bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial interventions following self-harm
Authors: Crawford Mike J. , Thomas Olivia , Khan Nusrat , Kulinskaya Elena
Published: December 2006

Background

With almost a million people dying by suicide worldwide each year, reducing the rate of suicidal behaviour is a priority in many countries.

Aims

To examine whether additional psychosocial interventions following an episode of self-harm reduce the likelihood of subsequent suicide.

Method

We conducted a systematic review and meta-analysis of data from randomised controlled trials of interventions for people following self-harm. Likelihood of suicide was compared by calculating the pooled root difference in suicide rate with 95% confidence intervals.

Results

We obtained suicide data from 18 studies with a total population of 3918. Eighteen suicides occurred among people offered active treatment and 19 among those offered standard care (pooled root difference in suicide rate 0.0, 95% CI – 0.03 to 0.03). The overall rate of suicide among people participating in trials was similar to that reported in observational studies of people who self-harm.

Conclusions

Results of this meta-analysis do not provide evidence that additional psychosocial interventions following self-harm have a marked effect on the likelihood of subsequent suicide.
Adult attention-deficit hyperactivity disorder: recognition and
treatment in general adult psychiatry
Authors: Asherson Philip , Chen Wai , Craddock Bridget , Taylor Eric
Published: December 2006

Attention-deficit hyperactivity disorder (ADHD) is a common disorder
affecting children and adults. Many young people treated with stimulants, as
well as those in whom ADHD went unrecognised in childhood, need treatment as
adults. Stimulants and atomoxetine effectively reduce ADHD symptoms at all
ages and should be a standard treatment in general adult psychiatric
practice.
Gene–environment interplay in attention-deficit hyperactivity
disorder and the importance of a developmental perspective
Authors: Thapar Anita , Langley Kate , Asherson Philip , Gill Michael
Published: December 2006

Attention-deficit hyperactivity disorder (ADHD) varies in its clinical
presentation and course. Susceptibility gene variants for ADHD and
associated antisocial behaviour are being identified with emerging evidence
of gene–environment interaction. Genes and environmental factors that
influence the origins of disorder are not necessarily the same as those that
contribute to its course and outcome.
How safe are patient interview rooms?
Authors: Campbell Helen L. , Fung Nicole K.
Published: December 2006

Aims and Method

A cross-sectional survey was conducted to investigate the safety of rooms used by medical staff to interview patients in out-patient and in-patient settings of a mental health trust. An assessment tool was designed, and examined the features of an interview room that were likely to promote safety.

Results

The survey included 112 rooms and demonstrated shortcomings that compromised interview room safety. Rooms were frequently overcrowded with furniture (n=30), cluttered with loose objects (n=101, 90%) and used for multiple purposes (n=82, 73%). Room layout often compromised either access to alarm systems (n=51, 46%) or exit from rooms (n=99, 88%). Necessary facilities for summoning assistance were found to be lacking.

Clinical Implications

The safety of interview rooms has not been emphasised sufficiently within everyday working practice and should be revisited.
Professional staff and carers' views of an integrated mental health service for adults with learning disabilities
Authors: Samuels Sarah , Hall Ian , Parkes Charles , Hassiotis Angela
Published: December 2006

Aims and Method

A study was undertaken to investigate the views of professional staff and paid and informal carers' views of a new integrated mental health service for people with learning disabilities.

Results

Twenty semi-structured interviews were conducted and transcribed. Most staff and carers were generally satisfied with the in-patient facility. However, information exchange, ward rounds and the ward environment were identified as areas requiring improvement.

Clinical Implications

Many of the participants had no previous experience of supporting a person with learning disabilities and mental health problems in an in-patient setting. However, over time they became supportive of the mental health service and provided valuable input in improving the service provision for people with learning disabilities.
Clozapine and speech dysfluency: two case reports
Authors: Lyall Marc , Pryor Angela , Murray Kevin
Published: December 2006

Aims and Method

We describe two patients, both diagnosed with psychotic illnesses, who developed stuttering while being treated with clozapine.

Results

In both patients the stuttering was severe and significantly impaired progress towards recovery. Deviant speech dimensions and voice quality were consistent with dysarthria and dystonia.

Clinical Implications

Patients who develop abnormal electroencephalogram activity and those who have a family or personal history of stuttering might be at increased risk of developing speech problems with clozapine. Speech dysfluency might be a consequence of clozapine's action in lowering the seizure threshold. Potential management strategies include the use of sodium valproate and changing the type of antipsychotic.
Service innovations: from depot clinic to medication review service – developing an evidence-based service within a community mental health team
Authors: Basu Amlan , McIvor Ronan J.
Published: December 2006

Over the years the ‘depot clinic’ has become little more than a conveyor belt for patients to receive depot medication from nursing staff within a hospital setting. Indeed, the concept of the depot clinic has not significantly changed since the introduction of neuroleptic medication in the 1950s. A lack of review of the service has resulted in suboptimal treatment, unchecked side-effects and a lack of monitoring of physical health. We describe the redesign of a depot service within an inner city community service, with emphasis on evidence-based practice, regular, patient-centred reviews, support, health promotion and education.
The Irish Mental Health Act 2001
Authors: Kelly Brendan D.
Published: December 2006

The Mental Health Act 2001 was formally enacted by the Irish Houses of Oireachtas (parliament) on 8 July 2001 and implemented in full on 1 November 2006. The Mental Health Act 2001 replaces and updates a number of older pieces of legislation, including the Mental Treatment Act 1945. The purpose of this paper is to outline the central provisions of the Mental Health Act 2001 as they relate to psychiatric practice in Ireland. This paper does not aim to examine the issues surrounding delays in the implementation of the Act; these issues are well explored elsewhere (Daly, 2005; Ganter, 2005; Lawlor, 2005; Owens, 2005).
In conversation with John Gunn
Authors: Grounds Adrian , Gordon Harvey
Published: December 2006

John Gunn CBE retired as Professor of Forensic Psychiatry at the Institute of Psychiatry, London in 2002. In February 2003 he agreed to an unrehearsed interview at the Annual Meeting of the Forensic Psychiatry Faculty in Glasgow. He was interviewed by Adrian Grounds.
Reading about books on passing MRCPsych exams
Authors: Husain Muzaffar
Published: December 2006

I recommend Pass the MRCPsych Parts I and II by Williams et al (2005) as a light read, accomplished in two sittings (one for the really committed). This book marks out the terrain of the exams, including the potholes, and offers pragmatic advice and helpful tips. Concluding the brief text is a sobering chapter ‘If at first you don't succeed…’ which I found somehow makes ‘the beast’ seem less ferocious. However, it is not a textbook or a revision aide. It is a good book to buy for a study group, but would be less valuable for the individual.
Money for medication: financial incentives to improve medication adherence in assertive outreach
Authors: Claassen Dirk , Fakhoury Walid K. , Ford Richard , Priebe Stefan
Published: December 2006

Aims and Method

Although financial incentives to improve treatment adherence have been found effective in various medical specialties, there are few systematic data on their use, ethical background and effectiveness in psychiatry. We explored the practice of and possible ethical problems associated with direct financial incentives to improve adherence in assertive outreach teams in England. We also report clinical observations of a money for medication scheme with five assertive outreach patients in East London.

Results

None of the assertive outreach teams that responded to the survey (response rate 47%) uses financial incentives. Attitudes of team managers towards the practice were mostly negative, often regarding it as unethical. Specific concerns were related to possible coercion and a negative impact on the therapeutic relationship. Out of five patients studied, four accepted the offer of money and had improved adherence; three remained without hospital admission since entering the scheme.

Clinical Implications

Money for medication might be a non-coercive and effective option to achieve medication adherence in otherwise non-adherent assertive outreach patients. However, ethical issues need further exploration and controlled trials are required to establish the effectiveness.
Audit of early intervention in psychosis service development in England in 2005
Authors: Pinfold Vanessa , Smith Jo , Shiers David
Published: December 2006

Aims and Method

This study provides an overview of the development of early intervention services for psychosis across England in February 2005. A bespoke self-report audit tool was completed by key informants across the eight regional development centres of the National Institute for Mental Health in England.

Results

Out of 117 teams identified, 86 have funding, of which 63 are operational with case-managed patients (as of February 2005). Only 3 teams meet all 10 audited early intervention fidelity requirements and there are variations in service model, delivery setting and resources across teams.

Clinical Implications

Current inequity of access and the early, fragile nature of service development means that early intervention in England has reached a critical phase requiring consolidation.
Role of Thymulin or Its Analogue as a New Analgesic Molecule
Authors: DARDENNE MIREILLE , SAADE NAYEF , SAFIEH‐GARABEDIAN BARED
Published: December 2006

Abstract:  The thymic peptide thymulin is known for its immunomodulatory role. However, several recent reports have indicated that thymulin is capable of interacting directly and/or indirectly with the nervous system. One of the first lines of evidence of this interaction was obtained in a series of experiments showing the hyperalgesic actions of this peptide. We demonstrated that, at low doses (ng), local (intraplantar) or systemic (intraperitoneal) injections of thymulin resulted in hyperalgesia with an increase in proinflammatory mediators, and that this peptide could act directly on the afferent nerve terminals through prostaglandin‐E2 (PGE2)‐dependent mechanisms, thus forming a neuroimmune loop involving capsaicin‐sensitive primary afferent fibers. In further experiments, systemic injections of relatively high doses (1–25 μg) of thymulin or of an analogue peptide (PAT) deprived of hyperalgesic effect, have been shown to reduce the inflammatory pain and the upregulated levels of cytokines induced by endotoxin (ET) injection. In addition, PAT treatment appeared to alleviate the sickness behavior (motor behavior and fever) induced by systemic inflammation. These effects could be attributed, at least partly, to the downregulation of proinflammatory mediators. Furthermore, when compared with the effects of other anti‐inflammatory drugs, PAT exerted equal or even stronger analgesic effects, and at much lower concentrations. Subsequent experiments were designed to examine the effects of intracerebroventricular (i.c.v.) injections of thymulin on cerebral inflammation induced by i.c.v. injection of ET. Pretreatment with thymulin reduced, in a dose‐dependant manner, the ET‐induced hyperalgesia, and exerted differential effects on the upregulated levels of cytokines in different areas of the brain, suggesting a neuroprotective role for thymulin in the central nervous system (CNS). Preliminary results demonstrate that thymulin inhibits in the hippocampus the ET‐induced nuclear activation of NF‐κB, the transcription factor required for the expression of proinflammatory cytokines genes. Although the mechanism of action of these molecules is not totally elucidated, our results indicate a possible therapeutic use of thymulin or PAT as analgesic and anti‐inflammatory drugs.
Neuroendocrine Regulation of Skin Dendritic Cells
Authors: SEIFFERT KRISTINA , GRANSTEIN RICHARD D.
Published: December 2006

Abstract: It has long been postulated that stress can affect certain skin conditions, and there is increasing experimental evidence that the neuroendocrine system can directly participate in cutaneous inflammation. Neurohormones, such as glucocorticoids and catecholamines, can reach the skin through the bloodstream after activation of the hypothalamic–pituitary–adrenal axis and the sympathetic nervous system, respectively. Multiple neuropeptides, among them calcitonin gene–related peptide, α‐melanocyte stimulating hormone, pituitary adenylate cyclase–activating peptide, substance P, vasoactive intestinal peptide, and norepinephrine, may be released by cutaneous nerves or resident and infiltrating cells within the skin. Systemic neuromediators and cutaneous nerves can influence a number of target cells within the skin, among them Langerhans cells. Most of the experimental evidence to date indicates a suppressive effect of the neurohormones and neuropeptides on Langerhans cell function and cutaneous inflammation, but it has become evident lately that the timing of exposure to a stimulus is critical to the outcome of the immune response. Thus, administration of a stress hormone or exposure to a stressor before the dendritic cell (DC) encounters an antigen (Ag) may diminish the immune response toward that Ag, while a stressor may enhance immune function when acting on a maturing DC or before reexposure to the Ag. The neuroendocrine regulation of skin DCs is a complex system allowing for a quick adaptation to various stressors. Such a system, originally evolved to defend the organism against invading pathogens and maintain homeostasis, may under certain conditions become unbalanced and ultimately exacerbate cutaneous inflammation.
Beyond Heart Rate Variability
Authors: THAYER JULIAN F. , STERNBERG ESTHER
Published: December 2006

Abstract:  The autonomic nervous system (ANS) plays a role in a wide range of somatic and mental diseases. Whereas the role of the ANS in the regulation of the cardiovascular system seems evident, its role in the regulation of other systems associated with allostasis is less clear. Using a model of neurovisceral integration we describe how the ANS and parasympathetic tone in particular may be associated with the regulation of allostatic systems associated with glucose regulation, hypothalamic‐pituitary‐adrenal (HPA) axis function, and inflammatory processes. Decreased vagal function and heart rate variability (HRV) were shown to be associated with increased fasting glucose and hemoglobin A1c levels, increased overnight urinary cortisol, and increased proinflammatory cytokines and acute‐phase proteins. All of these factors have been associated with increased allostatic load and poor health. Thus, vagal activity appears to play an inhibitory function in the regulation of allostatic systems. The prefrontal cortex and the amygdala are important central nervous system structures linked to the regulation of these allostatic systems via the vagus nerve. Finally, the identification of this neurovisceral regulatory system may help to illuminate the pathway via which psychosocial factors may influence health and disease.
Immunomodulation
Authors: TSITOURA DAPHNE C. , TASSIOS YANNIS
Published: December 2006

Abstract:  Allergies are the result of aberrant immune reactivity against common innocuous environmental proteins (allergens). A pivotal component of allergic pathogenesis is the generation of allergen‐specific Th cells with an effector phenotype. These Th cells activate a complex immune cascade that triggers the release of potent mediators and enhances the mobilization of several inflammatory cells types, which in turn elicit the acute allergic reactions and promote the development of chronic inflammation. The current therapies for allergic diseases focus primarily on pharmacological control of symptoms and suppression of inflammation. This approach is beneficial, but not curative, since the underlying immune pathology is not inhibited. In an attempt to develop more effective therapeutic strategies, the scientific interest has been directed toward methods down‐modulating the immune mechanisms that initiate and maintain the allergic cascade. Today, the only widely used disease‐modifying form of allergy treatment is the specific immunotherapy with allergen extracts. More recently the use of anti‐IgE has been approved for patients with allergic asthma. Other immunomodulatory methods being currently explored are the administration of microbial adjuvants that inhibit Th2 reactivity and the design of molecules that interrupt the activity of key allergic cytokines, chemokines, or other Th2 effector mediators.
The Role of Toll‐like Receptors in the Immune–Adrenal Crosstalk
Authors: BORNSTEIN S.R. , ZIEGLER C.G. , KRUG A.W. , KANCZKOWSKI W. , RETTORI V. , McCANN S.M. , WIRTH M. , ZACHAROWSKI K.
Published: December 2006

Abstract:  Sepsis and septic shock remain major health concerns worldwide, and rapid activation of adrenal steroid release is a key event in the organism's first line of defense during this form of severe illness. Toll‐like receptors (TLRs) are critical in the early immune response upon bacterial infection, and recent data from our lab demonstrate a novel link between the innate immune system and the adrenal stress response mediated by TLRs. Glucocorticoids and TLRs regulate each other in a bidirectional way. Bacterial toxins acting through TLRs directly activate adrenocortical steroid release. TLR‐2 and TLR‐4 are expressed in human and mice adrenals and TLR‐2 deficiency is associated with an impaired glucocorticoid response. Furthermore, TLR‐2 deficiency in mice is associated with marked cellular alterations in adrenocortical tissue. TLR‐2‐deficient mice have an impaired adrenal corticosterone release following inflammatory stress induced by bacterial cell wall compounds. This defect appears to be associated with a decrease in systemic and intraadrenal cytokine expression. In conclusion, TLRs play a crucial role in the immune–adrenal crosstalk. This close functional relationship needs to be considered in the treatment of inflammatory diseases requiring an intact adrenal stress response.
Local Amplification of Glucocorticoids by 11β‐Hydroxysteroid Dehydrogenase Type 1 and Its Role in the Inflammatory Response
Authors: CHAPMAN KAREN E. , COUTINHO AGNES , GRAY MOHINI , GILMOUR JAMES S. , SAVILL JOHN S. , SECKL JONATHAN R.
Published: December 2006

Abstract:  Glucocorticoids are widely used to treat chronic inflammatory conditions including rheumatoid arthritis. They promote mechanisms important for normal resolution of inflammation, notably macrophage phagocytosis of leukocytes undergoing apoptosis. Prereceptor metabolism of glucocorticoids by 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) amplifies intracellular levels of glucocorticoids by oxoreduction of intrinsically inert cortisone (in humans, 11‐dehydrocorticosterone in mice) into active cortisol (corticosterone in mice) within cells expressing the enzyme. Recently, we have shown in a mouse model of acute inflammation, high expression of 11β‐HSD oxoreductase but not dehydrogenase activity in cells elicited rapidly in the peritoneum by a single thioglycollate injection. 11β‐HSD oxoreductase activity remained high in peritoneal cells until the inflammation resolved. In vitro, the 11β‐HSD1 substrate, 11‐dehydrocorticosterone, increased macrophage phagocytosis of apoptotic neutrophils to the same extent as corticosterone. This effect was dependent upon 11β‐HSD1: these cells solely expressed the type 1 11β‐HSD isozyme (not 11β‐HSD2), and carbenoxolone, an 11β‐HSD inhibitor, prevented the increase in phagocytosis elicited by 11‐dehydrocorticosterone. Macrophages from 11β‐HSD1‐deficient mice failed to respond to 11‐dehydrocorticosterone. In vivo, 11β‐HSD1‐deficient mice showed a delay in acquisition of macrophage phagocytic competence and had an increased number of free apoptotic neutrophils during sterile peritonitis. Importantly, in preliminary experiments, 11β‐HSD1‐deficient mice exhibited delayed resolution of inflammation in experimental arthritis. These findings suggest 11β‐HSD1 may be a component of mechanisms engaged early during the inflammatory response that promote its subsequent resolution.
Dialogue between the Brain and the Immune System in Inflammatory Arthritis
Authors: VASSILOPOULOS DIMITRIOS , MANTZOUKIS DIMOSTHENIS
Published: December 2006

Abstract:  The crosstalk between the brain and the immune system in inflammatory arthritis is exerted mainly through the activation or downregulation of the hypothalamic‐pituitary‐adrenal (HPA), the hypothalamic‐pituitary‐gonadal (HPG), and the hypothalamic‐autonomic nervous system (HANS) axes. In this review, we will present an overview of the most recent data regarding the regulation of these complex pathways of neuroendocrine response during the different phases of inflammatory arthritides such as rheumatoid arthritis (RA). Furthermore, the effect of the most recently available biologic therapies like anti‐tumor necrosis factor (TNF‐a) on the neuroendocrine function in patients with RA will be reviewed.
Requirement of Cannabinoid Receptor Type 1 for the Basal Modulation of Hypothalamic-Pituitary-Adrenal Axis Function
Authors: Cota Daniela , Steiner Michel-Alexander , Marsicano Giovanni , Cervino Cristina , Herman James P. , Grübler Yvonne , Stalla Johanna , Pasquali Renato , Lutz Beat , Stalla Günter K. , Pagotto Uberto
Published: December 2006

The endocannabinoid system affects the neuroendocrine regulation of hormone secretion, including the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, the mechanisms by which endocannabinoids regulate HPA axis function have remained unclear. Here we demonstrate that mice lacking cannabinoid receptor type 1 (CB1−/−) display a significant dysregulation of the HPA axis. Although circadian HPA axis responsiveness is preserved, CB1−/− mice are characterized by an enhanced circadian drive on the HPA axis, resulting in elevated plasma corticosterone concentrations at the onset of the dark as compared with wild-type (CB1+/+) littermates. Moreover, CB1−/−-derived pituitary cells respond with a significantly higher ACTH secretion to CRH and forskolin challenges as compared with pituitary cells derived from CB1+/+ mice. Both CBL−/− and CB1+/+ mice properly respond to a high-dose dexamethasone test, but response to low-dose dexamethasone is influenced by genotype. In addition, CB1−/− mice show increased CRH mRNA levels in the paraventricular nucleus of the hypothalamus but not in other extrahypothalamic areas, such as the amygdala and piriform cortex, in which CB1 and CRH mRNA have been colocalized. Finally, CB1−/− mice have selective glucocorticoid receptor mRNA down-regulation in the CA1 region of the hippocampus but not in the dentate gyrus or paraventricular nucleus. Conversely, mineralocorticoid receptor mRNA expression levels were found unchanged in these brain areas. In conclusion, our findings indicate that CB1 deficiency enhances the circadian HPA axis activity peak and leads to central impairment of glucocorticoid feedback, thus further outlining the essential role of the endocannabinoid system in the modulation of neuroendocrine functions.
Proteomic Profiling of Cold Thyroid Nodules
Authors: Krause Kerstin , Karger Stefan , Schierhorn Angelika , Poncin Sylvie , Many Marie-Christine , Fuhrer Dagmar , Führer-Sakel Dagmar
Published: December 2006

Cold thyroid nodules (CTNs) represent a frequent endocrine disorder accounting for up to 85% of thyroid nodules in a population living in an iodine-deficient area. Benign CTNs need to be distinguished from thyroid cancer, which is relatively rare. The molecular etiology of benign CTNs is unresolved. To obtain novel insights into their pathogenesis, protein expression profiling was performed in a series of 27 solitary CTNs (10 follicular adenoma and 20 adenomatous nodules) and surrounding normal thyroid tissues using two-dimensional gel electrophoresis combined with mass spectrometry analysis, Western blotting, and immunohistochemistry. The proteome analysis revealed a specific fingerprint of CTNs with up-regulation of three functional systems: 1) thyroid cell proliferation, 2) turnover of thyroglobulin, and 3) H2O2 detoxification. Western blot analysis and immunohistochemistry confirmed the proteome data and showed that CTNs exhibit significant up-regulation of proteins involved in thyroid hormone synthesis yet are deficient in T4-containing thyroglobulin. This is consequential to intranodular iodide deficiency, mainly due to cytoplasmic sodium iodide symporter localization, and portrays the CTN as an activated proliferating lesion with an intranodular hypothyroid milieu. Furthermore, we provide preliminary evidence that up-regulation of H2O2 generation in CTNs could override the antioxidative system resulting in oxidative stress, which is suggested by the finding of raised 8-oxo-guanidine DNA adduct formation in CTNs.
Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength
Authors: Perrien Daniel S. , Akel Nisreen S. , Edwards Paul K. , Carver Adam A. , Bendre Manali S. , Swain Frances L. , Skinner Robert A. , Hogue William R. , Nicks Kristy M. , Pierson Tyler M. , Suva Larry J. , Gaddy Dana
Published: December 2006

Gonadal function plays a major role in bone homeostasis. It is widely held that the skeletal consequences of hypogonadism are solely due to a loss of sex steroids; however, increases in bone turnover begin during perimenopause before decreases in serum estradiol levels. These data and our demonstration that inhibins acutely regulate bone cell differentiation in vitro led us to test whether inhibin A (InhA) regulates bone mass in vivo. Using a transgenic model of inducible human InhA expression, InhA increased total body bone mineral density, increased bone volume, and improved biomechanical properties at the proximal tibia in intact mice and also prevented the loss of BMD and bone volume and strength associated with gonadectomy at both the spine and proximal tibia. In addition, InhA increased mineral apposition rate, double-labeled surface, and serum osteocalcin levels in vivo and osteoblastogenesis ex vivo without affecting osteoclast number or activity. Together these results demonstrate novel stimulatory effects of InhA on the skeleton in vivo. These studies provide in vivo evidence demonstrating that gonadal factors other than sex steroids play an important role in regulating bone mass and strength and, combined with our previous clinical data, suggest that gonadal InhA may be a component of the normal endocrine repertoire that regulates bone quality in both the axial and appendicular skeleton.
Corticotropin-Releasing Factor (CRF) and the Urocortins Differentially Regulate Catecholamine Secretion in Human and Rat Adrenals, in a CRF Receptor Type-Specific Manner
Authors: Dermitzaki E. , Tsatsanis C. , Minas V. , Chatzaki E. , Charalampopoulos I. , Venihaki M. , Androulidaki A. , Lambropoulou M. , Spiess J. , Michalodimitrakis E. , Gravanis A. , Margioris A. N.
Published: December 2006

Corticotropin-releasing factor (CRF) affects catecholamine production both centrally and peripherally. The aim of the present work was to examine the presence of CRF, its related peptides, and their receptors in the medulla of human and rat adrenals and their direct effect on catecholamine synthesis and secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1 (CRF1) and 2 (CRF2) were present in human and rat adrenal medulla as well as the PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT-PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF1 receptor agonists induced catecholamine secretion in a dose-dependent manner, an effect peaking at 30 min, whereas CRF2 receptor agonists suppressed catecholamine secretion. The respective effects were blocked by CRF1 and CRF2 antagonists. CRF peptides affected catecholamine secretion via changes of subplasmaliminal actin filament polymerization. CRF peptides also affected catecholamine synthesis. In rat chromaffin and PC12 cells, CRF1 and CRF2 agonists induced catecholamine synthesis via tyrosine hydroxylase. However, in human chromaffin cells, activation of CRF1 receptors induced tyrosine hydroxylase, whereas activation of CRF2 suppressed it. In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis.
Rapid Inhibition of Neurons in the Dorsal Motor Nucleus of the Vagus by Leptin
Authors: Williams K. W. , Zsombok A. , Smith B. N.
Published: December 2006

The peptide leptin conveys the availability of adipose energy stores to the brain. Increasing evidence implicates a significant role for extrahypothalamic sites of leptin action, including the dorsal vagal complex, a region critical for regulating visceral parasympathetic function. The hypothesis that leptin suppresses cellular activity in the dorsal motor nucleus of the vagus nerve (DMV) was tested using whole-cell patch-clamp recordings in brainstem slices. Leptin caused a rapid membrane hyperpolarization in 50% of rat DMV neurons. Leptin also hyperpolarized a subset of gastric-related neurons (62%), identified after gastric inoculation with a transneuronal retrograde viral tracer. The hyperpolarization was associated with a decrease in input resistance and cellular responsiveness and displayed characteristics consistent with an increased K+ conductance. Perfusion of tolbutamide (200 μm) reversed the leptin-induced hyperpolarization, and tolbutamide or wortmannin (10–100 nm) prevented the hyperpolarization, indicating that leptin activated an ATP-sensitive K+ channel via a phosphoinositide-3-kinase-dependent mechanism. Leptin reduced the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs), whereas inhibitory postsynaptic currents (IPSCs) were largely unaffected. Electrical stimulation of the nucleus tractus solitarii (NTS) resulted in constant-latency EPSCs, which were decreased in amplitude by leptin. The paired-pulse ratio was increased, suggesting leptin effects involved activation of receptors presynaptic to the recorded neuron. A leptin-induced suppression of EPSCs, but not IPSCs, evoked by focal photolytic uncaging of glutamate within the NTS was also observed, supportive of leptin effects on the glutamatergic NTS projection to the DMV. Therefore, leptin directly hyperpolarized and indirectly suppressed excitatory synaptic activity to DMV neurons involved in visceral regulation, including gastric-related neurons.
Development of Primordial Follicles in the Hamster: Role of Estradiol-17β
Authors: Wang Cheng , Roy Shyamal K.
Published: December 2006

The role of E2 on primordial follicle formation was examined by treating neonatal hamsters with 1 or 2 μg estradiol cypionate (ECP) at age postnatal d 1 (P1) and P4 or by in vitro culture of embryonic d 15 (E15) ovaries with 1, 5, or 10 ng/ml estradiol-17β (E2). The specificity of E2 action was examined by ICI 182,780. One microgram of ECP maintained serum levels of E2 within the physiological range, significantly reduced apoptosis, and stimulated the formation and development of primordial follicles. In contrast, 2 μg ECP increased serum E2 levels to 400 pg/ml and had significantly less influence on primordial follicle formation. In vivo, ICI 182,780 significantly increased apoptosis and caused a modest reduction in primordial follicle formation. The formation and development of primordial follicles in vitro increased markedly with 1 ng/ml E2, and the effect was blocked by ICI 182,780. Higher doses of E2 had no effect on primordial follicle formation but significantly up-regulated apoptosis, which was blocked by ICI 182,780. CYP19A1 mRNA expression occurred by E13 and increased with the formation of primordial follicles. P4 ovaries synthesized E2 from testosterone, which increased further by FSH. Both testosterone and FSH maintained ovarian CYP19A1 mRNA, but FSH up-regulated the expression. These results suggest that neonatal hamster ovaries produce E2 under FSH control and that E2 action is essential for the survival and differentiation of somatic cells and the oocytes leading to the formation and development of primordial follicles. This supportive action of E2 is lost when hormone levels increase above a threshold.
Role of the Central Melanocortin Circuitry in Adaptive Thermogenesis of Brown Adipose Tissue
Authors: Voss-Andreae Adriana , Murphy Jonathan G. , Ellacott Kate L. J. , Stuart Ronald C. , Nillni Eduardo A. , Cone Roger D. , Fan Wei
Published: December 2006

The central melanocortin 4 receptor (MC4R) plays a critical role in energy homeostasis, although little is known regarding its role in the regulation of adaptive thermogenesis of brown adipose tissue (BAT). Here we show using retrograde transsynaptic tracing with attenuated pseudorabies virus coupled with dual-label immunohistochemistry that specific subsets of MC4R-expressing neurons in multiple nuclei of the central nervous system known to regulate sympathetic outflow polysynaptically connect with interscapular BAT (IBAT). Furthermore, we show that MC4R−/− and agouti-related peptide-treated mice are defective in HF diet-induced up-regulation of uncoupling protein 1 in IBAT. Additionally, MC4R−/− mice exposed to 4 C for 4 h exhibit a defect in up-regulation of uncoupling protein 1 levels in IBAT. Our results provide a neuroanatomic substrate for MC4R regulating sympathetically mediated IBAT thermogenesis and demonstrate that the MC4R is critically required for acute high-fat- and cold-induced IBAT thermogenesis.
Analysis of fibre orientation effects on injection moulded components
Authors: O'Dowd F , Lévesque M , Gilchrist M D
Published: December 2006

Fibre orientation, and thus the mechanical behaviour of short-fibre-reinforced thermoplastics (SFRTPs), depends greatly on the flow conditions in the mould. In order to design with SFRTPs, a thorough understanding of the processing conditions is required, together with the influence that the fibre orientation distribution (FOD) has upon the resulting mechanical properties. This work investigates the influence of primary injection moulding process parameters on the final properties of a simple planar injection-moulded component through design of experiments (DOE) and analysis of variance (ANOVA) techniques. Four factors are seen to have greatest effect on the mechanical properties: cavity thickness, packing pressure, packing time, and melt temperature. A systematic procedure is then employed to vary the levels of each factor, and the FOD and mechanical properties are studied. The final orientation is complex and is shown to vary throughout the part and depend heavily on the values selected for each parameter. Experimentally measured orientation results are then compared against those predicted by commercially available software for this planar geometry component. It is found that the predicted orientations were significantly over-predicted (34 per cent on average), from a minimum of 15 per cent for a 2 mm mould cavity up to 40 per cent for the larger 5 mm cavity thickness. This discrepancy in turn leads to an over-prediction, of approximately 50–60 per cent, between predicted and measured stiffness.
A novel approach to collaborative product design and development environment
Authors: Tseng K C , Abdalla H
Published: December 2006

This paper presents a new approach to collaborative product design and development environment from a holistic perspective that facilitates virtual multidisciplinary activities. The approach accomplishes integration of a distributed collaborative product development strategy and user-centred environment. It embraces product development representation, a novel systematic framework to manage a collaborative product development (CPD) system, and a novel human-centred system. The advantage of the developed system is that it encompasses a marketing information system (MIS), a human resources management (HRM) system, a supply chain management (SCM) system, communication media, an integrated product design studio, user-centred interfaces, and databases. The developed system has been tested, with results showing major benefits such as reduced product development lead time and cost. The tangible benefit of implementing this system is that the complex product developing process is organized in a systematic, consistent, and concurrent manner to enable collaboration among team members throughout the development process. It accomplishes a guiding sequence that assists inexperienced users to follow the complex process. Therefore, an efficient product development process is generated. One of the advantageous features of this system is that the barriers between people and incompatible computer systems, resulting from non-standardization, have been eliminated.
Online prediction of diffusion wear on the flank through tool tip temperature in turning using artificial neural networks
Authors: Rao C H Srinivasa , Rao D Nageswara , Rao R N Someswara
Published: December 2006

Diffusion in cutting tool materials during machining contributes significantly to the tool wear and has been drawing the attention of several researchers for over a decade. The present work aims at employing a method to investigate tool material diffusion for online prediction of flank wear using artificial neural networks. Experimentation is carried on a lathe under different cutting conditions. Flank wear is measured at various intervals of time off-line. Back propagation neural network fortified with heuristic methods of optimization has been employed in the present work. The cutting conditions and nodal temperature measured by a remote thermocouple are used as inputs and the amount of diffusion wear is obtained as the output. The model is validated by comparing with the experimental results. The proposed methodology, which employs a diffusion parameter for the assessment of tool wear from estimated tool tip temperatures, can be adapted to any combination of tool and work material.
Laser-assisted machining of an austenitic stainless steel: P550
Authors: Anderson M C , Shin Y C
Published: December 2006

High-nitrogen, nickel-free stainless steels have much higher yield strength than typical stainless steels, and their high corrosion resistance and high strength makes them especially attractive in medical, aerospace, and oil drilling industries. The high strength also makes these materials difficult to machine owing to high cutting forces, and relatively short tool lives. Laser-assisted machining (LAM) is investigated as an economic alternative for machining these difficult-to-machine materials.

In the current study, surface temperature measurements are compared with model predictions to ascertain the accuracy of a thermal model. An experimental matrix is designed to determine the effects of temperature and surface speed, using tool life, cutting forces, surface roughness, and workpiece integrity as metrics to determine optimal processing conditions. Explanation of cutting temperatures and effects on tool life are discussed. Hardness measurements, X-ray diffraction, and microstructural analysis indicate little or no damage of the subsurface of the workpiece. An economic analysis shows the benefits that can be obtained over conventional machining through implementation of LAM in stainless steels.
Tool path generation for machining of optical freeform surfaces by an ultra-precision multiaxis machine tool
Authors: Gao D , To S , Lee W B
Published: December 2006

Optical freeform surfaces are crucial to the development of complex and optical-electromechanical devices used in many photonics products. The fabrication of high-quality freeform lens is based on ultra-precision freeform machining technology which allows direct machining of freeform surfaces with submicrometric form accuracy and nanometric surface finish. In this paper, the application of ultra-precision freeform machining to the fabrication of an optical freeform surface is addressed. The methodology for the development of the tool path generator for a progressive lens is discussed. According to the model of the freeform surface, which is represented by a double cubic B-spline surface, the method of changing parameters is used to calculate the numerically controlled (NC) machining tool path. The formula for calculating cutter location data, which considers the compensation of both the tool nose radius and tool swing radius of the fly cutter, is deduced. The cutting experiment of machining a freeform progressive optics lens by a multiaxis ultra-precision machine tool shows that the developed tool path generator can perform its function successfully.
Operation sequencing optimization using a particle swarm optimization approach
Authors: Guo Y W , Mileham A R , Owen G W , Li W D
Published: December 2006

Operation sequencing is one of the crucial tasks in process planning. However, it is an intractable process to identify an optimized operation sequence with minimal machining cost in a vast search space constrained by manufacturing conditions. In this paper, the complicated operation sequencing process has been modelled as a combinatorial optimization problem, and a modern evolutionary algorithm, i.e. the particle swarm optimization (PSO) algorithm, has been employed and modified to solve it effectively. Initial process plan solutions are formed and encoded into particles of the PSO algorithm. The particles ‘fly’ intelligently in the search space to achieve the best sequence according to the optimization strategies of the PSO algorithm. Meanwhile, to explore the search space comprehensively and to avoid being trapped into local optima, several new operators have been developed to improve the particles' movements, forming a modified PSO algorithm. A case study involving three prismatic parts has been used to verify the performance and efficiency of the modified PSO algorithm. A comparison has been made between the result of the modified PSO algorithm and the previous results using the genetic algorithm (GA) and the simulated annealing (SA) algorithm and the different characteristics of the three algorithms are indicated. Case studies show that the developed PSO can generate satisfactory results in optimizing the process planning problem.
Geometrical characterization of canted coil springs
Authors: Soler J M , Rangel R H
Published: December 2006

This article presents a geometrical description of canted coil springs as a particular type of space curve. The influence of the canted angle on the geometrical curvature and torsion is investigated in order to characterize the three-dimensional geometry of the springs. Geometrical descriptions of helical spring rings generated by joining together the two ends of a rectilinear-axis spring as well as several types of spring rings, obtained from rectilinear-axis canted coil springs, are proposed. To create such ring geometries, conservation of length of wire is assumed and approximate relations are derived in order to simplify computations. These geometrical descriptions are then applied to generate appropriate three-dimensional models. Such models can be further imported to computer-aided design and finite-element analysis programmes in order to estimate the mechanical response of such springs.
Determining both radial pressure distribution and torsional stiffness of involute spline couplings
Authors: Barrot A , Paredes M , Sartor M
Published: December 2006

In this paper, an analytical method is used to investigate the distortions of involute spline teeth. The following hypotheses are adopted: teeth geometry is in conformity with standardization, dimensions are nominal (no defect), there is no friction and the load is a pure torsional torque. Teeth distortions due to bending, shear, compression, and foundation rotation are analysed. As the load is distributed along the tooth height, the displacement calculation differs from the conventional approach used for gear teeth. Sliding over the contact surfaces is also considered as it emerged during the study that this phenomenon, that has not hitherto been taken into account, plays a significant role. A punch model is used to describe the radial distribution of the contact pressure. Ascribing an arbitrary value to the tilted angle between the two contacting flanks enables the pressure profile to be evaluated, from which calculation of teeth distortions can be arrived at so as finally to obtain a new estimation of the tilted angle. Thus, displacements and the contact load can be determined together by iterating the calculation procedure until convergence. Torsional stiffness, which is one of the main parameters required to predict the torque distribution along the spline coupling, is evaluated from the various displacement components. The results derived from the proposed analytical method are compared with finite-element results and show good correlation.
Techniques for increasing the effectiveness of anti-vibration in Scott-Russel linkage isolators
Authors: Luu T T , Park S T
Published: December 2006

The Scott-Russel horizontal isolator is a straight line linkage. When this structure is used, the stored energy can be reduced as much as possible, making the isolation system achieve a very low natural frequency. However, because of the existence of the weight of the isolator, the natural frequency is not as low as expected. In this paper, the equation of motion of the Scott-Russel isolator is proposed to find a method to reduce the natural frequency by choosing reasonable parameters and using the zero-length spring.