Effect of different doses of remifentanil on the cardiovascular response after endotracheal intubation: a randomized double-blind study.

OBJECTIVE: Laryngoscopy and endotracheal intubation (EI) often provoke a marked sympathetic response, which leads to tachycardia and hypertension. The aim of this study was to investigate the effect of different doses of remifentanil on the cardiovascular response to laryngoscopy and EI. PATIENTS AND METHODS: 100 patients were included in this randomized study. The participants were divided into four groups of 25 patients each. The patients in the control group did not receive remifentanil. The patients from other three groups received remifentanil prior to induction of anesthesia at doses of 0.5 µg/kg, 1 µg/kg, and 1.5 µg/kg. Hemodynamic parameters were measured before and after administration of remifentanil, after induction of anesthesia and one minute after EI. RESULTS: After administration of remifentanil and induction of anesthesia, a decrease in arterial pressure and heart rate occurred in most patients. After EI, an increase in arterial pressure and heart rate was observed in most patients. The largest increase was recorded in the group of patients who did not receive remifentanil. The best hemodynamic response was observed in patients who received 1 and 1.5 µg/kg of remifentanil. CONCLUSIONS: Remifentanil at the doses of 1-1.5 µg/kg is absolutely safe for co-induction of anesthesia with thiopental. Such dosing regimen provides optimal conditions for reducing hemodynamic response to laryngoscopy and EI.

Distinct effects of folate pathway genes MTHFR and MTHFD1L on ruminative response style: a potential risk mechanism for depression.

Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309). Post hoc analysis investigated whether the association could be replicated in each of the two samples, and the relationship between folate pathway genes, rumination, lifetime depression and Brief Symptom Inventory depression score. Despite its functional effect on folate metabolism, the MTHFR rs1801133 showed no effect on rumination. However, the A allele of MTHFD1L rs11754661 was significantly associated with greater rumination, and this effect was replicated in both the Budapest and Manchester samples. In addition, rumination completely mediated the effects of MTHFD1L rs11754661 on depression phenotypes. These findings suggest that the MTHFD1L gene, and thus the C1-THF synthase enzyme of the folate pathway localized in mitochondria, has an important effect on the pathophysiology of depression through rumination, and maybe via this cognitive intermediate phenotype on other mental and physical disorders. Further research should unravel whether the reversible metabolic effect of MTHFD1L is responsible for increased rumination or other long-term effects on brain development.

Malate Dehydrogenase and NAD Malic Enzyme in the Oxidation of Malate by Sweet Potato Mitochondria.

Over a range of concentrations from less than 0.1 mm to more than 70 mm, sweet potato root mitochondria display a bimodal substrate saturation isotherm for malate. The high affinity portion of the isotherm has an apparent Km for malate of 0.85 mm and fits a rectangular hyperbolic function. The low affinity portion of the isotherm is sigmoid in character and gives an apparent S(0.5) of 40.6 mm and a Hill number of 3.7.Extracts of sweet potato mitochondria contain both malate dehydrogenase and NAD malic enzyme. The malate dehydrogenase, assayed in the forward direction at pH 7.2, shows typical Michaelis-Menten kinetics with a Km for malate of 0.38 mm. The NAD malic enzyme shows pronounced sigmoidicity in response to malate with a Hill number of 3.5 and an S(0.5) of 41.6 mm.On the basis of the normal kinetics, the Km, and the fact that oxaloacetate production from malate by mitochondria appears most active at low malate concentrations, the high affinity portion of the malate isotherm with mitochondria is attributed to malate dehydrogenase. The low affinity portion of the malate isotherm with mitochondria is thought, on the basis of the similarity of S(0.5) values, the Hill numbers, and the greater production of pyruvate from malate at high malate concentrations, to represent the activity of the NAD malic enzyme.