bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective intermediate‐/small‐conductance calcium‐activated potassium channel (KCNN4) blockers are potent and effective therapeutics in experimental brain oedema and traumatic brain injury caused by acute subdural haematoma
Authors: Mauler Frank , Hinz Volker , Horváth Ervin , Schuhmacher Joachim , Hofmann Heiko A. , Wirtz Stephan , Hahn Michael G. , Urbahns Klaus 
Published: September 2004

AbstractEarly deterioration and death after brain injury is often the result of oedema in the injured and peri‐lesional tissue. So far, no pharmacotherapy is available that exhibits significant brain oedema‐reducing efficacy in patients. We selected two low molecular weight compounds from different chemical classes, a triazole (1‐[(2‐chlorophenyl)diphenylmethyl]‐1,2,3‐triazole) and a cyclohexadiene (methyl 4‐[4‐chloro‐3‐(trifluoromethyl)phenyl]‐6‐methyl‐3‐oxo‐1,4,7‐tetrahydroisobenzofuran‐5‐carboxylate) to characterize their pharmacological properties on KCNN4 channels (intermediate/small conductance calcium‐activated potassium channel, subfamily N, member 4) in vitro as well as in vivo. In vitro we replaced potassium by rubidium (Rb+) and determined Rb+ fluxes evoked by 10 µm of the calcium ionophore A23187 on C6BU1 rat glioma cells. Compared with known KCNN4 blockers, such as clotrimazole (IC50 = 360 ± 12 nm) and charybdotoxin (IC50 = 3.3 ± 1.9 nm), the triazole and cyclohexadiene were considerably more potent than clotrimazole and displayed similar potencies (IC50 = 12.1 ± 8.8 and 13.3 ± 4.7 nm, respectively). In the rat acute subdural haematoma model, both the triazole and cyclohexadiene displayed reduction of brain water content (−26% at 0.3 mg/kg and −24% at 0.01 mg/kg) and reduction of the intracranial pressure (−46% at 0.1 mg/kg and −60% at 0.003 mg/kg) after 24 h when administered as a 4‐h infusion immediately after brain injury. When infarct volumes were determined after 7 days, the triazole as well as the cyclohexadiene displayed strong neuroprotective efficacy (−52% infarct volume reduction at 1.2 mg/kg and −43% at 0.04 mg/kg, respectively). It is concluded that blockade of KCNN4 channels is a new pharmacological approach to attenuate acute brain damage caused by traumatic brain injury.
Why do we produce errors of commission? An ERP study of stimulus deviance detection and error monitoring in a choice go/no‐go task
Authors: Elton Martin , Spaan Marcus , Ridderinkhof K. Richard 
Published: September 2004

AbstractThe present study investigated event‐related brain potential (ERP) reflections of stimulus deviance detection and error monitoring recorded during a go/no‐go auditory oddball task. The mismatch negativity and error negativity were analysed as indices of these processes, respectively. We examined whether errors of commission occurred because of failures to detect stimulus deviance. On error trials the mismatch negativity amplitude did not differ between big and small deviant stimuli and was clearly reduced as compared with mismatch negativity amplitude on correct trials. Following an error response an error negativity was elicited, the amplitude of which was unaffected by stimulus deviancy. This pattern of ERP results was interpreted as supporting the defective deviance detection hypothesis.
Zonal ablation of the olfactory sensory neuroepithelium of the mouse: effects on odorant detection
Authors: Vedin Viktoria , Slotnick Burton , Berghard Anna 
Published: September 2004

AbstractOlfactory sensory neurons that express a specific odorant receptor, out of a thousand different, are unevenly distributed within, but restricted to one of four zones of the neuroepithelial sheet in the nasal cavity in the mouse. This zonal restriction of neurons expressing the same odorant receptor may have consequences, e.g. in case of localized injury. We found that the chemical dichlobenil can produce specific and permanent ablation of neurons in odorant receptor expression zone 1, while a higher dichlobenil dose causes reversible toxicity in neighboring zones. In behavior tests, mice lacking part of the olfactory epithelium had an increased detection threshold concentration of two–four orders of magnitude for some odorants but not others, resembling the phenomenon of specific hyposmia. This indicates that the broad tuning properties of single odorant receptors and their large number cannot fully compensate for loss of the receptor(s) with the highest sensitivity for a particular odorant.
Deficits in a lateralized associative learning task in dopamine‐depleted rats with functional recovery by dopamine‐rich transplants
Authors: Dowd Eilís , Dunnett Stephen B. 
Published: September 2004

AbstractExperimental therapies for Parkinson's disease (PD) are commonly validated in unilateral animal models using simple tests of motor asymmetry such as rotation, stepping and cylinder tests. However, the human disorder is considerably more complex than this, and alternative tests that permit a more complete evaluation of the efficacy and mechanism of action of novel treatments are needed. In this study, an operant task that assesses the selection, initiation and execution of lateralized movements was used to investigate the effects of embryonic dopamine cell transplants in the unilateral medial forebrain bundle (MFB) lesion model of PD. Lesioned Lister Hooded rats had a pronounced contralateral selection and initiation deficit, as well as an impairment in execution of movements bilaterally. They also attempted fewer trials and made more procedural errors than unlesioned rats. Transplantation of fetal dopaminergic neurons to the striatum led to a marked improvement in specific parameters and a more modest improvement in others. The graft improved the contralateral selection deficit and the execution of movements bilaterally, but had no effect on the initiation of contralateral movements. Transplanted rats also attempted more trials and made fewer errors. In contrast, the more commonly used stepping and cylinder tests revealed no functional effect of the graft. This data suggests that this operant task may be a powerful tool for validating and elucidating the mechanism of action of experimental brain repair therapies prior to entering the clinic.
GABAA receptors containing the α5 subunit mediate the trace effect in aversive and appetitive conditioning and extinction of conditioned fear
Authors: Yee Benjamin K. , Hauser Jonas , Dolgov Vadim V. , Keist Ruth , Möhler Hanns , Rudolph Uwe , Feldon Joram 
Published: September 2004

AbstractA reduction in α5 subunit‐containing γ‐aminobutyric acid (GABA)A receptors has been reported to enhance some forms of learning in mutant mouse models. This effect has been attributed to impaired α5 GABAA receptor‐mediated inhibitory modulation in the hippocampus. The introduction of a point mutation (H105R) in the α5 subunit is associated with a specific reduction of α5 subunit‐containing GABAA receptors in the hippocampus. The present study examined the modulation of associative learning and the extinction of conditioned response in these animals. The strength of classical conditioning can be weakened when a trace interval is interposed between the conditioned stimulus and unconditioned stimulus. Here we report that this ‘trace effect’ in classical conditioning was absent in the mutant mice − they were insensitive to the imposition of a 20‐s trace interval. This effect of the mutation was most clearly in the female mice using an aversive conditioning paradigm, and in the male mice using an appetitive conditioning paradigm. These gender‐specific phenotypes were accompanied by a resistance to extinction of conditioned fear response in the mutant mice that was apparent in both genders. Our results identify neuronal inhibition in the hippocampus mediated via α5 GABAA receptors as a critical control element in the regulation of the acquisition and expression of associative memory.
Changes in endocannabinoid levels in a rat model of behavioural sensitization to morphine
Authors: Viganò Daniela , Valenti Marta , Grazia Cascio Maria , Di Marzo Vincenzo , Parolaro Daniela , Rubino Tiziana 
Published: September 2004

AbstractThe opioid and cannabinoid systems co‐operate to regulate physiological processes such as nociception and reward. The endocannabinoid system may be a component of the brain reward circuitry and thus play a role not only in cannabinoid tolerance/dependence, but also in dependence/withdrawal for other misused drugs. We provide evidence of a cannabinoid mechanism in an animal model of morphine drug‐seeking behaviour, referred to as behavioural sensitization. The present study was designed to test the effects of the CB1 cannabinoid receptor antagonist SR141716A in two different phases of morphine sensitization (induction and expression) and to measure the brain contents of arachidonoylethanolamide (anandamide, AEA) and 2‐arachidonoylglycerol (2‐AG), the two main endogenous ligands for cannabinoid receptors in the different phases of morphine sensitization. The cannabinoid antagonist modified the signs of morphine sensitization when administered in the expression phase, whereas co‐administration of SR141716A and morphine in the induction phase only slightly affected the behavioural responses, suggesting that CB1 receptor blockade attenuates the behavioural manifestations of morphine sensitization but not its development. AEA and 2‐AG were affected differently by morphine during the two phases of behavioural sensitization. The alterations were in opposite directions and specific for the cerebral area analysed (caudate putamen, nucleus accumbens, hippocampus and prefrontal cortex). The results suggest that the endocannabinoid system undergoes profound changes during the different phases of sensitization to morphine in rats, providing a possible neurochemical basis for the previously observed cross‐sensitization between opiates and cannabinoids.
Induction of c‐fos in specific thalamic nuclei following stimulation of the pedunculopontine tegmental nucleus
Authors: Ainge James A. , Jenkins Trisha A. , Winn Philip 
Published: September 2004

AbstractThe pedunculopontine tegmental nucleus (PPTg) is a major source of cholinergic input to the thalamus. Tracing studies have established that the PPTg has projections to many thalamic nuclei and electrophysiological studies have shown acetylcholine (ACh) to have characteristic effects on thalamic neurons. Behavioural studies point to a role for the PPTg in attention and it is possible that a key substrate for this is the ability of the PPTg to modify sensorimotor gating through the thalamus. However, it is not clear how altered PPTg activity effects neuronal activity across the thalamus en masse. We have attempted to examine this by stimulating the PPTg in freely moving rats and measuring thalamic activation withc‐fos immunohistochemistry. The PPTg was stimulated by unilateral microinjection of the l‐glutamate uptake inhibitor l‐trans‐pyrrolidine‐2,4‐dicarboxylic acid (PDC) with the rationale that reuptake blockade increases locally the availability of endogenous neurotransmitter. It was shown that PDC microinjection into PPTg produced clear and consistent changes in Fos immunoreactivity in several thalamic nuclei, but most markedly in the centrolateral, ventrolateral and reticular nuclei. A second study was carried out to determine the gross behavioural effects of intra‐PPTg l‐glutamate blockade. No changes in locomotion or other general behaviours were observed, indicating that observed changes in thalamic Fos expression were not the result of increased behavioural output but rather a direct consequence of increased neuronal activity from PPTg input. The present data extend previous work establishing pedunculopontine–thalamic connections by specifying which particular nuclei are most affected by PPTg activation.
Hippocampal formation is required for geometric navigation in pigeons
Authors: Vargas Juan Pedro , Petruso Edward J. , Bingman Verner P. 
Published: September 2004

AbstractThe geometric properties of bounded space have attracted considerable attention as a source of spatial information that can guide goal navigation. Although the use of geometric information to navigate has been observed in every species studied to date, the neural mechanisms that support the representation of geometric information are still debated. With the purpose of investigating this topic, we trained pigeons with lesion to the hippocampal formation to search for food in a rectangular‐shaped arena containing one wall of a different color that served as the only distinctive environmental feature. Although lesioned pigeons learned the task even faster than control animals, probe trials showed that they were insensitive to geometric information. Control animals could encode and use both geometric and feature information to locate the goal. By contrast, lesioned pigeons relied exclusively on the feature information provided by the wall of a different color. The results indicate that the avian hippocampal formation is critical for learning the geometric properties of space in homing pigeons.
In vivo assessment of the efficacy of an innovative face care system in subjects with mild acne vulgaris1
Authors: Scherdin U. , Presto S. , Rippke F. , Nielsen J. , Strassner M. , Imadojemun A. , Gärtner E. , Herpens A. , Korting H. C. , Bielfeldt S. 
Published: September 2004

SynopsisThe purpose of our studies was to verify efficacy and skin compatibility of a medical face care system containing 2% lactic acid (LA) as active ingredient in a specially designed vehicle (Follicle Targeting System) in adult subjects with mild acne vulgaris. The first study (46 patients) demonstrated superiority of 2% LA in comparison to 2% salicylic acid with respect to number of comedones and inflammatory lesions. The second study evaluated 90 patients receiving distinct combinations of face care products (Eucerin® Impure Skin, Hamburg, Germany), i.e. cleansing gel, facial tonic (2% LA) and cream gel (2% LA). All treatments were performed twice daily over a 12 weeks period. Lesion counts, cyanoacrylate biopsies and determination of quality of life by questionnaires were performed at different timepoints. A reduction of comedones by 56% corresponding to an 46% increase of quality of life index was demonstrated in patients applying cleansing gel, facial tonic and cream gel. For the first time we were able to show a significant improvement concerning the quality of life after using a new face care line. Especially adults with mild forms of acne may benefit from this effective skin care regimen.
Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin1
Authors: Bissett D. L. , Miyamoto K. , Sun P. , Li J. , Berge C. A. 
Published: September 2004

SynopsisPrevious clinical testing of topical niacinamide (vitamin B3) has revealed a broad array of improvements in the appearance of aging facial skin. The study reported here was done to confirm some of those previous observations and to evaluate additional end points such as skin anti‐yellowing. Caucasian female subjects (n = 50, aged 40–60 years) participated in a 12‐week, double‐blind, placebo‐controlled, split‐face, left–right randomized clinical study assessing two topical products: moisturizer control product versus the same moisturizer product containing 5% niacinamide. Niacinamide was well tolerated by the skin and provided significant improvements versus control in end points evaluated previously: fine lines/wrinkles, hyperpigmentation spots, texture, and red blotchiness. In addition, skin yellowing (sallowness) versus control was significantly improved. The mechanism by which this array of benefits is achieved with niacinamide is discussed.
Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient‐controlled analgesia
Authors: McInnes Rhona J. , Hillan Edith , Clark Diana , Gilmour Harper 
Published: September 2004

Objectives  To compare the efficacy of diamorphine administered by a patient‐controlled pump (patient‐controlled analgesia) with intramuscular administration for pain relief in labour.Design  Randomised controlled trial.Setting  The South Glasgow University Hospitals NHS Trust.Sample  Primigravidae and multigravidae in labour at term (37–42 weeks).Methods  Women were randomised in labour to the study (patient‐controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks.Main outcome measures  Analgesia requirements during labour and women's satisfaction with the method of pain relief.Results  Women in the study group (patient‐controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS.Conclusions  Patient‐controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.
Umbilical artery blood gas parameters in neonates with early onset seizures who die
Authors: Williams Keith P. , Singh Avash 
Published: September 2004

Objective  To relate umbilical artery blood gas parameters to mortality among neonates with hypoxic–ischaemic encephalopathy related to early onset seizures.Design  Population cohort study.Setting  British Columbia Women's Hospital.Population  Forty‐seven infants at ≥32 weeks of gestation admitted to NICU with early onset seizures secondary to hypoxic–ischaemic encephalopathy with umbilical artery blood gases done at delivery.Methods  Patients were divided into two groups: (1) Infants with neonatal seizures who survived, and (2) infants with neonatal seizures who died related to hypoxic–ischaemic encephalopathy complications. Comparison of umbilical artery pH, PO2, PCO2, base deficit was done between the two groups with Student's t tests.Main outcome measures  Umbilical artery pH, PO2, PCO2 and base deficit.Results  The PO2 was significantly higher in the group that expired (18.36 ± 9.15 vs 12.33 ± 7.51). There were no significant differences in any other blood gas parameters between the groups.Conclusion  Neither the umbilical artery pH nor base deficit is predictive of neonatal death in infants with hypoxic–ischaemic encephalopathy with seizures. The finding of a high PO2 in neonates who died may indicate an inability of those infants to efficiently extract oxygen from blood.
A history of sexual abuse and health: a Nordic multicentre study
Authors: Hilden Malene , Schei Berit , Swahnberg Katarina , Halmesmäki Erja , Langhoff‐Roos Jens , Offerdal Kristin , Pikarinen Ulla , Sidenius Katrine , Steingrimsdottir Tora , Stoum‐Hinsverk Hildegun , Wijma Barbro 
Published: September 2004

Objectives  To determine if a history of sexual abuse is associated with objective and subjective indicators of health and if certain abusive incidents had a stronger impact on health than others.Design  A cross‐sectional, multicentre study.Setting  Five gynaecological departments in the five Nordic countries.Sample  Three thousand five hundred and thirty‐nine gynaecology patients.Methods  The NorVold Abuse Questionnaire (NorAQ) on abuse history and current health was mailed to all patients who consented to participate.Main outcome measures  Reason for index visit at the gynaeocological clinic as well as several questions on health were recorded. General health status was measured as self‐estimated health, psychosomatic symptoms (headache, abdominal pain, muscle, weakness, dizziness), number of health care visits and number of periods on sick leave.Result  A history of sexual abuse was reported by 20.7% of respondents. A history of sexual abuse was significantly associated with chronic pelvic pain as reason for index visit (P < 0.01), laparoscopic surgery (P < 0.01), psychosomatic symptoms (P < 0.01), self‐estimated poor health (P < 0.01), many health care visits (P < 0.01) and high incidence of sick leave (P < 0.01). Several subgroups within the group of sexually abused women were more likely to report poor health: women abused as both children and adults, women who experienced additional emotional and/or physical abuse and women abused by a person they knew.Conclusion  Sexual abuse has a profound impact on women's health. Taking a history of sexual abuse seems particularly warranted when the patient presents with chronic pelvic pain or symptoms of a vague and diffuse nature.
Maternal cardiac function during pregnancy at high altitude
Authors: Kametas Nikos A. , McAuliffe Fionnuala , Krampl Elisabeth , Chambers John , Nicolaides Kypros H. 
Published: September 2004

Objective  To investigate the maternal cardiovascular adaptation in pregnancy at high altitude, compared with that at sea level.Design  Cross sectional study.Setting  Two maternity units providing routine antenatal care: one at 4370 m above sea level (Cerro de Pasco, Peru) and one at sea level (Lima, Peru).Population  We examined 175 pregnant women at 5–41 weeks of gestation and 16 non‐pregnant controls resident at high altitude and 132 pregnant women and 18 non‐pregnant controls at sea level.Methods  Two‐dimensional and M‐mode echocardiography of the left ventricle.Main outcome measures  Maternal cardiac output and left ventricular longitudinal and transverse systolic function indices.Results  Pregnancy at high altitude, compared with sea level, is associated with 11% lower birthweight and 31% lower maternal cardiac output, due to 15% lower stroke volume and 11% lower heart rate. The lower stroke volume was due to a lower preload and impaired longitudinal and transverse left ventricular systolic function. Mean arterial pressure was about 8% lower during pregnancy at high altitude versus sea level. Pregnant women at high altitude failed to expand their intravascular space to the same extent as the sea level group: cardiac output increased by 17%, left atrial diameter by 12% and end‐diastolic diameter by 1% at high altitude versus 41%, 25% and 5%, respectively, at sea level.Conclusions  Pregnancy at high altitude, compared with sea level, is characterised by lower cardiac output due to lower heart rate and lower stroke volume and reduced expansion of the maternal intravascular space compared with the non‐pregnant state.