Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy

Background: The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis and may either suppress or trigger acute seizures. However, the effects of BCAAs on chronic (ie, spontaneous recurrent) seizures and epilepsy-associated neuron loss are incompletely understood. Materials and Methods: Sixteen rats with mesial temporal lobe epilepsy were randomized into 2 groups that could drink, ad libitum, either a 4% solution of BCAAs in water (n=8) or pure water (n=8). The frequency and relative percent of convulsive and nonconvulsive spontaneous seizures were monitored for a period of 21 days, and the brains were then harvested for immunohistochemical analysis. Results: Although the frequency of convulsive and nonconvulsive spontaneous recurrent seizures over a 3-week drinking/monitoring period were not different between the groups, there were differences in the relative percent of convulsive seizures in the first and third week of treatment. Moreover, the BCAA-treated rats had over 25% fewer neurons in the dentate hilus of the hippocampus compared with water-treated controls. Conclusions: Acute BCAA supplementation reduces seizure propagation, whereas chronic oral supplementation with BCAAs worsens seizure propagation and causes neuron loss in rodents with mesial temporal lobe epilepsy. These findings raise the question of whether such supplementation has a similar effect in humans. T.E. and R.D. are supported by grants from the National Institutes of Health (NIH): NINDS R01 NS070824. S.E.G. is supported by grants from the Foundation for Anesthesia Education and Research (FAER) and the NIH: T32 GM086287. This work was also made possible by a grant from the National Center for Advancing Translational Sciences (NCATS; UL1 TR000142), a component of the NIH and the NIH Roadmap for Medical Research. The authors have no conflicts of interest to disclose. Address correspondence to: Tore Eid, MD, PhD, Department of Laboratory Medicine, 330 Cedar St., P.O. Box 208035, Yale School of Medicine, New Haven, CT 06520 (e-mail: tore.eid@yale.edu). Received November 28, 2017 Accepted February 23, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Endoscopic management of maxillary sinus inverted papilloma attachment sites to minimize disease recurrence

Inverted papillomas (IPs) are benign neoplasms, most commonly arising from the mucosal lining of the maxillary sinus. IPs can have single or multifocal sites of attachment. Although pedicle location is an impo...

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In-office laryngeal procedures (IOLP) in Canada: current safety practices and procedural care

The advent of chip tip technology combined with advanced endoscopy has revolutionized the field of laryngology in the past decade. Procedures such as transnasal esophagoscopy, site-specific steroid injections,...

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Critical view of anaphylaxis epidemiology: open questions and new perspectives

In contrast to the majority of allergic or hypersensitivity conditions, worldwide anaphylaxis epidemiological data remain sparse with low accuracy, which hampers comparable morbidity statistics. Data can diffe...

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Interferon-α2b-induced STAT3 suppression in myeloid-derived suppressor cells in mycosis fungoides

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A Prospective Study of Predicting Prognosis and Recurrence of Thyroid Cancer Via New Biomarkers, Urinary Exosomal Thyroglobulin and Galectin-3

Condition:   Thyroid Cancer
Intervention:  
Sponsor:   National Taiwan University Hospital
Not yet recruiting

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Incidence, Risk Factors, and Outcomes of Clostridium difficile Infections in Kidney Transplant Recipients

Background Kidney transplant recipients (KTR) may be at increased risk for Clostridium difficile infections (CDI) but risk factors and outcomes in this population have not been well studied. Methods An observational cohort study was conducted to determine the incidence, risk factors, and outcomes of CDI in KTR. A total of 1,816 KTR transplanted between 2000 and 2013 at Toronto General Hospital were included. Sixty-eight patients developed CDI. Controls were selected at a 4:1 ratio using risk-set sampling and risk factors were explored using conditional logistic regression models. The impact of CDI on graft outcomes was evaluated using Cox proportional hazards models. Results The incidence rate of CDI was 0.64 cases/100 person-years. Independent predictors of CDI included antibiotic use (OR 2.88 [95%CI: 1.35, 6.15]), increased duration of hospitalization posttransplant (OR 1.04 [95%CI: 1.02, 1.06]), receiving a deceased donor kidney (OR 2.98 [95%CI: 1.47, 6.05]), and a history of biopsy-proven acute rejection (OR 5.82 [95%CI: 2.22, 15.26]). In the Cox proportional hazards model, CDI was found to be an independent risk factor for the subsequent development of biopsy-proven acute rejection (HR 2.18 [95% CI: 1.34, 3.55]). Conclusions Our results confirm that transplant-specific factors place KTR at a higher risk for CDI. CDI may increase the risk of adverse outcomes such as biopsy-proven acute rejection. These findings emphasize the importance of preventive strategies to reduce the morbidity associated with CDI in KTR. Address correspondence to: S. Joseph Kim, MD, PhD, MHS, FRCPC, Toronto General Hospital, University Health Network, 585 University Avenue, 11-PMB-129, Toronto, Ontario, Canada M5G 2N2. Email: joseph.kim@uhn.ca. Office: 416-340-3228. Fax: 416-340-4701 AUTHORSHIP Research design: G. Li, Trac, Husain, Famure, Y. Li, Kim Writing the paper: G. Li, Trac, Husain, Famure, Kim Performance of the research: G. Li, Trac, Husain, Famure, Kim Contributed analytic tools: G. Li, Trac, Y. Li, Kim Participated in data analysis: G. Li, Trac, Husain, Famure, Y. Li, Kim DISCLOSURE The authors have no conflicts of interest to disclose as it relates to this work. FUNDING No external funding was acquired to support this research. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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