bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Endothelial Nitric Oxide Synthase as a Trigger and Mediator of Isoflurane-induced Delayed Preconditioning in Rabbit Myocardium
Authors: Chiari Pascal C. , Bienengraeber Martin W. , Weihrauch Dorothee , Krolikowski John G. , Kersten Judy R. , Warltier David C. , Pagel Paul S. 
Published: June 2005

Background
Isoflurane produces delayed preconditioning in vivo. The authors tested the hypothesis that endothelial, inducible, or neuronal nitric oxide synthase (NOS) is a trigger or mediator of this protective effect.

Methods
In the absence or presence of exposure to isoflurane (1.0 minimum alveolar concentration) 24 h before experimentation, pentobarbital-anesthetized rabbits (n = 128) instrumented for hemodynamic measurement received 0.9% saline (control), the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (10 mg/kg), one of two of the selective inducible NOS antagonists aminoguanidine (300 mg/kg) or 1400W (0.5 mg/kg), or the selective neuronal NOS inhibitor 7-nitroindazole (50 mg/kg) administered before exposure to isoflurane (trigger; day 1) or left anterior descending coronary artery occlusion (mediator; day 2). All rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Tissue samples for reverse-transcription polymerase chain reaction and immunohistochemistry were also obtained in the presence or absence of N-nitro-l-arginine methyl ester with or without isoflurane pretreatment.

Results
Isoflurane significantly (P < 0.05) reduced infarct size (23 +/- 5% [mean +/- SD] of the left ventricular area at risk; triphenyltetrazolium chloride staining) as compared with control (42 +/- 7%). N-nitro-l-arginine methyl ester administered before isoflurane or coronary occlusion abolished protection (49 +/- 7 and 43 +/- 10%, respectively). Aminoguanidine, 1400W, and 7-nitroindazole did not alter infarct size or affect isoflurane-induced delayed preconditioning. Isoflurane increased endothelial but not inducible NOS messenger RNA transcription and protein translation immediately and 24 h after administration of the volatile agent. Pretreatment with N-nitro-l-arginine methyl ester attenuated isoflurane-induced increases in endothelial NOS expression.

Conclusions
The results suggest that endothelial NOS but not inducible or neuronal NOS is a trigger and mediator of delayed preconditioning by isoflurane in vivo.
Neuroprotective Effect of Epidural Electrical Stimulation against Ischemic Spinal Cord Injury in Rats
Authors: Kakinohana Manabu , Harada Hideki , Mishima Yasunori , Kano Tatsuhiko , Sugahara Kazuhiro 
Published: June 2005

Background
Electroconvulsion therapy is likely to serve as an effective preconditioning stimulus for inducing tolerance to ischemic brain injury. The current study examines whether electrical stimuli on the spinal cord is also capable of inducing tolerance to ischemic spinal cord injury by transient aortic occlusion.

Methods
Spinal cord ischemia was induced by occlusion of the descending thoracic aorta in combination with maintaining systemic hypotension (40 mmHg) during the procedure. Animals implanted with epidural electrodes were divided into four groups according to electrical stimulation and sham. Two groups consisted of rapid preconditioning (RE group, n = 8) and sham procedure (RC group, n = 8) 30 min before 9 min of spinal cord ischemia. In the two groups that underwent delayed preconditioning, rats were exposed to 9 min of aortic occlusion 24 h after either pretreatment with epidural electrical stimulation (DE group, n = 8) or sham (DC group, n = 8). In addition, rats were exposed to 6-11 min of spinal cord ischemia at 30 min or 24 h after epidural electrical stimulation or sham stimulation. The group P50 represents the duration of spinal cord ischemia associated with 50% probability of resultant paraplegia.

Results
Pretreatment with electrical stimulation in the DE group but not the RE group protected the spinal cord against ischemia, and this stimulation prolonged the P50 by approximately 15.0% in the DE group compared with the DC group.

Conclusions
Although the optimal setting for this electrical preconditioning should be determined in future studies, the results suggest that epidural electrical stimulation will be a useful approach to provide spinal protection against ischemia.
Differential Inhibition of Neuronal Na+–Ca2+Exchange versus Store-operated Ca2+Channels by Volatile Anesthetics in Pheochromocytoma (PC12) Cells
Authors: Ay Binnaz , Wallace Daniel , Mantilla Carlos B. , Prakash Yedotore S. 
Published: June 2005

Background
Ca2+ influx is a key component of neuronal intracellular Ca2+ ([Ca2+]i) regulation. The authors hypothesized that volatile anesthetic inhibition of neuronal activity is mediated by inhibition of Ca2+ influx via two major mechanisms: plasma membrane Na+-Ca2+ exchange (NCX) and the novel mechanism of Ca2+ influx triggered by endoplasmic reticulum Ca2+ depletion (store-operated Ca2+ channels [SOCCs]).

Methods
Differentiated rat pheochromocytoma cells loaded with the Ca2+ indicator fura-2 were Na+-loaded with 0 Ca2+, 145 mm Na+ Tyrode's and 5 microm cyclopiazonic acid plus 10 microm ryanodine (functionally isolating plasma membrane). Influx-mode NCX was rapidly reactivated by 0 Na+ and 2.5 mm Ca2+. The protocol was repeated in the presence of volatile anesthetics (0.5-1.5 minimum alveolar concentration [MAC] halothane, isoflurane, or sevoflurane) or other drugs to characterize NCX. To examine SOCCs, endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in 0 extracellular Ca2+, and Ca2+ influx was triggered by rapid reintroduction of extracellular Ca2+. The protocol was repeated in the presence of anesthetics or other drugs to characterize SOCCs.

Results
Influx via NCX was not inhibited by voltage-gated Ca2+ channel blockers but was sensitive to NCX inhibitors. Halothane and isoflurane (0.5-1.5 MAC) significantly inhibited NCX (P < 0.05; paired comparisons), whereas sevoflurane at less than 1.5 MAC did not inhibit NCX. SOCC-mediated Ca2+ influx was insensitive to a variety of Ca2+ channel blockers but was inhibited by Ni2+. Such influx was sensitive only to halothane at greater than 1 MAC but not isoflurane or sevoflurane.

Conclusions
These data indicate that volatile anesthetics, especially halothane and isoflurane, interfere with neuronal [Ca2+]i regulation by inhibiting NCX but not SOCC-mediated Ca2+ influx (except high concentrations of halothane).
Local Anesthetic Interaction with Human Ether-a-go-go –related Gene (HERG) Channels
Authors: Siebrands Cornelia C. , Schmitt Nicole , Friederich Patrick 
Published: June 2005

Background
Human ether-a-go-go-related gene (HERG) potassium channels constitute a potential target involved in cardiotoxic side effects of amino-amide local anesthetics. The molecular interaction site of these low-affinity blockers with HERG channels is currently unknown. The aim of this study was to determine the effect of the mutations Y652A and F656A in the putative drug binding region of HERG on the inhibition by bupivacaine, ropivacaine, and mepivacaine.

Methods
The authors examined the inhibition of wild-type and mutant HERG channels, transiently expressed in Chinese hamster ovary cells by bupivacaine, ropivacaine, and mepivacaine. Whole cell patch clamp recordings were performed at room temperature.

Results
Inhibition of HERG wild-type and mutant channels by the different local anesthetics was concentration dependent, stereoselective, and reversible. The sensitivity decreased in the order bupivacaine > ropivacaine > mepivacaine for wild-type and mutant channels. The mutant channels were approximately 4-30 times less sensitive to the inhibitory action of the different local anesthetics than the wild-type channel. The concentration-response data were described by Hill functions (bupivacaine: wild-type IC50 = 22 +/- 2 microm, n = 38; Y652A IC50 = 95 +/- 5 microm, n = 31). The mutations resulted in a change of the stereoselectivity of HERG channel block by ropivacaine. The potency of the local anesthetics to inhibit wild-type and mutant channels correlated with the lipophilicity of the drug (r > 0.9).

Conclusions
These results indicate that local anesthetics specifically but not exclusively interact with the aromatic residues Y652 and F656 in S6 of HERG channels.
Alfentanil and Placebo Analgesia
Authors: Olofsen Erik , Romberg Raymonda , Bijl Hans , Mooren René , Engbers Frank , Kest Benjamin , Dahan Albert 
Published: June 2005

Background
To assess whether patient sex contributes to the interindividual variability in alfentanil analgesic sensitivity, the authors compared male and female subjects for pain sensitivity after alfentanil using a pharmacokinetic-pharmacodynamic modeling approach.

Methods
Healthy volunteers received a 30-min alfentanil or placebo infusion on two occasions. Analgesia was measured during the subsequent 6 h by assaying tolerance to transcutaneous electrical stimulation (eight men and eight women) of increasing intensity or using visual analog scale scores during treatment with noxious thermal heat (five men and five women). Sedation was concomitantly measured. Population pharmacokinetic-pharmacodynamic models were applied to the analgesia and sedation data using NONMEM. For electrical pain, the placebo and alfentanil models were combined post hoc.

Results
Alfentanil and placebo analgesic responses did not differ between sexes. The placebo effect was successfully incorporated into the alfentanil pharmacokinetic-pharmacodynamic model and was responsible for 20% of the potency of alfentanil. However, the placebo effect did not contribute to the analgesic response variability. The pharmacokinetic-pharmacodynamic analysis of the electrical and heat pain data yielded similar values for the potency parameter, but the blood-effect site equilibration half-life was significantly longer for electrical pain (7-9 min) than for heat pain (0.2 min) or sedation (2 min).

Conclusions
In contrast to the ample literature demonstrating sex differences in morphine analgesia, neither sex nor subject expectation (i.e., placebo) contributes to the large between-subject response variability with alfentanil analgesia. The difference in alfentanil analgesia onset and offset between pain tests is discussed.
Topical 2% Amitriptyline and 1% Ketamine in Neuropathic Pain Syndromes
Authors: Lynch Mary E. , Clark Alexander J. , Sawynok Jana , Sullivan Michael J. L. 
Published: June 2005

Background
A double-blind, randomized, placebo-controlled 3-week study evaluated the efficacy of topical 2% amitriptyline, 1% ketamine, and a combination of both in treating patients with neuropathic pain.

Methods
Ninety-two patients with diabetic neuropathy, postherpetic neuralgia, or postsurgical/posttraumatic neuropathic pain with allodynia, hyperalgesia, or pinprick hypesthesia were randomly assigned to receive one of four creams (placebo, 2% amitriptyline, 1% ketamine, or 2% amitriptyline-1% ketamine combined). The primary outcome measure was change in average daily pain intensity (baseline week vs. final week) using an 11-point numerical pain rating scale. Secondary outcomes included the McGill Pain Questionnaire, measures of allodynia and hyperalgesia, and patient satisfaction.

Results
A reduction in pain scores of 1.1-1.5 units was observed in all groups, and there was no difference between groups. Blood concentrations revealed no significant systemic absorption. Minimal side effects were encountered.

Conclusion
This randomized, placebo-controlled trial examining topical 2% amitriptyline, 1% ketamine, and a combination in the treatment of neuropathic pain revealed no difference between groups. Optimization of doses may be required, because another study has revealed that higher concentrations of these agents combined do produce significant analgesia.
Sex- and Age-related Differences in Morphine Requirements for Postoperative Pain Relief
Authors: Aubrun Frédéric , Salvi Nadège , Coriat Pierre , Riou Bruno 
Published: June 2005

Background
Sex-related differences in the perception of pain and susceptibility to opioids remain a matter of debate. Intravenous morphine titration used to obtain pain relief in the immediate postoperative period is a unique clinical model for assessing the effect of sex on reported pain. Because of the wide variation in dose requirements for pain management, the authors conducted a prospective study in a large population and also assessed the effect of aging.

Methods
Intravenous morphine titration was administered as a bolus of 2 (body weight <or= 60 kg) or 3 mg (body weight > 60 kg) during the immediate postoperative period. The interval between each bolus was 5 min. The visual analog pain scale (VAS) threshold required to administer morphine was 30, and pain relief was defined as a VAS score of 30 or less. Data are expressed as mean +/- SD.

Results
Data from 4,317 patients were analyzed; 54% of the patients were male, and 46% were female. The mean morphine dose required to obtain pain relief was 11.9 +/- 6.8 mg or 0.173 +/- 0.103 mg/kg. Women had a higher initial VAS score (74 +/- 19 vs. 71 +/- 19; P < 0.001) and required a greater dose of morphine (0.183 +/- 0.111 vs. 0.165 +/- 0.095 mg/kg; P < 0.001). In contrast, no significant difference was noted in elderly (aged > 75 yr) patients (0.163 +/- 0.083 vs. 0.157 +/- 0.085 mg/kg).

Conclusion
Women experienced more severe postoperative pain and required a greater dose (+11%) of morphine than men in the immediate postoperative period. This sex-related difference disappeared in elderly patients.
The high‐temperature oxidation resistance of thin‐walled ingots of Ni3Al alloys with directional grain structure
Authors: Verin A.S. , Verin M.A. 
Published: June 2005

PurposeThis paper describes the changing of high‐temperature oxidation resistance (HTOR) at the temperature 1,200°C which is dependant on characteristics of alloying and microstructure. The aim of the research was to show a broad problem of using the intermetallic Ni3Al in the production of propulsion aircraft engines because this material has a very high HTOR and low density.Design/methodology/approachFor the estimation of a level of HTOR of Ni3Al (Ni‐12Al) and its alloying compositions, a method was used in which samples were heated in ambient atmosphere at 1,200°C for a period of 1,500 h. The samples were weighed every 100 h. The data was obtained for eight different compositions.FindingsThe process of researching indicated that a maximum HTOR has the composition Ni‐12Al without alloying which is obtaining by dosed directional solidification (DDS) method and having the largest structural stability at 1,200°C.Practical implicationsThis material is broadly used in the production of valves, electrical heaters, etc. However, these details are obtained by equiaxial casting or powder metallurgy methods. The material obtained by DDS method has higher strength characteristics and may be implicated in many components of aircraft engines (elements of the firing chamber or a stationary blades, etc.).Originality/valueThis research presents a new type of microstructure which has a matrix Ni3Al on a base of disordered gamma phase (DDS Method). Currently, this structure has had little studies carried out on it. However, it could become an object for detailed research for process phase precipitation using a super high magnifications.
Neoclassicism, artificial intelligence, and the marginalization of ethics
Authors: Davis John B. 
Published: June 2005

PurposeThe paper examines the dependence of the positivist and welfarist preference satisfaction paradigm of neoclassical economics upon an implicit functionalist philosophy of mind. Functionalism is the doctrine that mental states are strictly materialistic and understandable in cause‐effect terms. An important aspect of functionalism is the multiple realizability thesis, namely, that mental states can be realized in any type of hardware, whether human brain or computer.Design/methodology/approachThe approach used involves investigating the fact‐value distinction after Robbins in terms of the positivist meta‐ethical view known as emotivism, and then explaining emotivism as inherently functionalist. Functionalist thinking itself is explained in terms of contemporary philosophy of mind.FindingsAn important finding is that the preference satisfaction paradigm can be shown to be as suitable to artificial intelligence systems as to human beings. A consequence of this is that normative concerns are increasingly difficult to address in connection with the neoclassical thinking about economic agents.Research limitations/implicationsThe paper does not investigate more recent research programs in economics (such as behavioural economics) that depart from basic neoclassical assumptions.Practical implicationsA practical implication of the paper is that it shifts attention to previously un‐emphasized aspects of neoclassical thinking.Originality/valueThe paper's value to explain the relation of economics to ethics in neoclassical economics in connection with functionalist philosophy of mind.
An improved two‐tiered strategy to intrusion detection
Authors: Sodiya A.S. , Longe H.O.D. 
Published: June 2005

PurposeA work that combined strategies in designing anomaly‐based instruction detection system (IDS) was described in CSIDS. This new work seeks to improve on CSIDS.Design/methodology/approachThe shortcomings of CSIDS were first identified and critically analysed. An improved approach for combining data mining and expert system is then presented and implemented.FindingsThe result of the evaluation of the new design produced a better result in terms of the detection efficiency and false alarm rate.Research limitations/implicationsIt might be necessary to use data from diverse environments to test the design. However, it was effectively shown that an IDS that combines strategies has been designed.Practical implicationsThis work discusses the technical issues of IDS and will motivate researchers in IDS. It has also shown how strategies could be combined for effective intrusion detection.Originality/valueThis paper resulted from the existing problems in IDS and presents practical information in intrusion detection. It is definitely a tool needed by researchers in IDS.
The role of PFA‐100® testing in the investigation and management of haemostatic defects in children and adults
Authors: Harrison Paul 
Published: June 2005

SummaryThe PFA‐100® provides a simple global measure of high shear‐dependent platelet function, and as such is not diagnostic or specific to any disorder. Prolonged closure times must be interpreted in conjunction with a full blood count, von Willebrand factor (VWF) screen and other platelet tests. The PFA‐100® may also give false negative results with relatively common platelet defects. If clinical suspicion is high, further detailed platelet function testing and VWF screening are required to exclude abnormal platelet function, even if the PFA‐100® is normal. In more recent studies the PFA‐100® has been used for preoperative identification and management of surgical patients with haemostatic defects and for assessing the clinical effectiveness of platelet transfusion therapy. This review highlights the up to date, evidence‐based, advantages and disadvantages of the PFA‐100® test in the investigation and management of haemostatic disorders in both children and adults.
Can long‐term prophylaxis for severe haemophilia be stopped in adulthood? Results from Denmark and the Netherlands
Authors: van Dijk K. , Fischer K. , van der Bom J. G. , Scheibel E. , Ingerslev J. , van den Berg H. M. 
Published: June 2005

SummaryProphylaxis is the treatment of choice for children with severe haemophilia. As prophylaxis is especially important during the period of growth, the need for continued prophylaxis in adulthood should be considered. The aim of this study was to describe the incidence and outcome of stopping prophylaxis in patients with severe haemophilia who were offered prophylaxis during childhood. All patients with severe haemophilia (factor VIII/IX <0·01 IU/ml), born 1970–80, treated in two Danish and one Dutch treatment centre were studied. Data on discontinuation of prophylaxis, treatment, joint bleed frequency, clinical scores and radiological scores were collected. Eighty patients were studied. Median follow‐up was 19 years (range 7–29). A total of 35% of patients discontinued prophylaxis at a median age of 21·5 years [interquartile range (IQR) 18·4–24·4], experiencing only three joint bleeds per year (IQR 1·4–8·7). Median clinical scores were similar in patients who discontinued prophylaxis [4 points (IQR 0–6)] and those who continued [3 points (IQR 1–6)], as were median Pettersson scores at 13 (IQR 1–24) vs. 13 points (IQR 5–23) respectively. In conclusion one‐third of young adults with severe haemophilia on a prophylactic regimen discontinued prophylaxis in early adulthood, while maintaining a low joint bleed frequency and similar arthropathy after 4 years.
A novel human CD32 mAb blocks experimental immune haemolytic anaemia in FcγRIIA transgenic mice
Authors: van Royen‐Kerkhof Annet , Sanders Elisabeth A. M. , Walraven Vanessa , Voorhorst‐Ogink Marleen , Saeland Eirikur , Teeling Jessica L. , Gerritsen Arnout , van Dijk Marc A. , Kuis Wietse , Rijkers Ger T. , Vitale Laura , Keler Tibor , McKenzie Steven E. , Leusen Jeanette H. W. , van de Winkel Jan G. J. 
Published: June 2005

SummaryA fully human IgG1 kappa antibody (MDE‐8) was generated, which recognised Fc‐gamma receptor IIa (FcγRIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked FcγRIIa ligand‐binding via its F(ab′)2 fragment. Overnight incubation of monocytes with F(ab′)2 fragments of MDE‐8 leads to a c. 60% decrease in cell surface expression of FcγRIIa. MDE‐8 whole antibody induced a concomitant c. 30% decrease of FcγRI on THP‐1 cells and monocytes. In humans FcγRIIa plays an important role in the clearance of antibody‐coated red blood cells in vivo. As an equivalent of FcγRIIa does not exist in mice, the in vivo effect of MDE‐8 was studied in an FcγRIIa transgenic mouse model. In these mice, antibody‐induced anaemia could readily be blocked by MDE‐8. These data document a new human antibody that effectively blocks FcγRIIa, induces modulation of both FcγRIIa and FcγRI from phagocytic cells, and ameliorates antibody‐induced anaemia in vivo.
Autocrine/paracrine involvement of insulin‐like growth factor‐I and its receptor in chronic lymphocytic leukaemia
Authors: Schillaci Roxana , Galeano Adriana , Becu‐Villalobos Damasia , Spinelli Olga , Sapia Sandra , Bezares Raimundo F. 
Published: June 2005

SummaryChronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long‐lived B lymphocytes blocked in G0/1 by impaired apoptosis. As insulin‐like growth factor‐I (IGF‐I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF‐I and its receptor (IGF‐IR) participate in autocrine/paracrine loops affecting the survival of CLL cells. IGF‐IR protein and mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF‐IR expression in CLL patients was positively correlated with the expression of the antiapoptotic protein Bcl‐2 and was involved in CLL cell survival in vitro. Serum IGF‐I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells expressed IGF‐I mRNA and secreted the growth factor in vitro. Therefore, local production of IGF‐I can account for the increased levels of serum IGF‐I, independently of GH, and may be related to autocrine/paracrine control of lymphocyte survival acting at IGF‐IR. This is the first demonstration of IGF‐IR expression in a subgroup of CLL patients and of its antiapoptotic effects in vitro, highlighting the importance of this growth factor receptor as a possible therapeutic target in CLL.