Dexmedetomidine does not reduce emergence agitation in adults following orthognathic surgery.

BACKGROUND: Patients undergoing orthognathic surgery are at high risk of developing emergence agitation. We hypothesised that a single-dose of dexmedetomidine would reduce emergence agitation in adults with nasotracheal intubation after orthognathic surgery. METHODS: Seventy adults (20-45 years old) undergoing orthognathic surgery were randomly assigned to two groups. Patients received intravenous dexmedetomidine 1 µg/kg (dex group) or normal saline (control group) for 10 min at the end of surgery. Remifentanil was infused at 0.02 µg/kg/min during emergence in both groups. The severity of emergence agitation was assessed with the Richmond agitation-sedation scale. Cough, haemodynamic and respiratory profiles, pain, and time to eye opening were evaluated. RESULTS: The incidence of emergence agitation was not different between dex group and control group (38% vs. 47%, P = 0.45). However, severe cough during emergence was reduced in the dex group (P = 0.04). Tachycardia during emergence and recovery phases was attenuated in the dex group. The verbal numeric rating of pain was lower in the dex group. There were no differences in respiratory rate between the two groups. Time to eye opening was prolonged in the dex group. CONCLUSION: The addition of a single dose of dexmedetomidine (1 µg/kg) to low-dose remifentanil infusion did not attenuate emergence agitation in intubated patients after orthognathic surgery compared with low-dose remifentanil infusion alone. However, single-dose dexmedetomidine suppressed coughing, haemodynamic changes, and pain during emergence and recovery phases, without respiratory depression. Delayed awakening might be associated with this treatment.

Isoflurane-induced post-conditioning in senescent hearts is attenuated by failure to activate reperfusion injury salvage kinase pathway.

BACKGROUND: We investigated the cardioprotective effects of isoflurane administered at the onset of reperfusion in senescent rat in vivo, and the activation of the reperfusion injury salvage kinase (RISK) pathway to address a possible mechanism underlying age-related differences. METHODS: Male Wistar rats were assigned to age groups (young, 3-5 months; old, 20-24 months), and randomly selected to receive isoflurane (1 minimum alveolar concentration) or not for 3 min before and 2 min after reperfusion (ISO postC). Rats were subjected to coronary occlusion for 30 min followed by 2 h of reperfusion. Western blot analysis was used to assess the phosphorylation of extracellular signal-regulated kinase (ERK1/2), Akt, and GSK3ß 15 min after reperfusion. RESULTS: Brief administration of isoflurane 3 min before and 2 min after the initiation of early reperfusion reduced infarct size (56 ± 8% of left ventricular area at risk, mean ± standard deviation) compared with controls (68 ± 4%) in young rats, but had no effect in old rats (56 ± 8% in ISO postC and 56 ± 10% in control, respectively). Phosphorylation of ERK1/2, Akt, and GSK3ß were increased in the young ISO postC group but not in the old ISO postC group compared with control groups of the respective ages. CONCLUSIONS: We demonstrated that isoflurane post-conditions the heart in young but not in senescent rats. Failure to activate RISK pathway may contribute to attenuation of isoflurane-induced post-conditioning effect in senescent rats.

A multi-microbe probiotic formulation processed at low and high drying temperatures: effects on growth performance, nutrient retention and caecal microbiology of broilers.

1. Two experiments were conducted to evaluate a multi-microbe probiotic formulation processed at low (LT) or high (HT) drying temperature. 2. In both the experiments, 640 d-old Ross male chicks were randomly allotted to 4 treatments on the basis of initial BW for 35 d experiments. 3. In experiment one, dietary treatments were a negative control (NC; basal diet without any antimicrobial); positive control (PC; basal diet +10 mg/kg avilamycin); basal diet with 0·3% probiotic LT; and basal diet with 0·3% probiotic HT. 4. Improved overall weight gain, FCR and retention of CP were observed in birds fed the PC and probiotic diets when compared with birds fed the NC diet. At d 21, birds fed the probiotic and NC diets had more caecal Bifidobacterium and total anaerobes than birds fed the PC diet; while birds fed the PC and probiotic diets had fewer caecal Clostridium than birds fed the NC diet at d 35. 5. In experiment two, a 2 × 2 factorial arrangement of treatments was employed to evaluate the effects of two concentrations of probiotic HT (0·30 or 0·60%) and avilamycin (0 or 10 mg/kg). 6. Birds fed the 0·60% probiotic HT diet showed improved overall weight gain and CP retention, higher Lactobacillus and Bifidobacterium in the caecum, and reduced Clostridium and coliforms in the caecum. Inclusion of avilamycin improved the overall weight gain and feed intake, and reduced the caecal Clostridium and Bifidobacterium population. 7. In conclusion, high drying temperature had no effect on the efficacy of the multi-microbe probiotic formulation; while the probiotic HT formulation was more effective at the 0·60% level. Moreover, inclusion of avilamycin improved performance of birds but did not have any interaction with probiotics.

Effects of propofol on the expression of matric metalloproteinases in rat cardiac fibroblasts after hypoxia and reoxygenation.

BACKGROUND: Propofol is known to protect the myocardium against ischaemia/reperfusion (I/R) injury through its antioxidant and anti-inflammatory properties. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in cell migration and invasion, and mediate tissue remodelling during I/R injury. They are regulated by various mechanisms including oxidative stress and AKT and ERK pathways. We investigated whether propofol affected the expression of MMPs and subsequent cell migration and invasion and the signalling pathways involved in primary rat cardiac fibroblasts undergoing hypoxia and reoxygenation. METHODS: The phosphorylation of ERK and AKT signalling pathways was examined by western blot analysis in rat primary cardiac fibroblasts after hypoxia and reoxygenation. mRNA expression of MMP and TIMPS was analysed by real-time PCR, and proteolytic activities of MMP-2 and -9 were assessed. The effects of propofol on migration, invasion, wound healing, and cell proliferation activity were evaluated after reoxygenation. RESULTS: Propofol induced AKT and ERK1/2 activation. Subsequent activation of MMPs resulted in increased cell migration, invasion, and wound-healing activity under hypoxia-reoxygenation, which was decreased by LY294002 (AKT inhibitor) and U0126 (ERK inhibitor) in rat cardiac fibroblasts. However, propofol had no effect on proliferation or viability of cardiac fibroblasts after hypoxia-reoxygenation. CONCLUSIONS: Propofol affected the expression of MMPs and TIMPs and subsequently induced cell migration and invasive ability, through activation of the ERK and AKT signalling pathway in hypoxia-reoxygenated rat cardiac fibroblasts.

Pregabalin reduces post-operative pain after mastectomy: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Pregabalin is used for the treatment of neuropathic pain and has shown analgesic efficacy in post-operative pain. The aim of this randomized, double-blinded, placebo-controlled trial (Clinical Trials.gov ID NCT00938548) was to investigate the efficacy and safety of pregabalin for reducing post-operative pain in patients after mastectomy. METHODS: Eighty-four women scheduled for elective mastectomy were randomly assigned to groups that received either pregabalin (75 mg) or placebo, 1 h before surgery and 12 h after the initial dose. Assessments of pain [verbal numerical rating scale (VNRS), at rest and with arm abduction] and side effects were performed at 1, 6, 24 and 48 h post-operatively. After discharge from the hospital, pain was assessed by telephone interview at post-operative 1 week and 1 month. RESULTS: VNRS scores for pain at rest were lower in the pregabalin group (n=42) than the placebo group (n=42) at 1, 24 and 48 h post-operatively (P<0.05). VNRS scores for pain with arm abduction were lower in the pregabalin group (n=42) than the placebo group (n=42) at 1 and 24 h, and 1 week post-operatively (P<0.05). Incidences of side effects such as nausea and vomiting, headache, dizziness and blurred vision were similar in both groups. CONCLUSION: Perioperative administration of pregabalin for a single day (75 mg twice daily) was easy, safe and effective in reducing post-operative pain in patients undergoing mastectomy.

The effect of combining dexamethasone with ondansetron for nausea and vomiting associated with fentanyl-based intravenous patient-controlled analgesia.

We investigated whether combined dexamethasone and ondansetron is more effective than ondansetron alone in preventing postoperative nausea and vomiting in patients with fentanyl-based intravenous patient-controlled analgesia. One hundred and thirty patients undergoing video-assisted thoracoscopic surgery were assigned to either an ondansetron group or a dexamethasone and ondansetron group. In all patients, ondansetron 4 mg was administered at the end of surgery and 12 mg was added to the patient-controlled analgesia solution. The dexamethasone and ondansetron group received dexamethasone 8 mg at the induction of anaesthesia. The overall incidence of nausea and vomiting during the first 48 h postoperatively did not differ between groups (34/61 (56%) vs 28/62 (45%) in the ondansetron group and dexamethasone and ondansetron groups, respectively). The incidence of severe nausea and vomiting (≥ 7 nausea on an 11-point verbal numerical rating scale, retching or vomiting) was higher in the ondansetron group than in the dexamethasone and ondansetron group (15/61 (25%) vs 6/62 (10%, respectively, p=0.028). Combined dexamethasone and ondansetron is more effective in reducing severe nausea and vomiting than ondansetron alone in patients receiving fentanyl-based intravenous patient-controlled analgesia.

Optimal effect-site concentration of remifentanil for preventing cough during emergence from sevoflurane-remifentanil anaesthesia.

This randomised, double-blinded, controlled trial was designed to identify the optimal dose of remifentanil for cough suppression without adverse effects during emergence from sevoflurane-remifentanil anaesthesia for thyroidectomy. One hundred and four patients were randomly assigned to maintain target effect-site concentrations of remifentanil at 0 (control group), 1.0 (remifentail 1 group), or 1.5 ng.ml(-1) (remifentanil 1.5 group) during emergence. The incidence of coughing was lower in the remifentanil 1.5 group (31%) than in the control group (74%) or remifentanil 1 group (63%) (p = 0.0004). In addition, the severity of coughing during extubation was lower in the remifentanil 1.5 group (median (IQR [range]) 0 (0-1 [0-1]) than in the control group (1 (0-2 [0-3])) and remifentanil 1 group (1 (0-2 [0-3])) (p = 0.004). Haemodynamic changes were reduced, but emergence time and stay in the post-anaesthesia care unit was prolonged in the remifentanil 1.5 group. Maintaining the remifentanil effect-site concentration at 1.5 ng.ml(-1) during emergence from sevoflurane-remifentanil anaesthesia reduces the incidence and severity of coughing without serious adverse events and may provide haemodynamic stability in patients undergoing thyroidectomy. However, awakening may be delayed.

Processing diets containing corn distillers' dried grains with solubles in growing broiler chickens: effects on performance, pellet quality, ileal amino acids digestibility, and intestinal microbiota.

The present study investigated the effects of feed form and distillers' dried grains with solubles (DDGS) on growth performance, nutrient digestibility, and intestine microbiota in broilers. A total of 720 broilers (Ross 308; average BW 541 ± 6 g) was randomly allotted to 6 treatments on the basis of BW. There were 6 replicates in each treatment with 20 birds per replicate. Birds were fed 3 different feed forms (mash, simple pellet, and expanded pellet) and DDGS (0 or 20% of diet) in a 3 × 2 factorial arrangement. Simple pellet (SP) and expanded pellet (EP) fed birds showed an increase in BW gain (P < 0.05). The interaction between feed processing and DDGS level was observed on pellet hardness (P < 0.01). The lowest (P < 0.01) pellet durability index (PDI) and hardness were observed in the diet with DDGS. Values for PDI and hardness were higher for EP compared with SP (P < 0.01). Simple pellet decreased ileal digestibility of CP compared to mash feed. The inclusion of DDGS decreased the digestibility of CP, and tended to decrease digestibility of DM (P = 0.056) and gross energy (P = 0.069). Expanded pellet feeding decreased (P < 0.05) the ileal digestibility of isoleucine, lysine, methionine, phenylalanine, threonine, cysteine, and glutamine compared with mash diet. Processed feed increased (P < 0.01) pH in the gizzard and duodenum; however, processing decreased pH in ileum. The addition of DDGS to the diet reduced pH in the duodenum. The population of Lactobacillus spp. was lower in the duodenum of birds fed the EP diet compared to the mash diet. Processed feed increased the colonization of Clostridium spp. in the gizzard. These results indicated that SP and EP in broiler diet had a potential to improve BW gain, but EP compromised amino acid digestibility. In addition, DDGS supplementation (20%) decreased pellet quality and CP digestibility in broiler chickens; however, the growth performance and feed intake were not affected.

elt-1, an embryonically expressed Caenorhabditis elegans gene homologous to the GATA transcription factor family.

The short, asymmetrical DNA sequence to which the vertebrate GATA family of transcription factors binds is present in some Caenorhabditis elegans gene regulatory regions: it is required for activation of the vitellogenin genes and is also found just 5' of the TATA boxes of tra-2 and the msp genes. In vertebrates GATA-1 is specific to erythroid lineages, whereas GATA-2 and GATA-3 are present in multiple tissues. In an effort to identify the trans-acting factors that may recognize this sequence element in C. elegans, we used a degenerate oligonucleotide to clone a C. elegans homolog to this gene. We call this gene elt-1 (erythrocytelike transcription factor). It is single copy and specifies a 1.75-kb mRNA that is present predominantly, if not exclusively, in embryos. The region of elt-1 encoding two zinc fingers is remarkably similar to the DNA-binding domain of the vertebrate GATA-binding proteins. However, outside of the DNA-binding domains the amino acid sequences are quite divergent. Nevertheless, introns are located at identical or nearly identical positions in elt-1 and the mouse GATA-1 gene. In addition, elt-1 mRNA is trans-spliced to the 22-base untranslated leader, SL1. The DNA upstream of the elt-1 TATA box contains eight copies of the GATA recognition sequence within the first 300 bp, suggesting that elt-1 may be autogenously regulated. Our results suggest that the specialized role of GATA-1 in erythroid gene expression was derived after separation of the nematodes and the line that led to the vertebrates, since C. elegans lacks an erythroid lineage.

CpG island methylation in premalignant stages of gastric carcinoma.

There are limited reports on methylation analysis of the premalignant lesions of gastric carcinoma thus far. This is despite the fact that gastric carcinoma is one of the tumors with a high frequency of CpG island hypermethylation. To determine the frequency and timing of hypermethylation during multistep gastric carcinogenesis, non-neoplastic gastric mucosa (n = 118), adenomas (n = 61), and carcinomas (n = 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1), death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP-3) methylation status using methylation-specific PCR. Three different classes of methylation behaviors were found in the five tested genes. DAP-kinase was methylated at a similar frequency in all four stages, whereas hMLH1 and p16 were methylated in cancer samples (20.3% and 42.2%, respectively) more frequently than in intestinal metaplasia (6.3% and 2.1%, respectively) or adenomas (9.8% and 11.5%, respectively). However, hMLH1 and p16 were not methylated in chronic gastritis. THBS-1 and TIMP-3 were methylated in all stages but showed a marked increase in hypermethylation frequency from chronic gastritis (10.1% and 14.5%, respectively) to intestinal metaplasia (34.7% and 36.7%, respectively; P < 0.05) and from adenomas (28.3% and 26.7%, respectively) to carcinomas (48.4% and 57.4%, respectively: P < 0.05). The hMLH1, THBS1, and TIMP-3 hypermethylation frequencies were similar in both intestinal metaplasia and adenomas, but the p16 hypermethylation frequency tended to be higher in adenomas (11.5%) than in intestinal metaplasia (2.1%; P = 0.073). The average number of methylated genes was 0.6, 1.1, 1.1, and 2.0 per five genes per sample in chronic gastritis, intestinal metaplasia, adenomas, and carcinomas, respectively. This shows a marked increase in methylated genes from non-metaplastic mucosa to intestinal metaplasia (P = 0.001) as well as from premalignant lesions to carcinomas (P = 0.002). These results suggest that CpG island hypermethylation occur early in multistep gastric carcinogenesis and tend to accumulate along the multistep carcinogenesis.

Activity of a C. elegans GATA transcription factor, ELT-1, expressed in yeast.

The GATA motif (WGATAR) is found in the promoter regions of numerous Caenorhabditis elegans genes, including two intestine-specific genes, vit-2 and ges-1, in which it has been shown to be required for promoter function. The protein ELT-1, encoded by a single-copy gene homologous to the GATA family of vertebrate transcription factors, is potentially capable of interacting with this element. In order to determine whether ELT-1 is a transcriptional activator that recognizes this sequence, we have expressed it under the control of the GAL1 promoter in yeast. lacZ driven by the CYC1 promoter lacking an upstream activation sequence (UAS) but containing GATA sequences was used as a reporter. beta-Galactosidase was expressed upon induction only when GATA sequences were present, and expression was increased dramatically by additional binding sites. Deletion analysis demonstrated that the C terminus, containing only one of the two zinc fingers, is sufficient for activation. In addition, the DNA-binding domain and two transactivation regions were identified by fusing these isolated domains to previously defined domains of heterologous transcription factors. While most single base alterations in the GATA core sequence eliminated activity, an A to C change in position four, creating a GATC core, was found to increase activity significantly. The deleted ELT-1 protein containing only the C-terminal Zn finger was sufficient for activation in response to GATA, but both fingers were required for activation at GATC. A variety of sites with non-optimal sequences surrounding the GATA core also were found to be excluded better by the protein containing both Zn fingers. Furthermore, a fusion protein containing the entire ELT-1 DNA binding domain fused to the VP16 activation domain was found to have an even greater preference for the GATC core, as well as the optimal flanking bases. We conclude that, although ELT-1 having only its C-terminal finger is capable of activation in response to the WGATAR site, the presence of the upstream finger supplies additional base specificity.

Effect of angiotensin-converting enzyme inhibitors on phenylephrine responsiveness in patients with valvular heart disease.

We studied patients with valvular heart disease to investigate whether chronic preoperative treatment with angiotensin-converting enzyme (ACE) inhibitors modulates the effect of phenylephrine (PE) on anaesthesia-induced hypotension. Sixty-five patients were enrolled in the study and hypotension developed after anaesthesia in 36 (18 in the control group and 18 in the ACE inhibitor group). These patients received PE infusions, which were increased in a stepwise fashion at 10-min intervals. Increased mean arterial pressure due to PE infusion was significant only in the control group. There was no significant difference in pressor response or change in haemodynamic variables with PE infusion between the two groups. Treatment with ACE inhibitors did not increase the incidence of hypotensive episodes or significantly modify pressor response after anaesthesia in patients with valvular heart disease.

elt-1, a gene encoding a Caenorhabditis elegans GATA transcription factor, is highly expressed in the germ lines with msp genes as the potential targets.

The Caenorhabditis elegans ELT-1 protein, a homolog of the vertebrate GATA transcription factor family, is a transcription activator that can recognize the GATA motif. We previously showed that the elt-1 mRNA was primarily expressed in C. elegans embryos. To examine whether the elt-1 mRNA in embryos is maternal, paternal or zygotic, Northern blot analysis was performed with RNA isolated from the C. elegans germ-line mutant strains, fem-2 (b245)lf, fem-3 (q20)gf, him-8 (e1489), and glp-4 (bn2). This analysis revealed that the high level of elt-1 mRNA in the C. elegans embryos resulted from either the maternal or the paternal transcription, rather than from the zygotic expression. These results further demonstrated that elt-1 was highly expressed in the germ-line of both sexes. To investigate the possible target genes for the ELT-1 protein in the germ line, the ELT-1 protein was expressed and tested for its binding specificity to the GATA motif that is present in the promoter region of the C. elegans major sperm protein genes. It was found that two conserved cis-elements, AGATCT and AGATAA, in the proximal promoter region of the msp-113 gene provided the best recognition site for ELT-1. Mutational analysis showed that the GATC core sequence was necessary for strong transactivation of the reporter gene, and that the combination of GATC and GATA motif resulted in a stronger transactivation by ELT-1 than either the duplicated GATC or GATA motif. These results suggest that the potential target for the ELT-1 protein in the germ-line may be one of the major sperm protein gene family.

Anti-apoptotic role of Bfl-1 in staurosporine-treated B-lymphoblastic cells.

To examine the relationship between the expression level of Bfl-1 and the susceptibility to staurosporine-induced apoptosis in B-lymphoblastic cells, we tested cell survival in 4 cell lines: 2 that are Bfl-1-nonexpressing (Reh and JM-1) and 2 that are Bfl-1-expressing (IM-9 and Wil2-NS). Reh and JM-1 showed apoptosis levels of 62% (Reh) and 30% (JM-1) as early as 3 hours after treatment with staurosporine, whereas IM-9 and Wil2-NS showed apoptosis levels of only 40% and 26%, respectively, even after 1 day of treatment with staurosporine. Either induced expression of Bfl-1 with 12-o-tetradecanoyl phorbol-13-acetate or exogenous expression of Bfl-1 by transfection in Reh cells promoted cell survival. These results suggest that expression of Bfl-1 contributes to regulating apoptosis in the B-cell lines we examined.

In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy.

Although the current clinical formulation of paclitaxel (Taxol) has a promising clinical activity against a wide variety of tumors, it has significant toxic side effects, some of which are associated with its formulation in a 1:1 (v/v) mixture of Cremophor EL and dehydrated alcohol. One of the problems associated with the intravenous administration of paclitaxel is its low solubility in water. Our study was designed to evaluate the pharmacokinetics, tissue distribution, toxicity and efficacy of a paclitaxel (Genexol)-containing biodegradable polymeric micellar system (Genexol-PM) in comparison to Taxol. Genexol-PM was newly developed by using a low molecular weight, nontoxic and biodegradable amphiphilic diblock copolymer, monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) and paclitaxel (Genexol, Samyang Genex Co., Seoul, Korea). In a human cancer cell line model, Genexol-PM and Taxol showed comparable in vitro cytotoxicity against human ovarian cancer cell line OVCAR-3 and human breast cancer cell line MCF7. The maximum tolerated dose (MTD) of Genexol-PM and Taxol in nude mice was determined to be 60 and 20 mg/kg, respectively. The median lethal dose (LD(50)) in Sprague--Dawley rats was 205.4 mg/kg (male) and 221.6 mg/kg (female) for Genexol-PM, while 8.3 mg/kg (male) and 8.8 mg/kg (female) for Taxol. After intravenous administration of Genexol-PM in murine B16 melanoma-induced female SPF C57BL/6 mice at a dose of 50 mg/kg, the area under the plasma concentration-time curve (AUC) was similar to Taxol((R)) at a dose of 20 mg/kg, but biodistribution of paclitaxel after administration of Genexol-PM showed 2 to 3-fold higher levels in tissues including liver, spleen, kidneys, lungs, heart and tumor as compared to Taxol. The in vivo antitumor efficacy of Genexol-PM as measured by reduction in tumor volume of SKOV-3 human ovarian cancer implanted in nude (nu/nu) athymic mice and MX-1 human breast cancer implanted in Tac:Cr:(NCr)-nu athymic mice was significantly greater than that of Taxol. The results of cytotoxicity, MTD, LD(50) and antitumor efficacy suggest that Genexol-PM may have a great advantage over present-day chemotherapy with Taxol.

Do dialysis patients need extra folate supplementation?

To assess folate status and to evaluate the need for conventional folate supplementation in patients on dialysis, we measured serum folate, vitamin B12, and red cell folate concentrations by radioimmunoassay. Thirty-four continuous ambulatory peritoneal dialysis (CAPD) patients and 60 hemodialysis (HD) patients who had not been supplemented with folate were enrolled. Serum folate levels (5.8 +/- 3.6 ng/mL vs 2.0 +/- 1.1 ng/mL, p < 0.001) and vitamin B12 levels (831.4 +/- 416.9 pg/mL vs 513.9 +/- 213.3 pg/mL, p < 0.001) were significantly higher in CAPD patients than HD patients. The red cell folate levels (849.7 +/- 489.4 ng/mL vs 491.0 +/- 253.2 ng/mL, p < 0.001) were also significantly higher in CAPD patients. The incidences of folate deficiency in CAPD and HD patients were overestimated using the cut-off value for serum folate concentration (3.0% vs 71.7%, respectively), but the incidence of true folate deficiency was lower using the cut-off value for red cell folate level (0.0% vs 10.0%, respectively). In conclusion, the true incidence of folate deficiency in stable CAPD and HD patients is surprisingly low, even in patients who may not be taking folate supplements. The need for conventional folate supplementation in patients with end-stage renal disease on dialysis must therefore be re-evaluated. Before the decision is made to use folate supplementation, measurement of red cell folate is essential to assess of folate reserves of the patients on dialysis.

The optimal effect site concentration of remifentanil in combination with intravenous midazolam and topical lidocaine for awake fibreoptic nasotracheal intubation in patients undergoing cervical spine surgery.

BACKGROUND: Remifentanil has been suggested as a suitable agent for conscious sedation during fibreoptic intubation. We evaluated the optimal effect site concentration (Ce) of remifentanil target-controlled infusion (TCI) for awake nasotracheal fibreoptic intubation in patients undergoing elective cervical spine surgery. METHODS: Nineteen ASA I-II patients were enrolled. Patients were premedicated with midazolam (<70 kg 1.5 mg; >70 kg 2.0 mg) intravenously. The EC(50) and EC(95) of remifentanil Ce for smooth intubation were determined using Dixon's up-and-down method and isotonic regression. Smooth intubation was considered to have failed when patients exhibited sustained and repetitive coughing with head lift during the procedure. Intubation time, number of attempts, adverse events, and hemodynamic variables were also recorded. Patients were asked to recall the procedure and grade satisfaction at postoperative 24 h. RESULTS: The EC(50) of remifentanil Ce for smooth intubation was 2.33±0.38 ng·mL-1 as calculated by Dixon's method. The estimated EC(95) of remifentanil Ce was 3.38 (95% confidence interval 2.90-3.46) ng·mL-1. Median intubation time (min) was longer in failed smooth intubation than in smooth intubation (8.0 vs. 6.1, P=0.048). Eleven patients (58%) recalled the procedure and 16 patients (84%) rated their satisfaction score as good or excellent. CONCLUSION: The estimated EC(95) of remifentanil Ce for smooth nasotracheal fibreoptic intubation with conscious sedation was 3.38 (95% CI 2.90-3.46) ng·mL-1 when used in combination with midazolam and topical lidocaine. Remifentanil TCI may provide a tolerable experience of awake fibreoptic intubation despite the high incidence of recall.

Intravenous glucose-insulin-potassium during off-pump coronary artery bypass surgery does not reduce myocardial injury.

BACKGROUND: This randomized, double-blind, placebo-controlled study was designed to determine whether an intra-operative, intravenous infusion of glucose-insulin-potassium (GIK) could be helpful in the prevention of myocardial ischemia and in the maintenance of intra-operative cardiac performance in patients undergoing off-pump coronary artery bypass (OP-CAB) surgery. METHODS: Eighty two adults undergoing elective OP-CAB surgery were randomly divided into two groups that received intravenously either 5% dextrose in water or GIK (50% dextrose in 500 ml of water; regular insulin, 125 IU; potassium, 80 mmol) at 0.75 ml/kg/h immediately before the induction of anesthesia to the end of surgery. To evaluate myocardial damage, creatine kinase MB and troponin T were measured before surgery, immediately after arrival in the intensive care unit and on the first post-operative day. To assess cardiac performance, hemodynamic data were obtained before and after the induction of anesthesia, before and after the bypass graft and after sternal closure. Blood glucose was measured at the same time. RESULTS: There was no significant difference in cardiac enzymes, hemodynamic parameters and blood glucose between the two groups. The use of vasoactive, inotropic and/or anti-arrhythmic agents, insulin and supplemental glucose was not significantly different between the groups. CONCLUSION: The results suggest that the intravenous administration of GIK during OP-CAB surgery neither reduces myocardial damage nor improves intra-operative cardiac performance in patients without contractile dysfunction.

Effect of cryoprotectants on the reconstitution of surfactant-free nanoparticles of poly(DL-lactide-co-glycolide).

Various cryoprotectants were tested to reconstitute the surfactant-free nanoparticles of poly(DL-lactide-co-glycolide) (PLGA). When 2.0% (w/v) of sucrose, trehalose and lactose were used, nanoparticles were completely reconstituted into aqueous solution and particle size was not significantly changed. Above 1.0% (w/v) of sucrose, trehalose and lactose, nanoparticles are well reconstituted whereas it was precipitated with 1.0% (w/v) of mannitol. Drug-encapsulated surfactant-free nanoparticles were quite reconstituted when 2.0% (w/v) of sucrose, trehalose and lactose. Drug release kinetics of nanoparticles was not significantly changed by cryoprotectants.