bluuebunny/crossref_metadata_2025 huggingface dataset:
Baroreflex control of muscle sympathetic nerve activity during skin surface cooling
Authors: Cui Jian , Durand Sylvain , Crandall Craig G.
Published: August 2007

Skin surface cooling improves orthostatic tolerance through a yet to be identified mechanism. One possibility is that skin surface cooling increases the gain of baroreflex control of efferent responses contributing to the maintenance of blood pressure. To test this hypothesis, muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate were recorded in nine healthy subjects during both normothermic and skin surface cooling conditions, while baroreflex control of MSNA and heart rate were assessed during rapid pharmacologically induced changes in arterial blood pressure. Skin surface cooling decreased mean skin temperature (34.9 ± 0.2 to 29.8 ± 0.6°C; P < 0.001) and increased mean arterial blood pressure (85 ± 2 to 93 ± 3 mmHg; P < 0.001) without changing MSNA ( P = 0.47) or heart rate ( P = 0.21). The slope of the relationship between MSNA and diastolic blood pressure during skin surface cooling (−3.54 ± 0.29 units·beat−1·mmHg−1) was not significantly different from normothermic conditions (−2.94 ± 0.21 units·beat−1·mmHg−1; P = 0.19). The slope depicting baroreflex control of heart rate was also not altered by skin surface cooling. However, skin surface cooling shifted the “operating point” of both baroreflex curves to high arterial blood pressures (i.e., rightward shift). Resetting baroreflex curves to higher pressure might contribute to the elevations in orthostatic tolerance associated with skin surface cooling.
Skeletal muscle adaptations to testosterone and resistance training in men with COPD
Authors: Lewis Michael I. , Fournier Mario , Storer Thomas W. , Bhasin Shalender , Porszasz Janos , Ren Song-Guang , Da Xiaoyu , Casaburi Richard
Published: August 2007

We recently reported increased leg lean mass and strength in men with chronic obstructive pulmonary disease (COPD) receiving 10 wk of testosterone (T) and leg resistance training (R) (Casaburi R, Bhasin S, Cosentino L, Porszasz J, Somfay A, Lewis M, Fournier M, Storer T. Am J Respir Crit Care Med 170: 870–878, 2004). The present study evaluates the role of muscle IGF and related factors as potential mechanisms for our findings, using quadriceps muscle biopsies from the same cohort. Patient groups were 1) weekly placebo (P) injections + no R; 2) P and R; 3) weekly injections of T + no R; and 4) T + R (TR). Muscle fibers were classified histochemically, and their cross-sectional areas (CSAs) and fiber density (number of fibers per unit area) were determined. Gene transcripts were determined by real-time PCR and protein expression by RIA. While no significant changes in fiber CSAs were noted across groups, increased trends were observed after 10 wk, and significant decrements in muscle fiber density were noted in all treated groups. A global increase in all myosin heavy chain (MyHC) mRNA isoforms was observed in TR patients. Muscle IGF-IEa and IGF-IEc mRNAs were significantly increased with TR group. Muscle IGF-I protein was increased in all intervention groups (greatest in TR). While TR IGF-II mRNA was increased, protein levels were unaltered. IGF binding protein-4 mRNA was increased with TR. Myogenin mRNA was increased in both T groups, while MyoD and myostatin were unchanged. Muscle atrophy F-box mRNA tended to increase with TR. Our data suggest that the combined interventions produced an enhanced local anabolic milieu driven in large part by the muscle IGF system, despite potentially negative biochemical influences present in COPD patients.
The canine spleen in oxygen transport: gas exchange and hemodynamic responses to splenectomy
Authors: Hsia Connie C. W. , Johnson Robert L. , Dane D. Merrill , Wu Eugene Y. , Estrera Aaron S. , Wagner Harrieth E. , Wagner Peter D.
Published: August 2007

In athletic animals the spleen induces acute polycythemia by dynamic contraction that releases red blood cells into the circulation in response to increased O2 demand and metabolic stress; when energy demand is relieved, the polycythemia is rapidly reversed by splenic relaxation. We have shown in adult foxhounds that splenectomy eliminates exercise-induced polycythemia, thereby reducing peak O2 uptake and lung diffusing capacity for carbon monoxide (DLCO) as well as exaggerating preexisting DLCO impairment imposed by pneumonectomy (Dane DM, Hsia CC, Wu EY, Hogg RT, Hogg DC, Estrera AS, Johnson RL Jr. J Appl Physiol 101: 289–297, 2006). To examine whether the postsplenectomy reduction in DLCO leads to abnormalities in O2 diffusion, ventilation-perfusion inequality, or hemodynamic function, we studied these animals via the multiple inert gas elimination technique at rest and during exercise at a constant workload equivalent to 50% or 80% of peak O2 uptake while breathing 21% and 14% O2 in balanced order. From rest to exercise after splenectomy, minute ventilation was significantly elevated with respect to O2 uptake compared with exercise before splenectomy; cardiac output, O2 delivery, and mean pulmonary and systemic arterial blood pressures were 10–20% lower, while O2 extraction was elevated with respect to O2 uptake. Ventilation-perfusion inequality was unchanged, but O2 diffusing capacities of lung (DLO2) and peripheral tissue during exercise were lower with respect to cardiac output postsplenectomy by 32% and 25%, respectively. The relationship between DLO2 and DLCO was unchanged by splenectomy. We conclude that the canine spleen regulates both convective and diffusive O2 transport during exercise to increase maximal O2 uptake.
Expression and activity of cyclooxygenase isoforms in skeletal muscles and myocardium of humans and rodents
Authors: Testa Marco , Rocca Bianca , Spath Lucia , Ranelletti Franco O. , Petrucci Giovanna , Ciabattoni Giovanni , Naro Fabio , Schiaffino Stefano , Volpe Massimo , Reggiani Carlo
Published: August 2007

Conflicting data have been reported on cyclooxygenase (COX)-1 and COX-2 expression and activity in striated muscles, including skeletal muscles and myocardium, in particular it is still unclear whether muscle cells are able to produce prostaglandins (PGs). We characterized the expression and enzymatic activity of COX-1 and COX-2 in the skeletal muscles and in the myocardium of mice, rats and humans. By RT-PCR, COX-1 and COX-2 mRNAs were observed in homogenates of mouse and rat hearts, and in different types of skeletal muscles from all different species. By Western blotting, COX-1 and -2 proteins were detected in skeletal muscles and hearts from rodents, as well as in skeletal muscles from humans. Immunoperoxidase stains showed that COX-1 and -2 were diffusely expressed in the myocytes of different muscles and in the myocardiocytes from all different species. In the presence of arachidonic acid, which is the COX enzymatic substrate, isolated skeletal muscle and heart samples from rodents released predominantly PGE2. The biosynthesis of PGE2was reduced between 50 and 80% ( P < 0.05 vs. vehicle) in the presence of either COX-1- or COX-2-selective blockers, demonstrating that both isoforms are enzymatically active. Exogenous PGE2added to isolated skeletal muscle preparations from rodents did not affect contraction, whereas it significantly fastened relaxation of a slow type muscle, such as soleus. In conclusion, COX-1 and COX-2 are expressed and enzymatically active in myocytes of skeletal muscles and hearts of rodents and humans. PGE2appears to be the main product of COX activity in striated muscles.
Skin-surface cooling elicits peripheral and visceral vasoconstriction in humans
Authors: Wilson Thad E. , Sauder Charity L. , Kearney Matthew L. , Kuipers Nathan T. , Leuenberger Urs A. , Monahan Kevin D. , Ray Chester A.
Published: August 2007

Skin-surface cooling elicits a pronounced systemic pressor response, which has previously been reported to be associated with peripheral vasoconstriction and may not fully account for the decrease in systemic vascular conductance. To test the hypothesis that whole body skin-surface cooling would also induce renal and splanchnic vasoconstriction, 14 supine subjects performed 26 skin-surface cooling trials (15–18°C water perfused through a tube-lined suit for 20 min). Oral and mean skin temperature, heart rate, stroke volume (Doppler ultrasound), mean arterial blood pressure (MAP), cutaneous blood velocity (laser-Doppler), and mean blood velocity of the brachial, celiac, renal, and superior mesenteric arteries (Doppler ultrasound) were measured during normothermia and skin-surface cooling. Cardiac output (heart rate·stroke volume) and indexes of vascular conductance (flux or blood velocity/MAP) were calculated. Skin-surface cooling increased MAP ( n = 26; 78 ± 5 to 88 ± 5 mmHg; mean ± SD) and decreased mean skin temperature ( n = 26; 33.7 ± 0.7 to 27.5 ± 1.2°C) and cutaneous ( n = 12; 0.93 ± 0.68 to 0.36 ± 0.20 flux/mmHg), brachial ( n = 10; 32 ± 15 to 20 ± 12), celiac ( n = 8; 85 ± 22 to 73 ± 22 cm·s−1·mmHg−1), superior mesenteric ( n = 8; 55 ± 16 to 48 ± 10 cm·s−1·mmHg−1), and renal ( n = 8; 74 ± 26 to 64 ± 20 cm·s−1·mmHg−1; all P < 0.05) vascular conductance, without altering oral temperature, cardiac output, heart rate, or stroke volume. These data identify decreases in vascular conductance of skin and of brachial, celiac, superior mesenteric, and renal arteries. Thus it appears that vasoconstriction in both peripheral and visceral arteries contributes importantly to the pressor response produced during skin-surface cooling in humans.
Effect of exercise with and without a thermal clamp on the plasma heat shock protein 72 response
Authors: Whitham Martin , Laing Stewart J. , Jackson Anna , Maassen Norbert , Walsh Neil P.
Published: August 2007

The contribution of heat and exercise related stress to the release of heat shock protein 72 (HSP72) is currently unknown. The purpose of the present study was to determine the combined and independent effects of heat and exercise on the extracellular (e)HSP72 response. Eleven moderately trained male volunteers [means ± SD: age 21 ± 4 yr; body mass 75.7 ± 7.7 kg; maximal oxygen uptake (V̇o2 max) 57.8 ± 3.3 ml·kg−1·min−1] completed four 2-h, heat-manipulated, water-immersion trials. Trials were exercise-induced heat (EIH; rectal temperature change +2.2°C), clamped exercise (CEx; 0°C), passive heating (PHT; +2.3°C), and control (Con; 0°C). Exercise trials (EIH and CEx) comprised deep-water running at 58.5 ± 2.4 and 59.1 ± 1.7% v̇o2max. eHSP72 and catecholamine concentrations were determined by ELISA and HPLC, respectively, pre- and postimmersion. All trials induced an eHSP72 response ( P < 0.05) with postimmersion values significantly greater on EIH compared with other trials (6.0 ± 3.4; CEx 3.8 ± 2.6; PHT 2.7 ± 2.1; Con 2.2 ± 1.9 ng/ml). Exercising with a thermal clamp blunted the eHSP72 response, but postimmersion values were also greater than Con. PHT induced a large catecholamine response, but postimmersion eHSP72 values did not reach significance vs. Con. Given that exercising with a thermal clamp evoked a significant increase in plasma eHSP72 concentration, exercise-related stressors other than heat appeared influential in stimulating HSP72 release. Moreover, the catecholamine data from PHT suggest neither epinephrine nor norepinephrine was solely responsible for eHSP72 release.
A single bout of exercise with high mechanical loading induces the expression of Cyr61/CCN1 and CTGF/CCN2 in human skeletal muscle
Authors: Kivelä Riikka , Kyröläinen Heikki , Selänne Harri , Komi Paavo V. , Kainulainen Heikki , Vihko Veikko
Published: August 2007

High mechanical loading was hypothesized to induce the expression of angiogenic and/or lymphangiogenic extracellular matrix (ECM) proteins in skeletal muscle. Eight men performed a strenuous exercise protocol, which consisted of 100 unilateral maximal drop jumps followed by submaximal jumping until exhaustion. Muscle biopsies were taken 30 min and 48 h postexercise from the vastus lateralis muscle and analyzed for the following parameters: mRNA and protein expression of ECM-associated CCN proteins [cysteine-rich angiogenic protein 61 (Cyr61)/CCN1, connective tissue growth factor (CTGF)/CCN2], and mRNA expression of vascular endothelial growth factors (VEGFs) and hypoxia-inducible factor-1α. The mRNA expression of Cyr61 and CTGF increased 30 min after the exercise (14- and 2.5-fold, respectively; P < 0.001). Cyr61 remained elevated 48 h postexercise (threefold; P < 0.05). The mRNA levels of VEGF-A, VEGF-B, VEGF-C, VEGF-D, or hypoxia-inducible factor-1α did not change significantly at either 30 min or 48 h postexercise; however, the variation between subjects increased markedly in VEGF-A and VEGF-B mRNA. Cyr61 protein levels were higher at both 30 min and 48 h after the exercise compared with the control ( P < 0.05). Cyr61 and CTGF proteins were localized to muscle fibers and the surrounding ECM by immunohistochemistry. Fast fibers stained more intensively than slow fibers. In conclusion, mechanical loading induces rapid expression of CCN proteins in human skeletal muscle. This may be one of the early mechanisms involved in skeletal muscle remodeling after exercise, since Cyr61 and CTGF regulate the expression of genes involved in angiogenesis and ECM remodeling.
Effect of coactivation of tongue protrusor and retractor muscles on pharyngeal lumen and airflow in sleep apnea patients
Authors: Oliven Arie , Odeh Majed , Geitini Louis , Oliven Ron , Steinfeld Uri , Schwartz Alan R. , Tov Nave
Published: August 2007

The present study evaluated the effect of coactivation of tongue protrusors and retractors on pharyngeal patency in patients with obstructive sleep apnea. The effect of genioglossus (GG), hyoglossus (HG), and coactivation of both on nasal pressure (Pn):flow relationships was evaluated in a sleep study (SlS, n = 7) and during a propofol anesthesia study (AnS, n = 7). GG was stimulated with sublingual surface electrodes in SlS and with intramuscular electrodes in AnS, while HG was stimulated with surface electrodes in both groups. In the AnS, the cross-sectional area (CSA):Pn relationships was measured with a pharyngoscope to estimate velopharyngeal compliance . In the SlS, surface stimulation of GG had no effect on the critical pressure (Pcrit), HG increased Pcrit from 2.8 ± 1.7 to 3.7 ± 1.6 cmH2O, but coactivation lowered Pcrit to 0.2 ± 1.9 cmH2O ( P < 0.01 for both). In the AnS, intramuscular stimulation of GG lowered Pcrit from 2.6 ± 1.3 to 1.0 ± 2.8 cmH2O, HG increased Pcrit to 6.2 ± 2.5 cmH2O ( P < 0.01), and coactivation had a similar effect to that of GG (Pcrit = 1.2 ± 2.4 cmH2O, P < 0.05). None of the interventions affected significantly velopharyngeal compliance. We conclude that the beneficial effect of coactivation depends on the pattern of GG fiber recruitment: although surface stimulation of GG failed to protrude the tongue, it prevented the occlusive effect of the retractor, thereby improving pharyngeal patency during coactivation. Stimulation of deeper GG fibers with intramuscular electrodes enlarged the pharynx, and coactivation had no additive effect.
Stress System – Organization, Physiology and Immunoregulation
Authors: Elenkov Ilia J. , Chrousos George P.
Published: August 2007

Stress is defined as a state of threatened homeostasis. The principal effectors of the stress system include corticotropin-releasing hormone, arginine vasopressin, the glucocorticoids, and the catecholamines norepinephrine and epinephrine. Activation of the stress system leads to adaptive behavioral and physical changes. The principal stress hormones glucocorticoids and catecholamines affect major immune functions such as antigen presentation, leukocyte proliferation and traffic, secretion of cytokines and antibodies, and selection of the T helper (Th) 1 versus Th2 responses. A fully fledged systemic inflammatory reaction results in stimulation of the stress response, which in turn, through induction of a Th2 shift protects the organism from systemic overshooting with Th1/pro-inflammatory cytokines. Stress is often regarded as immunosuppressive, but recent evidence indicates that stress hormones influence the immune response in a less monochromatic way – systemically they inhibit Th1/pro-inflammatory responses and induce a Th2 shift, whereas in certain local responses they promote pro-inflammatory cytokine production and activation of the corticotropin-releasing hormone-mast cell-histamine axis. Through this mechanism a hyper- or hypoactive stress system associated with abnormalities of the systemic anti-inflammatory feedback and/or hyperactivity of the local pro-inflammatory factors may play a role in the pathogenesis of chronic inflammation and immune-related diseases.
HPA and Immune Axes in Stress: Involvement of the Serotonergic System
Authors: Leonard Brian E.
Published: August 2007

Chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis and the immune system, acts as a trigger for anxiety and depression. There is experimental and clinical evidence that the rise in the concentration of pro-inflammatory cytokines and glucocorticoids, which occurs in a chronically stressful situation and also in depression, contributes to the behavioural changes associated with depression. A defect in serotonergic function is associated with these hormonal and immune changes. Neurodegenerative changes in the hippocampus, prefrontal cortex and amygdalae are the frequent outcomes of the changes in the hypothalamic-pituitary-adrenal axis and the immune system. Such changes may provide evidence for the link between chronic depression and dementia in later life.
Stress as a Risk Factor in the Pathogenesis of Rheumatoid Arthritis
Authors: Cutolo Maurizio , Straub Rainer H.
Published: August 2007

Stress is now recognized as an important risk factor in the pathogenesis of autoimmune rheumatic diseases (i.e. rheumatoid arthritis) by considering that the activation of the stress response system influences the close relationships existing between the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system and the immune system. The stress response results in the release of neurotransmitters (norepinephrine), hormones (cortisol) and immune cells which serve to send an efferent message from the brain to the periphery. Major life events lead to an intense release of stress mediators (large time integral of released neurotransmitters and hormones), whereas in minor life events, only short-lived surges of neurotransmitters and hormones are expected. Therefore, it is suggested that neurotransmitters such as norepinephrine or stress hormones such as cortisol might have different effects on immune/inflammatory responses at high and low concentrations present during short or extended periods of time, respectively. Long-lasting (chronic) stress may lead to proinflammatory effects because no adequate long-term responses of stress axes (anti-inflammatory) are to be expected.
Stress and Coping Strategies in Systemic Lupus Erythematosus: A Review
Authors: Bricou Olivier , Taïeb Olivier , Baubet Thierry , Gal Béatrice , Guillevin Loïc , Moro Marie Rose
Published: August 2007

Systemic lupus erythematosus (SLE), a chronic and unpredictable disease accompanied by functional disability and a possible involvement of the central nervous system, leads to considerable psychological distress. A review of studies on stress and/or coping strategies in SLE since 1990 is presented. Many studies have investigated the place of major and minor stress and coping strategies in SLE morbidity (disease activity, organ damage, and physical and mental components of quality of life). Stress as a causal factor is not proved, but it seems to act as an exacerbating factor in disease activity and to have an impact on the quality of life. Coping strategies are more consistently associated with quality of life than with disease activity. Organ damage appears to be less associated with psychosocial factors than disease activity or quality of life. Despite the limitations of these studies, therapeutic interventions should be proposed to reduce psychological distress, to improve the quality of life and possibly to moderate the evolution of the disease.
Cortisol Circadian Rhythms and Stress Responses in Infants at Risk of Allergic Disease
Authors: Ball Thomas M.
Published: August 2007

Altered hypothalamic-pituitary-adrenal function associated with allergic disease has generally been thought to be secondary to the stress of chronic disease. However, recent studies suggest that altered cortisol circadian rhythm and cortisol stress hyper-responsiveness precede the inception of allergic disease and are possible links between preventive factors associated with the hygiene hypothesis and the development of allergies. Elevated endogenous cortisol responses to stressful stimuli could predispose susceptible hosts to atopy and allergic disease by biasing the developing immune system to a T helper 2-predominant immune response, greater total and allergen-specific serum immunoglobulin E responses, and/or inhibition of peripheral immune tolerance. Because glucocorticoid receptors are present throughout the human body and many genes contain glucocorticoid response elements, variances in endogenous cortisol concentrations could have an impact on the phenotypic plasticity of a wide range of immunologically active genes during early human immune development. Here, recent findings related to hypothalamic-pituitary-adrenal function in infants predisposed to developing allergic disease are discussed along with speculation regarding the potential causal role of endogenous cortisol in the inception of allergic disease.
Psychological Stress and the Risk of Diabetes-Related Autoimmunity: A Review Article
Authors: Sepa Anneli , Ludvigsson Johnny
Published: August 2007

The β cell stress hypothesis suggests that any phenomenon that induces insulin resistance, and thereby extra pressure on the β cells, should be regarded as a risk factor for type 1 diabetes (T1D). Psychological stress decreases insulin sensitivity and increases insulin resistance and may hence be important in the development/onset of T1D. The aim of the current review article was to evaluate existing empirical evidence concerning an association between psychological stress and development/onset of T1D as well as diabetes-related autoimmunity. Ten retrospective case-control studies were found. Nine studies showed a positive association between stress and development/onset of T1D in children, adolescents or adults. One study did not find an association between stress and development/onset of T1D. An association between stress and diabetes-related autoimmunity was found at 1 and 2– 3 years of age in a large epidemiological study of the general population. The hypothesis that psychological stress (via β cell stress or direct influence on the immune system) may contribute to the induction or progression of diabetes-related autoimmunity has gained some strong initial support, but is in need of further empirical verification. It seems much clearer that stress can precipitate manifest T1D, although the biological mechanisms are still not known.
Stress and Autoimmune Thyroid Diseases
Authors: Bagnasco Marcello , Bossert Irene , Pesce Giampaola
Published: August 2007

Autoimmune thyroid diseases (AITD) are the far most common autoimmune disorders, their prevalence in Western countries exceeding 5% of the general population. In the large majority of individual cases the clinical impact of AITD is not severe, however, their widespread diffusion renders them a significant health problem. AITD are heterogeneous in their clinical presentation: the two main forms are autoimmune thyroiditis (AT) and Graves’ disease (GD). Although they probably share, at least in part, a common genetic background and may occur in the same family as well as in the same individual, they are definitely two distinct diseases both in their clinical presentation and their pathophysiology. In fact, AT causes structural thyroid damage (mainly via cell-mediated immune destruction of thyroid follicular cells) which results, as a rule, in functional impairment (hypothyroidism); however, depending on clinical variants, evolution towards hypothyroidism may be very low, or thyroid function impairment occurs after an initial phase of mild thyrotoxicosis due to relatively rapid gland destruction. GD patients have hyperthyroidism, often severe, due to autoantibody-mediated thyrotropin receptor stimulation, with thyroid cell hyperplasia and hyperfunction. Such a functional heterogeneity is a key feature for the clinical management: as a matter of fact, therapy of AITD is mainly therapy of thyroid dysfunction. Moreover, since hyperthyroidism is quite early perceived by the patient as a cause of discomfort, the timing of the natural history of GD is relatively well defined; on the other hand, AT may be asymptomatic for a long time and defining its natural history in a single patient may be difficult. In some AITD patients (mainly, but not exclusively, with GD), clinical features not directly related to thyroid dysfunction, such as orbitopathy, are present. Graves’ orbitopathy is probably related, at least in part, to autoantibodies directed to thyrotropin receptor; it may be, in a minority of patients, severe and sight-threatening, and represents an independent clinical problem.
Stress and Disease Progression in Multiple Sclerosis and Its Animal Models
Authors: Gold Stefan M. , Heesen Christoph
Published: August 2007

Since the first description of multiple sclerosis (MS) by Charcot, stress has been hypothesized to be a potential trigger of relapses. In recent years, data from observational studies in MS patients have provided some support for an association between stress and MS relapses. Furthermore, studies employing the MS animal model experimental autoimmune encephalomyelitis have shown that certain stressors can exacerbate the disease if administered prior to disease induction. Several lines of research have explored the 2 major stress response systems – the hypothalamic-pituitary-adrenal axis and the autonomic nervous system – and their relation to disease course in MS and experimental autoimmune encephalomyelitis. These studies provide evidence that insensitivity of the immune system to signals from these systems may play a role in inflammatory events. These findings can be integrated into a biological model of stress response system alterations in MS.
From the Brain-Skin Connection: The Neuroendocrine-Immune Misalliance of Stress and Itch
Authors: Arck Petra , Paus Ralf
Published: August 2007

Perceived stress has long been allied with disturbances of the dynamic equilibrium established between the nervous, endocrine and immune systems, thus triggering or aggravating disease manifestation. Several common skin diseases are now acknowledged to be worsened by psychological stress, particularly immunodermatoses such as atopic dermatitis, psoriasis, seborrheic eczema, prurigo nodularis, lichen planus, chronic urticaria, alopecia areata and pruritus sine materia. Itch (pruritus) is perhaps the most common symptom associated with a majority of these inflammatory skin diseases, and acute as well as chronic stress perceptions are recognized to trigger or enhance pruritus. A wealth of mediators released systemically or locally in the skin in response to stress increase sensory innervation, upregulate the production of other pruritogenic agents, perpetuate (neurogenic) inflammation and lower the itch threshold. In the present review, we explore recent frontiers in both stress and pruritus research and portray the perpetuation of chronic skin inflammation and itch as a neuroendocrine-immune ‘misalliance’. We argue that key candidate molecules of the stress response with strong pruritogenic potential, such as nerve growth factor, corticotropin-releasing hormone and substance P, and mast cells, which may be considered as ‘central cellular switchboards of pruritogenic inflammation’, need to be further explored systematically in order to develop more effective therapeutic combination strategies for itch management in chronic, stress-vulnerable inflammatory skin diseases
Aluminium and Alzheimer's Disease: Review of Possible Pathogenic Mechanisms
Authors: Armstrong R.A. , Winsper S.J. , Blair J.A.
Published: August 2007

Chronic exposure to aluminium (Al) remains a controversial possible cause of sporadic forms of Alzheimer''s disease (AD). This article reviews the evidence that once Al enters the brain and individual brain cells, it may be involved in three pathological processes: (1) the production of abnormal forms of tau leading to the formation of cellular neurofibrillary tangles and neuropil threads; (2) the processing of the amyloid precursor protein, resulting in the formation of β-amyloid deposits and senile plaques, and (3) that via the mutual histocompatibility system, Al could be involved in the initiation of the immune response observed in AD patients. Despite recent evidence that Al could be involved in these processes, a conclusive case that exposure to Al initiates the primary pathological process in sporadic AD remains to be established.
Frontal Lobe Degeneration and Alzheimers Disease: A Controlled Study on Clinical Findings, Volumetric Brain Changes and Quantitative Electroencephalography Data
Authors: Förstl Hans , Besthorn Christoph , Hentschel Frank , Geiger-Kabisch Claudia , Sattel Heribert , Schreiter-Gasser Ursula
Published: August 2007

Ten patients with a clinical diagnosis of frontal lobe degeneration (FLD) were compared with a group of patients with probable Alzheimer’s disease (AD) and with nondemented controls matched for gender and age. In comparison with AD, the duration of illness was slightly shorter and cognitive performance was better in patients with FLD. The greatest enlargement of cerebro-spinal fluid volumes was found in FLD and this effect was most pronounced in the anterior fissure and lateral ventricles. Estimates of EEG band-power and EEG coherence in FLD were not remarkably different from nondemented controls, whereas delta- and theta-power were significantly increased in AD. These observations may indicate different disease processes with a dissociation of volumetric computed tomography and quantitative EEG changes, which may be of differential diagnostic value.
Deterioration of Spontaneous Speech in AD Patients during a 1-Year Follow-Up: Homogeneity of Profiles and Factors Associated with Progression
Authors: Romero Barbara , Kurz Alexander
Published: August 2007

This longitudinal study measured the rate of spontaneous speech decline in patients with Alzheimer''s disease (AD) at a 1-year follow-up and determined the effect of clinical and demographic factors on that rate. In addition the pattern of spontaneous speech impairment was examined. The expected pattern of spontaneous speech impairment with prominent disturbances of communication and semantics, moderate disturbances of automatic speech, but with retained phonematic structures, was found at baseline and at follow-up in the majority of our rather large sample (n = 63). This result is discussed in terms of intrafunctional homogeneity and of selective involvement of neuronal systems in AD. There was a trend for a more rapid language decline in patients with a family history of dementia. No relationship was detected between the rate of spontaneous speech decline and other clinical and demographic factors, with the exception of initial spontaneous speech impairment.
Senile Dementia of Alzheimer Type and Multi-Infarct Dementia Investigated by Transcranial Doppler Sonography
Authors: Sattel H. , Förstl H. , Biedert S.
Published: August 2007

Dementia of the Alzheimer type, senile onset (SDAT), and multi-infarct dementia (MID) exhibit differences in cerebrovascular blood flow velocity profiles, which were investigated by means of transcranial Doppler sonography. The pulsatility indices (PI), as angle-independent parameters of peripheral vascular resistance measured in the basal cerebral arteries, were significantly increased in MID patients with respect to SDAT cases. In an analysis of the correlations between several variables and the magnitude of PI, we found strong inverse correlations of the CAMCOG score, and strong direct correlations of the blood pressure and the duration of illness, with the PI of all basal cerebral arteries only in MID patients. In SDAT patients, we found a direct correlation between the Hachinski ischemia score and the PI of all basal cerebral arteries. All 3 ischemia scores (Hachinski, Rosen, Loeb and Gandolfo) were significantly correlated with the PI of the middle cerebral and basilar arteries. By analyzing the correlations of the single items of the 3 different ischemia scores with the PI values obtained, we only found a clearcut correlation with the item focal neurological signs. Thus, our findings stress the relative importance of a concomitant cerebrovascular factor in the development of dementia in old age, even in patients with probable SDAT. A raise of the PI in the basal cerebral arteries allows early suspicion of a cerebrovascular factor even in only slight dementia so that possible risk factors for further aggravation of this type of vascular dementia might be detected and treated early in the course of disease.
Visual and Somatosensory Evoked Potentials in Parkinson's and Binswanger's Disease
Authors: Okuda Bungo , Tachibana Hisao , Takeda Masanaka , Kawabata Keita , Sugita Minoru
Published: August 2007

To compare subcortical involvement of Parkinson''s disease (PD) with that of Binswanger''s disease (BD), we examined visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs) in 29 patients with PD and 7 patients with BD and 11 control subjects. The patients with PD were divided into two groups: PD without dementia (nD-PD: n = 18) and PD with dementia (D-PD: n = 11). The D-PD patients showed significantly longer P100 latencies in VEPs compared with the nD-PD patients or controls. The P100 latencies were negatively correlated with Mini-Mental State Examination (MMSE) score in the PD patients. The BD patients showed significantly Ionger central conduction time (CCT) in SEPs (interpeak Iatency between N13 and N20 responses) compared with the nD-PD patients or controls. There was no correlation between CCT and MMSE score in the BD patients. These results suggest that PD has a predilection for sensory system involvement distinct from that of BD. In D-PD, the visual system seems more vulnerable than the somatosensory system, but almost the reverse is true of BD.
Analysis of Amyloid Precursor Protein mRNAs in Skin Fibroblasts in Down's Syndrome
Authors: Urakami K. , Kataoka J. , Okada A.O. , Isoe K. , Wakutani Y. , Ji Y. , Adachi Y. , Ohno K. , Takahashi K.
Published: August 2007

We examined amyloid precursor protein (APP) mRNAs expression in skin fibroblasts from Down''s Syndrome (DS) patients of different ages to deter-mine the time of occurrence of abnormal splicing. The ratio of APP770 + 751 mRNA to APP695 mRNA (APP770 + 751/695) was significantly increased in the young DS group and adult DS group compared with the age-matched con-trol groups (p < 0.01, p < 0.05), but no significant increase was observed in the aged DS group compared with the age-matched control group. These findings suggest that metabolic abnormalities of the APP gene occur at a very early stage of DS, at a mean age of about 5 years. Therefore, metabolic abnormalities of the APP gene are considered to appear at a very young age also Alzheimer''s disease (AD). In this study, we confirmed that examination of the APP gene in skin fibroblasts might be useful for early diagnosis of AD.
The Role of Autoimmunity in Vascular Dementia
Authors: Tekin S. , Aykut C. , Özgün S. , Aktan S.
Published: August 2007

It is now known that immunologic mechanisms have a role in the initiation of atherosclerotic processes. No antibodies against vascular endothelial cell (VEC) specific antigenic systems have been demonstrated in the pathogenesis of small vessel (lacunar) infarcts, though autoantibodies have been detected in 80% of patients with multi-infarct dementia. We studied VEC-specific antibodies in 17 patients with a diagnosis of vascular dementia; in 17 nondemented patients with small vessel infarcts and in 16 healthy, nondemented control group patients by using the Terasaki microtoxicity method. All three groups were correlated according to known risk factors. VEC-specific antibodies were positive in 94% demented patients, whereas no antibodies were detected in patients with small vessel infarcts or in the control group. This result may suggest the existence of an immunoIogic mechanism in the etiopathogenesis of vascular dementia differing from small vessel infarcts.
Clustering of Pathological Features in Alzheimers Disease: Clinical and Neuroanatomical Aspects
Authors: Nagy Z. , Esiri M.M. , Jobst K.A. , Morris J.H. , King E.M.-F. , McDonald B. , Litchfield S. , Barnetson L.
Published: August 2007

We have analyzed the tendency of amyloid load, neuritic plaques and neurofibrillary tangles (NFT) in the hippocampus and neocortex to occur in Clusters in 49 consecutive cases of Alzheimers disease (AD). This clustering tendency of the pathology was analysed in relation to severity of clinical disease assessed within 6 months before death, duration and age at onset of disease and at death. Amyloid plaques showed only a slight tendency to cluster together while neuritic plaques and, even more, NFT were clearly clustered. A greater clustering tendency was associated with more severe clinical impairment with particularly strong correlations being found between the clustering tendency of NFT in the hippocampus and clinical memory deficit, and between the clustering tendency of NFT in the parietal neocortex and overall cognitive deficit. Neuritic plaques showed similar but less pronounced and robust correlations between clustering and cognitive status. In the hippocampus NFT clustering was also negatively correlated with age at death, but not duration of disease nor age of disease onset. We conclude that clustering characterises neuritic pathology but not diffuse amyloid deposits and significantly affects cognition. The discrepancies between the group diagnosed as AD-only and the patient group that contained all patients, including the ones with mixed pathology, lead us to believe that any additional pathology might have a signiflcant effect on the cognitive status of AD patients.
Acetylcholinesterase Activity of Synaptic Plasma Membranes during Ageing: Effect of L-Acetylcarnitine
Authors: Gorini A. , Ghigini B. , Villa R.F.
Published: August 2007

A physiopathological role for acetylcholine (ACh) was hypothesized during ageing and related neurodegenerative diseases, e.g. dementia. This research was aimed to study acetylcholinesterase (AChE) activity during development and ageing of the frontal cerebral cortex of 4-, 8-, 12-, 16-, 20- and 24-month-old rats. This study was performed on synaptic plasma membranes, the specific subcellular compartment where the enzyme is located in vivo both in control animals and after in vivo acute treatment with L-acetylcarnitine. Maximum AChE activity was unaffected by age, and L-acetylcarnitine treatment increased enzyme activity in synaptic plasma membranes of 8-month-old rats. A comprehensive analysis of these results suggests: (a) the observed alterations in protein can substantially affect neurochemical data if results are presented as specific activities per unit protein; (b) energy metabolism plays the major role in the disturbed ACh metabolism during ageing and (c) the understanding of the mode of action of L-acetylcarnitine in treatment of dementia.
Dementia of the Frontal Lobe Type Report of the Neuroimaging and Neuropsychological Results of a Case Study
Authors: Venneri A. , Grassi F. , Caffarra P.
Published: August 2007

We report the behavioural abnormalities, neuroimaging, and neuropsychological results of a 62-year-old patient, IP, who shows a clinical profile that fulfils all characteristics of dementia of frontal lobe type. The patient has been followed up over 5 years with psychometric testing. Comparing her cognitive profiles across examinations, her performance was substantially unchanged apart from behavioural disturbances and performance on frontal tasks which showed a progressive worsening. MRJ finding evidenced marked ventricular enlargement, prevalent frontal atrophy and hypertrophy of the genus of corpus callosum. SPECT investigation showed a considerable reduction of cerebral blood flow in the mesial parts of the frontal lobes, in the lateral surface of the right fronto-parietal lobe, and hypo-perfusion in the right thalamic area. The results are discussed with reference to the features (clinical and neuropsychological) which distinguish different profiles of dementia.
Sequential Changes of Tau-Site-Specific Phosphorylation during Development of Paired Helical Filaments
Authors: Kimura Takemi , Ono Tsunehiko , Takamatsu Junichi , Yamamoto Hideyuki , Ikegami Ken , Kondo Akira , Hasegawa Masato , Ihara Yasuo , Miyamoto Eishichi , Miyakawa Taihei
Published: August 2007

It has been reported that many tau sites in neurofibrillary tangles (NFT) are abnormally phosphorylated. We investigated the phosphorylation of tau in the hippocampus of nondemented patients and Alzheimer''s disease patients by immunostaining with five site-specific antibodies against phosphorylated tau. In the pretangle stage, tau in neuropil threads was phosphorylated at serines 199, 202 and 409, numbered according to the longest human tau isoform, whereas tau in some neuronal soma was phosphorylated at serines 199, 202, 409 and 422. Tau at the stage of NFT was phosphorylated at serine 396 and threonine 231 in addition to serines 199, 202, 409 and 422. In the advanced stage, tau in ghost tangles was phosphorylated mainly at serine 396. These results suggest that the phosphorylation of each site in tau differs among the maturing stages of neurofibrillary change and that abnormal phosphorylation of tau in the neuronal soma occurs at 199, 202, 409 and 422 earlier than at threonine 231 and serine 396.
Atrophy of Hippocampus in Patients with Alzheimer's Disease and Other Diseases with Memory Impairment
Authors: Horn R. , Ostertun B. , Fric M. , Solymosi L. , Steudel A. , Möller H.-J.
Published: August 2007

In clinical practice, Alzheimer''s disease (AD), multi-infarct Dementia (MID) and depression are often difficult to differentiate and may coexist. This study reports the findings of CT and MRI focused on hippocampal atrophy (HA). Quantitative volumetric MRI measurements of the hippocampus showed a reduced volume in AD patients compared to normal controls with no overlap. CT studies reported a significant widening of the hippocampal fissure in AD patients. Because volumetric measurements are not available for routine examinations, so far we are required to use the finding of hippocampal lucency in CT and dilatation of the directly visible hippocampal fissure in coronal MRI scans as criteria for HA. These findings were visually classified on a 4-point scale by 2 neuroradiologists, who had no knowledge of the clinical diagnosis. The examinations of 80 patients (42 with AD, 22 with major depression, 3 with MID, 6 classified as age-associated memory impairment (AAMI) and 8 ''normals'' with only subjective memory impairment) showed that the HA strongly supports the diagnosis of AD, by correctly identifying 95% of the AD patients and 47.8% of the patients without AD. These results suggest that CT and MRI examinations of the hippocampus are capable of demonstrating HA in clinical practice, which is strongly correlated with the diagnosis of AD.
PET Study of the M1-Agonists [11C]Xanomeline and [11C]Butylthio-TZTP in Monkey and Man
Authors: Farde Lars , Suhara Tetsuya , Halldin Christer , Nybäck Henrik , Nakashima Yoshifumi , Swahn Carl-Gunnar , Karlsson Per , Ginovart Nathalie , Bymaster Frank , Shannon Harlan , Foged Christian , Suzdak Peter D. , Sauerberg Per
Published: August 2007

Xanomeline, a substituted TZTP, is a new M1 selective muscarinic agonist in clinical trials for Alzheimer''s disease. The brain uptake of [11C]xanomeline and the analog [11C]butylthio-TZTP was examined by positron emission tomography (PET). Radioactivity accumulated most markedly in the neocortex and the striatum. Pharmacological characterization in vitro and in cynomolgus monkeys in vivo by PET indicated specific [11C]butylthio-TZTP binding to muscarinic receptors and to sigma-1 recognition sites. More than 5% of the radioactivity was in the human brain 5 min after i.v. injection of [11C]xanomeline or [11C]butylthio-TZTP. This high brain uptake may be clinically advantageous in the sense that substituted TZTP may induce central muscarinic agonist effects at a dose level for which there is a low risk of peripheral side-effects.
Psychotherapeutic Intervention in Dementia
Authors: Haupt Martin
Published: August 2007

Cognitive deficits are the most important symptoms in the diagnosis of dementia. Changes in noncognitive behavioural areas often go unrecognised at examination or are considered insignificant. These abnormalities, however, contribute most to the caregiver''s burden, interfere with the individual well-being of the patient, and are predictors of early institutionalization. Psychotherapeutic interventions in dementia complete the treatment effects achieved by psychopharmacology, cognitive enhancers, and cognitive training of target functions. Psychotherapy in dementia should be based on an interacting form of therapy, i.e. a contingency management in the natural environments of the dementia sufferer where the primary caregiver, as a mediator, takes over the main therapeutic tasks.
Cortical NMDA Receptor Properties and Membrane Fluidity Are Altered in Alzheimer's Disease
Authors: Scheuer K. , Maras A. , Gattaz W.F. , Cairns N. , Förstl H. , Müller W.E.
Published: August 2007

NMDA receptor density as measured by the specific binding of [3H]MK 801 was significantly decreased (about 20%) in the frontal but not in the parietal cortex of postmortem brain samples of Alzheimer''s disease (AD) patients (n = 21), when compared with control brains (n = 20). Membrane fluidity was not altered in the frontal cortex samples, but was slightly reduced in the parietal cortex samples of the AD patients. Since AD-specific histopathological changes (densities of senile plaques and neurofibrillary tangles) were about similar in both areas, it is concluded that the reductions of NMDA receptor densities in the frontal cortex is independent of AD-specific histopathological changes and of changes of membrane fluidity.
The Prevalence of Dementia in Down Syndrome
Authors: Johannsen Peter , Christensen Jens Erik Just , Mai Jesper
Published: August 2007

The prevalence of clinical dementia was assessed in three age groups of patients with Down syndrome in the county of Aarhus, Denmark: Group 1: 14-16 years (n = 13), group 2: 23-29 years (n = 34), group 3: 50-60 years (n = 25). Seventy-two (85%) of 85 patients participated. Caregivers were interviewed and a neurological examination was performed. An EEG was recorded in 50 patients. Definite clinical dementia was defined as an acquired and progressive decline in 4 or more out of 17 items that are considered to indicate dementia in Down syndrome. Possible dementia was considered when 1-3 items were affected. Six (24%) in group 3 had definite clinical dementia. A further 6 patients in group 3 and 2 (6%) in group 2 had possible dementia. This is the first population-based study with a clinical assessment of the prevalence of dementia in Down syndrome.