bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis
Authors: Que Yok-Ai , Haefliger Jacques-Antoine , Piroth Lionel , François Patrice , Widmer Eleonora , Entenza José M. , Sinha Bhanu , Herrmann Mathias , Francioli Patrick , Vaudaux Pierre , Moreillon Philippe
Published: May 2005

The expression of Staphylococcus aureus adhesins in Lactococcus lactis identified clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) as critical for valve colonization in rats with experimental endocarditis. This study further analyzed their role in disease evolution. Infected animals were followed for 3 d. ClfA-positive lactococci successfully colonized damaged valves, but were spontaneously eradicated over 48 h. In contrast, FnBPA-positive lactococci progressively increased bacterial titers in vegetations and spleens. At imaging, ClfA-positive lactococci were restricted to the vegetations, whereas FnBPA-positive lactococci also invaded the adjacent endothelium. This reflected the capacity of FnBPA to trigger cell internalization in vitro. Because FnBPA carries both fibrinogen- and fibronectin-binding domains, we tested the role of these functionalities by deleting the fibrinogen-binding domain of FnBPA and supplementing it with the fibrinogen-binding domain of ClfA in cis or in trans. Deletion of the fibrinogen-binding domain of FnBPA did not alter fibronectin binding and cell internalization in vitro. However, it totally abrogated valve infectivity in vivo. This ability was restored in cis by inserting the fibrinogen-binding domain of ClfA into truncated FnBPA, and in trans by coexpressing full-length ClfA and truncated FnBPA on two separate plasmids. Thus, fibrinogen and fibronectin binding could cooperate for S. aureus valve colonization and endothelial invasion in vivo.
Two Stable, Conducting Conformations of the Selectivity Filter in Shaker K+ Channels
Authors: Thompson Jill , Begenisich Ted
Published: May 2005

We have examined the voltage dependence of external TEA block of Shaker K+ channels over a range of internal K+ concentrations from 2 to 135 mM. We found that the concentration dependence of external TEA block in low internal K+ solutions could not be described by a single TEA binding affinity. The deviation from a single TEA binding isotherm was increased at more depolarized membrane voltages. The data were well described by a two-component binding scheme representing two, relatively stable populations of conducting channels that differ in their affinity for external TEA. The relative proportion of these two populations was not much affected by membrane voltage but did depend on the internal K+ concentration. Low internal K+ promoted an increase in the fraction of channels with a low TEA affinity. The voltage dependence of the apparent high-affinity TEA binding constant depended on the internal K+ concentration, becoming almost voltage independent in 5 mM. The K+ sensitivity of these low- and high-affinity TEA states suggests that they may represent one- and two-ion occupancy states of the selectivity filter, consistent with recent crystallographic results from the bacterial KcsA K+ channel. We therefore analyzed these data in terms of such a model and found a large (almost 14-fold) difference between the intrinsic TEA affinity of the one-ion and two-ion modes. According to this analysis, the single ion in the one-ion mode (at 0 mV) prefers the inner end of the selectivity filter twofold more than the outer end. This distribution does not change with internal K+. The two ions in the two-ion mode prefer to occupy the inner end of the selectivity filter at low K+, but high internal K+ promotes increased occupancy of the outer sites. Our analysis further suggests that the four K+ sites in the selectivity filter are spaced between 20 and 25% of the membrane electric field.
The Amino Terminus of Slob, Slowpoke Channel Binding Protein, Critically Influences Its Modulation of the Channel
Authors: Zeng Haoyu , Weiger Thomas M. , Fei Hong , Jaramillo Angela M. , Levitan Irwin B.
Published: May 2005

The Drosophila Slowpoke calcium-dependent potassium channel (dSlo) binding protein Slob was discovered by a yeast two-hybrid screen using the carboxy-terminal tail region of dSlo as bait. Slob binds to and modulates the dSlo channel. We have found that there are several Slob proteins, resulting from multiple translational start sites and alternative splicing, and have named them based on their molecular weights (in kD). The larger variants, which are initiated at the first translational start site and are called Slob71 and Slob65, shift the voltage dependence of dSlo activation, measured by the whole cell conductance–voltage relationship, to the left (less depolarized voltages). Slob53 and Slob47, initiated at the third translational start site, also shift the dSlo voltage dependence to the left. In contrast, Slob57 and Slob51, initiated at the second translational start site, shift the conductance–voltage relationship of dSlo substantially to more depolarized voltages, cause an apparent dSlo channel inactivation, and increase the deactivation rate of the channel. These results indicate that the amino-terminal region of Slob plays a critical role in its modulation of dSlo.
Cysteine Accessibility in ClC-0 Supports Conservation of the ClC Intracellular Vestibule
Authors: Engh Anita M. , Maduke Merritt
Published: May 2005

ClC chloride channels, which are ubiquitously expressed in mammals, have a unique double-barreled structure, in which each monomer forms its own pore. Identification of pore-lining elements is important for understanding the conduction properties and unusual gating mechanisms of these channels. Structures of prokaryotic ClC transporters do not show an open pore, and so may not accurately represent the open state of the eukaryotic ClC channels. In this study we used cysteine-scanning mutagenesis and modification (SCAM) to screen >50 residues in the intracellular vestibule of ClC-0. We identified 14 positions sensitive to the negatively charged thiol-modifying reagents sodium (2-sulfonatoethyl)methanethiosulfonate (MTSES) or sodium 4-acetamido-4'-maleimidylstilbene-2'2-disulfonic acid (AMS) and show that 11 of these alter pore properties when modified. In addition, two MTSES-sensitive residues, on different helices and in close proximity in the prokaryotic structures, can form a disulfide bond in ClC-0. When mapped onto prokaryotic structures, MTSES/AMS-sensitive residues cluster around bound chloride ions, and the correlation is even stronger in the ClC-0 homology model developed by Corry et al. (2004). These results support the hypothesis that both secondary and tertiary structures in the intracellular vestibule are conserved among ClC family members, even in regions of very low sequence similarity.
Effect of Low-dose Droperidol on the QT Interval during and after General Anesthesia
Authors: White Paul F. , Song Dajun , Abrao Joao , Klein Kevin W. , Navarette Bryan
Published: May 2005

Background

Since the effects of antiemetic doses of droperidol on the QT interval have not been previously studied, the authors designed a randomized, double-blind, placebo-controlled study to evaluate the intraoperative and postoperative effects of small-dose droperidol (0.625 and 1.25 mg intravenous) on the QT interval when used for antiemetic prophylaxis during general anesthesia.

Methods

One hundred twenty outpatients undergoing otolaryngologic procedures with a standardized general anesthetic technique were enrolled in this study. After anesthetic induction and before the surgical incision, 60 patients were given either saline or 0.625 or 1.25 mg intravenous droperidol in a total volume of 2 ml. A standard electrocardiographic lead II was recorded immediately before and every minute after the injection of the study medication during a 10-min observation period. The QTc (QT interval corrected for heart rate) was evaluated from the recorded electrocardiographic strips. In 60 additional patients, a 12-lead electrocardiogram was obtained before and at specific intervals up to 2 h after surgery to assess the effects of droperidol and general anesthesia on the QTc. Any abnormal heartbeats or arrhythmias during the operation or the subsequent 2-h monitoring interval were also noted.

Results

Intravenous droperidol, 0.625 and 1.25 mg, prolonged the QT interval by an average of 15 +/- 40 and 22 +/- 41 ms, respectively, at 3-6 min after administration during general anesthesia, but these changes did not differ significantly from that seen with saline (12 +/- 35 ms) (all values mean +/- SD). There were no statistically significant differences among the three study groups in the number of patients with greater than 10% prolongation in QTc (vs. baseline). Although general anesthesia was associated with a 14- to 16-ms prolongation of the QTc interval in the early postoperative period, there was no evidence of droperidol-induced QTc prolongation after surgery. Finally, there were no ectopic heartbeats observed on any of the electrocardiographic rhythm strips or 12-lead recordings during the perioperative period.

Conclusion

Use of a small dose of droperidol (0.625-1.25 mg intravenous) for antiemetic prophylaxis during general anesthesia was not associated with a statistically significant increase in the QTc interval compared with saline. More importantly, there was no evidence of any droperidol-induced QTc prolongation immediately after surgery.
Intubating Laryngeal Mask Airway in Morbidly Obese and Lean Patients
Authors: Combes Xavier , Sauvat Stéphane , Leroux Bertrand , Dumerat Marc , Sherrer Emanuel , Motamed Cyrus , Brain Archie , D’Honneur Gilles
Published: May 2005

Background

The intubating laryngeal mask airway (ILMA) was designed using the characteristics of healthy-weight subjects but was shown to be an effective airway device in morbidly obese patients. The authors compared airway management quality in morbidly obese and lean patients with use of the ILMA.

Methods

Fifty morbidly obese and 50 lean patients (mean body mass indexes, 42 and 27 kg/m, respectively) were enrolled in this prospective study. After induction of general anesthesia, characteristics of airway management were judged on safety and efficiency parameters, including success rate at ventilation and intubation and airway management quality criteria, such as the number of patients who required adjustment maneuvers, the number of failed tracheal intubation attempts, the total duration of airway management, and an overall difficulty visual analog scale score.

Results

The ILMA was successfully inserted and adequate ventilation through the ILMA was achieved in all 100 patients. The success rates of tracheal intubation through the ILMA were similar in obese and lean patients (96% and 94%, respectively). The numbers of failed blind tracheal access attempts and patients who required airway-adjustment maneuvers were significantly reduced in obese patients as compared with lean patients. Four obese patients experienced transient episodes of oxygen desaturation (oxygen saturation < 90%) before adequate bag ventilation was established with the ILMA.

Conclusion

The authors confirmed that the ILMA was an efficient airway device for airway management of both lean and obese patients. In the conditions of this study, the authors observed that airway management with the ILMA was simpler in obese patients as compared with lean patients.
Preoxygenation Is More Effective in the 25° Head-up Position Than in the Supine Position in Severely Obese Patients
Authors: Dixon Benjamin J. , Dixon John B. , Carden Jennifer R. , Burn Anthony J. , Schachter Linda M. , Playfair Julie M. , Laurie Cheryl P. , O’Brien Paul E.
Published: May 2005

Background

Class III obese patients have altered respiratory mechanics, which are further impaired in the supine position. The authors explored the hypothesis that preoxygenation in the 25 degrees head-up position allows a greater safety margin for induction of anesthesia than the supine position.

Methods

A randomized controlled trial measured oxygen saturation and the desaturation safety period after 3 min of preoxygenation in 42 consecutive (male:female 13:29) severely obese (body mass index > 40 kg/m) patients who were undergoing laparoscopic adjustable gastric band surgery and were randomly assigned to the supine position or the 25 degrees head-up position. Serial arterial blood gases were taken before and after preoxygenation and 90 s after induction. After induction, ventilation was delayed until blood oxygen saturation reached 92%, and this desaturation safety period was recorded.

Results

The mean body mass indexes for the supine and 25 degrees head-up groups were 47.3 and 44.9 kg/m, respectively (P = 0.18). The group randomly assigned to the 25 degrees head-up position achieved higher preinduction oxygen tensions (442 +/- 104 vs. 360 +/- 99 mmHg; P = 0.012) and took longer to reach an oxygen saturation of 92% (201 +/- 55 vs. 155 +/- 69 s; P = 0.023). There was a strong positive correlation between the induction oxygen tension achieved and the time to reach an oxygen saturation of 92% (r = 0.51, P = 0.001). There were no adverse events associated with the study.

Conclusion

Preoxygenation in the 25 degrees head-up position achieves 23% higher oxygen tensions, allowing a clinically significant increase in the desaturation safety period--greater time for intubation and airway control. Induction in the 25 degrees head-up position may provide a greater safety margin for airway control.
Development and Validation of a Perioperative Satisfaction Questionnaire
Authors: Auquier Pascal , Pernoud Nicolas , Bruder Nicolas , Simeoni Marie-Claude , Auffray Jean-Pierre , Colavolpe Christian , François Georges , Gouin François , Manelli Jean-Claude , Martin Claude , Sapin Christophe , Blache Jean-Louis
Published: May 2005

Background

Satisfaction is considered a valuable measure of outcome of healthcare processes. Only a few anesthesia-related validated questionnaires are reported. Because their scope is restricted to specific clinical contexts, their use remains limited. The objective of the current study was to develop and validate a self-reported questionnaire, Evaluation du Vecu de l'Anesthesie Generale (EVAN-G), assessing the satisfaction of the perioperative period surrounding general anesthesia.

Methods

Development of the EVAN-G questionnaire comprised a phase of item generation and a phase of psychometric validation. The patient sample was generated to be proportionally matched to the population of patients undergoing general anesthesia in France. The structure of the questionnaire was identified studying interitem, item-dimension, and interdimension correlations and factor analyses. Data were concurrently gathered to assess external validity. The discriminant validity was determined by comparison of scores across well known patient groups. Reliability was assessed by computation of Cronbach alpha coefficients and by test-retest.

Results

Eight hundred seventy-four patients were recruited in eight anesthesia departments. The EVAN-G includes 26 items; six specific scores and one global index score are available. Correlations between EVAN-G scores and other concurrent measures supported convergent validity. The EVAN-G correlated poorly with age, American Society of Anesthesiologists physical status, total anesthesia time, and number of previous anesthesias. Significantly higher satisfaction was reported by patients older than 65 yr, belonging to the laryngeal mask group. Reliability and reproducibility were shown.

Conclusion

The EVAN-G adds important information oriented toward patients' perceptions. The authors' approach provides a novel, valid, and reliable tool that may be used in anesthesia practice.
Involvement of Adenosine in the Antiinflammatory Action of Ketamine
Authors: Mazar Julia , Rogachev Boris , Shaked Gad , Ziv Nadav Y. , Czeiger David , Chaimovitz Cidio , Zlotnik Moshe , Mukmenev Igor , Byk Gerardo , Douvdevani Amos
Published: May 2005

Background

Ketamine is an anesthetic drug. Subanesthetic doses of ketamine have been shown to reduce interleukin-6 concentrations after surgery and to reduce mortality and the production of tumor necrosis factor alpha and interleukin 6 in septic animals. Similarly, adenosine was shown to reduce tumor necrosis factor alpha and mortality of septic animals. The aim of this study was to determine whether adenosine mediates the antiinflammatory effects of ketamine.

Methods

Sepsis was induced in mice by lipopolysaccharide or Escherichia coli inoculation. Leukocyte recruitment and cytokine concentrations were used as inflammation markers. Adenosine concentrations were assayed by high-performance liquid chromatography, and the involvement of adenosine in the effects of ketamine was demonstrated by adenosine receptor agonists and antagonists.

Results

Ketamine markedly reduced mortality from sepsis, leukocyte recruitment, and tumor necrosis factor-alpha and interleukin-6 concentrations. Ketamine administration in mice and rats was associated with a surge at 20-35 min of adenosine in serum (up to 5 microm) and peritoneal fluid. The adenosine A2A receptor agonist CGS-21680 mimicked the effect of ketamine in peritonitis, whereas the A2A receptor antagonists DMPX and ZM 241385 blocked its antiinflammatory effects. In contrast, A1 and A3 receptor antagonists had no effect. ZM 241385 reversed the beneficial effect of ketamine on survival from bacterial sepsis.

Conclusions

The current data suggest that the sepsis-protective antiinflammatory effects of ketamine are mediated by the release of adenosine acting through the A2A receptor.
Opposing Effects of Isoflurane and Sevoflurane on Neurogenic Pulmonary Edema Development in an Animal Model
Authors: Kandatsu Nobuhisa , Nan Yong-Shan , Feng Guo-Gang , Nishiwaki Kimitoshi , Hirokawa Mitsuru , Ishikawa Kiyonori , Komatsu Toru , Yokochi Takashi , Shimada Yasuhiro , Ishikawa Naohisa
Published: May 2005

Background

The current study was undertaken to investigate the effects of pretreatment with isoflurane and sevoflurane on the development of neurogenic pulmonary edema in an animal model.

Methods

Rats were exposed to room air (control), 1.5% isoflurane, or 2.5% sevoflurane for 4 h. They were then anesthetized with intraperitoneal injections of pentobarbital sodium, and fibrinogen and thrombin were injected into the cisterna magna to induce neurogenic pulmonary edema.

Results

Consecutive injections of fibrinogen and thrombin caused increases in blood pressure, with the peak values obtained in the isoflurane and sevoflurane groups being lower than the control values. The incidence of significant neurogenic pulmonary edema was 58%, 100%, and 8% in the control, isoflurane, and sevoflurane groups, respectively. The lung water ratio, an index of severity of edema, was 4.86 +/- 0.78, 6.15 +/- 0.64, and 4.40 +/- 0.32 in the control, isoflurane, and sevoflurane groups, respectively. Furthermore, immunohistochemical staining for vascular endothelial growth factor demonstrated an increase of expression in the rat lungs exposed to isoflurane. Treatment with an anti-vascular endothelial growth factor antibody during exposure to isoflurane completely inhibited the effect of isoflurane to promote neurogenic pulmonary edema in this model.

Conclusion

Exposure to 1.5% isoflurane enhances the development of neurogenic pulmonary edema development in this animal model, most likely via release of vascular endothelial growth factor from bronchial epithelial cells, an effect not observed with sevoflurane.
Effect of Postoperative Epidural Analgesia on Rehabilitation and Pain after Hip Fracture Surgery
Authors: Foss Nicolai Bang , Kristensen Morten Tange , Kristensen Billy Bjarne , Jensen Pia Søe , Kehlet Henrik
Published: May 2005

Background

Hip fracture surgery usually carries a high demand for rehabilitation and a significant risk of perioperative morbidity and mortality. Postoperative epidural analgesia may reduce morbidity and has been shown to facilitate rehabilitation in elective orthopedic procedures. No studies exist on the effect of postoperative epidural analgesia on pain and rehabilitation after hip fracture surgery.

Methods

Sixty elderly patients were included in a randomized, double-blind study comparing 4 days of continuous postoperative epidural infusion of 4 ml/h bupivacaine, 0.125%, and 50 mug/ml morphine versus placebo. Both patient groups received balanced analgesia and intravenous nurse-controlled analgesia with morphine. All patients followed a well-defined multimodal rehabilitation program. Pain, ability to participate in four basic physical functions, and any factors restricting participation were assessed on the first 4 postoperative days during physiotherapy.

Results

Epidural analgesia provided superior dynamic analgesia during all basic physical functions, and patients were significantly less restricted by pain, which was the dominating restricting factor in the placebo group. Motor blockade was not a restricting factor during epidural analgesia. Despite improved pain relief, scores for recovery of physical independence were not different between groups.

Conclusion

Postoperative epidural analgesia after hip fracture surgery provides superior analgesia attenuating pain as a restricting factor during rehabilitation without motor dysfunction. However, superior analgesia did not translate into enhanced rehabilitation. Future studies with multimodal rehabilitation are required to establish whether superior analgesia can be translated into enhanced rehabilitation and reduced morbidity in hip fracture patients.
Median Effective Dose (ED50) of Nefopam and Ketoprofen in Postoperative Patients
Authors: Delage Noémie , Maaliki Hilal , Beloeil Hélène , Benhamou Dan , Mazoit Jean-Xavier
Published: May 2005

Background

The analgesic efficacy of ketoprofen has been shown after moderate- and severe-pain surgery, and the analgesic efficacy of nefopam has been shown after moderate-pain surgery. The aim of this study was to define the median effective analgesic doses of each drug and to determine whether the interaction of nefopam and of ketoprofen is synergistic.

Methods

Seventy-two patients scheduled to undergo moderately painful surgery were enrolled in one of three groups. The dose of nefopam and ketoprofen received by a particular patient was determined by the response of the previous patient of the same group, using an up-and-down technique. Initial doses were 18 and 40 mg, with dose adjustment intervals of 2 and 5 mg, in the nefopam and ketoprofen groups, respectively. The initial doses of nefopam and ketoprofen were 8 and 20 mg, respectively, in the nefopam-ketoprofen group, with the same dose adjustment intervals. Analgesic efficacy was defined as a decrease to less than 3 on a 0-10 numeric pain scale, 45 min after the beginning of drug infusion.

Results

The median effective analgesic dose (median value and 95% confidence interval) of nefopam and ketoprofen were, respectively, 28 mg (17-39 mg) and 30 mg (14-46 mg). The median effective analgesic dose of the combination was 1.75 mg (0.9-2.3 mg) for nefopam and 4.3 mg (2.2-6.5 mg) for ketoprofen.

Conclusion

The isobolographic analysis demonstrated that the combination of the two drugs produces effective analgesia with an important synergistic interaction.
Painful Nerve Injury Decreases Resting Cytosolic Calcium Concentrations in Sensory Neurons of Rats
Authors: Fuchs Andreas , Lirk Philipp , Stucky Cheryl , Abram Stephen E. , Hogan Quinn H.
Published: May 2005

Background

Neuropathic pain is difficult to treat and poorly understood at the cellular level. Although cytoplasmic calcium ([Ca]c) critically regulates neuronal function, the effects of peripheral nerve injury on resting sensory neuronal [Ca]c are unknown.

Methods

Resting [Ca]c was determined by microfluorometry in Fura-2 AM-loaded neurons dissociated from dorsal root ganglia of animals with hyperalgesia to mechanical stimulation after spinal nerve ligation and section (SNL) at the fifth and sixth lumbar (L5 and L6) levels and from animals after skin incision alone (control group). Axotomized neurons from the L5 dorsal root ganglia were examined separately from adjacent L4 neurons that share the sciatic nerve with degenerating L5 fibers.

Results

After SNL, large (34 mum or larger) neurons from the L4 ganglion showed a 29% decrease in resting [Ca]c, whereas those from the L5 ganglion showed a 54% decrease. Small neurons only showed an effect of injury in the axotomized L5 neurons, in which resting [Ca]c decreased by 30%. A decrease in resting [Ca]c was not seen in neurons isolated from rats in which hyperalgesia did not develop after SNL. In separate experiments, SNL reduced resting [Ca]c in capsaicin-insensitive neurons of the L5 ganglion by 60%, but there was no change in neurons from L4. Resting [Ca]c of capsaicin-sensitive neurons was not affected by injury in either ganglion. SNL injury decreased the proportion of neurons sensitive to capsaicin in the L5 group but increased the proportion in the L4 group.

Conclusions

Painful SNL nerve injury depresses resting [Ca]c in sensory neurons. This is most marked in axotomized neurons, especially the large and capsaicin-insensitive neurons presumed to transmit non-nociceptive sensory information.
Developmental Age Influences the Effect of Epidural Dexmedetomidine on Inflammatory Hyperalgesia in Rat Pups
Authors: Walker Suellen M. , Howard Richard F. , Keay Kevin A. , Fitzgerald Maria
Published: May 2005

Background

Epidural alpha2-adrenergic agonists produce analgesic effects in children and adults, but efficacy and safety have not been established in neonates and infants. The aim of this study was to determine the effect of epidural dexmedetomidine on sensory processing, reversal of inflammatory hyperalgesia, and sedation during early development in rats.

Methods

In rat pups aged 3, 10, and 21 postnatal days, mechanical withdrawal thresholds of the hind limbs were measured at baseline and after unilateral inflammation due to carrageenan. The effect of epidural dexmedetomidine on withdrawal thresholds was measured for 90 min after injection, and dose-response curves were constructed for each age group. The duration of the righting reflex was measured to assess sedation. The effects of epidural and systemic administration of dexmedetomidine were compared.

Results

At all ages, carrageenan-induced hyperalgesia was reversed by doses of epidural dexmedetomidine that did not affect the threshold of the contralateral paw or prolong the righting reflex. Higher doses of epidural dexmedetomidine affected baseline nociception in the contralateral paw and produced sedation but had no effect when given systemically. Reversal of hyperalgesia and sedation were produced by lower doses of epidural dexmedetomidine in the youngest pups.

Conclusions

Spinally mediated selective reversal of inflammatory hyperalgesia by epidural dexmedetomidine can be achieved at all ages; relatively lower doses are effective in early life, but the therapeutic window is narrow. These data have implications for the use and dosing of epidural alpha2 agonists in neonates and infants.
Effects of Nonsteroidal Antiinflammatory Drugs on Patient-controlled Analgesia Morphine Side Effects
Authors: Marret Emmanuel , Kurdi Okba , Zufferey Paul , Bonnet Francis , Warltier David C.
Published: May 2005

Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly combined with intravenous morphine patient-controlled analgesia to relieve postoperative pain. NSAIDs have a documented 30-50% sparing effect on morphine consumption. However, most of the studies have not demonstrated a decrease in morphine adverse effects. A meta-analysis of randomized controlled trials was performed to evaluate the risk of morphine adverse effects in patients treated with NSAIDs. Twenty-two prospective, randomized, double-blind studies including 2,307 patients were selected. NSAIDs decreased significantly postoperative nausea and vomiting by 30%, nausea alone by 12%, vomiting alone by 32% and sedation by 29%. A regression analysis yielded findings indicating that morphine consumption was positively correlated with the incidence of nausea and vomiting. Pruritus, urinary retention, and respiratory depression were not significantly decreased by NSAIDs.
Endothelium-derived Hyperpolarizing Factor
Authors: Bryan Robert M. , You Junping , Golding Elke M. , Marrelli Sean P.
Published: May 2005

There is now strong evidence that an endothelial mechanism, other than nitric oxide or prostacyclin, exists for dilating arteries and arterioles. This third pathway has been named endothelium-derived hyperpolarizing factor (EDHF) and should not be confused with endothelium-derived relaxing factor, which is nitric oxide. Currently, there are several ideas for the mechanism of EDHF, which may vary among vessels of different organs and species. During some pathologic states, EDHF can be up-regulated. This up-regulation often occurs as the dilator effects of endothelium-derived nitric oxide are suppressed. The up-regulated EDHF may serve in a protective capacity to help maintain blood flow to organs and tissues during these stressful states. Many anesthetics attenuate the dilator actions of EDHF; however, the full clinical implications of this anesthetic-related attenuation are not known. Like its cousins, nitric oxide and prostacyclin, EDHF is an important regulator of blood flow and should prove to be an important clinical consideration as we gain more knowledge of its mechanisms of action.
Paradoxical polyembryony? Embryonic cloning in an ancient order of marine bryozoans
Authors: Hughes Roger N , D'Amato M. Eugenia , Bishop John D.D , Carvalho Gary R , Craig Sean F , Hansson Lars J , Harley Margaret A , Pemberton Andrew J
Published: May 2005

Prolific polyembryony is reported in few major taxa, but its occurrence has generated theoretical debate on potential conflict between sexual and asexual reproduction. It is, therefore, important to genetically confirm a widely cited inference, based on microscopy, that polyembryony characterizes marine bryozoans of the order Cyclostomata. Microsatellite genotyping of brooded embryos and maternal colonies conclusively demonstrated polyembryony, while genetic variation among broods within colonies indicated outcrossing via water-borne sperm, in the rocky-shore species
Crisia denticulata
. The characteristically voluminous brood chamber of cyclostomes is judged to be an adaptation linked to larval cloning and hence an indicator of polyembryony. We speculate that although the almost universal occurrence of polyembryony among crown-group Cyclostomata is probably attributable to phylogenetic constraint, adaptive consequences are likely to be significant.
Malaria parasite growth is stimulated by mosquito probing
Authors: Billingsley P.F , Snook L.S , Johnston V.J
Published: May 2005

The ability of malaria parasites to respond positively to the presence of feeding mosquito vectors would clearly be advantageous to transmission. In this study,
Anopheles stephensi
mosquitoes probed mice infected with the rodent malaria parasite,
Plasmodium chabaudi
. Growth of asexual stages was accelerated and gametocytes appeared 1–2 days earlier than in controls. This first study, to our knowledge, of the effects of mosquitoes on ‘in-host’ growth and development of
Plasmodium
has profound implications for malaria epidemiology, suggesting that individuals exposed to high mosquito numbers can contribute disproportionately high numbers of parasites to the transmission pool.
Success of ectoparasites: how important is timing of host contact?
Authors: Robb T , Forbes M.R
Published: May 2005

Hosts often differ in their degree of parasitism and their expression of resistance. Yet very little is known about how the availability (and allocation) of resources to parasites at pre-infective stages influences their success in initiating parasitism, or in inducing and succumbing to resistance from hosts. We studied a damselfly–mite association to address how experimental variation in the age of first contact with hosts (timing) influenced subsequent parasite fitness. We demonstrate that timing influenced the ability of larval mites to make the transition to parasitism, but was not associated with measures of physiological resistance by hosts. Timing presumably relates to the availability of resources remaining for individuals to exploit their hosts. More research is needed on the importance of such factors, from variation in host resistance and parasite success and, ultimately, to the numbers and distributions of parasites on hosts.
High progesterone during avian meiosis biases sex ratios toward females
Authors: Correa Stephanie M , Adkins-Regan Elizabeth , Johnson Patricia A
Published: May 2005

Evidence of altered primary sex ratios in birds shows that mothers can manipulate the sex of their offspring before oviposition. In birds, females are the heterogametic sex (ZW) and males are homogametic (ZZ). Sex is determined in the first meiotic division, when one sex chromosome is retained in the oocyte and the other segregates to the polar body. Altered primary sex ratios suggest that birds may be capable of biasing the segregation of sex chromosomes during meiosis I. During the time of meiosis I, follicular steroid production is limited primarily to progesterone (P4). We experimentally manipulated the levels of P4 in female domestic chickens during the approximate time of meiosis I. We advanced the ovulation of the first egg of a sequence (or clutch) with a subcutaneous injection of P4. We found a significant effect of P4 dose on the sex of the resulting egg. The high progesterone group produced 25% males whereas the low progesterone group produced 61% males and the control group produced 63% males in the first ovulation of the sequence. We propose that variation in maternal progesterone during the critical time for genetic sex determination is the mechanism for primary sex ratio manipulation in birds.
Scale analysis suggests frequent skipping of the second reproductive season in Atlantic herring
Authors: Engelhard Georg H , Heino Mikko
Published: May 2005

A common assumption in fish studies is that iteroparous fishes, once mature, normally reproduce in all consecutive seasons. An analysis of scales from Norwegian spring-spawning herring collected between 1935 and 1973 revealed a strong under-representation (47% of expected) of second-time spawners on the spawning grounds. This reduction is not satisfactorily explained by errors in scale-reading, suggesting that the second reproductive season is frequently skipped. Skipping a season may relate to trade-offs between growth, current and future reproduction, and survival, which are likely to be particularly strong for young adult herring.
Honeybee workers use cues other than egg viability for policing
Authors: Beekman Madeleine , Oldroyd Benjamin P
Published: May 2005

Worker policing, wherein social insect workers prevent their sisters from reproducing by eating worker-laid eggs, is recognized as a textbook example of kin selection in action. However, the evolutionary basis of policing was recently challenged in a study that suggested that police-workers remove worker-laid eggs not because rearing workers' sons reduces worker fitness, but merely because worker-laid eggs have low viability. Here, we refute Pirket al.'s conclusions. First, we confirm earlier work that showed equal viability of eggs laid by queens and workers. Second, a statistical analysis of the data of Pirket al.reveals that their own data do not support the conclusion that worker-laid eggs are policed merely because of their low viability. Third, we present data that unequivocally show that police-workers cannot discriminate between dead and live eggs. Hence, our study seriously weakens the challenge to the kin-selected basis of policing in honeybees.
Periodic variability in cetacean strandings: links to large-scale climate events
Authors: Evans K , Thresher R , Warneke R.M , Bradshaw C.J.A , Pook M , Thiele D , Hindell M.A
Published: May 2005

Cetacean strandings elicit much community and scientific interest, but few quantitative analyses have successfully identified environmental correlates to these phenomena. Data spanning 1920–2002, involving a total of 639 stranding events and 39 taxa groups from southeast Australia, were found to demonstrate a clear 11–13- year periodicity in the number of events through time. These data positively correlated with the regional persistence of both zonal (westerly) and meridional (southerly) winds, reflecting general long-term and large-scale shifts in sea-level pressure gradients. Periods of persistent zonal and meridional winds result in colder and presumably nutrient-rich waters being driven closer to southern Australia, resulting in increased biological activity in the water column during the spring months. These observations suggest that large-scale climatic events provide a powerful distal influence on the propensity for whales to strand in this region. These patterns provide a powerful quantitative framework for testing hypotheses regarding environmental links to strandings and provide managers with a potential predictive tool to prepare for years of peak stranding activity.
Residue-specific immobilization of protein molecules by size-selected clusters
Authors: Prisco Umberto , Leung Carl , Xirouchaki Chrisa , Jones Celine H , Heath John K , Palmer Richard E
Published: May 2005

The atomic force microscope (AFM), operating in contact mode, has been employed in buffer solution to study two proteins; (i) green fluorescent protein (GFP), from the hydromedusan jellyfish
Aequorea victoria
; and (ii) human oncostatin M (OSM), in the presence of size-selected gold nanoclusters pinned on to a highly oriented pyrolytic graphite substrate. The AFM images have revealed immobilization of single molecules of OSM, which are strongly bound to the gold nanoclusters. Conversely, no strong immobilization has been observed for the GFP, as these molecules were easily displaced by the scanning tip. The contrasting behaviour of the two proteins can be explained by the exposed molecular surface area of their cysteine residues as modelled on the basis of their respective X-ray crystallographic data structures. GFP contains two cysteine residues, but neither is readily available to chemisorb on the gold clusters, because the cysteines are largely inaccessible from the surface of the protein. In contrast, OSM has a total of five cysteine residues, with different degrees of accessibility, which make the protein amenable to anchoring on the nanoclusters. Statistical analysis of the height of the OSM molecules bound to the nanoclusters is in accordance with crystallographic data, and suggests various configurations of the proteins on the clusters, associated with the presence of different cysteine anchoring sites. These results suggest that the three-dimensional conformation of protein molecules is preserved when they are chemisorbed to size-selected gold clusters, thus opening a new route towards oriented immobilization of individual protein molecules.
Comparative study of corneal strip extensometry and inflation tests
Authors: Elsheikh Ahmed , Anderson Kevin
Published: May 2005

Strip extensometry tests are usually considered less reliable than trephinate inflation tests in studying corneal biomechanics. In spite of the evident simplicity of strip extensometry tests, several earlier studies preferred inflation tests in determining the constitutive relationship of the cornea and its other material properties, such as Young's modulus and the hysteresis behaviour. In this research, the deficiencies of the strip tests are discussed and a mathematical procedure presented to take account of these deficiencies when obtaining the corneal material properties. The study also involves testing 10 pairs of porcine corneas using both strip extensometry and trephinate inflation techniques and the results are subjected to mathematical back analysis in order to determine the stress–strain behaviour. The behaviour obtained from the strip extensometry tests and using the new mathematical analysis procedure is shown to match closely the inflation test results.
Examining the architecture of cellular computing through a comparative study with a computer
Authors: Wang Degeng , Gribskov Michael
Published: May 2005

The computer and the cell both use information embedded in simple coding, the binary software code and the quadruple genomic code, respectively, to support system operations. A comparative examination of their system architecture as well as their information storage and utilization schemes is performed. On top of the code, both systems display a modular, multi-layered architecture, which, in the case of a computer, arises from human engineering efforts through a combination of hardware implementation and software abstraction. Using the computer as a reference system, a simplistic mapping of the architectural components between the two is easily detected. This comparison also reveals that a cell abolishes the software–hardware barrier through genomic encoding for the constituents of the biochemical network, a cell's ‘hardware’ equivalent to the computer central processing unit (CPU). The information loading (gene expression) process acts as a major determinant of the encoded constituent's abundance, which, in turn, often determines the ‘bandwidth’ of a biochemical pathway. Cellular processes are implemented in biochemical pathways in parallel manners. In a computer, on the other hand, the software provides only instructions and data for the CPU. A process represents just sequentially ordered actions by the CPU and only virtual parallelism can be implemented through CPU time-sharing. Whereas process management in a computer may simply mean job scheduling, coordinating pathway bandwidth through the gene expression machinery represents a major process management scheme in a cell. In summary, a cell can be viewed as a super-parallel computer, which computes through controlled hardware composition. While we have, at best, a very fragmented understanding of cellular operation, we have a thorough understanding of the computer throughout the engineering process. The potential utilization of this knowledge to the benefit of systems biology is discussed.
Dynamics of an axisymmetric body spinning on a horizontal surface. II. Self-induced jumping
Authors: Shimomura Y , Branicki M , Moffatt H.K
Published: May 2005

Following part I of this series, the general spinning motion of an axisymmetric rigid body on a horizontal table is further analysed, allowing for slip and friction at the point of contact. Attention is focused on the case of spheroids whose density distribution is such that the centre-of-mass and centre-of-volume coincide. The governing dynamical system is treated by a multiple-scale technique in order to resolve the two time-scales intrinsic to the dynamics. An approximate solution for the high-frequency component of the motion reveals that the normal reaction can oscillate with growing amplitude, and in some circumstances will fall to zero, leading to temporary loss of contact between the spheroid and the table. The exact solution for the free motion that ensues after this ‘jumping’ is analysed, and the time-dependence of the gap between the spheroid and the table is obtained up to the time when contact with the table is re-established. The analytical results agree well with numerical simulations of the exact equations, both up to and after loss of contact.
Evidence of a shift in the cyclicity of Antarctic seabird dynamics linked to climate
Authors: Jenouvrier Stéphanie , Weimerskirch Henri , Barbraud Christophe , Park Young-Hyang , Cazelles Bernard
Published: May 2005

Ecosystems and populations are known to be influenced not only by long-term climatic trends, but also by other short-term climatic modes, such as interannual and decadal-scale variabilities. Because interactions between climatic forcing, biotic and abiotic components of ecosystems are subtle and complex, analysis of long-term series of both biological and physical factors is essential to understanding these interactions. Here, we apply a wavelet analysis simultaneously to long-term datasets on the environment and on the populations and breeding success of three Antarctic seabirds (southern fulmar, snow petrel, emperor penguin) breeding in Terre Adélie, to study the effects of climate fluctuations on Antarctic marine ecosystems. We show that over the past 40 years, populations and demographic parameters of the three species fluctuate with a periodicity of 3–5 years that was also detected in sea-ice extent and the Southern Oscillation Index. Although the major periodicity of these interannual fluctuations is not common to different species and environmental variables, their cyclic characteristics reveal a significant change since 1980. Moreover, sliding-correlation analysis highlighted the relationships between environmental variables and the demography of the three species, with important change of correlation occurring between the end of the 1970s and the beginning of the 1980s. These results suggest that a regime shift has probably occurred during this period, significantly affecting the Antarctic ecosystem, but with contrasted effects on the three species.
Climate change and seal survival: evidence for environmentally mediated changes in elephant seal,Mirounga leonina, pup survival
Authors: McMahon Clive R , Burton Harry R
Published: May 2005

Maternal and physical factors play a significant role in animal life-history variability, which means that large scale climate change has the potential to affect the size and dynamics of animal populations indirectly through maternal investment and directly through conditions that animals are exposed to. However, little is known about the effects of large-scale oceanographic events such as the El-Niño southern oscillation (ENSO) that influence productivity in the Southern Ocean and the abundance, quality and distribution of prey. The possible mechanisms by which physical factors and primary productivity could influence life-history traits, such as survival of apex predators, includes direct influences such as food availability and foraging success and indirect influences such as stored maternal investment and resource transfer during lactation. Here, we quantify the relative contribution of maternal investment and climate conditions at remote foraging sites to survival in the first year of life for southern elephant seals. We present evidence linking climate (ENSO) and variations in a key demographic parameter—first-year survival—and demonstrate that survival was highest during ENSO events and that the ability of mothers to store and acquire resources, which is typically related to ocean productivity, is the most important determinant of survival in the first year. This functional link provides valuable insights that can be used to model the responses of the seal populations to climate change scenarios.
Pathogen adaptation to seasonal forcing and climate change
Authors: Koelle Katia , Pascual Mercedes , Yunus Md
Published: May 2005

Many diverse infectious diseases exhibit seasonal dynamics. Seasonality in disease incidence has been attributed to seasonal changes in pathogen transmission rates, resulting from fluctuations in extrinsic climate factors. Multi-strain infectious diseases with strain-specific seasonal signatures, such as cholera, indicate that a range of seasonal patterns in transmission rates is possible in identical environments. We therefore consider pathogens capable of evolving their ‘seasonal phenotype’, a trait that determines the sensitivity of their transmission rates to environmental variability. We introduce a theoretical framework, based on adaptive dynamics, for predicting the evolution of disease dynamics in seasonal environments. Changes in the seasonality of environmental factors are one important avenue for the effects of climate change on disease. This model also provides a framework for examining these effects on pathogen evolution and associated disease dynamics. An application of this approach gives an explanation for the recent cholera strain replacement in Bangladesh, based on changes in monsoon rainfall patterns.