bluuebunny/crossref_metadata_2025 huggingface dataset:
A non‐invasive stress assay based upon measurement of free cortisol released into the water by rainbow trout
Authors: Ellis T. , James J. D. , Stewart C. , Scott A. P.
Published: November 2004

A procedure previously used for sex steroids was adapted to extract free cortisol and cortisone from water samples taken from rainbow trout Oncorhynchus mykiss tanks. Both corticosteroids could be readily detected by radioimmunoassay (RIA), with cortisol being predominant. All stages of the sampling, extraction and RIA procedure were validated for cortisol. An intermittent problem with poor replication was traced to the use of diethyl ether during the extraction procedure, and was overcome by the use of ethyl acetate. Other modifications were also introduced to speed up the procedure. The concentration and time course of release of both corticosteroids were shown to be related to the degree of stress that the fish had been subjected to. It was confirmed that cortisol concentrations in water and estimated cortisol release rates increased in response to handling stress, and that both were correlated with plasma cortisol concentrations. The potential for using water cortisol concentration and release rates to assess the primary stress response of fishes as a non‐invasive alternative to blood sampling is discussed.
Effects of confinement stress of variable duration on the growth and microincrement deposition in the otoliths of Oreochromis niloticus(Cichlidae)
Authors: Massou A. M. , Le Bail P.‐Y. , Panfili J. , Laë R. , Baroiller J. F. , Mikolasek O. , Fontenelle G. , Auperin B.
Published: November 2004

The effects of chronic confinement stress (1, 5 and 10 days) and of periodic blood sampling on somatic growth and the structure and growth of otoliths was studied in Oreochromis niloticus. During the study, the plasma concentrations of cortisol were measured at various times during the application of stress: they were significantly higher in confined fish than in control fish (mean ± s.d. 3·40 ± 0·47 v. 1·26 ± 0·62 ng ml−1, P < 0·05) up to 5 days after the start of a 10 day stress period. The somatic growth (standard length, LS, and mass) was affected by the confinement and by the sampling (from 16·21 ± 1·07 to 14·64 ± 1·15 cm for LS, and from 173·31 ± 33·14 to 110·50 ± 29·48 g for mass). But the confinement masked the effect of the sampling on somatic growth. Tetracycline was injected at the start of the experiment to mark the otoliths, and showed that the short and long duration confinements led to a clear check in the pattern of primary increments in the otoliths. The number of primary increments deposited during the resting periods that followed each period of confinement was always less than the number of days that these periods lasted. No relation was found between the duration of confinement and the structure of the resulting checks. These results suggest that there is a disruption in the laying down of primary increments during periods of confinement resulting in an underestimation of their number compared to the actual number of days of growth. These results call into question the use of otolith primary increments as a means of estimating the age of Nile tilapia that have experienced periods of stress.
A stable isotope analysis of trophic polymorphism among Arctic charr from Loch Ericht, Scotland
Authors: McCarthy I. D. , Fraser D. , Waldron S. , Adams C. E.
Published: November 2004

Analysis of nitrogen stable isotope ratios (δ15N) in white muscle and liver shows temporal stability in the trophic levels at which the two sympatric morphs of Arctic charr Salvelinus alpinus from Loch Ericht feed. The results confirm an ontogenetic dietary switch to a more piscivorous diet, occurred in all individuals of one of the morphs, above a size threshold of 16·5 cm fork length, indicating that this occurs at a high frequency in this population and that once made, the return to feeding to a lower trophic level is infrequent.
Growth, ingestion rates and metabolic activity of walleye in lakes with and without lake herring
Authors: Henderson B. A. , Morgan G. E. , Vaillancourt A.
Published: November 2004

Growth efficiencies, ingestions rates and activity levels of walleye Sander vitreus were compared in lakes with and without lake herring Coregonus artedi. Yellow perch Perca flavescens were the main prey in lakes without lake herring. Walleye were sampled in September and October from 38 lakes in Ontario in 1998 and 1999, using multimesh monofilament gillnets. Ingestion rates were estimated from annual increments in somatic mercury and body mass, and the mercury content of yellow perch and lake herring. Walleye had higher growth efficiencies, and lower ingestion and activity rates in lakes with lake herring. Lake herring grow larger than yellow perch and therefore could provide more profitable prey for larger walleye. The results are consistent with optimal foraging theory that predicts that walleye feeding on optimal prey sizes should grow more efficiently, if the ratio of feeding benefit (energy) to cost (search and seizure) is a function of the ratio of predator and prey size.
Comparison between two sampling methods to evaluate the structure of fish communities in the littoral zone of a Laurentian lake
Authors: Brind’Amour A. , Boisclair D.
Published: November 2004

The results of beach seining were compared with visual surveys, in habitats showing a gradient of macrophyte densities in Lake Drouin, Québec, Canada. Six community descriptors (species density, total fish density, relative abundance per species, presence or absence of given species, size structure of the fish community and total biomass of the fish community) were used to compare the sampling methods. Most of the fish community descriptors obtained by visual surveys were estimated with an accuracy similar to that of beach seining. Both methods sampled the same number of species (eight out of nine). Visual surveys assessed the relative abundance of the yellow perch Perca flavescens and white sucker Catostomus commersoni with an higher accuracy than the beach seine. The greatest discrepancies between the two sampling methods were for total fish density and the total fish biomass. Because of the sampling strategy, both descriptors were underestimated by visual surveys, notably in the higher macrophyte density. In a broad community survey to determine the relative importance of species abundance, the visual survey was effective and could be used to develop a within‐lake regular and fine‐scale sampling design of the spatial arrangement of fish communities and their habitats.
Fish functional design and swimming performance
Authors: Blake R. W.
Published: November 2004

Classifications of fish swimming are reviewed as a prelude to discussing functional design and performance in an ecological context. Webb (1984a, 1998) classified fishes based on body shape and locomotor mode into three basic categories: body and caudal fin (BCF) periodic, BCF transient (fast‐starts, turns) and median and paired fin (MPF) swimmers. Swimming performance and functional design is discussed for each of these categories. Webb hypothesized that specialization in any given category would limit performance in any other. For example, routine MPF swimmers should be penalized in BCF transient (fast‐start propulsion). Recent studies offer much support for Webb's construct but also suggest some necessary amendments. In particular, design and performance compromises for different swimming modes are associated with fish that employ the same propulsor for more than one task (coupled, e.g. the same propulsor for routine steady swimming and fast‐starts). For example, pike (BCF transient specialist) achieve better acceleration performance than trout (generalist). Pike steady (BCF periodic) performance, however, is inferior to that of trout. Fish that employ different propulsors for different tasks (decoupled, e.g. MPF propulsion for low‐speed routine swimming and BCF motions for fast‐starts) do not show serious performance compromises. For example, certain MPF low‐speed swimmers show comparable fast‐start performance to BCF forms. Arguably, the evolution of decoupled locomotor systems was a major factor underlying the adaptive radiation of teleosts. Low‐speed routine propulsion releases MPF swimmers from the morphological constraints imposed by streamlining allowing for a high degree of variability in form. This contrasts with BCF periodic swimming specialists where representatives of four vertebrate classes show evolutionary convergence on a single, optimal ‘thunniform’ design. However, recent experimental studies on the comparative performance of carangiform and thunniform swimmers contradict some of the predictions of hydromechanical models. This is addressed in regard to the swimming performance, energetics and muscle physiology of tuna. The concept of gait is reviewed in the context of coupled and decoupled locomotor systems. Biomimetic approaches to the development of Autonomous Underwater Vehicles have given a new context and impetus to research and this is discussed in relation to current views of fish functional design and swimming performance. Suggestions are made for possible future research directions.
Retinol binding protein isolated from acute renal failure patients inhibits polymorphonuclear leucocyte functions
Authors: Cohen G. , Hörl W. H.
Published: November 2004

Background  Protein factors accumulating in sera of patients with end‐stage renal disease (ESRD) that interfere with the nonspecific immune response by inhibiting essential functions of polymorphonuclear leucocytes (PMNLs) have previously been described. No such factor has been isolated from acute renal failure (ARF) patients to date.

Materials and methods  Using a three‐step chromatographic procedure involving ion exchange, size exclusion and hydrophobic interaction chromatography we purified the apo‐ and holo‐form of retinol binding protein (RBP) from high‐flux dialyser (polyacrylonitrile; AN69) ultrafiltrates of patients with ARF. Their effect on the chemotaxis of PMNLs isolated from healthy donors was determined by the under‐agarose method. Whole‐blood assays applying flow cytometry were used to assess phagocytosis and the oxidative metabolism of PMNLs. Apoptosis was assessed by determining the DNA content using propidium iodide.

Results  Isolated apo‐ and holo‐forms of RBP were truncated on their C‐terminus as determined by mass spectrometry. All isolates significantly inhibited the chemotactic movement of PMNLs obtained from healthy donors and the PMNL oxidative metabolism stimulated by E. coli. These effects were concentration dependent. Retinol binding protein had no influence on the PMNL oxidative metabolism stimulated by PMA and on PMNL phagocytosis. Commercially available RBP isolated from urine influenced PMNL functions in the same way. Inhibition of p38 mitogen‐activated protein kinase (MAPK) by SB203580 significantly attenuated the phagocytosis‐induced respiratory burst and RBP did not lead to a further decrease. Polymorphonuclear leucocyte apoptosis was significantly inhibited by RBP.

Conclusions  The apo‐ and holo‐forms of RBP isolated from the ultrafiltrate of ARF patients inhibit PMNL chemotaxis, oxidative metabolism and apoptosis. Therefore, RBP may be considered a uraemic toxin contributing to a disturbed immune defence.
Oxygen consumption is increased relative to work rate in patients with McArdle's disease
Authors: O'Dochartaigh C. S. , Ong H. Y. , Lovell S. M. , Riley M. S. , Patterson V. H. , Young I. S. , Nicholls D. P.
Published: November 2004

Background Patients with McArdle's disease suffer exercise incapacity as a result of myophosphorylase deficiency, and for a given work rate have excessive circulatory and ventilatory responses. We hypothesized that the rate of increase of oxygen consumption with work rate (ΔVO2‐ΔWR slope) would also be elevated in such patients as a result of these excessive responses.

Patients and methods Five patients with McArdle's disease and five matched controls carried out a maximal incremental cardiopulmonary exercise test. Controls then carried out a second test matched to the maximal test of a paired patient. Venous blood was sampled at rest, peak exercise and recovery.

Results During the matched test, the ΔVO2‐ΔWR slope was higher in the patients than in the controls [19·9 (15·0–24·6) vs. 11·7 (9·2–13·5) mL min−1 W−1; mean (range);P = 0·022], and the peak‐achievedVO2was also greater in the patient group [1201 (890–1575) vs. 918 (599–1248) mL min−1;P = 0·003]. A similar pattern was observed for heart rate [173 (165–182) vs. 108 (105–134) b.p.m.;P = 0·001] and plasma norepinephrine levels [12·6 (9·2–19·9) vs. 2·9 (2·2–4·9) nmol l−1;P = 0·003].

Conclusion There is an increased rate of rise inVO2relative to work rate during exercise in patients with McArdle's disease. There is also a greater rise in catecholamines, which may be the result of a physiological response to substrate starvation, and is likely to contribute to the increase inVO2.
Nurse–patient relationships in palliative care
Authors: Mok Esther , Chiu Pui Chi
Published: November 2004

Aim.  The aim of this paper is to report a study exploring aspects of nurse–patient relationships in the context of palliative care.

Background.  Although there are numerous studies addressing nurse–patient relationships, little research has focused on these in the context of palliative are. Furthermore, no previous study has examined the relationship in the Chinese context.

Methods.  Qualitative data were collected from 10 hospice nurses and 10 terminally ill patients by means of open ended unstructured interviews. Respondents were asked to reflect on practices and incidents that would allow an understanding of the meaning of nurse–patient relationships in palliative care.

Results.  Four major categories emerged from the perspectives of patients and nurses: (1) forming a relationship of trust; (2) being part of the family; (3) refilling with fuel along the journey of living and dying; and (4) enriched experiences. Responses revealed that a relationship of trust is formed, and that nurses are not only regarded as health professionals, but also become part of the family or a good friend. Nurses who develop trusting relationships demonstrate a holistic approach to caring, show their understanding of patients’ suffering, are aware of their unvoiced needs, provide comfort without actually being asked, and are reliable, proficient, competent and dedicated in their care.

Conclusion.  Trust, the achievement of the goals of patients and nurses, caring and reciprocity are important elements of nurse–patient relationships in palliative care. Such relationships not only improve patients’ physical and emotional state, but also facilitate their adjustment to their illness, ease pain and can ultimately lead to a good death experience. It is nurses’ personal qualities and skills, which are embedded in these relationships, that constitute excellence in nursing care. Nurses also derive satisfaction and are enriched through the relationships.
A framework for the introduction and evaluation of advanced practice nursing roles
Authors: Bryant‐Lukosius Denise , DiCenso Alba
Published: November 2004

Aim.  This paper describes a participatory, evidence‐based, patient‐focused process for advanced practice nursing (APN) role development, implementation, and evaluation (PEPPA framework).

Background.  Despite the growing demand for advanced practice nurses, there are limited data to guide the successful implementation and optimal utilization of these roles. The participatory, evidence‐based, patient‐focused process, for guiding the development, implementation, and evaluation of advanced practice nursing (PEPPA) framework is an adaptation of two existing frameworks and is designed to overcome role implementation barriers through knowledge and understanding of APN roles and environments. The principles of participatory action research directed the construction of the new framework.

Conclusions.  The process for implementing and evaluating APN roles is as complex and dynamic as the roles themselves. The PEPPA framework is shaped by the underlying principles and values consistent with APN, namely, a focus on addressing patient health needs through the delivery of coordinated care and collaborative relationships among health care providers and systems. Engaging environmental stakeholders as participants in the process provides opportunity to identify the need and shared goals for a clearly defined APN role. The process promotes increased understanding of APN roles and optimal use of the broad range of APN knowledge, skills, and expertise in all role domains and scope of practice. The steps for planning and implementation are designed to create environments to support APN role development and long‐term integration within health care systems. The goal‐directed and outcome‐based process also provides the basis for prospective ongoing evaluation and improvement of both the role and delivery of health care services.
Iontophoresis with glycopyrrolate for the treatment of palmoplantar hyperhidrosis
Authors: Dolianitis Con , Scarff Catherine E , Kelly John , Sinclair Rodney
Published: November 2004

SUMMARY To determine the comparative efficacy of tap water iontophoresis to iontophoresis with the anticholinergic glycopyrrolate, we undertook a single‐blinded right–left comparison study in 20 patients with palmoplantar hyperhidrosis. Most patients had their palms treated and one patient had the soles treated. We compared the duration of symptom relief following iontophoresis with glycopyrrolate unilaterally to iontophoresis with glycopyrrolate bilaterally. Patients filled in daily efficacy assessment cards. Each palm was rated as ‘dry’, ‘slightly wet’, ‘moderately wet’ or ‘very wet’. Following treatment with unilateral tap water iontophoresis, unilateral glycopyrrolate and bilateral glycopyrrolate, patients reported hand dryness for a median of 3, 5 and 11 days, respectively. As the data was paired, treatment differences were analysed using a sign‐rank test. Bilateral glycopyrrolate was superior to both unilateral glycopyrrolate and tap water in most patients. Unilateral glycopyrrolate was superior to tap water in most patients. All differences between groups were found to be statistically significant. We postulate that the increased efficacy of bilateral glycopyrrolate when compared with unilateral glycopyrrolate relates to its systemic absorption. We conclude that glycopyrrolate iontophoresis is more effective than tap water iontophoresis in the treatment of palmoplantar hyperhidrosis and that glycopyrrolate iontophoresis has both local and systemic effects on perspiration.
Use of gloves in protection from diallyl disulphide allergy
Authors: Moyle Mignon , Frowen Kath , Nixon Rosemary
Published: November 2004

SUMMARY Contact dermatitis, particularly affecting the fingertips, is a recognized presentation of garlic allergy. There have been no recommendations in the literature with respect to the type of gloves that offer the best protection against diallyl disulphide, the major allergen in garlic and onion. In fact, we have found that diallyl disulphide penetrates most commercially available glove types. Silver laminate gloves offered only slightly better protection.
An Essay on Some Topics Concerning Invasive Species
Authors: Brown James H. , Sax Dov F.
Published: November 2004

Abstract  There is a tendency for both scientists and lay people to regard invading alien species as inherently ‘bad’ and native species as inherently ‘good.’ Past invasions occurred commonly without human assistance. They rarely caused large, lasting decreases in species richness or ecological damage. Current invasions provide opportunities for scientific study. They are unintentional, uncontrolled experiments, which can provide insights into attributes of successful colonists, relationships with native species, and impacts on the structure and function of ecological systems.
Experimental analysis of retreat‐site selection by thick‐tailed geckos Nephrurus milii
Authors: Shah Bansi , Shine Richard , Hudson Simon , Kearney Michael
Published: November 2004

Abstract  Although animals use habitats non‐randomly in the wild, complex correlations among environmental features mean that proximate influences on habitat selection can be identified only by experimental manipulation of potential cues. Thick‐tailed geckos Nephrurus milii are large lizards that are widely distributed through southern Australia. These nocturnally active animals typically spend daylight hours under surface rocks. We presented captive geckos with alternative retreat‐sites (rock crevices) differing in attributes potentially relevant to habitat selection. The lizards showed strong preference for shelter‐sites that enhanced thermoregulation (warm rather than cool) and that reduced the animal's vulnerability to predators (narrow crevices with small openings and not containing the scent of a predatory snake). Horizontal rather than sloping crevices were also preferred. Overall crevice size and thickness of the overlying rock did not influence retreat‐site selection in the laboratory, but could be important in the field because of their influence on thermal regimes under rocks. The present study supports the idea that nocturnal reptiles base their selection of diurnal shelters on multiple aspects related to the fitness consequences of occupancy of alternative available retreat‐sites.
Evidence for rapid auditory perception as the foundation of speech processing: a sparse temporal sampling fMRI study
Authors: Zaehle T. , Wüstenberg T. , Meyer M. , Jäncke L.
Published: November 2004

We examined the processing of verbal and nonverbal auditory stimuli using an event‐related functional magnetic resonance imaging (fMRI) study to reveal the neural underpinnings of rapid temporal information processing and it's relevance during speech perception. In the context of a clustered sparse‐temporal fMRI data collection eight right‐handed native German speakers performed: (i) an auditory gap detection task; and (ii) a CV syllable discrimination task. A tone perception task served as a nontemporal control condition. Here we aimed to research to what extent the left hemisphere preferentially processes linguistically relevant temporal information available in speech and nonspeech stimuli. Furthermore, we sought to find out as to whether a left hemisphere's preference for linguistically relevant temporal information is specifically constrained to verbal utterances or if nonlinguistic temporal information may also activate these areas. We collected haemodynamic responses from three time points of acquisition (TPA) with varying temporal distance from stimulus onset to gain an insight on the time course of auditory processing. Results show exclusively left‐sided activations of primary and secondary auditory cortex associated with the perception of rapid temporal information. Furthermore, the data shows an overlap of activations evoked by nonspeech sounds and speech stimuli within primary and secondary auditory cortex of the left hemisphere. The present data clearly support the assumption of a shared neural network for rapid temporal information processing within the auditory domain for both speech and nonspeech signals situated in left superior temporal areas.
Two populations of cold‐sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor
Authors: Babes Alexandru , Zorzon Daniel , Reid Gordon
Published: November 2004

Cold sensing in mammals is not completely understood, although significant progress has been made recently with the cloning of two cold‐activated ion channels, TRPM8 and TRPA1. We have used rat DRG neurons in primary culture and calcium fluorimetry to identify distinct populations of cold‐sensitive neurons, which may underlie different functions. Menthol sensitivity clearly separated two classes of cold‐responding neurons. One group was menthol‐sensitive (MS), was activated at warmer temperatures and responded faster and with a larger increase in intracellular calcium concentration during cooling; the fraction of MS neurons in culture and their cold sensitivity were both increased in the presence of nerve growth factor. Neurons in the menthol‐insensitive (MI) group required stronger cooling for activation than MS cells and neither their proportion nor their cold sensitivity were significantly altered by nerve growth factor. The two groups of cold‐sensitive neurons also had different pharmacology. A larger fraction of MS cells were capsaicin‐sensitive and coexpression of menthol and capsaicin sensitivity was observed in the absence of NGF. MI neurons were not stimulated by the super‐cooling agent icilin or by the irritant mustard oil. Taken together these findings support a picture in which TRPM8 is the major player in detecting gentle cooling, while TRPA1 does not seem to be involved in cold sensing by MI neurons, at least in the temperature range between 32 and 12 °C.
Subregional changes in discharge rate, pattern, and drug sensitivity of putative GABAergic nigral neurons in the kindling model of epilepsy
Authors: Gernert Manuela , Fedrowitz Maren , Wlaz Piotr , Löscher Wolfgang
Published: November 2004

The substantia nigra pars reticulata (SNr) is thought to act as a seizure‐gating mechanism in kindling and other epilepsy models. We investigated whether the kindling process induces site‐specific (anterior‐posterior) and seizure‐outlasting alterations in the activity of putative GABAergic SNr neurons and in their response to pharmacological manipulation. Female Wistar rats were kindled via the basolateral amygdala by daily stimulation.In vivoextracellular single unit recordings of SNr neurons were performed in kindled rats 1 day after a generalized seizure in order to examine activity changes that outlast the kindled seizures. Sham‐kindled and naive rats served as controls. We found a significant and seizure‐outlasting increase of discharge rates within the posterior but not within the anterior SNr of kindled rats when compared to controls. Furthermore, kindling resulted in seizure‐outlasting burst‐like firing pattern of SNr neurons. The antiepileptic drug valproic acid (VPA; 100 mg/kg i.v.) significantly reduced SNr discharge rates in all animal groups. Interestingly, neurons located in the anterior SNr of kindled rats were significantly less depressed by VPA compared to the reduction obtained in naive controls. The present data disclose kindling induced functional plasticity within basal ganglia regions. The findings are relevant for a better understanding of the mechanisms underlying the seizure‐gating function of the SNr and might provide new targets for rational therapeutic manipulations, which aim to establish a remote control of epileptic seizures.
Spinal implantation of hNT neurons and neuronal precursors: graft survival and functional effects in rats with ischemic spastic paraplegia
Authors: Marsala Martin , Kakinohana Osamu , Yaksh Tony L. , Tomori Zoltan , Marsala Silvia , Cizkova Dasa
Published: November 2004

Transient spinal ischemia, a complication associated with aortic cross‐clamp may lead to spastic paraplegia. Once fully developed this deficit is permanent. Quantitative histopathological assessments and pharmacological studies show that the ischemic spasticity is secondary to the loss of lumbar GABA and glycinergic inhibitory interneurons. In the present study, we investigated whether human hNT neurons or committed Sprague–Dawley rat spinal neuronal precursors (SNPs) when grafted into previously ischemic spinal segments depleted of inhibitory neurons would restore local inhibitory tone and ameliorate spasticity. Rats with functionally and electrophysiologically defined spasticity that received spinal graft of hNT neurons or neuronal precursors and immunosuppressive treatment displayed a progressive recovery of motor function that correlated with the improvement of otherwise exacerbated peripheral motor response evoked by stimulation of motor cortex. In contrast, in control, medium‐injected or oligodendrocyte‐grafted animals no significant therapeutic effect was seen. Stereological quantification of grafted neurons revealed 1–2% survival at three months after transplantation. These surviving neurons displayed a robust axo‐dendritic sprouting and expression of markers typical of mature neurons including NSE, NeuN and synaptophysin. In both treatment groups a subpopulation of grafted neurons developed GABA immunoreactivity. These data provide evidence that a region specific grafting of hNT neurons or other neuronally committed cells, which have a potential to develop inhibitory neurotransmitter phenotype, represent an effective treatment modality to modulate ischemia‐induced spastic paraplegia.
Chronic interleukin‐6 exposure alters metabotropic glutamate receptor‐activated calcium signalling in cerebellar Purkinje neurons
Authors: Nelson Thomas E. , Netzeband Jeffrey G. , Gruol Donna L.
Published: November 2004

Chronic central nervous system expression of the cytokine interleukin‐6 (IL‐6) is thought to contribute to the histopathological, pathophysiological, and cognitive deficits associated with various neurological disorders. However, the effects of chronic IL‐6 expression on neuronal function are largely unknown. Previous studies have shown that chronic IL‐6 exposure alters intrinsic electrophysiological properties and intracellular Ca2+ signalling evoked by ionotropic glutamate receptor activation in cerebellar Purkinje neurons. In the current study, using primary cultures of rat cerebellum, we investigated the effects of chronic IL‐6 exposure on metabotropic glutamate receptor (mGluR)‐activated Ca2+ signalling and release from intracellular Ca2+ stores. Chronic exposure (6–10 days) of Purkinje neurons to 500 units/mL IL‐6 resulted in elevated resting Ca2+ levels and increased intracellular Ca2+ signals evoked by the group I mGluR agonist (S)‐3,5‐dihydroxyphenylglycine (DHPG) compared to untreated control neurons. Chronic IL‐6 treatment also augmented Ca2+ signals evoked by brief 100 mm K+ depolarization, although to a lesser degree than responses evoked by DHPG. Depleting intracellular Ca2+ stores with sarcoplasmic‐endoplasmic reticulum ATPase inhibitors (thapsigargin or cyclopiazonic acid) or blocking ryanodine receptor‐dependent release from intracellular stores (using ryanodine) resulted in a greater reduction of DHPG‐ and K+‐evoked Ca2+ signals in chronic IL‐6‐treated neurons than in control neurons. The present data show that chronic exposure to elevated levels of IL‐6, such as occurs in various neurological diseases, alters Ca2+ signalling involving release from intracellular stores. The results support the hypothesis that chronic IL‐6 exposure disrupts neuronal function and thereby may contribute to the pathophysiology associated with many neurological diseases.
Medial prefrontal cortical integration of psychological stress in rats
Authors: J. McDougall S. , Widdop Robert E. , Lawrence Andrew J.
Published: November 2004

The present study aimed to determine whether the medial prefrontal cortex (mPFC) (prelimbic and infralimbic regions) is implicated in the integration of a stress response. Sprague‐Dawely rats were implanted with telemetry probes and guide cannulae so that either muscimol or vehicle could be administered locally within the mPFC or dorsomedial hypothalamus (DMH). The heart rate and blood pressure of rats was continuously recorded as either muscimol or vehicle was administered centrally and rats were either exposed to restraint stress or left alone in their home cages. After the stress challenge, or equivalent period, rats that had received intra‐mPFC injections were processed for immunohistochemical detection of Fos throughout the neuraxis. Bilateral microinjection of muscimol into the mPFC had no effect upon either baseline cardiovascular parameters or restraint stress‐induced tachycardia or pressor responses whereas, in the DMH, pretreatment with muscimol attenuated the cardiovascular stress response. Analysis of Fos expression throughout the CNS of nonstressed rats showed no effect of muscimol injections into the mPFC on baseline expression in the nuclei examined. In contrast, rats that had received muscimol injections into their mPFC and were subsequently restrained exhibited an increase in the number of Fos‐positive cells in the DMH, medial amygdala, and medial nucleus tractus solitarius as compared to vehicle‐injected rats that experienced restraint stress. These results indicate that, during acute psychological stress, the mPFC does not modulate the cardiovascular system in rats but does inhibit specific subcortical nuclei to exert control over aspects of an integrated response to a stressor.
Cannabinoid‐mediated neuroprotection following interferon‐gamma treatment in a three‐dimensional mouse brain aggregate cell culture
Authors: Jackson Samuel J. , Baker David , Cuzner M. Louise , Diemel Lara T.
Published: November 2004

Multiple sclerosis is increasingly recognized as a neurodegenerative disease which is triggered by inflammation in the central nervous system (CNS). Demyelination‐associated axonal or neuronal damage is a primary cause of disability and has thus far not been successfully targeted by available drug therapies. The neuroprotective properties of both endogenous and administered cannabinoids have been shown in in vivo and in vitro models of CNS damage following excitotoxic, oxidative, traumatic and ischaemic insults, with a predominantly apoptotic effector mechanism. In this study a foetal mouse telencephalon aggregate cell culture system was developed to compare tissue from cannabinoid receptor 1 knockout mice with wildtype counterparts. Aggregate formation and neurofilament/myelin basic protein accumulation were dependent on the age of foetal dissection and species used. Following treatment with interferon‐γ, levels of myelin basic protein, neurofilament, neuronal dephosphorylation and caspase 3 activation were assessed in telencephalon tissue in vitro. Cytokine treatment resulted in significant loss of the neuronal marker neurofilament‐H in cannabinoid receptor 1 knockout cultures but not in wildtypes, indicating that presence of the cannabinoid receptor 1 gene can be neuroprotective. Caspase 3 activation was higher in cultures from knockout animals, indicating an apoptotic mechanism of cell death. Dephosphorylated neurofilament levels were significantly elevated in knockout mice, lending support to the premise that neurofilament dephosphorylation is a marker for neuronal damage. Taken together, these results indicate that neuroprotection could be elicited through the cannabinoid receptor 1, and point towards a potential therapeutic role for cannabinoid compounds in demyelinating conditions such as multiple sclerosis.
Self‐harm in young people: a perspective for mental health nursing care
Authors: Anderson M. , Woodward L. , Armstrong M.
Published: November 2004

Aims:  This paper addresses the assessment and management of self‐harm in young people by a nurse consultant‐led self‐harm service in the UK. The purpose of the paper is to present some of the theoretical perspectives of the service and how these have influenced current practice with this group of young people.

Background:  Self‐harm in young people continues to be a serious concern for health services globally. Rates of self‐harm in teenagers in the UK are among the highest in Europe. The current literature offers information on the nature of self‐harm and some evidence of specific interventions mainly from a ‘psychiatric perspective’. This paper examines the development of a locally based nurse‐led self‐harm team involved in the care of this group of young people. A sociological view of children and young people is applied in examining the way society construes self‐harm and the formation of the behaviour as a deviant act. Self‐harm is considered in the context of transition through adolescence and the growth of self‐identity.

Conclusion:  The locally based child and adolescent mental health service has drawn together the evolving nurse consultant role, mental health nursing and medical sociology. This integration of people and theory will enhance the services understanding of self‐harm in young people. At an international level, there is a need to consider the sociological dimensions of self‐harm in young people as a way forward for mental health nurses who are involved in working with this group of people.
Intracellullar peptides as putative natural regulators of protein interactions
Authors: Ferro Emer S. , Hyslop Stephen , Camargo Antonio C. M.
Published: November 2004

Extralysosomal proteolysis by multicatalytic complexes such as the 26S proteasome produces large amounts of peptides in the cytosol, mitochondria and nuclei of eukaryotic cells, and there is increasing evidence that the resulting free intracellular peptides can modulate specific protein interactions. The demonstration that free peptides added to the intracellular milieu can regulate cellular functions mediated by protein interactions suggests new putative roles for these molecules in gene regulation, metabolism, cell signaling and protein targeting. Such interactions frequently involve specific consensus amino acid sequences that can be predicted based on similarities in domain composition. We have recently developed a new strategy for identifying novel natural peptides, the sequences of which correspond to fragments of intracellular proteins and contain putative post‐translational modification sites. In this review, we examine the evidence that intracellular peptides released by proteasomes may be involved in regulating protein interactions. In particular, the role of endopeptidase 24.15 (thimet oligopeptidase; EC 3.4.24.15) is discussed in detail as this enzyme has been implicated in intracellular peptide metabolism in vivo in concert with the 26S proteasome.
Serotonin–GABA interactions modulate MDMA‐induced mesolimbic dopamine release
Authors: Bankson Michael G. , Yamamoto Bryan K.
Published: November 2004

3,4,‐Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) acts at monoamine nerve terminals to alter the release and re‐uptake of dopamine and 5‐HT. The present study used microdialysis in awake rats to measure MDMA‐induced changes in extracellular GABA in the ventral tegmental area (VTA), simultaneous with measures of extracellular dopamine (DA) in the nucleus accumbens (NAC) shell. (+)‐MDMA (0, 2.5, 5 and 10 mg/kg, i.p.) increased GABA efflux in the VTA with a bell‐shaped dose–response. This increase was blocked by application of TTX through the VTA probe. MDMA (5 mg/kg) increased 5‐HT efflux in VTA by 1037% (p < 0.05). The local perfusion of the 5‐HT2B/2C antagonist SB 206553 into the VTA reduced VTA GABA efflux after MDMA from a maximum of 229% to a maximum of 126% of basal values (p < 0.05), while having no effect on basal extracellular GABA concentrations. DA concentrations measured simultaneously in the NAC shell were increased from a maximum of 486% to 1320% (p < 0.05). The selective DA releaser d‐amphetamine (AMPH) (4 mg/kg) also increased VTA GABA efflux (180%), did not alter 5‐HT and increased NAC DA (875%) (p < 0.05), but the perfusion of SB 206553 into the VTA failed to alter these effects. These results suggest that MDMA‐mediated increases in DA within the NAC shell are dampened by increases in VTA GABA subsequent to activation of 5‐HT2B/2C receptors in the VTA.
Cloning of a novel neuronally expressed orphan G‐protein‐coupled receptor which is up‐regulated by erythropoietin, interacts with microtubule‐associated protein 1b and colocalizes with the 5‐hydroxytryptamine 2a receptor
Authors: Maurer Martin H. , Grünewald Sylvia , Gassler Nikolaus , Rossner Moritz , Propst Friedrich , Würz Rebecca , Weber Daniela , Kuner Thomas , Kuschinsky Wolfgang , Schneider Armin
Published: November 2004

G‐protein‐coupled receptors (GPCRs) are the largest group of cell surface molecules involved in signal transduction and are receptors for a wide variety of stimuli ranging from light, calcium and odourants to biogenic amines and peptides. It is assumed that systematic genomic data‐mining has identified the overwhelming majority of all remaining GPCRs in the genome. Here we report the cloning of a novel orphan GPCR which was identified in a search for erythropoietin‐induced genes in the brain as a strongly up‐regulated gene. This unknown gene coded for a protein which had a seven‐transmembrane topology and key features typical of GPCRs of the A family but a low overall identity to all known GPCRs. The protein, coded ee3, has an unusually high evolutionary conservation and is expressed in neurons in diverse areas of the CNS with relation to integrative functions or motor tasks. A yeast two‐hybrid screen for interacting proteins revealed binding to the microtubule‐associated protein (MAP) 1b. Coupling to MAP1a has been described for another cognate GPCR, the 5‐hydroxytryptamine (5HT) 2a receptor. Surprisingly, we found complete colocalization of ee3 and the 5HT2a receptor. The interaction with MAP1b proved to be critical for the stability or folding of ee3 as in mice lacking MAP1b the ee3 protein was undetectable by immunohistochemistry, although messenger RNA levels remained unchanged. We propose that ee3 is a highly interesting new orphan GPCR with potential connections to erythropoietin and 5HT2a receptor signalling.
Activation of PLC-δ1 by Gi/o-coupled receptor agonists
Authors: Murthy Karnam S. , Zhou Huiping , Huang Jiean , Pentyala Srinivas N.
Published: November 2004

The mechanism of phospholipase (PLC)-δ activation by G protein-coupled receptor agonists was examined in rabbit gastric smooth muscle. Ca2+ stimulated an eightfold increase in PLC-δ1 activity in permeabilized muscle cells. Treatment of dispersed or cultured muscle cells with three Gi/o-coupled receptor agonists (somatostatin, δ-opioid agonist [D-Pen2,D-Pen5]enkephalin, and A1 agonist cyclopentyl adenosine) caused delayed increase in phosphoinositide (PI) hydrolysis (8- to 10-fold) that was strongly inhibited by overexpression of dominant-negative PLC-δ1(E341R/D343R; 65–76%) or constitutively active RhoA(G14V). The response coincided with capacitative Ca2+ influx and was not observed in the absence of extracellular Ca2+, but was partly inhibited by nifedipine (16–30%) and strongly inhibited by SKF-96365, a blocker of store-operated Ca2+ channels. Treatment of the cells with a Gq/13-coupled receptor agonist, CCK-8, caused only transient, PLC-β1-mediated PI hydrolysis. Unlike Gi/o-coupled receptor agonists, CCK-8 activated RhoA and stimulated RhoA:PLC-δ1 association. Inhibition of RhoA activity with C3 exoenzyme or by overexpression of dominant-negative RhoA(T19N) or Gα13 minigene unmasked a delayed increase in PI hydrolysis that was strongly inhibited by coexpression of PLC-δ1(E341R/D343R) or by SKF-96365. Agonist-independent capacitative Ca2+ influx induced by thapsigargin stimulated PI hydrolysis (8-fold), which was partly inhibited by nifedipine (∼25%) and strongly inhibited by SKF-96365 (∼75%) and in cells expressing PLC-δ1(E341R/D343R). Agonist-independent Ca2+ release or Ca2+ influx via voltage-gated Ca2+ channels stimulated only moderate PI hydrolysis (2- to 3-fold), which was abolished by PLC-δ1 antibody or nifedipine. We conclude that PLC-δ1 is activated by Gi/o-coupled receptor agonists that do not activate RhoA. The activation is preferentially mediated by Ca2+ influx via store-operated Ca2+ channels.
Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice
Authors: Kawasaki Fumiko , Matsuda Masafumi , Kanda Yukiko , Inoue Hiroshi , Kaku Kohei
Published: November 2004

To evaluate preventive effects of pioglitazone on pancreatic β-cell damage in C57BL/KsJ db/ db mice, an obese diabetic animal model, the pancreatic islets were compared morphologically between pioglitazone-treated (100 mg/kg daily po) and untreated db/db mice ( n = 7 for each) after a 12-wk intervention (6–18 wk of age). The fasting blood glucose level was significantly improved by the treatment with pioglitazone (260 ± 12 vs. 554 ± 62 mg/dl, P < 0.05). The islet mass in the pancreas was significantly greater in pioglitazone-treated mice than in untreated mice (10.2 ± 1.1 vs. 4.6 ± 0.2 mg, P < 0.01). Subsequently, biochemical and physiological analyses of the β-cell function were employed using pioglitazone-treated and untreated db/db mice ( n = 6 for each) and pioglitazone-treated and untreated db/+ mice ( n = 6 for each). After 2 wk of treatment (10–12 wk of age), the plasma levels of triglyceride and free fatty acid were significantly decreased, whereas the plasma adiponectin level increased significantly compared with the untreated group (65.2 ± 18.0 vs. 18.3 ± 1.3 μg/ml, P < 0.05). Pioglitazone significantly reduced the triglyceride content in the islets (43.3 ± 3.6 vs. 65.6 ± 7.6 ng/islet, P < 0.05) with improved glucose-stimulated insulin secretion. Pioglitazone showed no significant effects on the biochemical and physiological parameters in db/+ mice. The present study first demonstrated that pioglitazone prevents β-cell damage in an early stage of the disease progression in db/db mice morphologically and physiologically. Our results suggest that pioglitazone improves glucolipotoxicity by increasing insulin sensitivity and reducing fat accumulation in the pancreatic islets.
Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia
Authors: Lee Jennifer H. , Bullen John W. , Stoyneva Violeta L. , Mantzoros Christos S.
Published: November 2004

Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice. We have thus comparatively assessed WAT resistin mRNA expression and serum resistin levels in lean C57BL/6J mice and various mouse models of obesity, including diet-induced obese (DIO) C57BL/6J mice, high fat-fed TNF-α−/− mice, and brown adipose tissue (BAT)-deficient uncoupling protein-diphtheria toxin A chain (UCP1-DTA) mice. We also studied whether treatment with the weight-reducing and insulin-sensitizing compounds, MTII, an α-melanocyte-stimulating hormone analog, or CNTFAx15, a ciliary neurotrophic factor analog, alters resistin mRNA expression and/or circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is similar in DIO and lean C57BL/6J mice, as well as in TNF-α−/− and wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed TNF-α−/−, and UCP1-DTA mice compared with lean controls. Moreover, although resistin mRNA expression is upregulated by MTII treatment for 24 h and downregulated by CNTFAx15 treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or CNTFAx15 treatment. In addition, serum resistin levels, but not resistin mRNA expression levels, are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels are correlated with serum insulin or glucose levels. We conclude that transcriptional regulation of resistin in WAT does not correlate with circulating resistin levels and that circulating resistin is unlikely to play a major endocrine role in insulin resistance or glycemia in mice.