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Sample records for autism pathophysiology biological

  1. Bridging from Cells to Cognition in Autism Pathophysiology: Biological Pathways to Defective Brain Function and Plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Matthew; Hooker, Brian S.; Herbert, Martha

    2008-01-01

    We review evidence to support the model that autism may begin when a maternal environmental, infectious, or autoantibody insult causes inflammation which increases reactive oxygen species (ROS) production in the fetus, leading to fetal DNA damage (nuclear and mitochondrial), and that these inflammatory and oxidative stressors persist beyond early development (with potential further exacerbations), producing ongoing functional consequences. In organs with a high metabolic demand such as the central nervous system, the continued use of mitochondria with DNA damage may generate additional ROS which will activate the innate immune system leading to more ROS production. Such a mechanism would self-sustain and possibly progressively worsen. The mitochondrial dysfunction and altered redox signal transduction pathways found in autism would conspire to activate both astroglia and microglia. These activated cells can then initiate a broad-spectrum proinflammatory gene response. Neurons may have acquired receptors for these inflammatory signals to inhibit neuronal signaling as a protection from excitotoxic damage during various pathologic insults (e.g., infection). In autism, over-zealous neuroinflammatory responses could not only influence neural developmental processes, but may more significantly impair neural signaling involved in cognition in an ongoing fashion. This model makes specific predictions in patients and experimental animal models and suggests a number of targets sites of intervention. Our model of potentially reversible pathophysiological mechanisms in autism motivates our hope that effective therapies may soon appear on the horizon.

  2. Autism: Pathophysiology and Promising Herbal Remedies.

    Science.gov (United States)

    Bahmani, Mahmoud; Sarrafchi, Amir; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

    2016-01-01

    Autism is a comprehensive growth abnormality in which social skills, language, communication, and behavioral skills are developed with delay and as diversionary. The reasons for autism are unclear, but various theories of genetics, immunity, biological, and psychosocial factors have been proffered. In fact, autism is a complex disorder with distinct causes that usually co-occur. Although no medicine has been recognized to treat this disorder, pharmacological treatments can be effective in reducing its signs, such as self-mutilation, aggression, repetitive and stereotyped behaviors, inattention, hyperactivity, and sleeping disorders. Recently, complementary and alternative approaches have been considered to treat autism. Ginkgo biloba is one of the most effective plants with an old history of applications in neuropsychological disorders which recently is used for autism. The present review discusses the recent findings, pathophysiology, and etiology of autism and thereafter addresses the promising results of herbal remedies. PMID:26561063

  3. Bridging from Cells to Cognition in Autism Pathophysiology: Biological Pathways to Defective Brain Function and Plasticity

    Directory of Open Access Journals (Sweden)

    Matthew P. Anderson

    2008-01-01

    Full Text Available We review evidence to support a model where the disease process underlying autism may begin when an in utero or early postnatal environmental, infectious, seizure, or autoimmune insult triggers an immune response that increases reactive oxygen species (ROS production in the brain that leads to DNA damage (nuclear and mitochondrial and metabolic enzyme blockade and that these inflammatory and oxidative stressors persist beyond early development (with potential further exacerbations, producing ongoing functional consequences. In organs with a high metabolic demand such as the central nervous system, the continued use of mitochondria with damaged DNA and impaired metabolic enzyme function may generate additional ROS which will cause persistent activation of the innate immune system leading to more ROS production. Such a mechanism would self-sustain and possibly progressively worsen. The mitochondrial dysfunction and altered redox signal transduction pathways found in autism would conspire to activate both astroglia and microglia. These activated cells can then initiate a broad-spectrum proinflammatory gene response. Beyond the direct effects of ROS on neuronal function, receptors on neurons that bind the inflammatory mediators may serve to inhibit neuronal signaling to protect them from excitotoxic damage during various pathologic insults (e.g., infection. In autism, over-zealous neuroinflammatory responses could not only influence neural developmental processes, but may more significantly impair neural signaling involved in cognition in an ongoing fashion. This model makes specific predictions in patients and experimental animal models and suggests a number of targets sites of intervention. Our model of potentially reversible pathophysiological mechanisms in autism motivates our hope that effective therapies may soon appear on the horizon.

  4. Deep brain stimulation for severe autism: from pathophysiology to procedure.

    Science.gov (United States)

    Sinha, Saurabh; McGovern, Robert A; Sheth, Sameer A

    2015-06-01

    Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges. PMID:26030703

  5. Biological sex affects the neurobiology of autism

    OpenAIRE

    Lai, Meng-Chuan; Lombardo, Michael V.; Suckling, John; Ruigrok, Amber N. V.; Chakrabarti, Bhismadev; Ecker, Christine; Deoni, Sean C.L.; Craig, Michael C.; Murphy, Declan G. M.; Bullmore, Edward T; ,; Baron-Cohen, Simon

    2013-01-01

    In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This stu...

  6. Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism.

    Science.gov (United States)

    Rossignol, Daniel A

    2007-01-01

    Autism is a neurodevelopmental disorder currently affecting as many as 1 out of 166 children in the United States. Numerous studies of autistic individuals have revealed evidence of cerebral hypoperfusion, neuroinflammation and gastrointestinal inflammation, immune dysregulation, oxidative stress, relative mitochondrial dysfunction, neurotransmitter abnormalities, impaired detoxification of toxins, dysbiosis, and impaired production of porphyrins. Many of these findings have been correlated with core autistic symptoms. For example, cerebral hypoperfusion in autistic children has been correlated with repetitive, self-stimulatory and stereotypical behaviors, and impairments in communication, sensory perception, and social interaction. Hyperbaric oxygen therapy (HBOT) might be able to improve each of these problems in autistic individuals. Specifically, HBOT has been used with clinical success in several cerebral hypoperfusion conditions and can compensate for decreased blood flow by increasing the oxygen content of plasma and body tissues. HBOT has been reported to possess strong anti-inflammatory properties and has been shown to improve immune function. There is evidence that oxidative stress can be reduced with HBOT through the upregulation of antioxidant enzymes. HBOT can also increase the function and production of mitochondria and improve neurotransmitter abnormalities. In addition, HBOT upregulates enzymes that can help with detoxification problems specifically found in autistic children. Dysbiosis is common in autistic children and HBOT can improve this. Impaired production of porphyrins in autistic children might affect the production of heme, and HBOT might help overcome the effects of this problem. Finally, HBOT has been shown to mobilize stem cells from the bone marrow to the systemic circulation. Recent studies in humans have shown that stem cells can enter the brain and form new neurons, astrocytes, and microglia. It is expected that amelioration of

  7. The role of immune dysfunction in the pathophysiology of autism

    OpenAIRE

    Onore, Charity; Careaga, Milo; Ashwood, Paul

    2011-01-01

    Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders encompassing impairments in communication, social interactions and restricted stereotypical behaviors. Although a link between altered immune responses and ASD was first recognized nearly 40 years ago, only recently has new evidence started to shed light on the complex multifaceted relationship between immune dysfunction and behavior in ASD. Neurobiological research in ASD has highlighted pathways involved in ...

  8. Effects of biological sex on the pathophysiology of the heart

    OpenAIRE

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

    2014-01-01

    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 th...

  9. Autism: is there a biological cause?

    Science.gov (United States)

    Stewart, J E

    1994-12-01

    1. Autism is the term used to describe certain characteristics observed in some children, including a preference for aloneness, and sameness. 2. The condition was thought for some time to be caused by a psychological disturbance resulting from a combination of stress and poor parental upbringing. 3. Recently emerging data suggests the symptoms are related to a cognitive deficit associated with a biological cause. 4. As research progresses, it is hoped it will become possible to improve the quality of life for people suffering from or looking after those with, autism. PMID:7862687

  10. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-08-01

    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

  11. Autism spectrum disorder in adults : biological dimensions

    OpenAIRE

    Manouilenko, Irina

    2013-01-01

    Autism Spectrum Disorder (ASD) is a group of neurodevelopmental conditions characterized by difficulties in social interaction, communication and the presence of repetitive or stereotyped behaviors. Previous studies have demonstrated structural and functional abnormalities in different brain regions in ASD. Motor difficulties, unusual percept ion and minor physical anomalies have been reported but not systematically investigated in the adult population with ASD and n...

  12. Autism

    Science.gov (United States)

    ... for problems with things like attention, hyperactivity, and sleep) Many other types of therapy (including diet, music, and art therapies) can help people with autism spectrum disorder. Teens with autism ...

  13. Aetiopathogenesis and pathophysiology of bulimia nervosa: biological bases and implications for treatment.

    Science.gov (United States)

    Brambilla, F

    2001-01-01

    Bulimia nervosa is an eating disorder characterised by recurrent episodes of binge eating and associated efforts to purge the ingested calories through self-induced vomiting, laxative or diuretic abuse, fasting or intensive exercise. The aetiopathogenesis and pathophysiology of the disorder are currently unclear. Biological bases have been proposed repeatedly, based on several lines of evidence: hunger, satiety and food choice are regulated by neurotransmitters and neuropeptides, and impairment of eating habits may be related to alterations in the secretion of these chemicals; genetic studies suggest that these neurotransmitter systems are dysfunctional in individuals with bulimia nervosa; and the frequent comorbidity of bulimia nervosa with major depressive and obsessive-compulsive disorders, conditions in which multiple alterations of brain biochemical functions have been demonstrated. Data in the literature suggest that levels of noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) are lower in individuals with bulimia nervosa than in healthy controls. Levels of dopamine are similar to, or lower than, those in controls. After remission of the disorder, noradrenergic function returns to that seen in controls, whereas dopaminergic and serotonergic function rebound to levels higher than in controls. Among the neuropeptides, alterations in the levels of neuropeptide Y, peptide YY, beta-endorphin, corticotrophin-releasing hormone, somatostatin, cholecystokinin and vasopressin have been found in the symptomatic phase of bulimia nervosa, with a return to levels seen in controls after remission. Pharmacological treatment of bulimia nervosa that is directed at correction of the neurochemical alterations observed is difficult because of the complexity of the impairments. However, such treatment is necessary and should be continued long after symptomatic remission to ensure reinstitution of cerebral biochemical homeostasis. PMID:11460890

  14. Autism

    Science.gov (United States)

    ... Anxiety Disorders Autism Bipolar Disorder Borderline Personality Disorder Depression Dissociative Disorders Eating Disorders Obsessive-Compulsive Disorder Posttraumatic Stress Disorder Schizoaffective ...

  15. Young Children with Autism Spectrum Disorder Do Not Preferentially Attend to Biological Motion

    Science.gov (United States)

    Annaz, Dagmara; Campbell, Ruth; Coleman, Mike; Milne, Elizabeth; Swettenham, John

    2012-01-01

    Preferential attention to biological motion can be seen in typically developing infants in the first few days of life and is thought to be an important precursor in the development of social communication. We examined whether children with autism spectrum disorder (ASD) aged 3-7 years preferentially attend to point-light displays depicting…

  16. Autism

    OpenAIRE

    Parr, Jeremy,

    2010-01-01

    Autism is one of a group of pervasive developmental disorders, and is characterised by qualitative impairments in communication and social interaction, and by repetitive and stereotyped behaviours and interests. Abnormal development is present before the age of 3 years. A quarter of affected children show developmental regression, with loss of previously acquired skills.One third of children with autism have epilepsy, and three quarters have mental retardation. Only 15% of adults with auti...

  17. Frontiers in the bioarchaeology of stress and disease: cross-disciplinary perspectives from pathophysiology, human biology, and epidemiology.

    Science.gov (United States)

    Klaus, Haagen D

    2014-10-01

    Over the last four decades, bioarchaeology has experienced significant technical growth and theoretical maturation. Early 21st century bioarchaeology may also be enhanced from a renewed engagement with the concept of biological stress. New insights on biological stress and disease can be gained from cross-disciplinary perspectives regarding human skeletal variation and disease. First, pathophysiologic and molecular signaling mechanisms can provide more precise understandings regarding formation of pathological phenotypes in bone. Using periosteal new bone formation as an example, various mechanisms and pathways are explored in which new bone can be formed under conditions of biological stress, particularly in bone microenvironments that involve inflammatory changes. Second, insights from human biology are examined regarding some epigenetic factors and disease etiology. While epigenetic effects on stress and disease outcomes appear profoundly influential, they are mostly invisible in skeletal tissue. However, some indirect and downstream effects, such as the developmental origins of adult health outcomes, may be partially observable in bioarchaeological data. Emerging perspectives from the human microbiome are also considered. Microbiomics involves a remarkable potential to understand ancient biology, disease, and stress. Third, tools from epidemiology are examined that may aid bioarchaeologists to better cope with some of the inherent limitations of skeletal samples to better measure and quantify the expressions of skeletal stress markers. Such cross-disciplinary synergisms hopefully will promote more complete understandings of health and stress in bioarchaeological science. PMID:25082158

  18. Biological Motion induced mu suppression is reduced in Early Psychosis (EP) patients with active negative symptoms and Autism Spectrum Disorders (ASD).

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    Minichino, Amedeo; Singh, Fiza; Pineda, Jaime; Friederich, Elisabeth; Cadenhead, Kristin S

    2016-04-30

    There is evidence of genetic and neural system overlap in Autism Spectrum Disorder (ASD) and Early Psychosis (EP). Five datasets were pooled to compare mu suppression index (MSI), a proxy of mirror neuron activity, in EP, high functioning ASD, and healthy subjects (HS). ASDs and EPs with "active" negative symptoms showed significant differences in mu suppression, in response to Biological Motion/point-light display animation, compared to HS. Preliminary findings suggest that similar neural network deficits in ASD and EP could be driven by the expression of negative symptoms in the latter group of patients. These findings may aid future studies on EP and ASD and facilitate the formulation of new hypotheses regarding their pathophysiology. PMID:26970656

  19. Autism

    OpenAIRE

    Levy, Susan E.; Mandell, David S.; Robert T. Schultz

    2009-01-01

    Autism spectrum disorders are characterised by severe deficits in socialisation, communication, and repetitive or unusual behaviours. Increases over time in the frequency of these disorders (to present rates of about 60 cases per 10 000 children) might be attributable to factors such as new administrative classifications, policy and practice changes, and increased awareness. Surveillance and screening strategies for early identification could enable early treatment and improved outcomes. Auti...

  20. Redox biology of hydrogen sulfide: Implications for physiology, pathophysiology, and pharmacology

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    Asaf Stein

    2013-01-01

    Full Text Available Hydrogen sulfide (H2S has emerged as a critical mediator of multiple physiological processes in mammalian systems. The pathways involved in the production, consumption, and mechanism of action of H2S appear to be sensitive to alterations in the cellular redox state and O2 tension. Indeed, the catabolism of H2S through a putative oxidation pathway, the sulfide quinone oxido-reductase system, is highly dependent on O2 tension. Dysregulation of H2S homeostasis has also been implicated in numerous pathological conditions and diseases. In this review, the chemistry and the main physiological actions of H2S are presented. Some examples highlighting the cytoprotective actions of H2S within the context of cardiovascular disease are also reported. Elucidation of the redox biology of H2S will enable the development of new pharmacological agents based on this intriguing new redox cellular signal.

  1. Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 1: Normal and Chronic Wounds: Biology, Causes, and Approaches to Care

    OpenAIRE

    Tatiana N Demidova-Rice; Michael R Hamblin; Herman, Ira M.

    2012-01-01

    This is the first installment of 2 articles that discuss the biology and pathophysiology of wound healing, review the role that growth factors play in this process, and describe current ways of growth factor delivery into the wound bed. Part 1 discusses the latest advances in clinicians’ understanding of the control points that regulate wound healing. Importantly, biological similarities and differences between acute and chronic wounds are considered, including the signaling pathways that ini...

  2. Recent advances in the involvement of long non-coding RNAs in neural stem cell biology and brain pathophysiology

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    PanagiotisKPolitis

    2014-04-01

    Full Text Available Exploration of non-coding genome has recently uncovered a growing list of formerly unknown regulatory long non-coding RNAs (lncRNAs with important functions in stem cell pluripotency, development and homeostasis of several tissues. Although thousands of lncRNAs are expressed in mammalian brain in a highly patterned manner, their roles in brain development have just begun to emerge. Recent data suggest key roles for these molecules in gene regulatory networks controlling neuronal and glial cell differentiation. Analysis of the genomic distribution of genes encoding for lncRNAs indicates a physical association of these regulatory RNAs with transcription factors (TFs with well-established roles in neural differentiation, suggesting that lncRNAs and TFs may form coherent regulatory networks with important functions in neural stem cells (NSCs. Additionally, many studies show that lncRNAs are involved in the pathophysiology of brain-related diseases/disorders. Here we discuss these observations and investigate the links between lncRNAs, brain development and brain-related diseases. Understanding the functions of lncRNAs in NSCs and brain organogenesis could revolutionize the basic principles of developmental biology and neuroscience.

  3. Robert Feulgen Prize Lecture 1993. The journey of the insulin receptor into the cell: from cellular biology to pathophysiology.

    Science.gov (United States)

    Carpentier, J L

    1993-09-01

    The data that we have reviewed indicate that insulin binds to a specific cell-surface receptor. The complex then becomes involved in a series of steps which lead the insulin-receptor complex to be internalized and rapidly delivered to endosomes. From this sorting station, the hormone is targeted to lysosomes to be degraded while the receptor is recycled back to the cell surface. This sequence of events presents two degrees of ligand specificity: (a) The first step is ligand-dependent and requires insulin-induced receptor phosphorylation of specific tyrosine residues. It consists in the surface redistribution of the receptor from microvilli where it preferentially localizes in its unoccupied form. (b) The second step is more general and consists in the association with clathrin-coated pits which represents the internalization gate common to many receptors. This sequence of events participates in the regulation of the biological action of the hormone and can thus be implicated in the pathophysiology of diabetes mellitus and various extreme insulin resistance syndromes, including type A extreme insulin resistance, leprechaunism, and Rabson-Mendehall syndrome. Alterations of the internalization process can result either from intrinsic abnormalities of the receptor or from more general alteration of the plasma membrane or of the cell metabolism. Type I diabetes is an example of the latter possibility, since general impairment of endocytosis could contribute to extracellular matrix accumulation and to an increase in blood cholesterol. Thus, better characterization of the molecular and cellular biology of the insulin receptor and of its journey inside the cell definitely leads to better understanding of disease states, including diabetes. PMID:8244769

  4. Recognizing biological motion and emotions from point-light displays in autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Evelien Nackaerts

    Full Text Available One of the main characteristics of Autism Spectrum Disorder (ASD are problems with social interaction and communication. Here, we explored ASD-related alterations in 'reading' body language of other humans. Accuracy and reaction times were assessed from two observational tasks involving the recognition of 'biological motion' and 'emotions' from point-light displays (PLDs. Eye movements were recorded during the completion of the tests. Results indicated that typically developed-participants were more accurate than ASD-subjects in recognizing biological motion or emotions from PLDs. No accuracy differences were revealed on two control-tasks (involving the indication of color-changes in the moving point-lights. Group differences in reaction times existed on all tasks, but effect sizes were higher for the biological and emotion recognition tasks. Biological motion recognition abilities were related to a person's ability to recognize emotions from PLDs. However, ASD-related atypicalities in emotion recognition could not entirely be attributed to more basic deficits in biological motion recognition, suggesting an additional ASD-specific deficit in recognizing the emotional dimension of the point light displays. Eye movements were assessed during the completion of tasks and results indicated that ASD-participants generally produced more saccades and shorter fixation-durations compared to the control-group. However, especially for emotion recognition, these altered eye movements were associated with reductions in task-performance.

  5. Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention

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    Hayes, Spencer J.; Andrew, Matthew; Elliott, Digby; Gowen, Emma; Bennett, Simon J.

    2016-01-01

    We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only…

  6. Multidisciplinary clinical and biological characteristics of hyperkinetic disorders in childhood autism

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    N. V. Simashkova

    2012-01-01

    Full Text Available The paper discusses the state of development of acquired hyperkinetic disorder in psychotic forms of autistic spectrum disorders. Attention deficit hyperactivity disorder (ADHD in childhood autism (childhood psychosis has pathopsychological markers as cognitive disontogenesis with delays in fine motor activity and visual motor coordination, neurophysiological markers as a high index of sensor motor rhythm, and immunological markers as preserved higher parameters of innate immunity in remission (the activity of leukocytic elastase, the level of acute phase proteins, such as α1-PI and C-reactive protein. The heterogeneity of ADHD requires that its nosological entities be identified to create clear differentiated habilitation algorithms in accordance with the principles of evidence-based medicine, by applying the multidisciplinary clinical and biological characteristics.

  7. Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.

    LENUS (Irish Health Repository)

    Anney, Richard J L

    2012-02-01

    Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O\\'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings.

  8. Autworks: a cross-disease network biology application for Autism and related disorders

    OpenAIRE

    Nelson Tristan H; Jung Jae-Yoon; DeLuca Todd F; Hinebaugh Byron K; St Gabriel Kristian; Wall Dennis P

    2012-01-01

    Abstract Background The genetic etiology of autism is heterogeneous. Multiple disorders share genotypic and phenotypic traits with autism. Network based cross-disorder analysis can aid in the understanding and characterization of the molecular pathology of autism, but there are few tools that enable us to conduct cross-disorder analysis and to visualize the results. Description We have designed Autworks as a web portal to bring together gene interaction and gene-disease association data on au...

  9. Autism Spectrum Disorders and Childhood-Onset Schizophrenia: Clinical and Biological Contributions to a Relation Revisited

    Science.gov (United States)

    Rapopart, Judith; Chavez, Alex; Greenstein, Deanna; Addington, Anjene; Gogtay, Nitin

    2009-01-01

    Clinical, demographic, and brain development data on childhood-onset schizophrenia (COS) and family, imaging and genetic data from studies of autism were reviewed. It is found that COS is preceded by and comorbid with autism/pervasive developmental disorder and schizophrenia in 30 to 50 percent of cases based on two large studies.

  10. Elevated fetal steroidogenic activity in autism.

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    Baron-Cohen, S; Auyeung, B; Nørgaard-Pedersen, B; Hougaard, D M; Abdallah, M W; Melgaard, L; Cohen, A S; Chakrabarti, B; Ruta, L; Lombardo, M V

    2015-03-01

    Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism. PMID:24888361

  11. Multidisciplinary Assessment and Treatment of Self-Injurious Behavior in Autism Spectrum Disorder and Intellectual Disability: Integration of Psychological and Biological Theory and Approach

    Science.gov (United States)

    Minshawi, Noha F.; Hurwitz, Sarah; Morriss, Danielle; McDougle, Christopher J.

    2015-01-01

    The objective of this review is to consider the psychological (largely behavioral) and biological [neurochemical, medical (including genetic), and pharmacological] theories and approaches that contribute to current thinking about the etiology and treatment of self-injurious behavior (SIB) in individuals with autism spectrum disorder and/or…

  12. Advances in autism.

    Science.gov (United States)

    Geschwind, Daniel H

    2009-01-01

    Autism is a common childhood neurodevelopmental disorder with strong genetic liability. It is not a unitary entity but a clinical syndrome, with variable deficits in social behavior and language, restrictive interests, and repetitive behaviors. Recent advances in the genetics of autism emphasize its etiological heterogeneity, with each genetic susceptibility locus accounting for only a small fraction of cases or having a small effect. Therefore, it is not surprising that no unifying structural or neuropathological features have been conclusively identified. Given the heterogeneity of autism spectrum disorder (ASD), approaches based on studying heritable components of the disorder, or endophenotypes, such as language or social cognition, provide promising avenues for genetic and neurobiological investigations. Early intensive behavioral and cognitive interventions are efficacious in many cases, but autism does not remit in the majority of children. Therefore, development of targeted therapies based on pathophysiologically and etiologically defined subtypes of ASD remains an important and achievable goal of current research. PMID:19630577

  13. Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation

    Science.gov (United States)

    Guilmatre, Audrey; Dubourg, Christèle; Mosca, Anne-Laure; Legallic, Solenn; Goldenberg, Alice; Drouin-Garraud, Valérie; Layet, Valérie; Rosier, Antoine; Briault, Sylvain; Bonnet-Brilhault, Frédérique; Laumonnier, Frédéric; Odent, Sylvie; Le Vacon, Gael; Joly-Helas, Géraldine; David, Véronique; Bendavid, Claude; Pinoit, Jean-Michel; Henry, Céline; Impallomeni, Caterina; Germano, Eva; Tortorella, Gaetano; Di Rosa, Gabriella; Barthelemy, Catherine; Andres, Christian; Faivre, Laurence; Frébourg, Thierry; Saugier Veber, Pascale; Campion, Dominique

    2009-01-01

    Context Comparative genomic hybridization (array-CGH) studies have suggested that rare copy number variations (CNVs) at numerous loci are involved in the etiology of mental retardation (MR), autism spectrum disorders (ASD) and schizophrenia. Objective The goal of the present paper was (i) to provide an estimate of the collective frequency of a set of recurrent/overlapping CNVs in three different groups of patients as compared with healthy controls and (ii) to assess whether each CNV is present in more than one clinical category. Design, setting and population We have investigated 28 candidate loci previously identified by array-CGH studies for gene dosage alteration in 247 subjects with MR, 260 with ASD, 236 with schizophrenia or schizoaffective disorder and 236 healthy controls. Main outcome measures Collective and individual frequency of the analyzed CNVs in patients as compared with controls. Results Recurrent or overlapping CNVs were found in patients at 40% of the selected loci. We show that the collective frequency of CNVs at these loci is significantly increased in autistic patients, patients with schizophrenia and patients with MR as compared with controls (p= 0.005, p< 0.001 and p= 0.001 respectively, Fisher exact test). Individual significance (p= 0.02) was reached for association between autism and a 350 kb deletion located in 22q11 and spanning the PRODH gene. Conclusions These results support the hypothesis that weakly to moderately recurrent CNVs, either transmitted or occurring de novo, are causing or contributory factors for these diseases. Second, we show that most of these CNVs, which contain genes involved in neurotransmission or synapse formation and maintenance, are present in the 3 pathological conditions, supporting the existence of shared biological pathways between these neurodevelopmental disorders. PMID:19736351

  14. Biological changes in auditory function following training in children with autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Nicol Trent

    2010-10-01

    Full Text Available Abstract Background Children with pervasive developmental disorders (PDD, such as children with autism spectrum disorders (ASD, often show auditory processing deficits related to their overarching language impairment. Auditory training programs such as Fast ForWord Language may potentially alleviate these deficits through training-induced improvements in auditory processing. Methods To assess the impact of auditory training on auditory function in children with ASD, brainstem and cortical responses to speech sounds presented in quiet and noise were collected from five children with ASD who completed Fast ForWord training. Results Relative to six control children with ASD who did not complete Fast ForWord, training-related changes were found in brainstem response timing (three children and pitch-tracking (one child, and cortical response timing (all five children after Fast ForWord use. Conclusions These results provide an objective indication of the benefit of training on auditory function for some children with ASD.

  15. Thalassemia: Pathophysiology and management. Part A

    International Nuclear Information System (INIS)

    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

  16. Gold Nanoparticles and Lipoic Acid as a Novel Anti-Inflammatory Treatment for Autism, A Hypothesis

    OpenAIRE

    Ahmad Ghanizadeh

    2012-01-01

    Autism is a neurodevelopment disorder. Its aetiology and pathophysiology are not clearly known. However, mitochondria may play a significant role at least in some cases of autism. There is no therapeutic approach for autism. Moreover, there are only few Food and Drug Administration (FDA)-approved medications for autism. Therefore, providing novel therapeutic approaches are highly required. Oxidative stress is suggested as an important factor in the aetiology of autism. Already some interventi...

  17. Neuroimaging of autism

    Energy Technology Data Exchange (ETDEWEB)

    Verhoeven, Judith S.; Cock, Paul de; Lagae, Lieven [University Hospitals of the Catholic University of Leuven, Department of Pediatrics, Leuven (Belgium); Sunaert, Stefan [University Hospitals of the Catholic University of Leuven, Department of Radiology, Leuven (Belgium)

    2010-01-15

    Neuroimaging studies done by means of magnetic resonance imaging (MRI) have provided important insights into the neurobiological basis for autism. The aim of this article is to review the current state of knowledge regarding brain abnormalities in autism. Results of structural MRI studies dealing with total brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala and the area of the corpus callosum are summarised. In the past 5 years also new MRI applications as functional MRI and diffusion tensor imaging brought considerable new insights in the pathophysiological mechanisms of autism. Dysfunctional activation in key areas of verbal and non-verbal communication, social interaction, and executive functions are revised. Finally, we also discuss white matter alterations in important communication pathways in the brain of autistic patients. (orig.)

  18. Neuroimaging of autism

    International Nuclear Information System (INIS)

    Neuroimaging studies done by means of magnetic resonance imaging (MRI) have provided important insights into the neurobiological basis for autism. The aim of this article is to review the current state of knowledge regarding brain abnormalities in autism. Results of structural MRI studies dealing with total brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala and the area of the corpus callosum are summarised. In the past 5 years also new MRI applications as functional MRI and diffusion tensor imaging brought considerable new insights in the pathophysiological mechanisms of autism. Dysfunctional activation in key areas of verbal and non-verbal communication, social interaction, and executive functions are revised. Finally, we also discuss white matter alterations in important communication pathways in the brain of autistic patients. (orig.)

  19. Autism Plus versus Autism Pure

    Science.gov (United States)

    Gillberg, Christopher; Fernell, Elisabeth

    2014-01-01

    The reported prevalence of autism is going up and up. We propose that some--even much--of the increase in the rate of autism spectrum disorder (ASD) is driven by "Autism Plus". Autism Plus refers to autism with comorbidities (including intellectual developmental disorder, language disorder, and attention-deficit/hyperactivity disorder),…

  20. Genetic heterogeneity in autism: From single gene to a pathway perspective.

    Science.gov (United States)

    An, Joon Yong; Claudianos, Charles

    2016-09-01

    The extreme genetic heterogeneity of autism spectrum disorder (ASD) represents a major challenge. Recent advances in genetic screening and systems biology approaches have extended our knowledge of the genetic etiology of ASD. In this review, we discuss the paradigm shift from a single gene causation model to pathway perturbation model as a guide to better understand the pathophysiology of ASD. We discuss recent genetic findings obtained through next-generation sequencing (NGS) and examine various integrative analyses using systems biology and complex networks approaches that identify convergent patterns of genetic elements associated with ASD. PMID:27317861

  1. Autism Society

    Science.gov (United States)

    Home Contact Us Home About Autism Symptoms Diagnosis Causes Asperger’s Syndrome Facts and Statistics Living with Autism Autism through the Lifespan Navigating Services Legal Resources Treatment Options ...

  2. Pathophysiology of nasal congestion

    Directory of Open Access Journals (Sweden)

    Robert M Naclerio

    2010-02-01

    Full Text Available Robert M Naclerio1, Claus Bachert2, James N Baraniuk31University of Chicago, Department of Surgery, Section of Otolaryngology – Head and Neck Surgery, Chicago, Illinois, USA; 2University of Ghent, Ghent, Belgium; 3Georgetown University, Washington, DC, USAAbstract: Nasal congestion is a common symptom in rhinitis (both allergic and nonallergic, rhinosinusitis and nasal polyposis. Congestion can also be caused by physical obstruction of nasal passages and/or modulation of sensory perception. Mucosal inflammation underlies many of the specific and interrelated factors that contribute to nasal congestion, as well as other symptoms of both allergic rhinitis and rhinosinusitis. A wide range of biologically active agents (eg, histamine, tumor necrosis factor-α, interleukins, cell adhesion molecules and cell types contribute to inflammation, which can manifest as venous engorgement, increased nasal secretions and tissue swelling/edema, ultimately leading to impaired airflow and the sensation of nasal congestion. Inflammation-induced changes in the properties of sensory afferents (eg, expression of peptides and receptors that innervate the nose can also contribute to altered sensory perception, which may result in a subjective feeling of congestion. Increased understanding of the mechanisms underlying inflammation can facilitate improved treatment selection and the development of new therapies for congestion.Keywords: allergic rhinitis, congestion, obstruction, pathophysiology, rhinosinusitis

  3. The pathophysiology of agitation.

    Science.gov (United States)

    Lindenmayer, J P

    2000-01-01

    Agitation is a nonspecific constellation of relatively unrelated behaviors that can be seen in a number of different clinical conditions, usually presenting a fluctuating course. Multiple underlying pathophysiologic abnormalities are mediated by dysregulations of dopaminergic, serotonergic, noradrenergic, and GABAergic systems. Pathophysiologic mechanisms of agitation that operate in the different clinical disorders where agitation occurs are discussed. These pathophysiologic abnormalities are not associated with distinct clinical features. Although there may be a final common pathway, there is no unifying etiologic pathophysiology. The author suggests that the clinician address the underlying pathophysiology through a treatment intervention that addresses the overarching psychiatric disorder. Generally, agents that reduce dopaminergic or noradrenergic tone or increase serotonergic or GABAergic tone will attenuate agitation, often irrespective of etiology. PMID:11154018

  4. The Pathophysiology of Insomnia

    OpenAIRE

    Levenson, Jessica C.; Kay, Daniel B.; Buysse, Daniel J.

    2015-01-01

    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 importa...

  5. The pathophysiology of insomnia.

    Science.gov (United States)

    Levenson, Jessica C; Kay, Daniel B; Buysse, Daniel J

    2015-04-01

    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

  6. Amygdala and Hippocampus Enlargement during Adolescence in Autism

    Science.gov (United States)

    Groen, Wouter; Teluij, Michelle; Buitelaar, Jan; Tendolkar, Indira

    2010-01-01

    Objective: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse.…

  7. Towards Identification of Individual Etiologies by Resolving Genomic and Biological Conundrums in Patients with Autism Spectrum Disorders

    OpenAIRE

    Poot, M.

    2013-01-01

    Recent genomic research into autism spectrum disorders (ASD) has revealed a remarkably complex genetic architecture. Large numbers of common variants, copy number variations and single nucleotide variants have been identified, yet each of them individually afforded only a small phenotypic impact. A polygenic model in which multiple genes interact either in an additive or a synergistic way appears the most plausible for the majority of ASD patients. Based on recently identified ASD candidate g...

  8. Gene ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders

    OpenAIRE

    Anney, Richard JL; Heron, Elizabeth A; Segurado, Ricardo; Kenny, Elaine M.; O'Dushlaine, Colm; Yaspan, Brian L.; Parkhomenko, Elena; Autism Genome Project, The; Buxbaum, Joseph,; Sutcliffe, James S; Gill, Micheal; Gallagher, Louise

    2011-01-01

    We gratefully acknowledge the families participating in the study and the main funders of the AGP: Autism Speaks (USA), the Health Research Board (HRB, Ireland; AUT/2006/1, AUT/2006/2, PD/2006/48), The Medical Research Council (MRC, UK), Genome Canada/Ontario Genomics Institute and the Hilibrand Foundation (USA). Additional support for individual groups was provided by the US National Institutes of Health (NIH Grants: HD055751, HD055782, HD055784, MH52708, MH55284, MH061009,...

  9. Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation

    OpenAIRE

    Guilmatre, Audrey; Dubourg, Christèle; Mosca, Anne-Laure; Legallic, Solenn; Goldenberg, Alice; Drouin-Garraud, Valérie; Layet, Valérie; Rosier, Antoine; Briault, Sylvain; Bonnet-Brilhault, Frédérique; Laumonnier, Frédéric; Odent, Sylvie; Le Vacon, Gael; Joly-Helas, Géraldine; David, Véronique

    2009-01-01

    International audience CONTEXT: Results of comparative genomic hybridization studies have suggested that rare copy number variations (CNVs) at numerous loci are involved in the cause of mental retardation, autism spectrum disorders, and schizophrenia. OBJECTIVES: To provide an estimate of the collective frequency of a set of recurrent or overlapping CNVs in 3 different groups of cases compared with healthy control subjects and to assess whether each CNV is present in more than 1 clinical c...

  10. Autism, oxytocin and interoception.

    Science.gov (United States)

    Quattrocki, E; Friston, Karl

    2014-11-01

    Autism is a pervasive developmental disorder characterized by profound social and verbal communication deficits, stereotypical motor behaviors, restricted interests, and cognitive abnormalities. Autism affects approximately 1% of children in developing countries. Given this prevalence, identifying risk factors and therapeutic interventions are pressing objectives—objectives that rest on neurobiologically grounded and psychologically informed theories about the underlying pathophysiology. In this article, we review the evidence that autism could result from a dysfunctional oxytocin system early in life. As a mediator of successful procreation, not only in the reproductive system, but also in the brain, oxytocin plays a crucial role in sculpting socio-sexual behavior. Formulated within a (Bayesian) predictive coding framework, we propose that oxytocin encodes the saliency or precision of interoceptive signals and enables the neuronal plasticity necessary for acquiring a generative model of the emotional and social 'self.' An aberrant oxytocin system in infancy could therefore help explain the marked deficits in language and social communication—as well as the sensory, autonomic, motor, behavioral, and cognitive abnormalities—seen in autism. PMID:25277283

  11. Psychosis and autism: magnetic resonance imaging study of brain anatomy.

    LENUS (Irish Health Repository)

    Toal, Fiona

    2009-05-01

    Autism-spectrum disorder is increasingly recognised, with recent studies estimating that 1% of children in South London are affected. However, the biology of comorbid mental health problems in people with autism-spectrum disorder is poorly understood.

  12. Autism Speaks

    Science.gov (United States)

    ... summary of House to Home Prize Congress highlights role of small business employing those with autism The Importance of Water Safety: Tips and Tools See all Families & Adults Adult Services Autism Apps and Technology Autism Response Team Community Outreach Grants Non-English Resources Resource Guide ...

  13. Autism Assets

    Science.gov (United States)

    Sarahan, Neal; Copas, Randy

    2014-01-01

    The Center for Disease Control estimates that 1 in 88 children have been identified with autism (CDC, 2012). Autism is often associated with other psychiatric, developmental, neurological, and genetic diagnoses. However, the majority (62%) of children identified on the autism spectrum do not have intellectual disability. Instead, they are hurting.…

  14. How autism became autism

    Science.gov (United States)

    Evans, Bonnie

    2013-01-01

    This article argues that the meaning of the word ‘autism’ experienced a radical shift in the early 1960s in Britain which was contemporaneous with a growth in epidemiological and statistical studies in child psychiatry. The first part of the article explores how ‘autism’ was used as a category to describe hallucinations and unconscious fantasy life in infants through the work of significant child psychologists and psychoanalysts such as Jean Piaget, Lauretta Bender, Leo Kanner and Elwyn James Anthony. Theories of autism were then associated both with schizophrenia in adults and with psychoanalytic styles of reasoning. The closure of institutions for ‘mental defectives’ and the growth in speech therapy services in the 1960s and 1970s encouraged new models for understanding autism in infants and children. The second half of the article explores how researchers such as Victor Lotter and Michael Rutter used the category of autism to reconceptualize psychological development in infants and children via epidemiological studies. These historical changes have influenced the form and function of later research into autism and related conditions. PMID:24014081

  15. Pathophysiology of migraine

    Directory of Open Access Journals (Sweden)

    Peter J Goadsby

    2012-01-01

    Full Text Available Migraine is a common disabling brain disorder whose pathophysiology is now being better understood. The study of anatomy and physiology of pain producing structures in the cranium and the central nervous system modulation of the input have led to the conclusion that migraine involves alterations in the sub-cortical aminergic sensory modulatory systems that influence the brain widely.

  16. Autism through the Lifespan

    Science.gov (United States)

    ... Contact Us Home About Autism Symptoms Diagnosis Causes Asperger’s Syndrome Facts and Statistics Living with Autism Autism through ... Lifespan Autism through the Lifespan In our culture, autism spectrum disorder is often thought of as a childhood condition, ...

  17. Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops.

    Science.gov (United States)

    Mullins, Caitlin; Fishell, Gord; Tsien, Richard W

    2016-03-16

    Understanding the mechanisms underlying autism spectrum disorders (ASDs) is a challenging goal. Here we review recent progress on several fronts, including genetics, proteomics, biochemistry, and electrophysiology, that raise motivation for forming a viable pathophysiological hypothesis. In place of a traditionally unidirectional progression, we put forward a framework that extends homeostatic hypotheses by explicitly emphasizing autoregulatory feedback loops and known synaptic biology. The regulated biological feature can be neuronal electrical activity, the collective strength of synapses onto a dendritic branch, the local concentration of a signaling molecule, or the relative strengths of synaptic excitation and inhibition. The sensor of the biological variable (which we have termed the homeostat) engages mechanisms that operate as negative feedback elements to keep the biological variable tightly confined. We categorize known ASD-associated gene products according to their roles in such feedback loops and provide detailed commentary for exemplar genes within each module. PMID:26985722

  18. Autism across Cultures: Rethinking Autism

    Science.gov (United States)

    Kim, Hyun Uk

    2012-01-01

    Whereas the autism prevalence rate has been very closely monitored in the United States, the same has not been observed in many other countries. This may be attributed to the fact that each culture views and defines autism differently. Using field notes and semi-structured interviews with family members with an individual with autism, teachers,…

  19. Moving from Capstones towards Cornerstones: Successes and challenges in applying systems biology to identify mechanisms of autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Nathan eKopp

    2015-10-01

    Full Text Available The substantial progress in the last few years towards uncovering genetic causes and risk factors for autism spectrum disorders (ASD has opened new experimental avenues for identifying the underlying neurobiological mechanism of the condition. The bounty of genetic findings has led to a variety of data-driven exploratory analyses aimed at deriving new insights about the shared features of these genes. These approaches leverage data from a variety of different sources such as co-expression in transcriptomic studies, protein-protein interaction networks, Gene Ontologies annotations, or multi-level combinations of all of these. Here, we review the recurrent themes emerging from these analyses and highlight some of the challenges going forward. Themes include findings that ASD associated genes discovered by a variety of methods have been shown to contain disproportionate amounts of neurite outgrowth/cytoskeletal, synaptic, and more recently Wnt-related and chromatin modifying genes. Expression studies have highlighted a disproportionate expression of ASD gene sets during mid fetal cortical development, particularly for rare-variants, with multiple analyses highlighting the striatum and cortical projection and interneurons as well. While these explorations have highlighted potentially interesting relationships among these ASD-related genes, there are challenges in how to best transition these insights into empirically testable hypotheses. Nonetheless, defining shared molecular or cellular pathology downstream of the diverse genes associated with autism spectrum disorders could provide the cornerstones needed to build towards broadly applicable therapeutic approaches.

  20. [PATHOPHYSIOLOGY OF CARDIORENAL SYNDROME].

    Science.gov (United States)

    Thervet, Éric

    2016-06-01

    The pathophysiology of cardiorenal syndromes (SCR) is becoming better understood. The traditional view was that the left ventricular systolic dysfunction leads to a decrease in renal blood flow. Although this mechanism still makes sense as a contributing factor to SCR, its role as the principal pathophysiological SCR component or even as essential hemodynamic underlying factor has been challenged by recent discoveries. Regarding hemodynamic, the role of increased venous pressure is more and more accepted as demonstrated by the increase in abdominal pressure. Moreover, the role of neurohormonal mechanisms is emphasized in particular through the autonomic nervous system, the renin angiotensin aldosterone system, arginine vasopressin, adenosine and inflammatory mediators. Abnormal endothelial function is also responsible for a worsening of lesions especially through the reduction of shear stress. Finally, atherosclerosis, proteinuria, anemia with iron metabolism modifications, the nutritional status and vitamin D deficiency as well as FGF23 changes may be important and could represent interesting new therapeutic approaches in patients with SCR. PMID:27538312

  1. Obesity: Pathophysiology and Intervention

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2014-11-01

    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.

  2. Pathophysiology of cancer cachexia

    OpenAIRE

    Younes Riad N.; Noguchi Yoshikazu

    2000-01-01

    Cancer cachexia is a frequent complication observed in patients with malignant tumors. Although several decades have passed since the first focus on the metabolic dysfunction's associated with cancer, few effective therapeutic interventions have been successfully introduced into the medical armamentarium. The present study thoroughly reviews the basic pathophysiology of cancer cachexia and the treatment options already investigated in that field. Experimental and clinical studies were evaluat...

  3. Reform in Teaching Preclinical Pathophysiology

    Science.gov (United States)

    Li, Yong-Yu; Li, Kun; Yao, Hong; Xu, Xiao-Juan; Cai, Qiao-Lin

    2015-01-01

    Pathophysiology is a scientific discipline that studies the onset and progression of pathological conditions and diseases, and pathophysiology is one of the core courses in most preclinical medical curricula. In China, most medical schools house a Department of Pathophysiology, in contrast to medical schools in many developed countries. The staff…

  4. Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging Technologies.

    Science.gov (United States)

    Nestor, Michael W; Phillips, Andre W; Artimovich, Elena; Nestor, Jonathan E; Hussman, John P; Blatt, Gene J

    2016-05-01

    Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental condition. Symptoms of ASD cover the spectrum from mild qualitative differences in social interaction to severe communication and social and behavioral challenges that require lifelong support. Attempts at understanding the pathophysiology of ASD have been hampered by a multifactorial etiology that stretches the limits of current behavioral and cell based models. Recent progress has implicated numerous autism-risk genes but efforts to gain a better understanding of the underlying biological mechanisms have seen slow progress. This is in part due to lack of appropriate models for complete molecular and pharmacological studies. The advent of induced pluripotent stem cells (iPSC) has reinvigorated efforts to establish more complete model systems that more reliably identify molecular pathways and predict effective drug targets and candidates in ASD. iPSCs are particularly appealing because they can be derived from human patients and controls for research purposes and provide a technology for the development of a personalized treatment regimen for ASD patients. The pluripotency of iPSCs allow them to be reprogrammed into a number of CNS cell types and phenotypically screened across many patients. This quality is already being exploited in protocols to generate 2-dimensional (2-D) and three-dimensional (3-D) models of neurons and developing brain structures. iPSC models make powerful platforms that can be interrogated using electrophysiology, gene expression studies, and other cell-based quantitative assays. iPSC technology has limitations but when combined with other model systems has great potential for helping define the underlying pathophysiology of ASD. Autism Res 2016, 9: 513-535. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26426199

  5. Development of Motion Processing in Children with Autism

    Science.gov (United States)

    Annaz, Dagmara; Remington, Anna; Milne, Elizabeth; Coleman, Mike; Campbell, Ruth; Thomas, Michael S. C.; Swettenham, John

    2010-01-01

    Recent findings suggest that children with autism may be impaired in the perception of biological motion from moving point-light displays. Some children with autism also have abnormally high motion coherence thresholds. In the current study we tested a group of children with autism and a group of typically developing children aged 5 to 12 years of…

  6. Pathophysiology of primary headaches

    DEFF Research Database (Denmark)

    Edvinsson, L

    2001-01-01

    The cerebral circulation is innervated by sympathetic, parasympathetic, and sensory nerves, which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide w...... normalized. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches.......The cerebral circulation is innervated by sympathetic, parasympathetic, and sensory nerves, which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide was...

  7. The pathophysiology of bronchiectasis

    Directory of Open Access Journals (Sweden)

    Paul T King

    2009-10-01

    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

  8. Perspective Biological Markers for Autism Spectrum Disorders: Advantages of the Use of Receiver Operating Characteristic Curves in Evaluating Marker Sensitivity and Specificity

    Directory of Open Access Journals (Sweden)

    Provvidenza M. Abruzzo

    2015-01-01

    Full Text Available Autism Spectrum Disorders (ASD are a heterogeneous group of neurodevelopmental disorders. Recognized causes of ASD include genetic factors, metabolic diseases, toxic and environmental factors, and a combination of these. Available tests fail to recognize genetic abnormalities in about 70% of ASD children, where diagnosis is solely based on behavioral signs and symptoms, which are difficult to evaluate in very young children. Although it is advisable that specific psychotherapeutic and pedagogic interventions are initiated as early as possible, early diagnosis is hampered by the lack of nongenetic specific biological markers. In the past ten years, the scientific literature has reported dozens of neurophysiological and biochemical alterations in ASD children; however no real biomarker has emerged. Such literature is here reviewed in the light of Receiver Operating Characteristic (ROC analysis, a very valuable statistical tool, which evaluates the sensitivity and the specificity of biomarkers to be used in diagnostic decision making. We also apply ROC analysis to some of our previously published data and discuss the increased diagnostic value of combining more variables in one ROC curve analysis. We also discuss the use of biomarkers as a tool for advancing our understanding of nonsyndromic ASD.

  9. Optical diffraction tomography techniques for the study of cell pathophysiology

    CERN Document Server

    Kim, Kyoohyun; Shin, Seungwoo; Lee, SangYun; Yang, Su-A; Park, YongKeun

    2016-01-01

    Three-dimensional imaging of biological cells is crucial for the investigation of cell biology, provide valuable information to reveal the mechanisms behind pathophysiology of cells and tissues. Recent advances in optical diffraction tomography (ODT) have demonstrated the potential for the study of various cells with its unique advantages of quantitative and label-free imaging capability. To provide insight on this rapidly growing field of research and to discuss its applications in biology and medicine, we present the summary of the ODT principle and highlight recent studies utilizing ODT with the emphasis on the applications to the pathophysiology of cells.

  10. Psychoactive Pharmaceuticals Induce Fish Gene Expression Profiles Associated with Human Idiopathic Autism

    OpenAIRE

    Thomas, Michael A.; Klaper, Rebecca D.

    2012-01-01

    Idiopathic autism, caused by genetic susceptibility interacting with unknown environmental triggers, has increased dramatically in the past 25 years. Identifying environmental triggers has been difficult due to poorly understood pathophysiology and subjective definitions of autism. The use of antidepressants by pregnant women has been associated with autism. These and other unmetabolized psychoactive pharmaceuticals (UPPs) have also been found in drinking water from surface sources, providing...

  11. Epigenetic Findings in Autism: New Perspectives for Therapy

    Directory of Open Access Journals (Sweden)

    James Jeffrey Bradstreet

    2013-09-01

    Full Text Available Autism and autism spectrum disorders (ASDs are complex neurodevelopmental disorders characterized by dysfunctions in social interactions, communications, restricted interests, and repetitive stereotypic behaviors. Despite extensive genetic and biological research, significant controversy surrounds our understanding of the specific mechanisms of their pathogenesis. However, accumulating evidence points to the involvement of epigenetic modifications as foundational in creating ASD pathophysiology. Epigenetic modifications or the alteration of DNA transcription via variations in DNA methylation and histone modifications but without alterations in the DNA sequence, affect gene regulation. These alterations in gene expression, obtained through DNA methylation and/or histone modifications, result from transcriptional regulatory influences of environmental factors, such as nutritional deficiencies, various toxicants, immunological effects, and pharmaceuticals. As such these effects are epigenetic regulators which determine the final biochemistry and physiology of the individual. In contrast to psychopharmacological interventions, bettering our understanding of how these gene-environmental interactions create autistic symptoms should facilitate the development of therapeutic targeting of gene expression for ASD biomedical care.

  12. National Database for Autism Research (NDAR)

    Data.gov (United States)

    U.S. Department of Health & Human Services — National Database for Autism Research (NDAR) is an extensible, scalable informatics platform for austism spectrum disorder-relevant data at all levels of biological...

  13. The Pathophysiology of Concussion.

    Science.gov (United States)

    Choe, Meeryo C

    2016-06-01

    Concussion is a significant issue in medicine and the media today. With growing interest on the long-term effects of sports participation, it is important to understand what occurs in the brain after an impact of any degree. While some of the basic pathophysiology has been elucidated, much is still unknown about what happens in the brain after traumatic brain injury, particularly with milder injuries where no damage can be seen at the structural level on standard neuroimaging. Understanding the chain of events from a cellular level using studies investigating more severe injuries can help to drive research efforts in understanding the symptomatology that is seen in the acute phase after concussion, as well as point to mechanisms that may underlie persistent post-concussive symptoms. This review discusses the basic neuropathology that occurs after traumatic brain injury at the cellular level. We also present the pathology of chronic traumatic encephalopathy and its similarities to other neurodegenerative diseases. We conclude with recent imaging and biomarker findings looking at changes that may occur after repeated subconcussive blows, which may help to guide efforts in understanding if cumulative subconcussive mechanical forces upon the brain are detrimental in the long term or if concussive symptoms mark the threshold for brain injury. PMID:27184060

  14. Global Autism: Autism, Autism Etiology, Perceptions, Epistemology, Prevalence and Action

    OpenAIRE

    Ganaie S.A; Bashir A

    2014-01-01

    Autism is a Neuro-Developmental Disorder affecting socialization and communication with stereotype behaviors. The research Scientists all over world found that genetic and environmental factors are causes of Autism Spectrum Disorders. Over the past decade, worldwide Autism, advanced rehabilitation services and research estimates of increase between 50% to over 2000% in cases of Autism Spectrum Disorder diagnoses. The rise in diagnoses of Autism Spectrum Disorder impacts us all....

  15. Pathophysiology of cancer cachexia

    Directory of Open Access Journals (Sweden)

    Riad N. Younes

    2000-10-01

    Full Text Available Cancer cachexia is a frequent complication observed in patients with malignant tumors. Although several decades have passed since the first focus on the metabolic dysfunction's associated with cancer, few effective therapeutic interventions have been successfully introduced into the medical armamentarium. The present study thoroughly reviews the basic pathophysiology of cancer cachexia and the treatment options already investigated in that field. Experimental and clinical studies were evaluated individually in order to clarify the intricate alterations observed in tumor-bearing patients. The difficulties in introducing sound and effective nutritional support or metabolic manipulation to reverse cancer cachexia are outlined in this review.A caquexia é uma complicação freqüentemente observada em pacientes portadores de tumores malignos. Apesar de várias décadas transcorrerem desde a descrição inicial das disfunções metabólicas associadas ao câncer, poucas medidas terapêuticas foram induzidas com sucesso na prática médica. O presente estudo apresenta uma revisão detalhada da fisiopatologia básica da caquexia em câncer, e as opções terapêuticas desenvolvidas nesta área. Estudos experimentais, assim como clínicos, são avaliados individualmente para esclarecer as alterações complexas observadas em pacientes portadores de tumores. As dificuldades encontradas para introduzir manipulações metabólicas e terapias de suporte nutricional eficientes são discutidas nesta revisão.

  16. Autism and Genes

    Science.gov (United States)

    National Institutes of Health, 2005

    2005-01-01

    This document defines and discusses autism and how genes play a role in the condition. Answers to the following questions are covered: (1) What are genes? (2) What is autism? (3) What causes autism? (4) Why study genes to learn about autism? (5) How do researchers look for the genes involved in autism? (screen the whole genome; conduct cytogenetic…

  17. [Autism: neuroimaging].

    Science.gov (United States)

    Zilbovicius, Mônica; Meresse, Isabelle; Boddaert, Nathalie

    2006-05-01

    Autism is a neurodevelopmental disorder with a range of clinical presentations. These presentations vary from mild to severe and are referred to as autism spectrum disorders. The most common clinical sign of autism spectrum disorders is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and repetitive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in autism spectrum disorders. Indeed, functional brain imaging, such as positron emission tomography, single foton emission tomography and functional MRI have opened a new perspective to study normal and pathological brain functioning. Three independent studies have found anatomical and rest functional temporal lobe abnormalities in autistic patients. These alterations are localized in the superior temporal sulcus bilaterally, an area which is critical for perception of key social stimuli. In addition, functional studies have shown hypoactivation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network in autism. The understanding of the functional alterations of this important mechanism may drive the elaboration of new and more adequate social re-educative strategies for autistic patients. PMID:16791388

  18. Autism Spectrum Disorder (ASD)

    Science.gov (United States)

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Autism spectrum disorder (ASD) is a group of developmental ... key findings. About Us Overview of CDC’s work. Autism: What's New New Data on Autism: Five Facts ...

  19. Self-Organization of an Artificial Neural Network Subjected to Attention Shift Impairments and Familiarity Preference, Characteristics Studied in Autism

    Science.gov (United States)

    Gustafsson, Lennart; Paplinski, Andrew

    2004-01-01

    Autism is a developmental disorder with possibly multiple pathophysiologies. It has been theorized that cortical feature maps in individuals with autism are inadequate for forming abstract codes and representations. Cortical feature maps make it possible to classify stimuli, such as phonemes of speech, disregarding incidental detail. Hierarchies…

  20. Neonatal chemokine levels and risk of autism spectrum disorders

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Larsen, Nanna; Grove, Jakob; Bonefeld-Jørgensen, Eva Cecilie; Nørgaard-Pedersen, Bent; Hougaard, David M; Mortensen, Erik L

    2013-01-01

    A potential role of chemokines in the pathophysiology of Autism Spectrum Disorders (ASDs) has been previously suggested. In a recent study we examined levels of three inflammatory chemokines (MCP-1, MIP-1a and RANTES) in samples of amniotic fluid of children diagnosed later in life with ASD and...

  1. Elevated fetal steroidogenic activity in autism

    OpenAIRE

    Baron-Cohen, S.; Auyeung, B; Nørgaard-Pedersen, B; Hougaard, D. M.; Abdallah, M. W.; Melgaard, L.; Cohen, A S; Chakrabarti, Bhisma; Ruta, L.; Lombardo, M V

    2015-01-01

    Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive deve...

  2. Potential Biomarkers for Diagnosis and Screening of Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2014-12-01

    Full Text Available BACKGROUND: Autism spectrum disorder (ASD is a highly heritable neurodevelopmental condition, which is typically characterized by a triad of symptoms: impaired social communication, social reciprocity and repetitive stereotypic behavior. While the behavioral phenotype of ASD is well described, the search for reliable ‘autism biomarkers’ continues. CONTENT: Insulin growth factor (IGF is essential for the myelination of developing fetal neurons; this is in addition to the well-known links between IGF, maternal inflammation, infection and autism supporting IGF as a potential marker. Combining IGF data with data regarding levels of the known markers, serotonin and anti-myelin basic protein, in order to calculate an autism index, could provide a new diagnostic method for at-risk neonates. Disruptions to multiple pathophysiological systems, including redox, folate, methylation, tryptophan metabolism, and mitochondrial metabolism, have been well documented in autistic patients. Maternal infection and inflammation have known links with autism. Autoimmunity has therefore been a well-studied area of autism research. The potential of using autoantibodies as novel biomarkers for autism, in addition to providing insights into the neurodevelopmental processes that lead to autism. SUMMARY: The six proposed causes of autism involve both metabolic and immunologic dysfunctions and include: increased oxidative stress; decreased methionine metabolism and trans-sulfuration: aberrant free and bound metal burden; gastrointestinal (GI disturbances; immune/inflammation dysregulation; and autoimmune targeting. A newborn screening program for early-onset ASD should be capable of utilizing a combination of ASD-associated biomarkers representative of the six proposed causes of autism in order to identify newborns at risk. The biomarkers discussed in this article are useful to guide the selection, efficacy and sufficiency of biomedical interventions, which would likely

  3. COPD exacerbations · 3: Pathophysiology

    OpenAIRE

    O'Donnell, D. E.; Parker, C M

    2006-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality. The effective management of COPD exacerbations awaits a better understanding of the underlying pathophysiological mechanisms that shape its clinical expression. The clinical presentation of exacerbations of COPD is highly variable and ranges from episodic symptomatic deterioration that is poorly responsive to usual treatment, to devastating life threatening events. This undersc...

  4. Mitochondrial Energy-Deficient Endophenotype in Autism

    Directory of Open Access Journals (Sweden)

    J. J. Gargus

    2008-01-01

    Full Text Available While evidence points to a multigenic etiology of most autism, the pathophysiology of the disorder has yet to be defined and the underlying genes and biochemical pathways they subserve remain unknown. Autism is considered to be influenced by a combination of various genetic, environmental and immunological factors; more recently, evidence has suggested that increased vulnerability to oxidative stress may be involved in the etiology of this multifactorial disorder. Furthermore, recent studies have pointed to a subset of autism associated with the biochemical endophenotype of mitochondrial energy deficiency, identified as a subtle impairment in fat and carbohydrate oxidation. This phenotype is similar, but more subtle than those seen in classic mitochondrial defects. In some cases the beginnings of the genetic underpinnings of these mitochondrial defects are emerging, such as mild mitochondrial dysfunction and secondary carnitine deficiency observed in the subset of autistic patients with an inverted duplication of chromosome 15q11-q13. In addition, rare cases of familial autism associated with sudden infant death syndrome (SIDS or associated with abnormalities in cellular calcium homeostasis, such as malignant hyperthermia or cardiac arrhythmia, are beginning to emerge. Such special cases suggest that the pathophysiology of autism may comprise pathways that are directly or indirectly involved in mitochondrial energy production and to further probe this connection three new avenues seem worthy of exploration: 1 metabolomic clinical studies provoking controlled aerobic exercise stress to expand the biochemical phenotype, 2 high-throughput expression arrays to directly survey activity of the genes underlying these biochemical pathways and 3 model systems, either based upon neuronal stem cells or model genetic organisms, to discover novel genetic and environmental inputs into these pathways.

  5. Autism and tuberous sclerosis.

    OpenAIRE

    Smalley, SL; Tanguay, PE; Smith, M.; Gutierrez, G.

    1992-01-01

    Autism is a behavior disorder with genetic influences indicated from twin and family studies and from the co-occurrence of autism with known genetic disorders. Tuberous sclerosis complex (TSC) is a known genetic disorder with behavioral manifestations including autism. A literature review of these two disorders substantiates a significant association of autism and TSC with 17-58% of TSC subjects manifesting autism and 0.4-3% of autistic subjects having TSC. In initial data collected on 13 TSC...

  6. Environmental Factors in Autism

    OpenAIRE

    Grabrucker, Andreas M

    2013-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an im...

  7. Environmental factors in autism

    OpenAIRE

    AndreasMartinGrabrucker

    2013-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an im...

  8. Epigenetic Findings in Autism: New Perspectives for Therapy

    OpenAIRE

    James Jeffrey Bradstreet; Nicola Antonucci; Alessandra Cirillo; Dario Siniscalco

    2013-01-01

    Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by dysfunctions in social interactions, communications, restricted interests, and repetitive stereotypic behaviors. Despite extensive genetic and biological research, significant controversy surrounds our understanding of the specific mechanisms of their pathogenesis. However, accumulating evidence points to the involvement of epigenetic modifications as foundational in creating ASD pathophysiol...

  9. Requirements for the formal representation of pathophysiology mechanisms by clinicians.

    Science.gov (United States)

    de Bono, B; Helvensteijn, M; Kokash, N; Martorelli, I; Sarwar, D; Islam, S; Grenon, P; Hunter, P

    2016-04-01

    Knowledge of multiscale mechanisms in pathophysiology is the bedrock of clinical practice. If quantitative methods, predicting patient-specific behaviour of these pathophysiology mechanisms, are to be brought to bear on clinical decision-making, the Human Physiome community and Clinical community must share a common computational blueprint for pathophysiology mechanisms. A number of obstacles stand in the way of this sharing-not least the technical and operational challenges that must be overcome to ensure that (i) the explicit biological meanings of the Physiome's quantitative methods to represent mechanisms are open to articulation, verification and study by clinicians, and that (ii) clinicians are given the tools and training to explicitly express disease manifestations in direct contribution to modelling. To this end, the Physiome and Clinical communities must co-develop a common computational toolkit, based on this blueprint, to bridge the representation of knowledge of pathophysiology mechanisms (a) that is implicitly depicted in electronic health records and the literature, with (b) that found in mathematical models explicitly describing mechanisms. In particular, this paper makes use of a step-wise description of a specific disease mechanism as a means to elicit the requirements of representing pathophysiological meaning explicitly. The computational blueprint developed from these requirements addresses the Clinical community goals to (i) organize and manage healthcare resources in terms of relevant disease-related knowledge of mechanisms and (ii) train the next generation of physicians in the application of quantitative methods relevant to their research and practice. PMID:27051514

  10. Pathophysiology of central sleep apneas.

    Science.gov (United States)

    Hernandez, Adam B; Patil, Susheel P

    2016-05-01

    The transition from wake to sleep is accompanied by a host of physiologic changes, which result in major alterations in respiratory control and may result in sleep-related breathing disorders. The central sleep apneas are a group of sleep-related breathing disorders that are characterized by recurrent episodes of airflow reduction or cessation due to a temporary reduction or absence of central respiratory drive. The fundamental hallmark of central sleep apnea (CSA) disorders is the presence of ventilatory control instability; however, additional mechanisms play a role in one or more specific manifestations of CSA. CSA may manifest during conditions of eucapnia/hypocapnia or chronic hypercapnia, which is a useful clinical classification that lends understanding to the underlying pathophysiology and potential therapies. In this review, an overview of normal breathing physiology is provided, followed by a discussion of pathophysiologic mechanisms that promote CSA and the mechanisms that are specific to different manifestations of CSA. PMID:26782104

  11. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  12. Menstrual Dysfunction in Pathophysiologic States

    OpenAIRE

    Neinstein, Lawrence S.

    1985-01-01

    The menstrual cycle is a complex entity involving many interactions of the central nervous system, hypothalamus, pituitary and ovaries. Normal menstrual function depends on a pulsatile gonadotropin-releasing hormone secretion leading to a pulsatile luteinizing hormone and follicle-stimulating hormone secretion that stimulates the ovaries. A cyclic burst of luteinizing hormone is also required for ovulation. Certain pathophysiologic states, such as those produced by stress, exercise and drugs,...

  13. On renal pathophysiology in preeclampsia

    OpenAIRE

    Penning, Maria Elisabeth (Marlies)

    2014-01-01

    Preeclampsia is a complication of pregnancy which can suddenly change from a relatively mild phenotype into a life-threatening situation. One of the organs that is always involved during preeclampsia is the kidney. The placenta plays an important role in the renal pathophysiology of preeclampsia. The placenta produces excessive amounts of anti-angiogenic factors which are associated with systemic endothelial dysfunction. Although the underlying mechanisms of renal injury during preeclampsia r...

  14. Narcolepsy: Pathophysiology and Neuropsychological Changes

    OpenAIRE

    Angela Naumann; Irene Daum

    2003-01-01

    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. Furth...

  15. Dystonia : emerging concepts in pathophysiology.

    OpenAIRE

    Madhusudanan M

    1999-01-01

    The essential pathophysiological feature of dystonia is co-contraction of antagonistic muscles. This may be due to derangement of the spinal cord or cortical mechanism. In the cord, there is disruption of the normal reciprocal inhibition of antagonists during agonist contraction. This decreased reciprocal inhibition is due to reduced presynaptic inhibition of muscle afferent input to the inhibitory interneuron. The reduced presynaptic inhibition may in turn be either due to defective supraseg...

  16. Pathophysiological basis of systemic treatments in psoriasis.

    Science.gov (United States)

    Volc, Sebastian; Ghoreschi, Kamran

    2016-06-01

    Over the past 15 years, the spectrum of systemic antipsoriatic treatments has dramatically expanded. Until the end of the last millennium, systemic therapy had been restricted to four oral agents: methotrexate, cyclosporine, acitretin, and fumaric acid esters. Today, there are additionally seven biologics and one new oral antipsoriatic drug, as well as the first available biosimilars. Six more biologics with novel target structures and at least four biosimilars are currently being developed (phase III). This progress has been based on new insights into the pathogenesis of psoriasis, in which tumor necrosis factor and especially Th17 immune responses with their associated cytokines interleukin 23 and 17 play a key role. The development of new-generation biologics as well as immunomodulatory small molecules can be attributed to these pathophysiological findings. Phosphodiesterase 4 inhibitors, dimethyl fumarate, and Janus kinase inhibitors all interact with Th17 immune responses. Some of these drugs are in advanced clinical development and are also beneficial in psoriatic arthritis. Today, psoriasis and psoriatic arthritis therefore rank among the most readily treatable inflammatory autoimmune disorders. Dermatology is increasingly becoming a specialty of modern targeted immunotherapies. PMID:27240060

  17. Autism: fifty years on from Kanner.

    Science.gov (United States)

    Tonge, B J; Dissanayake, C; Brereton, A V

    1994-04-01

    It is now 50 years since Leo Kanner first described autism as a distinctive pattern of symptoms in some children with severe developmental problems. Since then the assessment and diagnosis of children with pervasive disorders of development has been refined and much is known about the phenomenology and epidemiology. Autism is a biological disorder of the central nervous system (CNS) of unknown cause. It is associated with a number of organic disorders such as epilepsy and has comorbidity with other psychiatric disorders such as tic disorder. Cognitive abnormalities in social interactions, affect and language are present but there is still debate regarding which of these, if any, is the primary cognitive deficit. Special education and behavioral management has led to modest but important developmental improvement in many children with autism. Autism remains a life-long condition but patterns of symptoms change and skills develop from childhood into adult life. PMID:8198840

  18. The pathophysiology of restricted repetitive behavior

    OpenAIRE

    Lewis, Mark; Kim, Soo-Jeong

    2009-01-01

    Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, l...

  19. A comprehensive volumetric analysis of the cerebellum in children and adolescents with autism spectrum disorder

    OpenAIRE

    Scott, Julia A.; Schumann, Cynthia Mills; Goodlin-Jones, Beth L.; Amaral, David G.

    2009-01-01

    Magnetic resonance imaging (MRI) and postmortem neuropathological studies have implicated the cerebellum in the pathophysiology of autism. Controversy remains, however, concerning the nature and the consistency of cerebellar alterations. MRI studies of the cross-sectional area of the vermis have found both decreases and no difference in autism groups. Volumetric analysis of the vermis, which is less prone to “plane of section artifacts” may provide a more reliable assessment of size differenc...

  20. Corticosteroid therapy in regressive autism: Preliminary findings from a retrospective study

    OpenAIRE

    Golla, Sailaja; John A. Sweeney

    2014-01-01

    Some children with autism spectrum disorders (ASD; 15% to 30% of patients) show a significant and persistent regression in speech and social function during early childhood. There are no established treatments for the regressive symptoms. However, there are some known causes of this type of regression, such as Rett syndrome and Landau-Kleffner syndrome (LKS). In LKS, steroids have been used as a treatment. Some evidence suggests an autoimmune contribution to the pathophysiology of autism (Che...

  1. Pathogenic Mechanism of an Autism-Associated Neuroligin Mutation Involves Altered AMPA-Receptor Trafficking

    OpenAIRE

    Chanda, Soham; Aoto, Jason; Lee, Sung-Jin; Wernig, Marius; Südhof, Thomas C.

    2015-01-01

    Neuroligins are postsynaptic cell-adhesion molecules that bind to presynaptic neurexins. Although the general synaptic role of neuroligins is undisputed, their specific functions at a synapse remain unclear, even controversial. Moreover, many neuroligin gene mutations were associated with autism, but the pathophysiological relevance of these mutations is often unknown, and their mechanisms of action uninvestigated. Here, we examine the synaptic effects of an autism-associated neuroligin-4 sub...

  2. Pathophysiology of the Belgrade rat

    OpenAIRE

    Veuthey, Tania; Wessling-Resnick, Marianne

    2014-01-01

    The Belgrade rat is an animal model of divalent metal transporter 1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in ...

  3. Pathophysiology of the Belgrade Rat

    OpenAIRE

    MarianneWessling-Resnick

    2014-01-01

    The Belgrade rat is an animal model of Divalent Metal Transporter-1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 i...

  4. Kids' Quest: Autism

    Science.gov (United States)

    ... For... Parents / Educators National Center Homepage What is autism and how do I recognize a kid who might be diagnosed as having an autism spectrum disorder? Recommend on Facebook Tweet Share Compartir ...

  5. Learning about Autism

    Science.gov (United States)

    ... Genetics 101 Genomic Medicine and Health Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics ... have idiopathic autism. Exposure during pregnancy to rubella (German ... for new environmental causes of secondary autism has centered primarily ...

  6. Genetic Aspects of Autism Spectrum Disorders: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Swati eBanerjee

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute towards the formation, stabilization and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.

  7. Pathophysiology of Equine Neonatal Septicemia

    Directory of Open Access Journals (Sweden)

    Juan Carlos Ospina Chirivi

    2014-07-01

    Full Text Available Neonatal septicemia is a major cause of mortality and morbidity in horses in their first seven days of life and within their pathophysiology. It is important to consider the extrinsic and intrinsic predisposing factors which make foals susceptible to agents of primarily bacterial etiology. However, other types of infectious etiology (viruses and fungi should be considered too, as well as noninfectious etiologies. The paper mentions a wide variety of mechanisms that produce different injuries that must be addressed with measures of critical neonatal care, so it is imperative for the veterinarian to know the pathogenic mechanisms of the disease, its clinical presentation and anatomo-pathological lesions. Thus, systemic inflammatory response syndrome (SIRS, multiple organ dysfunction syndrome (MODS, and peripheral circulatory collapse or shock are some of the elements defined as the pillars of the pathophysiology of neonatal septicemia, extensively studied in equine medicine. This paper presents a short review of the triggering mechanisms of neonatal septicemia highlighting the importance of epidemiological investigations in Colombia. It shows the need for retrospective and prospective studies and for divulgation of some of the preventive measures of the disease in horses.

  8. The Pathophysiology of Eosinophilic Esophagitis

    Directory of Open Access Journals (Sweden)

    Daniel Avi Lemberg

    2014-05-01

    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.

  9. Pathophysiology of Retinopathy of Prematurity

    Directory of Open Access Journals (Sweden)

    İmren Akkoyun

    2012-12-01

    Full Text Available Retinopathy of prematurity (ROP, an ocular disease characterized by onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex multifactorial disease that occurs with microvascular degeneration followed by neovascularization which passing through different stages can progress to retinal detachment. Currently used ablative therapies like cryocoagulation and laser photocoagulation for proliferative ROP have limitations, and patients can still have long-term complications despite a successful treatment. Based on the knowledge regarding ROP pathophysiology, new treatment modalities are being developed. First results of intravitreal anti-VEGF therapy using bevacizumab are promising. Furthermore, besides intravitreal anti-VEGF therapy, systemic therapy with mediators like insulin-like growth factor (IGF-1 and/or ω3-fatty acids outlines the pharmacological approach to treatment of ROP. One of the most destructive manifestations of ROP is preretinal neovascularization. As we continue to decipher the underlying pathophysiological cellular mechanisms governing proliferative retinopathy, fostering normal retinal revascularization will open new therapeutic possibilities. All efforts should be focused on developing preventive strategies for ROP in order to avoid the need for nondestructive therapy modalities. (Turk J Ophthalmol 2012; 42: Supplement 63-7

  10. AUTISM SPECTRUM DISORDERS (ASD)

    OpenAIRE

    Middha Akanksha; Kataria Sahil; Sandhu Premjeet; Kapoor Bhawna

    2011-01-01

    Autism or Autism Spectrum Disorders (ASD) is a serious neurological disorder affecting communication skills, social interactions, adaptability in an individual, and also causes dramatic changes in behavioral patterns. This condition typically lasts throughout one’s lifetime and affects both, children as well as adults. Research has shown a tenfold increase in autism cases over the past decade and still rising at an alarming pace. The origins of autism are not known even to modern science. Aut...

  11. Autism and Tuberous Sclerosis.

    Science.gov (United States)

    Smalley, Susan L.

    1998-01-01

    Reviews the research on the relationship of autism and pervasive developmental disorders to tuberous sclerosis (TSC). Notes that, among TSC cases, the frequency of autism is 25% and among autistic populations, the frequency of TSC is 1% to 4%. It is thought that an abnormal TSC gene may directly influence the development of autism. (DB)

  12. [Gut microbiota: Description, role and pathophysiologic implications].

    Science.gov (United States)

    Landman, C; Quévrain, E

    2016-06-01

    The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. PMID:26749318

  13. Characteristics of autism spectrum disorders in a sample of egyptian and saudi patients: transcultural cross sectional study

    OpenAIRE

    Hussein Hanan; Taha Ghada RA; Almanasef Afrah

    2011-01-01

    Abstract Background Autism is a biological disorder with clearly defined phenomenology. Studies from the Middle East on this topic have been particularly rare. Little is known about the influence of culture on clinical features, presentations and management of autism. The current study was done to compare characteristics of autism in two groups of Egyptian as well as Saudi children. Methods The sample included 48 children with Autism Spectrum Disorder. They were recruited from the Okasha Inst...

  14. Fisiopatologia da enxaqueca Migraine pathophysiology

    Directory of Open Access Journals (Sweden)

    MAURICE B. VINCENT

    1998-12-01

    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

  15. Gold Nanoparticles and Lipoic Acid as a Novel Anti-Inflammatory Treatment for Autism, A Hypothesis

    Directory of Open Access Journals (Sweden)

    Ahmad Ghanizadeh

    2012-01-01

    Full Text Available Autism is a neurodevelopment disorder. Its aetiology and pathophysiology are not clearly known. However, mitochondria may play a significant role at least in some cases of autism. There is no therapeutic approach for autism. Moreover, there are only few Food and Drug Administration (FDA-approved medications for autism. Therefore, providing novel therapeutic approaches are highly required. Oxidative stress is suggested as an important factor in the aetiology of autism. Already some interventions targeting oxidative stress in autism are suggested.This article reviews evidence about the possible role of gold nanoparticles and lipoic acid (LA as anti-inflammatory agents. It mentions some evidence about the possible role of oxidative stress. Then, the role of gold nanoparticles and LA for the management of autism is discussed.According to the above-mentioned evidence, it is hypothesised that gold nanoparticles and LA may reduce neuro-inflammation in autism.Controlled experimental studies are needed to test whether gold nanoparticles plus LA enhance antioxidative stress system leading to the improvement of autism clinical symptoms.

  16. Evidence of Mitochondrial Dysfunction in Autism and Implications for Treatment

    Directory of Open Access Journals (Sweden)

    Daniel A. Rossignol

    2008-01-01

    Full Text Available Classical mitochondrial diseases occur in a subset of individuals with autism and are usually caused by genetic anomalies or mitochondrial respiratory pathway deficits. However, in many cases of autism, there is evidence of mitochondrial dysfunction (MtD without the classic features associated with mitochondrial disease. MtD appears to be more common in autism and presents with less severe signs and symptoms. It is not associated with discernable mitochondrial pathology in muscle biopsy specimens despite objective evidence of lowered mitochondrial functioning. Exposure to environ-mental toxins is the likely etiology for MtD in autism. This dysfunction then contributes to a number of diagnostic symptoms and comorbidities observed in autism including: cognitive impairment, language deficits, abnormal energy metabolism, chronic gastrointestinal problems, abnormalities in fatty acid oxidation, and increased oxidative stress. MtD and oxidative stress may also explain the high male to female ratio found in autism due to increased male vulnerability to these dysfunctions. Biomarkers for mitochondrial dysfunction have been identified, but seem widely under-utilized despite available therapeutic interventions. Nutritional supplementation to decrease oxidative stress along with factors to improve reduced glutathione, as well as hyperbaric oxygen therapy (HBOT represent supported and rationale approaches. The underlying pathophysiology and autistic symptoms of affected individuals would be expected to either improve or cease worsening once effective treatment for MtD is implemented.

  17. Pathophysiology and pathomorphology of osteoporosis

    International Nuclear Information System (INIS)

    Osteoporosis is a disease that leads to fragility fractures due to loss of bone mass and bone microstructure. This review presents an update on the fundamental pathophysiologic and pathomorphologic mechanisms of bone loss situations. Pathomorphologic characteristics such as perforations and microcallus formations are explained. The physiologic relevance of the remodeling process as well as its control by local-paracrine, systemic-endocrine and central-neural signaling pathways is discussed. Furthermore the role of hormones such as estrogen, FSH and leptin, of transcription-factors such as Runx2 and osterix and as well as that of the wnt signaling pathway for bone cell differentiation and function is presented. On the basis of current knowledge osteoporosis can be diagnosed, treated and fractures can be prevented. However, it is likely that new and even more effective diagnostic and therapeutic strategies will emerge as our understanding of the remodeling process that controls osteoblast and osteoclast function increases. (orig.)

  18. Dystonia : emerging concepts in pathophysiology.

    Directory of Open Access Journals (Sweden)

    Madhusudanan M

    1999-10-01

    Full Text Available The essential pathophysiological feature of dystonia is co-contraction of antagonistic muscles. This may be due to derangement of the spinal cord or cortical mechanism. In the cord, there is disruption of the normal reciprocal inhibition of antagonists during agonist contraction. This decreased reciprocal inhibition is due to reduced presynaptic inhibition of muscle afferent input to the inhibitory interneuron. The reduced presynaptic inhibition may in turn be either due to defective suprasegmental control or to changes in the tonic afferent input to the interneuron from cutaneous and muscle afferents. Alternatively, genesis of dystonia may entirely be a cortical mechanism. Overactivity of the premotor cortices, which receive projections from basal ganglia via ventral thalamus, could result in dystonia by abnormal activation of cortical motor neurons. This may again be due to a dopaminergic dysfunction of basal ganglia.

  19. Restless Legs Syndrome: Current Concepts about Disease Pathophysiology

    Science.gov (United States)

    Koo, Brian B.; Bagai, Kanika; Walters, Arthur S.

    2016-01-01

    Background In the past few decades, much has been learned about the pathophysiology of restless legs syndrome (RLS). Investigators have studied neuropathology, imaging, electrophysiology, and genetics of RLS, identifying brain regions and biological systems affected in RLS. This manuscript will review RLS pathophysiology literature, examining the RLS state through consideration of the neuroanatomy, then the biological, organ, and genetic systems. Methods Pubmed (1966 to April 2016) was searched for the term “restless legs syndrome” cross-referenced with “pathophysiology,” “pathogenesis,” “pathology,” or “imaging.” English language papers were reviewed. Studies that focused on RLS in relation to another disease were not reviewed. Results Although there are no gross structural brain abnormalities in RLS, widespread brain areas are activated, including the pre- and post-central gyri, cingulate cortex, thalamus, and cerebellum. Pathologically, the most consistent finding is striatal iron deficiency in RLS patients. A host of other biological systems are also altered in RLS, including the dopaminergic, oxygen-sensing, opioid, glutamatergic, and serotonergic systems. Polymorphisms in genes including BTBD9 and MEIS1 are associated with RLS. Discussion RLS is a neurologic sensorimotor disorder that involves pathology, most notably iron deficiency, in motor and sensory brain areas. Brain areas not subserving movement or sensation such as the cingulate cortex and cerebellum are also involved. Other biological systems including the dopaminergic, oxygen-sensing, opioid, glutamatergic, and serotonergic systems are involved. Further research is needed to determine which of these anatomic locations or biological systems are affected primarily, and which are affected in a secondary response. PMID:27536462

  20. Signs and Symptoms of Autism

    Science.gov (United States)

    ... content Start of Search Controls Search Form Controls Autism Cancel Submit Search The CDC CDC A-Z ... Z # Start of Search Controls Search Form Controls Autism Cancel Submit Search The CDC Autism Spectrum Disorder ( ...

  1. The Hypoxic Testicle: Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Juan G. Reyes

    2012-01-01

    Full Text Available Mammalian spermatogenesis is a complex biological process occurring in the seminiferous tubules in the testis. This process represents a delicate balance between cell proliferation, differentiation, and apoptosis. In most mammals, the testicles are kept in the scrotum 2 to 7°C below body core temperature, and the spermatogenic process proceeds with a blood and oxygen supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, pathologies such as varicocele or testicular torsion and environmental exposure to low oxygen (hypoxia can result in changes in blood flow, nutrients, and oxygen supply along with an increased local temperature that may induce adverse effects on Leydig cell function and spermatogenesis. These conditions may lead to male subfertility or infertility. Our literature analyses and our own results suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxia and varicocele and testicular torsion. Furthermore, oxidative damage seems to be present in these conditions during the initiation stages of germ cell damage and apoptosis. Other mechanisms like membrane-bound metalloproteinases and phospholipase A2 activation could also be part of the pathophysiological consequences of testicular hypoxia.

  2. Enhanced Visual Search in Infancy Predicts Emerging Autism Symptoms

    Science.gov (United States)

    Gliga, Teodora; Bedford, Rachael; Charman, Tony; Johnson, Mark H.; Baron-Cohen, Simon; Bolton, Patrick; Cheung, Celeste; Davies, Kim; Liew, Michelle; Fernandes, Janice; Gammer, Issy; Maris, Helen; Salomone, Erica; Pasco, Greg; Pickles, Andrew; Ribeiro, Helena; Tucker, Leslie

    2015-01-01

    Summary In addition to core symptoms, i.e., social interaction and communication difficulties and restricted and repetitive behaviors, autism is also characterized by aspects of superior perception [1]. One well-replicated finding is that of superior performance in visual search tasks, in which participants have to indicate the presence of an odd-one-out element among a number of foils [2–5]. Whether these aspects of superior perception contribute to the emergence of core autism symptoms remains debated [4, 6]. Perceptual and social interaction atypicalities could reflect co-expressed but biologically independent pathologies, as suggested by a “fractionable” phenotype model of autism [7]. A developmental test of this hypothesis is now made possible by longitudinal cohorts of infants at high risk, such as of younger siblings of children with autism spectrum disorder (ASD). Around 20% of younger siblings are diagnosed with autism themselves [8], and up to another 30% manifest elevated levels of autism symptoms [9]. We used eye tracking to measure spontaneous orienting to letter targets (O, S, V, and +) presented among distractors (the letter X; Figure 1). At 9 and 15 months, emerging autism symptoms were assessed using the Autism Observation Scale for Infants (AOSI; [10]), and at 2 years of age, they were assessed using the Autism Diagnostic Observation Schedule (ADOS; [11]). Enhanced visual search performance at 9 months predicted a higher level of autism symptoms at 15 months and at 2 years. Infant perceptual atypicalities are thus intrinsically linked to the emerging autism phenotype. PMID:26073135

  3. Contextual Autism

    DEFF Research Database (Denmark)

    Raahauge, Kirsten Marie

    2009-01-01

    This project deals with the notion of ghost anthropologically and artistic. The contextual autism of ghosting reveals itself as a sensation of in-betweeness in art as well as in everyday life. The ghost is not easily defined; as Jacques Derrida states in Spectres of Marx (1993/1994) about...... the spectre: ”It is something that one does not know, precisely, and one does not know if precisely it is, if it exists, if it responds to a name and corresponds to an essence.” (Derrida 1994:5). The ghost is hollow, it is not what it seems to be, and it seems to point to something that you don’t know....... As a non-present presence the ghost flavours its host with ghastly sensations of something dim, vague, and indifferently deadpan. On the basis of an ongoing anthropological research project about Haunted Houses and a parallel artistic artwork-process, joining forces in museum exhibitions and publishing...

  4. No Reduction of Spindle Neuron Number in Frontoinsular Cortex in Autism

    Science.gov (United States)

    Kennedy, Daniel P.; Semendeferi, Katerina; Courchesne, Eric

    2007-01-01

    It has been suggested that spindle neurons, an evolutionarily unique type of neuron, might be involved in higher-order social, emotional, and cognitive functions. As such, it was hypothesized that these neurons may be particularly important to the pathophysiology of autism, a disease characterized in part by disruption of higher-order social and…

  5. Body mass index in male and female children with infantile autism

    DEFF Research Database (Denmark)

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

    2002-01-01

    Morphometry, the measurement of forms, is an ancient practice. Recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of autism. Is the body, like the brain, affected by abnormal development in these patients? The aim of this study...

  6. Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study

    OpenAIRE

    Zerbo, Ousseny; Yoshida, Cathleen; Grether, Judith K.; Van de Water, Judy; Ashwood, Paul; Delorenze, Gerald N; Hansen, Robin L.; Kharrazi, Marty; Croen, Lisa A.

    2014-01-01

    Background Biologic markers of infection and inflammation have been associated with Autism Spectrum Disorders (ASD) but prior studies have largely relied on specimens taken after clinical diagnosis. Research on potential biologic markers early in neurodevelopment is required to evaluate possible causal pathways and screening profiles. Objective To investigate levels of cytokines and chemokines in newborn blood specimens as possible early biologic markers for autism. Methods We conducted a pop...

  7. Pathophysiology of anemia and erythrocytosis.

    Science.gov (United States)

    Hodges, Vivien M; Rainey, Susan; Lappin, Terence R; Maxwell, A Peter

    2007-11-01

    An increasing understanding of the process of erythropoiesis raises some interesting questions about the pathophysiology, diagnosis and treatment of anemia and erythrocytosis. The mechanisms underlying the development of many of the erythrocytoses, previously characterised as idiopathic, have been elucidated leading to an increased understanding of oxygen homeostasis. Characterisation of anemia and erythrocytosis in relation to serum erythropoietin levels can be a useful addition to clinical diagnostic criteria and provide a rationale for treatment with erythropoiesis stimulating agents (ESAs). Recombinant human erythropoietin as well as other ESAs are now widely used to treat anemias associated with a range of conditions, including chronic kidney disease, chronic inflammatory disorders and cancer. There is also heightened awareness of the potential abuse of ESAs to boost athletic performance in competitive sport. The discovery of erythropoietin receptors outside of the erythropoietic compartment may herald future applications for ESAs in the management of neurological and cardiac diseases. The current controversy concerning optimal hemoglobin levels in chronic kidney disease patients treated with ESAs and the potential negative clinical outcomes of ESA treatment in cancer reinforces the need for cautious evaluation of the pleiotropic effects of ESAs in non-erythroid tissues. PMID:17656101

  8. Wound pruritus: pathophysiology and management

    Directory of Open Access Journals (Sweden)

    Paul JC

    2015-08-01

    Full Text Available Julia C PaulSchool of Nursing, Oakland University, Rochester, MI, USAPurpose: The objective of this article is to review literature on wound pruritus, with a focus on summarizing pathophysiology and management.Method: Literature related to the physiology of itch was reviewed. PubMed, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL, and Embase were searched for all research studies written in English which include “wound” (injury/burn and “pruritus” (itch in the title or abstract. Articles were accepted if they involved wounds or acute burns. Literature related to options for management of wound pruritus was reviewed.Results: While all types of wounds can be the source of associated pruritus, most studies have been done concerning pruritus associated with burns. There are treatment options for pruritus which can be considered for management of wound pruritus. Conclusion: Further research is indicated to gain insights into the problem of wound pruritus. As more is learned about the physiology of wound pruritus, more effective management strategies can be developed and employed.Keywords: wound, chronic itch, C-fibers, spinothalamic tract, positron emission tomography, pruritogens

  9. Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension.

    OpenAIRE

    Aman, MG; Findling, RL; Hardan, AY; Hendren, RL; Melmed, RD; Kehinde-Nelson, O; Hsu, HA; Trugman, JM; Palmer, RH; Graham, SM; Gage, AT; Perhach, JL; Katz, E.

    2016-01-01

    Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension.A total of 121 children 6-12 years of age with Diagnostic and Statistical Manual of Ment...

  10. [Therapeutic approaches in autism spectrum disorders].

    Science.gov (United States)

    Ruggieri, Víctor L; Arberas, Claudia L

    2015-02-25

    Autistic spectrum disorders affect one out of every 68 persons, with a 4:1 dominance in males. Since they are dysfunctions rather than irreversible injuries to the central nervous system, which can be attributed to deficits in the neuronal networks and synaptogenesis and are modifiable thanks to the plasticity of the brain, starting therapy as early as possible is essential for more favourable progress. Very few treatments are backed by solid scientific evidence. We will analyse the therapeutic approaches oriented towards improving autism spectrum disorders which showed a clinical improvement that can be related to neurophysiological or functional changes in the central nervous system. We will classify the behavioural educational treatments and those in the research phase into a hierarchy, highlighting the neurogenetic entities with a high prevalence of autism, in which their pathophysiology and molecular base are known, that attempt to modify the consequences of those alterations by means of pharmacological agents. These entities include fragile X syndrome (GABAergic and metabotropic glutamate receptor inhibitors), tuberous sclerosis (mTOR inhibitors), Phelan-McDermid syndrome and Rett syndrome (insulin-like growth factor 1 inhibitors). Oxytocin, which has been shown to improve social cognition in persons with autism spectrum disorders, is analysed separately. PMID:25726823

  11. Beta-2-Microglobulin in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Paula Goines

    2007-01-01

    Full Text Available Autism spectrum disorders (ASD are heterogeneous neurodevelopmental diseases of unknown etiology. There are no biological markers for ASD and current diagnosis is based on behavioral criteria. Recent data has shown that MHC I, a compound involved in adaptive immune function, is also involved in neurodevelopment, synaptic plasticity and behavior. It has been suggested that altered MHC I expression could play a part in neurodevelopmental diseases like ASD. To address this possibility, we measured plasma levels of beta-2-microglobulin (β2m, a molecule that associates with MHC I and is indicative of MHC I expression, in 36 children with autism, 28 typically developing controls and subjects with developmental disabilities (n=16 but not autism. The age range of our study population was 17-120 months. We found no statistically significant differences in plasma ß 2m levels between groups. Therefore, plasma levels of ß2m measured in early childhood in autism may not reflect changes in MHC class I in autism.

  12. Reward Processing in Autism

    OpenAIRE

    Scott-Van Zeeland, Ashley A.; DAPRETTO, MIRELLA; Ghahremani, Dara G.; Poldrack, Russell A.; Bookheimer, Susan Y.

    2010-01-01

    The social motivation hypothesis of autism posits that infants with autism do not experience social stimuli as rewarding, thereby leading to a cascade of potentially negative consequences for later development. While possible downstream effects of this hypothesis such as altered face and voice processing have been examined, there has not been a direct investigation of social reward processing in autism. Here we use functional magnetic resonance imaging to examine social and monetary rewarded ...

  13. AUTISM ON THE INTERNET

    OpenAIRE

    Vladimir TRAJKOVSKI

    2000-01-01

    The Internet as the world wide information system is a global information network that provides instantly communication between a million users through its services. The Internet can be used in any science discipline especially in medicine. The aim of this paper is to show the possibilities of Internet in studying all the aspects of autism syndrome, introducing the public with some web-sites which treats autism and presenting the one and only web-site in Macedonia called Autism-Macedonia. In ...

  14. The pathophysiology of heart failure.

    Science.gov (United States)

    Kemp, Clinton D; Conte, John V

    2012-01-01

    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. PMID:22227365

  15. Autism Spectrum Disorder and Chiari 1 Malformation Co-occurring in a Child.

    Science.gov (United States)

    Osuagwu, Ferdnand C; Amalraj, Benedict; Noveloso, Bernard D; Aikoye, Salisu A; Bradley, Ronald

    2016-04-01

    Very few studies have shown associations between autism spectrum disorder, attention deficit hyperactivity disorder and Chiari 1 malformation. Here, we report an 10-year-old male that presented after having seizures with a history of Chiari 1 malformation, autism spectrum disorder and ADHD with moderate mental retardation and speech delay. This case highlights the fact that autism spectrum disorder as biologically based neurodevelopmental disorder with altered brain growth may be associated with Chiari 1 malformation and ADHD. PMID:27050897

  16. The motivation for very early intervention for infants at high risk for autism spectrum disorders

    OpenAIRE

    Webb, Sara Jane; Jones, Emily J.H.; Kelly, Jean; Dawson, Geraldine

    2014-01-01

    The first Autism Research Matrix (IACC, 2003) listed the identification of behavioural and biological markers of risk for autism as a top priority. This emphasis was based on the hypothesis that intervention with infants at-risk, at an early age when the brain is developing and before core autism symptoms have emerged, could significantly alter the developmental trajectory of children at risk for the disorder and impact long-range outcome. Research has provided support for specific models of ...

  17. Animal models of autism spectrum disorders: Information for neurotoxicologists

    OpenAIRE

    Halladay, Alycia K.; Amaral, David; Aschner, Michael; Bolivar, Valerie J.; Bowman, Aaron; DiCicco-Bloom, Emanuel; Hyman, Susan L.; Keller, Flavio; Lein, Pamela; Pessah, Isaac; Restifo, Linda; Threadgill, David W.

    2009-01-01

    Recent findings derived from large-scale datasets and biobanks link multiple genes to autism spectrum disorders. Consequently, novel rodent mutants with deletions, truncations and in some cases, overexpression of these candidate genes have been developed and studied both behaviorally and biologically. At the Annual Neurotoxicology Meeting in Rochester, NY in October of 2008, a symposium of clinicians and basic scientists gathered to present the behavioral features of autism, as well as strate...

  18. The autism inpatient collection: methods and preliminary sample description

    OpenAIRE

    Siegel, Matthew; Smith, Kahsi A.; Mazefsky, Carla; Gabriels, Robin L.; Erickson, Craig; Kaplan, Desmond; Morrow, Eric M; Wink, Logan; Santangelo, Susan L.; ,

    2015-01-01

    Background Individuals severely affected by autism spectrum disorder (ASD), including those with intellectual disability, expressive language impairment, and/or self-injurious behavior (SIB), are underrepresented in the ASD literature and extant collections of phenotypic and biological data. An understanding of ASD’s etiology and subtypes can only be as complete as the studied samples are representative. Methods The Autism Inpatient Collection (AIC) is a multi-site study enrolling children an...

  19. Autism Spectrum Disorder

    Science.gov (United States)

    ... Shared Neurobiology of Autism and Related Disorders NINDS Tuberous Sclerosis Complex Conference Summary Summary of Clinical Tuberous Sclerosis Complex Conference September 19-22, 2002. Publicaciones en ...

  20. Insights on the functional impact of microRNAs present in autism-associated copy number variants.

    Directory of Open Access Journals (Sweden)

    Varadarajan Vaishnavi

    Full Text Available Autism spectrum disorder is a complex neurodevelopmental disorder that appears during the first three years of infancy and lasts throughout a person's life. Recently a large category of genomic structural variants, denoted as copy number variants (CNVs, were established to be a major contributor of the pathophysiology of autism. To date almost all studies have focussed only on the genes present in the CNV loci, but the impact of non-coding regulatory microRNAs (miRNAs present in these regions remain largely unexplored. Hence we attempted to elucidate the biological and functional significance of miRNAs present in autism-associated CNV loci and their target genes by using a series of computational tools. We demonstrate that nearly 11% of the CNV loci harbor miRNAs and a few of these miRNAs were previously reported to be associated with autism. A systematic analysis of the CNV-miRNAs based on their interactions with the target genes enabled the identification of top 10 miRNAs namely hsa-miR-590-3p, hsa-miR-944, hsa-miR-570, hsa-miR-34a, hsa-miR-124, hsa-miR-548f, hsa-miR-429, hsa-miR-200b, hsa-miR-195 and hsa-miR-497 as hub molecules. Further, the CNV-miRNAs formed a regulatory loop with transcription factors and their downstream target genes, and annotation of these target genes indicated their functional involvement in neurodevelopment and synapse. Moreover, miRNAs present in deleted and duplicated CNV loci may explain the difference in dosage of the crucial genes controlled by them. These CNV-miRNAs can also impair the global processing and biogenesis of all miRNAs by targeting key molecules in the miRNA pathway. To our knowledge, this is the first report to highlight the significance of CNV-microRNAs and their target genes to contribute towards the genetic heterogeneity and phenotypic variability of autism.

  1. Multimodal approach to control postoperative pathophysiology and rehabilitation

    DEFF Research Database (Denmark)

    Kehlet, H

    1997-01-01

    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...

  2. Spontaneous pneumothorax: epidemiology, pathophysiology and cause

    OpenAIRE

    Noppen, M

    2010-01-01

    Spontaneous pneumothorax represents a common clinical problem. An overview of relevant and updated information on epidemiology, pathophysiology and cause(s) of spontaneous (primary and secondary) pneumothorax is described.

  3. Spontaneous pneumothorax: epidemiology, pathophysiology and cause

    Directory of Open Access Journals (Sweden)

    M. Noppen

    2010-09-01

    Full Text Available Spontaneous pneumothorax represents a common clinical problem. An overview of relevant and updated information on epidemiology, pathophysiology and cause(s of spontaneous (primary and secondary pneumothorax is described.

  4. Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats.

    Directory of Open Access Journals (Sweden)

    Syed Faraz Kazim

    Full Text Available Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF small peptide mimetic, Peptide 6 (P6, which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism.

  5. Current concepts in the pathophysiology of glaucoma

    OpenAIRE

    Agarwal Renu; Gupta Suresh; Agarwal Puneet; Saxena Rohit; Agrawal Shyam

    2009-01-01

    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...

  6. Acute Pancreatitis: Surgery, Pathophysiology and Probiotic Prophylaxis

    OpenAIRE

    van Minnen, L. P.

    2006-01-01

    Acute pancreatitis is a challenging disease with a clinical course that is often difficult to predict. In severe acute pancreatitis, mortality increases significantly if intestinal bacteria translocate from the intestine and infect pancreatic necrosis. Surgical and prophylactic treatment strategies are challenged by complex pathophysiology of the disease. This thesis addresses some key aspects of acute pancreatitis: surgical management, pathophysiology and probiotic prophylaxis. Outcome in pa...

  7. Are Molecules Involved in Neuritogenesis and Axon Guidance Related to Autism Pathogenesis?

    Science.gov (United States)

    Bakos, Jan; Bacova, Zuzana; Grant, Stephen G; Castejon, Ana M; Ostatnikova, Daniela

    2015-09-01

    Autism spectrum disorder is a heterogeneous disease, and numerous alterations of gene expression come into play to attempt to explain potential molecular and pathophysiological causes. Abnormalities of brain development and connectivity associated with alterations in cytoskeletal rearrangement, neuritogenesis and elongation of axons and dendrites might represent or contribute to the structural basis of autism pathology. Slit/Robo signaling regulates cytoskeletal remodeling related to axonal and dendritic branching. Components of its signaling pathway (ABL and Cdc42) are suspected to be molecular bases of alterations of normal development. The present review describes the most important mechanisms underlying neuritogenesis, axon pathfinding and the role of GTPases in neurite outgrowth, with special emphasis on alterations associated with autism spectrum disorders. On the basis of analysis of publicly available microarray data, potential biomarkers of autism are discussed. PMID:25989848

  8. Autism and Dyslexia

    OpenAIRE

    Frith, Uta

    2013-01-01

    Autism and dyslexia are wrongly classified as childhood disorders: They are lifelong and therefore have to be studied in adults as well as in children. Individual variability is enormous, and, as a result, behavioral diagnosis remains problematic. The study of the underlying cognitive abilities in autism and dyslexia has acted as a gateway for the emergence of developmental cognitive neuroscience.

  9. The Coherence of Autism

    Science.gov (United States)

    Hobson, R. Peter

    2014-01-01

    There is a growing body of opinion that we should view autism as fractionable into different, largely independent sets of clinical features. The alternative view is that autism is a coherent syndrome in which principal features of the disorder stand in intimate developmental relationship with each other. Studies of congenitally blind children…

  10. Stereotypes of autism.

    Science.gov (United States)

    Draaisma, Douwe

    2009-05-27

    In their landmark papers, both Kanner and Asperger employed a series of case histories to shape clinical insight into autistic disorders. This way of introducing, assessing and representing disorders has disappeared from today's psychiatric practice, yet it offers a convincing model of the way stereotypes may build up as a result of representations of autism. Considering that much of what society at large learns on disorders on the autism spectrum is produced by representations of autism in novels, TV-series, movies or autobiographies, it will be of vital importance to scrutinize these representations and to check whether or not they are, in fact, misrepresenting autism. In quite a few cases, media representations of talent and special abilities can be said to have contributed to a harmful divergence between the general image of autism and the clinical reality of the autistic condition. PMID:19528033

  11. Peroxisome Biogenesis Disorders: Biological, Clinical and Pathophysiological Perspectives

    Science.gov (United States)

    Braverman, Nancy E.; D'Agostino, Maria Daniela; MacLean, Gillian E.

    2013-01-01

    The peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders in which peroxisome assembly is impaired, leading to multiple peroxisome enzyme deficiencies, complex developmental sequelae and progressive disabilities. Mammalian peroxisome assembly involves the protein products of 16 "PEX" genes;…

  12. Identifying autism from neural representations of social interactions: neurocognitive markers of autism.

    Directory of Open Access Journals (Sweden)

    Marcel Adam Just

    Full Text Available Autism is a psychiatric/neurological condition in which alterations in social interaction (among other symptoms are diagnosed by behavioral psychiatric methods. The main goal of this study was to determine how the neural representations and meanings of social concepts (such as to insult are altered in autism. A second goal was to determine whether these alterations can serve as neurocognitive markers of autism. The approach is based on previous advances in fMRI analysis methods that permit (a the identification of a concept, such as the thought of a physical object, from its fMRI pattern, and (b the ability to assess the semantic content of a concept from its fMRI pattern. These factor analysis and machine learning methods were applied to the fMRI activation patterns of 17 adults with high-functioning autism and matched controls, scanned while thinking about 16 social interactions. One prominent neural representation factor that emerged (manifested mainly in posterior midline regions was related to self-representation, but this factor was present only for the control participants, and was near-absent in the autism group. Moreover, machine learning algorithms classified individuals as autistic or control with 97% accuracy from their fMRI neurocognitive markers. The findings suggest that psychiatric alterations of thought can begin to be biologically understood by assessing the form and content of the altered thought's underlying brain activation patterns.

  13. Environmental factors in autism

    Directory of Open Access Journals (Sweden)

    AndreasMartinGrabrucker

    2013-01-01

    Full Text Available Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.

  14. Early diagnosis of Autism Spectrum Disorders

    OpenAIRE

    Daalen, E. van

    2010-01-01

    The general aim of the SOSO-project (Screenings Onderzoek Sociale Ontwikkeling), which provided the basis for the largest part of this thesis, was to evaluate the early signs and symptoms of Autism Spectrum Disorders (ASDs) in children identified through screening and by surveillance and to determine their potential biological, behavioural, cognitive, and environmental correlates. This particular thesis has its focus on the early diagnosis of ASDs. This subject is divided into 3 separate part...

  15. Neuro-Immune Abnormalities in Autism and their interaction with the environment: A Variable Insult Model for Autism.

    Directory of Open Access Journals (Sweden)

    Daniel K Goyal

    2014-03-01

    Full Text Available Autism Spectrum Disorder (ASD is a heterogeneous condition affecting an individual’s ability to communicate and socialise and often presents with repetitive movements or behaviours. It tends to be severe with less than 10% achieving independent living with a marked variation in the progression of the condition. To date the literature supports a multi factorial model with the largest, most detailed twin study demonstrating strong environmental contribution to the development of the condition. Here we present a brief review of the neurological, immunological and autonomic abnormalities in ASD focusing on the causative roles of environmental agents and abnormal gut microbiota. We present a working hypothesis attempting to bring together the influence of environment on the abnormal neurological, immunological and neuroimmunological functions and we explain in brief how such pathophysiology can lead to, and/or exacerbate ASD symptomology. At present there is a lack of consistent findings relating to the neurobiology of autism. Whilst we postulate such variable findings may reflect the marked heterogeneity in clinical presentation and as such the variable findings may be of pathophysiological relevance, more research into the neurobiology of autism is necessary before establishing a working hypothesis. Both the literature review and hypothesis presented here explores possible neurobiological explanations with an emphasis of environmental aetiologies and is presented with this bias.

  16. The Complementary Role of High Sensitivity C-Reactive Protein in the Diagnosis and Severity Assessment of Autism

    Science.gov (United States)

    Khakzad, Mohammad Reza; Javanbakht, Maryam; Shayegan, Mohammad Reza; Kianoush, Sina; Omid, Fatemeh; Hojati, Maryam; Meshkat, Mojtaba

    2012-01-01

    C-reactive protein (CRP) is a beneficial diagnostic test for the evaluation of inflammatory response. Extremely low levels of CRP can be detected using high-sensitivity CRP (hs-CRP) test. A considerable body of evidence has demonstrated that inflammatory response has an important role in the pathophysiology of autism. In this study, we evaluated…

  17. Current concepts in the pathophysiology of glaucoma.

    Science.gov (United States)

    Agarwal, Renu; Gupta, Suresh K; Agarwal, Puneet; Saxena, Rohit; Agrawal, Shyam S

    2009-01-01

    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. PMID:19574692

  18. Current concepts in the pathophysiology of glaucoma

    Directory of Open Access Journals (Sweden)

    Agarwal Renu

    2009-01-01

    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.

  19. PACAP and its receptors in migraine pathophysiology

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2014-01-01

    Pituitary adenylate cyclase-activating peptide (PACAP) and its receptors (PAC1 , VPAC1 and VPAC2 ) are present in sensory neurons and in vascular smooth muscle related to the trigeminovascular system, a key factor in migraine pain. Recent data point to an involvement of PACAP, and in particular the...... PAC1 receptor, in the pathophysiology of migraine. Available data are discussed in relation to a study by Walker in this issue of the Journal with the goal of identifying possibilities for the development of novel antagonists and to further define the role of PACAP in migraine pathophysiology and as a...

  20. Etiology, pathophysiology, and staging of hallux rigidus.

    Science.gov (United States)

    Botek, Georgeanne; Anderson, Martha A

    2011-04-01

    The condition of hallux limitus is well understood and agreed on as visualized histologically and radiographically. But the historically described pathophysiology and anatomy that predisposes to hallux limitus has been challenged. Numerous investigators have proposed anatomic abnormalities of the foot as a primary cause of this condition, but perhaps trauma is the only unanimously agreed on cause. However, this accounts for only a small percentage of cases. To strive for better treatment outcomes, understanding the pathophysiology, assessing patient risk factors, and recognizing causative agents can better equip the foot and ankle surgeon in managing this condition. PMID:21669337

  1. Novel nuclear diagnostics as applied pathophysiology

    International Nuclear Information System (INIS)

    Novel Diagnostic Procedures in Nuclear Medicine reflect applied Pathophysiology: Basics and future aspects. In their capacity as 'image - assisted functional diagnostics', methods of nuclear medicine link morphological patterns of radiology with clinical presentation. Based on pathophysiology they supply an insight into both global and regional parameters, present as basal values or as reserves. Both, single photon emission computed tomography (SPECT) or highly defined positron ECT (PET), enable computerassisted topographical overlay and thus an exact comparative evaluation of regional function versus morphology. In addition, PET gives accress to a true physiological, absolute quantification employing process specific, carrierfree substrates. (orig./GDG)

  2. Mitochondrial disease in autism spectrum disorder patients: a cohort analysis.

    Directory of Open Access Journals (Sweden)

    Jacqueline R Weissman

    Full Text Available BACKGROUND: Previous reports indicate an association between autism spectrum disorders (ASD and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32% and unusual patterns of regression (40%. Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64% and complex III (20%. Two patients had rare mtDNA mutations of likely pathogenicity. CONCLUSIONS/SIGNIFICANCE: Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism.

  3. Autism Data & Statistics

    Science.gov (United States)

    ... 2006-2008, ranging from mild disabilities such as speech and language impairments to serious developmental disabilities, such as intellectual disabilities, cerebral palsy, and autism. [ Read summary ] Learn more about prevalence of ASD ...

  4. Autism spectrum disorder

    Science.gov (United States)

    ... is often based on guidelines from a medical book titled Diagnostic and Statistical Manual of Mental Disorders ( ... Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. Centers for Disease Control and Prevention. Autism ...

  5. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  6. Orthostatic hypotension: epidemiology, pathophysiology and management

    Science.gov (United States)

    Jacob, G.; Robertson, D.

    1995-01-01

    Orthostatic hypotension is characterized by low upright blood pressure levels and symptoms of cerebral hypoperfusion. Whereas orthostatic hypotension is heterogeneous, correct pathophysiologic diagnosis is important because of therapeutic and prognostic considerations. Although therapy is not usually curative, it can be extraordinarily beneficial if it is individually tailored. Management of the Shy-Drager syndrome (multiple-system atrophy) remains a formidable challenge.

  7. Pathophysiology of irradiated skin and breast

    International Nuclear Information System (INIS)

    The evolution, time course, and dose response of gross and histologic changes associated with the acute and late changes of the skin are noted and a composite pathophysiologic operational model given. This model focuses the selection of the observations to be 'scored' to assess the tolerance and cosmetic response of the skin and breast to different dose and combined therapy studies

  8. Retinal vein occlusion: pathophysiology and treatment options

    OpenAIRE

    Karia, Niral

    2010-01-01

    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

  9. Retinal vein occlusion: pathophysiology and treatment options

    Directory of Open Access Journals (Sweden)

    Niral Karia

    2010-07-01

    Full Text Available 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

  10. A Genome-Wide Association Study of Autism Incorporating Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and Social Responsiveness Scale

    Science.gov (United States)

    Connolly, John J.; Glessner, Joseph T.; Hakonarson, Hakon

    2013-01-01

    Efforts to understand the causes of autism spectrum disorders (ASDs) have been hampered by genetic complexity and heterogeneity among individuals. One strategy for reducing complexity is to target endophenotypes, simpler biologically based measures that may involve fewer genes and constitute a more homogenous sample. A genome-wide association…

  11. Environmental risk factors for autism

    OpenAIRE

    Dietert, Rodney R.; Janice M. Dietert; DeWitt, Jamie C.

    2011-01-01

    Autism is a devastating childhood condition that has emerged as an increasing social concern just as it has increased in prevalence in recent decades. Autism and the broader category of autism spectrum disorders are among the increasingly seen examples in which there is a fetal basis for later disease or disorder. Environmental, genetic, and epigenetic factors all play a role in determining the risk of autism and some of these effects appear to be transgenerational. Identification of the most...

  12. Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

    Science.gov (United States)

    Sykes, Edward A.; Dai, Qin; Sarsons, Christopher D.; Chen, Juan; Rocheleau, Jonathan V.; Hwang, David M.; Zheng, Gang; Cramb, David T.; Rinker, Kristina D.; Chan, Warren C. W.

    2016-03-01

    Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient's disease state to achieve optimal diagnostic and therapeutic outcomes.

  13. Pathophysiology of increased intestinal permeability in obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    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.

  14. Ion Channels in Obesity: Pathophysiology and Potential Therapeutic Targets.

    Science.gov (United States)

    Vasconcelos, Luiz H C; Souza, Iara L L; Pinheiro, Lílian S; Silva, Bagnólia A

    2016-01-01

    Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus, and Web of Science) to assess the role of ion channels in the pathophysiology of obesity. Ion channels present diverse key functions, such as the maintenance of physiological homeostasis and cell proliferation. Cell biology and pharmacological experimental evidences demonstrate that proliferating cells exhibit ion channel expression, conductance, and electrical properties different from the resting cells. Thereby, a large variety of ion channels has been identified in the pathogenesis of obesity such as potassium, sodium, calcium and chloride channels, nicotinic acetylcholine receptor and transient receptor potential channels. The fundamental involvement of these channels on the generation of obesity leads to the progress in the knowledge about the mechanisms responsible for the obesity pathophysiology, consequently emerging as new targets for pharmacological modulation. PMID:27065858

  15. Ion Channels in Obesity: Pathophysiology and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    LUIZ HENRIQUE CÉSAR VASCONCELOS

    2016-03-01

    Full Text Available Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus and Web of Science to assess the role of ion channels in the pathophysiology of obesity. Ion channels present diverse key functions, such as the maintenance of physiological homeostasis and cell proliferation. Cell biology and pharmacological experimental evidences demonstrate that proliferating cells exhibit ion channel expression, conductance and electrical properties different from the resting cells. Thereby, a large variety of ion channels has been identified in the pathogenesis of obesity such as potassium, sodium, calcium and chloride channels, nicotinic acetylcholine receptor and transient receptor potential channels. The fundamental involvement of these channels on the generation of obesity leads to the progress in the knowledge about the mechanisms responsible for the obesity pathophysiology, consequently emerging as new targets for pharmacological modulation.

  16. Nutritional management of (some) autism: a case for gluten- and casein-free diets?

    Science.gov (United States)

    Whiteley, Paul

    2015-08-01

    Autism spectrum disorders represent a diverse and heterogeneous array of conditions unified by the variable presence of specific behaviours impacting social and communicative functions (social affect) alongside other presentation. Common overt characteristics may come about as a consequence of several different genetic and biological processes differentially manifesting across different people or groups. The concept of plural 'autisms' is evolving, strengthened by an increasingly important evidence base detailing different developmental trajectories across the autism spectrum and the appearance of comorbidity variably interacting with core symptoms and onwards influencing quality of life. Reports that dietary intervention, specifically the removal of foods containing gluten and/or casein from the diet, may impact on the presentation of autism for some, complement this plural view of autism. Evidence suggestive of differing responses to the use of a gluten- and casein-free diet, defined as best- and non-response, has combined with some progress on determining the underlying genetic and biological correlates potentially related to such dietary elements. The preliminary suggestion of a possible diet-related autism phenotype is the result. This review will highlight several pertinent aspects onwards to an effect of food in some cases of autism including research on the pharmacological activity of food metabolites, immune response, issues with gut barrier function and some contribution from the gut microbiota. These represent promising areas in need of far greater research inspection in order to potentially define such a diet-related subgroup on the autism spectrum. PMID:25311313

  17. Autism and chromosome abnormalities-A review.

    Science.gov (United States)

    Bergbaum, Anne; Ogilvie, Caroline Mackie

    2016-07-01

    The neuro-behavioral disorder of autism was first described in the 1940s and was predicted to have a biological basis. Since that time, with the growth of genetic investigations particularly in the area of pediatric development, an increasing number of children with autism and related disorders (autistic spectrum disorders, ASD) have been the subject of genetic studies both in the clinical setting and in the wider research environment. However, a full understanding of the biological basis of ASDs has yet to be achieved. Early observations of children with chromosomal abnormalities detected by G-banded chromosome analysis (karyotyping) and in situ hybridization revealed, in some cases, ASD associated with other features arising from such an abnormality. The introduction of higher resolution techniques for whole genome screening, such as array comparative genome hybridization (aCGH), allowed smaller imbalances to be detected, some of which are now considered to represent autism susceptibility loci. In this review, we describe some of the work underpinning the conclusion that ASDs have a genetic basis; a brief history of the developments in genetic analysis tools over the last 50 years; and the most common chromosome abnormalities found in association with ASDs. Introduction of next generation sequencing (NGS) into the clinical diagnostic setting is likely to provide further insights into this complex field but will not be covered in this review. Clin. Anat. 29:620-627, 2016. © 2016 Wiley Periodicals, Inc. PMID:27012322

  18. [Current status of autism studies].

    Science.gov (United States)

    Kurita, H

    2001-01-01

    The current status of autism studies was reviewed based on English articles published during the 1990s. Although the concepts of autism and pervasive developmental disorders (PDD) are established, diagnostic criteria of PDDNOS or atypical autism, which is frequently difficult to differentiate from autism, need to be established. The prevalence of autism has been estimated as about 0.05% in the U.S and many European countries, while it was reported to be 0.1% or higher in Japan and some European countries, though the reasons for this difference are unclear. High-functioning (IQ > or = 70) autism may not be as rare a condition as previously thought and both its difference from and similarity to Asperger's syndrome, the highest functioning PDD subtype, need clarification. About 20 to 40% of children with autism lose meaningful words by the age of 2 years and display autistic symptoms thereafter. Such autism, called the setback type in Japan, has been demonstrated to have a poorer adolescent/adult outcome compared to autism without setback and its relationship with childhood disintegrative disorder, which displays a clearer regression after normal development for at least the first 2 years of life, needs to be addressed. The etiology of autism is now considered mostly genetic for reasons, such as the significantly higher concordance rate of autism in identical twin pairs (60-80%) than in fraternal twin pairs (0-10%) and an 3-5% incidence of autism among sibs of an autism proband, 30 to 100 times higher than that in the general population. The involvement of several genes is implicated to create susceptibility for autism, yet the responsible genes have not been identified. Although there is no medication to cure autism, some psychotropic drugs, such as antipsychotics and SSRIs, seem effective for behavior problems in autism patients. Psychosocial treatments are the main therapeutic approach to autism, though they are yet to be well systematized. It is important to

  19. Autism Advocacy: A Network Striving for Equity

    Science.gov (United States)

    Itkonen, Tiina; Ream, Robert

    2013-01-01

    In this exploratory case study, we examine the rise of autism on the policy agenda and the new generation of autism advocacy. We focus especially on interconnections between the rhetoric about autism in the media and the emergence and political effectiveness of Autism Speaks, the nation's largest autism advocacy group. We portray how…

  20. Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Emilio L. Streck

    2014-05-01

    Full Text Available Introduction: Mitochondrial dysfunction has been postulated to participate in the development of many neuropsychiatric disorders, but there is no consensus as to its role. The aim of this paper is to review recent studies and to outline the current understanding of the association between mitochondrial dysfunction and psychiatric disorders. Methodology: We reviewed articles that evaluated mitochondrial dysfunction and psychiatric disorders, with a particular focus on depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and autism spectrum disorder, and the association between mitochondrial dysfunction and development of these disorders. Results: Evidence suggests that alterations in mitochondrial morphology, brain energy metabolism, and mitochondrial enzyme activity may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in energy metabolism in the cell. Conclusions: Understanding the interactions between mitochondrial dysfunction and development of psychiatric disorders may help establish more effective therapeutic strategies for these disorders and thus lead to better outcomes for affected subjects.

  1. Mind and Body: Concepts of Human Cognition, Physiology and False Belief in Children with Autism or Typical Development

    Science.gov (United States)

    Peterson, Candida C.

    2005-01-01

    This study examined theory of mind (ToM) and concepts of human biology (eyes, heart, brain, lungs and mind) in a sample of 67 children, including 25 high functioning children with autism (age 6-13), plus age-matched and preschool comparison groups. Contrary to Baron-Cohen [1989, "Journal of Autism and Developmental Disorders," 19(4), 579-600],…

  2. Perception of Mirror Symmetry in Autism Spectrum Disorders

    Science.gov (United States)

    Falter, Christine M.; Bailey, Anthony J.

    2012-01-01

    Gestalt grouping in autism spectrum disorders (ASD) is selectively impaired for certain organization principles but for not others. Symmetry is a fundamental Gestalt principle characterizing many biological shapes. Sensitivity to symmetry was tested using the Picture Symmetry Test, which requires finding symmetry lines on pictures. Individuals…

  3. Kostmann syndrome : A clinical and pathophysiological study

    OpenAIRE

    Carlsson, Göran

    2004-01-01

    Kostmann syndrome or severe congenital neutropenia (SCN) is a rare disease, usually diagnosed during the first months of life, characterized by extremely low levels of neutrophils in the peripheral blood, a maturational arrest of the myelopoiesis in the bone marrow and severe bacterial infections. The purpose of this project was to improve the understanding of the clinical course and the pathophysiology of autosomal recessive SCN. Rolf Kostmann presented six patients with...

  4. Leptin in human physiology and pathophysiology

    OpenAIRE

    Mantzoros, Christos S.; Magkos, Faidon; Brinkoetter, Mary; Sienkiewicz, Elizabeth; Dardeno, Tina A.; Kim, Sang-Yong; Hamnvik, Ole-Petter R.; Koniaris, Anastasia

    2011-01-01

    Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, ...

  5. Pathophysiology and Classification of Respiratory Failure.

    Science.gov (United States)

    Lamba, Tejpreet Singh; Sharara, Rihab Saeed; Singh, Anil C; Balaan, Marvin

    2016-01-01

    Respiratory failure is a condition in which the respiratory system fails in one or both of its gas exchange functions. It is a major cause of morbidity and mortality in patients admitted to intensive care units. It is a result of either lung failure, resulting in hypoxemia, or pump failure, resulting in alveolar hypoventilation and hypercapnia. This article covers the basic lung anatomy, pathophysiology, and classification of respiratory failure. PMID:26919670

  6. Pathophysiology of dysarthria in cerebral palsy.

    OpenAIRE

    Neilson, P D; O'Dwyer, N J

    1981-01-01

    Electromyograms were recorded with hooked-wire electrodes from sixteen lip, tongue and jaw muscles in six normal and seven cerebral palsied adult subjects during a variety of speech and non-speech tasks. The recorded patterns of muscle activity fail to support a number of theories concerning the pathophysiology of dysarthria in cerebral palsy. There was no indication of weakness in individual articulator muscles. There was no evidence of uncontrolled sustained background activity or of abnorm...

  7. Otosclerosis update (1). Pathophysiology and diagnosis

    International Nuclear Information System (INIS)

    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)

  8. Pathophysiology of spontaneous venous gas embolism

    Science.gov (United States)

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

    1991-01-01

    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.

  9. Depression and sleep: pathophysiology and treatment

    OpenAIRE

    Thase, Michael E.

    2006-01-01

    This review examines the relationship between sleep and depression. Most depressive disorders are characterized by subjective sleep disturbances, and the regulation of sleep is intricately linked to the same mechanisms that are implicated in the pathophysiology of depression. After briefly reviewing the physiology and topography of normal sleep, the disturbances revealed in studies of sleep in depression using polysomnographic recordings and neuroimaging assessments are discussed. Next, treat...

  10. Pathophysiological characterization of asthma transitions across adolescence

    OpenAIRE

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

    2014-01-01

    Background 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. Methods The Isle of Wight Birth Cohort (N = 1456) was reviewed at 1, 2, 4, 10 and 18-years. Characterizat...

  11. GENETIC ASPECTS OF AUTISM

    Directory of Open Access Journals (Sweden)

    Anastas LAKOSKI

    1997-06-01

    Full Text Available In the first paper on the syndrome of autism, Kanner described it as innate and inborn. He drew attention to the abnormalities in infancy without evidence of prior normal development and the intellectual, non emotional qualities shown by many of the parents and grandparents. Subsequently, the supposed lack of parental warmth led many clinicians to abandon the notions of constitutional deficit in the child and instead to postulate a psychogenic origin etiology was likely, genetic factors probably did not play a major role. Attention was draw to the low rate of autism in siblings, the lack of chromosome anomalies, and the similarities with syndromes associated with known brain trauma. Although the rate of autism in siblings was indeed low, it was much higher than in the general population rate providing a strong pointer to the genetic factors. The recognition that this was so, associated with the parallel finding of apparently high familiar loading for language delay, stimulated the first, systematic, twin study of autism, which suggested a strong genetic component. Subsequent research has produced findings in the same direction, although many questions remain unanswered. In this paper the evidence that has accumulated on genetic influences on autism is summarized and the remained dilemmas on this field are discussed.

  12. The oscillopathic nature of language deficits in autism : from genes to language evolution

    OpenAIRE

    Benítez Burraco, Antonio; Murphy, Elliot

    2016-01-01

    Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders involving a number of deficits to linguistic cognition. The gap between genetics and the pathophysiology of ASD remains open, in particular regarding its distinctive linguistic profile. The goal of this article is to attempt to bridge this gap, focusing on how the autistic brain processes language, particularly through the perspective of brain rhythms. Due to the phenomenon of pleiotropy, which may take ...

  13. Modulation of corticospinal excitability by transcranial magnetic stimulation in children and adolescents with autism spectrum disorder

    OpenAIRE

    Oberman, Lindsay M.; Alvaro ePascual-Leone; Alexander eRotenberg

    2014-01-01

    The developmental pathophysiology of Autism Spectrum Disorders (ASD) is currently not fully understood. However, multiple lines of evidence suggest that the behavioral phenotype may result from dysfunctional inhibitory control over excitatory synaptic plasticity. Consistent with this claim, previous studies indicate that adults with Asperger’s Syndrome show an abnormally extended modulation of corticospinal excitability following a train of repetitive transcranial magnetic stimulation (rTMS...

  14. Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

    OpenAIRE

    Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T.; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young

    2016-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to as...

  15. Autism Spectrum Disorders and Drug Addiction: Common Pathways, Common Molecules, Distinct Disorders?

    OpenAIRE

    Rothwell, Patrick E.

    2016-01-01

    Autism spectrum disorders (ASDs) and drug addiction do not share substantial comorbidity or obvious similarities in etiology or symptomatology. It is thus surprising that a number of recent studies implicate overlapping neural circuits and molecular signaling pathways in both disorders. The purpose of this review is to highlight this emerging intersection and consider implications for understanding the pathophysiology of these seemingly distinct disorders. One area of overlap involves neural ...

  16. Astrocytes and Microglia and Their Potential Link with Autism Spectrum Disorders

    OpenAIRE

    Petrelli, Francesco; Pucci, Luca; Bezzi, Paola

    2016-01-01

    The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not fully understood although it has been shown that various genetic and environmental factors contribute to their etiology. As increasing evidence indicates that astrocytes and microglial cells play a major role in synapse maturation and function, and there is evidence of deficits in glial cell functions in ASDs, one current hypothesis is that glial dysfunctions directly contribute to their pathophysiology. The aim of ...

  17. Astrocytes and Microglia and Their Potential Link with Autism Spectrum Disorders.

    OpenAIRE

    Petrelli F.; Pucci L.; Bezzi P.

    2016-01-01

    The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not fully understood although it has been shown that various genetic and environmental factors contribute to their etiology. As increasing evidence indicates that astrocytes and microglial cells play a major role in synapse maturation and function, and there is evidence of deficits in glial cell functions in ASDs, one current hypothesis is that glial dysfunctions directly contribute to their pathophysiology. The aim of ...

  18. A genome-wide association study of autism incorporating autism diagnostic interview-revised, autism diagnostic observation schedule, and social responsiveness scale.

    Science.gov (United States)

    Connolly, John J; Glessner, Joseph T; Hakonarson, Hakon

    2013-01-01

    Efforts to understand the causes of autism spectrum disorders (ASDs) have been hampered by genetic complexity and heterogeneity among individuals. One strategy for reducing complexity is to target endophenotypes, simpler biologically based measures that may involve fewer genes and constitute a more homogenous sample. A genome-wide association study of 2,165 participants (mean age = 8.95 years) examined associations between genomic loci and individual assessment items from the Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, and Social Responsiveness Scale. Significant associations with a number of loci were identified, including KCND2 (overly serious facial expressions), NOS2A (loss of motor skills), and NELL1 (faints, fits, or blackouts). These findings may help prioritize directions for future genomic efforts. PMID:22935194

  19. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

    Directory of Open Access Journals (Sweden)

    Hansen Wang

    2015-02-01

    Full Text Available Autism spectrum disorders (ASDs are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases.

  20. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes.

    Science.gov (United States)

    Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C

    2015-01-01

    Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

  1. ETIOLOGY OF AUTISM

    Directory of Open Access Journals (Sweden)

    Vladimir TRAJKOVSKI

    2004-06-01

    Full Text Available Although there is good evidence that autism is a multifactorial disorder, an adequate understanding of the genetic and nongenetic causes has yet to be achieved. With empirical research findings review is made to evidence on possible causal influences. Much the strongest evidence concerns the importance of susceptibility genes, but such genes have yet to be identified. Specific somatic conditions (tuberous sclerosis and the fragile X syndrome account for a small proportion of cases. Over recent decades there has been a major rise in the rate of diagnosed autism. The main explanation for this rise is to be found in better ascertainment and a broadening of the diagnostic concept. Progress on the elucidation of the causes of autism will be crucially dependent on the combination of epidemiology with more basic science laboratory studies.

  2. Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Rebecca E. Rosenberg

    2011-01-01

    Full Text Available We used a national online registry to examine variation in cumulative prevalence of community diagnosis of psychiatric comorbidity in 4343 children with autism spectrum disorders (ASD. Adjusted multivariate logistic regression models compared influence of individual, family, and geographic factors on cumulative prevalence of parent-reported anxiety disorder, depression, bipolar disorder, and attention deficit/hyperactivity disorder or attention deficit disorder. Adjusted odds of community-assigned lifetime psychiatric comorbidity were significantly higher with each additional year of life, with increasing autism severity, and with Asperger syndrome and pervasive developmental disorder—not otherwise specified compared with autistic disorder. Overall, in this largest study of parent-reported community diagnoses of psychiatric comorbidity, gender, autistic regression, autism severity, and type of ASD all emerged as significant factors correlating with cumulative prevalence. These findings could suggest both underlying trends in actual comorbidity as well as variation in community interpretation and application of comorbid diagnoses in ASD.

  3. [Autism and Autism-associated Metabolites].

    Science.gov (United States)

    Watanabe, Kunitomo

    2016-06-01

    Gene-microbiota interactions are now proposed to be a special case of gene-environmental interaction. Preclinical and clinical data summarized in this article reveal that a specific serum metabolite, associated with alterations in gut microbiome composition, might have an emerging role in the onset and pathogenesis of autism. Altered level of this specified metabolite may induce perturbations in the epigenome and modulate the expression of key disease susceptible genes in neurons and their associated cells during critical periods of neurodevelopment. The gut microbiota itself is now regarded as a reservoir for environmental epigenetic factors. PMID:27279160

  4. [Review: pathophysiology and methodology of nasal packing].

    Science.gov (United States)

    Beule, A G; Weber, R K; Kaftan, H; Hosemann, W

    2004-08-01

    Nasal packing is a frequent procedure to control spontaneous nasal bleeding or postoperative oozing following different types of nasal surgery. It strives for internal stabilization of the nasal framework and for optimizing wound healing by prevention of stenosis or synechia. A lot of different materials is used and there is no accepted standard concerning the type and application. A review on pathophysiology of the packed nose is given together with a survey on customary packing materials focussing on the specific merits, demerits and side-effects including economical aspects. PMID:15316896

  5. A pathophysiological view of primary headaches

    DEFF Research Database (Denmark)

    Edvinsson, L

    2000-01-01

    The cerebral circulation is innervated by sympathetic, parasympathetic and sensory nerves which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide (CG...... release normalised. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches.......The cerebral circulation is innervated by sympathetic, parasympathetic and sensory nerves which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide (CGRP...

  6. Lafora disease: epidemiology, pathophysiology and management.

    LENUS (Irish Health Repository)

    Monaghan, Thomas S

    2010-07-01

    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.

  7. Pathophysiology and Biomechanics of the Aging Spine

    Science.gov (United States)

    Papadakis, Michael; Sapkas, Georgios; Papadopoulos, Elias C; Katonis, Pavlos

    2011-01-01

    Aging of the spine is characterized by two parallel but independent processes: the reduction of bone mineral density and the development of degenerative changes. The combination of degeneration and bone mass reduction contribute, to a different degree, to the development of a variety of lesions. This results in a number of painful and often debilitating disorders. The present review constitutes a synopsis of the pathophysiological processes that take place in the aging spine as well as of the consequences these changes have on the biomechanics of the spine. The authors hope to present a thorough yet brief overview of the process of aging of the human spine. PMID:21966338

  8. Deafness and Autism

    Science.gov (United States)

    Morton, Diane D.

    2008-01-01

    At the most basic level, autism is a neurological disorder that most likely involves a distinct abnormality in brain structure and affects a child's abilities in two areas: communication and social development. It also is marked by repetitive or stereotypical behavior. Because of the variability in the causes of deafness as well as…

  9. Autism and Mitochondrial Disease

    Science.gov (United States)

    Haas, Richard H.

    2010-01-01

    Autism spectrum disorder (ASD) as defined by the revised Diagnostic and Statistical Manual of Mental Disorders: DSM IVTR criteria (American Psychiatric Association [2000] Washington, DC: American Psychiatric Publishing) as impairment before the age of 3 in language development and socialization with the development of repetitive behaviors, appears…

  10. Diagnosis of Autism

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-10-01

    Full Text Available The identification and assessment process for children with autism and autistic spectrum disorder is reviewed by a developmental pediatrician, speech and language therapist, and consultant in pediatric disability at Guy’s and St Thomas’ Hospitals, and Great Ormond Street Children’s Hospital, London, UK.

  11. Sensational Stars with Autism

    Science.gov (United States)

    Simmons, Karen; Miller, Lucy Jane

    2008-01-01

    Sensory processing refers to the way the brain takes incoming sensory messages, converts them into meaningful messages, then makes a response. If the responses are disorganized or inappropriate given the sensory input, sensory processing disorder (SPD) may co-exist with autism. If a child has an occasional atypical response to sensation, he or she…

  12. Autism Spectrum Disorder

    Centers for Disease Control (CDC) Podcasts

    2014-04-02

    This podcast discusses autism spectrum disorder (ASD), a developmental disability that causes problems with social, communication, and behavioral skills. CDC estimates that one in 68 children has been identified as having ASD.  Created: 4/2/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 4/2/2014.

  13. Autism and art.

    Science.gov (United States)

    James, Ioan

    2010-01-01

    The link between mild forms of autism and artistic creativity is suggested by a number of individual cases. Here those of a well-known composer, Béla Bártok, and a famous visual artist, Andy Warhol, are considered. PMID:20375530

  14. Insights on the Functional Impact of MicroRNAs Present in Autism-Associated Copy Number Variants

    OpenAIRE

    Vaishnavi, Varadarajan; Manikandan, Mayakannan; Tiwary, Basant K.; Munirajan, Arasambattu Kannan

    2013-01-01

    Autism spectrum disorder is a complex neurodevelopmental disorder that appears during the first three years of infancy and lasts throughout a person’s life. Recently a large category of genomic structural variants, denoted as copy number variants (CNVs), were established to be a major contributor of the pathophysiology of autism. To date almost all studies have focussed only on the genes present in the CNV loci, but the impact of non-coding regulatory microRNAs (miRNAs) present in these regio...

  15. Pathophysiology and management of multivalvular disease.

    Science.gov (United States)

    Unger, Philippe; Clavel, Marie-Annick; Lindman, Brian R; Mathieu, Patrick; Pibarot, Philippe

    2016-07-01

    Multivalvular disease (MVD) is common among patients with valvular disease, and has a complex pathophysiology dependent on the specific combination of valve lesions. Diagnosis is challenging because several echocardiographic methods commonly used for the assessment of stenosis or regurgitation have been validated only in patients with single-valve disease. Decisions about the timing and type of treatment should be made by a multidisciplinary heart valve team, on a case-by-case basis. Several factors should be considered, including the severity and consequences of the MVD, the patient's life expectancy and comorbidities, the surgical risk associated with combined valve procedures, the long-term risk of morbidity and mortality associated with multiple valve prostheses, and the likelihood and risk of reoperation. The introduction of transcatheter valve therapies into clinical practice has provided new treatment options for patients with MVD, and decision-making algorithms on how to combine surgical and percutaneous treatment options are evolving rapidly. In this Review, we discuss the pathophysiology, diagnosis, and treatment of MVD, focusing on the combinations of valve pathologies that are most often encountered in clinical practice. PMID:27121305

  16. Bitter taste receptors: Extraoral roles in pathophysiology.

    Science.gov (United States)

    Shaik, Feroz Ahmed; Singh, Nisha; Arakawa, Makoto; Duan, Kangmin; Bhullar, Rajinder P; Chelikani, Prashen

    2016-08-01

    Over the past decade tremendous progress has been made in understanding the functional role of bitter taste receptors (T2Rs) and bitter taste perception. This review will cover the recent advances made in identifying the role of T2Rs in pathophysiological states. T2Rs are widely expressed in various parts of human anatomy and have been shown to be involved in physiology of respiratory system, gastrointestinal tract and endocrine system. Empirical evidence has shown T2Rs to be an integral component of antimicrobial immune responses in upper respiratory tract infections. The studies on human airway smooth muscle cells have shown that a potent bitter tastant induced bronchodilatory effects mediated by bitter taste receptors. Clinical data suggests a role for T2R38 polymorphism in predisposition of individuals to chronic rhinosinusitis. The role of genetic variation in T2Rs and its impact on disease susceptibility have been investigated in various other disease risk factors such as alcohol dependence, head and neck cancers. Preliminary reports have demonstrated differential expression of functional T2Rs in breast cancer cell lines. Studies on the role of T2Rs in pathophysiology of diseases including chronic rhinosinusitis, asthma, cystic fibrosis, and cancer have been promising. However, research in this field is in its nascent stages, and more confirmatory studies on animal models and in clinical settings are required. PMID:27032752

  17. Vertebrobasilar occlusions. Pathophysiology, diagnostics and treatment

    International Nuclear Information System (INIS)

    Acute vertebrobasilar occlusions (VBO) are dramatic clinical events with a mortality of up to 90% under standard medical treatment. If VBO is suspected a diagnosis of the vessel status has to be achieved immediately. For this purpose CT/CTA and MRI/MRA are equivalent diagnostic tools in the emergency setting. In contrast to the anterior circulation, local endovascular treatment is the established therapy for the posterior circulation as an underlying arteriosclerotic stenosis remains in 50% of the cases after intravenous fibrinolysis. Nevertheless, systemic fibrinolysis is considered the preferred option in cases where a neurointerventional center cannot be reached within a reasonable time frame and the patient can subsequently be transported for local therapy of a residual stenosis in order to prevent reocclusion (''drip and ship''). Profound clinical and pathophysiological knowledge is the absolute prerequisite for the correct application of state-of-the-art neurointerventional therapy. This review paper focuses on the clinical and pathophysiological details that are crucial for decision-making. (orig.)

  18. Pre-eclampsia: pathophysiology, diagnosis, and management

    Directory of Open Access Journals (Sweden)

    Asmar R

    2011-07-01

    Full Text Available Jennifer Uzan1, Marie Carbonnel1, Olivier Piconne1,3, Roland Asmar2, Jean-Marc Ayoubi11Department of Gynecology and Obstetrics, Hôpital Foch, Suresnes, France; 2Foundation Medical Research Institutes, Geneva, Switzerland; 3Department of Gynecology and Obstetrics, Hôpital Antoine Béclère, Clamart, FranceAbstract: The incidence of pre-eclampsia ranges from 3% to 7% for nulliparas and 1% to 3% for multiparas. Pre-eclampsia is a major cause of maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction. Unfortunately, the pathophysiology of this multisystem disorder, characterized by abnormal vascular response to placentation, is still unclear. Despite great polymorphism of the disease, the criteria for pre-eclampsia have not changed over the past decade (systolic blood pressure >140 mmHg or diastolic blood pressure ≥90 mmHg and 24-hour proteinuria ≥0.3 g. Clinical features and laboratory abnormalities define and determine the severity of pre-eclampsia. Delivery is the only curative treatment for pre-eclampsia. Multidisciplinary management, involving an obstetrician, anesthetist, and pediatrician, is carried out with consideration of the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery. Screening women at high risk and preventing recurrences are key issues in the management of pre-eclampsia.Keywords: pre-eclampsia, epidemiology, pathophysiology, therapeutic management

  19. Eosinophilic esophagitis: From pathophysiology to treatment

    Institute of Scientific and Technical Information of China (English)

    Alessandra; D’Alessandro; Dario; Esposito; Marcella; Pesce; Rosario; Cuomo; Giovanni; Domenico; De; Palma; Giovanni; Sarnelli

    2015-01-01

    Eosinophilic esophagitis(Eo E) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and refluxlike symptoms. Traditionally considered a pediatric disease, the number of adult patients with Eo E is continuously increasing, with a relatively higher incidence in western countries. Dysphagia and food impaction represent the main symptoms complained by patients, but gastroesophageal reflux-like symptoms may also be present. Esophageal biopsies are mandatory for the diagnosis of Eo E, though clinical manifestations and proton pump inhibitors responsiveness must be taken into consideration. The higher prevalence of Eo E in patients suffering from atopic diseases suggests a common background with allergy, however both the etiology and pathophysiology are not completely understood. Elimination diets are considered the firstline therapy in children, but this approach appears less effective in adults patients, who often require steroids; despite medical treatments, Eo E is complicated in some cases by esophageal stricture and stenosis, that require additional endoscopic treatments. This review summarizes the evidence on Eo E pathophysiology and illustrates the safety and efficacy of the most recent medical and endoscopic treatments.

  20. Stoppage in Autism Spectrum Disorders

    DEFF Research Database (Denmark)

    Grønborg, Therese Koops; Hansen, Stefan Nygaard; Nielsen, Svend V;

    2015-01-01

    bias in sibling recurrence risk estimation. This study investigated whether stoppage occurs in Danish families with a firstborn child diagnosed with autism spectrum disorders, and if stoppage was differential. We found that stoppage occurs moderately in Danish families affected by autism spectrum...... disorders, and that stoppage is differential. However, differential stoppage is a minor source of estimation bias in Danish sibling recurrence risk studies of autism spectrum disorders....

  1. A computational perspective on autism

    OpenAIRE

    Rosenberg, Ari; Patterson, Jaclyn Sky; Angelaki, Dora E.

    2015-01-01

    Autism is a pervasive disorder that broadly impacts perceptual, cognitive, social, and motor functioning. Across individuals, the disorder manifests with a large degree of phenotypic diversity. Here, we propose that autism symptomatology reflects alterations in neural computation. Using neural network simulations, we show that a reduction in the amount of inhibition occurring through a computation called divisive normalization can account for perceptual consequences reported in autism, as wel...

  2. The BTBR Mouse Model of Autism Spectrum Disorders Has Learning and Attentional Impairments and Alterations in Acetylcholine and Kynurenic Acid in Prefrontal Cortex

    OpenAIRE

    McTighe, Stephanie M.; Neal, Sarah J.; Qian Lin; Hughes, Zoë A.; Daniel G Smith

    2013-01-01

    Autism is a complex spectrum of disorders characterized by core behavioral deficits in social interaction, communication, repetitive stereotyped behaviors and restricted interests. Autism frequently presents with additional cognitive symptoms, including attentional deficits and intellectual disability. Preclinical models are important tools for studying the behavioral domains and biological underpinnings of autism, and potential treatment targets. The inbred BTBR T+tf/J (BTBR) mouse strain ha...

  3. Elucidation of the Developmental Role of Janus Kinase and Microtubule-Interacting Protein 1, JAKMIP1, an Autism Candidate Gene

    OpenAIRE

    Berg, Jamee Mae

    2013-01-01

    Autism Spectrum Disorders (ASD) are heritable neurodevelopmental disorders, affecting one in 88 children and involving hundreds of genes. The study of convergent biological pathways and simpler, monogenic forms of ASD are useful tools in understanding ASD. Fragile X syndrome (FXS) meets both criteria, as FMRP, the protein disrupted in FXS, regulates neuronal translation, a biological convergence point in autism, and is caused by a single gene mutation. Our group recently identified JAKMIP1...

  4. The psychophysics of visual motion and global form processing in autism

    OpenAIRE

    Koldewyn, Kami; Whitney, David; Rivera, Susan M.

    2009-01-01

    Several groups have recently reported that people with autism may suffer from a deficit in visual motion processing and proposed that these deficits may be related to a general dorsal stream dysfunction. In order to test the dorsal stream deficit hypothesis, we investigated coherent and biological motion perception as well as coherent form perception in a group of adolescents with autism and a group of age-matched typically developing controls. If the dorsal stream hypothesis were true, we wo...

  5. Microcephaly and Macrocephaly in Autism.

    Science.gov (United States)

    Fombonne, Eric; Roge, Bernadette; Claverie, Jacques; Courty, Stephanie; Fremolle, Jeanne

    1999-01-01

    Analysis of data from 126 children with autism found macrocephaly (head circumstance microcephaly (head circumference Microcephaly was significantly associated with the presence of medical disorders. (Author/DB)

  6. THE PATHOPHYSIOLOGIC RESPONSE TO SEVERE BURN INJURY

    Science.gov (United States)

    Jeschke, Marc G; Chinkes, David L; Finnerty, Celeste C; Kulp, Gabriela; Suman, Oscar E; Norbury, William B; Branski, Ludwik K; Gauglitz, Gerd G; Mlcak, Ronald P; Herndon, David N

    2014-01-01

    Objective To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial. Summary Background Data A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with morbidity and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated. Methods Two hundred forty-two severely burned pediatric patients [>30% total body surface area (TBSA)], who received no anabolic drugs, were enrolled in this study. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course. Results Average age was 8 ± 0.2 years, and average burn size was 56 ± 1% TBSA with 43 ± 1% third-degree TBSA. All patients were markedly hypermetabolic throughout acute hospital stay and had significant muscle protein loss as demonstrated by a negative muscle protein net balance (−0.05% ± 0.007 nmol/100 mL leg/min) and loss of lean body mass (LBM) (−4.1% ± 1.9%); P < 0.05. Patients lost 3% ± 1% of their bone mineral content (BMC) and 2 ± 1% of their bone mineral density (BMD). Serum proteome analysis demonstrated profound alterations immediately postburn, which remained abnormal throughout acute hospital stay; P < 0.05. Cardiac function was compromised immediately after burn and remained abnormal up to discharge; P < 0.05. Insulin resistance appeared during the first week postburn and persisted until discharge. Patients were hyperinflammatory with marked changes in IL-8, MCP-1, and IL-6, which were associated with 2.5 ± 0.2 infections and 17% sepsis. Conclusions In this large prospective clinical trial, we delineated the complexity of the postburn pathophysiologic response and conclude that the postburn

  7. Pathophysiology of Manganese-Associated Neurotoxicity

    Science.gov (United States)

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

    2012-01-01

    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

  8. Brady, Our Firstborn Son, Has Autism

    Science.gov (United States)

    Yeh-Kennedy, Mei

    2008-01-01

    Autism awareness is spreading like wildfire. Diagnoses have increased at an astounding rate. The statistic most often quoted is that 1 child in 150 has autism. As if the high rate of autism diagnoses were not worrisome enough, many doctors are not properly trained, or kept up to date, on how to detect autism at the earliest possible age. In many…

  9. Increasing Autism Prevalence in Metropolitan New Jersey

    Science.gov (United States)

    Zahorodny, Walter; Shenouda, Josephine; Howell, Sandra; Rosato, Nancy Scotto; Peng, Bo; Mehta, Uday

    2014-01-01

    High baseline autism spectrum disorder prevalence estimates in New Jersey led to a follow-up surveillance. The objectives were to determine autism spectrum disorder prevalence in the year 2006 in New Jersey and to identify changes in the prevalence of autism spectrum disorder or in the characteristics of the children with autism spectrum disorder,…

  10. Silent auction to benefit local autism services

    OpenAIRE

    Doss, Catherine

    2006-01-01

    "An Evening at the XYZ Gallery: Giving a Voice to Autism" will be held Wednesday, May 3 from 6 to 8:30 p.m. at the XYZ Gallery at 223 North Main Street in Blacksburg. Proceeds from the event will benefit the Virginia Tech Autism Clinic, the Radford University Autism Center, and the Blue Ridge Autism Center.

  11. Subregional differences in intrinsic amygdala hyperconnectivity and hypoconnectivity in autism spectrum disorder.

    Science.gov (United States)

    Kleinhans, Natalia M; Reiter, Maya A; Neuhaus, Emily; Pauley, Greg; Martin, Nathalie; Dager, Stephen; Estes, Annette

    2016-07-01

    The amygdala is a complex structure with distinct subregions and dissociable functional networks. The laterobasal subregion of the amygdala is hypothesized to mediate the presentation and severity of autism symptoms, although very little data are available regarding amygdala dysfunction at the subregional level. In this study, we investigated the relationship between abnormal amygdalar intrinsic connectivity, autism symptom severity, and anxiety and depressive symptoms. We collected resting state fMRI data on 31 high functioning adolescents and adults with autism spectrum disorder and 38 typically developing (TD) controls aged 14-45. Twenty-five participants with ASD and 28 TD participants were included in the final analyses. ASD participants were administered the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule. Adult participants were administered the Beck Depression Inventory II and the Beck Anxiety Inventory. Functional connectivity analyses were conducted from three amygdalar subregions: centromedial (CM), laterobasal (LB) and superficial (SF). In addition, correlations with the behavioral measures were tested in the adult participants. In general, the ASD group showed significantly decreased connectivity from the LB subregion and increased connectivity from the CM and SF subregions compared to the TD group. We found evidence that social symptoms are primarily associated with under-connectivity from the LB subregion whereas over-connectivity and under-connectivity from the CM, SF and LB subregions are related to co-morbid depression and anxiety in ASD, in brain regions that were distinct from those associated with social dysfunction, and in different patterns than were observed in mildly symptomatic TD participants. Our findings provide new evidence for functional subregional differences in amygdala pathophysiology in ASD. Autism Res 2016, 9: 760-772. © 2015 International Society for Autism Research, Wiley Periodicals, Inc

  12. Komunikasi Antarpribadi Pada Anak Penderita Autisme (Studi Kasus Mengenai Komunikasi Efektif Pada Anak Penderita Autisme di Sekolah Khusus Autisme YAKARI)

    OpenAIRE

    Sembiring, Camilla Emanuella

    2015-01-01

    This study, entitled Interpersonal Communication In Children Autism Patients (Case Study Regarding Effective Communication in Children with Autism in Autism Special School YAKARI). This study aims to determine the stages and the role of interpersonal communication in the formation of effective communication in children with autism in the Autism Special School YAKARI. The theory used in this study are: Communication, Interpersonal Communication, Communication Psychology and Self-Disclosure. Th...

  13. Task-specific dystonia: pathophysiology and management.

    Science.gov (United States)

    Sadnicka, Anna; Kassavetis, Panagiotis; Pareés, Isabel; Meppelink, Anne Marthe; Butler, Katherine; Edwards, Mark

    2016-09-01

    Task-specific dystonia is a form of isolated focal dystonia with the peculiarity of being displayed only during performance of a specific skilled motor task. This distinctive feature makes task-specific dystonia a particularly mysterious and fascinating neurological condition. In this review, we cover phenomenology and its increasingly broad-spectrum risk factors for the disease, critically review pathophysiological theories and evaluate current therapeutic options. We conclude by highlighting the unique features of task-specific dystonia within the wider concept of dystonia. We emphasise the central contribution of environmental risk factors, and propose a model by which these triggers may impact on the motor control of skilled movement. By viewing task-specific dystonia through this new lens which considers the disorder a modifiable disorder of motor control, we are optimistic that research will yield novel therapeutic avenues for this highly motivated group of patients. PMID:26818730

  14. Contrast medium-induced nephropathy: the pathophysiology

    DEFF Research Database (Denmark)

    Persson, P B; Tepel, Martin

    2006-01-01

    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...

  15. Gestational diabetes: emerging concepts in pathophysiology

    Science.gov (United States)

    Hodson, Kenneth; Robson, Stephen; Taylor, Roy

    2010-01-01

    Gestational diabetes affects 3 to 5% of pregnancies in the United Kingdom, contributing to significant maternal and fetal morbidity. Understanding the pathophysiology is important as it guides diagnostic screening and treatment. The insulin resistance of normal pregnancy facilitates provision of metabolic substrates to the fetus and is multifactorial in origin. Recent identification of hepatic and skeletal muscle lipid deposition in Type 2 diabetics, demonstrated by novel magnetic resonance spectroscopy techniques, is likely to be the underlying cause of pathological insulin resistance. Similar mechanisms almost certainly underlie gestational diabetes, although further studies are required to prove this. Women who develop gestational diabetes have demonstrable insulin resistance prior to pregnancy that is part of a chronic process of lipid accumulation ultimately leading to type 2 diabetes later in life. The importance of lifestyle advice and dietary modification and the rationale behind the use of metformin are thus explained.

  16. Mitophagy: mechanisms, pathophysiological roles, and analysis.

    Science.gov (United States)

    Ding, Wen-Xing; Yin, Xiao-Ming

    2012-07-01

    Abstract Mitochondria are essential organelles that regulate cellular energy homeostasis and cell death. The removal of damaged mitochondria through autophagy, a process called mitophagy, is thus critical for maintaining proper cellular functions. Indeed, mitophagy has been recently proposed to play critical roles in terminal differentiation of red blood cells, paternal mitochondrial degradation, neurodegenerative diseases, and ischemia or drug-induced tissue injury. Removal of damaged mitochondria through autophagy requires two steps: induction of general autophagy and priming of damaged mitochondria for selective autophagic recognition. Recent progress in mitophagy studies reveals that mitochondrial priming is mediated either by the Pink1-Parkin signaling pathway or the mitophagic receptors Nix and Bnip3. In this review, we summarize our current knowledge on the mechanisms of mitophagy. We also discuss the pathophysiological roles of mitophagy and current assays used to monitor mitophagy. PMID:22944659

  17. Role of leukotrienes in asthma pathophysiology

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    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...

  18. Takotsubo cardiomyopathy: Pathophysiology,diagnosis and treatment

    Institute of Scientific and Technical Information of China (English)

    Kazuo; Komamura; Miho; Fukui; Toshihiro; Iwasaku; Shinichi; Hirotani; Tohru; Masuyama

    2014-01-01

    In 1990,takotsubo cardiomyopathy(TCM)was first discovered and reported by a Japanese cardiovascular specialist.Since then,this heart disease has gained worldwide acceptance as an independent disease entity.TCM is an important entity that differs from acute myocardial infarction.It occurs more often in postmenopausal elderly women,is characterized by a transient hypokinesis of the left ventricular(LV)apex,and is associated with emotional or physical stress.Wall motion abnormality of the LV apex is generally transient and resolves within a few days to several weeks.Its prognosis is generally good.However,there are some reports of serious TCM complications,including hypotension,heart failure,ventricular rupture,thrombosis involving the LV apex,and torsade de pointes.It has been suggested that coronary spasm,coronary microvascular dysfunction,catecholamine toxicity and myocarditis might contribute to the pathogenesis of TCM.However,its pathophysiology is not clearly understood.

  19. The role of ADAMs in disease pathophysiology.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    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.

  20. Somnambulism: clinical aspects and pathophysiological hypotheses.

    Science.gov (United States)

    Zadra, Antonio; Desautels, Alex; Petit, Dominique; Montplaisir, Jacques

    2013-03-01

    Somnambulism, or sleepwalking, can give rise to a wide range of adverse consequences and is one of the leading causes of sleep-related injury. Accurate diagnosis is crucial for proper management and imperative in an ever-increasing number of medicolegal cases implicating sleep-related violence. Unfortunately, several widely held views of sleepwalking are characterised by key misconceptions, and some established diagnostic criteria are inconsistent with research findings. The traditional idea of somnambulism as a disorder of arousal might be too restrictive and a comprehensive view should include the idea of simultaneous interplay between states of sleep and wakefulness. Abnormal sleep physiology, state dissociation, and genetic factors might explain the pathophysiology of the disorder. PMID:23415568

  1. [Proliferative vitreoretinopathy: pathophysiology and clinical diagnosis].

    Science.gov (United States)

    Rouberol, F; Chiquet, C

    2014-09-01

    Proliferative vitreoretinopathy (PVR) remains one of the most common causes of failed retinal detachment (RD) surgery. Many histological and clinical studies have highlighted the chain of events leading to PVR: cellular migration into the vitreous cavity, cellular differentiation, myofibroblast proliferation and activation, synthesis of extracellular matrix proteins, then contraction of preretinal tissues. The development of PVR can be explained schematically by cellular exposure to growth factors and cytokines (particularly retinal pigment epithelial cells and glial cells), in the context of break-down of the blood-retinal barrier (inflammation, choroidal detachment, iatrogenic effect of cryotherapy and surgery) and of cellular contact with the vitreous. Although the pathophysiology of PVR is now better understood, its severity remains an issue. A systematic search for preoperative PVR risk factors allows the most suitable therapeutic option to be chosen. PMID:24997864

  2. Pathophysiology, Clinical, and Therapeutic Aspects of Narcolepsy

    Directory of Open Access Journals (Sweden)

    Pinar Guzel Ozdemir

    2014-09-01

    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

  3. Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Sajdel-Sulkowska

    2008-01-01

    Full Text Available It has been suggested that oxidative stress and/or mercury compounds play an important role in the pathophysiology of autism. This study compared for the first time the cerebellar levels of the oxidative stress marker 3-nitrotyrosine (3-NT, mercury (Hg and the antioxidant selenium (Se levels between control and autistic subjects. Tissue homogenates were prepared in the presence of protease inhibitors from the frozen cerebellar tissue of control (n=10; mean age, 15.5 years; mean PMI, 15.5 hours and autistic (n=9; mean age 12.1 years; mean PMI, 19.3 hours subjects. The concentration of cerebellar 3-NT, determined by ELISA, in controls ranged from 13.69 to 49.04 pmol g-1 of tissue; the concentration of 3-NT in autistic cases ranged from 3.91 to 333.03 pmol g-1 of tissue. Mean cerebellar 3-NT was elevated in autism by 68.9% and the increase was statistically significant (p=0.045. Cerebellar Hg, measured by atomic absorption spectrometry ranged from 0.9 to 35 pmol g-1 tissue in controls (n=10 and from 3.2 to 80.7 pmol g-1 tissue in autistic cases (n=9; the 68.2% increase in cerebellar Hg was not statistically significant. However, there was a positive correlation between cerebellar 3-NT and Hg levels (r=0.7961, p=0.0001. A small decrease in cerebellar Se levels in autism, measured by atomic absorption spectroscopy, was not statistically significant but was accompanied by a 42.9% reduction in the molar ratio of Se to Hg in the autistic cerebellum. While preliminary, the results of the present study add elevated oxidative stress markers in brain to the growing body of data reflecting greater oxidative stress in autism.

  4. Inhibition of IL-6 trans-signaling in the brain increases sociability in the BTBR mouse model of autism.

    Science.gov (United States)

    Wei, Hongen; Ma, Yuehong; Liu, Jianrong; Ding, Caiyun; Jin, Guorong; Wang, Yi; Hu, Fengyun; Yu, Li

    2016-10-01

    Autism is a severe neurodevelopmental disorder with a large population prevalence, characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. The BTBR T(+)Itpr3(tf) (BTBR) mice have emerged as strong candidates to serve as models of a range of autism-relevant behaviors. Increasing evidences suggest that interleukin (IL)-6, one of the most important neuroimmune factors, was involved in the pathophysiology of autism. It is of great importance to further investigate whether therapeutic interventions in autism can be achieved through the manipulation of IL-6. Our previous studies showed that IL-6 elevation in the brain could mediate autistic-like behaviors, possibly through the imbalances of neural circuitry and impairments of synaptic plasticity. In this study, we evaluate whether inhibiting IL-6 signaling in the brain is sufficient to modulate the autism-like behaviors on the BTBR mice. The results showed that chronic infusion of an analog of the endogenous IL-6 trans-signaling blocker sgp130Fc protein increased the sociability in BTBR mice. Furthermore, no change was observed in the number of excitatory synapse, level of synaptic proteins, density of dentitic spine and postsynaptic density in BTBR cortices after inhibiting IL-6 trans-signaling. However, inhibition of IL-6 trans-signaling increased the evoked glutamate release in synaptoneurosomes from the cerebral cortex of BTBR mice. Our findings suggest that inhibition of excessive production of IL-6 may have selective therapeutic efficacy in treating abnormal social behaviors in autism. PMID:27460706

  5. The Neuropathology of Autism

    OpenAIRE

    Blatt, Gene J.

    2012-01-01

    Autism is a behaviorally defined neurodevelopmental disorder that affects over 1% of new births in the United States and about 2% of boys. The etiologies are unknown and they are genetically complex. There may be epigenetic effects, environmental influences, and other factors that contribute to the mechanisms and affected neural pathway(s). The underlying neuropathology of the disorder has been evolving in the literature to include specific brain areas in the cerebellum, limbic system, and co...

  6. Autism spectrum disorders

    OpenAIRE

    Faras Hadeel; Al Ateeqi Nahed; Tidmarsh Lee

    2010-01-01

    Pervasive developmental disorders are a group of neurodevelopmental disorders characterized by impairments in communication, reciprocal social interaction and restricted repetitive behaviors or interests. The term autism spectrum disorders (ASD) has been used to describe their variable presentation. Although the cause of these disorders is not yet known, studies strongly suggest a genetic basis with a complex mode of inheritance. More research is needed to explore environmental factors that c...

  7. AUTISM AND TUBEROUS SCLEROSIS

    OpenAIRE

    KOPACHEV Dragoslav; Vladimir TRAJKOVSKI

    2000-01-01

    Autism is a frequent manifestation of tuberous sclerosis being reported in up to 60% of the patients. Tuberous sclerosis is developmental disorder of neurogenesis and neuronal migration. Symptoms of CNS involvement are prominent. Brain abnormalities underlying this neurological and behavioral phenotype include areas of focal cortical dysplasia, subependymal nodules, and cortical and subcortical tubers. The authors show case of tuberous sclerosis in 4 and half age girl where next symptoms domi...

  8. [Autism spectrum disorders in adults

    NARCIS (Netherlands)

    Kan, C.C.; Buitelaar, J.K.; Gaag, R.J. van der

    2008-01-01

    Early infantile autism' as defined by Kanner has grown into a spectrum of autistic disorders. The recognition of Asperger's disorder and of pervasive developmental disorder not otherwise specified (PDD-NOS), has led to increased demand for appropriate diagnostic assessment of autism in adults. The e

  9. Environmental risk factors for autism

    Directory of Open Access Journals (Sweden)

    Rodney R. Dietert

    2011-04-01

    Full Text Available Autism is a devastating childhood condition that has emerged as an increasing social concern just as it has increased in prevalence in recent decades. Autism and the broader category of autism spectrum disorders are among the increasingly seen examples in which there is a fetal basis for later disease or disorder. Environmental, genetic, and epigenetic factors all play a role in determining the risk of autism and some of these effects appear to be transgenerational. Identification of the most critical windows of developmental vulnerability is paramount to understanding when and under what circumstances a child is at elevated risk for autism. No single environmental factor explains the increased prevalence of autism. While a handful of environmental risk factors have been suggested based on data from human studies and animal research, it is clear that many more, and perhaps the most significant risk factors, remain to be identified. The most promising risk factors identified to date fall within the categories of drugs, environmental chemicals, infectious agents, dietary factors, and other physical/psychological stressors. However, the rate at which environmental risk factors for autism have been identified via research and safety testing has not kept pace with the emerging health threat posed by this condition. For the way forward, it seems clear that additional focused research is needed. But more importantly, successful risk reduction strategies for autism will require more extensive and relevant developmental safety testing of drugs and chemicals.

  10. Autism in Tuberous Sclerosis Complex.

    Science.gov (United States)

    Gutierrez, Griselda C.; Smalley, Susan L.; Tanguay, Peter E.

    1998-01-01

    The frequency and clinical presentation of autism in 28 probands with tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by benign tissue growths and a high frequency of seizure disorders and mental retardation, was examined. Eight probands met criteria for autism. Implications for understanding the association of…

  11. The Troubled Touch of Autism.

    Science.gov (United States)

    Tuttle, Alexander H; Bartsch, Victoria B; Zylka, Mark J

    2016-07-14

    A study finds that deficits in touch-sensing somatosensory neurons contribute to social interaction and anxiety phenotypes in mouse models of autism and Rett syndrome. These findings suggest that some core symptoms of autism might originate from aberrant development or function of the peripheral nervous system. PMID:27419865

  12. Material Voices: Intermediality and Autism

    Science.gov (United States)

    Trimingham, Melissa; Shaughnessy, Nicola

    2016-01-01

    Autism continues to be regarded enigmatically; a community that is difficult to access due to perceived disruptions of interpersonal connectedness. Through detailed observations of two children participating in the Arts and Humanities Research Council funded project "Imagining Autism: Drama, Performance and Intermediality as Interventions for…

  13. Sleep Disorders, Epilepsy, and Autism

    Science.gov (United States)

    Malow, Beth A.

    2004-01-01

    The purpose of this review article is to describe the clinical data linking autism with sleep and epilepsy and to discuss the impact of treating sleep disorders in children with autism either with or without coexisting epileptic seizures. Studies are presented to support the view that sleep is abnormal in individuals with autistic spectrum…

  14. Children with Autism & Their Siblings

    Science.gov (United States)

    Cancro, Ralph

    2008-01-01

    The parent of the child with autism is faced with many home management challenges, not the least of which is the achievement of intra-family harmony among siblings. Sibling rivalry occurs in all families. However, the presence of a child with autism may, in some instances, intensify this rivalry. In this article, the author provides tips for…

  15. Examining Sensory Quadrants in Autism

    Science.gov (United States)

    Kern, Janet K.; Garver, Carolyn R.; Carmody, Thomas; Andrews, Alonzo A.; Trivedi, Madhukar H.; Mehta, Jyutika A.

    2007-01-01

    The purpose of this study was to examine sensory quadrants in autism based on Dunn's Theory of Sensory Processing. The data for this study was collected as part of a cross-sectional study that examined sensory processing (using the Sensory Profile) in 103 persons with autism, 3-43 years of age, compared to 103 age- and gender-matched community…

  16. Autisme-spektrum forstyrrelser

    DEFF Research Database (Denmark)

    Laursen, Kathrine Bang

    2014-01-01

    Sammenfatning Autisme er blandt de alvorligste psykiske udviklingsforstyrrelser blandt børn og unge. Vi har set en stigning i diagnosticerede tilfælde igennem de sidste 20 år fra nogle få promille til omkring én procent. Stigningen i forekomsten skyldes formodentlig primært udvikling i diagnostisk...... praksis kombineret med stigende krav til sociale færdigheder og fleksibilitet. Autisme kan findes i forskellige grader og er fire gange hyppigere hos drenge end hos piger. Udenlandske studier har vist en højere forekomst af ASF hos familier med høj socioøkonomisk status, men det er uvist, om denne...... sammenhæng blot er udtryk for en ulige adgang til sundhedssystemet. I Danmark er der ikke tegn på større social skævhed i relation til denne diagnose. Der findes ingen medicinsk behandling for autisme, men en tidlig erkendelse af problemerne og efterfølgende støtte kan formodentlig forbedre livsforløbet....

  17. Brain imaging and autism

    Energy Technology Data Exchange (ETDEWEB)

    Zilbovicius, M. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), INSERM CEA 0205, 91 - Orsay (France)

    2006-07-01

    Autism is a neuro-developmental disorder with a range of clinical presentations, from mild to severe, referred to as autism spectrum disorders (ASD). The most common clinical ASD sign is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and obsessive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in ASD. Indeed, functional brain imaging, such as positron emission tomography (PET), single positron emission tomograph y (SPECT) and functional MRI (fMRI) have opened a new perspective to study normal and pathological brain functions. Three independent studies have found anatomical and rest functional temporal abnormalities. These anomalies are localized in the superior temporal sulcus bilaterally which are critical for perception of key social stimuli. In addition, functional studies have shown hypo-activation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network. The understanding of such crucial abnormal mechanism may drive the elaboration of new and more adequate social re-educative strategies in autism. (author)

  18. Brain imaging and autism

    International Nuclear Information System (INIS)

    Autism is a neuro-developmental disorder with a range of clinical presentations, from mild to severe, referred to as autism spectrum disorders (ASD). The most common clinical ASD sign is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and obsessive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in ASD. Indeed, functional brain imaging, such as positron emission tomography (PET), single positron emission tomograph y (SPECT) and functional MRI (fMRI) have opened a new perspective to study normal and pathological brain functions. Three independent studies have found anatomical and rest functional temporal abnormalities. These anomalies are localized in the superior temporal sulcus bilaterally which are critical for perception of key social stimuli. In addition, functional studies have shown hypo-activation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network. The understanding of such crucial abnormal mechanism may drive the elaboration of new and more adequate social re-educative strategies in autism. (author)

  19. The Broader Autism Phenotype and Its Implications on the Etiology and Treatment of Autism Spectrum Disorders

    OpenAIRE

    Jennifer Gerdts; Raphael Bernier

    2011-01-01

    The presence of autism-related traits has been well documented in undiagnosed family members of individuals with autism spectrum disorder (ASD). The most common finding is mild impairments in social and communication skills that are similar to those shown by individuals with autism, but exhibited to a lesser degree. Termed the broader autism phenotype (BAP), these traits suggest a genetic liability for autism-related traits in families. Genetic influence in autism is strong, with identical tw...

  20. Autism: Collaborative Perspektives in Education

    Directory of Open Access Journals (Sweden)

    Imanuel Hitipeuw

    2016-02-01

    Full Text Available Autism is the continuum of impairments. Children with autism show intellectual, social, emotional, and language or communication disorder. Collaboration is an important aspect in delivering education/intervention for children. Professionals have to have knowledge and skill related to autism and have to team up with parent in dealing with the disorder. The unique profile of the individual with autism calls for emphasis in the areas of communication skills, social-emotional, behavioral, and sensory regulation, and communication. Pre-identification of the children may help teachers and parents to make decisions whether the child needs a referral or not. In this case, Indonesia needs to make more political will in order to implement autism education in various setting to address immediate needs of the children before the problem becomes more complicated

  1. Altered brain connectivity in 3-to 7-year-old children with autism spectrum disorder ☆ ☆☆

    OpenAIRE

    Kikuchi, Mitsuru; Shitamichi, Kiyomi; Yoshimura, Yuko; Ueno, Sanae; Hiraishi, Hirotoshi; Hirosawa, Tetsu; Munesue, Toshio; Nakatani, Hideo; Tsubokawa, Tsunehisa; Haruta, Yasuhiro; Oi, Manabu; Niida, Yo; Gerard B. Remijn; Takahashi, Tsutomu; Suzuki, Michio

    2013-01-01

    Autism spectrum disorder (ASD) is often described as a disorder of aberrant neural connectivity and/or aberrant hemispheric lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, the physiological connectivity of the brain in young children with ASD under conscious conditions has not yet been described. Magnetoencephalography (MEG) is a noninvasive brain imaging technique that is practical for use in young children. MEG produces a reference-free si...

  2. The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)

    OpenAIRE

    Bhakar, Asha L.; Dölen, Gül; Bear, Mark F.

    2012-01-01

    Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper...

  3. Steroid-associated osteonecrosis: Epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview

    Directory of Open Access Journals (Sweden)

    Xin-Hui Xie

    2015-04-01

    Full Text Available Steroid-associated osteonecrosis (SAON is a common orthopaedic problem caused by administration of corticosteroids prescribed for many nonorthopaedic medical conditions. We summarised different pathophysiologies of SAON which have adverse effects on multiple systems such as bone marrow stem cells (BMSCs pool, bone matrix, cell apoptosis, lipid metabolism, and angiogenesis. Different animal models were introduced to mimic the pathophysiology of SAON and for testing the efficacy of both prevention and treatment effects of various chemical drugs, biological, and physical therapies. According to the classification of SAON, several prevention and treatment methods are applied at the different stages of SAON. For the current period, Chinese herbs may also have the potential to prevent the occurrence of SAON. In the future, genetic analysis might also be helpful to effectively predict the development of ON and provide information for personalised prevention and treatment of patients with SAON.

  4. Somatosensory dysfunctin in fibromyaligia : Implications for pathophysiological mechanisms

    OpenAIRE

    Kosek, Eva

    1996-01-01

    SOMATOSENSORY DYSFUNCTION IN FIBROMYALGIA. IMPLICATIONS FOR PATHOPHYSIOLOGICAL MECHANISMS. Eva KosekDissertation from the Department of Rehabilitation Medicine, Karolinska Institure/Hospital, Stoclcholm, Sweden Fibromyalgia is a chronic pain syndrome characterized by generalized pain, tenderness,disturbed sleep and pronounced fatigue. The pathophysiology is unknown ...

  5. Sunspot Dynamics Are Reflected in Human Physiology and Pathophysiology

    Science.gov (United States)

    Hrushesky, William J. M.; Sothern, Robert B.; Du-Quiton, Jovelyn; Quiton, Dinah Faith T.; Rietveld, Wop; Boon, Mathilde E.

    2011-03-01

    Periodic episodes of increased sunspot activity (solar electromagnetic storms) occur with 10-11 and 5-6 year periodicities and may be associated with measurable biological events. We investigated whether this sunspot periodicity characterized the incidence of Pap smear-determined cervical epithelial histopathologies and human physiologic functions. From January 1983 through December 2003, monthly averages were obtained for solar flux and sunspot numbers; six infectious, premalignant and malignant changes in the cervical epithelium from 1,182,421 consecutive, serially independent, screening Pap smears (59°9"N, 4°29"E); and six human physiologic functions of a healthy man (oral temperature, pulse, systolic and diastolic blood pressure, respiration, and peak expiratory flow), which were measured ∼5 times daily during ∼34,500 self-measurement sessions (44°56"N, 93°8"W). After determining that sunspot numbers and solar flux, which were not annually rhythmic, occurred with a prominent 10-year and a less-prominent 5.75-year periodicity during this 21-year study span, each biological data set was analyzed with the same curve-fitting procedures. All six annually rhythmic Pap smear-detected infectious, premalignant and malignant cervical epithelial pathologies showed strong 10-year and weaker 5.75-year cycles, as did all six self-measured, annually rhythmic, physiologic functions. The phases (maxima) for the six histopathologic findings and five of six physiologic measurements were very near, or within, the first two quarters following the 10-year solar maxima. These findings add to the growing evidence that solar magnetic storm periodicities are mirrored by cyclic phase-locked rhythms of similar period length or lengths in human physiology and pathophysiology.

  6. The biochemical, pathophysiological, and medical aspects of ubiquinone function.

    Science.gov (United States)

    Nohl, H; Gille, L; Staniek, K

    1998-11-20

    Ubiquinone (Q) shares its biological implication in membrane-associated redox reactions with a variety of other redox carriers, such as dehydrogenases, non-heme-iron proteins, and cytochromes. Peculiarities arise from the lack of transition metals, which in contrast to the other electron carriers do not participate in redox-shuttle activities of Q. Another peculiarity is the lipophilicity of Q, which allows free movement between reductants and oxidants of a membrane. The chemistry of Q reduction and ubiquinol oxidation requires the stepwise acceptance and transfer of two single electrons associated with the addition or release of two single H+. These special qualities are widely used in biological membranes for linear electron transfer and transmembranous H+ translocation. In mitochondria it was long reported that under certain conditions linear e- transfer from the semireduced form (SQ.) to native oxidants of the respiratory chain may run out of control, thereby establishing a permanent source of oxygen radical release. It should be mentioned that in mitochondria e- transfer to dioxygen out of sequence requires a particular treatment with inhibitors and uncouplers of the respiratory chain. Nevertheless, it is generally assumed that Q is mainly involved in mitochondrial O2.- generation and that mitochondria represent the major source of O2.- radicals under physiological and various pathophysiological conditions. The ever-increasing application of coenzyme Q as an antioxidant for the prophylaxis and treatment of a great variety of functional disorders, including senescence, has considerably stimulated our interest in the potential prooxidative potency of this natural electron carrier. Experimental evidence will be presented that under physiological conditions Q implicated in mitochondrial e- transfer of the respiratory chain is not involved in cellular oxygen activation. It will also be shown that alterations of Q from an e- carrier to an active radical promotor is

  7. Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome

    Directory of Open Access Journals (Sweden)

    Richard E. Frye

    2015-05-01

    Full Text Available Autism spectrum disorder (ASD affects a significant number of individuals worldwide with the prevalence continuing to grow. It is becoming clear that a large subgroup of individuals with ASD demonstrate abnormalities in mitochondrial function as well as gastrointestinal (GI symptoms. Interestingly, GI disturbances are common in individuals with mitochondrial disorders and have been reported to be highly prevalent in individuals with co-occurring ASD and mitochondrial disease. The majority of individuals with ASD and mitochondrial disorders do not manifest a primary genetic mutation, raising the possibility that their mitochondrial disorder is acquired or, at least, results from a combination of genetic susceptibility interacting with a wide range of environmental triggers. Mitochondria are very sensitive to both endogenous and exogenous environmental stressors such as toxicants, iatrogenic medications, immune activation, and metabolic disturbances. Many of these same environmental stressors have been associated with ASD, suggesting that the mitochondria could be the biological link between environmental stressors and neurometabolic abnormalities associated with ASD. This paper reviews the possible links between GI abnormalities, mitochondria, and ASD. First, we review the link between GI symptoms and abnormalities in mitochondrial function. Second, we review the evidence supporting the notion that environmental stressors linked to ASD can also adversely affect both mitochondria and GI function. Third, we review the evidence that enteric bacteria that are overrepresented in children with ASD, particularly Clostridia spp., produce short-chain fatty acid metabolites that are potentially toxic to the mitochondria. We provide an example of this gut–brain connection by highlighting the propionic acid rodent model of ASD and the clinical evidence that supports this animal model. Lastly, we discuss the potential therapeutic approaches that could be

  8. Autism Spectrum Disorder and Epilepsy: Two Sides of the Same Coin?

    Science.gov (United States)

    Jeste, Shafali Spurling; Tuchman, Roberto

    2015-12-01

    Autism spectrum disorders and epilepsy commonly co-occur. In this review, we consider some unresolved questions regarding the temporal relationship, causal mechanisms, and clinical stratification of this comorbidity, highlighting throughout the interplay between autism spectrum disorder, epilepsy, and intellectual disability. We present data on the clinical characterization of children with autism spectrum disorder and epilepsy, discussing distinctive phenotypes in children with this comorbidity. Although some distinctive clinical features emerge, this comorbidity also informs convergent pathways in genetic variants that cause synaptic dysfunction. We then move beyond diagnostic categorization and consider the extent to which electrophysiology as a quantitative biomarker may help guide efforts in clinical stratification and outcome prediction. Epilepsy, and atypical electrophysiological patterns, in autism spectrum disorder may inform the definition of biologically meaningful subgroups within the spectrum that, in turn, can shed light on potential targets for intervention. PMID:26374786

  9. Polycystic ovary syndrome: symptomatology, pathophysiology, and epidemiology.

    Science.gov (United States)

    Guzick, D

    1998-12-01

    Women with polycystic ovary syndrome seek health care for 3 major reasons: infertility, menstrual irregularity, and androgen excess. The infertility is associated with anovulation. The menstrual irregularity is typically chronic, beginning with menarche. Although amenorrhea may sometimes occur, the more common presentation is irregular bleeding characteristic of anovulation. Androgen excess may be manifested by varying degrees of hirsutism. Patients may also report acne. The rapid development of virilizing signs, such as deepening of the voice, increased muscle mass, and temporal balding, should prompt a search for a tumor and lead one away from a diagnosis of polycystic ovary syndrome. Typically treatment is directed at alleviating the symptoms: ovulation induction for infertility, oral contraceptives or a progestin for menstrual irregularity, and oral contraceptives or spironolactone for hirsutism. On the basis of recent epidemiologic data suggestive of increased cardiovascular risk among women with polycystic ovary syndrome, such treatment might be complemented by a long-term approach that addresses the underlying pathophysiology of insulin resistance. PMID:9855614

  10. Pathophysiology of constipation in the older adult

    Institute of Scientific and Technical Information of China (English)

    G Lindsay McCrea; Christine Miaskowski; Nancy A Stotts; Liz Macera; Madhulika G Varma

    2008-01-01

    This review provides information on the definition of constipation,normal continence and defecation and a description of the pathophysiologic mechanisms of constipation.In addition,changes in the anatomy and physiology of the lower gastrointestinal tract associated with aging that may contribute to constipation are described.MEDLINE (1966-2007) and CINAHL (1980-2007) were searched.The following MeSH terms were used:constipation/etiology OR constipation/physiology OR constipation/physiopathology) AND (age factors OR aged OR older OR 80 and over OR middle age).Constipation is not well defined in the literature.While self-reported constipation increases with age,findings from a limited number of clinical studies that utilized objective measures do not support this association.Dysmotility and pelvic floor dysfunction are important mechanisms associated with constipation.Changes in GI function associated with aging appear to be relatively subtle based on a limited amount of conflicting data.Additional research is warranted on the effects of aging on GI function,as well as on the timing of these changes.

  11. Pathophysiology and Immune Dysfunction in Endometriosis

    Directory of Open Access Journals (Sweden)

    Soo Hyun Ahn

    2015-01-01

    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.

  12. Pathophysiology of enteric infections with Giardia duodenalis

    Directory of Open Access Journals (Sweden)

    Buret A.G.

    2008-09-01

    Full Text Available Giardia is the most prevalent human intestinal parasitic protist in the world, and one of the most common parasite of companion animals and young livestock. Giardia is a major cause of diarrhea in children and in travelers. The host-microbial interactions that govern the outcome of infection remain incompletely understood. Findings available to date indicate that the infection causes diarrhea via a combination of intestinal malabsorption and hypersecretion. Malabsorption and maldigestion mainly result from a diffuse shortening of epithelial microvilli. This enterocytic injury is mediated by activated host T lymphocytes. Pathophysiological activation of lymphocytes is secondary to Giardia-induced disruption of epithelial tight junctions, which in turn increases intestinal permeability. Loss of epithelial barrier function is a result of Giardia-induced enterocyte apoptosis. Recent findings suggest that these effects may facilitate the development of chronic enteric disorders, including inflammatory bowel disease, irritable bowel syndrome, and allergies, via mechanisms that remain poorly understood. A newly discovered SGLT-1 glucose uptake-mediated host cytoprotective mechanism may represent an effective modulator of the epithelial apoptosis induced by this parasite, and, possibly, by other enteropathogens. A better understanding of the pathogenesis of giardiasis will shed light on new potential therapeutic targets.

  13. Neurophysiology of Tourette's syndrome: pathophysiological considerations.

    Science.gov (United States)

    Segawa, Masaya

    2003-12-01

    At present the neurophysiology of Tourette's syndrome (TS) has been investigated largely from two perspectives; one for evaluation of the dysfunction of the cerebral cortex and the other for clarification of the neuronal mechanisms that underlie tics and related symptoms. For the former the following examinations have been conducted: quantitative analyses of scalp electroencephalography (EEG), premovement EEG potentials, contingent negative variation, transcranial magnetic stimulation, and neuroimaging studies, including echo-planar images and positron emission tomography scans. These explorations have revealed the likely involvement of the subcortical and the cortical structures, particularly of the basal ganglia, in the pathophysiology of TS. For the latter, surface electromyography, evoked potentials, saccadic eye movements, and polysomnographies have been performed, and again have suggested a dysfunction of the basal ganglia and the brainstem neurons in TS patients. These neurophysiological studies suggest dysfunction of both motor and non-motor basal ganglia-thalamocortical circuitries in TS patients, which is hypothesized to be caused by hypofunction of the dopamine (DA) neurons associated with DA receptor supersensitivity, a well as hypofunction of the serotonergic neurons of the brainstem. Polysomnographical examination suggests that the dysfunction of the nigrostriatal (NS)-DA neurons is not a progressive process, but that the dysfunction is closely associated with an early occurrence of the developmental decrement of the activities of the NS-DA system to mature in a normal fashion. The associated DA receptor supersensitivity is assumed to be a consequence of this developmental abnormality and not due to denervation supersensitivity. PMID:14980375

  14. Clinical manifestations and pathophysiology of lissencephaly

    International Nuclear Information System (INIS)

    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.)

  15. Rare structural variation of synapse and neurotransmission genes in autism

    OpenAIRE

    Gai, X; Xie, H M; Perin, J C; Takahashi, N; Murphy, K.; Wenocur, A S; D'arcy, M; O'Hara, R J; Goldmuntz, E; Grice, D. E.; Shaikh, T H; Hakonarson, H.; Buxbaum, J D; Elia, J.; White, P S

    2011-01-01

    Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commonality of biological function among rare risk alleles, we compared functional knowledge of genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In ...

  16. Autism and ADHD – two ends of the same spectrum?

    OpenAIRE

    Duch, Włodzisław

    2014-01-01

    Analysis of dynamics of biologically motivated neural networks allows for studying non-linear processes responsible for cognitive functions and thus provides adequate language to understand complex mental processes, including psychiatric syndromes and disorders. Problems with attention shifts that are at the roots of Autism Spectrum Disorders (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD), have been investigated using network model of Posner Visual Orienting Task (PVOT). Changing p...

  17. Lectin-like oxidized low-density lipoprotein receptor-1: protein,ligands, expression and pathophysiological significance

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiu-ping; DU Guan-hua

    2007-01-01

    Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)including its protein, ligands, expression and pathophysiological significance.Data sources Information included in this article was identified by searching of PUBMED (1997-2006) online resources using the key term LOX-1.Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected.Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed.Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.

  18. DIAGNOSTIC AND MANAGEMENT OF AUTISM

    Directory of Open Access Journals (Sweden)

    Made Ovy Riandewi Griadhi

    2013-11-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Autism is a coalition condition of development disorders which the clinical symptoms are social interaction difficulty, verbal and nonverbal communication problem, repetition of behavior and actions, and shallow and obsessive of interest. Autism is caused by some kind of factors. Genetic and environment factors are thought have a significant role. For diagnosing autism need a kind of criterions from DSM IV, or screening by CARS rating system (Childhood Autism Rating Scale, Checklist for Autism in Toddlers (CHAT, and Autism Screening Questionnaire. Management of autism must be holistic consist of medication and non medication. The aim of therapy for autism is reducing behavior problems and increasing studying ability especially in language mastery. The autism that screened earlier then got a directly treatment can live independently but still depend on the type of autistic disorders and the age at that time. /* 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;}

  19. Breast Cancer and Autism

    OpenAIRE

    Radcliff, Lisa

    2013-01-01

    Case Study Amy is a 44-year-old woman with severe autism. She lives with her sister Susan, who is her caregiver and guardian. Amy is ambulatory and able to dress and feed herself. She is a healthy individual with no other significant comorbidities. She walks daily and enjoys her sister’s company. Amy’s life expectancy is greater than 10 years. However, she is difficult to care for medically, as she will not allow a physical examination and strikes out when strangers try to touch her. She is n...

  20. Autism and related disorders.

    Science.gov (United States)

    McPartland, James; Volkmar, Fred R

    2012-01-01

    The pervasive developmental disorders are a group of neurodevelopmental disorders that include autistic disorder, Asperger's disorder, pervasive developmental disorder - not otherwise specified (PDD-NOS), childhood disintegrative disorder (CDD), and Rett's disorder. All feature childhood onset with a constellation of symptoms spanning social interaction and communication and including atypical behavior patterns. The first three disorders (autistic disorder, Asperger's disorder, and PDD-NOS) are currently referred to as autism spectrum disorders, reflecting divergent phenotypic and etiological characteristics compared to Rett's disorder and CDD. This chapter reviews research and clinical information to appropriate medical diagnosis and treatment. PMID:22608634

  1. Quantifying and modeling birth order effects in autism.

    Directory of Open Access Journals (Sweden)

    Tychele Turner

    Full Text Available Autism is a complex genetic disorder with multiple etiologies whose molecular genetic basis is not fully understood. Although a number of rare mutations and dosage abnormalities are specific to autism, these explain no more than 10% of all cases. The high heritability of autism and low recurrence risk suggests multifactorial inheritance from numerous loci but other factors also intervene to modulate risk. In this study, we examine the effect of birth rank on disease risk which is not expected for purely hereditary genetic models. We analyzed the data from three publicly available autism family collections in the USA for potential birth order effects and studied the statistical properties of three tests to show that adequate power to detect these effects exist. We detect statistically significant, yet varying, patterns of birth order effects across these collections. In multiplex families, we identify V-shaped effects where middle births are at high risk; in simplex families, we demonstrate linear effects where risk increases with each additional birth. Moreover, the birth order effect is gender-dependent in the simplex collection. It is currently unknown whether these patterns arise from ascertainment biases or biological factors. Nevertheless, further investigation of parental age-dependent risks yields patterns similar to those observed and could potentially explain part of the increased risk. A search for genes considering these patterns is likely to increase statistical power and uncover novel molecular etiologies.

  2. The pathophysiology of restless legs syndrome

    International Nuclear Information System (INIS)

    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

  3. Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.

    Science.gov (United States)

    Rai, Vandana

    2016-08-01

    Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C = 1.48; 95 % CI: 1.18-1.86; P = 0.0007; ORTT + CT vs. CC = 1.70, 95 % CI = 0.96-2.9, p = 0.05; ORTT vs. CC = 1.84, 95 % CI = 1.12-3.02, p = 0.02; ORCT vs.CC = 1.60, 95 % CI = 1.2-2.1, p = 0.003; ORTT vs.CT+CC = 1.5, 95 % CI = 1.02-2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C = 1.43; 95 % CI = 1.1-1.87; p = 0.009) and Asian population (ORTvs.C = 1.68; 95 % CI = 1.02-2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism. PMID:26956130

  4. Chagas disease. A new pathophysiological assessment

    International Nuclear Information System (INIS)

    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

  5. Altered Mitochondrial Dynamics and TBI Pathophysiology

    Directory of Open Access Journals (Sweden)

    Tara Diane Fischer

    2016-03-01

    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

  6. Altered Mitochondrial Dynamics and TBI Pathophysiology.

    Science.gov (United States)

    Fischer, Tara D; Hylin, Michael J; Zhao, Jing; Moore, Anthony N; Waxham, M Neal; Dash, Pramod K

    2016-01-01

    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 (MOM) 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 h post-injury, followed by a significant decrease in length at 72 h. Post-TBI administration of Mitochondrial division inhibitor-1 (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

  7. Toward an immune-mediated subtype of autism spectrum disorder.

    Science.gov (United States)

    McDougle, Christopher J; Landino, Samantha M; Vahabzadeh, Arshya; O'Rourke, Julia; Zurcher, Nicole R; Finger, Beate C; Palumbo, Michelle L; Helt, Jessica; Mullett, Jennifer E; Hooker, Jacob M; Carlezon, William A

    2015-08-18

    A role for immunological involvement in autism spectrum disorder (ASD) has long been hypothesized. This review includes four sections describing (1) evidence for a relationship between familial autoimmune disorders and ASD; (2) results from post-mortem and neuroimaging studies that investigated aspects of neuroinflammation in ASD; (3) findings from animal model work in ASD involving inflammatory processes; and (4) outcomes from trials of anti-inflammatory/immune-modulating drugs in ASD that have appeared in the literature. Following each section, ideas are provided for future research, suggesting paths forward in the continuing effort to define the role of immune factors and inflammation in the pathophysiology of a subtype of ASD. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. PMID:25445995

  8. Prevalence of Autism Spectrum Disorders: Autism and Developmental Disabilities Monitoring Network, United States, 2006. Morbidity and Mortality Weekly Report. Surveillance Summaries. Volume 58, Number SS-10

    Science.gov (United States)

    Rice, Catherine

    2009-01-01

    Problem/Condition: Autism spectrum disorders (ASDs) are a group of developmental disabilities characterized by atypical development in socialization, communication, and behavior. ASDs typically are apparent before age 3 years, with associated impairments affecting multiple areas of a person's life. Because no biologic marker exists for ASDs,…

  9. Endocannabinoid Signaling in Autism.

    Science.gov (United States)

    Chakrabarti, Bhismadev; Persico, Antonio; Battista, Natalia; Maccarrone, Mauro

    2015-10-01

    Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions). In the last 25 years a good deal of information has been accumulated on the main components of the "endocannabinoid (eCB) system", a rather complex ensemble of lipid signals ("endocannabinoids"), their target receptors, purported transporters, and metabolic enzymes. It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders. Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD. PMID:26216231

  10. Rethinking language in autism.

    Science.gov (United States)

    Sterponi, Laura; de Kirby, Kenton; Shankey, Jennifer

    2015-07-01

    In this article, we invite a rethinking of traditional perspectives of language in autism. We advocate a theoretical reappraisal that offers a corrective to the dominant and largely tacitly held view that language, in its essence, is a referential system and a reflection of the individual's cognition. Drawing on scholarship in Conversation Analysis and linguistic anthropology, we present a multidimensional view of language, showing how it also functions as interactional accomplishment, social action, and mode of experience. From such a multidimensional perspective, we revisit data presented by other researchers that include instances of prototypical features of autistic speech, giving them a somewhat different-at times complementary, at times alternative-interpretation. In doing so, we demonstrate that there is much at stake in the view of language that we as researchers bring to our analysis of autistic speech. Ultimately, we argue that adopting a multidimensional view of language has wide ranging implications, deepening our understanding of autism's core features and developmental trajectory. PMID:24916453

  11. Family Process - Autism Spectrum Disorders

    OpenAIRE

    Benson, Mark

    2012-01-01

    Slides for a talk about family process and the importance of parenting dimensions in adolescent development. The slides list findings to date, and propose research into the influence of family on outcomes for those diagnosed with an autism spectrum disorder.

  12. IMUNODIAGNOSTIC AND IMMUNOTHERAPY OF AUTISM

    Directory of Open Access Journals (Sweden)

    Vladimir TRAJKOVSKI

    2000-06-01

    Full Text Available Infantile autism is one of the most disabling illnesses of neurological, emotional and intellectual development. The cause of autism remains unknown. However, recent investigations suggest that this disorder shares several features of established autoimmune disorders.The aim of this article is to describe the news of imunodiagnostic and immunotherapy in autism. Interpretation of data is made by conceptual and methodological differences between studies. The autoimmune response is most likely directed against the brain myelin, perhaps secondary to a viral infection. The idea that autism is an autoimmune disorder is further strengthened by the fact that autistic patients respond well to treatment with immune modulating drugs. Immune interventions can produce immune modulation-state of suppression or stimulation. Immune therapy should always be done in consultation with physicians.

  13. Autismo: neuroimagem Autism: neuroimaging

    Directory of Open Access Journals (Sweden)

    Mônica Zilbovicius

    2006-05-01

    Full Text Available O autismo é um transtorno de neurodesenvolvimento com diversas apresentações clínicas. Essas apresentações variam em gravidade (leves a graves e são denominadas transtornos do espectro do autismo. O sinal mais comum aos transtornos desse espectro é o déficit de interação social, que está associado a déficits de comunicação verbal e não-verbal e a comportamentos estereotipados e repetitivos. Graças a estudos recentes que utilizam métodos de imagem cerebral, os cientistas obtiveram uma idéia melhor dos circuitos neurais envolvidos nos transtornos do espectro do autismo. De fato, os exames de imagem cerebral funcionais, como tomografia por emissão de pósitrons, tomografia por emissão de fóton único e ressonância magnética funcional abriram uma nova perspectiva para o estudo do funcionamento cerebral normal e patológico. Três estudos independentes encontraram anormalidades da anatomia e do funcionamento em repouso do lobo temporal em pacientes autistas. Essas alterações estão localizadas bilateralmente nos sulcos temporais superiores. Essa região anatômica é de grande importância para a percepção de estímulos sociais essenciais. Além disso, estudos funcionais demonstraram hipoativação da maior parte das áreas envolvidas na percepção social (percepção de faces e voz e cognição social (teoria da mente. Esses dados sugerem um funcionamento anormal da rede de pensamentos do cérebro social no autismo. A compreensão das alterações nesse importante mecanismo pode estimular a elaboração de novas e mais adequadas estratégias sociais de reeducação para pacientes autistas.Autism is a neurodevelopmental disorder with a range of clinical presentations. These presentations vary from mild to severe and are referred to as autism spectrum disorders. The most common clinical sign of autism spectrum disorders is social interaction impairment, which is associated with verbal and non-verbal communication deficits

  14. Prostate cancer stem cell biology

    OpenAIRE

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...

  15. Biologic therapies for juvenile arthritis

    OpenAIRE

    Wilkinson, N; Jackson, G.; Gardner-Medwin, J.

    2003-01-01

    A group of therapies with exciting potential has emerged for children and young people with severe juvenile idiopathic arthritis (JIA) uncontrolled by conventional disease modifying drugs. Theoretical understanding from molecular biologic research has identified specific targets within pathophysiological pathways that control rheumatoid arthritis (RA) and JIA. This review identifies the pathways of autoimmunity to begin to show how biologic agents have been produced to replicate, mimic, or bl...

  16. 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 Pathophysiological role

  17. A Theoretical Model for Autism

    OpenAIRE

    Vidal de Caralho, Luís Alfred; Ferreira, Nívea de Carvalho; Fiszman, Adriana

    2001-01-01

    Autism is a mental disorder characterized by deficits in socialization, communication, and imagination. Along with the deficits, autistic children may show savant skills (“islets of ability”) of unknown origin that puzzles their families and the psychologists. Comorbidity with epilepsy and mental retardation has brought the researchers' attention to neurobiological and cognitive theories of the syndrome. The present article proposes a neurobiological model for the autism based on the fundamen...

  18. The clinician's guide to autism.

    Science.gov (United States)

    Harrington, John W; Allen, Korrie

    2014-02-01

    On the basis of the most recent epidemiologic research, Autism Spectrum Disorder (ASD) affects approximately 1% to 2% of all children. (1)(2) On the basis of some research evidence and consensus, the Modified Checklist for Autism in Toddlers isa helpful tool to screen for autism in children between ages 16 and 30 months. (11) The Diagnostic Statistical Manual of Mental Disorders, Fourth Edition, changes to a 2-symptom category from a 3-symptom category in the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition(DSM-5): deficits in social communication and social interaction are combined with repetitive and restrictive behaviors, and more criteria are required per category. The DSM-5 subsumes all the previous diagnoses of autism (classic autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified) into just ASDs. On the basis of moderate to strong evidence, the use of applied behavioral analysis and intensive behavioral programs has a beneficial effect on language and the core deficits of children with autism. (16) Currently, minimal or no evidence is available to endorse most complementary and alternative medicine therapies used by parents, such as dietary changes (gluten free), vitamins, chelation, and hyperbaric oxygen. (16) On the basis of consensus and some studies, pediatric clinicians should improve their capacity to provide children with ASD a medical home that is accessible and provides family-centered, continuous, comprehensive and coordinated, compassionate, and culturally sensitive care. (20) PMID:24488830

  19. microRNAs and Endometrial Pathophysiology.

    Science.gov (United States)

    Chill, Henry H; Dior, Uri P; Kogan, Liron; Revel, Ariel

    2015-01-01

    Embryo implantation requires a reciprocal interaction between the blastocyst and endometrium and is associated with complex regulatory mechanisms. Since their discovery, microRNAs became prominent candidates providing missing links for many biological pathways. In recent years, microRNAs were implicated as one of the important players in regulation of various biological and physiological endometrial related processes. This chapter aims to present recent knowledge pertaining to the diverse aspects of microRNAs in the embryo-endometrial relationship. We will focus on the role of microRNAs in decidualization and their part in natural and stimulated cycles. Next, we will present recent studies deliberating the role of microRNAs in recurrent pregnancy loss and in the important phenomenon of recurrent implantation failure. Lastly, demonstrating an important aspect of embryo implantation and invasion, we will outline few microRNA related shared pathways of implantation and carcinogenesis. PMID:26662990

  20. Intestinal bile acid physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

    Olga Mart(I)nez-Augustin; Ferm(I)n Sánchez de Medina

    2008-01-01

    Bile acids (Bas) have a long established role in fat digestion in the intestine by acting as tensioactives,due to their amphipatic characteristics.Bas are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver v/a transport mechanisms that have been largely elucidated.The transport and synthesis of Bas are tightly regulated in part by specific plasma membrane receptors and nuclear receptors.In addition to their primary effect,Bas have been claimed to play a role in gastrointestinal cancer,intestinal inflammation and intestinal ionic transport.Bas are not equivalent in any of these biological activities,and structural requirements have been generally identified.In particular,some Bas may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease,although further research is necessary in this field.This review covers the most recent developments in these aspects of BA intestinal biology.

  1. Autism Spectrum Disorder (ASD): Related Topics

    Science.gov (United States)

    ... Facebook Tweet Share Compartir Q: Do vaccines cause autism spectrum disorder (ASD)? A: Many studies that have ... whether there is a relationship between vaccines and autism spectrum disorder (ASD). To date, the studies continue ...

  2. Prenatal Inflammation Linked to Autism Risk

    Science.gov (United States)

    ... Thursday, January 24, 2013 Prenatal inflammation linked to autism risk Maternal inflammation during early pregnancy may be related to an increased risk of autism in children, according to new findings supported by ...

  3. Pathophysiological roles of peroxynitrite in circulatory shock

    OpenAIRE

    Szabó, Csaba; Módis, Katalin

    2010-01-01

    Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide, which reacts with proteins, lipids and DNA and promotes cytotoxic and pro-inflammatory responses. Here we overview the role of peroxynitrite in various forms of circulatory shock. Immunohistochemical and biochemical evidence demonstrate the production of peroxynitrite in various experimental models of endotoxic and hemorrhagic shock, both in rodents and in large animals. In addition, biological markers of pero...

  4. LPA receptor signaling: pharmacology, physiology, and pathophysiology

    OpenAIRE

    Yung, Yun C.; Stoddard, Nicole C.; Chun, Jerold

    2014-01-01

    Lysophosphatidic acid (LPA) is a small ubiquitous lipid found in vertebrate and nonvertebrate organisms that mediates diverse biological actions and demonstrates medicinal relevance. LPA’s functional roles are driven by extracellular signaling through at least six 7-transmembrane G protein-coupled receptors. These receptors are named LPA1–6 and signal through numerous effector pathways activated by heterotrimeric G proteins, including Gi/o, G12/13, Gq, and Gs. LPA receptor-mediated effects ha...

  5. Type 2 diabetes across generations: from pathophysiology to prevention and management

    DEFF Research Database (Denmark)

    Nolan, Christopher J; Damm, Peter; Prentki, Marc

    2011-01-01

    to chronic fuel excess, which results in so-called nutrient spillover, insulin resistance, and metabolic stress. The latter damages multiple organs. Insulin resistance, while forcing β cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues......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...

  6. Type 2 diabetes across generations: from pathophysiology to prevention and management

    DEFF Research Database (Denmark)

    Nolan, Christopher J; Damm, Peter; Prentki, Marc

    2011-01-01

    to chronic fuel excess, which results in so-called nutrient spillover, insulin resistance, and metabolic stress. The latter damages multiple organs. Insulin resistance, while forcing ß cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues......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...

  7. DNA repair gene XPD Asp312Asn and XRCC4 G-1394T polymorphisms and the risk of autism spectrum disorder.

    Science.gov (United States)

    Dasdemir, S; Guven, M; Pekkoc, K C; Ulucan, H; Dogangun, B; Kirtas, E; Kadak, M T; Kucur, M; Seven, M

    2016-01-01

    Autism spectrum disorder (ASD) is a complex disorder, and its extreme heterogeneity further complicates our understanding of its biology. Epidemiological evidence from family and twin studies supports a strong genetic component in ASD etiology. Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of ASD. Brain tissues from ASD cases showed higher levels of oxidative stress biomarkers than healthy controls in postmortem analysis. Association between oxidative stress and DNA damage has been well-known. Thus, we sought to investigate a potential link between DNA repair genes and ASD and analyze the role of XPD Asp312Asn and XRCC4 G-1394T gene polymorphisms for ASD in the Turkish population. Genotyping was conducted by PCR-RFLP based on 100 patients and 96 unrelated healthy controls. We, for the first time, demonstrated a positive association between XRCC4 gene variants and ASD risk. Frequencies of XRCC4-1394 T/G+G/G genotypes were higher in patients (%34) than the controls (%18.7). The statistical analysis revealed that the individuals who had XRCC4-1394 T/G+G/G genotype had an increased risk for ASD (OR = 2.23, 95% CI = 1.10-4.55). However, no significant association was found for XPD Asp312Asn polymorphism with the risk of ASD. Our findings suggest that XRCC4 G-1394T polymorphism might be associated with ASD pathogenesis. PMID:27064873

  8. Pilot study on pathophysiology mechanism of belching disorders

    Institute of Scientific and Technical Information of China (English)

    孙晓敏

    2013-01-01

    Objective To investigate the pathophysiology mechanism in belching by using high resolution manometry combined with impedance monitoring.Methods Ten belching patients (four male and six female,ages ranged from 28 to 50 years) received high resolution manometry

  9. Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms

    NARCIS (Netherlands)

    Kerckhoffs, A.P.M.

    2009-01-01

    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 co

  10. Endosomal system genetics and autism spectrum disorders: A literature review.

    Science.gov (United States)

    Patak, Jameson; Zhang-James, Yanli; Faraone, Stephen V

    2016-06-01

    Autism spectrum disorders (ASDs) are a group of debilitating neurodevelopmental disorders thought to have genetic etiology, due to their high heritability. The endosomal system has become increasingly implicated in ASD pathophysiology. In an attempt to summarize the association between endosomal system genes and ASDs we performed a systematic review of the literature. We searched PubMed for relevant articles. Simons Foundation Autism Research Initiative (SFARI) gene database was used to exclude articles regarding genes with less than minimal evidence for association with ASDs. Our search retained 55 articles reviewed in two categories: genes that regulate and genes that are regulated by the endosomal system. Our review shows that the endosomal system is a novel pathway implicated in ASDs as well as other neuropsychiatric disorders. It plays a central role in aspects of cellular physiology on which neurons and glial cells are particularly reliant, due to their unique metabolic and functional demands. The system shows potential for biomarkers and pharmacological intervention and thus more research into this pathway is warranted. PMID:27048963

  11. Autism and the Family: A Qualitative Perspective

    OpenAIRE

    Glass, Paul William

    2001-01-01

    AUTISM AND THE FAMILY: A QUALITATIVE PERSPECTIVE Paul W. Glass (ABSTRACT) The focus of this dissertation was to gain a better understanding of autism, and its effects on family life. Studies have been done on the behavioral and cognitive effects of autism on the affected child, and how those effects manifest themselves into family life. No studies were found, however, that give a rich, qualitative account of what it is like to live with autism using first hand accounts as data, and ...

  12. Anatomy and neuro-pathophysiology of the cough reflex arc

    OpenAIRE

    Polverino Mario; Polverino Francesca; Fasolino Marco; Andò Filippo; Alfieri Antonio; De Blasio Francesco

    2012-01-01

    Abstract Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. It accounts for a significant number of consultations both at the level of general practitioner and of respiratory specialists. In this review we first analyze the cough reflex under normal conditions; then we analyze the anatomy and the neuro-pathophysiology of the cough reflex arc. The aim of this review is to provide the anatomic and pathophysiologic elements of evaluation of the...

  13. Pathophysiology of acute small bowel disease with CT correlation

    International Nuclear Information System (INIS)

    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.

  14. Pathophysiology of acute small bowel disease with CT correlation

    Energy Technology Data Exchange (ETDEWEB)

    Sarwani, N., E-mail: nsarwani@hmc.psu.ed [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States); Tappouni, R.; Tice, J. [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States)

    2011-01-15

    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.

  15. Major Pathophysiological Correlations of Rosacea: A Complete Clinical Appraisal

    OpenAIRE

    Vemuri, Ravi Chandra; Gundamaraju, Rohit; Sekaran, Shamala Devi; Manikam, Rishya

    2015-01-01

    Background: Rosacea is a characteristic cutaneous disorder with a diverse clinical manifestations ranging from facial vascular hyper-reactivity to sebaceous gland hyperplasia. Many theories on pathophysiology of rosacea were proposed over the past decade, however the pathogenicity is poorly understood. Aim: To review the evidence on different pathophysiological correlations of rosacea. Methods: A literature search was conducted for studies published between 1990 to March 2014. The inclusion c...

  16. Relationship between Asthma and Rhinitis: Epidemiologic, Pathophysiologic, and Therapeutic Aspects

    Directory of Open Access Journals (Sweden)

    Bergeron Celine

    2005-06-01

    Full Text Available Abstract Over the last few years, the evidence of links between rhinitis and asthma has been strengthened. This has led to the introduction of the concept of united airway disease. Rhinitis and asthma appear to be interrelated at the epidemiologic level and at the pathophysiologic level. This article reviews current epidemiologic and pathophysiologic evidence of the relationship between rhinitis and asthma and discusses the effect of treatment of one site on the other site.

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

    OpenAIRE

    Melnikova, О. V.

    2013-01-01

    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...

  18. Astrocytes and Microglia and Their Potential Link with Autism Spectrum Disorders.

    Science.gov (United States)

    Petrelli, Francesco; Pucci, Luca; Bezzi, Paola

    2016-01-01

    The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not fully understood although it has been shown that various genetic and environmental factors contribute to their etiology. As increasing evidence indicates that astrocytes and microglial cells play a major role in synapse maturation and function, and there is evidence of deficits in glial cell functions in ASDs, one current hypothesis is that glial dysfunctions directly contribute to their pathophysiology. The aim of this review is to summarize microglia and astrocyte functions in synapse development and their contributions to ASDs. PMID:26903806

  19. A model for the induction of autism in the ecosystem of the human body: the anatomy of a modern pandemic?

    Directory of Open Access Journals (Sweden)

    Staci D. Bilbo

    2015-01-01

    Full Text Available Background: The field of autism research is currently divided based on a fundamental question regarding the nature of autism: Some are convinced that autism is a pandemic of modern culture, with environmental factors at the roots. Others are convinced that the disease is not pandemic in nature, but rather that it has been with humanity for millennia, with its biological and neurological underpinnings just now being understood. Objective: In this review, two lines of reasoning are examined which suggest that autism is indeed a pandemic of modern culture. First, given the widely appreciated derailment of immune function by modern culture, evidence that autism is strongly associated with aberrant immune function is examined. Second, evidence is reviewed indicating that autism is associated with ‘triggers’ that are, for the most part, a construct of modern culture. In light of this reasoning, current epidemiological evidence regarding the incidence of autism, including the role of changing awareness and diagnostic criteria, is examined. Finally, the potential role of the microbial flora (the microbiome in the pathogenesis of autism is discussed, with the view that the microbial flora is a subset of the life associated with the human body, and that the entire human biome, including both the microbial flora and the fauna, has been radically destabilized by modern culture. Conclusions: It is suggested that the unequivocal way to resolve the debate regarding the pandemic nature of autism is to perform an experiment: monitor the prevalence of autism after normalizing immune function in a Western population using readily available approaches that address the well-known factors underlying the immune dysfunction in that population.

  20. Low Endogenous Neural Noise in Autism

    Science.gov (United States)

    Davis, Greg; Plaisted-Grant, Kate

    2015-01-01

    "Heuristic" theories of autism postulate that a single mechanism or process underpins the diverse psychological features of autism spectrum disorder. Although no such theory can offer a comprehensive account, the parsimonious descriptions they provide are powerful catalysts to autism research. One recent proposal holds that…

  1. Developing Undergraduate Coursework in Autism Spectrum Disorders

    Science.gov (United States)

    Masterson, Tracy Loye; Dimitriou, Francine; Turko, Kristine; McPartland, James

    2014-01-01

    With rates of autism spectrum disorders (ASD) continuing to rise alongside improvements in early identification and treatment, service providers are in great demand. Providing undergraduate students with opportunities for education and applied experiences with autism spectrum disorders (ASD) can help fill a valuable niche in the autism community.…

  2. Navajo and Autism: The Beauty of Harmony

    Science.gov (United States)

    Kapp, Steven K.

    2011-01-01

    With so much unknown about autism, the disability tends to reflect the sociocultural preconceptions people project onto it. The predominant narrative in Western society of autism as a "disease" within the medical model contrasts with the more positive, empowering view of autism as a "difference" in the social model and neurodiversity movement.…

  3. Superior Visual Search in Adults with Autism

    Science.gov (United States)

    O'Riordan, Michelle

    2004-01-01

    Recent studies have suggested that children with autism perform better than matched controls on visual search tasks and that this stems from a superior visual discrimination ability. This study assessed whether these findings generalize from children to adults with autism. Experiments 1 and 2 showed that, like children, adults with autism were…

  4. Virginia Tech Center for Autism Research

    OpenAIRE

    Virginia Tech Center for Autism Research

    2012-01-01

    These slides serve as a welcome for the Autism Research Conference held at Virginia Tech on August 15 2012. The slides describe symptoms and prevalence of autism spectrum disorders, list goals for the proposed Center for Autism Research, and list the speakers and agenda for the conference.

  5. Why Autism Must Be Taken Apart

    Science.gov (United States)

    Waterhouse, Lynn; Gillberg, Christopher

    2014-01-01

    Although accumulated evidence has demonstrated that autism is found with many varied brain dysfunctions, researchers have tried to find a single brain dysfunction that would provide neurobiological validity for autism. However, unitary models of autism brain dysfunction have not adequately addressed conflicting evidence, and efforts to find a…

  6. Elderly with Autism: Executive Functions and Memory

    Science.gov (United States)

    Geurts, Hilde M.; Vissers, Marlies E.

    2012-01-01

    Cognitive autism research is mainly focusing on children and young adults even though we know that autism is a life-long disorder and that healthy aging already has a strong impact on cognitive functioning. We compared the neuropsychological profile of 23 individuals with autism and 23 healthy controls (age range 51-83 years). Deficits were…

  7. Autism and ADHD: Overlapping and Discriminating Symptoms

    Science.gov (United States)

    Mayes, Susan Dickerson; Calhoun, Susan L.; Mayes, Rebecca D.; Molitoris, Sarah

    2012-01-01

    Children with ADHD and autism have some similar features, complicating a differential diagnosis. The purpose of our study was to determine the degree to which core ADHD and autistic symptoms overlap in and discriminate between children 2-16 years of age with autism and ADHD. Our study demonstrated that 847 children with autism were easily…

  8. Survey of Bilingualism in Autism Spectrum Disorders

    Science.gov (United States)

    Kay-Raining Bird, Elizabeth; Lamond, Erin; Holden, Jeanette

    2012-01-01

    This survey study investigates issues related to bilingualism and autism. Bilingualism is common around the world but there is little published information to guide professionals and parents in making decisions about bilingualism for children with autism. Participants were 49 parents or guardians of children with autism who were members of a…

  9. Test Review: Autism Spectrum Rating Scales

    Science.gov (United States)

    Simek, Amber N.; Wahlberg, Andrea C.

    2011-01-01

    This article reviews Autism Spectrum Rating Scales (ASRS) which are designed to measure behaviors in children between the ages of 2 and 18 that are associated with disorders on the autism spectrum as rated by parents/caregivers and/or teachers. The rating scales include items related to behaviors associated with Autism, Asperger's Disorder, and…

  10. Color Perception in Children with Autism

    Science.gov (United States)

    Franklin, Anna; Sowden, Paul; Burley, Rachel; Notman, Leslie; Alder, Elizabeth

    2008-01-01

    This study examined whether color perception is atypical in children with autism. In experiment 1, accuracy of color memory and search was compared for children with autism and typically developing children matched on age and non-verbal cognitive ability. Children with autism were significantly less accurate at color memory and search than…

  11. Autism Spectrum Disorders and Maternal Serum α-Fetoprotein Levels During Pregnancy

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Grove, Jakob; Hougaard, David M;

    2011-01-01

    Objective: Numerous studies have been trying to disentangle the complex pathophysiology of autism spectrum disorders (ASD). In our study, we explored the potential role of maternal serum (MS) α-fetoprotein (AFP) in the prediction and the pathophysiology of ASD. Methods: A total of 112 patients with...... ASD and 243 control subjects were included in a case–control study using a historic birth cohort maintained at Statens Serum Institute. Measurements of MS-AFP were obtained from a multicentre screening program, whereas clinical data were obtained from nationwide registers. Association between MS-AFP...... and ASD status was analyzed using a logistic regression model and nonparametric tests. Results: Crude, but not adjusted estimates, showed that MS-AFP levels were slightly, but significantly, higher in mothers of children with ASD, compared with their control subject counterparts. People with ASD had...

  12. Autism Spectrum Disorders and Maternal Serum alpha-Fetoprotein Levels During Pregnancy

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Grove, Jakob; Hougaard, David M;

    2011-01-01

    Objective: Numerous studies have been trying to disentangle the complex pathophysiology of autism spectrum disorders (ASD). In our study, we explored the potential role of maternal serum (MS) alpha-fetoprotein (AFP) in the prediction and the pathophysiology of ASD. Methods: A total of 112 patients...... with ASD and 243 control subjects were included in a case-control study, using a historic birth cohort maintained at Statens Serum Institute. Measurements of MS-AFP were obtained from a multicentre screening program, whereas clinical data were obtained from nationwide registers. Association between MS-AFP...... and ASD status was analyzed using logistic regression models and nonparametric tests. Results: Crude, but not adjusted, estimates showed that MS-AFP levels were slightly, but significantly, higher in mothers of children with ASD, compared with their control subject counterparts. People with ASD had an...

  13. Computational Approach To Understanding Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Włodzisław Duch

    2012-01-01

    Full Text Available Every year the prevalence of Autism Spectrum of Disorders (ASD is rising. Is there a unifying mechanism of various ASD cases at the genetic, molecular, cellular or systems level? The hypothesis advanced in this paper is focused on neural dysfunctions that lead to problems with attention in autistic people. Simulations of attractor neural networks performing cognitive functions help to assess system long-term neurodynamics. The Fuzzy Symbolic Dynamics (FSD technique is used for the visualization of attractors in the semantic layer of the neural model of reading. Large-scale simulations of brain structures characterized by a high order of complexity requires enormous computational power, especially if biologically motivated neuron models are used to investigate the influence of cellular structure dysfunctions on the network dynamics. Such simulations have to be implemented on computer clusters in a grid-based architectures

  14. Loss of δ-catenin function in severe autism.

    Science.gov (United States)

    Turner, Tychele N; Sharma, Kamal; Oh, Edwin C; Liu, Yangfan P; Collins, Ryan L; Sosa, Maria X; Auer, Dallas R; Brand, Harrison; Sanders, Stephan J; Moreno-De-Luca, Daniel; Pihur, Vasyl; Plona, Teri; Pike, Kristen; Soppet, Daniel R; Smith, Michael W; Cheung, Sau Wai; Martin, Christa Lese; State, Matthew W; Talkowski, Michael E; Cook, Edwin; Huganir, Richard; Katsanis, Nicholas; Chakravarti, Aravinda

    2015-04-01

    Autism is a multifactorial neurodevelopmental disorder affecting more males than females; consequently, under a multifactorial genetic hypothesis, females are affected only when they cross a higher biological threshold. We hypothesize that deleterious variants at conserved residues are enriched in severely affected patients arising from female-enriched multiplex families with severe disease, enhancing the detection of key autism genes in modest numbers of cases. Here we show the use of this strategy by identifying missense and dosage sequence variants in the gene encoding the adhesive junction-associated δ-catenin protein (CTNND2) in female-enriched multiplex families and demonstrating their loss-of-function effect by functional analyses in zebrafish embryos and cultured hippocampal neurons from wild-type and Ctnnd2 null mouse embryos. Finally, through gene expression and network analyses, we highlight a critical role for CTNND2 in neuronal development and an intimate connection to chromatin biology. Our data contribute to the understanding of the genetic architecture of autism and suggest that genetic analyses of phenotypic extremes, such as female-enriched multiplex families, are of innate value in multifactorial disorders. PMID:25807484

  15. Calcium signaling in physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

    He-ping CHENG; Sheng WEI; Li-ping WEI; Alexei VERKHRATSKY

    2006-01-01

    Calcium ions are the most ubiquitous and pluripotent cellular signaling molecules that control a wide variety of cellular processes.The calcium signaling system is represented by a relatively limited number of highly conserved transporters and channels,which execute Ca2+ movements across biological membranes and by many thousands of Ca2+-sensitive effectors.Molecular cascades,responsible for the generation of calcium signals,are tightly controlled by Ca2+ ions themselves and by genetic factors,which tune the expression of different Ca2+-handling molecules according to adaptational requirements.Ca2+ ions determine normal physiological reactions and the development of many pathological processes.

  16. Autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Faras Hadeel

    2010-01-01

    Full Text Available Pervasive developmental disorders are a group of neurodevelopmental disorders characterized by impairments in communication, reciprocal social interaction and restricted repetitive behaviors or interests. The term autism spectrum disorders (ASD has been used to describe their variable presentation. Although the cause of these disorders is not yet known, studies strongly suggest a genetic basis with a complex mode of inheritance. More research is needed to explore environmental factors that could be contributing to the cause of these disorders. The occurrence of ASD has been increasing worldwide, with the most recent prevalence studies indicating that they are present in 6 per 1000 children. The objectives of this article are to provide physicians with relevant information needed to identify and refer children presenting with symptoms suggestive of ASDs to specialized centers early, and to make them feel comfortable in dealing with public concerns regarding controversial issues about the etiology and management of these disorders.

  17. AUTISM AND TUBEROUS SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Dragoslav KOPACHEV

    2000-12-01

    Full Text Available Autism is a frequent manifestation of tuberous sclerosis being reported in up to 60% of the patients. Tuberous sclerosis is developmental disorder of neurogenesis and neuronal migration. Symptoms of CNS involvement are prominent. Brain abnormalities underlying this neurological and behavioral phenotype include areas of focal cortical dysplasia, subependymal nodules, and cortical and subcortical tubers. The authors show case of tuberous sclerosis in 4 and half age girl where next symptoms dominate: epilepsy in early childhood, severe mental retardation and autistic behavior. The diagnostic of the problem is made with clinical-psychological examination (EEG and CT. The authors suggest that early diagnosis of autistic behavior in tuberous sclerosis is very important for making in time adequate program for educative-behavioral and general reeducative activities and for consultation the parents.

  18. Bile acids: Chemistry, physiology, and pathophysiology

    Institute of Scientific and Technical Information of China (English)

    Maria J Monte; Jose JG Marin; Alvaro Antelo; Jose Vazquez-Tato

    2009-01-01

    The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physicalchemical and biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways that are controlled by mechanisms involving fine-tuning by the levels of certain bile acid species. Although their bestknown role is their participation in the digestion and absorption of fat, they also play an important role in several other physiological processes. Thus, genetic abnormalities accounting for alterations in their synthesis, biotransformation and/or transport may result in severe alterations, even leading to lethal situations for which the sole therapeutic option may be liver transplantation. Moreover, the increased levels of bile acids reached during cholestatic liver diseases are known to induce oxidative stress and apoptosis, resulting in damage to the liver parenchyma and, ventually, extrahepatic tissues. When this occurs during pregnancy, the outcome of gestation may be challenged. In contrast, the physical-chemical and biological properties of these compounds have been used as the bases for the development of drugs and as pharmaceutical tools for the delivery of active agents.

  19. Simple Cyclic Movements As A Distinct Autism Feature - Computational Approach

    Directory of Open Access Journals (Sweden)

    Krzysztof Dobosz

    2013-01-01

    Full Text Available Diversity of symptoms in autism dictates a broad definition of Autism Spectrum of Disorders(ASD. Each year percentage of children diagnosed with ASD is growing. One common diag-nostic feature in individuals with ASD is the tendency to atypical simple cyclic movements.The motor brain activity seems to generate periodic attractor state that is hard to escape.Despite numerous studies scientists and clinicians do not know exactly if ASD is a result ofa simple but general mechanism, or a complex set of mechanisms, both on neural, molecularand system levels. Simulations using biologically relevant neural network model presentedhere may help to reveal simplest mechanisms that may be responsible for specific behavior.Abnormal neural fatigue mechanisms may be responsible for motor as well as many if notall other symptoms observed in ASD.

  20. Elevated cortisol during play is associated with age and social engagement in children with autism

    Directory of Open Access Journals (Sweden)

    Corbett Blythe A

    2010-09-01

    Full Text Available Abstract Background The hallmark characteristic of autism is impaired reciprocal social interaction. While children find social interaction stress-reducing, many children with autism may find social interaction stress-inducing. The current study was designed to examine stress responsivity as measured by cortisol by comparing children with autism to neurotypical peers during an ecologically valid 20-minute playground paradigm. Methods The experiment involved sets of three children: a child with autism, a neurotypical child, and a confederate. Participants included 45 prepubescent males between 8 and 12 years of age (21 with autism and 24 neurotypical children. Results Children with autism showed fewer initiations (χ²(1 = 4.03, P = 0.044, rejected initiations from others more (χ²(1 = 7.10, P = 0.008 and spent less time interacting during motor (F(1,43 = 16.7, P = 0.0002 and cooperative (F(1,43 = 14.78, P = 0.0004 play. Repeated measures analysis of the cortisol values revealed a significant model (χ²(4 = 22.76, P P = 0.006 and cooperative (χ²(3 = 8.24, P = 0.04 play as well as reduced nonverbal social skills during motor (χ²(1 = 5.52, P = 0.018 and cooperative play (χ²(1 = 4.53, P = 0.033. Conclusions Overall, children with autism engaged in fewer social overtures and spent less time interacting than typically developing peers during play. The peer interaction paradigm resulted in significantly higher levels of cortisol in many children with autism. Distinct patterns emerged within the autism group based on developmental (older, biological (cortisol responder and behavioral patterns (peripheral group interaction. The enhanced cortisol response was observed in children who voluntarily engaged in interaction; thus, it does not support the notion of a response to social threat. Rather, it appears to reflect attendant metabolic preparedness and enhanced arousal from engaging socially. The data suggest that many children with autism

  1. Assessing Early Communication Skills at 12 Months: A Retrospective Study of Autism Spectrum Disorder

    Science.gov (United States)

    Swain, Nathaniel Robert; Eadie, Patricia Ann; Prior, Margot Ruth; Reilly, Sheena

    2015-01-01

    Background: Early identification of Autism Spectrum Disorder (ASD) is currently limited by the absence of reliable biological markers for the disorder, as well as the reliability of screening and assessment tools for children aged between 6 and 18 months. Ongoing research has demonstrated the importance of early social communication skills in…

  2. The psychophysics of Visual Motion and Global form Processing in Autism

    Science.gov (United States)

    Koldewyn, Kami; Whitney, David; Rivera, Susan M.

    2010-01-01

    Several groups have recently reported that people with autism may suffer from a deficit in visual motion processing and proposed that these deficits may be related to a general dorsal stream dysfunction. In order to test the dorsal stream deficit hypothesis, we investigated coherent and biological motion perception as well as coherent form…

  3. Functional neuroimaging and childhood autism

    Energy Technology Data Exchange (ETDEWEB)

    Boddaert, Nathalie [Service de Radiologie Pediatrique, Necker-Enfants Malades Hospital, Paris (France); Service Hospitalier Frederic Joliot, DRM, DSV, CEA, Orsay (France); Zilbovicius, Monica [Service Hospitalier Frederic Joliot, DRM, DSV, CEA, Orsay (France); INSERM, Tours (France)

    2002-01-01

    Childhood autism is now widely viewed as being of developmental neurobiological origin. Yet, localised structural and functional brain correlates of autism have to be established. Structural brain-imaging studies performed in autistic patients have reported abnormalities such as increased total brain volume and cerebellar abnormalities. However, none of these abnormalities fully account for the full range of autistic symptoms. Functional brain imaging, such as positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional MRI (fMRI) have added a new perspective to the study of normal and pathological brain functions. In autism, functional studies have been performed at rest or during activation. However, first-generation functional imaging devices were not sensitive enough to detect any consistent dysfunction. Recently, with improved technology, two independent groups have reported bilateral hypoperfusion of the temporal lobes in autistic children. In addition, activation studies, using perceptive and cognitive paradigms, have shown an abnormal pattern of cortical activation in autistic patients. These results suggest that different connections between particular cortical regions could exist in autism. The purpose of this review is to present the main results of rest and activation studies performed in autism. (orig.)

  4. Functional neuroimaging and childhood autism

    International Nuclear Information System (INIS)

    Childhood autism is now widely viewed as being of developmental neurobiological origin. Yet, localised structural and functional brain correlates of autism have to be established. Structural brain-imaging studies performed in autistic patients have reported abnormalities such as increased total brain volume and cerebellar abnormalities. However, none of these abnormalities fully account for the full range of autistic symptoms. Functional brain imaging, such as positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional MRI (fMRI) have added a new perspective to the study of normal and pathological brain functions. In autism, functional studies have been performed at rest or during activation. However, first-generation functional imaging devices were not sensitive enough to detect any consistent dysfunction. Recently, with improved technology, two independent groups have reported bilateral hypoperfusion of the temporal lobes in autistic children. In addition, activation studies, using perceptive and cognitive paradigms, have shown an abnormal pattern of cortical activation in autistic patients. These results suggest that different connections between particular cortical regions could exist in autism. The purpose of this review is to present the main results of rest and activation studies performed in autism. (orig.)

  5. A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

    OpenAIRE

    Derrick F. MacFabe; Karina Rodríguez-Capote; Jennifer E.  Franklin; Martin Kavaliers; Fred Possmayer; Klaus-Peter Ossenkopp; Andrew E. Franklin

    2008-01-01

    Innate neuroinflammatory changes, increased oxidative stress and disorders of glutathione metabolism may be involved in the pathophysiology of autism spectrum disorders (ASD). Propionic acid (PPA) is a dietary and gut bacterial short chain fatty acid which can produce brain and behavioral changes reminiscent of ASD following intraventricular infusion in rats. Adult Long-Evans rats were given intraventricular infusions of either PPA (500ug uL-1, 4µl anima-1) or phosphate buffered saline (PBS) ...

  6. Sex differences in animal models of schizophrenia shed light on the underlying pathophysiology.

    Science.gov (United States)

    Hill, Rachel Anne

    2016-08-01

    Sex differences in schizophrenia are apparent in almost all features of the illness, from incidence and mean age of onset to symptomatology, course of illness and response to pharmacological treatments. Understanding how men and women with schizophrenia differ provides significant clues into the pathophysiology of the disorder. Animal models are powerful tools when dissecting the molecular biology which underlies behavioural disturbances, and allow structured comparisons of biological sex differences without the social environmental gender influence that so often confounds human sex comparison studies. This review will provide a summary of sex differences described in developmental, genetic and drug-induced animal models of schizophrenia and will link sex-specific molecular and behavioural phenotypes of these models in an attempt to unravel the role that sex plays in the pathophysiology of schizophrenia. Both sex and stress hormones interact to shape the developing brain and behaviour and animal models of schizophrenia that include both sexes provide significant insight into the complexities of these interactions and can direct toward novel therapeutic strategies. PMID:26743857

  7. Exploring 'The Autisms' at a Cognitive Level

    DEFF Research Database (Denmark)

    Cantio, Cathriona; Jepsen, Jens Richardt M; Madsen, Gitte;

    2016-01-01

    The autism spectrum is characterized by genetic and behavioral heterogeneity. However, it is still unknown whether there is a universal pattern of cognitive impairment in autism spectrum disorder (ASD) and whether multiple cognitive impairments are needed to explain the full range of behavioral...... symptoms. This study aimed to determine whether three widely acknowledged cognitive abnormalities (Theory of Mind (ToM) impairment, Executive Function (EF) impairment, and the presence of a Local Processing Bias (LB)) are universal and fractionable in autism, and whether the relationship between cognition...... characteristic heterogeneity of the autism spectrum, it remains a possibility therefore that a single cognitive cause may underlie the range of diagnostic symptoms in all individuals with autism. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc....

  8. Pathophysiological Distortions in Time Perception and Timed Performance

    Science.gov (United States)

    Allman, Melissa J.; Meck, Warren H.

    2012-01-01

    Distortions in time perception and timed performance are presented by a number of different neurological and psychiatric conditions (e.g. Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder and autism). As a consequence, the primary focus of this review is on factors that define or produce systematic changes in the…

  9. Progressive MS: from pathophysiology to drug discovery.

    Science.gov (United States)

    Salvetti, Marco; Landsman, Douglas; Schwarz-Lam, Peter; Comi, Giancarlo; Thompson, Alan J; Fox, Robert J

    2015-10-01

    Progressive multiple sclerosis (MS) will be a major area of research interest for years to come. No treatments exist and success in the field will generalise to other neurological conditions where neurodegeneration coexists with neuroinflammation. The issue is complex, and interdisciplinary approaches - uniting scientists with different competences (neurobiology, immunogenetics, etc.) and 'mindsets' (academia and industry) - will be decisive. The International Progressive MS Alliance is catalysing this process through various initiatives, the most recent of which was a meeting where scientists from academia (also outside the MS field) and from industry reviewed data and strategies to determine the next steps towards the translation of current knowledge into effective therapies.Key findings are:(i). Concerted efforts are essential to prioritise pathogenetic mechanisms according to impact on the disease and druggability.(ii). Combination therapies will probably be needed, possibly early in the disease, along with new trial designs and treatment schedules.(iii). Drug screenings are a pragmatic approach hopefully enriched by the use of neural and oligodendrocyte progenitors differentiated from induced pluripotent stem cells (iPSCs).(iv). The field of network biology will increase our ability to predict therapeutic targets.(v). Genome-wide association studies (GWAS) must try to identify variants associated with disease progression. PMID:26362902

  10. Autism Spectrum Disorders | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Autism Spectrum Disorders What Are Autism Spectrum Disorders (ASD)? Past Issues / Winter 2013 Table of Contents Fast Facts Autism Spectrum Disorders (ASD) are a group of developmental ...

  11. Velopharyngeal sphincter pathophysiologic aspects in the in cleft palat

    Directory of Open Access Journals (Sweden)

    Collares, Marcus Vinicius Martins

    2008-09-01

    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.

  12. Acute cerebral infarction: pathophysiology and modern treatment concepts

    International Nuclear Information System (INIS)

    This review focuses on the pathophysiological changes in acute cerebral ischemia, with special emphasis on disturbances of the cerebral blood flow (CBF) and the associated penumbra concept. Alternatively, the model of peri-infarct depolarization is demonstrated. Metabolic and molecular changes caused by cerebral ischemia and reperfusion are discussed, namely energy failure, release of glutamate with an excitatoric burst, calcium influx in neurons, generation of free radicals, activation of different proteases, disturbances of protein synthesis, induction of gene expression and apoptosis, loss of membrane integrity, edema formation and microvascular disturbances. In summary, the pathophysiological changes after focal cerebral ischemia and reperfusion are most adequately described by a network of interacting different mechanisms of tissue alterations. The simple concept of a cascade of ischemic effect which would be easy to block seems to be less applicable. A time window of approximately 6 h for the acute stroke therapy is postulated on the base of the above mentioned pathophysiological changes. (orig./AJ)

  13. Autism Spectrum Disorders in Iran

    OpenAIRE

    Mohammad Reza MOHAMMADI; Salmanian, Maryam; Akhondzadeh, Shahin

    2011-01-01

    How to Cite this Article: Mohammadi MR, Salmanian M, Akhondzadeh Sh. Autism Spectrum Disorders in Iran. Iranian Journal of Child Neurology2011;5(4):1-9.ObjectiveAutistic disorder, Asperger syndrome, and PDD-Not Otherwise Specified are subsets of autism spectrum disorders (ASDs), which are characterized by impairments in social communication and stereotyped behavior. This article reviews the prevalence, etiology, diagnosis, and treatment of ASDs in Iran.Materials & MethodsWe searched PubMe...

  14. Pathophysiological implications of the chemical messengers

    International Nuclear Information System (INIS)

    to many other processes, and all together constitute a new approach for a better knowledge of the biological processes and as a consequence of the diseases. (Author) 12 refs.

  15. Anatomy and neuro-pathophysiology of the cough reflex arc

    Directory of Open Access Journals (Sweden)

    Polverino Mario

    2012-06-01

    Full Text Available Abstract Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. It accounts for a significant number of consultations both at the level of general practitioner and of respiratory specialists. In this review we first analyze the cough reflex under normal conditions; then we analyze the anatomy and the neuro-pathophysiology of the cough reflex arc. The aim of this review is to provide the anatomic and pathophysiologic elements of evaluation of the complex and multiple etiologies of cough.

  16. What is this thing called autism? A critical analysis of the tenacious search for autism's essence

    NARCIS (Netherlands)

    Verhoeff, Berend

    2012-01-01

    Currently, autism is a widespread and diverse neurodevelopmental disorder that includes both severely impaired and institutionalized patients and the fairly geeky but brilliant university professor. Despite its heterogeneity, autism is often presented as a distinct nosological entity with a unifying

  17. Adrenomedullin regulates intestinal physiology and pathophysiology.

    Science.gov (United States)

    Martínez-Herrero, S; Martínez, A

    2016-07-01

    Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are 2 biologically active peptides produced by the same gene, ADM, with ubiquitous distribution and many physiological functions. Adrenomedullin is composed of 52 amino acids, has an internal molecular ring composed by 6 amino acids and a disulfide bond, and shares structural similarities with calcitonin gene-related peptide, amylin, and intermedin. The AM receptor consists of a 7-transmembrane domain protein called calcitonin receptor-like receptor in combination with a single transmembrane domain protein known as receptor activity-modifying protein. Using morphologic techniques, it has been shown that AM and PAMP are expressed throughout the gastrointestinal tract, being specially abundant in the neuroendocrine cells of the gastrointestinal mucosa; in the enterochromaffin-like and chief cells of the gastric fundus; and in the submucosa of the duodenum, ileum, and colon. This wide distribution in the gastrointestinal tract suggests that AM and PAMP may act as gut hormones regulating many physiological and pathologic conditions. To date, it has been proven that AM and PAMP act as autocrine/paracrine growth factors in the gastrointestinal epithelium, play key roles in the protection of gastric mucosa from various kinds of injury, and accelerate healing in diseases such as gastric ulcer and inflammatory bowel diseases. In addition, both peptides are potent inhibitors of gastric acid secretion and gastric emptying; they regulate the active transport of sugars in the intestine, regulate water and ion transport in the colon, modulate colonic bowel movements and small-intestine motility, improve endothelial barrier function, and stabilize circulatory function during gastrointestinal inflammation. Furthermore, AM and PAMP are antimicrobial peptides, and they contribute to the mucosal host defense system by regulating gut microbiota. To get a formal demonstration of the effects that endogenous AM and

  18. Psychotherapy for Anxiety in Children With Autism Spectrum Disorder

    Science.gov (United States)

    2016-03-07

    Autism Spectrum Disorders; Autism; Asperger's Syndrome; Pervasive Developmental Disability - Not Otherwise Specified; Obsessive-compulsive Disorder; Social Phobia; Generalized Anxiety Disorder; Specific Phobia; Separation Anxiety Disorder

  19. Evidence for association between Disrupted-in-schizophrenia 1 (DISC1 gene polymorphisms and autism in Chinese Han population: a family-based association study

    Directory of Open Access Journals (Sweden)

    Ruan Yan

    2011-05-01

    Full Text Available Abstract Background Disrupted-in-Schizophrenia 1 (DISC1 gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism. Methods We genotyped seven tag single nucleotide polymorphisms (SNPs in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT and Haploview software. Results We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02. After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values. Conclusions Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.

  20. Broader Autism Phenotype in Iranian Parents of Children with Autism Spectrum Disorders vs. Normal Children

    OpenAIRE

    Mohammad Reza Mohammadi; Hadi Zarafshan; Salehe Ghasempour

    2012-01-01

    Objective The aim of the present study was to compare the broader autism phenotype in Iranian parents of children with autism spectrum disorders and parents of typically developing children. Method Parents of children with ASD and parents of typically developing children were asked to complete the Persian version of the Autism Spectrum Quotient (AQ). In the ASD group, families included 204 parents (96 fathers and 108 mothers) of children diagnosed as having autism (Autistic Disorder, or AD) (...

  1. Using the Autism Detection in Early Childhood (ADEC) and Childhood Autism Rating Scales (CARS) to Predict Long Term Outcomes in Children with Autism Spectrum Disorders

    Science.gov (United States)

    Nah, Yong-Hwee; Young, Robyn L.; Brewer, Neil

    2014-01-01

    This study evaluated the predictive validity of the Autism Detection in Early Childhood (ADEC; Young, Autism detection in early childhood: ADEC. Australian Council of Educational Research, Camberwell, VIC 2007) and a well-established screening tool, the Childhood Autism Rating Scale (CARS; Schopler et al. The childhood autism rating scale (CARS).…

  2. Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes

    Directory of Open Access Journals (Sweden)

    Santangelo Susan L

    2004-05-01

    Full Text Available Abstract Background A substantial body of research supports a genetic involvement in autism. Furthermore, results from various genomic screens implicate a region on chromosome 7q31 as harboring an autism susceptibility variant. We previously narrowed this 34 cM region to a 3 cM critical region (located between D7S496 and D7S2418 using the Collaborative Linkage Study of Autism (CLSA chromosome 7 linked families. This interval encompasses about 4.5 Mb of genomic DNA and encodes over fifty known and predicted genes. Four candidate genes (NRCAM, LRRN3, KIAA0716, and LAMB1 in this region were chosen for examination based on their proximity to the marker most consistently cosegregating with autism in these families (D7S1817, their tissue expression patterns, and likely biological relevance to autism. Methods Thirty-six intronic and exonic single nucleotide polymorphisms (SNPs and one microsatellite marker within and around these four candidate genes were genotyped in 30 chromosome 7q31 linked families. Multiple SNPs were used to provide as complete coverage as possible since linkage disequilibrium can vary dramatically across even very short distances within a gene. Analyses of these data used the Pedigree Disequilibrium Test for single markers and a multilocus likelihood ratio test. Results As expected, linkage disequilibrium occurred within each of these genes but we did not observe significant LD across genes. None of the polymorphisms in NRCAM, LRRN3, or KIAA0716 gave p LAMB1, the allelic association analysis revealed suggestive evidence for a positive association, including one individual SNP (p = 0.02 and three separate two-SNP haplotypes across the gene (p = 0.007, 0.012, and 0.012. Conclusions NRCAM, LRRN3, KIAA0716 are unlikely to be involved in autism. There is some evidence that variation in or near the LAMB1 gene may be involved in autism.

  3. Perfusion impairments on brain SPECT in patients with infantile autism and nonautistic pervasive developmental disorders: comparison with MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Young Hoon; Lee, Jong Doo; Yoon, Pyeong Ho; Kim, Dong Ik; Jeon, Tae Joo; Shin, Yee Jin; Lee, Byung Hee; Shin, Hyung Cheol [College of Medecine, Soonchunhyang Univ., Chonan (Korea, Republic of)

    1998-07-01

    Neuroimaging findings of autism has been the subjects of continuing investigation. Because previous study had not demonstrated consistent and specific neuroimaging findings of autism and most studies comprised adults and school-aged children, we performed a retrospective review in search of common functional and structural abnormalities in pre-school aged autistic children using Tc-99m ECD brain SPECT and MRI and compared them with age-matched children with nonautistic pervasive developmental disorders (PDD). 58 children between 3 and 8 years of age infantile autism (n=37) and non-autistic PDD (n=21) were performed Tc-99m ECD brain SPECT and MRI. Diagnosis of autism and non-autistic PDD was based on the criteria of DSM-IV and Childhood Autism Rating Scale (CARS). Of the 37 autistic patients, 32 revealed decreased perfusion of cerebellar hemisphere, followed by hypoperfusion of thalami (n=30), parietal cortex (n=16), temporal cortex (n=12). Of those 21 PDD patients, 14 patients showed hypoperfusion of the thalami and 10 patients showed temporal hypoperfusion. However, cerebellar hemispheric (n=8) and parietal (n=1) hypoperfusion was infrequently seen. All autistic and nonautistic PDD patients had normal MRI scan. Cerebellar hemispheric and parietal hypoperfusion on brain SPECT showed statistically significant correlation with CARS. Cerebellar hemispheric and parietal hypoperfusion is significantly frequently noted in autistic patients although they had normal MRI and SPECT may be useful and more sensitive modality in reflecting pathophysiology of autism as evidenced by previous MRI and postmortem studies. Thalamic and temporal hypoperfusion can be seen in both autistic and nonautistic patients and further studies are necessary to determine the significance of the thalamic hypoperfusion.

  4. Perfusion impairments on brain SPECT in patients with infantile autism and nonautistic pervasive developmental disorders: comparison with MR findings

    International Nuclear Information System (INIS)

    Neuroimaging findings of autism has been the subjects of continuing investigation. Because previous study had not demonstrated consistent and specific neuroimaging findings of autism and most studies comprised adults and school-aged children, we performed a retrospective review in search of common functional and structural abnormalities in pre-school aged autistic children using Tc-99m ECD brain SPECT and MRI and compared them with age-matched children with nonautistic pervasive developmental disorders (PDD). 58 children between 3 and 8 years of age infantile autism (n=37) and non-autistic PDD (n=21) were performed Tc-99m ECD brain SPECT and MRI. Diagnosis of autism and non-autistic PDD was based on the criteria of DSM-IV and Childhood Autism Rating Scale (CARS). Of the 37 autistic patients, 32 revealed decreased perfusion of cerebellar hemisphere, followed by hypoperfusion of thalami (n=30), parietal cortex (n=16), temporal cortex (n=12). Of those 21 PDD patients, 14 patients showed hypoperfusion of the thalami and 10 patients showed temporal hypoperfusion. However, cerebellar hemispheric (n=8) and parietal (n=1) hypoperfusion was infrequently seen. All autistic and nonautistic PDD patients had normal MRI scan. Cerebellar hemispheric and parietal hypoperfusion on brain SPECT showed statistically significant correlation with CARS. Cerebellar hemispheric and parietal hypoperfusion is significantly frequently noted in autistic patients although they had normal MRI and SPECT may be useful and more sensitive modality in reflecting pathophysiology of autism as evidenced by previous MRI and postmortem studies. Thalamic and temporal hypoperfusion can be seen in both autistic and nonautistic patients and further studies are necessary to determine the significance of the thalamic hypoperfusion

  5. Review of Autism Screening Tests

    Directory of Open Access Journals (Sweden)

    Farin Soleimani

    2014-10-01

    Full Text Available Background: Autism is a neurodevelopmental disorder that onset in the first 3 years of life and led to lifelong disability.Despite the early onset of symptoms, diagnosis of thissyndromedoes not happenuntil severalyears later, somany childrenlosethe opportunityfor earlyintervention.There arevarious toolsforscreening anddiagnosis, buttheirdesign, strengths and weaknesses aredifferent. The aim of this study was assess these tools from various aspects to provide a comprehensive view. Materials and methods: This study is a narrative literature review on screeningtoolsof autism. Comprehensive searches of the scientific literature were conducted in textbooks and 8 electronic databases(proquest,wiley,google scholar,SID,Scopus, Web of Science ،Science Direct ، and Medline and Pediatric book. language restriction (Persian and English was applied. The search strategy consisted of keywords and medical subject headings for autism and various screening tests. Result: In this study, 28 screening tests were identified from 1992 to 2014. CHAT is oldest test and the most recent test is CAST The minimum age that can perform the screening is six months that related to ITC. Minimum time of testing was 5 minutes  for CHAT and the maximum time was 90-120 minutes for ASIEP-3.RAADS-R test was the highest specificity and specificity (100% and the lowest specificity was 14% in ESAT test Conclusion: The results of this study indicate that any of the autism screening tools consider specific skill and various aspects of the disease, careful evaluation is need to choose proper test.

  6. Mercury and Autism: A Review

    Science.gov (United States)

    Zhang, Jie; Wheeler, John J.

    2010-01-01

    The prevalence of autism has increased approximately four times in children in nearly one decade (California Health and Human Services Agency, 2003). It has been reported that explanations such as immigration, shifts in the interpretation of diagnostic criteria, improved identification, or diagnostic accuracies cannot explain the observed increase…

  7. Autism and Phthalate Metabolite Glucuronidation

    Science.gov (United States)

    Stein, T. Peter; Schluter, Margaret D.; Steer, Robert A.; Ming, Xue

    2013-01-01

    Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured…

  8. Autism Spectrum Disorders and Epigenetics

    Science.gov (United States)

    Grafodatskaya, Daria; Chung, Brian; Szatmari, Peter; Weksberg, Rosanna

    2010-01-01

    Objective: Current research suggests that the causes of autism spectrum disorders (ASD) are multifactorial and include both genetic and environmental factors. Several lines of evidence suggest that epigenetics also plays an important role in ASD etiology and that it might, in fact, integrate genetic and environmental influences to dysregulate…

  9. Neurofeedback in Autism Spectrum Disorders

    Science.gov (United States)

    Holtmann, Martin; Steiner, Sabina; Hohmann, Sarah; Poustka, Luise; Banaschewski, Tobias; Bolte, Sven

    2011-01-01

    Aim: To review current studies on the effectiveness of neurofeedback as a method of treatment of the core symptoms of autism spectrum disorders (ASD). Method: Studies were selected based on searches in PubMed, Ovid MEDLINE, EMBASE, ERIC, and CINAHL using combinations of the following keywords: "Neurofeedback" OR "EEG Biofeedback" OR "Neurotherapy"…

  10. Relative Carnitine Deficiency in Autism

    Science.gov (United States)

    Filipek, Pauline A.; Juranek, Jenifer; Nguyen, Minh T.; Cummings, Christa; Gargus, J. Jay

    2004-01-01

    A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine ([rho] less than 0.001), and pyruvate ([rho]=0.006) were significantly reduced…

  11. Savants, segments, art and autism.

    Science.gov (United States)

    Pring, L; Hermelin, B; Heavey, L

    1995-09-01

    This study describes two experiments which investigate pattern construction by graphically gifted, autistic savants. We explore whether the notion of weak central coherence in autism might be extended to account for the relatively high frequency of savants among the autistic population. We also suggest that an awareness of constituent segments in wholes may be relevant to artistic talent in general. PMID:7593399

  12. Expression of the Broad Autism Phenotype in Simplex Autism Families from the Simons Simplex Collection

    Science.gov (United States)

    Davidson, Julie; Goin-Kochel, Robin P.; Green-Snyder, Lee Anne; Hundley, Rachel J.; Warren, Zachary; Peters, Sarika U.

    2014-01-01

    The broad autism phenotype (BAP) refers to the phenotypic expression of an underlying genetic liability to autism, manifest in non-autistic relatives. This study examined the relationship among the "Broad Autism Phenotype Questionnaire" (BAPQ), "Social Responsiveness Scale: Adult Research Version" (SRS:ARV), and "Family…

  13. Which Terms Should Be Used to Describe Autism? Perspectives from the UK Autism Community

    Science.gov (United States)

    Kenny, Lorcan; Hattersley, Caroline; Molins, Bonnie; Buckley, Carole; Povey, Carol; Pellicano, Elizabeth

    2016-01-01

    Recent public discussions suggest that there is much disagreement about the way autism is and should be described. This study sought to elicit the views and preferences of UK autism community members--autistic people, parents and their broader support network--about the terms they use to describe autism. In all, 3470 UK residents responded to an…

  14. Glucocorticoid-induced myopathy: Pathophysiology, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    Anu Gupta

    2013-01-01

    Full Text Available Glucocorticoid-induced myopathy is the most common type of drug-induced myopathy. Nearly 60% of patients with Cushing′s syndrome have muscle weakness. Glucocorticoid-induced muscle atrophy affects mainly fast-twitch glycolytic muscle fibers (type IIb fibers. This brief review will discuss the pathophysiology behind glucocorticoid-induced myopathy, along with diagnostic features and treatment.

  15. Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms

    OpenAIRE

    Kerckhoffs, A.P.M.

    2009-01-01

    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 composition, intestinal mucosal barrier, serine protease and serotonergic signalling components which may play a role in the visceral hypersensitivity. We showed alterations in microbiota composition...

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

    DEFF Research Database (Denmark)

    Sutton, J R; Lassen, N

    1979-01-01

    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...

  17. Pathophysiology and treatment of edema following femoropopliteal bypass surgery

    NARCIS (Netherlands)

    te Slaa, A.; Dolmans, D. E. J. G. J.; Ho, G. H.; Moll, F. L.; van der Laan, L.

    2012-01-01

    Substantial lower-limb edema affects the majority of patients who undergo peripheral bypass surgery. Edema has impairing effects on the microvascular and the macrovascular circulation, causes discomfort and might delay the rehabilitation process of the patient. However, the pathophysiology of this e

  18. Current pathophysiological concepts and management of pulmonary hypertension

    OpenAIRE

    Lourenço, AP; Fontoura, D.; Henriques-Coelho, T; Leite-Moreira, AF

    2012-01-01

    Pulmonary hypertension (PH), increasingly recognized as a major health burden, remains underdiagnosed due mainly to the unspecific symptoms. Pulmonary arterial hypertension (PAH) has been extensively investigated. Pathophysiological knowledge derives mostly from experimental models. Paradoxically, common non-PAH PH forms remain largely unexplored. Drugs targeting lung vascular tonus became available during the last two decades, notwithstanding the disease progresses in many patients. The aim ...

  19. Examining Neural Synchrony in Autism During Resting State With Magnetoencephalography (MEG

    Directory of Open Access Journals (Sweden)

    Smith Tyronda D.

    2014-09-01

    Full Text Available Autism Spectrum Disorder (ASD comprises a group of neurodevelopmental disorders associated with the functioning of the central nervous system (American Psychiatric Association, 2013. The symptoms experienced by individuals with this disorder include social impairment, communication difficulties, and repetitive and stereotyped behaviors. The etiology of ASD has yet to be determined, and it is typically diagnosed based on behavioral criteria of the Diagnostic and Statistical Manual- 5th Edition (DSM-5; APA, 2013 and confirmed with “gold standard” assessment tools such as the Autism Diagnostic Observation Schedule (ADOS and Autism Diagnostic Interview- Revised (ADI-R; Johnson Center for Child Health Development, 2014. Abnormalities in synchronous neural activity have been hypothesized to be a core pathophysiological mechanism (Cornew et al., 2012. Magnetoencephalography (MEG can measure synchronous neural activity during resting state, when the brain is not consciously engaged in cognitive processing. Coherence is a measure of the synchronicity. We examined differences in coherence during resting state in ASD, compared to neurotypical developing individuals (NT, in an attempt to identify potential biomarkers and illuminate a core etiological mechanism.

  20. Pathophysiological distortions in time perception and timed performance

    OpenAIRE

    Allman, Melissa J.; Meck, Warren H.

    2011-01-01

    Distortions in time perception and timed performance are presented by a number of different neurological and psychiatric conditions (e.g. Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder and autism). As a consequence, the primary focus of this review is on factors that define or produce systematic changes in the attention, clock, memory and decision stages of temporal processing as originally defined by Scalar Expectancy Theory. These findings are used to evaluate ...

  1. Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism.

    Science.gov (United States)

    Watanabe, Takamitsu; Kuroda, Miho; Kuwabara, Hitoshi; Aoki, Yuta; Iwashiro, Norichika; Tatsunobu, Natsubori; Takao, Hidemasa; Nippashi, Yasumasa; Kawakubo, Yuki; Kunimatsu, Akira; Kasai, Kiyoto; Yamasue, Hidenori

    2015-11-01

    Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention were not larger than those seen in our previous single-dose intervention. These findings not only provide the evidence for clinically beneficial effects of continual oxytocin administration on the core social symptoms of autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies. PMID:26336909

  2. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances.

    Directory of Open Access Journals (Sweden)

    Brent L Williams

    Full Text Available Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism.

  3. Parental psychiatric disorders and autism spectrum disorders

    OpenAIRE

    Jokiranta, Elina; Brown, Alan S.; Heinimaa, Markus; Cheslack-Postava, Keely; Partanen, Auli; SOURANDER, ANDRE

    2013-01-01

    The present population-based, case-control study examines associations between specific parental psychiatric disorders and autism spectrum disorders (ASD) including childhood autism, Asperger’s syndrome and pervasive developmental disorder (PDD-NOS). The cohort includes 4713 children born between 1987 and 2005 with diagnoses of childhood autism, Asperger’s syndrome or PDD-NOS. Cases were ascertained from the Finnish Hospital Discharge Register, and each was matched to four controls by gender,...

  4. Autism and the development of face processing

    OpenAIRE

    Golarai, Golijeh; Grill-Spector, Kalanit; Reiss, Allan L.

    2006-01-01

    Autism is a pervasive developmental condition, characterized by impairments in non-verbal communication, social relationships and stereotypical patterns of behavior. A large body of evidence suggests that several aspects of face processing are impaired in autism, including anomalies in gaze processing, memory for facial identity and recognition of facial expressions of emotion. In search of neural markers of anomalous face processing in autism, much interest has focused on a network of brain ...

  5. Disrupted neural synchronization in toddlers with autism

    OpenAIRE

    Dinstein, Ilan; Pierce, Karen; Eyler, Lisa; Solso, Stephanie; Malach, Rafael; Behrmann, Marlene; Courchesne, Eric

    2011-01-01

    Autism is often described as a disorder of neural synchronization. However, it is unknown how early in development synchronization abnormalities emerge and whether they are related to the development of early autistic behavioral symptoms. Here, we show that disrupted synchronization is evident in the spontaneous cortical activity of naturally sleeping toddlers with autism, but not in toddlers with language delay or typical development. Toddlers with autism exhibited significantly weaker inter...

  6. Embodiment and sense-making in autism

    OpenAIRE

    Hanne De Jaegher

    2013-01-01

    Traditional functionalist approaches to autism consider cognition, communication, and perception separately, and can only provide piecemeal accounts of autism. Basing an integrative explanation on a single cause or common factor has proven difficult. Traditional theories are also disembodied and methodologically individualistic. In order to overcome these problems, I propose an enactive account of autism. For the enactive approach to cognition embodiment, interaction, and personal ex...

  7. Relaxin: new pathophysiological aspects and pharmacological perspectives for an old protein.

    Science.gov (United States)

    Cernaro, Valeria; Lacquaniti, Antonio; Lupica, Rosaria; Buemi, Antoine; Trimboli, Domenico; Giorgianni, Grazia; Bolignano, Davide; Buemi, Michele

    2014-01-01

    Human relaxin-2 (hereafter simply defined as "relaxin") is a 6-kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in-depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future. PMID:23401142

  8. Pathophysiological Characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease: a Review and Update

    Directory of Open Access Journals (Sweden)

    Jian-Xun Ren

    2016-10-01

    Full Text Available The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease (CHD has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation syndrome has become a dominant syndrome in CHD along with the improvement in living and dietary condition. The interaction between blood stasis and phlegm turbidity that is called Phlegm-stasis Cementation Syndrome exists in CHD and other diseases. The bridge linked blood stasis and phlegm turbidity lies in the adversely effects of lipid metabolism disorder on platelet activation, vascular function and hemorheology indexes. Lipid metabolism disorder also can induce persistent inflammation including monocyte/macrophage activation and oxidative stress. Inflammation also is an important stimulating factor for atherosclerosis and the biology that underlies the complications of CHD, which belonged to the concept of “toxin” in Traditional Chinese medicines (TCM. On the other hand, the important function of inflammatory process on abnormal hemorheology, platelet activation and vascular dysfunction can be used to elucidate the basic pathogenetic condition of the toxin inducing blood stasis in TCM. Therefore, it is this pathological process that can be used to address the basic pathogenetic theory of phlegm turbidity inducing the symptom of toxin and blood stasis, and subsequently phlegm-stasis cementation in TCM. We deduced that lipid metabolic disturbance, inflammation activation, vascular dyfunction and hemorheological disorders could be as pathophysiological characteristics of Phlegm-stasis cementation syndrome.

  9. The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease.

    Science.gov (United States)

    Zhu, Ping; Sun, Weiwei; Zhang, Chenliang; Song, Zhiyuan; Lin, Shu

    2016-10-01

    With average life expectancy rising greatly, the incidence rate of arteriosclerotic cardiovascular disease (ASCVD) has significantly increased. The heart disease has now become the number one killer that threatens the global population health, the second is stroke. It will be of great significance to investigate the underlying pathophysiological mechanisms of ASCVD in order to promote effective prevention and treatment. The neuropeptide Y (NPY) has now been discovered for more than thirty years and is widely distributed in the central nervous system (CNS) and peripheral tissues. By combining with certain receptors, NPY performs a variety of physiological functions, including the regulation of food intake, cardiovascular effects, development, hormonal secretion, sexual behavior, biological rhythms, temperature and emotion. In ASCVD, increased peripheral NPY was involved in the pathophysiological process of atherosclerosis through affecting the vascular endothelial dysfunction, the formation of foam cells, the proliferation of vascular smooth muscle cells, the local inflammatory response of plaques and the activation and aggregation of platelets. Via central and/or the peripheral nervous system, increased NPY was associated with dyslipidemia, hypertension, obesity, diabetes, impaired glucose tolerance, and smoking which are all risk factors for ASCVD. In this review, we summarize the role of neuropeptide Y in the development of atherosclerotic cardiovascular disease. PMID:27389447

  10. Sensory Features as Diagnostic Criteria for Autism: Sensory Features in Autism

    OpenAIRE

    Grapel, Jordan N.; Cicchetti, Domenic V.; Volkmar, Fred R.

    2015-01-01

    In this study, we examined the frequency of sensory-related issues as reported by parents in a large sample of school-age adolescents and adults with autism/autism spectrum disorder (ASD) [1] as compared to a group of individuals receiving similar clinical evaluations for developmental/behavioral difficulties but whose final diagnoses were not on the autism spectrum. In no comparison were the features examined predictive of autism or autism spectrum in comparison to the non-ASD sample. Only f...

  11. Autism Spectrum Disorders in Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Reza MOHAMMADI

    2011-12-01

    Full Text Available How to Cite this Article: Mohammadi MR, Salmanian M, Akhondzadeh Sh. Autism Spectrum Disorders in Iran. Iranian Journal of Child Neurology2011;5(4:1-9.ObjectiveAutistic disorder, Asperger syndrome, and PDD-Not Otherwise Specified are subsets of autism spectrum disorders (ASDs, which are characterized by impairments in social communication and stereotyped behavior. This article reviews the prevalence, etiology, diagnosis, and treatment of ASDs in Iran.Materials & MethodsWe searched PubMed, ISI Web of Science, and 4 Iranian databases (IranPsych,IranMedex, Irandoc and Scientific Information Database (SID to find Iranian studies on  ASDs. The results of 39 investigations, comprising original, review and editorial articles; proceedings; and available dissertations were categorized by prevalence, etiology, diagnosis, and treatment.ConclusionSeveral preliminary investigations have been done to evaluate the prevalence of ASDs, and risk factors and effective variables have been studied with regard to etiology. The diagnostic evaluation of ASDs, especially based on EEG, and several pharmacological and behavioral interventions for ASD have been implemented in Iran. Mental health, stress levels, and personality characteristics were examined in the parents of children with ASDs, which were focused on mothers.ReferencesFirst MB, Frances A, Pincus HA. DSM-IV-TR: Handbook of differential diagnosis. United States of America:American Psychiatric Publishing; 2002.Parker S, Zuckerman B, Augustyn M. Developmental and behavioral pediatrics, 2 th ed. United States of America:Lippincott Williams & Wilkins; 2005.Howlin P. Autism and Asperger syndrome, 2 th ed. United States of America: Routledge; 2005.Mohammadi MR, Akhondzadeh S. Autism Spectrum Disorders: Etiology and Pharmacotherapy. Curr Drug ther2007; 2: 97-103.Newschaffer CJ, Croen LA, Daniels J, Giarelli E, GretherJK, Levy SE, et al. The epidemiology of autism spectrumdisorders. Annu Rev Public Health

  12. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking

    OpenAIRE

    Bowton, E.; C. Saunders; Reddy, I A; Campbell, N G; Hamilton, P J; Henry, L K; Coon, H; Sakrikar, D; Veenstra-VanderWeele, J M; Blakely, R. D.; Sutcliffe, J; Matthies, H J G; Erreger, K; Galli, A.

    2014-01-01

    Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA...

  13. Co-Occurrence of Autism and Deafness: Diagnostic Considerations.

    Science.gov (United States)

    Roper, Louise; Arnold, Paul; Monteiro, Brendan

    2003-01-01

    Two parts of the Autism Screening Instrument were administered to 13 individuals with deafness and autism (ages 15-24), individuals with autism (n=12), and individuals with deafness and learning disabilities (n=15). No differences in symptomatology were found between those who had autism, although those with deafness were diagnosed with autism…

  14. The Relation between Social Engagement and Pretend Play in Autism

    Science.gov (United States)

    Hobson, Jessica A.; Hobson, R. Peter; Malik, Supriya; Bargiota, Kyratso; Calo, Susana

    2013-01-01

    The focus of this study is the nature and concomitants of pretend play among young children with autism. Age- and language-matched children with autism ("n"= 27), autism spectrum disorder ("n"= 14), and developmental disorders without autism ("n"= 16) were administered the Test of Pretend Play (ToPP; Lewis &…

  15. Comparison of Scores on the Checklist for Autism Spectrum Disorder, Childhood Autism Rating Scale, and Gilliam Asperger's Disorder Scale for Children with Low Functioning Autism, High Functioning Autism, Asperger's Disorder, ADHD, and Typical Development

    Science.gov (United States)

    Mayes, Susan Dickerson; Calhoun, Susan L.; Murray, Michael J.; Morrow, Jill D.; Yurich, Kirsten K. L.; Mahr, Fauzia; Cothren, Shiyoko; Purichia, Heather; Bouder, James N.; Petersen, Christopher

    2009-01-01

    Reliability and validity for three autism instruments were compared for 190 children with low functioning autism (LFA), 190 children with high functioning autism or Asperger's disorder (HFA), 76 children with attention deficit hyperactivity disorder (ADHD), and 64 typical children. The instruments were the Checklist for Autism Spectrum Disorder…

  16. Diagnosis and management of autism in adults.

    Science.gov (United States)

    Valkanova, Vyara; Rhodes, Fiona; Allan, Charlotte L

    2013-05-01

    Autism affects 1.1% of the adult population. The spectrum of symptoms is wide; some individuals have above average intelligence and are fully independent, while others have limited independence because of a learning disability. Developmental delay is a core feature, and autism is usually diagnosed in childhood. High-functioning individuals with autism, Asperger's syndrome, may remain undiagnosed until adulthood. Autism is a life-long condition characterised by problems in two core dimensions: difficulties with social communication and strongly repetitive behaviour, resistance to change or restricted interests.The history should identify early developmental and behavioural problems in different settings e.g. at home, in education or employment. Sensory and GI problems are very common, and should be asked about. The Autism-Spectrum Quotient (AQ-10) is a 10-item questionnaire for people with suspected autism. The advantage of using this in primary care is that it provides a time-efficient, structured way of ascertaining key symptoms and clearly signals those who should be referred for further assessment. Patients should be referred if autism is suspected clinically and a diagnosis of autism should be confirmed by a specialist multidisciplinary team. If a diagnosis of autism is made, clinicians should do a risk assessment and formulate risk and crisis management plans. These should include details of the roles and responsibilities of both the specialist team and primary care team in managing crisis situations. For adults with autism a group-based or an individual learning programme to improve social interaction is recommended. Adults with autism have high rates of unemployment, and employment programmes have been successfully used to support people PMID:23808126

  17. Subventricular zone cytoarchitecture changes in autism.

    Science.gov (United States)

    Kotagiri, Prasanti; Chance, Steven A; Szele, Francis G; Esiri, Margaret M

    2014-01-01

    Autism is thought to be a neurodevelopmental disorder with symptoms developing during neonatal neurogenesis in the subventricular zone (SVZ). Autism associated genes alter SVZ proliferation and cytoarchitecture, yet the response of the human SVZ in autism is unknown. Epilepsy drives neurogenesis in rodents, but it is unclear how epilepsy interacts with autism in SVZ responses. The striatal and septal SVZ derive from separate lineages in rodents and generate different interneuron types. Yet it is unclear if autism unevenly regulates the striatal and septal SVZ. The human SVZ was immunohistochemically examined post-mortem from individuals with autism (n = 11) and controls (n = 11). Autism showed a lower cell density in the septal, but not striatal, SVZ hypocellular gap only in the absence of epilepsy. There was a decline in septal hypocellular gap cells with age in autism, but no correlation with age in controls. In contrast, PCNA+ cell numbers increased only in autism with epilepsy both in the hypocellular gap and in the ependymal layer on the septal but not striatal side. Ependymal cells also became GFAP immunoreactive in autism irrespective of epilepsy co-morbidity; however, this only occurred on the striatal side. In examining these questions we also discovered a subset of ependymal, astrocyte ribbon and RMS cells which express PCNA and Ki67, PLP, and α-tubulin. These results are the first example of a neuropsychiatric disease differentially affecting the septal and striatal SVZ. Altered cell density in the hypocellular gap and proliferation marker expression suggest individuals with autism may follow a different growth-trajectory. PMID:24002902

  18. Breast cancer and autism.

    Science.gov (United States)

    Radcliff, Lisa

    2013-03-01

    Case Study Amy is a 44-year-old woman with severe autism. She lives with her sister Susan, who is her caregiver and guardian. Amy is ambulatory and able to dress and feed herself. She is a healthy individual with no other significant comorbidities. She walks daily and enjoys her sister's company. Amy's life expectancy is greater than 10 years. However, she is difficult to care for medically, as she will not allow a physical examination and strikes out when strangers try to touch her. She is nonverbal and unable to participate in decision-making. INITIAL DIAGNOSIS Amy has a history of breast cancer diagnosed 2 years ago, originally presenting as a stage I lesion (T2N0) that was palpated by her caregiver while bathing. She underwent right simple mastectomy with sentinel lymph node resection. Susan recalls that the mastectomy was a very challenging ordeal, as Amy kept pulling out IV lines, drains, and dressings. Susan felt that Amy withdrew from her after the procedure as she most likely associated Susan with the cause of the pain, making her role as caregiver more difficult. Pathology confirmed an invasive ductal carcinoma, moderately differentiated, 2.4 cm, estrogen/progesterone receptor negative, HER2/neu negative, with negative surgical margins. Two right axillary sentinel lymph nodes were negative for disease. The standard of care for a patient with these tumor features is surgery plus adjuvant chemotherapy (National Comprehensive Cancer Network [NCCN], 2012). According to the Adjuvant Online! database (2012), Amy's risk for relapse was approximately 40% without adjuvant treatment; her risk for mortality was approximately 29%. After meeting with a medical oncologist, Amy did not receive adjuvant chemotherapy. According to Susan, she was not offered the choice, and the decision was not explained to them. She was simply told that it was not necessary. Aside from pathology, previous records were unavailable for review. Medical assessment of Amy's level of autism

  19. A direct molecular link between the autism candidate gene RORa and the schizophrenia candidate MIR137

    Science.gov (United States)

    Devanna, Paolo; Vernes, Sonja C.

    2014-02-01

    Retinoic acid-related orphan receptor alpha gene (RORa) and the microRNA MIR137 have both recently been identified as novel candidate genes for neuropsychiatric disorders. RORa encodes a ligand-dependent orphan nuclear receptor that acts as a transcriptional regulator and miR-137 is a brain enriched small non-coding RNA that interacts with gene transcripts to control protein levels. Given the mounting evidence for RORa in autism spectrum disorders (ASD) and MIR137 in schizophrenia and ASD, we investigated if there was a functional biological relationship between these two genes. Herein, we demonstrate that miR-137 targets the 3'UTR of RORa in a site specific manner. We also provide further support for MIR137 as an autism candidate by showing that a large number of previously implicated autism genes are also putatively targeted by miR-137. This work supports the role of MIR137 as an ASD candidate and demonstrates a direct biological link between these previously unrelated autism candidate genes.

  20. A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism

    Directory of Open Access Journals (Sweden)

    Hussman John P

    2011-01-01

    Full Text Available Abstract Background Genome-wide Association Studies (GWAS have proved invaluable for the identification of disease susceptibility genes. However, the prioritization of candidate genes and regions for follow-up studies often proves difficult due to false-positive associations caused by statistical noise and multiple-testing. In order to address this issue, we propose the novel GWAS noise reduction (GWAS-NR method as a way to increase the power to detect true associations in GWAS, particularly in complex diseases such as autism. Methods GWAS-NR utilizes a linear filter to identify genomic regions demonstrating correlation among association signals in multiple datasets. We used computer simulations to assess the ability of GWAS-NR to detect association against the commonly used joint analysis and Fisher's methods. Furthermore, we applied GWAS-NR to a family-based autism GWAS of 597 families and a second existing autism GWAS of 696 families from the Autism Genetic Resource Exchange (AGRE to arrive at a compendium of autism candidate genes. These genes were manually annotated and classified by a literature review and functional grouping in order to reveal biological pathways which might contribute to autism aetiology. Results Computer simulations indicate that GWAS-NR achieves a significantly higher classification rate for true positive association signals than either the joint analysis or Fisher's methods and that it can also achieve this when there is imperfect marker overlap across datasets or when the closest disease-related polymorphism is not directly typed. In two autism datasets, GWAS-NR analysis resulted in 1535 significant linkage disequilibrium (LD blocks overlapping 431 unique reference sequencing (RefSeq genes. Moreover, we identified the nearest RefSeq gene to the non-gene overlapping LD blocks, producing a final candidate set of 860 genes. Functional categorization of these implicated genes indicates that a significant proportion of

  1. Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology.

    Science.gov (United States)

    Cayabyab, Rowena; Ramanathan, Rangasamy

    2016-01-01

    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

  2. Symptoms of Autism Among Children with Congenital Deafblindness

    DEFF Research Database (Denmark)

    Dammeyer, Jesper Herup

    2014-01-01

    Associations between congenital deafness or blindness and autism have been found. The main consequences of congenital sensory impairment, being barriers for communication, language and social interaction development, may lead to symptoms of autism. To date only few studies have been reported...... concerning individuals with congenital deafblindness. This study examines symptoms of autism among 71 children with congenital deafblindness using the Autism Behavior Checklist. The cohort of children with congenital deafblindness was found to have symptoms of autism on a level similar to children with...... another developmental disorder than autism for example intellectual disability. No association was found between severity of congenital sensory impairment and severity or type of symptoms of autism....

  3. The Association Between Children with Autism and Gastrointestinal Symptoms

    Directory of Open Access Journals (Sweden)

    Prince, Yasmeen

    2013-09-01

    Full Text Available Every day many thousands of children face the complications of Autism. According to Geraghty, Depasquale, and Lane (2010, Autism has become one of the most frequently diagnosed developmental disabilities, with one in one hundred children diagnosed with Autism in the United States every day. The etiology of Autism Spectrum Disorder (ASD has not been determined. One of many questions researchers are asking is whether an association exists between gastrointestinal disorders and Autism. This literature review examines the relationship between GI symptoms and eating patterns in children with Autism, and assesses whether special diets reduce symptoms of Autism Spectrum Disorder.

  4. Sleep disordered breathing: OSA, CSA, Pathophysiology and Diagnosis

    Directory of Open Access Journals (Sweden)

    V K Vijayan

    2014-03-01

    Full Text Available Obstructive sleep apnea syndrome (OSAS is a prevalent disorder that has beenreported to occur in 2 to 4% of middle-aged adults. A similar prevalence of OSAS hasbeen reported from India as well. However, this condition is frequently unrecognizedand underdiagnosed. Important pathophysiological changes in patients withobstructive sleep apnea (OSA is an alteration in human upper airway leading to areduction in cross-sectional area of the upper airway contributing to the easycollapsibility of upper airway during sleep. Other pathophysiological changes in OSAare oxidative stress, systemic inflammation, sympathetic nerve activation, endothelialdysfunction, procoagulant activity, intrathoracic pressure changes and metabolicdysregulation. The gold standard for diagnosis of OSA is full polysomnography.Key words: Obstructive sleep apnea, Central sleep apnea, Oxidative stress,Metabolic dysregulation, Polysomnography

  5. Pathophysiology of ageing, longevity and age related diseases

    Directory of Open Access Journals (Sweden)

    Santoni Angela

    2007-08-01

    Full Text Available Abstract On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life.

  6. Facial Erythema of Rosacea - Aetiology, Different Pathophysiologies and Treatment Options.

    Science.gov (United States)

    Steinhoff, Martin; Schmelz, Martin; Schauber, Jürgen

    2016-06-15

    Rosacea is a common chronic skin condition that displays a broad diversity of clinical manifestations. Although the pathophysiological mechanisms of the four subtypes are not completely elucidated, the key elements often present are augmented immune responses of the innate and adaptive immune system, and neurovascular dysregulation. The most common primary feature of all cutaneous subtypes of rosacea is transient or persistent facial erythema. Perilesional erythema of papules or pustules is based on the sustained vasodilation and plasma extravasation induced by the inflammatory infiltrates. In contrast, transient erythema has rapid kinetics induced by trigger factors independent of papules or pustules. Amongst the current treatments for facial erythema of rosacea, only the selective α2-adrenergic receptor agonist brimonidine 0.33% topical gel (Mirvaso®) is approved. This review aims to discuss the potential causes, different pathophysiologies and current treatment options to address the unmet medical needs of patients with facial erythema of rosacea. PMID:26714888

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

    DEFF Research Database (Denmark)

    Stidsen, Jacob

    2013-01-01

    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......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...... autoimmune diabetes (LADA) (GAD antibody titer >= 20 IE/ml and not T1D), secondary diabetes (recent history of pancreatitis, pancreatectomy or pancreas amylase > 65U/l, and GAD negativity), steroid-induced diabetes (oral glucocorticoid-treated subjects), insulinopenic (f-P-C-peptide < 333 pmol/l and not LADA...

  8. New insights into the pathophysiology of postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

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

    2010-01-01

    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 o...... minimal invasive surgery, multi-modal non-opioid pain management and pharmacological manipulation of the inflammatory response and sleep architecture....... appropriate controls. Furthermore, there are no internationally accepted criteria for defining POCD. This article aims to provide an update of current knowledge of the pathogenesis of POCD with a focus on perioperative pathophysiology and possible benefits achieved from an enhanced postoperative recovery...... using a fast-track methodology. It is concluded that the pathogenesis of POCD is multifactorial and future studies should focus on evaluating the role of postoperative sleep disturbances, inflammatory stress responses, pain and environmental factors. Potential prophylactic intervention may include...

  9. Molecular structure and pathophysiological roles of the Mitochondrial Calcium Uniporter.

    Science.gov (United States)

    Mammucari, Cristina; Raffaello, Anna; Vecellio Reane, Denis; Rizzuto, Rosario

    2016-10-01

    Mitochondrial Ca(2+) uptake regulates a wide array of cell functions, from stimulation of aerobic metabolism and ATP production in physiological settings, to induction of cell death in pathological conditions. The molecular identity of the Mitochondrial Calcium Uniporter (MCU), the highly selective channel responsible for Ca(2+) entry through the IMM, has been described less than five years ago. Since then, research has been conducted to clarify the modulation of its activity, which relies on the dynamic interaction with regulatory proteins, and its contribution to the pathophysiology of organs and tissues. Particular attention has been placed on characterizing the role of MCU in cardiac and skeletal muscles. In this review we summarize the molecular structure and regulation of the MCU complex in addition to its pathophysiological role, with particular attention to striated muscle tissues. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID:26968367

  10. Advanced MR diagnostic imaging in pediatric glial cell tumors: from morphological to pathophysiological evaluation

    International Nuclear Information System (INIS)

    Full text: Introduction: The conventional MR imaging is important, and in most cases necessary imaging tool for studying the macroscopic structure, for localization and distribution of a glial brain tumor. It is an integral part of the optimal MR protocol, which further comprises a diffusion, perfusion techniques, techniques for the permeability and oxygenation assessment, as well as MR spectroscopy to the metabolism assessment. What you will learn: Glial brain tumors in children - incidence, histology, classification, diagnosis; Nature and principles of MR diffusion, perfusion, techniques for permeability and oxygenation assessment, MR spectroscopy; Contemporary techniques allowing to obtain not only MR morphological information but also to evaluate the tumor the pathophysiology: the cellular atypia, cellularity, tumor neovascularization, oxygen consumption, metabolism, status of the blood-brain barrier. This assessment determines the biological potential of the tumor, treatment options and prognosis. Discussion: The findings from conventional MR examinations, incl. administration of gadolinium contrast agents are associated with the degree of glioma and can be useful for their classification. Taking into account that from 20% to 45 % of the unenhanced supratentorial gliomas are malignant, some low-grade gliomas enhance (ganglioglioma, pilocytic astrocytoma, oligodendroglioma), 9% of malignant gliomas have no contrast enhancement, and in general, the contrast enhancement is not seen as a reliable indicator for the infiltration extent. The contemporary MR techniques improve the assessment of the pathophysiology of the tumor which is relevant to its histology and biological potential. Conclusion: Modern MR techniques besides purely diagnostic advantages (determine the extent and distribution of glioma), enable: differentiation of tumor recurrence from radiation necrosis; identification of optimal locations for biopsy or operative resection; prognosis, planning and

  11. Head Circumference as an Early Predictor of Autism Symptoms in Younger Siblings of Children with Autism Spectrum Disorder

    Science.gov (United States)

    Elder, Lauren M.; Dawson, Geraldine; Toth, Karen; Fein, Deborah; Munson, Jeff

    2008-01-01

    Siblings of children with autism have an increased risk for autism spectrum disorders (ASD). As children with autism often exhibit an atypical trajectory of head circumference (HC) growth, HC may be an indicator of vulnerability to autism. This study investigated whether infant siblings of children with ASD (n = 77) with an atypical trajectory of…

  12. Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment

    OpenAIRE

    Hartmann, Matthias; Szalai, Cynthia; Saner, Fuat H.

    2016-01-01

    Recent findings in the pathophysiology and monitoring of hemostasis in patients with end stage liver disease have major impact on coagulation management during liver transplantation. There is increasing evidence, that the changes in both coagulation factors and platelet count regularly observed in patients with liver cirrhosis cannot be interpreted as a reliable indicator of diffuse bleeding risk. Instead, a differentiated view on hemostasis has led to the concept of a rebalanced coagulation ...

  13. The Pivotal Role of Airway Smooth Muscle in Asthma Pathophysiology

    OpenAIRE

    Patrick Berger; Roger Marthan; Thomas Trian; Pierre-Olivier Girodet; Benoit Allard; Imane Bara; Annaïg Ozier

    2011-01-01

    Asthma is characterized by the association of airway hyperresponsiveness (AHR), inflammation, and remodelling. The aim of the present article is to review the pivotal role of airway smooth muscle (ASM) in the pathophysiology of asthma. ASM is the main effector of AHR. The mechanisms of AHR in asthma may involve a larger release of contractile mediators and/or a lower release of relaxant mediators, an improved ASM cell excitation/contraction coupling, and/or an alteration in the contraction/lo...

  14. Recent developments in the pathophysiology of irritable bowel syndrome

    OpenAIRE

    El-Salhy, Magdy

    2015-01-01

    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 predispos...

  15. Sleep disordered breathing: OSA, CSA, Pathophysiology and Diagnosis

    OpenAIRE

    Vijayan, V. K.

    2014-01-01

    Obstructive sleep apnea syndrome (OSAS) is a prevalent disorder that has beenreported to occur in 2 to 4% of middle-aged adults. A similar prevalence of OSAS hasbeen reported from India as well. However, this condition is frequently unrecognizedand underdiagnosed. Important pathophysiological changes in patients withobstructive sleep apnea (OSA) is an alteration in human upper airway leading to areduction in cross-sectional area of the upper airway contributing to the easycollapsibility of up...

  16. Pathophysiology of Headaches with a Prominent Vascular Component

    Directory of Open Access Journals (Sweden)

    Juan A Pareja

    1996-01-01

    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.

  17. Experimental models for analysis of oligodendrocyte pathophysiology in stroke

    OpenAIRE

    Arai Ken; Lo Eng H

    2009-01-01

    Abstract White matter damage is a clinically important part of stroke. However, compared to the mechanisms of neuronal injury in gray matter, white matter pathophysiology remains relatively understudied and poorly understood. This mini-review aims at summarizing current knowledge on experimental systems for analyzing the role of white matter injury relevant to stroke. In vitro platforms comprise primary cultures of both mature oligodendrocytes (OLGs) as well as oligodendrocyte precursor cells...

  18. The pathophysiology of endometriosis and adenomyosis: tissue injury and repair

    OpenAIRE

    Leyendecker, G.; Wildt, L. de; Mall, G

    2009-01-01

    Introduction This study presents a unifying concept of the pathophysiology of endometriosis and adenomyosis. In particular, a physiological model is proposed that provides a comprehensive explanation of the local production of estrogen at the level of ectopic endometrial lesions and the endometrium of women affected with the disease. Methods In women suffering from endometriosis and adenomyosis and in normal controls, a critical analysis of uterine morphology and function was performed using ...

  19. Pathophysiology of the systemic inflammatory response after major accidental trauma

    OpenAIRE

    Brøchner Anne; Toft Palle

    2009-01-01

    Abstract Background The purpose of the present study was to describe the pathophysiology of the systemic inflammatory response after major trauma and the timing of final reconstructive surgery. Methods An unsystematic review of the medical literature was performed and articles pertaining to the inflammatory response to trauma were obtained. The literature selected was based on the preference and clinical expertise of authors. Discussion The inflammatory response consists of hormonal metabolic...

  20. Pathophysiology of thrombotic thrombocytopenic purpura: the "two-hit" paradigm

    OpenAIRE

    Lotta, Luca Andrea

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by acute episodes of widespread thrombosis in capillaries and small arteries. The discovery that the plasmatic activity of the von Willebrand factor cleaving protease, ADAMTS13, is severely deficient in patients with TTP represented a turning point in the understanding of the pathophysiology of the disease. In spite of recent advances, the clinical course of TTP is characterized by considerable heterog...

  1. The Pathophysiology of Obesity and Its Clinical Manifestations

    OpenAIRE

    Redinger, Richard N.

    2007-01-01

    Obesity is an exaggeration of normal adiposity and is a central player in the pathophysiology of diabetes mellitus, insulin resistance, dyslipidemia, hypertension, and atherosclerosis, largely due to its secretion of excessive adipokines. Obesity is a major contributor to the metabolic dysfunction involving lipid and glucose, but on a broader scale, it influences organ dysfunction involving cardiac, liver, intestinal, pulmonary, endocrine, and reproductive functions. Inflammatory, insulin-res...

  2. Acute Respiratory Distress Syndrome: Pathophysiology and Therapeutic Options

    OpenAIRE

    Pierrakos, Charalampos; Karanikolas, Menelaos; Scolletta, Sabino; Karamouzos, Vasilios; Velissaris, Dimitrios

    2012-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a common entity in critical care. ARDS is associated with many diagnoses, including trauma and sepsis, can lead to multiple organ failure and has high mortality. The present article is a narrative review of the literature on ARDS, including ARDS pathophysiology and therapeutic options currently being evaluated or in use in clinical practice. The literature review covers relevant publications until January 2011. Recent developments in the therapeut...

  3. Experiment 305: Pathophysiology of Mineral Loss During Space Flight

    Science.gov (United States)

    Arnaud, Claude D.; Cann, Christopher E.

    1995-01-01

    The objective of this SLS-2 experiment was to determine the pathophysiology of mineral loss during space flight. This was to be accomplished by (1) determining the concentrations of blood minerals and of calciotropic hormones (parathyroid hormone-PTH, vitamin D metabolites) before, during, and after a 14 day shuttle flight, and (2) determining, by calcium kinetic analysis (using stable calcium isotopes), the influence of space flight on intestinal calcium absorption .

  4. Carotid Stump Syndrome: Pathophysiology and Endovascular Treatment Options

    International Nuclear Information System (INIS)

    Carotid stump syndrome is one of the recognised causes of recurrent ipsilateral cerebrovascular events after occlusion of the internal carotid artery. It is believed that microemboli arising from the stump of the occluded internal carotid artery or the ipsilateral external carotid artery can pass into the middle cerebral artery circulation as a result of patent external carotid–internal carotid anastomotic channels. Different pathophysiologic causes of this syndrome and endovascular options for treatment are discussed.

  5. Pathophysiology and imaging in inflammatory and blastomatous synovial diseases

    International Nuclear Information System (INIS)

    Variable pathologies are subsumed under the term ''synovial disease'', including common pathologies such as rheumatoid arthritis. While formerly radiologists had to rely on conventional radiographs and bone scintigraphy with their inherent problems in visualizing soft tissue, noninvasive imaging of the synovium has recently improved substantially with the technical development of MRI and (Doppler) ultrasound. These imaging modalities allow differentiation of characteristic pathologic features based on a profound knowledge of normal anatomy and pathophysiology. (orig.)

  6. Velopharyngeal sphincter pathophysiologic aspects in the in cleft palat

    OpenAIRE

    Collares, Marcus Vinicius Martins; Costa, Sady Selaimen da; Paniagua, Lauren Medeiros; Dornelles, Sílvia; Silva, Daniela Preto da

    2008-01-01

    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 velophar...

  7. Craniosynostosis in Growing Children : Pathophysiological Changes and Neurosurgical Problems

    Science.gov (United States)

    Choi, Jung Won; Lim, So Young

    2016-01-01

    Craniosynostosis is defined as the premature fusion of one or more cranial sutures resulting in skull deformity. Characteristically, this disorder can cause diverse neurosurgical problems, as well as abnormal skull shape. Intracranial hypertension, hydrocephalus, Chiari malformation and neuropsychological dysfunction are the major neurosurgical concerns in children with craniosynostosis. In this review article, we investigate pathophysiology, characteristics and proper neurosurgical management of these neurosurgical issues, respectively. PMID:27226849

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

    OpenAIRE

    Hubbard, Tricia J.; Wikstrom, Erik A.

    2010-01-01

    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. Functi...

  9. Involvement of tumor acidification in brain cancer pathophysiology

    OpenAIRE

    AvinashHonasoge

    2013-01-01

    Gliomas, primary brain cancers, are characterized by remarkable invasiveness and fast growth. While they share many qualities with other solid tumors, gliomas have developed special mechanisms to convert the cramped brain space and other limitations afforded by the privileged central nervous system into pathophysiological advantages. In this review we discuss gliomas and other primary brain cancers in the context of acid-base regulation and interstitial acidification; namely, how the altered ...

  10. Physiological and pathophysiological cerebrovascular regulation monitored by transcranial doppler

    OpenAIRE

    Hellström, Gunnar

    1997-01-01

    PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CEREBROVASCULAR REGULATION MONITORED BY TRANSCRANIAL DOPPLER Thesis by Gunnar Hellström, M D., Department of Clinical Neuroscience, Division of Neurology, Karolinska Hospital and Insbtute, Stocknolm, Sweden Transcranial Doppler ultrasonography (TCD) became available in the middle of the 1980s as a new technique for examinmg cerebral circulation. With this technique it is possible to measure the velocity of blood flow in major ...

  11. Pulmonary arterial hypertension: Advances in pathophysiology and management

    OpenAIRE

    Sandeep Chopra; Dinesh K Badyal; P Chris Baby; Davis Cherian

    2012-01-01

    Pulmonary arterial hypertension (PAH) is a heterogeneous, hemodynamic, and pathophysiological state which is commonly found throughout the world, but the disease burden is greater in India and in other developing countries. It is a disease characterized by vascular obstruction and vasoconstriction leading to progressive increase in pulmonary vascular resistance and right ventricular failure. PAH is a progressive disorder carrying a poor prognosis; however, dramatic progress has occurred in ou...

  12. Role and applications of circulatory models in cardiovascular pathophysiology.

    OpenAIRE

    Ferrari, Gianfranco; Kozarski, Maciej; Lazzari, Claudio,; Gorczynska, Krystyna; Palko, Jakub K.; K Zielinski; Di Molfetta, Arianna; Darowski, Marek

    2009-01-01

    Circulatory models are relevant for research, education and prosthetic devices/components testing. Independently of its structure that can be numerical, physical or hybrid, the models can be used in different areas of cardiovascular pathophysiology. However, the models are often used to reproduce specific circulatory conditions instead of being used as "systemic" tools. That is to say, the models are used to evaluate the global effects of external disturbances such as pathologies, therapies, ...

  13. Pathophysiology of increased intestinal permeability in obstructive jaundice

    OpenAIRE

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

    2007-01-01

    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 immunol...

  14. Acetaminophen-induced nephrotoxicity: Pathophysiology, clinical manifestations, and management

    OpenAIRE

    Mazer, Maryann; Perrone, Jeanmarie

    2008-01-01

    Acetaminophen-induced liver necrosis has been studied extensively, but the extrahepatic manifestations of acetaminophen toxicity are currently not described well in the literature. Renal insufficiency occurs in approximately 1–2% of patients with acetaminophen overdose. The pathophysiology of renal toxicity in acetaminophen poisoning has been attributed to cytochrome P-450 mixed function oxidase isoenzymes present in the kidney, although other mechanisms have been elucidated, including the ro...

  15. Inflammation and the pathophysiology of work-related musculoskeletal disorders

    OpenAIRE

    Barbe, Mary F; Barr, Ann E

    2006-01-01

    Work-related musculoskeletal disorders (MSDs) have accounted for a significant proportion of work injuries and workers' compensation claims in industrialized nations since the late 1980s. Despite epidemiological evidence for the role of repetition and force in the onset and progression of work-related MSDs, complete understanding of these important occupational health problems requires further elucidation of pathophysiological mechanisms of the tissue response, particularly in the early stage...

  16. New insights into the pathophysiology of postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

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

    2010-01-01

    appropriate controls. Furthermore, there are no internationally accepted criteria for defining POCD. This article aims to provide an update of current knowledge of the pathogenesis of POCD with a focus on perioperative pathophysiology and possible benefits achieved from an enhanced postoperative recovery...... using a fast-track methodology. It is concluded that the pathogenesis of POCD is multifactorial and future studies should focus on evaluating the role of postoperative sleep disturbances, inflammatory stress responses, pain and environmental factors. Potential prophylactic intervention may include...

  17. Autism and Phthalate Metabolite Glucuronidation

    OpenAIRE

    Stein, T. Peter; Schluter, Margaret D.; Steer, Robert A.; Ming, Xue

    2013-01-01

    Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured the efficiency of glucuronidation for a series of metabolites derived from the commonly used plasticizer, diethylhexyl phthalate. Spot urines were co...

  18. The Thyroid-Autism Connection

    Science.gov (United States)

    Kellman, Raphael

    2010-01-01

    The center for Disease Control and Prevention (CDC) has found that 1 in 110 children in the US have been diagnosed with Autism Spectrum Disorder (ASD), up from 1 in 150 in 2007. A study in the "Journal of Pediatrics" in October 2009 revealed similar numbers. Parents of 1 in 90 children reported that their child has ASD. That report is now 1 in 58.…

  19. Review of Autism Screening Tests

    OpenAIRE

    Farin Soleimani; Ali Khakshour; Zohreh Abbasi; Samira Khayat; Seyede Zahra Ghaemi; Nayereh Azam Hajikhani Golchin

    2014-01-01

    Background: Autism is a neurodevelopmental disorder that onset in the first 3 years of life and led to lifelong disability.Despite the early onset of symptoms, diagnosis of thissyndromedoes not happenuntil severalyears later, somany childrenlosethe opportunityfor earlyintervention.There arevarious toolsforscreening anddiagnosis, buttheirdesign, strengths and weaknesses aredifferent. The aim of this study was assess these tools from various aspects to provide a comprehensive view. Materials an...

  20. Autism traits in the RASopathies

    OpenAIRE

    Adviento, B; Corbin, IL; Widjaja, F; Desachy, G; Enrique, N.; Rosser, T.; Risi, S; Marco, EJ; Hendren, RL; Bearden, CE; Rauen, KA; Weiss, LA

    2013-01-01

    Background Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Previous work has suggested potential genetic and phenotypic overlap between dysregulation of Ras/MAPK signalling and autism spectrum disorders (ASD). Although the literature offers conflicting evidence for association of NF1 and...

  1. Diabetic macular oedema: pathophysiology, management challenges and treatment resistance.

    Science.gov (United States)

    Bahrami, Bobak; Zhu, Meidong; Hong, Thomas; Chang, Andrew

    2016-08-01

    Diabetic macular oedema (DMO) is the leading cause of vision loss in patients living with diabetes. DMO results from hyperglycaemia-induced activation of pathways that lead to oxidative stress and release of cytokines, impairing the inner and outer blood-retinal barriers. Improved understanding of the pathophysiological mechanisms leading to DMO have led to the development of effective therapies, including vitreoretinal surgery, laser photocoagulation, intravitreal anti-vascular endothelial growth factor drugs and corticosteroids. Advances in imaging, including fluorescein angiography and optical coherence tomography, have also enhanced diagnosis and management of the condition. Despite these advances, there remain patients who do not respond completely to therapy, reflecting the complex pathophysiology of DMO. These patients may be considered treatment-resistant. In this review, we summarise the pathophysiology of DMO, as well as the available treatments and their mechanism of action. Additionally, we focus on treatment-resistant disease and review the literature on potential options for managing this complication of diabetes. PMID:27179659

  2. Blepharospasm: Update on Epidemiology, Clinical Aspects, and Pathophysiology.

    Science.gov (United States)

    Valls-Sole, Josep; Defazio, Giovanni

    2016-01-01

    Blepharospasm (BSP) is a rather distressing form of focal dystonia. Although many aspects of its pathophysiological mechanisms are already known, we lack fundamental evidence on etiology, prevention, and treatment. To advance in our knowledge, we need to review what is already known in various aspects of the disorder and use these bases to find future lines of interest. Some of the signs observed in BSP are cause, while others are consequence of the disorder. Non-motor symptoms and signs may be a cue for understanding better the disease. Various cerebral sites have been shown to be functionally abnormal in BSP, including the basal ganglia, the cortex, and the cerebellum. However, we still do not know if the dysfunction or structural change affecting these brain regions is cause or consequence of BSP. Further advances in neurophysiology and neuroimaging may eventually clarify the pathophysiological mechanisms implicated. In this manuscript, we aim to update what is known regarding epidemiology, clinical aspects, and pathophysiology of the disorder and speculate on the directions of research worth pursuing in the near future. PMID:27064462

  3. Deaf Children with Autism Spectrum Disorders

    Science.gov (United States)

    Szymanski, Christen A.; Brice, Patrick J.; Lam, Kay H.; Hotto, Sue A.

    2012-01-01

    Epidemiological studies investigating the prevalence of autism have increased in recent years, within the United States and abroad. However, statistics as to how many of those children may also have a comorbid hearing loss is lacking. The prevalence of school-administrator reported diagnosis of autism spectrum disorders (clinical diagnosis…

  4. Autism Parenting Stress Index: Initial Psychometric Evidence

    Science.gov (United States)

    Silva, Louisa M. T.; Schalock, Mark

    2012-01-01

    Data validating the Autism Parenting Stress Index (APSI) is presented for 274 children under age six. Cronbach's alpha was 0.827. As a measure of parenting stress specific to core and co-morbid symptoms of autism, the APSI is unique. It is intended for use by clinicians to identify areas where parents need support with parenting skills, and to…

  5. Early Identification of Autism: Implications for Counselors

    Science.gov (United States)

    Layne, Christina Mann

    2007-01-01

    The author reviews an article (L. C. Eaves & H. H. Ho, 2004) published in the Journal of Autism and Developmental Disorders that discussed screening tools and diagnostic assessments used to identify autism in 2-year-olds as well as a follow-up study 2 1/2 years later. The author also provides a discussion of the impact of receiving this diagnosis…

  6. Somatosensory evoked potentials in children with autism

    Directory of Open Access Journals (Sweden)

    Hanan Galal Azouz

    2014-06-01

    Conclusions: Children with autism have abnormal SSEP changes and were significantly related to the presence of sensory abnormalities, indicating central cortical dysfunction of somatosensory area. On the other hand, these abnormal SSEP changes were not related to the severity of autism.

  7. Deficit, Difference, or Both? Autism and Neurodiversity

    Science.gov (United States)

    Kapp, Steven K.; Gillespie-Lynch, Kristen; Sherman, Lauren E.; Hutman, Ted

    2013-01-01

    The neurodiversity movement challenges the medical model's interest in causation and cure, celebrating autism as an inseparable aspect of identity. Using an online survey, we examined the perceived opposition between the medical model and the neurodiversity movement by assessing conceptions of autism and neurodiversity among people with different…

  8. Brief Report: Stereotypes in Autism Revisited

    Science.gov (United States)

    Kirchner, Jennifer Christina; Schmitz, Florian; Dziobek, Isabel

    2012-01-01

    Autism involves core impairments in social cognition. Given that social learning underlies the acquisition of stereotypes, it was hypothesized that use of stereotypes would be reduced in autism. Contrary to this prediction, previous studies found the same use of stereotypes in autistic individuals as in controls. Measurement of stereotypes,…

  9. Response to Vestibular Sensory Events in Autism

    Science.gov (United States)

    Kern, Janet K.; Garver, Carolyn R.; Grannemann, Bruce D.; Trivedi, Madhukar H.; Carmody, Thomas; Andrews, Alonzo A.; Mehta, Jyutika A.

    2007-01-01

    The purpose of this study was to examine the response to vestibular sensory events in persons with autism. The data for this study was collected as part of a cross-sectional study that examined sensory processing (using the Sensory Profile) in 103 persons with autism, 3-43 years of age, compared to age- and gender-matched community controls. The…

  10. Autism Spectrum Disorders (Pervasive Developmental Disorders)

    Science.gov (United States)

    Strock, Margaret

    2007-01-01

    This booklet focuses on classic autism, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome, with brief descriptions of Rett syndrome and childhood disintegrative disorder. The booklet describes possible indicators of autism spectrum disorders (ASD), their diagnosis, available aids, treatment options, adults…

  11. Nutrition and Its Relationship to Autism.

    Science.gov (United States)

    Adams, Lynn; Conn, Susan

    1997-01-01

    Discusses the relationship between food allergies and sensitivities and autism. Information is provided on two dietary problems (candidiasis and gluten/casein intolerance) and case histories of two three-year-old children with autism are provided to illustrate each of the problems. Diet and vitamin therapy interventions are also described.…

  12. Trajectories of Autism Severity in Early Childhood

    Science.gov (United States)

    Venker, Courtney E.; Ray-Subramanian, Corey E.; Bolt, Daniel M.; Weismer, Susan Ellis

    2014-01-01

    Relatively little is known about trajectories of autism severity using calibrated severity scores (CSS) from the Autism Diagnostic Observation Schedule, but characterizing these trajectories has important theoretical and clinical implications. This study examined CSS trajectories during early childhood. Participants were 129 children with autism…

  13. Establishing Metaphorical Reasoning in Children with Autism

    Science.gov (United States)

    Persicke, Angela; Tarbox, Jonathan; Ranick, Jennifer; St. Clair, Megan

    2012-01-01

    Researchers have shown that children with autism have difficulty with non-literal language, such as irony, sarcasm, deception, humor, and metaphors. To date, few studies have attempted to remediate these deficits, and no studies of which we are aware have attempted to teach children with autism to understand metaphors. Metaphorical reasoning…

  14. [Recognition of autism spectrum disorders in adults

    NARCIS (Netherlands)

    Hengeveld, M.W.; Londen, L van; Gaag, R.J. van der

    2008-01-01

    Autism spectrum disorder was diagnosed in three adults. The first patient, a married man aged 41, was referred to a psychiatrist with 'impending burn-out'. The second was a 32-year-old male student with schizophrenia and a depressive disorder who was referred to a centre for autism because a friend

  15. Are There Enhanced MBP Autoantibodies in Autism?

    Science.gov (United States)

    Libbey, Jane E.; Coon, Hilary H.; Kirkman, Nikki J.; Sweeten, Thayne L.; Miller, Judith N.; Stevenson, Edward K.; Lainhart, Janet E.; McMahon, William M.; Fujinami, Robert S.

    2008-01-01

    Autoantibodies to central nervous system antigens, such as myelin basic protein (MBP), may play a role in autism. We measured autoantibody titers to MBP in children with autism, both classic onset and regressive onset forms, controls (healthy age- and gender-matched) and individuals with Tourette syndrome via enzyme-linked immunosorbent assays. We…

  16. ECT and Autism--Making the Connection.

    Science.gov (United States)

    McCloskey-Dale, Susan R.

    This report describes using Environmental Communication Teaching (ECT) to assist students with autism spectrum disorder. The paper compares several key points of the ECT approach with other common intervention methods for students with autism and identifies the features of intervention programs or approaches that should be considered when planning…

  17. Head Circumference as an Early Predictor of Autism Symptoms in Younger Siblings of Children with Autism Spectrum Disorder

    OpenAIRE

    Elder, Lauren M.; Dawson, Geraldine; Toth, Karen; Fein, Deborah; Munson, Jeff

    2007-01-01

    Siblings of children with autism have an increased risk for autism spectrum disorders (ASD). As children with autism often exhibit an atypical trajectory of head circumference (HC) growth, HC may be an indicator of vulnerability to autism. This study investigated whether infant siblings of children with ASD (n = 77) with an atypical trajectory of HC growth were more likely than those without an atypical HC trajectory to develop autism symptoms. Results showed that infants who had larger HC at...

  18. The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Daniel J. Guerra

    2011-01-01

    Full Text Available Autism spectrum disorders (ASDs have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD.

  19. Biological Threats

    Science.gov (United States)

    ... Workplace Plans School Emergency Plans Main Content Biological Threats Biological agents are organisms or toxins that can ... for Disease Control and Prevention . Before a Biological Threat Unlike an explosion, a biological attack may or ...

  20. Increased putamen volume in adults with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Wataru eSato

    2014-11-01

    Full Text Available Basal ganglia (BG abnormalities are implicated in the pathophysiology of autism spectrum disorder (ASD. However, studies measuring the volume of the entire BG in individuals with ASD have reported discrepant findings, and no study conducted volume measurement of the entire substructures of the BG (the caudate, putamen, nucleus accumbens, and globus pallidus in individuals with ASD. We delineated the BG substructures and measured their volumes in 29 adults with ASD without intellectual disabilities and 29 age- and gender-matched typically developed adult controls. We acquired T1-weighted anatomical images and performed semi-automated delineation and volume measurements of the above-mentioned subregions. Total cerebral volumes, sex, and ages were partialed out. Compared with controls, the putamen was significantly larger in the ASD group. The increased volume of the putamen found in high-functioning adults with ASD suggests that structural or histological abnormalities of the putamen may underlie the pathologies of ASD such as repetitive and stereotyped behaviors and impaired social interactions.

  1. Voltage-Gated Proton Channels: Molecular Biology, Physiology, and Pathophysiology of the HV Family

    OpenAIRE

    DeCoursey, Thomas E.

    2013-01-01

    Voltage-gated proton channels (HV) are unique, in part because the ion they conduct is unique. HV channels are perfectly selective for protons and have a very small unitary conductance, both arguably manifestations of the extremely low H+ concentration in physiological solutions. They open with membrane depolarization, but their voltage dependence is strongly regulated by the pH gradient across the membrane (ΔpH), with the result that in most species they normally conduct only outward current...

  2. Lipids in the nervous system: from biochemistry and molecular biology to patho-physiology.

    Science.gov (United States)

    Cermenati, Gaia; Mitro, Nico; Audano, Matteo; Melcangi, Roberto C; Crestani, Maurizio; De Fabiani, Emma; Caruso, Donatella

    2015-01-01

    Lipids in the nervous system accomplish a great number of key functions, from synaptogenesis to impulse conduction, and more. Most of the lipids of the nervous system are localized in myelin sheaths. It has long been known that myelin structure and brain homeostasis rely on specific lipid-protein interactions and on specific cell-to-cell signaling. In more recent years, the growing advances in large-scale technologies and genetically modified animal models have provided valuable insights into the role of lipids in the nervous system. Key findings recently emerged in these areas are here summarized. In addition, we briefly discuss how this new knowledge can open novel approaches for the treatment of diseases associated with alteration of lipid metabolism/homeostasis in the nervous system. This article is part of a Special Issue entitled Linking transcription to physiology in lipidomics. PMID:25150974

  3. Voltage-Gated Proton Channels: Molecular Biology, Physiology, and Pathophysiology of the HV Family

    Science.gov (United States)

    2013-01-01

    Voltage-gated proton channels (HV) are unique, in part because the ion they conduct is unique. HV channels are perfectly selective for protons and have a very small unitary conductance, both arguably manifestations of the extremely low H+ concentration in physiological solutions. They open with membrane depolarization, but their voltage dependence is strongly regulated by the pH gradient across the membrane (ΔpH), with the result that in most species they normally conduct only outward current. The HV channel protein is strikingly similar to the voltage-sensing domain (VSD, the first four membrane-spanning segments) of voltage-gated K+ and Na+ channels. In higher species, HV channels exist as dimers in which each protomer has its own conduction pathway, yet gating is cooperative. HV channels are phylogenetically diverse, distributed from humans to unicellular marine life, and perhaps even plants. Correspondingly, HV functions vary widely as well, from promoting calcification in coccolithophores and triggering bioluminescent flashes in dinoflagellates to facilitating killing bacteria, airway pH regulation, basophil histamine release, sperm maturation, and B lymphocyte responses in humans. Recent evidence that hHV1 may exacerbate breast cancer metastasis and cerebral damage from ischemic stroke highlights the rapidly expanding recognition of the clinical importance of hHV1. PMID:23589829

  4. Voltage-gated proton channels: molecular biology, physiology, and pathophysiology of the H(V) family.

    Science.gov (United States)

    DeCoursey, Thomas E

    2013-04-01

    Voltage-gated proton channels (H(V)) are unique, in part because the ion they conduct is unique. H(V) channels are perfectly selective for protons and have a very small unitary conductance, both arguably manifestations of the extremely low H(+) concentration in physiological solutions. They open with membrane depolarization, but their voltage dependence is strongly regulated by the pH gradient across the membrane (ΔpH), with the result that in most species they normally conduct only outward current. The H(V) channel protein is strikingly similar to the voltage-sensing domain (VSD, the first four membrane-spanning segments) of voltage-gated K(+) and Na(+) channels. In higher species, H(V) channels exist as dimers in which each protomer has its own conduction pathway, yet gating is cooperative. H(V) channels are phylogenetically diverse, distributed from humans to unicellular marine life, and perhaps even plants. Correspondingly, H(V) functions vary widely as well, from promoting calcification in coccolithophores and triggering bioluminescent flashes in dinoflagellates to facilitating killing bacteria, airway pH regulation, basophil histamine release, sperm maturation, and B lymphocyte responses in humans. Recent evidence that hH(V)1 may exacerbate breast cancer metastasis and cerebral damage from ischemic stroke highlights the rapidly expanding recognition of the clinical importance of hH(V)1. PMID:23589829

  5. Identifying Autism from Neural Representations of Social Interactions: Neurocognitive Markers of Autism

    OpenAIRE

    Just, Marcel Adam; Cherkassky, Vladimir L.; Buchweitz, Augusto; Keller, Timothy A.; Mitchell, Tom M

    2014-01-01

    Autism is a psychiatric/neurological condition in which alterations in social interaction (among other symptoms) are diagnosed by behavioral psychiatric methods. The main goal of this study was to determine how the neural representations and meanings of social concepts (such as to insult) are altered in autism. A second goal was to determine whether these alterations can serve as neurocognitive markers of autism. The approach is based on previous advances in fMRI analysis methods that permit ...

  6. The broad autism phenotype predicts child functioning in autism spectrum disorders

    OpenAIRE

    Maxwell, Christina R.; Parish-Morris, Julia; Hsin, Olivia; Bush, Jennifer C; Schultz, Robert T.

    2013-01-01

    Background Broad autism phenotype (BAP) is a milder expression of the social and communication impairments seen in autism spectrum disorders (ASD). While prior studies characterized the BAP in unaffected family members of probands with ASD, the relationship between parental BAP traits and proband symptomatology remains poorly understood. This study utilizes the Broad Autism Phenotype Questionnaire (BAPQ) in parents and the Social Responsiveness Scale (SRS) in children to examine this connecti...

  7. Mood Disorders in Mothers of Children on the Autism Spectrum Are Associated with Higher Functioning Autism

    OpenAIRE

    Vasa, Roma A.; Connie Anderson; Marvin, Alison R.; Rebecca E. Rosenberg; J. Kiely Law; Julia Thorn; Geeta Sarphare; Law, Paul A.

    2012-01-01

    Mood disorders occur more frequently in family members of individuals with autism spectrum disorders (ASD) than in the general population. There may be associations between maternal mood disorder history patterns and specific ASD phenotypes. We therefore examined the relationship between maternal mood disorders and child autism spectrum disorders in 998 mother-child dyads enrolled in a national online autism registry and database. Mothers of children with ASD completed online questionnaires a...

  8. Demographic and clinical correlates of autism symptom domains and autism spectrum diagnosis

    OpenAIRE

    Frazier, Thomas W.; Youngstrom, Eric A.; Embacher, Rebecca; Hardan, Antonio Y.; Constantino, John N.; Law, Paul; Findling, Robert L.; Eng, Charis

    2013-01-01

    Demographic and clinical factors may influence assessment of autism symptoms. This study evaluated these correlates and also examined whether social communication and interaction and restricted/repetitive behavior provided unique prediction of autism spectrum disorder diagnosis. We analyzed data from 7352 siblings included in the Interactive Autism Network registry. Social communication and interaction and restricted/repetitive behavior symptoms were obtained using caregiver-reports on the So...

  9. Investigating emotional impairments in adults with autism spectrum disorders and the broader autism phenotype

    OpenAIRE

    Berthoz, Sylvie; Lalanne, Christophe; Crane, Laura; Hill, Elisabeth L.

    2013-01-01

    There is an increasing interest in the socio-affective atypicalities observed in adults with autism spectrum disorder (ASD). The aim of this study was to further explore emotional responsiveness in adults with ASD using well-validated self-reports of alexithymia and extend these with consideration of anhedonia, and to determine whether these features are part of a broader autism phenotype. Thirty-eight adults with ASD, 87 parents of ASD individuals and 47 typical controls completed the Autism...

  10. Aminoglycoside antibiotics and autism: a speculative hypothesis

    Directory of Open Access Journals (Sweden)

    Manev Hari

    2001-10-01

    Full Text Available Abstract Background Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic. Here, we speculate how aminoglycoside antibiotics might be associated with autism. Presentation We hypothesize that aminoglycoside antibiotics could a trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism. Testing Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children and the onset of autism symptoms (hypothesis "a", or between amino glycoside use and improvement of these symptoms (hypothesis "b". Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b". Implications It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism.

  11. Nosology and epidemiology in autism: classification counts.

    Science.gov (United States)

    Fisch, Gene S

    2012-05-15

    Since its initial description by Kanner in 1943, the criteria by which a diagnosis of autism or autism-like disorders was made--and their alleged etiologies portrayed--have undergone manifold changes, from a psychiatric disorder engendered by "refridgerator" parents to a neurodevelopmental disability produced in the main by genetic abnormalities. In addition, the behavioral characterization of autism has also entered the public consciousness and professional domains increasingly in the past 30 years, the effects of which we are continually coming to terms. A diagnosis of autism that once seemed quite unusual is now considered almost epidemic. Increasing numbers of individuals diagnosed with autism and related pervasive developmental disabilities will, in turn, affect the calculated prevalence of the disorder. In this essay, I attempt to account for the increasing prevalence of autism and autism-related disorders by examining its changing criteria, the individuals and instruments used to make the diagnosis, the reliability and validity of same, and the sample sizes and other aspects of the methodology needed to make an accurate estimate of its prevalence. PMID:22499526

  12. Prenatal and newborn immunoglobulin levels from mother-child pairs and risk of autism spectrum disorders

    OpenAIRE

    Croen, Lisa A.; Grether, Judith K.; Paul eAshwood; Judy eVan de Water; Yolken, Robert H.; Anderson, Meredith C.; Anthony Ronald Torres; Jonna B Westover; Thayne eSweeten; Hansen, Robin L.; Martin eKharrazi

    2016-01-01

    Background. An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared ...

  13. Brief Report: Theatre as Therapy for Children with Autism Spectrum Disorder

    OpenAIRE

    Corbett, Blythe A.; Gunther, Joan R.; Comins, Dan; Price, Jenifer; Ryan, Niles; Simon, David; Schupp, Clayton W.; Rios, Taylor

    2010-01-01

    The pilot investigation evaluated a theatrical intervention program, Social Emotional NeuroScience Endocrinology (SENSE) Theatre, designed to improve socioemotional functioning and reduce stress in children with autism spectrum disorder (ASD). Eight children with ASD were paired with typically developing peers that served as expert models. Neuropsychological, biological (cortisol and oxytocin), and behavioral measures were assessed in a pretest–posttest design. The intervention was embedded i...

  14. The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

    OpenAIRE

    Guerra, Daniel J.

    2011-01-01

    Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting th...

  15. Open questions: What has genetics told us about autism spectrum disorders?

    OpenAIRE

    Raff, Martin

    2014-01-01

    Some of the most interesting questions in biology today, in my view, derive from the real advances in neuropsychiatry that have come largely from human genetics. Research in autism spectrum disorders (ASDs) has been leading the way, mainly because it has become especially well funded and has recently attracted many outstanding scientists. (I must make it clear that I am an outsider in this field, as I have never worked on any neuropsychiatric disorder).

  16. Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder

    OpenAIRE

    Hashimoto, Ryota; Nakazawa, Takanobu; Tsurusaki, Yoshinori; Yasuda, Yuka; Nagayasu, Kazuki; Matsumura, Kensuke; Kawashima, Hitoshi; Yamamori, Hidenaga; Fujimoto, Michiko; Ohi, Kazutaka; Umeda-Yano, Satomi; Fukunaga, Masaki; Fujino, Haruo; Kasai, Atsushi; Hayata-Takano, Atsuko

    2015-01-01

    Autism spectrum disorder (ASD) is a complex group of clinically heterogeneous neurodevelopmental disorders with unclear etiology and pathogenesis. Genetic studies have identified numerous candidate genetic variants, including de novo mutated ASD-associated genes; however, the function of these de novo mutated genes remains unclear despite extensive bioinformatics resources. Accordingly, it is not easy to assign priorities to numerous candidate ASD-associated genes for further biological analy...

  17. Benign prostatic hyperplasia - progress in pathophysiology and management.

    Science.gov (United States)

    Dobrek, Łukasz; Thor, Piotr Jan

    2015-11-01

    Benign prostatic hyperplasia (BPH) is a common disease of the aging male population, in affected individuals often accompanied by metabolic syndrome. BPH is manifested by a complex range of symptoms originating from the lower urinary tract (LUTS - lower urinary tract symptoms), including disturbances resulting from impaired bladder compliance and bladder overactivity (e.g. frequency, nocturia, urinary incontinence, dysuria) and symptoms associated with the bladder outlet obstruction (e.g. the difficulty in voiding initiating, intermittency, involuntary interruption of voiding, weak urinary stream, straining to void). Despite numerous studies, the pathogenesis of BPH remains not completely understood, and the condition awaits a comprehensive description. The current pathophysiological view emphasizes the role of hormonal dysregulation, locally released in the prostate growth factors action and a complex inflammatory, BPH-associated process with the release of a number of pro-proliferative mediators. The current BPH pharmacotherapy involves administration of α-1-blockers, 5-α-reductase inhibitors, antimuscarinic drugs (cholinolytics) and phosphodiesterase- 5-inhibitors. Progress in the BPH pathophysiology allows the disclosure of additional, potential targets of pharmacological intervention, such as β-3 adrenoreceptor or CB1 cannabinoid receptor agonists, P2X1 purinergic or ETA endothelin receptors antagonists, RhoA/Rho kinase system inhibitors, nitric oxide donors, drugs indirectly (luteinizing hormone - releasing hormone antagonists) or directly (antiandrogens) abolishing the effect of testosterone and its derivatives or agents blocking the action of proinflammatory cytokines. The article briefly discusses the pathophysiology of the aforementioned issues and the current BPH management along with the future, potential opportunities for pharmacotherapy of the. PMID:26637089

  18. Scrub typhus:pathophysiology, clinical manifestations and prognosis

    Institute of Scientific and Technical Information of China (English)

    Senaka Rajapakse; Chaturaka Rodrigo; Deepika Fernando

    2012-01-01

    ABSTRACT Scrub typhus is a zoonosis caused by the pathogenOrientia tsutsugamushi (O. tsutsugamushi). The disease has significant prevalence in eastern and Southeast Asia. Usually presenting as an acute febrile illness, the diagnosis is often missed because of similarities with other tropical febrile infections. Many unusual manifestations are present, and these are described in this review, together with an outline of current knowledge of pathophysiology. Awareness of these unusual clinical manifestations will help the clinician to arrive at an early diagnosis, resulting in early administration of appropriate antibiotics. Prognostic indicators for severe disease have not yet been clearly established.

  19. Pathophysiological and clinical aspects of carbonic dioxide pneumoperitoneum

    DEFF Research Database (Denmark)

    Larsen, Jens Fromholt

    cascade systems. As the laparoscopic procedures are also offered to patients with co-morbidity, it is mandatory to be aware of the specific, intraoperative, pathophysiological effects that are related to laparoscopic surgery, when using positive pressure CO 2 -PP and to evaluate alternative, minimally...... are needed to evaluate the long time effects on cancer related survival in patients undergoing laparoscopic surgery compared with that of open fast trac surgery and different laparoscopic techniques. In addition, the evidence of the effect of CO 2 -PP on high risk cardio-pulmonary patients are insufficient....

  20. [Cardiac potassium channels: molecular structure, physiology, pathophysiology and therapeutic implications].

    Science.gov (United States)

    Mironov, N Iu; Golitsyn, S P

    2013-01-01

    Potassium channels and currents play essential roles in cardiac repolarization. Potassium channel blockade by class III antiarrhythmic drugs prolongs cardiac repolarization and results in termination and prevention of cardiac arrhythmias. Excessive inhomogeneous repolarization prolongation may lead to electrical instability and proarrhythmia (Torsade de Pointes tachycardia). This review focuses on molecular structure, physiology, pathophysiology and therapeutic potential of potassium channels of cardiac conduction system and myocardium providing information on recent findings in pathogenesis of cardiac arrhythmias, including inherited genetic abnormalities, and future perspectives. PMID:24654438

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

    International Nuclear Information System (INIS)

    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)

  2. Pathophysiology of the nodular and micronodular small bowel fold

    International Nuclear Information System (INIS)

    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

  3. Cardiovascular Simulation of Heart Failure Pathophysiology and Therapeutics.

    Science.gov (United States)

    Doshi, Darshan; Burkhoff, Daniel

    2016-04-01

    Mathematical modeling and simulation allows for an in-depth examination of the cardiovascular system and provides the opportunity to develop deeper understanding. This review summarizes recent efforts at modeling the cardiovascular system and how these models have been useful in providing greater comprehension of the pathophysiology of heart failure, explaining the hemodynamic impact of various heart failure devices, predicting the hemodynamic effects and clinical outcomes of certain heart failure clinical trials, and perhaps aiding in patient selection for new therapies. The potential future use of these models in clinical research and clinical practice are also discussed. PMID:26703246

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

    Directory of Open Access Journals (Sweden)

    Scott E. Friedman

    2012-01-01

    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.

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

    International Nuclear Information System (INIS)

    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

  6. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances.

    Science.gov (United States)

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  7. Descriptive characteristics of children with autism at Autism Treatment Center, KSA.

    Science.gov (United States)

    Al Shirian, Sarah; Al Dera, Hussain

    2015-11-01

    Autism characteristics in sixty children (aged from 2 to 8) were assed. Their behavioral symptoms were evaluated using the Autism Treatment Evaluation Checklist (ATEC). ATEC has four main domains of autistic disorders (Speech/Language/Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) in children with clinical diagnosis by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and Childhood Autism Rating Scale (CARS) of autism spectrum disorder (ASD). Utilizing ATEC checklist, our study describes significant behavioral observations between autistic children which could effectively contribute to better understanding and treatment during their early intervention stage. PMID:26343774

  8. Does Rubella Cause Autism: A 2015 Reappraisal?

    Science.gov (United States)

    Hutton, Jill

    2016-01-01

    In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS), 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today's world. CRS cases are no longer typically seen; yet, autistic children often share findings of CRS including deafness, congenital heart defects, and to a lesser extent visual changes. Autistic children commonly have hyperactivity and spasticity, as do CRS children. Both autistic and CRS individuals may develop type 1 diabetes as young adults. Neuropathology of CRS infants may reveal cerebral vasculitis with narrowed lumens and cerebral necrosis. Neuroradiological findings of children with CRS show calcifications, periventricular leukomalacia, and dilated perivascular spaces. Neuroradiology of autism has also demonstrated hyperintensities, leukomalacia, and prominent perivascular spaces. PET studies of autistic individuals exhibit decreased perfusion to areas of the brain similarly affected by rubella. In both autism and CRS, certain changes in the brain have implicated the immune system. Several children with autism lack antibodies to rubella, as do children with CRS. These numerous similarities increase the probability of an association between rubella virus and autism. Rubella and autism cross many ethnicities in many countries. Contrary to current belief, rubella has not been eradicated and globally affects up to 5% of pregnant women. Susceptibility continues as vaccines are not given worldwide and are not fully protective. Rubella might still cause autism, even in vaccinated populations. PMID:26869906

  9. Does rubella cause autism: a 2015 reappraisal?

    Directory of Open Access Journals (Sweden)

    Jill eHutton

    2016-02-01

    Full Text Available In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS, 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today’s world. CRS cases are no longer typically seen, yet autistic children often share findings of CRS including deafness, congenital heart defects and to a lesser extent visual changes. Autistic children commonly have hyperactivity and spasticity, as do CRS children. Both autistic and CRS individuals may develop type 1 diabetes as young adults. Neuropathology of CRS infants may reveal cerebral vasculitis with narrowed lumens and cerebral necrosis. Neuroradiologic findings of children with CRS show calcifications, periventricular leukomalacia, and dilated perivascular spaces. Neuroradiology of autism has also demonstrated hyperintensities, leukomalacia and prominent perivascular spaces. PET studies of autistic individuals exhibit decreased perfusion to areas of the brain similarly affected by rubella. In both autism and CRS, certain changes in the brain have implicated the immune system. Several children with autism lack antibodies to rubella, as do children with CRS. These numerous similarities increase the probability of an association between rubella virus and autism.Rubella and autism cross many ethnicities in many countries. Contrary to current belief, rubella has not been eradicated and globally affects up to 5% of pregnant women. Susceptibility continues as vaccines are not given worldwide and are not fully protective. Rubella might still cause autism, even in vaccinated populations.

  10. Does rubella cause autism: a 2015 reappraisal?

    OpenAIRE

    Jill eHutton

    2016-01-01

    In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS), 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today’s world. CRS cases are no longer typically seen, yet a...

  11. Does Rubella Cause Autism: A 2015 Reappraisal?

    OpenAIRE

    Hutton, Jill

    2016-01-01

    In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS), 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today’s world. CRS cases are no longer typically seen; yet, ...

  12. Autism Speaks Toolkits: Resources for Busy Physicians.

    Science.gov (United States)

    Bellando, Jayne; Fussell, Jill J; Lopez, Maya

    2016-02-01

    Given the increased prevalence of autism spectrum disorders (ASD), it is likely that busy primary care providers (PCP) are providing care to individuals with ASD in their practice. Autism Speaks provides a wealth of educational, medical, and treatment/intervention information resources for PCPs and families, including at least 32 toolkits. This article serves to familiarize PCPs and families on the different toolkits that are available on the Autism Speaks website. This article is intended to increase physicians' knowledge on the issues that families with children with ASD frequently encounter, to increase their ability to share evidence-based information to guide treatment and care for affected families in their practice. PMID:26149848

  13. Trauma and Violence in Autism.

    Science.gov (United States)

    Westphal, Alexander

    2016-06-01

    Comorbidities of autism spectrum disorder are discussed as an introduction to the argument that, although ASD may modify presentation, it does not confer any protection against other disorder, including the negative effects of trauma (e.g., posttraumatic stress disorder). Dr. Im's hypotheses are discussed, and a case example of childhood disintegrative disorder (CDD) is raised to give clinical support to his hypotheses. CDD is a rare form of ASD that is defined by late onset, a traumatic prodrome, onset of behaviors including some with similarities to PTSD, and aggression. PMID:27236175

  14. Representations of autism: Implications for community healthcare practice

    OpenAIRE

    Brownlow, Charlotte; O'Dell, Lindsay

    2009-01-01

    The work presented in this paper is part of a larger project in which online asynchronous discussion groups were employed to examine how a range of contributors - including people with autism, parents of people with autism, and professionals working within the field of autism - view and understand autism. In this paper, we focus on the voices of people with autism. The terminology used in the paper takes its lead from the writings of people with autism, who frequently use the term 'AS' to ref...

  15. Gluten- and casein-free dietary intervention for autism spectrum conditions.

    Directory of Open Access Journals (Sweden)

    Paul eWhiteley

    2013-01-01

    Full Text Available Dietary intervention as a tool for maintaining and improving physical health and wellbeing is a widely researched and discussed topic. Speculation that diet may similarly affect mental health and wellbeing particularly in cases of psychiatric and behavioural symptomatology opens up various avenues for potentially improving quality of life. We examine evidence suggestive that a gluten-free, casein-free or combined gluten- and casein-free diet can ameliorate core and peripheral symptoms and improve developmental outcome in some cases of autism spectrum conditions. Although not wholly affirmative, the majority of published studies indicate statistically significant positive changes to symptom presentation following dietary intervention. In particular, changes to areas of communication, attention and hyperactivity are detailed, despite the presence of various methodological shortcomings. Specific characteristics of best- and non-responders to intervention have not been fully elucidated; neither has the precise mode of action for any universal effect outside of known individual cases of food-related co-morbidity. With the publication of controlled medium- and long-term group studies of a gluten- and casein-free diet alongside more consolidated biological findings potentially linked to intervention, the appearance of a possible diet-related autism phenotype seems to be emerging supportive of a positive dietary effect in some cases. Further debate on whether such dietary intervention should form part of best practice guidelines for autism spectrum conditions and onward representative of an autism dietary-sensitive enteropathy is warranted.

  16. Review: Cortical construction in autism spectrum disorder: columns, connectivity and the subplate.

    Science.gov (United States)

    Hutsler, Jeffrey J; Casanova, Manuel F

    2016-02-01

    The cerebral cortex undergoes protracted maturation during human development and exemplifies how biology and environment are inextricably intertwined in the construction of complex neural circuits. Autism spectrum disorders are characterized by a number of pathological changes arising from this developmental process. These include: (i) alterations to columnar structure that have significant implications for the organization of cortical circuits and connectivity; (ii) alterations to synaptic spines on individual cortical units that may underlie specific types of connectional changes; and (iii) alterations within the cortical subplate, a region that plays a role in proper cortical development and in regulating interregional communication in the mature brain. Although the cerebral cortex is not the only structure affected in the disorder, it is a fundamental contributor to the behaviours that characterize autism. These alterations to cortical circuitry likely underlie the behavioural phenotype in autism and contribute to the unique pattern of deficits and strengths that characterize cognitive functioning. Recent findings within the cortical subplate may indicate that alterations to cortical construction begin prenatally, before activity-dependent connections are established, and are in need of further study. A better understanding of cortical development in autism spectrum disorders will draw bridges between the microanatomical computational circuitry and the atypical behaviours that arise when that circuitry is modified. In addition, it will allow us to better exploit the constructional plasticity within the brain to design more targeted interventions that better manage atypical cortical construction and that can be applied very early in postnatal life. PMID:25630827

  17. Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children with Autism in Two Samples

    Directory of Open Access Journals (Sweden)

    Raymond F. Palmer

    2015-01-01

    Full Text Available Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures such as pesticides, plastics, or medications. The purpose of our study was to determine if organic chemicals previously detected in a sample of typically developing children could be detected in teeth from a sample of children with autism. Eighty-three deciduous teeth from children with autism spectrum disorders (ASD were chosen from our tooth repository. Organic compounds were assessed using liquid chromatography tandem mass spectrometry and gas chromatography methods. Consistent with a prior report from Camann et al., (2013, we have demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth. This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism.

  18. Gene X Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    SylvieTordjman

    2014-08-01

    Full Text Available Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model. However, despite advances in epidemiological, molecular and clinical genetics, the genetic risk factors remain difficult to identify, with the exception of a few chromosomal disorders and several single gene disorders associated with an increased risk for autism. Furthermore, several studies suggest a role of environmental factors in autism spectrum disorders (ASD. First, arguments for a genetic contribution to autism, based on updated family and twin studies, are examined. Second, a review of possible prenatal, perinatal and postnatal environmental risk factors for ASD are presented. Then, the hypotheses are discussed concerning the underlying mechanisms related to a role of environmental factors in the development of ASD in association with genetic factors. In particular, epigenetics as a candidate biological mechanism for gene X environment interactions is considered and the possible role of epigenetic mechanisms reported in genetic disorders associated with ASD is discussed. Furthermore, the example of in utero exposure to valproate provides a good illustration of epigenetic mechanisms involved in ASD and innovative therapeutic strategies. Epigenetic remodeling by environmental factors opens new perspectives for a better understanding, prevention and early therapeutic intervention of ASD.

  19. Pathophysiology and pathogenesis of circadian rhythm sleep disorders

    Directory of Open Access Journals (Sweden)

    Hida Akiko

    2012-03-01

    Full Text Available Abstract Metabolic, physiological and behavioral processes exhibit 24-hour rhythms in most organisms, including humans. These rhythms are driven by a system of self-sustained clocks and are entrained by environmental cues such as light-dark cycles as well as food intake. In mammals, the circadian clock system is hierarchically organized such that the master clock in the suprachiasmatic nuclei of the hypothalamus integrates environmental information and synchronizes the phase of oscillators in peripheral tissues. The transcription and translation feedback loops of multiple clock genes are involved in the molecular mechanism of the circadian system. Disturbed circadian rhythms are known to be closely related to many diseases, including sleep disorders. Advanced sleep phase type, delayed sleep phase type and nonentrained type of circadian rhythm sleep disorders (CRSDs are thought to result from disorganization of the circadian system. Evaluation of circadian phenotypes is indispensable to understanding the pathophysiology of CRSD. It is laborious and costly to assess an individual's circadian properties precisely, however, because the subject is usually required to stay in a laboratory environment free from external cues and masking effects for a minimum of several weeks. More convenient measurements of circadian rhythms are therefore needed to reduce patients' burden. In this review, we discuss the pathophysiology and pathogenesis of CRSD as well as surrogate measurements for assessing an individual's circadian phenotype.

  20. The Pathophysiology and Care of Exercise Related Muscle Cramps

    Directory of Open Access Journals (Sweden)

    Abhay Kumar Pandey

    2015-01-01

    Full Text Available Cramps are major concerns to competing athletes occurring during or after exercise, are common yet, poorly understood phenomena. Pain alone is not object of treatment as serious musculophysiologic and metabolic disturbance of fluid and electrolyte deserve correction. Acute muscle pain and stiffness may cause soreness for longer time. Based on observations, two etiological theories are construed, i.e. the muscle fatigue theory and sodium-water deficit theory. Either has supporting and contradicting facts, but these are relevant to guide prevention and management interventions. Cramps may be different in kind based on different local and/or general causes. Occurrence of cramps in varied situations, environmental conditions and populations, suggests of pleural causal determinents. These include neuromuscular and fluid-electrolyte disturbance factors directly responsible under specific circumstances of individual sports person. Degree of conditioning to particular kind of physical exertion appears most significant factor. Prevention exercises target theorised physiology of muscle tendon and golgi organ receptors, toward delaying fatigability and cramp risk. Occurrence of cramps mostly in hot environments emphasizes support to dehydration-electrolyte imbalance theory. Maintenance of hydration and adequate electrolyte levels in cramp-prone individuals thus makes sense. Worth of variety of measures empirically employed for cramp relief can be judged by scientific understanding. Drugs found useful may not be the best match to pathophysiologic proprieties and thus irrational. The pathophysiological details and relevant clinical information is presented and discussed as first hand understanding for the sports persons and their care givers.