Effect of intravenous S-ketamine on the MAC of sevoflurane: a randomised, placebo-controlled, double-blinded clinical trial.

BACKGROUND: Ketamine is routinely used in operating theatres, emergency departments, ICUs, and even outpatient units. Despite the widespread use of ketamine, only basic aspects of its interactions with inhalation anaesthetic agents are known, and formal testing of interactions in humans is lacking. The minimum alveolar concentration (MAC) of inhalation anaesthetics is used to guide the depth of anaesthesia, and several drugs are known to influence the MAC. The aim of this study was to investigate whether intravenous application of ketamine influences the MAC of sevoflurane in humans. METHODS: Adult patients undergoing elective surgery were included in this randomised, double-blinded, placebo-controlled study. Patients were assigned to one of three groups, each of which received a bolus of placebo, 0.5 mg kg-1S-ketamine, or 1 mg kg-1S-ketamine followed by an infusion of the same amount per hour after inhalation induction with sevoflurane was performed. The response to skin incision (movement vs non-movement) was recorded. The MAC of sevoflurane was assessed using an up-and-down titration method. RESULTS: Sixty patients aged 30-65 yr were included. Each group consisted of 20 patients. The MAC of sevoflurane was higher in the placebo group (2.1 (sd 0.1) %) than in the low-dose ketamine group (0.9 (0.1)%, P<0.01) and the high-dose ketamine group (0.5 (0.1)%, P<0.01). In addition, the MAC of sevoflurane was higher in the low-dose ketamine group compared with the high-dose ketamine group (P<0.01). CONCLUSIONS: The administration of S-ketamine significantly and dose-dependently reduced the MAC of sevoflurane in humans. CLINICAL TRIAL NUMBER: EudraCT ref. no. 2012-001908-38.

Intravenous lidocaine increases the depth of anaesthesia of propofol for skin incision--a randomised controlled trial.

BACKGROUND: The anaesthetic potency of intravenous propofol is quantified by its Cp50 value, which is defined as the plasma concentration required to prevent movement response in 50% of patients to surgical stimuli. We hypothesised that, in addition to propofol anaesthesia, an intravenous bolus of lidocaine 1.5 mg/kg will decrease the Cp50 value of propofol during anaesthesia. METHODS: We enrolled 54 elective surgical patients undergoing propofol-based anaesthesia, and randomised them to either lidocaine 1.5 mg/kg, lidocaine 0.5 mg/kg or placebo (NaCl 0.9%) 3 min before skin incision. The propofol Cp50 value was then calculated using the 'up-and-down' method of Dixon and Massey. RESULTS: There was no significant reduction in propofol requirements after the administration of 0.5 mg/kg lidocaine from 8.5 µg/ml [confidence interval (CI) 6.0-11.625] to 8.25 µg/ml (CI 6.75-9.76); however, a bolus of 1.5 mg/kg lidocaine decreased the Cp50 value of propofol by 42% from 8.5 µg/ml (CI 6.0-11.625) to 4.92 µg/ml (CI 4.5-5.78) (P < 0.05). CONCLUSION: An intravenous bolus injection of 1.5 mg/kg lidocaine 2% caused a significant reduction of the propofol Cp50 value.

Epidermal growth factor receptor is required for estradiol-stimulated bovine satellite cell proliferation.

The objective of this study was to assess the role of the epidermal growth factor receptor (EGFR) in estradiol-17ß (E2)-stimulated proliferation of cultured bovine satellite cells (BSCs). Treatment of BSC cultures with AG1478 (a specific inhibitor of EGFR tyrosine kinase activity) suppresses E2-stimulated BSC proliferation (P < 0.05). In addition, E2-stimulated proliferation is completely suppressed (P < 0.05) in BSCs in which EGFR expression is silenced by treatment with EGFR small interfering RNA (siRNA). These results indicate that EGFR is required for E2 to stimulate proliferation in BSC cultures. Both AG1478 treatment and EGFR silencing also suppress proliferation stimulated by LR3-IGF-1 (an IGF1 analogue that binds normally to the insulin-like growth factor receptor (IGFR)-1 but has little or no affinity for IGF binding proteins) in cultured BSCs (P < 0.05). Even though EGFR siRNA treatment has no effect on IGFR-1ß mRNA expression in cultured BSCs, IGFR-1ß protein level is substantially reduced in BSCs treated with EGFR siRNA. These data suggest that EGFR silencing results in post-transcriptional modifications that result in decreased IGFR-1ß protein levels. Although it is clear that functional EGFR is necessary for E2-stimulated proliferation of BSCs, the role of EGFR is not clear. Transactivation of EGFR may directly stimulate proliferation, or EGFR may function to maintain the level of IGFR-1ß which is necessary for E2-stimulated proliferation. It also is possible that the role of EGFR in E2-stimulated BSC proliferation may involve both of these mechanisms.

Ultrabroadband, coherent light source based on self-channeling of few-cycle pulses in helium.

Self-channeling of few-cycle laser pulses in helium at high pressure generates coherent light supercontinua spanning the range of 270-1000 nm, with the highest efficiency demonstrated to date. Our results open the door to the synthesis of powerful light waveforms shaped within the carrier field oscillation cycle and hold promise for the generation of pulses at the single-cycle limit.

TRP channels activated by extracellular hypo-osmoticity in epithelia.

TRP (transient receptor potential) channels comprise a superfamily of non-selective cation channels with at least seven subfamilies. The variety of subfamilies corresponds to the differences in the activation mechanisms and functions. TRPM3 (TRP melastatin 3) and TRPV4 (TRP vanilloid 3) have been characterized as cation channels activated by extracellular hypo-osmoticity. In addition, TRPV4 is activated by metabolites of arachidonic acid as well as alpha-isomers of phorbol esters known to be ineffective in stimulating proteins of the protein kinase C family. TRPM3 is responsive to sphingosine derivatives. The detection of splice variants with probably different activation mechanisms supports the idea that TRPM3 may have diverse cellular functions depending on the expression of a particular variant. The expression of TRPV4 in many epithelial cell types raised the question of the role of TRPV4 in epithelial physiology. Single-cell experiments as well as approaches using epithelial layers show that multiple cellular responses are triggered by TRPV4 activation and subsequent elevation of intracellular calcium. The TRPV4-induced responses increasing transcellular ion flux as well as paracellular permeability may allow the cells to adjust to changes in extracellular osmolarity. In summary, TRPV4 plays a central role in epithelial homoeostasis by modulating epithelial barrier function.

Burkholderia phytofirmans sp. nov., a novel plant-associated bacterium with plant-beneficial properties.

A Gram-negative, non-sporulating, rod-shaped, motile bacterium, with a single polar flagellum, designated strain PsJN(T), was isolated from surface-sterilized onion roots. This isolate proved to be a highly effective plant-beneficial bacterium, and was able to establish rhizosphere and endophytic populations associated with various plants. Seven related strains were recovered from Dutch soils. Based on 16S rRNA gene sequence data, strain PsJN(T) and the Dutch strains were identified as representing a member of the genus Burkholderia, as they were closely related to Burkholderia fungorum (98.7 %) and Burkholderia phenazinium (98.5 %). Analysis of whole-cell protein profiles and DNA-DNA hybridization experiments confirmed that all eight strains belonged to a single species. Strain PsJN(T) had a DNA G+C content of 61.0 mol%. Only low levels of DNA-DNA hybridization to closely related species were found. Qualitative and quantitative differences in fatty acid composition between strain PsJN(T) and closely related species were identified. The predominant fatty acids in strain PsJN(T) were 16 : 0, 18 : 1omega7c and summed feature 3 (comprising 16 : 1omega7c and/or iso-15 : 0 2-OH). Isolate PsJN(T) showed high 1-aminocyclopropane-1-carboxylate deaminase activity and is therefore able to lower the ethylene level in a developing or stressed plant. Production of the quorum-sensing signal compound 3-hydroxy-C8-homoserine lactone was detected. Based on the results of this polyphasic taxonomic study, strain PsJN(T) and the seven Dutch isolates are considered to represent a single, novel species, for which the name Burkholderia phytofirmans sp. nov. is proposed. The type strain is strain PsJN(T) (=LMG 22146(T) = CCUG 49060(T)).

Avian exocrine secretions. I. Chemical characterization of the volatile fraction of the uropygial secretion of the green woodhoopoe, Phoeniculus purpureus.

Using gas chromatography-mass spectrometry in conjunction with auxiliary techniques such as solid phase microextraction and determination of double bond positions by means of dimethyl disulfide derivatization, 45 constituents of the uropygial secretion of the green woodhoopoe, Phoeniculus purpureus, have been identified. The majority of these constituents are long-chain branched and unbranched alkanes, and (Z)-alkenes such as (Z)-9-tricosene, and a number of unidentified wax esters. The more volatile fraction of the secretion contained short-chain fatty acids, aldehydes, aliphatic and heterocyclic aromatic amines, ketones, and dimethyl sulfides. This group of volatile compounds is responsible for the obnoxious odor of the secretion and also for its defensive action against predators.

Mammalian exocrine secretions. XVIII: Chemical characterization of interdigital secretion of red hartebeest, Alcelaphus buselaphus caama.

Gas chromatography, coupled gas chromatography-mass spectrometry (electron impact mode and chemical ionization with methane as reactant gas), gas chromatography-infrared spectroscopy, and derivatization techniques were used to identity 53 compounds in the interdigital secretion of the red hartebeest, Alcelaphus buselaphus caama. These compounds included alkanes, isoalkanes, alcohols, ketones, carboxylic acids, oxiranes, furanoid linalool oxides, and a large number of branched and unbranched saturated and unsaturated aldehydes. The secretion probably plays a role in demarcation of territories by dominant bulls.

Common iliac artery pseudoaneurysm following inguinal hernia repair--a case report and literature review.

The authors report a patient presented with a ruptured infected iliac artery pseudoaneurysm 2 weeks after ipsilateral inguinal hernia repair. Pseudoaneurysms that occur because of infection develop rapidly and mandate ligation of the affected artery and extraanatomic bypass. Noninfected pseudoaneurysms are usually discovered incidentally and may be managed with either endovascular or standard surgical techniques. A percutaneously placed aortic occlusion balloon may prevent exsanguination, when used as an adjunct to surgical repair in cases of ruptured pseudoaneurysm.

Increased expression of cytochrome p450 1A1 and 1B1 genes in anti-estrogen-resistant human breast cancer cell lines.

The expression of CYP1A1 and CYP1B1, encoding enzymes known to play a central role in oxidative metabolism of a wide range of compounds including steroids, was significantly increased in anti-estrogen-resistant human breast cancer cell lines. This was a purely regulatory phenomenon because no gene amplification had occurred. In anti-estrogen-sensitive MCF-7 cells, the steroidal anti-estrogen, ICI 182780, is able to induce the expression of the arylhydrocarbon receptor (AhR)-regulated gene product, CYP1A1, via an estrogen receptor (ER)- mediated process. This observation suggests cross-talk between the AhR and ER systems. Surprisingly, the increased constitutive expression in anti-estrogen-resistant cells of CYP1A1 and CYP1B1 mRNAs, encoding detoxification enzymes, had no effect on the activity of the ICI 182780 compound. The ICI 182780 regulation of estradiol-inducible genes was found to be identical in the resistant and sensitive breast cancer cell lines. In conclusion, anti-estrogen resistance is not due to conversion of ICI 182780 to less active compounds.

Cloning and characterization of EstC from Burkholderia gladioli, a novel-type esterase related to plant enzymes.

By screening a genomic library of Burkholderia gladioli (formerly Pseudomonas marginata) for clones exhibiting esterolytic activity, the gene for a novel-type esterase (EstC) showing significant homology to plant enzymes could be isolated. High homology was found to two hydroxynitrile lyases originating from Hevea brasiliensis (tropical rubber tree) and Manihot esculenta (cassava), and to two proteins from Oryza sativa (rice) that are specifically induced upon infection by Pseudomonas syringae pv. syringae. The sequenced ORF encodes for a protein of 298 amino acids. The enzyme was efficiently overexpressed in Escherichia coli, purified and characterized with respect to enzymatic capabilities. The enzyme was able to hydrolyze a variety of esterase substrates of low to medium carbonic acid chain length, but no triglycerides were hydrolyzed. Despite the high sequence homology, no hydroxynitrile lyase activity could be recognized.

Determination of tocopherols and sterols in vegetable oils by solid-phase extraction and subsequent capillary gas chromatographic analysis.

In general, analyses of tocopherols and sterols are performed separately in vegetable oils. By applying solid-phase extraction (SPE) prior to capillary gas chromatography, a simple and reliable procedure for the quantification of both tocopherols and sterols in a single analytical run has been developed. SPE was used as sample clean up procedure for the separation of these minor components from the triacylglycerol matrix, replacing time consuming saponification or on-line LC-GC. The analysis of tocopherols and free sterols in five different vegetable oils illustrates robustness and reliability of this method outlined. Quantification of the analytes was performed by external calibration with reference substances and internal standardization. The recovery of the procedure as well as the repeatability of the quantitative results have been evaluated.

Skeletal muscle biochemical adaptations to exercise training in miniature swine.

The primary purpose of this study was to test the hypothesis that endurance exercise training induces increased oxidative capacity in porcine skeletal muscle. To test this hypothesis, female miniature swine were either trained by treadmill running 5 days/wk over 16-20 wk (Trn; n = 35) or pen confined (Sed; n = 33). Myocardial hypertrophy, lower heart rates during submaximal stages of a maximal treadmill running test, and increased running time to exhaustion during that test were indicative of training efficacy. A variety of skeletal muscles were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant enzymes. Fiber type composition of a representative muscle was also determined histochemically. The largest increase in CS activity (62%) was found in the gluteus maximus muscle (Sed, 14.7 +/- 1.1 mumol.min-1.g-1; Trn, 23.9 +/- 1.0; P < 0.0005). Muscles exhibiting increased CS activity, however, were located primarily in the forelimb; ankle and knee extensor and respiratory muscles were unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity was unchanged with training, as were activities of antioxidant enzymes. Histochemical analysis of the triceps brachii muscle (long head) revealed lower type IIB fiber numbers in Trn (Sed, 42 +/- 6%; Trn, 10 +/- 4; P < 0.01) and greater type IID/X fiber numbers (Sed, 11 +/- 2; Trn, 22 +/- 3; P < 0.025). These findings indicate that porcine skeletal muscle adapts to endurance exercise training in a manner similar to muscle of humans and other animal models, with increased oxidative capacity. Specific muscles exhibiting these adaptations, however, differ between the miniature swine and other species.

Estrogen receptor messenger RNA splice variants are not involved in antiestrogen resistance in sublines of MCF-7 human breast cancer cells.

Development of resistance to tamoxifen is a serious problem in treatment of breast cancer patients. Although the mechanisms for development of resistance are unclear, an altered expression of alternatively spliced estrogen receptor (ER) mRNA has been suggested to be involved. We have looked for differential expression of ER splice variants lacking exon 2 (ERdeltaE2), exon 3 (ERdeltaE3), exon 4 (ERdeltaE4), exon 5 (ERdeltaE5), exon 7 (ERdeltaE7), and exons 4 and 7 (ERdeltaE4, 7) in the human breast cancer cell line MCF-7 and 10 ER-positive MCF-7 sublines resistant to the antiestrogens tamoxifen, ICI 164,384 or ICI 182,780. No major differences in the expression were demonstrated between MCF-7 cells and resistant cells, indicating that ER splice variants are not involved in antiestrogen resistance in this model system. Furthermore, despite a high mRNA level of some of the ER splice variants, no corresponding proteins could be detected using Western blot analysis.

Popliteal vein compression due to popliteal artery aneurysm: effects of aneurysm size.

Unlike the venous compression associated with larger popliteal artery aneurysms, which frequently is associated with deep vein thrombosis, the venous compression caused by the moderate sized (greater than 2 cm and less than 3 cm) aneurysms in the reported cases is not associated with thrombosis. The extrinsic compressive effect of these moderate sized popliteal artery aneurysms on the adjacent vein is shown to vary with the patient's leg position. Three of the four patients with unilateral leg swelling discussed here had bilateral popliteal artery aneurysms. In these cases, the contralateral leg had a small popliteal aneurysm (less than 2 cm) and no leg swelling was present. The cases suggest that popliteal artery aneurysm size is an important factor in determining the type of venous obstruction that results from the extrinsic compression of the ipsilateral popliteal vein. The described phenomenon of a popliteal artery aneurysm having the effect of restricting flow in the ipsilateral popliteal vein must be included as a differential diagnosis among the causes of unilateral leg swelling in the absence of deep vein thrombosis.

Differential expression of estrogen receptor mRNA splice variants in the tamoxifen resistant human breast cancer cell line, MCF-7/TAMR-1 compared to the parental MCF-7 cell line.

Breast cancer patients with an estrogen receptor (ER) positive tumor can be treated with the anti-estrogen tamoxifen, but development of anti-estrogen resistance is a serious problem. We have analyzed a tamoxifen resistant human breast cancer cell line MCF-7/TAMR-1 for alterations in ER which might explain the tamoxifen resistance. The MCF-7/TAMR-1 cells expressed both wild-type ER mRNA and protein, and by RT-PCR we were able to clone ER cDNAs corresponding to the following mRNA splice variants: ER delta E2, ER delta E4, ER delta E5, ER delta E7 and a new double splice variant lacking both exon 4 and 7 (ER delta E4,7) The existence of the ER delta E4,7 variant was confirmed by RNase protection assay. Semi-quantitative RT-PCR revealed that ER delta E2 mRNA was expressed at a higher level in MCF-7/TAMR-1 cells, whereas the ER delta E5 mRNA was expressed at a significantly lower level in MCF-7/TAMR-1 cells compared with MCF-7 cells. The differential expression of the two ER mRNA splice variants indicates that they may be involved in anti-estrogen resistance, although the present knowledge of their biological function does not provide us with an explanation.

An object-oriented software for fate and exposure assessments.

The model system CemoS(1) (Chemical Exposure Model System) was developed for the exposure prediction of hazardous chemicals released to the environment. Eight different models were implemented involving chemicals fate simulation in air, water, soil and plants after continuous or single emissions from point and diffuse sources. Scenario studies are supported by a substance and an environmental data base. All input data are checked on their plausibility. Substance and environmental process estimation functions facilitate generic model calculations. CemoS is implemented in a modular structure using object-oriented programming.