bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen‐induced arthritis in rodents
Authors: Lin H‐S , Hu C‐Y , Chan H‐Y , Liew Y‐Y , Huang H‐P , Lepescheux L , Bastianelli E , Baron R , Rawadi G , Clément‐Lacroix P 
Published: February 2007

Background and purpose:Rheumatoid arthritis (RA) is a chronic inflammatory disease. Histone deacetylase inhibitors (HDACi), a new class of anti‐cancer agents, have recently been reported to exhibit potent anti‐inflammatory activities. A proof of concept study was carried out with suberoylanilide hydroxamic acid (SAHA) and MS‐275, two HDACi currently undergoing clinical investigations for various oncological indications.Experimental approach:The anti‐rheumatic effects of SAHA and MS‐275 were assessed in both mouse and rat collagen induced arthritis (CIA) models.Key results:SAHA exhibited moderate prophylactic efficacy. It attenuated paw swelling due to inflammation, decreased bone erosion in both mice and rats and reduced slightly the RA‐induced bone resorption in rats. However, SAHA could not inhibit the onset of arthritis. In contrast, MS‐275 displayed dramatic anti‐rheumatic activities. In prophylactic intervention, high doses of MS‐275 prevented bone erosion and markedly delayed the onset of arthritis; at low doses, MS‐275 strongly attenuated paw swelling, bone erosion, and bone resorption associated with RA. Furthermore, the therapeutic efficacy of MS‐275 was also documented. After the onset of arthritis, it could stop the disease progression and joint destruction. An anti inflammatory effect of MS‐275 was also confirmed through its capacity to decrease serum IL‐6 and IL‐1β levels in the CIA induced mouse model. The anti‐rheumatic activity of MS‐275 was also confirmed through histological observation. No synovial hyperplasia, pannus formation, cartilage or bone destruction were observed in the high dose prophylactic intervention in mice.Conclusion and implication:This study strongly supported HDACi as an innovative therapeutic strategy for RA.British Journal of Pharmacology (2007) 150, 862–872. doi:10.1038/sj.bjp.0707165
HDAC inhibitors as anti‐inflammatory agents
Authors: Adcock I M 
Published: February 2007

Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by changes in the acetylation status of histones and non‐histone proteins. Many human diseases, particularly cancer, have been associated with altered patterns of histone acetylation. Furthermore, abnormal expression and activation of histone acetyltransferases, which act as transcriptional co‐activators, has been reported in inflammatory diseases. Histone deacetylase (HDAC) inhibitors have been developed clinically for malignancies due to their effects on apoptosis. More recently, in vitro and in vivo data indicates that HDAC inhibitors may be anti‐inflammatory due to their effects on cell death acting through acetylation of non‐histone proteins. Although there are concerns over the long‐term safety of these agents, they may prove useful particularly in situations where current anti‐inflammatory therapies are suboptimal.British Journal of Pharmacology (2007) 150, 829–831. doi:10.1038/sj.bjp.0707166
FTY720 suppresses interleukin‐1β‐induced secretory phospholipase A2 expression in renal mesangial cells by a transcriptional mechanism
Authors: Xin C , Ren S , Eberhardt W , Pfeilschifter J , Huwiler A 
Published: February 2007

Background and purpose:FTY720 is a potent immunomodulatory prodrug that is converted to its active phosphorylated form by a sphingosine kinase. Here we have studied whether FTY720 mimicked the action of sphingosine‐1‐phosphate (S1P) and exerted an anti‐inflammatory potential in renal mesangial cells.Experimental approach:Prostaglandin E2 (PGE2) was quantified by an enzyme‐linked immunosorbent‐assay. Secretory phospholipase A2 (sPLA2) protein was detected by Western blot analyses. mRNA expression was determined by Northern blot analysis and sPLA2‐promoter activity was measured by a luciferase‐reporter‐gene assay.Key results:Stimulation of cells for 24 h with interleukin‐1β (IL‐1β) is known to trigger increased PGE2 formation which coincides with an induction of the mRNA for group‐IIA‐sPLA2 and protein expression. FTY720 dose‐dependently suppressed IL‐1β‐induced IIA‐sPLA2 protein secretion and activity in the supernatant. This effect is due to a suppression of cytokine‐induced sPLA2 mRNA expression which results from a reduced promoter activity. As a consequence of suppressed sPLA2 activity, PGE2 formation is also reduced by FTY720. Mechanistically, the FTY720‐suppressed sPLA2 expression results from an activation of the TGFβ/Smad signalling cascade since inhibition of the TGFβ receptor type I by a specific kinase inhibitor reverses the FTY720‐mediated decrease of sPLA2 protein expression and sPLA2 promoter activity.Conclusions and implications:In summary, our data show that FTY720 was able to mimic the anti‐inflammatory activity of TGFβ and blocked cytokine‐triggered sPLA2 expression and subsequent PGE2 formation. Thus, FTY720 may exert additional in vivo effects besides the well reported immunomodulation and its anti‐inflammatory potential should be considered.British Journal of Pharmacology (2007) 150, 943–950. doi:10.1038/sj.bjp.0707171
The ‘specific’ tyrosine kinase inhibitor genistein inhibits the enzymic hydrolysis of anandamide: implications for anandamide uptake
Authors: Thors L , Alajakku K , Fowler C J 
Published: February 2007

Background and Purpose:The cellular uptake of anandamide is reduced by inhibitors of fatty acid amide hydrolase (FAAH) and by agents disrupting endocytotic mechanisms. However, it is not clear if these events occur over the same time frame and if they occur to the same extent in different cells. We have therefore investigated the effects of such compounds in three cell lines of different origins using different assay incubation times and temperatures.Experimental approach:FAAH activity and cellular uptake of anandamide was measured using anandamide, radio‐labelled either in the ethanolamine or arachidonoyl part of the molecule.Key results:The FAAH inhibitor URB597 inhibited the uptake of anandamide into C6 glioma, RBL2H3 basophilic leukaemia cells and P19 embryonic carcinoma cells at incubation time 4 min. However, a time‐dependent and temperature‐sensitive residual uptake remained after URB597 treatment. The combination of progesterone and nystatin reduced the uptake, but also decreased the amount of anandamide retained by the wells. Genistein inhibited anandamide uptake in a manner that was not additive to that of URB597. However, genistein was a potent competitive inhibitor of FAAH (Kivalue 8 μM).Conclusions and implications:The reduction of anandamide uptake by genistein can be explained by its ability to inhibit FAAH with a potency which overlaps that for inhibition of tyrosine kinase. The FAAH‐ resistant but time‐dependent uptake of anandamide is seen in all three cell lines studied and is thus presumably a generally occurring process.British Journal of Pharmacology(2007)150,951–960. doi:10.1038/sj.bjp.0707172
New potent and selective cytochrome P450 2B6 (CYP2B6) inhibitors based on three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) analysis
Authors: Korhonen L E , Turpeinen M , Rahnasto M , Wittekindt C , Poso A , Pelkonen O , Raunio H , Juvonen R O 
Published: February 2007

Background and purpose:The cytochrome P450 2B6 (CYP2B6) enzyme metabolises a number of clinically important drugs. Drug‐drug interactions resulting from inhibition or induction of CYP2B6 activity may cause serious adverse effects. The aims of this study were to construct a three‐dimensional structure‐activity relationship (3D‐QSAR) model of the CYP2B6 protein and to identify novel potent and selective inhibitors of CYP2B6 forin vitroresearch purposes.Experimental approach:The inhibition potencies (IC50values) of structurally diverse chemicals were determined with recombinant human CYP2B6 enzyme. Two successive models were constructed using Comparative Molecular Field Analysis (CoMFA).Key results:Three compounds proved to be very potent and selective competitive inhibitors of CYP2B6in vitro(IC50<1μM): 4‐(4‐chlorobenzyl)pyridine (CBP), 4‐(4‐nitrobenzyl)pyridine (NBP), and 4‐benzylpyridine (BP). A complete inhibition of CYP2B6 activity was achieved with 0.1μM CBP, whereas other CYP‐related activities were not affected. Forty‐one compounds were selected for further testing and construction of the final CoMFA model. The created CoMFA model was of high quality and predicted accurately the inhibition potency of a test set (n=7) of structurally diverse compounds.Conclusions and implications:Two CoMFA models were created which revealed the key molecular characteristics of inhibitors of the CYP2B6 enzyme. The final model accurately predicted the inhibitory potencies of several structurally unrelated compounds. CBP, BP and NBP were identified as novel potent and selective inhibitors of CYP2B6 and CBP especially is a suitable inhibitor forin vitroscreening studies.British Journal of Pharmacology(2007)150,932–942. doi:10.1038/sj.bjp.0707173
5‐HT4receptor agonists increase sAPPα levels in the cortex and hippocampus of male C57BL/6j mice
Authors: Cachard‐Chastel M , Lezoualc'h F , Dewachter I , Deloménie C , Croes S , Devijver H , Langlois M , Van Leuven F , Sicsic S , Gardier A M 
Published: February 2007

Background and purpose:A strategy to treat Alzheimer's disease (AD) is to increase the soluble form of amyloid precursor protein (sAPPα), a promnesic protein, in the brain. Because strong evidence supports beneficial effects of 5‐hydroxytryptamine 5‐HT4receptor agonists in memory and learning, we investigated the role of 5‐HT4receptors on APP processing in 8 weeks‐old male C57BL/6j mice.Experimental approach:Mice were given, subcutaneously, prucalopride or ML 10302 (s.c.), two highly selective 5‐HT4receptor agonists and, up to 240 min later, the hippocampus and cortex were analysed by Western blot for sAPPα determination.Key results:Prucalopride (5 or 10 mg kg‐1) significantly increased sAPPαlevels in the hippocampus and cortex, but did not modify the expression level of APP mRNA as detected by quantitative RT‐PCR. A selective 5‐HT4receptor antagonist, GR125487 (1 mg kg‐1, s.c.) inhibited prucalopride induced‐ increase in sAPPα levels. In addition, levels of sAPPα were increased by ML10302 only at 20 mg kg‐1and was limited to the cortex. Also, prucalopride increased sAPPα levels in the cortex of a transgenic mouse model of AD, expressing the London mutation of APP. Furthermore, the combined injection of a selective acetylcholinesterase inhibitor, donepezil and prucalopride induced a synergic increase in sAPPα levels in the cortex and hippocampus.Conclusions and implications:Our results demonstrate that the 5‐HT4receptor plays a key role in the non‐amyloidogenic pathway of APP metabolismin vivoand give support to the beneficial use of 5‐HT4agonists for AD treatment.British Journal of Pharmacology(2007)150,883–892. doi:10.1038/sj.bjp.0707178
Sensitivity analysis, molecular systematics and natural history evolution of Scathophagidae (Diptera: Cyclorrhapha: Calyptratae)
Authors: Kutty Sujatha Narayanan , Bernasconi Marco Valerio , Šifner František , Meier Rudolf 
Published: February 2007

AbstractThe 60 000 described species of Cyclorrhapha are characterized by an unusual diversity in larval life‐history traits, which range from saprophagy over phytophagy to parasitism and predation. However, the direction of evolutionary change between the different modes remains unclear. Here, we use the Scathophagidae (Diptera) for reconstructing the direction of change in this relatively small family (≈ 250 spp.) whose larval habits mirror the diversity in natural history found in Cyclorrhapha. We subjected a molecular data set for 63 species (22 genera) and DNA sequences from seven genes (12S, 16S, Cytb, COI, 28S, Ef1‐alfa, Pol II) to an extensive sensitivity analysis and compare the performance of three different alignment strategies (manual, Clustal, POY). We find that the default Clustal alignment performs worst as judged by character incongruence, topological congruence and branch support. For this alignment, scoring indels as a fifth character state worsens character incongruence and topological congruence. However, manual alignment and direct optimization perform similarly well and yield near‐identical trees, although branch support is lower for the direct‐optimization trees. All three alignment techniques favor the upweighting of transversion. We furthermore confirm the independence of the concepts “node support” and “node stability” by documenting several cases of poorly supported nodes being very stable and cases of well supported nodes being unstable. We confirm the monophyly of the Scathophagidae, its two constituent subfamilies, and most genera. We demonstrate that phytophagy in the form of leaf mining is the ancestral larval feeding habit for Scathophagidae. From phytophagy, two shifts to saprophagy and one shift to predation has occurred while a second origin of predation is from a saprophagous ancestor.© The Willi Hennig Society 2006.
Distinguishing between convergence and parallelism is central to comparative biology: a reply to Williams and Ebach
Authors: Desutter‐Grandcolas Laure , Legendre Frédéric , Grandcolas Philippe , Robillard Tony , Murienne Jérôme 
Published: February 2007

AbstractThe definitions of character similarity, homology, homoplasy, heterology, parallelism and convergence are clarified in the framework of current phylogenetic methodology. They are all associated with definite patterns of character change and can consequently be tested by phylogeny building. Their crucial significance in comparative biology is illustrated using demonstrative examples.© The Willi Hennig Society 2006.
Arterial oxygen saturation during induction of anaesthesia
Authors: THORPE C. M. , GAUNTLETT I. S. 
Published: February 2007

SummaryThree groups of 10 ASA 1 patients were studied to determine the incidence of hypoxaemia (oxygen saturation ≤ 90%) using pulse oximetry during induction of ‘mask’ anaesthesia, and whether simple oxygenation techniques could prevent its occurrence. We also surveyed all anaesthetists in three major hospitals to ascertain their techniques for this method of anaesthesia. Anaesthesia was induced in all patients with thiopentone and maintained with nitrous oxide and isoflurane. The first group received 33% oxygen in nitrous oxide as carrier gases, a second group a few normal breaths of 100% oxygen during thiopentone administration followed by 33% oxygen in nitrous oxide, while a third group received 100% oxygen after loss of eyelash reflex until spontaneous breathing was established. No patient received positive pressure ventilation before spontaneous breathing was established. Six of the 10 patients in the first group became hypoxaemic compared to none in the second group, and three patients became hypoxaemic in the third group. Thirty‐seven percent of anaesthetists who responded to the survey either did not apply positive pressure ventilation before establishment of spontaneous breathing, or only did so if apnoea was prolonged. Only one anaesthetist fully pre‐oxygenated patients lungs. We conclude that to avoid the likely occurrence of hypoxaemia during induction of mask anaesthesia, a minimum of a few breaths pre‐oxygenation is necessary.
The effects of midazolam on cerebral blood flow and oxygen consumption Interaction with nitrous oxide in patients undergoing craniotomy for supratentorial cerebral tumours
Authors: KNUDSEN L. , COLD G. E. , HOLDGÅRD H. O. , And U. T. , JENSEN S. 
Published: February 2007

SummaryCerebral blood flow and the cerebral metabolic rate of oxygen were measured in 30‐patients during craniotomy for supratentorial cerebral tumours by a modification of the Kety‐Schmidt technique using Xenon 133 intravenously. Anaesthesia was induced with midazolam 0.3 mg/kg, fentanyl and pancuronium, and maintained with midazolam as a continuous infusion, fentanyl, pancuronium and nitrous oxide in oxygen or oxygen in air. The concentration of midazolam in the blood of 10 patients was about 300 ng/litre during two measurements; the patients’ lungs were ventilated with N2O in oxygen. The concentration of midazolam in the blood of another 10 patients was doubled to about 600 ng/litre during the second flow measurement; the patients’ lungs were ventilated with N2O/O2. The concentration of midazolam in the blood of the third group of 10 patients was doubled to 600 ng/litre during the second flow measurement; the patients’ lungs were ventilated with oxygen in air. No relationship was found between the dose of midazolam and cerebral blood flow or oxygen consumption. Nitrous oxide in combination with midazolam also had no effect on these variables.
Obstetric epidural analgesia with mixtures of bupivacaine, adrenaline and fentanyl
Authors: YAU G. , GREGORY M. A. , GIN T. , OH T. E. 
Published: February 2007

SummaryWe performed a double‐blind comparison of six solutions for epidural analgesia in 90 healthy Chinese women with uncomplicated pregnancies. Patients were randomly allocated to receive 10 ml bupivacaine 0.125% or 0.25% plain, bupivacaine 0.125% with adrenaline 1.25 μg/ml, bupivacaine 0.25% with adrenaline 2.5 μg/ml or the latter two solutions with added fentanyl 50 μg. Analgesia was unsatisfactory in 30% of the bupivacaine 0.125% groups without fentanyl. The addition of adrenaline, compared with bupivacaine 0.25% plain, gave faster onset and longer duration of analgesia (p < 0.05) which was similar to that found in both fentanyl groups. There were no differences in method of delivery or neonatal Apgar scores among groups. The least concentrated mixture that gave the best analgesia was the combination of bupivacaine 0.125% with adrenaline 1.25 μg/ml and fentanyl 50 μg.
A randomised double‐blind study of interpleural analgesia after cholecystectomy
Authors: LEE A. , BOON D. , BAGSHAW P. , KEMPTHORNE P. 
Published: February 2007

SummaryContinuous interpleural analgesia provided by 4 hourly injections of 20 ml bupivacaine 0.5% with adrenaline 5 μg/ml was compared with placebo in a randomised, double‐blind study after cholecystectomy. All patients self‐administered intravenous morphine using a patient‐controlled analgesia device. There was a highly significant difference in mean morphine consumption between the groups (72mg as compared with 22 mg). Visual analogue pain scores tended to be lower in the bupivacaine group throughout and this was significant at 2 hours. Respiratory function measurements were not significantly different between the groups. The mean peak venous plasma bupivacaine concentration after the sixth dose was 3.03 μg/ml and no symptoms suggestive of local anaesthetic toxicity occurred. It is concluded that this regimen can provide effective and continuous analgesia after cholecystectomy and that combined administration of interpleural bupivacaine and systemic morphine is more effective than morphine alone in the immediate postoperative period. The doses of bupivacaine required for optimal use of the technique lead to significant total plasma bupivacaine concentrations within 24 hours.
Anaphylactic anaesthetic reactions. The value of paper radioallergosorbent tests for IgE antibodies to muscle relaxants and thiopentone
Authors: ASSEM E. S. K. 
Published: February 2007

SummaryThe three currently available paper radioallergosorbent tests (‘suxamethonium’, alcuronium and thiopentone) were evaluated. ‘Suxamethonium’ radioallergosorbent test (which employs choline conjugated to paper discs) proved to be reliable in the detection of allergy to neuromuscular blockers, which were confirmed as the most common cause of anaphylactic reaction during general anaesthesia. Thiopentone radioallergosorbent test may also be useful, and is recommended in conjunction with ‘suxamethonium’ radioallergosorbent test in the preliminary investigation of reactions. Patients with positive ‘suxamethonium’ radioallergosorbent test usually require further testing, including alcuronium radioallergosorbent test, skin testing with a wide range of drug concentrations or leucocyte histamine release test.
Aspiration pneumonia and the laryngeal mask airway
Authors: GRIFFIN R. M. , Hatcher I. S. 
Published: February 2007

SummaryA case of aspiration pneumonia is reported after the use of a laryngeal mask airway in a young woman undergoing an elective cholecystectomy. The case illustrates the hazards of regurgitation with the laryngeal mask airway and the need for further evaluation when used with controlled mechanical ventilation.
Severe anaphylactoid reaction to hydroxyethyl starch
Authors: CULLEN M. J. , SINGER M. 
Published: February 2007

SummaryA case is presented of a severe anaphylactoid reaction to hydroxyethyl starch solution that occurred peri‐operatively and required extended intensive management of the resultant bronchospasm and hypotension. Subsequent intradermal injection of hetastarch produced a delayed positive response, suggestive of a complement‐mediated mechanism.
Pregnancy associated with Gorlin's syndrome
Authors: YOSHIZUMI J. , VAUGHAN R. S. , JASANI B. 
Published: February 2007

SummaryA pregnant woman with Gorlin's syndrome presented for the removal of malignant ovarian tumours. The main problem encountered by the anaesthetists was an unexpected increase in arterial blood pressure. This was most probably associated with surgical manipulation of the ovaries with an increase in prorenin/renin production.
Patients’ expectations of patient‐controlled analgesia
Authors: Kluger M. T. , Owen H. 
Published: February 2007

SummaryPatient‐controlled analgesia is an increasingly popular method of postoperative pain relief. However, patients often worry about new therapies. Eighty ASA 1 and 2 patients aged 18–65 years were asked to list the advantages and disadvantages of using patient‐controlled analgesia. The most important advantage as perceived by patients was the reduced time spent by nurses in giving medication, but there was concern that direct personal contact would also be lessened. Preservation of self control, autonomy, rapid onset of analgesia, ability to titrate analgesia and lack of injections were seen as an advantage. Addiction and machine faults were seen as minimal problems. Preservation of patient‐nurse contact is of great importance to ensure success of postoperative analgesia.
Paraesthesia with lumbar epidural catheters.
Authors: Sarna M. C. , Smith I. , James J. M. 
Published: February 2007

SummaryThe epidural space was located in 32 obstetric patients using loss of resistance to air, while in a further 35 saline was used. The incidence of paraesthesia was 56% in the air group and 57% in the saline group. There was no significant difference between the groups in terms of other complications or in the quality of analgesia provided.
Effects of hypnotics on sleep and psychomotor performance A double‐blind randomised study of lormetazepam, midazolam and zopiclone
Authors: Rettig H. C. , de Haan P. , Zuurmond W. W. A. , Leeuwen L. v. 
Published: February 2007

SummaryLormetazepam, midazolam and zopiclone were compared as night medication in patients scheduled for elective surgery the next morning. Sixty patients divided at random into three groups, received double‐blind lormetazepam 1 mg, midazolam 15 mg or zopiclone 7.5 mg, by mouth at 2200 hours. The quality of sleep was assessed at 0700 hours from responses to a questionnaire, and psychomotor function by comparing paper and pencil (p‐deletion) and Maddox Wing tests with reference values from the day before. The three hypnotics were equally effective as sleep medication for time until onset of sleep, duration of sleep and condition upon awakening, whereas zopiclone provided significantly fewer (p < 0.05) spontaneous awakenings. The p‐deletion test did not differ in any of the three groups from the reference values. The ocular imbalance test in all three groups was significantly different (p < 0.01) from control. The lormetazepam group scored significantly better (p < 0.05) than the zopiclone group. No side effects were seen.