Effect of General Anesthesia on Plasma Ascorbic Acid Level

Ascorbic acid (AsA) and dehydroascorbic acid (DHA) in plasma, and the total vitamin C (AsA + DHA) in urine after oral surgery were measured to investigate whether general anesthesia has effects on the level of plasma AsA. Plasma AsA decreased significantly on the 1st and 3rd post-operative day in the general anesthesia group, but not in the local anesthesia group. A decrease in the AsA level was seen in both the halothane group and the neuroleptanesthesia group. Plasma DHA was not detected pre-operatively, but increased post-operatively and the total vitamin C in the urine decreased on the 1st post-operative day in the general anesthesia group. It was concluded that general anesthesia caused a decrease in the plasma AsA level. This can be only partially explained by the oxidation of AsA. We are going to investigate other causes as the degree of decrease of AsA was larger than the degree of increase of DHA

Pharmacokinetic Study on Excretion of Inorganic Fluoride Ion, a Metabolite of Sevoflurane

Blood and urinary inorganic fluoride ion concentration was determined in six healthy volunteers after inhalation of 2% sevoflurane for one hour. The serum inorganic fluoride ion concentration increased 30 min after discontinuation of inhalation to 14.8 ± 3.0 μmol/liter, which was about 10 times higher than the level before inhalation. The serum elimination constant of inorganic fluoride was calculated to be 0.000467 and the half-life was 1,487 min. The urinary excretion rate of inorganic fluoride ion was the highest ( 452 nmol/min) after 12-24 hr. The urinary excretion rate constant of inorganic fluoride was calculated to be 0.000268 and the half-life was 2,583 min. The distribution volume of inorganic fluoride excreted in the urine was calculated to be 127 liters. This value showed that fluoride ion produced in the cell cannot readily pass through the cell membrane due to its polarity, resulting in a delay of the maximum excretion rate of inorganic fluoride until the first or second day after inhalation of the anesthetic.This study was supported in part by a Grant-in-aid for Science Research from the Ministry of Education, Science and Culture of Japan and a Grant-in-aid from the Association for the Advancement of Medicine of the Tsuchiya Foundation

EFFECTS OF SURFACE TENSION ON TWO-PHASE VOID DRIFT BETWEEN TRIANGLE TIGHT LATTICE SUBCHANNELS

ABSTRACT In this study, void drift phenomena, which are one of three components of the inter-subchannel fluid transfer, have been investigated experimentally and analytically. In the experiments, data on flow and void redistributions were obtained for hydraulically non-equilibrium flows in a multiple channel consisting of two subchannels simplifying a triangle tight lattice rod bundle. In order to know the effects of the reduced surface tension on the void drift, water and water with a surfactant were used as the test liquids. In addition, data on the void diffusion coefficient, D , needed in a void drift model, have been obtained from the redistribution data. In the analysis, the flow and the void redistributions were predicted by a subchannel analysis code based on a one-dimensional twofluid model. From a comparison between the experiment and the code prediction, the present analysis code was found to be valid against the present data if newly developed constitutive equations of wall and interfacial friction were incorporated in the model to account for the reduced surface tension effects

Effects of hydrophilic polymer-coated polysulfone membrane dialyzers on intradialytic hypotension in diabetic hemodialysis patients (ATHRITE BP Study) : a pilot study

Background: Intradialytic hypotension (IDH) is a common clinical manifestation associated with poor prognosis in hemodialysis (HD) patients. HD patients who suffer from diabetic nephropathy (DN) are increasing and diabetes is a major cause of IDH. Effective interventional treatments for IDH have yet to be fully evaluated. The aim of this multicenter prospective study is to clarify the effect of biocompatible hydrophilic polymer-coated polysulfone (PS) membrane, TORAYLIGHT® NV (NV) dialyzers on IDH. Methods: This is a prospective stratified-randomized multicenter trial. Forty DN patients undergoing HD and receiving two or more times of treatments for IDH per month were enrolled in this study. They were stratified by the number of treatments for IDH and divided to two groups using NV or conventional PS/polyethersulfone (PES) dialyzers. The number of treatments for IDH and changes in systolic blood pressure (SBP) were monitored for 6 months. Patients’ demographic and clinical characteristics were also collected at enrollment and the last month of the observation period. In order to clarify the patient characteristics that induced preferable effects by using NV dialyzers, responders were defined as the patients whose average SBP falls in 1 month improved from over 30 mmHg to no more than 30 mmHg. Results: The total number of treatments for IDH decreased significantly in NV group, even though pre-dialysis body weight and ultrafiltration volume were similar. In addition, patients using NV had significantly higher post-dialysis SBP and the lowest SBP during HD at sixth month compared as those in PS/PES group. NV responders had valuables suggesting malnutrition and microinflammation, and better lipid profiles than non-responders. However, the representative markers related to nutritional status, arteriosclerosis, and inflammation were not improved by NV treatment. Conclusions: NV had preferable effects on IDH in DN HD patients. Our results suggest the usefulness of NV as a possible method to deal with IDH. Further studies are needed to clarify the mechanism of NV effects on hemodynamic status

Inhibition of serotonin transporters by cocaine and meprylcaine

The present study examined whether the inhibition of serotonin transporters (SERT) contributes to cocaine- and other local anesthetics-induced convulsions, and which subtypes of 5-HT receptor are involved in the convulsions. For this purpose, cocaine, meprylcaine and lidocaine, all of which have different effects on SERT, were used as convulsants and the effects of serotonin reuptake inhibitors (SSRIs), specific agonists and antagonists for 5-HT receptor subtypes were evaluated in mice.Administration of SSRI, zimelidine, citalopram and fluoxetine, 5-HT2A,2C receptor agonist, R(-)-DOI and the 5-HT2C receptor agonists, mCPP and MK212 resulted in a marked increase in incidence of convulsions and a reduction in the threshold of lidocaine-induced convulsions, while the 5-HT2B receptor agonist, BW723C86, had little influence. On the other hand, SSRI did not affect the measured parameters in meprylcaine- and cocaine-induced convulsions. R(-)-DOI, mCPP and MK212 reduced the threshold of meprylcaine or cocaine with less extent than the reduction of lidocaine threshold. Incidence of cocaine- and meprylcaine-induced convulsions were significantly reduced by 5-HT2A,2B,2C antagonist, LY-53857 and 5-HT2C antagonist, RS 102221. The threshold of cocaine and meprylcaine was significantly increased by both antagonists. 5-HT2A antagonists MDL-11,939 and ketanserin, and 5-HT2B antagonist SB-204741 except at high doses had little effect on cocaine- and meprylcaine-induced convulsions. None of these antagonists altered the parameters of lidocaine-induced convulsions. Pretreatment with fluoxetine but not citalopram increased the plasma concentration of lidocaine. These results suggest that the increase of serotonergic neuronal activity through 5-HT2C receptor stimulation was responsible for increased activity of local anesthetics-induced convulsions and support the involvement of this mechanism in cocaine- and meprylcaine- but not in lidocaine- induced convulsions through their direct inhibitory action on central SERT

Serum Amyloid A Induces NLRP-3-Mediated IL-1β Secretion in Neutrophils

Background/Aims: Serum amyloid A (SAA) is an acute phase reactant with significant immunological activities, including effects on cytokine synthesis and neutrophil chemotaxis. Neutrophils can also release cytokines with proinflammatory properties. IL-1β is a key proinflammatory cytokine, the secretion of which is controlled by inflammasome. We investigated the proinflammatory effects of SAA in vitro in relation to the NLRP3 inflammasome in neutrophils. Methodology/Principal Findings: Human neutrophils isolated form healthy subjects were stimulated with serum amyloid A (SAA). The cellular supernatants were analyzed by western blot using anti-IL-1β or anti-caspase-1 antibodies. IL-1β or Nod-like receptor family, pyrin domain containing 3 (NLRP3) mRNA expressions were analyzed by real-time PCR or reverse transcription-PCR (RT-PCR) method. SAA stimulation induced pro-IL-1β mRNA expression in neutrophils. Furthermore, SAA engaged the caspase-1-activating inflammasome, resulting in the production of active IL-1β. SAA-induced pro-IL-1β expression was marginally suppressed by the Syk specific inhibitor, R406, and SAA-induced pro-IL-1β processing in neutrophils was prevented by R406. Furthermore, SAA-induced NLRP3 mRNA expression was completely blocked by R406. Analysis of intracellular signaling revealed that SAA stimulation activated the tyrosine kinase Syk and mitogen-activated protein kinase (MAPK). Conclusions/Significance: These results demonstrate that the innate neutrophil immune response against SAA involves a two-step activation process: an initial signal promoting expression of pro-IL-1β and a second signal involving Syk-dependent activation of the NLRP3 inflammasome and caspase-1, allowing processing of pro-IL-1β and secretion of mature IL-1β