Ketogenic diet, seizure control, and cardiometabolic risk in adult patients with pharmacoresistant epilepsy: a review.

Pharmacoresistant epilepsy causes serious deleterious effects on the patient's health and quality of life. For this condition, a ketogenic diet (KD) is a treatment option. The KD is a general term for a set of diets that contain high amounts of fat and low content of carbohydrates. The most prominent KD treatments are classical KD (4:1 ratio of fat to carbohydrate), modified Atkins diet (2:1 to 1:1 ratio), medium-chain triglycerides KD (with medium-chain triglyceride as a part of the fat content), and low glycemic index KD (using low glycemic carbohydrates). KD has been widely prescribed for children with epilepsy but not for adult patients. One of the main concerns about adult use of KD is its cardiovascular risk associated with high-fat and cholesterol intake. Therefore, this narrative review provides comprehensive information of the current literature on the effects of KD on lipid profile, glycemic-control biomarkers, and other cardiometabolic risk factors in adult patients with pharmacoresistant epilepsy.

Challenges in telemedicine for adult patients with drug-resistant epilepsy undergoing ketogenic diet treatment during the COVID-19 pandemic in the public healthcare system in Brazil.

Hygienic and sanitary measures and social distancing policies implemented during the new coronavirus disease - COVID-19 - pandemic have altered the care and follow-up provided by healthcare professionals for patients with chronic diseases, including patients with epilepsy (PWEs). Telemedicine has become a solution for the healthcare of PWEs in many developed countries. In this short communication, we trace a particular perspective for the application of telemedicine for PWEs undergoing ketogenic diet (KD) treatment, considering the social and economic difficulties faced by healthcare teams in resource-poor countries, such as Brazil. During the pandemic, financial strain was the main impediment to following KD. The pandemic increased socioeconomic insecurity and access to KD-related products, as well as increasing anxiety in 71% of PWE, impacting their KD treatment follow-up. The challenges of telemedicine in Brazil include not only social and economic issues but also access to food, healthcare services, and education for the population, in addition to digital inclusion.

Infliximab Trough Levels and Quality of Life in Patients with Inflammatory Bowel Disease in Maintenance Therapy.

OBJECTIVE: Investigate the association between infliximab trough levels and quality of life in inflammatory bowel disease patients in maintenance therapy. METHODS: We carried out a transversal study with inflammatory bowel disease patients in infliximab maintenance therapy. Infliximab trough levels were determined using a quantitative rapid test. Disease activity indices (partial Mayo Score and Harvey-Bradshaw Index) and endoscopic scores (endoscopic Mayo Score or Simple Endoscopic Score in Crohn's disease) were obtained. Quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Seventy-one consecutive subjects were included in the study (55 with Crohn's disease and 16 with ulcerative colitis). Drug levels were considered satisfactory (≥3 µg/mL) in 28 patients (39.4%) and unsatisfactory (<3 µg/mL) in 43 (60.6%). Satisfactory trough levels were associated with higher rates of clinical remission and mucosal healing. Higher trough levels were also associated with improved IBDQ scores, particularly regarding bowel symptoms, systemic function, and social function. CONCLUSION: Satisfactory trough levels of infliximab were associated with higher rates of clinical remission, mucosal healing, and improved quality of life in inflammatory bowel disease patients on maintenance therapy.

Caloric restriction improves basal redox parameters in hippocampus and cerebral cortex of Wistar rats.

Caloric restriction (CR) has been shown to either decrease or prevent the progression of several age-related pathologies. In previous work, we demonstrated that CR modulates astrocyte functions, suggesting that CR may exert neuroglial modulation. Here, we investigated the effects of CR on hippocampal (Hc) and cortical (Cx) oxidative stress parameters of male Wistar rats. Our results showed that CR-fed rats had 17% less body weight gain after 12 weeks of treatment. CR improved locomotion performance, increased glutathione levels and decreased glutathione peroxidase activity and the production of reactive oxygen species. However, no changes were observed in lipid peroxidation, nitric oxide content and catalase activity. Single cell gel electrophoresis assay (comet assay) revealed a reduction in the extent of basal DNA damage upon CR. Our data suggest that dietary CR could induce both hippocampal and cortical modulation resulting in metabolic changes and as a consequence, significant improvement of cellular defense-associated parameters.

Ketogenic diet-fed rats have increased fat mass and phosphoenolpyruvate carboxykinase activity.

The ketogenic diet (KD), characterized by high fat and low carbohydrate and protein contents, has been proposed to be beneficial in children with epilepsy disorders not helped by conventional anti-epileptic drug treatment. Weight loss and inadequate growth is an important drawback of this diet and metabolic causes are not well characterized. The aim of this study was to examine body weight variation during KD feeding for 6 wk of Wistar rats; fat mass and adipocyte cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity were also observed. PEPCK activity was determined based on the [H(14)CO(3) (-)]-oxaloacetate exchange reaction. KD-fed rats gained weight at a less rapid rate than normal-fed rats, but with a significant increment in fat mass. The fat mass/body weight ratio already differed between ketogenic and control rats after the first week of treatment, and was 2.4 x higher in ketogenic rats. The visceral lipogenesis was supported by an increment in adipocyte PEPCK, aiming to provide glycerol 3-phosphate to triacylglycerol synthesis and this fat accumulation was accompanied by glucose intolerance. These data contribute to our understanding of the metabolic effects of the KD in adipose tissue and liver and suggest some potential risks of this diet, particularly visceral fat accumulation.

DNA damage in rats after treatment with methylphenidate.

BACKGROUND: Methylphenidate (MPH) is a widely prescribed psychostimulant for the treatment of attention-deficit hyperactivity disorder (ADHD). Recently, some studies have addressed the genotoxic potential of the MPH, but the results have been contradictory. Hence, the present study aimed to investigate the index of cerebral and peripheral DNA damage in young and adult rats after acute and chronic MPH exposure. METHODS: We used (1) single cell gel electrophoresis (Comet assay) to measure early DNA damage in hippocampus, striatum and total blood, and (2) micronucleus test in total blood samples. RESULTS: Our results showed that MPH increased the peripheral index of early DNA damage in young and adult rats, which was more pronounced with chronic treatment and in the striatum compared to the hippocampus. Neither acute nor chronic MPH treatment increased micronucleus frequency in young or in adult rats. Peripheral DNA damage was positively correlated with striatal DNA damage. CONCLUSION: These results suggest that MPH may induce central and peripheral early DNA damage, but this early damage may be repaired.

Ketogenic diet increases glutathione peroxidase activity in rat hippocampus.

Ketogenic diets have been used in the treatment of refractory childhood epilepsy for almost 80 years; however, we know little about the underlying biochemical basis of their action. In this study, we evaluate oxidative stress in different brain regions from Wistar rats fed a ketogenic diet. Cerebral cortex appears to have not been affected by this diet, and cerebellum presented a decrease in antioxidant capacity measured by a luminol oxidation assay without changes in antioxidant enzyme activities--glutathione peroxidase, catalase, and superoxide dismutase. In the hippocampus, however, we observed an increase in antioxidant activity accompanied by an increase of glutathione peroxidase (about 4 times) and no changes in lipoperoxidation levels. We suggest that the higher activity of this enzyme induced by ketogenic diet in hippocampus might contribute to protect this structure from neurodegenerative sequelae of convulsive disorders.