Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The effect of a small dose of ketamine on postoperative analgesia and cytokine changes after laparoscopic cholecystectomy

Background and objectives: In this study we assesed the effect of a small dose of ketamine on the production of TNFα, IL-1β and IL-6 and the postoperative pain in patients undergoing laparoscopic cholecystectomy. Methods: Fifty patients undergoing laparoscopic cholecystectomy were randomized in two equal groups. Patients in the ketamine group after induction in anesthesia received ketamine – 025 mg/kg-1. At the same time patients from the control group received sodium chloride. Postoperatively, the pain was assessed with VAS at periods of 30 min at 1, 2, 4, 8, 18, 24 and 48 hours. TNFα, IL-1β and IL-6 were evaluated before surgery at 4, 18 and 24h after the operation. Results: Differences of mean values of TNFα and IL-1β between the two groups in the postoperative period were not significant. Mean values of IL-6 in the investigated group A were significantly lower than the mean values of IL-6 in the investigated group B after the 4th hour (p = 0.00990), after the 18th hour (p = 0.00133) and as after the 24th hour following surgery (p = 000860). the difference in pain intensityaccording to the VAS scale was also statistically significantly smaller in group A after 30 min, 1,2,8 and 12 hours after surgery. Conclusions: The addition of a small-dose of ketamine in patiens undergoing laparoscopic cholecystectomy resulted in attenuation of secretion of TNFα, IL-1β, IL-6 and reduction of postoperative pain. Key words: ketamine, postoperative pain, proinflammatory cytokines

Influence of potential gene polymorphisms on propofol dosage regimen in patients undergoing abdominal hysterectomy

Propofol (2,6-diisopropylphenol) is the most common intravenous anesthetic used in modern medicine. It is postulated that individual differences in genetic factors [polymorphism of single nucleotide polymorphisms (SNPs)] in the genes encoding metabolic enzymes, molecular targets and molecular binding sites of propofol can be responsible for susceptibility to propofol effects. The aim of our study was to investigate the influence of the cytochrome P450 2B6 isozyme CYP2B6 (rs3745274), γ-aminobutyric acid type A (GABAA) receptor α1 subunit GABRA1 (rs2279020) and ATP-binding cassette subfamily B member 1 ABCB1 (rs1045642) gene polymorphisms on propofol therapeutic outcomes in the patients undergoing abdominal hysterectomy. Ninety patients aged 29-74 years, with different ethnicities were included in this study. The presence of polymorphisms was analyzed using TaqMan SNP genotype analysis on Stratagene MxPro 3005P real-time polymerase chain reaction (qPCR). The distribution of all three genetic variants was within the Hardy-Weinberg equilibrium. There was no significant difference (p >0.05) in the allelic frequencies of polymorphic variants and genotype distributions between adult and older patients and between patients of different ethnicities. Our study did not detect a statistically significant influence of the CYP2B6 (c.516G>A), GABRA1 (c.1059+15G>A) and ABCB1 (c.3435T>C) variants on the variability of clinical parameters (doses for induction in anesthesia, additional doses, induction time and wake time after anesthesia and side effects of propofol). However, the observed trend on the possible influence of the CYP2B6 (c.516G>A) and GABRA1 (c.1059+15G>A) variants warrant an extension of these studies on a larger number of patients