, Zobaida; Al-Dhekri, Hasan; Al Ghonaium, Abdulaziz; Speckmann, Carsten; Fischer, Alain; Mahlaoui, Nizar; Nichols, Kim E.; Grunebaum, Eyal; Al Zahrani, Daifulah; Roifman, Chaim M.; Boelens, Jaap; Davies, E. Graham; Cavazzana-Calvo, Marina; Notarangelo, Luigi; Gaspar, H. Bobby

    2012-01-01

    Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed o

  17. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds.

    Directory of Open Access Journals (Sweden)

    Shinji Kataoka

    Full Text Available In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3 on taste nerves as well as metabotropic (P2Y purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate, but not anterior (fungiform, palate taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields.

  18. Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships

    Directory of Open Access Journals (Sweden)

    Siew Lee Cheong

    2011-01-01

    Full Text Available In the past few decades, medicinal chemistry research towards potent and selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3 has been evolving rapidly. These antagonists are deemed therapeutically beneficial in several pathological conditions including neurological and renal disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of compounds have been successfully synthesized and identified as potent human adenosine receptor antagonists. In this paper, an overview of the structure-activity relationship (SAR profiles of promising nonxanthine pyrazolo derivatives is reported and discussed. We have emphasized the SAR for some representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3-d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This overview not only clarifies the structural requirements deemed essential for affinity towards individual adenosine receptor subtypes, but it also sheds light on the rational design and optimization of existing structural templates to allow us to conceive new, more potent adenosine receptor antagonists.

  19. Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

    Directory of Open Access Journals (Sweden)

    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

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Stevanovic G,

    2011-06-01

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

  2. Ischemic nucleotide breakdown increases during cardiac development due to drop in adenosine anabolism/catabolism ratio

    NARCIS (Netherlands)

    J.W. de Jong (Jan Willem); E. Keijzer (Elisabeth); T. Huizer (Tom); B. Schoutsen

    1990-01-01

    markdownabstractAbstract Our earlier work on reperfusion showed that adult rat hearts released almost twice as much purine nucleosides and oxypurines as newborn hearts did [Am J Physiol 254 (1988) H1091]. A change in the ratio anabolism/catabolism of adenosine could be responsible for this effect.

  3. Interaction of Beta-Hydroxy-Beta-Methylbutyrate Free Acid and Adenosine Triphosphate on Muscle Mass, Strength, and Power in Resistance Trained Individuals.

    Science.gov (United States)

    Lowery, Ryan P; Joy, Jordan M; Rathmacher, John A; Baier, Shawn M; Fuller, John C; Shelley, Mack C; Jäger, Ralf; Purpura, Martin; Wilson, Stephanie M C; Wilson, Jacob M

    2016-07-01

    Lowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7): 1843-1854, 2016-Adenosine-5'-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of β-hydroxy-β-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3-5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who continuously train at high levels such as elite athletes or military personnel.

  4. Up-regulation of striatal adenosine A(2A) receptors with iron deficiency in rats: effects on locomotion and cortico-striatal neurotransmission.

    Science.gov (United States)

    Quiroz, César; Pearson, Virginia; Gulyani, Seema; Allen, Richard; Earley, Christopher; Ferré, Sergi

    2010-07-01

    Brain iron deficiency leads to altered dopaminergic function in experimental animals, which can provide a mechanistic explanation for iron deficiency-related human sensory-motor disorders, such as Restless Legs Syndrome (RLS). However, mechanisms linking both conditions have not been determined. Considering the strong modulation exerted by adenosine on dopamine signaling, one connection could involve changes in adenosine receptor expression or function. In the striatum, presynaptic A(2A) receptors are localized in glutamatergic terminals contacting GABAergic dynorphinergic neurons and their function can be analyzed by the ability of A(2A) receptor antagonists to block the motor output induced by cortical electrical stimulation. Postsynaptic A(2A) receptors are localized in the dendritic field of GABAergic enkephalinergic neurons and their function can be analyzed by studying the ability of A(2A) receptor antagonists to produce locomotor activity and to counteract striatal ERK1/2 phosphorylation induced by cortical electrical stimulation. Increased density of striatal A(2A) receptors was found in rats fed during 3 weeks with an iron-deficient diet during the post-weaning period. In iron-deficient rats, the selective A(2A) receptor antagonist MSX-3, at doses of 1 and 3 mg/kg, was more effective at blocking motor output induced by cortical electrical stimulation (presynaptic A(2A) receptor-mediated effect) and at enhancing locomotor activation and blocking striatal ERK phosphorylation induced by cortical electrical stimulation (postsynaptic A(2A) receptor-mediated effects). These results indicate that brain iron deficiency induces a functional up-regulation of both striatal pre- and postsynaptic A(2A) receptor, which could be involved in sensory-motor disorders associated with iron deficiency such as RLS.

  5. Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus.

    Science.gov (United States)

    Sheen, Jiunn-Ming; Hsieh, Chih-Sung; Tain, You-Lin; Li, Shih-Wen; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Miao-Meng; Chen, Yu-Chieh; Huang, Li-Tung

    2016-04-08

    Increasing evidence has shown that many chronic diseases originate from early life, even before birth, through what are termed as fetal programming effects. Glucocorticoids are frequently used prenatally to accelerate the maturation of the lungs of premature infants. High-fat diets are associated with insulin resistance, but the effects of prenatal glucocorticoid exposure plus a postnatal high-fat diet in diabetes mellitus remain unclear. We administered pregnant Sprague-Dawley rats' intraperitoneal dexamethasone (0.1 mg/kg body weight) or vehicle at gestational days 14-20. Male offspring were administered a normal or high-fat diet starting from weaning. We assessed the effects of prenatal steroid exposure plus postnatal high-fat diet on the liver, pancreas, muscle and fat at postnatal day 120. At 15 and 30 min, sugar levels were higher in the dexamethasone plus high-fat diet (DHF) group than the vehicle plus high-fat diet (VHF) group in the intraperitoneal glucose tolerance test (IPGTT). Serum insulin levels at 15, 30 and 60 min were significantly higher in the VHF group than in the vehicle and normal diet group. Liver insulin receptor and adenosine monophosphate-activated protein kinase mRNA expressions and protein levels were lower in the DHF group. Insulin receptor and insulin receptor substrate-1 mRNA expressions were lower in the epididymal adipose tissue in the VHF and DHF groups. "Programming" of liver or epididymal adipose tissue resulted from prenatal events. Prenatal steroid exposure worsened insulin resistance in animals fed a high-fat diet.

  6. Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Jiunn-Ming Sheen

    2016-04-01

    Full Text Available Increasing evidence has shown that many chronic diseases originate from early life, even before birth, through what are termed as fetal programming effects. Glucocorticoids are frequently used prenatally to accelerate the maturation of the lungs of premature infants. High-fat diets are associated with insulin resistance, but the effects of prenatal glucocorticoid exposure plus a postnatal high-fat diet in diabetes mellitus remain unclear. We administered pregnant Sprague-Dawley rats’ intraperitoneal dexamethasone (0.1 mg/kg body weight or vehicle at gestational days 14–20. Male offspring were administered a normal or high-fat diet starting from weaning. We assessed the effects of prenatal steroid exposure plus postnatal high-fat diet on the liver, pancreas, muscle and fat at postnatal day 120. At 15 and 30 min, sugar levels were higher in the dexamethasone plus high-fat diet (DHF group than the vehicle plus high-fat diet (VHF group in the intraperitoneal glucose tolerance test (IPGTT. Serum insulin levels at 15, 30 and 60 min were significantly higher in the VHF group than in the vehicle and normal diet group. Liver insulin receptor and adenosine monophosphate-activated protein kinase mRNA expressions and protein levels were lower in the DHF group. Insulin receptor and insulin receptor substrate-1 mRNA expressions were lower in the epididymal adipose tissue in the VHF and DHF groups. “Programming” of liver or epididymal adipose tissue resulted from prenatal events. Prenatal steroid exposure worsened insulin resistance in animals fed a high-fat diet.

  7. Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus

    Science.gov (United States)

    Sheen, Jiunn-Ming; Hsieh, Chih-Sung; Tain, You-Lin; Li, Shih-Wen; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Miao-Meng; Chen, Yu-Chieh; Huang, Li-Tung

    2016-01-01

    Increasing evidence has shown that many chronic diseases originate from early life, even before birth, through what are termed as fetal programming effects. Glucocorticoids are frequently used prenatally to accelerate the maturation of the lungs of premature infants. High-fat diets are associated with insulin resistance, but the effects of prenatal glucocorticoid exposure plus a postnatal high-fat diet in diabetes mellitus remain unclear. We administered pregnant Sprague-Dawley rats’ intraperitoneal dexamethasone (0.1 mg/kg body weight) or vehicle at gestational days 14–20. Male offspring were administered a normal or high-fat diet starting from weaning. We assessed the effects of prenatal steroid exposure plus postnatal high-fat diet on the liver, pancreas, muscle and fat at postnatal day 120. At 15 and 30 min, sugar levels were higher in the dexamethasone plus high-fat diet (DHF) group than the vehicle plus high-fat diet (VHF) group in the intraperitoneal glucose tolerance test (IPGTT). Serum insulin levels at 15, 30 and 60 min were significantly higher in the VHF group than in the vehicle and normal diet group. Liver insulin receptor and adenosine monophosphate-activated protein kinase mRNA expressions and protein levels were lower in the DHF group. Insulin receptor and insulin receptor substrate-1 mRNA expressions were lower in the epididymal adipose tissue in the VHF and DHF groups. “Programming” of liver or epididymal adipose tissue resulted from prenatal events. Prenatal steroid exposure worsened insulin resistance in animals fed a high-fat diet. PMID:27070590

  8. [Acne and diet].

    Science.gov (United States)

    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

  9. The rock diet

    OpenAIRE

    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.

  10. Role of nitric oxide in adenosine-induced vasodilation in humans

    Science.gov (United States)

    Costa, F.; Biaggioni, I.; Robertson, D. (Principal Investigator)

    1998-01-01

    Vasodilation is one of the most prominent effects of adenosine and one of the first to be recognized, but its mechanism of action is not completely understood. In particular, there is conflicting information about the potential contribution of endothelial factors. The purpose of this study was to explore the role of nitric oxide in the vasodilatory effect of adenosine. Forearm blood flow responses to intrabrachial adenosine infusion (125 microg/min) were assessed with venous occlusion plethysmography during intrabrachial infusion of saline or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (12.5 mg/min). Intrabrachial infusions of acetylcholine (50 microg/min) and nitroprusside (3 microg/min) were used as a positive and negative control, respectively. These doses were chosen to produce comparable levels of vasodilation. In a separate study, a second saline infusion was administered instead of L-NMMA to rule out time-related effects. As expected, pretreatment with L-NMMA reduced acetylcholine-induced vasodilation; 50 microg/min acetylcholine increased forearm blood flow by 150+/-43% and 51+/-12% during saline and L-NMMA infusion, respectively (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.

  11. Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs.

    Science.gov (United States)

    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

  12. Electrochemical aptasensor for the detection of adenosine by using PdCu@MWCNTs-supported bienzymes as labels.

    Science.gov (United States)

    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

  13. High blood pressure and diet

    Science.gov (United States)

    ... 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 ...

  14. Diet History Questionnaire: Suggested Citations

    Science.gov (United States)

    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.

  15. Is Dieting OK for Kids?

    Science.gov (United States)

    ... 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? ...

  16. Diet and Inflammatory Bowel Disease.

    Science.gov (United States)

    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

  17. Activation of adenosine receptors and inhibition of cyclooxygenases: two recent pharmacological approaches to modulation of radiation suppressed hematopoiesis

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    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 ...

  19. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women

    Directory of Open Access Journals (Sweden)

    Silvestre R

    2004-11-01

    Full Text Available Abstract 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

  20. 腺苷和睡眠觉醒调节%Adenosine and Sleep-Wake Regulation

    Institute of Scientific and Technical Information of China (English)

    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

  1. Ethnicity and children's diets

    DEFF Research Database (Denmark)

    Nielsen, Annemette Ljungdalh; Krasnik, Allan; Holm, Lotte

    2015-01-01

    This study explores concerns and dilemmas connected with diet, health and child-feeding in families with ethnic minority background. The aim is to contribute to better targeting of dietary advice to ethnic minority parents in Denmark. Four focus group interviews were carried out with mothers...... dilemmas in dietary change; and (5) sources of nutritional advice. Public health authorities in Denmark tend to link diet-related health problems among ethnic minority populations with their ethnic identity, dichotomising ethnic and Danish dietary habits. This may overlook values and concerns other than...... those related to ethnicity that are sometimes more important in determining food habits. The present study found that child-feeding practices were shaped by two main aims: (1) securing and improving child health; and (2) ensuring multi-cultural eating competence in children. The results confirm...

  2. My New Diet

    Institute of Scientific and Technical Information of China (English)

    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.

  3. Diet and psychological health.

    Science.gov (United States)

    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

  4. Growth inhibitory effect and apoptosis induced by extracellular ATP and adenosine on human gastric carcinoma cells: involvement of intracellular uptake of adenosine

    Institute of Scientific and Technical Information of China (English)

    Ming-xia WANG; Lei-ming REN

    2006-01-01

    Aim: To study the growth inhibitory and apoptotic effects of adenosine triphosphate (ATP) and adenosine (ADO) on human gastric carcinoma (HGC)-27 cells in vitro and the mechanisms related to the actions of ATP and ADO. Methods: MTT assay was used to determine the reduction of cell viability. The morphological changes of HGC-27 cells induced by ATP or ADO were observed under fluorescence light microscope by acridine orange/ethidium bromide double-stained cells. The internucleosomal fragmentation of genomic DNA was detected by agarose gel electrophoresis. The apoptotic rate and cell-cycle analysis after treatment with ATP or ADO was determined by flow cytometry. Results: ATP, ADO and the intermediate metabolites, ADP and AMP, and the agonist of purinergic receptors, reduced cell viability of HGC-27 cells at doses of 0.3 and 1.0 mmol·L-1. The distribution of cell cycle phase and proliferation index (PI) value of HGC-27 cells changed when exposed to ATP or ADO at the concentrations of 0.1,0.3 and 1 mmol/L for 48 h. ATP and ADO both altered the distribution of cell cycle phase via Go/G1-phase arrest and significantly decreased PI value. Under light microscope, the tumor cells exposed to 0.3 mmol·L-1 ATP or ADO displayed morphological changes of apoptosis; a ladder-like pattern of DNA fragmentation obtained from HGC-27 cells treated with 0.1-1 mmol·L-1 ATP or ADO appeared in agarose gel electrophoresis; ATP and ADO induced the apoptosis of HGC-27 cells in a dose-dependent manner at concentrations between 0.03-1 mmol·L-1. The maximum apoptotic rate of HGC-27 cells exposed to ATP or ADO for 48 h was 13.53% or 15.9%, respectively. HGC-27 cell death induced by ATP or ADO was significantly inhibited by dipy-ridamole (10 mmol·L-1), an inhibitor of adenosine transporter, but was not affected by aminophylline, a broad inhibitor of PI receptors and pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetrasodium salt (30 nmol·L-1), a non-selective antagonist of P2

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

    Directory of Open Access Journals (Sweden)

    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

  6. Diet-Regulated Anxiety

    OpenAIRE

    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...

  7. Diet and Longevity

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Diet and gastric cancer

    OpenAIRE

    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...

  9. Acne and diet.

    Science.gov (United States)

    Wolf, Ronni; Matz, Hagit; Orion, Edith

    2004-01-01

    Forbidden foods? "The first law of dietetics seems to be: If it tastes good, it's bad for you" (Isaac Asimov, Russian-born biochemist and science fiction writer). This was essentially the Magna Carta for dermatologists of the 1950s: anything coveted by the teenage palate was suspect for morning after acne. Today, half a century later, although the slant has shifted away for this line of thinking in our dermatologic textbooks, several articles on the beliefs and perceptions of acne patients showed that nothing much has changed and that they expect us to give them detailed instructions of what "acne-related" foods they should avoid. In one such study(1), diet was the third most frequently implicated factor (after hormones and genetics) as the cause of the disease, with 32% of the respondents selecting diet as the main cause, and 44% thinking that foods aggravate acne. In another study that analyzed knowledge about causes of acne among English teenagers, 11% of the responders blamed greasy food as the main cause of the disease(2), whereas in another study found that 41% of final-year medical students of the University of Melbourne chose diet as an important factor of acne exacerbation on a final examination.(3)

  10. [Diet and migraine].

    Science.gov (United States)

    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

  11. Protective effects of inhibition of adenosine monophosphate activated protein kinase activity against cerebral ischemia-reperfusion injury in mice

    Institute of Scientific and Technical Information of China (English)

    补娟

    2013-01-01

    Objective To observe the effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on shape,function and inflammatory factor of microglia for mice after cerebral ischemia-reperfusion

  12. Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer

    NARCIS (Netherlands)

    H.J. Agteresch; P.C. Dagnelie (Pieter); A. van der Gaast (Ate); Th. Stijnen (Theo); J.H.P. Wilson (Paul)

    2000-01-01

    textabstractBACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors. In nonrandomized studies invo

  13. Regulation of adenosine triphosphate-sensitive potassium channels suppresses the toxic effects of amyloid-beta peptide (25-35)

    Institute of Scientific and Technical Information of China (English)

    Min Kong; Maowen Ba; Hui Liang; Peng Shao; Tianxia Yu; Ying Wang

    2013-01-01

    In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nω-nitro-L-arginine, also protected PC12 cells from intracellular reactive oxygen species levels. However, the H2O2-degrading enzyme catalase could that the increases in both mitochondrial membrane potential and reactive oxygen species levels adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β

  14. Analgesic effects of adenosine in syndrome X are counteracted by theophylline: a double-blind placebo-controlled study.

    Science.gov (United States)

    Eriksson, B E; Sadigh, B; Svedenhag, J; Sylvén, C

    2000-01-01

    It has been proposed that adenosine mediates ischaemic pain in humans. Patients with cardiac Syndrome X are hypersensitive to potential pain stimuli, including adenosine. On the other hand, recent findings suggest that low-dose adenosine infusion may have analgesic effects. Our aim was to test two hypotheses: (1) that the analgesic effect of adenosine is peripheral in origin, and (2) that part of the hypersensitivity to pain of patients with cardiac Syndrome X results from a disturbed mechanism of adenosine analgesia. A total of 12 female Syndrome X patients and eight healthy age-matched female controls were studied in a randomized, double-blind and placebo-controlled study. Adenosine (70 microg/min) or placebo was infused into the forearm via an intra-arterial catheter. After 15 min of infusion, a tourniquet on the upper arm was inflated to 225 mmHg to ensure arterial occlusion. The patient then carried out dynamic handgrip work at 60 Hz. Pain or discomfort in the forearm was estimated continuously according to the Borg CR-10 scale. After the first test, theophylline was infused for 10 min intravenously at a dose of 5 mg/kg body weight. The ischaemic forearm test was then repeated. On a second occasion, the procedure was repeated with the opposite treatment (adenosine/placebo). Only six of 12 Syndrome X patients completed the protocol because of pain during the catheterization procedure or an inability to establish an intra-arterial line. The time to onset of pain in the working, ischaemic forearm was greater for subjects treated with adenosine than for those treated with placebo, both in those Syndrome X patients who tolerated catheterization (49+/-27 s compared with 32+/-18 s; P600654

  15. Ischemic preconditioning protects post-ischemic renal function in anesthetized dogs: role of adenosine and adenine nucleotides

    Institute of Scientific and Technical Information of China (English)

    Fan-zhu LI; Shoji KIMURA; Akira NISHIYAMA; Matlubur RAHMAN; Guo-xing ZHANG; Youichi ABE

    2005-01-01

    Aim: To investigate the effects of renal ischemic preconditioning (IPC) on both renal hemodynamics and the renal interstitial concentrations of adenosine and adenine nucleotides induced by ischemia-reperfusion injury.Methods: Renal hemodynamics responses to ischemia-reperfusion injury in mongrel dog models were determined with or without multiple brief renal ischemic preconditioning treatments, as well as the adenosine A1 receptor antagonist (KW-3902),respectively.The renal interstitial concentrations of adenosine and adenine nucleotides in response to ischemia-reperfusion injury, either following 1-3 cycles of IPC or not, were measured simultaneously using microdialysis sampling technology.Results: One 10-min IPC, adenosine A1 receptor antagonist (KW3902) also shortened the recovery time of renal blood flow (RBF) and urine flow (UF), as well as mean blood pressure (BP).Advanced renal IPC attenuated the increment of adenosine and adenine nucleotides, as well as recovery time during the 60-min reperfusion which followed the 60-min renal ischemia.All of these recovery times were dependent on the cycles of 10-min IPC.The renal interstitial concentrations of adenosine and adenine nucleotides increased and decreased during renal ischemia and reperfusion, respectively.Conclusion: A significant relativity in dog models exists between the cycles of 10-min renal IPC and the recovery time of BP, UF, and RBF during the 60-min renal reperfusion following 60-min renal ischemia, respectively.Renal IPC can protect against ischemiareperfusion injury and the predominant effect of endogenous adenosine induced by prolonged renal ischemia; renal adenosine A1 receptor activation during the renal ischemia-reperfusion injury is detrimental to renal function.

  16. Differential modulation of ATP-induced calcium signalling by A1 and A2 adenosine receptors in cultured cortical astrocytes

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  18. Efficient, low-cost protein factories: expression of human adenosine deaminase in baculovirus-infected insect larvae.

    OpenAIRE

    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...

  19. Nucleoside-Derived Antagonists to A3 Adenosine Receptors Lower Mouse Intraocular Pressure and Act across Species

    OpenAIRE

    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...

  20. Activation of NTS A(1) adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex.

    Science.gov (United States)

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

    2012-09-01

    Previously we have shown that adenosine operating via the A(1) receptor subtype may inhibit glutamatergic transmission in the baroreflex arc within the nucleus of the solitary tract (NTS) and differentially increase renal (RSNA), preganglionic adrenal (pre-ASNA), and lumbar (LSNA) sympathetic nerve activity (ASNA>RSNA≥LSNA). Since the cardiopulmonary chemoreflex and the arterial baroreflex are mediated via similar medullary pathways, and glutamate is a primary transmitter in both pathways, it is likely that adenosine operating via A(1) receptors in the NTS may differentially inhibit regional sympathetic responses evoked by activation of cardiopulmonary chemoreceptors. Therefore, in urethane-chloralose-anesthetized rats (n = 37) we compared regional sympathoinhibition evoked by the cardiopulmonary chemoreflex (activated with right atrial injections of serotonin 5HT(3) receptor agonist phenylbiguanide, PBG, 1-8 μg/kg) before and after selective stimulation of NTS A(1) adenosine receptors [microinjections of N(6)-cyclopentyl adenosine (CPA), 0.033-330 pmol/50 nl]. Activation of cardiopulmonary chemoreceptors evoked differential, dose-dependent sympathoinhibition (RSNA>ASNA>LSNA), and decreases in arterial pressure and heart rate. These differential sympathetic responses were uniformly attenuated in dose-dependent manner by microinjections of CPA into the NTS. Volume control (n = 11) and blockade of adenosine receptor subtypes in the NTS via 8-(p-sulfophenyl)theophylline (8-SPT, 1 nmol in 100 nl) (n = 9) did not affect the reflex responses. We conclude that activation of NTS A(1) adenosine receptors uniformly inhibits neural and cardiovascular cardiopulmonary chemoreflex responses. A(1) adenosine receptors have no tonic modulatory effect on this reflex under normal conditions. However, when adenosine is released into the NTS (i.e., during stress or severe hypotension/ischemia), it may serve as negative feedback regulator for depressor and sympathoinhibitory reflexes

  1. Alteration of membrane phospholipid methylation by adenosine analogs does not affect T lymphocyte activation

    International Nuclear Information System (INIS)

    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

  2. Synthesis and Pharmacological Evaluation of Modified Adenosines Joined to Mono-Functional Platinum Moieties

    Directory of Open Access Journals (Sweden)

    Stefano D'Errico

    2014-07-01

    Full Text Available The synthesis of four novel platinum complexes, bearing N6-(6-amino-hexyladenosine or a 1,6-di(adenosin-N6-yl-hexane respectively, as ligands of mono-functional cisplatin or monochloro(ethylendiamineplatinum(II, is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of the adenosine base system and a primary amine of an alkyl chain installed on the C6 position of the purine. The cytotoxic behaviour of the synthesized complexes has been studied in A549 adenocarcinomic human alveolar basal epithelial and MCF7 human breast adenocarcinomic cancer cell lines, in order to investigate their effects on cell viability and proliferation.

  3. Platelet aggregation and serum adenosine deaminase (ADA) activity in pregnancy associated with diabetes, hypertension and HIV.

    Science.gov (United States)

    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

  4. Adenosine A2B receptor: from cell biology to human diseases

    Science.gov (United States)

    Sun, Ying; Huang, Pingbo

    2016-08-01

    Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide array of biological processes. Recently, significant advances have been made in our understanding of A2B adenosine receptor (A2BAR). In this review, we first summarize some of the general characteristics of A2BAR, and then we describe the multiple binding partners of the receptor, such as newly identified α-actinin-1 and p105, and discuss how these associated proteins could modulate A2BAR’s functions, including certain seemingly paradoxical functions of the receptor. Growing evidence indicates a critical role of A2BAR in cancer, renal disease, and diabetes, in addition to its importance in the regulation of vascular diseases and lung disease. Here, we also discuss the role of A2BAR in cancer, renal disease, and diabetes and the potential of the receptor as a target for treating these three diseases.

  5. A Case of Hypogammaglobulinemia with Enteroviral Meningoencephalitis, Associated with Increased Adenosine Deaminase in Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Alborizi Abdolvahab

    2009-06-01

    Full Text Available We describe the development of enterovirus meningoencephalitis associated with increased adenosine deaminase in cerebrospinal fluid of a 12-year-old boy, a known case of hypogamaglobulinemia despite monthly replacement of IVIg.The patient was referred to our center with fever, headache and vomiting for 10 days. CSF analysis was compatible with aseptic meningoencephalitis but high CSF protein (>200mg/dl and high level of adenosine deaminase in CSF (30IU/L were against the diagnosis of simple viral meningoencephalitis. Nested PCR of CSF for entrovirus was positive. Treatment with daily high-dose IVIg was commenced, with significant clinical improvement. For patients with increased ADA and lymphocytic pleocytosis in CSF, differential diagnoses should include enteroviral meningitis. Antibodies, although crucial, cannot on their own prevent enteroviral infection in some hypogamaglbulinemic patients.

  6. Adenosine deaminase complexing protein (ADCP): a transformation sensitive protein with potentials of a cancer marker.

    Science.gov (United States)

    Herbschleb-Voogt, E; Ten Kate, J; Meera Khan, P

    1983-01-01

    Several observations by independent investigators in the past have indicated that adenosine deaminase complexing protein (ADCP), present in considerable quantities in certain human tissues, was absent or decreased in the cancers originated from them. During the present study, electrophoretic analysis of adenosine deaminase (ADA) isozymes and radioimmunoassay for ADCP in the primary fibroblasts and the transformed as well as certain tumor derived cell lines have demonstrated that ADCP present in large quantities in the primary cells was absent or nearly absent in the transformed or tumor-derived cell lines. Though the mechanisms involved are not yet clear, the above observations indicate that ADCP has the potentials of a useful marker in the studies on transformed cells and cancer tissues. PMID:6133497

  7. GIRK channel activation via adenosine or muscarinic receptors has similar effects on rat atrial electrophysiology

    DEFF Research Database (Denmark)

    Wang, Xiaodong; Liang, Bo; Skibsbye, Lasse;

    2013-01-01

    and compare the electrophysiological effects of acetylcholine (ACh) and adenosine on GIRK channels in rat atria. Action potential duration at 90% repolarization (APD90), effective refractory period (ERP), and resting membrane potential (RMP) were investigated in isolated rat atria by intracellular recordings....... Both the adenosine analog N6-cyclopentyladenosine (CPA) and ACh profoundly shortened APD90 and ERP and hyperpolarized the RMP. No additive or synergistic effect of CPA and ACh coapplication was observed. To antagonize GIRK channel activation, the specific inhibitor rTertiapin Q (TTQ) was applied....... The coapplication of TTQ reversed the CPA and ACh-induced effects. When TTQ was applied without exogenous receptor activator, both APD90 and ERP were prolonged and RMP was depolarized, confirming a basal activity of the GIRK current. The results reveal that activation of A1 and M2 receptors has a profound and equal...

  8. Interaction of Divalent Metal Ions with the Adenosine Triphosphate Measured Using Nuclear Magnetic Resonance

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The interaction of adenosine triphosphate with divalent metal ions is important in biochemical functions. The effects of pH and metal ions Mg2+, Ca2+, Zn2+, Mn2+, and Co2+ on the chemical shift of the phosphate group of ATP have been studied using Nuclear Magnetic Resonance. The chemical shift of the β-phosphate of ATP is the most sensitive to pH. Ca2+ and Mg2+ bind with the α- and β-phosphate groups of ATP. Zn2+ binds to the adenosine ring hydrogen as well as to phosphate. The paramagnetic ions Mn2+ and Co2+ do not cause chemical shifts of the phosphate or proton peak. Mn2+ and Co2+ broaden the resonance peak only.

  9. Tumour necrosis factor-α and adenosine in endotoxin shockleading related cardiovascular symptoms

    Directory of Open Access Journals (Sweden)

    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.

  10. Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

    OpenAIRE

    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...

  11. Respiratory activity in medulla oblongata and its modulation by adenosine and opioids

    OpenAIRE

    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...

  12. Adenosine receptors in the immature brain : with special reference to their role in hypoxic ischemia

    OpenAIRE

    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...

  13. A Review of Tandem Mass Spectrometry Characterization of Adenosine Diphosphate-Ribosylated Peptides

    OpenAIRE

    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...

  14. Autoimmune dysregulation and purine metabolism in adenosine deaminase (ADA)-deficiency

    OpenAIRE

    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 ...

  15. Adenosine kinase inhibition protects against cranial radiation-induced cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Munjal M Acharya

    2016-06-01

    Full Text Available Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting, however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK. Adult rats exposed to cranial irradiation (10 Gy showed significant declines in performance of hippocampal-dependent cognitive function tasks (novel place recognition, novel object recognition, and contextual fear conditioning 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the fear conditioning task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP. Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection also against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS

  16. The effects of adenosine on plasma homocysteine levels and some other biochemical parameters

    OpenAIRE

    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...

  17. CD73-mediated adenosine production promotes stem cell-like properties in mouse Tc17 cells.

    Science.gov (United States)

    Flores-Santibáñez, Felipe; Fernández, Dominique; Meza, Daniel; Tejón, Gabriela; Vargas, Leonardo; Varela-Nallar, Lorena; Arredondo, Sebastián; Guixé, Victoria; Rosemblatt, Mario; Bono, María Rosa; Sauma, Daniela

    2015-12-01

    The CD73 ectonucleotidase catalyses the hydrolysis of AMP to adenosine, an immunosuppressive molecule. Recent evidence has demonstrated that this ectonucleotidase is up-regulated in T helper type 17 cells when generated in the presence of transforming growth factor-β (TGF-β), and hence CD73 expression is related to the acquisition of immunosuppressive potential by these cells. TGF-β is also able to induce CD73 expression in CD8(+) T cells but the function of this ectonucleotidase in CD8(+) T cells is still unknown. Here, we show that Tc17 cells present high levels of the CD73 ectonucleotidase and produce adenosine; however, they do not suppress the proliferation of CD4(+) T cells. Interestingly, we report that adenosine signalling through A2A receptor favours interleukin-17 production and the expression of stem cell-associated transcription factors such as tcf-7 and lef-1 but restrains the acquisition of Tc1-related effector molecules such as interferon-γ and Granzyme B by Tc17 cells. Within the tumour microenvironment, CD73 is highly expressed in CD62L(+) CD127(+) CD8(+) T cells (memory T cells) and is down-regulated in GZMB(+) KLRG1(+) CD8(+) T cells (terminally differentiated T cells), demonstrating that CD73 is expressed in memory/naive cells and is down-regulated during differentiation. These data reveal a novel function of CD73 ectonucleotidase in arresting CD8(+) T-cell differentiation and support the idea that CD73-driven adenosine production by Tc17 cells may promote stem cell-like properties in Tc17 cells. PMID:26331349

  18. [Concentration of prostaglandins and cyclic adenosine-3',5'-monophosphate in the tissues of rats].

    Science.gov (United States)

    Komissarenko, V P; Slavnov, V N; Epsheĭn, E V; Malinkovich, V D

    1977-04-01

    The content of prostaglandines (PG) and cyclic 3',5'-adenosine monphosphate (cAMP) was investigated in rat tissues by the radioisotopic method of competitive binding. Maximum quantities of both PG and cAMP were revealed in the same most actively functioning organs: the brain, incretory glands, small intestine. Fatty tissue showed minimum quantities of these substances. Results indicate a close functional relationship between the PG synthesis and adenylatecyclase activity in the body tissues.

  19. Molecular structural investigation of adenosine using spectroscopic and quantum computational calculations

    Science.gov (United States)

    Bakkiyaraj, D.; Periandy, S.; Xavier, S.

    2016-09-01

    In this study; spectroscopic investigation of adenosine having clinical importance was studied computationally and obtained results were compared with experimental ones. In this scope, geometric optimization and conformational analysis were studied and vibrational spectroscopic properties were studied on the most stable form. NMR and TD-DFT studies on the title compound were conducted with its experimental data. In addition atomic charge distribution, NBO, frontier molecular analysis, thermodynamic analysis and hyperpolarization features were studied.

  20. Photophysical processes of the spectroscopic RNA probe 2-(1-ethynylpyrene-adenosine (PyA

    Directory of Open Access Journals (Sweden)

    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.

  1. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency.

    OpenAIRE

    Montiel-Equihua, Claudia A; Thrasher, Adrian J.; Bobby Gaspar, H

    2009-01-01

    Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID) and especially adenosine deaminase (ADA)-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a pr...

  2. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

    OpenAIRE

    Thrasher, Adrian

    2009-01-01

    Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID) and especially adenosine deaminase (ADA)-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a pr...

  3. The in vivo respiratory phenotype of the adenosine A1 receptor knockout mouse.

    Science.gov (United States)

    Heitzmann, Dirk; Buehler, Philipp; Schweda, Frank; Georgieff, Michael; Warth, Richard; Thomas, Joerg

    2016-02-01

    The nucleoside adenosine has been implicated in the regulation of respiration, especially during hypoxia in the newborn. In this study the role of adenosine A1 receptors for the control of respiration was investigated in vivo. To this end, respiration of unrestrained adult and neonatal adenosine A1 receptor knockout mice (A1R(-/-)) was measured in a plethysmographic device. Under control conditions (21% O2) and mild hypoxia (12-15% O2) no difference of respiratory parameters was observed between adult wildtype (A1R(+/+)) and A1R(-/-) mice. Under more severe hypoxia (6-10% O2) A1R(+/+) mice showed, after a transient increase of respiration, a decrease of respiration frequency (fR) and tidal volume (VT) leading to a decrease of minute volume (MV). This depression of respiration during severe hypoxia was absent in A1R(-/-) mice which displayed a stimulated respiration as indicated by the enhancement of MV by some 50-60%. During hypercapnia-hyperoxia (3-10% CO2/97-90 % O2), no obvious differences in respiration of A1R(-/-) and A1R(+/+) was observed. In neonatal mice, the respiratory response to hypoxia was surprisingly similar in both genotypes. However, neonatal A1R(-/-) mice appeared to have more frequently periods of apnea during hypoxia and in the post-hypoxic control period. In conclusion, these data indicate that the adenosine A1 receptor is an important molecular component mediating hypoxic depression in adult mice and it appears to stabilize respiration of neonatal mice. PMID:26593641

  4. Possible regulation of the Salmonella typhimurium histidine operon by adenosine triphosphate phosphoribosyltransferase: large metabolic effects.

    OpenAIRE

    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...

  5. Inhibition of adenosine deaminase (ADA)-mediated metabolism of cordycepin by natural substances

    OpenAIRE

    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...

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

    OpenAIRE

    Shafie, Davood; Dohaei, Abolfazl; AMIN, Ahmad; Taghavi, Sepideh; Naderi, Nasim

    2015-01-01

    Background: Acute pulmonary vasoreactivity testing has been recommended in the diagnostic work-up of patients with idiopathic pulmonary arterial hypertension (IPAH). Pulmonary arteriolar capacitance (Cp) approximated by stroke volume divided by pulmonary pulse pressure (SV/PP) is considered as an independent predictor of mortality in patients with IPAH. Objectives: We sought to evaluate any differences in baseline and adenosine Cp between vasoreactive and non-vasoreactive IPAH patients tested...

  7. Adenosine Preconditioning versus Ischemic Preconditioning in Patients undergoing Off-Pump Coronary Artery Bypass (OPCAB

    Directory of Open Access Journals (Sweden)

    SeyedKhalil Forouzannia

    2015-10-01

    Full Text Available Background: During off-pump coronary artery bypass (OPCAB, the heart is subjected to ischemic and reperfusion injury. Preconditioning is a mechanism that permits the heart to tolerate myocardial ischemia. The aim of this study was to compare the effects of Adenosine preconditioning with ischemic preconditioning on the global ejection fraction (EF in patients undergoing OPCAB.Methods: In this single-blind, randomized controlled trial, sixty patients undergoing OPCAB were allocated into three equally-numbered groups through simple randomization: Adenosine group, ischemic group, and control group. The patients in the Adenosine group received an infusion of Adenosine. In the ischemic group, ischemic preconditioning was induced by the temporary occlusion of the left anterior descending coronary artery twice for a 2-minute period, followed by 3-minute reperfusion before bypass grafting of the first coronary vessel. The control group received an intravenous infusion of 0.9% saline. Blood samples at different times were sent for the measurement of creatine kinase isoenzyme MB (CK-MB and cardiac troponin I (cTnI. We also recorded electrocardiographic indices and clinical parameters, including postoperative use of inotropic drugs and preoperative and postoperative EF.Results: History of myocardial infarction, hyperlipidemia, diabetes mellitus, kidney disease, preoperative arrhythmias, and utilization of postoperative inotrope was the same between the three groups. The incidence of postoperative arrhythmias was not significant between the three groups. Also, there were no significant differences in preoperative and postoperative EF and the serum levels of enzymes (cTnI and CK-MB between the groups.Conclusion: Based on the findings of this study, there was no significant difference in the postoperative EF between the groups. Although the incidence of arrhythmias was higher in the ischemic preconditioning group than in the other groups, the difference

  8. Outcome of Patients With Adenosine-Induced ST Segment Depression and Normal Myocardial Perfusion

    International Nuclear Information System (INIS)

    The aim of the present study was to determine the outcome of patients with normal MPS and adenosine-induced ST segment depression. A total of 1867 patients underwent adenosine Tc99m-tetrofosmin MPS in nuclear medicine unit in Saudi German Hospital, Saudi Arabia, between January 2004 and May 2008. Their ECGs were checked for ST segment depression during adenosine infusion. All patients with ≥ 1 mm horizontal or down-sloping ST segment depression or≥ 1.5 mm up-sloping ST segment depression were included in the study. Fifty-six patients met our inclusion criteria, of which 45 (80%) were females. During the follow-up period, a total of 15 of patients ended up doing coronary angiography, either for high clinical suspicion or following a second positive MPS performed 6-18 months after the first study. Seven of them were positive for coronary artery disease and were subsequently treated with revascularization procedure, and 8 returned either normal angiography or non-obstructive coronary artery disease. Male diabetic smoking patients were more prevalent and underwent revascularization. The patients were followed up for a mean of 22.8 ±7.8 months. No cardiac deaths or myocardial infarctions were reported. It could be concluded that adenosine-induced ST segment depression in patients with normal myocardial perfusion was a benign finding and did not increase the very low risk of cardiac events in those patients. However, male smokers and/or diabetics might need further investigation. This suggestion needs further evaluation

  9. Cellular mechanisms for the treatment of chronic heart failure: the nitric oxide- and adenosine-dependent pathways.

    Science.gov (United States)

    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

  10. [Thallium-201 myocardial perfusion imaging during adenosine-induced coronary vasodilation in patients with ischemic heart disease].

    Science.gov (United States)

    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

  11. Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on ocular blood flow in rabbits.

    Science.gov (United States)

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

    2007-02-27

    Previously, we reported that a relatively selective adenosine A(2A) receptor agonist 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) elicited ocular hypotension in rabbits (Journal of Pharmacological Sciences 2005;97:501-509). In the present study, we investigated the effect of 2-CN-Ado on ocular blood flow in rabbit eyes. An intravitreal injection of 2-CN-Ado increased ocular blood flow, measured by a non-contact laser flowmeter. 2-CN-Ado-induced increase in ocular blood flow was accompanied with the retinal vasodilation. The increase in ocular blood flow was inhibited by an adenosine A(2A) receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, but not by an adenosine A(2B) receptor antagonist alloxazine or an adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. The repetitive applications of topical 2-CN-Ado twice a day for 7 days produced a persistent increase in ocular blood flow with ocular hypotension. These results suggest that 2-CN-Ado increases the ocular blood flow mainly via adenosine A(2A) receptor, and that the topical application of 2-CN-Ado for several days not only increases the ocular blood flow but also prolong ocular hypotension, indicating that 2-CN-Ado may be a useful lead compound for the treatment of ischemic retinal diseases such as glaucoma.

  12. Comparison of adenosine and exercise stress 201Tl myocardial perfusion imaging for diagnosing coronary heart disease in women

    International Nuclear Information System (INIS)

    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)

  13. Value of the adenosine test for diagnosis of dual AV nodal physiology in patients with AV nodal reentrant tachycardia

    Institute of Scientific and Technical Information of China (English)

    周斌全; 胡申江; 鲁端; 王建安

    2002-01-01

    Objectives: This study was aimed at assessing the value of the adenosine test for noninvasive diagnosis of dual AV nodal physiology(DAVNP) in patients with AV nodal reentrant tachycardia (AVNRT). Methods: 53 patients with paroxysmal supraventricular tachycardia (PSVT) were given incremental doses of adenosine intravenously during sinus rhythm before electrophysiological study. The adenosine test was repeated on a subset of 18 patients with AVNRT after radiofrequency catheter ablation. Results: Sudden increments of PR interval of more than 60 msec between two consecutive beats were observed in 26(83.9%) of 31 patients with typical AVNRT and 2 (9.1%) of 22 patients with AVRT and AT (P<0.01). The maximal PR increment between 2 consecutive beats in the AVNRT group(105±45ms) was significantly greater than that in the AVRT and AT group (20±13ms) (P<0.01).In postablation adenosine test, DAVNP was eliminated in all 8 patients who underwent slow pathway abolition that EPS showed the slow pathway disappeared and 4 of 10 patients who underwent slow pathway modification that EPS showed the slow pathway persisted. Six of 10 patients who exhibited persistent duality showed a marked reduction in the number of beats conducted in the slow pathway after adenosine injection(P<0.01).Conclusions: Administration of adenosine during sinus rhythm may be a useful bedside test for diagnosis of DAVNP in high percentage of patients with typical AVNRT and additionally for evaluating the effects of radiofrequency ablation.

  14. Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on ocular blood flow in rabbits.

    Science.gov (United States)

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

    2007-02-27

    Previously, we reported that a relatively selective adenosine A(2A) receptor agonist 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) elicited ocular hypotension in rabbits (Journal of Pharmacological Sciences 2005;97:501-509). In the present study, we investigated the effect of 2-CN-Ado on ocular blood flow in rabbit eyes. An intravitreal injection of 2-CN-Ado increased ocular blood flow, measured by a non-contact laser flowmeter. 2-CN-Ado-induced increase in ocular blood flow was accompanied with the retinal vasodilation. The increase in ocular blood flow was inhibited by an adenosine A(2A) receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, but not by an adenosine A(2B) receptor antagonist alloxazine or an adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. The repetitive applications of topical 2-CN-Ado twice a day for 7 days produced a persistent increase in ocular blood flow with ocular hypotension. These results suggest that 2-CN-Ado increases the ocular blood flow mainly via adenosine A(2A) receptor, and that the topical application of 2-CN-Ado for several days not only increases the ocular blood flow but also prolong ocular hypotension, indicating that 2-CN-Ado may be a useful lead compound for the treatment of ischemic retinal diseases such as glaucoma. PMID:17239401

  15. An enzyme-free strategy for ultrasensitive detection of adenosine using a multipurpose aptamer probe and malachite green.

    Science.gov (United States)

    Zhao, Hui; Wang, Yong-Sheng; Tang, Xian; Zhou, Bin; Xue, Jin-Hua; Liu, Hui; Liu, Shan-Du; Cao, Jin-Xiu; Li, Ming-Hui; Chen, Si-Han

    2015-08-01

    We report on an enzyme-free and label-free strategy for the ultrasensitive determination of adenosine. A novel multipurpose adenosine aptamer (MAAP) is designed, which serves as an effective target recognition probe and a capture probe for malachite green. In the presence of adenosine, the conformation of the MAAP is converted from a hairpin structure to a G-quadruplex. Upon addition of malachite green into this solution, a noticeable enhancement of resonance light scattering was observed. The signal response is directly proportional to the concentration of adenosine ranging from 75 pM to 2.2 nM with a detection limit of 23 pM, which was 100-10,000 folds lower than those obtained by previous reported methods. Moreover, this strategy has been applied successfully for detecting adenosine in human urine and blood samples, further proving its reliability. The mechanism of adenosine inducing MAAP to form a G-quadruplex was demonstrated by a series of control experiments. Such a MAAP probe can also be used to other strategies such as fluorescence or spectrophotometric ones. We suppose that this strategy can be expanded to develop a universal analytical platform for various target molecules in the biomedical field and clinical diagnosis.

  16. A3 Adenosine Receptors Modulate Hypoxia-inducible Factor-1a Expression in Human A375 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Stefania Merighi

    2005-10-01

    Full Text Available Hypoxia-inducible factor-1 (HIF-1 is a key regulator of genes crucial to many aspects of cancer biology. The purine nucleoside, adenosine, accumulates within many tissues under hypoxic conditions, including that of tumors. Because the levels of both HIF-1 and adenosine are elevated within the hypoxic environment of solid tumors, we investigated whether adenosine may regulate HIF-1. Here we show that, under hypoxic conditions (< 2% 02, adenosine upregulates HIF-1α protein expression in a dose-dependent and timedependent manner, exclusively through the A3 receptor subtype. The response to adenosine was generated at the cell surface because the inhibition of A3 receptor expression, by using small interfering RNA, abolished nucleoside effects. A3 receptor stimulation in hypoxia also increases angiopoietin-2 (Ang-2 protein accumulation through the induction of HIF-1α. In particular, we found that A3 receptor stimulation activates p44/p42 and p38 mitogen-activated protein kinases, which are required for A3-induced increase of HIF-1a and Ang-2. Collectively, these results suggest a cooperation between hypoxic and adenosine signals that ultimately may lead to the increase in HIF-1-mediated effects in cancer cells.

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

    Directory of Open Access Journals (Sweden)

    Zhenzhen Hu

    2013-01-01

    Full Text Available Cordycepin (3′-deoxyadenosine is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs, like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs. Sleep was recorded using electroencephalogram (EEG for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM sleep. Interestingly, cordycepin increased θ (theta waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.

  18. Voltammetric determination of adenosine and guanosine using fullerene-C(60)-modified glassy carbon electrode.

    Science.gov (United States)

    Goyal, Rajendra N; Gupta, Vinod K; Oyama, Munetaka; Bachheti, Neeta

    2007-02-28

    A fullerene-C(60)-modified glassy carbon electrode (GCE) is used for the simultaneous determination of adenosine and guanosine by differential pulse voltammetry. Compared to a bare glassy carbon electrode, the modified electrode exhibits an apparent shift of the oxidation potentials in the cathodic direction and a marked enhancement in the voltammetric peak current response for both the biomolecules. Linear calibration curves are obtained over the concentration range 0.5muM-1.0mM in 0.1M phosphate buffer solution at pH 7.2 with a detection limit of 3.02x10(-7)M and 1.45x10(-7)M for individual determination of adenosine and guanosine, respectively. The interference studies showed that the fullerene-C(60)-modified glassy carbon electrode exhibited excellent selectivity in the presence of hypoxanthine, xanthine, uric acid and ascorbic acid. The proposed procedure was successfully applied to detect adenosine and guanosine in human blood plasma and urine, without any preliminary pre-treatment. PMID:19071420

  19. Effect of caffeine and adenosine on G2 repair: mitotic delay and chromosome damage.

    Science.gov (United States)

    González-Fernández, A; Hernández, P; López-Sáez, J F

    1985-04-01

    Proliferating plant cells treated during the late S period with 5-aminouracil (AU), give the typical response that DNA-damaging agents induce, characterized by: an important mitotic delay, and a potentiation of the chromosome damage by caffeine post-treatment. The study of labelled prophases, after a tritiated thymidine pulse, allowed evaluation of the mitotic delay induced by AU as well as its reversion by caffeine, while chromosome damage was estimated by the percentage of anaphases and telophases showing chromosomal aberrations. Post-treatment with adenosine alone has shown no effect on mitotic delay or chromosomal damage. However, when cells after AU were incubated in caffeine plus adenosine, the chromosome damage potentiation was abolished without affecting the caffeine action on mitotic delay. As a consequence, we postulate that caffeine could have two effects on G2 cells with damaged DNA: the first, to cancel their mitotic delay and the second to inhibit some DNA-repair pathway(s). Only this last effect could be reversed by adenosine.

  20. GIRK channel activation via adenosine or muscarinic receptors has similar effects on rat atrial electrophysiology.

    Science.gov (United States)

    Wang, Xiaodong; Liang, Bo; Skibsbye, Lasse; Olesen, Søren-Peter; Grunnet, Morten; Jespersen, Thomas

    2013-08-01

    G protein-coupled inwardly rectifying K⁺ channels (GIRK) are important in the regulation of heart rate and atrial electrophysiology. GIRK channels are activated by G protein-coupled receptors, including muscarinic M₂ receptors and adenosine A₁ receptors. The aim of this study was to characterize and compare the electrophysiological effects of acetylcholine (ACh) and adenosine on GIRK channels in rat atria. Action potential duration at 90% repolarization (APD₉₀), effective refractory period (ERP), and resting membrane potential (RMP) were investigated in isolated rat atria by intracellular recordings. Both the adenosine analog N6-cyclopentyladenosine (CPA) and ACh profoundly shortened APD₉₀ and ERP and hyperpolarized the RMP. No additive or synergistic effect of CPA and ACh coapplication was observed. To antagonize GIRK channel activation, the specific inhibitor rTertiapin Q (TTQ) was applied. The coapplication of TTQ reversed the CPA and ACh-induced effects. When TTQ was applied without exogenous receptor activator, both APD₉₀ and ERP were prolonged and RMP was depolarized, confirming a basal activity of the GIRK current. The results reveal that activation of A₁ and M₂ receptors has a profound and equal effect on the electrophysiology in rat atrium. This effect is to a major extent mediated through GIRK channels. Furthermore, these results support the notion that atrial GIRK currents from healthy hearts have a basal component and additional activation can be mediated via at least 2 different receptor mechanisms. PMID:23609329