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Sergei S Likhodii

Publications and source records attributed to Sergei S Likhodii.

10 recordsLinked to original sources
PubMed2006

A ketogenic diet and diallyl sulfide do not elevate afterdischarge thresholds in adult kindled rats.

INTRODUCTION: Acetone has been shown to have broad-spectrum anticonvulsant actions in animal seizure models and has been hypothesized to play a role in the anticonvulsant mechanism of the ketogenic diet (KD). The present study examined the ability of a KD to elevate amygdaloid afterdischarge thresholds (ADT) in fully kindled rats. The effects of the KD were studied in the presence and absence of diallyl sulfide (DAS), an inhibitor of acetone metabolism. METHODS: Twenty-four adult male rats were kindled to 30 stage 5 seizures. Afterdischarge thresholds (ADT) were determined. Subjects were then administered one of the following diets: (1) KD+V (vehicle; KD+V); (2) KD+DAS; (3) control diet+V (CD+V); (4) CD+DAS. They were stimulated every second day. Blood sampling was performed every second day--on non-stimulating days--to determine levels of glucose, beta-hydroxybutyrate, acetoacetate, and acetone. After 20 days, ADTs were re-determined. RESULTS: Blood acetone concentrations were significantly higher in the KD+DAS group as compared to the other groups, although they did not reach "therapeutic levels". None of the treatments, however, elevated ADTs. CONCLUSIONS: The KD was unable to elevate amygdaloid ADTs in fully kindled rats. Although subjects in the KD+DAS group achieved significant elevations of blood acetone, these concentrations (e.g. 0.2 mM) were much lower than those (>2.0 mM) previously shown to confer anticonvulsant activity. There appears to be large difference between humans and rats in their ability to produce elevated blood acetone levels on the KD. These data suggest that adult rats are not ideal subjects for modeling the anticonvulsant actions of the KD.

3-Hydroxybutyric Acid↗
PubMed2005

Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet.

OBJECTIVE: The high-fat ketogenic diet has long been used to treat refractory childhood seizures, but whether there is a relation between the degree of ketosis and effectiveness of seizure control remains unclear. Frequent measurements of plasma ketones are difficult in children so the goal was to determine the utility of breath acetone as a marker of systemic ketosis and seizure control in children given the ketogenic diet because of seizures refractory to medication. METHODS: In experiment I, breath acetone and plasma ketones were assessed every 2 h during an 8-h test day in seven children. In experiment II, a preliminary assessment of the possible relation between breath acetone and seizure frequency was made over 14 d in five children and one adolescent on the ketogenic diet. RESULTS: Breath acetone was positively and curvilinearly related to plasma acetone (r2 = 0.99, P < 0.0001), plasma acetoacetate (r2 = 0.89, P < 0.0001), and plasma beta-hydroxybutyrate (r2 = 0.94, P < 0.0001). No significant relation was found between breath acetone and seizure frequency or change in seizure frequency. CONCLUSIONS: Breath acetone is indicative of systemic ketosis while on the ketogenic diet. However, owing to the wide range of seizure types and plasma acetone, more subjects will be needed to determine whether there is a clear link between breath acetone and seizure frequency or decreased seizure frequency while on the high-fat ketogenic diet.

Adolescent↗
PubMed2004

Effect of the ketogenic diet on the activity level of Wistar rats.

Children, adolescents, and adults with epilepsy often also show symptoms associated with attention-deficit/hyperactivity disorder (ADHD). The ketogenic diet, which is administered to children with epilepsy refractory to drug therapy, seems to improve behavior in individuals with symptoms of ADHD. The basis for this improvement is unknown, although it seems to be unrelated to seizure control. The present research was designed to investigate the effect of two ketogenic diets on the behavior of normal adult male rats. Two experiments were conducted. In experiment 1, 36 subjects were placed on one of three diets: a control diet, a 6.3:1 ketogenic diet, and a 4:1 ketogenic diet. In experiment 2, 20 subjects were placed either on a control diet or on a 4:1 ketogenic diet. The activity level of each subject was measured using an open field test. Time spent immobile, grooming, and in exploratory behavior was measured for 600 s. Subjects were tested once before initiation of the diets and once while on the diets. No significant group differences were found in activity level before initiation of the diets. After initiation of the diets, subjects in both ketogenic groups showed a significantly lower activity level than the rats on the control diet. The ketogenic diet decreases activity level in an animal model. This behavioral change may relate to the improved behavior seen when children with symptoms of ADHD are placed on the diet.

Adolescent↗
PubMed2003

Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet.

The ketogenic diet (KD), a treatment for drug-resistant epilepsy, elevates brain acetone. Acetone has been shown to suppress experimental seizures. Whether elevation of acetone is the basis of the anticonvulsant effects of the KD and whether acetone, like the KD, antagonizes many different types of seizures, however, is unknown. This study investigated the spectrum of the anticonvulsant effects of acetone in animal seizure models. Rats were injected with acetone intraperitoneally. Dose-response effects were measured in four different models: (1) the maximal electroshock test, which models human tonic-clonic seizures; (2) the subcutaneous pentylenetetrazole test, which models human typical absence seizures; (3) the amygdala kindling test, which models human complex partial seizures with secondary generalization; and (4) the AY-9944 test, which models chronic atypical absence seizures, a component of the Lennox-Gastaut syndrome. Acetone suppressed seizures in all of the models, with the following ED(50)'s (expressed in mmol/kg): maximal electroshock, 6.6; pentylenetetrazole, 9.7; generalized kindled seizures, 13.1; focal kindled seizures, 26.5; AY-9944, 4.0. Acetone appears to have a broad spectrum of anticonvulsant effects. These effects parallel the effects of the KD. Elevation of brain acetone therefore may account for the efficacy of the KD in intractable epilepsy.

Acetone↗
PubMed2002

Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals.

BACKGROUND: Ketogenic diets are used therapeutically to treat intractable seizures. Clinically, it appears that the maintenance of ketosis is crucial to the efficacy of the diet in ameliorating seizures. To understand how ketosis and seizure protection are related, a reliable, noninvasive measure of ketosis that can be performed frequently with minimal discomfort is needed. OBJECTIVE: The objective was to determine which index, breath acetone or urinary acetoacetate, is more strongly related to the plasma ketones acetoacetate and beta-hydroxybutyrate. DESIGN: After fasting overnight for 12 h, 12 healthy adults consumed 4 ketogenic meals over 12 h. Blood, breath, and urine samples were collected hourly. Blood was analyzed for plasma acetoacetate and beta-hydroxybutyrate, breath for acetone, and urine for acetoacetate. RESULTS: By the end of the 12-h dietary treatment, plasma acetoacetate, plasma beta-hydroxybutyrate, and breath acetone had increased 3.5-fold, whereas urinary acetoacetate increased 13-fold when measured enzymatically and 25-fold when measured with urinary ketone dipsticks. Plasma acetoacetate was best predicted by breath acetone (R(2) = 0.70, P < 0.0001). Plasma beta-hydroxybutyrate was equally predicted by breath acetone and urinary acetoacetate (R(2) = 0.54, P = 0.0040). CONCLUSIONS: Breath acetone is as good a predictor of ketosis as is urinary acetoacetate. Breath acetone analysis is noninvasive and can be performed frequently with minimal discomfort to patients. As an indicator of ketosis in epilepsy patients consuming a ketogenic diet, breath acetone may be useful for understanding the mechanism of the diet, elucidating the importance of ketosis in seizure protection, and ultimately, enhancing the efficacy of the diet by improving patient monitoring.

3-Hydroxybutyric Acid↗
PubMed2002

Breath acetone as a measure of systemic ketosis assessed in a rat model of the ketogenic diet.

BACKGROUND: The mechanism of a high-fat, low-carbohydrate ketogenic diet (KD) in alleviating drug-resistant epilepsy is unknown but may be related to systemic ketosis induced under this treatment. The need for frequent measurement of systemic ketosis, which is essential for improving maintenance of the KD in patients and for studying mechanism of the KD action, has prompted us to validate the breath acetone test as a fast, reliable, and noninvasive tool for ketosis assessment. METHODS: A rat model of the KD that allowed frequent blood sampling was used to investigate how well breath acetone reflects plasma beta-hydroxybutyrate (beta-HBA), the most commonly measured ketone body. Rat pups (20 days of age) were introduced to and maintained on a KD or control diet for 33 days. During this period, breath acetone, plasma beta-HBA, blood glucose, and body weight were measured approximately every 4th day. A correlational analysis of breath acetone and plasma beta-HBA was conducted. RESULTS: Breath acetone was found to be a significant predictor of plasma beta-HBA over a clinically relevant range of beta-HBA concentrations (r(2) = 0.75; P <0.001). We have proposed a general formula that allows the value of plasma beta-HBA to be estimated based on breath acetone measurement. CONCLUSIONS: Breath acetone is an accurate measure of mild to moderate systemic ketosis. The noninvasive nature of this test will be useful for day-to-day implementation of the KD, searching for better forms of this diet, and understanding the role of ketosis in the mechanism of the KD action.

3-Hydroxybutyric Acid↗
PubMed2002

Ketogenic diet: does acetone stop seizures?

BACKGROUND: The mechanism of action of the ketogenic diet, a therapy for refractory epilepsy, is unknown. Our hypothesis is that acetone, one of three ketones elevated by the ketogenic diet, is directly responsible for the diet's anticonvulsant effects. This study examined the basic concepts of this hypothesis. MATERIAL/METHODS: Rats were acutely injected with acetone intraperitoneally at doses of 1 or 10 mmol/kg, or received acetone chronically in drinking water (1% v/v) for 10 days before being injected with a 1 mmol/kg dose of acetone. Controls consumed regular water and were injected with vehicle. A pentylenetetrazole seizure test was administered 15 min after the injections. Following the test, acetone was measured in the cerebrospinal fluid. RESULTS: A 10 mmol/kg injection of acetone suppressed seizures in 60% of rats (P<0.05). A chronic administration of acetone followed by a 1 mmol/kg injection suppressed seizures in 47% of rats (P<0.05). The acetone concentrations in these rats were 10.3I2.3 and 1.0I0.2 mmol/L, respectively. The effect of the acute 1 mmol/kg injection (without acetone pretreatment) was not statistically significant. This dose elevated acetone to 1.1I0.1 mmol/L in the cerebrospinal fluid. CONCLUSIONS: Our findings suggest that acetone is an anticonvulsant and that chronic administration may enhance its action. Linking acetone to the effects of the ketogenic diet requires further research. In particular, it will be important to confirm that the ketogenic diet generates relevant concentrations of acetone.

Acetone↗