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Sample records for adenosine ketogenic diet

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

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

    2009-09-01

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

  2. Ketogenic Diets and Pain

    Masino, Susan A.; Ruskin, David N.

    2013-01-01

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

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

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

    2012-07-01

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

  4. Nonfasting Versus Initial Fasting Ketogenic Diet

    J Gordon Millichap

    2005-02-01

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

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

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

    2016-01-01

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

  6. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

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

    2009-01-01

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

  7. Carnitine Level Changes with the Ketogenic Diet

    J Gordon Millichap

    2002-01-01

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

  8. Ketogenic diets, mitochondria, and neurological diseases

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

    2014-01-01

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

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

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

    2013-01-01

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

  10. Ketogenic Diet for Obesity: Friend or Foe?

    Antonio Paoli

    2014-02-01

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

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

    Korsholm, Kirsten; Law, Ian

    2013-01-01

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

  12. Ketogenic diets and physical performance

    Phinney SD

    2004-08-01

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

  13. Ketogenic diets and physical performance

    Phinney Stephen D

    2004-08-01

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

  14. Glut1 deficiency syndrome and novel ketogenic diets.

    Klepper, Joerg; Leiendecker, Baerbel

    2013-08-01

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

  15. The Ketogenic Diet 2011: How It Works

    Keren Politi

    2011-01-01

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

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

    J Gordon Millichap

    2006-09-01

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

  17. Ketogenic Diet for Epilepsy with Type 1 Diabetes

    J Gordon Millichap

    2010-01-01

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

  18. Ketogenic diets, mitochondria, and neurological diseases.

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

    2014-11-01

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

  19. Ketogenic diet and astrocyte/neuron metabolic interactions

    Vamecq Joseph

    2007-05-01

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

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

    Alberto VERROTTI

    2009-12-01

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

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

    J. Gordon Millichap

    2015-11-01

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

  2. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets

    GiuseppeBiagini

    2014-04-01

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

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

    Suvasini Sharma

    2014-01-01

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

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

    Sharma, Suvasini; Jain, Puneet

    2014-07-01

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

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

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

    2009-01-01

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

  6. Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets

    GiuseppeBiagini; MaddalenaMarchiò; ElenaTimofeeva

    2014-01-01

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

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

    Kossoff, Eric H.; Rho, Jong M

    2009-01-01

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

  8. The ketogenic diet for type II bipolar disorder.

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

    2013-01-01

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

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

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

    2014-01-01

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

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

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

    2013-01-01

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

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

    Yeou-mei Christiana Liu; Huei-Shyong Wang

    2013-01-01

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

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

    Suvasini Sharma; Puneet Jain

    2014-01-01

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

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

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

    2010-01-01

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

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

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

    2013-01-01

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

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

    Alonso-Moraga Ángeles

    2008-10-01

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

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

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

    2015-01-01

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

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

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

    2012-01-01

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

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

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

    2010-01-01

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

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

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

    2010-01-01

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

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

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

    2010-01-01

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

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

    Milene L Brownlow

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

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

    Servadei Franco

    2010-04-01

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

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

    Adithya Sivaraju

    2015-01-01

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

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

    Ahad GHAZAVI

    2014-07-01

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

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

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

    2012-01-01

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

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

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

    2014-01-01

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

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

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

    2013-08-01

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

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

    Yeou-mei Christiana Liu

    2013-02-01

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

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

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

    2014-01-01

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

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

    Mohammadreza ALAEI

    2010-04-01

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

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

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

    2014-01-01

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

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

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

    2016-01-01

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

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

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

    2016-06-01

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

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

    Dustin, Simone M.; Stafstrom, Carl E

    2016-01-01

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

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

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

    2016-01-01

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

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

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

    2016-01-01

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

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

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2014-01-01

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

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

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

    2016-07-01

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

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

    Mohammadreza ALAEI

    2010-03-01

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

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

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

    2014-03-01

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

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

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

    2011-01-01

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

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

    Antonio Paoli

    2013-12-01

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

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

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

    2012-01-01

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

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

    Adam Zajac

    2014-06-01

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

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

    Paoli Antonio

    2012-07-01

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

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

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

    2016-09-01

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

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

    Greene, Robert W

    2011-01-01

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

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

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

    2013-01-01

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

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

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

    2016-09-01

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

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

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

    2015-01-01

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

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

    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

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

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

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

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

    2012-01-01

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

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

    Lioudmila Pliss

    2016-06-01

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

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

    Huei-Shyong Wang

    2012-02-01

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

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

    Zhou Weihua

    2007-02-01

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

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

    Mukherjee Purna

    2008-11-01

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

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

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés

    2011-01-01

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

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

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

    2011-01-01

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

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

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

    2016-09-01

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

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

    Jones, A W; Rössner, S

    2007-03-01

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

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

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

    2016-09-01

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

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

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

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

    Humala Nelson

    2006-04-01

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

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

    Femke Streijger

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

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

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

    2016-05-01

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

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

    Seyfried B

    2009-09-01

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

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

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

    2016-01-01

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

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

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

    2016-01-01

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

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

    Angela M Poff

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

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

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

    2009-01-01

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

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

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés

    2011-01-01

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

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

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

    2015-08-01

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

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

    Naval Jordi

    2010-12-01

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

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

    Carla Barbosa Nonino-Borges

    2004-12-01

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

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

    Hendriksen Jos GM

    2011-01-01

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

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

    Vorgerd, M; Zange, J

    2007-01-01

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

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

    Mengmeng Lv

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

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

    Mavropoulos John C

    2008-12-01

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

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

    Hepburn Juanita

    2005-12-01

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

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

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

    2010-10-15

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

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

    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

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

    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

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

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

    2016-01-01

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

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

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

    2016-07-01

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

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

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

    2014-01-01

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

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

    李玲; 王纪文

    2014-01-01

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

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

    宣自学; 袁守军

    2016-01-01

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

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

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

    2014-10-01

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

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

    徐文成; 陶玺宬; 周自云; 吴德; 唐久来

    2015-01-01

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

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

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

    2016-08-01

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

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

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

    2006-01-01

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

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

    Mantis John G

    2004-10-01

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

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

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

    2015-10-01

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

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

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

    2016-05-01

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

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

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

    2015-01-01

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

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

    A M Poff

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

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

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

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

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

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

    2015-01-01

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

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

    Alexsandra Tomé

    2003-06-01

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

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

    郝光伟; 王海玉; 何德明; 陈榆升; 吴国豪; 张波

    2014-01-01

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

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

    Ligia M Marcos Plasencia

    2007-12-01

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

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

    Neal EG

    2014-01-01

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

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

    Neal, Elizabeth

    2014-01-01

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

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

    Sueli Rizzutti

    2006-10-01

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

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

    中华医学会儿科学分会神经学组生酮饮食疗法协作组

    2013-01-01

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

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

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

    2014-01-01

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

  8. Diets

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

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

    Neal EG

    2014-04-01

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

  10. The Modified Atkins Diet in Refractory Epilepsy

    Suvasini Sharma; Puneet Jain

    2014-01-01

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

  11. The modified atkins diet in refractory epilepsy.

    Sharma, Suvasini; Jain, Puneet

    2014-01-01

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

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

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

    2006-01-01

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

  13. Diets

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

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

    2010-04-01

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

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

    Andrew J Kim

    2015-04-01

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

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

    Gregory L Holmes

    2008-01-01

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

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

    Larsen, Mogens; Kristensen, Niels Bastian

    2012-01-01

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

  18. Adenosine in exercise adaptation.

    Simpson, R E; Phillis, J. W.

    1992-01-01

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

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

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

    2011-01-01

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

  20. Adenosine Receptors and Asthma

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

    2009-01-01

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

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

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

    2013-01-01

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

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

    周厚福; 李成荣; 廖建湘; 王国兵; 林素芳; 陈黎

    2015-01-01

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

  3. Adenosine and sleep

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A1 receptors, 3H-L-PIA binding was measured. The Bmax values for 3H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in 3H-L-PIA binding resulted from REM sleep deprivation and not from stress

  4. Adenosine and sleep

    Yanik, G.M. Jr.

    1987-01-01

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

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

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

    2013-12-01

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

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

    Liebhaber, Gisela Maria

    2005-01-01

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

  7. Adenosine and Sleep

    Bjorness, Theresa E.; Greene, Robert W.

    2009-01-01

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

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

    Gianfranco Cappello

    2012-01-01

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

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

    de Mello Maria; Ventrucci Gislaine; Gomes-Marcondes Maria

    2002-01-01

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

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

    Björklund, Olga

    2008-01-01

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

  11. Adenosine-Associated Delivery Systems

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

    2016-01-01

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

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

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

    2015-01-01

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

  13. MODIFIED ATKINS DIET FOR INTRACTABLE CHILDHOOD EPILEPSY

    Mohammad BARZEGAR

    2010-12-01

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

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

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

    2013-08-01

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

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

    Torgersen, Linn-Christin Haugland

    2014-01-01

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

  16. Adenosine-induced activation of esophageal nociceptors.

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

    2011-03-01

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

  17. Adenosine in inflammatory joint diseases

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

    2007-01-01

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

  18. Role of extracellular adenosine in Drosophila

    FENCKOVÁ, Michaela

    2011-01-01

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

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

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

    2013-11-01

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

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

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

    2014-04-01

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

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

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

  2. Optical Aptasensors for Adenosine Triphosphate

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

    2016-01-01

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

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

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

    2014-01-01

    Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies. Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of β-adrenergic receptors. Because BAT...... that adenosine-A2A signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies....

  4. Adenosine regulation of alveolar fluid clearance

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

    2007-01-01

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

  5. Adenosine triphosphate inhibition of yeast trehalase.

    Panek, A D

    1969-09-01

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

  6. Role of adenosine receptors in caffeine tolerance

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

  7. Electrocardiographic profile of adenosine pharmacological stress testing

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

    2015-01-01

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

  8. Adenosine stress protocols for myocardial perfusion imaging

    Baškot Branislav

    2008-01-01

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

  9. Internalization and desensitization of adenosine receptors

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

    2007-01-01

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

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

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

    2016-01-01

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

  11. Paleolithic diet

    Malus, Katja

    2014-01-01

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

  12. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    2010-04-01

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

  13. Study of Ectonucleotidases and Adenosine Deaminases in Drosophila

    PREUER, Kristina

    2013-01-01

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

  14. Internalization and desensitization of adenosine receptors.

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

    2008-01-01

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

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

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

  16. Adenosine: An immune modulator of inflammatory bowel diseases

    Jeff Huaqing Ye; Vazhaikkurichi M Rajendran

    2009-01-01

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

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

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

    2015-11-14

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

  18. Vegetarian Diet

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

  19. Vegetarian Diet

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

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

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

    2014-02-01

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

  1. Adenosine receptors and asthma in humans

    Wilson, C N

    2008-01-01

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

  2. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    Kleynhans, Janke

    2013-01-01

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

  3. Role of adenosine in oligodendrocyte precursor maturation

    Elisabetta Coppi

    2015-04-01

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

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

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

    1989-12-01

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

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

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

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

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

    2010-01-01

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

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

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

  8. Adenosine A1 receptor agonists inhibit trigeminovascular nociceptive transmission

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

    2002-01-01

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

  9. A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment

    Ohta, Akio

    2016-01-01

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

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

    V Haktan Ozacmak; Hale Sayan

    2007-01-01

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

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

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

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

    M Sudha Swaraga; L Charitha; M Adinarayana

    2005-07-01

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

  13. Characterization of adenosine binding proteins in human placental membranes

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

  14. Characterization of adenosine binding proteins in human placental membranes

    Hutchison, K.A.

    1989-01-01

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

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

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

    2008-01-01

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

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

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

    2016-01-01

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

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

    Sachdeva, Sakshi; Gupta, Monika

    2012-01-01

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

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

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

  19. A High-Affinity Adenosine Kinase from Anopheles Gambiae

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

    2011-12-31

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

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

    Lynge, J; Juel, C; Hellsten, Y

    2001-12-01

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

  1. IBS Diet

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

  2. Mediterranean Diet

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

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

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

    2014-01-01

    Aim: We investigated the role of adenosine in citalopram-induced cardiotoxicity. Materials and Methods: Protocol 1: Rats were randomized into four groups. Sodium cromoglycate was administered to rats. Citalopram was infused after the 5% dextrose, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; A 1 receptor antagonist), 8-(-3-chlorostyryl)-caffeine (CSC; A 2a receptor antagonist), or dimethyl sulfoxide (DMSO) administrations. Protocol 2: First group received 5% dextrose intraperitoneally 1 hour...

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

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

    2015-01-01

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

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

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

    2012-01-01

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

  6. Proton transfer in oxidized adenosine self-aggregates.

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

    2013-10-14

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

  7. Distribution of adenosine receptors in human sclera fibroblasts

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

    2008-01-01

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

  8. Diet and Spondylitis

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

  9. Nutrition and Diet

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

  10. Diet and Nutrition

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

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

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

    2016-03-15

    Adenosine is an important regulator of the immune response, and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies showed that adenosine receptor agonists can be anti- or proinflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1-20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8-14 d postimmunization, shortly before EAU expression; however, ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses, and this effect was γδ T cell dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help to improve the design of ADA- and adenosine receptor-targeted therapies. PMID:26856700

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

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

    1985-11-01

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

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

    Garvin Fiona

    2009-08-01

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

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

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

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

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

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

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

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

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

    2013-02-01

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

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

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

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

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

    2016-05-01

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

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

    Dela, F; Stallknecht, B

    1999-01-01

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

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

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

    1972-04-28

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

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

    Ross, Ashley E.; Venton, B. Jill

    2014-01-01

    Adenosine modulates dopamine in the brain via A1 and A2A receptors, but that modulation has only been characterized on a slow time scale. Recent studies have characterized a rapid signaling mode of adenosine that suggests a possible rapid modulatory role. Here, fast-scan cyclic voltammetry was used to characterize the extent to which transient adenosine changes modulate stimulated dopamine release (5 pulses at 60 Hz) in rat caudate putamen brain slices. Exogenous adenosine was applied and dop...

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

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

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

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

    2012-01-01

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

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

    ROBERTO PAES-DE-CARVALHO

    2002-01-01

    The nucleoside adenosine plays an important role as a neurotransmitter or neuromodulator in the central nervous system, including the retina. In the present paper we review compelling evidence showing that adenosine is a signaling molecule in the developing retina. In the chick retina, adenosine transporters are present since early stages of development before the appearance of adenosine A1 receptors modulating dopamine-dependent adenylate cyclase activity or A2 receptors that directly activa...

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

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

    2016-06-01

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

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

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

    2010-01-01

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

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

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

    2015-12-01

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

  9. Iodine in diet

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

  10. Caffeine in the diet

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

  11. Searching Inhibitors of Adenosine Kinase by Simulation Methods

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

    2006-01-01

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

  12. Adenosine receptor modulation of seizure susceptibility in rats

    Adenosine is considered to be a neuromodulator or cotransmitter in the periphery and CNS. This neuromodulatory action of adenosine may be observed as an anticonvulsant effect. Dose-response curves for R-phenylisopropyladenosine (PIA), cycohexyladenosine (CHA), 2-chloroadenosine (2-ClAdo), N-ethylcarboxamidoadenosine (NECA) and S-PIA were generated against PTZ seizure thresholds in the rat. The rank order of potency for adenosine agonists to elevate PTZ seizure threshold was R-PIA > 2-ClAdo > NECA > CHA > S-PIA. R-PIA was approximately 80-fold more potent than S-PIA. This 80-fold difference in potency between the diasteriomers of PIA was consistent with an A1 adenoise receptor-mediated response. The anticonvulsant action of 2-ClAdo was reversed by pretreatment with theoplylline. Chronic administration of theophylline significantly increased the specific binding of 3H-cyclohexyladenosine in membranes of the cerebral cortex and cerebellum of the rat. Chronic exposure to theophylline produced a significant increase in the densities of both the high- and low-affinity forms of A1 adenosine receptors in the cerebral cortex

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

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

    2016-09-01

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

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

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

    1991-04-01

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

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

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

    2012-12-01

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

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

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

    2009-01-01

    Adenosine can induce vasodilation in skeletal muscle, but to what extent adenosine exerts its effect via formation of other vasodilators and whether there is redundancy between adenosine and other vasodilators remain unclear. We tested the hypothesis that adenosine, prostaglandins, and NO act in...

  17. Low-salt diet

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

  18. Lifestyle and diet

    Opie, Lionel H

    2014-01-01

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

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

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

    2015-10-01

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

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

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

    2014-01-01

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

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

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

    2013-01-01

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

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

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

    2015-04-01

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

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

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

    2016-03-15

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

  4. Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

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

    2013-01-01

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

  5. The emerging role of adenosine deaminases in insects

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

    2005-01-01

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

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

    Kavianipour, Mohammad

    2002-01-01

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

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

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

    2013-09-01

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

  8. Anxiolytic activity of adenosine receptor activation in mice.

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

    1995-10-01

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

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

    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

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

    de Mello Maria

    2002-04-01

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