Sample records for neuroimmune-endocrine axis pathophysiological

  1. The neuroimmune-endocrine axis: pathophysiological implications for the central nervous system cytokines and hypothalamus-pituitary-adrenal hormone dynamics

    Directory of Open Access Journals (Sweden)

    J. Licinio


    Full Text Available Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are expressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms by which cytokine signaling affects the function of stress-related neuroendocrine systems are reviewed in this article.

  2. Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation. (United States)

    Langer, Arielle L; Ginzburg, Yelena Z


    Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development. © 2017 International Society for Hemodialysis.

  3. The hypothalamic–pituitary–adrenal axis and sex hormones in chronic stress and obesity: pathophysiological and clinical aspects (United States)

    Pasquali, Renato


    Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment. PMID:22612409

  4. Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic-pituitary-adrenal axis function. (United States)

    Haj-Mirzaian, A; Amiri, S; Kordjazy, N; Momeny, M; Razmi, A; Rahimi-Balaei, M; Amini-Khoei, H; Haj-Mirzaian, A; Marzban, H; Mehr, S E; Ghaffari, S H; Dehpour, A R


    The neuroimmune-endocrine dysfunction has been accepted as one of fundamental mechanisms contributing to the pathophysiology of psychiatric disorders including depression and anxiety. In this study, we aimed to evaluate the involvement of hypothalamic-pituitary-adrenal (HPA) axis, interleukin-1β, and nitrergic system in mediating the negative behavioral impacts of juvenile social isolation stress (SIS) in male mice. We also investigated the possible protective effects of lithium on behavioral and neurochemical changes in socially isolated animals. Results showed that experiencing 4-weeks of juvenile SIS provoked depressive and anxiety-like behaviors that were associated with hyper responsiveness of HPA axis, upregulation of interleukin-1β, and nitric oxide (NO) overproduction in the pre-frontal cortex and hippocampus. Administration of lithium (10 mg/kg) significantly attenuated the depressant and anxiogenic effects of SIS in behavioral tests. Lithium also restored the negative effects of SIS on cortical and hippocampal interleukin-1β and NO as well as HPA axis deregulation. Unlike the neutralizing effects of l-arginine (NO precursor), administration of l-NAME (3 mg/kg) and aminoguanidine (20 mg/kg) potentiated the positive effects of lithium on the behavioral and neurochemical profile of isolated mice. In conclusion, our results revealed that juvenile SIS-induced behavioral deficits are associated with abnormalities in HPA-immune function. Also, we suggest that alleviating effects of lithium on behavioral profile of isolated mice may be partly mediated by mitigating the negative impact of NO on HPA-immune function. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Dysregulation of the HPA axis as a core pathophysiology mediating co-morbid depression in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Xin eDu


    Full Text Available There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression, and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioural deficits and/or mood disorders. Dysregulation of the HPA axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, anti-depressant drugs such as the selective serotonin reuptake inhibitors (SSRI have been shown to alter HPA axis activity. In this review, we will summarize the current state of knowledge regarding HPA axis pathology in Alzheimer’s, Parkinson’s and Huntington’s diseases, differentiating between prodromal and later stages of disease progression where possible. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the pre-clinical evidence to better inform prospective, intervention studies.

  6. The Gut-Brain Axis and the Microbiome: Clues to Pathophysiology and Opportunities for Novel Management Strategies in Irritable Bowel Syndrome (IBS

    Directory of Open Access Journals (Sweden)

    Eamonn M.M. Quigley


    Full Text Available Irritable bowel syndrome (IBS is one of the most common of all medical disorders worldwide and, while for some it represents no more than a nuisance, for others it imposes significant negative impacts on daily life and activities. IBS is a heterogeneous disorder and may well have a number of causes which may lie anywhere from the external environment to the contents of the gut lumen and from the enteric neuromuscular apparatus and the gut immune system to the central nervous system. Consequently, the paradigm of the gut-brain axis, which includes the participation of these various factors, has proven a useful model to assist clinicians and patients alike in understanding the genesis of symptoms in IBS. Now, given the widespread interest in the gut microbiome in health and disease, in general, reports of disordered enteric bacterial communities in IBS, and experimental data to indicate that components of the gut microbiota can influence brain morphology and function, as well as behavior and cognition, this concept has been extended to encompass the microbiota-gut-brain axis. The implications of this novel concept to the assessment and management of IBS will be explored in this review.

  7. Pathophysiology of Glucocorticoid Signaling. (United States)

    Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc


    Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. The Pathophysiology of Insomnia (United States)

    Levenson, Jessica C.; Kay, Daniel B.


    Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality that is associated with difficulty falling asleep, frequent nighttime awakenings with difficulty returning to sleep, and/or awakening earlier in the morning than desired. Although progress has been made in our understanding of the nature, etiology, and pathophysiology of insomnia, there is still no universally accepted model. Greater understanding of the pathophysiology of insomnia may provide important information regarding how, and under what conditions, the disorder develops and is maintained as well as potential targets for prevention and treatment. The aims of this report are (1) to summarize current knowledge on the pathophysiology of insomnia and (2) to present a model of the pathophysiology of insomnia that considers evidence from various domains of research. Working within several models of insomnia, evidence for the pathophysiology of the disorder is presented across levels of analysis, from genetic to molecular and cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior, and self-report. We discuss the role of hyperarousal as an overarching theme that guides our conceptualization of insomnia. Finally, we propose a model of the pathophysiology of insomnia that integrates the various types of evidence presented. PMID:25846534

  9. Obesity: Pathophysiology and Intervention

    Directory of Open Access Journals (Sweden)

    Yi Zhang


    Full Text Available Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

  10. Pathophysiology of cervical myelopathy. (United States)

    Baptiste, Darryl C; Fehlings, Michael G


    Cervical myelopathy is a group of closely related disorders usually caused by spondylosis or by ossification of the posterior longitudinal ligament and is characterized by compression of the cervical spinal cord or nerve roots by varying degrees and number of levels. The decrease in diameter of the vertebral canal secondary to disc degeneration and osteophytic spurs compresses the spinal cord and nerve roots at one or several levels, producing direct damage and often secondary ischemic changes. Clinicians who treat cervical myelopathy cord injuries should have a basic understanding of the pathophysiology and the processes that are initiated after the spinal cord has been injured. Literature review. Literature review of human cervical myelopathy and clinically relevant animal models to further our understanding of the pathological mechanisms involved. The pathophysiology of cervical myelopathy involves static factors, which result in acquired or developmental stenosis of the cervical canal and dynamic factors, which involve repetitive injury to the cervical cord. These mechanical factors in turn result in direct injury to neurons and glia as well as a secondary cascade of events including ischemia, excitotoxicity, and apoptosis; a pathobiology similar to that occurring in traumatic spinal cord injury. This review summarizes some of the significant pathophysiological processes involved in cervical myelopathy.

  11. The pathophysiology of bronchiectasis

    Directory of Open Access Journals (Sweden)

    Paul T King


    Full Text Available Paul T KingDepartment of Medicine, Department of Respiratory and Sleep Medicine, Monash University, Monash Medical Centre, Melbourne, Victoria, AustraliaAbstract: Bronchiectasis is defined by permanent and abnormal widening of the bronchi. This process occurs in the context of chronic airway infection and inflammation. It is usually diagnosed using computed tomography scanning to visualize the larger bronchi. Bronchiectasis is also characterized by mild to moderate airflow obstruction. This review will describe the pathophysiology of noncystic fibrosis bronchiectasis. Studies have demonstrated that the small airways in bronchiectasis are obstructed from an inflammatory infiltrate in the wall. As most of the bronchial tree is composed of small airways, the net effect is obstruction. The bronchial wall is typically thickened by an inflammatory infiltrate of lymphocytes and macrophages which may form lymphoid follicles. It has recently been demonstrated that patients with bronchiectasis have a progressive decline in lung function. There are a large number of etiologic risk factors associated with bronchiectasis. As there is generally a long-term retrospective history, it may be difficult to determine the exact role of such factors in the pathogenesis. Extremes of age and smoking/chronic obstructive pulmonary disease may be important considerations. There are a variety of different pathogens involved in bronchiectasis, but a common finding despite the presence of purulent sputum is failure to identify any pathogenic microorganisms. The bacterial flora appears to change with progression of disease. Keywords: bronchiectasis, inflammation, obstructive lung disease, pathophysiology, pathology

  12. Pathophysiology of glucagon secretion

    International Nuclear Information System (INIS)

    Boettger, J.; Pabst, H.W.


    Pathophysiology of glucagon secretion is reviewed in brief separating hyperglucagonemic from hypoclucagonemic states. Many questions concerning the role of glucagon in diabetes mellitus and in other diseases are still unresolved. The clucagon RIA is of clinical significance in a few diseases like glucagonoma, which may present without symptoms of the 'glucagonoma syndrome', the probably very rare hyperglucagonemia and some of the spontaneous hypoglycemias. Glucagon secretion may be evaluated by the determination of fasting immunoreactive glucagon (IRG) and by appropriate function tests as stimulation with i.v. arginine and suppression with oral glucose. However, the glucagon RIA at present is not a routine method, although commercial kits are available. Many pitfalls of radioimmunological glucagon determination still exist. (orig.) [de

  13. Pathophysiology of nocturnal enuresis

    DEFF Research Database (Denmark)

    Rittig, Søren; Kamperis, Konstantinos


    The perception of the pathogenesis of enuresis has undergone marked changes over the past 30 years from a psychiatric/psychological background to a more somatic model where nighttime urine production and bladder capacity are main components together with an arousal dysfunction that prevents...... that dysfunction of the intrinsic circadian regulation located in the suprachiasmatic nucleus results in dysfunction of one or more of the brainstem centers involved in AVP secretion, arousal function, bladder control, and blood pressure regulation. Furthermore, nocturnal enuresis has a strong genetic influence...... that in some families present as autosomal dominant inheritance with high degree of penetrance. Linkage to several chromosomal areas have been confirmed in such families although a specific causative enuresis gene has not yet been identified. In conclusion, our understanding of enuresis pathophysiology has...

  14. Pathophysiology of Cushing's disease. (United States)

    Fehm, H L; Voigt, K H


    The term Cushing's disease is applied to those cases of Cushing's syndrome in which hypercortisolism is secondary to inappropriate secretion of ACTH by the pituitary. Studies on control of ACTH secretion in these patients reveal: (a) that the episodic secretion of ACTH is similar to the normal; however, frequency and amplitude of the secretory episodes lack the normal circadian rhythm; (b) that ACTH release can be stimulated by vasopressin and metyrapone in a normal or above-normal manner; and (c) that it can be suppressed by large doses of corticosteroids. When the dynamic aspects of the ACTH response to corticosteroid administration are studied, it appears that the normally negative differential feedback mechanism is converted into a positive one, whereas the delayed, integral mechanism is undisturbed. Patients with Cushing's disease in the presence of obvious pituitary tumors cannot be distinguished from those without pituitary tumors by studying only the pituitary function. All these and other well-known facts would favor the concept that ACTH secretion in Cushing's disease is under hypothalamic control whether or not a pituitary tumor is present. Moreover, there are observations that suggest that brain centers superior to the hypophysiotropic area of the hypothalamus are involved in the pathophysiology of Cushing's disease. This concept has led to the discovery of neurotropic drugs that are able to induce complete remission of Cushing's syndrome in a cerain percentage of patients. In some patients with severe psychiatric diseases, neuroendocrine abnormalities are present that resemble closely those characteristic for Cushing's disease. With the most refined neuroradiological methods, pituitary microadenomas are demonstrable in approximately 70% of patients with Cushing's disease, and this number compares well with those of earlier autopsy findings (70 to 80%). In a small number of patients (4 to 10%), these tumors are large and can easily be detected by

  15. [Functional pathophysiology of consciousness]. (United States)

    Jellinger, Kurt A


    from important somatic and sensory pathways and acts as a control system of neuronal activities of the cerebral cortex. The principal function of the ARAS is to focus our alertness on specific stimuli or internal processes, which run via complex neuronal cell groups and numerous neurotransmitters that influence various aspects of consciousness and wakefulness. Stimulation of the ARAS produces an arousal reaction as the electric correlate of consciousness; its destruction causes coma and related states. The highest level are cortical (prefrontal and association) networks for recognition, motor activity, longterm memory and attention, the left hemisphere being considered as the dominant one. Different levels of consciousness are distinguished: 1. hyperalertness, 2. alertness (normal state of wakefulness), 3. somnolence or lethargy, 4. obtundation with tendency to fall asleep, 5. stupor, 6. coma and its subtypes, like akinetic mutism, apallic syndrome or persistent vegative state, locked-in syndrome, delirium, and catatonia. They are caused by damages in various functional levels of the brain, by psychogenic factors or experimentally, and are accompanied by characteristic neurological and psychiatric disorders. The relevant morphological lesions can be detected by electrophysiological and imaging studies. The bases of functional anatomy and pathophysiology of consciousness, its cognitive aspects and its major disorders, their causes and functional substrates with reference to sleep and both spontaneous and iatrogenic disorders of consciousness are critically summarized.

  16. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.


    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the

  17. Pathophysiology of gastroesophageal reflux disease

    NARCIS (Netherlands)

    Boeckxstaens, Guy E.; Rohof, Wout O.


    Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases in the Western world, with typical symptoms, such as heartburn, regurgitation, or retrosternal pain, reported by 15% to 20% of the general population. The pathophysiology of GERD is multifactorial. Our understanding

  18. Gas embolism: pathophysiology and treatment

    NARCIS (Netherlands)

    van Hulst, Robert A.; Klein, Jan; Lachmann, Burkhard


    Based on a literature search, an overview is presented of the pathophysiology of venous and arterial gas embolism in the experimental and clinical environment, as well as the relevance and aims of diagnostics and treatment of gas embolism. The review starts with a few historical observations and

  19. Pathophysiological relationships between heart failure and depression and anxiety. (United States)

    Chapa, Deborah W; Akintade, Bimbola; Son, Heesook; Woltz, Patricia; Hunt, Dennis; Friedmann, Erika; Hartung, Mary Kay; Thomas, Sue Ann


    Depression and anxiety are common comorbid conditions in patients with heart failure. Patients with heart failure and depression have increased mortality. The association of anxiety with increased mortality in patients with heart failure is not established. The purpose of this article is to illustrate the similarities of the underlying pathophysiology of heart failure, depression, and anxiety by using the Biopsychosocial Holistic Model of Cardiovascular Health. Depression and anxiety affect biological processes of cardiovascular function in patients with heart failure by altering neurohormonal function via activation of the hypothalamic-pituitary-adrenal axis, autonomic dysregulation, and activation of cytokine cascades and platelets. Patients with heart failure and depression or anxiety may exhibit a continued cycle of heart failure progression, increased depression, and increased anxiety. Understanding the underlying pathophysiological relationships in patients with heart failure who experience comorbid depression and/or anxiety is critical in order to implement appropriate treatments, educate patients and caregivers, and educate other health professionals.

  20. Modern iron replacement therapy: clinical and pathophysiological insights. (United States)

    Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa


    Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

  1. Assessing pathophysiology of cancer anorexia. (United States)

    Laviano, Alessandro; Koverech, Angela; Seelaender, Marilia


    Cancer anorexia is a negative prognostic factor and is broadly defined as the loss of the interest in food. However, multiple clinical domains contribute to the phenotype of cancer anorexia. The characterization of the clinical and molecular pathophysiology of cancer anorexia may enhance the efficacy of preventive and therapeutic strategies. Clinical trials showed that cancer anorexia should be considered as an umbrella encompassing different signs and symptoms contributing to appetite disruption in cancer patients. Loss of appetite, early satiety, changes in taste and smell are determinants of cancer anorexia, whose presence should be assessed in cancer patients. Interestingly, neuronal correlates of cancer anorexia-related symptoms have been revealed by brain imaging techniques. The pathophysiology of cancer anorexia is complex and involves different domains influencing eating behavior. Limiting the assessment of cancer anorexia to questions investigating changes in appetite may impede correct identification of the targets to address.

  2. The pathophysiology of Peyronie's disease. (United States)

    El-Sakka, Ahmed I; Salabas, Emre; Dinçer, Murat; Kadioglu, Ates


    To review the contemporary knowledge of the pathophysiology of Peyronie's disease (PD). Medline was searched for papers published in English from 2000 to March 2013, using the keywords 'Peyronie's disease' and 'pathophysiology'. More than 300 relevant articles were identified for the purpose of this review. Unfortunately only a few studies had a high level of evidence, and the remaining studies were not controlled in their design. Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. This would provide the means to devise a possible gene therapy for this devastating condition. We discuss present controversies and new discoveries related to the pathophysiology of this condition. PD is one of the most puzzling diseases in urology. The pathogenesis remains uncertain and there is still controversy about the best management. The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease.

  3. Molecular pathophysiology of cerebral edema (United States)

    Gerzanich, Volodymyr; Simard, J Marc


    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

  4. Narcolepsy: Pathophysiology and Neuropsychological Changes

    Directory of Open Access Journals (Sweden)

    Angela Naumann


    Full Text Available Narcolepsy is now recognized as a distinctive disorder with specific pathophysiology and neurochemical abnormalities. Findings on the role of the neuropeptide hypocretin are opening new avenues of research and new strategies for therapy. Recently, neuropsychological and electrophysiological studies have provided evidence for reduced memory performance on standard memory tests in addition to subjective complaints of forgetfulness which may be related to changes in attentional processing. Further studies are, however, necessary to clarify the neuropsychological profile in narcolepsy. This review focuses on the recent advances in understanding narcolepsy.

  5. The Pathophysiology of Eosinophilic Esophagitis

    Directory of Open Access Journals (Sweden)

    Daniel Avi Lemberg


    Full Text Available Eosinophilic Esophagitis (EoE is an emerging disease characterised by esophageal eosinophilia (>15eos/hpf, lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with TGF-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.

  6. Fisiopatologia da enxaqueca Migraine pathophysiology

    Directory of Open Access Journals (Sweden)



    Full Text Available A fisiopatologia da enxaqueca ainda não foi completamente elucidada. As principais estruturas envolvidas parecem ser o sistema nervoso central (córtex e tronco cerebral, o sistema trigeminovascular e os vasos correspondentes, outras fibras autonômicas que inervam estes vasos, e os vários agentes vasoativos locais, como a SP, CGRP, NO, VIP, NPY, ACh, NA, NKA, entre outros. A depressão alastrante é o fenômeno neurológico que provavelmente justifica achados experimenais e clínicos na enxaqueca. Ela tem velocidade de propagação semelhante à aura, ativa o núcleo espinhal do trigêmeo e está relacionada à liberação de CGRP e NO. Alterações circulatórias detectadas por métodos complementares reforçam o papel da depressão alastrante. A identificação de anormalidades em pelo menos três loci (cromossomas 19 e 1 na enxaqueca hemiplégica familiar ocorreu recentemente. Elas estão relacionadas a anormalidades nos canais de cálcio voltagem dependentes tipo P/Q, específicos do sistema nervoso central, que regulam a liberação de vários neurotransmissores, incluindo possivelmente a serotonina. A exemplo de outras anormalidades neurológicas paroxísticas que resultam da hiperexcitabilidade da membrana plasmática, é possível que a enxaqueca ocorra devido a uma desordem de canais iônicos.The pathophysiology of migraine is not yet fully understood. The most important structures involved seem to be the central nervous system (cortex and brain stem, the trigeminovascular system and related cranial arteries, other autonomic fibres innervating such vessels, and various local vasoactive agents, including SP, CGRP, NO, VIP, NPY, ACh, NA, NKA, among others. The spreading depression phenomenon may explain clinical as well experimental findings in migraine. Its propagation velocity mirrors what is found in clinical aura, it may activate the spinal trigeminal nucleus and may induce CGRP and NO release. Circulatory changes detected with

  7. Understanding changes in cardiovascular pathophysiology. (United States)

    Chummun, Harry

    Cardiovascular pathophysiological changes, such as hypertension and enlarged ventricles, reflect the altered functions of the heart and its circulation during ill-health. This article examines the normal and altered anatomy of the cardiac valves, the contractile elements and enzymes of the myocardium, the significance of the different factors associated with cardiac output, and the role of the autonomic nervous system in the heart beat. It also explores how certain diseases alter these functions and result in cardiac symptoms. Nurses can benefit from knowledge of these specific changes, for example, by being able to ask relevant questions in order to ascertain the nature of a patients condition, by being able to take an effective patient history and by being able to read diagnostic results, such as electrocardiograms and cardiac enzyme results. All this will help nurses to promote sound cardiac care based on a physiological rationale.

  8. Pathophysiology of MDS: genomic aberrations. (United States)

    Ichikawa, Motoshi


    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  9. Preeclampsia: from Pathophysiology to Treatment

    Directory of Open Access Journals (Sweden)

    Kaculini Enton


    Full Text Available Preeclampsia is a multisystem disorder unique to human pregnancy and is its most common glomerular complication. It occurs in 2% to 8% of pregnancies and is a major contributor to maternal mortality worldwide. Although the pathophysiology of this syndrome is not fully understood, many pathogenetic mechanisms are involved in this disorder. The role of the placenta is crucial in the development of this disorder. Some pathogenetic mechanisms involved in this disease comprise defective deep placentation, autoantibodies to type-1 angiotensin II receptor, endothelial dysfunction, oxidative stress, platelet and thrombin activation, intravascular inflammation, and the imbalance between angiogenic and antiangiogenic factors which is thought to be one of the most crucial mechanisms. Further understanding of the full picture could enhance our current knowledge of the pathogenesis of preeclampsia and improve its treatment. Thus, based on specific biomarkers the diagnosis and subclassification of preeclampsia might be more accurate in identifying patients at risk, monitoring disease progression and providing effective interventions

  10. Tuberculosis 2: Pathophysiology and microbiology of pulmonary ...

    African Journals Online (AJOL)


    Aug 1, 2005 ... February 2013 Downloaded from MaIN arTIClES. 10. Tuberculosis 2: Pathophysiology and microbiology of pulmonary tuberculosis. Robert L. Serafino Wania MBBS, MrCP, MSc (Trop Med). Pathophysiology. Inhalation of Mycobacterium tuberculosis leads to one of.

  11. Pathophysiologic mechanisms of biomedical nanomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Liming, E-mail:; Chen, Chunying, E-mail:


    Nanomaterials (NMs) have been widespread used in biomedical fields, daily consuming, and even food industry. It is crucial to understand the safety and biomedical efficacy of NMs. In this review, we summarized the recent progress about the physiological and pathological effects of NMs from several levels: protein-nano interface, NM-subcellular structures, and cell–cell interaction. We focused on the detailed information of nano-bio interaction, especially about protein adsorption, intracellular trafficking, biological barriers, and signaling pathways as well as the associated mechanism mediated by nanomaterials. We also introduced related analytical methods that are meaningful and helpful for biomedical effect studies in the future. We believe that knowledge about pathophysiologic effects of NMs is not only significant for rational design of medical NMs but also helps predict their safety and further improve their applications in the future. - Highlights: • Rapid protein adsorption onto nanomaterials that affects biomedical effects • Nanomaterials and their interaction with biological membrane, intracellular trafficking and specific cellular effects • Nanomaterials and their interaction with biological barriers • The signaling pathways mediated by nanomaterials and related biomedical effects • Novel techniques for studying translocation and biomedical effects of NMs.

  12. Pathophysiologic mechanisms of biomedical nanomaterials

    International Nuclear Information System (INIS)

    Wang, Liming; Chen, Chunying


    Nanomaterials (NMs) have been widespread used in biomedical fields, daily consuming, and even food industry. It is crucial to understand the safety and biomedical efficacy of NMs. In this review, we summarized the recent progress about the physiological and pathological effects of NMs from several levels: protein-nano interface, NM-subcellular structures, and cell–cell interaction. We focused on the detailed information of nano-bio interaction, especially about protein adsorption, intracellular trafficking, biological barriers, and signaling pathways as well as the associated mechanism mediated by nanomaterials. We also introduced related analytical methods that are meaningful and helpful for biomedical effect studies in the future. We believe that knowledge about pathophysiologic effects of NMs is not only significant for rational design of medical NMs but also helps predict their safety and further improve their applications in the future. - Highlights: • Rapid protein adsorption onto nanomaterials that affects biomedical effects • Nanomaterials and their interaction with biological membrane, intracellular trafficking and specific cellular effects • Nanomaterials and their interaction with biological barriers • The signaling pathways mediated by nanomaterials and related biomedical effects • Novel techniques for studying translocation and biomedical effects of NMs

  13. TFOS DEWS II pathophysiology report. (United States)

    Bron, Anthony J; de Paiva, Cintia S; Chauhan, Sunil K; Bonini, Stefano; Gabison, Eric E; Jain, Sandeep; Knop, Erich; Markoulli, Maria; Ogawa, Yoko; Perez, Victor; Uchino, Yuichi; Yokoi, Norihiko; Zoukhri, Driss; Sullivan, David A


    The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjögren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The pathophysiology of heart failure. (United States)

    Kemp, Clinton D; Conte, John V


    Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome. (United States)

    Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A


    Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.

  16. Stroke MRI: pathophysiology, potential and perspectives

    International Nuclear Information System (INIS)

    Fiehler, J.; Kucinski, T.; Zeumer, H.


    Magnetic resonance imaging (MRT) is increasingly utilized as the primary imaging modality in major stroke centers. The ability to depict several aspects of individual pathophysiology makes the use of MRI in stroke both attractive and complex. Profound knowledge of the pathophysiology of the imaging findings is crucial for a rational diagnostic workup. The pathophysiology of MRI in stroke will be reviewed considering recent experiences in clinical application, and the potential of stroke MRI will be assessed. Further perspectives like application of 'blood oxygen level dependent' (BOLD) and the use of multiparametric prediction maps will be discussed. (orig.) [de

  17. Chemical sensitivity: pathophysiology or pathopsychology? (United States)

    Genuis, Stephen J


    symptoms in some cases. Sustained resolution of the CS state occurs after successful elimination of the accrued body burden of toxicants through natural mechanisms of toxicant bioelimination and/or interventions of clinical detoxification. Despite extensive clinical evidence to support the veracity of this clinical state, many members of the medical community are reluctant to accept this condition as a pathophysiologic disorder. The emerging problem of ubiquitous adverse toxicant exposures in modern society has resulted in escalating numbers of individuals developing a CS disorder. As usual in medical history, iconoclastic ideas and emerging evidence regarding novel disease mechanisms, such as the pathogenesis of CS, have been met with controversy, resistance, and sluggish knowledge translation. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

  18. Thalassemia: Pathophysiology and management. Part A

    International Nuclear Information System (INIS)

    Fucharoen, S.; Rowley, P.T.; Paul, N.W.


    This book contains papers divided among the following sections: molecular biology and pathogenesis; pathophysiology - molecular and cellular; clinical manifestations and hematologic changes; cardiopulmonary defects and platelet function; hormones and minerals; and infection and immunology

  19. A vicious circle in chronic lymphoedema pathophysiology?

    DEFF Research Database (Denmark)

    Cucchi, F; Rossmeislova, L; Simonsen, L


    Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These event....... Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle....

  20. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome (United States)

    Lee, Kang Nyeong; Lee, Oh Young


    Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 1014 cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS. PMID:25083061

  1. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome. (United States)

    Lee, Kang Nyeong; Lee, Oh Young


    Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10(14) cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.

  2. Role of phospholipids in the pathophysiology of the gut-liver axis

    NARCIS (Netherlands)

    Petruzzelli, M.


    Phospholipids represent essential components of bile. Together with bile acids and cholesterol, phospholipids form “mixed micelles”. If sufficient amounts of phospholipids are available, no simple bile acid micelles are present, with prevention of bile acid toxicity and cholesterol crystallization.

  3. The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations. (United States)

    Berryman, Darlene E; Glad, Camilla A M; List, Edward O; Johannsson, Gudmundur


    Obesity has become one of the most common medical problems in developed countries, and this disorder is associated with high incidences of hypertension, dyslipidaemia, cardiovascular disease, type 2 diabetes mellitus and specific cancers. Growth hormone (GH) stimulates the production of insulin-like growth factor 1 in most tissues, and together GH and insulin-like growth factor 1 exert powerful collective actions on fat, protein and glucose metabolism. Clinical trials assessing the effects of GH treatment in patients with obesity have shown consistent reductions in total adipose tissue mass, in particular abdominal and visceral adipose tissue depots. Moreover, studies in patients with abdominal obesity demonstrate a marked effect of GH therapy on body composition and on lipid and glucose homeostasis. Therefore, administration of recombinant human GH or activation of endogenous GH production has great potential to influence the onset and metabolic consequences of obesity. However, the clinical use of GH is not without controversy, given conflicting results regarding its effects on glucose metabolism. This Review provides an introduction to the role of GH in obesity and summarizes clinical and preclinical data that describe how GH can influence the obese state.

  4. Pathophysiology of the GH/IGF-1 axis : long-term consequences on joints and bone

    NARCIS (Netherlands)

    Claessen, Kim Maria Johanna Aldegonda


    In this thesis, a number of observations are described in acromegaly patients with cured or biochemically well-controlled disease during long-term follow-up. These observations focus on the long-term consequences of the disease on joints and bone. In addition, we investigated the role of the Growth

  5. Triple axis spectrometers

    International Nuclear Information System (INIS)

    Clausen, K.N.


    Conventional triple-axis neutron spectroscopy was developed by Brockhouse over thirty years ago' and remains today a versatile and powerful tool for probing the dynamics of condensed matter. The original design of the triple axis spectrometer is technically simple and probes momentum and energy space on a point-by-point basis. This ability to systematically probe the scattering function in a way which only requires a few angles to be moved under computer control and where the observed data in general can be analysed using a pencil and graph paper or a simple fitting routine, has been essential for the success of the method. These constraints were quite reasonable at the time the technique was developed. Advances in computer based data acquisition, neutron beam optics, and position sensitive area detectors have been gradually implemented on many triple axis spectrometer spectrometers, but the full potential of this has not been fully exploited yet. Further improvement in terms of efficiency (beyond point by point inspection) and increased sensitivity (use of focusing optics whenever the problem allows it) could easily be up to a factor of 10-20 over present instruments for many problems at a cost which is negligible compared to that of increasing the flux of the source. The real cost will be in complexity - finding the optimal set-up for a given scan and interpreting the data as the they are taken. On-line transformation of the data for an appropriate display in Q, ω space and analysis tools will be equally important for this task, and the success of these new ideas will crucially depend on how well we solve these problems. (author)

  6. Vertical axis wind turbines (United States)

    Krivcov, Vladimir [Miass, RU; Krivospitski, Vladimir [Miass, RU; Maksimov, Vasili [Miass, RU; Halstead, Richard [Rohnert Park, CA; Grahov, Jurij [Miass, RU


    A vertical axis wind turbine is described. The wind turbine can include a top ring, a middle ring and a lower ring, wherein a plurality of vertical airfoils are disposed between the rings. For example, three vertical airfoils can be attached between the upper ring and the middle ring. In addition, three more vertical airfoils can be attached between the lower ring and the middle ring. When wind contacts the vertically arranged airfoils the rings begin to spin. By connecting the rings to a center pole which spins an alternator, electricity can be generated from wind.

  7. Vertical axis wind turbine

    International Nuclear Information System (INIS)

    Obretenov, V.; Tsalov, T.; Chakarov, T.


    In recent years, the interest in wind turbines with vertical axis noticeably increased. They have some important advantages: low cost, relatively simple structure, reliable packaging system of wind aggregate long period during which require no maintenance, low noise, independence of wind direction, etc.. The relatively low efficiency, however, makes them applicable mainly for small facilities. The work presents a methodology and software for approximately aerodynamic design of wind turbines of this type, and also analyzed the possibility of improving the efficiency of their workflow

  8. Imaging Alzheimer's disease pathophysiology with PET

    Directory of Open Access Journals (Sweden)

    Lucas Porcello Schilling

    Full Text Available ABSTRACT Alzheimer's disease (AD has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI, and dementia stages. Positron emission tomography (PET associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD.

  9. Current concepts in the pathophysiology of glaucoma

    Directory of Open Access Journals (Sweden)

    Agarwal Renu


    Full Text Available Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. A better understanding of the pathophysiological mechanisms involved in the onset and progression of glaucomatous optic neuropathy is crucial in the development of better therapeutic options. This review is an effort to summarize the current concepts in the pathophysiology of glaucoma so that newer therapeutic targets can be recognized. The literature available in the National Medical Library and online Pubmed search engine was used for literature review.

  10. Dry eye disease: pathophysiology, classification, and diagnosis. (United States)

    Perry, Henry D


    Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface that results in eye discomfort, visual disturbance, and often ocular surface damage. Although recent research has made progress in elucidating DED pathophysiology, currently there are no uniform diagnostic criteria. This article discusses the normal anatomy and physiology of the lacrimal functional unit and the tear film; the pathophysiology of DED; DED etiology, classification, and risk factors; and DED diagnosis, including symptom assessment and the roles of selected diagnostic tests.

  11. Pathophysiology, Evaluation, and Treatment of Bloating (United States)

    Gabbard, Scott L.; Crowell, Michael D.


    Abdominal bloating is commonly reported by men and women of all ages. Bloating occurs in nearly all patients with irritable bowel syndrome, and it also occurs in patients with other functional and organic disorders. Bloating is frequently disturbing to patients and frustrating to clinicians, as effective treatments are limited and are not universally successful. Although the terms bloating and abdominal distention are often used interchangeably, these symptoms likely involve different pathophysiologic processes, both of which are still not completely understood. The goal of this paper is to review the pathophysiology, evaluation, and treatment of bloating and abdominal distention. PMID:22298969

  12. Retinal vein occlusion: pathophysiology and treatment options


    Karia, Niral


    Niral KariaDepartment of Ophthalmology, Southend Hospital, Prittlewell Chase, Westcliff on Sea, Essex, United KingdomAbstract: This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms.Keywords: central, hemispheric, branch, retinal vein occlusion, visual loss

  13. Pathophysiology of diurnal drooling in Parkinson's disease

    NARCIS (Netherlands)

    Kalf, J.G.; Munneke, M.; Engel-Hoek, L. van den; Swart, B.J.M. de; Borm, G.F.; Bloem, B.R.; Zwarts, M.J.


    Drooling is an incapacitating feature of Parkinson's disease. Better pathophysiological insights are needed to improve treatment. In this study, we tested the hypothesis that the cause of drooling is multifactorial. We examined 15 patients with Parkinson's disease with distinct diurnal saliva loss

  14. Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment. (United States)

    Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R


    Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression.

  15. Targeting the gut-liver axis in cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn S; Havelund, Troels; Krag, Aleksander


    The gut-liver axis in cirrhosis and portal hypertension is gaining increasing attention as a key pathophysiological mechanism responsible for progression of liver failure and development of complications such as spontaneous infections and hepatocellular carcinoma. Antibiotics and non-selective β......-blockers (NSBB) intercept this axis and each drug has proven efficacy in clinical trials. A synergistic effect is a hitherto unproven possibility. There is an increasing body of evidence supporting improved outcome with expanded use of NSBB and antibiotic therapy beyond current indications. This review addresses...... the issue of pharmacological treatment of cirrhosis and portal hypertension with antibiotics and NSBB. We discuss their mechanism of action and suggest that combining the two treatment modalities could potentially reduce the risk of complications....

  16. Pathophysiology of spontaneous venous gas embolism (United States)

    Lambertsen, C. J.; Albertine, K. H.; Pisarello, J. B.; Flores, N. D.


    The use of controllable degrees and durations of continuous isobaric counterdiffusion venous gas embolism to investigate effects of venous gas embolism upon blood, cardiovascular, and respiratory gas exchange function, as well as pathological effects upon the lung and its microcirculation is discussed. Use of N2O/He counterdiffusion permitted performance of the pathophysiologic and pulmonary microstructural effects at one ATA without hyperbaric or hypobaric exposures.

  17. Otosclerosis update (1). Pathophysiology and diagnosis

    International Nuclear Information System (INIS)

    Ogawa, Kaoru; Inoue, Yasuhiro; Saito, Hideyuki; Kanzaki, Sho; Okamoto, Yasuhide; Mizutari, Kunio; Suzuki, Takashi; Oishi, Naoki


    Otosclerosis is an otological disease that typicaly causes conductive hearing loss. This disease is an important clinical entity since hearing impairment in these case can be dramatically improved by surgery. In this review paper, we review recent research into the pathophysiology of otosclerosis and summarize clinical features, audiometry and diagnostic imaging examinations in 160 ears with otosclerosis that we treated surgically in our department. (author)

  18. [Irritable bowel syndrome: New pathophysiological hypotheses and practical issues]. (United States)

    Duboc, H; Dior, M; Coffin, B


    In 2015, besides the fact that it still fills the gastroenterologists' offices and impairs patient's quality of life, the irritable bowel syndrome has considerably evolved on several points. The pathophysiology is now organized around a consensual hypothesis called the "brain-gut axis", which gather all the influences of peripheral factors as gut microbiota or local serotonin secretion, on the central pain perception, contributing to visceral hypersensitivity and transit modifications. About the diagnosis, the key message is "avoid over-prescription" of additional tests, and reminds that a positive clinical diagnosis based on Rome III criteria is possible after the elimination of simple clinical warning signs. Finally, the food component, a neglected and historical claim of patients, finally finds a strong scientific rational, with a diet low in fermentable sugar and polyols, that gives positive and reproducible results. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  19. The pathophysiology of lifelong premature ejaculation (United States)


    For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of

  20. Diagnosing the pathophysiologic mechanisms of nocturnal polyuria. (United States)

    Goessaert, An-Sofie; Krott, Louise; Hoebeke, Piet; Vande Walle, Johan; Everaert, Karel


    Diagnosis of nocturnal polyuria (NP) is based on a bladder diary. Addition of a renal function profile (RFP) for analysis of concentrating and solute-conserving capacity allows differentiation of NP pathophysiology and could facilitate individualized treatment. To map circadian rhythms of water and solute diuresis by comparing participants with and without NP. This prospective observational study was carried out in Ghent University Hospital between 2011 and 2013. Participants with and without NP completed a 72-h bladder dairy. RFP, free water clearance (FWC), and creatinine, solute, sodium, and urea clearance were measured for all participants. The study participants were divided into those with (n=77) and those without (n=35) NP. The mean age was 57 yr (SD 16 yr) and 41% of the participants were female. Compared to participants without NP, the NP group exhibited a higher diuresis rate throughout the night (p=0.015); higher FWC (p=0.013) and lower osmolality (p=0.030) at the start of the night; and persistently higher sodium clearance during the night (p<0.001). The pathophysiologic mechanism of NP was identified as water diuresis alone in 22%, sodium diuresis alone in 19%, and a combination of water and sodium diuresis in 47% of the NP group. RFP measurement in first-line NP screening to discriminate between water and solute diuresis as pathophysiologic mechanisms complements the bladder diary and could facilitate optimal individualized treatment of patients with NP. We evaluated eight urine samples collected over 24h to detect the underlying problem in NP. We found that NP can be attributed to water or sodium diuresis or a combination of both. This urinalysis can be used to adapt treatment according to the underlying mechanism in patients with bothersome consequences of NP, such as nocturia and urinary incontinence. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  1. Pathophysiology of osteoporosis: new mechanistic insights. (United States)

    Armas, Laura A G; Recker, Robert R


    Understanding of the pathophysiology of osteoporosis has evolved to include compromised bone strength and skeletal fragility caused by several factors: (1) defects in microarchitecture of trabeculae, (2) defective intrinsic material properties of bone tissue, (3) defective repair of microdamage from normal daily activities, and (4) excessive bone remodeling rates. These factors occur in the context of age-related bone loss. Clinical studies of estrogen deprivation, antiresorptives, mechanical loading, and disuse have helped further knowledge of the factors affecting bone quality and the mechanisms that underlie them. This progress has led to several new drug targets in the treatment of osteoporosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Pathophysiology of the anorexia of aging. (United States)

    Morley, John E


    Anorexia represents a major problem for older persons leading to weight loss, sarcopenia, functional decline, and mortality. There is increasing information on the pathophysiological mechanisms that lead to anorexia. Increasing evidence has shown the importance of gastrointestinal hormones (ghrelin, cholecystokinin, and glucagon-like peptide) and adipokines in producing the anorexia of aging. Numerous neurotransmitters have been shown to be involved in this aging anorexia, but evidence in humans is lacking. The early recognition of anorexia of aging is important to allow intervention and prevent functional deterioration in older persons. Screening tests for anorexia have been developed. New approaches to managing anorexia are being tested.

  3. Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management. (United States)

    Taeb, Abdalsamih M; Hooper, Michael H; Marik, Paul E


    Sepsis is a clinical syndrome that results from the dysregulated inflammatory response to infection that leads to organ dysfunction. The resulting losses to society in terms of financial burden, morbidity, and mortality are enormous. We provide a review of sepsis, its underlying pathophysiology, and guidance for diagnosis and management of this common disease. Current established treatments include appropriate antimicrobial agents to target the underlying infection, optimization of intravascular volume to improve stroke volume, vasopressors to counteract vasoplegic shock, and high-quality supportive care. Appropriate implementation of established treatments combined with novel therapeutic approaches promises to continue to decrease the impact of this disease.

  4. 95th Anniversary of Pathophysiology in Croatia. (United States)

    Kovač, Zdenko


    University level of Pathophysiology research and teaching in Croatia had started with the third year of Medical School of Zagreb in academic year 1919./20. Ever since, despite historical changes of the main university stake holder, the state of Croatia, Department of Pathophysiology development progressed and has made visible academic achievements, with a broader effect in medical community. The first 95 years of academic tradition and major achievements are shortly described in this paper. Professor Miroslav Mikuličić envisioned Pathophysiology in close relations with Pharmacology and made the pioneering steps of establishing the "double" department at Šalata. His group was academically very pro-active, with strong international scientific participation and recruitment of professionals. The group published the first voluminous textbook of Pharmacology and Pathophysiology, in Croatian. In fifties, professor Pavao Sokolić established clinical pathophysiology within the Hospital Centre at Rebro. Out of "double" department two new departments were founded, the Pathophysiology one was completed with the clinical ward. That institutional move from Šalata hill to the Rebro hill was a necessary gigantic step and a prerequisite for the proper further development. It was in accordance with the concept of the Mikuličić's program of Pathophysiology from 1917. Pavao Sokolić has been remembered for his visions, deep insights into etiopathogenesis, ability to transfer knowledge and friendly relations to students. Sharp intellectual power, emanating charisma, academic erudition and unique clinical competencies made the legendary image of the "Teacher" - as students used to refer to him with admiration. He was second to no one when complex patient issues were to be resolved. Clinical Hospital Centre Zagreb and his Department at Rebro have become a referral point to whom to go to despair. Students recognized in their Teacher the landmark of Croatian medicine, which made a

  5. Lafora disease: epidemiology, pathophysiology and management.

    LENUS (Irish Health Repository)

    Monaghan, Thomas S


    Lafora disease is a rare, fatal, autosomal recessive, progressive myoclonic epilepsy. It may also be considered as a disorder of carbohydrate metabolism because of the formation of polyglucosan inclusion bodies in neural and other tissues due to abnormalities of the proteins laforin or malin. The condition is characterized by epilepsy, myoclonus and dementia. Diagnostic findings on MRI and neurophysiological testing are not definitive and biopsy or genetic studies may be required. Therapy in Lafora disease is currently limited to symptomatic management of the epilepsy, myoclonus and intercurrent complications. With a greater understanding of the pathophysiological processes involved, there is justified hope for future therapies.

  6. Pathophysiology of muscle contractures in cerebral palsy. (United States)

    Mathewson, Margie A; Lieber, Richard L


    Patients with cerebral palsy present with a variety of adaptations to muscle structure and function. These pathophysiologic symptoms include functional deficits such as decreased force production and range of motion, in addition to changes in muscle structure such as decreased muscle belly size, increased sarcomere length, and altered extracellular matrix structure and composition. On a cellular level, patients with cerebral palsy have fewer muscle stem cells, termed satellite cells, and altered gene expression. Understanding the nature of these changes may present opportunities for the development of new muscle treatment therapies. Published by Elsevier Inc.

  7. Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm Pain. (United States)

    Kortlever, Joost T P; Janssen, Stein J; Molleman, Jeroen; Hageman, Michiel G J S; Ring, David


    Nonspecific symptoms are common in all areas of medicine. Patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. We therefore asked the following questions: 1) Which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific arm pain to eventual identification of discrete pathophysiology that corresponds with symptoms? 2) What is the percentage of patients eventually diagnosed with discrete pathophysiology, what are those pathologies, and do they account for the symptoms? We evaluated 634 patients with an isolated diagnosis of nonspecific upper extremity pain to see if discrete pathophysiology was diagnosed on subsequent visits to the same hand surgeon, a different hand surgeon, or any physician within our health system for the same pain. There were too few patients with discrete pathophysiology at follow-up to address the primary study question. Definite discrete pathophysiology that corresponded with the symptoms was identified in subsequent evaluations by the index surgeon in one patient (0.16% of all patients) and cured with surgery (nodular fasciitis). Subsequent doctors identified possible discrete pathophysiology in one patient and speculative pathophysiology in four patients and the index surgeon identified possible discrete pathophysiology in four patients, but the five discrete diagnoses accounted for only a fraction of the symptoms. Nonspecific diagnoses are not harmful. Prospective randomized research is merited to determine if nonspecific, descriptive diagnoses are better for patients than specific diagnoses that imply pathophysiology in the absence of discrete verifiable pathophysiology.

  8. Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA axis

    Directory of Open Access Journals (Sweden)

    Mello Andrea de Abreu Feijó de


    Full Text Available Over the past 50 years, relationships between stress and the neurobiological changes seen in psychiatric disorders have been well-documented. A major focus of investigations in this area has been the role of the hypothalamic-pituitary-adrenal (HPA axis, both as a marker of stress response and as a mediator of additional downstream pathophysiologic changes. This review examines the emerging literature concerning the relationship between stress, HPA axis function, and depression, as well as the role of early life stress as an important risk factor for HPA axis dysregulation. The more recent studies reviewed suggest that the prominence of HPA axis hyperactivity in adults with depressive and anxiety disorders may constitute a link between the occurrence of adversity in childhood and the development of adult psychopathology

  9. Human Pathophysiological Adaptations to the Space Environment

    Directory of Open Access Journals (Sweden)

    Gian C. Demontis


    Full Text Available Space is an extreme environment for the human body, where during long-term missions microgravity and high radiation levels represent major threats to crew health. Intriguingly, space flight (SF imposes on the body of highly selected, well-trained, and healthy individuals (astronauts and cosmonauts pathophysiological adaptive changes akin to an accelerated aging process and to some diseases. Such effects, becoming manifest over a time span of weeks (i.e., cardiovascular deconditioning to months (i.e., loss of bone density and muscle atrophy of exposure to weightlessness, can be reduced through proper countermeasures during SF and in due time are mostly reversible after landing. Based on these considerations, it is increasingly accepted that SF might provide a mechanistic insight into certain pathophysiological processes, a concept of interest to pre-nosological medicine. In this article, we will review the main stress factors encountered in space and their impact on the human body and will also discuss the possible lessons learned with space exploration in reference to human health on Earth. In fact, this is a productive, cross-fertilized, endeavor in which studies performed on Earth yield countermeasures for protection of space crew health, and space research is translated into health measures for Earth-bound population.

  10. Pathophysiology and management of pediatric ascites. (United States)

    Sabri, Mahmoud; Saps, Miguel; Peters, John M


    Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the "underfill," "overflow," and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.

  11. Adropin – physiological and pathophysiological role

    Directory of Open Access Journals (Sweden)

    Natalia Marczuk


    Full Text Available Adropin is a peptide hormone that was discovered in 2008 by Kumar et al. This protein consists of 76 amino acids, and it was originally described as a secreted peptide, with residues 1-33 encoding a secretory signal peptide sequence. The amino acid sequence of this protein in humans, mice and rats is identical. While our knowledge of the exact physiological roles of this poorly understood peptide continues to evolve, recent data suggest a role in energy homeostasis and the control of glucose and fatty acid metabolism. This protein is encoded by the Enho gene, which is expressed primarily in the liver and the central nervous system. The regulation of adropin secretion is controversial. Adropin immunoreactivity has been reported by several laboratories in the circulation of humans, non-human primates and rodents. However, more recently it has been suggested that adropin is a membrane-bound protein that modulates cell-cell communication. Moreover, adropin has been detected in various tissues and body fluids, such as brain, cerebellum, liver, kidney, heart, pancreas, small intestine, endothelial cells, colostrum, cheese whey and milk. The protein level, as shown by previous research, changes in various physiological and pathophysiological conditions. Adropin is involved in carbohydrate-lipid metabolism, metabolic diseases, central nervous system function, endothelial function and cardiovascular disease. The knowledge of this interesting protein, its exact role and mechanism of action is insufficient. This article provides an overview of the existing literature about the role of adropin, both in physiological and pathophysiological conditions.

  12. [Current concepts in pathophysiology of CRPS I]. (United States)

    Nickel, F T; Maihöfner, C


    Knowledge about the pathophysiology underlying the complex regional pain syndrome (CRPS) has increased over the last years. Classically, CRPS has been considered to be mainly driven by sympathetic dysfunction with sympathetically maintained pain being its major pathogenetic mechanism. Currently, the disease is understood as result of a complex interplay between altered somatosensory, motor, autonomic and inflammatory systems. Peripheral and central sensitization is a common feature in CRPS as in other neuropathic pain syndromes. One important mechanism is the sensitization of spinal dorsal horn cells via activation of postsynaptic NMDA-receptors by chronic C-fiber input. Differential activity of endogenous pain modulating systems may play a pivotal role in the development of CRPS, too. Neuronal plasticity of the somatosensory cortex accounts for central sensory signs. Also the motor system is subject to central adaptive changes in patients with CRPS. Calcitonin-gene related peptide (CGRP) and substance P mediate neurogenic inflammation. Additionally other proinflammatory cytokines involved in the inflammatory response in CRPS have been identified. In terms of the sympathetic nervous system, recent evidence rather points to a sensitization of adrenergic receptors than to increased efferent sympathetic activity. Particularly the expression of alpha (1)-adrenoceptors on nociceptive C-fibers may play a major role. These pathophysiological ideas do not exclude each other. In fact they complement one another. The variety of the involved systems may explain the versatile clinical picture of CRPS. Georg Thieme Verlag KG Stuttgart, New York.

  13. Pathogenesis and Pathophysiology of Pneumococcal Meningitis (United States)

    Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik


    Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  14. Pathophysiology and Treatment of Alien Hand Syndrome

    Directory of Open Access Journals (Sweden)

    Harini Sarva


    Full Text Available Background: Alien hand syndrome (AHS is a disorder of involuntary, yet purposeful, hand movements that may be accompanied by agnosia, aphasia, weakness, or sensory loss. We herein review the most reported cases, current understanding of the pathophysiology, and treatments.Methods: We performed a PubMed search in July of 2014 using the phrases “alien hand syndrome,” “alien hand syndrome pathophysiology,” “alien hand syndrome treatment,” and “anarchic hand syndrome.” The search yielded 141 papers (reviews, case reports, case series, and clinical studies, of which we reviewed 109. Non‐English reports without English abstracts were excluded.Results: Accumulating evidence indicates that there are three AHS variants: frontal, callosal, and posterior. Patients may demonstrate symptoms of multiple types; there is a lack of correlation between phenomenology and neuroimaging findings. Most pathologic and functional imaging studies suggest network disruption causing loss of inhibition as the likely cause. Successful interventions include botulinum toxin injections, clonazepam, visuospatial coaching techniques, distracting the affected hand, and cognitive behavioral therapy.Discussion: The available literature suggests that overlap between AHS subtypes is common. The evidence for effective treatments remains anecdotal, and, given the rarity of AHS, the possibility of performing randomized, placebo‐controlled trials seems unlikely. As with many other interventions for movement disorders, identifying the specific functional impairments caused by AHS may provide the best guidance towards individualized supportive care.

  15. Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Hana Starobova


    Full Text Available Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

  16. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang


    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  17. Pathophysiology of Manganese-Associated Neurotoxicity (United States)

    Racette, Brad A.; Aschner, Michael; Guilarte, Tomas R.; Dydak, Ulrike; Criswell, Susan R.; Zheng, Wei


    Conference Summary Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide.(Couper, 1837) Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years later an outbreak of an atypical parkinsonian illness in a Chilean Mn mine provided a phenotypic description of a fulminant neurologic disorder with parkinsonism, dystonia, and neuropsychiatric symptoms.(Rodier J, 1955) Exposures associated with this syndrome were massive and an order of magnitude greater than modern exposures.(Rodier J, 1955; Hobson et al., 2011) The clinical syndrome associated with Mn neurotoxicity has been called manganism. Modern exposures to Mn occur primarily through occupations in the steel industry and welding. These exposures are often chronic and varied, occurring over decades in the healthy workforce. Although the severe neurologic disorder described by Rodier and Couper are no longer seen, several reports have suggested a possible increased risk of neurotoxicity in these workers.(Racette et al., 2005b; Bowler et al., 2007; Harris et al., 2011) Based upon limited prior imaging and pathologic investigations into the pathophysiology of neurotoxicity in Mn exposed workers,(Huang et al., 2003) many investigators have concluded that the syndrome spares the dopamine system distinguishing manganism from Parkinson disease (PD), the most common cause of parkinsonism in the general population, and a disease with characteristic degenerative changes in the dopaminergic system.(Jankovic, 2005) The purpose of this symposium was to highlight recent advances in the understanding of the pathophysiology of Mn associated neurotoxicity from C. elegans

  18. Vertical axis wind turbine airfoil (United States)

    Krivcov, Vladimir; Krivospitski, Vladimir; Maksimov, Vasili; Halstead, Richard; Grahov, Jurij Vasiljevich


    A vertical axis wind turbine airfoil is described. The wind turbine airfoil can include a leading edge, a trailing edge, an upper curved surface, a lower curved surface, and a centerline running between the upper surface and the lower surface and from the leading edge to the trailing edge. The airfoil can be configured so that the distance between the centerline and the upper surface is the same as the distance between the centerline and the lower surface at all points along the length of the airfoil. A plurality of such airfoils can be included in a vertical axis wind turbine. These airfoils can be vertically disposed and can rotate about a vertical axis.

  19. Contrast medium-induced nephropathy: the pathophysiology

    DEFF Research Database (Denmark)

    Persson, P B; Tepel, Martin


    A widespread, rather general, definition of contrast-induced nephropathy (CIN) is an impairment in renal function occurring within 3 days following the intravascular administration of contrast media (CM) and the absence of an alternative aetiology. In spite of the vast clinical importance of CIN...... haemodynamics, regional hypoxia, auto-, and paracrine factors (adenosine, endothelin, reactive oxygen species) to direct cytotoxic effects. Although these potential mediators of CIN will be discussed separately, several factors may act in concert to perturb kidney function after exposure to contrast media. From...... the current knowledge of the mechanisms causing CIN, it is not possible to recommend a certain class of contrast media, except to avoid large doses of CM of the first generation. From a pathophysiological perspective, volume expansion is effective in avoiding CIN, since water permeability of the collecting...

  20. [Pathophysiology and treatment of orofacial pain. (United States)

    Shinoda, Masamichi; Noma, Noboru

    "Pain" is one of body defense mechanisms and crucial for the life support. However, orofacial pain such as myofascial pain syndrome, burning mouth syndrome and trigeminal neuralgia plays no part in body defense mechanisms and requires therapeutic intervention. Recent studies have indicated that plastic changes in the activities of trigeminal neurons, satellite glial cells in trigeminal ganglion, secondary neurons, microglia and astrocytes in trigeminal spinal subnucleus following orofacial inflammation and trigeminal nerve injury are responsible for orofacial pain mechanisms. Clinically, it is well known that the etiologic differential diagnosis which consists of careful history-taking and physical examination is essential for therapeutic decision in patients with orofacial pain. This report outlines the current knowledge on the pathophysiology, diagnosis, treatment of orofacial pain.

  1. Pathophysiology, Clinical, and Therapeutic Aspects of Narcolepsy

    Directory of Open Access Journals (Sweden)

    Pinar Guzel Ozdemir


    Full Text Available Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. There have been advances in the understanding of the pathogenesis of narcolepsy. It has a negative effect on the quality of life and can restrict the patients from certain careers and activities. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioral modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Some novel modalities are being examined to expand options for treatment. In this review, the pathophysiological, clinical, and pharmacotherapeutic aspects of narcolepsy are discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 271-283

  2. Role of leukotrienes in asthma pathophysiology

    DEFF Research Database (Denmark)

    Bisgaard, H


    Inflammation is an essential component of asthma pathophysiology. While beta(2)-agonists are often used for short-term relief of acute bronchospasm, anti-inflammatory agents are required for the long-term management of chronic inflammation in this disease. Corticosteroids have emerged as the first......-line anti-inflammatory therapy for asthma management. However, in some patients, especially children, the high doses of corticosteroids that may be required to control features of hyperresponsiveness, including exercise-induced asthma, raise safety concerns. Thus, there is a need for complementary anti......-inflammatory, steroid-sparing agents in asthma therapy. Several inflammatory mediators have been targeted in an attempt to thwart this inflammatory process, but so far with little success. The cysteinyl leukotrienes (CysLT), LTC(4), LTD(4), and LTE(4), have been shown to be essential mediators in asthma, making them...

  3. The role of ADAMs in disease pathophysiology.

    LENUS (Irish Health Repository)

    Duffy, Michael J


    The ADAMs are a family of multidomain transmembrane and secreted proteins involved in both proteolysis and cell adhesion. Altered expression of specific ADAMs is implicated in the pathophysiology of several diseases including rheumatoid arthritis, Alzheimer\\'s disease, cardiac hypertrophy, asthma and cancer. Of these different diseases, it is in cancer where most research has been carried out. Multiple ADAMs, including ADAM-9, ADAM-10, ADAM-12, ADAM-15 and ADAM-17, have been shown to play a role in either cancer formation or progression. Consistent with these findings, increased expression of specific ADAMs in several cancer types was found to correlate with features of aggressive disease and poor prognosis. Currently, selective ADAM inhibitors against ADAM-10 and ADAM-17 are undergoing clinical trials for the treatment of cancer. Further work is required in order to establish a causative role for ADAMs in rheumatoid arthritis, Alzheimer\\'s disease, cardiac hypertrophy and asthma.

  4. New insights into pathophysiology of vestibular migraine

    Directory of Open Access Journals (Sweden)

    Juan Manuel Espinosa-Sanchez


    Full Text Available Vestibular migraine (VM is a common disorder in which genetic, epigenetic and environmental factors probably contribute to its development. The pathophysiology of VM is unknown; nevertheless in the last few years, several studies are contributing to understand the neurophysiological pathways involved in VM. The current hypotheses are mostly based on the knowledge of migraine itself. The evidence of trigeminal innervation of the labyrinth vessels and the localization of vasoactive neuropeptides in the perivascular afferent terminals of these trigeminal fibers support the involvement of the trigemino-vascular system. The neurogenic inflammation triggered by activation of the trigeminal-vestibulocochlear reflex, with the subsequent inner ear plasma protein extravasation and the release of inflammatory mediators, can contribute to a sustained activation and sensitization of the trigeminal primary afferent neurons explaining VM symptoms. The reciprocal connections between brainstem vestibular nuclei and the structures that modulate trigeminal nociceptive inputs (rostral ventromedial medulla, ventrolateral periaqueductal grey, locus coeruleus and nucleus raphe magnus are critical to understand the pathophysiology of VM. Although cortical spreading depression can affect cortical areas involved in processing vestibular information, functional neuroimaging techniques suggest a dysmodulation in the multimodal sensory integration and processing of vestibular and nociceptive information, resulting from a vestibulo-thalamo-cortical dysfunction, as the pathogenic mechanism underlying VM. The elevated prevalence of VM suggests that multiple functional variants may confer a genetic susceptibility leading to a dysregulation of excitatory-inhibitory balance in brain structures involved in the processing of sensory information, vestibular inputs and pain. The interactions among several functional and structural neural networks could explain the pathogenic

  5. Capillary leak syndrome: etiologies, pathophysiology, and management. (United States)

    Siddall, Eric; Khatri, Minesh; Radhakrishnan, Jai


    In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  6. Helical axis stellarator equilibrium model

    International Nuclear Information System (INIS)

    Koniges, A.E.; Johnson, J.L.


    An asymptotic model is developed to study MHD equilibria in toroidal systems with a helical magnetic axis. Using a characteristic coordinate system based on the vacuum field lines, the equilibrium problem is reduced to a two-dimensional generalized partial differential equation of the Grad-Shafranov type. A stellarator-expansion free-boundary equilibrium code is modified to solve the helical-axis equations. The expansion model is used to predict the equilibrium properties of Asperators NP-3 and NP-4. Numerically determined flux surfaces, magnetic well, transform, and shear are presented. The equilibria show a toroidal Shafranov shift

  7. Transforming pathophysiology instruction through narrative pedagogy and Socratic questioning. (United States)

    Rogge, M M


    Pathophysiology, heavily content driven, has typically been taught through the use of traditional behavioral pedagogy and a reliance on the formal lecture. The author describes the limitations of this approach to teaching pathophysiology and describes the use of narrative pedagogy and Socratic questioning as alternative methods of instruction to augment lecture methods. Specific strategies for transforming traditional classroom teaching by using Socratic questions in a pathophysiology course for nurse practitioners are described. Student and faculty reactions to the initial efforts to transform pathophysiology instruction are also described.

  8. An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?). (United States)

    Hammer, Heinz F


    This review focuses on seven aspects of physiology and pathophysiology of the exocrine pancreas that have been intensively discussed and studied within the past few years: (1) the role of neurohormonal mechanisms like melatonin, leptin, or ghrelin in the stimulation of pancreatic enzyme secretion; (2) the initiation processes of acute pancreatitis, like fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen by the lysosomal enzyme cathepsin B, or autoactivation of trypsinogen; (3) the role of genes in the pathogenesis of acute pancreatitis; (4) the role of alcohol and constituents of alcoholic beverages in the pathogenesis of acute pancreatitis; (5) the role of pancreatic hypertension, neuropathy, and central mechanisms for the pathogenesis of pain in chronic pancreatitis; (6) the relation between exocrine pancreatic function and diabetes mellitus; and (7) pathophysiology, diagnosis and treatment of pancreatic steatorrhea.

  9. Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review

    African Journals Online (AJOL)

    The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, ...

  10. Tinnitus: Network pathophysiology-network pharmacology

    Directory of Open Access Journals (Sweden)

    Ana Belen eElgoyhen


    Full Text Available Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for 1 in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single FDA-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in central nervous system pathologies is changing from that of magic bullets that target individual chemoreceptors or disease-causing genes into that of magic shotguns, promiscuous or dirty drugs that target disease-causing networks, also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  11. Tinnitus: network pathophysiology-network pharmacology. (United States)

    Elgoyhen, Ana B; Langguth, Berthold; Vanneste, Sven; De Ridder, Dirk


    Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for one in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single Food and Drug Administration (FDA)-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system (CNS) disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in CNS pathologies is changing from that of "magic bullets" that target individual chemoreceptors or "disease-causing genes" into that of "magic shotguns," "promiscuous" or "dirty drugs" that target "disease-causing networks," also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  12. Orthostatic intolerance: potential pathophysiology and therapy. (United States)

    Lu, Chih-Cherng; Tseng, Ching-Jiunn; Tang, Hung-Shang; Tung, Che-Se


    Orthostatic intolerance affects an estimated 1 in 500 persons and causes a wide range of disabilities. After essential hypertension, it is the most frequently encountered dysautonomia, accounting for the majority of patients referred to centers specializing in autonomic disorders. Patients are typically young females with symptoms such as dizziness, visual changes, head and neck discomfort, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, syncope. Syncope is the most hazardous symptom of orthostatic intolerance, presumably occurring because of impaired cerebral perfusion and in part to compensatory autonomic mechanisms. The etiology of this syndrome is still unclear but is heterogeneous. Orthostatic intolerance used to be characterized by an overall enhancement of noradrenergic tone at rest in some patients and by a patchy dysautonomia of postganglionic sympathetic fibers with a compensatory cardiac sympathetic activation in others. However, recent advances in molecular genetics are improving our understanding of orthostatic intolerance, such as several genetic diseases (such as Ehler-Danlos syndrome and norepinephrine transporter deficiency) presenting with symptoms typical of orthostatic intolerance. Future work will include investigation of genetic functional mutations underlying interindividual differences in autonomic cardiovascular control, body fluid regulation, and vascular regulation in orthostatic intolerance patients. The goal of this review article is to describe recent advances in understanding the pathophysiological mechanisms of orthostatic intolerance and their clinical significance.

  13. [Pathophysiology and new treatment of uveitis]. (United States)

    Yanai, Ryoji; Takeda, Atsunobu; Yoshimura, Takeru; Sonoda, Koh-Hei


    Uveitis is narrow-defined inflammation of the uvea, also clinically include all inflammatory conditions in the eye. Uveitis may occur as a consequence of various causes and background, such as autoimmune diseases, infections, and hematopoietic malignancy. We have to treat uveitis not only controlling the inflammation but also maintaining up the visual function of the eye because the most uveitis is chronic and relapsing inflammatory disorder. Behçét's disease is a systemic disease and results in loss of vision without adequate treatment. Behçét's disease was a representative of vision loss uveitis because Behçét's patient usually had treatment resistance of conventional treatment, such as colchicine and cyclosporine. However, biological therapy with TNF-α, which started from 2007, has revolutionized the treatment strategy of Behçét's disease. It is not too much to say that Behçét's patient is free from fear of vision loss by the dramatic decrease of ocular attach. Biological therapy is not approved as a treatment of uveitis except Behçét's disease. Some protracted cases of Sarcoidosis and Vogt-Koyanagi-Harada disease are resistant to corticosteroid therapy and require new treatment. In this review, we discuss the pathophysiology of uveitis and report new treatment of Behçét's disease by biological therapy.

  14. Orexinergic system and pathophysiology of epilepsy. (United States)

    Doreulee, N; Alania, M; Vashalomidze, G; Skhirtladze, E; Kapanadze, Ts


    Neuropeptids orexins, also known as the hypocretins, are expressed in the lateral hypothalamus. Orexin-containing cells project widely throughout the brains, are crucial for the regulation of wakefulness and dysfunction of this system is associated with pathophysiology of narcolepsy-cataplexy. Orexin neurons play an important role in motivation, feeding and adaptive behaviors. Distribution of orexinergic receptors in the hippocampus tended to the ideas that orexins might be involved in the functions relating to the hippocampus. Effects of neuropeptide orexin-A on epileptiform activity in hippocampal slices were investigated. 500 µm thick hippocampal slices from 8-10 week-old rodents were used. Field excitatory postsynaptic potential (pop-fEPSP) and population spike in CA1 of hippocamopus were registered using standard protocol of in vitro electrophysiological experiments. Initial slope of the fEPSP and amplitude of II pop-spike were measured. Bursting neurons in CA3 were recorded in modified saline. We have found that orexin-A decreases duration/amplitude of multiple discharges of pop-spikes and inhibits spontaneous epileptiform afterdischarges induced by bicuculline methiodide in CA1. Orexin-A also modulates the frequency of discharges of bursting neurons in CA3. Our results suggest possible involvement of orexinergic system in antiepileptic action. Supported by ISTC Grant G-1318.

  15. Metabolic syndrome pathophysiology and clinical presentation. (United States)

    Handelsman, Yehuda


    Metabolic syndrome is a relatively new definition, designed to help the health care practitioner to easily identify people at risk for the development of cardiovascular disease and diabetes. With the obesity epidemic, we are witnessing an epidemic of multiple-risk patients. Insulin resistance is the perceived pathophysiology of metabolic syndrome and defines its clinical presentation. Hypertension, dyslipedemia, polycystic ovarian syndrome, fatty liver disease, pre-diabetes, sleep and breathing disorder, certain cancers, and cognitive impairment are many of the presentations of the syndrome; patients with any of these conditions are at a high risk of developing cardiovascular disease and diabetes. The metabolic syndrome helps identify people at risk to allow early intervention for prevention. Lifestyle modification is the most important part of the management of people with the syndrome. Lately medications--though none approved by the U.S. Food and Drug Administration (FDA)--have been recommended by major medical societies when lifestyle modification is not enough or when it fails.

  16. Hemorrhoids: From basic pathophysiology to clinical management (United States)

    Lohsiriwat, Varut


    This review discusses the pathophysiology, epidemiology, risk factors, classification, clinical evaluation, and current non-operative and operative treatment of hemorrhoids. Hemorrhoids are defined as the symptomatic enlargement and distal displacement of the normal anal cushions. The most common symptom of hemorrhoids is rectal bleeding associated with bowel movement. The abnormal dilatation and distortion of the vascular channel, together with destructive changes in the supporting connective tissue within the anal cushion, is a paramount finding of hemorrhoids. It appears that the dysregulation of the vascular tone and vascular hyperplasia might play an important role in hemorrhoidal development, and could be a potential target for medical treatment. In most instances, hemorrhoids are treated conservatively, using many methods such as lifestyle modification, fiber supplement, suppository-delivered anti-inflammatory drugs, and administration of venotonic drugs. Non-operative approaches include sclerotherapy and, preferably, rubber band ligation. An operation is indicated when non-operative approaches have failed or complications have occurred. Several surgical approaches for treating hemorrhoids have been introduced including hemorrhoidectomy and stapled hemorrhoidopexy, but postoperative pain is invariable. Some of the surgical treatments potentially cause appreciable morbidity such as anal stricture and incontinence. The applications and outcomes of each treatment are thoroughly discussed. PMID:22563187

  17. The pathophysiology of trauma-induced coagulopathy. (United States)

    Frith, Daniel; Brohi, Karim


    Transfusion paradigms and protocols have evolved at a rapid pace in the last few years to ameliorate the adverse effects of trauma-induced coagulopathy (TIC). This has occurred despite fragmented and inadequate knowledge of the underlying pathophysiology that they are supposed to treat. This review will collate and assimilate the most recent data about TIC in order to present our state-of-the-art understanding of this condition. TIC was conventionally construed simply as depletion, dysfunction or dilution of procoagulant factors. However, contemporary understanding recognizes it as an imbalance of the dynamic equilibrium between procoagulant factors, anticoagulant factors, platelets, endothelium and fibrinolysis. The endogenous component of TIC (acute traumatic coagulopathy) is not merely a consumptive coagulopathy, but is characterized by isolated factor V inhibition, dysfibrinogenaemia, systemic anticoagulation, impaired platelet function and hyperfibrinolysis. Acute traumatic coagulopathy then becomes exacerbated by hypothermia, acidosis and resuscitation with hypocoagulable fluids. Further improvement in the outcome from trauma-haemorrhage is possible with more refined and tailored haemostatic resuscitation. Achieving this will depend upon a better understanding of the haemostatic defects that develop after injury.

  18. The pathophysiology of amenorrhea in the adolescent. (United States)

    Golden, Neville H; Carlson, Jennifer L


    Menstrual irregularity is a common occurrence during adolescence, especially within the first 2-3 years after menarche. Prolonged amenorrhea, however, is not normal and can be associated with significant medical morbidity, which differs depending on whether the adolescent is estrogen-deficient or estrogen-replete. Estrogen-deficient amenorrhea is associated with reduced bone mineral density and increased fracture risk, while estrogen-replete amenorrhea can lead to dysfunctional uterine bleeding in the short term and predispose to endometrial carcinoma in the long term. In both situations, appropriate intervention can reduce morbidity. Old paradigms of whom to evaluate for amenorrhea have been challenged by recent research that provides a better understanding of the normal menstrual cycle and its variability. Hypothalamic amenorrhea is the most prevalent cause of amenorrhea in the adolescent age group, followed by polycystic ovary syndrome. In anorexia nervosa, exercise-induced amenorrhea, and amenorrhea associated with chronic illness, an energy deficit results in suppression of hypothalamic secretion of GnRH, mediated in part by leptin. Administration of recombinant leptin to women with hypothalamic amenorrhea has been shown to restore LH pulsatility and ovulatory menstrual cycles. The use of recombinant leptin may improve our understanding of the pathophysiology of hypothalamic amenorrhea in adolescents and may also have therapeutic possibilities.

  19. Pathophysiology of AAA: heredity vs environment. (United States)

    Björck, Martin; Wanhainen, Anders


    Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Clinical manifestations and pathophysiology of lissencephaly

    International Nuclear Information System (INIS)

    Oi, Shizuo; Sasaki, Koji; Yamada, Hiroshi; Ando, Shoko; Tamura, Yasunori; Fukuda, Kuniaki; Furukawa, Seikyo; Matsumoto, Satoshi.


    Four cases of lissencephaly were analyzed in light of clinical manifestations, CT findings and the state of hydrocephalus. Lissencephaly had been diagnosed mainly by autopsy until CT scan was introduced in the early 1970's. Since then, diagnosis of lissencephaly early in life is possible. Presently the major interest in this congenital CNS anomaly, which is caused by a neuronal migration disorder in the relatively late stages of fetal development, is to learn the dynamic pathophysiological state and management. The purpose of this paper is to analyze those points of lissencephaly in diagnosis during life and possible treatment in the hydrocephalic state. The common findings in CT in all four cases are as follows: No. 1. smooth cortical surface (agyria--pachygyria), No. 2. wide sylvian fissure (complete or incomplete lack of opercularization, No. 3. ventricular dilatation (remarkable bilateral enlargement of lateral ventricle and third ventricle--colpocephaly), No. 4. wide subdural or subarachnoid space in supratentorial region, No. 5. periventricular low density, No. 6. midline cavum, No. 7. normal CT findings in posterior fossa structure. Three out of four patients demonstrated full or bulged and tense anterior fontanella. Because of this suggestion of increased intracranial pressure and enlarged ventricles with periventricular lucency in CT findings, one patient underwent CT cisternography for dynamic analysis of the CSF circulation and continuous ICP monitoring for dynamic evaluation of the ICP pattern. The results revealed very much delayed CSF circulation and intermittently increased. ICP, with pressure waves appearing in 35.7 % of all recordings. (J.P.N.)

  1. Pathophysiology and Immune Dysfunction in Endometriosis (United States)

    Ahn, Soo Hyun; Monsanto, Stephany P.; Miller, Caragh; Singh, Sukhbir S.; Thomas, Richard; Tayade, Chandrakant


    Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis. PMID:26247027

  2. Pathophysiology and Immune Dysfunction in Endometriosis

    Directory of Open Access Journals (Sweden)

    Soo Hyun Ahn


    Full Text Available Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis.

  3. The pathophysiology of restless legs syndrome

    International Nuclear Information System (INIS)

    Miyamoto, Masayuki; Miyamoto, Tomoyuki; Iwanami, Masaoki; Suzuki, Keisuke; Hirata, Koichi


    Restless legs syndrome (RLS) is a sensorimotor disorder that is frequently associated with periodic leg movements (PLMS). RLS is generally considered to be a central nervous system (CNS)-related disorder although no specific lesion has been found to be associated with the syndrome. Reduced intracortical inhibition has been demonstrated in RLS by transcranial magnetic stimulation. Some MRI studies have revealed the presence of morphologic changes in the somatosensory cortex, motor cortex and thalamic gray matter. The results of single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies showed that the limbic and opioid systems also play important roles in the pathophysiology of RLS. A functional MRI study revealed abnormal bilateral cerebellar and thalamic activation during the manifestation of sensory symptoms, with additional red nucleus and reticular formation activity during PLMS. PLMS is likely to occur in patients with spinal cord lesions, and some patients with sensory polyneuropathy may exhibit RLS symptoms. RLS symptoms seem to depend on abnormal spinal sensorimotor integration at the spinal cord level and abnormal central somatosensory processing. PLMS appears to depend on increased excitability of the spinal cord and a decreased supraspinal inhibitory mechanism from the A11 diencephalic dopaminergic system. RLS symptoms respond very dramatically to dopaminergic therapy. The results of analysis by PET and SPECT studies of striatal D2 receptor binding in humans are inconclusive. However, studies in animal models suggest that the participation of the A11 dopaminergic system and the D3 receptor in RLS symptoms. The symptoms of RLS are aggravated in those with iron deficiency, and iron treatment ameliorates the symptoms in some patients. Neuroimaging studies, analysis of the cerebrospinal fluid, and studies on postmortem tissue and use of animal models have indicated that low brain iron concentrations and dysfunction of

  4. Altered Mitochondrial Dynamics and TBI Pathophysiology

    Directory of Open Access Journals (Sweden)

    Tara Diane Fischer


    Full Text Available Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS, and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1, which translocates to the mitochondrial outer membrane to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 hours post-injury, followed by a significant decrease in length at 72 hours. Post-TBI administration of Mdivi-1, a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the hippocampus and improved

  5. Pathophysiological characterization of asthma transitions across adolescence. (United States)

    Arshad, Syed Hasan; Raza, Abid; Lau, Laurie; Bawakid, Khalid; Karmaus, Wilfried; Zhang, Hongmei; Ewart, Susan; Patil, Veersh; Roberts, Graham; Kurukulaaratchy, Ramesh


    Adolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of transitional adolescent asthma phenotypes in a longitudinal birth cohort. The Isle of Wight Birth Cohort (N = 1456) was reviewed at 1, 2, 4, 10 and 18-years. Characterization included questionnaires, skin tests, spirometry, exhaled nitric oxide, bronchial challenge and (in a subset of 100 at 18-years) induced sputum. Asthma groups were "never asthma" (no asthma since birth), "persistent asthma" (asthma at age 10 and 18), "remission asthma" (asthma at age 10 but not at 18) and "adolescent-onset asthma" (asthma at age 18 but not at age 10). Participants whose asthma remitted during adolescence had lower bronchial reactivity (odds ratio (OR) 0.30; CI 0.10 -0.90; p = 0.03) at age 10 plus greater improvement in lung function (forced expiratory flow 25-75% gain: 1.7 L; 1.0-2.9; p = 0.04) compared to persistent asthma by age 18. Male sex (0.3; 0.1-0.7; p adolescent-onset asthma showed eosinophilic airway inflammation (3.0%, 0.7-6.6), not seen in persistent asthma (1.0%, 0-3.9), while remission group had the lowest sputum eosinophil count (0.3%, 0-1.4) and lowest eosinophils/neutrophils ratio of 0.0 (Interquartile range: 0.1). Asthma remission during adolescence is associated with lower initial BHR and greater gain in small airways function, while adolescent-onset asthma is primarily eosinophilic.

  6. Chagas disease. A new pathophysiological assessment

    International Nuclear Information System (INIS)

    Redruello, M.; Masoli, O.; Hasson, I.; Cragnolino, D.; Traverso, S.; Perez Balino, N.; Sarmiento, R.; Lazzari, J.; Luluaga, E.


    Background: There is scarce information on myocardial perfusion abnormalities and on the coronary vasomotor condition in Chagas disease patients. Aims: To assess regional perfusion abnormalities and the coronary vasomotor response of patients in the chronic phase of Chagas disease. Methods: With the use of 99mTc-sestamibi SPECT imaging and cold pressor test and intracoronary acetylcoline (ACH) perfusion, we studied 9 patients aged 42,6±12 years, 4 males, in the chronic stage of Chagas disease (5 with the indeterminate form and 4 with heart lesion) with normal coronary arteries. Vasomotor responses to intracoronary increasing doses of ACH and to a single dose of nitroglycerine (NTG) were assessed with digital quantitative angiography. Regional myocardial perfusion was evaluated at rest and after cold pressor test by a semi quantitative score analysis in an 18-segment model with 99mTc-sestamibi SPECT images. Results were expressed as mean ± 2SD. Differences between continuous variables were measured by two tails Student's t test for paired variables and the significance level was set at 5 %. Results: All patients had regional perfusion defects and abnormal vasomotor response. The diameter of the left anterior descending artery decreased 34% from a basal diameter of 3.66∫0.95 mm down to 2.42±0.74 mm after maximal response to ACH (p<0.002). NTG infusion augmented its diameter to 3.86±0.77 mm (p<0.0002) that is a 60% increase from post ACH diameter. Myocardial perfusion score was 1∫2.66 at rest and 6.22±3.6 after cold pressor test (p<0.0001). Conclusions: This group of patients in the chronic phase of Chagas disease showed an abnormal vasoconstrictive response to intracoronary ACH and cold-induced perfusion defects suggesting that endothelial dysfunction plays a role in the pathophysiology of chronic Chagas heart disease

  7. Epilepsy in autism: A pathophysiological consideration. (United States)

    Nomura, Yoshiko; Nagao, Yuri; Kimura, Kazue; Hachimori, Kei; Segawa, Masaya


    Eighty cases of idiopathic autism with epilepsy and 97 cases without epilepsy were studied to evaluate the pathophysiology of epilepsy in autism. The initial visit to this clinic ranged 8months-30years 3months of age, and the current ages are 5years 8months-42years 3months, 60% reaching to over 30years of age. The average follow up duration is 22.2years±9.4years. The ages of onset of epilepsy were from 7months to 30years of age, with the two peaks at 3.2years and 16.7years. EEG central focus appeared earlier than frontal focus. Abnormality of locomotion and atonic NREM were observed more frequently in epileptic group. These suggest the neuronal system related to abnormality of locomotion and atonic NREM, which are the hypofunction of the brainstem monoaminergic system, is the pathomechanism underling the epilepsy in autism. By showing the abnormal sleep-wake rhythm and locomotion being the very initial symptoms in autism, we had shown the hypofunction of the brainstem monoaminergic system is the initial pathomechanism of autism. Thus, epilepsy in autism is not the secondary manifestation, but one of the pathognomonic symptoms of autism. The brainstem monoaminergic system project to the wider cortical area, and the initial monoaminergic hypofunction may lead to the central focus which appears earlier. The failure of the monoaminergic (serotonergic) system causes dysfunction of the pedunculo-pontine nucleus (PPN) and induces dysfunction of the dopamine (DA) system, and with development of the DA receptor supersensitivity consequently disinhibits the thalamo-frontal pathway, which after maturation of this pathway in teens cause the epileptogenesis in the frontal cortex. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Pathophysiology of heatstroke in dogs - revisited. (United States)

    Bruchim, Yaron; Horowitz, Michal; Aroch, Itamar


    Heatstroke results from a failure to dissipate accumulated heat during exposure to hot environments, or during strenuous physical exercise under heat stress. It is characterized by core body temperatures > 41°C, with central nervous system dysfunction. Functional morphology and thermoregulatory effectors differences between dogs and humans may require special heatstroke protective adaptations in dogs, however, the risk factors for developing heatstroke are similar in both. In dogs, these include hot, especially highly humid environments, excessive physical activity, obesity, large (>15 kg) body weight, being of certain breed (e.g., Labrador retrievers and brachycephalic breeds), upper airway obstruction and prolonged seizures. Lack of acclimation to heat and physical fitness decreases the survival of heat stroked dogs. At the systemic level, blood pooling within the large internal organs (e.g., spleen, liver) is a major contributor to the development of shock and consequent intestinal ischemia, hypoxia and endothelial hyperpermeability, commonly occurring in heatstroke patients. Evoked serious complications include rhabdomyolysis, acute kidney injury, acute respiratory distress syndrome and ultimately, sepsis and disseminated intravascular coagulation. The most common clinical signs in dogs include acute collapse, tachypnea, spontaneous bleeding, shock signs and mental abnormalities, including depression, disorientation or delirium, seizures, stupor and coma. In such dogs, presence of peripheral blood nucleated red blood cells uniquely occurs, and is a highly sensitive diagnostic and prognostic biomarker. Despite early, appropriate body cooling, and intensive supportive treatment, with no available specific treatment to ameliorate the severe inflammatory and hemostatic derangements, the mortality rate is around 50%, similar to that of human heatstroke victims. This review discusses the pathophysiology of canine heatstroke from a veterinarian's point of view

  9. Faecal soiling: pathophysiology of postdefaecatory incontinence. (United States)

    Pucciani, F


    Passive postdefaecatory incontinence is poorly understood and yet is an important clinical problem. The aim of this study was to characterize the pathophysiology of postdefaecatory incontinence in patients affected by faecal soiling. Seventy-two patients (30 women, age range 49-79 years; 42 men, age range, 53-75 years) affected by faecal passive incontinence with faecal soiling were included in the study. Two patient groups were identified: Group 1 comprised 42 patients with postdefaecatory incontinence and Group 2 had 30 patients without incontinence after bowel movements. After a preliminary clinical evaluation, including the Faecal Incontinence Severity Index (FISI) score and the obstructed defaecation syndrome (ODS) score, all patients of Groups 1 and 2 were studied by means of endoanal ultrasound and anorectal manometry. The results were compared with those from 20 healthy control subjects. A significantly higher ODS score was found in Group 1 (P IAS) in Group 2 (P IAS atrophy and the FISI score (ρs 0.78; P < 0.03). Anal resting pressure (Pmax and Pm ) was significantly lower in Group 2 (P < 0.04). The straining test was considered positive in 30 (71.4%) patients in Group 1, significantly greater than in Group 2 (P < 0.01). A significantly higher conscious rectal sensitivity threshold (CRST) was found in Group 1 patients (P < 0.01). The ODS score, a positive straining test and high CRST values suggest that postdefaecatory incontinence is secondary to impaired defaecation. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  10. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression. (United States)

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H


    Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

  11. The Role of Hippocampus in the Pathophysiology of Depression

    Directory of Open Access Journals (Sweden)

    Özlem Donat Eker


    Full Text Available Hippocampus, as a part of the limbic cortex, has a variety of functions ranging from mating behavior to memory besides its role in the regulation of emotions. The hippocampus has reciprocal interactions of with other brain regions which act in the pathophysiology of major depressive disorder (MDD. Moreover, since the hippocampus is a scene for the neurogenesis, which can be seen as a response to antidepressant treatment, the hippocampus became a focus of attention in neuroimaging studies of MDD. It has been shown that brain derived neurotrophic factor (BDNF, that is responsible from the neurogenesis, is associated with the response to the antidepressants and antidepressant drugs are ineffective if neurogenesis is hindered.Hippocampal atrophy is expected with the decrease of neurogenesis as a result of the lower BDNF levels with the deleterious effects of glucocorticoids in depression. Recurrent and severe depression seems to cause such a volume reduction though first episode MDD subjects do not differ from healthy individuals in respect to their hippocampal volumes (HCVs measured by magnetic resonance imaging methods. One may argue regarding these findings that the atrophy in the hippocampus may be observed in the long term and the decrease in BDNF levels may predispose the volume reduction. Although it has been postulated that smaller HCV as a result of genetic and environmental factors and prior to the illness, may cause a vulnerability to MDD, sufficient evidence has not been accumulated yet and the view that HCV loss develops as depression progresses is widely accepted. Findings that serum BDNF (sBDNF is lower in MDD patients though HCVs of patients do not differ from healthy individuals and the positive correlation of sBDNF with HCV seen only in the patient group support this view. It can be assumed that depressed patients have sensitivity for the fluctuations in BDNF levels. Follow-up studies which consider effects of hipotalamo

  12. Therapy of rheumatic polymyalgia: the pathophysiologic management

    Directory of Open Access Journals (Sweden)

    M.A. Cimino


    Full Text Available Polymyalgia rheumatica (PMR is an inflammatory syndrome affecting older people whose prevalence has increased in recent years. The suppression of the hypothalamic-pituitary-adrenal axis (HPA and ageing may contribute to the pathogenesis of PMR. Chronic stress (i.e. interpersonal, chronic infections etc. in elderly people may represent a risk factor for the development of PMR. In fact, elderly represent per se a condition of endocrine senescence including adrenal hypofunction, in addition chronic stress represents a further harmful stimulus to seriously compromise endogenous glucocorticoid production. Synovitis and vasculitis characterize the majority of the patients. Serum cytokine and steroidal hormone patterns suggest that patients with PMR have an intensive inflammatory reaction. As a matter of fact, glucocorticoids represent the most useful temporary “replacement” treatment during the active phase of PMR. The use of modified-release glucocorticoids that might induce higher levels during the night (circadian rhythms as in physiological conditions, will represent another important approach to optimize PMR treatment and reduce the side effects. Combination therapy between glucocorticoids and inhibitors of pro-inflammatory cytokines should be tested in large studies and early cases of PMR.

  13. Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease. (United States)

    Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam


    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Reframing the Teenage Wasteland: Adolescent Microbiota-Gut-Brain Axis. (United States)

    McVey Neufeld, Karen-Anne; Luczynski, Pauline; Dinan, Timothy G; Cryan, John F


    Human adolescence is arguably one of the most challenging periods of development. The young adult is exposed to a variety of stressors and environmental stimuli on a backdrop of significant physiological change and development, which is especially apparent in the brain. It is therefore unsurprising that many psychiatric disorders are first observable during this time. The human intestine is inhabited by trillions of microorganisms, and evidence from both preclinical and clinical research focusing on the established microbiota-gut-brain axis suggests that the etiology and pathophysiology of psychiatric disorders may be influenced by intestinal dysbiosis. Provocatively, many if not all of the challenges faced by the developing teen have a documented impact on these intestinal commensal microbiota. In this review, we briefly summarize what is known about the developing adolescent brain and intestinal microbiota, discuss recent research investigating the microbiota-gut-brain axis during puberty, and propose that pre- and probiotics may prove useful in both the prevention and treatment of psychiatric disorders specifically benefitting the young adult. © The Author(s) 2016.

  15. Prenatal cocaine exposure and its impact on cognitive functions of offspring: a pathophysiological insight. (United States)

    Gkioka, Eleana; Korou, Laskarina Maria; Daskalopoulou, Afrodite; Misitzi, Angelica; Batsidis, Eleni; Bakoyiannis, Ioannis; Pergialiotis, Vasilios


    It is estimated that approximately 0.5%-3% of fetuses are prenatally exposed to cocaine (COC). The neurodevelopmental implications of this exposure are numerous and include motor skill impairments, alterations of social function, predisposition to anxiety, and memory function and attention deficits; these implications are commonly observed in experimental studies and ultimately affect both learning and IQ. According to previous studies, the clinical manifestations of prenatal COC exposure seem to persist at least until adolescence. The pathophysiological cellular processes that underlie these impairments include dysfunctional myelination, disrupted dendritic architecture, and synaptic alterations. On a molecular level, various neurotransmitters such as serotonin, dopamine, catecholamines, and γ-aminobutyric acid seem to participate in this process. Finally, prenatal COC abuse has been also associated with functional changes in the hormones of the hypothalamic-pituitary-adrenal axis that mediate neuroendocrine responses. The purpose of this review is to summarize the neurodevelopmental consequences of prenatal COC abuse, to describe the pathophysiological pathways that underlie these consequences, and to provide implications for future research in the field.

  16. Effects of high fat diet on the basal activity of the hypothalamus- pituitary-adrenal axis in mice: A systematic review

    NARCIS (Netherlands)

    Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.


    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the

  17. Pathophysiological basis of pharmacotherapy in the hepatorenal syndrome

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming; Henriksen, Jens H


    Hepatorenal syndrome (HRS) is a functional and reversible impairment of renal function in patients with severe cirrhosis. Major pathophysiological elements include liver dysfunction, a circulatory derangement with central hypovolaemia and neurohumoral activation of potent vasoactive systems leading...

  18. Pathophysiology of shunt dysfunction in shunt treated hydrocephalus

    DEFF Research Database (Denmark)

    Blegvad, C.; Skjolding, A D; Broholm, H


    We hypothesized that shunt dysfunction in the ventricular catheter and the shunt valve is caused by different cellular responses. We also hypothesized that the cellular responses depend on different pathophysiological mechanisms....

  19. Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms

    NARCIS (Netherlands)

    Kerckhoffs, A.P.M.


    Irritable Bowel Syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with a disordered defecation. No unique pathophysiological mechanism has been identified. It is most likely a multifactorial disease involving alterations in intestinal microbiota

  20. Pathophysiology of acute small bowel disease with CT correlation

    International Nuclear Information System (INIS)

    Sarwani, N.; Tappouni, R.; Tice, J.


    The objective of this article is to review the pathophysiology of acute small bowel diseases, and to correlate the mechanisms of disease with computed tomography (CT) findings. Disease entities will be classified into the following: immune mediated and infectious causes, vascular causes, mechanical causes, trauma, and others. Having an understanding of acute small bowel pathophysiology is a useful teaching tool, and can lead to imaging clues to the most likely diagnosis of acute small bowel disorders.

  1. The role of beta-endorphin in the pathophysiology of major depression. (United States)

    Hegadoren, K M; O'Donnell, T; Lanius, R; Coupland, N J; Lacaze-Masmonteil, N


    A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta

  2. Modulation of HPA axis response to social stress in schizophrenia by childhood trauma. (United States)

    Lange, Claudia; Huber, Christian G; Fröhlich, Daniela; Borgwardt, Stefan; Lang, Undine E; Walter, Marc


    HPA axis functioning plays an important role in the etiology of schizophrenia spectrum disorders (SSD). However, only few studies have examined HPA axis responsivity to psychosocial stress in SSD, and results are heterogeneous. Furthermore, childhood trauma is known to influence psychopathology and treatment outcome in SSD, but studies on the influence of childhood trauma on stress related HPA axis activity are missing. The purpose of this study was to investigate cortisol response to a psychosocial stress challenge in SSD patients, and to examine its association with severity of childhood trauma. The present study included 25 subacutely ill patients with a current episode of a chronic SSD and 25 healthy controls. Participants underwent the modified Trier Social Stress Test, and salivary cortisol levels were assessed. The childhood trauma questionnaire was used to assess severity of adverse life events. Overall, cortisol response was blunted in the patient group compared to the control group (pchildhood trauma experience: responders had experienced more emotional abuse in their past (pchildhood trauma might influence stress-related HPA axis activity in SSD. Our data contribute to the hypothesis that severity of childhood trauma may be of pathophysiological relevance in schizophrenia. In addition, it may be an overlooked factor contributing to inconsistent findings regarding HPA axis response to psychosocial stress in SSD. Copyright © 2017. Published by Elsevier Ltd.

  3. Anterior fixation of the axis. (United States)

    Traynelis, Vincent C; Fontes, Ricardo B V


    Although anterior fixation of the axis is not commonly performed, plate fixation of C2 is an important technique for treating select upper cervical traumatic injuries and is also useful in the surgical management of spondylosis. To report the technique and outcomes of C2 anterior plate fixation for a series of patients in which the majority presented with symptomatic degenerative spondylosis. Forty-six consecutive patients underwent single or multilevel fusions over a 7-year period; 30 of these had advanced degenerative disease manifested by myelopathy or deformity. Exposure was achieved with rostral extension of the standard anterior cervical exposure via careful soft tissue dissection, mobilization of the superior thyroid artery, and the use of a table-mounted retractor. It was not necessary to remove the submandibular gland, section the digastric muscle, or make additional skin incisions. Screws were placed an average of 4.6 mm (+/- 2.3 mm) from the inferior C2 endplate with a mean sagittal trajectory of 15.7 degrees (+/- 7.6 degrees). Short- and long-term procedure-related mortality was 4.4%, and perioperative morbidity was 8.9%. Patients remained intubated an average of 2.5 days following surgery. Dysphagia was initially reported by 15.2% of patients but resolved by the 8th postoperative week in all patients. Arthrodesis was achieved in all patients available for long-term follow-up. Multilevel fusions were not associated with longer hospitalization or morbidity. Anterior plate fixation of the axis for degenerative disease can be accomplished with acceptable morbidity employing an extension of the standard anterolateral route.

  4. Velopharyngeal sphincter pathophysiologic aspects in the in cleft palat

    Directory of Open Access Journals (Sweden)

    Collares, Marcus Vinicius Martins


    Full Text Available Introduction: Cleft lip and palate are common congenital abnormalities with typical functional disorders on speech, deglutition and middle ear function. Objective: This article reviews functional labiopalatine disorders through a pathophysiological view. Method: We performed a literature search on line, as well as books and periodicals related to velopharyngeal sphincter. Our sources were LILACS, MEDLINE and SciELO databases, and we applied to the research Keywords of interest on the velopharyngeal pathophysiology, for articles published between 1965 and 2007. Conclusion: Velopharyngeal sphincter plays a central role in speech, swallowing and middle ear physiology in patients with labiopalatine cleft. At the end of our bibliographic review, pursuant to the velopharyngeal physiology in individuals with this disorder in the functional speech, deglutition and otologic function, we observed that although there is a great number of published data discussing this issue, further studies are necessary to completely understand the pathophysiology, due to the fact they have been exploited superficially.

  5. A Unified Pathophysiological Construct of Diabetes and its Complications. (United States)

    Schwartz, Stanley S; Epstein, Solomon; Corkey, Barbara E; Grant, Struan F A; Gavin Iii, James R; Aguilar, Richard B; Herman, Mary E


    Advances in understanding diabetes mellitus (DM) through basic and clinical research have helped clarify and reunify a disease state fragmented into numerous etiologies and subtypes. It is now understood that a common pathophysiology drives the diabetic state throughout its natural history and across its varied clinical presentations, a pathophysiology involving metabolic insults, oxidative damage, and vicious cycles that aggravate and intensify organ dysfunction and damage. This new understanding of the disease requires that we revisit existing diagnostics and treatment approaches, which were built upon outmoded assumptions. 'The Common Pathophysiologic Origins of Diabetes Mellitus and its Complications Construct' is presented as a more accurate, foundational, and translatable construct of DM that helps make sense of the hitherto ambiguous findings of long-term outcome studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Vincenzo Salpietro


    Full Text Available Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency has been reported with neurological and magnetic resonance imaging (MRI abnormalities (e.g., delayed myelination and brain atrophy due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH, a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric CNS seems to be particularly vulnerable to alterations induced by

  7. Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

    Directory of Open Access Journals (Sweden)

    Marcella Balbo


    Full Text Available The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment.

  8. Idiopathic Intracranial Hypertension – Pathophysiology Based on Case Series

    Directory of Open Access Journals (Sweden)

    Ljubisavljević Srdjan


    Full Text Available According to the definition, idiopathic intracranial hypertension (IIH is a pathological state characterized by an increase in intracranial pressure; however, there are no obvious intracranial pathological processes. The pathophysiology of this disorder is not clear, although there are many reports related to it.

  9. Pathophysiology of diurnal drooling in Parkinson’s disease

    NARCIS (Netherlands)

    Lenie van den Engel-Hoek; Johanna Kalf; Bastiaan Bloem; George Borm; Machiel Zwarts; Bert de Swart; Marten Munneke


    Drooling is an incapacitating feature of Parkinson's disease. Better pathophysiological insights are needed to improve treatment. In this study, we tested the hypothesis that the cause of drooling is multifactorial. We examined 15 patients with Parkinson's disease with distinct diurnal saliva loss

  10. New insights into the pathophysiology of postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

    Krenk, Lene; Rasmussen, Lars Simon; Kehlet, H


    There is evidence that postoperative cognitive dysfunction (POCD) is a significant problem after major surgery, but the pathophysiology has not been fully elucidated. The interpretation of available studies is difficult due to differences in neuropsychological test batteries as well as the lack...

  11. Parkinson's disease : The syndrome, the pathogenesis and pathophysiology

    NARCIS (Netherlands)

    Bartels, Anna L.; Leenders, Klaus L.

    Parkinson's disease (PD) is characterised by a slowly expanding degeneration of neurons particularly in the mesencephalon. The causes are unknown although risk factors in the genetic and toxic domain are being discovered. An important pathophysiological feature in PD is the loss of part of the

  12. Pathophysiology and Contributing Factors in Postprostatectomy Incontinence: A Review

    NARCIS (Netherlands)

    Heesakkers, J.P.F.A.; Farag, F.; Bauer, R.M.M.J.; Sandhu, J.; Ridder, D. de; Stenzl, A.


    CONTEXT: The incidence and awareness of postprostatectomy incontinence (PPI) has increased during the past few years, probably because of an increase in prostate cancer surgery. Many theories have been postulated to explain the pathophysiology of PPI. OBJECTIVE: The current review scrutinizes

  13. Pathophysiology of acute mountain sickness and high altitude pulmonary oedema

    DEFF Research Database (Denmark)

    Sutton, J R; Lassen, N


    We review the evidence that acute mountain sickness (AMS) and high altitude pulmonary oedema (HAPO) occur together more often than is realized. We hypothesize that AMS and HAPO have a common pathophysiological basis: both are due to increased pressure and flow in the microcirculation, causing...

  14. Elucidation of pathophysiology and treatment of neuropathic pain

    NARCIS (Netherlands)

    Vranken, Jan H.


    Neuropathic pain, pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, is relatively common, occurring in about 1% of the population. Studies in animal models describe a number of peripheral and central pathophysiological processes after nerve injury that

  15. An update on oxidative stress-mediated organ pathophysiology. (United States)

    Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C


    Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs

    NARCIS (Netherlands)

    van Zwieten, P. A.; Blauw, G. J.; van Brummelen, P.


    A survey shall be given on the physiological, pathophysiological and pharmacotherapeutic backgrounds of the biogenic amine 5-hydroxytryptamine (serotonin; 5HT), to be preceded by a few historical remarks. 5HT is biosynthesized from L-tryptophan via hydroxylation and subsequent decarboxylation. 5HT

  17. Unravelling narcolepsy : from pathophysiology to measuring treatment effects

    NARCIS (Netherlands)

    Heide, van der A.


    Narcolepsy is a disorder of the regulation of sleep and wakefulness, with as its major features excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed nocturnal sleep. The first part of this thesis concernes an overview of the pathophysiology,

  18. Effects of Triphasic Exercise on Blood Rheology and Pathophysiology

    African Journals Online (AJOL)

    The aim of this work is to study the relevance of physiology and pathophysiology in blood rheology as effects of triphasic exercise. Regular exercise which has been established as life prolonging has led to decrease in both peripheral vascular and coronary morbidity that has been associated with certain improvements in ...

  19. UMAPRM: Uniformly sampling the medial axis

    KAUST Repository

    Yeh, Hsin-Yi Cindy


    © 2014 IEEE. Maintaining clearance, or distance from obstacles, is a vital component of successful motion planning algorithms. Maintaining high clearance often creates safer paths for robots. Contemporary sampling-based planning algorithms That utilize The medial axis, or The set of all points equidistant To Two or more obstacles, produce higher clearance paths. However, They are biased heavily Toward certain portions of The medial axis, sometimes ignoring parts critical To planning, e.g., specific Types of narrow passages. We introduce Uniform Medial Axis Probabilistic RoadMap (UMAPRM), a novel planning variant That generates samples uniformly on The medial axis of The free portion of Cspace. We Theoretically analyze The distribution generated by UMAPRM and show its uniformity. Our results show That UMAPRM\\'s distribution of samples along The medial axis is not only uniform but also preferable To other medial axis samplers in certain planning problems. We demonstrate That UMAPRM has negligible computational overhead over other sampling Techniques and can solve problems The others could not, e.g., a bug Trap. Finally, we demonstrate UMAPRM successfully generates higher clearance paths in The examples.

  20. Pathophysiological significance and therapeutic applications of snake venom protease inhibitors. (United States)

    Thakur, Rupamoni; Mukherjee, Ashis K


    Protease inhibitors are important constituents of snake venom and play important roles in the pathophysiology of snakebite. Recently, research on snake venom protease inhibitors has provided valuable information to decipher the molecular details of various biological processes and offer insight for the development of some therapeutically important molecules from snake venom. The process of blood coagulation and fibrinolysis, in addition to affecting platelet function, are well known as the major targets of several snake venom protease inhibitors. This review summarizes the structure-functional aspects of snake venom protease inhibitors that have been described to date. Because diverse biological functions have been demonstrated by protease inhibitors, a comparative overview of their pharmacological and pathophysiological properties is also highlighted. In addition, since most snake venom protease inhibitors are non-toxic on their own, this review evaluates the different roles of individual protease inhibitors that could lead to the identification of drug candidates and diagnostic molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Different Pathophysiological Phenotypes among Newly Diagnosed Type 2 Diabetes Patients

    DEFF Research Database (Denmark)

    Stidsen, Jacob


    Type 2 diabetes (T2D) can be considered a syndrome with several different pathophysiological mechanisms leading to hyperglycemia. Nonetheless, T2D is treated according to algorithms as if it was one disease entity. Methods: We investigated the prevalence of different pathophysiological phenotypes...... or secondary diabetes), classic obesity-associated insulin resistant diabetes ( f-P-C-peptide >= 568 pmol/l) and a normoinsulinopenic group (333 age of our new T2D patients was 61 years (range 21-95 years), 57% were men. We found that 3.0% newly diagnosed T2D patients...... suffered from LADA, 3.9% from secondary diabetes, 6.0% from steroid induced diabetes 5.9% had insulinopenic diabetes, whereas 56.7% presented the classic obesity-associated insulin-resistant phenotype. 24.6% was classified as normoinsulinopenic patients. Conclusion: We conclude that newly diagnosed T2D...

  2. Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals. (United States)

    Matsumoto, Naoyuki; Kobayashi, Naoki; Uda, Natsu; Hirota, Miwako; Kawasaki, Hiroshi


    Leptomeningeal glioneuronal heterotopia (LGH) is a focal malformation of the cerebral cortex and frequently found in patients with thanatophoric dysplasia (TD). The pathophysiological mechanisms underlying LGH formation are still largely unclear because of difficulties in obtaining brain samples from human TD patients. Recently, we established a new animal model for analysing cortical malformations of human TD by utilizing our genetic manipulation technique for gyrencephalic carnivore ferrets. Here we investigated the pathophysiological mechanisms underlying the formation of LGH using our TD ferrets. We found that LGH was formed during corticogenesis in TD ferrets. Interestingly, we rarely found Ki-67-positive and phospho-histone H3-positive cells in LGH, suggesting that LGH formation does not involve cell proliferation. We uncovered that vimentin-positive radial glial fibers and doublecortin-positive migrating neurons were accumulated in LGH. This result may indicate that preferential cell migration into LGH underlies LGH formation. Our findings provide novel mechanistic insights into the pathogenesis of LGH in TD.

  3. The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming


    transplantation and point to the pathophysiological significance of portal hypertension. In this paper we aimed to review current knowledge on the pathophysiology of arterial vasodilatation and the hyperdynamic circulation in cirrhosis. This article is protected by copyright. All rights reserved.......Patients with cirrhosis and portal hypertension often develop complications from a variety of organ systems leading to a multiple organ failure. The combination of liver failure and portal hypertension result in a hyperdynamic circulatory state partly owing to simultaneous splanchnic and peripheral...... arterial vasodilatation. Increases in circulatory vasodilators are believed to be due to portosystemic shunting and bacterial translocation leading to redistribution of the blood volume with central hypovolemia. Portal hypertension per se and increased splanchnic blood flow are mainly responsible...

  4. Hypertension in women--pathophysiological and clinical aspects. (United States)

    Erdine, Serap; Arslan, Eren; Olszanecka, Agnieszka


    Hypertension is the most important risk factor, responsible for cardiovascular morbidity and mortality worldwide, both in men and women. Cardiovascular disorders in women are still underestimated, due to lower absolute risk calculations and the underdetection of classical risk factors. In recent years the differences in pathophysiology and the clinical presentation and treatment of cardiac diseases in women have become fields of interest and research. Several studies have examined gender-related differences in the pathophysiology of hypertension, its prevalence and control. The influence of menopause, obesity and salt-sensitivity on the pathogenesis of hypertension in women has been widely investigated. This article presents current data on differences in prevalence, control and mechanisms of hypertension in women.

  5. Gender Differences in Epidemiology, Pathophysiology, and Treatment of Hypertension. (United States)

    Di Giosia, Paolo; Giorgini, Paolo; Stamerra, Cosimo Andrea; Petrarca, Marco; Ferri, Claudio; Sahebkar, Amirhossein


    This review aims to examine gender differences in both the epidemiology and pathophysiology of hypertension and to explore gender peculiarities on the effects of antihypertensive agents in decreasing BP and CV events. Men and women differ in prevalence, awareness, and control rate of hypertension in an age-dependent manner. Studies suggest that sex hormones changes play a pivotal role in the pathophysiology of hypertension in postmenopausal women. Estrogens influence the vascular system inducing vasodilatation, inhibiting vascular remodeling processes, and modulating the renin-angiotensin aldosterone system and the sympathetic system. This leads to a protective effect on arterial stiffness during reproductive age that is dramatically reversed after menopause. Data on the efficacy of antihypertensive therapy between genders are conflicting, and the underrepresentation of aged women in large clinical trials could influence the results. Therefore, further clinical research is needed to uncover potential gender differences in hypertension to promote the development of a gender-oriented approach to antihypertensive treatment.

  6. Pathophysiology of obstructive sleep apnea-hypopnea syndrome (OSAHS

    Directory of Open Access Journals (Sweden)

    Marco Venegas-Mariño


    Full Text Available Obstructive sleep apnea-hypopnea syndrome (OSAHS is a disease characterized by recurrent upper airway obstruction (UAO, with decreased airflow, intermittent hypoxemia, and awakening during sleep. Two essential factors are related to the pathophysiology of OSAHS: anatomical alterations and reduction or absence of neural control. While studying OSAHS, the site or sites of obstruction of the UA should be identified; they may extend from the nasal wings to the hypopharynx. Another important factor in this syndrome is the nervous influence on muscle tone of the hypopharynx, as well as the changes in blood pH, which are secondary to micro-arousals. Body position and sleep stage determine the severity. The pathophysiology of OSAHS should be understood to properly study a patient and provide the best treatment option.

  7. Actuator assembly including a single axis of rotation locking member (United States)

    Quitmeyer, James N.; Benson, Dwayne M.; Geck, Kellan P.


    An actuator assembly including an actuator housing assembly and a single axis of rotation locking member fixedly attached to a portion of the actuator housing assembly and an external mounting structure. The single axis of rotation locking member restricting rotational movement of the actuator housing assembly about at least one axis. The single axis of rotation locking member is coupled at a first end to the actuator housing assembly about a Y axis and at a angle to an X and Z axis providing rotation of the actuator housing assembly about the Y axis. The single axis of rotation locking member is coupled at a second end to a mounting structure, and more particularly a mounting pin, about an X axis and at a angle to a Y and Z axis providing rotation of the actuator housing assembly about the X axis. The actuator assembly is thereby restricted from rotation about the Z axis.

  8. Migraine aura pathophysiology: the role of blood vessels and microembolisation


    Dalkara, Turgay; Nozari, Ala; Moskowitz, Michael A


    Migraine attacks with auras are sometimes associated with underlying hereditary or acquired cerebrovascular disorders. A unifying pathophysiological explanation linking migraine to these conditions has been diffcult to identify. On the basis of genetic and epidemiological evidence, we suggest that changes in blood vessels, hypoperfusion disorders, and microembolisation can cause neurovascular dysfunction and evoke cortical spreading depression, an event that is widely thought to underlie aura...

  9. Pathophysiology of pelvic organ prolapse and stress urinary incontinence

    Directory of Open Access Journals (Sweden)

    Payal D Patel


    Full Text Available Although they may present with significant morbidity, pelvic organ prolapse and stress urinary incontinence are mainly afflicitions that affect quality of life. To appropiately treat these entities, comprehension of the various theories of pathophysiology is paramount. Utilizing a Medline search, this article reviews recent data concerning intrinsic (i.e., genetics, postmenopausal status and extrinsic factors (i.e., previous hysterectomy, childbirth leading to organ prolapse or stress incontinence

  10. Pathophysiology of Headaches with a Prominent Vascular Component

    Directory of Open Access Journals (Sweden)

    Juan A Pareja


    Full Text Available Vascular changes, whether preliminary or secondary, seem to accompany most headaches. The literature concerning pathophysiological mechanisms in headaches where vascular phenomena are a major, integral part, ie, migraine and cluster headache syndrome, is reviewed and the most common forms of headache associated with cerebrovascular disease are discussed. Emphasis is placed on the vascular phenomena and on the abundant hypotheses and theories regarding headache mechanisms. This review also presents alternative explanatory models, and compares the available anatomical, physiological and biochemical results.

  11. Pancreatitis in dogs and cats – definitions and pathophysiology


    Watson, Penelope Jayne


    Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats and presents a spectrum of disease severities from acute to chronic and mild to severe. It is usually sterile, but the causes and pathophysiology remain poorly understood. The acute end of the disease spectrum is associated with a high mortality but the potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either species c...

  12. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal-axis (HPA-axis)


    Lee, Richard; Sawa, Akira


    In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the hypothalamic-pituitary-adrenal axis (HPA)-axis function and behavior. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA-axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, duration, and intensity during di...

  13. Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth (United States)

    Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore


    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome. PMID:25763405

  14. Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas


    Full Text Available Polycystic ovary syndrome (PCOS is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR, and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

  15. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. (United States)

    Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore


    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

  16. Blended Learning Versus Traditional Lecture in Introductory Nursing Pathophysiology Courses. (United States)

    Blissitt, Andrea Marie


    Currently, many undergraduate nursing courses use blended-learning course formats with success; however, little evidence exists that supports the use of blended formats in introductory pathophysiology courses. The purpose of this study was to compare the scores on pre- and posttests and course satisfaction between traditional and blended course formats in an introductory nursing pathophysiology course. This study used a quantitative, quasi-experimental, nonrandomized control group, pretest-posttest design. Analysis of covariance compared pre- and posttest scores, and a t test for independent samples compared students' reported course satisfaction of the traditional and blended course formats. Results indicated that the differences in posttest scores were not statistically significant between groups. Students in the traditional group reported statistically significantly higher satisfaction ratings than students in the blended group. The results of this study support the need for further research of using blended learning in introductory pathophysiology courses in undergraduate baccalaureate nursing programs. Further investigation into how satisfaction is affected by course formats is needed. Copyright 2016, SLACK Incorporated.

  17. Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals. (United States)

    Matsumoto, Naoyuki; Hoshiba, Yoshio; Morita, Kazuya; Uda, Natsu; Hirota, Miwako; Minamikawa, Maki; Ebisu, Haruka; Shinmyo, Yohei; Kawasaki, Hiroshi


    Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  18. Tics and Tourette's: update on pathophysiology and tic control. (United States)

    Ganos, Christos


    To describe recent advances in the pathophysiology of tics and Tourette syndrome, and novel insights on tic control. The cortico-basal ganglia-thalamo-cortical loops are implicated in generation of tics. Disruption of GABAergic inhibition lies at the core of tic pathophysiology, but novel animal models also implicate cholinergic and histaminergic neurotransmission. Tourette syndrome patients have altered awareness of volition and enhanced formation of habits. Premonitory urges are not the driving force behind all tics. The intensity of premonitory urges depends on patients' capacity to perceive interoceptive signals. The insular cortex is a key structure in this process. The trait intensity of premonitory urges is not a prerequisite of voluntary tic inhibition, a distinct form of motor control. Voluntary tic inhibition is most efficient in the body parts that tic the least. The prefrontal cortex is associated with the capacity to inhibit tics. The management of tics includes behavioral, pharmacological and surgical interventions. Treatment recommendations differ based on patients' age. The study of Tourette syndrome pathophysiology involves different neural disciplines and provides novel, exciting insights of brain function in health and disease. These in turn provide the basis for innovative treatment approaches of tics and their associations.

  19. Spasmodic Dysphonia: A Review. Part 2: Characterization of Pathophysiology. (United States)

    Hintze, Justin M; Ludlow, Christy L; Bansberg, Stephen F; Adler, Charles H; Lott, David G


    Objective The purpose of this review is to describe the recent advances in characterizing spasmodic dysphonia. Spasmodic dysphonia is a task-specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. The pathophysiology is poorly understood, and there are diagnostic difficulties. Data Sources PubMed, Google Scholar, and Cochrane Library. Review Methods The data sources were searched using the following search terms: ( spasmodic dysphonia or laryngeal dystonia) and ( etiology, aetiology, diagnosis, pathogenesis, or pathophysiology). Conclusion The diagnosis of spasmodic dysphonia can be difficult due to the lack of a scientific consensus on diagnostic criteria and the fact that other voice disorders may present similarly. Confusion can arise between spasmodic dysphonia and muscle tension dysphonia. Spasmodic dysphonia symptoms are tied to particular speech sounds, whereas muscle tension dysphonia is not. With the advent of more widespread use of high-speed laryngoscopy and videokymography, measures of the disruptions in phonation and delays in the onset of vocal fold vibration after vocal fold closure can be quantified. Recent technological developments have expanded our understanding of the pathophysiology of spasmodic dysphonia. Implications for Practice A 3-tiered approach, involving a questionnaire, followed by speech assessment and nasolaryngoscopy is the most widely accepted method for making the diagnosis in most cases. More experimental and invasive techniques such as electromyography and neuroimaging have been explored to further characterize spasmodic dysphonia and aid in diagnosing difficult cases.

  20. Central voice production and pathophysiology of spasmodic dysphonia. (United States)

    Mor, Niv; Simonyan, Kristina; Blitzer, Andrew


    Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. NA.Laryngoscope, 128:177-183, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes. (United States)

    Makris, Konstantinos; Spanou, Loukia


    Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

  2. Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Shiyi Guo


    Full Text Available Restless legs syndrome (RLS, a common neurological sensorimotor disorder in western countries, has gained more and more attention in Asian countries. The prevalence of RLS is higher in older people and females. RLS is most commonly related to iron deficiency, pregnancy and uremia. The RLS symptoms show a significant circadian rhythm and a close relationship to periodic limb movements (PLMs in clinical observations, while the pathophysiological pathways are still unknown. The diagnostic criteria have been revised in 2012 to improve the validity of RLS diagnosis. Recent studies have suggested an important role of iron decrease of brain in RLS pathophysiology. Dopaminergic (DA system dysfunction in A11 cell groups has been recognized long ago from clinical treatment and autopsy. Nowadays, it is believed that iron dysfunction can affect DA system from different pathways and opioids have a protective effect on DA system. Several susceptible single nucleotide polymorphisms such as BTBD9 and MEIS1, which are thought to be involved in embryonic neuronal development, have been reported to be associated with RLS. Several pharmacological and non-pharmacological treatment are discussed in this review. First-line treatments of RLS include DA agents and α2δ agonists. Augmentation is very common in long-term treatment of RLS which makes prevention and management of augmentation very important for RLS patients. A combination of different types of medication is effective in preventing and treating augmentation. The knowledge on RLS is still limited, the pathophysiology and better management of RLS remain to be discovered.

  3. Pancreatitis in dogs and cats: definitions and pathophysiology. (United States)

    Watson, P


    Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats and presents a spectrum of disease severities from acute to chronic and mild to severe. It is usually sterile, but the causes and pathophysiology remain poorly understood. The acute end of the disease spectrum is associated with a high mortality but the potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either species can cause refractory pain and reduce quality of life. It may also result in progressive exocrine and endocrine functional impairment. There is confusion in the veterinary literature about definitions of acute and chronic pancreatitis and there are very few studies on the pathophysiology of naturally occurring pancreatitis in dogs and cats. This article reviews histological and clinical definitions and current understanding of the pathophysiology and causes in small animals by comparison with the much more extensive literature in humans, and suggests many areas that need further study in dogs and cats. © 2015 British Small Animal Veterinary Association.

  4. Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis (United States)

    Tsang, S.W.; Auyeung, K.K.W.; Bian, Z.X.; Ko, J.K.S.


    Background Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. Results When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Conclusion Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients. PMID:27009115

  5. DMPD: Pathophysiological roles of interleukin-18 in inflammatory liver diseases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10807517 Pathophysiological roles of interleukin-18 in inflammatory liver diseases....l) Show Pathophysiological roles of interleukin-18 in inflammatory liver diseases. PubmedID 10807517 Title P...athophysiological roles of interleukin-18 in inflammatory liver diseases. Authors

  6. Nitric oxide in the stress axis. (United States)

    López-Figueroa, M O; Day, H E; Akil, H; Watson, S J


    In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

  7. Neutral axis as damage sensitive feature

    International Nuclear Information System (INIS)

    Sigurdardottir, D H; Glisic, B


    Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature. (paper)

  8. Neutral axis as damage sensitive feature (United States)

    Sigurdardottir, D. H.; Glisic, B.


    Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature.

  9. Aeroelastically coupled blades for vertical axis wind turbines (United States)

    Paquette, Joshua; Barone, Matthew F.


    Various technologies described herein pertain to a vertical axis wind turbine blade configured to rotate about a rotation axis. The vertical axis wind turbine blade includes at least an attachment segment, a rear swept segment, and optionally, a forward swept segment. The attachment segment is contiguous with the forward swept segment, and the forward swept segment is contiguous with the rear swept segment. The attachment segment includes a first portion of a centroid axis, the forward swept segment includes a second portion of the centroid axis, and the rear swept segment includes a third portion of the centroid axis. The second portion of the centroid axis is angularly displaced ahead of the first portion of the centroid axis and the third portion of the centroid axis is angularly displaced behind the first portion of the centroid axis in the direction of rotation about the rotation axis.

  10. Theoretical tool movement required to diamond turn an off-axis paraboloid on axis

    International Nuclear Information System (INIS)

    Thompson, D.C.


    Current techniques for manufacturing off-axis paraboloids are both expensive and insufficiently accurate. An alternative method, turning the workpiece about its axis on a diamond-turning machine, is presented, and the equations describing the necessary tool movement are derived. A discussion of a particular case suggests that the proposed technique is feasible

  11. New Urban Vertical Axis Wind Turbine Design

    Directory of Open Access Journals (Sweden)

    Alexandru-Mihai CISMILIANU


    Full Text Available This paper develops a different approach for enhancing the performance of Vertical Axis Wind Turbines for the use in the urban or rural environment and remote isolated residential areas. Recently the vertical axis wind turbines (VAWT have become more attractive due to the major advantages of this type of turbines in comparison to the horizontal axis wind turbines. We aim to enhance the overall performance of the VAWT by adding a second set of blades (3 x 2=6 blades following the rules of biplane airplanes. The model has been made to operate at a maximum power in the range of the TSR between 2 to 2.5. The performances of the VAWT were investigated numerically and experimentally and justify the new proposed design.

  12. RITA: The reinvented triple axis spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Mason, T.E. [Toronto Univ., ON (Canada). Dept. of Physics; Clausen, K.N.; Aeppli, G.; McMorrow, D.R.; Kjems, J.K. [Risoe National Lab., Roskilde (Denmark)


    Risoe National Laboratory was reported to be in the process of developing a new spectrometer design, RITA, based on the triple axis design. The spectrometer will attempt to incorporate more recent innovations such as multilayer supermirrors and microstrip proportional counters into a rethinking of the triple-axis spectrometer. By optimizing the beam optics, using supermirrors and extending the analyser to map regions of (Q, {omega}) space using an array of independently controllable pyrolytic graphite crystals focussed on an area detector, it was hoped that the efficiency of single-crystal inelastic experiments could be increased by as much as a factor of 20. 7 figs., 20 refs.

  13. Equilibrium studies of helical axis stellarators

    International Nuclear Information System (INIS)

    Hender, T.C.; Carreras, B.A.; Garcia, L.; Harris, J.H.; Rome, J.A.; Cantrell, J.L.; Lynch, V.E.


    The equilibrium properties of helical axis stellarators are studied with a 3-D equilibrium code and with an average method (2-D). The helical axis ATF is shown to have a toroidally dominated equilibrium shift and good equilibria up to at least 10% peak beta. Low aspect ratio heliacs, with relatively large toroidal shifts, are shown to have low equilibrium beta limits (approx. 5%). Increasing the aspect ratio and number of field periods proportionally is found to improve the equilibrium beta limit. Alternatively, increasing the number of field periods at fixed aspect ratio which raises and lowers the toroidal shift improves the equilibrium beta limit

  14. The control of independent students’ work effectiveness during pathophysiology study

    Directory of Open Access Journals (Sweden)

    О. V. Melnikova


    Full Text Available The course of Pathophysiology study includes both auditoria hours (lectures and practical classes and independent work of students. The latter makes up 38% of total hours given for Pathophysiology study. Independent work of students includes the following items: preparation for practical classes, writing reviews on different topics, preparation for current and final computer testing, study of the topics which are not discussed during lectures and practical classes. In order to assimilate the course of Pathophysiology completely students should effectively use their hours given for independent work. Unfortunately, the level of students’ independent individual work is low; it includes only learning of single facts, that is not enough for higher medical education. THE AIM OF STUDY: To propose the method of control of the effectiveness of students’ independent work. The most important part of student’s individual work is preparation for study in auditoria, because it determines the qualitative level of study during practical classes. The student should enter the class not only with the knowledge of basic sciences (Anatomy, Histology, Biochemistry, Normal Physiology etc. but also with the understanding of key items of the topic of the practical class. The problem consists in the following: the teacher can’t check the level of basic knowledge in each student – there is not enough time during practical class for this procedure. In order to increase the effectiveness of individual students’ work a special workbook for the practical classes was developed at the Pathophysiology department. While preparing for practical classes students write down basic items of the topic, refresh some questions from Normal Physiology, Biochemistry and other subjects. In the beginning of the practical class the teacher controls the level of student’s preparation to the topic by checking the fulfillment of tasks in the workbook. It takes a little time, but it

  15. Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need (United States)

    Corcoran, David


    The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation. PMID:29030424

  16. Bone pain induced by metastatic cancer: pathophysiology and treatment

    International Nuclear Information System (INIS)

    Salas-Herrera, Isaias; Huertas-Gabert, Luis Carlos


    Cancer patients who develop bone metastases are an estimated 60 to 84% . Of these 79% experienced pain syndromes are difficult to manage, of which 50% die without adequate pain relief and with a poor quality of life. Therefore, it is necessary to have accessible and effective medications for the management of this condition. The pathophysiology of pain in bone is reviewed and the drugs used most frequently in the management of this type of cancer pain are described. Furthermore an algorithm of 6 steps is presented and can guide the physician when making a therapeutic decision. (author) [es

  17. Pathophysiology of Portal Hypertension and Its Clinical Links (United States)

    Seo, Yeon Seok; Shah, Vijay H


    Portal hypertension is a major cause of morbidity and mortality in patients with liver cirrhosis. Intrahepatic vascular resistance due to architectural distortion and intrahepatic vasoconstriction, increased portal blood flow due to splanchnic vasodilatation, and development of collateral circulation have been considered as major factors for the development of portal hypertension. Recently, sinusoidal remodeling and angiogenesis have been focused as potential etiologic factors and various researchers have tried to improve portal hypertension by modulating these new targets. This article reviews potential new treatments in the context of portal hypertension pathophysiology concepts. PMID:25755320

  18. The pathophysiology of the nodular and micronodular small bowel fold

    International Nuclear Information System (INIS)

    Olmsted, W.W.; Ros, P.R.; Moser, R.P.; Shekita, K.M.; Lichtenstein, J.E.


    The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is at the limit of resolution of current roentgenographic technique. When the villi are enlarged, they appear radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor,inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold

  19. Pathophysiology of the nodular and micronodular small bowel fold

    International Nuclear Information System (INIS)

    Olmstead, W.W.; Ros, P.R.; Moser, R.P.; Shekitka, K.M.; Lichtenstein, J.E.; Buck, J.L.


    The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is just at the resolution of current roentgenographic technique. When the villi are enlarged, they can be seen radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor, inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold

  20. Obesity and Pulmonary Hypertension: A Review of Pathophysiologic Mechanisms

    Directory of Open Access Journals (Sweden)

    Scott E. Friedman


    Full Text Available Pulmonary hypertension (PH is a potentially life-threatening condition arising from a wide variety of pathophysiologic mechanisms. Effective treatment requires a systematic diagnostic approach to identify all reversible mechanisms. Many of these mechanisms are relevant to those afflicted with obesity. The unique mechanisms of PH in the obese include obstructive sleep apnea, obesity hypoventilation syndrome, anorexigen use, cardiomyopathy of obesity, and pulmonary thromboembolic disease. Novel mechanisms of PH in the obese include endothelial dysfunction and hyperuricemia. A wide range of effective therapies exist to mitigate the disability of PH in the obese.

  1. The Sphenopalatine Ganglion: Anatomy, Pathophysiology, and Therapeutic Targeting in Headache. (United States)

    Robbins, Matthew S; Robertson, Carrie E; Kaplan, Eugene; Ailani, Jessica; Charleston, Larry; Kuruvilla, Deena; Blumenfeld, Andrew; Berliner, Randall; Rosen, Noah L; Duarte, Robert; Vidwan, Jaskiran; Halker, Rashmi B; Gill, Nicole; Ashkenazi, Avi


    The sphenopalatine ganglion (SPG) has attracted the interest of practitioners treating head and face pain for over a century because of its anatomical connections and role in the trigemino-autonomic reflex. In this review, we discuss the anatomy of the SPG, as well as what is known about its role in the pathophysiology of headache disorders, including cluster headache and migraine. We then address various therapies that target the SPG, including intranasal medication delivery, new SPG blocking catheter devices, neurostimulation, chemical neurolysis, and ablation procedures. © 2015 American Headache Society.

  2. Pathophysiological aspects of ureterorenoscopic management of upper urinary tract calculi

    DEFF Research Database (Denmark)

    Osther, Palle J S; Pedersen, Katja V; Lildal, Søren K


    PURPOSE OF REVIEW: Indications for ureterorenoscopy are expanding without hard scientific evidence to support its efficacy. Therefore, it is extremely important to focus on potential harmful effects of the procedure itself. This review explores how physiology of the upper urinary tract reacts...... of the β-receptor agonist isoproterenol in the irrigation fluid has shown a potential for reducing both intrarenal pressure and ureteral tone during ureterorenoscopy. SUMMARY: Upper urinary tract physiology has unique features that may be pushed into pathophysiological processes by the unique elements...

  3. Oral submucous fibrosis: An update on pathophysiology of malignant transformation. (United States)

    Arakeri, Gururaj; Patil, Shekar Gowda; Aljabab, Abdulsalam S; Lin, Kuan-Chou; Merkx, M A W; Gao, Shan; Brennan, Peter A


    Oral submucous fibrosis (OSMF) is a potentially malignant condition associated with areca nut chewing. Formerly confined to the Indian subcontinent, it is now often seen in Asian populations of the United Kingdom, USA and other developed countries, and is therefore a serious problem for global health. What makes it more sinister is the malignant transformation rate, which has been reported to be around 7.6% over a 17-year period. In this concise article, we review the current trends in the pathophysiology of malignant transformation of OSMF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Role of renal vascular potassium channels in physiology and pathophysiology

    DEFF Research Database (Denmark)

    Salomonsson, Max; Brasen, Jens Christian; Sorensen, Charlotte Mehlin


    The control of renal vascular tone is important for the regulation of salt and water balance, blood pressure and the protection against damaging elevated glomerular pressure. The K+ conductance is a major factor in the regulation of the membrane potential (Vm ) in vascular smooth muscle (VSMC...... the ambiguous in vitro and in vivo results. We discuss the role of single types of K+ channels and the integrated function of several classes. We also deal with the possible role of renal vascular K+ channels in the pathophysiology of hypertension, diabetes mellitus and sepsis. This article is protected...

  5. The pathophysiology of the trigeminal autonomic cephalalgias, with clinical implications

    DEFF Research Database (Denmark)

    Barloese, Mads C J


    , it is obvious that this brainstem reflex is regulated by higher centers that seemingly play a pivotal role in the attacks and the wide range of other symptoms indicating a homeostatic disturbance. These symptoms, as well as a number of well-validated findings, implicate the hypothalamus in the pathophysiology....... over the course of the past 2-3 decades, novel therapies and technological advances have helped increase our knowledge of these clinical syndromes, and will likely continue to do so in the coming years as we witness the arrival of new drugs and neurostimulation options. In this review, the clinical...

  6. Pathophysiological Mechanisms of Laser Correction in Critical Conditions

    Directory of Open Access Journals (Sweden)

    V. L. Kozhura


    Full Text Available The paper provides the generalized results of studies dealing with the use of low-intensive laser irradiation in blood loss-induced critical conditions in an experiment and in patients with severe mechanical injury. In the light of recent data and the data available in the literature, the authors consider some pathophysiological mechanisms of action of laser radiation at all living matter organization levels: molecular, cellular, organ, and systemic. The feasibilities of laser correction of hemostastic disorders are defined in relation to the volume of blood loss and the functional state of compensatory systems. 

  7. Triple-axis spectrometer DruechaL

    International Nuclear Information System (INIS)

    Buehrer, W.; Keller, P.


    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs

  8. Vortex capturing vertical axis wind turbine

    International Nuclear Information System (INIS)

    Zannetti, L; Gallizio, F; Ottino, G


    An analytical-numerical study is presented for an innovative lift vertical axis turbine whose blades are designed with vortex trapping cavities that act as passive flow control devices. The unsteady flow field past one-bladed and two-bladed turbines is described by a combined analytical and numerical method based on conformal mapping and on a blob vortex method

  9. The Trading Axis in Irkutsk Downtown

    Directory of Open Access Journals (Sweden)

    Elena Grigoryeva


    Full Text Available The article reveals a linear concentration of the trading function in the historical center of Irkutsk. It features historical prerequisites and continuation of the tradition in the post-Soviet period, given the conversion of plants and factories. The article analyses the current state and prospects of modernization of the trading axis with its transformation into a modern public space.

  10. Triple-axis spectrometer DruechaL

    Energy Technology Data Exchange (ETDEWEB)

    Buehrer, W; Keller, P [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)


    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs.

  11. Epidemiology, genetics, pathophysiology, and prognostic classifications of cerebral arteriovenous malformations. (United States)

    Ozpinar, Alp; Mendez, Gustavo; Abla, Adib A


    Arteriovenous malformations (AVMs) are vascular deformities involving fistula formation of arterial to venous structures without an intervening capillary bed. Such anomalies can prove fatal as the high arterial flow can disrupt the integrity of venous walls, thus leading to dangerous sequelae such as hemorrhage. Diagnosis of these lesions in the central nervous system can often prove challenging as intracranial AVMs represent a heterogeneous vascular pathology with various presentations and symptomatology. The literature suggests that most brain AVMs (bAVMs) are identified following evaluation of the etiology of acute cerebral hemorrhage, or incidentally on imaging associated with seizure or headache workup. Given the low incidence of this disease, most of the data accrued on this pathology comes from single-center experiences. This chapter aims to distill the most important information from these studies as well as examine meta-analyses on bAVMs in order to provide a comprehensive introduction into the natural history, classification, genetic underpinnings of disease, and proposed pathophysiology. While there is yet much to be elucidated about AVMs of the central nervous system, we aim to provide an overview of bAVM etiology, classification, genetics, and pathophysiology inherent to the disease process. © 2017 Elsevier B.V. All rights reserved.

  12. Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment. (United States)

    Pittenger, Christopher; Bloch, Michael H; Williams, Kyle


    Obsessive compulsive disorder is prevalent, disabling, incompletely understood, and often resistant to current therapies. Established treatments consist of specialized cognitive-behavioral psychotherapy and pharmacotherapy with medications targeting serotonergic and dopaminergic neurotransmission. However, remission is rare, and more than a quarter of OCD sufferers receive little or no benefit from these approaches, even when they are optimally delivered. New insights into the disorder, and new treatment strategies, are urgently needed. Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder. Here we review the current state of this evidence, including neuroimaging studies, genetics, neurochemical investigations, and insights from animal models. Finally, we review recent findings from small clinical trials of glutamate-modulating medications in treatment-refractory OCD. The precise role of glutamate dysregulation in OCD remains unclear, and we lack blinded, well-controlled studies demonstrating therapeutic benefit from glutamate-modulating agents. Nevertheless, the evidence supporting some important perturbation of glutamate in the disorder is increasingly strong. This new perspective on the pathophysiology of OCD, which complements the older focus on monoaminergic neurotransmission, constitutes an important focus of current research and a promising area for the ongoing development of new therapeutics. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Jaundice associated pruritis: a review of pathophysiology and treatment. (United States)

    Bassari, Ramez; Koea, Jonathan B


    To review the underlying pathophysiology and currently available treatments for pruritis associated with jaundice. English language literature was reviewed using MEDLINE, PubMed, EMBASE and for papers and trails addressing the pathophysiology and potential treatments for pruritis associated with jaundice. Recent advances in the understanding of the peripheral anatomy of itch transmission have defined a histamine stimulated pathway and a cowhage stimulated pathway with sensation conveyed centrally via the contralateral spinothalamic tract. Centrally, cowhage and histamine stimulated neurons terminate widely within the thalamus and sensorimotor cortex. The causative factors for itch in jaundice have not been clarified although endogenous opioids, serotonin, steroid and lysophosphatidic acid all play a role. Current guidelines for the treatment of itching in jaundice recommend initial management with biliary drainage where possible and medical management with ursodeoxycholic acid, followed by cholestyramine, rifampicin, naltrexone and sertraline. Other than biliary drainage no single treatment has proved universally effective. Pruritis associated with jaundice is a common but poorly understood condition for which biliary drainage is the most effective therapy. Pharmacological therapy has advanced but remains variably effective.

  14. Pathophysiology of increased intestinal permeability in obstructive jaundice (United States)

    Assimakopoulos, Stelios F; Scopa, Chrisoula D; Vagianos, Constantine E


    Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome. PMID:18161914

  15. Concussion: the history of clinical and pathophysiological concepts and misconceptions. (United States)

    McCrory, P R; Berkovic, S F


    Concussion is a well-recognized clinical entity; however, its pathophysiologic basis remains a mystery. One unresolved issue is whether concussion is associated with lesser degrees of diffuse structural change seen in severe traumatic brain injury, or is the mechanism entirely caused by reversible functional changes. This issue is clouded not only by the lack of critical data, but also by confusion in terminology, even in contemporary literature. This confusion began in ancient times when no distinction was made between the transient effects of concussion and severe traumatic brain injury. The first clear separate recognition of concussion was made by the Persian physician, Rhazes, in the 10th century. Lanfrancus subsequently expanded this concept as brain "commotion" in the 13th century, although other Renaissance physicians continued to obscure this concept. By the 18th century, a variety of hypotheses for concussion had emerged. The 19th century discovery of petechial hemorrhagic lesions in severe traumatic brain injury led to these being posited as the basis of concussion, and a similar logic was used later to suggest diffuse axonal injury was responsible. The neuropathology and pathophysiology of concussion has important implications in neurology, sports medicine, medicolegal medicine, and in the understanding of consciousness. Fresh approaches to these questions are needed and modern research tools, including functional imaging and experimental studies of ion-channel function, could help elucidate this puzzle that has evolved over the past 3,000 years.

  16. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology. (United States)

    Shimano, Hitoshi; Sato, Ryuichiro


    Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.

  17. Pathophysiology, diagnosis, and treatment of canine hip dysplasia

    International Nuclear Information System (INIS)

    Cook, J.L.; Tomlinson, J.L.; Constantinescu, G.M.


    Dogs with hip dysplasia are commonly presented to veterinarians for evaluation. Although many causes of the condition have been proposed, a definitive cause has not been established. The multifactorial nature of canine hip dysplasia can confuse client education and management ofthe disease. The basic concept involved is the biomechanical imbalance between the forces on the coxofemoral joint and the associated muscle mass; the result is joint laxity in young, growing dogs. This laxity leads to incongruity; the eventual result is degenerative joint disease. Canine hip dysplasia can affect any breed but is most often reported in large and giant breeds. Understanding the pathophysiology and biomechanics involved with this developmental disease is important in providing clients with diagnostic, therapeutic, and prognostic information. The selection of treatment is influenced by the following factors:the age, health, and intended use of the patient; clinical signs; diagnostic findings; the availability of treatment; and the financial constraints of the owner. This article discusses the current concepts concerning the pathophysiology and biomechanics of canine hip dysplasia and outlines diagnostic and therapeutic options. The objective of the article is to provide practitioners with a reference for decision making and client education

  18. Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology (United States)


    Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits. PMID:29670770

  19. Extra-osseous uterine pathophysiology demonstrated on skeletal scintigraphy

    International Nuclear Information System (INIS)

    Mansberg, R.; Lewis, G.


    Full text: Skeletal scintigraphy is a sensitive procedure for evaluating disease and trauma involving the skeleton. Extra-skeletal pathophysiology is also often demonstrated. This may include uptake by tumours, soft tissue calcification and infection as well as renal pathology. Skeletal scintigraphy is often performed to evaluate hip and back pain and extra-osseous uterine pathophysiology can be demonstrated in both the early and late phases of the study as in the following cases. Three women underwent skeletal scintigraphy for the investigation of low back pain in two patients and post-partum hip pain in one. A large vascular uterus with deviation of the bladder was demonstrated in the post-partum patient. Increased pelvic vascularity and bladder deviation in the second patient was shown by ultrasound to correspond to a left-sided fibroid with associated adenomyosis. In the third case, right-sided pelvic vascularity and left bladder deviation were shown on ultrasound to be due to an anteverted, anteflexed uterus tilted to the right. These cases illustrate the importance of documenting extra-osseous findings on skeletal scintigraphy and the benefits of correlation with anatomical imaging

  20. Transcranial magnetic stimulation and sleep disorders: pathophysiologic insights. (United States)

    Nardone, Raffaele; Höller, Yvonne; Brigo, Francesco; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen


    The neural mechanisms underlying the development of the most common intrinsic sleep disorders are not completely known. Therefore, there is a great need for noninvasive tools which can be used to better understand the pathophysiology of these diseases. Transcranial magnetic stimulation (TMS) offers a method to noninvasively investigate the functional integrity of the motor cortex and its corticospinal projections in neurologic and psychiatric diseases. To date, TMS studies have revealed cortical and corticospinal dysfunction in several sleep disorders, with cortical hyperexcitability being a characteristic feature in some disorders (i.e., the restless legs syndrome) and cortical hypoexcitability being a well-established finding in others (i.e., obstructive sleep apnea syndrome narcolepsy). Several research groups also have applied TMS to evaluate the effects of pharmacologic agents, such as dopaminergic agent or wake-promoting substances. Our review will focus on the mechanisms underlying the generation of abnormal TMS measures in the different types of sleep disorders, the contribution of TMS in enhancing the understanding of their pathophysiology, and the potential diagnostic utility of TMS techniques. We also briefly discussed the possible future implications for improving therapeutic approaches. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Studies on the Pathophysiology and Genetic Basis of Migraine (United States)

    Gasparini, Claudia F; Sutherland, Heidi G.; Griffiths, Lyn R


    Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies. PMID:24403849

  2. Postoperative ileus: Recent developments in pathophysiology and management. (United States)

    Bragg, Damian; El-Sharkawy, Ahmed M; Psaltis, Emmanouil; Maxwell-Armstrong, Charles A; Lobo, Dileep N


    Postoperative ileus (POI) is a frequent occurrence after abdominal and other types of surgery, and is associated with significant morbidity and costs to health care providers. The aims of this narrative review were to provide an update of classification systems, preventive techniques, pathophysiological mechanisms, and treatment options for established POI. The Web of Science, MEDLINE, PubMed and Google Scholar databases were searched using the key phrases 'ileus', 'postoperative ileus' and 'definition', for relevant studies published in English from January 1997 to August 2014. POI is still a problematic and frequent complication of surgery. Fluid overload, exogenous opioids, neurohormonal dysfunction, and gastrointestinal stretch and inflammation are key mechanisms in the pathophysiology of POI. Evidence is supportive of thoracic epidural analgesia, avoidance of salt and water overload, alvimopan and gum chewing as measures for the prevention of POI, and should be incorporated into perioperative care protocols. Minimal access surgery and avoidance of nasogastric tubes may also help. Novel strategies are emerging, but further studies are required for the treatment of prolonged POI, where evidence is still lacking. Although POI is often inevitable, methods to reduce its duration and facilitate recovery of postoperative gastrointestinal function are evolving rapidly. Utilisation of standardised diagnostic classification systems will help improve applicability of future studies. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  3. Air leak after lung resection: pathophysiology and patients' implications. (United States)

    Pompili, Cecilia; Miserocchi, Giuseppe


    Protocols for the management of air leaks are critical aspects in the postoperative course of patients following lung resections. Many investigations in the last decade are focusing on the chest tube modalities or preventative measures, however, little is known about the pathophysiology of air leak and the patient perception of this common complication. This review concentrates on understanding the reasons why a pulmonary parenchyma may start to leak or an air leak may be longer than others. Experimental works support the notion that lung overdistension may favor air leak. These studies may represent the basis of future investigations. Furthermore, the standardization of nomenclature in the field of pleural space management and the creation of novel air leak scoring systems have contributed to improve the knowledge among thoracic surgeons and facilitate the organization of trials on this matter. We tried to summarize available evidences about the patient perception of a prolonged air leak and about what would be useful for them in order to prevent worsening of their quality of life. Future investigations are warranted to better understand the pathophysiologic mechanisms responsible of prolonged air leak in order to define tailored treatments and protocols. Improving the care at home with web-based telemonitoring or real time connected chest drainage may in a future improve the quality of life of the patients experience this complication and also enhance hospital finances.

  4. Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction? (United States)

    Basson, M D; Fielding, L P; Bilchik, A J; Zucker, K A; Ballantyne, G H; Sussman, J; Adrian, T E; Modlin, I M


    We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24-hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP.

  5. Recent developments in the pathophysiology of irritable bowel syndrome. (United States)

    El-Salhy, Magdy


    Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.

  6. Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

    Directory of Open Access Journals (Sweden)

    Roshan Dadachanji


    Full Text Available Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.

  7. The Donders model of the circulation in normo- and pathophysiology

    DEFF Research Database (Denmark)

    Noordergraaf, Gerrit J.; Ottesen, Johnny T.; Kortsmit, Wil J.P.M.


    the continuum of physiological conditions to cardiopulmonary resuscitation effects within the circulation.   Within the model, Harvey's view of the circulation has been broadened to include impedance-defined flow as a unifying concept. The cardiac function curve, the relation between ventricular filling...... and output, changes during exercise. First, it rotates counterclockwise and stretches along the output axis, second, it shifts along the filling axis. The first is induced by sympathetic control, the second by respiratory control. The model shows that depth of respiration, sympathetic stimulation of cardiac......A model of the closed human cardiovascular loop is developed. This model, using one set of 88 equations, allows variations from normal resting conditions to exercise, as well as to the extreme condition of a circulation following cardiac arrest. The principal purpose of the model is to evaluate...

  8. UARS PEM Level 2 AXIS 2 V001 (UARPE2AXIS2) at GES DISC (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 2 daily product contains the X-ray high-resolution spectral...

  9. UARS PEM Level 2 AXIS 1 V001 (UARPE2AXIS1) at GES DISC (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 1 daily product contains the X-ray high-resolution spectral...

  10. Retinovascular physiology and pathophysiology: new experimental approach/new insights (United States)

    Puro, Donald G.


    An important challenge in visual neuroscience is understand the physiology and pathophysiology of the intra-retinal vasculature, whose function is required for ophthalmoception by humans and most other mammals. In the quest to learn more about this highly specialized portion of the circulatory system, a newly developed method for isolating vast microvascular complexes from the rodent retina has opened the way for using techniques such as patch-clamping, fluorescence imaging and time-lapse photography to elucidate the functional organization of a capillary network and its pre-capillary arteriole. For example, the ability to obtain dual perforated-patch recordings from well-defined sites within an isolated microvascular complex permitted the first characterization of the electrotonic architecture of a capillary/arteriole unit. This analysis revealed that this operational unit is not simply a homogenous synctium, but has a complex functional organization that is dynamically modulated by extracellular signals such as angiotensin II. Another recent discovery is that a capillary and its pre-capillary arteriole have distinct physiological differences; capillaries have an abundance of ATP-sensitive potassium (KATP) channels and a dearth of voltage-dependent calcium channels (VDCCs) while the converse is true for arterioles. In addition, voltage transmission between abluminal cells and the endothelium is more efficient in the capillaries. Thus, the capillary network is well-equipped to generate and transmit voltages, and the pre-capillary arteriole is well-adapted to transduce a capillary-generated voltage into a change in abluminal cell calcium and thereby, a vasomotor response. Use of microvessels isolated from the diabetic retina has led to new insights concerning retinal vascular pathophysiology. For example, soon after the onset of diabetes, the efficacy of voltage transmission through the endothelium is diminished; arteriolar VDCCs is inhibited, and there is increased

  11. Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts (United States)

    Robinson, Shenandoah


    Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identifed in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is

  12. Resolution of a triple axis spectrometer

    DEFF Research Database (Denmark)

    Nielsen, Mourits; Bjerrum Møller, Hans


    A new method for obtaining the resolution function for a triple-axis neutron spectrometer is described, involving a combination of direct measurement and analytical calculation. All factors which contribute to the finite resolution of the instrument may be taken into account, and Gaussian...... or experimentally determined probability distributions may be used. The application to the study of the dispersion relation for excitations in a crystal is outlined...

  13. Interplay between tilted and principal axis rotation

    International Nuclear Information System (INIS)

    Datta, Pradip; Roy, Santosh; Chattopadhyay, S.


    At IUAC-INGA, our group has studied four neutron rich nuclei of mass-110 region, namely 109,110 Ag and 108,110 Cd. These nuclei provide the unique platform to study the interplay between Tilted and Principal axis rotation since these are moderately deformed and at the same time, shears structures are present at higher spins. The salient features of the high spin behaviors of these nuclei will be discussed which are the signatures of this interplay

  14. Interplay between tilted and principal axis rotation

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Pradip [Ananda Mohan College, 102/1 Raja Rammohan Sarani, Kolkata 700 009 (India); Roy, Santosh; Chattopadhyay, S. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700 064 (India)


    At IUAC-INGA, our group has studied four neutron rich nuclei of mass-110 region, namely {sup 109,110}Ag and {sup 108,110}Cd. These nuclei provide the unique platform to study the interplay between Tilted and Principal axis rotation since these are moderately deformed and at the same time, shears structures are present at higher spins. The salient features of the high spin behaviors of these nuclei will be discussed which are the signatures of this interplay.

  15. The pathophysiology of migraine: implications for clinical management. (United States)

    Charles, Andrew


    The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea (United States)

    Camilleri, Michael; Sellin, Joseph H.; Barrett, Kim E.


    Chronic watery diarrhea poses a diagnostic and therapeutic challenge and is often a disabling condition for patients. Although acute diarrhea is likely to be caused by infection, the causes of chronic diarrhea (more than 4 weeks in duration) are more elusive. We review on the pathophysiology, diagnosis, and treatment of chronic diarrhea. Drawing on recent insights into the molecular mechanisms of intestinal epithelial transport and barrier function, we discuss how diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both, as well as derangements in barrier properties. We also describe the various extra-epithelial factors that activate diarrheal mechanisms. Finally, clinical evaluation and tests used in assessment of patients presenting with chronic diarrhea are reviewed, and an algorithm guiding therapeutic decisions and pharmacotherapy is presented. PMID:27773805

  17. Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications. (United States)

    Regenboog, Martine; van Kuilenburg, André B P; Verheij, Joanne; Swinkels, Dorine W; Hollak, Carla E M


    Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Gaucher Disease: The Metabolic Defect, Pathophysiology, Phenotypes And Natural History (United States)

    Baris, Hagit N.; Cohen, Ian J.; Mistry, Pramod K.


    Gaucher disease (GD), a prototype lysosomal storage disorder, results from inherited deficiency of lysosomal glucocerebrosidase due to biallelic mutations in GBA. The result is widespread accumulation of macrophages engorged with predominantly lysosomal glucocerebroside. A complex multisystem phenotype arises involving the liver, spleen, bone marrow and occasionally the lungs in type 1 Gaucher disease; in neuronopathic fulminant type 2 and chronic type 3 disease there is in addition progressive neurodegenerative disease. Manifestations of Gaucher disease type 1 (GD1) include hepatosplenomegaly, cytopenia, a complex pattern of bone involvement with avascular osteonecrosis (AVN), osteoporosis, fractures and lytic lesions. Enzyme replacement therapy became the standard of care in 1991, and this has transformed the natural history of GD1. This article reviews the clinical phenotypes of GD, diagnosis, pathophysiology and its natural history. A subsequent chapter discusses the treatment options. PMID:25345088

  19. Sexual and gonadal dysfunction in chronic kidney disease: Pathophysiology

    Directory of Open Access Journals (Sweden)

    Manish Rathi


    Full Text Available Sexual and gonadal dysfunction/infertility are quite common in patients with chronic kidney disease. Forty percent of male and 55% of female dialysis patients do not achieve orgasm. The pathophysiology of gonadal dysfunction is multifactorial. It is usually a combination of psychological, physiological, and other comorbid factors. Erectile dysfunction in males is mainly due to arterial factors, venous leakage, psychological factors, neurogenic factors, endocrine factors, and drugs. Sexual dysfunction in females is mainly due to hormonal factors and manifests mainly as menstrual irregularities, amenorrhea, lack of vaginal lubrication, and failure to conceive. Treatment of gonadal dysfunction in chronic kidney disease is multipronged and an exact understanding of underlying pathology is essential in proper management of these patients.

  20. Etiology, pathophysiology and classifications of the diabetic Charcot foot (United States)

    Papanas, Nikolaos; Maltezos, Efstratios


    In people with diabetes mellitus, the Charcot foot is a specific manifestation of peripheral neuropathy that may involve autonomic neuropathy with high blood flow to the foot, leading to increased bone resorption. It may also involve peripheral somatic polyneuropathy with loss of protective sensation and high risk of unrecognized acute or chronic minor trauma. In both cases, there is excess local inflammatory response to foot injury, resulting in local osteoporosis. In the Charcot foot, the acute and chronic phases have been described. The former is characterized by local erythema, edema, and marked temperature elevation, while pain is not a prominent symptom. In the latter, signs of inflammation gradually recede and deformities may develop, increasing the risk of foot ulceration. The most common anatomical classification describes five patterns, according to the localization of bone and joint pathology. This review article aims to provide a brief overview of the diabetic Charcot foot in terms of etiology, pathophysiology, and classification. PMID:23705058

  1. Female Pattern Hair Loss: a clinical and pathophysiological review. (United States)

    Ramos, Paulo Müller; Miot, Hélio Amante


    Female Pattern Hair Loss or female androgenetic alopecia is the main cause of hair loss in adult women and has a major impact on patients' quality of life. It evolves from the progressive miniaturization of follicles that lead to a subsequent decrease of the hair density, leading to a non-scarring diffuse alopecia, with characteristic clinical, dermoscopic and histological patterns. In spite of the high frequency of the disease and the relevance of its psychological impact, its pathogenesis is not yet fully understood, being influenced by genetic, hormonal and environmental factors. In addition, response to treatment is variable. In this article, authors discuss the main clinical, epidemiological and pathophysiological aspects of female pattern hair loss.

  2. Negative pressure pulmonary edema revisited: Pathophysiology and review of management

    Directory of Open Access Journals (Sweden)

    Balu Bhaskar


    Full Text Available Negative pressure pulmonary edema (NPPE is a dangerous and potentially fatal condition with a multifactorial pathogenesis. Frequently, NPPE is a manifestation of upper airway obstruction, the large negative intrathoracic pressure generated by forced inspiration against an obstructed airway is thought to be the principal mechanism involved. This negative pressure leads to an increase in pulmonary vascular volume and pulmonary capillary transmural pressure, creating a risk of disruption of the alveolar-capillary membrane. The early detection of the signs of this syndrome is vital to the treatment and to patient outcome. The purpose of this review is to highlight the available literature on NPPE, while probing the pathophysiological mechanisms relevant in both the development of this condition and that involved in its resolution.

  3. [Refeeding syndrome : Pathophysiology, risk factors, prevention, and treatment]. (United States)

    Wirth, R; Diekmann, R; Janssen, G; Fleiter, O; Fricke, L; Kreilkamp, A; Modreker, M K; Marburger, C; Nels, S; Pourhassan, M; Schaefer, R; Willschrei, H-P; Volkert, D


    Refeeding syndrome is a life-threatening complication that may occur after initiation of nutritional therapy in malnourished patients, as well as after periods of fasting and hunger. Refeeding syndrome can be effectively prevented and treated if its risk factors and pathophysiology are known. The initial measurement of thiamine level and serum electrolytes, including phosphate and magnesium, their supplementation if necessary, and a slow increase in nutritional intake along with close monitoring of serum electrolytes play an important role. Since refeeding syndrome is not well known and the symptoms can be extremely heterogeneous, this complication is poorly recognized, especially against the background of severe disease and multimorbidity. This overview aims to summarize the current knowledge and increase awareness about refeeding syndrome.

  4. Pathology and pathophysiology of pulmonary manifestations in leptospirosis

    Directory of Open Access Journals (Sweden)

    Marisa Dolhnikoff

    Full Text Available Leptospirosis is a re-emerging zoonosis occurring as large outbreaks throughout the world caused by Leptospira interrogans. The incidence of pulmonary involvement in leptospirosis has been reported to be increasing in the last years, affecting up to 70% of the patients. Alveolar hemorrhage presented as dyspnea and hemoptysis is the main pulmonary manifestation. The emergence of massive hemoptysis and acute respiratory distress syndrome has characterized the recent changes reported in the clinical patterns of leptospirosis. The pulmonary involvement has been emerged as a serious life threat, becoming the main cause of death due to leptospirosis in some countries. In this review we present the main clinical and pathological manifestations of pulmonary involvement in leptospirosis, with special focus on recent data concerning the pathophysiological mechanisms underlying lung injury.

  5. Narcolepsy and Psychiatric Disorders: Comorbidities or Shared Pathophysiology?

    Directory of Open Access Journals (Sweden)

    Anne Marie Morse


    Full Text Available Narcolepsy and psychiatric disorders have a significant but unrecognized relationship, which is an area of evolving interest, but unfortunately, the association is poorly understood. It is not uncommon for the two to occur co-morbidly. However, narcolepsy is frequently misdiagnosed initially as a psychiatric condition, contributing to the protracted time to accurate diagnosis and treatment. Narcolepsy is a disabling neurodegenerative condition that carries a high risk for development of social and occupational dysfunction. Deterioration in function may lead to the secondary development of psychiatric symptoms. Inversely, the development of psychiatric symptoms can lead to the deterioration in function and quality of life. The overlap in pharmaceutical intervention may further enhance the difficulty to distinguish between diagnoses. Comprehensive care for patients with narcolepsy should include surveillance for psychiatric illness and appropriate treatment when necessary. Further research is necessary to better understand the underlying pathophysiology between psychiatric disease and narcolepsy.

  6. Pathophysiology-based phenotyping in type 2 diabetes

    DEFF Research Database (Denmark)

    Stidsen, Jacob V; Henriksen, Jan E; Olsen, Michael H


    clinically diagnosed type 2 diabetes. METHODS: We first identified all patients with rare subtypes of diabetes, latent autoimmune diabetes of adults (LADA), secondary diabetes, or glucocorticoid-associated diabetes. We then used the homeostatic assessment model to subphenotype all remaining patients......BACKGROUND: Type 2 diabetes may be a more heterogeneous disease than previously thought. Better understanding of pathophysiological subphenotypes could lead to more individualized diabetes treatment. We examined the characteristics of different phenotypes among 5813 Danish patients with new...... into insulinopenic (high insulin sensitivity and low beta cell function), classical (low insulin sensitivity and low beta cell function), or hyperinsulinemic (low insulin sensitivity and high beta cell function) type 2 diabetes. RESULTS: Among 5813 patients diagnosed with incident type 2 diabetes in the community...

  7. Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights. (United States)

    Antoine, Clemence; Mantovani, Francesca; Benfari, Giovanni; Mankad, Sunil V; Maalouf, Joseph F; Michelena, Hector I; Enriquez-Sarano, Maurice


    Despite its high prevalence, little is known about mechanisms of mitral regurgitation in degenerative mitral valve disease apart from the leaflet prolapse itself. Mitral valve is a complex structure, including mitral annulus, mitral leaflets, papillary muscles, chords, and left ventricular walls. All these structures are involved in physiological and pathological functioning of this valvuloventricular complex but up to now were difficult to analyze because of inherent limitations of 2-dimensional imaging. The advent of 3-dimensional echocardiography, computed tomography, and cardiac magnetic resonance imaging overcoming these limitations provides new insights into mechanistic analysis of degenerative mitral regurgitation. This review will detail the contribution of quantitative and qualitative dynamic analysis of mitral annulus and mitral leaflets by new imaging methods in the understanding of degenerative mitral regurgitation pathophysiology. © 2018 American Heart Association, Inc.

  8. BACE inhibition-dependent repair of Alzheimer's pathophysiology. (United States)

    Keskin, Aylin D; Kekuš, Maja; Adelsberger, Helmuth; Neumann, Ulf; Shimshek, Derya R; Song, Beomjong; Zott, Benedikt; Peng, Tingying; Förstl, Hans; Staufenbiel, Matthias; Nelken, Israel; Sakmann, Bert; Konnerth, Arthur; Busche, Marc Aurel


    Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral Aβ levels, whether it also can ameliorate neural circuit and memory impairments remains unclear. Using histochemistry, in vivo Ca 2+ imaging, and behavioral analyses in a mouse model of AD, we demonstrate that along with reducing prefibrillary Aβ surrounding plaques, the inhibition of BACE activity can rescue neuronal hyperactivity, impaired long-range circuit function, and memory defects. The functional neuronal impairments reappeared after infusion of soluble Aβ, mechanistically linking Aβ pathology to neuronal and cognitive dysfunction. These data highlight the potential benefits of BACE inhibition for the effective treatment of a wide range of AD-like pathophysiological and cognitive impairments.

  9. Multimodal approach to control postoperative pathophysiology and rehabilitation

    DEFF Research Database (Denmark)

    Kehlet, H


    Major surgery is still associated with undesirable sequelae such as pain, cardiopulmonary, infective and thromboembolic complications, cerebral dysfunction, nausea and gastrointestinal paralysis, fatigue and prolonged convalescence. The key pathogenic factor in postoperative morbidity, excluding...... failures of surgical and anaesthetic technique, is the surgical stress response with subsequent increased demands on organ function. These changes in organ function are thought to be mediated by trauma-induced endocrine metabolic changes and activation of several biological cascade systems (cytokines......, complement, arachidonic acid metabolites, nitric oxide, free oxygen radicals, etc). To understand postoperative morbidity it is therefore necessary to understand the pathophysiological role of the various components of the surgical stress response and to determine if modification of such responses may...

  10. Dysmotility in Esophageal Atresia: Pathophysiology, Characterization, and Treatment (United States)

    Faure, Christophe; Righini Grunder, Franziska


    Esophageal dysmotility is almost universal after esophageal atresia (EA) repair and is mainly related to the developmental anomaly of the esophagus. Esophageal dysmotility is involved in the pathophysiology of numerous symptoms and comorbidities associated with EA such as gastroesophageal reflux disease, aspiration and respiratory complications, and symptoms of dysphagia and feeding disorders. High-resolution esophageal manometry (HREM) has facilitated the characterization of the dysmotility, but there is an incomplete correlation between symptoms and manometrical patterns. Impedance coupled to HREM should help to predict the clinical outcome and therefore personalize patient management. Nowadays, the management of esophageal dysmotility in patients with EA is essentially based on treatment of associated inflammation related to peptic or eosinophilic esophagitis. PMID:28620599

  11. Effects of biological sex on the pathophysiology of the heart. (United States)

    Fazal, Loubina; Azibani, Feriel; Vodovar, Nicolas; Cohen Solal, Alain; Delcayre, Claude; Samuel, Jane-Lise


    Cardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of biological sex on cardiovascular pathophysiology have long been known, the sex-specific mechanisms mediating these processes have been further elucidated over recent years. This review aims at analysing the sex-based differences in cardiac structure and function in adult mammals, and the sex-based differences in the main molecular mechanisms involved in the response of the heart to pathological situations. It emerged from this review that the sex-based difference is a variable that should be dealt with, not only in basic science or clinical research, but also with regards to therapeutic approaches. © 2013 The British Pharmacological Society.

  12. Geographical, environmental and pathophysiological influences on the human blood transcriptome. (United States)

    Tabassum, Rubina; Nath, Artika; Preininger, Marcela; Gibson, Greg


    Gene expression variation provides a read-out of both genetic and environmental influences on gene activity. Geographical, genomic and sociogenomic studies have highlighted how life circumstances of an individual modify the expression of hundreds and in some cases thousands of genes in a co-ordinated manner. This review places such results in the context of a conserved set of 90 transcripts known as Blood Informative Transcripts (BIT) that capture the major conserved components of variation in the peripheral blood transcriptome. Pathophysiological states are also shown to associate with the perturbation of transcript abundance along the major axes. Discussion of false negative rates leads us to argue that simple significance thresholds provide a biased perspective on assessment of differential expression that may cloud the interpretation of studies with small sample sizes.

  13. Acetazolamide in cerebral diagnosis: Physiological and pathophysiological aspects

    International Nuclear Information System (INIS)

    Lerch, H.; Franke, W.G.; Templin, A.


    The sensitivity in the diagnosis of cerebrovascular diseases using radiotracers can be enhanced by the use of the acetazolamide test. In this paper we present and discuss some physiological and pathophysiological aspects of its mechanism. The physiological action of the carboanhydrase inhibitor is like the action of enhanced pCO 2 in the tissue, thus acting at the site of metabolic regulation. The reaction of the vascular bed is influenced in part by subcortical structures. Pathologically the reaction can be disturbed at first by an altered regulation with the vessels being mechanically intact, e.g. in hypoxia or transient ischemia. Secondly, the mechanics of the vessels may be not intact e.g., in atherosclerosis or surrounding edema. Lastly, the vessels have already dilated, e.g. poststenotically. All these facts have to be taken into consideration interpreting an acetazolamid test. (orig.) [de

  14. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Costas Tsioufis


    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  15. The Postural Tachycardia Syndrome (POTS: Pathophysiology, Diagnosis & Management

    Directory of Open Access Journals (Sweden)

    Satish R Raj


    Full Text Available Postural tachycardia syndrome (POTS, characterized by orthostatic tachycardia in the absence of orthostatic hypotension, has been the focus of increasing clinical interest over the last 15 years 1. Patients with POTS complain of symptoms of tachycardia, exercise intolerance, lightheadedness, extreme fatigue, headache and mental clouding. Patients with POTS demonstrate a heart rate increase of ≥30 bpm with prolonged standing (5-30 minutes, often have high levels of upright plasma norepinephrine (reflecting sympathetic nervous system activation, and many patients have a low blood volume. POTS can be associated with a high degree of functional disability. Therapies aimed at correcting the hypovolemia and the autonomic imbalance may help relieve the severity of the symptoms. This review outlines the present understanding of the pathophysiology, diagnosis, and management of POTS.

  16. Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis. (United States)

    Azaña, J M; Torrelo, A; Matito, A


    Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  17. Epidural haematoma: pathophysiological significance of extravasation and arteriovenous shunting

    International Nuclear Information System (INIS)

    Habash, A.H.; Sortland, O.; Zwetnow, N.N.


    35 patients with epidural bleeding operated on at Rikshospitalet, Oslo, during the period 1965 - 1980 had preoperative angiography with visualization of the external carotid artery. Twenty-one patients had extravasation of contrast medium from meningeal arteries. Seventeen of the 21 had also shunting of contrast medium from meningeal arteries to meningeal or diploic veins, while 20 of the 21 also had bled from a ruptured meningeal artery at operation. It was further found that of 20 patients who deteriorated after trauma 18 had an epidural arteriovenous shunt or extravasation. Conversely, of 15 patients who improved after trauma 12 had no evidence of a shunt. The strong correlation between the clinical course and the occurrence of extravasation supports previous experimental and clinical data, indicating the epidural arteriovenous shunt to be a major factor in the pathophysiology and the outcome of epidural bleeding. (author)

  18. Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale. (United States)

    Böhm, Michael; Ewen, Sebastian; Mahfoud, Felix


    The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome.

  19. Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale (United States)

    Ewen, Sebastian; Mahfoud, Felix


    The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome. PMID:28154583

  20. Missing cells: pathophysiology, diagnosis and management of (pancytopenia in childhood

    Directory of Open Access Journals (Sweden)

    Miriam eErlacher


    Full Text Available Peripheral blood cytopenia in children can be due to a variety of acquired or inherited diseases. Genetic disorders affecting a single hematopoietic lineage are frequently characterized by typical bone marrow findings such as lack of progenitors or maturation arrest in congenital neutropenia or a lack of megakaryocytes in congenital amegakaryocytic thrombocytopenia whereas antibody mediated diseases such as autoimmune neutropenia are associated with a rather unremarkable bone marrow morphology. In contrast, pancytopenia is frequently associated with a hypocellular bone marrow and the differential diagnosis includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita and a variety of immunological disorders including hemophagocytic lymphohistiocytosis. Thorough bone marrow analysis is of special importance for the diagnostic work-up of most patients. Cellularity, cellular composition and dysplastic signs are the cornerstones of the differential diagnosis. Pancytopenia in the presence of a normo- or hypercellular marrow with dysplastic changes may indicate myelodysplastic syndrome. More challenging for the hematologist is the evaluation of the hypocellular bone marrow. Although aplastic anemia and hypocellular refractory cytopenia of childhood (RCC can reliably be differentiated on a morphological level the overlapping pathophysiology remains a significant challenge for the choice of the therapeutic strategy. Furthermore, inherited bone marrow failure syndromes are usually associated with the morphological picture of RCC and the recognition of these entities is essential as they often present a multisystem disease requiring different diagnostic and therapeutic approaches. This paper gives an overview over the different disease entities presenting with (pancytopenia, their pathophysiology, characteristic bone marrow findings and therapeutic approaches.

  1. Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Tadashige; Tanaka, Masao; Takeda, Tadashi; Kawashima, Akira; Kubo, Keiji; Kobayashi, Toshio; Handa, Kenjiro; Yoshimura, Kazuhiko (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine)


    In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc-MAA were performed in 19 cases of polycythemia including polycythemia rubra vera and in 11 cases of secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV 1.0%, V25 and PaO[sub 2] and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases. It seems to be important to evaluate the pathophysiology of pulmonary circulation in polycythemia rubra vera as well as secondary polycythemia due to cardio-pulmonary diseases, because pulmonary perfusion impairment and moderate right ventricular visualization are observed frequently in polycythemia rubra vera. (author).

  2. Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy

    International Nuclear Information System (INIS)

    Fujii, Tadashige; Tanaka, Masao; Takeda, Tadashi; Kawashima, Akira; Kubo, Keiji; Kobayashi, Toshio; Handa, Kenjiro; Yoshimura, Kazuhiko


    In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc-MAA were performed in 19 cases of polycythemia including polycythemia rubra vera and in 11 cases of secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV 1.0%, V25 and PaO 2 and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases. It seems to be important to evaluate the pathophysiology of pulmonary circulation in polycythemia rubra vera as well as secondary polycythemia due to cardio-pulmonary diseases, because pulmonary perfusion impairment and moderate right ventricular visualization are observed frequently in polycythemia rubra vera. (author)

  3. Insights into Pathophysiology from Medication-induced Tremor

    Directory of Open Access Journals (Sweden)

    John C. Morgan


    Full Text Available Background: Medication-induced tremor (MIT is common in clinical practice and there are many medications/drugs that can cause or exacerbate tremors. MIT typically occurs by enhancement of physiological tremor (EPT, but not all drugs cause tremor in this way. In this manuscript, we review how some common examples of MIT have informed us about the pathophysiology of tremor.Methods: We performed a PubMed literature search for published articles dealing with MIT and attempted to identify articles that especially dealt with the medication’s mechanism of inducing tremor.Results: There is a paucity of literature that deals with the mechanisms of MIT, with most manuscripts only describing the frequency and clinical settings where MIT is observed. That being said, MIT emanates from multiple mechanisms depending on the drug and it often takes an individualized approach to manage MIT in a given patient.Discussion: MIT has provided some insight into the mechanisms of tremors we see in clinical practice. The exact mechanism of MIT is unknown for most medications that cause tremor, but it is assumed that in most cases physiological tremor is influenced by these medications. Some medications (epinephrine that cause EPT likely lead to tremor by peripheral mechanisms in the muscle (β-adrenergic agonists, but others may influence the central component (amitriptyline. Other drugs can cause tremor, presumably by blockade of dopamine receptors in the basal ganglia (dopamine-blocking agents, by secondary effects such as causing hyperthyroidism (amiodarone, or by other mechanisms. We will attempt to discuss what is known and unknown about the pathophysiology of the most common MITs.

  4. Hypothalamic-pituitary-adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters. (United States)

    Ambrus, Livia; Lindqvist, Daniel; Träskman-Bendz, Lil; Westrin, Åsa


    Both decreased levels of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be involved in the pathophysiology of suicidal behaviour, as well as cognitive symptoms of depression. Pre-clinical and clinical studies have shown interactions between HPA-axis activity and BDNF, but this has not been studied in a clinical cohort of suicidal subjects. The purpose of this study was, therefore, to investigate associations between HPA-axis activity and BDNF in suicide attempters. Furthermore, this study examined the relationship between the HPA-axis, BDNF, and cognitive symptoms in suicidal patients. Since previous data indicate gender-related differences in BDNF and the HPA axis, males and females were examined separately. Seventy-five recent suicide attempters (n = 41 females; n = 34 males) were enrolled in the study. The Dexamethasone Suppression Test (DST) was performed and BDNF in plasma were analysed. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which items 'Concentration difficulties' and 'Failing memory' were extracted. Only among females, DST non-suppressors had significantly lower BDNF compared to DST suppressors (p = 0.022), and there was a significant correlation between post-DST serum cortisol at 8 a.m. and BDNF (rs = -0.437, p = 0.003). Concentration difficulties correlated significantly with post-DST cortisol in all patients (rs = 0.256, p = 0.035), in females (rs = 0.396, p = 0.015), and with BDNF in females (rs = -0.372, p = 0.020). The findings suggest an inverse relationship between the HPA-axis and BDNF in female suicide attempters. Moreover, concentration difficulties may be associated with low BDNF and DST non-suppression in female suicide attempters.

  5. Quantitative Phase Imaging Techniques for the Study of Cell Pathophysiology: From Principles to Applications

    Directory of Open Access Journals (Sweden)

    Hyunjoo Park


    Full Text Available A cellular-level study of the pathophysiology is crucial for understanding the mechanisms behind human diseases. Recent advances in quantitative phase imaging (QPI techniques show promises for the cellular-level understanding of the pathophysiology of diseases. To provide important insight on how the QPI techniques potentially improve the study of cell pathophysiology, here we present the principles of QPI and highlight some of the recent applications of QPI ranging from cell homeostasis to infectious diseases and cancer.

  6. Current challenges and problems in teaching pathophysiology in Ukraine - another reaction to Churilov's paper. (United States)

    Ataman, Oleksandr V


    Pathophysiology in Ukraine has rich traditions and achievements in the scientific areas, as well as in teaching academic discipline. Its history, the main Ukrainian scientific schools and their famous representatives are briefly described. The content of existing study program, the main approaches to teaching, and some methodological and organizational problems needed to be solved are characterized. The necessity and usefulness of developing and implementing the three separate courses of discipline (Essential, Clinical and Advanced Pathophysiology) are substantiated. The place of Pathophysiology in the training of physicians with different kinds of their future activity is discussed. Relation of teaching Pathophysiology to Translational and Personalized Medicine is tried to be shown.

  7. Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression. (United States)

    Kunugi, Hiroshi; Hori, Hiroaki; Adachi, Naoki; Numakawa, Tadahiro


    Although the pathophysiology of depressive disorder remains elusive, two hypothetical frameworks seem to be promising: the involvement of hypothalamic pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor (BDNF) in the pathogenesis and in the mechanism of action of antidepressant treatments. In this review, we focused on research based on these two frameworks in relation to depression and related conditions and tried to formulate an integrated theory of the disorder. Hormonal challenge tests, such as the dexamethasone/corticotropin-releasing hormone test, have revealed elevated HPA activity (hypercortisolism) in at least a portion of patients with depression, although growing evidence has suggested that abnormally low HPA axis (hypocortisolism) has also been implicated in a variety of stress-related conditions. Several lines of evidence from postmortem studies, animal studies, blood levels, and genetic studies have suggested that BDNF is involved in the pathogenesis of depression and in the mechanism of action of biological treatments for depression. Considerable evidence has suggested that stress reduces the expression of BDNF and that antidepressant treatments increase it. Moreover, the glucocorticoid receptor interacts with the specific receptor of BDNF, TrkB, and excessive glucocorticoid interferes with BDNF signaling. Altered BDNF function is involved in the structural changes and possibly impaired neurogenesis in the brain of depressed patients. Based on these findings, an integrated schema of the pathological and recovery processes of depression is illustrated. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

  8. Hypothalamic-pituitary-adrenal axis activity in patients with pathological gambling and internet use disorder. (United States)

    Geisel, Olga; Panneck, Patricia; Hellweg, Rainer; Wiedemann, Klaus; Müller, Christian A


    Alterations in secretion of stress hormones within the hypothalamic-pituitary-adrenal (HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might contribute to the development and maintenance of substance use disorders by facilitatory effects on behavioral responses to substances of abuse. The objective of this pilot study was to investigate HPA axis activity in patients with non-substance-related addictive disorders, i.e. pathological gambling and internet use disorder. We measured plasma levels of copeptin, a vasopressin surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with pathological gambling (n=14), internet use disorder (n=11) and matched healthy controls for pathological gambling (n=13) and internet use disorder (n=10). Plasma levels of copeptin, ACTH and cortisol in patients with pathological gambling or internet use disorder did not differ among groups. However, cortisol plasma levels correlated negatively with the severity of pathological gambling as measured by the PG-YBOCS. Together with our findings of increased serum levels of brain-derived neurotrophic factor (BDNF) in pathological gambling but not internet use disorder, these results suggest that the pathophysiology of pathological gambling shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in internet use disorder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Theoretical tool movement required to diamond turn an off-axis paraboloid on axis

    International Nuclear Information System (INIS)

    Thompson, D.C.


    High-quality, off-axis parabolic reflectors, required by the CTR and laser-fusion programs at Lawrence Livermore Laboratory (LLL) and other ERDA laboratories, are currently manufactured by hand. There are several drawbacks to this method, including lead times of up to a year, costs in excess of dollars 75,000 for a small reflector, and unsatisfactory limits to the tolerances obtainable. This situation has led to a search for cheaper and more accurate methods of manufacturing off-axis paraboloids. An alternative method, turning the workpiece about its axis on a diamond-turning machine, is presented, and the equations describing the necessary tool movement are derived. A discussion of a particular case suggests that the proposed technique is feasible

  10. The Triple Axis and SPINS Spectrometers. (United States)

    Trevino, S F


    In this paper are described the triple axis and spin polarized inelastic neutron scattering (SPINS) spectrometers which are installed at the NIST Cold Neutron Research Facility (CNRF). The general principle of operation of these two instruments is described in sufficient detail to allow the reader to make an informed decision as to their usefulness for his needs. However, it is the intention of the staff at the CNRF to provide the expert resources for their efficient use in any given situation. Thus, this work is not intended as a user manual but rather as a guide into the range of applicability of the two instruments.

  11. Equilibrium calculations for helical axis stellarators

    International Nuclear Information System (INIS)

    Hender, T.C.; Carreras, B.A.


    An average method based on a vacuum flux coordinate system is presented. This average method permits the study of helical axis stellarators with toroidally dominated shifts. An ordering is introduced, and to lowest order the toroidally averaged equilibrium equations are reduced to a Grad-Shafranov equation. Also, to lowest order, a Poisson-type equation is obtained for the toroidally varying corrections to the equilibium. By including these corrections, systems that are toroidally dominated, but with significant helical distortion to the equilibrium, may be studied. Numerical solutions of the average method equations are shown to agree well with three-dimensional calculations

  12. Three-axis asymmetric radiation detector system (United States)

    Martini, Mario Pierangelo; Gedcke, Dale A.; Raudorf, Thomas W.; Sangsingkeow, Pat


    A three-axis radiation detection system whose inner and outer electrodes are shaped and positioned so that the shortest path between any point on the inner electrode and the outer electrode is a different length whereby the rise time of a pulse derived from a detected radiation event can uniquely define the azimuthal and radial position of that event, and the outer electrode is divided into a plurality of segments in the longitudinal axial direction for locating the axial location of a radiation detection event occurring in the diode.


    Directory of Open Access Journals (Sweden)

    M. T. Vatutin


    Full Text Available Chronic obstructive pulmonary disease: definition, epidemiology, pathophysiology, clinical picture (GOLD 2013. Vatutin M.T., Smyrnova G.S., Taradin G.G. The represented translation of the new international guidelines (GOLD 2013 reflected the epidemiology, pathophysiology, clinical picture and treatment of chronic obstructive pulmonary disease.

  14. Hypothalamic-Pituitary-Adrenal Axis Dysfunction and Illness Progression in Bipolar Disorder (United States)

    Vasconcelos-Moreno, Mirela Paiva; Gubert, Carolina; dos Santos, Bárbara Tietböhl Martins Quadros; Sartori, Juliana; Eisele, Bárbara; Ferrari, Pamela; Fijtman, Adam; Rüegg, Joëlle; Gassen, Nils Christian; Kapczinski, Flávio; Rein, Theo; Kauer-Sant’Anna, Márcia


    Background: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. Methods: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). Results: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. Conclusions: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness. PMID:25522387

  15. A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial stress in irritable bowel syndrome. (United States)

    Kennedy, P J; Cryan, J F; Quigley, E M M; Dinan, T G; Clarke, G


    Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS. Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre- and post-exposure to the TSST. The hypothalamic-pituitary-adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUCG) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups. Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.

  16. Targeting autophagy in obesity: from pathophysiology to management. (United States)

    Zhang, Yingmei; Sowers, James R; Ren, Jun


    Obesity poses a severe threat to human health, including the increased prevalence of hypertension, insulin resistance, diabetes mellitus, cancer, inflammation, sleep apnoea and other chronic diseases. Current therapies focus mainly on suppressing caloric intake, but the efficacy of this approach remains poor. A better understanding of the pathophysiology of obesity will be essential for the management of obesity and its complications. Knowledge gained over the past three decades regarding the aetiological mechanisms underpinning obesity has provided a framework that emphasizes energy imbalance and neurohormonal dysregulation, which are tightly regulated by autophagy. Accordingly, there is an emerging interest in the role of autophagy, a conserved homeostatic process for cellular quality control through the disposal and recycling of cellular components, in the maintenance of cellular homeostasis and organ function by selectively ridding cells of potentially toxic proteins, lipids and organelles. Indeed, defects in autophagy homeostasis are implicated in metabolic disorders, including obesity, insulin resistance, diabetes mellitus and atherosclerosis. In this Review, the alterations in autophagy that occur in response to nutrient stress, and how these changes alter the course of obesogenesis and obesity-related complications, are discussed. The potential of pharmacological modulation of autophagy for the management of obesity is also addressed.

  17. The Pathophysiological Effects of Acrylamide in Albino Wister Rats

    Directory of Open Access Journals (Sweden)

    Shler Akram Faqe Mahmood


    Full Text Available Studies of the pathophysiological effects of suspected compounds are conducted in rodent species, especially rats and mice, to determine the potential toxic effects of a particular compound. In the assessment of acrylamide (ACR which is available as a dietary compound in daily food stuffs, the potential toxicity was determined following the method described earlier. In this study, Albino Wister rats were used and were observed for clinical abnormalities, changes in food consumption, a n d s y m p t o m s o f toxicity over a period of two months following the oral administration of ACR. Among the parameters used to assess the effect of ACR were include ovarian histopathology, blood sugar, haemogram and lipid profile. The most notable clinical abnormalities observed in a few rats were a rough coat and decreased activity. None of the rats died or howedbehavioural change resulting from treatment with ACR. The concentration of serum biochemical parameters and haemogram showed significant differences between normal and treated rats. Histological examination of the ovaries of the treated rats showed great abnormalities as well. In fact, oral ACR doses are practically toxic with regard to rats after exposure for two months at a dose rate of 30 mg/kg, suggesting the compound is quite non-innocuous.

  18. Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis. (United States)

    Wei, Diana Yi-Ting; Yuan Ong, Jonathan Jia; Goadsby, Peter James


    Cluster headache is a primary headache disorder affecting up to 0.1% of the population. Patients suffer from cluster headache attacks lasting from 15 to 180 min up to 8 times a day. The attacks are characterized by the severe unilateral pain mainly in the first division of the trigeminal nerve, with associated prominent unilateral cranial autonomic symptoms and a sense of agitation and restlessness during the attacks. The male-to-female ratio is approximately 2.5:1. Experimental, clinical, and neuroimaging studies have advanced our understanding of the pathogenesis of cluster headache. The pathophysiology involves activation of the trigeminovascular complex and the trigeminal-autonomic reflex and accounts for the unilateral severe headache, the prominent ipsilateral cranial autonomic symptoms. In addition, the circadian and circannual rhythmicity unique to this condition is postulated to involve the hypothalamus and suprachiasmatic nucleus. Although the clinical features are distinct, it may be misdiagnosed, with patients often presenting to the otolaryngologist or dentist with symptoms. The prognosis of cluster headache remains difficult to predict. Patients with episodic cluster headache can shift to chronic cluster headache and vice versa. Longitudinally, cluster headache tends to remit with age with less frequent bouts and more prolonged periods of remission in between bouts.

  19. [Bacterial Translocation from Intestine: Microbiological, Immunological and Pathophysiological Aspects]. (United States)

    Podoprigora, G I; Kafarskaya, L I; Bainov, N A; Shkoporov, A N


    Bacterial translocation (BT) is both pathology and physiology phenomenon. In healthy newborns it accompanies the process of establishing the autochthonous intestinal microbiota and the host microbiome. In immunodeficiency it can be an aethio-pathogenetic link and a manifestation of infection or septic complications. The host colonization resistance to exogenous microbic colonizers is provided by gastrointestinal microbiota in concert with complex constitutional and adaptive defense mechanisms. BT may be result of barrier dysfunction and self-purification mechanisms involving the host myeloid cell phagocytic system and opsonins. Dynamic cell humoral response to microbial molecular patterns that occurs on the mucous membranes initiates receptorsignalingpathways and cascade ofreactions. Their vector and results are largely determined by cross-reactivity between microbiome and the host genome. Enterocyte barriers interacting with microbiota play leading role in providing adaptive, homeostatic and stress host reactivity. Microcirculatory ischemic tissue alterations and inflammatory reactions increase the intestinal barrier permeability and BT These processes a well as mechanisms for apoptotic cells and bacteria clearance are justified to be of prospective research interest. The inflammatory and related diseases caused by alteration and dysfunction of the intestinal barrier are reasonably considered as diseases of single origin. Maternal microbiota affects theformation of the innate immune system and the microbiota of the newborn, including intestinal commensal translocation during lactation. Deeper understanding of intestinal barrier mechanisms needs complex microbiological, immunological, pathophysiological, etc. investigations using adequate biomodels, including gnotobiotic animals.

  20. Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues. (United States)

    Classen, Joseph; Koschel, Jiri; Oehlwein, Christian; Seppi, Klaus; Urban, Peter; Winkler, Christian; Wüllner, Ullrich; Storch, Alexander


    Parkinson's disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients' quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.

  1. Molecular Pathophysiology of Epithelial Barrier Dysfunction in Inflammatory Bowel Diseases

    Directory of Open Access Journals (Sweden)

    Jessica Y. Lee


    Full Text Available Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD. The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms in IBD. More and more scientists and clinicians are embracing the concept of the impaired intestinal epithelial barrier and its role in the pathogenesis and natural history of IBD. However, we are missing a key tool that bridges these scientific insights to clinical practice. Our goal is to overcome the limitations in understanding the molecular physiology of intestinal barrier function and develop a clinical tool to assess and quantify it. This review article explores the proteins in the intestinal tissue that are pivotal in regulating intestinal permeability. Understanding the molecular pathophysiology of impaired intestinal barrier function in IBD may lead to the development of a biochemical method of assessing intestinal tissue integrity which will have a significant impact on the development of novel therapies targeting the intestinal mucosa.

  2. [Dysphagia in Parkinson's Disease: Pathophysiology, Diagnosis and Therapy]. (United States)

    Suttrup, I; Warnecke, T


    Oropharyngeal and esophageal dysphagia are a frequent, but seldom diagnosed symptom of Parkinson's disease (PD). More than 80 % of patients with PD develop dysphagia during the course of their disease leading to a reduced quality of life, complicated medication intake, malnutrition and aspiration pneumonia, which is a major cause of death in PD. The underlying pathophysiology is poorly understood. Impaired dopaminergic and non-dopaminergic mechanisms of the cortical swallowing network as well as peripheral neuromuscular involvement have been suggested to contribute to its multifactorial genesis. Diagnostic screening methods include PD-specific questionnaires and a modified water test. Fiber optic endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallowing study (VFSS), which complement each other, are the gold standard for evaluation of PD-related dysphagia. For evaluation of esophageal dysphagia, the high-resolution manometry (HRM) may be a helpful tool. In addition to dysphagia-specific treatment by speech and language therapists (SLTs), optimized dopaminergic medication is a meaningful therapeutic option. A promising novel method is intensive training of expiratory muscle strength (EMST). Deep brain stimulation does not seem to have a clinically relevant effect on swallowing function in PD. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Ankle sprain: pathophysiology, predisposing factors, and management strategies

    Directory of Open Access Journals (Sweden)

    Tricia J Hubbard


    Full Text Available Tricia J Hubbard, Erik A WikstromUNC Charlotte, Department of Kinesiology, CharlotteAbstract: With the high percentage (up to 75% of initial lateral ankle sprains (LAS leading to repetitive sprains and chronic symptoms, it is imperative to better understand how best to treat and rehabilitate LAS events. The purpose of this paper is to review LAS pathophysiology, predisposing factors, and the current evidence regarding therapeutic modalities and exercises used in the treatment of LAS. Functional rehabilitation, early mobilization with support, is the current standard of care for LAS. However, the high percentage of reinjury occurrence and development of chronic symptoms (up to 75% after a LAS, suggests the current standard of care may not be effective. Recent evidence has shown the need for more stringent immobilization to facilitate ligament healing and restoration of joint stability and function after a LAS. Additionally, the importance of adding adjunctive therapies, specifically joint mobilizations and balance training have been shown to improve function and decrease the incidence of reinjury after a LAS. Modifying current rehabilitation protocols to include protecting the ankle joint with stringent immobilization, and including joint mobilizations and balance training may be the first step to decreasing the incidence of short and long term ankle joint dysfunction.Keywords: rehabilitation, recurrent sprains, chronic ankle instability (CAI

  4. Dissecting carboxypeptidase E: properties, functions and pathophysiological roles in disease

    Directory of Open Access Journals (Sweden)

    Lin Ji


    Full Text Available Since discovery in 1982, carboxypeptidase E (CPE has been shown to be involved in the biosynthesis of a wide range of neuropeptides and peptide hormones in endocrine tissues, and in the nervous system. This protein is produced from pro-CPE and exists in soluble and membrane forms. Membrane CPE mediates the targeting of prohormones to the regulated secretory pathway, while soluble CPE acts as an exopeptidase and cleaves C-terminal basic residues from peptide intermediates to generate bioactive peptides. CPE also participates in protein internalization, vesicle transport and regulation of signaling pathways. Therefore, in two types of CPE mutant mice, Cpefat/Cpefat and Cpe knockout, loss of normal CPE leads to a lot of disorders, including diabetes, hyperproinsulinemia, low bone mineral density and deficits in learning and memory. In addition, the potential roles of CPE and ΔN-CPE, an N-terminal truncated form, in tumorigenesis and diagnosis were also addressed. Herein, we focus on dissecting the pathophysiological roles of CPE in the endocrine and nervous systems, and related diseases.

  5. Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications

    Directory of Open Access Journals (Sweden)

    Susana Rovira-Llopis


    Full Text Available Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1, mitofusin-2 (MFN2 and optic atrophy (OPA-1, while fission is controlled by mitochondrial fission 1 (FIS1, dynamin-related protein 1 (DRP1 and mitochondrial fission factor (MFF. PARKIN and (PTEN-induced putative kinase 1 (PINK1 participate in the process of mitophagy, for which mitochondrial fission is necessary. In this review, we discuss the molecular pathways of mitochondrial dynamics, their impairment under type 2 diabetes, and pharmaceutical approaches for targeting mitochondrial dynamics, such as mitochondrial division inhibitor-1 (mdivi-1, dynasore, P110 and 15-oxospiramilactone. Furthermore, we discuss the pathophysiological implications of impaired mitochondrial dynamics, especially in type 2 diabetes.

  6. Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome (United States)

    Ellis, Demetrius


    Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na+) and water retention; this is known as the “underfill hypothesis.” Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is “primary” or “pathophysiological,” Na+ and water retention; this is known as the “overfill hypothesis.” A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema. PMID:26793696

  7. Physiological and pathophysiological bone turnover - role of the immune system. (United States)

    Weitzmann, M Neale; Ofotokun, Ighovwerha


    Osteoporosis develops when the rate of osteoclastic bone breakdown (resorption) exceeds that of osteoblastic bone formation, which leads to loss of BMD and deterioration of bone structure and strength. Osteoporosis increases the risk of fragility fractures, a cause of substantial morbidity and mortality, especially in elderly patients. This imbalance between bone formation and bone resorption is brought about by natural ageing processes, but is frequently exacerbated by a number of pathological conditions. Of importance to the aetiology of osteoporosis are findings over the past two decades attesting to a deep integration of the skeletal system with the immune system (the immuno-skeletal interface (ISI)). Although protective of the skeleton under physiological conditions, the ISI might contribute to bone destruction in a growing number of pathophysiological states. Although numerous research groups have investigated how the immune system affects basal and pathological osteoclastic bone resorption, recent findings suggest that the reach of the adaptive immune response extends to the regulation of osteoblastic bone formation. This Review examines the evolution of the field of osteoimmunology and how advances in our understanding of the ISI might lead to novel approaches to prevent and treat bone loss, and avert fractures.

  8. Genetics of liver disease: From pathophysiology to clinical practice. (United States)

    Karlsen, Tom H; Lammert, Frank; Thompson, Richard J


    Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  9. Insights into pathophysiology of punding reveal possible treatment strategies. (United States)

    Fasano, A; Petrovic, I


    Punding is a stereotyped behavior characterized by an intense fascination with a complex, excessive, nongoal oriented, repetitive activity. Men tend to repetitively tinker with technical equipment such as radio sets, clocks, watches and car engines, the parts of which may be analyzed, arranged, sorted and cataloged but rarely put back together. Women, in contrast, incessantly sort through their handbags, tidy continuously, brush their hair or polish their nails. Punders are normally aware of the inapposite and obtuse nature of the behavior; however, despite the consequent self-injury, they do not stop such behavior. The most common causes of punding are dopaminergic replacement therapy in patients affected by Parkinson's disease (PD) and cocaine and amphetamine use in addicts. The vast majority of information about punding comes from PD cases. A critical review of these cases shows that almost all afflicted patients (90%) were on treatment with drugs acting mainly on dopamine receptors D1 and D2, whereas only three cases were reported in association with selective D2 and D3 agonists. Epidemiological considerations and available data from animal models suggest that punding, drug-induced stereotypies, addiction and dyskinesias all share a common pathophysiological process. Punding may be related to plastic changes in the ventral and dorsal striatal structures, including the nucleus accumbens, and linked to psychomotor stimulation and reward mechanisms. Possible management guidelines are proposed.

  10. Physiology and pathophysiology of ClC-K/barttin channels. (United States)

    Fahlke, Christoph; Fischer, Martin


    ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology, and pathophysiology of ClC-K/barttin channels.

  11. Neurobehavioral aspects, pathophysiology, and management of Tourette syndrome. (United States)

    Shprecher, David R; Schrock, Lauren; Himle, Michael


    This update summarizes progress in understanding Tourette syndrome clinical characteristics, etiology, and treatment over the past year. Premonitory sensory phenomena were found to have important impacts on Tourette syndrome quality of life. A rare genetic form of Tourette syndrome due to L-histidine-decarboxylase mutation, with similar features in human and rodent, has inspired new research on functional anatomy of Tourette syndrome. In response to new data, treatment guidelines have been revised to include behavioral therapy as first-line treatment. Novel dopamine receptor antagonists aripiprazole and ecopipam have shown potential efficacy - as well as tolerability concerns. Recent work has suggested efficacy and tolerability of topiramate and fluphenazine, but more rigorous studies are needed to further understand their role in Tourette syndrome management. Recent consensus guidelines explain when deep brain stimulation can be considered for severe refractory cases under a multidisciplinary team. More research is needed to identify better tolerated treatments for, to understand pathophysiology or functional anatomy of, and to predict or influence longitudinal outcome of Tourette syndrome.

  12. Epileptic Seizures Versus Syncope: Pathophysiology and Clinical Approach

    Directory of Open Access Journals (Sweden)

    Marios Charalambous


    Full Text Available Generalised epileptic seizures and syncope are two syndromes with similar clinical manifestation and their differentiation can be quite challenging. The aim of this review is to use an evidence-based approach in differentiating these two syndromes through the comprehension of the pathophysiological mechanisms involved and their clinical signs. Both syndromes affect regions of the forebrain and consciousness level, although, different mechanisms are involved. Syncope is a paroxysmal event secondary to a short-term decrease in cerebral perfusion, oxygenation or essential nutrients delivery. Generalised epileptic seizure activity is defined as the clinical manifestation of transient paroxysmal disturbances in brain function secondary to an imbalance between excitatory and inhibitory neurotransmitters. Clinical criteria, including precipitating events, clinical signs preceding, during and following the episodes and event duration, can be used to differentiate the two syndromes. Although these criteria might be useful for the practitioner, definite conclusions should be precluded due to the lack of original research articles and weak evidence on this specific field.Application: The review might be a useful tool for the general practitioner and clinical scientist as it will aid towards the differentiation of two syndromes, i.e. generalised epileptic seizures and syncope, with similar clinical presentation.

  13. Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease* (United States)

    Masters, Seth L.; Simon, Anna; Aksentijevich, Ivona; Kastner, Daniel L.


    The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells. The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes. This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system. Herein we propose an updated classification scheme based on the molecular insights garnered over the past decade, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us. We define six categories of autoinflammatory disease: IL-1β activation disorders (inflammasomopathies), NF-κB activation syndromes, protein misfolding disorders, complement regulatory diseases, disturbances in cytokine signaling, and macrophage activation syndromes. A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and at the bedside. PMID:19302049

  14. Nondopaminergic neurotransmission in the pathophysiology of Tourette syndrome. (United States)

    Udvardi, Patrick T; Nespoli, Ester; Rizzo, Francesca; Hengerer, Bastian; Ludolph, Andrea G


    A major pathophysiological role for the dopaminergic system in Tourette's syndrome (TS) has been presumed ever since the discovery that dopamine-receptor antagonists can alleviate tics. Especially recent molecular genetic studies, functional imaging studies, and some rare postmortem studies have given more and more hints that other neurotransmitter systems are involved as well. Dysfunction in the dopamine metabolism-in particular during early development-might lead to counter-regulations in the other systems or vice versa. This chapter will give an overview of the studies that prove the involvement of other neurotransmitter systems such as the major monoaminergic neurotransmitters norepinephrine, serotonin, and histamine; the most important excitatory neurotransmitter, the amino acid glutamate; the major inhibitory neurotransmitter y-aminobutyric acid, as well as acetylcholine, endocannabinoid, corticoid; and others. These studies will hopefully lead to fundamental advances in the psychopharmacological treatment of TS. While tic disorders have been previously treated mainly with dopamine antagonists, some authors already favor alpha-agonists. Clinical trials with glutamate agonists and antagonists and compounds influencing the histaminergic system are currently being conducted. Since the different neurotransmitter systems consist of several receptor subtypes which might mediate different effects on locomotor activity, patients with TS may respond differentially to selective agonists or antagonists. Effects of agonistic or antagonistic compounds on tic symptoms might also be dose dependent. Further studies will lead to a broader spectrum of psychopharmacological treatment options in TS. © 2013 Elsevier Inc. All rights reserved.

  15. Pathophysiology and pathological findings of heatstroke in dogs

    Directory of Open Access Journals (Sweden)

    Romanucci M


    Full Text Available Mariarita Romanucci, Leonardo Della SaldaDepartment of Comparative Biomedical Sciences, Faculty of Veterinary Medicine, University of Teramo, Teramo, ItalyAbstract: Canine heatstroke is a life-threatening condition resulting from an imbalance between heat dissipation and production, and characterized by a nonpyrogenic elevation in core body temperature above 41°C (105.8°F. Several exogenous and endogenous factors may predispose dogs to the development of heatstroke; on the other hand, adaptive mechanisms also exists which allow organisms to combat the deleterious effects of heat stress, which are represented by the cellular heat-shock response and heat acclimatization. The pathophysiology and consequences of heatstroke share many similarities to those observable in sepsis and are related to the interaction between the direct cytotoxicity of heat, the acute physiological alterations associated with hyperthermia, such as increased metabolic demand, hypoxia, and circulatory failure, and the inflammatory and coagulation responses of the host to the widespread endothelial and tissue injuries, which may culminate in disseminated intravascular coagulation, systemic inflammatory response syndrome, and multiple organ dysfunction.Keywords: thermoregulation, acclimatization, heat shock proteins, hyperthermia, systemic inflammatory response, multiple organ dysfunction

  16. Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

    Directory of Open Access Journals (Sweden)

    Stylianos Michalakis


    Full Text Available The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP or cyclic adenosine monophosphate (cAMP. Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN channels and voltage-gated potassium channels (KCN. In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application.

  17. Estrogens and Androgens in Skeletal Physiology and Pathophysiology. (United States)

    Almeida, Maria; Laurent, Michaël R; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A; Bouillon, Roger; Vanderschueren, Dirk; Manolagas, Stavros C


    Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. Copyright © 2017 the American Physiological Society.

  18. Left main coronary artery disease: pathophysiology, diagnosis, and treatment. (United States)

    Collet, Carlos; Capodanno, Davide; Onuma, Yoshinobu; Banning, Adrian; Stone, Gregg W; Taggart, David P; Sabik, Joseph; Serruys, Patrick W


    The advent of coronary angiography in the 1960s allowed for the risk stratification of patients with stable angina. Patients with unprotected left main coronary artery disease have an increased risk of death related to the large amount of myocardium supplied by this vessel. Although coronary angiography remains the preferred imaging modality for the evaluation of left main coronary artery stenosis, this technique has important limitations. Angiograms of the left main coronary artery segment can be difficult to interpret, and almost one-third of patients can be misclassified when fractional flow reserve is used as the reference. In patients with clinically significant unprotected left main coronary artery disease, surgical revascularization was shown to improve survival compared with medical therapy and has been regarded as the treatment of choice for unprotected left main coronary artery disease. Two large-scale clinical trials published in 2016 support the usefulness of catheter-based revascularization in selected patients with unprotected left main coronary artery disease. In this Review, we describe the pathophysiology of unprotected left main coronary artery disease, discuss diagnostic approaches in light of new noninvasive and invasive imaging techniques, and detail risk stratification models to aid the Heart Team in the decision-making process for determining the best revascularization strategy for these patients.

  19. Tics and Tourette: a clinical, pathophysiological and etiological review. (United States)

    Dale, Russell C


    Describe developments in the etiological understanding of Tourette syndrome. Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors. Only recently have some vulnerability gene findings been replicated, including histidine decarboxylase and neurexin 1, yet these rare variants only explain a small proportion of patients. Planned large genetic studies will improve genetic understanding. The role of inflammation as a contributor to disease expression is now supported by large epidemiological studies showing an association with maternal autoimmunity and childhood infection. Investigation of blood cytokines, blood mRNA and brain mRNA expression support the role of a persistent immune activation, and there are similarities with the immune literature of autistic spectrum disorder. Current treatment is symptomatic, although there is a better appreciation of factors that influence treatment response. At present, therapeutics is focused on symptom-based treatments, yet with improved etiological understanding, we will move toward disease-modifying therapies in the future.

  20. Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms. (United States)

    Campos, Derbis; Monaga, Madelyn


    Mucopolysaccharidosis type I is one of the most frequent lysosomal storage diseases. It has a high morbidity and mortality, causing in many cases severe neurological and somatic damage in the first years of life. Although the clinical phenotypes have been described for decades, and the enzymatic deficiency and many of the mutations that cause this disease are well known, the underlying pathophysiological mechanisms that lead to its development are not completely understood. In this review we describe and discuss the different pathogenic mechanisms currently proposed for this disease regarding its neurological damage. Deficiency in the lysosomal degradation of heparan sulfate and dermatan sulfate, as well as its primary accumulation, may disrupt a variety of physiological and biochemical processes: the intracellular and extracellular homeostasis of these macromolecules, the pathways related to gangliosides metabolism, mechanisms related to the activation of inflammation, receptor-mediated signaling, oxidative stress and permeability of the lysosomal membrane, as well as alterations in intracellular ionic homeostasis and the endosomal pathway. Many of the pathogenic mechanisms proposed for mucopolysaccharidosis type I are also present in other lysosomal storage diseases with neurological implications. Results from the use of methods that allow the analysis of multiple genes and proteins, in both patients and animal models, will shed light on the role of each of these mechanisms and their combination in the development of different phenotypes due to the same deficiency.

  1. Pathophysiologic insights into motor axonal function in Kennedy disease. (United States)

    Vucic, Steve; Kiernan, Matthew C


    Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD. Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis. Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity. In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

  2. Vitiligo: An Update on Pathophysiology and Treatment Options. (United States)

    Speeckaert, Reinhart; van Geel, Nanja


    The pathophysiology of vitiligo is becoming increasingly clarified. In non-segmental vitiligo, early factors include activation of innate immunity, inflammasome activation, oxidative stress, and loss of melanocyte adhesion. Nonetheless, the main mechanism leading to non-segmental vitiligo involves an immune-mediated destruction of melanocytes. Anti-melanocyte-specific cytotoxic T cells exert a central role in the final effector stage. Genetic research revealed a multi-genetic inheritance displaying an overlap with other autoimmune disorders. However, some melanocyte-specific genes were also affected. Segmental vitiligo carries a different pathogenesis with most evidence indicating a mosaic skin disorder. Current management includes topical corticosteroids and immunomodulators. Narrow-band ultraviolet B can be used in patients not responding to topical treatment or in patients with extensive disease. Pigment cell transplantation offers an alternative for the treatment of segmental vitiligo or stable non-segmental lesions. Recent findings have revealed new targets for treatment that could lead to more efficient therapies. Targeted immunotherapy may halt the active immune pathways, although combination therapy may still be required to induce satisfying repigmentation. A recently established core set of outcome measures, new measurement instruments, and biomarker research pave the way for future standardized clinical trials.

  3. Astroglial role in the pathophysiology of status epilepticus: an overview. (United States)

    Vargas-Sánchez, Karina; Mogilevskaya, Maria; Rodríguez-Pérez, John; Rubiano, María G; Javela, José J; González-Reyes, Rodrigo E


    Status epilepticus is a medical emergency with elevated morbidity and mortality rates, and represents a leading cause of epilepsy-related deaths. Though status epilepticus can occur at any age, it manifests more likely in children and elderly people. Despite the common prevalence of epileptic disorders, a complete explanation for the mechanisms leading to development of self-limited or long lasting seizures (as in status epilepticus) are still lacking. Apart from neurons, research evidence suggests the involvement of immune and glial cells in epileptogenesis. Among glial cells, astrocytes represent an ideal target for the study of the pathophysiology of status epilepticus, due to their key role in homeostatic balance of the central nervous system. During status epilepticus, astroglial cells are activated by the presence of cytokines, damage associated molecular patterns and reactive oxygen species. The persistent activation of astrocytes leads to a decrease in glutamate clearance with a corresponding accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Moreover, major alterations in astrocytic gap junction coupling, inflammation and receptor expression, facilitate the generation of seizures. Astrocytes are also involved in dysregulation of inhibitory transmission in the central nervous system and directly participate in ionic homeostatic alterations during status epilepticus. In the present review, we focus on the functional and structural changes in astrocytic activity that participate in the development and maintenance of status epilepticus, with special attention on concurrent inflammatory alterations. We also include potential astrocytic treatment targets for status epilepticus.

  4. Physiology and pathophysiology of ClC-K/barttin channels

    Directory of Open Access Journals (Sweden)

    Christoph eFahlke


    Full Text Available ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology and pathophysiology of ClC-K/barttin channels.

  5. Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options. (United States)

    Bunevicius, Robertas; Prange, Arthur J


    Graves' disease is an autoimmune disorder that is the most common cause of hyperthyroidism. Other symptoms associated with the disease are goitre, ophthalmopathy, and psychiatric manifestations such as mood and anxiety disorders and, sometimes, cognitive dysfunction. Graves' hyperthyroidism may result in these latter manifestations via the induction of hyperactivity of the adrenergic nervous system. This review addresses the psychiatric presentations, and their pathophysiology and treatment, in patients with hyperthyroidism, based on literature identified by a PubMed/MEDLINE database search. Although the focus is on mental symptoms associated with Graves' disease, it is not always clear from the literature whether patients had Graves' disease: in some studies, the patients were thought to have Graves' disease based on clinical findings such as diffuse goitre or ophthalmopathy or on measurements of thyroid antibodies in serum; however, in other studies, no distinction was made between Graves' hyperthyroidism and hyperthyroidism from other causes. Antithyroid drugs combined with beta-adrenoceptor antagonists are the treatments of choice for hyperthyroidism, as well as for the psychiatric disorders and mental symptoms caused by hyperthyroidism. A substantial proportion of patients have an altered mental state even after successful treatment of hyperthyroidism, suggesting that mechanisms other than hyperthyroidism, including the Graves' autoimmune process per se and ophthalmopathy, may also be involved. When psychiatric disorders remain after restoration of euthyroidism and after treatment with beta-adrenoceptor antagonists, specific treatment for the psychiatric symptoms, especially psychotropic drugs, may be needed.

  6. Pathophysiology of septic shock: From bench to bedside. (United States)

    McConnell, Kevin W; Coopersmith, Craig M


    Our understanding of sepsis and its resultant outcomes remains a paradox. On the one hand, we know more about the pathophysiology of sepsis than ever before. However, this knowledge has not been successfully translated to the bedside, as the vast majority of clinical trials for sepsis have been negative. Yet even in the general absence of positive clinical trials, mortality from sepsis has fallen to its lowest point in history, in large part due to educational campaigns that stress timely antibiotics and hemodynamic support. While additional improvements in outcome will assuredly result from further compliance with evidence based practices, a deeper understanding of the science that underlies the host response in sepsis is critical to the development of novel therapeutics. In this review, we outline immunopathologic abnormalities in sepsis, and then look at potential approaches to therapeutically modulate them. Ultimately, an understanding of the science underlying sepsis should allow the critical care community to utilize precision medicine to combat this devastating disease on an individual basis leading to improved outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome. (United States)

    Ellis, Demetrius


    Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na(+)) and water retention; this is known as the "underfill hypothesis." Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is "primary" or "pathophysiological," Na(+) and water retention; this is known as the "overfill hypothesis." A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema.


    Directory of Open Access Journals (Sweden)



    Full Text Available Epidemiological and clinical studies suggested the association of the particulate matter ambient air pollution and the increased morbidity and mortality, mainly from respiratory and cardiovascular diseases. The size of particles has great influence on their toxicity, because it determines the site in the respiratory tract where they deposit. The most well established theory explaining the mechanisms behind the increased toxicity of ultrafine particles (UFP, < 0.1 µm is that it has to do with the increased surface area and/or the combination with the increased number of particles. Biological effects of UFP are also determined by their shape and chemical composition, so it is not possible to estimate their toxicity in a general way. General hypothesis suggested that exposure to inhaled particles induces pulmonary alveolar inflammation as a basic pathophysiological event, triggering release of various proinflammatory cytokines. Chronic inflammation is a very important underlying mechanism in the genesis of atherosclerosis and cardiovascular diseases. UFP can freely move through the circulation, but their effects on the secondary organs are not known yet, so more studies on recognizing toxicological endpoints of UFP are needed. Determination of UFP toxicity and the estimation of their internal and biologically active dose are necessary for the evidence based conclusions connecting air pollution by UFP and human diseases.

  9. Improvised explosive devices: pathophysiology, injury profiles and current medical management. (United States)

    Ramasamy, A; Hill, A M; Clasper, J C


    The improvised explosive device (IED), in all its forms, has become the most significant threat to troops operating in Afghanistan and Iraq. These devices range from rudimentary home made explosives to sophisticated weapon systems containing high-grade explosives. Within this broad definition they may be classified as roadside explosives and blast mines, explosive formed pojectile (EFP) devices and suicide bombings. Each of these groups causeinjury through a number of different mechanisms and can result in vastly different injury profiles. The "Global War on Terror" has meant that incidents which were previously exclusively seen in conflict areas, can occur anywhere, and clinicians who are involved in emergency trauma care may be required to manage casualties from similar terrorist attacks. An understanding of the types of devices and their pathophysiological effects is necessary to allow proper planning of mass casualty events and to allow appropriate management of the complex poly-trauma casualties they invariably cause. The aim of this review article is to firstly describe the physics and injury profile from these different devices and secondly to present the current clinical evidence that underpins their medical management.

  10. Extracellular matrix dynamics during vertebrate axis formation. (United States)

    Czirók, András; Rongish, Brenda J; Little, Charles D


    The first evidence for the dynamics of in vivo extracellular matrix (ECM) pattern formation during embryogenesis is presented below. Fibrillin 2 filaments were tracked for 12 h throughout the avian intraembryonic mesoderm using automated light microscopy and algorithms of our design. The data show that these ECM filaments have a reproducible morphogenic destiny that is characterized by directed transport. Fibrillin 2 particles initially deposited in the segmental plate mesoderm are translocated along an unexpected trajectory where they eventually polymerize into an intricate scaffold of cables parallel to the anterior-posterior axis. The cables coalesce near the midline before the appearance of the next-formed somite. Moreover, the ECM filaments define global tissue movements with high precision because the filaments act as passive motion tracers. Quantification of individual and collective filament "behaviors" establish fate maps, trajectories, and velocities. These data reveal a caudally propagating traveling wave pattern in the morphogenetic movements of early axis formation. We conjecture that within vertebrate embryos, long-range mechanical tension fields are coupled to both large-scale patterning and local organization of the ECM. Thus, physical forces or stress fields are essential requirements for executing an emergent developmental pattern-in this case, paraxial fibrillin cable assembly.

  11. VERITAS: Versatile Triple-Axis Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il


    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, {approx} 5 m Curved Guide, {approx} 26 m w/ R 1500 m Straight Guide before the Instrument, {approx} 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world.

  12. VERITAS: Versatile Triple-Axis Spectrometer

    International Nuclear Information System (INIS)

    Park, Sung Il


    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, ∼ 5 m Curved Guide, ∼ 26 m w/ R 1500 m Straight Guide before the Instrument, ∼ 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world

  13. Pathophysiology and treatment of psychosis in Parkinson's disease: a review. (United States)

    Zahodne, Laura B; Fernandez, Hubert H


    Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past 15 years, from an initial interpretation of symptoms as dopaminergic drug adverse effects to the current view of a complex interplay of extrinsic and disease-related factors.PD psychosis has unique clinical features, namely that it arises within a context of a clear sensorium and retained insight, there is relative prominence of visual hallucinations and progression occurs over time. PD psychosis tends to emerge later in the disease course, and disease duration represents one risk factor for its development. The use of anti-PD medications (particularly dopamine receptor agonists) has been the most widely identified risk factor for PD psychosis. Other risk factors discussed in the literature include older age, disease severity, sleep disturbance, cognitive impairment, dementia and/or depression.Recent efforts have aimed to explore the complex pathophysiology of PD psychosis, which is now known to involve an interaction between extrinsic, drug-related and intrinsic, disease-related components. The most important extrinsic factor is use of dopaminergic medication, which plays a prominent role in PD psychosis. Intrinsic factors include visual processing deficits (e.g. lower visual acuity, colour and contrast recognition deficits, ocular pathology and functional brain abnormalities identified amongst hallucinating PD patients); sleep dysregulation (e.g. sleep fragmentation and altered dream phenomena); neurochemical (dopamine, serotonin, acetylcholine, etc.) and structural abnormalities involving site-specific Lewy body deposition; and genetics (e.g. apolipoprotein E epsilon4 allele and tau H1H1 genotype). Preliminary reports have also shown a potential relationship

  14. Caveolins and caveolae in ocular physiology and pathophysiology. (United States)

    Gu, Xiaowu; Reagan, Alaina M; McClellan, Mark E; Elliott, Michael H


    Caveolae are specialized, invaginated plasma membrane domains that are defined morphologically and by the expression of signature proteins called, caveolins. Caveolae and caveolins are abundant in a variety of cell types including vascular endothelium, glia, and fibroblasts where they play critical roles in transcellular transport, endocytosis, mechanotransduction, cell proliferation, membrane lipid homeostasis, and signal transduction. Given these critical cellular functions, it is surprising that ablation of the caveolae organelle does not result in lethality suggesting instead that caveolae and caveolins play modulatory roles in cellular homeostasis. Caveolar components are also expressed in ocular cell types including retinal vascular cells, Müller glia, retinal pigment epithelium (RPE), conventional aqueous humor outflow cells, the corneal epithelium and endothelium, and the lens epithelium. In the eye, studies of caveolae and other membrane microdomains (i.e., "lipid rafts") have lagged behind what is a substantial body of literature outside vision science. However, interest in caveolae and their molecular components has increased with accumulating evidence of important roles in vision-related functions such as blood-retinal barrier homeostasis, ocular inflammatory signaling, pathogen entry at the ocular surface, and aqueous humor drainage. The recent association of CAV1/2 gene loci with primary open angle glaucoma and intraocular pressure has further enhanced the need to better understand caveolar functions in the context of ocular physiology and disease. Herein, we provide the first comprehensive review of literature on caveolae, caveolins, and other membrane domains in the context of visual system function. This review highlights the importance of caveolae domains and their components in ocular physiology and pathophysiology and emphasizes the need to better understand these important modulators of cellular function. Copyright © 2016 Elsevier Ltd. All


    Directory of Open Access Journals (Sweden)

    Aji Kristianto Wijaya


    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Stroke is one of the most common cause of death worldwide and the third leading cause of death in the United States. Stroke composed 90,000 deaths of women and 60,000 men each year. In Indonesia, 8 of 1000 people suffered a stroke. Stroke is divided into two, non-hemorrhagic stroke and hemorrhagic stroke. Most of them (80% is non-hemorrhagic stroke. Non-hemorrhagic stroke can be caused by thrombi or emboli. Understanding the pathophysiology of non-hemorrhagic stroke caused by a thrombus is very important in regard with providing appropriate patient management. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  16. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    Gina Manda


    Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

  17. Gait post-stroke: Pathophysiology and rehabilitation strategies. (United States)

    Beyaert, C; Vasa, R; Frykberg, G E


    We reviewed neural control and biomechanical description of gait in both non-disabled and post-stroke subjects. In addition, we reviewed most of the gait rehabilitation strategies currently in use or in development and observed their principles in relation to recent pathophysiology of post-stroke gait. In both non-disabled and post-stroke subjects, motor control is organized on a task-oriented basis using a common set of a few muscle modules to simultaneously achieve body support, balance control, and forward progression during gait. Hemiparesis following stroke is due to disruption of descending neural pathways, usually with no direct lesion of the brainstem and cerebellar structures involved in motor automatic processes. Post-stroke, improvements of motor activities including standing and locomotion are variable but are typically characterized by a common postural behaviour which involves the unaffected side more for body support and balance control, likely in response to initial muscle weakness of the affected side. Various rehabilitation strategies are regularly used or in development, targeting muscle activity, postural and gait tasks, using more or less high-technology equipment. Reduced walking speed often improves with time and with various rehabilitation strategies, but asymmetric postural behaviour during standing and walking is often reinforced, maintained, or only transitorily decreased. This asymmetric compensatory postural behaviour appears to be robust, driven by support and balance tasks maintaining the predominant use of the unaffected side over the initially impaired affected side. Based on these elements, stroke rehabilitation including affected muscle strengthening and often stretching would first need to correct the postural asymmetric pattern by exploiting postural automatic processes in various particular motor tasks secondarily beneficial to gait. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Pathophysiological mechanisms of severe anaemia in Malawian children.

    Directory of Open Access Journals (Sweden)

    Michaël Boele van Hensbroek


    Full Text Available Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success.We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl] studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%. Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis.RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome.

  19. Pathophysiological study of experimental hydrocephalus with computed tomography (CT) scan

    International Nuclear Information System (INIS)

    Murata, Takaho


    In order to investigate the pathophysiological changes during a development of hydrocephalus, the observations employing computed tomography (CT) scans and monitorings of intracranial epidural pressure (EDP) were performed in a series of kaolin-induced canine hydrocephalus. According to ''volume index'' of ventricles which was calculated from printed-out CT numbers, great individual variations were recognized in the degree of a ventricular enlargement as well as the rate of EDP. They are thought to be due to the difference in types of hydrocephalus, which have been induced by a discrepancy in the site and degree of an obstruction caused by kaolin. Periventricular lucency (PVL) of various degrees were also detected on CT scans of experimental hydrocephalus. It was always marked in the superolateral angle of frontal horn of the lateral ventricles, and differed in degree from severe to mild. PVLs were distinct in the acute stage with high EDP, and gradually became indistinct and had a tendency to disappear thereafter along with decreased EDP. They immediately disappeared after shunting operation. The pathogenesis of PVL was investigated with histological examinations, as well as by using contrast enhancement, Metrizamide ventriculography, the analysis of linear density profiles, and the measurement of regional cerebral blood flow (rCBF). Consequently, PVLs in hydrocephalus are considered to represent an acute edema or a chronic CSF retention in the periventricular white matter caused by increase of water content. In other words, they are regarded as a sign of present or preceding intraventricular hypertension on CT scan, and may become a clinical indication for shunting operation. (author)

  20. Metabolic syndrome, its pathophysiology and the role of melatonin. (United States)

    Srinivasan, Venkataramanujam; Ohta, Yoshiji; Espino, Javier; Pariente, Jose A; Rodriguez, Ana B; Mohamed, Mahaneem; Zakaria, Rahimah


    Metabolic syndrome (MetS) is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involved dysregulation of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia. Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action. Melatonin reduced both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesityinduced metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration has been shown to inhibit insulin release by acting through both MT1 and MT2 melatonin receptors present in pancreatic β-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high sucrose diet. Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist like luzindole. Ramelteon, the newly available melatonin agonist will also have more promising role in the control of MetS. The numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is used for treatment of MetS (US Patent No. 2008001400450). Anti-oxidants like S-adenosyl-methionine, Vitamin E, and Vitamin C have been found beneficial in treating MetS (US Patent No. 8063024). Melatonin being a powerful Antioxidant will have a promising role in treating patients with metabolic syndrome.

  1. Involvement of the kynurenine pathway in human glioma pathophysiology.

    Directory of Open Access Journals (Sweden)

    Seray Adams

    Full Text Available The kynurenine pathway (KP is the principal route of L-tryptophan (TRP catabolism leading to the production of kynurenine (KYN, the neuroprotectants, kynurenic acid (KYNA and picolinic acid (PIC, the excitotoxin, quinolinic acid (QUIN and the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD(+. The enzymes indoleamine 2,3-dioxygenase-1 (IDO-1, indoleamine 2,3-dioxygenase-2 (IDO-2 and tryptophan 2,3-dioxygenase (TDO-2 initiate the first step of the KP. IDO-1 and TDO-2 induction in tumors are crucial mechanisms implicated to play pivotal roles in suppressing anti-tumor immunity. Here, we report the first comprehensive characterisation of the KP in 1 cultured human glioma cells and 2 plasma from patients with glioblastoma (GBM. Our data revealed that interferon-gamma (IFN-γ stimulation significantly potentiated the expression of the KP enzymes, IDO-1 IDO-2, kynureninase (KYNU, kynurenine hydroxylase (KMO and significantly down-regulated 2-amino-3-carboxymuconate semialdehyde decarboxylase (ACMSD and kynurenine aminotransferase-I (KAT-I expression in cultured human glioma cells. This significantly increased KP activity but significantly lowered the KYNA/KYN neuroprotective ratio in human cultured glioma cells. KP activation (KYN/TRP was significantly higher, whereas the concentrations of the neuroreactive KP metabolites TRP, KYNA, QUIN and PIC and the KYNA/KYN ratio were significantly lower in GBM patient plasma (n = 18 compared to controls. These results provide further evidence for the involvement of the KP in glioma pathophysiology and highlight a potential role of KP products as novel and highly attractive therapeutic targets to evaluate for the treatment of brain tumors, aimed at restoring anti-tumor immunity and reducing the capacity for malignant cells to produce NAD(+, which is necessary for energy production and DNA repair.

  2. Pathophysiological consequences of hemolysis. Role of cell-free hemoglobin

    Directory of Open Access Journals (Sweden)

    Tomasz Misztal


    Full Text Available Abundant hemolysis is associated with a number of inherent and acquired diseases including sickle-cell disease (SCD, polycythemia, paroxysmal nocturnal hemoglobinuria (PNH and drug-induced hemolytic anemia. Despite different etiopathology of hemolytic diseases, many concomitant symptoms are comparable and include e.g. hypertension, hemoglobinuria and hypercoagulation state. Studies in the last years have shown a growing list of mechanisms lying at the basis of those symptoms, in particular irreversible reaction between cell-free hemoglobin (Hb and nitric oxide (NO – endogenous vasorelaxant and anti-thrombotic agent. Saturation of protective physiological cell-free Hb-scavenging mechanisms results in accumulation of Hb in plasma and hemoglobinemia. Extensive hemoglobinemia subsequently leads to hemoglobinuria, which may cause kidney damage and development of Fanconi syndrome. A severe problem in patients with SCD and PNH is pulmonary and systemic hypertension. It may lead to circulation failure, including stroke, and it is related to abolition of NO bioavailability for vascular smooth muscle cells. Thrombotic events are the major cause of death in SCD and PNH. It ensues from lack of platelet inhibition evoked by Hb-mediated NO scavenging. A serious complication that affects patients with excessive hemolysis is erectile dysfunction. Also direct cytotoxic, prooxidant and proinflammatory effects of cell-free hemoglobin and heme compose the clinical picture of hemolytic diseases. The pathophysiological role of plasma Hb, mechanisms of its elimination, and direct and indirect (via NO scavenging deleterious effects of cell-free Hb are presented in detail in this review. Understanding the critical role of hemolysis and cell-free Hb is important in the perspective of treating patients with hemolytic diseases and to design new effective therapies in future.

  3. Pompe disease: from pathophysiology to therapy and back again

    Directory of Open Access Journals (Sweden)

    Jeong-A eLim


    Full Text Available Pompe disease is a lysosomal storage disorder in which acid alpha-glucosidase is deficient or absent. Deficiency of this lysosomal enzyme results in progressive expansion of glycogen-filled lysosomes in multiple tissues, with cardiac and skeletal muscle being the most severely affected. The clinical spectrum ranges from fatal hypertrophic cardiomyopathy and skeletal muscle myopathy in infants to relatively attenuated forms, which manifest as a progressive myopathy without cardiac involvement. The currently available enzyme replacement therapy proved to be successful in reversing cardiac but not skeletal muscle abnormalities. Although the overall understanding of the disease has progressed, the pathophysiology of muscle damage remains poorly understood. Lysosomal enlargement/rupture has long been considered a mechanism of relentless muscle damage in Pompe disease. In past years, it became clear that this simple view of the pathology is inadequate; the pathological cascade involves dysfunctional autophagy, a major lysosome-dependent intracellular degradative pathway. The autophagic process in Pompe skeletal muscle is affected at the termination stage - impaired autophagosomal-lysosomal fusion. Yet another abnormality in the diseased muscle is the accelerated production of large, unrelated to ageing, lipofuscin deposits - a marker of cellular oxidative damage and a sign of mitochondrial dysfunction. The massive autophagic buildup and lipofuscin inclusions appear to cause a greater effect on muscle architecture than the enlarged lysosomes outside the autophagic regions. Furthermore, the dysfunctional autophagy affects the trafficking of the replacement enzyme and interferes with its delivery to the lysosomes. Several new therapeutic approaches have been tested in Pompe mouse models: substrate reduction therapy, lysosomal exocytosis following the overexpression of transcription factor EB and a closely related but distinct factor E3, and genetic

  4. [Mirror neurons: from anatomy to pathophysiological and therapeutic implications]. (United States)

    Mathon, B


    Mirror neurons are a special class of neurons discovered in the 1990s. They respond when we perform an action and also when we see someone else perform that action. They play a role in the pathophysiology of some neuropsychiatric diseases. Mirror neurons have been identified in humans: in Broca's area and the inferior parietal cortex. Their responses are qualitative and selective depending on the observed action. Emotions (including disgust) and empathy seem to operate according to a mirror mechanism. Indeed, the mirror system allows us to encode the sensory experience and to simulate the emotional state of others. This results in our improved identification of the emotions in others. Additionally, mirror neurons can encode an observed action in motor stimuli and allow its reproduction; thus, they are involved in imitation and learning. Current studies are assessing the role of mirror neurons in the pathopysiology of social-behavior disorders, including autism and schizophrenia. Understanding this mirror system will allow us to develop psychotherapy practices based on empathic resonance between the patient and the therapist. Also, some authors report that a passive rehabilitation technique, based on stimulation of the mirror-neuron system, has a beneficial effect in the treatment of patients with post-stroke motor deficits. Mirror neurons are an anatomical entity that enables improved understanding of behavior and emotions, and serves as a base for developing new cognitive therapies. Additional studies are needed to clarify the exact role of this neuronal system in social cognition and its role in the development of some neuropsychiatric diseases. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. The Proline Regulatory Axis and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Phang, James Ming; Liu, Wei; Hancock, Chad; Christian, Kyle J., E-mail: [Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States)


    Studies in metabolism and cancer have characterized changes in core pathways involving glucose and glutamine, emphasizing the provision of substrates for building cell mass. But recent findings suggest that pathways previously considered peripheral may play a critical role providing mechanisms for cell regulation. Several of these mechanisms involve the metabolism of non-essential amino acids, for example, the channeling of glycolytic intermediates into the serine pathway for one-carbon transfers. Historically, we proposed that the proline biosynthetic pathway participated in a metabolic interlock with glucose metabolism. The discovery that proline degradation is activated by p53 directed our attention to the initiation of apoptosis by proline oxidase/dehydrogenase. Now, however, we find that the biosynthetic mechanisms and the metabolic interlock may depend on the pathway from glutamine to proline, and it is markedly activated by the oncogene MYC. These findings add a new dimension to the proline regulatory axis in cancer and present attractive potential targets for cancer treatment.

  6. Polarized triple-axis spectrometer TASP

    Energy Technology Data Exchange (ETDEWEB)

    Boeni, P; Keller, P [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)


    The polarized triple-axis spectrometer TASP at SINQ has been optimized for measuring magnetic cross sections in condensed matter. The neutrons are polarized or analyzed either by means of benders or Heusler monochromators. The beam divergence, i.e. the intensity, and the spectral range of the neutrons is rather large because of the supermirror coatings of the feeding neutron guide. The intensity can be further increased at the sample position by means of a focussing monochromator and a focussing anti-trumpet. The end position of TASP allows the tailoring of the neutron beam already before the monochromator and to scatter neutrons over very wide ranges of angles. (author) 6 figs., 1 tab., 8 refs.

  7. A Portable Single Axis Magnetic Gradiometer

    DEFF Research Database (Denmark)

    Merayo, José M.G.; Petersen, Jan Raagaard; Nielsen, Otto V


    not provide vector information about the magnetic field. Secondly, one of the sensors measures the ambient magnetic field and is used to compensate for the main field at both sensors. Several methods have been developed for characterization of the 2 gradiometer, and the calibration of the gradient......The single axis magnetic gradiometer based on two compact detector compensation (CDC) fluxgate ringcore sensors separated 20 cm is described. Despite its high stability and precision better than 1 nT, the calibration procedures are not straightforward. Firstly, the mono-axial measurement does...... measurements is achieved by using a magnetic dipole of strength 2 mAm(2). In a coil facility, the gradient can be determined with an accuracy of 0.3 nT/m(RMS)....

  8. RITA-type triple axis spectrometers

    International Nuclear Information System (INIS)

    Roennow, H.M.


    The RITA spectrometer at Risoe National Laboratory was the first to incorporate a complete re-thinking of the neutron-path from source, through detector to analysis. Since then, other RITA-type spectrometers such as SPINS at NIST, RITA-II at PSI have been built, and several new spectrometers around the world are adapting the same philosophy. The main novelty of RITA was the introduction of a single back-end tank featuring both an analyser block with multiple individually turnable analyser blades and a 2D position sensitive detector. Several new triple-axis spectrometers are presently being built at existing and future sources, and almost all of them have learnt from the experience with RITA. (R.P.)

  9. Cognitive dysfunction in depression - pathophysiology and novel targets. (United States)

    Carvalho, Andre F; Miskowiak, Kamilla K; Hyphantis, Thomas N; Kohler, Cristiano A; Alves, Gilberto S; Bortolato, Beatrice; G Sales, Paulo Marcelo; Machado-Vieira, Rodrigo; Berk, Michael; McIntyre, Roger S


    Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

  10. Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus (United States)

    Abell, Sally K.; De Courten, Barbora; Boyle, Jacqueline A.; Teede, Helena J.


    Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM. PMID:26110385

  11. Analysis and design of a vertical axis wind turbine


    Goyena Iriso, Joseba


    The main objective of this project is to design a new vertical axis wind turbine, specifically one Giromill wind turbine. The project development requires performing a previous study of the vertical axis wind turbines currently development. This study has to be performed before starting to design the wind turbine. Other very important aim is the development of a new vertical axis wind turbine. The after analyses that will result in the final design of the wind turbine will b...

  12. Self-starting aerodynamics analysis of vertical axis wind turbine


    Jianyang Zhu; Hailin Huang; Hao Shen


    Vertical axis wind turbine is a special type of wind-force electric generator which is capable of working in the complicated wind environment. The self-starting aerodynamics is one of the most important considerations for this kind of turbine. This article aims at providing a systematic synthesis on the self-starting aerodynamic characteristics of vertical axis wind turbine based on the numerical analysis approach. First, the physical model of vertical axis wind turbine and its parameter defi...

  13. Pathophysiology of esophageal impairment due to button battery ingestion. (United States)

    Völker, Johannes; Völker, Christine; Schendzielorz, Philipp; Schraven, Sebastian P; Radeloff, Andreas; Mlynski, Robert; Hagen, Rudolf; Rak, Kristen


    The increased use of button batteries with high energy densities in devices of daily life presents a high risk of injury, especially for toddlers and young children. If an accidental ingestion of a button battery occurs, this foreign body can become caught in the constrictions of the esophagus and cause serious damage to the adjacent tissue layers. The consequences can be ulcerations, perforations with fistula formation and damage to the surrounding anatomical structures. In order to gain a better understanding of the pathophysiology after ingestion, we carried out systematic studies on fresh preparations of porcine esophagi. The lithium button battery type CR2032, used most frequently in daily life, was exposed in preparations of porcine esophagi and incubated under the addition of artificial saliva at 37 °C. A total of eight esophagi were analysed by different methods. Measurements of the pH value around the battery electrodes and histological studies of the tissue damage were carried out after 0.5-24 h exposure time. In addition, macroscopic time-lapse images were recorded. Measurements of the battery voltage and the course of the electric current supplemented the experiments. The investigations showed that the batteries caused an electrolysis reaction in the moist environment. The positive electrode formed an acidic and the negative electrode a basic medium. Consequently, a coagulation necrosis at the positive pole, and a deep colliquation necrosis at the minus pole occurred. After an exposure time of 12 h, tissue damage caused by the lye corrosion was observed on the side of the negative electrode up to the lamina muscularis. The corrosion progressed up to the final exposure time of 24 h, but the batteries still had sufficient residual voltage, such that further advancing damage would be expected. Button battery ingestion in humans poses an acute life-threatening danger and immediate endoscopic removal of the foreign body is essential. After only 2

  14. Melatonin plays a protective role in postburn rodent gut pathophysiology. (United States)

    Al-Ghoul, Walid M; Abu-Shaqra, Steven; Park, Byeong Gyu; Fazal, Nadeem


    Melatonin is a possible protective agent in postburn gut pathophysiological dynamics. We investigated the role of endogenously-produced versus exogenously-administered melatonin in a major thermal injury rat model with well-characterized gut inflammatory complications. Our rationale is that understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end, we tested the hypothesis that the gut is both a source and a target for melatonin and that mesenteric melatonin plays an anti-inflammatory role following major thermal injury in rats with 3rd degree hot water scald over 30% TBSA. Our methods for assessing the gut as a source of melatonin included plasma melatonin ELISA measurements in systemic and mesenteric circulation as well as rtPCR measurement of jejunum and terminal ileum expression of the melatonin synthesizing enzymes arylalkylamine N-acetyltransferase (AA-NAT) and 5-hydroxyindole-O-methyltransferase (HIOMT) in sham versus day-3 postburn rats. Our melatonin ELISA results revealed that mesenteric circulation has much higher melatonin than systemic circulation and that both mesenteric and systemic melatonin levels are increased three days following major thermal injury. Our rtPCR results complemented the ELISA data in showing that the melatonin synthesizing enzymes AA-NAT and HIOMT are expressed in the ileum and jejunum and that this expression is increased three days following major thermal injury. Interestingly, the rtPCR data also revealed negative feedback by melatonin as exogenous melatonin supplementation at a dose of 7.43 mg (32 micromole/kg), but not 1.86 mg/kg (8 micromole/kg) drastically suppressed AA-NAT mRNA expression. Our methods also included an assessment of the gut as a target for melatonin utilizing computerized immunohistochemical measurements to quantify the effects of exogenous melatonin

  15. Evidence-Based Revised View of the Pathophysiology of Preeclampsia. (United States)

    Ahmed, Asif; Rezai, Homira; Broadway-Stringer, Sophie


    Preeclampsia is a life-threatening vascular disorder of pregnancy due to a failing stressed placenta. Millions of women risk death to give birth each year and globally each year, almost 300,000 lose their life in this process and over 500,000 babies die as a consequence of preeclampsia. Despite decades of research, we lack pharmacological agents to treat it. Maternal endothelial oxidative stress is a central phenomenon responsible for the preeclampsia phenotype of high maternal blood pressure and proteinuria. In 1997, it was proposed that preeclampsia arises due to the loss of VEGF activity, possibly due to elevation in anti-angiogenic factor, soluble Flt-1 (sFlt-1). Researchers showed that high sFlt-1 and soluble endoglin (sEng) elicit the severe preeclampsia phenotype in pregnant rodents. We demonstrated that heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway prevents placental stress and suppresses sFlt-1 and sEng release. Likewise, hydrogen sulphide (H 2 S)/cystathionine-γ-lyase (Cth) systems limit sFlt-1 and sEng and protect against the preeclampsia phenotype in mice. Importantly, H 2 S restores placental vasculature, and in doing so improves lagging fetal growth. These molecules act as the inhibitor systems in pregnancy and when they fail, preeclampsia is triggered. In this review, we discuss what are the hypotheses and models for the pathophysiology of preeclampsia on the basis of Bradford Hill causation criteria for disease causation and how further in vivo experimentation is needed to establish 'proof of principle'. Hypotheses that fail to meet the Bradford Hill causation criteria include abnormal spiral artery remodelling and inflammation and should be considered associated or consequential to the disorder. In contrast, the protection against cellular stress hypothesis that states that the protective pathways mitigate cellular stress by limiting elevation of anti-angiogenic factors or oxidative stress and the subsequent clinical signs of preeclampsia

  16. Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management. (United States)

    Baruteau, Alban-Elouen; Pass, Robert H; Thambo, Jean-Benoit; Behaghel, Albin; Le Pennec, Solène; Perdreau, Elodie; Combes, Nicolas; Liberman, Leonardo; McLeod, Christopher J


    Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities. Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for

  17. Effects of high fat diet on the Basal activity of the hypothalamus-pituitary-adrenal axis in mice: a systematic review. (United States)

    Auvinen, H E; Romijn, J A; Biermasz, N R; Havekes, L M; Smit, J W A; Rensen, P C N; Pereira, A M


    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the hypothalamus-pituitary-adrenal-axis activation. The aim of this review was to assess the effects of high fat feeding on the activity of the hypothalamus-pituitary-adrenal-axis in mice. PubMed, EMBASE, Web of Science, the Cochrane database, and Science Direct were electronically searched and reviewed by 2 individual researchers. We included only original mouse studies reporting parameters of the hypothalamus-pituitary-adrenal-axis after high fat feeding, and at least 1 basal corticosterone level with a proper control group. Studies with adrenalectomized mice, transgenic animals only, high fat diet for less than 2 weeks, or other interventions besides high fat diet, were excluded. 20 studies were included. The hypothalamus-pituitary-adrenal-axis evaluation was the primary research question in only 5 studies. Plasma corticosterone levels were unchanged in 40%, elevated in 30%, and decreased in 20% of the studies. The effects in the peripheral tissues and the central nervous system were also inconsistent. However, major differences were found between mouse strains, experimental conditions, and the content and duration of the diets. This systematic review demonstrates that the effects of high fat feeding on the basal activity of the hypothalamus-pituitary-adrenal-axis in mice are limited and inconclusive. Differences in experimental conditions hamper comparisons and accentuate the need for standardized evaluations to discern the effects of diet-induced obesity on the hypothalamus-pituitary-adrenal-axis. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Concept of a Programmable Fixture for 3-Axis CNC

    Directory of Open Access Journals (Sweden)

    Ahmad Dalloul


    Full Text Available CNC machine is the one of the major reasons for industrial advancement in recent decades for its ability of producing accurate parts. The most commen CNC machines are of 3-axis and adopted widely in the industrial sector. However, for producing more complicated parts 5-axis CNC machines are required. Although the introduction of the 5-axis machine came after the 3-axis CNC machine has established itself and many manufacturers did not make the move toward the newer model and its high pricing compared to the 3-axis model did not help either. In this time the development of a fixture or a platform to help transfer the 3-axis to a 5-axis to some degree. This paper discusses the concept of a programmable fixture that gives 3-axis CNC machine the freedom to act in similar manner as the 5-axis. The paper describes the mechanism with some initial results of the testing. Result showed that the platform moves in translation manner with an average error of 5.58 % and 7.303% average error for rotation movement.

  19. Suicidal behavior on Axis VI: clinical data supporting a sixth Axis for DSM-V. (United States)

    Van Orden, Kimberly A; Witte, Tracy K; Holm-Denoma, Jill; Gordon, Kathryn H; Joiner, Thomas E


    Oquendo and colleagues (Oquendo, Baca-García, Mann, & Giner, 2008; Oquendo & Currier, 2009) recommend that DSM-V emphasize suicide risk assessment on a sixth axis, thereby increasing regularity of suicide risk assessments. We propose that evidence of nonredundancy with Axis V - Global Assessment of Functioning (GAF) is one piece of data that can serve as a starting point for a line of research establishing incremental predictive utility for a separate suicide risk assessment in the DSM framework. A standardized suicide risk assessment protocol, measures of depressive, anxious, and eating disordered symptomatology, as well as an index of comorbidity were administered to a sample of 412 adult outpatients. Our data indicate that data from standardized suicide risk assessments are associated with indices of symptomatology severity as well as comorbidity, controlling for GAF. These results support the nonredundancy of the assessments and suggest the utility of longitudinal investigations of the predictive utility of a sixth DSM axis in the assessment of suicide risk.

  20. Pathophysiology and multifactorial etiology of acquired vasospastic disease (Raynaud syndrome) in vibration-exposed workers. (United States)

    Gemne, G


    The article reviews available pathophysiological evidence for a multifactorial etiology of the Raynaud type of peripheral circulation disorder in persons exposed to vibration from handheld tools and discusses the consequences this viewpoint may have for diagnostics, preventive work, and research.

  1. Symptoms in Inflammatory Bowel Disease: pathophysiologic aspects and their relation with disease activity

    NARCIS (Netherlands)

    Minderhoud, I.M.


    Symptoms in Inflammatory Bowel Disease: pathophysiologic aspects and their relation with disease activity Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn's disease (CD). IBD patients frequently complain of fatigue, and a substantial proportion of the patients have

  2. The rise of pathophysiologic research in the United States: the role of two Harvard hospitals. (United States)

    Tishler, Peter V


    Pathophysiologic research, the major approach to understanding and treating disease, was created in the 20th century, and two Harvard-affiliated hospitals, the Peter Bent Brigham Hospital and Boston City Hospital, played a key role in its development. After the Flexner Report of 1910, medical students were assigned clinical clerkships in teaching hospitals. Rockefeller-trained Francis Weld Peabody, who was committed to investigative, pathophysiologic research, was a critical leader in these efforts. At the Brigham, Harvard medical students observed patients closely and asked provocative questions about their diseases. Additionally, physicians returned from World War I with questions concerning the pathophysiology of wartime injuries. At the Boston City Hospital's new Thorndike Memorial Laboratory, Peabody fostered investigative question-based research by physicians. These physicians expanded pathophysiologic investigation from the 1920s. Post-war, Watson and Crick's formulation of the structure of DNA led shortly to modern molecular biology and new research approaches that are being furthered at the Boston Hospitals.

  3. Encapsulating Peritoneal Sclerosis: A study on pathophysiology, clinical aspects and management

    NARCIS (Netherlands)

    S.M. Habib (Meelad)


    markdownabstract__Abstract__ This thesis describes the results of studies focusing on the pathophysiology, clinical aspects, and management of encapsulating peritoneal sclerosis (EPS). We have reported on the presence of inflammation in EPS, described several clinical aspects, and focused on

  4. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome. (United States)

    El-Salhy, Magdy; Hausken, Trygve; Gilja, Odd Helge; Hatlebakk, Jan Gunnar


    The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed. Expert commentary: The abnormalities observed in the gastrointestinal endocrine cells in IBS patients explains their visceral hypersensitivity, gastrointestinal dysmotility, and abnormal intestinal secretion, as well as the interchangeability of symptoms over time. Clarifying the role of the intestinal stem cells in the pathophysiology of IBS may lead to new treatment methods for IBS.

  5. Effective solidity in vertical axis wind turbines (United States)

    Parker, Colin M.; Leftwich, Megan C.


    The flow surrounding vertical axis wind turbines (VAWTs) is investigated using particle imaging velocimetry (PIV). This is done in a low-speed wind tunnel with a scale model that closely matches geometric and dynamic properties tip-speed ratio and Reynolds number of a full size turbine. Previous results have shown a strong dependance on the tip-speed ratio on the wake structure of the spinning turbine. However, it is not clear whether this is a speed or solidity effect. To determine this, we have measured the wakes of three turbines with different chord-to-diameter ratios, and a solid cylinder. The flow is visualized at the horizontal mid-plane as well as the vertical mid-plane behind the turbine. The results are both ensemble averaged and phase averaged by syncing the PIV system with the rotation of the turbine. By keeping the Reynolds number constant with both chord and diameter, we can determine how each effects the wake structure. As these parameters are varied there are distinct changes in the mean flow of the wake. Additionally, by looking at the vorticity in the phase averaged profiles we can see structural changes to the overall wake pattern.

  6. Mitochondrial–Lysosomal Axis in Acetaminophen Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Anna Moles


    Full Text Available Acetaminophen (APAP toxicity is the most common cause of acute liver failure and a major indication for liver transplantion in the United States and Europe. Although significant progress has been made in understanding the molecular mechanisms underlying APAP hepatotoxicity, there is still an urgent need to find novel and effective therapies against APAP-induced acute liver failure. Hepatic APAP metabolism results in the production of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI, which under physiological conditions is cleared by its conjugation with glutathione (GSH to prevent its targeting to mitochondria. APAP overdose or GSH limitation leads to mitochondrial NAPQI-protein adducts formation, resulting in oxidative stress, mitochondrial dysfunction, and necrotic cell death. As mitochondria are a major target of APAP hepatotoxicity, mitochondrial quality control and clearance of dysfunctional mitochondria through mitophagy, emerges as an important strategy to limit oxidative stress and the engagement of molecular events leading to cell death. Recent evidence has indicated a lysosomal–mitochondrial cross-talk that regulates APAP hepatotoxicity. Moreover, as lysosomal function is essential for mitophagy, impairment in the fusion of lysosomes with autophagosomes-containing mitochondria may compromise the clearance of dysfunctional mitochondria, resulting in exacerbated APAP hepatotoxicity. This review centers on the role of mitochondria in APAP hepatotoxicity and how the mitochondrial/lysosomal axis can influence APAP-induced liver failure.

  7. Yaw dynamics of horizontal axis wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A.C. (Utah Univ., Salt Lake City, UT (United States))


    Designers of a horizontal axis wind turbine yaw mechanism are faced with a difficult decision. They know that if they elect to use a yaw- controlled rotor then the system will suffer increased initial cost and increased inherent maintenance and reliability problems. On the other hand, if they elect to allow the rotor to freely yaw they known they will have to account for unknown and random, though bounded, yaw rates. They will have a higher-risk design to trade-off against the potential for cost savings and reliability improvement. The risk of a yaw-free system could be minimized if methods were available for analyzing and understanding yaw behavior. The complexity of yaw behavior has, until recently, discouraged engineers from developing a complete yaw analysis method. The objectives of this work are to (1) provide a fundamental understanding of free-yaw mechanics and the design concepts most effective at eliminating yaw problems, and (2) provide tested design tools and guidelines for use by free-yaw wind systems manufacturers. The emphasis is on developing practical and sufficiently accurate design methods.

  8. Six axis force feedback input device (United States)

    Ohm, Timothy (Inventor)


    The present invention is a low friction, low inertia, six-axis force feedback input device comprising an arm with double-jointed, tendon-driven revolute joints, a decoupled tendon-driven wrist, and a base with encoders and motors. The input device functions as a master robot manipulator of a microsurgical teleoperated robot system including a slave robot manipulator coupled to an amplifier chassis, which is coupled to a control chassis, which is coupled to a workstation with a graphical user interface. The amplifier chassis is coupled to the motors of the master robot manipulator and the control chassis is coupled to the encoders of the master robot manipulator. A force feedback can be applied to the input device and can be generated from the slave robot to enable a user to operate the slave robot via the input device without physically viewing the slave robot. Also, the force feedback can be generated from the workstation to represent fictitious forces to constrain the input device's control of the slave robot to be within imaginary predetermined boundaries.

  9. Creating a Multi-axis Machining Postprocessor

    Directory of Open Access Journals (Sweden)

    Petr Vavruška


    Full Text Available This paper focuses on the postprocessor creation process. When using standard commercially available postprocessors it is often very difficult to modify its internal source code, and it is a very complex process, in many cases even impossible, to implement the newly-developed functions. It is therefore very important to have a method for creating a postprocessor for any CAM system, which allows CL data (Cutter Location data to be generated to a separate text file. The goal of our work is to verify the proposed method for creating a postprocessor. Postprocessor functions for multi-axis machiningare dealt with in this work. A file with CL data must be translated by the postprocessor into an NC program that has been customized for a specific production machine and its control system. The postprocessor is therefore verified by applications for machining free-form surfaces of complex parts, and by executing the NC programs that are generated on real machine tools. This is also presented here.

  10. Elucidating the Role of Neurotensin in the Pathophysiology and Management of Major Mental Disorders

    Directory of Open Access Journals (Sweden)

    Mona M Boules


    Full Text Available Neurotensin (NT is a neuropeptide that is closely associated with, and is thought to modulate, dopaminergic and other neurotransmitter systems involved in the pathophysiology of various mental disorders. This review outlines data implicating NT in the pathophysiology and management of major mental disorders such as schizophrenia, drug addiction, and autism. The data suggest that NT receptor analogs have the potential to be used as novel therapeutic agents acting through modulation of neurotransmitter systems dys-regulated in these disorders.

  11. Physiology and Pathophysiology in Ultra-Marathon Running

    Directory of Open Access Journals (Sweden)

    Beat Knechtle


    Full Text Available In this overview, we summarize the findings of the literature with regards to physiology and pathophysiology of ultra-marathon running. The number of ultra-marathon races and the number of official finishers considerably increased in the last decades especially due to the increased number of female and age-group runners. A typical ultra-marathoner is male, married, well-educated, and ~45 years old. Female ultra-marathoners account for ~20% of the total number of finishers. Ultra-marathoners are older and have a larger weekly training volume, but run more slowly during training compared to marathoners. Previous experience (e.g., number of finishes in ultra-marathon races and personal best marathon time is the most important predictor variable for a successful ultra-marathon performance followed by specific anthropometric (e.g., low body mass index, BMI, and low body fat and training (e.g., high volume and running speed during training characteristics. Women are slower than men, but the sex difference in performance decreased in recent years to ~10–20% depending upon the length of the ultra-marathon. The fastest ultra-marathon race times are generally achieved at the age of 35–45 years or older for both women and men, and the age of peak performance increases with increasing race distance or duration. An ultra-marathon leads to an energy deficit resulting in a reduction of both body fat and skeletal muscle mass. An ultra-marathon in combination with other risk factors, such as extreme weather conditions (either heat or cold or the country where the race is held, can lead to exercise-associated hyponatremia. An ultra-marathon can also lead to changes in biomarkers indicating a pathological process in specific organs or organ systems such as skeletal muscles, heart, liver, kidney, immune and endocrine system. These changes are usually temporary, depending on intensity and duration of the performance, and usually normalize after the race. In

  12. Pathophysiology of cerebral circulatory disorders in idiopathic normal pressure hydrocephalus

    International Nuclear Information System (INIS)

    Takeuchi, Totaro; Goto, Hiromi; Izaki, Kenji


    -score images, revealed a reduction or disappearance of the hypoperfusion site in 19 of 31 (61.3%) cases, either no-change or a shift of the hypoperfusion site in 12 of 31 (38.7%) cases, and a correlation between the pattern of cortical blood flow reduction on ARG method and the pattern of cerebral cortex hypoperfusion on 3D-SSP Z-score images after surgery. Cerebral circulatory disorders in iNPH manifest as either of two pathophysiological conditions: the ''circulatory disorder of the cerebral cortical region'' and the ''circulatory disorder of the thalamus-basal ganglia region.'' Various patterns develop according to the disease stage. (author)

  13. Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology. (United States)

    Cayabyab, Rowena; Ramanathan, Rangasamy


    Retinopathy of prematurity (ROP) continues to be a major preventable cause of blindness and visual handicaps globally. With improved perinatal care, improved survival of moderately preterm infants, and limited resources for oxygen delivery and monitoring, more mature preterm infants are developing severe ROP in developing countries. The pathophysiology of ROP is characterized by two phases. Phase I ROP is due to vaso-obliteration beginning immediately after birth secondary to a marked decrease in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Phase II begins around 33 weeks' postmenstrual age (PMA). During this phase, VEGF levels increase, especially if there is retinal hypoxia with increasing retinal metabolism and demand for oxygen leading to abnormal vasoproliferation. Since the original description of ROP in 1942 by Terry et al. [Am J Ophthalmol 1942;25:203-204], four epidemics of ROP have been observed. Prevention or early treatment of ROP involves careful titration of oxygen saturation by pulse oximeter (SpO2). Optimal SpO2 target remains elusive. Most of the large trials have focused on either a low SpO2 (85-89%) or a high SpO2 (91-95%) from the first day of birth to 36 weeks' PMA. Although the incidence of severe ROP and bronchopulmonary dysplasia decreased significantly, predischarge mortality was higher in these studies. Use of graded SpO2 during the 2 different phases of ROP (early, low SpO2 during phase I vs. late, high SpO2 during phase II) may be the best approach to prevent this disabling condition. Further trials should focus on this strategy. Other biological agents that are currently being studied include IGF-1 with IGF-binding protein-3 (rhIGF-1 + rhIGFBP-3) and propranolol. For advanced stages of ROP, laser ablation of avascular retina, early treatment of ROP (ETROP) protocol, intravitreal injection of anti-VEGF antibodies (e.g. bevacizumab) and vitrectomy are used to protect central vision and prevent

  14. Distortion definition and correction in off-axis systems (United States)

    Da Deppo, Vania; Simioni, Emanuele; Naletto, Giampiero; Cremonese, Gabriele


    Off-axis optical configurations are becoming more and more used in a variety of applications, in particular they are the most preferred solution for cameras devoted to Solar System planets and small bodies (i.e. asteroids and comets) study. Off-axis designs, being devoid of central obstruction, are able to guarantee better PSF and MTF performance, and thus higher contrast imaging capabilities with respect to classical on-axis designs. In particular they are suitable for observing extended targets with intrinsic low contrast features, or scenes where a high dynamical signal range is present. Classical distortion theory is able to well describe the performance of the on-axis systems, but it has to be adapted for the off-axis case. A proper way to deal with off-axis distortion definition is thus needed together with dedicated techniques to accurately measure and hence remove the distortion effects present in the acquired images. In this paper, a review of the distortion definition for off-axis systems will be given. In particular the method adopted by the authors to deal with the distortion related issues (definition, measure, removal) in some off-axis instruments will be described in detail.

  15. A psychology of the human brain-gut-microbiome axis. (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F


    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  16. Late Presentation of a Type III Axis Fracture with Spondyloptosis (United States)

    Jayakumar, Prakash; Choi, David; Casey, Adrian


    A 58-year-old man presented with an undiagnosed Effendi type III classification fracture and spondyloptosis of the axis with remarkably normal neurology. We discuss his surgery 4 years since the initial injury, and the presentation, features and management of fractures of the axis. PMID:18430325

  17. Axis: Generating Explanations at Scale with Learnersourcing and Machine Learning (United States)

    Williams, Joseph Jay; Kim, Juho; Rafferty, Anna; Heffernan, Neil; Maldonado, Samuel; Gajos, Krzysztof Z.; Lasecki, Walter S.; Heffernan, Neil


    While explanations may help people learn by providing information about why an answer is correct, many problems on online platforms lack high-quality explanations. This paper presents AXIS (Adaptive eXplanation Improvement System), a system for obtaining explanations. AXIS asks learners to generate, revise, and evaluate explanations as they solve…

  18. Angular momentum projection of tilted axis rotating states

    Energy Technology Data Exchange (ETDEWEB)

    Oi, M; Onishi, N; Tajima, N [Tokyo Univ. (Japan); Horibata, T


    We applied an exact angular momentum projection to three dimensional cranked HFB (3d-CHFB) states. Tilted axis rotating states (TAR) and principal axis rotating states (PAR) are compared. It is shown that TAR is more adequate than PAR for description of the back bending phenomena driven by tilted rotation or wobbling motion. (author)

  19. A psychology of the human brain–gut–microbiome axis (United States)

    Allen, Andrew P.; Dinan, Timothy G.; Clarke, Gerard


    Abstract In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain–gut–microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress‐related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain–gut–microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain–gut–microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain–gut–microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain–gut–microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology. PMID:28804508

  20. The Performance Characteristics of a Closed Loop, One Axis ...

    African Journals Online (AJOL)

    This paper presents a closed loop one axis solar tracking device of the polar axis type, which achieves an accurate tracking of the sun with a steady state error of less, than 2%. This prototype uses a photo-sensing system to generate an error signal. This error signal switches on a relay, which actuates an electromechanical ...

  1. ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation. (United States)

    Nishioka, Tatsuji; Arima, Naoaki; Kano, Kuniyuki; Hama, Kotaro; Itai, Eriko; Yukiura, Hiroshi; Kise, Ryoji; Inoue, Asuka; Kim, Seok-Hyung; Solnica-Krezel, Lilianna; Moolenaar, Wouter H; Chun, Jerold; Aoki, Junken


    The lipid mediator lysophosphatidic acid (LPA) signals via six distinct G protein-coupled receptors to mediate both unique and overlapping biological effects, including cell migration, proliferation and survival. LPA is produced extracellularly by autotaxin (ATX), a secreted lysophospholipase D, from lysophosphatidylcholine. ATX-LPA receptor signaling is essential for normal development and implicated in various (patho)physiological processes, but underlying mechanisms remain incompletely understood. Through gene targeting approaches in zebrafish and mice, we show here that loss of ATX-LPA1 signaling leads to disorganization of chondrocytes, causing severe defects in cartilage formation. Mechanistically, ATX-LPA1 signaling acts by promoting S-phase entry and cell proliferation of chondrocytes both in vitro and in vivo, at least in part through β1-integrin translocation leading to fibronectin assembly and further extracellular matrix deposition; this in turn promotes chondrocyte-matrix adhesion and cell proliferation. Thus, the ATX-LPA1 axis is a key regulator of cartilage formation.

  2. The hypothalamo-pituitary-adrenal axis in major affective disorder

    DEFF Research Database (Denmark)

    Christensen, M V; Kessing, L V


    disorder. The HPA axis is a complex neuroendocrine network with multiple integrated levels of control, and it is likely that the dysregulation involves abnormalities at several sites within the axis. At present, it is not clear whether the abnormalities are related to the affective episodes only......This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis activity in patients with affective disorders. It is concluded that, despite methodological drawbacks in most studies, dysregulation of the HPA axis seems to be a consistent finding in a proportion of patients with affective...... or to the disorder itself. There is a need for prospective studies of larger samples of patients to be followed during successive affective episodes with a combination of measurements of the HPA-axis activity and brain imaging....

  3. Shot H3837: Darht's First Dual-Axis Explosive Experiment (United States)

    Mendez, Jacob; McNeil, Wendy Vogan; Harsh, James; Hull, Lawrence


    Test H3837 was the first explosive shot performed in front of both flash x-ray axes at the Los Alamos Dual Axis Radiographic HydroTest (DARHT) facility. Executed in November 2009, the shot was an explosively-driven metal flyer plate in a series of experiments designed to explore equation-of-state properties of shocked materials. Imaging the initial shock wave traveling through the flyer plate, DARHT Axis II captured the range of motion from the shock front emergence in the flyer to breakout at the free surface; the Axis I pulse provided a perpendicular perspective of the shot at a time coinciding with the third pulse of Axis II. Since the days of the Manhattan Project, penetrating radiography with multiple frames from different viewing angles has remained a high-profile goal at the Laboratory. H3837 is merely the beginning of a bright future for two-axis penetrating radiography.

  4. Three-Axis Ground Reaction Force Distribution during Straight Walking. (United States)

    Hori, Masataka; Nakai, Akihito; Shimoyama, Isao


    We measured the three-axis ground reaction force (GRF) distribution during straight walking. Small three-axis force sensors composed of rubber and sensor chips were fabricated and calibrated. After sensor calibration, 16 force sensors were attached to the left shoe. The three-axis force distribution during straight walking was measured, and the local features of the three-axis force under the sole of the shoe were analyzed. The heel area played a role in receiving the braking force, the base area of the fourth and fifth toes applied little vertical or shear force, the base area of the second and third toes generated a portion of the propulsive force and received a large vertical force, and the base area of the big toe helped move the body's center of mass to the other foot. The results demonstrate that measuring the three-axis GRF distribution is useful for a detailed analysis of bipedal locomotion.

  5. Theoretical performance of cross-wind axis turbines with results for a catenary vertical axis configuration (United States)

    Muraca, R. J.; Stephens, M. V.; Dagenhart, J. R.


    A general analysis capable of predicting performance characteristics of cross-wind axis turbines was developed, including the effects of airfoil geometry, support struts, blade aspect ratio, windmill solidity, blade interference and curved flow. The results were compared with available wind tunnel results for a catenary blade shape. A theoretical performance curve for an aerodynamically efficient straight blade configuration was also presented. In addition, a linearized analytical solution applicable for straight configurations was developed. A listing of the computer program developed for numerical solutions of the general performance equations is included in the appendix.

  6. Effective shunt impedance comparison between s-band standing wave accelerators with on-axis and off-axis couplers

    International Nuclear Information System (INIS)

    Schriber, S.O.; Funk, L.W.; Hutcheon, R.M.


    The effective shunt impedances of a side-coupled S-band standing wave accelerating structure and a structure employing on-axis couplers have been compared by measuring the energy of accelerated electrons. Criteria for choosing an on-axis coupled structure compared to side-coupled and ''disk and washer'' accelerating structures are given. (author)

  7. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.


    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  8. Non-uniform muscle fat replacement along the proximodistal axis in Duchenne muscular dystrophy. (United States)

    Hooijmans, M T; Niks, E H; Burakiewicz, J; Anastasopoulos, C; van den Berg, S I; van Zwet, E; Webb, A G; Verschuuren, J J G M; Kan, H E


    The progressive replacement of muscle tissue by fat in Duchenne muscular dystrophy (DMD) has been studied using quantitative MRI between, but not within, individual muscles. We studied fat replacement along the proximodistal muscle axis using the Dixon technique on a 3T MR scanner in 22 DMD patients and 12 healthy controls. Mean fat fractions per muscle per slice for seven lower and upper leg muscles were compared between and within groups assuming a parabolic distribution. Average fat fraction for a small central slice stack and a large coverage slice stack were compared to the value when the stack was shifted one slice (15 mm) up or down. Higher fat fractions were observed in distal and proximal muscle segments compared to the muscle belly in all muscles of the DMD subjects (p muscle end regions are exposed to higher mechanical strain, which points towards mechanical disruption of the sarcolemma as one of the key factors in the pathophysiology. Overall, this non-uniformity in fat replacement needs to be taken into account to prevent sample bias when applying quantitative MRI as biomarker in clinical trials for DMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Thoughts on the so-called 'radius-capitellum axis'

    International Nuclear Information System (INIS)

    Schild, H.; Mueller, H.A.; Wagner, H.; Baetz, W.; Mainz Univ.


    We have studied 438 patients radiologically in order to observe the so-called 'radius-capitellum axis'. In about a quarter of people with normal elbows the axis passes lateral to the middle portion of the capitellum, so that even when there is marked deviation, there is no certainty that the humero-radial joint is abnormal. Deviation of the axis can be caused by changes in the shape of the capitellum or of the radius, or by distension of the capsule of the elbow joint, or by various changes in muscular pull. (orig.) [de

  10. Thoughts on the so-called radius-capitellum axis

    Energy Technology Data Exchange (ETDEWEB)

    Schild, H; Mueller, H A; Wagner, H; Baetz, W


    We have studied 438 patients radiologically in order to observe the so-called 'radius-capitellum axis'. In about a quarter of people with normal elbows the axis passes lateral to the middle portion of the capitellum, so that even when there is marked deviation, there is no certainty that the humero-radial joint is abnormal. Deviation of the axis can be caused by changes in the shape of the capitellum or of the radius, or by distension of the capsule of the elbow joint, or by various changes in muscular pull.

  11. [Localization and registration of the hinge axis in black Africans]. (United States)

    Assi, K D; N'Guessan, K S; N'Dindin, C; Bamba, A


    The study of the cinematic method using "SAM" and "Quick Axis of FAG" added to mandibular condyle palpation for the hinge axis limited points, show that the Black Africans mandibular condyle rotation axis position is higher (3.5 mm) and backer (2 mm) than the Caucasians. The axial points are located to between 11 and 12 mm in front of the tragus and between 7 and 8 mm below on the perpendicular line to the furrow defining the tragus superior side to the Ectocanthus.

  12. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis (United States)

    Jenkins, Trisha A.; Nguyen, Jason C. D.; Polglaze, Kate E.; Bertrand, Paul P.


    The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis. PMID:26805875

  13. Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine. (United States)

    Jones, B A; Gores, G J


    Cell death of gastrointestinal epithelial cells occurs by a process referred to as apoptosis. In this review, we succinctly define apoptosis and summarize the role of apoptosis in the physiology and pathophysiology of epithelial cells in the liver, pancreas, and small and large intestine. The physiological mediators regulating apoptosis in gastrointestinal epithelial cells, when known, are discussed. Selected pathophysiological consequences of excessive apoptosis and inhibition of apoptosis are used to illustrate the significance of apoptosis in disease processes. These examples demonstrate that excessive apoptosis may result in epithelial cell atrophy, injury, and dysfunction, whereas inhibition of apoptosis results in hyperplasia and promotes malignant transformation. The specific cellular mechanisms responsible for dysregulation of epithelial cell apoptosis during pathophysiological disturbances are emphasized. Potential future areas of physiological research regarding apoptosis in gastrointestinal epithelia are highlighted when appropriate.

  14. A Method for Modeling of Floating Vertical Axis Wind Turbine

    DEFF Research Database (Denmark)

    Wang, Kai; Hansen, Martin Otto Laver; Moan, Torgeir


    It is of interest to investigate the potential advantages of floating vertical axis wind turbine (FVAWT) due to its economical installation and maintenance. A novel 5MW vertical axis wind turbine concept with a Darrieus rotor mounted on a semi-submersible support structure is proposed in this paper....... In order to assess the technical and economic feasibility of this novel concept, a comprehensive simulation tool for modeling of the floating vertical axis wind turbine is needed. This work presents the development of a coupled method for modeling of the dynamics of a floating vertical axis wind turbine....... This integrated dynamic model takes into account the wind inflow, aerodynamics, hydrodynamics, structural dynamics (wind turbine, floating platform and the mooring lines) and a generator control. This approach calculates dynamic equilibrium at each time step and takes account of the interaction between the rotor...

  15. design and implementation of a microcontroller based dual axis

    African Journals Online (AJOL)


    In this paper, an efficient microcontroller-based dual axis solar radiation tracker which can be used to align a single photovoltaic (PV) ... replaced them with wind turbine generating stations. ... tracker which has both horizontal and vertical axle.

  16. The effects of lateral head tilt on ocular astigmatic axis

    Directory of Open Access Journals (Sweden)

    Hamid Fesharaki


    Conclusion: Any minimal angle of head tilt may cause erroneous measurement of astigmatic axis and should be avoided during refraction. One cannot rely on the compensatory function of ocular counter-torsion during the refraction.

  17. Particle orbit analysis for LHD helical axis configurations

    International Nuclear Information System (INIS)

    Guasp, J.; Yamazaki, K.; Motojima, O.


    Fast ion orbits for helical magnetic axis configurations in LHD (Large Helical Device) are analyzed and compared with the standard circular axis case. Boundaries between passing and helically trapped particle regions show clear differences: in the non-planar axis case the helically trapped region spreads, near the magnetic axis, over a much wider band across the 90deg pitch angle value and shows a very marked asymmetry. The locally trapped particle region is also wider than in the standard case. The differences in the loss cone boundaries of the two cases are rather small, however, the effects of re-entering criteria are very important in both cases. On the contrary, effects of finite coil size are not significant. (author)

  18. Space/Flight Operable Miniature Six Axis Transducer, Phase II (United States)

    National Aeronautics and Space Administration — FUTEK will fully design and manufacture a sensor capable of measuring forces in and about each axis. The unit will measure forces up to 300 Newton's in the principle...

  19. Off-axis vortex breakdown in a shallow whirlpool. (United States)

    Herrada, Miguel A; Shtern, Vladimir N; López-Herrera, José María


    The off-axis emergence of vortex breakdown (VB) is revealed. The steady axisymmetric flow in a vertical sealed cylinder, which is partially filled with water and the rest is filled with air, is driven by the rotating bottom disk. The numerical simulations show that VB can emerge away from the rotation axis, interface, and walls. As the rotation intensifies, VB first develops in the water region. If the water height is less (larger) than nearly one half of the cylinder radius, VB emerges off (on) the axis. As the rotation further increases, the off-axis VB ring touches the interface and then a thin countercirculation layer develops in the air flow above the water VB domain. This two-fluid VB ring shrinks (it even disappears in a very shallow whirlpool) as the interface approaches the bottom disk.

  20. Helical-axis stellarators with noninterlocking planar coils

    International Nuclear Information System (INIS)

    Reiman, A.; Boozer, A.


    The properties of helical axis stellarator fields generated by unlinked, planar coils are described. It is shown that such fields can have a magnetic well and large rotational transform, implying large equilibrium and stability beta limits

  1. Helical-axis stellarators with noninterlocking planar coils

    Energy Technology Data Exchange (ETDEWEB)

    Reiman, A.; Boozer, A.


    The properties of helical axis stellarator fields generated by unlinked, planar coils are described. It is shown that such fields can have a magnetic well and large rotational transform, implying large equilibrium and stability beta limits.

  2. Design of a Three-Axis Machine Tool Module

    National Research Council Canada - National Science Library

    Childers, Marshal


    This report documents the design improvement process of the components in a tool module for a three-axis machine tool, which occurred during the period of March-April 2002 in support of a critical U.S...

  3. Proper time axis of a closed relativistic system

    International Nuclear Information System (INIS)

    Chernikov, N.A.; Fadeev, N.G.; Shavokhina, N.S.


    The definition of a proper time axis of a closed relativistic system of colliding particles is given. The solution of the proper time axis problem is presented. If the light velocity c equals the imaginary unit i, then in the case of a plane motion of the system the problem about the proper time axis turns out to be equivalent to the known in engineering mechanics problem about the reduction of any system of forces, applied to a rigid body, to the dynamic screw. In the general case, when c=i, the problem about the proper time axis turns out to be equivalent to the problem about the reduction to the dynamic screw of a system of forces, applied to a rigid body in a four-dimensional Euclidean space

  4. UARS PEM Level 2 AXIS 1 V001 (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 1 daily product contains the X-ray high-resolution spectral...

  5. UARS PEM Level 2 AXIS 2 V001 (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 2 daily product contains the X-ray high-resolution spectral...

  6. Dual Axis Controller for Extreme Environments, Phase II (United States)

    National Aeronautics and Space Administration — The Dual Axis Controller for Extreme Environments (DACEE) addresses a critical need of NASA's future exploration plans to investigate extreme environments within our...

  7. Three-Axis Gasless Sounding Rocket Payload Attitude Control (United States)

    National Aeronautics and Space Administration — Gas released by current sounding rocket payload attitude control systems (ACS) has the potential to interfere with some types of science instruments. A single-axis...

  8. Microbiota-gut-brain axis and the central nervous system


    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei


    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated ...

  9. Self-starting aerodynamics analysis of vertical axis wind turbine

    Directory of Open Access Journals (Sweden)

    Jianyang Zhu


    Full Text Available Vertical axis wind turbine is a special type of wind-force electric generator which is capable of working in the complicated wind environment. The self-starting aerodynamics is one of the most important considerations for this kind of turbine. This article aims at providing a systematic synthesis on the self-starting aerodynamic characteristics of vertical axis wind turbine based on the numerical analysis approach. First, the physical model of vertical axis wind turbine and its parameter definitions are presented. Secondary, the interaction model between the vertical axis wind turbine and fluid is developed by using the weak coupling approach; the numerical data of this model are then compared with the wind tunnel experimental data to show its feasibility. Third, the effects of solidity and fixed pitch angle on the self-starting aerodynamic characteristics of the vertical axis wind turbine are analyzed systematically. Finally, the quantification effects of the solidity and fixed pitch angle on the self-starting performance of the turbine can be obtained. The analysis in this study will provide straightforward physical insight into the self-starting aerodynamic characteristics of vertical axis wind turbine.

  10. Energy Efficient Hybrid Dual Axis Solar Tracking System

    Directory of Open Access Journals (Sweden)

    Rashid Ahammed Ferdaus


    Full Text Available This paper describes the design and implementation of an energy efficient solar tracking system from a normal mechanical single axis to a hybrid dual axis. For optimizing the solar tracking mechanism electromechanical systems were evolved through implementation of different evolutional algorithms and methodologies. To present the tracker, a hybrid dual-axis solar tracking system is designed, built, and tested based on both the solar map and light sensor based continuous tracking mechanism. These light sensors also compare the darkness and cloudy and sunny conditions assisting daily tracking. The designed tracker can track sun’s apparent position at different months and seasons; thereby the electrical controlling device requires a real time clock device for guiding the tracking system in seeking solar position for the seasonal motion. So the combination of both of these tracking mechanisms made the designed tracker a hybrid one. The power gain and system power consumption are compared with a static and continuous dual axis solar tracking system. It is found that power gain of hybrid dual axis solar tracking system is almost equal to continuous dual axis solar tracking system, whereas the power saved in system operation by the hybrid tracker is 44.44% compared to the continuous tracking system.

  11. Design and optimize of 3-axis filament winding machine (United States)

    Quanjin, Ma; Rejab, M. R. M.; Idris, M. S.; Bachtiar, B.; Siregar, J. P.; Harith, M. N.


    Filament winding technique is developed as the primary process for composite cylindrical structures fabrication at low cost. Fibres are wound on a rotating mandrel by a filament winding machine where resin impregnated fibres pass through a pay-out eye. This paper aims to develop and optimize a 3-axis, lightweight, practical, efficient, portable filament winding machine to satisfy the customer demand, which can fabricate pipes and round shape cylinders with resins. There are 3 main units on the 3-axis filament winding machine, which are the rotary unit, the delivery unit and control system unit. Comparison with previous existing filament winding machines in the factory, it has 3 degrees of freedom and can fabricate more complex shape specimens based on the mandrel shape and particular control system. The machine has been designed and fabricated on 3 axes movements with control system. The x-axis is for movement of the carriage, the y-axis is the rotation of mandrel and the z-axis is the movement of the pay-out eye. Cylindrical specimens with different dimensions and winding angles were produced. 3-axis automated filament winding machine has been successfully designed with simple control system.

  12. Major and minor axis kinematics of 22 ellipticals

    International Nuclear Information System (INIS)

    Franx, M.; Illingworth, G.; Heckman, T.


    Rotation curves and velocity dispersion profiles have been determined for the major and the minor axes of 22 elliptical galaxies. Rotation was detected in all but one galaxy, even though the sample was biased toward round ellipticals. Minor axis rotation larger than major axis rotation was measured in two galaxies, NGC 4406 and NGC 7507. Roughly 10 percent of ellipticals may show large minor axis velocities relative to those on the major axis. A simple model is used to derive a rotational axis from the observed minor and major axis velocities to a typical accuracy of 6 deg. The rotational and photometric minor axes aligned to better than 10 deg for 60 percent of the sample, implying that the direction of the angular momentum is related to the orientation of the figure of the galaxy. IC 1459 has a kinematically distinct core with its angular momentum opposite to the angular momentum of the outer parts, and NGC 4406 has a core with its angular momentum perpendicular to that of the outer parts. 46 refs

  13. Optic axis-driven new horizons for hyperbolic metamaterials

    Directory of Open Access Journals (Sweden)

    Boardman Allan D.


    Full Text Available The broad assertion here is that the current hyperbolic metamaterial world is only partially served by investigations that incorporate only some limited version of anisotropy. Even modest deviations of the optic axis from the main propagation axis lead to new phase shifts, which not only compete with those created by absorption but end up dominating them. Some progress has been attempted in the literature by introducing the terms “asymmetric hyperbolic media”, but it appears that this kind of asymmetry only involves an optic axis at an angle to the interface of a uniaxial crystal. From a device point of view, many new prospects should appear and the outcomes of the investigations presented here yield a new general theory. It is emphasised that the orientation of the optic axis is a significant determinant in the resulting optical properties. Whereas for conventional anisotropic waveguides homogeneous propagating waves occur over a limited range of angular dispositions of the optic axis it is shown that for a hyperbolic guide a critical angular setting exists, above which the guided waves are always homogeneous. This has significant implications for metawaveguide designs. The resulting structures are more tolerant to optic axis misalignment.

  14. The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas. (United States)

    Hegyi, Péter; Rakonczay, Zoltán


    Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.

  15. Design Of Single-Axis And Dual-Axis Solar Tracking Systems Protected Against High Wind Speeds

    Directory of Open Access Journals (Sweden)

    Mai Salaheldin Elsherbiny


    Full Text Available Solar energy is rapidly gaining ground as an important mean of expanding renewable energy use. Solar tracking is employed in order to maximize collected solar radiation by a photovoltaic panel. In this paper we present a prototype for Automatic solar tracker that is designed using Arduino UNO with Wind sensor to Cease Wind effect on panels if wind speed exceeds certain threshold. The Proposed solar tracker tracks the location of the sun anywhere in any time by calculating the position of the sun. For producing the maximum amount of solar energy a solar panel must always be perpendicular to the source of light. Because the sun motion plane varies daily and during the day it moves from east to west one needs two axis tracking to follow the suns position. Maximum possible power is collected when two axis tracking is done. However two axis tracking is relatively costly and complex. A compromise between maximum power collection and system simplicity is obtained by single axis tracking where the plane North south axis is fixed while the east west motion is accomplished. This work deals with the design of both single and two axis tracking systems. Automatic trackers is also compared to Fixed one in terms of Energy generated Efficiency Cost and System reliability.

  16. Postnatal development of the atlas and axis: CT study

    International Nuclear Information System (INIS)

    Byun, Sung Su; Kim, Hyung Jin; Lim, Myung Kwan; Kim, Won Hong; Jeon, Yong Sun; Kim, Jeong Ho; Kim, Sung Tae


    To evaluate normal postnatal development of the atlas and axis by means of CT scanning. We prospectively analyzed CT scans of the developing atlas and axis of 200 normal children aged less than 14, investigating the CT appearance of these regions with particular attenuation to two synchondroses related to the atlas and four synchondroses and one ossification center related to the axis. Fusion varying was categorized as either low (grade1-5) or high (grade4-5), according to the varying degrees of fusion at each synchondrosis of ossification center. Neurocentral synchondrosis of the atlas was low grade in all children less than five, and high grade in all aged nine or more, while posterior synchondrosis of the atlas was low grade in 97% of children less than three and high grade in 99% aged three or more. As for the axis, neurocentral synchondrosis was low grade in all children less than three, and high grade in 97% of children aged five or more. PS of the axis was low grade in both children less than 6 months, and high grade in all aged two years or more. Dentocentral synchondrosis of the axis was low grade in 93% of children less than three and high grade in 96% of those aged at least five. Intradental axial synchondrosis was high grade in all children. Fusion of the terminal ossicle with the remainder of the dens was low in all children less than five and high in 97% of those aged nine of more. CT can help determine the parameters of normal postnatal development of the atlas and axis. A knowledge of normal ossification patterns of these regions may help provide an understanding of developmental anomalies and also help prevent confusion with fractures

  17. Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future. (United States)

    Holl, Dana C; Volovici, Victor; Dirven, Clemens M F; Peul, Wilco C; van Kooten, Fop; Jellema, Korné; van der Gaag, Niels A; Miah, Ishita P; Kho, Kuan H; den Hertog, Heleen M; Lingsma, Hester F; Dammers, Ruben


    Chronic subdural hematoma (CSDH) is one of the more frequent pathologic entities in daily neurosurgical practice. Historically, CSDH was considered progressive recurrent bleeding with a traumatic cause. However, recent evidence has suggested a complex intertwined pathway of inflammation, angiogenesis, local coagulopathy, recurrent microbleeds, and exudates. The aim of the present review is to collect existing data on pathophysiology of CSDH to direct further research questions aiming to optimize treatment for the individual patient. We performed a thorough literature search in PubMed, Ovid, EMBASE, CINAHL, and Google scholar, focusing on any aspect of the pathophysiology and nonsurgical treatment of CSDH. After a (minor) traumatic event, the dural border cell layer tears, which leads to the extravasation of cerebrospinal fluid and blood in the subdural space. A cascade of inflammation, impaired coagulation, fibrinolysis, and angiogenesis is set in motion. The most commonly used treatment is surgical drainage. However, because of the pathophysiologic mechanisms, the mortality and high morbidity associated with surgical drainage, drug therapy (dexamethasone, atorvastatin, tranexamic acid, or angiotensin-converting enzyme inhibitors) might be a beneficial alternative in many patients with CSDH. Based on pathophysiologic mechanisms, animal experiments, and small patient studies, medical treatment may play a role in the treatment of CSDH. There is a lack of level I evidence in the nonsurgical treatment of CSDH. Therefore, randomized controlled trials, currently lacking, are needed to assess which treatment is most effective in each individual patient. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Depressive Disorder, Anxiety Disorder and Chronic Pain: Multiple Manifestations of a Common Clinical and Pathophysiological Core. (United States)

    Arango-Dávila, Cesar A; Rincón-Hoyos, Hernán G

    A high proportion of depressive disorders are accompanied by anxious manifestations, just as depression and anxiety often present with many painful manifestations, or conversely, painful manifestations cause or worsen depressive and anxious expressions. There is increasingly more evidence of the pathophysiological, and neurophysiological and technical imaging similarity of pain and depression. Narrative review of the pathophysiological and clinical aspects of depression and chronic pain comorbidity. Research articles are included that emphasise the most relevant elements related to understanding the pathophysiology of both manifestations. The pathological origin, physiology and clinical approach to these disorders have been more clearly established with the latest advances in biochemical and cellular techniques, as well as the advent of imaging technologies. This information is systematised with comprehensive images and clinical pictures. The recognition that the polymorphism of inflammation-related genes generates susceptibility to depressive manifestations and may modify the response to antidepressant treatments establishes that the inflammatory response is not only an aetiopathogenic component of pain, but also of stress and depression. Likewise, the similarity in approach with images corroborates not only the structural, but the functional and pathophysiological analogy between depression and chronic pain. Knowledge of depression-anxiety-chronic pain comorbidity is essential in the search for effective therapeutic interventions. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  19. Pathophysiology of brain ischemia as it relates to the therapy of acute ischemic stroke

    DEFF Research Database (Denmark)

    Lassen, N A


    Current knowledge of the pathophysiology of cerebral ischemia, summarized in the present study, predicts that neurological deficits caused by moderate ischemia (flows in the penumbral range between 23 and 10 ml/100 g/min) are reversible provided flow is restored within 3-4 h of onset. It also...

  20. A Comprehensive Pathophysiology of Dandruff and Seborrheic Dermatitis - Towards a More Precise Definition of Scalp Health

    DEFF Research Database (Denmark)

    Schwartz, James R; Messenger, Andrew G; Tosti, Antonella


    Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review publish...

  1. [Circadian blood pressure variation under several pathophysiological conditions including secondary hypertension]. (United States)

    Imai, Yutaka; Hosaka, Miki; Satoh, Michihiro


    Abnormality of circadian blood pressure (BP) variation, i.e. non-dipper, riser, nocturnal hypertension etc, is brought by several pathophysiological conditions especially by secondary hypertension. These pathophysiological conditions are classified into several categories, i.e. disturbance of autonomic nervous system, metabolic disorder, endocrine disorder, disorder of Na and water excretion (e.g. sodium sensitivity), severe target organ damage and ischemia, cardiovascular complications and drug induced hypertension. Each pathophysiological condition which brings disturbance of circadian BP variation is included in several categories, e.g. diabetes mellitus is included in metabolic disorder, autonomic imbalance, sodium sensitivity and endocrine disorder. However, it seems that unified principle of the genesis of disturbance of circadian BP variation in many pathophysiological conditions is autonomic imbalance. Thus, it is concluded that disturbance of circadian BP variation is not purposive biological behavior but the result of autonomic imbalance which looks as if compensatory reaction such as exaggerated Na-water excretion during night in patient with Na-water retention who reveals disturbed circadian BP variation.

  2. Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review. (United States)

    Kolkka-Palomaa, M; Jääskeläinen, S K; Laine, M A; Teerijoki-Oksa, T; Sandell, M; Forssell, H


    Primary burning mouth syndrome (BMS) is a chronic oral condition characterized by burning pain often accompanied with taste dysfunction and xerostomia. The most compelling evidence concerning BMS pathophysiology comes from studies on the somatosensory system using neurophysiologic or psychophysical methods such as blink reflex, thermal quantitative sensory testing, as well as functional brain imaging. They have provided convincing evidence for neuropathic involvement at several levels of the somatosensory system in BMS pain pathophysiology. The number of taste function studies trying to substantiate the subjective taste disturbances or studies on salivary factors in BMS is much more limited, and most of them suffer from definitional and methodological problems. This review aims to critically evaluate the existing literature on the pathophysiology of BMS, paying special attention to the correctness of case selection and the methodology used in published studies, and to summarize the current state of knowledge. Based on the recognition of several gaps in the current understanding of the pathophysiology of BMS especially as regards taste and pain system interactions, the review ends with future scenarios for research in this area. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Alzheimer's disease: pathophysiology and applications of magnetic nanoparticles as MRI theranostic agents.

    NARCIS (Netherlands)

    Amiri, H.; Saeidi, K.; Borhani, P.; Manafirad, A.; Ghavami, M.; Zerbi, V.


    Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade

  4. Recent progress in migraine pathophysiology: role of cortical spreading depression and magnetic resonance imaging

    NARCIS (Netherlands)

    Bhaskar, S.; Saeidi, K.; Borhani, P.; Amiri, H.


    Migraine is characterised by debilitating pain, which affects the quality of life in affected patients in both the western and the eastern worlds. The purpose of this article is to give a detailed outline of the pathophysiology of migraine pain, which is one of the most confounding pathologies among

  5. Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure. (United States)

    Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner


    An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

  6. Anthracycline-induced cardiotoxicity, a pathophysiology based approach for early detection and protective strategies

    NARCIS (Netherlands)

    Broeyer, Frederik Jan Ferdinand


    In this thesis the development of a pathophysiology-based method for the early evaluation of anthracycline-induced cardiotoxicity was described. We evaluated a comprehensive array of biomarkers, representing several aspects of anthracycline-induced cardiotoxicity, including cardiac injury and

  7. Type 2 diabetes across generations: from pathophysiology to prevention and management

    DEFF Research Database (Denmark)

    Nolan, Christopher J; Damm, Peter; Prentki, Marc


    Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility ...

  8. From cell to bedside: some pathophysiologic considerations about the cardiac stimulation

    International Nuclear Information System (INIS)

    Gutierrez, O.


    Myocardial cell pathophysiology is presented as related to possible modification by electrical stimulation of the myocardium. The objective is a diagnostic and therapeutic clinical application such as is seen with bradyarrhythmias and tachyarrhythmias. In addition, the E C is an essential tool during catheter ablation procedures

  9. Pathophysiological Concepts in Mild Traumatic Brain Injury : Diffusion Tensor Imaging Related to Acute Perfusion CT Imaging

    NARCIS (Netherlands)

    Metting, Zwany; Cerliani, Leonardo; Rodiger, Lars A.; van der Naalt, Joukje


    Background: A subgroup of patients with mild traumatic brain injury (TBI) experiences residual symptoms interfering with their return to work. The pathophysiological substrate of the suboptimal outcome in these patients is a source of debate. Objective: To provide greater insight into the

  10. Experience with an Independent Study Program in Pathophysiology for Doctor of Pharmacy Students. (United States)

    Nahata, Milap C.


    A pharmacy doctoral program's independent-study component in pathophysiology, supported by computer-assisted instruction and self-evaluation, has the advantages of self-pacing, reduced faculty time commitment, and increased ability to work effectively with physicians. Disadvantages include student feeling of isolation, imbalanced content, and…

  11. The Physiology of Female Sexual Function and the Pathophysiology of Female Sexual Dysfunction (Committee 13A)

    NARCIS (Netherlands)

    Levin, Roy J.; Both, Stephanie; Georgiadis, Janniko; Kukkonen, Tuuli; Park, Kwangsung; Yang, Claire C.

    Introduction: The article consists of six sections written by separate authors that review female genital anatomy, the physiology of female sexual function, and the pathophysiology of female sexual dysfunction but excluding hormonal aspects. Aim: To review the physiology of female sexual function

  12. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity

    DEFF Research Database (Denmark)

    Polk, Anne; Vistisen, Kirsten; Vaage-Nilsen, Merete


    BACKGROUND: Cardiotoxicity is a serious side effect to treatment with 5-fluorouracil (5-FU), but the underlying mechanisms are not fully understood. The objective of this systematic review was to evaluate the pathophysiology of 5-FU- induced cardiotoxicity. METHODS: We systematically searched Pub...


    Directory of Open Access Journals (Sweden)

    V.F. Kirichuk


    Full Text Available Modern patho-physiological mechanisms with the help of which tobacco smoking contributes to the development of cardiovascular pathology are represented in the review. The most significant of them are endothelial dysfunction, progressing of atherosclerotic processes, alteration of rheologic properties of blood, increase of carboxyhemoglobin levels, activation of sympathetic nervous system of the heart.

  14. Mechanical impedance of the sitting human body in single-axis compared to multi-axis whole-body vibration exposure. (United States)

    Holmlund, P; Lundström, R


    The study was aimed to investigate the mechanical impedance of the sitting human body and to compare data obtained in laboratory single-axis investigations with multi-axis data from in vehicle measurements. The experiments were performed in a laboratory for single-axis measurements. The multi-axis exposure was generated with an eight-seat minibus where the rear seats had been replaced with a rigid one. The subjects in the multi-axis experiment all participated in the single-axis experiments. There are quite a few investigations in the literature describing the human response to single-axis exposure. The response from the human body can be expected to be affected by multi-axis input in a different way than from a single-axis exposure. The present knowledge of the effect of multiple axis exposure is very limited. The measurements were performed using a specially designed force and accelerometer plate. This plate was placed between the subject and the hard seat. Outcome shows a clear difference between mechanical impedance for multi-axis exposure compared to single-axis. This is especially clear in the x-direction where the difference is very large. The conclusion is that it seems unlikely that single-axis mechanical impedance data can be directly transferred to a multi-axis environment. This is due to the force cross-talk between different directions.

  15. Craniospinal axis irradiation: an improved electron technique for irradiation of the spinal axis

    International Nuclear Information System (INIS)

    Chun Li; Vijayakumar, S.; Myrianthopoulos, L.C.; Kuchnir, F.T.; Muller-Runkel, R.


    The authors review dosimetric features of craniospinal axis irradiation in the areas of matching cranial and spinal fields, with reference to normal structures within the spinal field. The implications of the use of photon or electron modalities for the spinal port were evaluated. A novel method of matching the cranial photon and the spinal electron fields involving a computer-aided junction design is presented, involving moving the photon beam in three steps to degrade its penumbra to match that of the electron field. Thermoluminescent dosimetry in a Rando phantom and computed tomography-based dose-volume histogram study for an illustrative paediatric case were used to compare dose to normal structures within the spinal field. Results show that the use of electrons for the spinal field leads to better sparing of deep seated normal structures. For bone marrow, the use of a customized bolus for the spinal field results in an improved dose distribution, making electrons potentially superior to photons for radiobiological reasons. (author)

  16. Measurement Axis Searching Model for Terrestrial Laser Scans Registration

    Directory of Open Access Journals (Sweden)

    Shaoxing Hu


    Full Text Available Nowadays, terrestrial Lidar scans can cover rather a large area; the point densities are strongly varied because of the line-of-sight measurement principle in potential overlaps with scans taken from different viewpoints. Most of the traditional methods focus on registration algorithm and ignore searching model. Sometimes the traditional methods are directly used to align two point clouds; a large critically unsolved problem of the large biases will be created in areas distant from the overlaps while the local overlaps are often aligned well. So a novel measurement axis searching model (MASM has been proposed in this paper. The method includes four steps: (1 the principal axis fitting, (2 the measurement axis generation, (3 low-high-precision search, and (4 result generation. The principal axis gives an orientation to the point cloud; the search scope is limited by the measurement axis. The point cloud orientation can be adjusted gradually until the achievement of the global optimum using low- and high-precision search. We perform some experiments with simulated point clouds and real terrestrial laser scans. The results of simulated point clouds have shown the processing steps of our method, and the results of real terrestrial laser scans have shown the sensitivity of the approach with respect to the indoor and outdoor scenes.

  17. Ankle-foot orthosis bending axis influences running mechanics. (United States)

    Russell Esposito, Elizabeth; Ranz, Ellyn C; Schmidtbauer, Kelly A; Neptune, Richard R; Wilken, Jason M


    Passive-dynamic ankle-foot orthoses (AFOs) are commonly prescribed to improve locomotion for people with lower limb musculoskeletal weakness. The clinical prescription and design process are typically qualitative and based on observational assessment and experience. Prior work examining the effect of AFO design characteristics generally excludes higher impact activities such as running, providing clinicians and researchers limited information to guide the development of objective prescription guidelines. The proximal location of the bending axis may directly influence energy storage and return and resulting running mechanics. The purpose of this study was to determine if the location of an AFO's bending axis influences running mechanics. Marker and force data were recorded as 12 participants with lower extremity weakness ran overground while wearing a passive-dynamic AFO with posterior struts manufactured with central (middle) and off-centered (high and low) bending axes. Lower extremity joint angles, moments, powers, and ground reaction forces were calculated and compared between limbs and across bending axis conditions. Bending axis produced relatively small but significant changes. Ankle range of motion increased as the bending axis shifted distally (pbenefits during running, although individual preference and physical ability should also be considered. Published by Elsevier B.V.

  18. Role of Met Axis in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yiru, E-mail:; Fisher, Gary J., E-mail: [Department of Dermatology, University of Michigan, Ann Arbor, MI 48109 (United States)


    Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.

  19. Subquadratic medial-axis approximation in $\\mathbb{R}^3$

    Directory of Open Access Journals (Sweden)

    Christian Scheffer


    Full Text Available We present an algorithm that approximates the medial axis of a smooth manifold in $\\mathbb{R}^3$ which is given by a sufficiently dense point sample. The resulting, non-discrete approximation is shown to converge to the medial axis as the sampling density approaches infinity. While all previous algorithms guaranteeing convergence have a running time quadratic in the size $n$ of the point sample, we achieve a running time of at most $\\mathcal{O}(n\\log^3 n$. While there is no subquadratic upper bound on the output complexity of previous algorithms for non-discrete medial axis approximation, the output of our algorithm is guaranteed to be of linear size.

  20. Small Vertical Axis Wind Turbines: aerodynamics and starting behavior

    Directory of Open Access Journals (Sweden)



    Full Text Available In urban areas the wind is very turbulent and unstable with fast changes in direction andvelocity. In these environments, the use of small vertical axis wind turbines (VAWT becomesincreasingly attractive due to several advantages over horizontal axis wind turbines (HAWT.However, such designs have received much less attention than the more common propeller-typedesigns and the understanding of same aspects of their operation remains, to this day, incomplete.This is particularly true of their starting characteristics. Indeed, same authors heuristically maintainthat they cannot start without external assistance. This paper reviews the cause of the inability of thelow solidity fixed pitch vertical axis wind turbines to self-start, and investigates the way ofovercoming this draw back.

  1. Off-axis and inline electron holography: Experimental comparison

    International Nuclear Information System (INIS)

    Latychevskaia, Tatiana; Formanek, Petr; Koch, C.T.; Lubk, Axel


    Electron holography is a very powerful technique for mapping static electric and magnetic potentials down to atomic resolution. While electron holography is commonly considered synonymous with its off-axis variant in the high energy electron microscopy community, inline electron holography is widely applied in low-energy electron microscopy, where the realization of the off-axis setup is still an experimental challenge. This paper demonstrates that both inline and off-axis holography may be used to recover amplitude and phase shift of the very same object, in our example latex spheres of 90 and 200 nm in diameter, producing very similar results, provided the object does not charge under the electron beam.

  2. Vertical axis wind turbines: a survey and bibliography

    Energy Technology Data Exchange (ETDEWEB)

    Abramovich, H


    The stimulus for the development of modern, big wind turbines has been the world-wide oil crisis during the seventies. Although the horizontal axis wind turbines (HAWT) was the most popular type of wind turbine the Darrieus vertical axis wind turbine (VAWT) has been recognized as a machine with competitive economic potential. The state of the art of the VAWT is reviewed. The wind turbine carrying the name of Darrieus was first proposed by the French inventor in 1925. His original patent covered a range of vertical-axis configurations but the term 'Darrieus' is now generally associated with the curved-blade geometry. In 1966 two researchers at the Canadian NRC again raised the idea of both the straight and curved-blade versions of the Darrieus VAWT.

  3. Calibration of three-axis magnetometers with differential evolution algorithm

    International Nuclear Information System (INIS)

    Pang, Hongfeng; Zhang, Qi; Wang, Wei; Wang, Junya; Li, Ji; Luo, Shitu; Wan, Chengbiao; Chen, Dixiang; Pan, Mengchun; Luo, Feilu


    The accuracy of three-axis magnetometers is influenced by different scale and bias of each axis and nonorthogonality between axes. One limitation of traditional iteration methods is that initial parameters influence the calibration, thus leading to the local optimal or wrong results. In this paper, a new method is proposed to calibrate three-axis magnetometers. To employ this method, a nonmagnetic rotation platform, a proton magnetometer, a DM-050 three-axis magnetometer and the differential evolution (DE) algorithm are used. The performance of this calibration method is analyzed with simulation and experiment. In simulation, the calibration results of DE, unscented Kalman filter (UKF), recursive least squares (RLS) and genetic algorithm (GA) are compared. RMS error using DE is least, which is reduced from 81.233 nT to 1.567 nT. Experimental results show that comparing with UKF, RLS and GA, the DE algorithm has not only the least calibration error but also the best robustness. After calibration, RMS error is reduced from 68.914 nT to 2.919 nT. In addition, the DE algorithm is not sensitive to initial parameters, which is an important advantage compared with traditional iteration algorithms. The proposed algorithm can avoid the troublesome procedure to select suitable initial parameters, thus it can improve the calibration performance of three-axis magnetometers. - Highlights: • The calibration results and robustness of UKF, GA, RLS and DE algorithm are analyzed. • Calibration error of DE is the least in simulation and experiment. • Comparing with traditional calibration algorithms, DE is not sensitive to initial parameters. • It can improve the calibration performance of three-axis magnetometers

  4. Research on Parameter Design of Multi - axis Hydrostatic Transmission Vehicle

    Directory of Open Access Journals (Sweden)

    Zhao Liang


    Full Text Available In order to obtain reasonable parameters in the design of driving system of multi-axis hydrostatic transmission vehicle, the working principle of single-side drive of hydrostatic transmission vehicle is introduced. The matching and control of engine and hydraulic pump are analyzed. According to the driving equation of vehicle, The driving force required for driving system is determined, and the parameters of hydraulic motor, hydraulic pump, system working pressure and braking system are designed and calculated, which provides the parameter design for driving system of multi-axis hydrostatic transmission Reliable theoretical basis.

  5. Microbiota-gut-brain axis and the central nervous system. (United States)

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei


    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

  6. Three axis vector atomic magnetometer utilizing polarimetric technique

    Energy Technology Data Exchange (ETDEWEB)

    Pradhan, Swarupananda, E-mail:, E-mail: [Laser and Plasma Technology Division, Bhabha Atomic Research Centre, Mumbai 400085, India and Homi Bhabha National Institute, Department of Atomic Energy, Mumbai 400094 (India)


    The three axis vector magnetic field measurement based on the interaction of a single elliptically polarized light beam with an atomic system is described. The magnetic field direction dependent atomic responses are extracted by the polarimetric detection in combination with laser frequency modulation and magnetic field modulation techniques. The magnetometer geometry offers additional critical requirements like compact size and large dynamic range for space application. Further, the three axis magnetic field is measured using only the reflected signal (one polarization component) from the polarimeter and thus can be easily expanded to make spatial array of detectors and/or high sensitivity field gradient measurement as required for biomedical application.

  7. Interpretation and quality of the tilted axis cranking approximation

    International Nuclear Information System (INIS)

    Frauendorf, S.; Meng, J.


    Comparing with the exact solutions of the model system of one and two particles coupled to an axial rotor, the quality of the semi classical tilted axis cranking approximation is investigated. Extensive comparisons of the energies and M1 and E2 transition probabilities are carried out for the lowest bands. Very good agreement is found, except near band crossings. Various recipes to take into account finite K within the frame of the usual principal axis cranking are included into the comparison. A set of rules is suggested that permits to construct the excited bands from the cranking configurations, avoiding spurious states. (orig.)

  8. Optical Three-Axis Tactile Sensor for Robotic Fingers


    Ohka, Masahiro; Takata, Jumpei; Kobayashi, Hiroaki; Suzuki, Hirofumi; Morisawa, Nobuyuki; Yussof, Hanafiah Bin


    A new three-axis tactile sensor to be mounted on multi-fingered hands is developed based on the principle of an optical waveguide-type tactile sensor comprised of an acrylic hemispherical dome, a light source, an array of rubber sensing elements, and a CCD camera. The sensing element of the present tactile sensor includes one columnar feeler and eight conical feelers. A three-axis force applied to the tip of the sensing element is detected by the contact areas of the conical feelers, which ma...

  9. Fatigue in Multiple Sclerosis: Is it related to cytokines and hypothalamic-pituitary-adrenal axis? (United States)

    Akcali, Aylin; Zengin, Fatma; Aksoy, Sefika Nur; Zengin, Orhan


    Fatigue is a common symptom of Multiple Sclerosis (MS) that diminishes the quality of life of patients, but its exact mechanism remains poorly understood. There is not a generally adopted scale to determine MS fatigue. Studies that investigated physiopathology of fatigue symptom have shown dysregulation of hypothalamic-pituitaryadrenal (HPA) axis. In the current study, we aimed to compare the results obtained with two separate scales, namely the Fatigue Severity Scale (FSS) and the Neurological Fatigue Index-Multiple Sclerosis (NFI-MS), and assess the relationship between fatigue and serum IL-1β, TNF-α, IL-35, IL-2, IL-10, ACTH, cortisol, α-MSH, β-MSH, γ-MSH and CLIP (Corticotropinlike intermediate lobe peptide) in MS patients categorized as fatigued and non-fatigued on the basis of FSS scores. For the study, a total of 54 (29 females, 25 males) patients diagnosed with RRMS including 26 with fatigue symptom (48.1%), and 26 healthy controls (13 females, 13 males) were enrolled. A FSS score ≥36 was considered as cut-off score to separate fatigued patients from nonfatigued patients. A significant positive correlation was determined between FSS score and NFI-MS scale, NFI-MS 1, NFI-MS 2, NFI-MS 3 and NFI-MS 4 scores. IL-1β, IL-10 and TNF-α levels did not differ between patient and control groups. IL-35 and IL-2 levels were significantly higher among MS patients (pfatigued and nonfatigued patients in the cytokines and HPA parameters studied. ACTH, cortisol and α-MSH were significantly higher in MS group (p=0.02, pfatigue; thus, it may also be widely used to evaluate that symptom. Generally HPA axis is hyperactive in MS patients, but it is not correlated with fatigue in our study. For the first time, levels of CLIP (a type of melanocortin) are studied, and determined to be lower among MS patients. Elevated levels of IL-35 and IL-2 suggest that these cytokines may have a prominent role in MS pathophysiology and can be investigated as potential targets for

  10. Experimental characterization of individual pitch controlled vertical axis wind turbine

    NARCIS (Netherlands)

    Leblanc, B.P.; Simao Ferreira, C.


    Research into the Vertical Axis Wind Turbine (VAWT) has been progressing over the last few years due to
    the large shift in design constraints for large floating offshore wind turbines by leveraging tools and experience
    from research beginning in the 1970s and lasting until the HAWT

  11. Comparison of aerodynamic models for Vertical Axis Wind Turbines

    DEFF Research Database (Denmark)

    Ferreira, C. Simão; Aagaard Madsen, Helge; Barone, M.


    Multi-megawatt Vertical Axis Wind Turbines (VAWTs) are experiencing an increased interest for floating offshore applications. However, VAWT development is hindered by the lack of fast, accurate and validated simulation models. This work compares six different numerical models for VAWTS: a multiple...

  12. Local charge measurement using off-axis electron holography

    DEFF Research Database (Denmark)

    Beleggia, Marco; Gontard, L.C.; Dunin-Borkowski, R.0E.


    A model-independent approach based on Gauss’ theorem for measuring the local charge in a specimen from an electron-optical phase image recorded using off-axis electron holography was recently proposed. Here, we show that such a charge measurement is reliable when it is applied to determine the to...

  13. Tilted axis rotation in odd-odd {sup 164}Tm

    Energy Technology Data Exchange (ETDEWEB)

    Reviol, W.; Riedinger, L.L.; Wang, X.Z.; Zhang, J.Y. [Univ. of Tennessee, Knoxville, TN (United States)] [and others


    Ten band structures are observed in {sup 164}Tm, among them sets of parallel and anti-parallel couplings of the proton and neutron spins. The Tilted Axis Cranking scheme is applied for the first time to an odd-odd nucleus in a prominent region of nuclear deformation.

  14. An improved computer controlled triple-axis neutron spectrometer

    International Nuclear Information System (INIS)

    Cooper, M.J.; Hall, J.W.; Hutchings, M.T.


    A description is given of the computer-controlled triple-axis neutron spectrometer installed at the PLUTO reactor at Harwell. The reasons for an nature of recent major improvements are discussed. Following a general description of the spectrometer, details are then given of the new computerised control system, including the functions of the various programs which are now available to the user. (author)

  15. The GH/IGF-1 axis in ageing and longevity (United States)

    List, Edward O.; Berryman, Darlene E.; Murrey, John W.


    Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the ‘somatopause’, has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans. PMID:23591370

  16. Lake Malawi cichlid evolution along a benthic/limnetic axis. (United States)

    Hulsey, C D; Roberts, R J; Loh, Y-H E; Rupp, M F; Streelman, J T


    Divergence along a benthic to limnetic habitat axis is ubiquitous in aquatic systems. However, this type of habitat divergence has largely been examined in low diversity, high latitude lake systems. In this study, we examined the importance of benthic and limnetic divergence within the incredibly species-rich radiation of Lake Malawi cichlid fishes. Using novel phylogenetic reconstructions, we provided a series of hypotheses regarding the evolutionary relationships among 24 benthic and limnetic species that suggests divergence along this axis has occurred multiple times within Lake Malawi cichlids. Because pectoral fin morphology is often associated with divergence along this habitat axis in other fish groups, we investigated divergence in pectoral fin muscles in these benthic and limnetic cichlid species. We showed that the eight pectoral fin muscles and fin area generally tended to evolve in a tightly correlated manner in the Lake Malawi cichlids. Additionally, we found that larger pectoral fin muscles are strongly associated with the independent evolution of the benthic feeding habit across this group of fish. Evolutionary specialization along a benthic/limnetic axis has occurred multiple times within this tropical lake radiation and has produced repeated convergent matching between exploitation of water column habitats and locomotory morphology.

  17. The somatotropic axis: Effects on brain and cognitive functions

    NARCIS (Netherlands)

    Quik, E.H.


    Both hormones of the somatotropic axis, insulin-like growth factor-1 (IGF-1) and growth hormone (GH) can cross the blood-brain barrier and bind to their receptors in neurons and glia throughout the brain. Features of aging resemble those of GHD and aging is also associated with a decline in the

  18. Locating an axis-parallel rectangle on a Manhattan plane

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Körner, Mark-Christoph


    In this paper we consider the problem of locating an axis-parallel rectangle in the plane such that the sum of distances between the rectangle and a finite point set is minimized, where the distance is measured by the Manhattan norm 1. In this way we solve an extension of the Weber problem...

  19. Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Hay-Schmidt, Anders; Kiss, Alexander


    Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these recept...

  20. Off-axis electron holography of ferromagnetic multilayer nanowires

    DEFF Research Database (Denmark)

    Akhtari-Zavareh, Azadeh; Carignan, L. P.; Yelon, A.


    with respect to the axis of the wires. In thinner Cu/CoFeB ((multilayer, magnetic field vortices were detected, associated with opposing magnetization in neighbouring layers. The measured crystallinity, compositions, and layer thicknesses of individual NWs were found to be significantly different...

  1. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases. (United States)

    Quigley, Eamonn M M


    The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

  2. On the Turbulent Mixing in Horizontal Axis Wind Turbine Wakes

    NARCIS (Netherlands)

    Lignarolo, L.E.M.


    The wake flow of a horizontal axis wind turbine is characterised by lower wind speed and higher turbulence than the free-stream conditions. When clustered in large wind farms, wind turbines regularly operate inside the wake of one or more upstream machines. This is a major cause of energy production

  3. Phytochemicals for taming agitated immune-endocrine-neural axis. (United States)

    Patel, Seema


    Homeostasis of immune-endocrine-neural axis is paramount for human health. If this axis gets agitated due to age, genetic variations, environmental exposures or lifestyle assaults, a cascade of adverse reactions occurs in human body. Cytokines, hormones and neurotransmitters, the effector molecules of this axis behave erratically, leading to a gamut of neural, endocrine, autoimmune, and metabolic diseases. Current panel of drugs can tackle some of them but not in a sustainable, benign way as a myriad of side effects, causal of them have been documented. In this context, phytochemicals, the secondary metabolites of plants seem beneficial. These bioactive constituents encompassing polyphenols, alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol), saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic, anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective, neuroprotective, dermatoprotective, and antimicrobial properties, among a litany of other biological effects. This review presents a holistic perspective of common afflictions resultant of immune-endocrine-neural axis disruption, and the phytochemicals capable of restoring their normalcy and mitigating the ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. A four-axis hand controller for helicopter flight control (United States)

    Demaio, Joe


    A proof-of-concept hand controller for controlling lateral and longitudinal cyclic pitch, collective pitch and tail rotor thrust was developed. The purpose of the work was to address problems of operator fatigue, poor proprioceptive feedback and cross-coupling of axes associated with many four-axis controller designs. The present design is an attempt to reduce cross-coupling to a level that can be controlled with breakout force, rather than to eliminate it entirely. The cascaded design placed lateral and longitudinal cyclic in their normal configuration. Tail rotor thrust was placed atop the cyclic controller. A left/right twisting motion with the wrist made the control input. The axis of rotation was canted outboard (clockwise) to minimize cross-coupling with the cyclic pitch axis. The collective control was a twist grip, like a motorcycle throttle. Measurement of the amount of cross-coupling involved in pure, single-axis inputs showed cross coupling under 10 percent of full deflection for all axes. This small amount of cross-coupling could be further reduced with better damping and force gradient control. Fatigue was not found to be a problem, and proprioceptive feedback was adequate for all flight tasks executed.

  5. Nuclear medicine to image applied pathophysiology: Evaluation of reserves by emission computerized tomography

    International Nuclear Information System (INIS)

    Buell, U.; Schicha, H.


    Nuclear procedures have long been successful in displaying parameters related to physiological and/or pathophysiological mechanisms inherent in organs or systems. Since a major advantage of PET is its ability to measure actual concentration, we now expect to gain such data in absolute terms. The use of stimuli, however, makes it possible to determine parameters in the form of ratios (stimulus-to-rest). Moreover, these ratios are correlated closely with the capacity of reserve mechanisms experienced from applied pathophysiology, in addition to which some are accessible by means of SPET. The clinical validity of findings related to coronary and cerebrovascular perfusion reserves have already been confirmed by SPET and/or PET. These results, if complemented by parameters of metabolic reserve, would constitute a most powerful tool in functional clinical diagnostics, allowing determination of differences between actual values and critical thresholds. This is one of the most promising approaches exclusively available from PET. (orig.)

  6. MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation. (United States)

    Lee, Juneyoung; Park, Eun Jeong; Kiyono, Hiroshi


    The intestine represents the largest and most elaborate immune system organ, in which dynamic and reciprocal interplay among numerous immune and epithelial cells, commensal microbiota, and external antigens contributes to establishing both homeostatic and pathologic conditions. The mechanisms that sustain gut homeostasis are pivotal in maintaining gut health in the harsh environment of the gut lumen. Intestinal epithelial cells are critical players in creating the mucosal platform for interplay between host immune cells and luminal stress inducers. Thus, knowledge of the epithelial interface between immune cells and the luminal environment is a prerequisite for a better understanding of gut homeostasis and pathophysiologies such as inflammation. In this review, we explore the importance of the epithelium in limiting or promoting gut inflammation (e.g., inflammatory bowel disease). We also introduce recent findings on how small RNAs such as microRNAs orchestrate pathophysiologic gene regulation. [BMB Reports 2016; 49(5): 263-269].

  7. Cardiovascular metabolic syndrome: mediators involved in the pathophysiology from obesity to coronary heart disease. (United States)

    Roos, Cornelis J; Quax, Paul H A; Jukema, J Wouter


    Patients with obesity and diabetes mellitus are at increased risk for cardiovascular events and have a higher cardiovascular morbidity and mortality. This worse prognosis is partly explained by the late recognition of coronary heart disease in these patients, due to the absence of symptoms. Early identification of coronary heart disease is vital, to initiate preventive medical therapy and improve prognosis. At present, with the use of cardiovascular risk models, the identification of coronary heart disease in these patients remains inadequate. To this end, biomarkers should improve the early identification of patients at increased cardiovascular risk. The first part of this review describes the pathophysiologic pathway from obesity to coronary heart disease. The second part evaluates several mediators from this pathophysiologic pathway for their applicability as biomarkers for the identification of coronary heart disease.

  8. Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects. (United States)

    Bianchin, Marino Muxfeldt; Londero, Renata Gomes; Lima, José Eduardo; Bigal, Marcelo Eduardo


    The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.

  9. Gerbode defect: A comprehensive review of its history, anatomy, embryology, pathophysiology, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    Erfanul Saker


    Full Text Available The purpose of this paper is to survey the literature on Gerbode defect and provide an overview of its history, anatomy, development, pathophysiology, diagnosis, and treatment options. The available literature on this topic, including case reports, was thoroughly reviewed. Gerbode defect is defined as abnormal shunting between the left ventricle and right atrium resulting from either a congenital defect or prior cardiac insults. The pathophysiology underlying the development of Gerbode defect is a disease process that injures the atrioventricular septum and leads to the abnormal shunting of blood. Although the most prevalent cause of Gerbode defect has historically been congenital, an increasing trend towards acquired cases has recently been reported owing to improved diagnostic capabilities and a greater number of invasive cardiac procedures. In conclusion, Gerbode defect is an increasingly recognized condition that warrants further study.

  10. The Physiology of Female Sexual Function and the Pathophysiology of Female Sexual Dysfunction (Committee 13A). (United States)

    Levin, Roy J; Both, Stephanie; Georgiadis, Janniko; Kukkonen, Tuuli; Park, Kwangsung; Yang, Claire C


    The article consists of six sections written by separate authors that review female genital anatomy, the physiology of female sexual function, and the pathophysiology of female sexual dysfunction but excluding hormonal aspects. To review the physiology of female sexual function and the pathophysiology of female sexual dysfunction especially since 2010 and to make specific recommendations according to the Oxford Centre for evidence based medicine (2009) "levels of evidence" wherever relevant. Recommendations were made for particular studies to be undertaken especially in controversial aspects in all six sections of the reviewed topics. Despite numerous laboratory assessments of female sexual function, genital assessments alone appear insufficient to characterise fully the complete sexual response. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  11. The Emerging Role of Chronic Low-Grade Inflammation in the Pathophysiology of Polycystic Ovary Syndrome. (United States)

    Shorakae, Soulmaz; Teede, Helena; de Courten, Barbora; Lambert, Gavin; Boyle, Jacqueline; Moran, Lisa J


    Polycystic ovary syndrome (PCOS) has become increasingly common over recent years and is associated with reproductive features as well as cardiometabolic risk factors, including visceral obesity, dyslipidemia and impaired glucose homeostasis, and potentially cardiovascular disease. Emerging evidence suggests that these long-term metabolic effects are linked to a low-grade chronic inflammatory state with the triad of hyperinsulinemia, hyperandrogenism, and low-grade inflammation acting together in a vicious cycle in the pathophysiology of PCOS. Dysregulation of the sympathetic nervous system may also act as an important component, potentially creating a tetrad in the pathophysiology of PCOS. The aim of this review is to examine the role of chronic inflammation and the sympathetic nervous system in the development of obesity and PCOS and review potential therapeutic options to alleviate low-grade inflammation in this setting. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Pathophysiology and clinical characteristics of pain in most common locations in cancer patients. (United States)

    Leppert, W; Zajaczkowska, R; Wordliczek, J; Dobrogowski, J; Woron, J; Krzakowski, M


    Pain is one of the most common symptoms in cancer patients, especially in advanced disease. However, pain also accompanies a significant percentage of patients during diagnostic and therapeutic procedures. In some patients pain may be the first symptom of the disease. The causes of pain in cancer patients are often multifactorial including direct and indirect cancer effects, anticancer therapy and co-morbidities. Moreover, pain in cancer patients often has mixed pathophysiology including both nociceptive and neuropathic components, especially in patients with bone metastases. In this article, basic knowledge regarding epidemiology, pathophysiology and clinical features of pain in cancer patients with a primary tumour localised in lung, gastrointestinal tract (stomach, colon and pancreas), breast in women and prostate in men are presented. Pain is a common symptom in cancer patients and its appropriate assessment and treatment may significantly improve in patients' and families' quality of life.

  13. New insights into the pathophysiology of dyslipidemia in type 2 diabetes. (United States)

    Taskinen, Marja-Riitta; Borén, Jan


    Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for patients with type 2 diabetes, despite recent significant advances in management strategies to lessen CVD risk factors. A major cause is the atherogenic dyslipidemia, which consists of elevated plasma concentrations of both fasting and postprandial triglyceride-rich lipoproteins (TRLs), small dense low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) cholesterol. The different components of diabetic dyslipidemia are not isolated abnormalities but closely linked to each other metabolically. The underlying disturbances are hepatic overproduction and delayed clearance of TRLs. Recent results have unequivocally shown that triglyceride-rich lipoproteins and their remnants are atherogenic. To develop novel strategies for the prevention and treatment of dyslipidaemia, it is essential to understand the pathophysiology of dyslipoproteinaemia in humans. Here, we review recent advances in our understanding of the pathophysiology of diabetic dyslipidemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Hypertension and obesity after pediatric kidney transplantation: management based on pathophysiology: A mini review

    Directory of Open Access Journals (Sweden)

    Eunice G John


    Full Text Available Hypertension after pediatric renal transplant is a common and important risk factor for graft loss and patient survival. The mechanism of post kidney transplant hypertension is complex and multifactorial. Control of blood pressure in renal transplant patients is important but often times blood pressures remain uncontrolled. The management of hypertension and obesity in pediatric kidney transplant patients is based on the pathophysiology. Compared to the general pediatric hypertensive population, special attention needs to be focused on the additional impact of immunosuppressive medications side effects and interactions, recurrent disease, and donor and recipient comorbidities such as obesity on blood pressure control with thoughtful consideration of the risk of graft failure. In general, there is a need for prospective studies in pediatric kidney transplant patients to understand the pathophysiology of hypertension and obesity and the appropriate approach to achieve a balance between the primary need to avoid rejection and the need to lower blood pressure and prevent obesity.

  15. Acid-Base Disorders in Patients with Chronic Obstructive Pulmonary Disease: A Pathophysiological Review

    Directory of Open Access Journals (Sweden)

    Cosimo Marcello Bruno


    Full Text Available The authors describe the pathophysiological mechanisms leading to development of acidosis in patients with chronic obstructive pulmonary disease and its deleterious effects on outcome and mortality rate. Renal compensatory adjustments consequent to acidosis are also described in detail with emphasis on differences between acute and chronic respiratory acidosis. Mixed acid-base disturbances due to comorbidity and side effects of some drugs in these patients are also examined, and practical considerations for a correct diagnosis are provided.

  16. Recent Developments in the Classification, Evaluation, Pathophysiology, and Management of Scleroderma Renal Crisis. (United States)

    Ghossein, Cybele; Varga, John; Fenves, Andrew Z


    Scleroderma renal crisis (SRC) is an uncommon complication of systemic sclerosis. Despite the advent of angiotensin-converting inhibitor therapy, SRC remains a life-threatening complication. Recent studies have contributed to a better understanding of SRC, but much remains unknown regarding its pathophysiology, risk factors, and optimal management. Genetic studies provide evidence that immune dysregulation might be a contributing factor, providing hope that further research in this direction might illuminate pathogenesis and provide novel predictors for this complication.

  17. Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics


    Pakbaz, Zahra; Wun, Ted


    Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the pot...

  18. A theoretical framework informing research about the role of stress in the pathophysiology of bipolar disorder. (United States)

    Brietzke, Elisa; Mansur, Rodrigo Barbachan; Soczynska, Joanna; Powell, Alissa M; McIntyre, Roger S


    The staggering illness burden associated with Bipolar Disorder (BD) invites the need for primary prevention strategies. Before preventative strategies can be considered in individuals during a pre-symptomatic period (i.e., at risk), unraveling the mechanistic steps wherein external stress is transduced and interacts with genetic vulnerability in the early stages of BD will be a critical conceptual necessity. Herein we comprehensively review extant studies reporting on stress and bipolar disorder. The overarching aim is to propose a conceptual framework to inform research about the role of stress in the pathophysiology of BD. Computerized databases i.e. PubMed, PsychInfo, Cochrane Library and Scielo were searched using the following terms: "bipolar disorder" cross-referenced with "stress", "general reaction to stress", "resilience", "resistance", "recovery" "stress-diathesis", "allostasis", and "hormesis". Data from literature indicate the existence of some theoretical models to understand the influence of stress in the pathophysiology of BD, including classical stress-diathesis model and new models such as allostasis and hormesis. In addition, molecular mechanisms involved in stress adaptation (resistance, resilience and recovery) can also be translated in research strategies to investigate the impact of stress in the pathophysiology of BD. Most studies are retrospective and/or cross sectional, do not consider the period of development, assess brain function with only one or few methodologies, and use animal models which are not always similar to human phenotypes. The interaction between stress and brain development is dynamic and complex. In this article we proposed a theoretical model for investigation about the role of stress in the pathophysiology of BD, based on the different kinds of stress adaptation response and their putative neurobiological underpinnings. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. MALDI imaging mass spectrometry: Discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures


    Klein, O.; Strohschein, K.; Nebrich, G.; Oetjen, J.; Trede, D.; Thiele, H.; Alexandrov, T.; Giavalisco, P.; Duda, G.N.; Roth, P. von; Geissler, S.; Klose, J.; Winkler, T.


    Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological region...

  20. Pathogenesis and treatment of psoriasis: exploiting pathophysiological pathways for precision medicine. (United States)

    Alwan, Wisam; Nestle, Frank O


    Psoriasis is a common, chronic inflammatory skin disease associated with multi-system manifestations including arthritis and obesity. Our knowledge of the aetiology of the condition, including the key genomic, immune and environmental factors, has led to the development of targeted, precision therapies that alleviate patient morbidity. This article reviews the key pathophysiological pathways and therapeutic targets and highlights future areas of interest in psoriasis research.

  1. Current Understanding of the Pathophysiology of Myocardial Fibrosis and Its Quantitative Assessment in Heart Failure

    Directory of Open Access Journals (Sweden)

    Tong Liu


    Full Text Available Myocardial fibrosis is an important part of cardiac remodeling that leads to heart failure and death. Myocardial fibrosis results from increased myofibroblast activity and excessive extracellular matrix deposition. Various cells and molecules are involved in this process, providing targets for potential drug therapies. Currently, the main detection methods of myocardial fibrosis rely on serum markers, cardiac magnetic resonance imaging, and endomyocardial biopsy. This review summarizes our current knowledge regarding the pathophysiology, quantitative assessment, and novel therapeutic strategies of myocardial fibrosis.

  2. Effects of ADMA upon gene expression: an insight into the pathophysiological significance of raised plasma ADMA.

    Directory of Open Access Journals (Sweden)

    Caroline L Smith


    Full Text Available Asymmetric dimethylarginine (ADMA is a naturally occurring inhibitor of nitric oxide synthesis that accumulates in a wide range of diseases associated with endothelial dysfunction and enhanced atherosclerosis. Clinical studies implicate plasma ADMA as a major novel cardiovascular risk factor, but the mechanisms by which low concentrations of ADMA produce adverse effects on the cardiovascular system are unclear.We treated human coronary artery endothelial cells with pathophysiological concentrations of ADMA and assessed the effects on gene expression using U133A GeneChips (Affymetrix. Changes in several genes, including bone morphogenetic protein 2 inducible kinase (BMP2K, SMA-related protein 5 (Smad5, bone morphogenetic protein receptor 1A, and protein arginine methyltransferase 3 (PRMT3; also known as HRMT1L3, were confirmed by Northern blotting, quantitative PCR, and in some instances Western blotting analysis to detect changes in protein expression. To determine whether these changes also occurred in vivo, tissue from gene deletion mice with raised ADMA levels was examined. More than 50 genes were significantly altered in endothelial cells after treatment with pathophysiological concentrations of ADMA (2 microM. We detected specific patterns of changes that identify pathways involved in processes relevant to cardiovascular risk and pulmonary hypertension. Changes in BMP2K and PRMT3 were confirmed at mRNA and protein levels, in vitro and in vivo.Pathophysiological concentrations of ADMA are sufficient to elicit significant changes in coronary artery endothelial cell gene expression. Changes in bone morphogenetic protein signalling, and in enzymes involved in arginine methylation, may be particularly relevant to understanding the pathophysiological significance of raised ADMA levels. This study identifies the mechanisms by which increased ADMA may contribute to common cardiovascular diseases and thereby indicates possible targets for therapies.

  3. Deep Brain Stimulation in Huntington’s Disease—Preliminary Evidence on Pathophysiology, Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Lars Wojtecki


    Full Text Available Huntington’s disease (HD is one of the most disabling degenerative movement disorders, as it not only affects the motor system but also leads to cognitive disabilities and psychiatric symptoms. Deep brain stimulation (DBS of the pallidum is a promising symptomatic treatment targeting the core motor symptom: chorea. This article gives an overview of preliminary evidence on pathophysiology, safety and efficacy of DBS in HD.

  4. Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System. (United States)

    Rachdaoui, Nadia; Sarkar, Dipak K


    Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.

  5. The manufacturing and metrology of off-axis mirrors (United States)

    Penzkofer, Karlheinz; Rascher, Rolf; Küpper, Lutz; Liebl, Johannes


    Especially in the area of the large mirror manufacturing only a few manufacturers are capable to produce optical surfaces of high quality. Therefore a deterministic process should be developed in the project IFasO. In the field of telescope optics off-axis optical systems are becoming increasingly important. These systems try to avoid an obstructing of the incoming light by moving the secondary mirror out of the primary mirror's optical axis. This advantage leads to an increasing market for this type of optical surface. Until now off-axis mirrors were difficult or almost impossible to produce. With the processes developed in IFasO, high quality mirrors become possible. For this reason, this paper describes the manufacturing of off-axis surfaces and its problems. The mirror production used in the project IFasO is based on the specific design of the CNC center developed by the company Optotech. This center UPG2000 is capable of grinding, polishing, sagitta measurement and interferometric measurement in one mounting of the specimen. Usually a large optics has to be transported during their manufacturing after every individual process step. There is always a risk of damage of the specimen. The exact orientation of the surface relatively to the tool position is also required. This takes a huge amount of time and makes up most of the production time. In this presentation the use of UPG2000 and the next steps within the process development are described. In the current status the manufacturing of large off-axis elements with a PV < λ/10 rms is reproducible.

  6. GRB 170817A: a short GRB seen off-axis (United States)

    He, Xin-Bo; Tam, Pak-Hin Thomas; Shen, Rong-Feng


    The angular distribution of gamma-ray burst (GRB) jets is not yet clear. The observed luminosity of GRB 170817A is the lowest among all known short GRBs, which is best explained by the fact that our line of sight is outside of the jet opening angle, θ obs > θ j , where θ obs is the angle between our line of sight and the jet axis. As inferred by gravitational wave observations, as well as radio and X-ray afterglow modeling of GRB 170817A, it is likely that θ obs ∼ 20° – 28°. In this work, we quantitatively consider two scenarios of angular energy distribution of GRB ejecta: a top-hat jet and a structured jet with a power law index s. For the top-hat jet model, we get a large θ j (e.g., θ j > 10°), a rather high local (i.e., z 7.5 × 104, keV (∼500, keV for a typical short GRB). For the structured jet model, we use θ obs to give limits on s and θj for typical on-axis luminosity of a short GRB (e.g., 1049 erg s‑1 ∼ 1051 erg s‑1), and a low on-axis luminosity case (e.g., 1049 erg s‑1) gives more reasonable values of s. The structured jet model is more feasible for GRB 170817A than the top-hat jet model due to the rather high local short GRB rate, and the extremely high on-axis E peak,0 almost rules out the top-hat jet model. GRB 170817A is likely a low on-axis luminosity GRB (1049 erg s‑1) with a structured jet.

  7. Analytical Aerodynamic Simulation Tools for Vertical Axis Wind Turbines

    International Nuclear Information System (INIS)

    Deglaire, Paul


    Wind power is a renewable energy source that is today the fastest growing solution to reduce CO 2 emissions in the electric energy mix. Upwind horizontal axis wind turbine with three blades has been the preferred technical choice for more than two decades. This horizontal axis concept is today widely leading the market. The current PhD thesis will cover an alternative type of wind turbine with straight blades and rotating along the vertical axis. A brief overview of the main differences between the horizontal and vertical axis concept has been made. However the main focus of this thesis is the aerodynamics of the wind turbine blades. Making aerodynamically efficient turbines starts with efficient blades. Making efficient blades requires a good understanding of the physical phenomena and effective simulations tools to model them. The specific aerodynamics for straight bladed vertical axis turbine flow are reviewed together with the standard aerodynamic simulations tools that have been used in the past by blade and rotor designer. A reasonably fast (regarding computer power) and accurate (regarding comparison with experimental results) simulation method was still lacking in the field prior to the current work. This thesis aims at designing such a method. Analytical methods can be used to model complex flow if the geometry is simple. Therefore, a conformal mapping method is derived to transform any set of section into a set of standard circles. Then analytical procedures are generalized to simulate moving multibody sections in the complex vertical flows and forces experienced by the blades. Finally the fast semi analytical aerodynamic algorithm boosted by fast multipole methods to handle high number of vortices is coupled with a simple structural model of the rotor to investigate potential aeroelastic instabilities. Together with these advanced simulation tools, a standard double multiple streamtube model has been developed and used to design several straight bladed

  8. DARHT Axis-I Diode Simulations II: Geometrical Scaling

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Carl A. Jr. [Los Alamos National Laboratory


    Flash radiography of large hydrodynamic experiments driven by high explosives is a venerable diagnostic technique in use at many laboratories. Many of the largest hydrodynamic experiments study mockups of nuclear weapons, and are often called hydrotests for short. The dual-axis radiography for hydrodynamic testing (DARHT) facility uses two electron linear-induction accelerators (LIA) to produce the radiographic source spots for perpendicular views of a hydrotest. The first of these LIAs produces a single pulse, with a fixed {approx}60-ns pulsewidth. The second axis LIA produces as many as four pulses within 1.6-{micro}s, with variable pulsewidths and separation. There are a wide variety of hydrotest geometries, each with a unique radiographic requirement, so there is a need to adjust the radiographic dose for the best images. This can be accomplished on the second axis by simply adjusting the pulsewidths, but is more problematic on the first axis. Changing the beam energy or introducing radiation attenuation also changes the spectrum, which is undesirable. Moreover, using radiation attenuation introduces significant blur, increasing the effective spot size. The dose can also be adjusted by changing the beam kinetic energy. This is a very sensitive method, because the dose scales as the {approx}2.8 power of the energy, but it would require retuning the accelerator. This leaves manipulating the beam current as the best means for adjusting the dose, and one way to do this is to change the size of the cathode. This method has been proposed, and is being tested. This article describes simulations undertaken to develop scaling laws for use as design tools in changing the Axis-1 beam current by changing the cathode size.

  9. Velocity measurement of model vertical axis wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.A.; McWilliam, M. [Waterloo Univ., ON (Canada). Dept. of Mechanical Engineering


    An increasingly popular solution to future energy demand is wind energy. Wind turbine designs can be grouped according to their axis of rotation, either horizontal or vertical. Horizontal axis wind turbines have higher power output in a good wind regime than vertical axis turbines and are used in most commercial class designs. Vertical axis Savonius-based wind turbine designs are still widely used in some applications because of their simplistic design and low wind speed performance. There are many design variables that must be considered in order to optimize the power output in a given wind regime in a typical wind turbine design. Using particle image velocimetry, a study of the air flow around five different model vertical axis wind turbines was conducted in a closed loop wind tunnel. A standard Savonius design with two semi-circular blades overlapping, and two variations of this design, a deep blade and a shallow blade design were among the turbine models included in this study. It also evaluated alternate designs that attempt to increase the performance of the standard design by allowing compound blade curvature. Measurements were collected at a constant phase angle and also at random rotor orientations. It was found that evaluation of the flow patterns and measured velocities revealed consistent and stable flow patterns at any given phase angle. Large scale flow structures are evident in all designs such as vortices shed from blade surfaces. An important performance parameter was considered to be the ability of the flow to remain attached to the forward blade and redirect and reorient the flow to the following blade. 6 refs., 18 figs.

  10. Practical study on the integrated course of general pathology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

    Qian ZHAO; Guo-hui FU; Ying HUANG; Wei LIU


    This paper aims at summarizing the experience of offering the integrated course of general pathology and pathophysiology for eight-year clinical medicine program, providing references for further improving the teaching quality,and laying a foundation for expanding the course to five-year clinical medicine program. Teaching contents of the integrated course of general pathology and pathophysiology focus on the crossing and integration of relevant discipline knowledge and properly integrating the traditional pathological knowledge,which emphasizes morphological changes of human body,with the pathophysiological knowledge,which emphasizes functional and metabolic changes of human body. It is helpful for breaking the boundaries of disciplines and enabling students to understand the laws of occurrence and development of diseases as a whole.The teaching model has been improved by introducing new teaching methods such as PBL,so as to avoid the shortcomings of traditional teaching method. The innovation consciousness,spirit of active learning,and critical thinking of students are trained via discussions of clinical cases,so as to lay a solid foundation for the learning of subsequent clinical courses and academic research in the future. In summary,integrated course benefits the overall optimization of the structure of medical courses,promotes the improvement of teaching quality,and can be expanded to five-year clinical medicine program in the future.

  11. A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). (United States)

    Sharma, Alok; Couture, Justin


    To review the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). A literature search was conducted in PubMed and EMBASE using the terms attention deficit hyperactive disorder, ADHD, pathophysiology, etiology, and neurobiology. Limits applied were the following: published in the past 10 years (January 2003 to August 2013), humans, review, meta-analysis, and English language. These yielded 63 articles in PubMed and 74 in EMBASE. After removing duplicate/irrelevant articles, 86 articles and their relevant reference citations were reviewed. ADHD is a neurological disorder that affects children, but symptoms may persist into adulthood. Individuals suffering from this disorder exhibit hyperactivity, inattention, impulsivity, and problems in social interaction and academic performance. Medications used to treat ADHD such as methylphenidate, amphetamine, and atomoxetine indicate a dopamine/norepinephrine deficit as the neurochemical basis of ADHD, but the etiology is more complex. Moreover, these agents have poor adverse effect profiles and a multitude of drug interactions. Because these drugs are also dispensed to adults who may have concomitant conditions or medications, a pharmacist needs to be aware of these adverse events and drug interactions. This review, therefore, focuses on the pathophysiology, etiology, and treatment of ADHD and details the adverse effects and drug interaction profiles of the drugs used to treat it. Published research shows the benefit of drug therapy for ADHD in children, but given the poor adverse effect and drug interaction profiles, these must be dispensed with caution.

  12. IDO chronic immune activation and tryptophan metabolic pathway: A potential pathophysiological link between depression and obesity. (United States)

    Chaves Filho, Adriano José Maia; Lima, Camila Nayane Carvalho; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Maes, Michael; Macedo, Danielle


    Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs). In the CNS, TRYCATs have been related to oxidative damage, inflammation, mitochondrial dysfunction, cytotoxicity, excitotoxicity, neurotoxicity and lowered neuroplasticity. The pathophysiology of obesity is also associated with a state of aberrant inflammation that activates aryl hydrocarbon receptor (AHR), a pathway involved in the detection of intracellular or environmental changes as well as with increases in the production of TRYCATs, being KYN an agonists of AHR. Both AHR and TRYCATS are involved in obesity and related metabolic disorders. These changes in the TRYCAT pathway may contribute to the onset of neuropsychiatric symptoms in obesity. This paper reviews the role of immune activation, IDO stimulation and increased TRYCAT production in the pathophysiology of depression and obesity. Here we suggest that increased synthesis of detrimental TRYCATs is implicated in comorbid obesity and depression and is a new drug target to treat both diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology. (United States)

    Yu, Huimin; Hasan, Nesrin M; In, Julie G; Estes, Mary K; Kovbasnjuk, Olga; Zachos, Nicholas C; Donowitz, Mark


    The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.

  14. The importance of obstructive sleep apnoea and hypopnea pathophysiology for customized therapy. (United States)

    Bosi, Marcello; De Vito, Andrea; Gobbi, Riccardo; Poletti, Venerino; Vicini, Claudio


    The objective of this study is to highlight the importance of anatomical and not-anatomical factors' identification for customized therapy in OSAHS patients. The data sources are: MEDLINE, The Cochrane Library and EMBASE. A systematic review was performed to identify studies that analyze the role of multiple interacting factors involved in the OSAHS pathophysiology. 85 out of 1242 abstracts were selected for full-text review. A variable combinations pathophysiological factors contribute to realize differentiated OSAHS phenotypes: a small pharyngeal airway with a low resistance to collapse (increased critical closing pressure), an inadequate responses of pharyngeal dilator muscles (wakefulness drive to breathe), an unstable ventilator responsiveness to hypercapnia (high loop gain), and an increased propensity to wake related to upper airway obstruction (low arousal threshold). Identifying if the anatomical or not-anatomical factors are predominant in each OSAHS patient represents the current challenge in clinical practice, moreover for the treatment decision-making. In the future, if a reliable and accurate pathophysiological pattern for each OSAHS patient can be identified, a customized therapy will be feasible, with a significant improvement of surgical success in sleep surgery and a better understanding of surgical failure.

  15. MALDI imaging mass spectrometry: discrimination of pathophysiological regions in traumatized skeletal muscle by characteristic peptide signatures. (United States)

    Klein, Oliver; Strohschein, Kristin; Nebrich, Grit; Oetjen, Janina; Trede, Dennis; Thiele, Herbert; Alexandrov, Theodore; Giavalisco, Patrick; Duda, Georg N; von Roth, Philipp; Geissler, Sven; Klose, Joachim; Winkler, Tobias


    Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological regions in injured skeletal muscle is inadequate, underlying mechanisms of the beneficial effects of mesenchymal stromal cell transplantation on primary trauma and trauma adjacent muscle area remain elusive. For discrimination of these pathophysiological regions, formalin-fixed injured skeletal muscle tissue was analyzed by MALDI imaging MS. By using two computational evaluation strategies, a supervised approach (ClinProTools) and unsupervised segmentation (SCiLS Lab), characteristic m/z species could be assigned to primary trauma and trauma adjacent muscle regions. Using "bottom-up" MS for protein identification and validation of results by immunohistochemistry, we could identify two proteins, skeletal muscle alpha actin and carbonic anhydrase III, which discriminate between the secondary damage on adjacent tissue and the primary traumatized muscle area. Our results underscore the high potential of MALDI imaging MS to describe the spatial characteristics of pathophysiological changes in muscle. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Histidine Decarboxylase Knockout Mice as a Model of the Pathophysiology of Tourette Syndrome and Related Conditions. (United States)

    Pittenger, Christopher


    While the normal functions of histamine (HA) in the central nervous system have gradually come into focus over the past 30 years, the relationship of abnormalities in neurotransmitter HA to human disease has been slower to emerge. New insight came with the 2010 description of a rare nonsense mutation in the biosynthetic enzyme histidine decarboxylase (Hdc) that was associated with Tourette syndrome (TS) and related conditions in a single family pedigree. Subsequent genetic work has provided further support for abnormalities of HA signaling in sporadic TS. As a result of this genetic work, Hdc knockout mice, which were generated more than 15 years ago, have been reexamined as a model of the pathophysiology of TS and related conditions. Parallel work in these KO mice and in human carriers of the Hdc mutation has revealed abnormalities in the basal ganglia system and its modulation by dopamine (DA) and has confirmed the etiologic, face, and predictive validity of the model. The Hdc-KO model thus serves as a unique platform to probe the pathophysiology of TS and related conditions, and to generate specific hypotheses for subsequent testing in humans. This chapter summarizes the development and validation of this model and recent and ongoing work using it to further investigate pathophysiological changes that may contribute to these disorders.

  17. A review on Alzheimer's disease pathophysiology and its management: an update. (United States)

    Kumar, Anil; Singh, Arti; Ekavali


    Alzheimer's disease acknowledged as progressive multifarious neurodegenerative disorder, is the leading cause of dementia in late adult life. Pathologically it is characterized by intracellular neurofibrillary tangles and extracellular amyloidal protein deposits contributing to senile plaques. Over the last two decades, advances in the field of pathogenesis have inspired the researchers for the investigation of novel pharmacological therapeutics centered more towards the pathophysiological events of the disease. Currently available treatments i.e. acetylcholinesterase inhibitors (rivastigmine, galantamine, donepezil) and N-methyl d-aspartate receptor antagonist (memantine) contribute minimal impact on the disease and target late aspects of the disease. These drugs decelerate the progression of the disease, provide symptomatic relief but fail to achieve a definite cure. While the neuropathological features of Alzheimer's disease are recognized but the intricacies of the mechanism have not been clearly defined. This lack of understanding regarding the pathogenic process may be the likely reason for the non-availability of effective treatment which can prevent onset and progression of the disease. Owing to the important progress in the field of pathophysiology in the last couple of years, new therapeutic targets are available that should render the underlying disease process to be tackled directly. In this review, authors will discusses the different aspects of pathophysiological mechanisms behind Alzheimer's disease and its management through conventional drug therapy, including modern investigational therapeutic strategies, recently completed and ongoing. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. A Web-based e-learning course: integration of pathophysiology into pharmacology. (United States)

    Tse, Mimi M Y; Lo, Lisa W L


    The Internet is becoming the preferred place to find information. Millions of people go online in search of health and medical information. Likewise, the demand for Web-based courses is growing. This paper presents the development, utilization, and evaluation of a Web-based e-learning course for nursing students, entitled Integration of Pathophysiology into Pharmacology. The pathophysiology component included cardiovascular, respiratory, central nervous and immune system diseases, while the pharmacology component was developed based on 150 commonly used drugs. One hundred and nineteen Year 1 nursing students took part in the course. The Web-based e-learning course materials were uploaded to a WebCT for students' self-directed learning and attempts to pass two scheduled online quizzes. At the end of the semester, students were given a questionnaire to measure the e-learning experience. Their experience in the e-learning course was a positive one. Students stated that they were able to understand rather than memorize the subject content, and develop their problem solving and critical thinking abilities. Online quizzes yielded satisfactory results. In the focus group interview, students indicated that they appreciated the time flexibility and convenience associated with Web-based learning, and also made good suggestions for enhancing Web-based learning. The Web-based approach is promising for teaching and learning pathophysiology and pharmacology for nurses and other healthcare professionals.

  19. Short overview on metabolomics approach to study pathophysiology of oxidative stress in cancer

    Directory of Open Access Journals (Sweden)

    Luka Andrisic


    Full Text Available Association of oxidative stress with carcinogenesis is well known, but not understood well, as is pathophysiology of oxidative stress generated during different types of anti-cancer treatments. Moreover, recent findings indicate that cancer associated lipid peroxidation might eventually help defending adjacent nonmalignant cells from cancer invasion. Therefore, untargeted metabolomics studies designed for advanced translational and clinical studies are needed to understand the existing paradoxes in oncology, including those related to controversial usage of antioxidants aiming to prevent or treat cancer. In this short review we have tried to put emphasis on the importance of pathophysiology of oxidative stress and lipid peroxidation in cancer development in relation to metabolic adaptation of particular types of cancer allowing us to conclude that adaptation to oxidative stress is one of the main driving forces of cancer pathophysiology. With the help of metabolomics many novel findings are being achieved thus encouraging further scientific breakthroughs. Combined with targeted qualitative and quantitative methods, especially immunochemistry, further research might reveal bio-signatures of individual patients and respective malignant diseases, leading to individualized treatment approach, according to the concepts of modern integrative medicine. Keywords: Carcinogenesis, Cancer, Oxidative stress, Lipid peroxidation, 4-hydroxynonenal, Glutathione, Metabolomics, Immunochemistry, Biomarkers, Omics science

  20. Multi-disciplinary management of athletes with post-concussion syndrome: an evolving pathophysiological approach

    Directory of Open Access Journals (Sweden)

    Michael John Ellis


    Full Text Available Historically, patients with sports-related concussion (SRC have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS. Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually-tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further validate this evolving pathophysiological approach.

  1. Multi-Disciplinary Management of Athletes with Post-Concussion Syndrome: An Evolving Pathophysiological Approach. (United States)

    Ellis, Michael J; Leddy, John; Willer, Barry


    Historically, patients with sports-related concussion (SRC) have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS). Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review, we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further evaluate this evolving pathophysiological approach.

  2. Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents

    Directory of Open Access Journals (Sweden)

    Ja Hye Kim


    Full Text Available The hypothalamus plays a key role in the regulation of body weight by balancing the intake of food, energy expenditure, and body fat stores, as evidenced by the fact that most monogenic syndromes of morbid obesity result from mutations in genes expressed in the hypothalamus. Hypothalamic obesity is a result of impairment in the hypothalamic regulatory centers of body weight and energy expenditure, and is caused by structural damage to the hypothalamus, radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R and CART genes. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as leptin, dysregulated insulin secretion, and impaired activity of the sympathetic nervous system. Dysregulation of 11β-hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the development of hypothalamic obesity. Intervention of this complex entity requires simultaneous targeting of several mechanisms that are deranged in patients with hypothalamic obesity. Despite a great deal of theoretical understanding, effective treatment for hypothalamic obesity has not yet been developed. Therefore, understanding the mechanisms that control food intake and energy homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of the development of new treatments options. Early identification of patients at-risk can relieve the severity of weight gain by the provision of dietary and behavioral modification, and antiobesity medication. This review summarizes recent advances of the pathophysiology, endocrine characteristics, and treatment strategies of hypothalamic obesity.

  3. The emerging role of the microbial-gastrointestinal-neural axis

    Directory of Open Access Journals (Sweden)

    Peter G. McLean


    Full Text Available The gastrointestinal tract and its associated mucosal immune system have been extensively studied in the context of their involvement in disease processes, both within the tract itself and in its associated organs. However, historically a number of aspects of both gastrointestinal physiology and pathophysiology have been to some extent overlooked. In particular, the relationship of the gastrointestinal tract with its indigenous microbiota, and also the influence of the tract on behavior and neural systems and vice versa. Here, we describe recent advances in our knowledge and understanding of these areas, and attempt to put these advances in perspective with regard to potential therapeutic strategies.

  4. Experimental hyperthyroidism and central mediators of stress axis and thyroid axis activity in common carp (Cyprinus carpio L.). (United States)

    Geven, Edwin J W; Verkaar, Folkert; Flik, Gert; Klaren, Peter H M


    The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators of the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction in basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels in the hypothalamus, measured by real-time quantitative PCR, were significantly elevated by 40%, but CRH, urotensin-I, prepro-TRH, prohormone convertase-1 (PC1), and POMC mRNA levels were unchanged. In the pituitary pars distalis, PC1, CRH receptor-1, and POMC mRNA levels were unaffected, as was ACTH content. Plasma alpha-MSH concentrations were significantly elevated by 30% in hyperthyroid fish, and this was reflected in PC1 and POMC mRNA levels in pituitary pars intermedia that were increased 1.5- and 2.4-fold respectively. The alpha-MSH content of the pars intermedia was unchanged. Hyperthyroidism has profound effects on the basal levels of a central mediator, i.e., CRH-BP, of HPI-axis function in unstressed carp in vivo, and we conclude that HPI- and hypothalamo-pituitary-thyroid-axis functions are strongly interrelated. We suggest that the changes in plasma cortisol, thyroid hormone, and alpha-MSH levels reflect their concerted actions on energy metabolism.

  5. Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome. (United States)

    Calis, M; Gökçe, C; Ates, F; Ulker, S; Izgi, H B; Demir, H; Kirnap, M; Sofuoglu, S; Durak, A C; Tutus, A; Kelestimur, F


    Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.

  6. Preclinical chorioamnionitis dysregulates CXCL1/CXCR2 signaling throughout the placental-fetal-brain axis. (United States)

    Yellowhair, Tracylyn R; Noor, Shahani; Maxwell, Jessie R; Anstine, Christopher V; Oppong, Akosua Y; Robinson, Shenandoah; Milligan, Erin D; Jantzie, Lauren L


    In the United States, perinatal brain injury (PBI) is a major cause of infant mortality and childhood disability. For a large proportion of infants with PBI, central nervous system (CNS) injury begins in utero with inflammation (chorioamnionitis/CHORIO) and/or hypoxia-ischemia. While studies show CHORIO contributes to preterm CNS injury and is also a common independent risk factor for brain injury in term infants, the molecular mechanisms mediating inflammation in the placental-fetal-brain axis that result in PBI remain a gap in knowledge. The chemokine (C-X-C motif) ligand 1 (CXCL1), and its cognate receptor, CXCR2, have been clinically implicated in CHORIO and in mature CNS injury, although their specific role in PBI pathophysiology is poorly defined. Given CXCL1/CXCR2 signaling is essential to neural cell development and neutrophil recruitment, a key pathological hallmark of CHORIO, we hypothesized CHORIO would upregulate CXCL1/CXCR2 expression in the placenta and fetal circulation, concomitant with increased CXCL1/CXCR2 signaling in the developing brain, immune cell activation, neutrophilia, and microstructural PBI. On embryonic day 18 (E18), a laparotomy was performed in pregnant Sprague Dawley rats to induce CHORIO. Specifically, uterine arteries were occluded for 60min to induce placental transient systemic hypoxia-ischemia (TSHI), followed by intra-amniotic injection of lipopolysaccharide (LPS). Pups were born at E22. Placentae, serum and brain were collected along an extended time course from E19 to postnatal day (P)15 and analyzed using multiplex electrochemiluminescence (MECI), Western blot, qPCR, flow cytometry (FC) and diffusion tensor imaging (DTI). Results demonstrate that compared to sham, CHORIO increases placental CXCL1 and CXCR2 mRNA levels, concomitant with increased CXCR2 + neutrophils. Interestingly, pup serum CXCL1 expression in CHORIO parallels this increase, with sustained elevation through P15. Analyses of CHORIO brains reveal similarly

  7. Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis. (United States)

    Raisingani, Manish; Preneet, Brar; Kohn, Brenda; Yakar, Shoshana


    Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases diagnosed in childhood. Childhood and adolescent years are also the most important period for growth in height and acquisition of skeletal bone mineral density (BMD). The growth hormone (GH)/insulin like growth factor -1 (IGF-1) axis which regulates growth, is affected by T1DM, with studies showing increased GH and decreased IGF-1 levels in children with T1DM. There is conflicting data as to whether adolescents with TIDM are able to achieve their genetically-determined adult height. Furthermore, data support that adolescents with T1DM have decreased peak BMD, although the pathophysiology of which has not been completely defined. Various mechanisms have been proposed for the decrease in BMD including low osteocalcin levels, reflecting decreased bone formation; increased sclerostin, an inhibitor of bone anabolic pathways; and increased leptin, an adipocytokine which affects bone metabolism via central and peripheral mechanisms. Other factors implicated in the increased bone resorption in T1DM include upregulation of the osteoprotegerin/ receptor-activator of the nuclear factor-κB ligand pathway, elevated parathyroid hormone levels, and activation of other cytokines involved in chronic systemic inflammation. In this review, we summarize the clinical studies that address the alterations in the GH/IGF-I axis, linear growth velocity, and BMD in children and adolescents with T1DM; and we review the possible molecular mechanisms that may contribute to an attenuation of linear growth and to the reduction in the acquisition of peak bone mass in the child and adolescent with T1DM. Copyright © 2017. Published by Elsevier Ltd.

  8. Development of triple axis neutron spectrometer (Paper No. 24)

    International Nuclear Information System (INIS)

    Pal, B.C.; Wadhwa, N.R.; Goveas, S.H.


    The triple axis neutron spectrometers are the basic instruments intended for use with neutron beams from reactors. Various types of spectrometers, each devoted to different kinds of measurement can be designed and manufactured, once a prototype having all the attributes of a versatile instrument is designed and developed. With the view to achieving self reliance in this field, Central Workshops of Bhabha Atomic Research Centre (BARC), Bombay designed and developed a prototype of triple axis spectrometer meeting the specifications prepared by Nuclear Physics Division of BARC . This spectrometer, with a moving wedge system was successfully manufactured and installed at 'DHRUVA'. Another version of this spectrometer, called the 'Polarised Neutron Spectrometer' was also built and exported to South Korea and installed at Korea Advanced Energy Research Institute, Seoul. This paper deals with basic concept, development of design, engineering of mechanical assemblies, the manufacturing approach and problems encountered during manufacture. (author). 3 figs

  9. Self-assembly of orthogonal three-axis sensors

    International Nuclear Information System (INIS)

    Cho, J. H.; Hu, S.; Gracias, D. H.


    Conventional planar microfabrication is widely utilized to construct sensors for the measurement of physical or chemical properties. However, in these devices, the information component measured is typically restricted to only one vectorial axis. Here, we describe a self-assembling strategy that can be utilized to construct three dimensional (3D) cubic devices that facilitate measurement along three axes. This 3D measurement is achieved by arranging sensing elements orthogonally; any sensing element that can be lithographically patterned can be utilized. The 3D arrangement of sensors allows for the measurement of angular and orientation parameters. As an example, we describe a three-axis cantilever based sensor and demonstrate measurement of an evaporated analyte using resonant frequency shifts of cantilevers in each of the x, y, and z axes

  10. Dynamic Compensation for Two-Axis Robot Wrist Force Sensors

    Directory of Open Access Journals (Sweden)

    Junqing Ma


    Full Text Available To improve the dynamic characteristic of two-axis force sensors, a dynamic compensation method is proposed. The two-axis force sensor system is assumed to be a first-order system. The operation frequency of the system is expanded by a digital filter with backward difference network. To filter high-frequency noises, a low-pass filter is added after the dynamic compensation network. To avoid overcompensation, parameters of the proposed dynamic compensation method are defined by trial and error. Step response methods are utilized in dynamic calibration experiments. Compared to experiment data without compensation, the response time of the dynamic compensated data is reduced by 30%~40%. Experiments results demonstrate the effectiveness of our method.

  11. Efficiency of the DOMUS 750 vertical-axis wind turbine (United States)

    Hallock, Kyle; Rasch, Tyler; Ju, Guoqiang; Alonso-Marroquin, Fernando


    The aim of this paper is to present some preliminary results on the efficiency of a wind turbine for an off-grid housing unit. To generate power, the unit uses a photovoltaic solar array and a vertical-axis wind turbine (VAWT). The existing VAWT was analysed to improve efficiency and increase power generation. There were found to be two main sources of inefficiency: 1. the 750W DC epicyclic generator performed poorly in low winds, and 2. the turbine blades wobbled, allowing for energy loss due to off-axis rotation. A 12V DC permanent magnet alternator was chosen that met the power requirements of the housing unit and would generate power at lower wind speeds. A support bracket was designed to prevent the turbine blades from wobbling.

  12. Design optimization and analysis of vertical axis wind turbine blade

    International Nuclear Information System (INIS)

    Jarral, A.; Ali, M.; Sahir, M.H.


    Wind energy is clean and renwable source of energy and is also the world's fastest growing energy resource. Keeping in view power shortages and growing cost of energy, the low cost wind energy has become a primary solution. It is imperative that economies and individuals begin to conserve energy and focus on the production of energy from renewable sources. Present study describes a wind turbine blade designed with enhanced aerodynamic properties. Vertical axis turbine is chosen because of its easy installment, less noisy and having environmental friendly characteristics. Vertical axis wind turbines are thought to be ideal for installations where wind conditions are not consistent. The presented turbine blade is best suitable for roadsides where the rated speed due to vehicles is most /sup -1/ often 8 ms .To get an optimal shape design symmetrical profile NACA0025 has been considered which is then analyzed for stability and aerodynamic characteristics at optimal conditions using analysis tools ANSYS and CFD tools. (author)

  13. A new vertical axis wind turbine design for urban areas (United States)

    Frunzulica, Florin; Cismilianu, Alexandru; Boros, Alexandru; Dumitrache, Alexandru; Suatean, Bogdan


    In this paper we aim at developing the model of a Vertical Axis Wind Turbine (VAWT) with the short-term goal of physically realising this turbine to operate at a maximmum power of 5 kW. The turbine is designed for household users in the urban or rural areas and remote or isolated residential areas (hardly accsessible). The proposed model has a biplane configuration on each arm of the VAWT (3 × 2 = 6 blades), allowing for increased performance of the turbine at TSR between 2 and 2.5 (urban area operation) compared to the classic vertical axis turbines. Results that validate the proposed configuration as well as passive control methods to increase the performance of the classic VAWTs are presented.

  14. Tuning the DARHT Axis-II linear induction accelerator focusing

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Carl A. [Los Alamos National Laboratory


    Flash radiography of large hydrodynamic experiments driven by high explosives is a well-known diagnostic technique in use at many laboratories, and the Dual-Axis Radiography for Hydrodynamic Testing (DARHT) facility at Los Alamos produces flash radiographs of large hydrodynamic experiments. Two linear induction accelerators (LIAs) make the bremsstrahlung radiographic source spots for orthogonal views of each test. The 2-kA, 20-MeV Axis-I LIA creates a single 60-ns radiography pulse. The 1.7-kA, 16.5-MeV Axis-II LIA creates up to four radiography pulses by kicking them out of a longer pulse that has a 1.6-{mu}s flattop. The Axis-II injector, LIA, kicker, and downstream transport (DST) to the bremsstrahlung converter are described. Adjusting the magnetic focusing and steering elements to optimize the electron-beam transport through an LIA is often called 'tuning.' As in all high-current LIAs, the focusing field is designed to be as close to that of the ideal continuous solenoid as physically possible. In ideal continuous solenoidal transport a smoothly varying beam size can easily be found for which radial forces balance, and the beam is said to be 'matched' to the focusing field. A 'mismatched' beam exhibits unwanted oscillations in size, which are a source of free energy that contributes to emittance growth. This is undesirable, because in the absence of beam-target effects, the radiographic spot size is proportional to the emittance. Tuning the Axis-II LIA is done in two steps. First, the solenoidal focusing elements are set to values designed to provide a matched beam with little or no envelope oscillations, and little or no beam-breakup (BBU) instability growth. Then, steering elements are adjusted to minimize the motion of the centroid of a well-centered beam at the LIA exit. This article only describes the design of the tune for the focusing solenoids. The DARHT Axis-II LIA was required to be re-tuned after installing an

  15. Ground Vibration Attenuation Measurement using Triaxial and Single Axis Accelerometers (United States)

    Mohammad, A. H.; Yusoff, N. A.; Madun, A.; Tajudin, S. A. A.; Zahari, M. N. H.; Chik, T. N. T.; Rahman, N. A.; Annuar, Y. M. N.


    Peak Particle Velocity is one of the important term to show the level of the vibration amplitude especially traveling wave by distance. Vibration measurement using triaxial accelerometer is needed to obtain accurate value of PPV however limited by the size and the available channel of the data acquisition module for detailed measurement. In this paper, an attempt to estimate accurate PPV has been made by using only a triaxial accelerometer together with multiple single axis accelerometer for the ground vibration measurement. A field test was conducted on soft ground using nine single axis accelerometers and a triaxial accelerometer installed at nine receiver location R1 to R9. Based from the obtained result, the method shows convincing similarity between actual PPV with the calculated PPV with error ratio 0.97. With the design method, vibration measurement equipment size can be reduced with fewer channel required.

  16. Vertical-axis turbine/propeller for ship propulsion

    Energy Technology Data Exchange (ETDEWEB)

    Barkla, H.M.


    There are so many variables in the design and operating conditions of a vertical-axis turbine/propeller for the propulsion of a ship by wind that a preliminary study is offered, based on two simplified models. Study of a linear motion of blades in air and water shows optimum conditions for blade-speed and blade-incidence. Analysis of the second, cyclical model is simplified by the assumption of constant angles of incidence. While the logical superiority of the vertical-axis system, with its low transmission loss, may not alone give it the advantage over all other systems in upwind and downwind sailing, there are indications that in the beam wind it is in a class of its own; the Voith-Schneider-Type propeller then produces a thrust with a major component to windward, so that the combined unit leaves little or no athwartships force.


    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yipeng; Borland, M.; Lindberg, R.; Sajaev, V.


    A 67-pm hybrid-seven-bend achromat (H7BA) lattice is being proposed for a future Advanced Photon Source (APS) multi-bend-achromat (MBA) upgrade project. This lattice design pushes for smaller emittance and requires use of a swap-out (on-axis) injection scheme due to limited dynamic acceptance. Alternate lattice design work has also been performed for the APS upgrade to achieve better beam dynamics performance than the nominal APS MBA lattice, in order to allow off-axis accumulation. Two such alternate H7BA lattice designs, which target a still-low emittance of 90 pm, are discussed in detail in this paper. Although the single-particle-dynamics performance is good, simulations of collective effects indicate that surprising difficulty would be expected accumulating high single-bunch charge in this lattice. The brightness of the 90-pm lattice is also a factor of two lower than the 67-pm H7BA lattice.

  18. Axis-switching of a micro-jet (United States)

    Cabaleiro, Juan Martin; Aider, Jean-Luc


    In this study, it is shown that free microjets can undergo complex transitions similar to large-scale free jets despite relatively low Reynolds numbers. Using an original experimental method allowing for the 3D reconstruction of the instantaneous spatial organization of the microjet, the axis-switching of a micro-jet is observed for the first time. This is the first experimental evidence of such complex phenomena for free micro-jets. Combining these experimental results with Direct Numerical Simulations it is shown that the mechanism responsible for the axis-switching is the deformation of a micro-vortex ring due to induction by the corner vortices, as it occurs in large scale non-circular jets.

  19. Averaging scheme for atomic resolution off-axis electron holograms. (United States)

    Niermann, T; Lehmann, M


    All micrographs are limited by shot-noise, which is intrinsic to the detection process of electrons. For beam insensitive specimen this limitation can in principle easily be circumvented by prolonged exposure times. However, in the high-resolution regime several instrumental instabilities limit the applicable exposure time. Particularly in the case of off-axis holography the holograms are highly sensitive to the position and voltage of the electron-optical biprism. We present a novel reconstruction algorithm to average series of off-axis holograms while compensating for specimen drift, biprism drift, drift of biprism voltage, and drift of defocus, which all might cause problematic changes from exposure to exposure. We show an application of the algorithm utilizing also the possibilities of double biprism holography, which results in a high quality exit-wave reconstruction with 75 pm resolution at a very high signal-to-noise ratio. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Development of a Single-Axis Edge Detection System

    Energy Technology Data Exchange (ETDEWEB)

    Hanshaw, R.A.


    A SIP (Societe Genevoise d'Instruments de Physique) Trioptic coordinate measuring machine was modified for calibration of high quality single-axis glass standards to an uncertainty of {+-}0.000020 inch. The modification was accomplished through the addition of a frame grabber board, vision software, a high-resolution camera, stepper motors, a two-axis motor controller, and an HP-IB interface card. An existing temperature system (hygrometer, barometer, laser interferometer system, and optics) was retained as part of the system. An existing Hewlett Packard computer was replaced with a personal computer to accommodate the frame grabber board. Each component was integrated into the existing system using Visual Basic. The system was automated for unattended measurements by creating a machine programming language, which is recognized within the main program.

  1. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie [Univ. of Rochester, NY (United States)


    Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

  2. Application of one-axis sun tracking system

    Energy Technology Data Exchange (ETDEWEB)

    Sefa, Ibrahim; Demirtas, Mehmet; Colak, Ilhami [Gazi University, Faculty of Technical Education, Department of Electrical Education, GEMEC-Gazi Electric Machines and Control Group, Ankara (Turkey)


    This paper introduces design and application of a novel one-axis sun tracking system which follows the position of the sun and allows investigating effects of one-axis tracking system on the solar energy in Turkey. The tracking system includes a serial communication interface based on RS 485 to monitor whole processes on a computer screen and to plot data as graphic. In addition, system parameters such as the current, the voltage and the panel position have been observed by means of a microcontroller. The energy collected is measured and compared with a fixed solar system for the same solar panel. The results show that the solar energy collected on the tracking system is considerably much efficient than the fixed system. The tracking system developed in this study provides easy installation, simple mechanism and less maintenance. (author)

  3. Summary of tower designs for large horizontal axis wind turbines (United States)

    Frederick, G. R.; Savino, J. M.


    Towers for large horizontal axis wind turbines, machines with a rotor axis height above 30 meters and rated at more than 500 kW, have varied in configuration, materials of construction, type of construction, height, and stiffness. For example, the U.S. large HAWTs have utilized steel truss type towers and free-standing steel cylindrical towers. In Europe, the trend has been to use only free-standing and guyed cylindrical towers, but both steel and reinforced concrete have been used as materials of construction. These variations in materials of construction and type of construction reflect different engineering approaches to the design of cost effective towers for large HAWTs. Tower designs are the NASA/DOE Mod-5B presently being fabricated. Design goals and requirements that influence tower configuration, height and materials are discussed. In particular, experiences with United States large wind turbine towers are elucidated. Finally, current trends in tower designs for large HAWTs are highlighted.

  4. Application of one-axis sun tracking system

    International Nuclear Information System (INIS)

    Sefa, Ibrahim; Demirtas, Mehmet; Colak, Ilhami


    This paper introduces design and application of a novel one-axis sun tracking system which follows the position of the sun and allows investigating effects of one-axis tracking system on the solar energy in Turkey. The tracking system includes a serial communication interface based on RS 485 to monitor whole processes on a computer screen and to plot data as graphic. In addition, system parameters such as the current, the voltage and the panel position have been observed by means of a microcontroller. The energy collected is measured and compared with a fixed solar system for the same solar panel. The results show that the solar energy collected on the tracking system is considerably much efficient than the fixed system. The tracking system developed in this study provides easy installation, simple mechanism and less maintenance.

  5. Proposed Pathophysiologic Framework to Explain Some Excess Cardiovascular Death Associated with Ambient Air Particle Pollution: Insights for Public Health Translation (United States)

    The paper proposes a pathophysiologic framework to explain the well-established epidemiological association between exposure to ambient air particle pollution and premature cardiovascular mortality, and offers insights into public health solutions that extend beyond regularory en...

  6. Device for passive flow control around vertical axis marine turbine (United States)

    Coşoiu, C. I.; Georgescu, A. M.; Degeratu, M.; Haşegan, L.; Hlevca, D.


    The power supplied by a turbine with the rotor placed in a free stream flow may be increased by augmenting the velocity in the rotor area. The energy of the free flow is dispersed and it may be concentrated by placing a profiled structure around the bare turbine in order to concentrate more energy in the rotor zone. At the Aerodynamic and Wind Engineering Laboratory (LAIV) of the Technical University of Civil Engineering of Bucharest (UTCB) it was developed a concentrating housing to be used for hydro or aeolian horizontal axis wind turbines, in order to increase the available energy in the active section of turbine rotor. The shape of the concentrating housing results by superposing several aero/hydro dynamic effects, the most important being the one generated by the passive flow control devices that were included in the housing structure. Those concentrating housings may be also adapted for hydro or aeolian turbines with vertical axis. The present paper details the numerical research effectuated at the LAIV to determine the performances of a vertical axis marine turbine equipped with such a concentrating device, in order to increase the energy quantity extracted from the main flow. The turbine is a Darrieus type one with three vertical straight blades, symmetric with respect to the axis of rotation, generated using a NACA4518 airfoil. The global performances of the turbine equipped with the concentrating housing were compared to the same characteristics of the bare turbine. In order to validate the numerical approach used in this paper, test cases from the literature resulting from experimental and numerical simulations for similar situations, were used.

  7. Device for passive flow control around vertical axis marine turbine

    International Nuclear Information System (INIS)

    Coşoiu, C I; Georgescu, A M; Degeratu, M; Haşegan, L; Hlevca, D


    The power supplied by a turbine with the rotor placed in a free stream flow may be increased by augmenting the velocity in the rotor area. The energy of the free flow is dispersed and it may be concentrated by placing a profiled structure around the bare turbine in order to concentrate more energy in the rotor zone. At the Aerodynamic and Wind Engineering Laboratory (LAIV) of the Technical University of Civil Engineering of Bucharest (UTCB) it was developed a concentrating housing to be used for hydro or aeolian horizontal axis wind turbines, in order to increase the available energy in the active section of turbine rotor. The shape of the concentrating housing results by superposing several aero/hydro dynamic effects, the most important being the one generated by the passive flow control devices that were included in the housing structure. Those concentrating housings may be also adapted for hydro or aeolian turbines with vertical axis. The present paper details the numerical research effectuated at the LAIV to determine the performances of a vertical axis marine turbine equipped with such a concentrating device, in order to increase the energy quantity extracted from the main flow. The turbine is a Darrieus type one with three vertical straight blades, symmetric with respect to the axis of rotation, generated using a NACA4518 airfoil. The global performances of the turbine equipped with the concentrating housing were compared to the same characteristics of the bare turbine. In order to validate the numerical approach used in this paper, test cases from the literature resulting from experimental and numerical simulations for similar situations, were used.

  8. Small-Scale vertical axis wind turbine design


    Castillo Tudela, Javier


    The thesis focuses on the design of a small vertical axis wind turbine rotor with solid wood as a construction material. The aerodynamic analysis is performed implementing a momentum based model on a mathematical computer program. A three bladed wind turbine is proposed as candidate for further prototype testing after evaluating the effect of several parameters in turbine efficiency, torque and acceleration. The results obtained indicate that wood is a suitable material for rotor cons...

  9. Gonadal Steroid Hormones and the Hypothalamo-Pituitary-Adrenal Axis


    Handa, Robert J.; Weiser, Michael J.


    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, pr...

  10. Classification of threespine stickleback along the benthic-limnetic axis


    Willacker, James J.; von Hippel, Frank A.; Wilton, Peter R.; Walton, Kelly M.


    Many species of fish display morphological divergence between individuals feeding on macroinvertebrates associated with littoral habitats (benthic morphotypes) and individuals feeding on zooplankton in the limnetic zone (limnetic morphotypes). Threespine stickleback (Gasterosteus aculeatus L.) have diverged along the benthic-limnetic axis into allopatric morphotypes in thousands of populations and into sympatric species pairs in several lakes. However, only a few well known populations have b...

  11. From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis

    Directory of Open Access Journals (Sweden)

    Jakob Triebel


    Full Text Available The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin (PRL and vasoinhibins regulate blood vessel growth and function, the secretion of other hormones, inflammatory and immune processes, coagulation, and behavior. The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins, which consists in the proteolytic cleavage of their precursor molecule PRL. Vasoinhibins can interact with multiple different partners to mediate their effects in various tissues and anatomical compartments, indicating their pleiotropic nature. Based on accumulating knowledge about the PRL/vasoinhibin axis, two clinical trials were initiated, in which vasoinhibin levels are the target of therapeutic interventions. One trial investigates the effect of levosulpiride, a selective dopamine D2-receptor antagonist, on retinal alterations in patients with diabetic macular edema and retinopathy. The rationale of this trial is that the levosulpiride-induced hyperprolactinemia resulting in increased retinal vasoinhibins could lead to beneficiary outcomes in terms of a vasoinhibin-mediated antagonization of diabetes-induced retinal alterations. Another trial investigated the effect of bromocriptine, a dopamine D2-receptor agonist, for the treatment of peripartum cardiomyopathy. The rationale of treatment with bromocriptine is the inhibition of vasoinhibin generation by substrate depletion to prevent detrimental effects on the myocardial microvascularization. The trial demonstrated that bromocriptine treatment was associated with a high rate of left ventricular recovery and low morbidity and mortality. Therapeutic interventions into the PRL/vasoinhibin axis bear the risk of side effects in the areas of blood coagulation, blood pressure, and alterations of the mental state.

  12. Roll-Axis Hydrofluidic Stability Augmentation System Development (United States)


    lifi .1035 SW 30 left for znro time delay - r Ight for other. 17 Preceding page Hank Recordings of the simulated aircraft performance to...DESIGN The analytical effort defined the gains and shaping networks required for the roll-axis damper system for the OH-58A helicopter, and the...Shaping Networks Usually a combination of resistors and capacitors (bellows) is designed to provide the following functions: a) b) 3.1.4 1 Lag

  13. Three-axis orthogonal transceiver coil for eddy current sounding (United States)

    Sukhanov, D.; Zavyalova, K.; Goncharik, M.


    We propose the new structure of three-axis transceiver magnetic-induction coil for eddy current probing. Due to the orientation of the coils, the direct signal from the transmitting coil to the receiving coil is minimized, which provided a high dynamic range. Sensitivity in all directions is provided by combining coils of different orientations. Numerical simulation and experimental studies of such a system have been carried out and confirmed the applicability of the proposed method and the mathematical model.

  14. Inelastic scattering using the three-axis spectrometer technique

    International Nuclear Information System (INIS)

    Currat, R.


    The three-axis technique is a basic neutron scattering technique for inelastic work on single-crystal specimens. There is, at the moment, a fair degree of complementarity between TAS instruments on steady-state sources and TOF instruments on steady-state or pulsed sources. The technique is described, the issue of TAS versus TOF method is discussed, and investigations relating to the resolution functions are presented. (K.A.)

  15. Estimation of power in low velocity vertical axis wind turbine (United States)

    Sampath, S. S.; Shetty, Sawan; Chithirai Pon Selvan, M.


    The present work involves in the construction of a vertical axis wind turbine and the determination of power. Various different types of turbine blades are considered and the optimum blade is selected. Mechanical components of the entire setup are built to obtain maximum rotation per minute. The mechanical energy is converted into the electrical energy by coupling coaxially between the shaft and the generator. This setup produces sufficient power for consumption of household purposes which is economic and easily available.

  16. MARRT: Medial Axis biased rapidly-exploring random trees

    KAUST Repository

    Denny, Jory


    © 2014 IEEE. Motion planning is a difficult and widely studied problem in robotics. Current research aims not only to find feasible paths, but to ensure paths have certain properties, e.g., shortest or safest paths. This is difficult for current state-of-the-art sampling-based techniques as they typically focus on simply finding any path. Despite this difficulty, sampling-based techniques have shown great success in planning for a wide range of applications. Among such planners, Rapidly-Exploring Random Trees (RRTs) search the planning space by biasing exploration toward unexplored regions. This paper introduces a novel RRT variant, Medial Axis RRT (MARRT), which biases tree exploration to the medial axis of free space by pushing all configurations from expansion steps towards the medial axis. We prove that this biasing increases the tree\\'s clearance from obstacles. Improving obstacle clearance is useful where path safety is important, e.g., path planning for robots performing tasks in close proximity to the elderly. Finally, we experimentally analyze MARRT, emphasizing its ability to effectively map difficult passages while increasing obstacle clearance, and compare it to contemporary RRT techniques.

  17. A New, Adaptable, Optical High-Resolution 3-Axis Sensor

    Directory of Open Access Journals (Sweden)

    Niels Buchhold


    Full Text Available This article presents a new optical, multi-functional, high-resolution 3-axis sensor which serves to navigate and can, for example, replace standard joysticks in medical devices such as electric wheelchairs, surgical robots or medical diagnosis devices. A light source, e.g., a laser diode, is affixed to a movable axis and projects a random geometric shape on an image sensor (CMOS or CCD. The downstream microcontroller’s software identifies the geometric shape’s center, distortion and size, and then calculates x, y, and z coordinates, which can be processed in attached devices. Depending on the image sensor in use (e.g., 6.41 megapixels, the 3-axis sensor features a resolution of 1544 digits from right to left and 1038 digits up and down. Through interpolation, these values rise by a factor of 100. A unique feature is the exact reproducibility (deflection to coordinates and its precise ability to return to its neutral position. Moreover, optical signal processing provides a high level of protection against electromagnetic and radio frequency interference. The sensor is adaptive and adjustable to fit a user’s range of motion (stroke and force. This recommendation aims to optimize sensor systems such as joysticks in medical devices in terms of safety, ease of use, and adaptability.

  18. Blade pitch optimization methods for vertical-axis wind turbines (United States)

    Kozak, Peter

    Vertical-axis wind turbines (VAWTs) offer an inherently simpler design than horizontal-axis machines, while their lower blade speed mitigates safety and noise concerns, potentially allowing for installation closer to populated and ecologically sensitive areas. While VAWTs do offer significant operational advantages, development has been hampered by the difficulty of modeling the aerodynamics involved, further complicated by their rotating geometry. This thesis presents results from a simulation of a baseline VAWT computed using Star-CCM+, a commercial finite-volume (FVM) code. VAWT aerodynamics are shown to be dominated at low tip-speed ratios by dynamic stall phenomena and at high tip-speed ratios by wake-blade interactions. Several optimization techniques have been developed for the adjustment of blade pitch based on finite-volume simulations and streamtube models. The effectiveness of the optimization procedure is evaluated and the basic architecture for a feedback control system is proposed. Implementation of variable blade pitch is shown to increase a baseline turbine's power output between 40%-100%, depending on the optimization technique, improving the turbine's competitiveness when compared with a commercially-available horizontal-axis turbine.

  19. A procedure for denoising dual-axis swallowing accelerometry signals

    International Nuclear Information System (INIS)

    Sejdić, Ervin; Chau, Tom; Steele, Catriona M


    Dual-axis swallowing accelerometry is an emerging tool for the assessment of dysphagia (swallowing difficulties). These signals however can be very noisy as a result of physiological and motion artifacts. In this note, we propose a novel scheme for denoising those signals, i.e. a computationally efficient search for the optimal denoising threshold within a reduced wavelet subspace. To determine a viable subspace, the algorithm relies on the minimum value of the estimated upper bound for the reconstruction error. A numerical analysis of the proposed scheme using synthetic test signals demonstrated that the proposed scheme is computationally more efficient than minimum noiseless description length (MNDL)-based denoising. It also yields smaller reconstruction errors than MNDL, SURE and Donoho denoising methods. When applied to dual-axis swallowing accelerometry signals, the proposed scheme exhibits improved performance for dry, wet and wet chin tuck swallows. These results are important for the further development of medical devices based on dual-axis swallowing accelerometry signals. (note)

  20. l=1 helical axis heliotron device in Kyoto university

    International Nuclear Information System (INIS)

    Nagasaki, K.; Sano, F.; Mizuuchi, T.; Hanatani, K.; Okada, H.; Obiki, T.


    Helical systems are an attractive candidate for magnetic fusion reactor. Recently, there has been great progress in theoretical research of three dimensional magnetic field structures, resulting in several kinds of confinement optimization being proposed for toroidal magnetic confinement system. For example, some sophisticated ideas have appeared on stage such as quasi-helical symmetry and quasi-isodynamic system. To find experimentally which way is the best Optimisation, a new helical axis heliotron device, so called 'Heliotron J', is under construction in the Institute of Advanced Energy, Kyoto University, Japan. In this conference, the basic concept and the present status will be presented. In the conventional plane axis helical system, it was difficult to have both good particle confinement and good MHD stability simultaneously. The goal of Heliotron J project is to clarify their compatibility in the spatial axis toroidal device. The best way for Optimising the helical magnetic field configuration will be explored by investigating the plasma response to the change in the field components. The main subjects for plasma experiment are: demonstration of the existence of good magnetic flux surfaces, reduction of neoclassical transport in collisionless regime, MHD Stabilisation in high β plasma, controllability of bootstrap current, good confinement of high energy particles