Antiretroviral therapy has revolutionized the treatment of the human immunodeficiency virus because it has improved the clinical outcomes of patients. It is essential that these drugs cross the blood-brain barrier, since the virus is present in the central nervous system (CNS). Efavirenz passes through this barrier satisfactorily and can reduce the deleterious central effects of the human immunodeficiency virus. However, patients treated with efavirenz have been observed to experience psychiatric symptoms such as mania, depression, suicidal thoughts, psychosis, and hallucinations. The aim of this review is to describe the pharmacokinetic and pharmacodynamic properties of efavirenz and its major neuropsychiatric symptoms and the neurochemical pathways associated with these changes in the CNS. The databases Medline and Lilacs were used to search for review articles and preclinical and clinical research articles published from January 1996 to 2010. The search terms used were efavirenz, central nervous system, neuropsychiatry, neurotransmitters, adverse effects, and neurochemistry. Subject categories considered included effects on viral replication, pharmacokinetic and pharmacodynamic properties of efavirenz, and neuropsychiatric adverse effects including time course, duration, and probable mechanisms involved. The mechanisms involved in these changes include interference with cytochrome P450 enzymes, cytokines, tryptophan-2-3-dioxygenase, and brain creatine kinase.
Background: CrossFit® involves high-intensity functional movements and research has shown that the program increases metabolic rates in participants. Objective: To measure resting energy expenditure (REE) in CrossFit® participants using indirect calorimetry (IC) and to verify the most appropriate predictive equation to estimate REE. Methods: Overall, 142 CrossFit® participants (18–59 years; 91 [64.1%], women) underwent weight, height, waist circumference, and body mass index (BMI) measurements. Body composition was evaluated using a portable ultrasound system (BodyMetrix®). REEs were measured (mREE) by IC and predicted by six different equations (pREE): Harris-Benedict, World Health Organization (WHO), Henry and Rees, Cunningham (1980 and 1991), and Mifflin–St. Jeor. Results: The mean age was 33.0 (6.3) years, with no significant difference between men and women; mean mREE, 1583.2(404.4) kcal/d; and pREE, 1455.5(230.9) to 1711.3(285.5) kcal/d. The best REE predictive equations for this population were Cunningham (1991) (P=0.338), WHO (P=0.494), and Harris-Benedict (P=0.705) equations. The Harris-Benedict equation presented a smaller difference compared with IC [12.9(307.6) kcal], the Cunningham (1991) equation showed improved adequacy (102.5%), and the WHO equation presented highest accuracy (59.9%). The equations that were closest to the mREE were the Harris-Benedict for women and the WHO equation for men. Conclusion: Therefore, for CrossFit® participants, the REE can accurately be predicted with the Cunningham (1991), WHO, and Harris-Benedict equations.
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