bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyr‐c[D‐Orn‐Tyr(Bzl)‐Pro‐Gly]: a novel antiproliferative acting somatostatin receptor agonist with μ‐opioid receptor‐sensitizing properties
Authors: Stirnweiss Jörg , Hartrodt Bianka , Greksch Gisela , Stürzebecher Uta , Böhmer Frank‐D , Neubert Klaus , Liebmann Claus 
Published: September 2003

Here, we introduce a β‐casomorphin‐5‐derived cyclic pentapeptide, cCD‐2 (Tyr‐cyclo[D‐Orn‐Tyr(Bzl)‐Pro‐Gly]), which inhibits the cell growth of a variety of human cancer cell lines.
This opioid‐derived peptide possesses only low affinity for μ‐receptors, but enhances the agonist binding to μ‐receptors in vitro and potentiates the analgesic effect of morphin in vivo. The molecular mechanism of μ‐receptor sensitization by cCD‐2 is not yet known.
The antiproliferative effect of cCD‐2 is independent of μ‐, δ‐, and κ‐receptors.
Using SH‐SY5Y cells as model, we can demonstrate that cCD‐2 specifically binds to somatostatin receptors and stimulates the activity of protein tyrosine phosphatases, which are early downstream targets of SST receptors.
In SH‐SY5Y cells, cCD‐2 specifically increases the activity of the cytosolic PTP SHP‐2, stimulates the activity of mitogen‐activated protein kinase (MAPK), and elevates the expression of the cyclin‐dependent kinase inhibitor p21 (WAF1/Cip1), suggesting the involvement of SSTR1 receptor subtype in cCD‐2 action in this cell type.
In COS‐7 cells, for comparison, we found a stimulation of SHP‐2 as well as SHP‐1 in response to cCD‐2. The activation of SHP‐1, which is attributed to the SSTR2 receptor and negatively regulates the EGF receptor, corresponds with the ability of cCD‐2 to inhibit the EGF‐induced MAPK activation in COS‐7 cells.
Our results show that in SH‐SY5Y cells cCD‐2 inhibits cell growth via the SSTR1 receptor‐signalling pathway but may, in other cells, also use other SSTR subtypes and their signalling mechanisms.
cCD‐2 represents a novel type of opioid‐derived antiproliferative SST receptor agonist, which possesses low μ‐receptor affinity but may induce μ‐receptor sensitization and is structurally different from the hitherto known SST receptor agonists.

British Journal of Pharmacology (2003) 140, 13–22. doi:10.1038/sj.bjp.0705416
Different distribution of morphine and morphine‐6β‐glucuronide after intracerebroventricular injection in rats
Authors: Okura Takashi , Saito Masanori , Nakanishi Misato , Komiyama Noriyuki , Fujii Aki , Yamada Shizuo , Kimura Ryohei 
Published: September 2003

We investigated the distribution of morphine and morphine‐6β‐glucuronide (M6G) in the brain and spinal cord after intracerebroventricular (i.c.v.) injection of each drug in rats.
The cerebrospinal fluid (CSF) concentration of M6G was 5–37 times greater than that of morphine 10, 60 and 120 min after the i.c.v. injection. The apparent elimination clearance of M6G from the CSF was 10 times lower than that of morphine.
The intrathecal CSF concentration of M6G measured by the microdialysis method was 29–79 times greater than that of morphine, and M6G was rapidly distributed into the intrathecal space after the i.c.v. injection.
M6G was detected in the cerebrum, brainstem, cerebellum and spinal cord at concentrations 2–21 times higher than morphine after the i.c.v. injection of each drug. The distribution volume of M6G in rat brain slices was three times lower than that of morphine, and close to the extracellular fluid space in the brain regions corresponding to the vicinity of the opioid receptors.
These brain distribution characteristics of M6G, namely, low clearance from the central nervous system, localization in the extracellular fluid and rapid distribution into the intrathecal space, may contribute to the potent analgesic effect of M6G after i.c.v. injection.

British Journal of Pharmacology (2003) 140, 211–217. doi:10.1038/sj.bjp.0705418
Atypical β‐adrenoceptors, different from β3‐adrenoceptors and probably from the low‐affinity state of β1‐adrenoceptors, relax the rat isolated mesenteric artery
Authors: Kozłowska Hanna , Szymska Urszula , Schlicker Eberhard , Malinowska Barbara 
Published: September 2003

We examined whether β3‐ and/or atypical β‐adrenoceptors relax the rat isolated mesenteric artery.
Mesenteric arteries precontracted with phenylephrine were relaxed by β‐agonists with the following potencies (pD2): nonselective agonist isoprenaline (6.00)>nonconventional partial agonist cyanopindolol (5.45)>β2‐agonist fenoterol (4.98)>nonconventional partial agonist CGP 12177 (4.19)>β3‐agonist ZD 2079 (3.72). The β3‐agonist CL 316243 1 mM relaxed the vessel only marginally.
The concentration–response curves (CRCs) for cyanopindolol, CGP 12177 and ZD 2079 were not affected by the nonselective β‐antagonist propranolol 0.3 μM, the β2‐antagonist ICI 118551 1 μM and by CL 316243 60 μM, but shifted to the right by bupranolol (pA2 5.3–5.7), CGP 20712 (5.4) and SR 59230A (6.5–6.7) (the latter three drugs block atypical and/or β3‐adrenoceptors at high concentrations).
The CRC for isoprenaline was shifted to the right by propranolol (pA2 7.0) but, in the presence of propranolol 0.3 μM, not affected by SR 59230A 1 μM. The CRC for fenoterol was shifted to the right by propranolol (pA2 6.9) and ICI 118551 (6.8).
Removal of endothelium diminished the vasorelaxant effects of cyanopindolol, CGP 12177 and ZD 2079.
Fenoterol and cyanopindolol also relaxed (endothelium‐intact) mesenteric arteries precontracted with serotonin. The relaxant effect of cyanopindolol was antagonized by bupranolol to about the same degree as in phenylephrine‐contracted vessels.
In conclusion, β2‐ and atypical β‐adrenoceptors (but not β3‐adrenoceptors) relax the rat mesenteric artery. The atypical β‐adrenoceptor, which is partially located endothelially, may differ from the low‐affinity state of the β1‐adrenoceptor.

British Journal of Pharmacology (2003) 140, 3–12. doi:10.1038/sj.bjp.0705421
Pharmacological comparison of the alternatively spliced short and long CCK2 receptors
Authors: Morton M F , Harper E A , Tavares I A , Shankley N P 
Published: September 2003

The alternatively spliced, short and long cholecystokinin receptors (CCK2S and CCK2L) were expressed in NIH3T3 cells, and compared using radioligand‐binding assays with identical buffer and incubation conditions.
As judged by a saturation analysis, the selective CCK2‐receptor antagonist radioligand [3H]‐JB93182 did not discriminate between the CCK2S or CCK2L receptors.
A global analysis of competition studies, using a range of structurally diverse, CCK‐receptor selective ligands, provided further evidence that these receptor subtypes were pharmacologically indistinguishable. However, when analysed individually a number of small, yet significant differences were observed with some of the compounds.
These data are consistent with previous study that suggested a possible pharmacological difference between these isoforms, at least in terms of the CCK2‐receptor antagonist, L‐365,260. However, it would appear that the pharmacological profile of these compounds is not consistent with their affinity at the putative G1/G2 receptors previously described by Harper et al.

British Journal of Pharmacology (2003) 140, 218–224. doi:10.1038/sj.bjp.0705423
Perinatal Malnutrition Programs Sympathoadrenal and Hypothalamic‐Pituitary‐Adrenal Axis Responsiveness to Restraint Stress in Adult Male Rats
Authors: Lesage J. , Dufourny L. , Laborie C. , Bernet F. , Blondeau B. , Avril I. , Bréant B. , Dupouy J. P. 
Published: September 2003

AbstractIn humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic‐pituitary‐adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long‐lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis and sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4‐month‐old male rats malnourished during their perinatal life and on age‐matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid‐binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma‐free corticosterone concentration was significantly higher and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative‐feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.
Cardiac scoring systems – what is their value?
Authors: Ridley S. 
Published: September 2003

SummaryEstimating the peri‐operative risk of major adverse cardiac events is one of the functions of cardiac risk scoring systems. Fortunately, peri‐operative cardiac complications are relatively infrequent in most patients. Clinical algorithms use sequential screening tests to detect patients most at risk of cardiac complications. However, because the sensitivity and specificity of the tests used are low, the predictive performance of the commonly‐used cardiac screening tests may not be completely satisfactory. The purpose of this review is to describe measures of performance of cardiac screening tests and illustrate their potential benefits and weaknesses.
A new mirrored laryngoscope*
Authors: McMorrow R. C. N. , Mirakhur R. K. 
Published: September 2003

SummaryA new laryngoscope has been designed, incorporating an adjustable mirror and a levered tip similar to the McCoy blade, in an attempt to bridge the gulf between simple direct laryngoscopy and fiberoptic laryngoscopy. Manual in‐line neck stabilisation was used to simulate difficult laryngoscopy in 14 anaesthetised patients after full neuromuscular blockade. The best view at laryngoscopy was assessed using a standard Macintosh laryngsocope, a size 3 McCoy laryngoscope and the mirrored laryngoscope. The best laryngeal view obtained in all cases with the Macintosh blade was a grade 3. The mirrored laryngoscope improved this view in 10 cases (71%) compared with five cases (36%) with the McCoy laryngoscope (p = 0.005); in seven cases (50%), the view improved to a grade 1 compared with no cases when the McCoy was used (p = 0.02). We conclude that the mirrored laryngoscope offers considerable advantages over the Macintosh and the McCoy laryngoscopes in simulated difficult laryngoscopy, is simple to use and requires no special training.
Pharmacokinetics of sevoflurane uptake into the brain and body
Authors: Lu C. C. , Tsai C. S. , Ho S. T. , Chen W. Y. , Wong C. S. , Wang J. J. , Hu O. Y. P. , Lin C. Y. 
Published: September 2003

SummaryThe aim of this study was to investigate the pharmacokinetics of sevoflurane uptake into the brain and body by comparing sevoflurane concentrations in internal jugular‐bulb blood (Jsev), arterial blood (Asev) and pulmonary arterial blood (PAsev) over a fixed inspired sevoflurane concentration. Ten patients (aged 51–73 years), undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 3.5% inspired sevoflurane concentration (CIsev) during the first hour of anaesthesia. During constant volume‐controlled ventilation, we measured CIsev and end‐tidal sevoflurane (CEsev) using infrared analysis. The sevoflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti‐Q pulmonary artery catheter. We found that it took 40 min for the brain concentration to equilibrate with arterial blood (Asev). Both CIsev–CEsev and Asev–PAsev gradients persisted during the study period. There was no further uptake of sevoflurane into the brain after 40 min; however, there was near‐constant uptake into the body.
Assessing the learning needs of college tutors in anaesthesia: proposals for an introductory learning package*
Authors: Edgar J. , Glavin R. 
Published: September 2003

SummaryAt present there is no nationwide formal training course at which college tutors in anaesthesia can develop the specific skills required to perform their important role effectively. The purpose of this study was to ascertain whether there is a need for an introductory learning package for college tutors and if so, what learning needs ought to be addressed in such a package. A needs assessment was performed involving the use of individual interviews and the administration of two sequential questionnaires. The questionnaire was completed by 208 college tutors, a return rate of 83%. Most college tutors (93%) said they had had no formal training to perform their role and 94% felt there was a need for an introductory course for college tutors in anaesthesia. Of those, 77% said they would be interested in taking such a course. The study identified a number of learning needs.
Intragastric pressure and its relevance to protective cricoid force*
Authors: Haslam N. , Syndercombe A. , Zimmer C. R. , Edmondson L. , Duggan J. E. 
Published: September 2003

SummaryCricoid pressure is frequently used to protect the anaesthetised and paralysed patient from passive regurgitation. Although intragastric pressure (Pga) drives regurgitation, its relevance in the setting of protective cricoid force has been largely ignored. We sought to define the likely range of Pga encountered in the population at risk. We studied 100 consecutive patients presenting for surgery requiring mechanical ventilation. We measured respiratory swings in Pga during mechanical ventilation in the paralysed state following rapid sequence induction (n = 24) and routine induction of anaesthesia (n = 76). Pga (mmHg) in the whole group recorded at end‐inspiration (Pga‐In) and end‐expiration (Pga‐Ex) was [mean (SD)]: Pga‐In 6.48 (2.60) mmHg and Pga‐Ex 3.23 (2.24) mmHg. We found no correlation between Pga and body mass index (r2 = 0.018). These findings have implications for the level of cricoid force required to protect a patient during the induction of anaesthesia.
Assessment of the effect upon maternal knowledge of an information leaflet about pain relief in labour*
Authors: Stewart A. , Sodhi V. , Harper N. , Yentis S. M. 
Published: September 2003

SummaryPregnant women were randomly assigned to receive, at booking, the usual written information pack either with or without the Obstetric Anaesthetists' Association's (OAA's) leaflet ‘Pain Relief in Labour’. At 36 weeks' gestation, a structured interview was conducted at which we assessed the sources of information the women had used and their knowledge of specific aspects of obstetric analgesia and anaesthesia described in the OAA leaflet. The most useful sources of information overall were friends, family, midwives, books and information leaflets (no significant difference between the groups); 72% of all women felt they had received adequate information although 70% said they would have liked to have discussed methods of analgesia with an anaesthetist before delivery. Parturients allocated to receive the leaflet (n = 37) were more knowledgeable than those who received only standard booking information (n = 39) about all analgesic and anaesthetic techniques except for systemic pethidine, although this difference in knowledge only reached statistical significance for extending epidural analgesia for emergency Caesarean section. We conclude that the OAA leaflet improves women's knowledge of analgesic techniques and suggest that all information of this type be formally assessed in this manner; furthermore given the practical difficulties in conducting studies of this type, the latter should be adequately resourced, perhaps by the bodies that issue such leaflets.
Recent trends in tracheal intubation: a retrospective analysis of 97 904 cases
Authors: Yarrow S. , Hare J. , Robinson K. N. 
Published: September 2003

SummaryWe conducted a review of routine anaesthetic audit data collected between April 1995 and December 2001 at Northampton General Hospital. A total of 97 904 anaesthetics were given. The average monthly rate of tracheal intubation fell during the study period from ∼450 per month to ∼280 per month. This was largely at the expense of tracheal tubes used during normal working hours, which fell by 40% (from ∼390 per month to ∼230 per month). Use outside normal working hours did not change. Of those cases managed in normal working hours with a tracheal tube, the decline in use over time was most obvious in patients of ASA physical status 1–2, and whose surgery was classified as elective or scheduled. The proportion of cases classified as ASA 3–5 or whose surgery was urgent or emergency increased (from 15.5% to 22.3%, and from 7.5% to 15.5%, respectively.) There was considerable variation across surgical specialities, with the greatest decline in tracheal intubation in head and neck surgery. These changes in practice have implications for the teaching of airway management skills.
Sacrococcygeal local anaesthesia versus general anaesthesia for pilonidal sinus surgery: a prospective randomised trial
Authors: Naja M. Z. , Ziade M. F. , El Rajab M. 
Published: September 2003

SummarySixty patients scheduled for pilonidal sinus surgery were prospectively randomly assigned to receive general anaesthesia or sacrococcygeal local anaesthesia with a newly‐described technique. Patients in the general anaesthesia group spent more time in the operating theatre and recovery room than did those in the local anaesthesia group (p < 0.05). Two thirds (67%) of the patients in the local anaesthesia group left hospital on the day of surgery compared to only 17% of patients in the general anaesthesia group (p < 0.05). Visual analogue scale pain scores performed during the 3‐day follow‐up period favoured the local anaesthetic technique (p < 0.05). Postoperative analgesia requirements were greater in the general anaesthesia group than in the local anaesthesia group (p < 0.05). The majority of patients and surgeons expressed satisfaction with local anaesthesia. Sacrococcygeal local anaesthesia appears to be a successful alternative to general anaesthesia for pilonidal sinus surgery.
Conservation ethics and anaesthesia
Authors: Houghton I. T. 
Published: September 2003

SummaryThe current attitude of conservators towards restoration is to preserve objects and materials in the condition as they are but without attempting to restore them ‘as new’. Museum objects have generally ceased to serve their original utilitarian function but have become objects for study, information and inspiration. Conservation and restoration are discussed in relation to anaesthetic exhibits. Conservation is the prevention, detection, containment, control and recovery but risk avoidance and monitoring hopefully will lessen the need for conservation. Some objects such as rubber and plastic items are, by their very nature, prone to ageing, accident and mistreatment. Cleaning and maintenance may lead to loss of original detail and is ‘an act of critical interpretation’. Reshaping of distorted objects and repair of broken pieces can sometimes be justified but, in other work, the actual restoration may become part of the object's history that should not be lost in trying to restore something to a presumed earlier state. The mind interprets images by reference to earlier patterns and so imperfections, if not disguised, may be unduly distracting. Museums exist for information, evidence, enlightenment and even entertainment. Conservation must serve these purposes and is not an end in its own right. The professional actions of the conservator must be governed by a total respect for physical, historic, and aesthetic integrity but this must be interpreted widely.
A comparison of bispectral index and ARX‐derived auditory evoked potential index in measuring the clinical interaction between ketamine and propofol anaesthesia
Authors: Vereecke H. E. M. , Struys M. M. R. F. , Mortier E. P. 
Published: September 2003

SummaryWe evaluated the effects of a bolus (0.4 mg.kg−1) and continuous infusion (1 mg.kg−1.h−1) of ketamine on Bispectral Index (BIS) and A‐Line® ARX Index (AAI) during propofol anaesthesia. We included 15 ASA I patients scheduled for general anaesthesia. Induction was performed by infusion of propofol at 100 ml.h−1 until loss of consciousness. Both BIS and AAI monitors responded appropriately at that time. The calculated effect site concentration of propofol at loss of consciousness was maintained by means of a computer controlled infusion system. A ‘pseudo’ steady‐state effect site concentration was reached after 4 min. After 1 min of baseline measurements, ketamine was administered. BIS values increased from the 3rd to the 8th min after the administration of ketamine. The AAI showed no significant increase or decrease, but between‐patient variability increased.
Consent and anaesthetic risk
Authors: Jenkins K. , Baker A B. 
Published: September 2003

SummaryThe incidences of mortality and morbidity associated with anaesthesia were reviewed. Most of the published incidences for common complications of anaesthesia vary considerably. Where possible, a realistic estimate of the incidence of each morbidity has been made, based on the best available data. Perception of risk and communication of anaesthetic risk to patients are discussed. The incidences of anaesthetic complications are compared with the relative risks of everyday events, using a community cluster logarithmic scale, in order to place the risks in perspective when compared with other complications and with the inherent risks of surgery. Documentation of these risks and discussion with patients should allow them to be better informed of the relative risks of anaesthetic complications. Depending on specific comorbidities and the severity of operation, these risks associated with anaesthesia may increase for any one individual.
Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages
Authors: Benson R M , Minter L M , Osborne B A , Granowitz E V 
Published: September 2003

SUMMARYHyperbaric oxygen (HBO) is 100% oxygen administered at elevated atmospheric pressure to patients with inflammatory diseases. We developed an in vitro model to investigate the effects of HBO on stimulus-induced proinflammatory cytokine transcription and translation. Human blood-derived monocyte-macrophages were stimulated before being transferred to an HBO chamber where they were incubated at 97·9% O2, 2·1% CO2, 2·4 atmospheres absolute, 37°C. Controls were maintained in the same warm room at normoxia at sea level, hyperoxia or increased pressure alone. A 90-min HBO exposure inhibited IL-1β synthesized in response to lipopolysaccharide by 23%, lipid A by 45%, phytohaemagglutinin A (PHA) by 68%, and tumour necrosis factor (TNF)-α by 27%. HBO suppressed lipopolysaccharide-, lipid A- and PHA-induced TNF-α by 29%, 31% and 62%, respectively. HBO transiently reduced PHA-induced steady state IL-1β mRNA levels. Hyperoxia alone and pressure alone did not affect cytokine production. The immunosuppressive effect of HBO was no longer evident in monocyte-macrophages exposed to HBO for more than 3 h. Interestingly, cells exposed to HBO for 12 h synthesized more IL-1β than cells cultured under control conditions. In summary, HBO exposure transiently suppresses stimulus-induced proinflammatory cytokine production and steady state RNA levels.