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Insulin glargine 300 U/mL and insulin detemir are synthetic long-acting insulin analogs associated with minimal day-to-day variability or episodes of hypoglycemia in people. Here, 8 healthy purpose-bred dogs each received 2.4 nmol/kg subcutaneous injections of insulin detemir (0.1 U/kg) and insulin glargine 300 U/mL (0.4 U/kg) on 2 different days, >1 wk apart, in random order. Blood glucose (BG) was measured every 5 min, and glucose was administered intravenously at a variable rate with the goal of maintaining BG within 10% of baseline BG ("isoglycemic clamp"). Endogenous and exogenous insulin were measured for up to 24 h after insulin injection. The effect of exogenous insulin was defined by glucose infusion rate or a decline in endogenous insulin. Isoglycemic clamps were generated in all 8 dogs after detemir but only in 4 dogs after glargine. Median time to onset of action was delayed with glargine compared to detemir (4.0 h [3.3-5.8 h] vs 0.6 h [0.6-1.2 h], P = 0.002). There was no difference in time to peak (median [range] = 6.3 h [5.0-21.3 h] vs 4.3 h [2.9-7.4 h], P = 0.15) or duration of action (16.3 h [6.1-20.1 h] vs 10.8 h [8.8-14.8 h], P = 0.21) between glargine and detemir, respectively. Glargine demonstrated a peakless time-action profile in 4/8 dogs. The total metabolic effect and peak action of detemir was significantly greater than glargine. Significant concentrations of glargine were detected in all but 1 dog following administration. Glargine might be better suited than detemir as a once-daily insulin formulation in some dogs based on its long duration of action and peakless time-action profile. Day-to-day variability in insulin action should be further assessed for both formulations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Strongylus vulgaris has become a rare parasite in Germany during the past 50 years due to the practice of frequent prophylactic anthelmintic therapy. To date, the emerging development of resistance in Cyathostominae and Parascaris spp. to numerous equine anthelmintics has changed deworming management and the frequency of anthelmintic usage. In this regard, reliable detection of parasitic infections, especially of the highly pathogenic S. vulgaris is essential. In the current study, two diagnostic methods for the detection of infections with S. vulgaris were compared and information on the occurrence of this parasite in German horses was gained. For this purpose, faecal samples of 501 horses were screened for S. vulgaris with real-time PCR and an additional larval culture was performed in samples of 278 horses. A subset of 26 horses underwent multiple follow-up examinations with both methods in order to evaluate both the persistence of S. vulgaris infections and the reproducibility of each diagnostic method., Results: The real-time PCR revealed S. vulgaris-DNA in ten of 501 investigated equine samples (1.9%). The larval culture demonstrated larvae of S. vulgaris in three of the 278 samples (1.1%). A direct comparison of the two methods was possible in 321 samples including 43 follow-up examinations with the result of 11 S. vulgaris-positive samples by real-time PCR and 4 S. vulgaris-positive samples by larval culture. The McNemar's test (p-value = 0.016) revealed a significant difference and the kappa values (0.525) showed a moderate agreement between real-time PCR and larval culture., Conclusions: The real-time PCR detected a significantly higher proportion of positives of S. vulgaris compared to larval culture and should thus be considered as a routine diagnostic method for the detection of S. vulgaris in equine samples.

Background: The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block, that is, a train-of-four ratio (TOFR) ≥0.2., Methods: Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1) i.v. for tracheal intubation and, if necessary, incremental doses of 0.1-0.2 mg kg(-1). Neuromuscular monitoring was performed by calibrated electromyography. Once the TOFR recovered to 0.2, patients were randomized to receive sugammadex (0.25, 0.5, 0.75, 1.0, or 1.25 mg kg(-1) i.v.), neostigmine (10, 25, 40, 55, or 70 µg kg(-1) i.v.), or saline (n=9 per group). Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95% of patients, respectively., Results: Neostigmine was not able to fulfil the end points. Based on the best-fitting model, the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95% of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1), respectively., Conclusion: A residual neuromuscular block of a TOFR of 0.2 cannot be reversed reliably with neostigmine within 10 min. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2., Clinical Trial Registration: NCT01006720., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Similar to volatile anaesthetics, propofol may influence neuromuscular transmission. We hypothesised that the administration of propofol influenced the potency of rocuronium depending on the duration of the administration., Methods: After consent, patients scheduled for elective surgery randomly received rocuronium either after induction of anaesthesia with propofol (2 min of propofol, n = 36) or after 30 min of propofol infusion (30 min of propofol, n = 36). Remifentanil was given in both groups. Neuromuscular monitoring was performed by calibrated electromyography. The dose-response relationship of rocuronium was determined with a single-bolus technique (0.07, 0.1, 0.15, 0.2, 0.3 and 0.45 mg/kg rocuronium). The primary endpoints were the ED50 and ED95 of rocuronium after 2 and 30 min propofol. Data are presented as means with (95% confidence interval). The trial is registered with the Eudra-CT: 2009-012815-16., Results: A total of 72 patients were included. Time to maximal neuromuscular blockade was significantly shorter in patients after 30 min of propofol [3.3 min (2.9-3.7)] compared with patients anaesthetised with 2 min of propofol [4.6 min (4.0-5.2)]. After 30 min of propofol, the slope of the dose-response curve was significantly steeper (30 min of propofol: 4.34 [3.62-5.05]; 2 min of propofol: [3.34 (2.72-3.96)], resulting in lower ED95 values of rocuronium (30 min of propofol: 0.287 mg/kg [0.221-0.368]; 2 min of propofol [0.391 mg/kg (0.296-0.520)]. The ED50 were not different between groups., Conclusion: The potency of rocuronium was significantly enhanced after propofol infusion for 30 min. Estimates of potency those are usually determined during steady-state anaesthesia might underestimate rocuronium requirements for endotracheal intubation at the time of induction., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: A train-of-four ratio (TOFR) ≥0.9 measured by quantitative neuromuscular monitoring is accepted as an indication of sufficient neuromuscular recovery for extubation, even though many postsynaptic acetylcholine receptors may still be inhibited. We investigated whether antagonism with sugammadex after spontaneous recovery to TOFR≥0.9 further improves muscle function or subjective well-being., Methods: Following recovery to TOFR≥0.9 and emergence from anaesthesia, 300 patients randomly received either sugammadex 1.0 mg kg(-1) or placebo. Fine motor function (Purdue Pegboard Test) and maximal voluntary grip strength were measured before and after surgery (before and after test drug administration). At discharge from the postanaesthesia care unit, well-being was assessed with numerical analogue scales and the Quality-of-Recovery Score 40 (QoR-40)., Results: Patients' fine motor function [6 (sd 4) vs 15 (3) pegs (30 s)(-1), P<0.05] and maximal voluntary grip strength (284 (126) vs 386 (125) N, P<0.05) were significantly lower after anaesthesia compared with the pre-anaesthesia baseline. After sugammadex or placebo, motor function was significantly improved in both groups but did not reach the preoperative level. There was no difference between groups at any time. Global well-being was unaffected (QoR-40: placebo, 174 vs 185; sugammadex, 175 vs 186, P>0.05)., Conclusions: Antagonizing rocuronium at TOF≥0.9 with sugammadex 1.0 mg kg(-) (1) did not improve patients' motor function or well-being when compared with placebo. Our data support the view that TOFR≥0.9 measured by electromyography signifies sufficient recovery of neuromuscular function., Clinical Trial Registration: The trial is registered at ClinicalTrials.gov (NCT01101139)., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Dopaminergic, serotonergic, and adrenergic receptors are targets for therapeutic actions in schizophrenia. Dopamine D2 receptor partial agonists such as aripiprazole represent a treatment option for patients with this severe disorder. The ineffectiveness of terguride, another D2 receptor partial agonist, in treating schizophrenia was recently attributed to its considerably high intrinsic activity at D2 receptors. In this study, we used functional assays for recombinant D2 receptors and native 5-hydroxytryptamine 2A (5-HT2A), α2C-adrenergic, and histamine H1 receptors to compare the pharmacological properties of terguride and three of its halogenated derivatives (2-chloro-, 2-bromo-, 2-iodoterguride) with those of aripiprazole. Subsequently, we studied the antidopaminergic effects of 2-bromoterguride using amphetamine-induced locomotion (AIL). Its influence on spontaneous behavior was tested in the open field. Extrapyramidal side effect (EPS) liability was evaluated by catalepsy test. In a guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding assay, 2-chloro-, 2-bromo-, and 2-iodoterguride produced intrinsic activities at human D2short (hD2S) receptors that were half as high as the intrinsic activity for terguride; aripiprazole lacked agonist activity. 2-Bromoterguride and aripiprazole activated D2S receptor-mediated inhibition of cAMP accumulation to the same extent; intrinsic activity was half as high as that of terguride. All compounds tested behaved as antagonists at human D2long/Gαo (hD2L/Gαo) receptors. Compared with aripiprazole, terguride and its derivatives displayed higher affinity at porcine 5-HT2A receptors and α2C-adrenoceptors and lower affinity at H1 receptors. 2-Bromoterguride inhibited AIL and did not induce catalepsy in rats. Because of its in vitro and in vivo properties, 2-bromoterguride may be a strong candidate for the treatment of schizophrenia with a lower risk to induce EPS.

Introduction: The free exploratory paradigm is regarded as a reliable test for trait anxiety in mice but it may also be useful in rats. Previously, we showed that rat strains differ in their free exploration of novel areas, i.e. the surroundings of their familiar home cage when the lid was removed., Aim: Therefore, the purpose of the present study was to further examine strain, sex, and age differences in animals from different breeders in combination with pharmacological treatment designed to modify anxiety., Methods: In the present study free exploratory behaviour test was evaluated in Sprague Dawley and Wistar rats from different breeders. We assessed seasonal variation, habituation to the test, and the impact of gender and age on exploration. Furthermore, we monitored exploration following intraperitoneal diazepam, 8-OH-DPAT and caffeine administration. Parameters measured were latency to start exploring the outside of the cage, the percentage of rats that explored the outside, as well as the number of visits., Results: There was no seasonal variability in free exploratory behaviour. However, strains and sexes differed in the test results, though age-related differences had less impact. Diazepam (2mg/kg) and 8-OH-DPAT (30, 100 and 300μg/kg) decreased neophobia while caffeine (50mg/kg) increased the latency to explore the outside the next day., Discussion: The free exploratory behaviour test can be used as a simple and complementary test to study trait anxiety-related behaviour in rats., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Serotonin is a major neurotransmitter in the central nervous system (CNS). Dysregulation of serotonin transmission in the CNS is reported to be related to different psychiatric disorders in humans including depression, impulsive aggression and anxiety disorders. The most frequently prescribed antidepressants and anxiolytics target the serotonergic system. However, these drugs are not effective in 20-30% of cases. The causes of this failure as well as the molecular mechanisms involved in the origin of psychological disorders are poorly understood. Biosynthesis of serotonin in the CNS is initiated by tryptophan hydroxylase 2 (TPH2). In this study, we used Tph2-deficient (Tph2(-/-)) mice to evaluate the impact of serotonin depletion in the brain on mouse behavior. Tph2(-/-) mice exhibited increased depression-like behavior in the forced swim test but not in the tail suspension test. In addition, they showed decreased anxiety-like behavior in three different paradigms: elevated plus maze, marble burying and novelty-suppressed feeding tests. These phenotypes were accompanied by strong aggressiveness observed in the resident-intruder paradigm. Despite carrying only one copy of the gene, heterozygous Tph2(+/-) mice showed only 10% reduction in brain serotonin, which was not sufficient to modulate behavior in the tested paradigms. Our findings provide unequivocal evidence on the pivotal role of central serotonin in anxiety and aggression.

Pharmacologic reversal of neuromuscular blockade is a topic not very well acknowledged and controversially discussed. Reasons for this are numerous and include missing perception of the potential complications of residual neuromuscular paralysis including an increased morbidity and mortality, as well as low efficacy and numerous unwanted side effects of the available antagonists. Duration of action of muscle relaxants cannot be pharmacologically predicted. Objective neuromuscular monitoring is the only way to detect residual paralysis. This review article would like to discuss in its first part some of the myths which revolve around the use of muscle relaxants, then highlight the problems regarding the use of acetylcholine esterase inhibitors and, in the third part, discuss the steroidal muscle relaxant encapsulator sugammadex.

Medical emergencies in pregnant patients pose a great challenge. Due to a lack of experience many emergency care providers are uncertain about which drugs can be used and the dosage. The following article reviews the physiological changes during pregnancy, general considerations about pharmacotherapy in pregnant patients and highlights typical emergency scenarios with the corresponding recommendations for which drugs to use in pregnant patients.

This study investigated risk assessment and anxiolytic/anxiogenic drug effects in "low brain angiotensinogen" transgenic rats (TGR) in comparison to wild-type Sprague-Dawley rats (SD) in the canopy test of anxiety-related behaviour. TGR showed a higher frequency of the risk assessment behaviour as indicated by performance of stretched attend posture (SAP) compared to SD. Diazepam (0.25mg/kg) reduced SAP in both strains, whereas FG-7142 had no significant effect. The 5-HT(1B/2C) agonist mCPP (0.5-2mg/kg) reduced SAP in both strains. Diazepam (0.25-1mg/kg) increased head dips and decreased the time spent under the canopy in SD rats. There were significant anxiogenic effects of both FG-7142 (3-6 mg/kg) and mCPP (0.5-2mg/kg) on these parameters for SD but not TGR. Diazepam (1mg/kg) increased the number of entries into the open zone in both strains. mCPP reduced this parameter in SD (2mg/kg) and TGR (0.5-2mg/kg). FG-7142 had a similar effect in SD (3-6 mg/kg) and TGR (6 mg/kg). This study showed a significant transgenic effect on SAP. The increased number of SAP seen in TGR could be reduced with diazepam. Although both FG-7142 and mCPP are generally anxiogenic, no significant effects of FG-7142 on SAP were observed and mCPP even reduced SAP., ((c) 2010. Published by Elsevier Inc. All rights reserved.)

Disperse dyes, which are suitable for dyeing synthetic fibres, are responsible for the great majority of allergic contact dermatitis (ACD) cases to textile dyes. The aim of the present study was to investigate the sensitising potential of various disperse dyes using a biphasic protocol of the local lymph node assay (LLNA). Briefly, mice were shaved over a surface of approximately 2 cm(2) on their backs and treated using a "sensitisation-challenge protocol". The shaved surface was treated once daily on days 1-3 with 50 microl of the test solution. Animals remained untreated on days 4-14. On days 15-17, mice were treated with 25 microl of the test solution on the dorsum of both ears. Mice were killed on day 19 with deep CO(2) anaesthesia, the lymph nodes prepared and various end points, such as ear thickness, ear punch weight, lymph node weight, lymph node cell count and the proportion of various lymphocyte subpopulations, were determined by flow cytometry. The results were compared to control group treated with the vehicle alone. Our results showed that almost all of the tested textile dyes caused a significant increase in lymph node cell count and lymph node weight. We also observed an increase in ear thickness and ear punch weight in most of the concentrations tested for various textile dyes. We observed a decrease in CD4+ and CD8+ cells and an increase in CD19+, CD45+ and CD45+/1A+ cells in most of the cases, which is characteristic for allergens. The CD4+/CD69+ cells increased in only few experiments mainly with Disperse Blue 124 and Disperse Blue 106. Based on our results, the disperse dyes could be arranged in four groups on the basis of their sensitising potency in the following decreasing order (in parenthesis: lowest concentration causing a significant increase in lymph node cell number): group 1, strong: Disperse Blue 124 and Disperse Blue 106 (0.003%); group 2, moderate: Disperse Red 1 and Disperse Blue 1 (3%); group 3, weak: Disperse Orange 37 and Disperse Blue 35 (10%); and group 4, very weak: Disperse yellow 3 and Disperse Orange 3 (increase at 30% or no increase at 30%). In conclusion, our study shows that the biphasic LLNA protocol was proficient enough to study the sensitisation potential of tested textile dyes and provides data allowing to discriminate them according to their potency.

Myasthenia gravis, affecting neuromuscular transmission, leads to a large variability in sensitivity to depolarising and non-depolarising neuromuscular blocking drugs. We report the successful use of the modified mu-cyclodextrin sugammadex in a myasthenic patient to reverse a rocuronium-induced deep level of neuromuscular block. After spontaneous neuromuscular recovery of T2 (second twitch of the train-of-four series), we administered 2 mg.kg(-1) of sugammadex intravenously, reversing neuromuscular blockade to a train-of-four ratio (T4/T1) > 90% within 210 s. Sugammadex, in combination with objective neuromuscular monitoring, can be used to reverse rocuronium-induced neuromuscular blockade in patients with myasthenia gravis, thereby avoiding the need for reversal with acetylcholinesterase inhibitors.

Neuronal activity is tightly coupled with brain energy metabolism; and glucose is an important energy substrate for neurons. The present in vivo microdialysis study was aimed at investigating changes in extracellular glucose concentrations in the rat ventral hippocampus due to exposure to the elevated plus maze. Determination of basal hippocampal glucose and lactate/pyruvate ratio in male Wistar rats was conducted in the home cage using in vivo microdialysis. Rats were exposed to the elevated plus maze, a rodent model of anxiety-related behaviour, or to unspecific stress induced by white noise (95dB) as a control condition. Basal hippocampal levels of glucose, as determined by zero-net-flux, and the basal lactate/pyruvate ratio were 1.49+/-0.05mmol/l and 13.8+/-1.1, respectively. In rats without manipulation, glucose levels remained constant throughout the experiment (120min). By contrast, exposure to the elevated plus maze led to a temporary decline in hippocampal glucose (-33.2+/-4.4%) which returned to baseline level in the home cage. White noise caused only a non-significant decrease in extracellular glucose level (-9.3+/-3.5%). In all groups, the lactate/pyruvate ratio remained unchanged by the experimental procedures. Our microdialysis study demonstrates that exposure to the elevated plus maze induces a transient decrease in extracellular hippocampal glucose concentration. In contrast, an unspecific stimulus did not change hippocampal glucose. The latter suggests that only specific behavioural stimuli increase hippocampal glucose utilization in the ventral hippocampus.

Objectives: Aim of this Germany-wide study was to evaluate the use and application customs of neuromuscular blocking drugs (NMBDs) for tracheal intubation in children of age 5 years or younger., Material and Methods: In the year 2005, a total of 3260 questionnaires were sent out to all heads of anesthesia departments at all types of hospitals as well as ambulatory anesthesia centers in Germany. The fields covered by the questionnaire were regarding institutional size, amount of general anesthesia and specifically pediatric cases, number of intubations and NMBDs used, frequency of use of the individual relaxants and techniques utilized when administering muscle relaxants., Results: Of the sent-out questionnaires 66.9% could be analyzed: 82% of hospitals use 1-3 muscle relaxants in children; 91% of the ambulatory anesthesia centers use a repertoire of 1-2 neuromuscular blockers for pediatric cases. However, general anesthesia with tracheal intubation in children is often induced without using any NMBD at all. Mivacurium is the predominantly used NMBD for pediatric intubation in Germany. In contrast, the use of succinylcholine is far less in ambulatory anesthesia centers than in hospitals. Despite controversial discussion, precurarization, priming, and timing are still utilized in German anesthesia practice., Conclusion: In Germany, mivacurium, with its favorable pharmacologic profile for short cases, is the predominantly used NMBD for pediatric tracheal intubation. Despite the known adverse effects of intubation without muscle relaxation, this technique is also wide-spread, especially among German anesthetists in ambulatory anesthesia centers. Surveys like these are important to determine a status quo of use and application customs of NMBDs in pediatric anesthesia and provide a basis for numerous other studies.

The serotonin 1A (5-HT(1A))-receptor is involved in a wide range of physiological functions, but has also been implicated in the pathophysiology of anxiety disorders and depression. Although the 5-HT(1A)-receptor is one of the best described receptor subtypes of the serotonergic system, its complex distribution pattern, pre- and postsynaptic localisation, and its impact on various neurotransmitters aggravate the attribution of 5-HT(1A)-agonistic effects to behavioural outcomes. The role of 5-HT(1A)-receptors for cognitive processes seems undisputed. However, the exact involvement of pre- and postsynaptic sites remains unexplained. Genetically modified animals are a complementary approach to pharmacological studies for further investigations of the role of the 5-HT(1A)-receptor. Next to 5-HT(1A)-receptor knockout mice, two transgenic mouse lines exist that either overexpress the 5-HT(1A)-receptor transiently or permanently. The latter mouse line stands out due to the fact that a distinct overexpression is primarily found in the outer cortical layers and hippocampus, both projection areas of serotonergic neurons. Here, we discuss the findings obtained from 5-HT(1A)-receptor knockout and overexpressing mice concerning their learning and memory abilities.

Beagle dogs continue to be used in experimental studies and preclinical and clinical trials, many of which address the usage of anaesthesia. In order to reduce the number of animals, researchers tend to conduct several experiments on a single animal. The question arises, however, as to whether or not this frequent usage involves more than simply additional stress and discomfort for the individual animal. Within the framework of an existing study involving six female Beagle dogs, we investigated the effects of repeated (5) isoflurane anaesthesia with xylazine/levomethadone/fenpipramide premedication carried out at short intervals (2 weeks) and compared these with the effects of two treatments intermitted by a longer resting period (8 weeks). To verify our hypothesis that frequent anaesthesia affects the dog's wellbeing more than the occasional anaesthesia, the following parameters were measured at regular intervals: body weight, body temperature, respiratory rate, blood pressure, reflexes and heart rate, both at rest and during a treadmill exercise. In addition, recovery behaviour subsequent to anaesthesia was monitored for one hour. Our observations indicate that the anaesthetic effects are most prominent 24 h after the anaesthetic treatment. However, crossover analysis of our data cannot show that there is no statistical difference of whether dogs were anaesthetized occasionally or frequently. In our study, it appears that frequent anaesthesia within a two-week period did not affect the wellbeing and general health of Beagle dogs in a super-additive manner and that a minimum of two-week testing-free period is sufficient to ensure complete recovery from the unwanted effects induced by anaesthesia.

The aim of the present study was to evaluate application customs of neuromuscular monitoring in hospitals and private practice. Of the 3,260 questionnaires sent out, 2,182 could be analyzed. Of these 54% were from anaesthetists in private practice, 41% from heads of hospital anaesthesia departments and 5% from heads of level 1 hospital anaesthesia departments. In 12.1% of the hospital departments and 66.7% of private practices, no neuromuscular monitoring was available at all. In both hospital departments and private practices, clinical signs were the most often applied criteria for timing of reinjection of myorelaxants as well as for evaluation of neuromuscular recovery.

In transgenic rats, TGR(ASrAOGEN)680, with reduced glial expression of angiotensinogen, changes in brain angiotensinogen are associated with reductions in serotonin (5-HT) content and/or 5-HT metabolism as determined in various brain regions, including the hypothalamus. These rats showed an anxious phenotype upon a first behavioural screen. The present study aimed to extend the search for functional consequences of changes in brain 5-HT with respect to feeding behaviour in these transgenic rats. In feeding experiments, rats were treated with the anorectic drug fenfluramine to probe for functional changes in the serotonergic satiety system. Fenfluramine (0.3 mg/kg, i.p.) reduced food intake in TGR(ASrAOGEN)680 rats whereas the minimal effective dose in wild-type rats was 3 mg/kg, i.p. Although, in the cortex, no differences were apparent in the expression of serotonin 5-HT(1A), 5-HT(1B), 5-HT(2C) receptor and 5-HT transporter mRNAs between TGR(ASrAOGEN)680 and wild-type rats, the expression of mRNAs for the 5-HT(2C) receptor and 5-HT transporter mRNA were significantly higher in the hypothalamus of TGR(ASrAOGEN)680 rats compared to wild-type rats. No differences were found in the mRNA levels for hypothalamic 5-HT(1A) and 5-HT(1B) receptors between TGR(ASrAOGEN)680 and wild-type rats. Taken together, these findings suggest that the transgenic effect on the brain 5-HT system is paralleled by functional changes of the serotonergic feeding system.

Unlabelled: Blood vessels are subjected to forces due to the flow. Endothelial cells (EC) are recipients, cross-talk with smooth muscle cells (SMC), and regulate physiology. It was hypothesized that both EC and SMC respond to shear stress, which alters the expression of factors in coagulation and fibrinolysis., Methods: A co-culture of human saphenous vein EC (HSVEC) and human saphenous vein SMC (HSVSMC) was exposed to shear, following which the cells were separated. Gene expression of tissue factor, thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) were analyzed with real-time RT-PCR. Protein expression was studied with ELISA. In HSVEC, the expression of PAI-1 (x2.1), tPA (x1.8), uPA (x1.6), tissue factor (x2.5) and TM (x1.9) was upregulated after 4 h of shear compared to controls. After 24 h of shear, expression was still upregulated in tPA (x2.3) and TM (x1.6). In HSVSMC, change in expression of PAI-1 (x2.1) was present after 4 h and in uPA (x2.1), and TM (x0.4) after 24 h. Both HSVEC and HSVSMC responded to shear, which led to altered expression of coagulation and fibrinolytic factors. This indicates that SMC, and interactions between EC and SMC, are more important in the regulation of vascular wall hemostasis than earlier studies have reported., (2008 S. Karger AG, Basel.)