Effect of ketogenic diet on nucleotide hydrolysis and hepatic enzymes in blood serum of rats in a lithium-pilocarpine-induced status epilepticus

The ketogenic diet (KD) is a high-fat and low-carbohydrate diet, used for treating refractory epilepsy in children. We have previously shown alterations in nucleotidase activities from the central nervous system and blood serum of rats submitted to different models of epilepsy. In this study we investigated the effect of KD on nucleotidase activities in the blood serum, as well if KD has any influence in the activity of liver enzymes such as alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities in Wistar rats submitted to the lithium–pilocarpine model of epilepsy. At 21 days of age, rats received an injection of lithium chloride and, 18–19 h later, they received an injection of pilocarpine hydrochloride for status epilepticus induction. The results reported herein show that seizures induced by lithium–pilocarpine elicit a significant increase in ATP hydrolysis and alkaline phosphatase activity, as well as a decrease in ADP hydrolysis and aspartate aminotransferase activity. The KD is a rigorous regimen that can be associated with hepatic damage, as shown herein by the elevated activities of liver enzymes and 5′-nucleotidase in blood serum. Further studies are necessary to investigate the mechanism of inhibition of lithium on nucleotidases in blood serum.     

A review of low-carbohydrate ketogenic diets

In response to the emerging epidemic of obesity in the United States, a renewal of interest in alternative diets has occurred, especially in diets that limit carbohydrate intake. Recent research has demonstrated that low-carbohydrate ketogenic diets can lead to weight loss and favorable changes in serum triglycerides and high-density lipoprotein cholesterol. This review summarizes the physiology and recent clinical studies regarding this type of diet.     

A ketogenic diet did not prevent effects on the ectonucleotidases pathway promoted by lithium-pilocarpine-induced status epilepticus in rat hippocampus

A Ketogenic Diet (KD) mimics the anticonvulsant effects of fasting, which are known to suppress seizures. The purinergic system has been investigated in the matter of epilepsy development, especially the nucleoside adenosine, which has been considered a natural brain anticonvulsant. During epileptic seizures, extracellular adenosine concentration rises rapidly to micromolar levels. Adenosine can exert its anticonvulsant functions, after its release by nucleoside bidirectional transport, or by production through the sequential catabolism of ATP by ectonucleotidases, such as E-NTPDases (ectonucleoside triphosphate diphosphohydrolases) and ecto-5??-nucleotidase. Here, we have investigated the effect of a ketogenic diet on the nucleotide hydrolysis and NTPDases expression in the lithium-pilocarpine (Li-Pilo) model of epilepsy. For the induction of Status Epileticus (SE), 21-day-old female Wistar rats received an i.p. injection of lithium chloride (127?mg/kg) and 18?C19?h later an i.p. injection of pilocarpine hydrochloride (60?mg/kg). The control groups received an injection of saline. After induction of SE, the control and Li-Pilo groups received standard or ketogenic diets for 6?weeks. The lithium-pilocarpine exposure affected the ATP (a decrease of between 8?% and 16?%) and ADP (an increase of between 18?% and 22?%) hydrolysis in both groups whereas the diet did not impact the nucleotide hydrolysis. NTPDase2 and 3 mRNA expressions decreased in the Li-Pilo group (41?% and 42?%). This data highlights the participation of the purinergic system in the pathophysiology of this model of epilepsy, since nucleotide hydrolysis and NTPDase expressions were altered by Li-Pilo exposure, with no significant effects of the ketogenic diet. However, the interaction between purinergic signaling and a ketogenic diet on epilepsy still needs to be better elucidated.     

Confusion in the nomenclature of ketogenic diets blurs evidence

Reviews in Endocrine and Metabolic Disorders - Ketogenic diets have been proposed as a non-pharmacological strategy for the management of several chronic conditions. Their efficacy and safety have...     

The management of status epilepticus

Status epilepticus is a major medical emergency associated with significant morbidity and mortality. Status epilepticus is best defined as a continuous, generalized, convulsive seizure lasting > 5 min, or two or more seizures during which the patient does not return to baseline consciousness. Lorazepam in a dose of 0.1 mg/kg is the drug of first choice for terminating status epilepticus. Patients who continue to have clinical or EEG evidence of seizure activity after treatment with lorazepam should be considered to have refractory status epileptics and should be treated with a continuous infusion of propofol or midazolam. This article reviews current information regarding the management of status epilepticus in adults.     

Metabolic syndrome and low-carbohydrate ketogenic diets in the medical school biochemistry curriculum

One of Robert Atkins contributions was to define a diet strategy in terms of an underlying metabolic principle ("the science behind Atkins"). The essential feature is that, by reducing insulin fluxes, lipids are funnelled away from storage and oxidized. Ketosis can be used as an indicator of lipolysis. A metabolic advantage is also proposed: controlled carbohydrates leads to greater weight loss per calorie than other diets. Although the Atkins diet and its scientific rationale are intended for a popular audience, the overall features are consistent with current metabolic ideas. We have used the Atkins controlled-carbohydrate diet as a focal point for teaching nutrition and metabolism in the first-year medical school curriculum. By presenting metabolism in the context of the current epidemic of obesity and of metabolic syndrome and related disorders, we provide direct application of the study of metabolic pathways, a subject not traditionally considered by medical students to be highly relevant to medical practice. We present here a summary of the metabolic basis of the Atkins diet as we teach it to medical students. We also discuss a proposed mechanism for metabolic advantage that is consistent with current ideas and that further brings out ideas in metabolism for students. The topics that are developed include the role of insulin and glucagon in lipolysis, control of lipoprotein lipase, the glucose-glycogen-gluconeogenesis interrelations, carbohydrate-protein interactions and ketosis. In essence, the approach is to expand the traditional feed-fast (post-absorptive) cycles to include the effect of low-carbohydrate meals: the disease states studied are generalized from traditional study of diabetes to include obesity and metabolic syndrome. The ideal diet for weight loss and treatment of metabolic syndrome, if it exists, remains to be determined, but presenting metabolism in the context of questions raised by the Atkins regimen prepares future physicians for critical analysis of clinical and basic metabolic information.     

Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets

Ketogenic diets (KDs) are used for treatment of refractory epilepsy and metabolic disorders. The classic saturated fatty acid-enriched (SAT) KD has a fat:carbohydrate plus protein ratio of 4:1, in which the predominant fats are saturated. We hypothesized that a polyunsaturated fat-enriched (POLY) KD would induce a similar degree of ketosis with less detrimental effects on carbohydrate and lipid metabolism. Twenty healthy adults were randomized to two different weight-maintaining KDs for 5 d. Diets were 70% fat, 15% carbohydrate, and 15% protein. The fat contents were 60 or 15% saturated, 15 or 60% polyunsaturated, and 25% monounsaturated for SAT and POLY, respectively. Changes in serum beta-hydroxybutyrate, insulin sensitivity (S(I)), and lipid profiles were measured. Mean circulating beta-hydroxybutyrate levels increased 8.4 mg/dl in the POLY group (P = 0.0004), compared with 3.1 mg/dl in the SAT group (P = 0.07). S(I) increased significantly in the POLY group (P = 0.02), whereas total and low-density lipoprotein cholesterol increased significantly in the SAT group (both P = 0.002). These data demonstrate that a short-term POLY KD induces a greater level of ketosis and improves S(I), without adversely affecting total and low-density lipoprotein cholesterol, compared with a traditional SAT KD. Thus, a POLY KD may be superior to a classical SAT KD for chronic administration.     

Effect of short-term ketogenic diet on redox status of human blood

The present study investigated the effect of a ketogenic diet on the blood redox status of healthy female subjects. Twenty healthy females with mean body mass index of 21.45 +/- 2.05 kg/m(2) were provided a low-carbohydrate (55 +/- 6 g; 13% total energy), high-fat (138 +/- 16 g; 74% total energy), calorie-restricted (-465 +/- 115 kcal/d) diet. The followings were tested prior to and after 14 days consumption of the diet: Whole body, body weight and total body fat; blood, complete blood count, red blood cells, white blood cells, hemoglobin, and hematocrit; plasma, 3-beta-hydroxybutyrate, total antioxidative status, and uric acid; red blood cells, total sulfhydryl content, malondialdehyde, superoxide dismutase activity, and catalase activity. After 14 days, weight loss was significant whereas no changes were detected in body fat. No alterations were observed in blood count or morphology. 3-beta-hydroxybutyrate, total antioxidative status, uric acid, and sulfhydryl content were significantly increased. There were no alterations in malondialdehyde, or superoxide dismutase or catalase activity. The present study demonstrates that 14 days of a ketogenic diet elevates blood antioxidative capacity and does not induce oxidative stress in healthy subjects.     

不同脂肪酸饮食对Wistar大鼠胰岛素敏感性的影响

目的 探讨饱和脂肪酸(SFA)、单不饱和脂肪酸(MUFA)、多不饱和脂肪酸(PUFA)饮食对大鼠胰岛素敏感性的影响.方法 48只雄性Wistar大鼠随机分为正常对照组、SFA组、MUFA组、PUFA组.正常对照组给基础饲料(脂肪占10.3%);SFA组饲料在基础饲料中添加15%猪油;MUFA组饲料在基础饲料中添加15%茶油;PUFA组饲料在基础饲料中添加15%豆油(脂肪占35.4%).8 w后4组各随机选8只大鼠行高胰岛素-正葡萄糖钳夹实验,同时留取空腹血清测定血脂、胰岛素等指标.结果 实验第8周末,与其他3组相比,正常对照组大鼠进食量有所增加,差异有统计学意义(P>0.05).除外进食量的影响,与SFA组相比,正常对照组、MUFA组、PUFA组血清TC、TG降低,差异有统计学意义(P<0.05),而正常对照组、MUFA、PUFA三组间无统计学意义(P>0.05).与正常对照组、MUFA组相比,SFA、PUFA组FINS、FPG升高,差异有统计学意义(P<0.05),GIR明显下降,差异有统计学意义(P<0.05),但该两组间无统计学差异(P>0.05).与正常对照组相比,MUFA组血清FINS、FPG有升高趋势,差异无统计学意义(P>0.05),GIR下降,差异有统计学意义(P<0.05). 结论 MUFA饮食较PUFA、SFA饮食可以改善胰岛素敏感性.     

Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus

Substance P (SP), a member of the tachykinin family, is widely distributed in the central nervous system and is involved in a variety of physiological processes including cardiovascular function, inflammatory responses, and nociception. We show here that intrahippocampal administration of SP triggers self-sustaining status epilepticus (SSSE) in response to stimulation of the perforant path for periods too brief to have any effect in control rats, and this SSSE generates a pattern of acute hippocampal damage resembling that known to occur in human epilepsy. The SP receptor (SPR) antagonists, spantide II and RP-67,580, block both the initiation of SSSE and SSSE-induced hippocampal damage and terminate established anticonvulsant-resistant SSSE. SSSE results in a rapid and dramatic increase in the expression of preprotachykinin A (a precursor of SP) mRNA and SP in principal neurons in CA3, CA1, and the dentate gyrus as well as in hippocampal mossy fibers. SP also increases glutamate release from hippocampal slices. Enhanced expression of SP during SSSE may modulate hippocampal excitability and contribute to the maintenance of SSSE. Thus, SPR antagonists may constitute a novel category of drugs in antiepileptic therapy.     

Effects of diets containing different proportions of macronutrients on longevity of normotensive Wistar rats

The present investigation examined effects of diets containing different proportions of macronutrients on longevity in two substrains of normotensive Wistar rats - Wistar Kyoto (WKY), the most widely accepted normotensive control for spontaneously hypertensive rats (SHR) and Munich Wistar rats (WAM as designated here). Each substrain was divided into five dietary groups composed of 15 rats each. Compared to a baseline diet composed of near equal calories of sucrose, fat, and protein, the remaining four diets were high sucrose-low protein, high sucrose-low fat, low sucrose-high protein, and low sucrose-high fat. Significantly higher systolic blood pressures were found in the two groups of WKY and WAM ingesting the high sucrose diets compared to the other three groups. The high sucrose groups were also hyperinsulinemic. Although only the group of WKY consuming the high sucrose-low fat diet showed a significantly shortened lifespan, the lifespan of WKY positively correlated with systolic blood pressure when data from all dietary groups were combined. WKY and WAM with an average systolic blood pressure exceeding 150 mm Hg had a significantly shorter lifespan than the rats with lower average blood pressure. Accordingly, elevated systolic blood pressure, especially when the blood pressure exceeds 150 mm Hg, significantly shortens lifespan.     

Bilateral posterior fracture-dislocations of the shoulder after convulsive status epilepticus

Presented is the case of a 30-year-old man who sustained bilateral posterior fracture-dislocations of the shoulder as an unusual complication of status epilepticus. Initial evaluation failed to reveal this unsuspected diagnosis. After improvement in the patient's mental status, his subjective complaints made the diagnosis evident. He subsequently underwent hemiarthroplasty for one shoulder and active assisted range of motion exercises for the other, with partial return of function in both arms.     

Effects of stigmasterol-supplemented diets on fecal neutral sterols and bile acid excretion in rats

To study the effects of dietary stigmasterol on sterol and bile acids metabolism, Wistar rats were fed diets containing various amounts of stigmasterol. Feeding high stigmasterol doses (11, 26 or 52 mg/day) led to increased cholesterol, coprostanol and bile acid output. These effects were dose-dependent, and likely to be related to the inhibitory effect of plant sterols on cholesterol absorption. Moreover, it accounts for the beneficial effect of the stigmasterol on cholesterol lowering.     

Effects of soy components on blood and liver lipids in rats fed high-cholesterol diets

AIM: To assess the effects of soy protein, isoflavone, and saponin on liver and blood lipid in rats that consumed high-cholesterol diets. METHODS: High-cholesterol diets (1%) with or without soy material were fed to 6-wk-old male Sprague-Dawley rats for 8 wk. Blood lipids, liver lipids, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) levels were measured. The in vitro bile acid-binding ability of soy materials was analyzed. RESULTS: The results of in vitro studies showed that soy protein isolate had a significantly higher bile acid-binding ability (8.4±0.8%) than soy saponin (3.1±0.7%) and isoflavone (1.3±0.4%, P<0.05). On the other hand, at the end of the experimental period, rats that consumed soy protein diets had lower GOT and GPT levels than rats that consumed casein under high-cholesterol diets. Rats that consumed soy protein also had lower total cholesterol (TC) levels in the liver than those that consumed casein under high-cholesterol diets. Rats that consumed the soy protein diet containing both saponin and isoflavone had lower hepatic TC level than those that consumed the soy protein diet without isoflavone alone. The effect of different types of proteins on triglyceride was not significant. CONCLUSION: Consumption of soy provided benefits to control lipid levels under high-cholesterol dieting conditions in this rat model of hypercholesterolemia. The major component that reduced hepatic TC was not saponin, but possibly isoflavone.