Thermogenesis inhibition in brown adipocytes is a specific property of volatile anesthetics

BACKGROUND: This investigation examined the possibility that the inhibitory effect of halothane on nonshivering thermogenesis (heat production) in brown adipocytes is not a universal effect of all anesthetic agents but related to the type of anesthetic. METHODS: Brown adipocytes from hamster were isolated with a collagenase digestion method and incubated with anesthetic agents. The rate of oxygen consumption was measured with an oxygen electrode. The effect of clinically relevant (and higher) doses of anesthetics of different classes on basal and norepinephrine-induced thermogenesis (oxygen consumption) was tested. RESULTS: Two distinct groups of anesthetics could be distinguished: thermogenesis inhibitors and noninhibitors. Thermogenesis inhibitors include volatile anesthetics such as halothane (IC(50), 1.1 mm), ether (IC(50), 20 mm), and chloroform (IC(50), 2.2 mm) (nominal concentrations), but also tribromoethanol (IC(50), 0.6 mm), all inducing inhibition of norepinephrine-induced thermogenesis without affecting the EC for norepinephrine. Thermogenesis noninhibitors include the nonvolatile anesthetics pentobarbital, propofol, ketamine, and urethane, the inhalation anesthetic nitrous oxide, and, notably, also the volatile nonanesthetics (nonimmobilizers) 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane; none of these compounds had any effect on norepinephrine-induced thermogenesis at any concentration tested. CONCLUSIONS: There are two distinct classes of anesthetics with regard to effects on thermogenesis, thermogenesis inhibitors and thermogenesis noninhibitors. The results are important for the interpretation of studies in thermal biology in general; specifically, they indicate that conclusions concerning regulation of nonshivering thermogenesis during anesthesia depend on the type of anesthetic used. Of clinical importance is that the volatile anesthetics are inhibitory for nonshivering thermogenesis and thus for an alternative heat production when myorelaxants prevent shivering. As the distinction between thermogenesis inhibitors and thermogenesis noninhibitors corresponds to the distinction between volatile and nonvolatile anesthetics, it may be related to the mode of action of the volatile anesthetics.     

Cardiovascular function during the first 24 hours after off pump coronary artery bypass grafting--a prospective, randomized study

We hypothesized that cardiovascular performance during the first 24 postoperative hours would be better in patients after off pump coronary artery bypass grafting compared to conventional on pump surgery. Fifty-nine patients were randomized to on or off pump coronary artery bypass grafting. Hemodynamic parameters, including cardiac index and systemic vascular resistance index were measured before and at 1, 4, and 20 h after surgery. Troponin T and creatine kinase-MB (CK-MB) were measured before and at 1, 6, and 20 h after surgery. There was no difference in age, sex, ejection fraction or number of grafts between groups. Cardiac index was higher (p=0.05) and systemic vascular resistance index was lower (p=0.007) in the off pump group 1 h after arrival in the intensive care unit. CK-MB and troponin T were significantly lower in the off pump group after 1 h (CK-MB p<0.001, troponin T p<0.001) and after 6 h (CK-MB p=0.02, troponin T p<0.001). After 24 h there was no difference between the two groups. In conclusion, immediately after surgery there was better cardiovascular performance and less release of markers of myocardial damage after off pump coronary surgery. After 24 h all differences were eliminated.     

Dietary prevention of allergic diseases in infants and small children.

Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.     

THE T CELL REPERTOIRE TO ACETYLCHOLINE RECEPTOR SUBUNITS IN MYASTHENIA GRAVIS AND CONTROLS

（１）目的：多数重症肌无力（ＭＧ）患者可见作为烟碱样乙酰胆碱受体（ｎＡＣｈＲ）抗体（Ａｂ）升高基础的抗原特异性辅助性Ｔ细胞（Ｔｈ）增多，本研究目的在于探讨此类细胞的可能作用。（２）方法：设重症肌无力、其它神经科患者和正常对照三组。用体外测试的免疫酶点法，即以电鳗的ＡＣｈＲα－，β－，γ－，和δ－亚单位作为特异性抗原以及ＰＰＤ和与多发性硬化相关的髓鞘碱性蛋白作为非特异性抗原，于抗原刺激后计数分泌γ干扰素（ＩＦＮ－γ）的Ｔｈ１细胞数。测定周围血中针对这些抗原的Ｔ细胞亚群计数。（３）结果：ＭＧ患者识别ＡＣｈＲ四种亚单位的Ｔ细胞数均增高，依次为：１／２５０００，１／５９０００，１／８３０００和１／２５０００个细胞。６５％ＭＧ患者的Ｔ细胞主要识别α－亚单位，有些则主要识别γ－和δ－亚单位。少数ＭＧ患者测不到对任何亚单位起反应的Ｔ细胞。（４）结论：ＭＧ患者中，ＡＣｈＲ的四种亚单位均为通过分泌ＩＦＮγ的Ｔｈ１样细胞自身免疫攻击的靶。     

Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals

Aims/hypothesis

Roux-en-Y gastric bypass surgery (RYGB) improves glucose tolerance in patients with type 2 diabetes, but also changes the glucose profile in response to a meal in glucose-tolerant individuals. We hypothesised that the driving force for the changed postprandial glucose profiles after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production.

Methods

We determined glucose absorption and metabolism and the rate of lipolysis before and 3 months after RYGB in obese glucose-tolerant individuals using the double-tracer technique during a mixed meal.

Results

After RYGB, the postprandial plasma glucose profile changed, with a higher peak glucose concentration followed by a faster return to lower than basal levels. These changes were brought about by changes in glucose kinetics: (1) a more rapid appearance of ingested glucose in the systemic circulation, and a concomitant increase in insulin and glucagon-like peptide-1 secretion; (2) postprandial glucose disappearance was maintained at a high rate for a longer time after RYGB. Endogenous glucose production was similar before and after surgery. Postoperative glucagon secretion increased and showed a biphasic response after RYGB. Adipose tissue basal rate of lipolysis was higher after RYGB.

Conclusions/interpretation

A rapid rate of absorption of ingested glucose into the systemic circulation, followed by increased insulin secretion and glucose disappearance appears to drive the changes in the glucose profile observed after RYGB, while endogenous glucose production remains unchanged.

Trial registration

ClinicalTrials.gov NCT01559792.

Funding

The study was part of the UNIK program: Food, Fitness & Pharma for Health and Disease (see www.foodfitnesspharma.ku.dk). Funding was received from the Novo Nordisk foundation and the Strategic Research Counsel for the Capital Area and Danish Research Agency. The primary investigator received a PhD scholarship from the University of Copenhagen, which was one-third funded by Novo Nordisk.     

The action of 5-HT on calcium-dependent potassium channels and on the spinal locomotor network in lamprey is mediated by 5-HT1A-like receptors

5-HT has a powerful modulatory action on the firing properties of single neurons as well as on locomotor activity. In lamprey, 5-HT increases the neuronal firing frequency in spinal neurons by reducing the conductance in Ca²⁺-dependent K⁺ channels (K_Ca) underlying the slow afterhyperpolarization (sAHP), and it also lowers burst frequency of the spinal locomotor network. To elucidate which type of 5-HT receptor mediates these effects, different specific receptor agonists and antagonists were applied during intracellular current lamp recordings and during NMDA-induced fictive locomotion in the lamprey spinal cord in vitro preparation. The 5-HT_1A receptor agonist 8-OH-DPAT ((±)-8-hydroxy-dipropylaminotetralin hydrobromide), the 5-HT₁ receptor agonist 5-CT (5-car☐yamidotryptamine maleate) and the 5-HT₂ receptor agonist α-CH₃-5-HT (α-methylserotonin maleate) all reproduced the actions of 5-HT at both the cellular and the network levels. The effects of all agonists were completely or partially blocked by the 5-HT_1A and 5-HT₂ receptor antagonist spiperone (spiroperidol hydrochloride) while selective 5-HT₂ receptor antagonists were ineffective. The selective 5-HT_1A receptor antagonist S(−)-UH301 (S(−)-5-fluoro-8-hydroxy-dipropylaminotetralin hydrochloride) also counteracted the effect of 5-HT on the sAHP. 5-HT₃ and 5-HT₄ receptor agonists and antagonists were without effects. The intracellular coupling mechanism was not sensitive to pertussis toxin nor to the cAMP dependent protein kinase blocker (Rp)-cAMPS. These results indicate that the intracellular coupling mechanism is not likely to be due to a down regulation of adenylate cyclase activity or through a direct modulation of K⁺ channels, as is common for 5-HT₁ receptors. The present results taken together with previous data indicates that the receptor responsible for the effects of 5-HT on the sAHP, and on the locomotor pattern generator in lamprey shares certain features, but is not identical to the mammalian 5-HT_1A receptor.