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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

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    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.

  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. 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...

  5. Biological Motion Perception in Autism

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    J Cusack

    2011-04-01

    Full Text Available Typically developing adults can readily recognize human actions, even when conveyed to them via point-like markers placed on the body of the actor (Johansson, 1973. Previous research has suggested that children affected by autism spectrum disorder (ASD are not equally sensitive to this type of visual information (Blake et al, 2003, but it remains unknown why ASD would impact the ability to perceive biological motion. We present evidence which looks at how adolescents and adults with autism are affected by specific factors which are important in biological motion perception, such as (eg, inter-agent synchronicity, upright/inverted, etc.

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

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    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. Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism

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    Abu Shmais Ghada A

    2012-02-01

    Full Text Available Abstract Background There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism. Methods The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA, glutamate:glutamine (Glu:Gln ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA were determined in plasma samples from both groups. Results We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio. Conclusion A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.

  9. 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...

  10. 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

  11. Identification and Treatment of Pathophysiological Comorbidities of Autism Spectrum Disorder to Achieve Optimal Outcomes.

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    Frye, Richard E; Rossignol, Daniel A

    2016-01-01

    Despite the fact that the prevalence of autism spectrum disorder (ASD) continues to rise, no effective medical treatments have become standard of care. In this paper we review some of the pathophysiological abnormalities associated with ASD and their potential associated treatments. Overall, there is evidence for some children with ASD being affected by seizure and epilepsy, neurotransmitter dysfunction, sleep disorders, metabolic abnormalities, including abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, redox and mitochondrial metabolism, and immune and gastrointestinal disorders. Although evidence for an association between these pathophysiological abnormalities and ASD exists, the exact relationship to the etiology of ASD and its associated symptoms remains to be further defined in many cases. Despite these limitations, treatments targeting some of these pathophysiological abnormalities have been studied in some cases with high-quality studies, whereas treatments for other pathophysiological abnormalities have not been well studied in many cases. There are some areas of more promising treatments specific for ASD including neurotransmitter abnormalities, particularly imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways. There is some evidence for treatments of epilepsy and seizures, mitochondrial and immune disorders, and gastrointestinal abnormalities, particularly imbalances in the enteric microbiome, but further clinical studies are needed in these areas to better define treatments specific to children with ASD. Clearly, there are some promising areas of ASD research that could lead to novel treatments that could become standard of care in the future, but more research is needed to better define subgroups of children with ASD who are affected by specific pathophysiological abnormalities and

  12. The redox biology network in cancer pathophysiology and therapeutics

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    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

  13. 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...

  14. 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 ...

  15. 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 ...

  16. Autism: A Review of Biological Bases, Assessment, and Intervention

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    Volker, Martin A.; Lopata, Christopher

    2008-01-01

    The number of children classified with autism in US schools has risen sharply over the past decade. School psychologists are being called upon with increasing frequency to assist in the identification, assessment, and treatment of these children. The diagnostic complexities and heterogeneity of the disorder make dealing effectively with this…

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

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    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…

  18. IQ Predicts Biological Motion Perception in Autism Spectrum Disorders

    Science.gov (United States)

    Rutherford, M. D.; Troje, Nikolaus F.

    2012-01-01

    Biological motion is easily perceived by neurotypical observers when encoded in point-light displays. Some but not all relevant research shows significant deficits in biological motion perception among those with ASD, especially with respect to emotional displays. We tested adults with and without ASD on the perception of masked biological motion…

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

    Science.gov (United States)

    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

  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

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    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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    Daphne eAntoniou

    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.

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    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. 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.

  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. 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.

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

    Science.gov (United States)

    Nackaerts, Evelien; Wagemans, Johan; Helsen, Werner; Swinnen, Stephan P; Wenderoth, Nicole; Alaerts, Kaat

    2012-01-01

    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.

  8. Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1: normal and chronic wounds: biology, causes, and approaches to care.

    Science.gov (United States)

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

    2012-07-01

    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 initiate cellular and tissue responses after injury, which may be impeded during chronic wound healing.

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. Autism Society

    Science.gov (United States)

    ... is Autism? What is Autism? Symptoms Diagnosis Causes Asperger’s Syndrome Facts and Statistics Living with Autism Living with ... is Autism? What is Autism? Symptoms Diagnosis Causes Asperger’s Syndrome Facts and Statistics Living with Autism Living with ...

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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),…

  19. 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.)

  20. 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.)

  1. 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...

  2. 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

  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.

    NARCIS (Netherlands)

    Groen, W.B.; Teluij, M.; Buitelaar, J.K.; Tendolkar, I.

    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

  7. 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

  8. 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...

  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 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 ...

  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. 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

  13. 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.

  14. 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...... normalized. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches....

  15. 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,…

  16. Brief Report: A Preference for Biological Motion Predicts a Reduction in Symptom Severity One Year Later in Preschoolers with an Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Martina Franchini

    2016-08-01

    Full Text Available Recent research has consistently demonstrated reduced orienting to social stimuli in samples of young children with Autism Spectrum Disorders (ASD. However, social orienting greatly varies between individual children on the spectrum. Better understanding this heterogeneity in social orienting may contribute to our comprehension of the mechanisms underlying autistic symptoms thereby improving our ability to intervene. Indeed, children on the autism spectrum who show higher levels of interest in social stimuli demonstrate reduced clinical symptoms and increased adaptive functioning. However, longitudinal studies examining the influence of social orienting on subsequent outcome are critically lacking. Here, we aim to explore the relationship between social interest at the age of 3 and changes in severity of autistic symptoms over the subsequent year, in 20 children with ASD and 20 age-matched typically developing (TD children. A visual preference for social stmuli was measured using an eye-tracking task at baseline, consisting of a previously studied visual preference paradigm presenting biological and geometric motion side-by-side. The task was altered for the current study by alternating presentation side for each type of stimuli to keep visual perseveration from influencing participants’ first fixation location. Clinical data were collected both at baseline and one year later at follow-up. As a group, we observed reduced interest for biological motion in children with ASD compared to TD children, corroborating previous findings. We also confirmed that a preference for biological motion is associated with better adaptive functioning in preschoolers with ASD. Most importantly, our longitudinal results showed that a preference for biological motion strongly predicted decreased severity of diagnostic symptoms. Participants who preferred social stimuli at the age of 3 showed drastic reductions in their severity level of autistic symptoms one year

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

    Directory of Open Access Journals (Sweden)

    Mona M Boules

    2014-06-01

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

  18. 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.

  19. Pathophysiologic mechanisms of biomedical nanomaterials.

    Science.gov (United States)

    Wang, Liming; Chen, Chunying

    2016-05-15

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

  20. [Functional pathophysiology of consciousness].

    Science.gov (United States)

    Jellinger, Kurt A

    2009-01-01

    Consciousness (Latin conscientia "moral conscience"), according to the English philosopher John Locke (1632-1704) [103], is the awareness of all that occurs in the mind of a person, whereas the American philosopher John Searle (2000) defined it as "inner qualitative, subjective states and processes of awareness". In modern science it is defined as a continuous state of full awareness of the Self and one's relationship to the external and internal environment, describing the degree of wakefulness in which an organism recognizes stimuli. This widely discussed biological term for complex neuronal processes that allow an individuum to recognize itself and its environment and to act accordingly, has been and still is the subject of much research in philosophy and natural/neuroscience. Its definition is often used for awareness and recognition, too. While the Egyptians in the papyrus Edwin Smith already recognized the brain as the seat of consciousness, René Descartes (1644 [36]) believed its special structure should be "a small gland in the middle", but the anatomical structures and physiological processes involved in consciousness were elucidated only in the middle of the 20th century. Neuronal substrates include several functional networks that are hierarchically organized and cooperate functionally. The lowest level is the mesencephalic formatio reticularis and its projections to the thalamus that were identified als ascending reticular system (ARAS) by the classical experiments of Moruzzi and Magoun, whereas later analyses of patients with impaired consciousness provided further insights. The mesencephalic ARAS as motor of the function of higher structures projects 1. via the reticular thalamus diffusely to the cortex, 2. via hypothalamus to the basal forebrain and limbic system, and 3. to the medial raphe of the brainstem and locus coeruleus and their diffuse cortical projections. The reticular system is stimulated directly and indirectly via numerous collaterals

  1. [Functional pathophysiology of consciousness].

    Science.gov (United States)

    Jellinger, Kurt A

    2009-01-01

    Consciousness (Latin conscientia "moral conscience"), according to the English philosopher John Locke (1632-1704) [103], is the awareness of all that occurs in the mind of a person, whereas the American philosopher John Searle (2000) defined it as "inner qualitative, subjective states and processes of awareness". In modern science it is defined as a continuous state of full awareness of the Self and one's relationship to the external and internal environment, describing the degree of wakefulness in which an organism recognizes stimuli. This widely discussed biological term for complex neuronal processes that allow an individuum to recognize itself and its environment and to act accordingly, has been and still is the subject of much research in philosophy and natural/neuroscience. Its definition is often used for awareness and recognition, too. While the Egyptians in the papyrus Edwin Smith already recognized the brain as the seat of consciousness, René Descartes (1644 [36]) believed its special structure should be "a small gland in the middle", but the anatomical structures and physiological processes involved in consciousness were elucidated only in the middle of the 20th century. Neuronal substrates include several functional networks that are hierarchically organized and cooperate functionally. The lowest level is the mesencephalic formatio reticularis and its projections to the thalamus that were identified als ascending reticular system (ARAS) by the classical experiments of Moruzzi and Magoun, whereas later analyses of patients with impaired consciousness provided further insights. The mesencephalic ARAS as motor of the function of higher structures projects 1. via the reticular thalamus diffusely to the cortex, 2. via hypothalamus to the basal forebrain and limbic system, and 3. to the medial raphe of the brainstem and locus coeruleus and their diffuse cortical projections. The reticular system is stimulated directly and indirectly via numerous collaterals

  2. [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

  3. 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.

  4. 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...

  5. Physiology and pathophysiology of carnosine.

    Science.gov (United States)

    Boldyrev, Alexander A; Aldini, Giancarlo; Derave, Wim

    2013-10-01

    Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides. This review aims to decipher the physiological roles of carnosine, based on its biochemical properties. The latter include pH-buffering, metal-ion chelation, and antioxidant capacity as well as the capacity to protect against formation of advanced glycation and lipoxidation end-products. For these reasons, the therapeutic potential of carnosine supplementation has been tested in numerous diseases in which ischemic or oxidative stress are involved. For several pathologies, such as diabetes and its complications, ocular disease, aging, and neurological disorders, promising preclinical and clinical results have been obtained. Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide. This paper summarizes a century of scientific exploration on the (patho)physiological role of carnosine and related compounds. However, far more experiments in the fields of physiology and related disciplines (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a full understanding of the function and applications of this intriguing molecule. PMID:24137022

  6. 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…

  7. Pathophysiology of nocturnal enuresis

    DEFF Research Database (Denmark)

    Rittig, Søren; Kamperis, Konstantinos

    2015-01-01

    important part of enuresis pathogenesis is reduced bladder capacity, either during night-time only or present during daytime also (i.e. reduced MVV on a FV chart). The background behind the reduced nocturnal reservoir function is not fully clarified but may involve CNS regulatory centers, detrusor...... overactivity, or a defect intrinsic circadian control of bladder function. The role of sleep is currently under scrutiny as recent evidence point towards poor sleep with increased sleep fragmentation, arousal index, and periodic limb movements as important factors. One unifying pathophysiologic theory suggests...

  8. 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…

  9. Brief Report: A Preference for Biological Motion Predicts a Reduction in Symptom Severity 1 Year Later in Preschoolers with Autism Spectrum Disorders

    Science.gov (United States)

    Franchini, Martina; Wood de Wilde, Hilary; Glaser, Bronwyn; Gentaz, Edouard; Eliez, Stephan; Schaer, Marie

    2016-01-01

    Recent research has consistently demonstrated reduced orienting to social stimuli in samples of young children with autism spectrum disorders (ASD). However, social orienting greatly varies between individual children on the spectrum. Better understanding this heterogeneity in social orienting may contribute to our comprehension of the mechanisms underlying autistic symptoms thereby improving our ability to intervene. Indeed, children on the autism spectrum who show higher levels of interest in social stimuli demonstrate reduced clinical symptoms and increased adaptive functioning. However, longitudinal studies examining the influence of social orienting on subsequent outcome are critically lacking. Here, we aim to explore the relationship between social interest at the age of 3 and changes in severity of autistic symptoms over the subsequent year, in 20 children with ASD and 20 age-matched typically developing (TD) children. A visual preference for social stimuli was measured using an eye-tracking task at baseline, consisting of a previously studied visual preference paradigm presenting biological and geometric motion side-by-side. The task was altered for the current study by alternating presentation side for each type of stimuli to keep visual perseveration from influencing participants’ first fixation location. Clinical data were collected both at baseline and 1 year later at follow-up. As a group, we observed reduced interest for biological motion (BIO-M) in children with ASD compared to TD children, corroborating previous findings. We also confirmed that a preference for BIO-M is associated with better adaptive functioning in preschoolers with ASD. Most importantly, our longitudinal results showed that a preference for BIO-M strongly predicted decreased severity of diagnostic symptoms. Participants who preferred social stimuli at the age of 3 showed drastic reductions in their severity level of autistic symptoms 1 year later, whereas participants who

  10. 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

  11. Reform in teaching preclinical pathophysiology.

    Science.gov (United States)

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

    2015-12-01

    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 in Chinese Departments of Pathophysiology generally consists of full-time instructors or lecturers who teach medical students. These lecturers are sometimes lacking in clinic knowledge and experiences. To overcome this, in recent years, we have been trying to bring new trends in teaching pathophysiology into our curriculum. Our purpose in writing this article was to share our experiences with our colleagues and peers worldwide in the hope that the insights we have gained in pathophysiology teaching will be of some value to educators who advocate teaching reform in medical schools.

  12. 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.

  13. [Autism, genetics and synaptic function alterations].

    Science.gov (United States)

    Perche, O; Laumonnier, F; Baala, L; Ardourel, M-Y; Menuet, A; Robin, V; Mortaud, S; Montécot-Dubourg, C; Richard, O; Pichon, J; Briault, S

    2010-10-01

    Autism is a neurodevelopmental disorder characterized by a deficit of language and communication both associated with a restricted repertoire of activities and interests. The current prevalence of autistic disorder stricto sensu is estimated at 1/500 whereas autism spectrum disorders (ASD) increases up to 1/150 to 1/200. Mental deficiency (MD) and epilepsy are present in numerous autistic individuals. Consequently, autism is as a major public health issue. Autism was first considered as a non biological disease; however various rational approaches for analysing epidemiological data suggested the possibility of the influence of genetic factors. In 2003, this hypothesis was clearly illustrated by the characterization of genetic mutations transmitted through a mendelian manner. Subsequently, the glutamate synapse appeared as a preferential causal target in autism because the identified genes encoded proteins present in this structure. Strikingly, the findings that an identical genetic dysfunction of the synapse might also explain some MD suggested the possibility of a genetic comorbidity between these neurodevelopmental conditions. To date, various identified genes are considered indifferently as "autism" or "MD" genes. The characterization of mutations in the NLGN4X gene in patients with Asperger syndrome, autism without MD, or MD without autism, was the first example. It appears that a genetic continuum between ASD on one hand, and between autism and MD on the other hand, is present. Consequently, it is likely that genes already involved in MD will be found mutated in autistic patients and will represent future target for finding new factors in autism.

  14. 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.

  15. 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...

  16. Pathophysiology of favism.

    Science.gov (United States)

    Arese, P; Mannuzzu, L; Turrini, F

    1989-01-01

    Haemolytic crises occurring in G6PD-deficient individuals after ingestion of fava beans (favism) are much less frequent than in the past. However, favism is a unique natural model of oxidant damage in vivo, useful for the study of senescent or damaged red blood cells (RBC) clearance from circulation. The following aspects have been considered: 1. Pathophysiology of favism, including incidence, salient features, and sequence of events. 2. RBC alterations during the haemolytic crisis: biochemical, rheological and morphological alterations occurring in RBC isolated at different stages of the crisis. 3. Toxic substances of Vicia faba and their mechanism of action: treatment of G6PD-deficient RBC with divicine or isouramil (redox substances present in fava beans) provokes the same changes as observed during favism. 4. Intravascular vs. extravascular haemolysis: extravascular (i.e. phagocytic) removal of damages RBC seems predominant in favism. 5. The signal for RBC removal: in analogy with a recent model for recognition and removal of oxidant-stressed or senescent RBC, we propose removal of fava bean damaged RBC be mediated by apposition of antiband 3 antibodies and complement C3 fragments, recognized as non-self recognition signal by monocytes and macrophages. PMID:2481620

  17. 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...

  18. 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....

  19. 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...

  20. 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...

  1. 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.

  2. Association of transcription factor gene LMX1B with autism.

    Directory of Open Access Journals (Sweden)

    Ismail Thanseem

    Full Text Available Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217 showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008. Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049. Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

  3. Association of transcription factor gene LMX1B with autism.

    Science.gov (United States)

    Thanseem, Ismail; Nakamura, Kazuhiko; Anitha, Ayyappan; Suda, Shiro; Yamada, Kazuo; Iwayama, Yoshimi; Toyota, Tomoko; Tsujii, Masatsugu; Iwata, Yasuhide; Suzuki, Katsuaki; Matsuzaki, Hideo; Iwata, Keiko; Sugiyama, Toshiro; Yoshikawa, Takeo; Mori, Norio

    2011-01-01

    Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217) showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008). Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049). Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

  4. 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…

  5. The pathophysiology of delayed ejaculation

    Science.gov (United States)

    2016-01-01

    Delayed ejaculation (DE) is probably least studied, and least understood of male sexual dysfunctions, with an estimated prevalence of 1–4% of the male population. Pathophysiology of DE is multifactorial and including psychosexual-behavioral and cultural factors, disruption of ejaculatory apparatus, central and peripheral neurotransmitters, hormonal or neurochemical ejaculatory control and psychosocial factors. Although knowledge of the physiology of the DE has increased in the last two decade, our understanding of the different pathophysiological process of the causes of DE remains limited. To provide a systematic update on the pathophysiology of DE. A systematic review of Medline and PubMed for relevant publications on ejaculatory dysfunction (EjD), DE, retarded ejaculation, inhibited ejaculation, and climax was performed. The search was limited to the articles published between the January 1960 and December 2015 in English. Of 178 articles, 105 were selected for this review. Only those publications relevant to the pathophysiology, epidemiology and prevalence of DE were included. The pathophysiology of DE involves cerebral sensory areas, motor centers, and several spinal nuclei that are tightly interconnected. The biogenic, psychogenic and other factors strongly affect the pathophysiology of DE. Despite the many publications on this disorder, there still is a paucity of publications dedicated to the subject.

  6. 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 ...

  7. [Autism: toward a necessary cultural revolution].

    Science.gov (United States)

    Chamak, Brigitte; Cohen, David

    2003-11-01

    Autism is a pervasive developmental disorder of childhood characterised by disturbances in both social interactions and communication as well as stereotyped patterns of activities and behaviour. The increase in estimates of the prevalence of autism has raised the question of an "epidemic" of autism. More active case assessment and changes in diagnostic criteria probably account in large part for such increase. Investigators have attempted to define the neural pathophysiology of autism ever since the hypothesis of "refrigerator mother" as its cause was replaced by the view that it is a developmental disorder of the immature brain. However consensus is yet to be reached concerning the brain regions implicated. Psychoanalysis, cognitive psychology, neurophysiology, neuropharmacology, and genetics propose restricted view of the major issues leaving extensive areas unexplored. Therapeutic approaches induce only partial and uncertain results. There is no cure for autism but substantial evidence indicates that early, intensive, individualised education is beneficial for children. All modern intervention programs for autism affected children share a high degree of environmental structuring and predictability and an extensive individual approach. Autism being a behaviourally defined syndrome, it gave rise to a number of controversies concerning definition, classification, etiopathogenesis and therapeutics. In the 1990s a crisis has occurred in France with a loss of confidence between parents and psychiatrists with a problem concerning the means and ways of care of the autistic individual. The aim of this paper is to point out the different questions raised by autism in order to better understand this syndrome which touches upon essential behaviour-related aspects such as self consciousness, reality perception, the functioning of the thought and communication, as well as the role of hereditary and acquired influences in normal and pathological development.

  8. A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement

    DEFF Research Database (Denmark)

    Li, Jiong; Vestergaard, Mogens; Obel, Carsten;

    2009-01-01

    OBJECTIVE: Prenatal stress has been linked to several adverse neurobehavioral outcomes, which may share a common pathophysiology with autism. We aimed to examine whether prenatal stress exposure after maternal bereavement is associated with an increased risk of autism later in life. METHODS: We...... compared with those in the unexposed group. RESULTS: Maternal bereavement during the prenatal period was not associated with an increased risk of autism in the offspring. The hazard ratios did not differ by the nature of the exposure (maternal relationship to the deceased or cause of death). The hazard...... in childhood. Our data do not support any strong association between prenatal stress after maternal bereavement and the risk of autism....

  9. 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…

  10. Neonatal chemokine levels and risk of autism spectrum disorders

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Larsen, Nanna; Grove, Jakob;

    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...

  11. [Autism spectrum syndrome replaces Asperger syndrome and autism].

    Science.gov (United States)

    Bejerot, Susanne; Nordin, Viviann

    2014-09-23

    Autism spectrum disorder describes a behaviourally defined impairment in social interaction and communication, along with the presence of restricted interests and repetitive behaviours. Although the etiology is mostly unknown, it is evident that biological factors affect the brain and result in the autistic clinical presentation. Assessment for diagnosing autism spectrum disorder should be comprehensive in order to cover all sorts of problems related to the disorder. Knowledge and experience from working with neurological and psychiatric disorders are a prerequisite for quality in the examination. Up to now, there is no cure for autism spectrum disorder, but support and adaptations in education are nevertheless important for obtaining sufficient life quality for the patients and the family.

  12. 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...

  13. Pathophysiology of autoimmune polyneuropathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2013-06-01

    The most common autoimmune neuropathies include the acute inflammatory polyneuropathy [the Guillain-Barré Syndrome(s)]; chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and IgM anti-MAG-antibody mediated paraproteinemic neuropathy. These neuropathies occur when immunologic tolerance to peripheral nerve components (myelin, Schwann cell, axon, and motor or ganglionic neurons) is lost. Based on the immunopathologic similarities with experimental allergic neuritis induced after immunization with nerve proteins, disease transfer experiments with the patients' serum or with intraneural injections, and immunocytochemical studies on the patients' nerves, it appears that both cellular and humoral factors, either independently or in concert with each other, play a role in the cause of these neuropathies. Although in some of them there is direct evidence for autoimmune reactivity mediated by specific antibodies or autoreactive T lymphocytes, in others the underlying immune-mediated mechanisms have not been fully elucidated, in spite of good response to immunotherapies. The review highlights the factors associated with breaking the T-cell tolerance, the T-cell activation and costimulatory molecules, the immunoregulatory T-cells and relevant cytokines and the antibodies against peripheral nerve glycolipids or glycoproteins that seem to be of pathogenic relevance. Antigens in the nodal, paranodal and juxtaparanodal regions are discussed as potentially critical targets in explaining conduction failure and rapid recovery. Based on the immunopathologic network believed to play a fundamental role in the pathogenesis of these neuropathies, future therapeutic directions are highlighted using new biological agents against T-cells, cytokines, B-cells, transmigration and transduction molecules.

  14. Reverse Engineering Human Pathophysiology with Organs-on-Chips.

    Science.gov (United States)

    Ingber, Donald E

    2016-03-10

    While studies of cultured cells have led to new insights into biological control, greater understanding of human pathophysiology requires the development of experimental systems that permit analysis of intercellular communications and tissue-tissue interactions in a more relevant organ context. Human organs-on-chips offer a potentially powerful new approach to confront this long-standing problem.

  15. Behavioral phenotypes of genetic mouse models of autism.

    Science.gov (United States)

    Kazdoba, T M; Leach, P T; Crawley, J N

    2016-01-01

    More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism.

  16. 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

  17. 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...

  18. Utilization of Lymphoblastoid Cell Lines as a System for the Molecular Modeling of Autism

    Science.gov (United States)

    Baron, Colin A.; Liu, Stephenie Y.; Hicks, Chindo; Gregg, Jeffrey P.

    2006-01-01

    In order to provide an alternative approach for understanding the biology and genetics of autism, we performed statistical analysis of gene expression profiles of lymphoblastoid cell lines derived from children with autism and their families. The goal was to assess the feasibility of using this model in identifying autism-associated genes.…

  19. 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...

  20. 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...

  1. 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.

  2. Structural brain abnormalities in autism : neuroimaging and neuropathology studies

    NARCIS (Netherlands)

    Palmen, Saskia Johanna Maria Christina

    2005-01-01

    JUSTIFY Autism is currently viewed as a largely genetically determined neurodevelopmental disorder. Over the last decades, an increasing number of studies have been performed, trying to establish the underlying biological causes of autism. However, its exact etiology still remains unclear. In this t

  3. 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

  4. 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.

  5. 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

  6. 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,...

  7. 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...

  8. Erythrodermic psoriasis: pathophysiology and current treatment perspectives

    Directory of Open Access Journals (Sweden)

    Singh RK

    2016-07-01

    Full Text Available Rasnik K Singh,1 Kristina M Lee,2 Derya Ucmak,2 Merrick Brodsky,3 Zaza Atanelov,4 Benjamin Farahnik,5 Michael Abrouk,3 Mio Nakamura,2 Tian Hao Zhu,6 Wilson Liao2 1Department of Medicine, University of California – Los Angeles, David Geffen School of Medicine, Los Angeles, 2Department of Dermatology, University of California – San Francisco, San Francisco, 3Department of Medicine, University of California – Irvine, School of Medicine, Irvine, CA, 4Department of Medicine, New York Medical College, Valhalla, NY, 5Department of Medicine, University of Vermont College of Medicine, Burlington, VT, 6Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA Abstract: Erythrodermic psoriasis (EP is a rare and severe variant of psoriasis vulgaris, with an estimated prevalence of 1%–2.25% among psoriatic patients. The condition presents with distinct histopathologic and clinical findings, which include a generalized inflammatory erythema involving at least 75% of the body surface area. The pathogenesis of EP is not well understood; however, several studies suggest that the disease is associated with a predominantly T helper 2 (Th2 phenotype. Given the morbidity and potential mortality associated with the condition, there is a need for a better understanding of its pathophysiology. The management of EP begins with a comprehensive assessment of the patient’s presentation and often requires multidisciplinary supportive measures. In 2010, the medical board of the US National Psoriasis Foundation published consensus guidelines advocating the use of cyclosporine or infliximab as first-line therapy in unstable cases, with acitretin and methotrexate reserved for more stable cases. Since the time of that publication, additional information regarding the efficacy of newer agents has emerged. We review the latest data with regard to the treatment of EP, which includes biologic therapies such as ustekinumab and

  9. 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

  10. [Autism: exploring historical psychiatric and psychological concepts].

    Science.gov (United States)

    Kumbier, E; Haack, K; Herpertz, S C

    2008-08-01

    Autism today is a widely used term, yet what is understood by autism has changed considerably since first being introduced in scientific discourse almost 100 years ago. Autism is one example for the influence of the psychoanalytic school of Sigmund Freud on scientific psychiatry at the beginning of the 20th century. In particular psychoanalysis had an impact on Eugen Bleuler's concept of schizophrenia. The Swiss psychiatrist did not only acknowledge and follow a biological, but also a psychological approach to psychiatry and thus opened up his subject to psychoanalytic thoughts. This paper provides insights into the term's conceptual history--or, more specifically and precisely--sheds light on the expansion of the term's scope, which has gotten to be used for more and more symptoms and phenomena. When Bleuler first presented the term autism, he used it to refer to a classical schizophrenic symptom. Since, however, Bleuler was not very specific and exclusive in his definition, the term was soon used for other phenomena as well, such as to describe a schizoid symptom in the sense of today's schizoid personality disorder (schizoid autism). The concepts of autistic hebephrenia and depressive autism are further examples how the term was used and give insight into how the contents behind the term changed, got less and less specific and widened its scope. Due to its growing vagueness its suitability and usability as a psychopathological term decreased. This process further was strengthened when the word autism got more and more widely used in colloquial language for different aspects of day-to-day routine and thinking. Thus in psychiatry today, autism is exclusively used in connection with the so-called autism spectrum disorders, but has, as other formerly exclusively technical terms, different and rather unspecific meanings in everyday communication.

  11. 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...

  12. 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.

  13. 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 ...

  14. 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...

  15. 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 ...

  16. 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 ...

  17. 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...

  18. 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.

  19. Pathophysiology of the Belgrade Rat

    Directory of Open Access Journals (Sweden)

    Tania eVeuthey

    2014-04-01

    Full Text Available 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 iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis.

  20. 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.

  1. Roses for Autism

    Science.gov (United States)

    Tomaino, Robert

    2011-01-01

    This article discusses Roses for Autism, a program that provides training, guidance and employment opportunities for older students and adults on the autistic spectrum. Roses for Autism tackles one of the biggest challenges currently facing the autism community--a disproportionally high unemployment rate that hovers around 88 percent. Although a…

  2. 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

  3. 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.

  4. 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.

  5. Configuring the autism epidemic

    DEFF Research Database (Denmark)

    Christensen, Fie Lund Lindegaard; Seeberg, Jens

    2017-01-01

    Autism has been described as an epidemic, but this claim is contested and may point to an awareness epidemic, i.e. changes in the definition of what autism is and more attention being invested in diagnosis leading to a rise in registered cases. The sex ratio of children diagnosed with autism...... is skewed in favour of boys, and girls with autism tend to be diagnosed much later than boys. Building and further developing the notion of ‘configuration’ of epidemics, this article explores the configuration of autism in Denmark, with a particular focus on the health system and social support to families...

  6. Pathophysiological Study of Sensitive Skin.

    Science.gov (United States)

    Buhé, Virginie; Vié, Katell; Guéré, Christelle; Natalizio, Audrey; Lhéritier, Céline; Le Gall-Ianotto, Christelle; Huet, Flavien; Talagas, Matthieu; Lebonvallet, Nicolas; Marcorelles, Pascale; Carré, Jean-Luc; Misery, Laurent

    2016-03-01

    Sensitive skin is a clinical syndrome characterized by the occurrence of unpleasant sensations, such as pruritus, burning or pain, in response to various factors, including skincare products, water, cold, heat, or other physical and/or chemical factors. Although these symptoms suggest inflammation and the activation of peripheral innervation, the pathophysiogeny of sensitive skin remains unknown. We systematically analysed cutaneous biopsies from 50 healthy women with non-sensitive or sensitive skin and demonstrated that the intraepidermal nerve fibre density, especially that of peptidergic C-fibres, was lower in the sensitive skin group. These fibres are involved in pain, itching and temperature perception, and their degeneration may promote allodynia and similar symptoms. These results suggest that the pathophysiology of skin sensitivity resembles that of neuropathic pruritus within the context of small fibre neuropathy, and that environmental factors may alter skin innervation.

  7. 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.)

  8. 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.

  9. Pathophysiological Study of Sensitive Skin.

    Science.gov (United States)

    Buhé, Virginie; Vié, Katell; Guéré, Christelle; Natalizio, Audrey; Lhéritier, Céline; Le Gall-Ianotto, Christelle; Huet, Flavien; Talagas, Matthieu; Lebonvallet, Nicolas; Marcorelles, Pascale; Carré, Jean-Luc; Misery, Laurent

    2016-03-01

    Sensitive skin is a clinical syndrome characterized by the occurrence of unpleasant sensations, such as pruritus, burning or pain, in response to various factors, including skincare products, water, cold, heat, or other physical and/or chemical factors. Although these symptoms suggest inflammation and the activation of peripheral innervation, the pathophysiogeny of sensitive skin remains unknown. We systematically analysed cutaneous biopsies from 50 healthy women with non-sensitive or sensitive skin and demonstrated that the intraepidermal nerve fibre density, especially that of peptidergic C-fibres, was lower in the sensitive skin group. These fibres are involved in pain, itching and temperature perception, and their degeneration may promote allodynia and similar symptoms. These results suggest that the pathophysiology of skin sensitivity resembles that of neuropathic pruritus within the context of small fibre neuropathy, and that environmental factors may alter skin innervation. PMID:26337000

  10. [Pruritus: considerable progress in pathophysiology].

    Science.gov (United States)

    Misery, Laurent

    2014-12-01

    Pruritus is defined as "an unpleasant sensation that causes the need to scratch". This is not a small pain. It seems that pruriceptors exist but their level of separation from nociceptive receptors is still debated. Pathways of pruritus were identified from the skin (around the dermo-epidermal junction) to the brain. Many mediators are involved in pruritus but there are at least a histaminergic and a non-histaminergic pathway (PAR-2dependent). Similarly to pain, gate control or peripheral and central sensitization mechanisms have been highlighted in pruritus. These pathophysiological advances are important and anticipate therapeutic advances, that will be very useful for the symptomatic treatment of pruritus (poorly efficient at present).

  11. 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

  12. 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 ( ...

  13. 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.

  14. The Charcot foot: pathophysiology, diagnosis and classification.

    Science.gov (United States)

    Trieb, K

    2016-09-01

    Neuropathic changes in the foot are common with a prevalence of approximately 1%. The diagnosis of neuropathic arthropathy is often delayed in diabetic patients with harmful consequences including amputation. The appropriate diagnosis and treatment can avoid an extensive programme of treatment with significant morbidity for the patient, high costs and delayed surgery. The pathogenesis of a Charcot foot involves repetitive micro-trauma in a foot with impaired sensation and neurovascular changes caused by pathological innervation of the blood vessels. In most cases, changes are due to a combination of both pathophysiological factors. The Charcot foot is triggered by a combination of mechanical, vascular and biological factors which can lead to late diagnosis and incorrect treatment and eventually to destruction of the foot. This review aims to raise awareness of the diagnosis of the Charcot foot (diabetic neuropathic osteoarthropathy and the differential diagnosis, erysipelas, peripheral arterial occlusive disease) and describe the ways in which the diagnosis may be made. The clinical diagnostic pathways based on different classifications are presented. Cite this article: Bone Joint J 2016;98-B:1155-9.

  15. 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…

  16. 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

  17. 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

  18. 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...

  19. 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...

  20. 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 ...

  1. 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 ...

  2. 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.

  3. 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

  4. 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

  5. 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 ...

  6. 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...

  7. 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...

  8. The rise of pathophysiologic research in the United States: the role of two Harvard hospitals.

    Science.gov (United States)

    Tishler, Peter V

    2013-01-01

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

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. Mirror me: Imitative responses in adults with autism.

    Science.gov (United States)

    Schunke, Odette; Schöttle, Daniel; Vettorazzi, Eik; Brandt, Valerie; Kahl, Ursula; Bäumer, Tobias; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K; Brass, Marcel; Münchau, Alexander

    2016-02-01

    Dysfunctions of the human mirror neuron system have been postulated to underlie some deficits in autism spectrum disorders including poor imitative performance and impaired social skills. Using three reaction time experiments addressing mirror neuron system functions under simple and complex conditions, we examined 20 adult autism spectrum disorder participants and 20 healthy controls matched for age, gender and education. Participants performed simple finger-lifting movements in response to (1) biological finger and non-biological dot movement stimuli, (2) acoustic stimuli and (3) combined visual-acoustic stimuli with different contextual (compatible/incompatible) and temporal (simultaneous/asynchronous) relation. Mixed model analyses revealed slower reaction times in autism spectrum disorder. Both groups responded faster to biological compared to non-biological stimuli (Experiment 1) implying intact processing advantage for biological stimuli in autism spectrum disorder. In Experiment 3, both groups had similar 'interference effects' when stimuli were presented simultaneously. However, autism spectrum disorder participants had abnormally slow responses particularly when incompatible stimuli were presented consecutively. Our results suggest imitative control deficits rather than global imitative system impairments.

  14. 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…

  15. 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.

  16. Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling.

    Science.gov (United States)

    Wen, Ya; Alshikho, Mohamad J; Herbert, Martha R

    2016-01-01

    We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging--they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)-and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process "calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK" is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG's category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic conditions

  17. 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

  18. 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;…

  19. Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy.

    Science.gov (United States)

    Liblau, Roland S; Vassalli, Anne; Seifinejad, Ali; Tafti, Mehdi

    2015-03-01

    The discovery of hypocretins (orexins) and their causal implication in narcolepsy is the most important advance in sleep research and sleep medicine since the discovery of rapid eye movement sleep. Narcolepsy with cataplexy is caused by hypocretin deficiency owing to destruction of most of the hypocretin-producing neurons in the hypothalamus. Ablation of hypocretin or hypocretin receptors also leads to narcolepsy phenotypes in animal models. Although the exact mechanism of hypocretin deficiency is unknown, evidence from the past 20 years strongly favours an immune-mediated or autoimmune attack, targeting specifically hypocretin neurons in genetically predisposed individuals. These neurons form an extensive network of projections throughout the brain and show activity linked to motivational behaviours. The hypothesis that a targeted immune-mediated or autoimmune attack causes the specific degeneration of hypocretin neurons arose mainly through the discovery of genetic associations, first with the HLA-DQB1*06:02 allele and then with the T-cell receptor α locus. Guided by these genetic findings and now awaiting experimental testing are models of the possible immune mechanisms by which a specific and localised brain cell population could become targeted by T-cell subsets. Great hopes for the identification of new targets for therapeutic intervention in narcolepsy also reside in the development of patient-derived induced pluripotent stem cell systems.

  20. Inflammatory bowel disease: exploring gut pathophysiology for novel therapeutic targets.

    Science.gov (United States)

    Yadav, Vipul; Varum, Felipe; Bravo, Roberto; Furrer, Esther; Bojic, Daniela; Basit, Abdul W

    2016-10-01

    Ulcerative colitis and Crohn's disease are the 2 major phenotypes of inflammatory bowel disease (IBD), which are influenced by a complex interplay of immunological and genetic elements, though the precise etiology still remains unknown. With IBD developing into a globally prevailing disease, there is a need to explore new targets and a thorough understanding of the pathophysiological differences between the healthy and diseased gut could unearth new therapeutic opportunities. In this review, we provide an overview of the major aspects of IBD pathogenesis and thereafter present a comprehensive analysis of the gut pathophysiology leading to a discussion on some of the most promising targets and biologic therapies currently being explored. These include various gut proteins (CXCL-10, GATA-3, NKG2D, CD98, microRNAs), immune cells recruited to the gut (mast cells, eosinophils, toll-like receptors 2, 4), dysregulated proinflammatory cytokines (interleukin-6, -13, -18, -21), and commensal microbiota (probiotics and fecal microbiota transplantation). We also evaluate some of the emerging nonconventional therapies being explored in IBD treatment focusing on the latest developments in stem cell research, oral targeting of the gut-associated lymphoid tissue, novel anti-inflammatory signaling pathway targeting, adenosine deaminase inhibition, and the beneficial effects of antioxidant and nutraceutical therapies. In addition, we highlight the growth of biologics and their targets in IBD by providing information on the preclinical and clinical development of over 60 biopharmaceuticals representing the state of the art in ulcerative colitis and Crohn's disease drug development. PMID:27220087

  1. 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.

  2. 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.

  3. [Current insights into the pathophysiology of rosacea].

    Science.gov (United States)

    Schauber, J; Homey, B; Steinhoff, M

    2013-07-01

    Rosacea is a chronic inflammatory skin disease mainly affecting the face. Four major clinical subtypes of rosacea can be identified: erythemato-telangiectatic, papulopustular, phymatous and ocular rosacea. Still, it is currently unclear whether these subtypes develop consecutively or if any subtypes may occur individually as part of a syndrome. Rosacea is characterized by facial flushing, erythema, chronic inflammation, edema and fibrosis. Several trigger factors can worsen the disease or cause recurring episodes of inflammation. Although some aspects in the pathophysiology of rosacea have been characterized in more detail during the past years, the precise interplay of the various dysregulated systems is still poorly understood. In early disease manifestations and milder stages, dysfunction of neurovascular regulation and the innate immune system seem to be driving forces in rosacea pathophysiology. A disturbed chemokine and cytokine network further contributes to disease progression. This current review highlights some of the recent findings in rosacea pathophysiology and points out novel targets for therapeutic intervention.

  4. 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.

  5. 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.

  6. 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

  7. 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)

  8. 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...

  9. [Autism and neuropsychology].

    Science.gov (United States)

    Labruyère, Nelly; Sonie, Sandrine

    2014-01-01

    In neuropsychology, the deficiencies associated with autism are generally classed into three areas: social cognition, executive functioning and central coherence. Autistic people however have singular capacities, notably with regard to their perceptual processing focused on details.

  10. 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.

  11. 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 ...

  12. Autism Spectrum Disorder

    Science.gov (United States)

    Autism spectrum disorder (ASD) is a neurological and developmental disorder that begins early in childhood and lasts throughout a person's life. ... be known as Asperger syndrome and pervasive developmental disorders. It is called a "spectrum" disorder because people ...

  13. Opioid peptides and gastrointestinal symptoms in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Cristiane P. Lázaro

    2016-01-01

    Full Text Available Autism spectrum disorders (ASDs are characterized by deficits in the individual’s ability to socialize, communicate, and use the imagination, in addition to stereotyped behaviors. These disorders have a heterogenous phenotype, both in relation to symptoms and regarding severity. Organic problems related to the gastrointestinal tract are often associated with ASD, including dysbiosis, inflammatory bowel disease, exocrine pancreatic insufficiency, celiac disease, indigestion, malabsorption, food intolerance, and food allergies, leading to vitamin deficiencies and malnutrition. In an attempt to explain the pathophysiology involved in autism, a theory founded on opioid excess has been the focus of various investigations, since it partially explains the symptomatology of the disorder. Another hypothesis has been put forward whereby the probable triggers of ASDs would be related to the presence of bacteria in the bowel, oxidative stress, and intestinal permeability. The present update reviews these hypotheses.

  14. 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.

  15. 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

  16. 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 (CGRP...... normalised. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches....

  17. 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…

  18. 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...

  19. Sleep in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Singh, Kanwaljit; Zimmerman, Andrew W

    2015-06-01

    Sleep problems are common in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Sleep problems in these disorders may not only worsen daytime behaviors and core symptoms of ASD and ADHD but also contribute to parental stress levels. Therefore, the presence of sleep problems in ASD and ADHD requires prompt attention and management. This article is presented in 2 sections, one each for ASD and ADHD. First, a detailed literature review about the burden and prevalence of different types of sleep disorders is presented, followed by the pathophysiology and etiology of the sleep problems and evaluation and management of sleep disorders in ASD and ADHD. PMID:26072341

  20. The Broad Autism Phenotype Questionnaire

    Science.gov (United States)

    Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

    2007-01-01

    The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

  1. 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.

  2. Measuring entropy in functional neuroscience: pathophysiological and clinical applications

    Directory of Open Access Journals (Sweden)

    Chung CC

    2016-07-01

    Full Text Available Chen-Chih Chung,1 Jiunn-Horng Kang,2,3 Chaur-Jong Hu,1 1Department of Neurology, Shuang Ho Hospital, College of Medicine, Taipei Medical University, New Taipei, 2Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, 3Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China Abstract: A biological system obtains information, reacts to stimuli, and modifies its behavior to adapt to the environment via complex control systems. A healthy system is expected to adequately adapt to a variety of changes. Physiological signals obtained from a healthy individual should contain rich information and complex behaviors. Entropy-derived measures have been used to access the complexity of the physiological signals. Aging or diseased status usually shows reduced entropy values and loss of complexity within the dynamics of physiological output. In this article, we aim to review the available evidence related to the pathophysiological nature of complexity and the clinical applications of entropy-derived measures in varied neurological disorders. Keywords: complexity, entropy, nerve system, electroencephalography, pathophysiology

  3. 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

  4. 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.

  5. 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.

  6. [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

  7. 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

  8. Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.

    Directory of Open Access Journals (Sweden)

    Michael A Thomas

    Full Text Available 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 another possible exposure route and raising questions about human health consequences. Here, we examined gene expression patterns of fathead minnows treated with a mixture of three psychoactive pharmaceuticals (fluoxetine, venlafaxine & carbamazepine in dosages intended to be similar to the highest observed conservative estimates of environmental concentrations. We conducted microarray experiments examining brain tissue of fish exposed to individual pharmaceuticals and a mixture of all three. We used gene-class analysis to test for enrichment of gene sets involved with ten human neurological disorders. Only sets associated with idiopathic autism were unambiguously enriched. We found that UPPs induce autism-like gene expression patterns in fish. Our findings suggest a new potential trigger for idiopathic autism in genetically susceptible individuals involving an overlooked source of environmental contamination.

  9. 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…

  10. Immunological findings in autism.

    Science.gov (United States)

    Cohly, Hari Har Parshad; Panja, Asit

    2005-01-01

    The immunopathogenesis of autism is presented schematically in Fig. 1. Two main immune dysfunctions in autism are immune regulation involving pro-inflammatory cytokines and autoimmunity. Mercury and an infectious agent like the measles virus are currently two main candidate environmental triggers for immune dysfunction in autism. Genetically immune dysfunction in autism involves the MHC region, as this is an immunologic gene cluster whose gene products are Class I, II, and III molecules. Class I and II molecules are associated with antigen presentation. The antigen in virus infection initiated by the virus particle itself while the cytokine production and inflammatory mediators are due to the response to the putative antigen in question. The cell-mediated immunity is impaired as evidenced by low numbers of CD4 cells and a concomitant T-cell polarity with an imbalance of Th1/Th2 subsets toward Th2. Impaired humoral immunity on the other hand is evidenced by decreased IgA causing poor gut protection. Studies showing elevated brain specific antibodies in autism support an autoimmune mechanism. Viruses may initiate the process but the subsequent activation of cytokines is the damaging factor associated with autism. Virus specific antibodies associated with measles virus have been demonstrated in autistic subjects. Environmental exposure to mercury is believed to harm human health possibly through modulation of immune homeostasis. A mercury link with the immune system has been postulated due to the involvement of postnatal exposure to thimerosal, a preservative added in the MMR vaccines. The occupational hazard exposure to mercury causes edema in astrocytes and, at the molecular level, the CD95/Fas apoptotic signaling pathway is disrupted by Hg2+. Inflammatory mediators in autism usually involve activation of astrocytes and microglial cells. Proinflammatory chemokines (MCP-1 and TARC), and an anti-inflammatory and modulatory cytokine, TGF-beta1, are consistently

  11. 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.

  12. 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.

  13. 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],…

  14. 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

  15. 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)

  16. 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.

  17. 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...

  18. 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...

  19. 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, ...

  20. 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...

  1. 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...

  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. Autism spectrum disorders: toward a gendered embodiment model.

    Science.gov (United States)

    Cheslack-Postava, Keely; Jordan-Young, Rebecca M

    2012-06-01

    One of the most consistent observations in the epidemiology of autism spectrum disorders (ASD) is the preponderance of male cases. A few hypotheses have been put forth which attempt to explain this divergence in terms of sex-linked biology, with limited success. Feminist epidemiologists suggest the importance of investigating specific mechanisms for male-female differences in health outcomes, which may include sex-linked biology and/or gender relations, as well as complex biosocial interactions. Neither domain has been systematically investigated for autism, and the possible role of gender has been particularly neglected. In this article, we posit hypotheses about how social processes based on perception of persons as male or female, particularly patterns of social and physical interaction in early development, may affect the observed occurrence and diagnosis of ASD. We gesture toward an embodiment model, incorporating hypotheses about initial biological vulnerabilities to autism--which may or may not be differentially distributed in relation to sex biology--and their interactions with gender relations, which are demonstrably different for male and female infants. Toward building such a model, we first review the epidemiology of ASD with an eye toward male-female differences, then present a theory of gender as a "pervasive developmental environment" with relevance for the excess burden of autism among males. Finally, we suggest research strategies to further investigate this issue.

  4. 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

  5. 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.

  6. Walk like me, talk like me. The connection between mirror neurons and autism spectrum disorder.

    Science.gov (United States)

    Saffin, Jillian M; Tohid, Hassaan

    2016-04-01

    Understanding social cognition has become a hallmark in deciphering autism spectrum disorder. Neurobiological theories are taking precedence in causation studies as researchers look to abnormalities in brain development as the cause of deficits in social behavior, cognitive processes, and language. Following their discovery in the 1990s, mirror neurons have become a dominant theory for that the mirror neuron system may play a critical role in the pathophysiology of various symptoms of autism. Over the decades, the theory has evolved from the suggestion of a broken mirror neuron system to impairments in mirror neuron circuitry. The mirror neuron system has not gained total support due to inconsistent findings; a comprehensive analysis of the growing body of research could shed light on the benefits, or the disadvantage of continuing to study mirror neurons and their connection to autism.

  7. Walk like me, talk like me. The connection between mirror neurons and autism spectrum disorder.

    Science.gov (United States)

    Saffin, Jillian M; Tohid, Hassaan

    2016-04-01

    Understanding social cognition has become a hallmark in deciphering autism spectrum disorder. Neurobiological theories are taking precedence in causation studies as researchers look to abnormalities in brain development as the cause of deficits in social behavior, cognitive processes, and language. Following their discovery in the 1990s, mirror neurons have become a dominant theory for that the mirror neuron system may play a critical role in the pathophysiology of various symptoms of autism. Over the decades, the theory has evolved from the suggestion of a broken mirror neuron system to impairments in mirror neuron circuitry. The mirror neuron system has not gained total support due to inconsistent findings; a comprehensive analysis of the growing body of research could shed light on the benefits, or the disadvantage of continuing to study mirror neurons and their connection to autism. PMID:27094520

  8. Autism in Angelman syndrome: implications for autism research.

    Science.gov (United States)

    Peters, S U; Beaudet, A L; Madduri, N; Bacino, C A

    2004-12-01

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, ataxia, and a happy/sociable disposition. Maternally, but not paternally, derived defects, such as duplications, within the AS critical region result in autistic symptomatology, suggesting that the UBE3A gene might be implicated in the causation of autism. This study examined the prevalence of autism in AS in 19 children representing three known molecular classes of AS. Children were studied over the course of 1 year. Forty-two percent of this population, eight of 19 children, met criteria for autism according to the Autism Diagnostic Observation Schedule (ADOS). Parents of children who were diagnosed with autism according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria as well as the ADOS - Generic, Module 1 (ADOS-G) were administered the Autism Diagnostic Interview - Revised (ADI-R). Data from the ADI-R were convergent with data from the ADOS-G in all cases. Children with comorbid autism and AS scored lower on measures of language, adaptive behavior, and cognition, and demonstrated a slower rate of improvement over the course of the study. Furthermore, they demonstrated deficits in communication and socialization that mirror those observed in children with idiopathic autism. The study highlights the phenotypic overlap between autism and AS and increases the probability that dysregulation of UBE3A may play a role in the causation of autism.

  9. Looping Genomes: Diagnostic Change and the Genetic Makeup of the Autism Population.

    Science.gov (United States)

    Navon, Daniel; Eyal, Gil

    2016-03-01

    This article builds on Hacking's framework of "dynamic nominalism" to show how knowledge about biological etiology can interact with the "kinds of people" delineated by diagnostic categories in ways that "loop" or modify both over time. The authors use historical materials to show how "geneticization" played a crucial role in binding together autism as a biosocial community and how evidence from genetics research later made an important contribution to the diagnostic expansion of autism. In the second part of the article, the authors draw on quantitative and qualitative analyses of autism rates over time in several rare conditions that are delineated strictly according to genomic mutations in order to demonstrate that these changes in diagnostic practice helped to both increase autism's prevalence and create its enormous genetic heterogeneity. Thus, a looping process that began with geneticization and involved the social effects of genetics research itself transformed the autism population and its genetic makeup.

  10. Behavioural methods used in rodent models of autism spectrum disorders: current standards and new developments.

    Science.gov (United States)

    Wöhr, Markus; Scattoni, Maria Luisa

    2013-08-15

    Autism is a behaviourally defined disorder including attenuated or abnormal social interaction and communication, as well as aberrant repetitive behaviour, with symptoms emerging early in childhood. Although the cause of autism has not been discovered, several data strongly support the role of genetic factors in autism aetiology. For this reason, preclinical research is now focusing on generating transgenic and knockout mice, and more recently also rats, with mutations in genes identified in autistic children, with the main aim of understanding the role of those genes in autism aetiology, discovering the biological mechanisms underlying autistic behaviours detected in these mutant lines and evaluating potential treatments. Over the last years, a huge number of behavioural phenotyping assays for rodent models of autism and related disorders have been designed. In the first part of our review, we focus on current standards, i.e. state-of-the-art behavioural phenotyping tasks to assess autism core symptoms in rodent models. The second part is devoted to some few, in our view, very promising examples of new developments, namely an autism severity score, scent marking behaviour as an additional, ethologically valid measure for communication, plus a number of new developments in the behavioural domains of social facilitation, observational learning, and empathy. Finally, we will highlight the huge potential impact of newly generated rat knockout models of autism. PMID:23769995

  11. Cognitive function assessment in the biological parents of the children with autism%孤独症患儿生物学父母的认知功能研究

    Institute of Scientific and Technical Information of China (English)

    殷青云; 王白兰; 陈劲梅; 李雪荣; 罗学荣; 张荣花

    2011-01-01

    目的 比较孤独症父母和健康对照的认知功能,探索孤独症核心家系中神经心理的改变.方法 选用11个效能可靠的神经心理测验,通过与正常对照的比较,来探索孤独症父母的认知损害.结果 孤独症父母在数字符号、木块图、Stroop CW、言语流畅性测验的重复数、WCST的持续错误数、WCST的非持续错误数、坚持性反应数和概括力水平百分数、Hanoi塔的执行时间、Hanoi塔的总分和总分/执行时间测验上与正常对照组有明显差异.结论 孤独症父母存在一定程度的认知功能损害,特别是构建功能、注意和执行功能方面,这些神经心理指标可能是孤独症遗传的表型标记.%Objective Comparing the cognitive neuropsychological function between the autistic children's parents and the normal controls,to exploring the neuropsychological defects in the pedigree of autism.Methods We choose eleven neuropsychological tests to compare the neuropsychological function of the autism's parents and normal controls.Results Compared with normal controls, the parents of children with autism showed the impairments of the cognitive functions,which included digit-symbol,block design,verbal fluency,ToH and WCST.Conclusions Compared with normal controls,the parents of the children with autism show the impairment of some cognitive functions.It suggests that the cognition defects are possible genetic marker in autism.

  12. The pathophysiology of lifelong premature ejaculation.

    Science.gov (United States)

    Waldinger, Marcel D

    2016-08-01

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

  13. The pathophysiology of lifelong premature ejaculation

    Science.gov (United States)

    2016-01-01

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

  14. 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…

  15. 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.

  16. Autism and sleep disorders

    Directory of Open Access Journals (Sweden)

    Preeti A Devnani

    2015-01-01

    Full Text Available “Autism Spectrum Disorders” (ASDs are neurodevelopment disorders and are characterized by persistent impairments in reciprocal social interaction and communication. Sleep problems in ASD, are a prominent feature that have an impact on social interaction, day to day life, academic achievement, and have been correlated with increased maternal stress and parental sleep disruption. Polysomnography studies of ASD children showed most of their abnormalities related to rapid eye movement (REM sleep which included decreased quantity, increased undifferentiated sleep, immature organization of eye movements into discrete bursts, decreased time in bed, total sleep time, REM sleep latency, and increased proportion of stage 1 sleep. Implementation of nonpharmacotherapeutic measures such as bedtime routines and sleep-wise approach is the mainstay of behavioral management. Treatment strategies along with limited regulated pharmacotherapy can help improve the quality of life in ASD children and have a beneficial impact on the family. PubMed search was performed for English language articles from January 1995 to January 2015. Following key words: Autism spectrum disorder, sleep disorders and autism, REM sleep and autism, cognitive behavioral therapy, sleep-wise approach, melatonin and ASD were used. Only articles reporting primary data relevant to the above questions were included.

  17. 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…

  18. 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.

  19. 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

  20. 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…

  1. [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

  2. Rho kinases in cardiovascular physiology and pathophysiology.

    Science.gov (United States)

    Loirand, Gervaise; Guérin, Patrice; Pacaud, Pierre

    2006-02-17

    Rho kinases (ROCKs) are the first and the best-characterized effectors of the small G-protein RhoA. In addition to their effect on actin organization, or through this effect, ROCKs have been found to regulate a wide range of fundamental cell functions such as contraction, motility, proliferation, and apoptosis. Abnormal activation of the RhoA/ROCK pathway has been observed in major cardiovascular disorders such as atherosclerosis, restenosis, hypertension, pulmonary hypertension, and cardiac hypertrophy. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of ROCK signaling and its roles in cardiovascular physiology and pathophysiology.

  3. 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.

  4. Stoppage in Autism Spectrum Disorders

    DEFF Research Database (Denmark)

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

    2015-01-01

    of 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....

  5. 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...

  6. 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

  7. 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.)

  8. 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.

  9. 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)

  10. 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...

  11. 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

  12. 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…

  13. 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.

  14. 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,…

  15. 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

  16. 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...

  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. 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

  19. 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.

  20. Eyelid aging: pathophysiology and clinical management

    Directory of Open Access Journals (Sweden)

    Renato Wendell Damasceno

    2015-10-01

    Full Text Available ABSTRACTLife expectancy is increasing in most countries. With increasing age, many individuals may develop involutional ophthalmic diseases, such as eyelid aging. Dermatochalasis, ptosis, ectropion, and entropion are common disorders in middle-aged and older adults. This review outlines the pathophysiology and clinical management of these involutional eyelid disorders. Recently, a decrease in elastic fibers with ultrastructural abnormalities and an overexpression of elastin-degrading enzymes have been demonstrated in involutional ectropion and entropion. This may be the consequence of local ischemia, inflammation, and/or chronic mechanical stress. Eyelid aging with progressive loss of tone and laxity may affect the ocular surface and adnexal tissues, resulting in different clinical symptoms and signs. Surgical management depends on the appropriate correction of the underlying anatomical defect.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. [Neuropathic pain: pathophysiology, assessment, and therapy].

    Science.gov (United States)

    Sommer, C

    2013-12-01

    Neuropathic pain is caused by lesions in the somatosensory system. Characteristic but not exclusive features are spontaneous burning pain, electrifying and shooting pain, hyperalgesia, and allodynia. The basic concept of the pathophysiology of neuropathic pain is the combination of peripheral and central sensitization. Knowledge on the molecular mechanisms has grown exponentially in recent years. The problem lies in identifying the individual mechanisms and in determining a comprehensive concept. Progress has also been made in assessment, e.g., methods for detecting dysfunction of nociceptors have significantly improved. In addition, there are many more therapeutic options available than 15 years ago. The drugs available include antidepressants, anticonvulsants, opioids, and topical medications. Data from controlled trials and recommendations from guidelines are available. PMID:24217854

  7. Emerging hepatic syndromes: pathophysiology, diagnosis and treatment.

    Science.gov (United States)

    Bertino, Gaetano; Privitera, Graziella; Purrello, Francesco; Demma, Shirin; Crisafulli, Emanuele; Spadaro, Luisa; Koukias, Nikolaos; Tsochatzis, Emmanuel A

    2016-10-01

    Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. In this article, we review the current understanding on the pathophysiology, the diagnostic criteria and the available therapeutic options for patients with emerging hepatic syndromes in cirrhosis, namely the hepatorenal, hepato-adrenal and hepatopulmonary syndrome. The hepatorenal syndrome is a well-recognized complication of advanced cirrhosis and is usually associated with an accelerated course to death unless liver transplantation is performed. The hepatopulmonary syndrome is often missed in the evaluation of patients with cirrhosis; however, early recognition is essential for the efficient management of individual patients. The hepato-adrenal syndrome, although not fully characterized, offers an exciting field for research and potential therapeutic interventions. PMID:27273018

  8. Biomarkers in Autism

    Directory of Open Access Journals (Sweden)

    Robert eHendren

    2014-08-01

    Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

  9. Circadian molecular clock in lung pathophysiology.

    Science.gov (United States)

    Sundar, Isaac K; Yao, Hongwei; Sellix, Michael T; Rahman, Irfan

    2015-11-15

    Disrupted daily or circadian rhythms of lung function and inflammatory responses are common features of chronic airway diseases. At the molecular level these circadian rhythms depend on the activity of an autoregulatory feedback loop oscillator of clock gene transcription factors, including the BMAL1:CLOCK activator complex and the repressors PERIOD and CRYPTOCHROME. The key nuclear receptors and transcription factors REV-ERBα and RORα regulate Bmal1 expression and provide stability to the oscillator. Circadian clock dysfunction is implicated in both immune and inflammatory responses to environmental, inflammatory, and infectious agents. Molecular clock function is altered by exposomes, tobacco smoke, lipopolysaccharide, hyperoxia, allergens, bleomycin, as well as bacterial and viral infections. The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors. Environmental agents and redox modulation may alter the levels of REV-ERBα and RORα in lung tissue in association with a heightened DNA damage response, cellular senescence, and inflammation. A reciprocal relationship exists between the molecular clock and immune/inflammatory responses in the lungs. Molecular clock function in lung cells may be used as a biomarker of disease severity and exacerbations or for assessing the efficacy of chronotherapy for disease management. Here, we provide a comprehensive overview of clock-controlled cellular and molecular functions in the lungs and highlight the repercussions of clock disruption on the pathophysiology of chronic airway diseases and their exacerbations. Furthermore, we highlight the potential for the molecular clock as a novel chronopharmacological target for the management of lung pathophysiology.

  10. 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.

  11. 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

  12. 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

  13. [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

  14. 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…

  15. 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.

  16. 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…

  17. 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…

  18. 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)

  19. 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....

  20. 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)

  1. 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...

  2. Young Children with Autism Spectrum Disorder: Strategies that Work

    Science.gov (United States)

    Willis, Clarissa

    2009-01-01

    Five types of autism are recognized under autism spectrum disorder (ASD). The author discusses the major characteristics associated with autism and offers some simple strategies for helping children with autism function in preschool settings.

  3. 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...

  4. 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...

  5. 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 ...

  6. 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.

  7. Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes

    Directory of Open Access Journals (Sweden)

    Lee Norman H

    2006-05-01

    Full Text Available Abstract Background The autism spectrum encompasses a set of complex multigenic developmental disorders that severely impact the development of language, non-verbal communication, and social skills, and are associated with odd, stereotyped, repetitive behavior and restricted interests. To date, diagnosis of these neurologically based disorders relies predominantly upon behavioral observations often prompted by delayed speech or aberrant behavior, and there are no known genes that can serve as definitive biomarkers for the disorders. Results Here we demonstrate, for the first time, that lymphoblastoid cell lines from monozygotic twins discordant with respect to severity of autism and/or language impairment exhibit differential gene expression patterns on DNA microarrays. Furthermore, we show that genes important to the development, structure, and/or function of the nervous system are among the most differentially expressed genes, and that many of these genes map closely in silico to chromosomal regions containing previously reported autism candidate genes or quantitative trait loci. Conclusion Our results provide evidence that novel candidate genes for autism may be differentially expressed in lymphoid cell lines from individuals with autism spectrum disorders. This finding further suggests the possibility of developing a molecular screen for autism based on expressed biomarkers in peripheral blood lymphocytes, an easily accessible tissue. In addition, gene networks are identified that may play a role in the pathophysiology of autism.

  8. 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.

  9. Autism overflows: increasing prevalence and proliferating theories.

    Science.gov (United States)

    Waterhouse, Lynn

    2008-12-01

    This selective review examines the lack of an explanation for the sharply increasing prevalence of autism, and the lack of any synthesis of the proliferating theories of autism. The most controversial and most widely disseminated notion for increasing prevalence is the measles-mumps-rubella/thimerosal vaccine theory. Less controversial causes that have been proposed include changes in autism diagnostic criteria, increasing services for autism, and growing awareness of the disorder. Regardless of its causes, the increasing prevalence of autism has put pressure on the field of autism research to generate productive and predictive theories of autism. However, the heterogeneity of brain deficits, impaired behaviors, and genetic variants in autism have challenged researchers and theorists, and despite 45 years of research, no standard causal synthesis has emerged. Research going forward should assume that autism is an aggregation of myriad independent disorders of impaired sociality, social cognition, communication, and motor and cognitive skills.

  10. 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

  11. 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.)

  12. Tinnitus: Network pathophysiology-network pharmacology

    Directory of Open Access Journals (Sweden)

    Ana Belen eElgoyhen

    2012-01-01

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

  13. 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.

  14. Catamenial epilepsy: definition, prevalence pathophysiology and treatment.

    Science.gov (United States)

    Herzog, Andrew G

    2008-03-01

    Seizures do not occur randomly. They tend to cluster in the majority of men and women with epilepsy. Seizure clusters, in turn, often show a periodicity. When the periodicity of seizure exacerbation aligns itself with that of the menstrual cycle, it is designated as catamenial epilepsy. The neuroactive properties of reproductive steroids and the cyclic variation in their serum concentrations are important pathophysiologic factors. Recent investigations have demonstrated and confirmed the existence of at least three patterns of catamenial seizure exacerbation: perimenstrual and periovulatory in ovulatory cycles and entire luteal phase in anovulatory cycles. A rational mathematical basis for the categorization of seizure exacerbation as catamenial epilepsy has been developed. It identifies approximately one third of women as having catamenial epilepsy. If seizures show hormonal sensitivity in their occurrence, they may also respond to hormonal treatment. Successful open label trials using cyclic natural progesterone supplement, depomedroxyprogesterone and gonadotropin-releasing hormone analogues in women and using testosterone with or without aromatase inhibitor in men have been reported. Prospective, randomized, placebo-controlled, double-blind investigations are warranted and under way.

  15. 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.

  16. Pathophysiology of congenital and neonatal hydrocephalus.

    Science.gov (United States)

    McAllister, James P

    2012-10-01

    The pathophysiology of congenital and neonatal hydrocephalus is not well understood although the prognosis for patients with this disorder is far from optimal. A major obstacle to advancing our knowledge of the causes of this disorder and the cellular responses that accompany it is the multifactorial nature of hydrocephalus. Not only is the epidemiology varied and complex, but the injury mechanisms are numerous and overlapping. Nevertheless, several conclusions can be made with certainty: the age of onset strongly influences the degree of impairment; injury severity is dependent on the magnitude and duration of ventriculomegaly; the primary targets are periventricular axons, myelin, and microvessels; cerebrovascular injury mechanisms are prominent; gliosis and neuroinflammation play major roles; some but not all changes are preventable by draining cerebrospinal fluid with shunts and third ventriculostomies; cellular plasticity and physiological compensation probably occur but this is a major under-studied area; and pharmacologic interventions are promising. Rat and mouse models have provided important insights into the pathogenesis of congenital and neonatal hydrocephalus. Ependymal denudation of the ventricular lining appears to affect the development of neural progenitors exposed to cerebrospinal fluid, and alterations of the subcommissural organ influence the patency of the cerebral aqueduct. Recently these impairments have been observed in patients with fetal-onset hydrocephalus, so experimental findings are beginning to be corroborated in humans. These correlations, coupled with advanced genetic manipulations in animals and successful pharmacologic interventions, support the view that improved treatments for congenital and neonatal hydrocephalus are on the horizon. PMID:22800608

  17. 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.

  18. Obesity-related hypertension: possible pathophysiological mechanisms.

    Science.gov (United States)

    Vaněčková, Ivana; Maletínská, Lenka; Behuliak, Michal; Nagelová, Veronika; Zicha, Josef; Kuneš, Jaroslav

    2014-12-01

    Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine.

  19. 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.

  20. Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder

    Science.gov (United States)

    Wang, Yiqin; Picard, Martin; Gu, Zhenglong

    2016-01-01

    Increasing clinical and biochemical evidence implicate mitochondrial dysfunction in the pathophysiology of Autism Spectrum Disorder (ASD), but little is known about the biological basis for this connection. A possible cause of ASD is the genetic variation in the mitochondrial DNA (mtDNA) sequence, which has yet to be thoroughly investigated in large genomic studies of ASD. Here we evaluated mtDNA variation, including the mixture of different mtDNA molecules in the same individual (i.e., heteroplasmy), using whole-exome sequencing data from mother-proband-sibling trios from simplex families (n = 903) where only one child is affected by ASD. We found that heteroplasmic mutations in autistic probands were enriched at non-polymorphic mtDNA sites (P = 0.0015), which were more likely to confer deleterious effects than heteroplasmies at polymorphic mtDNA sites. Accordingly, we observed a ~1.5-fold enrichment of nonsynonymous mutations (P = 0.0028) as well as a ~2.2-fold enrichment of predicted pathogenic mutations (P = 0.0016) in autistic probands compared to their non-autistic siblings. Both nonsynonymous and predicted pathogenic mutations private to probands conferred increased risk of ASD (Odds Ratio, OR[95% CI] = 1.87[1.14–3.11] and 2.55[1.26–5.51], respectively), and their influence on ASD was most pronounced in families with probands showing diminished IQ and/or impaired social behavior compared to their non-autistic siblings. We also showed that the genetic transmission pattern of mtDNA heteroplasmies with high pathogenic potential differed between mother-autistic proband pairs and mother-sibling pairs, implicating developmental and possibly in utero contributions. Taken together, our genetic findings substantiate pathogenic mtDNA mutations as a potential cause for ASD and synergize with recent work calling attention to their unique metabolic phenotypes for diagnosis and treatment of children with ASD. PMID:27792786

  1. 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

  2. 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...

  3. 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.

  4. [Psychobiosocial interventions for autism].

    Science.gov (United States)

    Bölte, S

    2011-05-01

    A multitude of interventions is offered for the treatment of autism spectrum disorders (ASD). However, only few have demonstrated scientific evidence, and even the evaluated methods need further examination of their mechanisms and scope. This article provides a brief summary of the premises and principles of successful psychobiosocial ASD intervention. ABA, TEACCH, PECS, social skills and cognitive training are described as examples for established approaches to ASD. Training of μ-suppression using neurofeedback and reanimation of the fusiform gyrus and amygdala using computer-aided facial affect recognition training are introduced as neurobiologically based ASD interventions. PMID:21523442

  5. 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

  6. Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases.

    Science.gov (United States)

    Jaggi, Amteshwar Singh; Kaur, Aalamjeet; Bali, Anjana; Singh, Nirmal

    2015-01-01

    Sodium potassium chloride co-transporter (NKCC) belongs to cation-dependent chloride co-transporter family, whose activation allows the entry of Na(+), K(+) and 2Cl(-) inside the cell. It acts in concert with K(+) Cl(-) co-transporter (KCC), which extrudes K(+) and Cl(-) ions from cell. NKCC1 is widely distributed throughout the body, while NKCC2 is exclusively present in kidney. Protein kinase A, protein kinase C, Ste20-related proline-alanine-rich kinase, oxidative stress responsive kinases, With No K=lysine kinase and protein phosphatase type 1 control the phosphorylation/dephosphorylation of key threonine residues of in regulatory domain of NKCC1. The selective inhibitors of NKCC1 including bumetanide and furosemide are conventionally employed as diuretics. However, recent studies have indicated that NKCC1 may be involved in the pathophysiology of anxiety, cerebral ischemia, epilepsy, neuropathic pain, fragile X syndrome, autism and schizophrenia. The inhibitors of NKCC1 are shown to produce anxiolytic effects; attenuate cerebral ischemia-induced neuronal injury; produce antiepileptic effects and attenuate neuropathic pain. In the early developing brain, GABAA activation primarily produces excitatory actions due to high NKCC1/KCC2 ratio. However, as the development progresses, the ratio of NKCC1/KCC2 ratio reverses and there is switch in the polarity of GABAA actions and latter acquires the inhibitory actions. The recapitulation of developmental-like state during pathological state may be associated with increase in the expression and functioning of NKCC1, which decreases the strength of inhibitory GABAergic neurotransmission. The present review describes the expanding role and mechanism of NKCC1 in the pathophysiology of different diseases. PMID:26411965

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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...

  16. 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,…

  17. 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

  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)

  19. Mercury and autism: accelerating evidence?

    Science.gov (United States)

    Mutter, Joachim; Naumann, Johannes; Schneider, Rainer; Walach, Harald; Haley, Boyd

    2005-10-01

    The causes of autism and neurodevelopmental disorders are unknown. Genetic and environmental risk factors seem to be involved. Because of an observed increase in autism in the last decades, which parallels cumulative mercury exposure, it was proposed that autism may be in part caused by mercury. We review the evidence for this proposal. Several epidemiological studies failed to find a correlation between mercury exposure through thimerosal, a preservative used in vaccines, and the risk of autism. Recently, it was found that autistic children had a higher mercury exposure during pregnancy due to maternal dental amalgam and thimerosal-containing immunoglobulin shots. It was hypothesized that children with autism have a decreased detoxification capacity due to genetic polymorphism. In vitro, mercury and thimerosal in levels found several days after vaccination inhibit methionine synthetase (MS) by 50%. Normal function of MS is crucial in biochemical steps necessary for brain development, attention and production of glutathione, an important antioxidative and detoxifying agent. Repetitive doses of thimerosal leads to neurobehavioral deteriorations in autoimmune susceptible mice, increased oxidative stress and decreased intracellular levels of glutathione in vitro. Subsequently, autistic children have significantly decreased level of reduced glutathione. Promising treatments of autism involve detoxification of mercury, and supplementation of deficient metabolites.

  20. 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

  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. 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

  4. 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.

  5. 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...

  6. Pathophysiology of shunt dysfunction in shunt treated hydrocephalus

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  7. 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

  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. 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 ...

  10. 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

    is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena. Maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Diabetes develops because of inadequate islet β-cell and adipose-tissue responses...... such as the heart. Reversal of overnutrition, healing of the β cells, and lessening of adipose tissue defects should be treatment priorities.......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...

  11. 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

    is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena. Maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Diabetes develops because of inadequate islet ß-cell and adipose-tissue responses...... such as the heart. Reversal of overnutrition, healing of the ß cells, and lessening of adipose tissue defects should be treatment priorities.......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...

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  16. Brief Report: Enhanced Picture Naming in Autism

    Science.gov (United States)

    Walenski, Matthew; Mostofsky, Stewart H.; Gidley-Larson, Jennifer C.; Ullman, Michael T.

    2008-01-01

    Language and communication deficits are key diagnostic criteria for autism. However, not all aspects of language are equally affected. Here we present evidence of "enhanced" performance of a critical aspect of language--word processing--in children with autism. The results have implications for explanatory theories of autism and language, and for…

  17. Change in Autism Core Symptoms with Intervention

    Science.gov (United States)

    Zachor, Ditza A.; Ben-Itzchak, Esther; Rabinovich, Ana-Lia; Lahat, Eli

    2007-01-01

    It is still debated what is the best early intervention approach for autism. This study compared two intervention approaches, Eclectic-Developmental (ED) and Applied Behavioral Analysis (ABA) in very young children with autism/autism spectrum disorder (ASD). Nineteen children received ED intervention, using combination of methods. Twenty children…

  18. 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…

  19. 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…

  20. Grammaticality Judgments in Autism: Deviance or Delay

    Science.gov (United States)

    Eigsti, Inge-Marie; Bennetto, Loisa

    2009-01-01

    Language in autism has been the subject of intense interest, because communication deficits are central to the disorder, and because autism serves as an arena for testing theories of language acquisition. High-functioning older children with autism are often considered to have intact grammatical abilities, despite pragmatic impairments. Given the…

  1. 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.

  2. Ubiquinol Improves Symptoms in Children with Autism

    NARCIS (Netherlands)

    Gvozdjakova, Anna; Kucharska, Jarmila; Ostatnikova, Daniela; Babinska, Katarina; Nakladal, Dalibor; Crane, Fred L.

    2014-01-01

    Background. Autism is a spectrum of neurodevelopmental disorders with manifestation within 3 years after birth. Manifestations of autism include behavior problems (hyperactivity, toys destruction, self-harm, and agression) and sleep and eating disorders. Etiology of autism is poorly understood. Oxid

  3. 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…

  4. 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.…

  5. Children Grow Up: Autism in Adolescents & Adults.

    Science.gov (United States)

    Meyers, Kathleen; Griesman, Brenda

    The booklet examines issues associated with autism in adolescents and adults. Teenagers with autism exhibit behaviors not unlike their nondisabled peers, and standard definitions of the syndrome may not be relevant at that age. Brief articles explore the range of emotions families may encounter with a young adult or adult who has autism, typical…

  6. 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…

  7. 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…

  8. 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…

  9. 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...

  10. 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...

  11. 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

  12. 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

  13. 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.

  14. Pathophysiology and a Rational Basis of Therapy.

    Science.gov (United States)

    Gracia-Sancho, Jordi; Maeso-Díaz, Raquel; Bosch, Jaime

    2015-01-01

    sufficiently to promote the development of intrahepatic shunts and portal-systemic collaterals, including varices, through which portal blood flow bypasses the liver. In human portal hypertension collateralization and hyperdynamic circulation start at a portal pressure gradient >10 mm Hg. Rational therapy for portal hypertension aims at correcting these pathophysiological abnormalities: liver injury, fibrogenesis, increased hepatic vascular tone and splanchnic vasodilatation. Continuing liver injury may be counteracted specifically by etiological treatments (the best example being the direct-acting antivirals for hepatitis C viral infection), while architectural disruption and fibrosis can be ameliorated by a variety of antifibrotic drugs and antiangiogenic strategies. Several drugs in this category are currently under investigation in phase II-III randomized controlled trials. Sinusoidal endothelial dysfunction is ameliorated by statins as well as by other drugs increasing NO availability. It is of note that simvastatin has already been proven to be clinically effective in two randomized controlled trials. Splanchnic hyperemia can be counteracted by nonselective β-blockers (NSBBs), vasopressin analogs and somatostatin analogs, drugs that until recently were the only available treatments for portal hypertension, but that are not very effective in the initial stages of cirrhosis. There is experimental and clinical evidence indicating that a more effective reduction of portal pressure is obtained by combining agents acting on these different pathways. It is likely that the treatment of portal hypertension will evolve to use etiological treatments together with antifibrotic agents and/or drugs improving sinusoidal endothelial function in the initial stages of cirrhosis (preprimary prophylaxis), while NSBBs will be added in advanced stages of the disease.

  15. Pathophysiology and a Rational Basis of Therapy.

    Science.gov (United States)

    Gracia-Sancho, Jordi; Maeso-Díaz, Raquel; Bosch, Jaime

    2015-01-01

    sufficiently to promote the development of intrahepatic shunts and portal-systemic collaterals, including varices, through which portal blood flow bypasses the liver. In human portal hypertension collateralization and hyperdynamic circulation start at a portal pressure gradient >10 mm Hg. Rational therapy for portal hypertension aims at correcting these pathophysiological abnormalities: liver injury, fibrogenesis, increased hepatic vascular tone and splanchnic vasodilatation. Continuing liver injury may be counteracted specifically by etiological treatments (the best example being the direct-acting antivirals for hepatitis C viral infection), while architectural disruption and fibrosis can be ameliorated by a variety of antifibrotic drugs and antiangiogenic strategies. Several drugs in this category are currently under investigation in phase II-III randomized controlled trials. Sinusoidal endothelial dysfunction is ameliorated by statins as well as by other drugs increasing NO availability. It is of note that simvastatin has already been proven to be clinically effective in two randomized controlled trials. Splanchnic hyperemia can be counteracted by nonselective β-blockers (NSBBs), vasopressin analogs and somatostatin analogs, drugs that until recently were the only available treatments for portal hypertension, but that are not very effective in the initial stages of cirrhosis. There is experimental and clinical evidence indicating that a more effective reduction of portal pressure is obtained by combining agents acting on these different pathways. It is likely that the treatment of portal hypertension will evolve to use etiological treatments together with antifibrotic agents and/or drugs improving sinusoidal endothelial function in the initial stages of cirrhosis (preprimary prophylaxis), while NSBBs will be added in advanced stages of the disease. PMID:26159267

  16. 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.

  17. 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.

  18. 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

  19. 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.)

  20. 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.)

  1. 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) ...

  2. 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…

  3. 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…

  4. 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.

  5. 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

  6. 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 ...

  7. MUC1 and colorectal cancer pathophysiology considerations

    Institute of Scientific and Technical Information of China (English)

    Yaron Niv

    2008-01-01

    Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer.A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Hukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and coinvestigators showed recently that MUC1 inhibits cell proliferation by a β-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through β-catenin binding,disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUCl-β-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H,which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation,differentiation or migration when ligand bound.

  8. The pathophysiology of acquired premature ejaculation.

    Science.gov (United States)

    McMahon, Chris G; Jannini, Emmanuele A; Serefoglu, Ege C; Hellstrom, Wayne J G

    2016-08-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE. PMID:27652216

  9. Pathophysiological mechanisms of angiogenesis in atherogenesis

    Directory of Open Access Journals (Sweden)

    Vučević Danijela

    2013-01-01

    Full Text Available Introduction. Atherosclerosis is a progressive, multifactorial, diffuse, multisystemic, chronic, inflammatory disease, which is manifested by disorders of vascular, immune and metabolic system. Pathogenesis of this disease is not fully understood. Accordingly, angiogenesis represents a special field of research due to its role in atherogenesis. Steps of Angiogenesis. Angiogenesis is a complex biological process, which requires the precise coordination of its four steps (vasodilatation and permeability, vessel destabilization and matrix degradation, endothelial cell proliferation and migration, and lumen formation and vessel stabilization. Mediators of Angiogenic Process. The process of forming new blood vessels is regulated by a delicate balance between proangiogenic and antiangiogenic molecules. Numerous soluble growth factors and inhibitors, cytokines, proteases, extracellular matrix proteins and adhesion molecules, as well as hypoxia, inflammatory process, shear stress, hypertension and interaction between cells and extracellular matrix strictly control the angiogenic process. Neovascularization is halted due to the downregulation of angiogenic factors or the increase of inhibitors of this process. Tumor Vascularization. In the asymptomatic phase of cancerogenesis, cancer rarely exceeds the diameter of 1-2 millimeters. However, when the metabolic demand increases, it leads to tumor vascularization. In this way, tumor switches to an angiogenic phenotype. The molecular basis of angiogenic switch refers to increased production of angiogenic factors and/or loss of angiogenic inhibitors. Conclusion. The contribution of angiogenic process has become increasingly meaningful in understanding the pathogenesis of atherosclerosis. [Projekat Ministarstva nauke Republike Srbije, br. 175015

  10. Pathophysiological roles of peroxynitrite in circulatory shock.

    Science.gov (United States)

    Szabó, Csaba; Módis, Katalin

    2010-09-01

    Peroxynitrite is a reactive oxidant produced from nitric oxide and superoxide, which reacts with proteins, lipids, and DNA, and promotes cytotoxic and proinflammatory responses. Here, we overview the role of peroxynitrite in various forms of circulatory shock. Immunohistochemical and biochemical evidences 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 peroxynitrite have been identified in human tissues after circulatory shock. Peroxynitrite can initiate toxic oxidative reactions in vitro and in vivo. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+/K+ ATPase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of peroxynitrite. In addition, peroxynitrite is a potent trigger of DNA strand breakage, with subsequent activation of the nuclear enzyme poly(ADP-ribose) polymerase, which promotes cellular energetic collapse and cellular necrosis. Additional actions of peroxynitrite that contribute to the pathogenesis of shock include inactivation of catecholamines and catecholamine receptors (leading to vascular failure) and endothelial and epithelial injury (leading to endothelial and epithelial hyperpermeability and barrier dysfunction), as well as myocyte injury (contributing to loss of cardiac contractile function). Neutralization of peroxynitrite with potent peroxynitrite decomposition catalysts provides cytoprotective and beneficial effects in rodent and large-animal models of circulatory shock.

  11. Autism Spectrum Disorders in Iran

    OpenAIRE

    Mohammadi, Mohammad Reza; 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...

  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. Inflammation and Arterial Hypertension: From Pathophysiological Links to Risk Prediction.

    Science.gov (United States)

    Pietri, Panagiota; Vlachopoulos, Charalambos; Tousoulis, Dimitris

    2015-01-01

    Over the last years, ample data have demonstrated the pivotal role of low-grade inflammation in the pathophysiology of atherosclerosis and cardiovascular disease. It is well established that inflammatory activation, serving either as a substrate, in the chronic phase of atherosclerotic disease, or as a trigger, in the acute phase, increases cardiovascular events. Considering hypertension, the inflammatory process is implicated in its pathophysiology through a bidirectional relationship since arterial hypertension may enhance inflammation and vice versa. Inflammatory biomarkers such as high-sensitivity C-reactive protein, have shown predictive value for both the incidence of hypertension and the clinical outcomes in hypertensive patients. In the present review, data on the association between arterial hypertension and low-grade inflammation will be reported and potential pathophysiological pathways and clinical implications underlying this association will be discussed.

  14. 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.

  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. Role of perfumes in pathogenesis of autism.

    Science.gov (United States)

    Bagasra, Omar; Golkar, Zhabiz; Garcia, Miranda; Rice, Lakya N; Pace, Donald Gene

    2013-06-01

    Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system and underdeveloped olfactory bulb (OB) has been associated with the disorder. It has been reported that the number of children who have ASD has increased considerably since the early 1990 s. In developed countries, it is now reported that 1-1.5% of children have ASD, and in the US it is estimated that one in 88 children suffer from ASD. Currently, there is no known cause for ASD. During the last three decades, the most commonly accepted paradigm about autism is that it is a genetically inherited disease. The recent trio analyses, in which both biological parents and the autistic child's exomes are sequenced, do not support this paradigm. On the other hand, the environmental factors that may induce genetic mutations in vitro have not been clearly identified, and there is little irrefutable evidence that pesticides, water born chemicals, or food preservatives play critical roles in inducing the genetic mutations associated with known intellectual deficiencies that have been linked to autism spectrum disorder (ASD). Here, we hypothesize and provide scientific evidence that ASD is the result of exposure to perfumes and cosmetics. The highly mutagenic, neurotoxic, and neuromodulatory chemicals found in perfumes are often overlooked and ignored as a result of a giant loophole in the Federal Fair Packaging and Labeling Act of 1973, which explicitly exempts fragrance producers from having to disclose perfume ingredients on product labels. We hypothesize that perfumes and cosmetics may be important factors in the pathogenesis of ASD. Synthetic perfumes have gained global utility not only as perfumes but also as essential chemicals in detergents

  18. Psychotherapy for Anxiety in Children With Autism Spectrum Disorder

    Science.gov (United States)

    2016-10-25

    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. 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

  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. 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.

  3. 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

  4. 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.

  5. 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…

  6. 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"…

  7. 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…

  8. The Broad Autism Phenotype Questionnaire: Mothers versus Fathers of Children with an Autism Spectrum Disorder

    Science.gov (United States)

    Seidman, Ifat; Yirmiya, Nurit; Milshtein, Shahaf; Ebstein, Richard P.; Levi, Shlomit

    2012-01-01

    Parents of individuals with autism were examined using the Broad Autism Phenotype Questionnaire (BAPQ; Hurley et al. in "J Autism Dev Disord" 37:1679-1690, 2007) assessing BAP-related personality and language characteristics. The BAPQ was administered to parents as a self-report and as an informant (spouse)-based measure. Results indicated the…

  9. 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…

  10. 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…

  11. The Association between Epilepsy and Autism Symptoms and Maladaptive Behaviors in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Viscidi, Emma W.; Johnson, Ashley L.; Spence, Sarah J.; Buka, Stephen L.; Morrow, Eric M.; Triche, Elizabeth W.

    2014-01-01

    Epilepsy is common in children with autism spectrum disorder (ASD) but little is known about how seizures impact the autism phenotype. The association between epilepsy and autism symptoms and associated maladaptive behaviors was examined in 2,645 children with ASD, of whom 139 had epilepsy, from the Simons Simplex Collection. Children with ASD and…

  12. 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

  13. 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...

  14. Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

    Directory of Open Access Journals (Sweden)

    D. C. Damasceno

    2014-01-01

    Full Text Available Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

  15. Pathophysiological Mechanisms of Severe Anaemia in Malawian Children

    NARCIS (Netherlands)

    M.B. van Hensbroek; J.C.J. Calis; K.S. Phiri; R. de Vet; F. Munthali; R. Kraaijenhagen; H. van den Berg; B. Faragher; I. Bates; M.E. Molyneux

    2010-01-01

    Background: Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success. Methods and Findings: We assessed the contribution of different pathophysiologic

  16. Insulin resistance : pathophysiology in South Asians & therapeutic strategies

    NARCIS (Netherlands)

    Sleddering, Maria Alexandra

    2014-01-01

    This thesis describes the pathophysiology of insulin resistance in the South Asian population and comprises studies on pharmacological and weight loss interventions in insulin resistant patients. Because of the increasing number of patients with obesity and T2DM, more research is needed to identify

  17. Inflammatory Cytokines: Potential Biomarkers of Immunologic Dysfunction in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Ningan Xu

    2015-01-01

    Full Text Available Autism is a disorder of neurobiological origin characterized by problems in communication and social skills and repetitive behavior. After more than six decades of research, the etiology of autism remains unknown, and no biomarkers have been proven to be characteristic of autism. A number of studies have shown that the cytokine levels in the blood, brain, and cerebrospinal fluid (CSF of autistic subjects differ from that of healthy individuals; for example, a series of studies suggests that interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and interferon-γ (IFN-γ are significantly elevated in different tissues in autistic subjects. However, the expression of some cytokines, such as IL-1, IL-2, transforming growth factor-β (TGF-β, and granulocyte-macrophage colony-stimulating factor (GM-CSF, is controversial, and different studies have found various results in different tissues. In this review, we focused on several types of proinflammatory and anti-inflammatory cytokines that might affect different cell signal pathways and play a role in the pathophysiological mechanism of autistic spectrum disorders.

  18. 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,...

  19. 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...

  20. 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 ...

  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 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.

  2. A question of balance: a proposal for new mouse models of autism.

    Science.gov (United States)

    Murcia, Crystal L; Gulden, Forrest; Herrup, Karl

    2005-01-01

    Autism spectrum disorder (ASD) represents a major mental health problem with estimates of prevalence ranging from 1/500 to 1/2000. While generally recognized as developmental in origin, little to nothing is certain about its etiology. Currently, diagnosis is made on the basis of a variety of early developmental delays and/or regressions in behavior. There are no universally agreed upon changes in brain structure or cell composition. No biomarkers of any type are available to aid or confirm the clinical diagnosis. In addition, while estimates of the heritability of the condition range from 60 to 90%, as of this writing no disease gene has been unequivocally identified. The prevalence of autism is three- to four-fold higher in males than in females, but the reason for this sexual dimorphism is unknown. In light of all of these ambiguities, a proposal to discuss potential animal models may seem the heart of madness. However, parsing autism into its individual genetic, behavioral, and neurobiological components has already facilitated a 'conversation' between the human disease and the neuropathology and biochemistry underlying the disorder. Building on these results, it should be possible to not just replicate one aspect of autism but to connect the developmental abnormalities underlying the ultimate behavioral phenotype. A reciprocal conversation such as this, wherein the human disease informs on how to make a better animal model and the animal model teaches of the biology causal to autism, would be highly beneficial.

  3. Clinical practice guideline: screening and diagnosing autism.

    Science.gov (United States)

    Blackwell, J

    2001-12-01

    The clinical practice guideline (CPG) reviewed in this month's column concerns the screening and diagnosis of autism. Autism is the third most common developmental disability and affects more than 1 in 500 children, or nearly 400,000 people in the United States, in some form. Primary care providers of children, including pediatric nurse practitioners (PNPs) and family nurse practitioners (FNPs), should reasonably expect to care for at least one child with autism (CWA). The American Academy of Neurology (AAN) has therefore developed guidelines to help healthcare providers facilitate the early identification of children with autism.

  4. 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...

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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...

  10. 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…

  11. 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 &…

  12. Children with Autism: Sleep Problems and Symptom Severity

    Science.gov (United States)

    Tudor, Megan E.; Hoffman, Charles D.; Sweeney, Dwight P.

    2012-01-01

    Relationships between the specific sleep problems and specific behavioral problems of children with autism were evaluated. Mothers' reports of sleep habits and autism symptoms were collected for 109 children with autism. Unlike previous research in this area, only children diagnosed with autism without any commonly comorbid diagnoses (e.g.,…

  13. 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…

  14. 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

  15. 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

  16. 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

  17. 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....

  18. 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.

  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. 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

  1. 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

  2. Control of hypertension in the critically ill: a pathophysiological approach.

    Science.gov (United States)

    Salgado, Diamantino Ribeiro; Silva, Eliezer; Vincent, Jean-Louis

    2013-01-01

    Severe acute arterial hypertension can be associated with significant morbidity and mortality. After excluding a reversible etiology, choice of therapeutic intervention should be based on evaluation of a number of factors, such as age, comorbidities, and other ongoing therapies. A rational pathophysiological approach should then be applied that integrates the effects of the drug on blood volume, vascular tone, and other determinants of cardiac output. Vasodilators, calcium channel blockers, and beta-blocking agents can all decrease arterial pressure but by totally different modes of action, which may be appropriate or contraindicated in individual patients. There is no preferred agent for all situations, although some drugs may have a more attractive profile than others, with rapid onset action, short half-life, and fewer adverse reactions. In this review, we focus on the main mechanisms underlying severe hypertension in the critically ill and how using a pathophysiological approach can help the intensivist decide on treatment options. PMID:23806076

  3. 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

  4. Hypertrophic cardiomyopathy: Part 1 - Introduction, pathology and pathophysiology

    Directory of Open Access Journals (Sweden)

    Praveen Kerala Varma

    2014-01-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is the most common genetic cardiovascular disease with many genotype and phenotype variations. Earlier terminologies, hypertrophic obstructive cardiomyopathy and idiopathic hypertrophic sub-aortic stenosis are no longer used to describe this entity. Patients present with or without left ventricular outflow tract (LVOT obstruction. Resting or provocative LVOT obstruction occurs in 70% of patients and is the most common cause of heart failure. The pathology and pathophysiology of HCM includes hypertrophy of the left ventricle with or without right ventricular hypertrophy, systolic anterior motion of mitral valve, dynamic and mechanical LVOT obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, and fibrosis. Thorough understanding of pathology and pathophysiology is important for anesthetic and surgical management.

  5. 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

  6. 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...

  7. 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.…

  8. 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...

  9. 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...

  10. 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...

  11. 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

  12. 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 ...

  13. 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...

  14. 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...

  15. 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 .

  16. 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.

  17. 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.)

  18. 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.

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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

  4. A Comprehensive Book on Autism Spectrum Disorders

    Science.gov (United States)

    Mohammadi, Mohammad-Reza, Ed.

    2011-01-01

    The aim of the book is to serve for clinical, practical, basic and scholarly practices. In twentyfive chapters it covers the most important topics related to Autism Spectrum Disorders in the efficient way and aims to be useful for health professionals in training or clinicians seeking an update. Different people with autism can have very different…

  5. 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…

  6. Catatonia in Autism: A Distinct Subtype?

    Science.gov (United States)

    Ghaziuddin, M.; Quinlan, P.; Ghaziuddin, N.

    2005-01-01

    Catatonia is a life-threatening disorder characterized by motor abnormalities, mutism, and disturbances of behaviour, which is increasingly being diagnosed in persons with autism. In this report, we describe the presentation and course of catatonia in an adolescent with autism who responded to electroconvulsive therapy (ECT). The illness started…

  7. Microglia in the Cerebral Cortex in Autism

    Science.gov (United States)

    Tetreault, Nicole A.; Hakeem, Atiya Y.; Jiang, Sue; Williams, Brian A.; Allman, Elizabeth; Wold, Barbara J.; Allman, John M.

    2012-01-01

    We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities. Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had…

  8. Parental Voices and Controversies in Autism

    Science.gov (United States)

    Langan, Mary

    2011-01-01

    Parents of children with autism have played a prominent role in controversies surrounding this condition. Parental voices were critical in challenging the "refrigerator mother" theory and more recently have attracted public attention for claims that autism may be caused by childhood vaccinations and that "unorthodox biomedical" treatments may…

  9. 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…

  10. Unbroken Mirror Neurons in Autism Spectrum Disorders

    Science.gov (United States)

    Fan, Yang-Teng; Decety, Jean; Yang, Chia-Yen; Liu, Ji-Lin; Cheng, Yawei

    2010-01-01

    Background: The "broken mirror" theory of autism, which proposes that a dysfunction of the human mirror neuron system (MNS) is responsible for the core social and cognitive deficits in individuals with autism spectrum disorders (ASD), has received considerable attention despite weak empirical evidence. Methods: In this electroencephalographic…

  11. Health Care: Role of ICT in Autism

    Science.gov (United States)

    Shahid, Hafiza Maimoona; Tariq, Sohaib; Saleem, Imran; Butt, Muhammad Adil; Tariq, Arslan; Tariq, Iqra

    2015-01-01

    Recently, considerable advancement has been seen for educating the people with autism. Research has shown that people with autism reveals positive behavior while interacting with innovative information technologies as compared to therapies. This review focuses on the possible use of ICT in the education and development of the people with autism…

  12. 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.…

  13. 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…

  14. Teaching Children with Autism to Request Information

    Science.gov (United States)

    Shillingsburg, M. Alice; Valentino, Amber L.; Bowen, Crystal N.; Bradley, Danielle; Zavatkay, Dana

    2011-01-01

    Question asking behavior, or requesting information, is often deficient in children with autism and can prove challenging to teach. Currently, there exists a paucity of research regarding the types of teaching strategies that are effective in teaching children with autism this crucial skill. The purpose of the present study was to examine…

  15. Trends in Autism Prevalence: Diagnostic Substitution Revisited

    Science.gov (United States)

    Coo, Helen; Ouellette-Kuntz, Helene; Lloyd, Jennifer E. V.; Kasmara, Liza; Holden, Jeanette J. A.; Lewis, M. E. Suzanne

    2008-01-01

    There has been little evidence to support the hypothesis that diagnostic substitution may contribute to increases in the administrative prevalence of autism. We examined trends in assignment of special education codes to British Columbia (BC) school children who had an autism code in at least 1 year between 1996 and 2004, inclusive. The proportion…

  16. 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…

  17. 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.

  18. [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

  19. 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…

  20. 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,…

  1. Cognitive Underpinnings of Pretend Play in Autism.

    Science.gov (United States)

    Rutherford, M. D.; Rogers, Sally J.

    2003-01-01

    A study examined the cognitive underpinnings of spontaneous and prompted pretend play in 28 children with autism (ages 2-3), 24 children with developmental disorders, and 26 controls (ages 1-3). Children with autism were significantly delayed on pretend play scores. They also had significant deficits in a theory of mind measure. (Contains…

  2. 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…

  3. 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…

  4. New insights into rosacea pathophysiology: a review of recent findings.

    Science.gov (United States)

    Steinhoff, Martin; Schauber, Jürgen; Leyden, James J

    2013-12-01

    Rosacea is a common, chronic inflammatory skin disease of poorly understood origin. Based on its clinical features (flushing, chronic inflammation, fibrosis) and trigger factors, a complex pathobiology involving different regulatory systems can be anticipated. Although a wealth of research has shed new light over recent years on its pathophysiology, the precise interplay of the various dysregulated systems (immune, vascular, nervous) is still poorly understood. Most authors agree on 4 major clinical subtypes of rosacea: erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. Still, it needs to be elucidated whether these subtypes develop in a consecutive serial fashion or if any subtypes may occur individually as part of a syndrome. Because rosacea often affects multiple family members, a genetic component is also suspected, but the genetic basis of rosacea remains unclear. During disease manifestation and early stage, the innate immune system and neurovascular dysregulation seem to be driving forces in rosacea pathophysiology. Dissection of major players for disease progression and in advanced stages is severely hampered by the complex activation of the innate and adaptive immune systems, enhanced neuroimmune communication, profound blood vessel and possibly lymphatic vessel changes, and activation of almost every resident cell in the skin. This review discusses some of the recent findings and aims to build unifying hypotheses for a modern understanding of rosacea pathophysiology.

  5. 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

  6. ASD: What Are Autism Spectrum Disorders? | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... any part of a vaccine or combination of vaccines causes autism. There is also no proof that any material ... research on autism and vaccines. Its Concerns About Vaccines and Autism ( www.cdc.gov/vaccinesafety/Concerns/Autism/Index.html ) ...

  7. Autismo: genética Autism: genetics

    Directory of Open Access Journals (Sweden)

    Abha R Gupta

    2006-05-01

    Full Text Available O autismo é um transtorno fortemente genético, com uma herdabilidade estimada de mais de 90%. Uma combinação de heterogeneidade fenotípica e o provável envolvimento de múltiplos loci que interagem entre si dificultam os esforços de descobertas de genes. Conseqüentemente, a etiologia genética dos transtornos relacionados ao autismo permanece, em grande parte, desconhecida. Nos últimos anos, a convergência entre tecnologias genômicas em rápido avanço, a finalização do projeto genoma humano e os crescentes e exitosos esforços em colaboração para aumentar o número de pacientes disponíveis para estudo conduziram às primeiras pistas sólidas sobre as origens biológicas desses transtornos. Este artigo revisará a literatura até nossos dias, resumindo os resultados de estudos de ligação genética, citogenéticos e de genes candidatos com um foco no progresso recente. Além disso, são consideradas as vias promissoras para pesquisas futuras.Autism is a strongly genetic disorder, with an estimated heritability of greater than 90%. A combination of phenotypic heterogeneity and the likely involvement of multiple interacting loci have hampered efforts at gene discovery. As a consequence, the genetic etiology of the spectrum of autism related disorders remains largely unknown. Over the past several years, the convergence of rapidly advancing genomic technologies, the completion of the human genome project, and increasingly successful collaborative efforts to increase the number of patients available for study have led to the first solid clues to the biological origins of these disorders. This paper will review the literature to date summarizing the results of linkage, cytogenetic, and candidate gene studies with a focus on recent progress. In addition, promising avenues for future research are considered.

  8. 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.

  9. Core Challenges of Autism. Sensory aspects of autism

    Directory of Open Access Journals (Sweden)

    Nason William

    2016-10-01

    Full Text Available An american clincal psychologist Bill Nason tells us about the differences in ways of functioning between people on the autistic spectrum and neurotypical people. The third part of his Blue book «The Autism Discussion Page» talks about the sensory differences in autistic people. Sensory hypersensitivity, fragmented or distorted perception, problems of sensoru processing — these are the differences that make the external world experience very special, overwhelming and even painful. The author gives the signs of hyper- and hypo-sensitivity in basical sensory areas. Translated from English by L.G. Borodina

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. Ubiquinol Improves Symptoms in Children with Autism

    Directory of Open Access Journals (Sweden)

    Anna Gvozdjáková

    2014-01-01

    Full Text Available Background. Autism is a spectrum of neurodevelopmental disorders with manifestation within 3 years after birth. Manifestations of autism include behavior problems (hyperactivity, toys destruction, self-harm, and agression and sleep and eating disorders. Etiology of autism is poorly understood. Oxidative stress and antioxidants can participate in pathobiochemical mechanisms of autism. Methods. Twenty-four children, aged 3–6 years, with autism according to the DSM IV criteria and using CARS were included in the study. Concentrations of CoQ10-TOTAL, γ- and α-tocopherol, β-carotene, and lipid peroxidation were determined in plasma before and after three months of supportive therapy with ubiquinol at a daily dose 2×50 mg. Data on behavior of the children were collected from parents at the same time. Results. Ubiquinol supportive therapy improved symptoms in children with autism, as communication with parents (in 12%, verbal communication (in 21%, playing games of children (in 42%, sleeping (in 34%, and food rejection (in 17%, with CoQ10-TOTAL plasma level above 2.5 μmol/L. Conclusions. Beneficial effect of ubiquinol in children with autism has been demonstrated for the first time. We assume that plasma concentration of CoQ10-TOTAL and lipid peroxidation could be used as relevant biomarkers of ubiquinol supportive therapy.

  17. 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

  18. Neural Correlates of Visuomotor Learning in Autism.

    Science.gov (United States)

    Sharer, Elizabeth; Crocetti, Deana; Muschelli, John; Barber, Anita D; Nebel, Mary Beth; Caffo, Brian S; Pekar, Jim J; Mostofsky, Stewart H

    2015-12-01

    Motor impairments are prevalent in children with autism spectrum disorder. The Serial Reaction Time Task, a well-established visuomotor sequence learning probe, has produced inconsistent behavioral findings in individuals with autism. Moreover, it remains unclear how underlying neural processes for visuomotor learning in children with autism compare to processes for typically developing children. Neural activity differences were assessed using functional magnetic resonance imaging during a modified version of the Serial Reaction Time Task in children with and without autism. Though there was no group difference in visuomotor sequence learning, underlying patterns of neural activation significantly differed when comparing sequence (i.e., learning) to random (i.e., nonlearning) blocks. Children with autism demonstrated decreased activity in brain regions implicated in visuomotor sequence learning: superior temporal sulcus and posterior cingulate cortex. The findings implicate differences in brain mechanisms that support initial sequence learning in autism and can help explain behavioral observations of autism-associated impairments in skill development (motor, social, communicative) reliant on visuomotor integration.

  19. 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

  20. 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.

  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. Neurogenesis and Alzheimer's disease: biology and pathophysiology in mice and men

    NARCIS (Netherlands)

    M.W. Marlatt; P.J. Lucassen

    2010-01-01

    The hippocampus is critical for learning and memory and heavily affected in dementia. The presence of stem cells in this structure has led to an increased interest in the phenomenon of adult neurogenesis and its role in hippocampal functioning. Not surprising, investigators of Alzheimer's disease ha

  6. [Advances in the research of biological characters and pathophysiological effects of dendritic epidermal T lymphocytes].

    Science.gov (United States)

    Li, Y S; He, W F; Wu, J

    2016-01-01

    The maturation of dendritic epidermal T lymphocytes (DETCs) in thymus needs ligand-mediated positive selection, and positive selection together with V3γ(+) γδT lymphocytes intrinsic program features order DETCs to specifically migrate to epidermis. Positive selection promotes DETCs to express CD122, which is vital for DETCs to survive and proliferate in skin. DETCs possess memory-like phenotype and are able to rapidly respond to danger signals when they move out from thymus. NKG2D, junctional adhesion molecule-like protein and 2B4 are demonstrated to participate in DETCs activation, except for ligands of T lymphocytes receptor. Effective DETCs secrete cytokines such as interferon-γ, insulin-like growth factor-2, keratinocyte growth factor and gain cytotoxicity to directly kill tumor cells. DETCs participate in skin immune surveillance, regulation of local inflammation, and wound healing promotion. PMID:27426071

  7. 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...

  8. 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 ...

  9. 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...

  10. 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.

  11. [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

  12. 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)

  13. 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

  14. 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...... 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...... minimal invasive surgery, multi-modal non-opioid pain management and pharmacological manipulation of the inflammatory response and sleep architecture....

  15. 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....... 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...

  16. Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management.

    Science.gov (United States)

    Singhal, Rajni; Brimble, K Scott

    2006-01-01

    Patients with the nephrotic syndrome are at increased risk of developing venous and arterial thromboembolism, the most common of which is renal vein thrombosis. There are several unanswered or controversial issues relating to the nephrotic syndrome and thromboembolism, which include the mechanism of thromboembolism, and optimal diagnostic and anticoagulant management strategies. This review will discuss several of these issues: the epidemiology and clinical spectrum of thromboembolic disease occurring in patients with the nephrotic syndrome; the pathophysiology of the hypercoagulable state associated with the nephrotic syndrome; the diagnosis of renal vein thrombosis in the nephrotic syndrome; and the evidence for prophylactic and therapeutic anticoagulation strategies in such patients.

  17. 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.

  18. 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...

  19. 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, ...

  20. 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.

  1. Impaired vitality form recognition in autism.

    Science.gov (United States)

    Rochat, Magali J; Veroni, Vania; Bruschweiler-Stern, Nadia; Pieraccini, Cinzia; Bonnet-Brilhault, Frédérique; Barthélémy, Catherine; Malvy, Joëlle; Sinigaglia, Corrado; Stern, Daniel N; Rizzolatti, Giacomo

    2013-08-01

    Along with the understanding of the goal of an action ("what" is done) and the intention underlying it ("why" it is done), social interactions largely depend on the appraisal of the action from the dynamics of the movement: "how" it is performed (its "vitality form"). Do individuals with autism, especially children, possess this capacity? Here we show that, unlike typically developing individuals, individuals with autism reveal severe deficits in recognizing vitality forms, and their capacity to appraise them does not improve with age. Deficit in vitality form recognition appears, therefore, to be a newly recognized trait marker of autism.

  2. [Autism-friendly dental care].

    Science.gov (United States)

    Kind, L S; van Gemert-Schriks, M C M; Elhorst, J H

    2016-02-01

    Autism Spectrum Disorder (ASD) occurs in approximately 1% of the Dutch population. Among the group of patients with this disorder, there is a substantial diversity regarding skills, intelligence and treatability. However, there are also common characteristics; people with ASD often have difficulty with social interaction, communication, and exhibit typical patterns of behaviour. Therefore, problems may arise in the various areas of development, such as language development and responding to sensory stimuli. Dental practitioners will also be confronted with individuals with ASD. Care can be significantly improved, considering that negative experiences and dental anxiety are widespread at this time.

  3. Cortical interneuron dysfunction in epilepsy associated with autism spectrum disorders.

    Science.gov (United States)

    Jacob, John

    2016-02-01

    Autism and epilepsy are two associated disorders that are highly prevalent, share common developmental origins, and demonstrate substantial heritability. In this review, cross-disciplinary data in a rapidly evolving field that bridges neurology and psychiatry are synthesized to identify shared biologic mechanisms. The relationship between these debilitating, lifelong conditions is examined at the clinical, genetic, and neurophysiologic levels in humans and in animal models. Scopus and PubMed searches were used to identify relevant literature. Clinical observations have prompted speculation about the interdependence of autism and epilepsy, but causal relationships have proved difficult to determine. Despite their heritability, the genetic basis of autism spectrum disorder (ASD) and epilepsy has remained largely elusive until the advent of next-generation sequencing. This approach has revealed that mutations that are either causal or confer an increased disease risk are found in numerous different genes, any one of which accounts for only a small percentage of cases. Conversely, even cases with identical clinical phenotypes can be genetically heterogeneous. Candidate gene identification has facilitated the development of mouse genetic models, which in parallel with human studies have implicated shared brain regions and circuits that mediate disease expression. Diverse genetic causes of ASD and epilepsy converge on cortical interneuron circuits as one important mediator of both disorders. Cortical interneurons are among the most diverse cell types in the brain and their unique chemical and electrical coupling exert a powerful inhibitory influence on excitatory neurons via the release of the neurotransmitter, γ-aminobutyric acid (GABA). These multifaceted approaches have validated theories derived from the field of developmental neurobiology, which propose that the neurologic and neuropsychiatric manifestations are caused by an altered ratio of excitation to

  4. 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...

  5. Pathophysiological mechanisms of local (pulmonary inflammatory reaction at the traumatic disease of the spinal cord

    Directory of Open Access Journals (Sweden)

    Uljanov V.Yu.

    2015-06-01

    Full Text Available Objective: to study pathophysiological mechanisms of local (pulmonary inflammatory reaction in the sharp and early periods of a traumatic disease of a spinal cord on the basis of an assessment of dynamic changes of cellular structure of a bronchial secret, an alveolar epithelium and a microbic landscape of a tracheobronchial tree at patients with the complicated damages of cervical department of a backbone. Materials and methods. Methods of cytologic, immunofermental and bacteriological researches at 40 patients with the complicated damages of cervical department of a backbone to dynamics studied the contents the neutrofil of leukocytes and alveolar macrophages in a bronchial secret, a mutsin antigene 3GE5 and surfaktant protein D in serum of blood, character of microbic flora of a tracheobronchial tree and its some biological properties. Results. Activation of local (pulmonary inflammatory reaction in the sharp and early periods of a traumatic disease of a spinal cord is characterized by increase of the contents the neutrofil of leukocytes in a bronchial secret for the 7-14th days, lymphocyts — for the 1-14th days increase in the maintenance of a mutsin antigene 3GE5 for the 14th days and SP-D —for the 1-14th days, allocation from respiratory substrata of opportunistic microorganisms in clinically significant concentration; knocking over — increase of quantity of alveolar macrophages, decrease in the maintenance of a mutsin antigene 3GE5 and SP-D for the 21-30th days and sanitation of a locus of an infection in a tracheobronchial tree. Conclusion. The pathophysiological mechanisms defining changes of cellular structure of a bronchial secret, an alveolar epithelium and a microbic landscape of a tracheobronchial tree in the sharp and early periods of a traumatic disease of a spinal cord play an important role in development of organ (pulmonary inflammatory reaction.

  6. The interaction between the immune system and epigenetics in the etiology of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Stefano Nardone

    2016-07-01

    Full Text Available Recent studies have firmly established that the etiology of autism includes both genetic and environmental components. However, we are only just beginning to elucidate the environmental factors that might be involved in the development of autism, as well as the molecular mechanisms through which they function. Mounting epidemiological and biological evidence suggest that prenatal factors that induce a more activated immune state in the mother are involved in the development of autism. In parallel, molecular studies have highlighted the role of epigenetics in brain development as process susceptible to environmental influences and potentially causative of ASD. In this review, we will discuss converging evidence for a multidirectional interaction between immune system activation in the mother during pregnancy and epigenetic regulation in the brain of the fetus that may cooperate to produce an autistic phenotype. This interaction includes immune factor-induced changes in epigenetic signatures in the brain, dysregulation of epigenetic modifications specifically in genomic regions that encode immune functions, and aberrant epigenetic regulation of microglia. Overall, the interaction between immune system activation in the mother and the subsequent epigenetic dysregulation in the developing fetal brain may be a main consideration for the environmental factors that cause autism.

  7. 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.

  8. 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.

  9. 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 ...

  10. 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.

  11. Pathophysiological Implication of Computed Tomography Images of Chronic Pulmonary Aspergillosis.

    Science.gov (United States)

    Ando, Tsunehiro; Tochigi, Naobumi; Gocho, Kyoko; Moriya, Atsuko; Ikushima, Soichiro; Kumasaka, Toshio; Takemura, Tamiko; Shibuya, Kazutoshi

    2016-03-23

    Chronic pulmonary aspergillosis (CPA) is a refractory disorder that needs long-term antifungal treatment and occasionally results in fatal respiratory failure and hemoptysis. However, the pathological features of the disorder have not been thoroughly delineated. Thirty cases were therefore analyzed clinically and histologically to elucidate the pathophysiology of CPA. The subjects comprised 14 individuals who underwent surgical removal and 16 patients who died. No subject exhibited a severely immunocompromised state. The main symptoms included cough, hemosputum, and dyspnea. Chest computed tomography (CT) findings revealed a cavity, fungus ball, and consolidation and/or ground glass opacity (GGO); 27 serial CT scans showed enlarged consolidation and/or GGO (70%), dilatation of the cavity (26%), and extension to the opposite lung (22%). Histopathological findings revealed a cavity with ulceration, bronchitis, and various degrees of organizing pneumonia (OP) that were correlated with the area of consolidation and GGO on the CT scan. The essential pathophysiology of CPA can be understood as an active state of ulceration of the cavity and/or erosive bronchitis caused by contact with the fungus ball, which may play a significant role in the development of OP. Consequently, OP is thought to reflect respiratory failure that relates to the prognosis of CPA. PMID:26166500

  12. Etiology, pathophysiology and conservative management of degenerative joint disease

    Directory of Open Access Journals (Sweden)

    Jandrić Slavica

    2002-01-01

    Full Text Available Etiology of degenerative joint diseases Etiology of degenerative joint diseases is still not clearly understood and there is no specific management for this group of diseases. Various pathological conditions cause damage of the articular cartilage and lead to clinically and radiographically recognized impairment. Biomechanical, metabolic, genetic factors inflammation and other risk factors contribute to development of osteoarthrosis. Pathophysiology of degenerative joint diseases Osteoarthrosis is characterized by progressive erosion of articular cartilage and bone overgrowth at the joint margins. Cartilage integrity requires balance between synthesis and degradation of matrix components. Chondrocytes react to various mechanical and chemical stresses in order to stabilize and restore the tissue. Failures in stabilizing and restoring the tissue lead to cartilage degeneration that may be irreversibile. For better understanding of conservative management of degenerative joint diseases it is important to know the impact of pathophysiology mechanisms on development of degenerative joint diseases. There is great variability in the rate of progression of erosive processes in articular cartilage in clinical radiographic signs and course of the disease. This is in relation with many factors, as well as with management and response to therapy. Treatment of degenerative joint diseases Treatment should vary depending on the severity of disease and patient's expectations and level of activity. Besides analgesic and anti-inflammatory drugs, conventional and not conventional treatment and techniques can be used for management of osteoarthrosis. Physical therapy and exercises are very important for maintaining muscle strength, joint stability and mobility, but should be closely monitored for optimal efficacy.

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

    International Nuclear Information System (INIS)

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

  14. Extra-osseous uterine pathophysiology demonstrated on skeletal scintigraphy

    International Nuclear Information System (INIS)

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

  15. Etiology and pathophysiology of inflammatory bowel disease--environmental factors.

    Science.gov (United States)

    Andus, T; Gross, V

    2000-01-01

    Environmental factors play an important role in the pathophysiology of inflammatory bowel disease. There is a strong and consistent association between smoking and Crohn's disease, and between nonsmoking and ulcerative colitis. Despite extensive research, the exact pathophysiological mechanisms for these associations remain unclear. In spite of this, some clinical trials with nicotine-patches showed beneficial effects for the treatment of ulcerative colitis. Associations of Crohn's disease and ulcerative colitis with other environmental factors are weaker like the association with use of oral contraceptives or those less well investigated such as the association with childhood hygiene. Most studies suggesting a potential pathogenetic role of Mycobacterium paratuberculosis or an effect of tuberculostatic therapy in Crohn's disease could not be reproduced by others. Perinatal or childhood infections by viruses like measles are heavily debated, but not proven to be causal for inflammatory bowel disease. Coagulation disorders have been described as protecting from inflammatory bowel disease, suggesting hypercoagulability to be a pathogenetic factor. Some studies described that appendectomy may prevent the onset of ulcerative colitis in man and mice. Other environmental factors such as hydrogen sulfide, tonsillectomy, diet, blood transfusions, and Listeria also require confirmation. There are, however, convincing data from genetic animal models and twin studies that environmental factors as the intestinal bacterial flora interact with susceptible hosts to cause inflammatory bowel disease. Inflammatory bowel diseases have multifactorial etiologies, which require a differentiated approach for treatment and prevention. PMID:10690583

  16. Recent developments in the pathophysiology of irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy

    2015-07-01

    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 predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients. PMID:26167065

  17. Pathophysiology of septic shock and implications for therapy.

    Science.gov (United States)

    Barron, R L

    1993-11-01

    Current knowledge about the pathophysiology of septic shock is reviewed, and biotechnology-based therapies under development are discussed. Patients with septic shock begin their clinical course with leukocytosis, fever, tachycardia, tachypnea, and organ hypoperfusion; shock ensues as immunologic and vasoactive mediators produce hypotension. There are many metabolic and cardiovascular responses, and single- or multiple-organ failure is common. Patients may experience adult respiratory distress syndrome. A multitude of endogenous and exogenous factors have been linked to the pathophysiology of sepsis and septic shock, including (1) endotoxin from gram-negative bacteria, (2) peptidoglycan and exotoxins from gram-negative bacteria, (3) endotoxin-binding proteins and receptors, (4) bactericidal proteases, (5) exotoxins from gram-positive bacteria, (6) acute-phase proteins and proteases, (7) cytokines, (8) arachidonic acid metabolites, (9) complement, (10) beta-endorphin, (11) histamine, (12) stimulation of intrinsic and extrinsic coagulation pathways and proteases, and (13) endothelium-derived factors and adhesion molecules. Molecular entities and strategies under development to combat septic shock include monoclonal antibodies to endotoxin, active immunization with lipid-A analogues, bactericidal permeability-increasing protein, interleukin inhibitors, and inhibitors of tumor necrosis factor-alpha. Successful treatment of septic shock will probably require a combination of agents, including antimicrobials. An ideal goal for biotechnology in the area of septic shock is to prevent invading pathogens from overstimulating the host's immune system and to systematically eliminate those pathogens. Biotechnology is opening new avenues to the treatment of septic shock.

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

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Toft, Palle

    2009-01-01

    ABSTRACT: BACKGROUND: 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 in......ABSTRACT: BACKGROUND: 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 and immunological components and the extent correlates with the magnitude of the tissue injury. After trauma...... and uncomplicated surgery a delicate balance between pro- and anti-inflammatory mediators is observed.Trauma patients are, however, often exposed, not only to the trauma, but to several evens in the form of initial surgery and later final reconstructive surgery. In this case immune paralysis associated...

  19. Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques

    Science.gov (United States)

    Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F.; Ebihara, Hideki; Scott, Dana P.; Hjelle, Brian; Feldmann, Heinz

    2014-01-01

    The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases. PMID:24778254

  20. Ceramide Signaling and Metabolism in Pathophysiological States of the Lung.

    Science.gov (United States)

    Petrache, Irina; Berdyshev, Evgeny V

    2016-01-01

    Following the discovery of ceramide as the central signaling and metabolic relay among sphingolipids, studies of its involvement in lung health and pathophysiology have exponentially increased. In this review, we highlight key studies in the context of recent progress in metabolomics and translational research methodologies. Evidence points toward an important role for the ceramide/sphingosine-1-phosphate rheostat in maintaining lung cell survival, vascular barrier function, and proper host response to airway microbial infections. Sphingosine kinase 1 has emerged as an important determinant of sphingosine-1-phosphate lung levels, which, when aberrantly high, contribute to lung fibrosis, maladaptive vascular remodeling, and allergic asthma. New sphingolipid metabolites have been discovered as potential biomarkers of several lung diseases. Although multiple acute and chronic lung pathological conditions involve perturbations in sphingolipid signaling and metabolism, there are specific patterns, unique sphingolipid species, enzymes, metabolites, and receptors, which have emerged that deepen our understanding of lung pathophysiology and inform the development of new therapies for lung diseases. PMID:26667073