bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraplantar PGE2 causes nociceptive behaviour and mechanical allodynia: the role of prostanoid E receptors and protein kinases
Authors: Kassuya C A L , Ferreira J , Claudino R F , Calixto J B 
Published: February 2007

Background and purpose:Receptor subtypes involved in PGE2‐induced nociception are still controversial. The present study investigated the prostanoid E receptor (EP) subtypes and the protein kinase (PK) pathways involved in the nociception induced by PGE2 injection in the mouse paw.Experimental approach:Paw‐licking and mechanical allodynia were measured in vivo and protein kinase activation ex vivo by Western blots of extracts of paw skin.Key results:Intraplantar (i.pl.) injection of PGE2 into the mouse paw caused nociceptive behaviour of short duration with mean ED50 of 1.43 nmol. PGE2 produced a longer‐lasting mechanical allodynia, with an ED50 of 0.05 nmol. Intraplantar injection of antagonists at EP3 or EP4, but not at EP1 or EP2 receptors inhibited PGE2‐induced paw‐licking. Paw‐licking caused by PGE2 was blocked by an inhibitor of PKA but only partially decreased by inhibition of the extracellular‐regulated kinase (ERK). Selective inhibitors of PKC, c‐Jun N‐terminal kinase (JNK) or p38, all failed to affect PGE2‐induced paw‐licking. An EP3 antagonist inhibited PGE2‐induced mechanical allodynia. However, inhibitors of PKA, PKC or ERK, but not p38 or JNK, also partially inhibited PGE2‐induced mechanical allodynia. Western blot analyses confirmed that i.pl. injection of PGE2 activated PKA, PKCα, and mitogen activated kinases (MAPKs) in the paw. Co‐treatment with EP3 or EP4 receptor antagonists reduced PGE2‐induced PKA and ERK, but not PKCα activation.Conclusions and Implications:The present results indicate that the nociceptive behaviour and mechanical allodynia caused by i.pl. PGE2 are mediated through activation of distinct EP receptors and PK‐dependent mechanisms.British Journal of Pharmacology (2007) 150, 727–737. doi:10.1038/sj.bjp.0707149
Simulating psoriasis by altering transit amplifying cells
Authors: Grabe Niels , Neuber Karsten 
Published: February 2007

AbstractComputational models of tissue homeostasis will facilitate a deeper understanding of many diseases. They link molecular networks, cellular differentiation and the spatial and temporal organization of tissues. Here we show an approach which is able to computationally turn a healthy in silico epidermis into one with four central properties of psoriatic epidermis. We achieve this by altering a single simulation parameter in the cellular differentiation program of the simulated epidermal keratinocytes: the fractional time period during which transit amplifying cells proliferate (τ). Prolonging τ results in the four main pathological characteristics of psoriatic skin: (1) an absolute increase of the germinative compartment, (2) an absolute increase of the differentiated compartment, (3) a higher proportion of germinative cells and (4) a marked reduction in turnover time. The prolongation of τ is able to increase the proliferation capacity of the epidermal tissue without altering the cell cycle frequency.Contact: niels.grabe@med.uni-heidelberg.de
A multi-stage approach to clustering and imputation of gene expression profiles
Authors: Wong Dorothy S. V. , Wong Frederick K. , Wood Graham R. 
Published: February 2007

AbstractMotivation: Microarray experiments have revolutionized the study of gene expression with their ability to generate large amounts of data. This article describes an alternative to existing approaches to clustering of gene expression profiles; the key idea is to cluster in stages using a hierarchy of distance measures. This method is motivated by the way in which the human mind sorts and so groups many items. The distance measures arise from the orthogonal breakup of Euclidean distance, giving us a set of independent measures of different attributes of the gene expression profile. Interpretation of these distances is closely related to the statistical design of the microarray experiment. This clustering method not only accommodates missing data but also leads to an associated imputation method.Results: The performance of the clustering and imputation methods was tested on a simulated dataset, a yeast cell cycle dataset and a central nervous system development dataset. Based on the Rand and adjusted Rand indices, the clustering method is more consistent with the biological classification of the data than commonly used clustering methods. The imputation method, at varying levels of missingness, outperforms most imputation methods, based on root mean squared error (RMSE).Availability: Code in R is available on request from the authors.Contact: dwong@efs.mq.edu.au
Gene Regulatory Control of Myocardial Energy Metabolism Predicts Postoperative Cardiac Function in Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery
Authors: Lucchinetti Eliana , Hofer Christoph , Bestmann Lukas , Hersberger Martin , Feng Jianhua , Zhu Min , Furrer Lukas , Schaub Marcus C. , Tavakoli Reza , Genoni Michele , Zollinger Andreas , Zaugg Michael 
Published: February 2007

Background
Anesthetic gases modulate gene expression and provide organ protection. This study aimed at identifying myocardial transcriptional phenotypes to predict cardiovascular biomarkers and function in patients undergoing off-pump coronary artery bypass graft surgery.

Methods
In a prospective randomized trial, patients undergoing elective off-pump coronary artery bypass graft surgery were allocated to receive either the anesthetic gas sevoflurane (n = 10) or the intravenous anesthetic propofol (n = 10). Blood samples were collected perioperatively to determine cardiac troponin T, N-terminal pro-brain natriuretic peptide, and pregnancy-associated plasma protein A. Cardiac function was measured with transesophageal echocardiography and pulmonary artery thermodilution. Atrial biopsies were collected at the beginning and end of bypass surgery to determine gene expression profiles.

Results
N-terminal pro-brain natriuretic peptide and pregnancy-associated plasma protein A blood levels were decreased with sevoflurane treatment. Echocardiography showed preserved postoperative cardiac function in sevoflurane patients, which paralleled higher cardiac index measurements. N-terminal pro-brain natriuretic peptide release was predicted by sevoflurane-induced transcriptional reduction in fatty acid oxidation, whereas changes in cardiac index were predicted by preoperative gene activity of the peroxisome proliferator-activated receptor gamma coactivator-1alpha pathway. Sevoflurane-mediated attenuation of transcripts involved in DNA-damage signaling and activation of the granulocyte colony-stimulating factor survival pathway predicted improved postoperative cardiac index and diastolic heart function, respectively.

Conclusions
Anesthetic-induced and constitutive gene regulatory control of myocardial substrate metabolism predicts postoperative cardiac function in patients undergoing off-pump coronary artery bypass graft surgery. The authors' analysis further points to novel cardiac survival pathways as potential therapeutic targets in perioperative cardioprotection.
Effects of Hemoglobin Concentration, Skull Thickness, and the Area of the Cerebrospinal Fluid Layer on Near-infrared Spectroscopy Measurements
Authors: Yoshitani Kenji , Kawaguchi Masahiko , Miura Norikazu , Okuno Takashi , Kanoda Tomoko , Ohnishi Yoshihiko , Kuro Masakazu 
Published: February 2007

Background
Previous studies documented that near-infrared spectroscopy values were affected by factors related to optical path length, such as hemoglobin concentration, the differential path length factor, skull thickness (t-skull), and the area of the cerebrospinal fluid layer (a-CSFL). Lately, the NIRO-100 (Hamamatsu Photonics, Hamamatsu, Japan) has provided a tissue oxygen index (TOI) that theoretically is not supposed to be affected by optical path length. Therefore, the authors hypothesized that TOI is not influenced by the above-described individual factors.

Methods
Cardiac surgical or neurosurgical 103 patients (65 men and 39 women; aged 63 +/- 14 yr) were studied. TOI and regional cerebral oxygen saturation (rSO2) (INVOS 4100; Somanetics, Troy, MI) were measured sequentially on patients in a resting state. The t-skull and a-CSFL were calculated using computed tomographic image slices of the head corresponding with the position of near-infrared spectroscopy sensors. The effects of these two factors, hemoglobin concentration and mean arterial pressure, on TOI and rSO2 values were evaluated by linear regression analysis.

Results
Simple linear regression analysis showed that mean arterial pressure (r = 0.27, P = 0.008), t-skull (r = 0.22, P = 0.034), a-CSFL (0.26, P = 0.012), and hemoglobin concentration (r = 0.42, P < 0.0001) were significant determinants of rSO2. Multiple linear regression analysis showed that hemoglobin concentration (r = 0.34, P < 0.001), a-CSFL (r = -0.252, P = 0.012), and t-skull (r = 0.22, P = 0.037) were significant determinants of rSO2. On the other hand, simple and multiple linear regression analysis showed that there was no significant determinant of TOI.

Conclusion
rSO2 values were affected by hemoglobin concentration, a-CSFL, and t-skull, but TOI values were not affected by individual factors.
When Is a Bispectral Index of 60 Too Low?
Authors: Manyam Sandeep C. , Gupta Dhanesh K. , Johnson Ken B. , White Julia L. , Pace Nathan L. , Westenskow Dwayne R. , Egan Talmage D. 
Published: February 2007

Background
Opioids are commonly used in conjunction with sedative drugs to provide anesthesia. Previous studies have shown that opioids reduce the clinical requirements of sedatives needed to provide adequate anesthesia. Processed electroencephalographic parameters, such as the Bispectral Index (BIS; Aspect Medical Systems, Newton, MA) and Auditory Evoked Potential Index (AAI; Alaris Medical Systems, San Diego, CA), can be used intraoperatively to assess the depth of sedation. The aim of this study was to characterize how the addition of opioids sufficient to change the clinical level of sedation influenced the BIS and AAI.

Methods
Twenty-four adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the modified Observer's Assessment of Alertness/Sedation score, BIS, and AAI were measured at each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for each pharmacodynamic endpoint.

Results
Response surface models adequately characterized all pharmacodynamic endpoints. Despite the fact that sevoflurane-remifentanil interactions were strongly synergistic for clinical sedation, BIS and AAI were minimally affected by the addition of remifentanil to sevoflurane anesthetics.

Conclusion
Although clinical sedation increases significantly even with the addition of a small to moderate dose of remifentanil to a sevoflurane anesthetic, the BIS and AAI are insensitive to this change in clinical state. Therefore, during "opioid-heavy" sevoflurane-remifentanil anesthetics, targeting a BIS less than 60 or an AAI less than 30 may result in an unnecessarily deep anesthetic state.
Measurement of Pressure–Time Product during Spontaneous Assisted Breathing by Rapid Interrupter Technique
Authors: Bellani Giacomo , Patroniti Nicolò , Weismann Dieter , Galbiati Lucia , Curto Francesco , Foti Giuseppe , Pesenti Antonio 
Published: February 2007

Background
Measuring the work of breathing of patients undergoing spontaneous assisted ventilation can be useful to monitor and titrate ventilatory support. The aim of this study was to obtain measurements of the pressure generated by the respiratory muscles (PMUSC) and the derived pressure-time product (PTP; a good indicator of the metabolic work of breathing), performing the rapid interrupter technique with a commercial ventilator.

Methods
A Draeger Evita 4 ventilator (Draeger Medical, Lubeck, Germany) was controlled by a personal computer to rapidly interrupt the airway flow at different times and volumes of the respiratory cycle during pressure-support ventilation. From the airway pressure tracing after the occlusion, the authors estimated the alveolar pressure and PMUSC; the integration of PMUSC values over the inspiratory time yields the measurement of PTP. Esophageal pressure measurements were used as a reference. After a bench study of the valves' performance, the authors performed 11 measurement sequences in eight patients.

Results
The closure times for the inspiratory and expiratory valves were 74 +/- 10 and 61 +/- 13 ms, respectively. The interrupter technique provided a reliable estimate of PMUSC (PMUSC, occl = 1.00 . PMUSC, pes + 0.19; r = 0.88; 95% confidence interval for agreement, +5.49/-5.32 cm H2O). PTPoccl tightly correlated with PTPpes (PTPoccl = 0.95 . PTPpes + 0.13; r = 0.96; 95% confidence interval, 1.94/-1.61 cm H2O . s).

Conclusion
The rapid interrupter technique can be performed by means of a commercial ventilator, providing reliable measurement of PMUSC and PTP.
Acetylcholine Activates Protein Kinase C-α in Pulmonary Venous Smooth Muscle
Authors: Ding Xueqin , Murray Paul A. 
Published: February 2007

Background
The authors investigated whether acetylcholine-induced contraction in pulmonary venous smooth muscle (PVSM) is associated with the activation of specific protein kinase C (PKC) isoforms.

Methods
Isolated canine pulmonary venous rings without endothelium were suspended in modified Krebs-Ringer's buffer for measurement of isometric tension. The effects of nonspecific PKC inhibition (bisindolylmaleimide I; 3 x 10 m) and conventional PKC isoform inhibition (Gö7936 10 m) on the acetylcholine dose-response relation were assessed. The expression of conventional PKC isoforms (alpha, beta, gamma), novel PKC isoforms (delta, epsilon, theta), and atypical PKC isoforms (zeta, iota, mu) was measured in PVSM cells by Western blot analysis. The immunofluorescence technique and confocal microscopy were used to localize the cellular distribution of PKC isoforms before and after the addition of acetylcholine.

Results
Acetylcholine caused dose-dependent contraction in E-pulmonary veins. Pretreatment with bisindolylmaleimide I or Gö7936 attenuated acetylcholine contraction. PKC-alpha, -iota, -mu, and -zeta were expressed, whereas PKC-beta, -gamma, -delta, -epsilon;, and -theta were not expressed in PVSM cells. Immunofluorescence staining for PKC isoforms showed that in unstimulated cells, PKC-alpha and PKC-mu were detected only in the cytoplasm. PKC-iota and PKC-zeta also exhibited a cytoplasmic immunofluorescence pattern, which was especially abundant in the perinuclear zone. Activation with acetylcholine induced translocation of PKC-alpha from cytoplasm to membrane, whereas acetylcholine had no effect on the other PKC isoforms. Translocation of PKC-alpha in response to acetylcholine was blocked by the muscarinic receptor antagonist, atropine.

Conclusion
Acetylcholine contraction is attenuated by PKC inhibition in PVSM. Acetylcholine induces translocation of PKC-alpha from cytoplasm to membrane in PVSM. These results suggest that PKC-dependent acetylcholine contraction in PVSM may involve activation and translocation of PKC-alpha.
Induction of Cerebral Ischemic Tolerance by Erythromycin Preconditioning Reprograms the Transcriptional Response to Ischemia and Suppresses Inflammation
Authors: Koerner Ines P. , Gatting Matthias , Noppens Ruediger , Kempski Oliver , Brambrink Ansgar M. 
Published: February 2007

Background
A single dose of the macrolide antibiotic erythromycin can induce tolerance against cerebral ischemia in vivo (pharmacologic preconditioning). This study identified potential mechanisms of tolerance induction by assessing effects of erythromycin preconditioning on the cerebral transcriptional response to transient global cerebral ischemia.

Methods
Preconditioned and nonpreconditioned rats were exposed to 15 min of global cerebral ischemia, and changes in cerebral gene expression were identified by complementary DNA expression array and quantified by real-time reverse-transcription polymerase chain reaction.

Results
Ischemia caused a widespread up-regulation of transcription in nonpreconditioned brains in this model. Tolerance induction by erythromycin preconditioning reversed this pattern and caused a net down-regulation of a majority of genes, effectively reprogramming the brain's response pattern to ischemia. The most striking change in transcriptional response found in preconditioned animals was an almost complete suppression of the otherwise profound induction of proinflammatory genes by global ischemia. In contrast, the same treatment had little effect on the expression of apoptosis-inducing genes after ischemia.

Conclusions
These findings present a new molecular correlate for the induction of ischemic tolerance achieved by erythromycin preconditioning and will further the understanding of this clinically important new regimen of preemptive neuroprotection.
Gabapentin Activates Spinal Noradrenergic Activity in Rats and Humans and Reduces Hypersensitivity after Surgery
Authors: Hayashida Ken-ichiro , DeGoes Sophia , Curry Regina , Eisenach James C. 
Published: February 2007

Background
Gabapentin has been reported to inhibit various acute and chronic pain conditions in animals and humans. Although the efficacy of gabapentin depends on the alpha2delta subunit of voltage-gated calcium channels, its analgesic mechanisms in vivo are still unknown. Here, the authors tested the role of spinal noradrenergic inhibition in gabapentin's analgesia for postoperative pain.

Methods
Gabapentin was administered orally and intracerebroventricularly to rats on the day after paw incision, and withdrawal threshold to paw pressure was measured. The authors also measured cerebrospinal fluid concentration of norepinephrine and postoperative morphine use after surgery in patients who received oral placebo or gabapentin.

Results
Both oral and intracerebroventricular gabapentin attenuated postoperative hypersensitivity in rats in a dose-dependent manner. This effect of gabapentin was blocked by intrathecal administration of the alpha2-adrenergic receptor antagonist idazoxan and the G protein-coupled inwardly rectifying potassium channel antagonist tertiapin-Q, but not by atropine. In humans, preoperative gabapentin, 1,200 mg, significantly increased norepinephrine concentration in cerebrospinal fluid and decreased morphine requirements.

Conclusions
These data suggest that gabapentin activates the descending noradrenergic system and induces spinal norepinephrine release, which produces analgesia via spinal alpha2-adrenoceptor stimulation, followed by activation of G protein-coupled inwardly rectifying potassium channels. The authors' clinical data suggest that gabapentin activates the descending noradrenergic system after preoperative oral administration at the time of surgery. These data support a central mechanism of oral gabapentin to reduce postoperative pain and suggest that this effect could be magnified by treatments that augment the effect of norepinephrine release.
Characterization of the Antinociceptive and Pronociceptive Effects of Methadone in Rats
Authors: Holtman Joseph R. , Wala Elzbieta P. 
Published: February 2007

Background
Recently, it has been appreciated that in addition to their antinociceptive properties, opioid analgesics also can enhance pain sensitivity (opioid-induced hyperalgesia [OIH]). OIH may enhance preexisting pain and contribute to dose escalation, tolerance, and misuse/abuse of opioids. Better information is needed to determine which opioid or opioid combinations may be least likely to produce OIH and therefore possibly represent better choices for pain management. Herein the authors have examined the hyperalgesic and antinociceptive properties of racemic methadone and its enantiomers alone and in combination with morphine in rats. Methadone is of particular interest because it possesses both micro-receptor agonist and N-methyl-d-aspartate receptor antagonist activities.

Methods
The antinociceptive and hyperalgesic properties of d,l-methadone, l-methadone, and d-methadone were characterized by dose and sex using the thermal tail-flick test (high and low intensity). The responses to l- and d-methadone combinations with morphine were also determined with this model.

Results
Antinociceptive and hyperalgesic effects of d,l-methadone were demonstrated. These effects were related to dose but not to sex. The degree of hyperalgesia was greater with l-methadone compared with d,l-methadone. In contrast, d-methadone (N-methyl-d-aspartate antagonist) did not produce hyperalgesia. Furthermore, d-methadone blocked morphine hyperalgesia, enhanced antinociception, and abolished sex-related differences. This seems to be the result of antagonistic activity of d-methadone at the N-methyl-d-aspartate receptor.

Conclusion
The current findings with methadone are supportive of previous findings implicating mu-opioid and N-methyl-d-aspartate receptor mechanisms in OIH. Better understanding of OIH may help in choosing the most appropriate opioids for use in the treatment of pain.
Fermented Infant Formulae Without Live Bacteria
Authors: Agostoni Carlo , Goulet Olivier , Kolacek Sanja , Koletzko Berthold , Moreno Luis , Puntis John , Rigo Jacques , Shamir Raanan , Szajewska Hania , Turck Dominique ,   ESPGHAN Committee on Nutrition:
Published: February 2007

ABSTRACTInfant and follow‐on (or “follow‐up”) formulae fermented with lactic acid–producing bacteria during the production process contain no viable bacteria in the final product due to their inactivation by heat or other means. In this article the ESPGHAN Committee on Nutrition reviews published information on their clinical evaluation. In a systematic literature review, 2 randomized clinical trials including 933 infants were identified as meeting our predefined inclusion criteria. Our analysis reveals that only limited published data are available on the effects of fermented infant formulae. There are indications from 2 studies that some fermented infant formulae may reduce the occurrence or severity of infectious diarrhea in infants. It is recommended that the effects of fermented infant formulae on infectious diarrhea and other relevant outcomes should be assessed in further randomized controlled trials according to current scientific standards. The available data do not allow general conclusions to be drawn on the use and effects of fermented formulae for infants.