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Sample records for disorders involving calcium

  1. [Bone involvement in idiopathic calcium lithiasis].

    Science.gov (United States)

    Ghazali, A; Bataille, P; Solal, M C; Marié, A; Brazier, M; Sebert, J L; Prin, L; Fournier, A

    1995-01-01

    Bone involvement in idiopathic calcium nephrolithiasis is characterized by the following abnormalities: a) the bone density is decreased, the severity of bone loss being dependent upon the existence of hypercalciuria and upon the pathophysiology of this latter: it is inconsistent in the absence of hypercalciuria or when hypercalciuria is of the absorptive type I or II, whereas it is almost constant in fasting hypercalciuria without secondary hyperparathyroidism and constant and severe in the rare true renal hypercalciuria. b) The bone histology (which has been evaluated only in idiopathic hypercalciuric patients) mainly shows a defect in bone formation at the exception of the rare renal hypercalciuria. Osteoclastic hyperresorption is only seen in this latter type of hypercalciuria whereas in the other types of hypercalciuria only an increase of the total or inactive resorption surface is observed. This phenomenon is possibly explained only by a delayed refilling of the resorption lacunae secondary to the decreased bone formation. The osteoid thickness is either normal or decreased despite decrease in mineralization apposition rate which seems therefore to be secondary to the decreased bone formation. c) Symptomatic bone disease in hypercalciuric stone formers is exceptional and always related to a severe long term calcium restriction. d) The biochemical markers of bone resorption tend to be increased in idiopathic hypercalciuria. Hydroxyprolinuria is more often elevated than pyridinolinuria. However pyridinolinuria is negatively correlated to bone density. The contrast between the increase of these bone resorption markers and the usual normality of plasma PTH and of the osteoclastic resorptive surfaces, suggest the role of meat induced acid load which may favor inactive resorption by dissolution of bone buffers. A disturbed profile synthesis of cytokines which induce differentiation and proliferation of the osteoclasts and which modulate the osteoblastic

  2. Dental Problems in Calcium Metabolism Disorders

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    Ali Rabbani M.D.

    2011-06-01

    Full Text Available Background: Calcium metabolism disorders can be acute or chronic and chronic disorders can cause different disease states such as dental problems. Methods: In this descriptive cross-sectional study done in Children's Medical Center affiliated to Tehran University of Medical Sciences during 2005-2009, all (93 patients with hypoparathyroidism, nutritional rickets, hypophosphatemic rickets and renal osteodysthrophy from the endocrinology and nephrology departments of the Center were referred to a dentist there for orodental examination. Subsequently, the frequency of dental problems including taurodontism, enamel hypoplasia, dental abscess, dental caries and gingivitis were recorded and analyzed. Results: Nutritional rickets was the most common disorder in this study and delay in dentition was the most frequent dental problem in the patients (61.9%. Most cases of taurdontism and enamel hypoplasia were seen in patients with hypoparathyroidism (33% and 50%, respectively. Dental abscess, dental caries and gingivitis were more common in patients with renal osteodysthrophia (50%, 90% and 20%, respectively. In addition, dental caries and delay in dentition were the most prevalent disorders in this study (69.8% and 49.5%, respectively. Conclusion: According to the above findings, it seems that effective screening, regular periodic examinations, proper diagnosis and timely treatment of dental diseases are the main principles of prevention of orodental problems. Moreover, dentists as well as pediatricians should be aware of the features of the aforesaid disorders which lead to dental problems so that early intervention could prevent subsequent serious and more invasive dental problems.

  3. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

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    Yajin Liao

    2017-02-01

    Full Text Available The mitochondrial calcium uniporter (MCU—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP; however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.

  4. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

    Science.gov (United States)

    Liao, Yajin; Dong, Yuan; Cheng, Jinbo

    2017-01-01

    The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders. PMID:28208618

  5. Mechanisms involved in calcium deficiency development in tomato fruit in response to gibberellins

    Science.gov (United States)

    Although gibberellins (GAs) have been shown to induce the calcium deficiency disorder, blossom-end rot (BER), development in tomato fruit (Solanum lycopersicum), the mechanisms involved remain largely unexplored. Our objectives were to better understand how GAs and a GA biosynthesis inhibitor affect...

  6. Voltage-gated Calcium Channels and Autism Spectrum Disorders.

    Science.gov (United States)

    Breitenkamp, Alexandra F; Matthes, Jan; Herzig, Stefan

    2015-01-01

    Autism spectrum disorder is a complex-genetic disease and its etiology is unknown for the majority of cases. So far, more than one hundred different susceptibility genes were detected. Voltage-gated calcium channels are among the candidates linked to autism spectrum disorder by results of genetic studies. Mutations of nearly all pore-forming and some auxiliary subunits of voltage gated calcium channels have been revealed from investigations of autism spectrum disorder patients and populations. Though there are only few electrophysiological characterizations of voltage-gated calcium channel mutations found in autistic patients these studies suggest their functional relevance. In summary, both genetic and functional data suggest a potential role of voltage-gated calcium channels in autism spectrum disorder. Future studies require refinement of the clinical and systems biological concepts of autism spectrum disorder and an appropriate holistic approach at the molecular level, e.g. regarding all facets of calcium channel functions.

  7. Involvement of TRPV2 and SOCE in calcium influx disorder in DMD primary human myotubes with a specific contribution of α1-syntrophin and PLC/PKC in SOCE regulation.

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    Harisseh, Rania; Chatelier, Aurélien; Magaud, Christophe; Déliot, Nadine; Constantin, Bruno

    2013-05-01

    Calcium homeostasis is critical for several vital functions in excitable and nonexcitable cells and has been shown to be impaired in many pathologies including Duchenne muscular dystrophy (DMD). Various studies using murine models showed the implication of calcium entry in the dystrophic phenotype. However, alteration of store-operated calcium entry (SOCE) and transient receptor potential vanilloid 2 (TRPV2)-dependant cation entry has not been investigated yet in human skeletal muscle cells. We pharmacologically characterized basal and store-operated cation entries in primary cultures of myotubes prepared from muscle of normal and DMD patients and found, for the first time, an increased SOCE in DMD myotubes. Moreover, this increase cannot be explained by an over expression of the well-known SOCE actors: TRPC1/4, Orai1, and stromal interaction molecule 1 (STIM1) mRNA and proteins. Thus we investigated the modes of regulation of this cation entry. We firstly demonstrated the important role of the scaffolding protein α1-syntrophin, which regulates SOCE in primary human myotubes through its PDZ domain. We also studied the implication of phospholipase C (PLC) and protein kinase C (PKC) in SOCE and showed that their inhibition restores normal levels of SOCE in DMD human myotubes. In addition, the involvement of TRPV2 in calcium deregulation in DMD human myotubes was explored. We showed an abnormal elevation of TRPV2-dependant cation entry in dystrophic primary human myotubes compared with normal ones. These findings show that calcium homeostasis mishandling in DMD myotubes depends on SOCE under the influence of Ca(2+)/PLC/PKC pathway and α1-syntrophin regulation as well as on TRPV2-dependant cation influx.

  8. Genetic disorders involving adrenal development.

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    Lin, Lin; Ferraz-de-Souza, Bruno; Achermann, John C

    2007-01-01

    The past decade has seen significant advances in our understanding of the genetic aetiology of several forms of adrenal failure that present in infancy or childhood. Several of these disorders affect adrenal development and are termed 'adrenal hypoplasia'. These conditions can be broadly divided into: (1) secondary forms of adrenal hypoplasia due to panhypopituitarism (e.g. HESX1, LHX4, SOX3) or abnormalities in ACTH synthesis (TPIT) or processing (e.g. POMC or PC1); (2) adrenal hypoplasia as part of an ACTH resistance syndrome [MC2R/ACTH receptor, MRAP, AAAS (triple A syndrome)], and (3) primary defects in the development of the adrenal gland itself (primary adrenal hypoplasia). Primary adrenal hypoplasia most commonly occurs in an X-linked form due to mutations in the nuclear receptor DAX1 (NR0B1) but can occur in a poorly understood recessive form or as part of the IMAGe (intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia, genitourinary anomalies) syndrome. Defining the molecular basis of these conditions can have significant clinical implications for management, counselling and presymptomatic diagnosis, as well as providing fascinating insight into normal and abnormal mechanisms of adrenal development in humans.

  9. Calcium and bone disorders in pregnancy

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    Shriraam Mahadevan

    2012-01-01

    Full Text Available Significant transplacental calcium transfer occurs during pregnancy, especially during the last trimester, to meet the demands of the rapidly mineralizing fetal skeleton. Similarly, there is an obligate loss of calcium in the breast milk during lactation. Both these result in considerable stress on the bone mineral homeostasis in the mother. The maternal adaptive mechanisms to conserve calcium are different in pregnancy and lactation. During pregnancy, increased intestinal absorption of calcium from the gut mainly due to higher generation of calcitriol (1,25 dihydroxy vitamin D helps in maintaining maternal calcium levels. On the other hand, during lactation, the main compensatory mechanism is skeletal resorption due to increased generation of parathormone related peptide (PTHrP from the breast. Previous studies suggest that in spite of considerable changes in bone mineral metabolism during pregnancy, parity and lactation are not significantly associated with future risk for osteoporosis. However, in India, the situation may not be the same as a significant proportion of pregnancies occur in the early twenties when peak bone mass is not yet achieved. Further, malnutrition, anemia and vitamin D deficiency are commonly encountered in this age group. This may have an impact on future bone health of the mother. It may also probably provide an opportunity for health care providers for prevention. Other metabolic bone diseases like hypoparathyroidism, hyperparathyroidism and pseudohypoparathyroidism are rarely encountered in pregnancy. Their clinical implications and management are also discussed.

  10. P12 - PTHC1: A Continuing Cell Line Expressing PTH and Genes Involved in Calcium Homeostasis

    OpenAIRE

    Fabbri, S.; Mazzotta, C.; Ciuffi, S.; Mavilia, C; Galli, G; Zonefrati, R.; Strigoli, D.; Cavalli, L.; Cavalli, T.; Brandi, M L

    2010-01-01

    The main organs regulating serum levels of ionised calcium (Ca2+) are the parathyroids, which are composed of two different cell types: chief cells and oxyphil cells. Chief cells, through the calcium sensing receptor (CaSR), are affected by changes in calcium concentration, modifying PTH secretion in proportion to calcium levels. Current understanding of calcium regulation mechanisms connected to PTH and of the signalling pathways involved derive from in vitro studies carried out on primary c...

  11. Calcium channelopathies in inherited neurological disorders: relevance to drug screening for acquired channel disorders.

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    Lory, Philippe; Mezghrani, Alexandre

    2010-07-01

    Mutations located in the human genes encoding voltage-gated calcium channels are responsible for a variety of diseases referred to as calcium channelopathies, including familial hemiplegic migraine, episodic ataxia type 2, spinocerebellar ataxia type 6, childhood absence epilepsy and autism spectrum disorder, all of which are rare inherited forms of common neurological disorders. The genetic basis of these calcium channelopathies provides a unique opportunity to investigate their underlying mechanisms from the molecular to whole-organism levels. Studies of channelopathies provide insight on the relationships between channel structure and function, and reveal diverse and unexpected physiological roles for the channels. Importantly, these studies may also lead to the identification of drugs for the treatment of genetically acquired channel disorders, as well as to novel therapeutic practices. In this feature review, recent findings regarding neurological calcium channelopathies are discussed.

  12. Major Channels Involved In Neuropsychiatric Disorders And Therapeutic Perspectives

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    Paola eImbrici

    2013-05-01

    Full Text Available Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders or schizophrenia. Moreover, point mutations in calcium, sodium and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium and potassium channels in bipolar disorder, schizophrenia and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests.

  13. Cyclical Changes in Calcium Metabolism across the Menstrual Cycle in Women with Premenstrual Dysphoric Disorder

    National Research Council Canada - National Science Library

    Thys-Jacobs, Susan; McMahon, Don; Bilezikian, John P

    2007-01-01

    ...: Our objective was to measure fluctuations and group differences in calcium-regulating hormones across the menstrual cycle in women with and without premenstrual dysphoric disorder (PMDD). Design...

  14. Panic Disorder: Is the PAG Involved?

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    Cristina Marta Del-Ben

    2009-01-01

    Full Text Available Data from studies with humans have suggested that abnormalities of midbrain structures, including the periaqueductal gray matter (PAG, could be involved in the neurobiology of panic disorder (PD. The electrical stimulation of the PAG in neurosurgical patients induces panic-like symptoms and the effect of drugs that are effective in the treatment of PD in the simulation of public speaking model of anxiety is in agreement with data from animal models of PD. Structural neuroimaging studies have shown increases in gray matter volume of midbrain and pons of PD patients. There is also evidence of lower serotonin transporter and receptor binding, and increases of metabolism in the midbrain of PD patients. Nevertheless, these midbrain abnormalities can not be considered as specific findings, since neuroimaging data indicate that PD patients have abnormalities in other brain structures that process fear and anxiety.

  15. Panic disorder: is the PAG involved?

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    Del-Ben, Cristina Marta; Graeff, Frederico Guilherme

    2009-01-01

    Data from studies with humans have suggested that abnormalities of midbrain structures, including the periaqueductal gray matter (PAG), could be involved in the neurobiology of panic disorder (PD). The electrical stimulation of the PAG in neurosurgical patients induces panic-like symptoms and the effect of drugs that are effective in the treatment of PD in the simulation of public speaking model of anxiety is in agreement with data from animal models of PD. Structural neuroimaging studies have shown increases in gray matter volume of midbrain and pons of PD patients. There is also evidence of lower serotonin transporter and receptor binding, and increases of metabolism in the midbrain of PD patients. Nevertheless, these midbrain abnormalities can not be considered as specific findings, since neuroimaging data indicate that PD patients have abnormalities in other brain structures that process fear and anxiety.

  16. Support for calcium channel gene defects in autism spectrum disorders

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    Lu Ake Tzu-Hui

    2012-12-01

    Full Text Available Abstract Background Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD. Calcium channel genes (CCG contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis. Methods A total of 2,176 single-nucleotide polymorphisms (SNP (703 genotyped and 1,473 imputed covering the genes that encode the α1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP. SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel. Results Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations. Conclusions These associations support a role for common CCG SNPs in ASD.

  17. Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis

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    Hannan, Fadil M; Babinsky, Valerie N

    2016-01-01

    The extracellular calcium (Ca2+o)-sensing receptor (CaSR) is a family C G protein-coupled receptor, which detects alterations in Ca2+o concentrations and modulates parathyroid hormone secretion and urinary calcium excretion. The central role of the CaSR in Ca2+o homeostasis has been highlighted by the identification of mutations affecting the CASR gene on chromosome 3q21.1. Loss-of-function CASR mutations cause familial hypocalciuric hypercalcaemia (FHH), whereas gain-of-function mutations lead to autosomal dominant hypocalcaemia (ADH). However, CASR mutations are only detected in ≤70% of FHH and ADH cases, referred to as FHH type 1 and ADH type 1, respectively, and studies in other FHH and ADH kindreds have revealed these disorders to be genetically heterogeneous. Thus, loss- and gain-of-function mutations of the GNA11 gene on chromosome 19p13.3, which encodes the G-protein α-11 (Gα11) subunit, lead to FHH type 2 and ADH type 2, respectively; whilst loss-of-function mutations of AP2S1 on chromosome 19q13.3, which encodes the adaptor-related protein complex 2 sigma (AP2σ) subunit, cause FHH type 3. These studies have demonstrated Gα11 to be a key mediator of downstream CaSR signal transduction, and also revealed a role for AP2σ, which is involved in clathrin-mediated endocytosis, in CaSR signalling and trafficking. Moreover, FHH type 3 has been demonstrated to represent a more severe FHH variant that may lead to symptomatic hypercalcaemia, low bone mineral density and cognitive dysfunction. In addition, calcimimetic and calcilytic drugs, which are positive and negative CaSR allosteric modulators, respectively, have been shown to be of potential benefit for these FHH and ADH disorders. PMID:27647839

  18. The involvement of Reelin in neurodevelopmental disorders.

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    Folsom, Timothy D; Fatemi, S Hossein

    2013-05-01

    Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adulthood (maintenance of synaptic function). A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer's disease and lissencephaly share a common feature of abnormal Reelin expression in the brain. Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plasticity, leading ultimately to the cognitive deficits present in these disorders. The mechanisms for abnormal Reelin expression in some of these disorders are currently unknown although possible explanations include early developmental insults, mutations, hypermethylation of the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, FMRP underexpression and Reelin processing abnormalities. Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. The Involvement of Reelin in Neurodevelopmental Disorders

    OpenAIRE

    Folsom, Timothy D.; Fatemi, S. Hossein

    2012-01-01

    Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adults (maintenance of synaptic function). A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer’s disease and lissencephaly share a common feature of abnormal Reelin expression in the brain. Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plastici...

  20. Tic disorders and obsessive-compulsive disorder : Is autoimmunity involved?

    NARCIS (Netherlands)

    Hoekstra, PJ; Minderaa, RB

    2006-01-01

    The precise cause of tic disorders and paediatric obsessive-compulsive disorder (OCD) is unknown. In addition to genetic factors, autoimmunity may play a role, possibly as a sequela of preceding streptococcal throat infections in susceptible children. Here we review the most recent findings, from Ju

  1. Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders.

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    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine; Dimke, Henrik; Eladari, Dominique

    2016-12-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis. Copyright © 2016 by the American Society of Nephrology.

  2. Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement

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    Carey, Caitlin E.; Agrawal, Arpana; Bucholz, Kathleen K.; Hartz, Sarah M.; Lynskey, Michael T.; Nelson, Elliot C.; Bierut, Laura J.; Bogdan, Ryan

    2016-01-01

    Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European–American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium’s Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the five psychiatric disorders which comprised CROSS—attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)—and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p cannabis use, (B) MDD PRS and severe cocaine dependence, (C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and (D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity. PMID:27574527

  3. Involvement of inositol 1,4,5-trisphosphate in nicotinic calcium responses in dystrophic myotubes assessed by near-plasma membrane calcium measurement.

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    Basset, Olivier; Boittin, François-Xavier; Dorchies, Olivier M; Chatton, Jean-Yves; van Breemen, Cornelis; Ruegg, Urs T

    2004-11-05

    In skeletal muscle cells, plasma membrane depolarization causes a rapid calcium release from the sarcoplasmic reticulum through ryanodine receptors triggering contraction. In Duchenne muscular dystrophy (DMD), a lethal disease that is caused by the lack of the cytoskeletal protein dystrophin, the cytosolic calcium concentration is known to be increased, and this increase may lead to cell necrosis. Here, we used myotubes derived from control and mdx mice, the murine model of DMD, to study the calcium responses induced by nicotinic acetylcholine receptor stimulation. The photoprotein aequorin was expressed in the cytosol or targeted to the plasma membrane as a fusion protein with the synaptosome-associated protein SNAP-25, thus allowing calcium measurements in a restricted area localized just below the plasma membrane. The carbachol-induced calcium responses were 4.5 times bigger in dystrophic myotubes than in control myotubes. Moreover, in dystrophic myotubes the carbachol-mediated calcium responses measured in the subsarcolemmal area were at least 10 times bigger than in the bulk cytosol. The initial calcium responses were due to calcium influx into the cells followed by a fast refilling/release phase from the sarcoplasmic reticulum. In addition and unexpectedly, the inositol 1,4,5-trisphosphate receptor pathway was involved in these calcium signals only in the dystrophic myotubes. This surprising involvement of this calcium release channel in the excitation-contraction coupling could open new ways for understanding exercise-induced calcium increases and downstream muscle degeneration in mdx mice and, therefore, in DMD.

  4. Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement

    Directory of Open Access Journals (Sweden)

    Caitlin E Carey

    2016-08-01

    Full Text Available Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS for cross-disorder psychopathology (CROSS were generated based on the Psychiatric Genomics Consortium’s Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB. Follow-up analyses evaluated specific associations between each of the 5 psychiatric disorders which comprised CROSS—attention deficit hyperactivity disorder (ADHD, autism spectrum disorder (AUT, bipolar disorder (BIP, major depressive disorder (MDD, and schizophrenia (SCZ—and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p<0.001. After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: A MDD PRS and non-problem cannabis use, B MDD PRS and severe cocaine dependence, C SCZ PRS and non-problem cannabis use and severe cannabis dependence, and D SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity.

  5. Neurofilament dynamics and involvement in neurological disorders.

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    Gentil, Benoit J; Tibshirani, Michael; Durham, Heather D

    2015-06-01

    Neurons are extremely polarised cells in which the cytoskeleton, composed of microtubules, microfilaments and neurofilaments, plays a crucial role in maintaining structure and function. Neurofilaments, the 10-nm intermediate filaments of neurons, provide structure and mechanoresistance but also provide a scaffolding for the organization of the nucleus and organelles such as mitochondria and ER. Disruption of neurofilament organization and expression or metabolism of neurofilament proteins is characteristic of certain neurological syndromes including Amyotrophic Lateral Sclerosis, Charcot-Marie-Tooth sensorimotor neuropathies and Giant Axonal Neuropathy. Microfluorometric live imaging techniques have been instrumental in revealing the dynamics of neurofilament assembly and transport and their functions in organizing intracellular organelle networks. The insolubility of neurofilament proteins has limited identifying interactors by conventional biochemical techniques but yeast two-hybrid experiments have revealed new roles for oligomeric, nonfilamentous structures including vesicular trafficking. Although having long half-lives, new evidence points to degradation of subunits by the ubiquitin-proteasome system as a mechanism of normal turnover. Although certain E3-ligases ubiquitinating neurofilament proteins have been identified, the overall process of neurofilament degradation is not well understood. We review these mechanisms of neurofilament homeostasis and abnormalities in motor neuron and peripheral nerve disorders. Much remains to discover about the disruption of processes that leads to their pathological aggregation and accumulation and the relevance to pathogenesis. Understanding these mechanisms is crucial for identifying novel therapeutic strategies.

  6. Spermidine-Induced Improvement of Reconsolidation of Memory Involves Calcium-Dependent Protein Kinase in Rats

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    Girardi, Bruna Amanda; Ribeiro, Daniela Aymone; Signor, Cristiane; Muller, Michele; Gais, Mayara Ana; Mello, Carlos Fernando; Rubin, Maribel Antonello

    2016-01-01

    In this study, we determined whether the calcium-dependent protein kinase (PKC) signaling pathway is involved in the improvement of fear memory reconsolidation induced by the intrahippocampal administration of spermidine in rats. Male Wistar rats were trained in a fear conditioning apparatus using a 0.4-mA footshock as an unconditioned stimulus.…

  7. Membrane Properties Involved in Calcium-Stimulated Microparticle Release from the Plasma Membranes of S49 Lymphoma Cells

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    Lauryl E. Campbell

    2014-01-01

    Full Text Available This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32–42°C. A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

  8. Membrane properties involved in calcium-stimulated microparticle release from the plasma membranes of S49 lymphoma cells.

    Science.gov (United States)

    Campbell, Lauryl E; Nelson, Jennifer; Gibbons, Elizabeth; Judd, Allan M; Bell, John D

    2014-01-01

    This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32-42°C). A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

  9. Calcium

    Science.gov (United States)

    ... in luck if you like sardines and canned salmon with bones. Almond milk. previous continue Working Calcium ... drinks, and cereals. Other Considerations for Building Bones Vitamin D is essential for calcium absorption, so it's ...

  10. Genetic Evidence for Possible Involvement of the Calcium Channel Gene CACNA1A in Autism Pathogenesis in Chinese Han Population.

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    Jun Li

    Full Text Available Autism spectrum disorders (ASD are a group of neurodevelopmental disorders. Recent studies suggested that calcium channel genes might be involved in the genetic etiology of ASD. CACNA1A, encoding an alpha-1 subunit of voltage-gated calcium channel, has been reported to play an important role in neural development. Previous study detected that a single nucleotide polymorphism (SNP in CACNA1A confers risk to ASD in Central European population. However, the genetic relationship between autism and CACNA1A in Chinese Han population remains unclear. To explore the association of CACNA1A with autism, we performed a family-based association study. First, we carried out a family-based association test between twelve tagged SNPs and autism in 239 trios. To further confirm the association, the sample size was expanded to 553 trios by recruiting 314 additional trios. In a total of 553 trios, we identified association of rs7249246 and rs12609735 with autism though this would not survive after Bonferroni correction. Our findings suggest that CACNA1A might play a role in the etiology of autism.

  11. Calcium carbonate mineralization: involvement of extracellular polymeric materials isolated from calcifying bacteria.

    Science.gov (United States)

    Ercole, Claudia; Bozzelli, Paola; Altieri, Fabio; Cacchio, Paola; Del Gallo, Maddalena

    2012-08-01

    This study highlights the role of specific outer bacterial structures, such as the glycocalix, in calcium carbonate crystallization in vitro. We describe the formation of calcite crystals by extracellular polymeric materials, such as exopolysaccharides (EPS) and capsular polysaccharides (CPS) isolated from Bacillus firmus and Nocardia calcarea. Organic matrices were isolated from calcifying bacteria grown on synthetic medium--in the presence or absence of calcium ions--and their effect on calcite precipitation was assessed. Scanning electron microscopy observations and energy dispersive X-ray spectrometry analysis showed that CPS and EPS fractions were involved in calcium carbonate precipitation, not only serving as nucleation sites but also through a direct role in crystal formation. The utilization of different synthetic media, with and without addition of calcium ions, influenced the biofilm production and protein profile of extracellular polymeric materials. Proteins of CPS fractions with a molecular mass between 25 and 70 kDa were overexpressed when calcium ions were present in the medium. This higher level of protein synthesis could be related to the active process of bioprecipitation.

  12. 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

  13. Molecular and biochemical evidence for the involvement of calcium/calmodulin in auxin action

    Science.gov (United States)

    Yang, T.; Poovaiah, B. W.

    2000-01-01

    -dependent manner suggests that calcium/CaM regulate ZmSAUR1 at the post-translational level. Our data provide the first direct evidence for the involvement of calcium/CaM-mediated signaling in auxin-mediated signal transduction.

  14. Molecular and biochemical evidence for the involvement of calcium/calmodulin in auxin action

    Science.gov (United States)

    Yang, T.; Poovaiah, B. W.

    2000-01-01

    -dependent manner suggests that calcium/CaM regulate ZmSAUR1 at the post-translational level. Our data provide the first direct evidence for the involvement of calcium/CaM-mediated signaling in auxin-mediated signal transduction.

  15. [CT imaging features of pulmonary involvement in connective tissue disorders].

    Science.gov (United States)

    Brillet, P Y; Mama, N; Nunes, H; Uzunhan, Y; Abbad, S; Brauner, M W

    2009-11-01

    Connective tissue disorders correspond to a heterogeneous group of inflammatory diseases characterized by abnormal immune system activity leading to connective tissue alterations in multiple parts of the body. In adults, connective tissue disorders include rheumatoid arthritis, progressive systemic sclerosis, Sjögren syndrome, systemic lupus erythematosus, dermatomyositis and polymyositis, ankylosing spondylitis, and mixed connective tissue disease. Broncho-pulmonary involvement may be variable with involvement of all anatomical components of the lung. Involvement of other intrathoracic structures (pleura, respiratory muscles, heart, rib cage) is frequent. The most specific manifestations include interstitial lung diseases and pulmonary hypertension. During follow-up, progressive respiratory diseases may occur due to the treatment, infections, pulmonary embolism or neoplasms.

  16. Study on the Effect of Calcium and Potassium Spray on Date Bunch Fading Disorder

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    Hosein Shekofteh

    2017-02-01

    Full Text Available Introduction: Date bunch fading disorder has been one of the most important problems, which caused economic damage to date plantation area of Iran. It has been first reported on Mozafti cultivar in Kahnuj area, Kerman province. It has often been observed on soft and mid ripening cultivars such as Mozafti, Mordaseng and Kalote. Furthermore, it usually appears on Mozafti cultivar when fruits change from Khalal to Rutab stage. The most important symptoms of this disorder are sudden wilting of fruits and necrotic strips on the upper surface of the main bunch stalk. Incidence and development of these symptoms increase by high temperature, low relative humidity, and hot and dry wind. Several research studies have been carried out on this disorder so far, but the only research about the effect of nutrition on disorder was performed by Rosta (2003. The aim of the present study was to investigate the effect of calcium and potassium spray on date bunch fading and some traits of date fruit in Rigan region, Kerman province. Materials and Methods: The experiment was conducted based on randomized complete block designs with three replicates in Rigan located in east south of Kerman province, Iran, in 2012. Treatments were: T1: control, T2: spray of calcium nitrate at the concentration of 5 ppm, T3: spray of potassium sulfate at the concentration of 5 ppm, and T4: combined spray of calcium nitrate and potassium sulfate at the concentration of 5 ppm. Treatments were applied at Kimri, Hobabok and Khalal stages. Sampling was performed from 3 date palms (3 bunches from each date palm were selected randomly at the second date harvest. Totally, the traits of 200 fruits were measured in each date palm. The traits measured in the present study were: fruit length, fruit diameter, fruit weight, stone weight, stone diameter, and bunch fading percentage. Results and Discussions: According to the data of variance analysis, treatments had a significant effect on wet fruit

  17. Congenital disorders of glycosylation with emphasis on cerebellar involvement.

    Science.gov (United States)

    Barone, Rita; Fiumara, Agata; Jaeken, Jaak

    2014-07-01

    Congenital disorders of glycosylation (CDG) are genetic diseases due to defective glycosylation of proteins and lipids. The authors present an update on these disorders affecting the central nervous system with a focus on cerebellar involvement. The rate of identification of novel CDG shows an exponential increase. Some 76 CDG are actually known, not taking into account the defects in glycan-modifying proteins. Neurologic involvement is present in the large majority of CDG. Screening methods are limited to serum transferrin isoelectrofocusing (for N-glycosylation disorders with sialic acid deficiency), and serum apolipoprotein C-III isoelectrofocusing (for core 1 mucin-type O-glycosylation disorders). Whole exome/genome sequencing is increasingly used in the diagnostic workup of patients with CDG-X. Treatment is greatly lagging behind because only one CDG is efficiently treatable (MPI-CDG). Cerebellar involvement is an important feature of PMM2-CDG, the congenital muscular dystrophies due to dystroglycanopathy, and SRD5A3-CDG. It has also been reported in some patients with ALG1-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, ALG8-CDG, PIGA-CDG, DPM1-CDG, DPM2-CDG, B4GALT1-CDG, SLC35A2-CDG, COG1-CDG, COG5-CDG, COG7-CDG, and COG8-CDG.

  18. Cardiac involvement in children with neuro-muscular disorders

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    E. N. Arkhipova

    2015-01-01

    Full Text Available Many inherited neuromuscular disorders include cardiac involvement as a typical clinical feature. Among the most common of them is the group of muscular dystrophies. Dilated cardiomyopathy, ventricular arrhythmias, atrial fibrillations, atrioventricular and intraventricular conduction abnormalities, and sudden cardiac death are well known pathological findings in Duchenne muscular dystrophies, myotonic dystrophy type I and 2, Emery-Dreifuss muscular dystrophies and different types of limb-girdle muscular dystrophies and other disorders. Detection of cardiac pathology in patients with different muscular dystrophies is possible with ECG, echocardiography and cardiovascular magnetic resonance imaging, which are recommended for screening and early cardioprotective treatment.

  19. Lung Involvement in Children with Hereditary Autoinflammatory Disorders

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    Giusyda Tarantino

    2016-12-01

    Full Text Available Short-lived systemic inflammatory reactions arising from disrupted rules in the innate immune system are the operating platforms of hereditary autoinflammatory disorders (HAIDs. Multiple organs may be involved and aseptic inflammation leading to disease-specific phenotypes defines most HAIDs. Lungs are infrequently involved in children with HAIDs: the most common pulmonary manifestation is pleuritis in familial Mediterranean fever (FMF and tumor necrosis factor receptor-associated periodic syndrome (TRAPS, respectively caused by mutations in the MEFV and TNFRSF1A genes, while interstitial lung disease can be observed in STING-associated vasculopathy with onset in infancy (SAVI, caused by mutations in the TMEM173 gene. The specific pleuropulmonary diseases may range from sub-clinical abnormalities during inflammatory flares of FMF and TRAPS to a severe life-threatening disorder in children with SAVI.

  20. Lung Involvement in Children with Hereditary Autoinflammatory Disorders

    Science.gov (United States)

    Tarantino, Giusyda; Esposito, Susanna; Andreozzi, Laura; Bracci, Benedetta; D’Errico, Francesca; Rigante, Donato

    2016-01-01

    Short-lived systemic inflammatory reactions arising from disrupted rules in the innate immune system are the operating platforms of hereditary autoinflammatory disorders (HAIDs). Multiple organs may be involved and aseptic inflammation leading to disease-specific phenotypes defines most HAIDs. Lungs are infrequently involved in children with HAIDs: the most common pulmonary manifestation is pleuritis in familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively caused by mutations in the MEFV and TNFRSF1A genes, while interstitial lung disease can be observed in STING-associated vasculopathy with onset in infancy (SAVI), caused by mutations in the TMEM173 gene. The specific pleuropulmonary diseases may range from sub-clinical abnormalities during inflammatory flares of FMF and TRAPS to a severe life-threatening disorder in children with SAVI. PMID:27983684

  1. Calcium Disorders in the Emergency Department: Independent Risk Factors for Mortality.

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    Thomas C Sauter

    Full Text Available Calcium disorders are common in both intensive care units and in patients with chronic kidney disease and are associated with increased morbidity and mortality. It is unknown whether calcium abnormalities in unselected emergency department admissions have an impact on in-hospital mortality.This cross-sectional analysis included all admissions to the Emergency Department at the Inselspital Bern, Switzerland from 2010 to 2011. For hyper- and hypocalcaemic patients with a Mann-Whitney U-test, the differences between subgroups divided by age, length of hospital stay, creatinine, sodium, chloride, phosphate, potassium and magnesium were compared. Associations between calcium disorders and 28-day in-hospital mortality were assessed using the Cox proportional hazard regression model.8,270 patients with calcium measurements were included in our study. Overall 264 (3.2% patients died. 150 patients (6.13% with hypocalcaemia and 7 patients with hypercalcaemia (6.19% died, in contrast to 104 normocalcaemic patients (1.82%. In univariate analysis, calcium serum levels were associated with sex, mortality and pre-existing diuretic therapy (all p<0.05. In multivariate Cox regression analysis, hypocalcaemia and hypercalcaemia were independent risk factors for mortality (HR 2.00 and HR 1.88, respectively; both p<0.01.Both hypocalcaemia and hypercalcaemia are associated with increased 28-day in-hospital mortality in unselected emergency department admissions.

  2. Pulmonary involvement and allergic disorders in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Nikolaos; E; Tzanakis; Ioanna; G; Tsiligianni; Nikolaos; M; Siafakas

    2010-01-01

    Inflammatory bowel disease (IBD) has been associated with either clinical or subclinical airway and parenchymal lung involvement and interstitial lung complications. Several studies have reported that atopy has a high prevalence in IBD patients. Overlapping allergic disorders seem to be present in both the respiratory and gastrointestinal systems. The purpose of this review is to update clinicians on recent available literature and to discuss the need for a highly suspicious approach by clinicians.

  3. Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

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    Natalia Gustavsson

    Full Text Available BACKGROUND: Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. CONCLUSIONS: Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

  4. [Bipolar affective disorders and role of intraneuronal calcium. Therapeutic effects of the treatment with lithium salts and/or calcium antagonist in patients with rapid polar inversion].

    Science.gov (United States)

    Manna, V

    1991-11-01

    Treatment with lithium salts produces improvements in bipolar affective disorders. Up to date, the relationship between neurochemical and behavioural effects of lithium and its actions on intraneuronal free calcium ions is not well known. Some calcium antagonist drugs resulted active in the treatment of bipolar affective syndromes, with therapeutic effects similar to lithium salts. Some studies suggest that also lithium salts act as calcium antagonist at intraneuronal level. In this preliminary open study the activity of nimodipine, a selective neuronal calcium antagonist drug, was evaluated alone and in association with lithium salts in the treatment of rapid cycling bipolar manic-depressive illness. During three periods of 6 months 12 rapid cycling patients were treated with lithium salts, lithium salts plus nimodipine 30 mg x 3/day, nimodipine 30 mg x 3/day. The association of lithium with nimodipine resulted more effective than lithium alone or nimodipine alone in the reduction of episodes of affective disorder. These results suggest a probable sinergic activity of both treatments. Further studies will be necessary to confirm the mechanism of action, perhaps calcium antagonism, at the basis of therapeutic effects of both treatments. The results seem to confirm the hypothesis that a calcium-ionic disorders play a role in the pathogenesis of bipolar affective disorders.

  5. Effects of acute and chronic nicotine on elevated plus maze in mice: involvement of calcium channels.

    Science.gov (United States)

    Biala, Grazyna; Budzynska, Barbara

    2006-05-30

    The current experiments examined the anxiety-related effects of acute and repeated nicotine administration using the elevated plus maze test in mice. Nicotine (0.1 mg/kg s.c., 5 and 30 min after injection; 0.5 mg/kg, s.c., 5 min after injection) had an anxiogenic effect, shown by specific decreases in the percentage of time spent on the open arms and in the percentage of open arm entries. Tolerance developed to this anxiogenic action after 6 days of daily nicotine administration (0.1 mg/kg, s.c.). Five minutes after the seventh injection, an anxiolytic effect was observed, i.e., specific increases in the percentage of time spent on the open arms and in the percentage of open arm entries. L-type voltage-dependent calcium channel antagonists nimodipine (5 and 10 mg/kg, i.p.), flunarizine (5 and 10 mg/kg, i.p.), verapamil (5, 10, 20 mg/kg) and diltiazem (5, 10, 20 mg/kg, i.p.) were also injected prior to an acute low dose of nicotine or to each injection of chronic nicotine. Our results revealed that calcium channel blockers dose-dependently attenuated both an anxiogenic effect of nicotine as well as the development of tolerance to this effect. Our results suggest that neural calcium-dependent mechanisms are involved in the anxiety-related responses to acute and chronic nicotine injection that may ultimately lead to addiction and smoking relapse in human smokers.

  6. Vitamin D and Calcium Status in South African Adolescents with Alcohol Use Disorders

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    George Fein

    2012-08-01

    Full Text Available Adequate vitamin D and calcium are essential for optimal adolescent skeletal development. Adolescent vitamin D insufficiency/deficiency and poor calcium intake have been reported worldwide. Heavy alcohol use impacts negatively on skeletal health, which is concerning since heavy adolescent drinking is a rising public health problem. This study aimed to examine biochemical vitamin D status and dietary intakes of calcium and vitamin D in 12–16 year-old adolescents with alcohol use disorders (AUD, but without co-morbid substance use disorders, compared to adolescents without AUD. Substance use, serum 25-hydroxyvitamin D (s-25(OHD concentrations, energy, calcium and vitamin D intakes were assessed in heavy drinkers (meeting DSM-IV criteria for AUD (n = 81 and in light/non-drinkers without AUD (non-AUD (n = 81, matched for age, gender, language, socio-economic status and education. Lifetime alcohol dose was orders of magnitude higher in AUD adolescents compared to non-AUD adolescents. AUD adolescents had a binge drinking pattern and “weekends-only” style of alcohol consumption. Significantly lower (p = 0.038 s-25(OHD (adjusted for gender, smoking, vitamin D intake were evident in AUD adolescents compared to non-AUD adolescents. High levels of vitamin D insufficiency/deficiency (s-25(OHD < 29.9 ng/mL were prevalent in both groups, but was significantly higher (p = 0.013 in the AUD group (90% compared to the non-AUD group (70%. All participants were at risk of inadequate calcium and vitamin D intakes (Estimated Average Requirement cut-point method. Both groups were at risk of inadequate calcium intake and had poor biochemical vitamin D status, with binge drinking potentially increasing the risk of the latter. This may have negative implications for peak bone mass accrual and future osteoporosis risk, particularly with protracted binge drinking.

  7. Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels.

    Science.gov (United States)

    Zemkova, Hana; Tomić, Melanija; Kucka, Marek; Aguilera, Greti; Stojilkovic, Stanko S

    2016-04-01

    Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial single spiking and sustained bursting; in active cells, CRH further facilitated or inhibited electrical activity and calcium spiking, depending on the initial activity pattern and CRH concentration. The stimulatory but not inhibitory action of CRH on electrical activity was mimicked by cAMP independently of the presence or absence of arachidonic acid. Removal of bath sodium silenced spiking and hyperpolarized the majority of cells; in contrast, the removal of bath calcium did not affect RMP but reduced CRH-induced depolarization, which abolished bursting electrical activity and decreased the spiking frequency but not the amplitude of single spikes. Corticotrophs with inhibited voltage-gated sodium channels fired calcium-dependent action potentials, whereas cells with inhibited L-type calcium channels fired sodium-dependent spikes; blockade of both channels abolished spiking without affecting the RMP. These results indicate that the background voltage-insensitive sodium conductance influences RMP, the CRH-depolarization current is driven by a cationic conductance, and the interplay between voltage-gated sodium and calcium channels plays a critical role in determining the status and pattern of electrical activity and calcium signaling.

  8. Detergent resistant membrane fractions are involved in calcium signaling in Müller glial cells of retina.

    Science.gov (United States)

    Krishnan, Gopinath; Chatterjee, Nivedita

    2013-08-01

    Compartmentalization of the plasma membrane into lipid microdomains promotes efficient cellular processes by increasing local molecular concentrations. Calcium signaling, either as transients or propagating waves require integration of complex macromolecular machinery. Calcium waves represent a form of intercellular signaling in the central nervous system and the retina. We hypothesized that the mechanism for calcium waves would require effector proteins to aggregate at the plasma membrane in lipid microdomains. The current study shows that in Müller glia of the retina, proteins involved in calcium signaling aggregate in detergent resistant membranes identifying rafts and respond by redistributing on stimulation. We have investigated Purinoreceptor-1 (P2Y1), Ryanodine receptor (RyR), and Phospholipase C (PLC-β1). P2Y1, RyR and PLC-β1, redistribute from caveolin-1 and flotillin-1 positive fractions on stimulation with the agonists, ATP, 2MeS-ATP and Thapsigargin, an inhibitor of sarcoplasmic-endoplasmic reticulum Ca-ATPase (SERCA). Redistribution is absent on treatment with cyclopiazonic acid, another SERCA inhibitor. Disruption of rafts by removing cholesterol cause proteins involved in this machinery to redistribute and change agonist-induced calcium signaling. Cholesterol depletion from raft lead to increase in time to peak of calcium levels in agonist-evoked calcium signals in all instances, as seen by live imaging. This study emphasizes the necessity of a sub-population of proteins to cluster in specialized lipid domains. The requirement for such an organization at the raft-like microdomains may have implications on intercellular communication in the retina. Such concerted interaction at the rafts can regulate calcium dynamics and could add another layer of complexity to calcium signaling in cells.

  9. Lipid rafts and their possible involvements in neuroimmunological disorders.

    Science.gov (United States)

    Asakura, Kunihiko; Ueda, Akihiro; Mutoh, Tatsuro

    2015-01-01

    Multiple sclerosis (MS) and neuromyelitis optica (NMO) are presumed to be an autoimmune disease in the central nervous system (CNS). Although lipids are most abundant components in the nervous system, it has been believed that cellular and/or humoral immunity to various myelin proteins causes these neuroinflammatory diseases. Recent research advances enable us to study lipids in the membranes and some key molecules involved in various neurological disorders including Guillain-Barré syndrome, Alzheimer's disease, Parkinson's disease, and prion disease, are localized in lipid rafts. In MS and NMO, the key molecules for the pathogenesis or the target molecules for the treatments of MS and NMO are also localized in lipid rafts. Here in this article, we highlight on the possible involvement of lipid rafts in the pathogenesis and treatment of MS and NMO and introduce our recent observation of aquaporin 4 regarding NMO.

  10. Mechanisms involved in calcium oxalate endocytosis by Madin-Darby canine kidney cells

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    A.H. Campos

    2000-01-01

    Full Text Available Calcium oxalate (CaOx crystals adhere to and are internalized by tubular renal cells and it seems that this interaction is related (positively or negatively to the appearance of urinary calculi. The present study analyzes a series of mechanisms possibly involved in CaOx uptake by Madin-Darby canine kidney (MDCK cells. CaOx crystals were added to MDCK cell cultures and endocytosis was evaluated by polarized light microscopy. This process was inhibited by an increase in intracellular calcium by means of ionomycin (100 nM; N = 6; 43.9% inhibition; P<0.001 or thapsigargin (1 µM; N = 6; 33.3% inhibition; P<0.005 administration, and via blockade of cytoskeleton assembly by the addition of colchicine (10 µM; N = 8; 46.1% inhibition; P<0.001 or cytochalasin B (10 µM; N = 8; 34.2% inhibition; P<0.001. Furthermore, CaOx uptake was reduced when the activity of protein kinase C was inhibited by staurosporine (10 nM; N = 6; 44% inhibition; P<0.01, or that of cyclo-oxygenase by indomethacin (3 µM; N = 12; 17.2% inhibition; P<0.05; however, the uptake was unaffected by modulation of potassium channel activity with glibenclamide (3 µM; N = 6, tetraethylammonium (1 mM; N = 6 or cromakalim (1 µM; N = 6. Taken together, these data indicate that the process of CaOx internalization by renal tubular cells is similar to the endocytosis reported for other systems. These findings may be relevant to cellular phenomena involved in early stages of the formation of renal stones.

  11. Mechanisms involved in vitamin D mediated intestinal calcium absorption and in non-classical actions of vitamin D.

    Science.gov (United States)

    Christakos, Sylvia; Dhawan, Puneet; Ajibade, Dare; Benn, Bryan S; Feng, Jingjing; Joshi, Sneha S

    2010-07-01

    Recent studies in our laboratory using calbindin-D9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inducible epithelial calcium channel TRPV6 provide evidence for calbindin-D9k and TRPV6 independent regulation of active intestinal calcium absorption. These findings suggest that in the knock out (KO) mice there is compensation by another calcium channel or protein and that other novel factors are involved in 1,25(OH)2D3 mediated active intestinal calcium absorption. In addition, 1,25(OH)2D3 mediated paracellular transport of calcium may have contributed to the normalization of serum calcium in the null mutant mice. 1,25(OH)2D3 downregulates cadherin-17 and upregulates claudin-2 and claudin-12 in the intestine, suggesting that 1,25(OH)2D3, by regulating these epithelial cell junction proteins, can route calcium through the paracellular path. With regard to non-classical actions, 1,25(OH)2D3 has been reported to inhibit the proliferation of a number of malignant cells and to regulate adaptive as well as innate immunity. This article will review new developments related to the function and regulation of vitamin D target proteins in classical and non-classical vitamin D target tissues that have provided novel insight into mechanisms of vitamin D action.

  12. A study of serum magnesium and serum calcium in major depressive disorder

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    Niladri Deb

    2016-01-01

    Full Text Available Background: Depression is arguably the epidemic of our time. In one of the reports of the World Health Organization, it was projected that depression and heart disease will be the most common diseases on Earth by 2020. The paper attempts to determine the relationship between the pathophysiology of major depressive disorder (MDD and serum magnesium and serum calcium levels. Methodology: The study is based on a sample of 60 subjects–30 healthy normal individuals and 30 indoor and outdoor patients of the Department of Psychiatry of Gauhati Medical College and Hospital, Guwahati, who were identified by psychiatrist as having MDD as per the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV criteria. Estimation of the parameters of the study was done by using spectrophotometre (Spectra scan UV 2600. The result values of both the groups were compared by using independent ‘t’ test. Further, the correlation between serum magnesium and serum calcium among individuals of control as well as case groups were carried out by using Pearson’s correlation test. Results: Analysis of data reveals the mean value of serum magnesium among subjects of control group was higher than that of the subjects of the case (before treatment group while in case of serum calcium, it was the vice versa. Moreover, in both the cases, the differences in mean values were found to be statistically significant. Conclusion: The present study shows that alterations in the concentrations of magnesium and calcium may play a role in depressive illnesses and thus, may have a possible role in causing various mood disorders like MDD.

  13. Calcium Alternans is Due to an Order-Disorder Phase Transition in Cardiac Cells

    Science.gov (United States)

    Alvarez-Lacalle, Enrique; Echebarria, Blas; Spalding, Jon; Shiferaw, Yohannes

    2015-03-01

    Electromechanical alternans is a beat-to-beat alternation in the strength of contraction of a cardiac cell, which can be caused by an instability of calcium cycling. Using a distributed model of subcellular calcium we show that alternans occurs via an order-disorder phase transition which exhibits critical slowing down and a diverging correlation length. We apply finite size scaling along with a mapping to a stochastic coupled map model, to show that this transition in two dimensions is characterized by critical exponents consistent with the Ising universality class. These findings highlight the important role of cooperativity in biological cells, and suggest novel approaches to investigate the onset of the alternans instability in the heart.

  14. Differential expression of genes involved in the calcium homeostasis in masticatory muscles of MDX mice.

    Science.gov (United States)

    Kunert-Keil, C H; Gredes, T; Lucke, S; Botzenhart, U; Dominiak, M; Gedrange, T

    2014-04-01

    Duchenne Muscular Dystrophy (DMD) and its murine model, mdx, are characterized by Ca(2+) induced muscle damage and muscle weakness followed by distorted dentofacial morphology. In both, DMD patients and in mdx mice, could be proven so far that only the extraocular muscles (EOM) are not affected by muscular dystrophy. The EOMs are protected against calcium overload by enhanced expression of genes involved in the Ca(2+) homeostasis. We could recently demonstrate that masticatory muscles of mdx mice are differentially affected by muscle dystrophy. The dystrophic masseter and temporalis shows muscle histology comparable to all other skeletal muscles in this animal model, whereas dystrophic tongue muscles seem to develop a milder phenotype. Due to this fact it is to hypothesize that an altered Ca(2+) homeostasis seems to underlie the mdx masticatory muscle pathology. Aim of this study was to examine the mRNA and protein levels of the sarcoplasmic reticulum Ca(2+) ATPases SERCA1 and SERCA2, the plasma membrane Ca(2+) ATPases Atp2b1 and Atp2b4, the sodium/calcium exchanger NCX1, the ryanodine receptor 1, parvalbumin, sarcolipin, phospholamban and the L-type Ca(2+) channel alpha-1 subunit (Cacna1s) in Musculus masseter, temporalis, and tongue of 100 day old control and mdx mice. In mdx masseter muscle significant increased mRNA levels of NCX1 and Cacna1s were found compared to control mice. In contrast, the mRNA amount of RYR1 was significant reduced in mdx temporalis muscle, whereas ATP2b4 was significant increased. In mdx tongue a down-regulation of the ATP2b1, sarcolipin and parvalbumin mRNA expression was found, whereas the phospholamban mRNA level was significantly increased compared to controls. These data were verified by western blot analyses. Our findings revealed that mdx masticatory muscles showed an unequally altered expression of genes involved in the Ca(2+) homeostasis that can support the differences in masticatory muscles response to dystrophin deficiency.

  15. Involvement of intracellular calcium stores during oxygen/glucose deprivation in striatal large aspiny interneurons.

    Science.gov (United States)

    Pisani, A; Bonsi, P; Centonze, D; Giacomini, P; Calabresi, P

    2000-05-01

    Striatal large aspiny interneurons were recorded from a slice preparation using a combined electrophysiologic and microfluorometric approach. The role of intracellular Ca2+ stores was analyzed during combined oxygen/glucose deprivation (OGD). Before addressing the role of the stores during energy deprivation, the authors investigated their function under physiologic conditions. Trains of depolarizing current pulses caused bursts of action potentials coupled to transient increases in intracellular calcium concentration ([Ca2+]i). In the presence of cyclopiazonic acid (30 micromol/L), a selective inhibitor of the sarcoendoplasmic reticulum Ca2+ pumps, or when ryanodine receptors were directly blocked with ryanodine (20 [micromol/L), the [Ca2+]i transients were progressively smaller in amplitude, suggesting that [Ca2+]i released from intracellular stores helps to maintain a critical level of [Ca2+]i during physiologic firing activity. As the authors have recently reported, brief exposure to combined OGD induced a membrane hyperpolarization coupled to an increase in [Ca2+]i. In the presence of cyclopiazonic acid or ryanodine, the hyperpolarization and the rise in [Ca2+]i induced by OGD were consistently reduced. These data support the hypothesis that Ca2+ release from ryanodine-sensitive Ca2+ pools is involved not only in the potentiation of the Ca2+ signals resulting from cell depolarization, but also in the amplification of the [Ca2+]i rise and of the concurrent membrane hyperpolarization observed in course of OGD in striatal large aspiny interneurons.

  16. Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition disease. An ultrasound study.

    Science.gov (United States)

    Filippucci, E; Riveros, M Gutierrez; Georgescu, D; Salaffi, F; Grassi, W

    2009-02-01

    The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference. A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow. Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity=99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity=97.6%). The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.

  17. Are calcium oxalate crystals involved in the mechanism of acute renal failure in ethylene glycol poisoning?

    Science.gov (United States)

    McMartin, Kenneth

    2009-11-01

    Ethylene glycol (EG) poisoning often results in acute renal failure, particularly if treatment with fomepizole or ethanol is delayed because of late presentation or diagnosis. The mechanism has not been established but is thought to result from the production of a toxic metabolite. A literature review utilizing PubMed identified papers dealing with renal toxicity and EG or oxalate. The list of papers was culled to those relevant to the mechanism and treatment of the renal toxicity associated with either compound. ROLE OF METABOLITES: Although the "aldehyde" metabolites of EG, glycolaldehyde, and glyoxalate, have been suggested as the metabolites responsible, recent studies have shown definitively that the accumulation of calcium oxalate monohydrate (COM) crystals in kidney tissue produces renal tubular necrosis that leads to kidney failure. In vivo studies in EG-dosed rats have correlated the severity of renal damage with the total accumulation of COM crystals in kidney tissue. Studies in cultured kidney cells, including human proximal tubule (HPT) cells, have demonstrated that only COM crystals, not the oxalate ion, glycolaldehyde, or glyoxylate, produce a necrotic cell death at toxicologically relevant concentrations. COM CRYSTAL ACCUMULATION: In EG poisoning, COM crystals accumulate to high concentrations in the kidney through a process involving adherence to tubular cell membranes, followed by internalization of the crystals. MECHANISM OF TOXICITY: COM crystals have been shown to alter membrane structure and function, to increase reactive oxygen species and to produce mitochondrial dysfunction. These processes are likely to be involved in the mechanism of cell death. Accumulation of COM crystals in the kidney is responsible for producing the renal toxicity associated with EG poisoning. The development of a pharmacological approach to reduce COM crystal adherence to tubular cells and its cellular interactions would be valuable as this would decrease the renal

  18. Actin filaments as the fast pathways for calcium ions involved in auditory processes

    Indian Academy of Sciences (India)

    Miljko V Sataric; Dalibor L Sekulic; Bogdan M Sataric

    2015-09-01

    We investigated the polyelectrolyte properties of actin filaments which are in interaction with myosin motors, basic participants in mechano-electrical transduction in the stereocilia of the inner ear. Here, we elaborated a model in which actin filaments play the role of guides or pathways for localized flow of calcium ions. It is well recognized that calcium ions are implicated in tuning of actin-myosin cross-bridge interaction, which controls the mechanical property of hair bundle. Actin filaments enable much more efficient delivery of calcium ions and faster mechanism for their distribution within the stereocilia. With this model we were able to semiquantitatively explain experimental evidences regarding the way of how calcium ions tune the mechanosensitivity of hair cells.

  19. Calcium Channel Genes Associated with Bipolar Disorder Modulate Lithium's Amplification of Circadian Rhythms

    Science.gov (United States)

    McCarthy, Michael J.; LeRoux, Melissa; Wei, Heather; Beesley, Stephen; Kelsoe, John R.; Welsh, David K.

    2015-01-01

    Bipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells. We used fluorescent dyes to measure Ca2+ changes in BD and control fibroblasts after lithium treatment, and bioluminescent reporters to measure Per2∷luc rhythms in fibroblasts from BD patients, human controls, and mice while pharmacologically or genetically manipulating calcium channels. Longitudinal expression of LTCC genes (CACNA1C, CACNA1D and CACNB3) was then measured over 12-24 hr in BD and control cells. Our results indicate that independently of LTCCs, lithium stimulated intracellular Ca2+ less effectively in BD vs. control fibroblasts. In longitudinal studies, pharmacological inhibition of LTCCs or knockdown of CACNA1A, CACNA1C, CACNA1D and CACNB3 altered circadian rhythm amplitude. Diltiazem and knockdown of CACNA1C or CACNA1D eliminated lithium's ability to amplify rhythms. Knockdown of CACNA1A or CACNB3 altered baseline rhythms, but did not affect rhythm amplification by lithium. In human fibroblasts, CACNA1C genotype predicted the amplitude response to lithium, and the expression profiles of CACNA1C, CACNA1D and CACNB3 were altered in BD vs. controls. We conclude that in cells from BD patients, calcium signaling is abnormal, and that LTCCs underlie the failure of lithium to amplify circadian rhythms. PMID:26476274

  20. Water Channels Are Involved in Stomatal Oscillations Encoded by Parameter-Specific Cytosolic Calcium Oscillations

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Earlier studies have shown that various stimuli can induce specific cytosolic calcium ([Ca2+]cyt) oscillations in guard cells and various oscillations in stomatal apertures. Exactly how [Ca2+]cyt oscillation signaling functions in stomatal oscillation is not known. In the present study, the epidermis of broad bean (Vicia faba L.)was used and a rapid ion-exchange treatment with two shifting buffers differing in K+ and Ca2+ concentrations was applied. The treatment for five transients at a 10-min transient period induced clear and regular stomatal oscillation. However, for other transient numbers and periods, the treatments induced some irregular oscillations or even no obvious oscillations in stomatal aperture. The results indicate that stomatal oscillation is encoded by parameter-specific [Ca2+]cyt oscillation: the parameters of [Ca2+]cyt oscillation affected the occurrence rate and the parameters of stomatal oscillation. The water channel inhibitor HgCl2 completely inhibited stomatal oscillation and the inhibitory effect could be partially reversed by β-mercaptoethanol (an agent capable of reversing water channel inhibition by HgCl2). Other inhibitory treatments against ion transport (i.e. the application of LaCl3, EGTA, or tetraethylammonium chloride (TEACl))weakly impaired stomatal oscillation when the compounds were added after rapid ion-exchange treatment.If these compounds were added before rapid-ion exchange treatment, the inhibitory effect was much more apparent (except in the case of TEACI). The results of the present study suggest that water channels are involved in stomatal oscillation as a downstream element of [Ca2+]cyt oscillation signaling.

  1. Fetal calcium regulates branching morphogenesis in the developing human and mouse lung: involvement of voltage-gated calcium channels.

    Science.gov (United States)

    Brennan, Sarah C; Finney, Brenda A; Lazarou, Maria; Rosser, Anne E; Scherf, Caroline; Adriaensen, Dirk; Kemp, Paul J; Riccardi, Daniela

    2013-01-01

    Airway branching morphogenesis in utero is essential for optimal postnatal lung function. In the fetus, branching morphogenesis occurs during the pseudoglandular stage (weeks 9-17 of human gestation, embryonic days (E)11.5-16.5 in mouse) in a hypercalcaemic environment (~1.7 in the fetus vs. ~1.1-1.3 mM for an adult). Previously we have shown that fetal hypercalcemia exerts an inhibitory brake on branching morphogenesis via the calcium-sensing receptor. In addition, earlier studies have shown that nifedipine, a selective blocker of L-type voltage-gated Ca(2+) channels (VGCC), inhibits fetal lung growth, suggesting a role for VGCC in lung development. The aim of this work was to investigate the expression of VGCC in the pseudoglandular human and mouse lung, and their role in branching morphogenesis. Expression of L-type (CaV1.2 and CaV1.3), P/Q type (CaV2.1), N-type (CaV2.2), R-type (CaV2.3), and T-type (CaV3.2 and CaV3.3) VGCC was investigated in paraffin sections from week 9 human fetal lungs and E12.5 mouse embryos. Here we show, for the first time, that Cav1.2 and Cav1.3 are expressed in both the smooth muscle and epithelium of the developing human and mouse lung. Additionally, Cav2.3 was expressed in the lung epithelium of both species. Incubating E12.5 mouse lung rudiments in the presence of nifedipine doubled the amount of branching, an effect which was partly mimicked by the Cav2.3 inhibitor, SNX-482. Direct measurements of changes in epithelial cell membrane potential, using the voltage-sensitive fluorescent dye DiSBAC2(3), demonstrated that cyclic depolarisations occur within the developing epithelium and coincide with rhythmic occlusions of the lumen, driven by the naturally occurring airway peristalsis. We conclude that VGCC are expressed and functional in the fetal human and mouse lung, where they play a role in branching morphogenesis. Furthermore, rhythmic epithelial depolarisations evoked by airway peristalsis would allow for branching to match

  2. Fetal calcium regulates branching morphogenesis in the developing human and mouse lung: involvement of voltage-gated calcium channels.

    Directory of Open Access Journals (Sweden)

    Sarah C Brennan

    Full Text Available Airway branching morphogenesis in utero is essential for optimal postnatal lung function. In the fetus, branching morphogenesis occurs during the pseudoglandular stage (weeks 9-17 of human gestation, embryonic days (E11.5-16.5 in mouse in a hypercalcaemic environment (~1.7 in the fetus vs. ~1.1-1.3 mM for an adult. Previously we have shown that fetal hypercalcemia exerts an inhibitory brake on branching morphogenesis via the calcium-sensing receptor. In addition, earlier studies have shown that nifedipine, a selective blocker of L-type voltage-gated Ca(2+ channels (VGCC, inhibits fetal lung growth, suggesting a role for VGCC in lung development. The aim of this work was to investigate the expression of VGCC in the pseudoglandular human and mouse lung, and their role in branching morphogenesis. Expression of L-type (CaV1.2 and CaV1.3, P/Q type (CaV2.1, N-type (CaV2.2, R-type (CaV2.3, and T-type (CaV3.2 and CaV3.3 VGCC was investigated in paraffin sections from week 9 human fetal lungs and E12.5 mouse embryos. Here we show, for the first time, that Cav1.2 and Cav1.3 are expressed in both the smooth muscle and epithelium of the developing human and mouse lung. Additionally, Cav2.3 was expressed in the lung epithelium of both species. Incubating E12.5 mouse lung rudiments in the presence of nifedipine doubled the amount of branching, an effect which was partly mimicked by the Cav2.3 inhibitor, SNX-482. Direct measurements of changes in epithelial cell membrane potential, using the voltage-sensitive fluorescent dye DiSBAC2(3, demonstrated that cyclic depolarisations occur within the developing epithelium and coincide with rhythmic occlusions of the lumen, driven by the naturally occurring airway peristalsis. We conclude that VGCC are expressed and functional in the fetal human and mouse lung, where they play a role in branching morphogenesis. Furthermore, rhythmic epithelial depolarisations evoked by airway peristalsis would allow for branching to

  3. Intrinsic disorder in proteins involved in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Santamaria, Nikolas; Alhothali, Marwa; Alfonso, Maria Harreguy; Breydo, Leonid; Uversky, Vladimir N

    2017-04-01

    Five structurally and functionally different proteins, an enzyme superoxide dismutase 1 (SOD1), a TAR-DNA binding protein-43 (TDP-43), an RNA-binding protein FUS, a cofilin-binding protein C9orf72, and polypeptides generated as a result of its intronic hexanucleotide expansions, and to lesser degree actin-binding profilin-1 (PFN1), are considered to be the major drivers of amyotrophic lateral sclerosis. One of the features common to these proteins is the presence of significant levels of intrinsic disorder. The goal of this study is to consider these neurodegeneration-related proteins from the intrinsic disorder perspective. To this end, we employed a broad set of computational tools for intrinsic disorder analysis and conducted intensive literature search to gain information on the structural peculiarities of SOD1, TDP-43, FUS, C9orf72, and PFN1 and their intrinsic disorder predispositions, and the roles of intrinsic disorder in their normal and pathological functions.

  4. Integration of gene expression and GWAS results supports involvement of calcium signaling in Schizophrenia.

    Science.gov (United States)

    Hertzberg, L; Katsel, P; Roussos, P; Haroutunian, V; Domany, E

    2015-05-01

    The number of Genome Wide Association Studies (GWAS) of schizophrenia is rapidly growing. However, the small effect of individual genes limits the number of reliably implicated genes, which are too few and too diverse to perform reliable pathway analysis; hence the biological roles of the genes implicated in schizophrenia are unclear. To overcome these limitations we combine GWAS with genome-wide expression data from human post-mortem brain samples of schizophrenia patients and controls, taking these steps: 1) Identify 36 GWAS-based genes which are expressed in our dataset. 2) Find a cluster of 19 genes with highly correlated expression. We show that this correlation pattern is robust and statistically significant. 3) GO-enrichment analysis of these 19 genes reveals significant enrichment of ion channels and calcium-related processes. This finding (based on analyzing a small number of coherently expressed genes) is validated and enhanced in two ways: First, the emergence of calcium channels and calcium signaling is corroborated by identifying proteins that interact with those encoded by the cluster of 19. Second, extend the 19 cluster genes into 1028 genes, whose expression is highly correlated with the cluster's average profile. When GO-enrichment analysis is performed on this extended set, many schizophrenia related pathways appear, with calcium-related processes enriched with high statistical significance. Our results give further, expression-based validation to GWAS results, support a central role of calcium-signaling in the pathogenesis of schizophrenia, and point to additional pathways potentially related to the disease.

  5. Calcium Signaling is Involved in Negative Phototropism of Rice Seminal Roots

    Institute of Scientific and Technical Information of China (English)

    CHEN Juan; MO Yi-wei; XU Hua-wei

    2014-01-01

    Calcium ions (Ca2+) act as an intracellular second messenger and affect nearly all aspects of cellular life. They are functioned by interacting with polar auxin transport, and the negative phototropism of plant roots is caused by the transport of auxin from the irradiated side to the shaded side of the roots. To clarify the role of calcium signaling in the modulation of rice root negative phototropism, as well as the relationship between polar auxin transport and calcium signaling, calcium signaling reagents were used to treat rice seminal roots which were cultivated in hydroculture and unilaterally illuminated at an intensity of 100-200μmol/(m2·s) for 24 h. Negative phototropism curvature and growth rate of rice roots were both promoted by exogenous CaCl2 lower than 100 μmol/L, but inhibited by calcium channel blockers (verapamil and LaCl3), calcineurin inhibitor (chlorpromazine, CPZ), and polar auxin transport inhibitor (N-1-naphthylphthalamic acid, NPA). Roots stopped growing and negative phototropism disappeared when the concentrations increased to 100μmol/L verapamil, 12.500μmol/L LaCl3, 60μmol/L CPZ, and 6μmol/L NPA. Moreover, 100 μmol/L CaCl2 could relieve the inhibition of LaCl3, verapamil and NPA. The enhanced negative phototropism curvature was caused by the transportation of more auxin from the irradiated side to the shaded side in the presence of exogenous Ca2+. Calcium signaling plays a key role as a second messenger in the process of light signal regulation of rice root growth and negative phototropism.

  6. Comparison Of Serum Calcium, Phosphorus And Total Protein Levels, In Pregnancy With Or Without Hypertensive Disorders

    Directory of Open Access Journals (Sweden)

    Rashid Pooraei M

    2005-06-01

    Full Text Available Background: Pre-eclampsia is characterized by hypertension development and proteinuria during pregnancy. Hypertension disorder is a leading cause of maternal and fetal morbidity and death in worldwide. Although the pathophysiology of hypertension during pregnancy is unclear, but there is consensus that early diagnosis and aggressive treatment is warranted to prevent complicated to both fetus and mother. The changes of serum trace elements during pregnancy are paramount important to predict and good understanding the situation of patients. The aim of this study was about this issue. Materials and Methods: In a case-control study we investigated the possible differences in the level of serum calcium, phosphorus and total protein in 55 healthy pregnant and 52 pregnant with hypertensive disease at 32-40 weeks of gestational age during the recent two years in Loghman hospital of Tehran. Some information such as age, blood group, parity number and blood pressure was taken from patients by a questionnaire. Results: The case population consisted of 22 sever preeclampsia, 15 mild preeclampsia, 8 eclampsia, and 7 chronic hypertensive. The mean serum calcium concentration (mg/dl was 9.180.74 in control group, 8.810.9 in mild preeclampsia, 7.850.38 in sever preeclampsia, 7.83 0.47 in eclampsia, 8.91 0.3 in chronic blood pressure. The mean serum phosphorus (mg/dl level observed, 4.27 in sever preeclampsia, 3.74 in eclampsia, 3.59 in mild eclampsia, 4.09 in chronic blood pressure, and 3.43 in control pregnant women. The mean serum total protein concentration level in sever preeclampsia and eclampsia was 5.46 and 5.04 mg/dl respectively. Conclusion: In conclusion, sever preeclampsia and eclampsia are associated with decreased level of calcium, total protein, and increased concentration of phosphorus.

  7. The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence.

    Directory of Open Access Journals (Sweden)

    Patrícia Alves de Castro

    Full Text Available Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. Calcium homeostasis and signaling is essential for numerous biological processes and also influences A. fumigatus pathogenicity. The presented study characterized the function of the A. fumigatus homologues of three Saccharomyces cerevisiae calcium channels, voltage-gated Cch1, stretch-activated Mid1 and vacuolar Yvc1. The A. fumigatus calcium channels cchA, midA and yvcA were regulated at transcriptional level by increased calcium levels. The YvcA::GFP fusion protein localized to the vacuoles. Both ΔcchA and ΔmidA mutant strains showed reduced radial growth rate in nutrient-poor minimal media. Interestingly, this growth defect in the ΔcchA strain was rescued by the exogenous addition of CaCl2. The ΔcchA, ΔmidA, and ΔcchA ΔmidA strains were also sensitive to the oxidative stress inducer, paraquat. Restriction of external Ca(2+ through the addition of the Ca(2+-chelator EGTA impacted upon the growth of the ΔcchA and ΔmidA strains. All the A. fumigatus ΔcchA, ΔmidA, and ΔyvcA strains demonstrated attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Infection with the parental strain resulted in a 100% mortality rate at 15 days post-infection, while the mortality rate of the ΔcchA, ΔmidA, and ΔyvcA strains after 15 days post-infection was only 25%. Collectively, this investigation strongly indicates that CchA, MidA, and YvcA play a role in A. fumigatus calcium homeostasis and virulence.

  8. Potassium-induced contraction in the lamb proximal urethra: Involvement of norepinephrine and different calcium entry pathways

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Pascual, A.; Costa, G.; Isla, M.; Jimenez, E.; Garcia-Sacristan, A. (Universidad Complutense de Madrid (Spain))

    1991-01-01

    The purpose of this work was to investigate the mechanisms involved in the peculiar biphasic response of the lamb urethral smooth muscle to high K+ solutions. The relative amplitude of the phasic and tonic components of the contraction and its reproducibility were dependent on the concentration of K+ used. Only concentrations higher than 80 mM (i.e., 120 mM) showed a tonic component greater in amplitude than the phasic one and manifested a tachyphylactic effect. Phentolamine (10(-6) M), prazosin (10(-6) M) and chemical denervation with 6-hydroxydopamine significantly inhibited the tonic component of the K+ (120 mM)-induced contraction, modifying its morphology. Reproducible contractions to K+ (120 mM) could be obtained in the presence of prazosin (10(-6) M) or cocaine (10(-6) M). The preparations were also shown to accumulate (3H)noradrenaline and release it upon depolarization with K+ (60 and 120 mM). Calcium removal inhibited the K+ (120 mM)-induced contraction. After addition of calcium (0.5-5 mM) the contractile activity was restored. Nifedipine (10(-6) M) and verapamil (10(-6) M) but not sodium nitroprusside (10(-6) M) significantly blocked the contractile response for calcium as well as the phasic component of the K+ contraction in calcium-containing medium. In preparations treated with prazosin (10(-6) M) the tonic component of the K+ (120 mM) contraction was more sensitive to nifedipine and removal of extracellular calcium than the phasic one.

  9. Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload

    Directory of Open Access Journals (Sweden)

    Teng Ma

    2015-08-01

    Full Text Available Lead (Pb poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3 mRNA expression, one of the major means of calcium (Ca2+ extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP expression and cell branching. Ca2+ response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca2+ concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.

  10. Fruit Calcium: Transport and Physiology

    Directory of Open Access Journals (Sweden)

    Bradleigh eHocking

    2016-04-01

    Full Text Available Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact fruit development, physical traits and disease susceptibility through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to ripening and the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g. blossom end rot in tomatoes or bitter pit in apples. This review works towards an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved

  11. 钙代谢紊乱的临床治疗分析%Clinical Treatment of Calcium Metabolism Disorders

    Institute of Scientific and Technical Information of China (English)

    王鹤辉

    2015-01-01

    Objective To investigate the calcium metabolism disorder clinical treatment effect.Methods The clinical treatment of disorders of calcium metabolism data from March 2014 to June 2015 were treated for analysis.Results The clinical treatment of clinical symptoms, results were satisfactory.Conclusion Hypocalcemia remove the cause, correct alkalosis. Asymptomatic, oral calcium and vitamin D2. There are symptoms, should intravenous calcium. Patients need long-term calcium, calcium lactate can be taken orally. There are obvious symptoms or serum calcium up 3.5 to 3.75 mmol/L (ie, 14 to 15 mg/L), regardless of symptoms, should immediately press the accident and emergency treatment.%目的:探讨钙代谢紊乱的临床治疗方法效果。方法选取2014年3月~2015年6月收治的钙代谢紊乱的临床治疗方法资料进行分析。结果经临床治疗临床症状改善,效果满意。结论低钙血症去除病因,纠正碱中毒。无症状者,可口服钙和维生素D2。有症状者,应静脉补钙。对需要长期补钙的患者,可口服乳酸钙。有明显症状或血清钙高达3.5~3.75 mmol/L(即14~15 mg/L),不论有无症状,均应立即按急症治疗。

  12. Neuroprotective activity of stiripentol with a possible involvement of voltage-dependent calcium and sodium channels.

    Science.gov (United States)

    Verleye, Marc; Buttigieg, Dorothée; Steinschneider, Rémy

    2016-02-01

    A growing body of data has shown that recurrent epileptic seizures may be caused by an excessive release of the excitatory neurotransmitter glutamate in the brain. Glutamatergic overstimulation results in massive neuronal influxes of calcium and sodium through N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainic acid glutamate subtype receptors and also through voltage-gated calcium and sodium channels. These persistent and abnormal sodium and calcium entry points have deleterious consequences (neurotoxicity) for neuronal function. The therapeutic value of an antiepileptic drug would include not only control of seizure activity but also protection of neuronal tissue. The present study examines the in vitro neuroprotective effects of stiripentol, an antiepileptic compound with γ-aminobutyric acidergic properties, on neuronal-astroglial cultures from rat cerebral cortex exposed to oxygen-glucose deprivation (OGD) or to glutamate (40 µM for 20 min), two in vitro models of brain injury. In addition, the affinity of stiripentol for the different glutamate receptor subtypes and the interaction with the cell influx of Na(+) and of Ca(2+) enhanced by veratridine and NMDA, respectively, are assessed. Stiripentol (10-100 µM) included in the culture medium during OGD or with glutamate significantly increased the number of surviving neurons relative to controls. Stiripentol displayed no binding affinity for different subtypes of glutamate receptors (IC50  >100 µM) but significantly blocked the entry of Na(+) and Ca(2+) activated by veratridine and NMDA, respectively. These results suggest that Na(+) and Ca(2+) channels could contribute to the neuroprotective properties of sitiripentol.

  13. The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects.

    LENUS (Irish Health Repository)

    Lyng, F M

    2006-04-01

    Much evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of

  14. Involvement of the calcium-sensing receptor in human taste perception.

    Science.gov (United States)

    Ohsu, Takeaki; Amino, Yusuke; Nagasaki, Hiroaki; Yamanaka, Tomohiko; Takeshita, Sen; Hatanaka, Toshihiro; Maruyama, Yutaka; Miyamura, Naohiro; Eto, Yuzuru

    2010-01-08

    By human sensory analyses, we found that various extracellular calcium-sensing receptor (CaSR) agonists enhance sweet, salty, and umami tastes, although they have no taste themselves. These characteristics are known as "kokumi taste" and often appear in traditional Japanese cuisine. Although GSH is a typical kokumi taste substance (taste enhancer), its mode of action is poorly understood. Here, we demonstrate how the kokumi taste is enhanced by the CaSR, a close relative of the class C G-protein-coupled receptors T1R1, T1R2, and T1R3 (sweet and umami receptors). We identified a large number of CaSR agonist gamma-glutamyl peptides, including GSH (gamma-Glu-Cys-Gly) and gamma-Glu-Val-Gly, and showed that these peptides elicit the kokumi taste. Further analyses revealed that some known CaSR agonists such as Ca(2+), protamine, polylysine, L-histidine, and cinacalcet (a calcium-mimetic drug) also elicit the kokumi taste and that the CaSR-specific antagonist, NPS-2143, significantly suppresses the kokumi taste. This is the first report indicating a distinct function of the CaSR in human taste perception.

  15. Noscapine protects OLN-93 oligodendrocytes from ischemia-reperfusion damage: Calcium and nitric oxide involvement.

    Science.gov (United States)

    Nadjafi, S; Ebrahimi, S-A; Rahbar-Roshandel, N

    2015-12-01

    This study was carried out to evaluate the effects of noscapine, a benzylisoquinoline alkaloid from opium poppy, on oligodendrocyte during ischemia/reperfusion-induced excitotoxic injury. Changes in intracellular calcium levels due to chemical ischemia and nitric oxide (NO) production during ischemia/reperfusion were evaluated as the hallmarks of ischemia-derived excitotoxic event. OLN-93 cell line (a permanent immature rat oligodendrocyte) was used as a model of oligodendrocyte. 30- or 60-minute-oxygen-glucose deprivation/24 hours reperfusion were used to induce excitotoxicity. MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used to evaluate cell viability. Ratiometric fluorescence microscopy using Ca(2+)-sensitive indicator Fura-2/AM was utilized to assess intracellular calcium levels. NO production was evaluated by Griess method. Noscapine (4 μM) significantly attenuated intracellular Ca(2+) elevation (P noscapine significantly decreased NO production during a 30-minute oxygen-glucose deprivation/reperfusion (P noscapine (4 μM) on intracellular Ca(2+) was greater than ionotropic glutamate receptors antagonists. Noscapine is protective against ischemia/reperfusion-induced excitotoxic injury in OLN-93 oligodendrocyte. This protective effect seems to be related to attenuation of intracellular Ca(2+) overload and NO production.

  16. Involvement of phospholipase D in store-operated calcium influx in vascular smooth muscle cells.

    Science.gov (United States)

    Walter, M; Tepel, M; Nofer, J R; Neusser, M; Assmann, G; Zidek, W

    2000-08-11

    In non-excitable cells, sustained intracellular Ca2+ increase critically depends on influx of extracellular Ca2+. Such Ca2+ influx is thought to occur by a 'store-operated' mechanism, i.e. the signal for Ca2+ entry is believed to result from the initial release of Ca2+ from inositol 1,4,5-trisphosphate-sensitive intracellular stores. Here we show that the depletion of cellular Ca2+ stores by thapsigargin or bradykinin is functionally linked to a phosphoinositide-specific phospholipase D (PLD) activity in cultured vascular smooth muscle cells (VSMC), and that phosphatidic acid formed via PLD enhances sustained calcium entry in this cell type. These results suggest a regulatory role for PLD in store-operated Ca2+ entry in VSMC.

  17. Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death.

    Science.gov (United States)

    Liao, Yajin; Hao, Yumin; Chen, Hong; He, Qing; Yuan, Zengqiang; Cheng, Jinbo

    2015-06-01

    Mitochondrial calcium uniporter (MCU) is a conserved Ca(2+) transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress-induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca(2+) uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca(2+) uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.

  18. A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development

    Science.gov (United States)

    Cipriani, A; Saunders, K; Attenburrow, M-J; Stefaniak, J; Panchal, P; Stockton, S; Lane, T A; Tunbridge, E M; Geddes, J R; Harrison, P J

    2016-01-01

    l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of ‘brain-selective' LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes. PMID:27240535

  19. The Calcium Sensor CBL-CIPK Is Involved in Plant’s Response to Abiotic Stresses

    Directory of Open Access Journals (Sweden)

    S. M. Nuruzzaman Manik

    2015-01-01

    Full Text Available Abiotic stress halts the physiological and developmental process of plant. During stress condition, CBL-CIPK complex is identified as a primary element of calcium sensor to perceive environmental signals. Recent studies established that this complex regulates downstream targets like ion channels and transporters in adverse stages conditions. Crosstalks between the CBL-CIPK complex and different abiotic stresses can extend our research area, which can improve and increase the production of genetically modified crops in response to abiotic stresses. How this complex links with environmental signals and creates adjustable circumstances under unfavorable conditions is now one of the burning issues. Diverse studies are already underway to delineate this signalling mechanism underlying different interactions. Therefore, up to date experimental results should be concisely published, thus paving the way for further research. The present review will concisely recapitulate the recent and ongoing research progress of positive ions (Mg2+, Na+, and K+, negative ions (NO3-, PO4-, and hormonal signalling, which are evolving from accumulating results of analyses of CBL and CIPK loss- or gain-of-function experiments in different species along with some progress and perspectives of our works. In a word, this review will give one step forward direction for more functional studies in this area.

  20. Involvement of mouse and porcine PLCζ-induced calcium oscillations in preimplantation development of mouse embryos

    Energy Technology Data Exchange (ETDEWEB)

    Yoneda, Akihiro, E-mail: ayoneda@sci.hokudai.ac.jp [Laboratory of Animal Breeding and Reproduction, Graduate School of Agriculture, Hokkaido University (Japan); Division of Molecular Therapeutics, Center for Food & Medical Innovation, Hokkaido University (Japan); Watanabe, Tomomasa [Laboratory of Animal Breeding and Reproduction, Graduate School of Agriculture, Hokkaido University (Japan)

    2015-05-01

    In mammals, phospholipase Cζ (PLCζ) has the ability to trigger calcium (Ca{sup 2+}) oscillations in oocytes, leading to oocyte activation. Although there is a species-specific difference in the PLCζ-induced Ca{sup 2+} oscillatory pattern, whether PLCζ-induced Ca{sup 2+} oscillations affect preimplantation embryonic development remains unclear. Here, we show that Ca{sup 2+} oscillations in mouse PLCζ cRNA-injected oocytes stopped just before pronuclear formation, while that in porcine PLCζ cRNA-injected oocytes continued for several hours after pronuclei had been formed. This difference of Ca{sup 2+} oscillations in oocytes after pronuclear formation was dependent on the difference in the nuclear localization signal (NLS) sequence of PLCζ between the mouse and pig. However, mouse and porcine PLCζ cRNA-injected oocytes parthenogenetically developed to blastocysts regardless of the absence or presence of Ca{sup 2+} oscillations after pronuclear formation. Furthermore, the developmental rate of mouse or porcine PLCζ-activated oocytes injected with round spermatids to the blastocyst stage was not significantly different from that of strontium-activated oocytes injected with round spermatids. These results suggest that the PLCζ-induced Ca{sup 2+} oscillatory pattern in mouse oocytes is dependent on the NLS sequence of PLCζ and injection of PLCζ may be a useful method for activation of round spermatid-injected and somatic nuclear transferred oocytes. - Highlights: • Porcine PLCζ-induced Ca{sup 2+} oscillations continued after pronuclear formation. • The Ca{sup 2+} oscillatory pattern was dependent on the difference in the NLS sequence of PLCζ. • PLCζ-activated oocytes parthenogenetically developed to blastocysts. • PLCζ-activated oocytes injected with round spermatids developed to blastocysts.

  1. Calcium paradox induces apoptosis in the isolated perfused Rana ridibunda heart: involvement of p38-MAPK and calpain

    National Research Council Canada - National Science Library

    Aggeli, Ioanna-Katerina; Zacharias, Triantafyllos; Papapavlou, Georgia; Gaitanaki, Catherine; Beis, Isidoros

    2013-01-01

    "Calcium paradox" as a term describes the deleterious effects conferred to a heart perfused with a calcium-free solution followed by repletion, including loss of mechanical activity and sarcomere disruption...

  2. Involvement in Transition Planning Meetings among High School Students with Autism Spectrum Disorders

    Science.gov (United States)

    Griffin, Megan M.; Taylor, Julie Lounds; Urbano, Richard C.; Hodapp, Robert M.

    2014-01-01

    Although students with autism spectrum disorders (ASD) are least likely to attend and participate in transition planning meetings, little is known about factors related to their involvement. Using a national data set, we conducted regressions to identify predictors of the involvement of 320 youth with ASD. Attendance positively related to higher…

  3. An Evaluation of School Involvement and Satisfaction of Parents of Children with Autism Spectrum Disorders

    Science.gov (United States)

    Zablotsky, Benjamin; Boswell, Katelyn; Smith, Christopher

    2012-01-01

    Parental school involvement and satisfaction are unstudied in families raising a child with an autism spectrum disorder (ASD). To fill this gap, the current study utilized a national sample of families (N = 8,978) from the 2007 Parent and Family Involvement in Education survey (U.S. Department of Education, National Center for Education…

  4. Wasted tongue in neuromyelitis optica spectrum disorders due to hypoglossal nerve involvement.

    Science.gov (United States)

    Viswanathan, Shanthi

    2015-04-01

    We report two cases of neuromyelitis optica spectrum disorder with hypoglossal nerve involvement resulting in a wasted tongue associated with other brainstem symptoms of hypogeusia, hypersalivation, hiccough, increased sweating, hyperemesis and myelitis (in the second patient). This occurred due to involvement of the hypoglossal, tractus solitarius and dorsal vagal nuclei. Though the myelitis and other brainstem signs recovered the hypoglossal nerve involvement resulting in a unilateral wasted tongue did not. It is important to consider neuromyelitis optica and its spectrum disorders in the differential diagnosis of a wasted tongue though its occurrence is rare.

  5. [Clinical efficacy of calcium channel blockers slow the third generation of lercanidipine in the treatment of patients with arterial hypertension and metabolic disorders (review)].

    Science.gov (United States)

    Tabidze, G A; Gezeli, T D; Tsibadze, T A; Dolidze, N M

    2015-02-01

    Arterial hypertension is the most common risk factor in patients with metabolic disorders. In the selection of antihypertensive therapy it is necessary to consider not only the anti-hypertensive and organoprotective effects of drugs and their metabolic effects, which has prognostic value. Calcium antaginists, along. Lercanidipine related to the third generation dihydripyridine calcium antagonist, has been much more selective for the so-called slow calcium channels of vascular smooth muscle cells, which is associated with a good hypertensive, organo and metabolic action. Combination therapy with an ACE inhibitor and a calcium channel blocker is also a justified tactic for the management of patients with high-risk cardiovascular and metabolic disorders. Attention is paid new fixed combinations, including angiotensin converting enzyme inhibitors and calcium antagonists.

  6. Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

    Directory of Open Access Journals (Sweden)

    Andreas Totzeck

    2016-09-01

    Full Text Available Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

  7. P/Q-type and T-type voltage-gated calcium channels are involved in the contraction of mammary and brain blood vessels from hypertensive patients

    DEFF Research Database (Denmark)

    Thuesen, A D; Lyngsø, K S; Rasmussen, L

    2017-01-01

    channels are involved in the contraction of mammary arteries from hypertensive patients but not from normotensive patients. Furthermore, in cerebral arterioles P/Q-type channels importance was restricted to hypertensive patients might lead to that T- and P/Q-type channels could be a new target......AIM: Calcium channel blockers are widely used in cardiovascular diseases. Besides L-type channels, T- and P/Q-type calcium channels are involved in the contraction of human renal blood vessels. It was hypothesized that T- and P/Q-type channels are involved in the contraction of human brain...... contraction in cerebral arterioles from hypertensive patients. L-type blocker nifedipine abolished the contraction in mammary arteries. PCR analysis showed expression of P/Q-type (Cav 2.1), T-type (Cav 3.1 and Cav 3.2) and L-type (Cav 1.2) calcium channels in mammary and cerebral arteries. Immunohistochemical...

  8. The Involvement of Ser1898 of the Human L-Type Calcium Channel in Evoked Secretion

    Directory of Open Access Journals (Sweden)

    Niv Bachnoff

    2011-01-01

    Full Text Available A PKA consensus phosphorylation site S1928 at the α11.2 subunit of the rabbit cardiac L-type channel, CaV1.2, is involved in the regulation of CaV1.2 kinetics and affects catecholamine secretion. This mutation does not alter basal CaV1.2 current properties or regulation of CaV1.2 current by PKA and the beta-adrenergic receptor, but abolishes CaV1.2 phosphorylation by PKA. Here, we test the contribution of the corresponding PKA phosphorylation site of the human α11.2 subunit S1898, to the regulation of catecholamine secretion in bovine chromaffin cells. Chromaffin cells were infected with a Semliki-Forest viral vector containing either the human wt or a mutated S1898A α11.2 subunit. Both subunits harbor a T1036Y mutation conferring nifedipine insensitivity. Secretion evoked by depolarization in the presence of nifedipine was monitored by amperometry. Depolarization-triggered secretion in cells infected with either the wt α11.2 or α11.2/S1898A mutated subunit was elevated to a similar extent by forskolin. Forskolin, known to directly activate adenylyl-cyclase, increased the rate of secretion in a manner that is largely independent of the presence of S1898. Our results are consistent with the involvement of additional PKA regulatory site(s at the C-tail of α11.2, the pore forming subunit of CaV1.2.

  9. Factors involved in the etiology of temporomandibular disorders - a literature review

    OpenAIRE

    CHISNOIU, ANDREA MARIA; PICOS, ALINA MONICA; POPA, SEVER; CHISNOIU, PETRE DANIEL; LASCU, LIANA; PICOS, ANDREI; CHISNOIU, RADU

    2015-01-01

    Background and aim This review aims at presenting a current view on the most frequent factors involved in the mechanisms causing temporomandibular disorders (TMD). Method We conducted a critical review of the literature for the period January 2000 to December 2014 to identify factors related to TMD development and persistence. Results The etiology of TMD is multidimensional: biomechanical, neuromuscular, bio-psychosocial and biological factors may contribute to the disorder. Occlusal overload...

  10. The involvement of intracellular calcium ion concentration and calmodulin in the 25-hydroxylation of cholecalciferol in ovine and rat liver.

    Science.gov (United States)

    Corlett, S C; Chaudhary, M S; Tomlinson, S; Care, A D

    1987-08-01

    The effect of Ca2+ ion concentration on the 25 hydroxylation of tritiated cholecalciferol (3HD3) was investigated using homogenates of ovine liver from vitamin D replete sheep. A significant decrease in the production of 25 hydroxycholecalciferol (25OHD3) was observed when the concentration of Ca2+ in the homogenate was raised above 0.68 mmol/l by the addition of calcium gluconate. Similarly, a final concentration of 37 mumol EGTA/1 (equivalent to a Ca2+ concentration of 26.5 nmol/l) was associated with a 50% reduction of 25OHD3 production. That is, a broad bell-shaped relationship was observed between the production of 25OHD3 and the Ca2+ concentration in the homogenate. These changes in the rate of production of 25OHD3 were reproduced with hepatocytes from vitamin D replete rats, prepared by collagenase perfusion, using the drugs dantrolene sodium (DaNa) to reduce (ED50 = 57 mmol/l) and veratridine to increase (ED50 = 550 mmol/l) the intracellular Ca2+ concentration. Hepatocytes from vitamin D replete rats also showed a reduction in 25 hydroxylation of D3 (ED50 = 6 ng/ml) in response to the addition of 1-25 dihydroxycholecalciferol (1-25 (OH)2D3). The calmodulin antagonists; W7, compound 48/80, trifluoperazine (TFP) and calmidazolium (R24571) were all found to effect a dose response inhibition of the 25 hydroxylation of cholecalciferol by homogenates of ovine liver. R24571 had a similar inhibitory effect (ED50 = 70 mumol/l) upon the 25 hydroxylase enzyme of rat hepatocytes. It is concluded that the 25 hydroxylation of cholecalciferol in liver of vitamin D replete rats and sheep is calcium sensitive and is reduced in the presence of increased concentrations of 1,25(OH)2D3. Calmodulin may also be involved in the regulation of hepatocyte 25-hydroxylase activity by Ca2+.

  11. Is childhood bullying involvement a precursor of eating disorder symptoms? A prospective analysis

    Science.gov (United States)

    Copeland, William E.; Bulik, Cynthia M.; Zucker, Nancy; Wolke, Dieter; Lereya, Suzet Tanya; Costello, E. Jane

    2015-01-01

    Objective Bullying is a common childhood experience with enduring psychosocial consequences. The aim of this study was to test whether bullying increases risk for eating disorder symptoms. Method Ten waves of data on 1420 participants between ages 9 and 25 were used from the prospective population-based Great Smoky Mountains Study. Structured interviews were used to assess bullying involvement and symptoms of anorexia nervosa and bulimia nervosa as well as associated features. Bullying involvement was categorized as not involved, bully only, victim only, or both bully and victim (bully-victims). Results Within childhood/adolescence, victims of bullying were at increased risk for symptoms of anorexia nervosa and bulimia nervosa as well as associated features. These associations persisted after accounting for prior eating disorder symptom status as well as preexisting psychiatric status and family adversities. Bullies were at increased risk of symptoms of bulimia and associated features of eating disorders, and bully-victims had higher levels of anorexia symptoms. In terms of individual items, victims were at risk for binge eating and bully-victims had more binge eating and use of vomiting as a compensatory behavior. There was little evidence in this sample that these effects differed by sex. Childhood bullying status was not associated with increased risk for persistent eating disorder symptoms into adulthood (ages 19, 21, and 25). Discussion Bullying predicts eating disorder symptoms for both bullies and victims. Bullying involvement should be a part of risk assessment and treatment planning for children with eating problems. PMID:26337405

  12. Endogenous and Exogenous Calcium Involved in the Betulin Production from Submerged Culture of Phellinus linteus Induced by Hydrogen Sulfide.

    Science.gov (United States)

    Fan, Guizhi; Jian, Duan; Sun, Meiling; Zhan, Yaguang; Sun, Feifei

    2016-02-01

    Using pharmacological and biochemical approaches, Ca(2+) involved in the betulin production in mycelia of Phellinus linteus induced by hydrogen sulfide (H2S) were investigated. The results showed that 2 mM H2S donor NaHS or 10 mM CaCl2 was found to enhance the betulin content in the mycelia of Phellinus to the maximum, which were 112.43 and 93.24% higher than that in the control, respectively. Further, NaHS and CaCl2 co-treatment also showed positive outcome, which were 128.95 or 24.52% higher than that in the control or NaHS treatment. At the same time, NaHS also enhanced the content of Ca(2+) and CaM. But, the above positive inductive effects for Ca(2+), CaM, and betulin production can be blocked with either Ca(2+) channel blocker (LaCl3, 2-aminoethoxydiphenyl borate) or Ca(2+) chelator (ethylenediaminetetraacetic acid (EDTA)). Among of them, betulin content was reduced 35.06% by NaHS and EGTA to the minimum, and this reduction could be reversed by the application of CaCl2 (NaHS + EGTA + CaCl2). From above results, it can be concluded that endogenous and exogenous calcium involved in the betulin production from submerged culture of P. linteus induced by hydrogen sulfide.

  13. Interactions between salinity and boron toxicity in tomato plants involve apoplastic calcium.

    Science.gov (United States)

    Bastías, Elizabeth; Alcaraz-López, Carlos; Bonilla, Ildefonso; Martínez-Ballesta, M Carmen; Bolaños, Luis; Carvajal, Micaela

    2010-01-01

    The lack of consensus about the mutual relations between salinity and boron (B) toxicity with respect to the physiological response of plants necessitates investigation of the interactions of soluble B with salinity. In this investigation, the effect of B was compared with Ca in order to elucidate whether the two nutrients have similar effects and/or to elucidate a relationship under salinity. Following addition of B or Ca, salinity was applied to tomato plants and the cell wall and plasma membrane permeability, measured as water permeability and electrolyte leakage, in relation to amino acid and ion cell wall composition, were determined. As the relationship between B and salinity was complex, several hypotheses are established. The increase of aquaporin functionality due to the presence of B and Ca compared with NaCl-treated plants could be the most feasible, whereas there is currently no satisfactory explanation for the results for the cell wall amino acid composition. In addition, the elemental composition results revealed that, in addition the known interactions between B and Ca with respect to cell wall stability, Mg and Mn were also increased in NaCl+B and NaCl+Ca treatments, suggesting their possible involvement in the cell wall function necessary for plant growth.

  14. Dose calcium channel blocker verapamil decrease urinary VMA levels in sympathoadrenal hyperactive patients with posttraumatic stress disorder?

    Institute of Scientific and Technical Information of China (English)

    Munawar Alam Ansari; Shahida PAhmed; Zahida Memon

    2008-01-01

    Objective:The majority of the patients with posttraumatic stress disorders (PTSD)embrace augmented urina-ry flow of Vanillylmandelic Acid (VMA)than normal subjects owing to superior sympathetic doings,which steer to cardiovascular catastrophe.Urinary flow of VMA was evaluated as sympathoadrenal bustle marker in patients with posttraumatic stress disorder.Calcium ion shows a noteworthy dependability in nervousness owing to its special effects on brain synaptosomes.So this study was conducted to explore the effects of Verapamil on sympathoadrenal motion in patients with PTSD.Methods:Placebo controlled clinical tryout was conducted. At first hundred (100)PTSD patients were chosen and enrolled in the study,from department of Psychological Medicine Dow University of Health Sciences,Karachi.Verapamil 120 mg/day was specified in divided doses to group-I (n =50)patients and group-II (n =50)patients received placebo therapy on a daily basis for nine weeks.Each and every patient was monitored weekly,all the way through extent of study.Results:Under-neath the posttraumatic stress disorder,urinary excretion of VMA was greater.Calcium channel blocker vera-pamil additionally abolished the embellished retort in urinary flow of VMA appreciably in patients with PTSD. Conclusion:Verapamil was experiential to be exceedingly effectual treatment.It reduces VMA levels in u-rine,and on the whole cardiovascular threat in PTSD patients.

  15. Absence of aquaporin-4 in skeletal muscle alters proteins involved in bioenergetic pathways and calcium handling.

    Directory of Open Access Journals (Sweden)

    Davide Basco

    Full Text Available Aquaporin-4 (AQP4 is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4 on the morphology and protein composition of sarcolemma as well as on the whole skeletal muscle proteome. Immunofluorescence analysis showed that the absence of AQP4 did not perturb the expression and cellular localization of the dystrophin-glycoprotein complex proteins, aside from those belonging to the extracellular matrix, and no alteration was found in sarcolemma integrity by dye extravasation assay. With the use of a 2DE-approach (BN/SDS-PAGE, protein maps revealed that in quadriceps, out of 300 Coomassie-blue detected and matched spots, 19 proteins exhibited changed expression in AQP4(-/- compared to WT mice. In particular, comparison of the protein profiles revealed 12 up- and 7 down-regulated protein spots in AQP4-/- muscle. Protein identification by MS revealed that the perturbed expression pattern belongs to proteins involved in energy metabolism (i.e. GAPDH, creatine kinase, as well as in Ca(2+ handling (i.e. parvalbumin, SERCA1. Western blot analysis, performed on some significantly changed proteins, validated the 2D results. Together these findings suggest AQP4 as a novel determinant in the regulation of skeletal muscle metabolism and better define the role of this water channel in skeletal muscle physiology.

  16. Absence of aquaporin-4 in skeletal muscle alters proteins involved in bioenergetic pathways and calcium handling.

    Science.gov (United States)

    Basco, Davide; Nicchia, Grazia Paola; D'Alessandro, Angelo; Zolla, Lello; Svelto, Maria; Frigeri, Antonio

    2011-04-28

    Aquaporin-4 (AQP4) is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4 on the morphology and protein composition of sarcolemma as well as on the whole skeletal muscle proteome. Immunofluorescence analysis showed that the absence of AQP4 did not perturb the expression and cellular localization of the dystrophin-glycoprotein complex proteins, aside from those belonging to the extracellular matrix, and no alteration was found in sarcolemma integrity by dye extravasation assay. With the use of a 2DE-approach (BN/SDS-PAGE), protein maps revealed that in quadriceps, out of 300 Coomassie-blue detected and matched spots, 19 proteins exhibited changed expression in AQP4(-/-) compared to WT mice. In particular, comparison of the protein profiles revealed 12 up- and 7 down-regulated protein spots in AQP4-/- muscle. Protein identification by MS revealed that the perturbed expression pattern belongs to proteins involved in energy metabolism (i.e. GAPDH, creatine kinase), as well as in Ca(2+) handling (i.e. parvalbumin, SERCA1). Western blot analysis, performed on some significantly changed proteins, validated the 2D results. Together these findings suggest AQP4 as a novel determinant in the regulation of skeletal muscle metabolism and better define the role of this water channel in skeletal muscle physiology.

  17. Gastrointestinal involvement of posttransplant lymphoproliferative disorder in lung transplant recipients: report of a case.

    Science.gov (United States)

    Shitrit, David; Shitrit, Ariella Bar-Gil; Dickman, Ram; Sahar, Gidon; Saute, Milton; Kramer, Mordechai R

    2005-11-01

    Lymphoproliferative disorder is a well-recognized complication of lung transplantation. Risk factors include Epstein-Barr virus infection and immunosuppression. The gastrointestinal manifestations of post-transplant lymphoproliferative disorder in lung transplant recipients have not been fully characterized. Case presentation and 16 previously reported cases of post-transplant lymphoproliferative disorder with gastrointestinal involvement are reviewed. Patient ages ranged from 25 to 65 (median, 52) years. Median time from lung transplantation to onset of posttransplant lymphoproliferative disorder was 36 (range, 1-109) months; 35 percent of cases (6/17) occurred within 18 months; Eighty-eight percent of patients (15/17) had positive Epstein-Barr virus serology before transplantation. In five patients (29 percent), the posttransplant lymphoproliferative disorder also involved sites other than the gastrointestinal tract. The most common gastrointestinal site of posttransplant lymphoproliferative disorder was the colon, followed by the small intestine and stomach. Clinical features included abdominal pain, nausea, and bloody diarrhea. Diagnosis was based on typical pathologic changes on gastrointestinal tract biopsy obtained mainly by colonoscopy. Treatment included a reduction in the immunosuppressive regimen in 15 of 17 cases (88 percent) and surgical resection in 10 (59 percent). One patient was untreated. Seven of 16 patients (44 percent) responded to treatment and 9 patients died. Median time from onset of posttransplant lymphoproliferative disorder to death was 70 (range, 10-85) days. Posttransplant lymphoproliferative disorder with gastrointestinal involvement is a unique entity that should be considered in all Epstein-Barr-Virus-positive lung transplant recipients who present with abdominal symptoms. Although immunosuppressive modulation and resection can lead to remission, the risk of death is 50 percent.

  18. Calcium Influx Inhibition is Involved in the Hypotensive and Vasorelaxant Effects Induced by Yangambin

    Directory of Open Access Journals (Sweden)

    Islania Giselia Albuquerque Araújo

    2014-05-01

    Full Text Available The pharmacological effects on the cardiovascular system of yangambin, a lignan isolated from Ocotea duckei Vattimo (Lauraceae, were studied in rats using combined functional and biochemical approaches. In non-anaesthetized rats, yangambin (1, 5, 10, 20, 30 mg/kg, i.v. induced hypotension (−3.5 ± 0.2; −7.1 ± 0.8; −8.9 ± 1.3; −14 ± 2.3, −25.5% ± 2.6%, respectively accompanied by tachycardia (5.9 ± 0.5; 5.9 ± 1.6; 8.8 ± 1.4; 11.6, 18.8% ± 3.4%, respectively. In isolated rat atria, yangambin (0.1 µM–1 mM had very slight negative inotropic (Emax = 35.6% ± 6.4% and chronotropic effects (Emax = 10.2% ± 2.9%. In endothelium-intact rat mesenteric artery, yangambin (0.1 µM–1 mM induced concentration-dependent relaxation (pD2 = 4.5 ± 0.06 of contractions induced by phenylephrine and this effect was not affected by removal of the endothelium. Interestingly, like nifedipine, the relaxant effect induced by yangambin was more potent on the contractile response induced by KCl 80 mM (pD2 = 4.8 ± 0.05 when compared to that induced by phenylephrine. Furthermore, yangambin inhibited CaCl2-induced contractions in a concentration-dependent manner. This lignan also induced relaxation (pD2 = 4.0 ± 0.04 of isolated arteries pre-contracted with S(−-Bay K 8644. In fura-2/AM-loaded myocytes of rat mesenteric arteries, yangambin inhibited the Ca2+ signal evoked by KCl 60 mM. In conclusion, these results suggest that the hypotensive effect of yangambin is probably due to a peripheral vasodilatation that involves, at least, the inhibition the Ca2+ influx through voltage-gated Ca2+ channels.

  19. Disordered gambling, type of gambling and gambling involvement in the British Gambling Prevalence Survey 2007

    OpenAIRE

    LaPlante, Debi A.; Nelson, Sarah E.; LaBrie, Richard A.; Shaffer, Howard J.

    2009-01-01

    Background: The purpose of this study was to examine the relationships between types of gambling and disordered gambling, with and without controlling for gambling involvement (i.e. the number of types of games with which respondents were involved during the past 12 months). Methods: We completed a secondary data analysis of the 2007 British Gambling Prevalence Survey (BGPS), which collected data in England, Scotland and Wales between September 2006 and March 2007. The sample included 9003 re...

  20. High School Sports Involvement Diminishes the Association Between Childhood Conduct Disorder and Adult Antisocial Behavior.

    Science.gov (United States)

    Samek, Diana R; Elkins, Irene J; Keyes, Margaret A; Iacono, William G; McGue, Matt

    2015-07-01

    Life course-persistent antisocial behavior manifests as a display of aggressive and antisocial behavior beginning in childhood (conduct disorder [CD]) and lasting through adulthood (adult antisocial personality disorder). This study aimed to build on prior research by evaluating whether involvement in high school sports helped attenuate the association between CD and subsequent adult antisocial behavior (AAB). A prospective sample of 967 male and female adolescents (56% adopted) was used. Structured interviews were used to assess CD (symptoms before the age of 15 years), involvement in sports during high school, and past-year adult antisocial personality disorder symptoms in young adulthood (M age = 22.4 years). As expected, the association between CD and AAB was significantly less for those involved in sports (β = .28; p sports (β = .49; p behavior in the model (age, gender, adoption status), and results were consistent across males and females. Involvement in other extracurricular activities (e.g., student government, plays, clubs) did not significantly moderate the relationship between CD and AAB. Although selection effects were evident (those with more CD symptoms were less likely to be involved in sports), findings nevertheless suggest high school sports involvement may be a notable factor related to disrupting persistent antisocial behavior beginning in childhood and adolescence and lasting through young adulthood. Implications are discussed. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  1. Parental Beliefs and Experiences Regarding Involvement in Intervention for Their Child with Speech Sound Disorder

    Science.gov (United States)

    Watts Pappas, Nicole; McAllister, Lindy; McLeod, Sharynne

    2016-01-01

    Parental beliefs and experiences regarding involvement in speech intervention for their child with mild to moderate speech sound disorder (SSD) were explored using multiple, sequential interviews conducted during a course of treatment. Twenty-one interviews were conducted with seven parents of six children with SSD: (1) after their child's initial…

  2. Sibling Involvement in Interventions for Individuals with Autism Spectrum Disorders: A Systematic Review

    Science.gov (United States)

    Shivers, Carolyn M.; Plavnick, Joshua B.

    2015-01-01

    Many researchers have studied various interventions for individuals with autism spectrum disorder (ASD). Occasionally, siblings will be included in intervention studies, participating in programs designed to address a number of challenges faced by individuals with ASD. Although sibling involvement in such interventions is not a new phenomenon,…

  3. Potential processes involved in the initiation and maintenance of whiplash-associated disorders : discussion paper 3

    NARCIS (Netherlands)

    Sterling, Michele; McLean, Samuel A.; Sullivan, Michael J. L.; Elliott, James M.; Buitenhuis, Jan; Kamper, Steven J.

    2011-01-01

    Study Design. Nonsystematic review and discussion of the etiological processes involved in whiplash-associated disorders (WAD). Objective. To summarize the research and identify priorities for future research. Summary of Background Data. Although there is convergent evidence of a peripheral lesion i

  4. Extracellular calcium is involved in egg yolk-induced head-to-head agglutination of bull sperm.

    Science.gov (United States)

    Yang, D H; McMillan, A G; Standley, N T; Shannon, P; Xu, Z Z

    2012-10-15

    Head-to-head agglutination of bull sperm occurs when semen is highly diluted in an egg yolk-citrate diluent without streptomycin. The objectives were to investigate causes of sperm agglutination and the underlying mechanism. Aliquots of bull semen were diluted in a base diluent (BD) supplemented with various test components and the percentage of agglutinated sperm (% AggSp) was quantified at 1, 5, 24, 48, and 72 h of incubation. When sperm were incubated at 22 °C, no agglutination was observed in BD for up to 72 h, whereas the % AggSp was 5.0, 41.7, 72.2, 91.1, and 92.8% in BD + 5% egg yolk (BD + EY) at 1, 5, 24, 48 and 72 h, respectively. However, no sperm agglutination was observed in BD + EY if incubation temperature was 37 °C. Addition of 5 or 10 mM ethylenebis (oxyethyleneni-trilo) tetra-acetic acid to BD + EY reduced the % AggSp from 95% to sperm agglutination in the absence of egg yolk, implicating calcium and other factors in egg yolk. Addition of the citrate-soluble fraction (CSF) of egg yolk to BD induced sperm agglutination similar to whole egg yolk, whereas water- and saline-soluble fractions of egg yolk were ineffective. The sperm-agglutinating efficacy of CSF (the % AggSp = 95% at 72 h) was reduced by dialysis (20%; P sperm agglutination, whereas addition of 2 mM of a cAMP analogue, dbcAMP, to a nonagglutinating diluent failed to induce sperm agglutination. Agglutination status had no effect on sperm plasma membrane/acrosome status and mitochondrial membrane potential. In conclusion, calcium and other component(s) in the CSF of egg yolk induced head-to-head agglutination of bull sperm in a time- and temperature-dependent manner. Although the mechanism of agglutination was not determined, the cAMP- protein kinase A signaling pathway was not involved.

  5. 21q21 deletion involving NCAM2: report of 3 cases with neurodevelopmental disorders.

    Science.gov (United States)

    Petit, Florence; Plessis, Ghislaine; Decamp, Matthieu; Cuisset, Jean-Marie; Blyth, Moira; Pendlebury, Maria; Andrieux, Joris

    2015-01-01

    Here we report three patients affected with neurodevelopmental disorders and harbouring 21q21 deletions involving NCAM2 gene. NCAM (Neural Cell Adhesion Molecule) proteins are involved in axonal migration, synaptic formation and plasticity. Poor axonal growth and fasciculation is observed in animal models deficient for NCAM2. Moreover, this gene has been proposed as a candidate for autism, based on genome-wide association studies. In this report, we provide a comprehensive molecular and phenotypical characterisation of three deletion cases giving additional clues for the involvement of NCAM2 in neurodevelopment.

  6. Calcium paradox induces apoptosis in the isolated perfused Rana ridibunda heart: involvement of p38-MAPK and calpain.

    Science.gov (United States)

    Aggeli, Ioanna-Katerina; Zacharias, Triantafyllos; Papapavlou, Georgia; Gaitanaki, Catherine; Beis, Isidoros

    2013-12-01

    "Calcium paradox" as a term describes the deleterious effects conferred to a heart perfused with a calcium-free solution followed by repletion, including loss of mechanical activity and sarcomere disruption. Given that the signaling mechanisms triggered by calcium paradox remain elusive, in the present study, we tried to investigate them in the isolated perfused heart from Rana ridibunda. Calcium paradox was found to markedly activate members of the MAPKs (p43-ERK, JNKs, p38-MAPK). In addition to lactate dehydrogenase (LDH) release in the perfusate (indicative of necrosis), we also confirmed the occurrence of apoptosis by using the TUNEL assay and identifying poly(ADP-ribose) polymerase (PARP) fragmentation and upregulated Bax expression. Furthermore, using MDL28170 (a selective calpain inhibitor), a role for this protease was revealed. In addition, various divalent cations were shown to exert a protective effect against the calcium paradox. Interestingly, SB203580, a p38-MAPK inhibitor, alleviated calcium-paradox-conferred apoptosis. This result indicates that p38-MAPK plays a pro-apoptotic role, contributing to the resulting myocardial dysfunction and cell death. To our knowledge, this is the first time that the calcium paradox has been shown to induce apoptosis in amphibians, with p38-MAPK and calpain playing significant roles.

  7. Idiopathic Calcium Nephrolithiasis And Hypercalciuria: The Role Of Genes

    Science.gov (United States)

    Gambaro, Giovanni; Abaterusso, Cataldo

    2007-04-01

    Idiopathic calcium nephrolithiasis and hypercalciuria are multifactorial disease conditions, the pathogenesis of which involves the interaction of environmental and individual factors. Data support a strong role of genes in the pathogenesis of these two conditions. Findings obtained in monogenic disorders characterized by renal calcium stones, and/or hypercalciuria, and/or nephrocalcinosis have proposed a number of genes as candidate genes in the pathogenesis of the common idiopathic calcium nephrolithiasis and hypercalciuria. The physiological role of these genes, and findings in monogenic disorders and idiopathic, multifactorial disorders will be presented.

  8. There and back again: The study of mental disorder and terrorist involvement.

    Science.gov (United States)

    Gill, Paul; Corner, Emily

    2017-04-01

    For the past 40 years, researchers studied the relationship between mental disorder and terrorist involvement. The literature developed in 4 paradigms, each of which differs in terms of their empirical evidence, the specific mental disorders studied, and their conceptualizations of terrorist involvement. These paradigms have not, however, witnessed linear and incremental improvements upon 1 another. Although 1 paradigm has generally tended to dominate a temporal period, many false assumptions and incorrect interpretations of earlier work permeate into today's discourse. This article provides a history of the study of mental disorders and the terrorist. First, we briefly outline the core fundamental principles of the first 2 paradigms, The article then outlines the core arguments produced by the seminal reviews conducted in Paradigm 3. We highlight how these findings were consistently misinterpreted in subsequent citations. We then highlight recent innovations in the study of terrorism and mental disorder since the various influential literature reviews of 1997-2005. We conclude by outlining how future research in this area may improve in the coming years by broadening our understanding of both terrorist involvement and psychopathology away from simple dichotomous thinking. (PsycINFO Database Record

  9. Painful tonic spasms and brainstem involvement in a patient with neuromyelitis optica spectrum disorder.

    Science.gov (United States)

    Roman-Filip, Corina; Ungureanu, Aurelian; Cernuşcă-Miţaru, Mihaela

    2016-01-01

    Neuromyelitis optica (NMO) is an inflammatory-demyelinating disease of the central nervous system classically characterized by optic neuritis and severe myelitis. New diagnostic criteria defined neuromyelitis optica spectrum disorder as limited forms of NMO or diverse neurologic presentations in the presence of specific antiaquaporin-4 antibodies. We report the case of a 57-year-old woman admitted in our department for recurrent attacks of optic neuritis, tetraparesis with severe painful tonic spasms of the left limbs and brainstem involvement. Painful tonic spasms have been described as movement disorders associated with multiple sclerosis, but a growing number of reports describe them in cases of NMO.

  10. Types of voltage—dependent calcium channels involved in high potassium depolarization—induced amylase secretion in the exocrine pancreatic tumour cell line AR4—2J

    Institute of Scientific and Technical Information of China (English)

    CUIZONGJIE

    1998-01-01

    In the perifused fura-2 loaded exocrine pancreatic acinar cell line AR4-2J pulses of high potassium induced repetitive increases in intracellular calcium,Attached cells when stimulated with high potassium secreted large amount of amylase.High potassium-induced secretion was dependent both on the concentration of potassium and duration of stimulation.High potassium induced increases in intracellular calcium were inhibited by voltage-dependent calcium channel anatagonists with an order of potency as follows:nifedipine>ω-agatoxin IVA>ω-conotoxin GVIA.In contrast,the L-type calcium channel anatagonist nifedipine almost completely inhibited potassium-induced amylase secretion,whereas the N-type channel antagonist ω-conotoxin GVIA was without effect.The P-type channel antagonist ω-agatoxin IVA had a small inhibitory effect,but this inhibition was not significant at the level of amylase secretion.In conclusion,the AR4-2J cell line posesses different voltage-dependent calcium channels(L,P,N)with the L-type predominantly involved in depolarization induced amylase secretion.

  11. Alleviation of cadmium toxicity in Brassica juncea L. (Czern. & Coss. by calcium application involves various physiological and biochemical strategies.

    Directory of Open Access Journals (Sweden)

    Parvaiz Ahmad

    Full Text Available Calcium (Ca plays important role in plant development and response to various environmental stresses. However, its involvement in mitigation of heavy metal stress in plants remains elusive. In this study, we examined the effect of Ca (50 mM in controlling cadmium (Cd uptake in mustard (Brassica juncea L. plants exposed to toxic levels of Cd (200 mg L(-1 and 300 mg L(-1. The Cd treatment showed substantial decrease in plant height, root length, dry weight, pigments and protein content. Application of Ca improved the growth and biomass yield of the Cd-stressed mustard seedlings. More importantly, the oil content of mustard seeds of Cd-stressed plants was also enhanced with Ca treatment. Proline was significantly increased in mustard plants under Cd stress, and exogenously sprayed Ca was found to have a positive impact on proline content in Cd-stressed plants. Different concentrations of Cd increased lipid peroxidation but the application of Ca minimized it to appreciable level in Cd-treated plants. Excessive Cd treatment enhanced the activities of antioxidant enzymes superoxide dismutase, ascorbate peroxidase and glutathione reductase, which were further enhanced by the addition of Ca. Additionally, Cd stress caused reduced uptake of essential elements and increased Cd accumulation in roots and shoots. However, application of Ca enhanced the concentration of essential elements and decreased Cd accumulation in Cd-stressed plants. Our results indicated that application of Ca enables mustard plant to withstand the deleterious effect of Cd, resulting in improved growth and seed quality of mustard plants.

  12. The relationship between religious involvement and clinical status of patients with bipolar disorder

    Science.gov (United States)

    Cruz, Mario; Pincus, Harold Alan; Welsh, Deborah E; Greenwald, Devra; Lasky, Elaine; Kilbourne, Amy M

    2009-01-01

    Objective Religion and spirituality are important coping strategies in depression but have been rarely studied within the context of bipolar disorder. The present study assessed the association between different forms of religious involvement and the clinical status of individuals treated for bipolar disorder. Methods A cross-sectional observation study of follow-up data from a large cohort study of patients receiving care for bipolar disorder (n = 334) at an urban Veterans Affairs mental health clinic was conducted. Bivariate and multivariate analyses were performed to assess the association between public (frequency of church attendance), private (frequency of prayer/meditation), as well as subjective forms (influence of beliefs on life) of religious involvement and mixed, manic, depressed, and euthymic states when demographic, anxiety, alcohol abuse, and health indicators were controlled. Results Multivariate analyses found significant associations between higher rates of prayer/meditation and participants in a mixed state [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.10-1.52, chi square = 9.42, df = 14, p < 0.05], as well as lower rates of prayer/meditation and participants who were euthymic (OR = 0.84; 95% CI = 0.72-0.99, chi square = 4.60, df = 14, p < 0.05). Depression and mania were not associated with religious involvement. Conclusions Compared to patients with bipolar disorder in depressed, manic, or euthymic states, patients in mixed states have more active private religious lives. Providers should assess the religious activities of individuals with bipolar disorder in mixed states and how they may complement/deter ongoing treatment. Future longitudinal studies linking bipolar states, religious activities, and treatment-seeking behaviors are needed. PMID:20148868

  13. Factors involved in the etiology of temporomandibular disorders - a literature review

    Science.gov (United States)

    CHISNOIU, ANDREA MARIA; PICOS, ALINA MONICA; POPA, SEVER; CHISNOIU, PETRE DANIEL; LASCU, LIANA; PICOS, ANDREI; CHISNOIU, RADU

    2015-01-01

    Background and aim This review aims at presenting a current view on the most frequent factors involved in the mechanisms causing temporomandibular disorders (TMD). Method We conducted a critical review of the literature for the period January 2000 to December 2014 to identify factors related to TMD development and persistence. Results The etiology of TMD is multidimensional: biomechanical, neuromuscular, bio-psychosocial and biological factors may contribute to the disorder. Occlusal overloading and parafunctions (bruxism) are frequently involved as biomechanical factors; increased levels of estrogen hormones are considered biological factors affecting the temporo-mandibular-joint. Among bio-psychosocial factors, stress, anxiety or depression, were frequently encountered. Conclusions The etiopathogenesis of this condition is poorly understood, therefore TMDs are difficult to diagnose and manage. Early and correct identification of the possible etiologic factors will enable the appropriate treatment scheme application in order to reduce or eliminate TMDs debilitating signs and symptoms. PMID:26732121

  14. The Involvement of a Concerned Significant Other in Gambling Disorder Treatment Outcome.

    Science.gov (United States)

    Jiménez-Murcia, Susana; Tremblay, Joël; Stinchfield, Randy; Granero, Roser; Fernández-Aranda, Fernando; Mestre-Bach, Gemma; Steward, Trevor; Del Pino-Gutiérrez, Amparo; Baño, Marta; Moragas, Laura; Aymamí, Neus; Gómez-Peña, Mónica; Tárrega, Salomé; Valenciano-Mendoza, Eduardo; Giroux, Isabelle; Sancho, Marta; Sánchez, Isabel; Mallorquí-Bagué, Núria; González, Vega; Martín-Romera, Virginia; Menchón, José M

    2016-11-17

    Interpersonal distress is a common feature in gambling disorder and adding a concerned significant other (CSO) to the recovery process could be an effective tool for improving treatment outcome. However, little empirical evidence is available regarding the effectiveness of including a CSO to interventions. We aimed to compare treatment outcomes (i.e. compliance with therapy guidelines, dropout from treatment, and relapse during treatment) in a CBT program involving a CSO to CBT treatment as usual (TAU) without a CSO. The sample comprised male gambling disorder patients (N = 675). The manualized CBT intervention consisted of 16 weekly outpatient group sessions and a 3-month follow-up period. Patient CSOs attended a predetermined number of sessions with the patient and were provided with resources to acquire a better understanding of the disorder, to manage risk situations, and to aid patients in adhering to treatment guidelines. Patients with a CSO had significant higher treatment attendance and reduced dropout compared to patients receiving TAU. Moreover, patients whose spouse was involved in the treatment program were less likely to relapse and adhered to the treatment guidelines more than those with a non-spousal CSO. Our results suggest that incorporating interpersonal support to gambling disorder interventions could potentially improve treatment outcomes.

  15. Prenatal nicotine is associated with reduced AMPA and NMDA receptor-mediated rises in calcium within the laterodorsal tegmentum: a pontine nucleus involved in addiction processes.

    Science.gov (United States)

    McNair, L F; Kohlmeier, K A

    2015-06-01

    Despite huge efforts from public sectors to educate society as to the deleterious physiological consequences of smoking while pregnant, 12-25% of all babies worldwide are born to mothers who smoked during their pregnancies. Chief among the negative legacies bestowed to the exposed individual is an enhanced proclivity postnatally to addict to drugs of abuse, which suggests that the drug exposure during gestation changed the developing brain in such a way that biased it towards addiction. Glutamate signalling has been shown to be altered by prenatal nicotine exposure (PNE) and glutamate is the major excitatory neurotransmitter within the laterodorsal tegmental nucleus (LDT), which is a brainstem region importantly involved in responding to motivational stimuli and critical in development of drug addiction-associated behaviours, however, it is unknown whether PNE alters glutamate signalling within this nucleus. Accordingly, we used calcium imaging, to evaluate AMPA and NMDA receptor-mediated calcium responses in LDT brain slices from control and PNE mice. We also investigated whether the positive AMPA receptor modulator cyclothiazide (CYZ) had differential actions on calcium in the LDT following PNE. Our data indicated that PNE significantly decreased AMPA receptor-mediated calcium responses, and altered the neuronal calcium response to consecutive NMDA applications within the LDT. Furthermore, CYZ strongly potentiated AMPA-induced responses, however, this action was significantly reduced in the LDT of PNE mice when compared with enhancements in responses in control LDT cells. Immunohistochemical processing confirmed that calcium imaging recordings were obtained from the LDT nucleus as determined by presence of cholinergic neurons. Our results contribute to the body of evidence suggesting that neurobiological changes are induced if gestation is accompanied by nicotine exposure. We conclude that in light of the role played by the LDT in motivated behaviour, the

  16. Experimental evidence for the involvement of PDLIM5 in mood disorders in hetero knockout mice.

    Directory of Open Access Journals (Sweden)

    Yasue Horiuchi

    Full Text Available BACKGROUND: Reports indicate that PDLIM5 is involved in mood disorders. The PDLIM5 (PDZ and LIM domain 5 gene has been genetically associated with mood disorders; it's expression is upregulated in the postmortem brains of patients with bipolar disorder and downregulated in the peripheral lymphocytes of patients with major depression. Acute and chronic methamphetamine (METH administration may model mania and the evolution of mania into psychotic mania or schizophrenia-like behavioral changes, respectively. METHODS: To address whether the downregulation of PDLIM5 protects against manic symptoms and cause susceptibility to depressive symptoms, we evaluated the effects of reduced Pdlim5 levels on acute and chronic METH-induced locomotor hyperactivity, prepulse inhibition, and forced swimming by using Pdlim5 hetero knockout (KO mice. RESULTS: The homozygous KO of Pdlim5 is embryonic lethal. The effects of METH administration on locomotor hyperactivity and the impairment of prepulse inhibition were lower in Pdlim5 hetero KO mice than in wild-type mice. The transient inhibition of PDLIM5 (achieved by blocking the translocation of protein kinase C epsilon before the METH challenge had a similar effect on behavior. Pdlim5 hetero KO mice showed increased immobility time in the forced swimming test, which was diminished after the chronic administration of imipramine. Chronic METH treatment increased, whereas chronic haloperidol treatment decreased, Pdlim5 mRNA levels in the prefrontal cortex. Imipramine increased Pdlim5 mRNA levels in the hippocampus. CONCLUSION: These findings are partially compatible with reported observations in humans, indicating that PDLIM5 is involved in psychiatric disorders, including mood disorders.

  17. An Australian survey of parent involvement in intervention for childhood speech sound disorders.

    Science.gov (United States)

    Sugden, Eleanor; Baker, Elise; Munro, Natalie; Williams, A Lynn; Trivette, Carol M

    2017-08-17

    To investigate how speech-language pathologists (SLPs) report involving parents in intervention for phonology-based speech sound disorders (SSDs), and to describe the home practice that they recommend. Further aims were to describe the training SLPs report providing to parents, to explore SLPs' beliefs and motivations for involving parents in intervention, and to determine whether SLPs' characteristics are associated with their self-reported practice. An online survey of 288 SLPs working with SSD in Australia was conducted. The majority of SLPs (96.4%) reported involving parents in intervention, most commonly in providing home practice. On average, these tasks were recommended to be completed five times per week for 10 min. SLPs reported training parents using a range of training methods, most commonly providing opportunities for parents to observe the SLP conduct the intervention. SLPs' place of work and years of experience were associated with how they involved and trained parents in intervention. Most (95.8%) SLPs agreed or strongly agreed that family involvement is essential for intervention to be effective. Parent involvement and home practice appear to be intricately linked within intervention for phonology-based SSDs in Australia. More high-quality research is needed to understand how to best involve parents within clinical practice.

  18. Calcium Test

    Science.gov (United States)

    ... if a person has symptoms of a parathyroid disorder , malabsorption , or an overactive thyroid. A total calcium level is often measured as part of a routine health screening. It is included in the comprehensive metabolic panel (CMP) and the basic metabolic panel (BMP) , ...

  19. Involvement of parents in intervention for childhood speech sound disorders: a review of the evidence.

    Science.gov (United States)

    Sugden, Eleanor; Baker, Elise; Munro, Natalie; Williams, A Lynn

    2016-11-01

    Internationally, speech and language therapists (SLTs) are involving parents and providing home tasks in intervention for phonology-based speech sound disorder (SSD). To ensure that SLTs' involvement of parents is guided by empirical research, a review of peer-reviewed published evidence is needed. To provide SLTs and researchers with a comprehensive appraisal and analysis of peer-reviewed published intervention research reporting parent involvement and the provision of home tasks in intervention studies for children with phonology-based SSD. A systematic search and review was conducted. Academic databases were searched for peer-reviewed research papers published between 1979 and 2013 reporting on phonological intervention for SSD. Of the 176 papers that met the criteria, 61 were identified that reported on the involvement of parents and/or home tasks within the intervention. These papers were analysed using a quality appraisal tool. Details regarding the involvement of parents and home tasks were extracted and analysed to provide a summary of these practices within the evidence base. Parents have been involved in intervention research for phonology-based SSD. However, most of the peer-reviewed published papers reporting this research have provided limited details regarding what this involved. This paucity of information presents challenges for SLTs wishing to integrate external evidence into their clinical services and clinical decision-making. It also raises issues regarding treatment fidelity for researchers wishing to replicate published intervention research. The range of tasks in which parents were involved, and the limited details reported in the literature, present challenges for SLTs wanting to involve parents in intervention. Further high-quality research reporting more detail regarding the involvement of parents and home tasks in intervention for SSD is needed. © 2016 Royal College of Speech and Language Therapists.

  20. The Bcl-2 gene polymorphism rs956572AA increases inositol 1,4,5-trisphosphate receptor-mediated endoplasmic reticulum calcium release in subjects with bipolar disorder.

    Science.gov (United States)

    Machado-Vieira, Rodrigo; Pivovarova, Natalia B; Stanika, Ruslan I; Yuan, Peixiong; Wang, Yun; Zhou, Rulun; Zarate, Carlos A; Drevets, Wayne C; Brantner, Christine A; Baum, Amber; Laje, Gonzalo; McMahon, Francis J; Chen, Guang; Du, Jing; Manji, Husseini K; Andrews, S Brian

    2011-02-15

    Bipolar disorder (BPD) is characterized by altered intracellular calcium (Ca(2+)) homeostasis. Underlying mechanisms involve dysfunctions in endoplasmic reticulum (ER) and mitochondrial Ca(2+) handling, potentially mediated by B-cell lymphoma 2 (Bcl-2), a key protein that regulates Ca(2+) signaling by interacting directly with these organelles, and which has been implicated in the pathophysiology of BPD. Here, we examined the effects of the Bcl-2 gene single nucleotide polymorphism (SNP) rs956572 on intracellular Ca(2+) dynamics in patients with BPD. Live cell fluorescence imaging and electron probe microanalysis were used to measure intracellular and intra-organelle free and total calcium in lymphoblasts from 18 subjects with BPD carrying the AA, AG, or GG variants of the rs956572 SNP. Analyses were carried out under basal conditions and in the presence of agents that affect Ca(2+) dynamics. Compared with GG homozygotes, variant AA-which expresses significantly reduced Bcl-2 messenger RNA and protein-exhibited elevated basal cytosolic Ca(2+) and larger increases in inositol 1,4,5-trisphosphate receptor-mediated cytosolic Ca(2+) elevations, the latter in parallel with enhanced depletion of the ER Ca(2+) pool. The aberrant behavior of AA cells was reversed by chronic lithium treatment and mimicked in variant GG by a Bcl-2 inhibitor. In contrast, no differences between SNP variants were found in ER or mitochondrial total Ca(2+) content or in basal store-operated Ca(2+) entry. These results demonstrate that, in patients with BPD, abnormal Bcl-2 gene expression in the AA variant contributes to dysfunctional Ca(2+) homeostasis through a specific ER inositol 1,4,5-trisphosphate receptor-dependent mechanism. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. The Bcl-2 Gene Polymorphism rs956572AA Increases Inositol 1,4,5-Trisphosphate Receptor–Mediated Endoplasmic Reticulum Calcium Release in Subjects with Bipolar Disorder

    Science.gov (United States)

    Machado-Vieira, Rodrigo; Pivovarova, Natalia B.; Stanika, Ruslan I.; Yuan, Peixiong; Wang, Yun; Zhou, Rulun; Zarate, Carlos A.; Drevets, Wayne C.; Brantner, Christine A.; Baum, Amber; Laje, Gonzalo; McMahon, Francis J.; Chen, Guang; Du, Jing; Manji, Husseini K.; Andrews, S. Brian

    2011-01-01

    Background Bipolar disorder (BPD) is characterized by altered intracellular calcium (Ca2+) homeostasis. Underlying mechanisms involve dysfunctions in endoplasmic reticulum (ER) and mitochondrial Ca2+ handling, potentially mediated by B-cell lymphoma 2 (Bcl-2), a key protein that regulates Ca2+ signaling by interacting directly with these organelles, and which has been implicated in the pathophysiology of BPD. Here, we examined the effects of the Bcl-2 gene single nucleotide polymorphism (SNP) rs956572 on intracellular Ca2+ dynamics in patients with BPD. Methods Live cell fluorescence imaging and electron probe microanalysis were used to measure intracellular and intra-organelle free and total calcium in lymphoblasts from 18 subjects with BPD carrying the AA, AG, or GG variants of the rs956572 SNP. Analyses were carried out under basal conditions and in the presence of agents that affect Ca2+ dynamics. Results Compared with GG homozygotes, variant AA—which expresses significantly reduced Bcl-2 messenger RNA and protein—exhibited elevated basal cytosolic Ca2+ and larger increases in inositol 1,4,5-trisphosphate receptor–mediated cytosolic Ca2+ elevations, the latter in parallel with enhanced depletion of the ER Ca2+ pool. The aberrant behavior of AA cells was reversed by chronic lithium treatment and mimicked in variant GG by a Bcl-2 inhibitor. In contrast, no differences between SNP variants were found in ER or mitochondrial total Ca2+ content or in basal store-operated Ca2+ entry. Conclusions These results demonstrate that, in patients with BPD, abnormal Bcl-2 gene expression in the AA variant contributes to dysfunctional Ca2+ homeostasis through a specific ER inositol 1,4,5-trisphosphate receptor–dependent mechanism. PMID:21167476

  2. Anomalous composition-dependent dynamics of nanoconfined water in the interlayer of disordered calcium-silicates.

    Science.gov (United States)

    Qomi, Mohammad Javad Abdolhosseini; Bauchy, Mathieu; Ulm, Franz-Josef; Pellenq, Roland J-M

    2014-02-07

    With shear interest in nanoporous materials, the ultraconfining interlayer spacing of calcium-silicate-hydrate (C-S-H) provides an excellent medium to study reactivity, structure, and dynamic properties of water. In this paper, we present how substrate composition affects chemo-physical properties of water in ultraconfined hydrophilic media. This is achieved by performing molecular dynamics simulation on a set of 150 realistic models with different compositions of calcium and silicon contents. It is demonstrated that the substrate chemistry directly affects the structural properties of water molecules. The motion of confined water shows a multi-stage dynamics which is characteristic of supercooled liquids and glassy phases. Inhomogeneity in that dynamics is used to differentiate between mobile and immobile water molecules. Furthermore, it is shown that the mobility of water molecules is composition-dependent. Similar to the pressure-driven self-diffusivity anomaly observed in bulk water, we report the first study on composition-driven diffusion anomaly, the self diffusivity increases with increasing confined water density in C-S-H. Such anomalous behavior is explained by the decrease in the typical activation energy required for a water molecule to escape its dynamical cage.

  3. Are cognitive "insomnia" processes involved in the development and maintenance of delayed sleep wake phase disorder?

    Science.gov (United States)

    Richardson, Cele E; Gradisar, Michael; Barbero, Sebastian C

    2016-04-01

    Although individuals with delayed sleep wake phase disorder (DSWPD) and chronic insomnia disorder (CID) share many of the same phenomenological experiences, theories relating to the development and maintenance of these disorders are distinct in focus. Unlike CID, theory relating to DSWPD is primarily physiologically based and assumes almost no cognitive pathway. However, recent research findings suggest that individuals with DSWPD also display many of the sleep-disordered cognitive processes that were previously assumed to be unique to the insomnia experience. As such, this review aims to summarise current research findings to address the question "Could cognitive processes be involved in the development and maintenance of DSWPD?" In particular, the presence of cognitive and physiological pre-sleep arousal, sleep-related attentional bias, distorted perception of sleep and daytime functioning, dysfunctional beliefs and safety behaviours will be investigated. As this emerging area of research requires a stronger evidence base, we highlight suggestions for future investigation and provide preliminary practice points for clinicians assessing and treating "insomnia" in patients with DSWPD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Multiplex ligation-dependent probe amplification (MLPA) screening for exon copy number variation in the calcium sensing receptor gene: no large rearrangements identified in patients with calcium metabolic disorders

    DEFF Research Database (Denmark)

    Nissen, Peter H; Christensen, Signe E; Wallace, Andrew;

    2010-01-01

    samples were previously found negative for CASR mutations. Multiplex ligation-dependent probe amplification was used to screen the patients for exon copy number variations. Results. All exons were amplified with mean normalised ratios between 0.98 and 1.06. We did not identify any exon copy number......Summary Background. Mutation screening of the CASR by DNA sequencing is commonly used in the diagnosis of disorders of calcium metabolism, such as familial hypocalciuric hypercalcaemia (FHH). Exon copy number variation is not detected by currently used molecular genetic screening methods, and might...... be a genetic cause of inherited forms of hyper- or hypocalcaemia caused by the CASR. Objective. We wanted to further evaluate possible genetic causes for disorders of calcium metabolism, by investigating the prevalence of exon copy number variations, such as large deletions or duplications of the CASR...

  5. Borderline personality disorder features and history of childhood maltreatment in mothers involved with child protective services.

    Science.gov (United States)

    Perepletchikova, Francheska; Ansell, Emily; Axelrod, Seth

    2012-05-01

    This study examines the history of childhood maltreatment and Borderline Personality Disorder (BPD) symptoms in mothers whose children were removed from the home by Child Protective Services (CPS) to identify potential targets for future intervention efforts. Forty-one mothers of children removed from the home due to abuse and/or neglect and 58 community-control mothers without CPS involvement were assessed for history of childhood maltreatment, alcohol and drug use, and BPD features. CPS-involved mothers scored significantly higher on measures of childhood maltreatment history and BPD features than did control mothers. The highest BPD scores were associated with the most severe histories of mothers' childhood maltreatment. In total, 50% of CPS-involved mothers reported elevated BPD features, compared with 15% of control mothers. Further, 19% of CPS-involved mothers had self-reported scores consistent with a BPD diagnosis, compared with 4% of control mothers. BPD features rather than maltreatment history per se predicted maternal involvement with CPS, controlling for alcohol and drug use predictors. The present data suggest that evidence-based treatments to address BPD symptoms may be indicated for some CPS-involved parents.

  6. High-throughput screen detects calcium signaling dysfunction in typical sporadic autism spectrum disorder

    Science.gov (United States)

    Schmunk, Galina; Nguyen, Rachel L.; Ferguson, David L.; Kumar, Kenny; Parker, Ian; Gargus, J. Jay

    2017-01-01

    Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders without any defined uniting pathophysiology. Ca2+ signaling is emerging as a potential node in the genetic architecture of the disorder. We previously reported decreased inositol trisphosphate (IP3)-mediated Ca2+ release from the endoplasmic reticulum in several rare monogenic syndromes highly comorbid with autism – fragile X and tuberous sclerosis types 1 and 2 syndromes. We now extend those findings to a cohort of subjects with sporadic ASD without any known mutations. We developed and applied a high throughput Fluorometric Imaging Plate Reader (FLIPR) assay to monitor agonist-evoked Ca2+ signals in human primary skin fibroblasts. Our results indicate that IP3 -mediated Ca2+ release from the endoplasmic reticulum in response to activation of purinergic receptors is significantly depressed in subjects with sporadic as well as rare syndromic forms of ASD. We propose that deficits in IP3-mediated Ca2+ signaling represent a convergent hub function shared across the spectrum of autistic disorders – whether caused by rare highly penetrant mutations or sporadic forms – and holds promise as a biomarker for diagnosis and novel drug discovery. PMID:28145469

  7. Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion.

    Science.gov (United States)

    Nishitani, Wagner Shin; Alencar, Adriano Mesquita; Wang, Yingxiao

    2015-01-01

    A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs) in terms of calcium signaling. The intracellular calcium ion concentration was measured by the genetically encoded Cameleon biosensor, with the Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7) expression inhibited. As TRPM7 expression also regulates adhesion, a relatively simple method for measuring adhesion of cells was also developed, tested and used to study the effect of adhesion alone. Three adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking and fibronectin. The other two conditions had increasingly reduced adhesion: partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at 5% of the normal amount) and non-treated polyacrylamide gels. The cells showed adhesion and calcium response to the mechanical stimulation correlated to the degree of gel treatment: highest for fully treated gels and lowest for non-treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion relative to control (no siRNA treatment) and non-targeting siRNA, but a decrease to 80% of calcium response relative to non-targeting siRNA which confirms the important role of TRPM7 in mechanotransduction despite the increase in adhesion.

  8. Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion.

    Directory of Open Access Journals (Sweden)

    Wagner Shin Nishitani

    Full Text Available A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs in terms of calcium signaling. The intracellular calcium ion concentration was measured by the genetically encoded Cameleon biosensor, with the Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7 expression inhibited. As TRPM7 expression also regulates adhesion, a relatively simple method for measuring adhesion of cells was also developed, tested and used to study the effect of adhesion alone. Three adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking and fibronectin. The other two conditions had increasingly reduced adhesion: partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at 5% of the normal amount and non-treated polyacrylamide gels. The cells showed adhesion and calcium response to the mechanical stimulation correlated to the degree of gel treatment: highest for fully treated gels and lowest for non-treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion relative to control (no siRNA treatment and non-targeting siRNA, but a decrease to 80% of calcium response relative to non-targeting siRNA which confirms the important role of TRPM7 in mechanotransduction despite the increase in adhesion.

  9. Parental involvement moderates etiological influences on attention deficit hyperactivity disorder behaviors in child twins.

    Science.gov (United States)

    Nikolas, Molly A; Klump, Kelly L; Burt, S Alexandra

    2015-01-01

    Although few would now contest the presence of Gene × Environment (G × E) effects in the development of child psychopathology, it remains unclear how these effects manifest themselves. Alternative G × E models have been proposed (i.e., diathesis-stress, differential susceptibility, bioecological), each of which has notably different implications for etiology. Child twin studies present a powerful tool for discriminating between these models. The current study examined whether and how parental involvement moderated etiological influences on attention deficit hyperactivity disorder (ADHD) within 500 twin pairs aged 6-11 years. Results indicated moderation of genetic and nonshared environmental contributions to ADHD by parental involvement, and moreover, suggested both differential susceptibility and bioecological models of G × E. Results highlight the utility of child twin samples in testing different manifestations of G × E effects.

  10. Insulinotropic actions of Moringa oleifera involves the induction of membrane depolarization and enhancement of intracellular calcium concentration

    Directory of Open Access Journals (Sweden)

    Opeolu O. Ojo

    2015-03-01

    Methods: Phytochemical composition of M.oleifera extract was determined using standard procedures. Total flavonoid and total phenolic compounds in the extract were also quantified. Effects of the extracts on glucose stimulated insulin secretion, membrane depolarization and intracellular calcium concentration were investigated using BRIN-BD11 clonal pancreatic beta cells. Results: Results obtained showed the preponderance of alkaloids, flavonoids, glycosides, phenols, saponins and tannins in the extract. The glucose dependent insulinotropic effects of the extract were significantly inhibited in the presence of diazoxide (48% or verapamil (35% and in the absence of extracellular calcium (47%. Co-incubation of cells with the extract and IBMX (3-isobutyl-1-methylxanthine or tolbutamide increased insulin secretion by 2-fold while a 1.2-fold increase was observed in cells depolarized with 30 mM KCl in the presence of the plant extract. The extract significantly induced membrane depolarization (7.1-fold and enhanced intracellular calcium concentration (2.6-fold in BRIN-BD11 cells. Conclusion: These observations suggest that the insulinotropic actions of acetone extract of M.oleifera may be mediated via the KATP-dependent pathway of insulin release. [J Exp Integr Med 2015; 5(1.000: 36-41

  11. Identification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma

    Science.gov (United States)

    Neira, José L.; Bintz, Jennifer; Arruebo, María; Rizzuti, Bruno; Bonacci, Thomas; Vega, Sonia; Lanas, Angel; Velázquez-Campoy, Adrián; Iovanna, Juan L.; Abián, Olga

    2017-01-01

    Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed and involved in pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, and their interactions with NUPR1 were characterized by experimental and simulation techniques. The protein remained disordered upon binding to all fifteen candidates. These compounds were tested in PDAC-derived cell-based assays, and all induced cell-growth arrest and senescence, reduced cell migration, and decreased chemoresistance, mimicking NUPR1-deficiency. The most effective compound completely arrested tumor development in vivo on xenografted PDAC-derived cells in mice. Besides reporting the discovery of a compound targeting an intact IDP and specifically active against PDAC, our study proves the possibility to target the ‘fuzzy’ interface of a protein that remains disordered upon binding to its natural biological partners or to selected drugs.

  12. Mepivacaine-induced contraction involves increased calcium sensitization mediated via Rho kinase and protein kinase C in endothelium-denuded rat aorta.

    Science.gov (United States)

    Ok, Seong-Ho; Kwon, Seong-Chun; Yeol Han, Jeong; Yu, Jongsun; Shin, Il-Woo; Lee, Heon-Keun; Chung, Young-Kyun; Choi, Mun-Jeoung; Sohn, Ju-Tae

    2014-01-15

    Mepivacaine is an aminoamide local anesthetic that produces vasoconstriction in vivo and in vitro. The goals of this in vitro study were to determine whether mepivacaine-induced contraction involves calcium sensitization in isolated endothelium-denuded aortas, and to investigate the specific protein kinases involved. The effects of mepivacaine and potassium chloride on intracellular calcium concentrations ([Ca(2+)]i) and tension in the presence or absence of Y-27632 or GF 109203X were measured simultaneously using the acetoxymethyl ester of fura-2-loaded aortic strips. Cumulative mepivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: Rho kinase inhibitor Y-27632, protein kinase C (PKC) inhibitor GF 109203X, extracellular signal-regulated kinase (ERK) inhibitor PD 98059, c-Jun NH2-terminal kinase (JNK) inhibitor SP600125, and p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580. Phosphorylation of PKC and MAPK, and membrane translocation of Rho kinase were detected in vascular smooth muscle cells by Western blotting. The slope of the mepivacaine-induced [Ca(2+)]i-tension curve was higher than that of the KCl-induced [Ca(2+)]i-tension curve. Pretreatment with Y-27632 or GF 109203X shifted the mepivacaine-induced [Ca(2+)]i-tension curve to the lower right. Pretreatment with Y-27632, GF 109203X, PD 98059, or SP600125 attenuated mepivacaine-induced contraction in a concentration-dependent manner. Y-27632 and GF 109203X attenuated mepivacaine-induced Rho kinase membrane translocation and PKC phosphorylation, respectively. PD 98059 and SP600125 attenuated mepivacaine-induced ERK and JNK phosphorylation, respectively. Taken together, these results indicate that mepivacaine-induced contraction involves increased calcium sensitization mediated by Rho kinase and PKC. Such contraction mainly involves activation of ERK- and JNK-mediated pathways. © 2013 Published by Elsevier B.V.

  13. Effect of Calcium Borogluconate Injection pre and Immediately Postpartum on Production Performance, Incidence of Metabolic Disorders and Situation of the Uterus After Calving in Cows Fed Anionic Diets

    Directory of Open Access Journals (Sweden)

    H. Amanlou

    2012-10-01

    Full Text Available The objective of this study was to determine the effect of calcium borogluconate injection 48 and 24 hours prepartum and immediately after parturition on dry matter intake at day of calving, milk yield, incidence of metabolic disorders and uterine conditions during the first 21 days postpartum in cows fed anionic diets. Thirty six lactating dairy cows were balanced by parity (1, 2, 3+ and allocated to 4 subcutaneous injection treatments of 15.2 gr calcium as borogluconate at different times pre and postpartum than expected calving date . Group 1 consisted of 9 cows receiving no treatment before or after parturition. Group 2 consisted of 9 cows receiving calcium borogluconate 48 h prepartum.Group 3 consisted of 9 cows receiving calcium borogluconate 24 h prepartum. Group 4 consisted of 9 cows receiving 15.2 gr of ca as borogluconate immediately postpartum. Dry matter intake was in treatments 1, 2, 3 and 4 was 10.87, 12.32, 12.63 and 15.03 kg in the first 24 h after calving, respectively And indicated significantly difference among treatments. milk yield in 2, 3 and 4 treatments was significantly greater than group 1 in the first 21 days of lactation (38.7, 38.9, 40.3 vs 36.07 kg/d. Treatment had a significant effect on the subclinical hypocalcemia incidence so incidence risk of subclinical hypocalcemia in 1 treatment was 10 times more likely than 4 treatment. Data regression analysis indicated that 4 treatment had a significant effect on the ketosis incidence. So that the cows no calcium injection 2.43 times more likely to experience ketosis than 4 treatment. But experimental treatments were not significantly effect on the incidence of milk fever, displacement abomasum, retained placenta, metritis and endometritis. In general, calcium injection, especially immediately after parturation increased the dry matter intake in day of calving and reduced metabolic disorders such as hypocalcaemia and ketosis.

  14. ROS and calcium signaling mediated pathways involved in stress responses of the marine microalgae Dunaliella salina to enhanced UV-B radiation.

    Science.gov (United States)

    Zhang, Xinxin; Tang, Xuexi; Wang, Ming; Zhang, Wei; Zhou, Bin; Wang, You

    2017-08-01

    UV-B ray has been addressed to trigger common metabolic responses on marine microalgae, however, the upstream events responsible for these changes in marine microalgae are poorly understood. In the present study, a species of marine green microalgae Dunaliella salina was exposed to a series of enhanced UV-B radiation ranging from 0.25 to 1.00 KJ·m(-2) per day. The role of ROS and calcium signaling in the D. salina responses to UV-B was discussed. Results showed that enhanced UV-B radiation markedly decreased the cell density in a dose-dependent manner, but the contents of protein and glycerol that were essential for cell growth increased. It suggested that it was cell division instead of cell growth that UV-B exerted negative effects on. The subcellular damages on nuclei and plasmalemma further evidenced the hypothesis. The nutrient absorption was affected with UV-B exposure, and the inhibition on PO4(3-) uptake was more serious compared to NO3(-) uptake. UV-B radiation promoted reactive oxygen species (ROS) formation and thiobarbituric acid reactive substances (TBARS) contents, decreased the redox status and altered the antioxidant enzyme activities. The addition of the ROS scavenger and the glutathione biosynthesis precursor N-acetyl-l-cysteine (NAC) alleviated the stress degree, implying ROS-mediated pathway was involved in the stress response to UV-B radiation. Transient increase in Ca(2+)-ATPase was triggered simultaneously with UV-B exposure. Meanwhile, the addition of an intracellular free calcium chelator aggravated the damage of cell division, but exogenous calcium and ion channel blocker applications did not, inferring that endogenously initiated calcium signaling played roles in response to UV-B. Cross-talk analysis showed a relatively clear relationship between ROS inhibition and Ca(2+)-ATPase suppression, and a relation between Ca(2+) inhibition and GPx activity change was also observed. It was thus presumed that ROS-coupled calcium signaling via the

  15. Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone

    Directory of Open Access Journals (Sweden)

    Sergio Perez-Alvarez

    2012-01-01

    Full Text Available Previously, we have shown that SH-SY5Y cells exposed to high concentrations of methadone died due to a necrotic-like cell death mechanism related to delayed calcium deregulation (DCD. In this study, we show that, in terms of their Ca2+ responses to 0.5 mM methadone, SH-SY5Y cells can be pooled into four different groups. In a broad pharmacological survey, the relevance of different Ca2+-related mechanisms on methadone-induced DCD was investigated including extracellular calcium, L-type Ca2+ channels, μ-opioid receptor, mitochondrial inner membrane potential, mitochondrial ATP synthesis, mitochondrial Ca2+/2Na+-exchanger, reactive oxygen species, and mitochondrial permeability transition. Only those compounds targeting mitochondria such as oligomycin, FCCP, CGP 37157, and cyclosporine A were able to amend methadone-induced Ca2+ dyshomeostasis suggesting that methadone induces DCD by modulating the ability of mitochondria to handle Ca2+. Consistently, mitochondria became dramatically shorter and rounder in the presence of methadone. Furthermore, analysis of oxygen uptake by isolated rat liver mitochondria suggested that methadone affected mitochondrial Ca2+ uptake in a respiratory substrate-dependent way. We conclude that methadone causes failure of intracellular Ca2+ homeostasis, and this effect is associated with morphological and functional changes of mitochondria. Likely, this mechanism contributes to degenerative side effects associated with methadone treatment.

  16. Magnesium/calcium related neurological disorders in the ALS focus of the Kii Peninsula

    Energy Technology Data Exchange (ETDEWEB)

    Yasui, Masayuki; Yoshida, Munehito; Tamaki, Tetsuya; Taniguchi, Yasunori; Minamide, Akihito; Ota, Kiichiro [Wakayama Medical Coll. (Japan); Sasajima, Kazuhisa

    1997-01-01

    Current epidemiological surveys in the Western Pacific area and Kii Peninsula have suggested that low calcium(Ca), magnesium(Mg) and high aluminum(Al) and manganese(Mn) in river, soil and drinking water may be implicated in the pathogenetic process of amyotrophic lateral sclerosis(ALS) and Parkinsonism-dementia(PD). The condition of unbalanced minerals was experimentally mimicked in this study using rats. Male Wistar rats, weighing 200 g, were maintained for 90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. In the groups maintained on unbalanced mineral diets, Ca and Mg contents of the bones were lower than standard diet. On the other hand, Ca content of CNS showed higher values in the unbalanced diet groups than those in the standard diet group. This was determined by neutron activation analysis(NAA) at KUR. Also, Ca content in soft tissues of rats given unbalanced mineral diets was higher than those on standard diet. Mg content of soft tissues and spinal cord of rats was markedly lower in the low Ca-Mg plus high Al diet group than the other three groups as determined by inductively coupled plasma emission spectrometry(ICP). Six Kii cases with amyotrophic lateral sclerosis(ALS) also showed higher Ca and lower Mg contents in the CNS tissues than those of neurologically normal controls. The calcification of the spinal ligaments(CSL) has been reported in only 120 cases in the world and 28 cases of CSL in the Kii Peninsula have been found in the same foci as ALS. We analyzed Mg content of 7 spinal bones and 10 ligaments of the CSL and Ca content of 5 spinal bones compared with controls. The CSL showed lower values of Mg contents in bones and ligaments compared to controls. The Ca content in bones of CSL was significantly lower than that of controls. This suggests that the environmental factor may contribute to the pathogenesis of CSL due to low Ca and Mg intake as well as for ALS. (J.P.N.)

  17. Structural and functional deficits in a neuronal calcium sensor-1 mutant identified in a case of autistic spectrum disorder.

    Directory of Open Access Journals (Sweden)

    Mark T W Handley

    Full Text Available Neuronal calcium sensor-1 (NCS-1 is a Ca(2+ sensor protein that has been implicated in the regulation of various aspects of neuronal development and neurotransmission. It exerts its effects through interactions with a range of target proteins one of which is interleukin receptor accessory protein like-1 (IL1RAPL1 protein. Mutations in IL1RAPL1 have recently been associated with autism spectrum disorders and a missense mutation (R102Q on NCS-1 has been found in one individual with autism. We have examined the effect of this mutation on the structure and function of NCS-1. From use of NMR spectroscopy, it appeared that the R102Q affected the structure of the protein particularly with an increase in the extent of conformational exchange in the C-terminus of the protein. Despite this change NCS-1(R102Q did not show changes in its affinity for Ca(2+ or binding to IL1RAPL1 and its intracellular localisation was unaffected. Assessment of NCS-1 dynamics indicated that it could rapidly cycle between cytosolic and membrane pools and that the cycling onto the plasma membrane was specifically changed in NCS-1(R102Q with the loss of a Ca(2+ -dependent component. From these data we speculate that impairment of the normal cycling of NCS-1 by the R102Q mutation could have subtle effects on neuronal signalling and physiology in the developing and adult brain.

  18. Assessing the influence of researcher-partner involvement on the process and outcomes of participatory research in autism spectrum disorder and neurodevelopmental disorders: a scoping review.

    Science.gov (United States)

    Jivraj, Jamil; Sacrey, Lori-Ann; Newton, Amanda; Nicholas, David; Zwaigenbaum, Lonnie

    2014-10-01

    Participatory research aims to increase the relevance and broaden the implementation of health research by involving those affected by the outcomes of health studies. Few studies within the field of neurodevelopmental disorders, particularly autism spectrum disorders, have involved autistic individuals as partners. This study sought to identify and characterize published participatory research partnerships between researchers and individuals with autism spectrum disorder or other neurodevelopmental disorders and examine the influence of participatory research partnerships on the research process and reported study outcomes. A search of databases and review of gray literature identified seven studies that described participatory research partnerships between academic researchers and individuals with autism spectrum disorder or other neurodevelopmental disorders. A comparative analysis of the studies revealed two key themes: (1) variations in the participatory research design and (2) limitations during the reporting of the depth of the partner's involvement. Both themes potentially limit the application and generalizability of the findings. The results of the review are discussed in relation to the use of evaluative frameworks for such participatory research studies to determine the potential benefits of participatory research partnerships within the neurodevelopmental and autism spectrum disorder populations.

  19. [Civil competence assessment of the mental disorders involved in contract dispute].

    Science.gov (United States)

    Zhang, Qin-Ting; Pang, Yan-Xia; Cai, Wei-Xiong; Tang, Tao; Wang, Jian-Jun

    2009-04-01

    To search the criteria for evaluating the civil competence of the mental disorders involved in contract dispute. Data on the interviewee's mental status and the forensic expertise were collected retrospectively. And 6 indexes were selected and graded: awareness of situation, factual understanding of issues, appreciation of likely consequences, rational manipulation of information, functioning in one's own environment and communication of choice. All of the data were analyzed by SPSS. Fifty six cases were included and interviewee's civil competence was graded to three levels: full civil competence, diminished civil competence, and no civil competence. These cases included two types of contract: the real estate related contract (38 cases) and the labor related contract (14 cases). All of the 6 indexes were well correlated to the forensic expertise. The related coefficient was from 0.703 to 0.834, and the interrelated coefficient of the 6 items was also high, from 0.712 to 0.877. It is feasible to divide the civil competence of the mental disorders into three grades. As the basis, these 6 indexes mentioned above are representative and can be applied in further standardized and quantified assessment of civil competence.

  20. INVOLVEMENT OF SYNAPTIC GENES IN THE PATHOGENESIS OF AUTISM SPECTRUM DISORDERS: THE CASE OF SYNAPSINS

    Directory of Open Access Journals (Sweden)

    Silvia eGiovedi

    2014-09-01

    Full Text Available Autism spectrum disorders (ASDs are heterogeneous neurodevelopmental disorders characterized by deficits in social interaction and social communication, restricted interests and repetitive behaviors. Many synaptic protein genes are linked to the pathogenesis of ASDs, making them prototypical synaptopathies. An array of mutations in the synapsin (Syn genes in humans have been recently associated with ASD and epilepsy, diseases that display a frequent comorbidity. Synapsins are presynaptic proteins regulating synaptic vesicle traffic, neurotransmitter release and short-term synaptic plasticity. In doing so, Syn isoforms control the tone of activity of neural circuits and the balance between excitation and inhibition. As ASD pathogenesis is believed to result from dysfunctions in the balance between excitatory and inhibitory transmissions in neocortical areas, Syns are novel ASD candidate genes. Accordingly, deletion of single Syn genes in mice, in addition to epilepsy, causes core symptoms of ASD by affecting social behavior, social communication and repetitive behaviors. Thus, Syn knockout mice represent a good experimental model to define synaptic alterations involved in the pathogenesis of ASD and epilepsy.

  1. Neonatal neurological disorders involving the brainstem: neurosonographic approaches through the squamous suture and the foramen magnum

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Yi-Fang [National Cheng Kung University Hospital, Department of Emergency Medicine, Tainan (Taiwan); Chen, Cheng-Yu [National Defense Medical Center, Department of Radiology, Taipei (Taiwan); Lin, Yuh-Jey [National Cheng Kung University Hospital, Department of Pediatrics, Tainan (Taiwan); Chang, Ying-Chao [Kaohsiung Chang Gung Children Hospital, Department of Pediatrics, Kaohsiung (Taiwan); Huang, Chao-Ching [National Cheng Kung University Hospital, Department of Pediatrics, Tainan (Taiwan); National Cheng Kung University Hospital, Department of Institute of Molecular Medicine, Tainan (Taiwan)

    2005-09-01

    Brainstem damage which often indicates a critical condition is usually underestimated by trans-anterior-fontanel neurosonography (NS) owing to the far-field limitations. Instead, NS alternately scanning through the squamous suture of the temporal bones and the foramen magnum could provide a better visualization of the brainstem structures. The NS characteristics of brainstem lesions caused by various neonatal neurological disorders, such as hypoxic-ischemic encephalopathy (HIE), metabolic encephalopathy, birth trauma and bacterial meningoencephalitis, can be depicted at the acute stage. An echogenic change in the midbrain was found in patients with HIE or metabolic encephalopathy. In addition to the echogenic change, bilateral transtentorial temporal lobe herniation distorting the contour of the midbrain was observed in a patient with group B streptococcus meningoencephalitis, whereas echogenic changes at the level of the pons and/or the medulla oblongata, mainly localized in the dorsal part, could be observed in newborns with severe HIE, maple syrup urine disease or birth trauma. In this pictorial assay, we demonstrate the feasibility of NS imaging in evaluating the entire brainstem structure of critically ill neonates in the near field and illustrate the characteristic features of brainstem involvement in various neonatal neurological disorders along with computed tomography or magnetic resonance imaging correlation. (orig.)

  2. Is fever suppression involved in the etiology of autism and neurodevelopmental disorders?

    Directory of Open Access Journals (Sweden)

    Torres Anthony R

    2003-09-01

    Full Text Available Abstract Background There appears to be a significant increase in the prevalence rate of autism. Reasons for the increase are unknown, however, there is a substantial body of evidence that suggests the etiology involves infections of the pregnant mother or of a young child. Most infections result in fever that is routinely controlled with antipyretics such as acetaminophen. The blocking of fever inhibits processes that evolved over millions of years to protect against microbial attack. Immune mechanisms in the central nervous system are part of this protective process. Hypothesis The blockage of fever with antipyretics interferes with normal immunological development in the brain leading to neurodevelopmental disorders such as autism in certain genetically and immunologically disposed individuals. Testing the hypothesis Epidemiological studies to determine associations between the use of antipyretics and neurodevelopmental disorders should be undertaken. Biochemical tests will involve the examination of fluids/serum by mass spectrometry and the determination of cytokine/chemokine levels in serum and cell culture fluids after stimulation with fever-inducing molecules from bacteria, viruses and yeast. Postmortem brain can be examined by immunohistochemistry or other methods such as fluorescent in situ hybridization (FISH to determine altered expression levels of chemokines/cytokines and other molecules. Implications of the hypothesis 1 The use of antipyretics during pregnancy or in young children may be reserved for more severe fevers. 2 The perplexing genetic findings in autism may be better understood by categorizing genes along functional pathways. 3 New treatments based on immune, cell, pharmacological or even heat therapies may be developed.

  3. Biomedical research involving patients with disorders of consciousness: ethical and legal dimensions

    Directory of Open Access Journals (Sweden)

    Michele Farisco

    2014-09-01

    Full Text Available The directive 2001/20/UE and the research involving patients with docs. Research involving patients with disorders of consciousness (DOCs deserves special ethical and legal attention because of its Janus-faced nature. On the one hand, it raises concerns about the risk to expose the involved subjects to disproportionate risks not respecting their individual dignity, particularly their right to be cared for; on the other hand, research is an essential tool in order to improve the clinical condition of patients with DOCs. The present paper concerns the ethical and legal dimensions of biomedical research involving patients with disorders of consciousness. In particular, it focuses on informed consent to experimental treatments, which is a challenging issue both from an ethical and legal point of view. The first part reads the Directive 2001/20/EU in the light of the experimentation of patients with DOCs, and suggests a revision in order to better assess the issue of informed consent. The particular case of informed consent for observational studies of non-communicative patients. The second part presents an informed consent form for studies through video-recording of patients unable to communicate their own consent. This form has been elaborated by the bioethics unit of the project "Review of the nosography of vegetative states: application of methods of behavioral analysis to individuals in coma or vegetative state" developed at the Italian National Institute of Health. Relevance of the suggested form. The paper describes the conceptual framework of the form for informed consent to studies through video-recoding, which is a relevant example of what issues should be included in an informed consent for any type of studies through video-recording of patients unable to express their own consent. The article has been sent on November the 7th 2013, before the adoption of the Regulation (EU no. 536/2014 (and consequent abrogation of the Directive 2001

  4. Biomedical research involving patients with disorders of consciousness: ethical and legal dimensions.

    Science.gov (United States)

    Farisco, Michele; Evers, Kathinka; Petrini, Carlo

    2014-01-01

    THE DIRECTIVE 2001/20/UE AND THE RESEARCH INVOLVING PATIENTS WITH DOCS: Research involving patients with disorders of consciousness (DOCs) deserves special ethical and legal attention because of its Janus-faced nature. On the one hand, it raises concerns about the risk to expose the involved subjects to disproportionate risks not respecting their individual dignity, particularly their right to be cared for; on the other hand, research is an essential tool in order to improve the clinical condition of patients with DOCs. The present paper concerns the ethical and legal dimensions of biomedical research involving patients with disorders of consciousness. In particular, it focuses on informed consent to experimental treatments, which is a challenging issue both from an ethical and legal point of view. The first part reads the Directive 2001/20/EU in the light of the experimentation of patients with DOCs, and suggests a revision in order to better assess the issue of informed consent. THE PARTICULAR CASE OF INFORMED CONSENT FOR OBSERVATIONAL STUDIES OF NON-COMMUNICATIVE PATIENTS: The second part presents an informed consent form for studies through video-recording of patients unable to communicate their own consent. This form has been elaborated by the bioethics unit of the project "Review of the nosography of vegetative states: application of methods of behavioral analysis to individuals in coma or vegetative state" developed at the Italian National Institute of Health. RELEVANCE OF THE SUGGESTED FORM: The paper describes the conceptual framework of the form for informed consent to studies through video-recoding, which is a relevant example of what issues should be included in an informed consent for any type of studies through video-recording of patients unable to express their own consent. The article has been sent on November the 7th 2013, before the adoption of the Regulation (EU) no. 536/2014 (and consequent abrogation of the Directive 2001/20/EU) and the release

  5. Peeping into human renal calcium oxalate stone matrix: characterization of novel proteins involved in the intricate mechanism of urolithiasis.

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    Kanu Priya Aggarwal

    Full Text Available BACKGROUND: The increasing number of patients suffering from urolithiasis represents one of the major challenges which nephrologists face worldwide today. For enhancing therapeutic outcomes of this disease, the pathogenic basis for the formation of renal stones is the need of hour. Proteins are found as major component in human renal stone matrix and are considered to have a potential role in crystal-membrane interaction, crystal growth and stone formation but their role in urolithiasis still remains obscure. METHODS: Proteins were isolated from the matrix of human CaOx containing kidney stones. Proteins having MW>3 kDa were subjected to anion exchange chromatography followed by molecular-sieve chromatography. The effect of these purified proteins was tested against CaOx nucleation and growth and on oxalate injured Madin-Darby Canine Kidney (MDCK renal epithelial cells for their activity. Proteins were identified by Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF MS followed by database search with MASCOT server. In silico molecular interaction studies with CaOx crystals were also investigated. RESULTS: Five proteins were identified from the matrix of calcium oxalate kidney stones by MALDI-TOF MS followed by database search with MASCOT server with the competence to control the stone formation process. Out of which two proteins were promoters, two were inhibitors and one protein had a dual activity of both inhibition and promotion towards CaOx nucleation and growth. Further molecular modelling calculations revealed the mode of interaction of these proteins with CaOx at the molecular level. CONCLUSIONS: We identified and characterized Ethanolamine-phosphate cytidylyltransferase, Ras GTPase-activating-like protein, UDP-glucose:glycoprotein glucosyltransferase 2, RIMS-binding protein 3A, Macrophage-capping protein as novel proteins from the matrix of human calcium oxalate stone which play a critical role in kidney stone

  6. Involvement in Bullying among Children with Autism Spectrum Disorders: Parents' Perspectives on the Influence of School Factors

    Science.gov (United States)

    Zablotsky, Benjamin; Bradshaw, Catherine P.; Anderson, Connie; Law, Paul

    2012-01-01

    Children with developmental disabilities are at an increased risk for involvement in bullying, and children with autism spectrum disorders (ASDs) may be at particular risk because of challenges with social skills and difficulty maintaining friendships, yet there has been little empirical research on involvement in bullying among children with ASD.…

  7. "Light cupula" involving all three semicircular canals: A frequently misdiagnosed disorder.

    Science.gov (United States)

    Kim, Chang-Hee; Shin, Jung Eun; Shin, Dong Hyuk; Kim, Yong Won; Ban, Jae Ho

    2014-11-01

    Though benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder causing positional vertigo, patients with typical positional vertigo in which the findings of positional nystagmus do not meet the diagnostic criteria for BPPV are often encountered in the clinic. Recently a concept of the light cupula was introduced, which accounts for some of positional vertigo. Under a normal condition in which the specific gravity of the cupula is same as that of the surrounding endolymph, semicircular canals (SCCs) are not influenced by the gravity. The light cupula, which indicates cupula with lower specific gravity than the surrounding endolymph, is characterized by persistent geotropic direction-changing positional nystagmus (DCPN) without latency on the supine head-roll test and the presence of a null plane. Unless the duration and pattern of positional nystagmus are carefully examined, the light cupula can be misdiagnosed as other types of BPPV. We present a patient with light cupula on the right side who reported recurrent episodes of positional vertigo and had been diagnosed as BPPV with multiple canal involvement (posterior and lateral SCCs) on the opposite side. In this study, we present the mechanism of typical positional nystagmus patterns in patients with light cupula involving all of the unilateral SCCs, and discuss the possible causes of misdiagnosis of the light cupula.

  8. Effects of calcium propionate by different numbers of applications in first week postpartum of dairy cows on hypocalcemia, milk production and reproductive disorders

    Directory of Open Access Journals (Sweden)

    Arda Kovanlıkaya

    2010-01-01

    Full Text Available This study was conducted to evaluate effects of calcium propionate on hypocalcemia, dry matter intake, body condition score, milk production and reproductive disorders in dairy cows. Twenty four multiparous Holstein cows were sorted by parity, body condition score (BCS in close-up period and season of calving and assigned to one of the three treatments. The cows in treatment 1 (T1 received two drenches at calving and 24h after calving. The cows in treatment 2 (T2 received three drenches at calving, 24h after calving and 7 days after calving. The cows in treatment 3 (T3 were the control. Each drench contained 143g of calcium as calcium propionate (0.68kg. Parameters studied were serum calcium, glucose and nonesterified fatty acid (NEFA concentrations, dry matter intake (DMI, BCS, milk production (MP, incidence of retained placenta (RP and metritis. Milk fever developed in 5 of 8 cows, in 3 of 8 cows and in 3 of 8 cows in T1, T2 and T3, respectively, at calving. There was no cow with milk fever in T1 and T2 at 4h after second drench (about 28h after calving but 3 of 8 cows in T3 had still milk fever at this time. The cows receiving two drenches recovered from milk fever in a shorter term as compared to the cows in T3. There were no differences among treatments for DMI, BCS, MP, RP, serum glucose and NEFA concentrations during the experimental period. There was no difference for metritis between T1 and T3 but incidence of metritis in T2 was significantly lower as compared to T3 (P<0.05. Two drenches of calcium propionate were beneficial in treating milk fever and three drenches of calcium propionate were considered to have had a preventive effect for metritis.

  9. Involvement of the modifier gene of a human Mendelian disorder in a negative selection process.

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    Isabelle Jéru

    Full Text Available BACKGROUND: Identification of modifier genes and characterization of their effects represent major challenges in human genetics. SAA1 is one of the few modifiers identified in humans: this gene influences the risk of renal amyloidosis (RA in patients with familial Mediterranean fever (FMF, a Mendelian autoinflammatory disorder associated with mutations in MEFV. Indeed, the SAA1 alpha homozygous genotype and the p.Met694Val homozygous genotype at the MEFV locus are two main risk factors for RA. METHODOLOGY/PRINCIPAL FINDINGS: HERE, WE INVESTIGATED ARMENIAN FMF PATIENTS AND CONTROLS FROM TWO NEIGHBORING COUNTRIES: Armenia, where RA is frequent (24%, and Karabakh, where RA is rare (2.5%. Sequencing of MEFV revealed similar frequencies of p.Met694Val homozygotes in the two groups of patients. However, a major deficit of SAA1 alpha homozygotes was found among Karabakhian patients (4% as compared to Armenian patients (24% (p = 5.10(-5. Most importantly, we observed deviations from Hardy-Weinberg equilibrium (HWE in the two groups of patients, and unexpectedly, in opposite directions, whereas, in the two control populations, genotype distributions at this locus were similar and complied with (HWE. CONCLUSIONS/SIGNIFICANCE: The excess of SAA1alpha homozygotes among Armenian patients could be explained by the recruitment of patients with severe phenotypes. In contrast, a population-based study revealed that the deficit of alpha/alpha among Karabakhian patients would result from a negative selection against carriers of this genotype. This study, which provides new insights into the role of SAA1 in the pathophysiology of FMF, represents the first example of deviations from HWE and selection involving the modifier gene of a Mendelian disorder.

  10. The possible involvement of root-cap mucilage in gravitropism and calcium movement across root tips of Allium cepa L

    Science.gov (United States)

    Moore, R.; Fondren, W. M.

    1986-01-01

    Roots of Allium cepa L. grown in aerated water elongate rapidly, but are not graviresponsive. These roots (1) possess extensive columella tissues comprised of cells containing numerous sedimented amyloplasts, (2) lack mucilage on their tips, and (3) are characterized by a weakly polar movement of calcium (Ca) across their tips. Placing roots in humid air correlates positively with the (1) onset of gravicurvature, (2) appearance of mucilage on tips of the roots, and (3) onset of the ability to transport Ca polarly to the lower side of the root tip. Gravicurvature of roots previously submerged in aerated water is more rapid when roots are oriented vertically for 1-2 h in humid air prior to being oriented horizontally. The more rapid gravicurvature of these roots correlates positively with the accumulation of mucilage at the tips of roots during the time the roots are oriented vertically. Therefore, the onset of gravicurvature and the ability of roots to transport Ca to the lower sides of their tips correlate positively with the presence of mucilage at their tips. These results suggest that mucilage may be important for the transport of Ca across root caps.

  11. Calcium involved in the poly(γ-glutamic acid)-mediated promotion of Chinese cabbage nitrogen metabolism.

    Science.gov (United States)

    Xu, Zongqi; Lei, Peng; Feng, Xiaohai; Xu, Xianju; Liang, Jinfeng; Chi, Bo; Xu, Hong

    2014-07-01

    Plant growth can reportedly be promoted by poly(γ-glutamic acid) (γ-PGA). However, the underlying mechanism is unknown. To reveal the mechanism of γ-PGA, we designed an experiment that investigated the effect of γ-PGA on the nitrogen metabolism of Chinese cabbage hydroponic cultured at different calcium (Ca) levels and varied exogenous Ca(2+) inhibitors. The results showed that nitrate reductase (NR), glutamine synthetase (GS), glutamate synthase, and glutamate dehydrogenase activities in leaves and roots were obviously enhanced by γ-PGA at the normal Ca(2+) level (4.0 mM). Meanwhile, γ-PGA increased the content of total nitrogen, soluble protein, and soluble amino acids in leaves. However, the promotional effect of γ-PGA on fresh weight weakened when Ca(2+) was inadequate. Moreover, γ-PGA not only induced the influx of extracellular Ca(2+) and Ca(2+) in organelles into cytoplasm, but also increased the Ca(2+)-ATPase level to modify Ca(2+) homeostasis in plant cells. In addition, exogenous Ca(2+) inhibitors significantly suppressed the γ-PGA-mediated promotion of cytoplasmic free Ca(2+) level, calmodulin (CaM) content, GS and glutamate dehydrogenase activities. In summary, γ-PGA accelerated the nitrogen metabolism of plants through the Ca(2+)/CaM signaling pathway, thereby improving the growth of the plant.

  12. Inhibition of ATP-induced calcium influx in HT4 cells by glucocorticoids: involvement of protein kinase A

    Institute of Scientific and Technical Information of China (English)

    Jian-zhong HAN; Wen LIN; Yi-zhang CHEN

    2005-01-01

    Aim: In our previous observations, adenosine triphosphate (ATP) was found to evoke immediate elevations in intracellular free calcium concentration ([Ca2+]i) in HT4 neuroblastoma cells of mice. We tried to see if a brief pretreatment of glucocorticoids could inhibit the Ca2+ response and reveal the underlying signal ing mechanism. Methods: Measurement of [Ca2+]i was carried out using the dual-wavelength fluorescence method with Fura-2 as the indicator. Results: Pre incubation of HT4 cells for 5 min with corticosterone (B) or bovine serum albumin conjugated corticosterone (B-BSA) inhibited the peak [Ca2+]i increments in a concentration-dependent manner. Cortisol and dexamethasone had a similar action, while deoxycorticosterone and cholesterol were ineffective. Both extracellular Ca2+ influx and internal Ca2+ release contributed to ATP-induced [Ca2+]i elevation. The brief treatment with only B attenuated Ca2+ influx. Furthermore, the [Ca2+]i elevation induced by the P2X receptor agonist adenosine 5'-(β,γ-methylene) triphosphate (β,γ-meATP) was also suppressed. The rapid inhibitory effect of B can be reproduced by forskolin 1 mmol/L and blocked by H89 20 mmol/L. Neither nuclear glucocorticoid receptor antagonist mifepristone nor protein kinase C in hibitors influenced the rapid action of B. Conclusion: Our results suggest that glucocorticoids modulate P2X receptor-medicated Ca2+ influx through a membrane-initiated, non-genomic and PKA-dependent pathway in HT4 cells.

  13. Calcium and Vitamin D Supplement Prescribing Practices among Providers Caring for Children with Autism Spectrum Disorders: Are We Addressing Bone Health?

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    Shylaja Srinivasan

    2016-01-01

    Full Text Available Children with autism spectrum disorders (ASD have several risk factors for low bone mineral density. The gluten-free, casein-free (GFCF diet is a complementary therapy sometimes used in ASD that raises concerns for the adequacy of calcium and vitamin D intake. This study evaluated the prescribing practices of calcium and vitamin D supplements and the practice of checking 25-hydroxy vitamin D (25(OHD levels by providers in 100 children with ASD, 50 of whom were on the GFCF diet. Fifty-two percent and 46% of children on the GFCF diet were on some form of vitamin D and calcium supplements, respectively, compared to 18% and 14% of those not on this diet. Twenty-four percent of children in the GFCF group had a documented 25(OHD level compared to none in the non-GFCF group. The data highlight a gap in calcium and vitamin D supplement prescribing practices among providers caring for children with ASD as well as a gap in the practice of checking 25(OHD levels.

  14. Neuromyelitis optica spectrum disorder presenting with repeated hypersomnia due to involvement of the hypothalamus and hypothalamus-amygdala linkage.

    Science.gov (United States)

    Kume, Kodai; Deguchi, Kazushi; Ikeda, Kazuyo; Takata, Tadayuki; Kokudo, Yohei; Kamada, Masaki; Touge, Tetsuo; Takahashi, Toshiyuki; Kanbayashi, Takashi; Masaki, Tsutomu

    2015-06-01

    We report the case of a 46-year-old Japanese woman with neuromyelitis optica spectrum disorder presenting with repeated hypersomnia accompanied by decreased CSF orexin level. First episode associated with hypothalamic-pituitary dysfunction showed bilateral hypothalamic lesions that can cause secondary damage to the orexin neurons. The second episode associated with impaired memory showed a left temporal lesion involving the amygdala. The mechanism remains unknown, but the reduced blood flow in the hypothalamus ipsilateral to the amygdala lesion suggested trans-synaptic hypothalamic dysfunction secondary to the impaired amygdala. A temporal lesion involving the amygdala and hypothalamus could be responsible for hypersomnia due to neuromyelitis optica spectrum disorder.

  15. Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk.

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    Daria Salyakina

    Full Text Available Copy number variations (CNVs are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than by single nucleotide polymorphisms (SNPs. In the multifaceted etiology of autism spectrum disorders (ASDs, CNVs appear to contribute significantly to our understanding of the pathogenesis of this complex disease. A unique resource of 42 extended ASD families was genotyped for over 1 million SNPs to detect CNVs that may contribute to ASD susceptibility. Each family has at least one avuncular or cousin pair with ASD. Families were then evaluated for co-segregation of CNVs in ASD patients. We identified a total of five deletions and seven duplications in eleven families that co-segregated with ASD. Two of the CNVs overlap with regions on 7p21.3 and 15q24.1 that have been previously reported in ASD individuals and two additional CNVs on 3p26.3 and 12q24.32 occur near regions associated with schizophrenia. These findings provide further evidence for the involvement of ICA1 and NXPH1 on 7p21.3 in ASD susceptibility and highlight novel ASD candidates, including CHL1, FGFBP3 and POUF41. These studies highlight the power of using extended families for gene discovery in traits with a complex etiology.

  16. [Civil competence assessment of the mental disorders involved in compensation of personal injury].

    Science.gov (United States)

    Pang, Yan-xia; Zhang, Qin-ting; Cai, Wei-xiong; Huang, Fu-yin; Tang, Tao; Wu, Jia-sheng; Wang, Jian-jun; Dong, Ri-xia

    2009-02-01

    To seek and ascertain indicators that can be used in the civil competence assessment of the mental disorders involved in compensation of personal injury. A retrospective study was made on the data related to the interviewee's mental status assessed by forensic experts during the period from 2003 to 2005 in Institute of Forensic Science, Ministry of Justice, P.R.China. The 6 indicators, including awareness of situation, factual understanding of issues, appreciation of likely consequences, rational manipulation of information, functioning in one's own environment, and communication of choice, were graded and statistically analyzed using SPSS 11.5 software. The 6 indicators correlated well with the assessment of forensic experts ,with the related coefficient between 0.632 and 0.876, and the inter-related coefficient among the 6 indicators between 0.575 and 0.911. The 6 indicators could be used for the civil competence assessment and may also be taken as the basis for further standardization and quantification of civil competence.

  17. Greater disruption to control of voluntary saccades in autistic disorder than Asperger's disorder: evidence for greater cerebellar involvement in autism?

    Science.gov (United States)

    Stanley-Cary, Chloe; Rinehart, Nicole; Tonge, Bruce; White, Owen; Fielding, Joanne

    2011-03-01

    It remains unclear whether autism and Asperger's disorder (AD) exist on a symptom continuum or are separate disorders with discrete neurobiological underpinnings. In addition to impairments in communication and social cognition, motor deficits constitute a significant clinical feature in both disorders. It has been suggested that motor deficits and in particular the integrity of cerebellar modulation of movement may differentiate these disorders. We used a simple volitional saccade task to comprehensively profile the integrity of voluntary ocular motor behaviour in individuals with high functioning autism (HFA) or AD, and included measures sensitive to cerebellar dysfunction. We tested three groups of age-matched young males with normal intelligence (full scale, verbal, and performance IQ estimates >70) aged between 11 and 19 years; nine with AD, eight with HFA, and ten normally developing males as the comparison group. Overall, the metrics and dynamics of the voluntary saccades produced in this task were preserved in the AD group. In contrast, the HFA group demonstrated relatively preserved mean measures of ocular motricity with cerebellar-like deficits demonstrated in increased variability on measures of response time, final eye position, and movement dynamics. These deficits were considered to be consistent with reduced cerebellar online adaptation of movement. The results support the notion that the integrity of cerebellar modulation of movement may be different in AD and HFA, suggesting potentially differential neurobiological substrates may underpin these complex disorders.

  18. Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement.

    Science.gov (United States)

    Paul, Lynn K

    2011-03-01

    This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)-the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome).

  19. A Historical Analysis of the Quest for the Origins of Aging Macula Disorder, the Tissues Involved, and Its Terminology

    NARCIS (Netherlands)

    de Jong, Paulus T V M

    2016-01-01

    Although ocular tissues involved in aging macula disorder (AMD) were already known in 300 BC, the last type of photoreceptors was discovered only 10 years ago. The earliest descriptions of AMD appeared around 1850. It took over 150 years, till a clearer concept of AMD was formulated and even longer

  20. Role of calcium supplementation during pregnancy in reducing risk of developing gestational hypertensive disorders: a meta-analysis of studies from developing countries

    Directory of Open Access Journals (Sweden)

    Bhutta Zulfiqar A

    2011-04-01

    Full Text Available Abstract Background Hypertension in pregnancy stand alone or with proteinuria is one of the leading causes of maternal mortality and morbidity in the world. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy though the effect varies based on baseline calcium intake and pre-existing risk factors. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries. Methods A literature search was carried out on PubMed, Cochrane Library and WHO regional databases. Data were extracted into a standardized excel sheet. Identified studies were graded based on strengths and limitations of studies. All the included studies were from developing countries. Meta-analyses were generated where data were available from more than one study for an outcome. Primary outcomes were maternal mortality, eclampsia, pre-eclampsia, and severe preeclampsia. Neonatal outcomes like neonatal mortality, preterm birth, small for gestational age and low birth weight were also evaluated. We followed standardized guidelines of Child Health Epidemiology Reference Group (CHERG to generate estimates of effectiveness of calcium supplementation during pregnancy in reducing maternal and neonatal mortality in developing countries, for inclusion in the Lives Saved Tool (LiST. Results Data from 10 randomized controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy was associated with a significant reduction of 45% in risk of gestational hypertension [Relative risk (RR 0.55; 95 % confidence interval (CI 0.36-0.85] and 59% in the risk of pre-eclampsia [RR 0.41; 95 % CI 0.24-0.69] in developing countries. Calcium supplementation during pregnancy was also associated with a significant reduction

  1. Attention-deficit hyperactivity disorder medication use: factors involved in prescribing, safety aspects and outcomes

    Science.gov (United States)

    Martinez-Raga, Jose; Ferreros, Amparo; Knecht, Carlos; de Alvaro, Raquel; Carabal, Eloisa

    2016-01-01

    While treatment of patients with attention-deficit hyperactivity disorder (ADHD) is based on a multimodal approach that combines medication with specific psychological interventions, pharmacotherapy alone is generally considered an essential and cost-effective element. This paper aims to comprehensively and critically review factors involved in prescribing and medication use in individuals diagnosed with ADHD, focusing on the difficulties facing patients with ADHD seeking treatment, as well as the safety and tolerability aspects of ADHD pharmacotherapies, with particular attention on the cardiovascular adverse events and the potential risk of misuse or diversion of ADHD medications. A comprehensive and systematic literature search of PubMed/MEDLINE database was conducted to identify studies published in peer-reviewed journals until 1 August 2016. Children, adolescents and adults often encounter significant difficulties in the process of accessing specialist assessment and treatment for ADHD as a consequence of disparities in service organization and available treatment provision. Despite the well-established efficacy and overall safety profile, ADHD medications are not exempt from adverse events. The cardiovascular safety of pharmacotherapies used for treating individuals with ADHD has raised particular concerns; however there is little evidence of serious cardiovascular adverse events, including no serious corrected QT (QTc) abnormalities associated with stimulants, atomoxetine or α2-adrenergic receptor agonists. Although the abuse of prescription stimulant drugs, particularly, short-acting stimulants is a prevalent and growing problem, nonmedical use of prescription stimulants within the clinical context is very limited. In addition, nonstimulant ADHD medications lack any reinforcing effects and consequently any abuse potential.

  2. Pathophysiology of autism spectrum disorders: revisiting gastrointestinal involvement and immune imbalance.

    Science.gov (United States)

    Samsam, Mohtashem; Ahangari, Raheleh; Naser, Saleh A

    2014-08-07

    Autism spectrum disorders (ASD) comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors. Several genes have been implicated in the pathogenesis of ASD, most of them are involved in neuronal synaptogenesis. A number of environmental factors and associated conditions such as gastrointestinal (GI) abnormalities and immune imbalance have been linked to the pathophysiology of ASD. According to the March 2012 report released by United States Centers for Disease Control and Prevention, the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms. Although there is a strong genetic base for the disease, several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem. Many children suffering from ASD have GI problems such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, and intestinal infections. A number of studies focusing on the intestinal mucosa, its permeability, abnormal gut development, leaky gut, and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas. GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children. Maternal infection or autoimmune diseases have been suspected. Activation of the immune system during early development may have deleterious effect on various organs including the nervous system. In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.

  3. The Impact of Criminal Justice Involvement and Housing Outcomes Among Homeless Persons with Co-occurring Disorders.

    Science.gov (United States)

    Mitchell, Jessica N; Clark, Colleen; Guenther, Christina C

    2017-02-02

    The relationship between criminal justice involvement and housing among homeless persons with co-occurring disorders was examined. Program participants assisted in moving to stable housing were interviewed at baseline, six months, and discharge. Those who remained homeless at follow-up and discharge had significantly more time in jail in the past month than those who were housed. However, criminal justice involvement was not significantly related to housing status at the six month follow-up or discharge. Findings suggest that housing people with complex behavioral health issues reduces the likelihood of further criminal justice involvement.

  4. Parental Involvement in Infant Sleep Routines Predicts Differential Sleep Patterns in Children With and Without Anxiety Disorders.

    Science.gov (United States)

    Cowie, Jennifer; Palmer, Cara A; Hussain, Hira; Alfano, Candice A

    2016-08-01

    This study compared parents' retrospective reports of their involvement in infant settling strategies and their relation to current sleep patterns among children (N = 84, ages 7-11) with generalized anxiety disorder (GAD) and healthy controls. Parents of children with GAD were significantly more likely to report rocking their infants to sleep and putting infants down when they were already asleep than parents of healthy controls, even when accounting for infant health-related factors and parental anxiety. Greater involvement in infant sleep routines also predicted sleep patterns (measured via actigraphy) during childhood, though opposite relationships were observed in the two groups. Early involvement was related to poorer sleep in control children but better sleep for children with GAD even after controlling for current parenting practices. Findings suggest differential effects of early sleep-related parenting for children with and without later anxiety disorders with possible implications for early intervention.

  5. The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity.

    Science.gov (United States)

    Geier, Mark R; Geier, David A

    2005-01-01

    Autism is a neurodevelopmental disorder that according to the Centers for Disease Control and Prevention (CDC) affects 1 in 150 children in the United States. Autism is characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movements, and sensory dysfunction. Recently emerging evidence suggests that mercury, especially from childhood vaccines, appears to be a factor in the development of the autistic disorders, and that autistic children have higher than normal body-burdens of mercury. In considering mercury toxicity, it has previously been shown that testosterone significantly potentates mercury toxicity, whereas estrogen is protective. Examination of autistic children has shown that the severity of autistic disorders correlates with the amount of testosterone present in the amniotic fluid, and an examination of a case-series of autistic children has shown that some have plasma testosterone levels that were significantly elevated in comparison neurotypical control children. A review of some of the current biomedical therapies for autistics, such as glutathione and cysteine, chelation, secretin, and growth hormone, suggests that they may in fact lower testosterone levels. We put forward the medical hypothesis that autistic disorders, in fact, represents a form of testosterone mercury toxicity, and based upon this observation, one can design novel treatments for autistics directed towards higher testosterone levels in autistic children. We suggest a series of experiments that need to be conducted in order to evaluate the exact mechanisms for mercury-testosterone toxicity, and various types of clinical manipulations that may be employed to control testosterone levels. It is hoped by devising therapies that address the steroid hormone pathways, in addition to the current treatments that successful lower heavy metal body-burdens of mercury, will work synergistically to improve clinical outcomes. In light of the fact that

  6. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx.

    Science.gov (United States)

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Wewer Albrechtsen, Nicolai Jacob; Hartmann, Bolette; Holst, Jens Juul

    2015-06-15

    Neurotensin (NT) is a neurohormone produced in the central nervous system and in the gut epithelium by the enteroendocrine N cell. NT may play a role in appetite regulation and may have potential in obesity treatment. Glucose ingestion stimulates NT secretion in healthy young humans, but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATP channel opener diazoxide, which causes hyperpolarization, eliminated the response. Luminal inhibition of the sodium-glucose cotransporter 1 (SGLT1) (by phloridzin) eliminated glucose-stimulated release as well as secretion stimulated by luminal methyl-α-D-glucopyranoside (20% wt/vol), a metabolically inactive SGLT1 substrate, suggesting that glucose stimulates secretion by initial uptake by this transporter. However, secretion was also sensitive to GLUT2 inhibition (by phloretin) and blockage of oxidative phosphorylation (2-4-dinitrophenol). Direct KATP channel closure by sulfonylureas stimulated secretion. Therefore, glucose stimulates NT secretion by uptake through SGLT1 and GLUT2, both causing depolarization either as a consequence of sodium-coupled uptake (SGLT1) or by closure of KATP channels (GLUT2 and SGLT1) secondary to the ATP-generating metabolism of glucose.

  7. A selective involvement of putamen functional connectivity in youth with internet gaming disorder.

    Science.gov (United States)

    Hong, Soon-Beom; Harrison, Ben J; Dandash, Orwa; Choi, Eun-Jung; Kim, Seong-Chan; Kim, Ho-Hyun; Shim, Do-Hyun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

    2015-03-30

    Brain cortico-striatal circuits have consistently been implicated in the pathology of addiction related disorders. We applied a reliable seed-based analysis of the resting-state brain activity to comprehensively delineate the subdivisions of striatal functional connectivity implicated in internet gaming disorder. Among twelve right-handed male adolescents with internet gaming disorder and 11 right-handed and gender-matched healthy controls, we examined group differences in the functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen, as well as the association of these connectivity indices with behavioral measures of internet use. Adolescents with internet gaming disorder showed significantly reduced dorsal putamen functional connectivity with the posterior insula-parietal operculum. More time spent playing online games predicted significantly greater functional connectivity between the dorsal putamen and bilateral primary somatosensory cortices in adolescents with internet gaming disorder, and significantly lower functional connectivity between the dorsal putamen and bilateral sensorimotor cortices in healthy controls. The dorsal putamen functional connectivity was significantly and specifically different in adolescents with internet gaming disorder. The findings suggest a possible biomarker of internet gaming disorder.

  8. Calcium signaling and epilepsy.

    Science.gov (United States)

    Steinlein, Ortrud K

    2014-08-01

    Calcium signaling is involved in a multitude of physiological and pathophysiological mechanisms. Over the last decade, it has been increasingly recognized as an important factor in epileptogenesis, and it is becoming obvious that the excess synchronization of neurons that is characteristic for seizures can be linked to various calcium signaling pathways. These include immediate effects on membrane excitability by calcium influx through ion channels as well as delayed mechanisms that act through G-protein coupled pathways. Calcium signaling is able to cause hyperexcitability either by direct modulation of neuronal activity or indirectly through calcium-dependent gliotransmission. Furthermore, feedback mechanisms between mitochondrial calcium signaling and reactive oxygen species are able to cause neuronal cell death and seizures. Unravelling the complexity of calcium signaling in epileptogenesis is a daunting task, but it includes the promise to uncover formerly unknown targets for the development of new antiepileptic drugs.

  9. Mastication dyspraxia: a neurodevelopmental disorder reflecting disruption of the cerebellocerebral network involved in planned actions.

    Science.gov (United States)

    Mariën, Peter; Vidts, Annelies; Van Hecke, Wim; De Surgeloose, Didier; De Belder, Frank; Parizel, Paul M; Engelborghs, Sebastiaan; De Deyn, Peter P; Verhoeven, Jo

    2013-04-01

    This paper reports the longitudinal clinical, neurocognitive, and neuroradiological findings in an adolescent patient with nonprogressive motor and cognitive disturbances consistent with a diagnosis of developmental coordination disorder (DCD). In addition to prototypical DCD, the development of mastication was severely impaired, while no evidence of swallowing apraxia, dysphagia, sensorimotor disturbances, abnormal tone, or impaired general cognition was found. He suffered from bronchopulmonary dysplasia and was ventilated as a newborn for 1.5 months. At the age of 3 months, a ventriculoperitoneal shunt was surgically installed because of obstructive hydrocephalus secondary to perinatal intraventricular bleeding. At the age of 5 years, the patient's attempts to masticate were characterized by rough, effortful, and laborious biting movements confined to the vertical plane. Solid food particles had a tendency to get struck in his mouth and there was constant spillage. As a substitute for mastication, he moved the unground food with his fingers in a lateral direction to the mandibular and maxillary vestibule to externally manipulate and squeeze the food between cheek and teeth with the palm of his hand. Once the food was sufficiently soft, the bolus was correctly transported by the tongue in posterior direction and normal deglutition took place. Repeat magnetic resonance imaging (MRI) during follow-up disclosed mild structural abnormalities as the sequelae of the perinatal intraventricular bleeding, but this could not explain impaired mastication behavior. Quantified Tc-99m-ethylcysteinate dimer single-photon emission computed tomography (Tc-99m-ECD SPECT), however, revealed decreased perfusion in the left cerebellar hemisphere, as well as in both inferior lateral frontal regions, both motor cortices, and the right anterior and lateral temporal areas. Anatomoclinical findings in this patient with DCD not only indicate that the functional integrity of the

  10. Bone marrow involvement by lymphoproliferative disorders after renal transplantation: PTLD. Int. Survey

    Directory of Open Access Journals (Sweden)

    Morteza Izadi

    2012-01-01

    Conclusions: Renal recipients with BM PTLD represent worse outcome and more unfavorable histopathological phenomenon than in other organ involvements. Moreover, a concomitant PTLD involvement site in liver was found which necessitates full hepatic evaluation for a potential complication by the disease in renal recipients whose BM is involved.

  11. Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

    Science.gov (United States)

    Nakagawa, Yutaka; Chiba, Kenji

    2016-09-01

    Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide

    OpenAIRE

    Barde, Swapnali; Rüegg, Joelle; Prud'homme, Josée; EKSTRÖM, TOMAS J.; Palkovits, Miklos; Turecki, Gustavo; Bagdy, Gyorgy; Ihnatko, Robert; Theodorsson, Elvar; Juhasz, Gabriella; Diaz-Heijtz, Rochellys; Mechawar, Naguib; Hökfelt, Tomas G. M.

    2016-01-01

    Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL(1-3), are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system...

  13. Interactions among stakehoklders involved in return to work after sick leave due to mental disorders: a meta-ethnography.

    Science.gov (United States)

    Neves, Robson da Fonseca; Nunes, Mônica de Oliveira; Magalhães, Lilian

    2015-11-01

    Mental disorders cause impact in the work environment. Investigations of interaction among stakeholders who are involved in the return to work are scarce. Meta-ethnography serves to synthesize qualitative studies by means of ongoing interpretation and comparison of the ideas presented in the articles. The goal of this study is to present a meta-ethnography of the interactions among the stakeholders involved in the return to work process after leave of absence due to mental disorders. It aims: (1) to investigate the interactions among stakeholders involved in return to work; (2) to identify enablers or obstacles for the return to work. The database search found 619 articles, 16 of which met the inclusion criteria. Analysis of the articles revealed six second-order concepts that resulted in two syntheses. The first is about performance ethos in the return to work, and the second shows return to work as a catalyst of new life styles. Models that favor the worker's performance ethos, as well as a perspective oriented by psychosocial aspects may enable return to work practices after leave of absence due to mental disorders.

  14. Predictors of recurrent sickness absence due to depressive disorders : A delphi approach involving scientists and physicians

    NARCIS (Netherlands)

    Norder, G.; Roelen, C.A.M.; Rhenen, van W.; Buitenhuis, J.; Bültmann, U.

    2013-01-01

    Depression is a common and highly recurrent mental disorder that is accompanied by poor functioning at home and at work. Not all depressed employees report sick and little is known about variables associated with sickness absence (SA) due to depression. Recurrent SA due to depression tends to margin

  15. Mastication Dyspraxia: A Neurodevelopmental Disorder Reflecting Disruption of the Cerebellocerebral Network Involved in Planned Actions

    OpenAIRE

    2013-01-01

    This paper reports the longitudinal clinical, neurocognitive, and neuroradiological findings in an adolescent patient with nonprogressive motor and cognitive disturbances consistent with a diagnosis of developmental coordination disorder (DCD). In addition to prototypical DCD, the development of mastication was severely impaired, while no evidence of swallowing apraxia, dysphagia, sensorimotor disturbances, abnormal tone, or impaired general cognition was found. He suffered from bronchopulmon...

  16. Predictors of Recurrent Sickness Absence Due to Depressive Disorders - A Delphi Approach Involving Scientists and Physicians

    NARCIS (Netherlands)

    Norder, Giny; Roelen, Corne A. M.; van Rhenen, Willem; Buitenhuis, Jan; Bultmann, Ute; Anema, Johannes R.

    2012-01-01

    Background: Depression is a common and highly recurrent mental disorder that is accompanied by poor functioning at home and at work. Not all depressed employees report sick and little is known about variables associated with sickness absence (SA) due to depression. Recurrent SA due to depression ten

  17. Polyamine regulates tolerance to water stress in leaves of white clover associated with antioxidant defense and dehydrin genes via involvement in calcium messenger system and hydrogen peroxide signaling

    Directory of Open Access Journals (Sweden)

    Zhou eLi

    2015-10-01

    Full Text Available Endogenous polyamine (PA may play a critical role in tolerance to water stress in plants acting as a signaling molecule activator. Water stress caused increases in endogenous PA content in leaves, including putrescine (Put, spermidine (Spd, and spermine (Spm. Exogenous application of Spd could induce the instantaneous H2O2 burst and accumulation of cytosolic free Ca2+, and activate NADPH oxidase and CDPK gene expression in cells. To a great extent, PA biosynthetic inhibitor reduced the water stress-induced H2O2 accumulation, free cytosolic Ca2+ release, antioxidant enzyme activities and genes expression leading to aggravate water stress-induced oxidative damage, while these suppressing effects were alleviated by the addition of exogenous Spd, indicating PA was involved in water stress-induced H2O2 and cytosolic free Ca2+ production as well as stress tolerance. Dehydrin genes (Y2SK, Y2K, and SK2 were showed to be highly responsive to exogenous Spd. PA-induced antioxidant defense and dehydrin genes expression could be blocked by the scavenger of H2O2 and the inhibitors of H2O2 generation or Ca2+ channels blockers, a calmodulin antagonist, as well as the inhibitor of CDPK. These findings suggested that PA regulated tolerance to water stress in white clover associated with antioxidant defenses and dehydrins via involvement in the calcium messenger system and H2O2 signaling pathways. PA-induced H2O2 production required Ca2+ release, while PA-induced Ca2+ release was also essential for H2O2 production, suggesting an interaction between PA-induced H2O2 and Ca2+ signaling.

  18. Calcium channels and migraine.

    Science.gov (United States)

    Pietrobon, Daniela

    2013-07-01

    Missense mutations in CACNA1A, the gene that encodes the pore-forming α1 subunit of human voltage-gated Ca(V)2.1 (P/Q-type) calcium channels, cause a rare form of migraine with aura (familial hemiplegic migraine type 1: FHM1). Migraine is a common disabling brain disorder whose key manifestations are recurrent attacks of unilateral headache that may be preceded by transient neurological aura symptoms. This review, first, briefly summarizes current understanding of the pathophysiological mechanisms that are believed to underlie migraine headache, migraine aura and the onset of a migraine attack, and briefly describes the localization and function of neuronal Ca(V)2.1 channels in the brain regions that have been implicated in migraine pathogenesis. Then, the review describes and discusses i) the functional consequences of FHM1 mutations on the biophysical properties of recombinant human Ca(V)2.1 channels and native Ca(V)2.1 channels in neurons of knockin mouse models carrying the mild R192Q or severe S218L mutations in the orthologous gene, and ii) the functional consequences of these mutations on neurophysiological processes in the cerebral cortex and trigeminovascular system thought to be involved in the pathophysiology of migraine, and the insights into migraine mechanisms obtained from the functional analysis of these processes in FHM1 knockin mice. This article is part of a Special Issue entitled: Calcium channels. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Disordered glycometabolism involved in pathogenesis of Kashin–Beck disease, an endemic osteoarthritis in China

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cuiyan, E-mail: xj.cy.69@stu.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Lei, Ronghui, E-mail: leirh@mail.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Tiainen, Mika, E-mail: mika.tiainen@uef.fi [School of Pharmacy, University of Eastern Finland, Kuopio (Finland); Wu, Shixun, E-mail: wushixun313@stu.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Zhang, Qiang, E-mail: wdrr@163.com [Department of Kashin–Beck Disease, Qinghai Institute for Endemic Disease Control and Prevention, Xining, Qinghai 811602 (China); Pei, Fuxing, E-mail: peifuxing@vip.163.com [Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Guo, Xiong, E-mail: guox@mail.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China)

    2014-08-15

    Kashin–Beck disease (KBD) is a chronic endemic osteoarthritis in China. Previous studies have suggested a role of metabolic dysfunction in causation of this disease. In this investigation, the metabolomics approach and cell experiments were used to discover the metabolic changes and their effects on KBD chondrocytes. Nuclear magnetic resonance ({sup 1}H NMR) spectroscopy was used to examine serum samples from both the KBD patients and normal controls. The pattern recognition multivariate analysis (OSC–PLS) and quantitative analysis (QMTLS iterator) revealed altered glycometabolism in KBD, with increased glucose and decreased lactate and citrate levels. IPA biological analysis showed the centric location of glucose in the metabolic network. Massive glycogen deposits in chondrocytes and increased uptake of glucose by chondrocytes further confirmed disordered glycometabolism in KBD. An in vitro study showed the effects of disordered glycometabolism in chondrocytes. When chondrocytes were treated with high glucose, expression of type II collagen and aggrecan were decreased, while TNF-α expression, the level of cellular reactive oxygen species and cell apoptosis rates all were increased. Therefore, our results demonstrated that disordered glycometabolism in patients with KBD was linked to the damage of chondrocytes. This may provide a new basis for understanding the pathogenesis of KBD. - Highlights: • Disordered glycometabolism in KBD was demonstrated by combining serum metabolomics and chondrocyte studies. • Glucose and TNF-α were key molecules linked to altered metabolism and inflammation in the pathophysiology of KBD. • The glycometabolism disorder was linked to expression of type II collagen and aggrecan, ROS and apoptosis of KBD chondrocytes.

  20. Regulation of the genes involved in neurotransmission in Attention Deficit/Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Cuch Barbara

    2015-06-01

    Full Text Available Attention Deficit Hyperactivity Disorder is the full name of the disease commonly deemed ADHD. This disease is most frequently diagnosed in childhood, and it affects up to 12 % of all children world-wide. The current clinical criteria (the base for diagnosis can be found in DSM -V. The core symptoms are divided in three groups: hyperactivity, impulsivity and impaired attention. The aetiology of the disorder is combined, including a wide range of factors, and the genetic, environmental, toxic, perinatal background is taken into account. Because, currently, more and more studies are seeking to explore the heritability of the disorder, the aim of this study is to review the information provided by different research centres which discuss the genetic background of the disease. Herein, we present the results of different studies gathered from the online database. Our findings indicate that the participation of genetic factors within this disorder is supported by family, twin and adoption studies. Indeed, in current literature, researchers estimate that there is a higher risk of developing ADHD among children from families with an ADHD history. Of particular note is that there are some studies indicating particular genes that determine the susceptibility to ADHD. Such studies make mention that most of these genes encode components of the dompaminergic and serotoninergic neurotransmission systems. Researchers in the field, thus, are attempting to link the presence of certain alleles in affected children with their response to treatment. Yet, while ADHD is now considered as being a disorder of genetic background, we cannot indicate a single gene or its mutation that would be crucial in the aetiology and diagnosis. Still, a number of candidate genes have been reported so far.

  1. Nonruminant Nutrition Symposium: Involvement of gut neural and endocrine systems in pathological disorders of the digestive tract.

    Science.gov (United States)

    Furness, J B; Poole, D P

    2012-04-01

    The functioning of the gastrointestinal tract is under the control of the most extensive system of peripheral neurons in the body, the enteric nervous system, and the largest endocrine system of the body, the GEP endocrine system. The enteric nervous system in large mammals contains 500 million neurons, and the GEP endocrine system produces more than 30 hormones. Numerous enteric neuropathies affecting both humans and animals have been described and digestive disorders affect commercially important species, such as horses and cattle. The most severe enteric neuropathies (e.g., lethal white syndrome in horses or Hirschsprung's disease in humans) can be fatal. Also, horses with ileus or other digestive disorders are commonly euthanized. In this review we discuss examples of enteric neuropathies that affect agricultural animals and humans: prion disease, postoperative ileus, distal enteric aganglionosis, and infective diarrhea. Enteric neurons and glia are a location of prion proteins and are involved in transmission of the infection from gut to brain and brain to gut. Postoperative ileus is a complex disorder involving the local inhibitory effects of sympathetic nervous system activation and the release of opioids, presumably from enteric neurons. Intestinal inflammation, especially of the external muscle that includes enteric ganglia, also occurs in ileus. Congenital distal bowel aganglionosis, responsible for lethal white syndrome in horses, Hirschsprung's disease in humans, and similar conditions in mice and rats, is a fatal condition if untreated. Mutations of the same genes can cause the condition in each of these species. The only effective current treatment is surgical removal of the aganglionic bowel. Infectious diarrheas involve activation of enteric secretomotor neurons by pathogens and the toxins they produce, which causes substantial fluid loss. Strategies to target enteric neurons in the treatment of secretory diarrheas have not been developed. Disorders

  2. Cells, Biomarkers, and Posttraumatic Stress Disorder: Evidence for Peripheral Involvement in a Central Disease

    Science.gov (United States)

    2012-01-01

    effects, including local and systemic inflammation and apoptosis Spivak et al. (1997), Tucker et al. (2004) IL-6 IL-6 Elevated in PTSD patients...n = 19) PTSD patients and (n = 19) controls, and IL-1b levels also correlated with length of PTSD symptoms ( Spivak et al. 1997). Another study showed...disorder: a meta-analysis of structural MRI studies. Hippocampus 15, 798–807. Spivak B., Shohat B., Mester R., Avraham S., Gil-Ad I., Bleich A., Valevski A

  3. Collony Collapse Disorder (CCD). A review of the possible Factors and Agents involved

    OpenAIRE

    Espinosa del Alba, Laura

    2014-01-01

    Póster Colony collapse disorder is a complex phenomenon that affects managed honey bee (Apis mellifera) colonies, whose main trait is a rapid loss of adult worker bees. Adult worker bees are responsible of the majority of the hive tasks, so their absence means shortly after the collapse and dead of the colony. CCD has been reported mainly from USA, but also from Europe.

  4. Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

    Science.gov (United States)

    O'Dushlaine, C; Kenny, E; Heron, E; Donohoe, G; Gill, M; Morris, D; Corvin, A

    2011-03-01

    Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (PSchizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

  5. Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

    LENUS (Irish Health Repository)

    O'Dushlaine, C

    2011-03-01

    Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the \\'enrichment\\' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

  6. Calcium signaling in neurodegeneration

    Directory of Open Access Journals (Sweden)

    Dreses-Werringloer Ute

    2009-05-01

    Full Text Available Abstract Calcium is a key signaling ion involved in many different intracellular and extracellular processes ranging from synaptic activity to cell-cell communication and adhesion. The exact definition at the molecular level of the versatility of this ion has made overwhelming progress in the past several years and has been extensively reviewed. In the brain, calcium is fundamental in the control of synaptic activity and memory formation, a process that leads to the activation of specific calcium-dependent signal transduction pathways and implicates key protein effectors, such as CaMKs, MAPK/ERKs, and CREB. Properly controlled homeostasis of calcium signaling not only supports normal brain physiology but also maintains neuronal integrity and long-term cell survival. Emerging knowledge indicates that calcium homeostasis is not only critical for cell physiology and health, but also, when deregulated, can lead to neurodegeneration via complex and diverse mechanisms involved in selective neuronal impairments and death. The identification of several modulators of calcium homeostasis, such as presenilins and CALHM1, as potential factors involved in the pathogenesis of Alzheimer's disease, provides strong support for a role of calcium in neurodegeneration. These observations represent an important step towards understanding the molecular mechanisms of calcium signaling disturbances observed in different brain diseases such as Alzheimer's, Parkinson's, and Huntington's diseases.

  7. Vitamin D and Intestinal Calcium Absorption

    OpenAIRE

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J.; Seth, Tanya

    2011-01-01

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D3 (1,25(OH)2D3) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium throu...

  8. Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response.

    Directory of Open Access Journals (Sweden)

    Elio A Cino

    Full Text Available Intrinsically disordered proteins (IDPs are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2, with a common binding partner, Kelch-like ECH-associated protein 1(Keap1, are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5-1.0 microsecond atomistic molecular dynamics (MD simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.

  9. A Comparison Study of Adults with Intellectual Disability and Psychiatric Disorder with and without Forensic Involvement

    Science.gov (United States)

    Raina, P.; Lunsky, Y.

    2010-01-01

    The current study describes and compares profiles of patients in the same specialized hospital program for patients with intellectual disability with and without forensic involvement. A retrospective chart review of 78 individuals (39 forensic and 39 non-forensic) served between 2006 and 2008 was completed. The forensic sample was more likely to…

  10. Order-disorder transitions in comb-like polymer-surfactant systems involving hydrogen bonds

    NARCIS (Netherlands)

    ten Brinke, G.; Huh, J; Ruokolainen, J.; Torkkeli, M.; Serimaa, R.; Ikkala, O.

    Conditions to obtain micro-phase separated morphologies in polymer-surfactant systems involving hydrogen bonds have been investigated using poly(4-vinyl pyridine) (P4VP) and surfactants capable of forming hydrogen bonds of different strength with the basic nitrogen of P4VP. Depending on the tail

  11. A Comparison Study of Adults with Intellectual Disability and Psychiatric Disorder with and without Forensic Involvement

    Science.gov (United States)

    Raina, P.; Lunsky, Y.

    2010-01-01

    The current study describes and compares profiles of patients in the same specialized hospital program for patients with intellectual disability with and without forensic involvement. A retrospective chart review of 78 individuals (39 forensic and 39 non-forensic) served between 2006 and 2008 was completed. The forensic sample was more likely to…

  12. Parental Involvement in Cognitive Behavior Therapy for Children with Anxiety Disorders

    DEFF Research Database (Denmark)

    Walczak, Monika; Esbjørn, Barbara H; Breinholst, Sonja

    2016-01-01

    Parental factors have been linked to childhood anxiety, hence, parental involvement in cognitive behavioral therapy (CBT) for anxious children has been examined. However, findings do not consistently show added effects of parent-enhanced CBT, longitudinal investigations are scarce and long...

  13. Child Involvement, Alliance, and Therapist Flexibility: Process Variables in Cognitive-Behavioural Therapy for Anxiety Disorders in Childhood

    Science.gov (United States)

    Hudson, Jennifer L.; Kendall, Philip C.; Chu, Brian C.; Gosch, Elizabeth; Martin, Erin; Taylor, Alan; Knight, Ashleigh

    2013-01-01

    Background This study examined the relations between treatment process variables and child anxiety outcomes. Method Independent raters watched/listened to taped therapy sessions of 151 anxiety-disordered (6 -14 yr-old; M = 10.71) children (43% boys) and assessed process variables (child alliance, therapist alliance, child involvement, therapist flexibility and therapist functionality) within a manual-based cognitive-behavioral treatment. Latent growth modelling examined three latent variables (intercept, slope, and quadratic) for each process variable. Child age, gender, family income and ethnicity were examined as potential antecedents. Outcome was analyzed using factorially derived clinician, mother, father, child and teacher scores from questionnaire and structured diagnostic interviews at pretreatment, posttreatment and 12-month follow-up. Results Latent growth models demonstrated a concave quadratic curve for child involvement and therapist flexibility over time. A predominantly linear, downward slope was observed for alliance, and functional flexibility remained consistent over time. Increased alliance, child involvement and therapist flexibility showed some albeit inconsistent, associations with positive treatment outcome. Conclusion Findings support the notion that maintaining the initial high level of alliance or involvement is important for clinical improvement. There is some support that progressively increasing alliance/involvement also positively impacts on treatment outcome. These findings were not consistent across outcome measurement points or reporters. PMID:24246476

  14. Children with autism spectrum disorder: teaching conversation involving feelings about events.

    Science.gov (United States)

    Conallen, K; Reed, P

    2017-03-01

    Two procedures were developed to teach individuals with Autism Spectrum Disorders labels (tacts) for various private events (emotions): Study 1 attempted to distinguish them from pure tacts and mands (requests); and Study 2 attempted to train initiating a conversation with grammatically correct subject-verb-comment construction. A multiple treatment reversal design was used in both studies, followed by a probe to see if the tacts were used across novel settings. The children were prompted to initiate a series of language exchanges, which resulted in an increased ability to participate in conversations about private events. Together, the results of both studies suggest that, by providing an effective and reinforcing means of teaching both the function and the form of these tacts, conversations can be successfully initiated by children with ASD. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  15. Sexual attitudes and activities in women with borderline personality disorder involved in romantic relationships.

    Science.gov (United States)

    Bouchard, Sébastien; Godbout, Natacha; Sabourin, Stéphane

    2009-01-01

    Women with Borderline Personality Disorder (BPD) are prone to have sexual relationship difficulties and dysfunctional attitudes toward sexuality. A sample of 34 heterosexual couples composed of women meeting BPD criteria was compared to a sample of dating or married women from the general population. A short form of the Sexual Activities and Attitudes Questionnaire (SAAQ) was used to measure six types of sexual attitudes. Women diagnosed with BPD did not differ from controls on the frequency of three types of sexual activities in the last year but their subjective sexual experiences differed: they showed stronger negative attitudes, felt sexually pressured by their partners, and expressed ambivalence toward sexuality. Regression analyses suggest that anxious attachment mediates the association between BPD and feeling pressured to engage in sex.

  16. Involvement of tryptophan hydroxylase 2 gene polymorphisms in susceptibility to tic disorder in Chinese Han population

    Directory of Open Access Journals (Sweden)

    Zheng Ping

    2013-01-01

    Full Text Available Abstract Background Tryptophan hydroxylase-2 (TPH2 is a potential candidate gene for screening tic disorder (TD. Methods A case–control study was performed to examine the association between the TPH2 gene and TD. The Sequenom® Mass ARRAY iPLEX GOLD System was used to genotype two single nucleotide polymorphisms (SNPs of the TPH2 gene in 149 TD children and in 125 normal controls. Results For rs4565946, individuals with the TT genotype showed a significantly higher risk of TD than those with TC plus CC genotypes [odds ratio (OR =3.077, 95% confidence interval (CI: 1.273–7.437; P = 0.009], as did male TD children with the TT genotype (OR = 3.228, 95% CI: 1.153–9.040; P = 0.020. The G allele of rs4570625 was significantly more frequent in TD children with higher levels of tic symptoms (Yale Global Tic Severity Scale, YGTSS than those in controls among the male children (OR = 1.684, 95%: 1.097–2.583; P = 0.017]. TD children with severe tic symptoms had significantly higher frequencies of rs4546946 TT genotype than did normal controls in boys (OR = 3.292, 95% CI: 1.139–9.513; P = 0.022. We also found that genotype distributions of both SNPs were different between the Asian and European populations. Conclusions Our results indicated that the TT genotype of rs4565946 is a potential genetic risk factor for TD, and the allele G of rs4570625 might be associated with the severity of tic symptoms in boys. These polymorphisms might be susceptibility loci for TD in the Chinese Han population. Because of the confounding of co-existing attention deficit hyperactivity disorder (ADHD,these findings need to be confirmed by studies in much larger samples.

  17. Pathophysiological mechanisms involved in the relationship between diabetes and major depressive disorder.

    Science.gov (United States)

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Strassi, Ana Paula; Abelaira, Helena M; Ceretta, Luciane B; Quevedo, João

    2017-08-15

    Diabetes mellitus (DM) and major depressive disorder (MDD) are diseases that are expanding globally. Separately, each presents with several comorbidities for patients. When the two diseases present simultaneously in the same subject, there is a drastic worsening in the quality of life of the patient. This study reviewed the literature relating to the relationship between MDD and DM, bringing forward studies showing that DM develops due to MDD, and others that report the opposite. According to the studies reviewed, DM and MDD are both debilitating conditions that are associated with significant morbidity, mortality, and healthcare costs. When these two diseases coexist, the association results in a decreased adherence to treatment, poor metabolic control, higher rates of complications, a decrease in the quality of life for the patient, increased healthcare use and cost, increased disability and lost productivity, and an increased risk of death. Therefore, it becomes essential that there are larger studies targeting the association of these two diseases, as for the patient, preventing even one of them will ensure improvements in their quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Synapsin II is involved in the molecular pathway of lithium treatment in bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Cristiana Cruceanu

    Full Text Available Bipolar disorder (BD is a debilitating psychiatric condition with a prevalence of 1-2% in the general population that is characterized by severe episodic shifts in mood ranging from depressive to manic episodes. One of the most common treatments is lithium (Li, with successful response in 30-60% of patients. Synapsin II (SYN2 is a neuronal phosphoprotein that we have previously identified as a possible candidate gene for the etiology of BD and/or response to Li treatment in a genome-wide linkage study focusing on BD patients characterized for excellent response to Li prophylaxis. In the present study we investigated the role of this gene in BD, particularly as it pertains to Li treatment. We investigated the effect of lithium treatment on the expression of SYN2 in lymphoblastoid cell lines from patients characterized as excellent Li-responders, non-responders, as well as non-psychiatric controls. Finally, we sought to determine if Li has a cell-type-specific effect on gene expression in neuronal-derived cell lines. In both in vitro models, we found SYN2 to be modulated by the presence of Li. By focusing on Li-responsive BD we have identified a potential mechanism for Li response in some patients.

  19. Review of endocrine disorders associated with environmental toxicants and possible involved mechanisms.

    Science.gov (United States)

    Maqbool, Faheem; Mostafalou, Sara; Bahadar, Haji; Abdollahi, Mohammad

    2016-01-15

    Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. [Reducing maternal parenting stress of children with autism spectrum disorder: father's involvement].

    Science.gov (United States)

    Hu, C C; Li, Y; Zhou, B R; Liu, C X; Li, C Y; Zhang, Y; Xu, Q; Xu, X

    2017-05-04

    Objective: To explore the relationship between fathers' nursing time and maternal parenting stress of children with autism spectrum disorder(ASD). Method: Mothers of 98 ASD children who were first diagnosed in the department of Child Health Care, Children's Hospital of Fudan University during June 2015 to January 2016 were included in the ASD group, with mothers of 92 typical children from a Community Maternal and Child Health Hospital and a kindergarten in the control group. The evaluation of parenting stress, parents' nursing time and other related factors were cross-sectionally analyzed. Interview was conducted with the following tools: Parental Stress Index-Short Form(PSI-SF)for maternal parenting stress, and self-made General Parenting Information Questionnaire for nursing time of both parents and other related factors. The relationships were analyzed by Multiple Linear Regression analysis and Wilcoxon Rank-Sum test. Result: Maternal parenting stress of ASD children had a significant negative correlation with father's nursing time in total score of parenting stress, PCDI domain and PD domain (t=-2.76, -2.98, -2.79; P=0.007, 0.004, 0.006), within which PD domain also included family annual income and mothers' nursing time (R(2)=0.22, 0.24, 0.25); while no such correlation was found in control group in terms of father's nursing time(P=0.22, 0.42, 0.06). Wilcoxon Rank-Sum test showed that in 62 (63.3%) double-income ASD families and 72(78.3%) double-income typical families, there were significant differences between ASD fathers' and ASD mothers'and typical fathers'nursing time(2.0(0.5, 2.1)vs. 3.5(2.4, 6.0)vs. 3.0(2.0, 4.7)h, t=-86.32、-49.65, all Pparenting stress and improve the intervention pattern of ASD children.

  1. Analysis and interpretation of RNA splicing alterations in genes involved in genetic disorders.

    Science.gov (United States)

    Vreeswijk, Maaike P G; van der Klift, Heleen M

    2012-01-01

    Germ line mutations in genes involved in hereditary cancer syndromes, such as BRCA1 and BRCA2 in breast cancer and MSH2, MSH6, MLH1, and PSM2 in hereditary nonpolyposis colorectal cancer (HNPCC, more recently indicated as Lynch syndrome), confer a high risk to develop cancer. Mutation analysis in these genes has resulted in the identification of a large number of sequence variants, of which mutations causing frame shifts and nonsense codons are considered undoubtedly to be pathogenic. Many variants, however, cannot be classified as either disease-causing mutations or neutral variants and are therefore called unclassified variants (UVs). A subset of these variants may have an effect on RNA splicing. Appropriate RNA analysis will enable the characterization of the exact molecular nature of this effect and hence, is essential to determine the clinical relevance of the genomic variant. This chapter describes the design and implementation of RNA analysis as an indispensible tool in today's clinical diagnostic setting.

  2. Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders

    Science.gov (United States)

    Kubota, Akira; O'Meara, Conor M.; Lamb, David C.; Tanguay, Robert L.; Goldstone, Jared V.

    2016-01-01

    Cytochrome P450 (CYP) enzymes for which there is no functional information are considered “orphan” CYPs. Previous studies showed that CYP20A1, an orphan, is expressed in human hippocampus and substantia nigra, and in zebrafish (Danio rerio) CYP20A1 maternal transcript occurs in eggs, suggesting involvement in brain and in early development. Moreover, hyperactivity is reported in humans with chromosome 2 microdeletions including CYP20A1. We examined CYP20A1 in zebrafish, including impacts of chemical exposure on expression. Zebrafish CYP20A1 cDNA was cloned, sequenced, and aligned with cloned human CYP20A1 and predicted vertebrate orthologs. CYP20A1s share a highly conserved N-terminal region and unusual sequences in the I-helix and the heme-binding CYP signature motifs. CYP20A1 mRNA expression was observed in adult zebrafish organs including liver, heart, gonads, spleen and brain, as well as eye and optic nerve. Putative binding sites in proximal promoter regions of CYP20A1s, and response of zebrafish CYP20A1 to selected nuclear and xenobiotic receptor agonists, point to up-regulation by agents involved in steroid hormone response, cholesterol and lipid metabolism. There also was a dose-dependent reduction of CYP20A1 expression in embryos exposed to environmentally relevant levels of methylmercury. Morpholino knockdown of CYP20A1 in developing zebrafish resulted in behavioral effects, including hyperactivity and a slowing of the optomotor response in larvae. The results suggest that altered expression of CYP20A1 might be part of a mechanism linking methylmercury exposure to neurobehavioral deficits. The expanded information on CYP20A1 brings us closer to “deorphanization”, that is, identifying CYP20A1 functions and its roles in health and disease. PMID:26853319

  3. Evidence for the involvement of carbonic anhydrase and urease in calcium carbonate formation in the gravity-sensing organ of Aplysia californica

    Science.gov (United States)

    Pedrozo, H. A.; Schwartz, Z.; Dean, D. D.; Harrison, J. L.; Campbell, J. W.; Wiederhold, M. L.; Boyan, B. D.

    1997-01-01

    To better understand the mechanisms that could modulate the formation of otoconia, calcium carbonate granules in the inner ear of vertebrate species, we examined statoconia formation in the gravity-sensing organ, the statocyst, of the gastropod mollusk Aplysia californica using an in vitro organ culture model. We determined the type of calcium carbonate present in the statoconia and investigated the role of carbonic anhydrase (CA) and urease in regulating statocyst pH as well as the role of protein synthesis and urease in statoconia production and homeostasis in vitro. The type of mineral present in statoconia was found to be aragonitic calcium carbonate. When the CA inhibitor, acetazolamide (AZ), was added to cultures of statocysts, the pH initially (30 min) increased and then decreased. The urease inhibitor, acetohydroxamic acid (AHA), decreased statocyst pH. Simultaneous addition of AZ and AHA caused a decrease in pH. Inhibition of urease activity also reduced total statoconia number, but had no effect on statoconia volume. Inhibition of protein synthesis reduced statoconia production and increased statoconia volume. In a previous study, inhibition of CA was shown to decrease statoconia production. Taken together, these data show that urease and CA play a role in regulating statocyst pH and the formation and maintenance of statoconia. CA produces carbonate ion for calcium carbonate formation and urease neutralizes the acid formed due to CA action, by production of ammonia.

  4. Involvement of Toxoplasma gondii in reproductive disorders in Swiss pig farms.

    Science.gov (United States)

    Basso, Walter; Handke, Martin; Sydler, Titus; Borel, Nicole; Grimm, Felix; Sidler, Xaver; Deplazes, Peter

    2015-04-01

    To determine the role of Toxoplasma gondii in reproductive failure, 108 of 113 sows that had aborted or delivered stillborn or weak piglets from 58 Swiss farms were serologically tested for specific antibodies against T. gondii tachyzoite antigens by ELISA. Additionally, formalin-fixed and paraffin-embedded tissues from 123 foetuses or stillborn piglets derived from 25 seropositive and 27 seronegative sows were analyzed by real-time PCR for T. gondii DNA. Tissues from animals showing a positive reaction in real-time PCR were subsequently tested by immunohistochemistry for the presence of T. gondii antigens. Antibodies against T. gondii were detected in 24.1% (26 out of 108) of sows with reproductive failure, and 37.3% (22 of 58) of the 58 tested farms had seropositive sows. No significant differences in the prevalences were observed in relation to the housing system (exclusive indoor housing, indoor housing with outdoor yard and exclusive outdoor housing) neither at the individual nor at the farm levels. By real time-PCR, T. gondii DNA was detected in three placentas from one seropositive sow (abortion at 71 gestation days [gd]), and in brain tissues from one foetus (abortion at 76 gd), one stillborn (116 gd) and one mummy (112 gd) delivered by three further seropositive sows, but in no sample derived from seronegative dams. By immunohistochemical staining, the presence of T. gondii could be confirmed only in placenta samples. In one of the cases, a co-infection with porcine parvovirus (PPV) was detected. These results suggest vertical transmission of T. gondii and/or placental infection in at least 3.5% (4 of 113) of sows with reproductive disorders. Therefore, T. gondii should be more frequently included in the routine differential diagnosis of reproductive failure in sows. In addition, a proper disposal of placentas and abortion material beyond the reach of cats could help to interrupt the further dissemination of this parasite at the farm level. Copyright

  5. Disorder and the extent of polymerization in calcium silicate and aluminosilicate glasses: O-17 NMR results and quantum chemical molecular orbital calculations

    Science.gov (United States)

    Lee, Sung Keun; Stebbins, Jonathan F.

    2006-08-01

    Estimation of the framework connectivity and the atomic structure of depolymerized silicate melts and glasses (NBO/T > 0) remains a difficult question in high-temperature geochemistry relevant to magmatic processes and glass science. Here, we explore the extent of disorder and the nature of polymerization in binary Ca-silicate and ternary Ca-aluminosilicate glasses with varying NBO/T (from 0 to 2.67) using O-17 NMR at two different magnetic fields of 9.4 and 14.1 T in conjunction with quantum chemical calculations. Non-random distributions among framework cations (Si and Al) are demonstrated in the variation of relative populations of oxygen sites with NBO/T. The proportion of non-bridging oxygen (NBO, Ca-O-Si) in the binary and ternary aluminosilicate glasses increases with NBO/T. While the trend is consistent with predictions from composition, the detailed fractions apparently deviate from the predicted values, suggesting further complications in the nature of polymerization. The proportion of each bridging oxygen in the glasses also varies with NBO/T. The fractions of Al-O-Si and Al-O-Al increase with increasing polymerization as CaO is replaced with Al 2O 3, while that of Si-O-Si seems to decrease, implying that activity of silica may decrease from calcium silicate to polymerized aluminosilicates (X=constant). Quantum chemical molecular orbital calculations based on density functional theory show that a silicate chain with Al-NBO (Ca-O-Al) has an energy penalty (calculated cluster energy difference) of about 108 kJ/mol compared with the cluster with Ca-O-Si, consistent with preferential depolymerization of Si-networks, reported in an earlier O-17 NMR study [Allwardt, J., Lee, S.K., Stebbins, J.F., 2003. Bonding preferences of non-bridging oxygens in calcium aluminosilicate glass: Evidence from O-17 MAS and 3QMAS NMR on calcium aluminate glass. Am. Mineral.88, 949-954]. These prominent types of non-randomness in the distributions suggest significant chemical

  6. Role of Class III phosphoinositide 3-kinase in the brain development: possible involvement in specific learning disorders.

    Science.gov (United States)

    Inaguma, Yutaka; Matsumoto, Ayumi; Noda, Mariko; Tabata, Hidenori; Maeda, Akihiko; Goto, Masahide; Usui, Daisuke; Jimbo, Eriko F; Kikkawa, Kiyoshi; Ohtsuki, Mamitaro; Momoi, Mariko Y; Osaka, Hitoshi; Yamagata, Takanori; Nagata, Koh-Ichi

    2016-10-01

    Class III phosphoinositide 3-kinase (PIK3C3 or mammalian vacuolar protein sorting 34 homolog, Vps34) regulates vesicular trafficking, autophagy, and nutrient sensing. Recently, we reported that PIK3C3 is expressed in mouse cerebral cortex throughout the developmental process, especially at early embryonic stage. We thus examined the role of PIK3C3 in the development of the mouse cerebral cortex. Acute silencing of PIK3C3 with in utero electroporation method caused positional defects of excitatory neurons during corticogenesis. Time-lapse imaging revealed that the abnormal positioning was at least partially because of the reduced migration velocity. When PIK3C3 was silenced in cortical neurons in one hemisphere, axon extension to the contralateral hemisphere was also delayed. These aberrant phenotypes were rescued by RNAi-resistant PIK3C3. Notably, knockdown of PIK3C3 did not affect the cell cycle of neuronal progenitors and stem cells at the ventricular zone. Taken together, PIK3C3 was thought to play a crucial role in corticogenesis through the regulation of excitatory neuron migration and axon extension. Meanwhile, when we performed comparative genomic hybridization on a patient with specific learning disorders, a 107 Kb-deletion was identified on 18q12.3 (nt. 39554147-39661206) that encompasses exons 5-23 of PIK3C3. Notably, the above aberrant migration and axon growth phenotypes were not rescued by the disease-related truncation mutant (172 amino acids) lacking the C-terminal kinase domain. Thus, functional defects of PIK3C3 might impair corticogenesis and relate to the pathophysiology of specific learning disorders and other neurodevelopmental disorders. Acute knockdown of Class III phosphoinositide 3-kinase (PIK3C3) evokes migration defects of excitatory neurons during corticogenesis. PIK3C3-knockdown also disrupts axon outgrowth, but not progenitor proliferation in vivo. Involvement of PIK3C3 in neurodevelopmental disorders might be an interesting future

  7. Cerebellar Neural Circuits Involving Executive Control Network Predict Response to Group Cognitive Behavior Therapy in Social Anxiety Disorder.

    Science.gov (United States)

    MinlanYuan; Meng, Yajing; Zhang, Yan; Nie, Xiaojing; Ren, Zhengjia; Zhu, Hongru; Li, Yuchen; Lui, Su; Gong, Qiyong; Qiu, Changjian; Zhang, Wei

    2017-02-02

    Some intrinsic connectivity networks including the default mode network (DMN) and executive control network (ECN) may underlie social anxiety disorder (SAD). Although the cerebellum has been implicated in the pathophysiology of SAD and several networks relevant to higher-order cognition, it remains unknown whether cerebellar areas involved in DMN and ECN exhibit altered resting-state functional connectivity (rsFC) with cortical networks in SAD. Forty-six patients with SAD and 64 healthy controls (HC) were included and submitted to the baseline resting-state functional magnetic resonance imaging (fMRI). Seventeen SAD patients who completed post-treatment clinical assessments were included after group cognitive behavior therapy (CBT). RsFC of three cerebellar subregions in both groups was assessed respectively in a voxel-wise way, and these rsFC maps were compared by two-sample t tests between groups. Whole-brain voxel-wise regression was performed to examine whether cerebellar connectivity networks can predict response to CBT. Lower rsFC circuits of cerebellar subregions compared with HC at baseline (p circuits involving DMN and ECN are possible neuropathologic mechanisms of SAD. Stronger pretreatment cerebellar rsFC circuits involving ECN suggest potential neural markers to predict CBT response.

  8. Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by proteoliposomes and cultured rat sertoli cells: Evidence for involvement of voltage-activated and voltage-independent calcium channels

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Reichert, L.E. Jr. (Albany Medical College, NY (USA))

    1989-12-01

    We have previously reported incorporation into liposomes of Triton X-100-solubilized FSH receptor-G-protein complexes derived from purified bovine calf testis membranes. In the present study we have used this model system to show that FSH induces flux of 45Ca2+ into such proteoliposomes in a hormone-specific concentration-dependent manner. FSH, inactivated by boiling, had no stimulatory effect on 45Ca2+ flux, nor did isolated alpha- or beta-subunits of FSH. Addition of GTP (or its analogs 5'-guanylylimidodiphosphate and guanosine-5'-O-(3-thiotriphosphate)) or sodium fluoride (in the presence or absence of GTP or its analogs) failed to induce 45Ca2+ flux into proteoliposomes, suggesting that the uptake of 45Ca2+ was receptor, and not G-protein, related. Voltage-independent (ruthenium red and gadolinium chloride) and voltage-activated (methyoxyverapamil and nifedipine) calcium channel-blocking agents reduced FSH-stimulated 45Ca2+ flux into proteoliposomes to control levels. FSH also induced uptake of 45Ca2+ by cultured rat Sertoli cells. Ruthenium red and gadolinium chloride had no effect on basal levels of 45Ca2+ uptake or estradiol secretion by cultured rat Sertoli cells, nor did methoxyverapamil or nifedipine. All four calcium channel blockers, however, were able to reduce FSH-induced 45Ca2+ uptake to basal levels and FSH-stimulated conversion of androstenedione to estradiol by up to 50%, indicating an involvement of Ca2+ in FSH-stimulated steroidogenesis. Our results suggest that the well documented changes in intracellular calcium levels consequent to FSH binding may be due, at least in part, to an influx of calcium through FSH receptor-regulated calcium channels.

  9. Capsaicin mimics mechanical load-induced intracellular signaling events: involvement of TRPV1-mediated calcium signaling in induction of skeletal muscle hypertrophy.

    Science.gov (United States)

    Ito, Naoki; Ruegg, Urs T; Kudo, Akira; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

    2013-01-01

    Mechanical load-induced intracellular signaling events are important for subsequent skeletal muscle hypertrophy. We previously showed that load-induced activation of the cation channel TRPV1 caused an increase in intracellular calcium concentrations ([Ca ( 2+) ]i) and that this activated mammalian target of rapamycin (mTOR) and promoted muscle hypertrophy. However, the link between mechanical load-induced intracellular signaling events, and the TRPV1-mediated increases in [Ca ( 2+) ]i are not fully understood. Here we show that administration of the TRPV1 agonist, capsaicin, induces phosphorylation of mTOR, p70S6K, S6, Erk1/2 and p38 MAPK, but not Akt, AMPK or GSK3β. Furthermore, the TRPV1-induced phosphorylation patterns resembled those induced by mechanical load. Our results continue to highlight the importance of TRPV1-mediated calcium signaling in load-induced intracellular signaling pathways.

  10. Gossypol increases expression of the pro-apoptotic BH3-only protein NOXA through a novel mechanism involving phospholipase A2, cytoplasmic calcium, and endoplasmic reticulum stress.

    Science.gov (United States)

    Soderquist, Ryan S; Danilov, Alexey V; Eastman, Alan

    2014-06-06

    Gossypol is a putative BH3 mimetic proposed to inhibit BCL2 and BCLXL based on cell-free assays. We demonstrated previously that gossypol failed to directly inhibit BCL2 in cells or induce apoptosis in chronic lymphocytic leukemia (CLL) cells or platelets, which require BCL2 or BCLXL, respectively, for survival. Here, we demonstrate that gossypol rapidly increased activity of phospholipase A2 (PLA2), which led to an increase in cytoplasmic calcium, endoplasmic reticulum (ER) stress, and up-regulation of the BH3-only protein NOXA. Pretreatment with the PLA2 inhibitor, aristolochic acid, abrogated the increase in calcium, ER stress, and NOXA. Calcium chelation also abrogated the gossypol-induced increase in calcium, ER stress, and NOXA, but not the increase in PLA2 activity, indicating that PLA2 is upstream of these events. In addition, incubating cells with the two products of PLA2 (lysophosphatidic acid and arachidonic acid) mimicked treatment with gossypol. NOXA is a pro-apoptotic protein that functions by binding the BCL2 family proteins MCL1 and BFL1. The BCL2 inhibitor ABT-199 is currently in clinical trials for CLL. Resistance to ABT-199 can occur from up-regulation of other BCL2 family proteins, and this resistance can be mimicked by culturing CLL cells on CD154(+) stroma cells. We report here that AT-101, a derivative of gossypol in clinical trials, overcomes stroma-mediated resistance to ABT-199 in primary CLL cells, suggesting that a combination of these drugs may be efficacious in the clinic.

  11. Involvement of reactive oxygen species and high-voltage-activated calcium currents in nanoparticle zinc oxide-induced cytotoxicity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Jingxia [Nankai University, College of Medicine (China); Yao Yang [Tianjin First Central Hospital (China); Liu Shichang [Nankai University, College of Medicine (China); Zhang Tao [Nankai University, College of Life Science (China); Ren Guogang [University of Hertfordshire, Science and Technology Research Institute (United Kingdom); Yang Zhuo, E-mail: zhuoyang@nankai.edu.cn [Nankai University, College of Medicine (China)

    2012-11-15

    This study was to determine the possible neurotoxicity and mechanisms underlying the effects of nano-ZnO with sizes of 20-80 nm on central nervous system (CNS). The cytotoxicity of nano-ZnO was investigated in PC12 cells. The viability of cells was observed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the generation of reactive oxygen species (ROS) for cells was evaluated by a fluorometry assay. The apoptosis of cells was detected and analyzed by flow cytometry. In addition, effects of nano-ZnO on the properties of high-voltage-activated (HVA) calcium currents were studied in acutely isolated rat hippocampal pyramidal neurons using the whole-cell patch clamp technique. The results of MTT assay showed that nano-ZnO (10{sup -4} g/mL) caused a significant decrease in cell viability (P < 0.05). Nano-ZnO induced intracellular accumulation of ROS and the apoptosis of PC12 cells with the increasing concentration of nano-ZnO in flow cytometric assay (P < 0.05). Further results of electrophysiological recording indicated that 10{sup -4} g/mL nano-ZnO first altered the current-voltage curve and the peak amplitudes of HVA calcium currents at 10 min of the recording, and the peak current amplitudes were increased significantly at the end of 30 min (P < 0.05). All these results suggested that the increase of intracellular ROS was one of potential mechanisms of cellular apoptosis induced by nano-ZnO. Nano-ZnO could cause the elevation of cytosolic calcium levels by enhancement of HVA calcium currents, which would increase the generation of intracellular ROS, and consequently promote the neuronal apoptosis.

  12. Involvement of transient receptor potential melastatin-8 (TRPM8) in menthol-induced calcium entry, reactive oxygen species production and cell death in rheumatoid arthritis rat synovial fibroblasts.

    Science.gov (United States)

    Zhu, Shuyan; Wang, Yuxiang; Pan, Leiting; Yang, Shuang; Sun, Yonglin; Wang, Xinyu; Hu, Fen

    2014-02-15

    Rheumatoid arthritis is most prominently characterized by synoviocyte hyperplasia which therefore serves as an important target for clinical therapy. In the present study, it was observed that menthol, the specific agonist of transient receptor potential melastatin subtype 8 (TRPM8), could induce sustained increases of cytosolic calcium concentration ([Ca(2+)]c) in synoviocytes isolated from collagen-induced arthritis rats in dose-dependent manner, which was evidently blocked by applying an extracellular Ca(2+)-free buffer. Menthol-induced [Ca(2+)]c increase was also significantly inhibited by potent TRPM8 antagonist capsazepine (CZP), indicating that this [Ca(2+)]c elevation was mostly attributed to TRPM8-mediated Ca(2+) entry. Besides, RT-PCR indeed demonstrated presence of TRPM8 in the synoviocytes. Meanwhile, it was found that menthol evoked production of intracellular reactive oxygen species, which could be abolished by Ca(2+) free solutions or CZP. Further experiments showed that menthol reduced the cell numbers and survival of synoviocytes. This reduction was associated with apoptosis as suggested by mitochondrial membrane depolarization, nuclear condensation and a caspase 3/7 apoptotic assay. Menthol-induced death and apoptosis of synoviocytes both were obviously inhibited by CZP, intracellular calcium chelator BAPTA-AM, and reactive oxygen species inhibitor diphenylene iodonium, respectively. Taken together, our data indicated that menthol resulted in synoviocyte death associated with apoptosis via calcium entry and reactive oxygen species production depending on TRPM8 activation.

  13. CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type calcium channels.

    Science.gov (United States)

    Pinggera, Alexandra; Lieb, Andreas; Benedetti, Bruno; Lampert, Michaela; Monteleone, Stefania; Liedl, Klaus R; Tuluc, Petronel; Striessnig, Jörg

    2015-05-01

    Cav1.3 voltage-gated L-type calcium channels (LTCCs) are part of postsynaptic neuronal signaling networks. They play a key role in brain function, including fear memory and emotional and drug-taking behaviors. A whole-exome sequencing study identified a de novo mutation, p.A749G, in Cav1.3 α1-subunits (CACNA1D), the second main LTCC in the brain, as 1 of 62 high risk-conferring mutations in a cohort of patients with autism and intellectual disability. We screened all published genetic information available from whole-exome sequencing studies and identified a second de novo CACNA1D mutation, p.G407R. Both mutations are present only in the probands and not in their unaffected parents or siblings. We functionally expressed both mutations in tsA-201 cells to study their functional consequences using whole-cell patch-clamp. The mutations p.A749G and p.G407R caused dramatic changes in channel gating by shifting (~15 mV) the voltage dependence for steady-state activation and inactivation to more negative voltages (p.A749G) or by pronounced slowing of current inactivation during depolarizing stimuli (p.G407R). In both cases, these changes are compatible with a gain-of-function phenotype. Our data, together with the discovery that Cav1.3 gain-of-function causes primary aldosteronism with seizures, neurologic abnormalities, and intellectual disability, suggest that Cav1.3 gain-of-function mutations confer a major part of the risk for autism in the two probands and may even cause the disease. Our findings have immediate clinical relevance because blockers of LTCCs are available for therapeutic attempts in affected individuals. Patients should also be explored for other symptoms likely resulting from Cav1.3 hyperactivity, in particular, primary aldosteronism. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Fairness decisions in response to emotions: a functional MRI study among criminal justice-involved boys with conduct disorder.

    Science.gov (United States)

    Klapwijk, Eduard T; Lelieveld, Gert-Jan; Aghajani, Moji; Boon, Albert E; van der Wee, Nic J A; Popma, Arne; Vermeiren, Robert R J M; Colins, Olivier F

    2016-04-01

    Research suggests that individuals with conduct disorder (CD) are marked by social impairments, such as difficulties in processing the affective reactions of others. Little is known, though, about how they make decisions during social interactions in response to emotional expressions of others. In this study, we therefore investigated the neural mechanisms underlying fairness decisions in response to communicated emotions of others in aggressive, criminal justice-involved boys with CD (N = 32) compared with typically developing (TD) boys (N = 33), aged 15-19 years. Participants received written emotional responses (angry, disappointed or happy) from peers in response to a previous offer and then had to make fairness decisions in a version of the Dictator Game. Behavioral results showed that CD boys did not make differential fairness decisions in response to the emotions, whereas the TD boys did show a differentiation and also responded more unfair to happy reactions than the CD boys. Neuroimaging results revealed that when receiving happy vs disappointed and angry reactions, the CD boys showed less activation than the TD boys in the temporoparietal junction and supramarginal gyrus, regions involved in perspective taking and attention. These results suggest that boys with CD have difficulties with processing explicit emotional cues from others on behavioral and neural levels. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Validity and reliability of the Spanish version of the Involvement Evaluation Questionnaire among caregivers of patients with eating disorders.

    Science.gov (United States)

    González, Nerea; Bilbao, Amaia; Padierna, Angel; Martín, Josune; Orive, Miren; Quintana, José M

    2012-12-30

    The Involvement Evaluation Questionnaire (IEQ) was developed to evaluate burden among caregivers of patients with schizophrenia. We aimed to examine its psychometric properties among caregivers of patients with eating disorders (ED). A prospective study was carried out, recruiting caregivers of patients with an ED attending two outpatient clinics in Bizkaia, Spain. Caregivers provided sociodemographic information and completed the Involvement Evaluation Questionnaire (IEQ), the Hospital Anxiety and Depression Scale (HADS), the Short-Form 12 (SF-12) and the Anorectic Behaviour Observation Scale (ABOS). The same information was requested one year later. The confirmatory factor analysis (CFA) provided satisfactory fit indexes. Almost all of the factor loadings were above 0.40. Cronbach's alpha coefficients were mostly superior to 0.70. The correlation coefficients between the IEQ domains and the other questionnaires were lower than the Cronbach's alpha coefficients. Known-groups validity was supported by significant differences in the IEQ mean scores according to certain variables, as contact hours, living with the patient, type of caregiver and gender. The indexes employed for the evaluation of responsiveness were between 0.13 and 0.99. The IEQ has good psychometric properties and can be used to evaluate burden among caregivers of patients with ED.

  16. [Helper T cell paradigm: Th17 and regulatory T cells involved in autoimmune inflammatory disorders, pathogen defense and allergic diseases].

    Science.gov (United States)

    Noma, Takeshi

    2010-01-01

    The helper T cell paradigm, divided into two distinct subsets, Th1 and Th2 cells, characterized by distinct cytokine and functions, has been expanded to IL-17-producing Th17 cells. Th1 cells producing IFN-γ are involved in delayed-type hypersensitivity, effective in intracellular pathogens defense, while Th2 cells secrete IL-4, IL-5, IL-13 and IL-25 and has a central role in IgE production, eosinophilic inflammation, and the protection for helminthic parasite infection. Th17 cell lineages, expressing IL-17 family of cytokines and IL-23-mediated functions on T cells, plays a role in immune response to fungi and extracellular pathogens and autoimmune inflammatory disorders. Th17 cells are required the combination of IL-6 and TGF-β and the transcription factors, RORC2/RORgt (mice) and STAT3 for differentiation, and produce IL-17, IL-22, IL-17F, IL-21 and CCL20. FOXP3+ regulatory T (Treg) cells produce TGF-β and IL-10, which regulate effector T cells, and thus maintain peripheral tolerance. Four functionally unique CD4+ T cells, including the regulatory T (Treg) cells are now involved in the regulation of immune responses to pathogens, self-antigens and allergens. Any defect in the entire CD4+T cell population might results in human diseases. In this review, the biology of Th17 cells and Treg cells and their role in immune diseases are presented.

  17. Parathyroid Disorders

    Science.gov (United States)

    ... much phosphorous. Causes include injury to the glands, endocrine disorders, or genetic conditions. Treatment is aimed at restoring the balance of calcium and phosphorous. NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  18. Effects of lactic acid and glycolic acid on human osteoblasts: a way to understand PLGA involvement in PLGA/calcium phosphate composite failure.

    Science.gov (United States)

    Meyer, Florent; Wardale, John; Best, Serena; Cameron, Ruth; Rushton, Neil; Brooks, Roger

    2012-06-01

    The use of degradable composite materials in orthopedics remains a field of intense research due to their ability to support new bone formation and degrade in a controlled manner, broadening their use for orthopedic applications. Poly (lactide-co-glycolide) acid (PLGA), a degradable biopolymer, is now a popular material for different orthopedic applications and is proposed for use in tissue engineering scaffolds either alone or combined with bioactive ceramics. Interference screws composed of calcium phosphates and PLGA are readily available in the market. However, some reports highlight problems of screw migration or aseptic cyst formation following screw degradation. In order to understand these phenomena and to help to improve implant formulation, we have evaluated the effects of PLGA degradation products: lactic acid and glycolic acid on human osteoblasts in vitro. Cell proliferation, differentiation, and matrix mineralization, important for bone healing were studied. It was found that the toxicity of polymer degradation products under buffering conditions was limited to high concentrations. However, non-toxic concentrations led to a decrease in cell proliferation, rapid cell differentiation, and mineralization failure. Calcium, whilst stimulating cell proliferation was not able to overcome the negative effects of high concentrations of lactic and glycolic acids on osteoblasts. These effects help to explain recently reported clinical failures of calcium phosphate/PLGA composites, but further in vitro analyses are needed to mimic the dynamic situation which occurs in the body by, for example, culture of osteoblasts with materials that have been pre-degraded to different extents and thus be able to relate these findings to the degradation studies that have been performed previously.

  19. Involvement of intracellular calcium and src tyrosine-kinase in capacitation of cryopreserved bovine spermatozoa Participación del calcio intracelular y src tirosina quinasas en la capacitación del espermatozoide bovino criopreservado

    Directory of Open Access Journals (Sweden)

    M Satorre

    2010-06-01

    Full Text Available Increase of intracellular calcium concentration and tyrosine kinase involvement are pivotal in sperm capacitation. The aim was to determine the involvement of intracellular calcium and tyrosine kinases activity in frozen-thawed spermatozoa capacitated with heparin or quercetin. Genistein or PP2 (4-amino-5-(4-chlorophenyl-7-(t-butylpyrazolo3,4, pyrimidine were used to inhibit tyrosine kinases, and methoxyverapamil to inhibit voltage dependent calcium channels. Capacitation was determined by chlortetracycline and calcium by fl uorescence spectrophotometry. Protein tyrosine-phosphorylation was determined by western blot. Pooled frozen semen samples from four bulls were used. In presence of heparin or quercetin capacitated spermatozoa percentage and intracellular calcium were greater (PEl incremento de calcio intracelular [Ca]i y la participación de tirosina quinasa son pasos cruciales en la inducción de la capacitación. El objetivo fue determinar en espermatozoides criopreservados, la variación [Ca]i y la actividad de tirosina quinasa en la capacitación con heparina o quercetina. Genisteina o PP2(4-amino-5-(4-clorofenil-7-(t-butilpirazolo3,4,d pirimidina son inhibidores de tirosinas quinasas y de la isoforma SRC, respectivamente. Metoxiverapamil es un inhibidor de canales de calcio voltaje dependiente (CCVD. La capacitación, [Ca]i y fosforilación en tirosina se evaluaron con clorotetraciclina, espectrofl uorometría y western blot, respectivamente. El porcentaje de espermatozoides capacitados y [Ca]i fueron mayores (P<0.05 en muestras con heparina o quercetina respecto a sus controles. Genisteina o PP2 disminuyeron (P<0.05 la capacitación y el incremento de [Ca]i en las muestras con heparina pero no en las tratadas con quercetina. Genisteina o PP2 inhibió diferencialmente la fosforilación de proteínas espermáticas con ambos inductores. Methoxiverapamil bloqueó el incremento de [Ca]i sólo en la muestras con heparina. Siendo los

  20. Involvement of phospholipase C and intracellular calcium signaling in the gonadotropin-releasing hormone regulation of prolactin release from lactotrophs of tilapia (Oreochromis mossambicus)

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Weber, G M; Strom, C N

    2005-01-01

    pituitary gland from which a nearly pure population of PRL cells can be isolated, we examined whether GnRH might stimulate PRL release through an increase in phospholipase C (PLC), inositol triphosphate (IP3), and intracellular calcium (Ca(i)2+) signaling. Using Ca(i)2+ imaging and the calcium-sensitive dye...... fura-2, we found that chicken GnRH-II (cGnRH-II) induced a rapid dose-dependent increase in Ca(i)2+ in dispersed tilapia lactotrophs. The Ca(i)2+ signal was abolished by U-73122, an inhibitor of PLC-dependent phosphoinositide hydrolysis. Correspondingly, cGnRH-II-induced tPRL188 secretion was inhibited...... by U-73122, suggesting that activation of PLC mediates cGnRH-II's stimulatory effect on PRL secretion. Pretreatment with 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of Ca2+ release from intracellular stores, impeded the effect of cGnRH-II on Ca(i)2...

  1. Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders.

    Science.gov (United States)

    Terrón, José A

    2014-01-01

    A hyperactive hypothalamic-pituitary-adrenal (HPA) axis is a common feature of stress-related disorders, and the brain serotonin (5-HT) system plays a major role in HPA axis modulation. Glucocorticoids and stress profoundly affect the 5-HT system so it is possible that alterations of endocrine 5-HT mechanisms may underlie HPA axis overdrive in stress-related diseases. Available evidence suggests a role of 5-HT1A, 5-HT2A/2C and 5-HT7 receptors in HPA system activation, and pharmacological blockade of 5-HT7 receptors produces a fast-acting antidepressant-like action and shortens the onset of antidepressant-like effects of various classes of antidepressants. The mechanisms involved in this effect have not been elucidated, but recent findings suggest a role of 5-HT7 receptors in the development of HPA axis overdrive as a result of chronic stress. Remarkably, clinical findings have shown an association between corticosteroid-producing adenomas and expression of ectopic 5-HT7 receptors in corticosteroid-producing adrenocortical cells. These observations might therefore reveal an endocrine mechanism for the antidepressant-like action of 5-HT7 receptor blockers, possibly through normalization of HPA axis function. If such a preliminary hypothesis is confirmed, the potential therapeutic usefulness of 5-HT7 receptor antagonists could extend beyond depression to include other diseases, the pathophysiology of which has been associated with chronic stress and HPA axis dysregulation.

  2. Calcium/calmodulin-dependent serine protein kinase (CASK), a protein implicated in mental retardation and autism-spectrum disorders, interacts with T-Brain-1 (TBR1) to control extinction of associative memory in male mice

    Science.gov (United States)

    Huang, Tzyy-Nan; Hsueh, Yi-Ping

    2017-01-01

    Background Human genetic studies have indicated that mutations in calcium/calmodulin-dependent serine protein kinase (CASK) result in X-linked mental retardation and autism-spectrum disorders. We aimed to establish a mouse model to study how Cask regulates mental ability. Methods Because Cask encodes a multidomain scaffold protein, a possible strategy to dissect how CASK regulates mental ability and cognition is to disrupt specific protein–protein interactions of CASK in vivo and then investigate the impact of individual specific protein interactions. Previous in vitro analyses indicated that a rat CASK T724A mutation reduces the interaction between CASK and T-brain-1 (TBR1) in transfected COS cells. Because TBR1 is critical for glutamate receptor, ionotropic, N-methyl-d-aspartate receptor subunit 2B (Grin2b) expression and is a causative gene for autism and intellectual disability, we then generated CASK T740A (corresponding to rat CASK T724A) mutant mice using a gene-targeting approach. Immunoblotting, coimmunoprecipitation, histological methods and behavioural assays (including home cage, open field, auditory and contextual fear conditioning and conditioned taste aversion) were applied to investigate expression of CASK and its related proteins, the protein–protein interactions of CASK, and anatomic and behavioural features of CASK T740A mice. Results The CASK T740A mutation attenuated the interaction between CASK and TBR1 in the brain. However, CASK T740A mice were generally healthy, without obvious defects in brain morphology. The most dramatic defect among the mutant mice was in extinction of associative memory, though acquisition was normal. Limitations The functions of other CASK protein interactions cannot be addressed using CASK T740A mice. Conclusion Disruption of the CASK and TBR1 interaction impairs extinction, suggesting the involvement of CASK in cognitive flexibility. PMID:28234597

  3. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder

    OpenAIRE

    Williams, H J; Norton, N; Dwyer, S.; Moskvina, V; Nikolov, I.; Carroll, L.; Georgieva, L; Williams, N. M.; Morris, D.W.; Quinn, E.M.; Giegling, I; M. Ikeda(Kyoto University); Wood, J; Lencz, T; Hultman, C.

    2011-01-01

    Abstract A recent genome wide association study reported evidence for association between rs1344706 within ZNF804A (encoding zinc finger protein 804A) and schizophrenia (P=1.61 x10-7), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 x10-9). Here we provide additional evidence for association through meta-analysis of a larger dataset (schizophrenia/schizoaffective disorder N = 18945, schizophrenia plus bipolar disorder N =21274, controls N ...

  4. Calcium in diet

    Science.gov (United States)

    ... D is needed to help your body use calcium. Milk is fortified with vitamin D for this reason. ... of calcium dietary supplements include calcium citrate and calcium carbonate. Calcium citrate is the more expensive form of ...

  5. The antiatherogenic potential of calcium antagonists.

    Science.gov (United States)

    Weinstein, D B

    1988-01-01

    Atherosclerosis is an arterial disease characterized by focal accumulation of collagen, elastin, lipids, and calcium at sites associated with macrophage infiltration and altered smooth muscle metabolic function. Studies in several types of animal models, especially cholesterol-fed rabbits, have shown that calcium competitors, calcium chelators, anticalcifying agents, and calcium channel blockers can reduce the accumulation of atherogenic lesion components and thus apparently decrease the progression of lesions. Although there are some conflicting data in the animal model studies using calcium channel antagonists, as a result of differences in experimental designs, it is now apparent that several classes of calcium channel blockers inhibit the progression of early arterial lesions induced by cholesterol feeding. The dihydropyridine calcium channel blockers appear to be more potent antiatherosclerotic agents than other classes of calcium channel antagonists. Several mechanisms involving regulation of endothelial cell, smooth muscle cell, and macrophage metabolic functions may be responsible for the calcium channel blocker effects on early lesion progression. For example, recent studies in cell culture model systems suggest that calcium channel blockers may significantly alter activities that regulate lipoprotein-derived cholesterol accumulation by cells. Some of these activities are independent of calcium flux across voltage-operated calcium channels. Thus, calcium channel blockers may reduce the progression of atherogenic lesions by a combination of decreasing calcium accumulation within arterial wall cells and by altering calcium-independent metabolic activities.

  6. 膳食钙、骨密度与儿童肥胖相关代谢异常的关系%Effects of dietary calcium intake on bone mineral density and obesity-related metabolic disorders in children

    Institute of Scientific and Technical Information of China (English)

    阮慧娟; 汤庆娅

    2009-01-01

    越来越多研究支持增加钙摄入可减少代谢综合征的发生率,儿童时期的牛奶摄入水平及保持饮用牛奶的习惯与成年后骨密度呈正相关,有助于获得更高的骨峰值.本文总结了膳食钙摄入量对骨密度和儿童肥胖相关代谢异常之间的关系.%More studies have shown that dietary calcium intake can decrease the incidence of metabolic syndrome. Milk consumption in childhood and the habit of milk drinking are positively correlated with bone mineral density in adult-hood. This article summarizes the relationship between dietary calcium and bone mineral density and obesity-related metabolic disorder in children.

  7. A Putative Chloroplast-Localized Ca(2+)/H(+) Antiporter CCHA1 Is Involved in Calcium and pH Homeostasis and Required for PSII Function in Arabidopsis.

    Science.gov (United States)

    Wang, Chao; Xu, Weitao; Jin, Honglei; Zhang, Taijie; Lai, Jianbin; Zhou, Xuan; Zhang, Shengchun; Liu, Shengjie; Duan, Xuewu; Wang, Hongbin; Peng, Changlian; Yang, Chengwei

    2016-08-01

    Calcium is important for chloroplast, not only in its photosynthetic but also nonphotosynthetic functions. Multiple Ca(2+)/H(+) transporters and channels have been described and studied in the plasma membrane and organelle membranes of plant cells; however, the molecular identity and physiological roles of chloroplast Ca(2+)/H(+) antiporters have remained unknown. Here we report the identification and characterization of a member of the UPF0016 family, CCHA1 (a chloroplast-localized potential Ca(2+)/H(+) antiporter), in Arabidopsis thaliana. We observed that the ccha1 mutant plants developed pale green leaves and showed severely stunted growth along with impaired photosystem II (PSII) function. CCHA1 localizes to the chloroplasts, and the levels of the PSII core subunits and the oxygen-evolving complex were significantly decreased in the ccha1 mutants compared with the wild type. In high Ca(2+) concentrations, Arabidopsis CCHA1 partially rescued the growth defect of yeast gdt1Δ null mutant, which is defective in a Ca(2+)/H(+) antiporter. The ccha1 mutant plants also showed significant sensitivity to high concentrations of CaCl2 and MnCl2, as well as variation in pH. Taken these results together, we propose that CCHA1 might encode a putative chloroplast-localized Ca(2+)/H(+) antiporter with critical functions in the regulation of PSII and in chloroplast Ca(2+) and pH homeostasis in Arabidopsis.

  8. The role of the mitochondrial calcium uniporter in cerebral ischemia/reperfusion injury in rats involves regulation of mitochondrial energy metabolism.

    Science.gov (United States)

    Zhao, Qin; Wang, Shilei; Li, Yu; Wang, Peng; Li, Shuhong; Guo, Yunliang; Yao, Ruyong

    2013-04-01

    The mitochondrial calcium uniporter (MCU) maintains intracellular Ca2+ homeostasis by transporting Ca2+ from the cell cytosol into the mitochondrial matrix and is important for shaping Ca2+ signals and the activation of programmed cell death. Inhibition of MCU by ruthenium red (RR) or Ru360 has previously been reported to protect against neuronal death. The aim of the present study was to analyze the mechanisms underlying the effects of MCU activity in a rat model of cerebral ischemia/reperfusion (I/R) injury. Adult male Wistar rats were divided into 4 groups; sham, I/R, I/R + RR and I/R + spermine (Sper) and were subjected to reversible middle cerebral artery occlusion for 2 h followed by 24 h of reperfusion. A bolus injection of RR administered 30 min prior to ischemia was found to significantly decrease the total infarct volume and reduce neuronal damage and cell apoptosis compared with ischemia/reperfusion values. However, treatment with Sper, an activator of the MCU, increased the injury induced by I/R. Analysis of energy metabolism revealed that I/R induced progressive inhibition of complexes I‑IV of the electron transport chain, decreased ATP production, dissipated the mitochondrial membrane potential and increased the generation of reactive oxygen species. Treatment with RR ameliorated the condition, while spermine had the opposite effect. In conclusion, blocking MCU was demonstrated to exert protective effects against I/R injury and this process may be mediated by the prevention of energy failure.

  9. Emanuel Strehler’s work on calcium pumps and calcium signaling

    Institute of Scientific and Technical Information of China (English)

    Emanuel; E; Strehler

    2011-01-01

    Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca 2+ ). Inappropriate Ca 2+ signaling and abnormal Ca 2+ levels are involved in many clinical disorders including heart disease, Alzheimer’s disease and stroke. Ca 2+ also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Accordingly, research in the Strehler laboratory is focused on a better understanding of the molecular "toolkit" needed to ensure proper Ca 2+ homeostasis in the cell, as well as on the mechanisms of localized Ca 2+ signaling. A longterm focus has been on the plasma membrane calcium pumps (PMCAs), which are linked to multiple disorders including hearing loss, neurodegeneration, and heart disease. Our work over the past 20 years or more has revealed a surprising complexity of PMCA isoforms with different functional characteristics, regulation, and cellular localization. Emerging evidence shows how specific PMCAs contribute not only to setting basal intracellular Ca 2+ levels, but also to local Ca 2+ signaling and vectorial Ca 2+ transport. A second major research arearevolves around the calcium sensor protein calmodulin and an enigmatic calmodulin-like protein (CALML3) that is linked to epithelial differentiation. One of the cellular targets of CALML3 is the unconventional motor protein myosin-10, which raises new questions about the role of CALML3 and myosin-10 in cell adhesion and migration in normal cell differentiation and cancer.

  10. Calcium supplements

    Science.gov (United States)

    ... Related Bone Diseases National Resource Center. Calcium and vitamin D: Important at every age. NIAMS.NIH.gov website. www.niams.nih.gov/Health_Info/Bone/Bone_Health/Nutrition . Updated May 2015. Accessed March ...

  11. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha;

    2015-01-01

    BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...... efficacy-and normal cell sensitivity. METHODS: Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780......), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p

  12. Diagnosing attention-deficit hyperactivity disorder (ADHD) in children involved with child protection services: are current diagnostic guidelines acceptable for vulnerable populations?

    Science.gov (United States)

    Klein, B; Damiani-Taraba, G; Koster, A; Campbell, J; Scholz, C

    2015-03-01

    Children involved with child protection services (CPS) are diagnosed and treated for attention-deficit hyperactivity disorder (ADHD) at higher rates than the general population. Children with maltreatment histories are much more likely to have other factors contributing to behavioural and attentional regulation difficulties that may overlap with or mimic ADHD-like symptoms, including language and learning problems, post-traumatic stress disorder, attachment difficulties, mood disorders and anxiety disorders. A higher number of children in the child welfare system are diagnosed with ADHD and provided with psychotropic medications under a group care setting compared with family-based, foster care and kinship care settings. However, children's behavioural trajectories change over time while in care. A reassessment in the approach to ADHD-like symptoms in children exposed to confirmed (or suspected) maltreatment (e.g. neglect, abuse) is required. Diagnosis should be conducted within a multidisciplinary team and practice guidelines regarding ADHD diagnostic and management practices for children in CPS care are warranted both in the USA and in Canada. Increased education for caregivers, teachers and child welfare staff on the effects of maltreatment and often perplexing relationship with ADHD-like symptoms and co-morbid disorders is also necessary. Increased partnerships are needed to ensure the mental well-being of children with child protection involvement.

  13. Calcium regulation in endosymbiotic organelles of plants

    OpenAIRE

    Bussemer, Johanna; Vothknecht, Ute C.; Chigri, Fatima

    2009-01-01

    In plant cells calcium-dependent signaling pathways are involved in a large array of biological processes in response to hormones, biotic/abiotic stress signals and a variety of developmental cues. This is generally achieved through binding of calcium to diverse calcium-sensing proteins, which subsequently control downstream events by activating or inhibiting biochemical reactions. Regulation by calcium is considered as a eukaryotic trait and has not been described for prokaryotes. Neverthele...

  14. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofi-brillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers in-volved in Alzheimer's disease therapy.

  15. Calcium Forms,Subcelluar Distribution and Ultrastructure of Pulp Cells as Influenced by Calcium Deficiency in Apple (Malus pumila) Fruits

    Institute of Scientific and Technical Information of China (English)

    CHEN Jian-hui; ZHOU Wei

    2004-01-01

    Calcium in Red Fuji and Starkrimson apples during storage were fractionated by sequent extracting. Localization and distribution of calcium and influence of calcium nutrition on cell ultrastructure were observed by transmission electron microscopy combined with in situ precipitation of calcium with an improved method of potassium pyroantimonate technique. Results indicated that spraying calcium solution on surface of young fruits increased contents of calcium in all forms. During storage, contents of soluble calcium and pectic calcium declined and thosein calcium phosphate, calcium oxalate and calcium silicate increased. Calcium contents of Red Fuji in all forms were higher than those of Starkrimson, indicating that calcium accumulating capability of Red Fuji fruits preceded that of Starkrimson. Under transmission electron microscopy, calcium antimonite precipitates (CaAP) was mainly distributed in cell wall, tonoplast, nuclear membrane and nucleoplasm,much more CaAP deposited in vacuole. Calcium deficiency during storage leads to decrease of CaAP in locations mentioned above, disappearance of compartmentation, and entrance of CaAP to cytoplasm. Transformation from soluble calcium and pectic calcium to calcium phosphate,oxalate and damages of biomembranes structuraly and functionally resulted from calcium deficiency during storage were the crucial causation of physiological disorder.

  16. Identification of functional FKB protein in Echinococcus granulosus: its involvement in the protoscolicidal action of rapamycin derivates and in calcium homeostasis.

    Science.gov (United States)

    Cumino, Andrea C; Lamenza, Pamela; Denegri, Guillermo M

    2010-05-01

    FK506 (tacrolimus) and polyketide macrolides such as rapamycin and its derivates bind to FK506-binding proteins (FKBPs). These proteins display a peptidyl-prolyl rotamase function that is believed to catalyze protein folding and they are well-validated anti-proliferative drug targets in certain pathogenic microorganisms, and their functions have been characterized in parasitic protozoa. However, much less is known in helminths and trials with rapalogs on cestoda have not yet been reported. Due to a growing need for new treatment options for human cystic echinococcosis, the in vitro efficacy of rapalogs in Echinococcus granulosus was investigated. We determined the effect of ramapycin, FK506 and everolimus against this cestode, demonstrating their protoscolicidal ability. Also, we observed synergic scolicidal actions during combined therapy with rapalogs plus cyclosporine A, proposing dual administration of drugs to improve pharmacological effects in vivo. We have identified an E. granulosus (Eg)-fkb1 gene that encodes Eg-FKBP, an archetypal protein of the FKBP family, which includes all residues implicated in the binding of pharmacological ligands, in the enzymatic activity and in interactions with possible target proteins. Levels of Eg-fkb1 mRNA are over-expressed by acid but not rapalog treatment. We also described the presence of receptor-operated calcium channels in the larval stage, suggesting that exogenous ligands may dissociate the interaction of Eg-FKBP from these intracellular channels, enhancing the activity of the Ca(2+) release and interfering with their normal regulatory functions. As rapamycin sensitivity is the major criterion used to detect targets of rapamycin kinase, we identified and analyzed in silico critical residues of putative homologs in the Echinococcus genome. These preliminary results will allow us to continue subsequent studies that could reveal the precise intracellular functions of Eg-FKBP, providing greater knowledge for further

  17. Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: a retrospective cohort study.

    Science.gov (United States)

    Agrawal, Arpana; Nelson, Elliot C; Bucholz, Kathleen K; Tillman, Rebecca; Grucza, Richard A; Statham, Dixie J; Madden, Pamela Af; Martin, Nicholas G; Heath, Andrew C; Lynskey, Michael T

    2017-09-01

    Early and frequent cannabis use are associated with an increased likelihood of major depressive disorder (MDD) as well as suicidal thoughts and behaviours. We identify associations between aspects of cannabis use, MDD, and suicidal thoughts and behaviours and examine whether such associations persist after accounting for those predisposing factors, including genetic liability and early family environment, that are shared by identical twins who are discordant for cannabis exposure. Any residual association in such identical pairs might be indicative of individual-specific pathways that might be of a causal nature. We did a logistic regression analysis of cannabis use from retrospective data on same-sex male and female twin pairs drawn from 3 studies that had recruited twins from the Australian Twin Registry, 1992-93 (sample 1), 1996-2000 (sample 2), and 2005-09 (sample 3). We studied associations between early use and frequent use of cannabis and MDD, suicidal ideation (ever and persistent), and suicide plan and attempt in the full sample as well as in pairs of monozygotic and dizygotic twins that were discordant for each measure of cannabis involvement at a single timepoint. Significant monozygotic associations were further adjusted for covariates, such as early alcohol or nicotine use, early dysphoric or anhedonic mood, conduct disorder, and childhood sexual abuse. Interactions between each cannabis measure and sex, sample or study effects, and birth year category were also examined as covariates. In 13 986 twins (6181 monozygotic and 7805 dizygotic), cannabis use ranged from 1345 (30·4%) of 4432 people in sample 1 to 2275 (69·0%) of 3299 in sample 3. Mean age of first cannabis use ranged from 17·9 years (SD 3·3) in sample 3 to 21·1 years (5·2) in sample 1, and frequent use (≥100 times) was reported by 214 (15·9%) of 1345 users in sample 1 and 499 (21·9%) of 2275 in sample 3. The prevalence of suicidal ideation ranged from 1102 (24·9%) of 4432 people

  18. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau

    2014-04-01

    Full Text Available The paper gives the review on the role of calcium in many physiological processes of plant organisms, including growth and development, protection from pathogenic influences, response to changing environmental factors, and many other aspects of plant physiology. Initial intake of calcium ions is carried out by Ca2+-channels of plasma membrane and they are further transported by the xylem owing to auxins’ attractive ability. The level of intake and selectivity of calcium transport to ove-ground parts of the plant is controlled by a symplast. Ca2+enters to the cytoplasm of endoderm cells through calcium channels on the cortical side of Kaspary bands, and is redistributed inside the stele by the symplast, with the use of Ca2+-АТPases and Ca2+/Н+-antiports. Owing to regulated expression and activity of these calcium transporters, calclum can be selectively delivered to the xylem. Important role in supporting calcium homeostasis is given to the vacuole which is the largest depo of calcium. Regulated quantity of calcium movement through the tonoplast is provided by a number of potential-, ligand-gated active transporters and channels, like Ca2+-ATPase and Ca2+/H+ exchanger. They are actively involved in the inactivation of the calcium signal by pumping Ca2+ to the depo of cells. Calcium ATPases are high affinity pumps that efficiently transfer calcium ions against the concentration gradient in their presence in the solution in nanomolar concentrations. Calcium exchangers are low affinity, high capacity Ca2+ transporters that are effectively transporting calcium after raising its concentration in the cell cytosol through the use of protons gradients. Maintaining constant concentration and participation in the response to stimuli of different types also involves EPR, plastids, mitochondria, and cell wall. Calcium binding proteins contain several conserved sequences that provide sensitivity to changes in the concentration of Ca2+ and when you

  19. Overlapping prefrontal systems involved in cognitive and emotional processing in euthymic bipolar disorder and following sleep deprivation: A review of functional neuroimaging studies

    Science.gov (United States)

    McKenna, Benjamin S; Eyler, Lisa T

    2013-01-01

    Prefrontal cortex (PFC) mediated cognitive and emotional processing deficits in bipolar disorder lead to functional limitations even during periods of mood stability. Alterations of sleep and circadian functioning are well-documented in bipolar disorder, but there is little research directly examining the mechanistic role of sleep and/or circadian rhythms in the observed cognitive and emotional processing deficits. We systematically review the cognitive and emotional processing deficits reliant upon PFC functioning of euthymic patients with bipolar disorder and in healthy individuals deprived of sleep. The evidence from two parallel lines of investigation suggests that sleep and circadian rhythms may be involved in the cognitive and emotional processing deficits seen in bipolar disorder through overlapping neurobiological systems. We discuss current models of bipolar highlighting the PFC-limbic connections and discuss inclusion of sleep-related mechanisms. Sleep and circadian dysfunction is a core feature of bipolar disorder and models of neurobiological abnormalities should incorporate chronobiological measures. Further research into the role of sleep and circadian rhythms in cognition and emotional processing in bipolar disorder is warranted. PMID:22926687

  20. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2 leading to cell depolarization and calcium influx

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Hartmann, Bolette

    2015-01-01

    , but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways...

  1. [Microbial geochemical calcium cycle].

    Science.gov (United States)

    Zavarzin, G A

    2002-01-01

    The participation of microorganisms in the geochemical calcium cycle is the most important factor maintaining neutral conditions on the Earth. This cycle has profound influence on the fate of inorganic carbon, and, thereby, on the removal of CO2 from the atmosphere. The major part of calcium deposits was formed in the Precambrian, when prokaryotic biosphere predominated. After that, calcium recycling based on biogenic deposition by skeletal organisms became the main process. Among prokaryotes, only a few representatives, e.g., cyanobacteria, exhibit a special calcium function. The geochemical calcium cycle is made possible by the universal features of bacteria involved in biologically mediated reactions and is determined by the activities of microbial communities. In the prokaryotic system, the calcium cycle begins with the leaching of igneous rock predominantly through the action of the community of organotrophic organisms. The release of carbon dioxide to the soil air by organotrophic aerobes leads to leaching with carbonic acid and soda salinization. Under anoxic conditions, of major importance is the organic acid production by primary anaerobes (fermentative microorganisms). Calcium carbonate is precipitated by secondary anaerobes (sulfate reducers) and to a smaller degree by methanogens. The role of the cyanobacterial community in carbonate deposition is exposed by stromatolites, which are the most common organo-sedimentary Precambrian structures. Deposition of carbonates in cyanobacterial mats as a consequence of photoassimilation of CO2 does not appear to be a significant process. It is argued that carbonates were deposited at the boundary between the "soda continent", which emerged as a result of subaerial leaching with carbonic acid, and the ocean containing Ca2+. Such ecotones provided favorable conditions for the development of the benthic cyanobacterial community, which was a precursor of stromatolites.

  2. The search for neuroimaging and cognitive endophenotypes: A critical systematic review of studies involving unaffected first-degree relatives of individuals with bipolar disorder.

    Science.gov (United States)

    Miskowiak, Kamilla W; Kjærstad, Hanne L; Meluken, Iselin; Petersen, Jeff Zarp; Maciel, Beatriz R; Köhler, Cristiano A; Vinberg, Maj; Kessing, Lars V; Carvalho, André F

    2017-02-01

    The phenomenology and underlying pathophysiology of bipolar disorder (BD) are heterogeneous. The identification of putative endophenotypes for BD can aid in the investigation of unique patho-etiological pathways, which may lead to the development of personalised preventative and therapeutic approaches for this multi-faceted disorder. We included original studies involving unaffected first-degree relatives of BD patients (URs) and a healthy control (HC) comparison group with no first-degree family history of mental disorders, investigating: 'cold' and 'hot' cognition and functional and structural neuroimaging. Seventy-seven cross-sectional studies met the inclusion criteria. The present review revealed that URs in comparison with HCs showed: (i) widespread deficits in verbal memory, sustained attention, and executive function; (ii) abnormalities in the reactivity to and regulation of emotional information along with aberrant reward processing, and heightened attentional interference by emotional stimuli; and (iii) less consistency in the findings regarding structural and resting state neuroimaging, and electrophysiological measures.

  3. Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study

    Science.gov (United States)

    Pang, Junxiong; Hsu, Jung Pu; Yeo, Tsin Wen; Leo, Yee Sin; Lye, David C.

    2017-01-01

    Progression to severe organ involvement due to dengue infection has been associated with severe dengue disease, intensive care treatment, and mortality. However, there is a lack of understanding of the impact of pre-existing comorbidities and other risk factors of severe organ involvement among dengue adults. The aim of this retrospective case-control study is to characterize and identify risk factors that predispose dengue adults at risk of progression with severe organ involvement. This study involved 174 dengue patients who had progressed with severe organ involvement and 865 dengue patients without severe organ involvement, matched by the year of presentation of the cases, who were admitted to Tan Tock Seng Hospital between year 2005 and 2008. Age group of 60 years or older, diabetes, cardiac disorders, asthma, and having two or more pre-existing comorbidities were independent risk factors of severe organ involvement. Abdominal pain, clinical fluid accumulation, and hematocrit rise and rapid platelet count drop at presentation were significantly associated with severe organ involvement. These risk factors, when validated in a larger study, will be useful for triage by clinicians for prompt monitoring and clinical management at first presentation, to minimize the risk of severe organ involvement and hence, disease severity. PMID:28045096

  4. Involvement of striatal lipid peroxidation and inhibition of calcium influx into brain slices in neurobehavioral alterations in a rat model of short-term oral exposure to manganese.

    Science.gov (United States)

    Avila, Daiana Silva; Gubert, Priscila; Fachinetto, Roselei; Wagner, Caroline; Aschner, Michael; Rocha, João Batista Teixeira; Soares, Félix Alexandre Antunes

    2008-11-01

    Manganese is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorder, characterized by excessive Mn accumulation, especially in astrocytes of basal ganglia and symptoms closely resembling idiopathic Parkinson's disease (PD). The purpose of this study was to evaluate behavioral and biochemical alterations in adult rats exposed for 30 days to 10 and 25mg/mL of MnCl(2) in their drinking water. MnCl(2) intoxicated rats showed impaired locomotor activity in comparison to control animals. Furthermore, lipid peroxidation were increased, delta-aminolevulinate dehydratase (delta-ALA-D, an enzyme sensitive to pro-oxidant situations) activity was inhibited and (45)Ca(2+) influx into striatal slices was decreased in rats exposed to 25mg/mL of Mn, indicating that this brain region was markedly affected by short-term Mn exposure. In contrast, Mn exposure was not associated with characteristic extrapyramidal effects and did not modify protein oxidation, suggesting that the striatal damage represents early stages of Mn-induced damage. In addition, treatment with Mn was associated with reduced body weight gain, but there were no discernible alterations in liver and kidney function. In conclusion, Mn caused increased oxidative stress and decreased (45)Ca(2+) influx into the striatum, which are likely linked to impaired locomotor activity, but not with the occurrence of orofacial dyskinesia.

  5. SKA2 Methylation is Involved in Cortisol Stress Reactivity and Predicts the Development of Post-Traumatic Stress Disorder (PTSD) after Military Deployment

    OpenAIRE

    Boks, Marco P; Rutten, Bart P. F.; Geuze, Elbert; Houtepen, Lotte C.; Vermetten, Eric; Kaminsky, Zachary; Vinkers, Christiaan H

    2016-01-01

    Genomic variation in the SKA2 gene has recently been identified as a promising suicide biomarker. In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD). Increased SKA2 methylation was significantly associated with lower cortisol stress reactivity in 85 healthy individuals exposed to the Trier Social Stress Test (B=-173.40, t=...

  6. Cardiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low-grade skeletal muscle disease activity.

    Science.gov (United States)

    Hughes, Michael; Lilleker, James B; Herrick, Ariane L; Chinoy, Hector

    2015-05-01

    Primary cardiac involvement, an under-recognised manifestation of the idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc)-spectrum disorders, is associated with significant mortality. Within these two conditions, traditional skeletal muscle enzyme testing may not effectively distinguish between skeletal and cardiac muscle involvement, especially in patients with subclinical cardiac disease. Accurate biomarkers are thus required to screen for cardiac disease, to better inform both therapeutic decision-making and treatment response. The widespread uptake of cardiac troponin testing has revolutionised the management of acute coronary syndromes. While cardiac troponin I (cTnI) appears specific to the myocardium, cardiac troponin T (cTnT) is also expressed by skeletal muscle, including regenerating skeletal muscle tissue. There is increasing interest about the role of cardiac troponins as a putative biomarker of primary cardiac involvement in IIM and SSc-spectrum disorders. Herewith we discuss subclinical cardiac disease in IIM and SSc-spectrum disorders, the respective roles of cTnI and cTnT testing, and the re-expression of cTnT within regenerating skeletal muscle tissue. There remains wide variation in access to cardiac troponin testing nationally and internationally. We propose two pragmatic clinical pathways using cardiac troponins, preferably measuring concomitant cTnT followed by confirmatory (cardiac) cTnI to screen patients for subclinical cardiac disease and/or low-grade skeletal muscle disease activity, and also an agenda for future research.

  7. Autism Spectrum Disorder and New Jersey Administrative Law Decisions: An Analysis of Case Law Involving Public School Students

    Science.gov (United States)

    Barcadepone, Michael J.

    2012-01-01

    The purpose of this case study was to investigate existing New Jersey case law for the special education population classified as Autism Spectrum Disorder (ASD) and analyze New Jersey Administrative Law Judge (ALJ) decisions to identify why districts win or lose cases, adding to the limited body of research in New Jersey. In addition, the purpose…

  8. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder

    NARCIS (Netherlands)

    Williams, H.J.; Norton, N.; Dwyer, S.; Moskvina, V.; Nikolov, I.; Carroll, L.; Georgieva, L.; Williams, N.M.; Morris, D.W.; Quinn, E.M.; Giegling, I.; Ikeda, M.; Wood, J.; Lencz, T.; Hultman, C.; Lichtenstein, P.; Thiselton, D.; Maher, B.S.; Malhotra, A.K.; Riley, B.; Kendler, K.S.; Gill, M.; Sullivan, P.; Sklar, P.; Purcell, S.; Nimgaonkar, V.L.; Kirov, G.; Holmans, P.; Corvin, A.; Rujescu, D.; Craddock, N.; Owen, M.J.; O'Donovan, M.C.; GROUP investigators, [No Value

    2011-01-01

    A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P = 1.61 x 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P = 9.96 x 10(-9)). In this

  9. Potential involvement of Notch1 signalling in the pathogenesis of primary cutaneous CD30-positive lymphoproliferative disorders

    DEFF Research Database (Denmark)

    Kamstrup, M.R.; Ralfkiaer, E.; Skovgaard, G.L.;

    2008-01-01

    to coexpress Notch1 and activated Akt kinase. Conclusions These results imply a potential role for the Notch signalling pathway in the pathogenesis of primary cutaneous CD30+ lymphoproliferative disorders and provide a rationale for the exploration of the activity of Notch antagonists in the therapy...

  10. Vitamin D and intestinal calcium absorption.

    Science.gov (United States)

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J; Seth, Tanya

    2011-12-05

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)(2)D(3) can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed.

  11. Relationship of intracellular calcium and oxygen radicals to Cisplatin-related renal cell injury.

    Science.gov (United States)

    Kawai, Yoshiko; Nakao, Takafumi; Kunimura, Naoshi; Kohda, Yuka; Gemba, Munekazu

    2006-01-01

    We investigated the involvement of reactive oxygen species (ROS) and intracellular calcium in nephrotoxicity related to an antitumor agent, cisplatin. In this study, we employed cultured renal epithelial cells (LLC-PK1). Cisplatin at 500 microM significantly increased the production of ROS 5 h and caused cell injury. This agent significantly increased the intracellular calcium level ([Ca2+]i) in a dose-dependent manner 1 h or more after exposure. DPPD (N,N'-diphenyl-p-phenylenediamine), an antioxidant, inhibited a cisplatin-related increase in active oxygen production and cell injury but did not inhibit an early increase in the [Ca2+]i level. An intracellular calcium-chelating compound BAPTA-AM (1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester) inhibited an increase in ROS production and cell injury induced by cisplatin. Furthermore, BAPTA-AM suppressed the rise of [Ca2+]i level in 1 h after exposure; however, an extracellular calcium chelator EGTA and a calcium antagonist nicardipine did not inhibit the rise in [Ca2+]i level in the early phase. An NADPH oxidase inhibitor inhibited a cisplatin-related increase in ROS production and cell disorder. These results suggest that cisplatin-related calcium release from the site of intracellular calcium storage in the early phase causes oxidative stress in renal tubular epithelial cells. Cisplatin may increase the intracellular production of ROS via NADPH oxidase.

  12. Limestone reaction in calcium aluminate cement–calcium sulfate systems

    Energy Technology Data Exchange (ETDEWEB)

    Bizzozero, Julien, E-mail: julien.bizzozero@gmail.com; Scrivener, Karen L.

    2015-10-15

    This paper reports a study of ternary blends composed of calcium aluminate cement, calcium sulfate hemihydrate and limestone. Compressive strength tests and hydration kinetics were studied as a function of limestone and calcium sulfate content. The phase evolution and the total porosity were followed and compared to thermodynamic simulation to understand the reactions involved and the effect of limestone on these binders. The reaction of limestone leads to the formation of hemicarboaluminate and monocarboaluminate. Increasing the ratio between sulfate and aluminate decreases the extent of limestone reaction.

  13. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Williams, H J; Norton, N; Dwyer, S; Moskvina, V; Nikolov, I; Carroll, L; Georgieva, L; Williams, N M; Morris, D W; Quinn, E M; Giegling, I; Ikeda, M; Wood, J; Lencz, T; Hultman, C; Lichtenstein, P; Thiselton, D; Maher, B S; Malhotra, A K; Riley, B; Kendler, K S; Gill, M; Sullivan, P; Sklar, P; Purcell, S; Nimgaonkar, V L; Kirov, G; Holmans, P; Corvin, A; Rujescu, D; Craddock, N; Owen, M J; O'Donovan, M C

    2011-04-01

    A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 × 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 × 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N=18 945, schizophrenia plus bipolar disorder N=21 274 and controls N=38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.

  14. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.

    LENUS (Irish Health Repository)

    Williams, H J

    2011-04-01

    A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 × 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 × 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia\\/schizoaffective disorder N=18 945, schizophrenia plus bipolar disorder N=21 274 and controls N=38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.

  15. Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling.

    Science.gov (United States)

    Logan, Clare V; Szabadkai, György; Sharpe, Jenny A; Parry, David A; Torelli, Silvia; Childs, Anne-Marie; Kriek, Marjolein; Phadke, Rahul; Johnson, Colin A; Roberts, Nicola Y; Bonthron, David T; Pysden, Karen A; Whyte, Tamieka; Munteanu, Iulia; Foley, A Reghan; Wheway, Gabrielle; Szymanska, Katarzyna; Natarajan, Subaashini; Abdelhamed, Zakia A; Morgan, Joanne E; Roper, Helen; Santen, Gijs W E; Niks, Erik H; van der Pol, W Ludo; Lindhout, Dick; Raffaello, Anna; De Stefani, Diego; den Dunnen, Johan T; Sun, Yu; Ginjaar, Ieke; Sewry, Caroline A; Hurles, Matthew; Rizzuto, Rosario; Duchen, Michael R; Muntoni, Francesco; Sheridan, Eamonn

    2014-02-01

    Mitochondrial Ca(2+) uptake has key roles in cell life and death. Physiological Ca(2+) signaling regulates aerobic metabolism, whereas pathological Ca(2+) overload triggers cell death. Mitochondrial Ca(2+) uptake is mediated by the Ca(2+) uniporter complex in the inner mitochondrial membrane, which comprises MCU, a Ca(2+)-selective ion channel, and its regulator, MICU1. Here we report mutations of MICU1 in individuals with a disease phenotype characterized by proximal myopathy, learning difficulties and a progressive extrapyramidal movement disorder. In fibroblasts from subjects with MICU1 mutations, agonist-induced mitochondrial Ca(2+) uptake at low cytosolic Ca(2+) concentrations was increased, and cytosolic Ca(2+) signals were reduced. Although resting mitochondrial membrane potential was unchanged in MICU1-deficient cells, the mitochondrial network was severely fragmented. Whereas the pathophysiology of muscular dystrophy and the core myopathies involves abnormal mitochondrial Ca(2+) handling, the phenotype associated with MICU1 deficiency is caused by a primary defect in mitochondrial Ca(2+) signaling, demonstrating the crucial role of mitochondrial Ca(2+) uptake in humans.

  16. Calcium and bones

    Science.gov (United States)

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  17. Ectopic expression of a maize calreticulin mitigates calcium deficiency-like disorders in "sCAX1"-expressing tobacco and tomato

    Science.gov (United States)

    Deregulated expression of an Arabidopsis H(+)/Ca(2+) antiporter (sCAX1) in agricultural crops increases total calcium (Ca(2+)) but may result in yield losses due to Ca(2+) deficiency-like symptoms. Here we demonstrate that co-expression of a maize calreticulin (CRT, a Ca(2+) binding protein located ...

  18. Calcium Carbonate

    Science.gov (United States)

    ... doctor if you have or have ever had kidney disease or stomach conditions.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking calcium carbonate, call your doctor.

  19. Involvement of calpains in adult neurogenesis: implications for stroke

    OpenAIRE

    2015-01-01

    Calpains are ubiquitous proteases involved in cell proliferation, adhesion and motility. In the brain, calpains have been associated with neuronal damage in both acute and neurodegenerative disorders, but their physiological function in the nervous system remains elusive. During brain ischemia, there is a large increase in the levels of intracellular calcium, leading to the activation of calpains. Inhibition of these proteases has been shown to reduce neuronal death in a variety of stroke mod...

  20. Grape seed extract triggers apoptosis in Caco-2 human colon cancer cells through reactive oxygen species and calcium increase: extracellular signal-regulated kinase involvement.

    Science.gov (United States)

    Dinicola, Simona; Mariggiò, Maria Addolorata; Morabito, Caterina; Guarnieri, Simone; Cucina, Alessandra; Pasqualato, Alessia; D'Anselmi, Fabrizio; Proietti, Sara; Coluccia, Pierpaolo; Bizzarri, Mariano

    2013-09-14

    Grape seed extract (GSE) from Italia, Palieri and Red Globe cultivars inhibits cell growth and induces apoptosis in Caco-2 human colon cancer cells in a dose-dependent manner. In order to investigate the mechanism(s) supporting the apoptotic process, we analysed reactive oxygen species (ROS) production, intracellular Ca2+ handling and extracellular signal-regulated kinase (ERK) activation. Upon exposure to GSE, ROS and intracellular Ca2+ levels increased in Caco-2 cells, concomitantly with ERK inactivation. As ERK activity is thought to be essential for promoting survival pathways, inhibition of this kinase is likely to play a relevant role in GSE-mediated anticancer effects. Indeed, pretreatment with N-acetyl cysteine, a ROS scavenger, reversed GSE-induced apoptosis, and promoted ERK phosphorylation. This effect was strengthened by ethylene glycol tetraacetic acid-mediated inhibition of extracellular Ca2+ influx. ROS and Ca2+ influx inhibition, in turn, increased ERK phosphorylation, and hence almost entirely suppressed GSE-mediated apoptosis. These data suggested that GSE triggers a previously unrecognised ERK-based mechanism, involving both ROS production and intracellular Ca2+ increase, eventually leading to apoptosis in cancer cells.

  1. Progression of impairment in adolescents with attention-deficit/hyperactivity disorder through the transition out of high school: Contributions of parent involvement and college attendance.

    Science.gov (United States)

    Howard, Andrea L; Strickland, Noelle J; Murray, Desiree W; Tamm, Leanne; Swanson, James M; Hinshaw, Stephen P; Arnold, L Eugene; Molina, Brooke S G

    2016-02-01

    Long-term, prospective follow-up studies of children diagnosed with attention-deficit/hyperactivity disorder (ADHD) show that symptoms tend to decline with age, but impairments in daily life functioning often persist into adulthood. We examined the developmental progression of impairments before and after the transition out of high school in relation to parent involvement during adolescence, parent support during adulthood, and college attendance, using 8 waves of data from the prospective 16-year follow-up of the Multimodal Treatment of ADHD (MTA) study. Participants were 548 proband children diagnosed with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV; American Psychiatric Association, 2000) ADHD Combined Type and 258 age- and sex-matched comparison children (Local Normative Comparison Group; LNCG) randomly sampled from probands' schools. Impairment was assessed consistently by parent report from childhood through adulthood. Results showed that impairment worsens over time both before and after the transition to adulthood for those with ADHD histories, in contrast to non-ADHD peers, whose impairments remained stably low over time. However, impairment stabilized after leaving high school for young adults with ADHD histories who attended college. Involved parenting in adolescence was associated with less impairment overall. Attending college was associated with a stable post-high school trajectory of impairment regardless of parents' involvement during adolescence, but young adults with histories of involved parenting and who attended college were the least impaired overall.

  2. A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement

    Science.gov (United States)

    Prasad, Megana K; Geoffroy, Véronique; Vicaire, Serge; Jost, Bernard; Dumas, Michael; Le Gras, Stéphanie; Switala, Marzena; Gasse, Barbara; Laugel-Haushalter, Virginie; Paschaki, Marie; Leheup, Bruno; Droz, Dominique; Dalstein, Amelie; Loing, Adeline; Grollemund, Bruno; Muller-Bolla, Michèle; Lopez-Cazaux, Séréna; Minoux, Maryline; Jung, Sophie; Obry, Frédéric; Vogt, Vincent; Davideau, Jean-Luc; Davit-Beal, Tiphaine; Kaiser, Anne-Sophie; Moog, Ute; Richard, Béatrice; Morrier, Jean-Jacques; Duprez, Jean-Pierre; Odent, Sylvie; Bailleul-Forestier, Isabelle; Rousset, Monique Marie; Merametdijan, Laure; Toutain, Annick; Joseph, Clara; Giuliano, Fabienne; Dahlet, Jean-Christophe; Courval, Aymeric; El Alloussi, Mustapha; Laouina, Samir; Soskin, Sylvie; Guffon, Nathalie; Dieux, Anne; Doray, Bérénice; Feierabend, Stephanie; Ginglinger, Emmanuelle; Fournier, Benjamin; de la Dure Molla, Muriel; Alembik, Yves; Tardieu, Corinne; Clauss, François; Berdal, Ariane; Stoetzel, Corinne; Manière, Marie Cécile; Dollfus, Hélène; Bloch-Zupan, Agnès

    2016-01-01

    Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824. PMID:26502894

  3. Reduction in traumatic brain injury-induced oxidative stress, apoptosis, and calcium entry in rat hippocampus by melatonin: Possible involvement of TRPM2 channels.

    Science.gov (United States)

    Yürüker, Vehbi; Nazıroğlu, Mustafa; Şenol, Nilgün

    2015-02-01

    Melatonin, which is a very effective reactive oxygen species (ROS) scavenger, acts through a direct reaction with free radicals. Ca(2+) entry induced by traumatic brain injury (TBI) has deleterious effects on human hippocampal function. TRPM2 is a Ca(2+) permeable non-selective channel in hippocampal neurons, and its activation of during oxidative stress has been linked to cell death. Despite the importance of oxidative stress in TBI, its role in apoptosis and Ca(2+) entry in TBI is poorly understood. Therefore, we tested the effects of melatonin on apoptosis, oxidative stress, and Ca(2+) entry through the TRPM2 channel in the hippocampal neurons of TBI-induced rats. Thirty-two rats were divided into the following four groups: control, melatonin, TBI, and TBI + melatonin groups. Melatonin (5 mg/kg body weight) was intraperitoneally given to animals in the melatonin group and the TBI + melatonin group after 1 h of brain trauma. Hippocampal neurons were freshly isolated from the four groups, incubated with a nonspecific TRPM2 blocker (2-aminoethyl diphenylborinate, 2-APB), and then stimulated with cumene hydroperoxide. Apoptosis, caspase-3, caspase-9, intracellular ROS production, mitochondrial membrane depolarization and intracellular free Ca(2+) ([Ca(2+)]i) values were high in the TBI group, and low in the TBI + melatonin group. The [Ca(2+)]i concentration was decreased in the four groups by 2-APB. In our TBI experimental model, TRPM2 channels were involved in Ca(2+) entry-induced neuronal death, and the negative modulation of the activity of this channel by melatonin pretreatment may account for the neuroprotective activity of TRPM2 channels against oxidative stress, apoptosis, and Ca(2+) entry.

  4. Rapid Diagnosis of Imprinting Disorders Involving Copy Number Variation and Uniparental Disomy Using Genome-Wide SNP Microarrays.

    Science.gov (United States)

    Liu, Weiqiang; Zhang, Rui; Wei, Jun; Zhang, Huimin; Yu, Guojiu; Li, Zhihua; Chen, Min; Sun, Xiaofang

    2015-01-01

    Imprinting disorders, such as Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Angelman syndrome (AS), can be detected via methylation analysis, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), or other methods. In this study, we applied single nucleotide polymorphism (SNP)-based chromosomal microarray analysis to detect copy number variations (CNVs) and uniparental disomy (UPD) events in patients with suspected imprinting disorders. Of 4 patients, 2 had a 5.25-Mb microdeletion in the 15q11.2q13.2 region, 1 had a 38.4-Mb mosaic UPD in the 11p15.4 region, and 1 had a 60-Mb detectable UPD between regions 14q13.2 and 14q32.13. Although the 14q32.2 region was classified as normal by SNP array for the 14q13 UPD patient, it turned out to be a heterodisomic UPD by short tandem repeat marker analysis. MS-MLPA analysis was performed to validate the variations. In conclusion, SNP-based microarray is an efficient alternative method for quickly and precisely diagnosing PWS, AS, BWS, and other imprinted gene-associated disorders when considering aberrations due to CNVs and most types of UPD.

  5. Involvement of HDAC1 and HDAC3 in the Pathology of Polyglutamine Disorders: Therapeutic Implications for Selective HDAC1/HDAC3 Inhibitors

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Thomas

    2014-05-01

    Full Text Available Histone deacetylases (HDACs enzymes, which affect the acetylation status of histones and other important cellular proteins, have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Emerging studies have demonstrated that different types of HDAC inhibitors show beneficial effects in various experimental models of neurological disorders. HDAC enzymes comprise a large family of proteins, with18 HDAC enzymes currently identified in humans. Hence, an important question for HDAC inhibitor therapeutics is which HDAC enzyme(s is/are important for the amelioration of disease phenotypes, as it has become clear that individual HDAC enzymes play different biological roles in the brain. This review will discuss evidence supporting the involvement of HDAC1 and HDAC3 in polyglutamine disorders, including Huntington’s disease, and the use of HDAC1- and HDAC3-selective HDAC inhibitors as therapeutic intervention for these disorders. Further, while HDAC inhibitors are known alter chromatin structure resulting in changes in gene transcription, understanding the exact mechanisms responsible for the preclinical efficacy of these compounds remains a challenge. The potential chromatin-related and non-chromatin-related mechanisms of action of selective HDAC inhibitors will also be discussed.

  6. Brain activation in teenagers with isolated spelling disorder during tasks involving spelling assessment and comparison of pseudowords. fMRI study.

    Science.gov (United States)

    Borkowska, Aneta Rita; Francuz, Piotr; Soluch, Paweł; Wolak, Tomasz

    2014-10-01

    The present study aimed at defining the specific traits of brain activation in teenagers with isolated spelling disorder in comparison with good spellers. fMRI examination was performed where the subject's task involved taking a decision 1/whether the visually presented words were spelled correctly or not (the orthographic decision task), and 2/whether the two presented letters strings (pseudowords) were identical or not (the visual decision task). Half of the displays showing meaningful words with an orthographic difficulty contained pairs with both words spelled correctly, and half of them contained one misspelled word. Half of the pseudowords were identical, half of them were not. The participants of the study included 15 individuals with isolated spelling disorder and 14 good spellers, aged 13-15. The results demonstrated that the essential differences in brain activation between teenagers with isolated spelling disorder and good spellers were found in the left inferior frontal gyrus, left medial frontal gyrus and right cerebellum posterior lobe, i.e. structures important for language processes, working memory and automaticity of behaviour. Spelling disorder is not only an effect of language dysfunction, it could be a symptom of difficulties in learning and automaticity of motor and visual shapes of written words, rapid information processing as well as automating use of orthographic lexicon. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  7. Synaptic Interactome Mining Reveals p140Cap as a New Hub for PSD Proteins Involved in Psychiatric and Neurological Disorders

    Science.gov (United States)

    Alfieri, Annalisa; Sorokina, Oksana; Adrait, Annie; Angelini, Costanza; Russo, Isabella; Morellato, Alessandro; Matteoli, Michela; Menna, Elisabetta; Boeri Erba, Elisabetta; McLean, Colin; Armstrong, J. Douglas; Ala, Ugo; Buxbaum, Joseph D.; Brusco, Alfredo; Couté, Yohann; De Rubeis, Silvia; Turco, Emilia; Defilippi, Paola

    2017-01-01

    Altered synaptic function has been associated with neurological and psychiatric conditions including intellectual disability, schizophrenia and autism spectrum disorder (ASD). Amongst the recently discovered synaptic proteins is p140Cap, an adaptor that localizes at dendritic spines and regulates their maturation and physiology. We recently showed that p140Cap knockout mice have cognitive deficits, impaired long-term potentiation (LTP) and long-term depression (LTD), and immature, filopodia-like dendritic spines. Only a few p140Cap interacting proteins have been identified in the brain and the molecular complexes and pathways underlying p140Cap synaptic function are largely unknown. Here, we isolated and characterized the p140Cap synaptic interactome by co-immunoprecipitation from crude mouse synaptosomes, followed by mass spectrometry-based proteomics. We identified 351 p140Cap interactors and found that they cluster to sub complexes mostly located in the postsynaptic density (PSD). p140Cap interactors converge on key synaptic processes, including transmission across chemical synapses, actin cytoskeleton remodeling and cell-cell junction organization. Gene co-expression data further support convergent functions: the p140Cap interactors are tightly co-expressed with each other and with p140Cap. Importantly, the p140Cap interactome and its co-expression network show strong enrichment in genes associated with schizophrenia, autism, bipolar disorder, intellectual disability and epilepsy, supporting synaptic dysfunction as a shared biological feature in brain diseases. Overall, our data provide novel insights into the molecular organization of the synapse and indicate that p140Cap acts as a hub for postsynaptic complexes relevant to psychiatric and neurological disorders. PMID:28713243

  8. Primary mucosal CD30-positive T-cell lymphoproliferative disorders of the head and neck rarely involving epiglottis: clinicopathological, immunohistomchemical and genetic features of a case.

    Science.gov (United States)

    Zhou, Jun; Wang, Guannan; Zhang, Dandan; Yin, Yuhui; Pang, Xia; Zhang, Jing; Zhang, Yanpin; Li, Wencai

    2015-01-01

    A case of primary mucosal CD30-positive T-cell lymphoproliferative disorder of the head and neck rarely involving epiglottis in a 59-year-old male was reported. Histologically, the ulcerative mucosa was affected by sheets of mixed inflammatory infiltration, with scattered large atypical lymphoid cells arranging in an individual or small clusters with focal epidermotropism. Immunohistochemically, tumor cells were uniformly immunoreactive to antibodies against CD2, CD3, CD7, CD43, CD4, TIA-1, with a heterogeneous expression of CD30, but negative for CD20, CD79a, CD21, CD8, CD56, ALK, EMA, granzyme B. Epstein-Barr virus encoded RNA (EBER) were detected. Genetically, T-cell receptor (TCR) γ gene showed an oligoclonal rearrangement. This first case developing in epiglottis demonstrates mucosal CD30-positive T-cell lymphoproliferative disorders are characteristic of a broad clinicopathologic spectrum similar to the counterpart in the skin with a favorable prognosis.

  9. Calcium paradox and calcium entry blockers

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Slade, A.M.; Nayler, W.G.; Meijler, F.L.

    1984-01-01

    Reperfusion of isolated hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). This phenomenon is characterized by an excessive influx of calcium into the cells, the rapid onset of myocardial contracture, exhausti

  10. Genetic and phenotypic heterogeneity in disorders of peroxisome biogenesis--a complementation study involving cell lines from 19 patients.

    Science.gov (United States)

    Roscher, A A; Hoefler, S; Hoefler, G; Paschke, E; Paltauf, F; Moser, A; Moser, H

    1989-07-01

    Disorders of peroxisomal biogenesis include the Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum syndrome, and hyperpipecolic acidemia. These names were assigned before the recognition of the peroxisomal defect and the distinction between phenotypes is uncertain. Recent studies have identified at least four complementation groups, and indicate the presence of at least that number of distinct genotypes. The purpose of the present study was to examine the relationship between genotype and phenotype. We studied cultured skin fibroblasts from 19 patients in whom deficiency of peroxisomes had been established. Complementation analysis was performed with the criterion of complementation being the restoration of the capacity to synthesize plasmalogens when fibroblasts from two patients were fused. Six complementation groups were identified, and consisted of one 13 member group, one two member group, and four groups comprising single cases. The phenotype of each group was examined with respect to age of survival, clinical manifestations, and biochemical alterations. The 13 member group included patients with all of the four currently designated phenotypic entities, while the most common phenotype (Zellweger syndrome) was distributed among five of the six groups. We conclude that the currently used clinical categories do not represent distinct genotypes. Apparently different genes code for a similar phenotype and one defective gene may lead to variant phenotypes. Definitive classification and understanding of these disorders await definition of the specific biochemical defect in each of the genotypes.

  11. The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments.

    Science.gov (United States)

    Bortolato, Beatrice; Carvalho, Andre F; Soczynska, Joanna K; Perini, Giulia I; McIntyre, Roger S

    2015-01-01

    Major depressive disorder is a highly prevalent, chronic and recurring disorder, associated with substantial impairment in cognitive and interpersonal functions. Accumulating evidence suggests that inflammatory processes play an important role in the etio-pathogenesis, phenomenology, comorbidity and treatment of MDD. Suboptimal remission rates and the persistence of cognitive deficits contribute to functional impairment in MDD inviting the need for the development of mechanistically novel and domain specific treatment approaches. The MEDLINE/ Pubmed database was searched from inception to February, 9th, 2014 with combinations of the following search terms: 'TNF-alpha', 'depression', 'infliximab', 'etanercept', 'adalimumab', 'golimumab' and 'certolizumab'. Preclinical and clinical evidence linking TNF-α to MDD pathophysiology were reviewed as well as the current status of TNF-α modulators as novel agents for the treatment of MDD. Experimental models and clinical studies provide encouraging preliminary evidence for the efficacy of TNF- α antagonists in mitigating depressive symptoms and improving cognitive deficits. Further studies are warranted to confirm these data in larger randomized controlled trials in primary psychiatric populations. Translational research provides a promising perspective that may aid the development and/or repurposing of mechanism-based treatments for depressive symptoms and cognitive impairment in MDD.

  12. Calcium antagonists and vasospasm.

    Science.gov (United States)

    Meyer, F B

    1990-04-01

    A critical review of the clinical data supports the conclusion that nimodipine decreases the severity of neurologic deficits and improves outcome after subarachnoid hemorrhage. The mechanisms by which mortality and morbidity are reduced are still controversial. First, the frequency of vasospasm is not altered (Figs. 5 and 6). Second, the consistent reversal of vasospasm once present has not been demonstrated either angiographically or by noninvasive cerebral blood flow studies. These observations suggest that there is either modification of microcirculatory flow (i.e., dilation of pial conducting vessels or decreased platelet aggregation) or a direct neuronal protective effect. As suggested previously, support for either mechanism is not resolute, and further investigation is necessary. Currently, nimodipine has been the most thoroughly investigated calcium antagonist both from an experimental and clinical perspective. Oral administration has had few reported complications. Therefore, the benefit/risk ratio clearly supports the prophylactic use of this calcium antagonist in patients of all clinical grades after subarachnoid hemorrhage. Evidence also indicates that starting nimodipine after the onset of delayed ischemic deficits is of benefit. Finally, it can be predicted that in the future additional calcium antagonists with more selective vascular or neuronal effects will be developed for use in neurologic disorders.

  13. Calcium regulation in endosymbiotic organelles of plants.

    Science.gov (United States)

    Bussemer, Johanna; Vothknecht, Ute C; Chigri, Fatima

    2009-09-01

    In plant cells calcium-dependent signaling pathways are involved in a large array of biological processes in response to hormones, biotic/abiotic stress signals and a variety of developmental cues. This is generally achieved through binding of calcium to diverse calcium-sensing proteins, which subsequently control downstream events by activating or inhibiting biochemical reactions. Regulation by calcium is considered as a eukaryotic trait and has not been described for prokaryotes. Nevertheless, there is increasing evidence indicating that organelles of prokaryotic origin, such as chloroplasts and mitochondria, are integrated into the calcium-signaling network of the cell. An important transducer of calcium in these organelles appears to be calmodulin. In this review we want to give an overview over present data showing that endosymbiotic organelles harbour calcium-dependent biological processes with a focus on calmodulin-regulation.

  14. Store-operated calcium signaling in neutrophils.

    Science.gov (United States)

    Clemens, Regina A; Lowell, Clifford A

    2015-10-01

    Calcium signals in neutrophils are initiated by a variety of cell-surface receptors, including formyl peptide and other GPCRs, FcRs, and integrins. The predominant pathway by which calcium enters immune cells is termed SOCE, whereby plasma membrane CRAC channels allow influx of extracellular calcium into the cytoplasm when intracellular ER stores are depleted. The identification of 2 key families of SOCE regulators, STIM calcium "sensors" and ORAI calcium channels, has allowed for genetic manipulation of SOCE pathways and provided valuable insight into the molecular mechanism of calcium signaling in immune cells, including neutrophils. This review focuses on our current knowledge of the molecules involved in neutrophil SOCE and how study of these molecules has further informed our understanding of the role of calcium signaling in neutrophil activation.

  15. The Administrative Problems Involved in Executing Clinical Recommendations for the Treatment of Severe Reading Disorders Within an Ongoing Educational System.

    Science.gov (United States)

    Schiffman, Gilbert B.

    Developing a program of treatment for dyslexic readers involves four major problems: (1) definition of the reading isability, (2) administrative and educational inertia, (3) organization of the treatment program, and (4) the need for evaluatio and research. There is great disagreement over definitions of reading disabilities, yet an effective…

  16. "What Brings Him Here Today?": Medical Problem Presentation Involving Children with Autism Spectrum Disorders and Typically Developing Children

    Science.gov (United States)

    Solomon, Olga; Heritage, John; Yin, Larry; Maynard, Douglas W.; Bauman, Margaret L.

    2016-01-01

    Conversation and discourse analyses were used to examine medical problem presentation in pediatric care. Healthcare visits involving children with ASD and typically developing children were analyzed. We examined how children's communicative and epistemic capabilities, and their opportunities to be socialized into a competent patient role are…

  17. Calcium renal lithiasis: metabolic diagnosis and medical treatment

    OpenAIRE

    Miguel Angel Arrabal-Polo; Miguel Arrabal-Martin; Juan Garrido-Gomez

    2013-01-01

    Calcium renal lithiasis is a frequent condition that affects the worldwide population and has a high recurrence rate. Different metabolic changes may trigger the onset of calcium stone disorders, such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and others. There are also other very prevalent disorders that are associated with calcium calculi, such as arterial hypertension, obesity and loss of bone mineral density. A correct diagnosis needs to be obtained through examinin...

  18. 焦虑性神经症患者投入超脱程度及相关因素研究%A Study on the Degree of Involvement in Anxiety Disorder Patients and Its Relating Factors

    Institute of Scientific and Technical Information of China (English)

    裴渝; 柳春旺; 周亮

    2003-01-01

    Objective: To assess the difference between the degree of involvement of anxiety disorder patients and normal con-trois , and to evaluate the relationship between the degree of involvement and the personality, type A behavior, and clinical sympomsof the patients. Methods:76 patients who met one of the diagnostic criteria of general anxiety disorder , panic disorder, obsessive-compulsive disorder ,or phobic disorder in CCMD were chosed - 3 were enrolled in this study and were required to complet in-volvement - detachment scale, type A behavior scale , EPQ , and SCL - 90.78 normal controls, who matched with the patient group in age , sex , and education, were derived from a community sample and completed involvement- detachhment scale, Results:The degree and the unbalance of involvement were higher in the patient group than those in the control group, The degree of detachment of patients was positively related to the type A behavior and the scores of SCL- 90( r = - 0.312, - 0.306, P < 0.05) .And the unbalance of involvment was positively related to the scores of SCL - 90 and N score of EPQ and negatively related to the P score of EPQ( r = 0.373,0.424, - 0.339, P < 0.05). Conclusion: Cognitive characteristics including over involvement and unbalance of involvement that were found in anxity disorder patients were related to the clinical symptoms and warranted clinical psychological intervention.

  19. Small intestinal involvement by lymphoproliferative disorders post-renal transplantation: A report from the post-transplant lymphoproliferative disorder international survey

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2013-01-01

    Full Text Available In this study, data on post-renal transplant lymphoproliferative disorders (PTLD collected from the existing literature were pooled and analyzed to compare the characteristics, predictors and prognosis of small intestinal PTLDs. We performed a comprehensive search for the available data by Pubmed and Google scholar search engines for reports on this subject. Data from 18 previously published studies, comprising 120 renal allograft recipients, were included in the analysis. Renal transplant recipients with intestinal PTLD were significantly less likely to have Hogkin′s and Hogkin′s-like lesions (P = 0.044 and to be younger at the time of transplan-tation (P = 0.07. Except for Hodgkin′s-like lesions, histopathological evaluations elsewhere were comparable between the group with PTLD in the small intestine and age- and sex-matched renal transplant recipients with PTLD in other sites. The overall mortality was relatively higher in the control group (P = 0.09. When death only due to PTLD was used as the outcome, a trend toward better outcome was seen for the intestinal PTLD group compared with the other localizations (P = 0.1. The 1- and 5-year survival rates for intestinal PTLD patients were 57% and 37%, respectively, compared with 54% and 21%, respectively, for the control group. According to our findings based on analysis of international data, renal transplant patients with small intestinal PTLD are more likely to be of younger age but less frequently represent Hodgkin′s and Hodgkin′s-like lesions. They also have better patient survival compared with transplant recipients with PTLD in other locations. Further multi-center prospective studies are needed to confirm our results.

  20. Susceptibility to calcium dysregulation during brain aging

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2009-11-01

    Full Text Available Calcium (Ca2+ is a highly versatile intracellular signaling molecule that is essential for regulating a variety of cellular and physiological processes ranging from fertilization to programmed cell death. Research has provided ample evidence that brain aging is associated with altered Ca2+ homeostasis. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review takes a broader perspective, assessing age-related changes in Ca2+ sources, Ca2+ sequestration, and Ca2+ binding proteins throughout the nervous system. The nature of altered Ca2+ homeostasis is cell specific and may represent a deficit or a compensatory mechanism, producing complex patterns of impaired cellular function. Incorporating the knowledge of the complexity of age-related alterations in Ca2+ homeostasis will positively shape the development of highly effective therapeutics to treat brain disorders.

  1. 76 FR 19692 - Revised Medical Criteria for Evaluating Endocrine Disorders

    Science.gov (United States)

    2011-04-08

    ..., such as tetany and muscle spasms, under 11.00. 4. Adrenal gland disorders affect bone calcium levels... tetany and muscle spasms, under 111.00. 4. Adrenal gland disorders affect bone calcium levels, blood...

  2. Electroconvulsive stimulations prevent chronic stress-induced increases in L-type calcium channel mRNAs in the hippocampus and basolateral amygdala

    DEFF Research Database (Denmark)

    Maigaard, Katrine; Pedersen, Ida Hageman; Jørgensen, Anders;

    2012-01-01

    Although affective disorders have high prevalence, morbidity and mortality, we do not fully understand disease etiopathology, nor have we determined the exact mechanisms by which treatment works. Recent research indicates that intracellular calcium ion dysfunction might be involved. Here we use...... the chronic restraint stress model of affective disorder (6 h restraint per day for 21 days) in combination with electroconvulsive stimulations to examine the effects of stress and an effective antidepressive treatment modality on L-type voltage gated calcium channel subunit mRNA expression patterns......, while stress only upregulated Ca(v)1.3 channel expression significantly in the dentate gyrus. ECS effects on Ca(v)1.2 channel expression were generally specific to stressed animals. Our findings are consistent with and extent previous studies on the involvement of intracellular calcium ion dysfunction...

  3. Cognitive-behavioral high parental involvement treatments for pediatric obsessive-compulsive disorder: A meta-analysis.

    Science.gov (United States)

    Iniesta-Sepúlveda, Marina; Rosa-Alcázar, Ana I; Sánchez-Meca, Julio; Parada-Navas, José L; Rosa-Alcázar, Ángel

    2017-06-01

    A meta-analysis on the efficacy of cognitive-behavior-family treatment (CBFT) on children and adolescents with obsessive-compulsive disorder (OCD) was accomplished. The purposes of the study were: (a) to estimate the effect magnitude of CBFT in ameliorating obsessive-compulsive symptoms and reducing family accommodation on pediatric OCD and (b) to identify potential moderator variables of the effect sizes. A literature search enabled us to identify 27 studies that fulfilled our selection criteria. The effect size index was the standardized pretest-postest mean change index. For obsessive-compulsive symptoms, the adjusted mean effect size for CBFT was clinically relevant and statistically significant in the posttest (dadj=1.464). For family accommodation the adjusted mean effect size was also positive and statistically significant, but in a lesser extent than for obsessive-compulsive symptoms (dadj=0.511). Publication bias was discarded as a threat against the validity of the meta-analytic results. Large heterogeneity among effect sizes was found. Better results were found when CBFT was individually applied than in group (d+=2.429 and 1.409, respectively). CBFT is effective to reduce obsessive-compulsive symptoms, but offers a limited effect for family accommodation. Additional modules must be included in CBFT to improve its effectiveness on family accommodation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Personality Disorders

    Science.gov (United States)

    Personality disorders are a group of mental illnesses. They involve long-term patterns of thoughts and behaviors ... serious problems with relationships and work. People with personality disorders have trouble dealing with everyday stresses and ...

  5. Predictors of recurrent sickness absence due to depressive disorders--a Delphi approach involving scientists and physicians.

    Directory of Open Access Journals (Sweden)

    Giny Norder

    Full Text Available BACKGROUND: Depression is a common and highly recurrent mental disorder that is accompanied by poor functioning at home and at work. Not all depressed employees report sick and little is known about variables associated with sickness absence (SA due to depression. Recurrent SA due to depression tends to marginalize employees from the workforce and exclude them from social participation. Therefore, this study sought group consensus on factors predicting recurrent SA due to depression. METHODOLOGY/PRINCIPAL FINDINGS: 23 scientists in the field of work and mental health and 23 physicians with expertise in assessing work disability were invited for a Delphi study. Sixty-seven factors retrieved from the literature were scored for their impact on the recurrence of SA due to depression, range 1 (no impact to 10 (very high impact in two Delphi rounds. The third Delphi round addressed the assessability and modifiability of elected predictors. Group consensus was defined as 75% agreement. In the first round (response 78%, group consensus was reached on a high impact of 13 factors on recurrent SA due to depression. The second round (response 79% added another 8 factors with high impact on recurrent SA due to depression. The panelists were of the opinion that stressful life and work events, age at first diagnosis, duration of the last depressive episode, anxiety, lifetime number of depressive episodes, and psychological work demands were readily assessable in consultation with patients. Furthermore, work factors, particularly decision latitude, psychological job demands, and commitment to work, were recognized as modifiable. CONCLUSIONS/SIGNIFICANCE: Although results have to be validated with further quantitative research, physicians may identify employees at risk of recurrent SA due to depression and may support them to adjust their work aimed at increasing commitment to work and preventing future SA due to depression.

  6. Identification of the hydrate gel phases present in phosphate-modified calcium aluminate binders

    Energy Technology Data Exchange (ETDEWEB)

    Chavda, Mehul A.; Bernal, Susan A. [Department of Materials Science and Engineering, The University of Sheffield, Sheffield S1 3JD (United Kingdom); Apperley, David C. [Solid-State NMR Group, Department of Chemistry, Durham University, Durham DH1 3LE (United Kingdom); Kinoshita, Hajime [Department of Materials Science and Engineering, The University of Sheffield, Sheffield S1 3JD (United Kingdom); Provis, John L., E-mail: j.provis@sheffield.ac.uk [Department of Materials Science and Engineering, The University of Sheffield, Sheffield S1 3JD (United Kingdom)

    2015-04-15

    The conversion of hexagonal calcium aluminate hydrates to cubic phases in hydrated calcium aluminate cements (CAC) can involve undesirable porosity changes and loss of strength. Modification of CAC by phosphate addition avoids conversion, by altering the nature of the reaction products, yielding a stable amorphous gel instead of the usual crystalline hydrate products. Here, details of the environments of aluminium and phosphorus in this gel were elucidated using solid-state NMR and complementary techniques. Aluminium is identified in both octahedral and tetrahedral coordination states, and phosphorus is present in hydrous environments with varying, but mostly low, degrees of crosslinking. A {sup 31}P/{sup 27}Al rotational echo adiabatic passage double resonance (REAPDOR) experiment showed the existence of aluminium–phosphorus interactions, confirming the formation of a hydrated calcium aluminophosphate gel as a key component of the binding phase. This resolves previous disagreements in the literature regarding the nature of the disordered products forming in this system.

  7. Are lipid disorders involved in the predominance of human T-lymphotropic virus-1 infections in women?

    Directory of Open Access Journals (Sweden)

    Luciana Debortoli de Carvalho

    2015-12-01

    Full Text Available Abstract INTRODUCTION : The human T-lymphotropic virus-1 (HTLV-1 is associated with chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, a chronic inflammatory disease. Disturbances in lipid metabolism are involved in inflammatory and demyelinating diseases. METHODS : Plasma levels of triglycerides, total cholesterol, and fractions of HTLV-1-infected individuals of both sexes with different clinical progressions were determined. RESULTS : Elevated levels of triglyceride and very low-density lipoproteins (VLDL were exclusively detected in HTLV-1-infected women from asymptomatic and HAM/TSP groups compared with uninfected individuals (p = 0.02. CONCLUSIONS : Elevated triglyceride and VLDL levels in HTLV-1-infected women may be related to the predominance of HAM/TSP in women.

  8. Diagnosis of posttraumatic stress disorder (PTSD) based on correlations of prewhitened fMRI data: outcomes and areas involved.

    Science.gov (United States)

    Christova, Peka; James, Lisa M; Engdahl, Brian E; Lewis, Scott M; Georgopoulos, Apostolos P

    2015-09-01

    Successful diagnosis of PTSD has been achieved using neural correlations from prewhitened magnetoencephalographic (MEG) time series (Georgopoulos et al. in J Neural Eng 7:16011, 2010. doi:10.1088/1741-2560/7/1/016011; James et al. 2015). Here, we show that highly successful classification of PTSD and control subjects can be obtained using neural correlations from prewhitened resting-state fMRI data. All but one PTSD (14/15; sensitivity = 93.3 %) and all but one control (20/21; specificity = 95.2 %) subjects were correctly classified using 15 out of 2701 possible correlations between 74 brain areas. In contrast, correlations of the same but non-prewhitened data yielded chance-level classifications. We conclude that, if properly processed, fMRI has the prospect of aiding significantly in PTSD diagnosis. Twenty-five brain areas were most prominently involved in correct subject classification, including areas from all cortical lobes and the left pallidum.

  9. Simulating complex calcium-calcineurin signaling network

    NARCIS (Netherlands)

    Cui, J.; Kaandorp, J.A.

    2008-01-01

    Understanding of processes in which calcium signaling is involved is of fundamental importance in systems biology and has many applications in medicine. In this paper we have studied the particular case of the complex calcium-calcineurin-MCIP-NFAT signaling network in cardiac myocytes, the understan

  10. Calcium, essential for health

    Science.gov (United States)

    Martínez de Victoria, Emilio

    2016-07-12

    Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.

  11. Calcium D-saccharate

    DEFF Research Database (Denmark)

    Garcia, André Castilho; Hedegaard, Martina Vavrusova; Skibsted, Leif Horsfelt

    2016-01-01

    K-1. Equilibria in supersaturated solutions of calcium d-saccharate seem only to adjust slowly, as seen from calcium activity measurements in calcium d-saccharate solutions made supersaturated by cooling. Solutions formed by isothermal dissolution of calcium d-gluconate in aqueous potassium d......-saccharate becomes spontaneously supersaturated with both d-gluconate and d-saccharate calcium salts, from which only calcium d-saccharate slowly precipitates. Calcium d-saccharate is suggested to act as a stabilizer of supersaturated solutions of other calcium hydroxycarboxylates with endothermic complex formation...

  12. Osteoblasts detect pericellular calcium concentration increase via neomycin-sensitive voltage gated calcium channels.

    Science.gov (United States)

    Sun, Xuanhao; Kishore, Vipuil; Fites, Kateri; Akkus, Ozan

    2012-11-01

    The mechanisms underlying the detection of critically loaded or micro-damaged regions of bone by bone cells are still a matter of debate. Our previous studies showed that calcium efflux originates from pre-failure regions of bone matrix and MC3T3-E1 osteoblasts respond to such efflux by an increase in the intracellular calcium concentration. The mechanisms by which the intracellular calcium concentration increases in response to an increase in the pericellular calcium concentration are unknown. Elevation of the intracellular calcium may occur via release from the internal calcium stores of the cell and/or via the membrane bound channels. The current study applied a wide range of pharmaceutical inhibitors to identify the calcium entry pathways involved in the process: internal calcium release from endoplasmic reticulum (ER, inhibited by thapsigargin and TMB-8), calcium receptor (CaSR, inhibited by calhex), stretch-activated calcium channel (SACC, inhibited by gadolinium), voltage-gated calcium channels (VGCC, inhibited by nifedipine, verapamil, neomycin, and ω-conotoxin), and calcium-induced-calcium-release channel (CICRC, inhibited by ryanodine and dantrolene). These inhibitors were screened for their effectiveness to block intracellular calcium increase by using a concentration gradient induced calcium efflux model which mimics calcium diffusion from the basal aspect of cells. The inhibitor(s) which reduced the intracellular calcium response was further tested on osteoblasts seeded on mechanically loaded notched cortical bone wafers undergoing damage. The results showed that only neomycin reduced the intracellular calcium response in osteoblasts, by 27%, upon extracellular calcium stimulus induced by concentration gradient. The inhibitory effect of neomycin was more pronounced (75% reduction in maximum fluorescence) for osteoblasts seeded on notched cortical bone wafers loaded mechanically to damaging load levels. These results imply that the increase in

  13. Calcium levels during the initiation of labor.

    Science.gov (United States)

    Papandreou, Lampros; Chasiotis, Georgios; Seferiadis, Konstantinos; Thanasoulias, Nikos C; Dousias, Vasilis; Tsanadis, Georgios; Stefos, Theodor

    2004-07-15

    To investigate the physiological role of calcium in the labor process. Eighty-eight term healthy pregnant women who gave birth to normal healthy neonates participated in our study. We compared calcium levels between pregnant women who had normal delivery and those who underwent scheduled cesarean section. The control group consisted of pregnant women with gestation > or =37 weeks without contractions. The groups were compared with respect to calcium levels: (a) in maternal blood serum; (b) in blood serum of the neonates and mothers; and (c) in blood serum between neonates. Significantly higher calcium levels were found in the group of pregnant women who delivered vaginally compared to those who delivered by scheduled cesarean section and those of the control group. We assume that the increased calcium levels during the first stage of labor are involved with a possible role of calcium in the mechanism of initiation of labor.

  14. Depression Case Control (DeCC) Study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder.

    Science.gov (United States)

    Cohen-Woods, Sarah; Gaysina, Daria; Craddock, Nick; Farmer, Anne; Gray, Joanna; Gunasinghe, Cerisse; Hoda, Farzana; Jones, Lisa; Knight, Jo; Korszun, Ania; Owen, Michael J; Sterne, Abram; Craig, Ian W; McGuffin, Peter

    2009-04-15

    It has been suggested that alteration in the muscarinic-cholinergic system is involved in modulation of mood. Three studies have reported linkage on chromosome 7 with major depressive disorder (MDD) in or close to a region containing the muscarinic receptor CHRM2 gene. A haplotype of SNPs located in CHRM2 (rs1824024-rs2061174-rs324650) has been significantly associated with MDD in a previous study. We report the first study investigating this gene in a large, adequately powered, clinical depression case-control sample (n = 1420 cases, 1624 controls). Our data fail to support association with the CHRM2 polymorphisms previously implicated in the genetic aetiology of depression. It is possible our failure to replicate may be a consequence of differences in definition of the MDD phenotype and/or ethnic differences.

  15. Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion.

    Science.gov (United States)

    Wang, Can; Xu, Bin; Ma, Zhuo; Liu, Chang; Deng, Yu; Liu, Wei; Xu, Zhao-Fa

    2017-06-16

    Overexposure to manganese (Mn) could disrupt neurotransmitter release via influencing the formation of SNARE complex, but the underlying mechanisms are still unclear. A previous study demonstrated that SNAP-25 is one of substrate of calpains. The current study investigated whether calpains were involved in Mn-induced disorder of SNARE complex. After mice were treated with Mn for 24 days, Mn deposition increased significantly in basal nuclei in Mn-treated and calpeptin pre-treated groups. Behaviorally, less time spent in the center of the area and decreased average velocity significantly in an open field test after 24 days of Mn exposure. With the increase in MnCl2 dosage, intracellular Ca(2+) increased significantly, but pretreatment with calpeptin caused a dose-dependent decrease in calpains activity. There were fragments of N-terminal of SNAP-25 protein appearance in Mn-treated groups, but it is decreased with pretreatment of calpeptin. FM1-43-labeled synaptic vesicles also provided evidence that the treatment with Mn resulted in increasing first and then decreasing, which was consistent with Glu release and the 80 kDa protein levels of SNARE complexes. In summary, Mn induced the disorder of neurotransmitter release through influencing the formation of SNARE complex via cleaving SNAP-25 by overactivation of calpains in vivo.

  16. Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level.

    Science.gov (United States)

    Wermter, Anne-Kathrin; Kamp-Becker, Inge; Hesse, Philipp; Schulte-Körne, Gerd; Strauch, Konstantin; Remschmidt, Helmut

    2010-03-05

    An increasing number of animal studies advert to a substantial role of the neuropeptide oxytocin in the regulation of social attachment and affiliation. Furthermore, animal studies showed anxiety and stress-reduced effects of oxytocin. First human studies confirm these findings in animal studies and implicate a crucial role of oxytocin in human social attachment behavior and in social interactions. Thus, the oxytocin system might be involved in the impairment of social interaction and attachment in autism spectrum disorders (ASD). The human oxytocin receptor gene (OXTR) represents a plausible candidate gene for the etiology of ASD. To analyze whether genetic variants in the OXTR gene are associated with ASD we performed family-based single-marker and haplotype association analyses with 22 single nucleotide polymorphisms (SNPs) in the OXTR and its 5' region in 100 families with autistic disorders on high-functioning level (Asperger syndrome (AS), high-functioning autism (HFA), and atypical autism (AA)). Single-marker and haplotype association analyses revealed nominally significant associations of one single SNP and one haplotype with autism, respectively. Furthermore, employing a "reverse phenotyping" approach, patients carrying the haplotype associated with autism showed nominally significant impairments in comparison to noncarriers of the haplotype in items of the Autism Diagnostic Interview-Revised algorithm describing aspects of social interaction and communication. In conclusion, our results implicate that genetic variation in the OXTR gene might be relevant in the etiology of autism on high-functioning level.

  17. Changes in Families' Caregiving Experiences through Involvement as Participants then Facilitators in a Family Peer-Education Program for Mental Disorders in Japan.

    Science.gov (United States)

    Kageyama, Masako; Yokoyama, Keiko; Nakamura, Yukako; Kobayashi, Sayaka

    2017-06-01

    A family peer-education program for mental disorders was developed in Japan, similar to existing programs in the United States and Hong Kong. Families that serve as facilitators in such programs may enhance their caregiving processes and, thereby, their well-being. This study's aim was to describe how families' caregiving experiences change, beginning with the onset of a family member's mental illness, through their involvement in a family group or peer-education program as participants then facilitators. Thus, this study was conducted in a family peer-education program for mental disorders in Japan. Group interviews were conducted with 27 facilitators from seven program sites about their experiences before, during, and after becoming facilitators. Interview data were coded and categorized into five stages of caregiving processes: (1) withdrawing and suppressing negative experiences with difficulty and regret; (2) finding comfort through being listened to about negative experiences; (3) supporting participants' sharing as facilitators; (4) understanding and affirming oneself through repeated sharing of experiences; and (5) finding value and social roles in one's experiences. The third, fourth, and fifth stages were experienced by the facilitators. The value that the facilitators placed on their caregiving experiences changed from negative to positive, which participants regarded as helpful and supportive. We conclude that serving as facilitators may improve families' caregiving processes. © 2015 Family Process Institute.

  18. The three CARMA sisters: so different, so similar: a portrait of the three CARMA proteins and their involvement in human disorders.

    Science.gov (United States)

    Scudiero, Ivan; Vito, Pasquale; Stilo, Romania

    2014-08-01

    Initially identified by their ability to modulate the functional activity of BCL10, the three CARMA proteins, CARMA1, -2, and -3, have recently themselves taken a leading role on the stage of molecular medicine. Although considered for some time as simple ancillary proteins, increasingly accumulating recent data evidently indicate a role of primary importance for these three proteins in the pathophysiology of several human tumors and inflammatory disorders. In fact, recent scientific literature clearly establishes that CARMA1 is one of the most mutated genes in a subtype of B-cell lymphoma and, at the same time, responsible for some rare human immunodeficiency conditions. On the other hand, mutations in CARMA2 are responsible for the hereditary transmission of some inflammatory disorders of the skin, including familial psoriasis and ptiriasis; whereas expression of CARMA3 appears to be deregulated in different human tumors. Here we describe and summarize the mutations found in the genes coding for the three CARMA proteins in these different human pathological conditions, and offer an interpretation of the molecular mechanisms from which arise the biological outcomes in which these proteins are involved.

  19. The calcium paradox - What should we have to fear?

    Science.gov (United States)

    de Oliveira, Marcos Aurélio Barboza; Brandi, Antônio Carlos; dos Santos, Carlos Alberto; Botelho, Paulo Henrique Husseni; Cortez, José Luís Lasso; Goissis, Gilberto; Braile, Domingo Marcolino

    2014-01-01

    The calcium paradox was first mentioned in 1966 by Zimmerman et al. Thereafter gained great interest from the scientific community due to the fact of the absence of calcium ions in heart muscle cells produce damage similar to ischemia-reperfusion. Although not all known mechanisms involved in cellular injury in the calcium paradox intercellular connection maintained only by nexus seems to have a key role in cellular fragmentation. The addition of small concentrations of calcium, calcium channel blockers, and hyponatraemia hypothermia are important to prevent any cellular damage during reperfusion solutions with physiological concentration of calcium. PMID:25140476

  20. Are dopaminergic genes involved in a predisposition to pathological aggression? Hypothesizing the importance of "super normal controls" in psychiatricgenetic research of complex behavioral disorders.

    Science.gov (United States)

    Chen, Thomas J H; Blum, Kenneth; Mathews, Daniel; Fisher, Larry; Schnautz, Nancy; Braverman, Eric R; Schoolfield, John; Downs, Bernard W; Comings, David E

    2005-01-01

    We hypothesize that pathological aggression, a complex behavioral disorder, in adolescents may in part involve polymorphisms of the dopaminergic system. While a number of neurotransmitter systems must be involved, due to polygenic inheritance, one major pathway should involve the dopaminergic system. Advances in our knowledge of the neurobiology of aggression and violence have given rise to rational pharmacological treatments for these behaviors. The main biological systems that are known to be involved are certain reward neurotransmitters including: serotonin, opioid peptides, gamma-aminobutyric acid, and the catecholamines (dopamine and norepinephrine). It is our notion that pathological aggressive behavior is in part similar mechanistically to other forms of impulsive behaviors such as pathological gambling. By analogy to drug dependence, it has been speculated that the underlying pathology in pathological gambling is a reduction in the sensitivity of the reward system. While studying pathological gamblers and controls during a guessing game using functional Magnetic Resonance Imaging, Reuter et al. observed a reduction of ventral striatal and ventromedial prefrontal activation in the pathological gamblers that were negatively correlated with gambling severity. Subsequently, linking hypo activation of these areas to disease severity. A positive correlation of both the dopamine D2 receptor gene (DRD2) and the dopamine transporter gene (DAT1) polymorphisms were observed with pathological violence in adolescents in a blinded clinical trial. Thus, this and other cited work preliminary suggest a role for both the DRD2 and DAT genes in pathological aggressive behavior. We further hypothesize that follow-up gene research in this area, albeit premature, resulting in confirmation of positive correlations with dopaminergic polymorphisms, and utilizing highly screened controls (eliminating any addictive, compulsive and impulsive behaviors in both proband and family) may

  1. Role of calcium in gravity perception of plant roots

    Science.gov (United States)

    Evans, Michael L.

    1986-01-01

    Calcium ions may play a key role in linking graviperception by the root cap to the asymmetric growth which occurs in the elongation zone of gravistimulated roots. Application of calcium-chelating agents to the root cap inhibits gravitropic curvature without affecting growth. Asymmetric application of calcium to one side of the root cap induces curvature toward the calcium source, and gravistimulation induces polar movement of applied (Ca-45)(2+) across the root cap toward the lower side. The action of calcium may be linked to auxin movement in roots since: (1) auxin transport inhibitors interfere both with gravitropic curvature and graviinduced polar calcium movement and (2) asymmetric application of calcium enhances auxin movement across the elongation zone of gravistimulated roots. Indirect evidence indicates that the calcium-modulated regulator protein, calmodulin, may be involved in either the transport or action of calcium in the gravitropic response mechanism of roots.

  2. Effects of modulation of calcium levels and calcium fluxes on ABA- induced gene expression in barley aleurone

    NARCIS (Netherlands)

    Meulen, R.M. van der; Visser, K.; Wang, M.

    1996-01-01

    We present data to elucidate the involvement of calcium ions in abscisic acid (ABA)-induced gene expression. Modulation of external calcium concentrations was able to affect ABA-induced specific RAB gene expression. At a constant ABA level with increasing extracellular calcium level, an increasing R

  3. Effects of modulation of calcium levels and calcium fluxes on ABA- induced gene expression in barley aleurone

    NARCIS (Netherlands)

    Meulen, R.M. van der; Visser, K.; Wang, M.

    1996-01-01

    We present data to elucidate the involvement of calcium ions in abscisic acid (ABA)-induced gene expression. Modulation of external calcium concentrations was able to affect ABA-induced specific RAB gene expression. At a constant ABA level with increasing extracellular calcium level, an increasing R

  4. Comparative analysis of serum zinc, copper, manganese, iron, calcium, and magnesium level and complexity of interelement relations in generalized anxiety disorder patients.

    Science.gov (United States)

    Islam, Md Reazul; Ahmed, Maizbha Uddin; Mitu, Shahida Akter; Islam, Mohammad Safiqul; Rahman, G K M Mustafizur; Qusar, M M A Shalahuddin; Hasnat, Abul

    2013-07-01

    The purpose of the study was to determine the concentration of serum trace and other essential elements of generalized anxiety disorder patients and to find out the relationship between element levels and nutritional status or socioeconomic factors. The study was conducted among 50 generalized anxiety disorder patients and 51 healthy volunteers. Patients were selected and recruited in the study with the help of a clinical psychologist by random sampling. The concentrations of serum trace elements (Zn, Cu, Mn, and Fe) and other two essential elements (Ca and Mg) were determined by graphite furnace and flame atomic absorption spectroscopy. Data were analyzed by independent t test, Pearson's correlation analysis, regression analysis, and analysis of variance. The serum concentrations of Zn, Cu, Mn, Fe, Ca, and Mg in generalized anxiety disorder patients were 1.069 ± 0.40, 1.738 ± 0.544, 1.374 ± 0.750, 3.203 ± 2.065, 108.65 ± 54.455, and 21 ± 4.055 mg/L, while those were 1.292 ± 0.621, 0.972 ± 0.427, 0.704 ± 0.527, 1.605 ± 1.1855, 101.849 ± 17.713, and 21.521 ± 3.659 mg/L in control subjects. Significantly decreased (p  0.05). Socioeconomic data revealed that most of the patients were in the lower middle class group and middle-aged. Mean BMI of the control group (23.63 ± 3.91 kg/m(2)) and the patient group (23.62 ± 3.77 kg/m(2)) was within the normal range (18.5-25.0 kg/m(2)). The data obtained from different interelement relations in the generalized anxiety disorder patients and control group strongly suggest that there is a disturbance in the element homeostasis. So changes in the serum trace element level in generalized anxiety disorder patients occur independently and they may provide a prognostic tool for the diagnosis and treatment of this disease.

  5. Calcium sensing in exocytosis

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Wu, Bingbing; Han, Weiping

    2012-01-01

    an increase in intracellular calcium levels. Besides the triggering role, calcium signaling modulates the precise amount and kinetics of vesicle release. Thus, it is a central question to understand the molecular machineries responsible for calcium sensing in exocytosis. Here we provide an overview of our...... current understanding of calcium sensing in neurotransmitter release and hormone secretion....

  6. Imaging calcium in neurons.

    Science.gov (United States)

    Grienberger, Christine; Konnerth, Arthur

    2012-03-08

    Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the general mechanisms of neuronal calcium signaling. We then introduce the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices that are used in freely moving animals. We provide an overview of the classical chemical fluorescent calcium indicators and of the protein-based genetically encoded calcium indicators. Using application examples, we introduce new developments in the field, such as calcium imaging in awake, behaving animals and the use of calcium imaging for mapping single spine sensory inputs in cortical neurons in vivo. We conclude by providing an outlook on the prospects of calcium imaging for the analysis of neuronal signaling and plasticity in various animal models.

  7. Renal Calcium Oxalate Deposits Induce a Pro-Atherosclerotic and Pro-Osteoporotic Response in Mice.

    Science.gov (United States)

    Kusumi, Kirsten; Barr-Beare, Evan; Saxena, Vijay; Safedi, Fayez; Schwaderer, Andrew

    2017-09-01

    Urinary stone disease (USD) is increasing in adult and pediatric populations. Adult and pediatric studies have demonstrated decreased bone mineral density and increased fracture rates. USD has also been independently linked to increased rates of myocardial infarction and cerebral vascular accidents. Although USD is a multisystem disorder involving the kidneys, bone, and vasculature, the molecular mechanisms linking these three organs remain unknown. Calcium oxalate nephropathy was induced in C57BL/6J mice with intra-peritoneal (ip) injection of sodium glyoxolate. Half of each kidney underwent Pizzalato staining and half was snap frozen for RNA extraction. RT(2) Profiler Mouse Atherosclerosis, Osteoporosis, and Calcium Signaling PCR Arrays (Qiagen) were performed. Only results that passed quality checks in PCR array reproducibility and genomic DNA contamination were included. Genes had to show at least fourfold differential expression and P 10-fold increase. All 10 have P ≤ 0.003. The calcium signaling array showed significant fourfold upregulation of 10 genes, four of which were ≥10-fold. All 10 have P ≤ 0.03. We have demonstrated that calcium oxalate nephropathy can induce upregulation of atherosclerotic, metabolic bone, and calcium homeostasis genes in a murine model. This may be and initial step in identifying the molecular mechanisms linking stone, bone, and cardiovascular disease. J. Cell. Biochem. 118: 2744-2751, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Calcium channelopathies and Alzheimer's disease: insight into therapeutic success and failures.

    Science.gov (United States)

    Chakroborty, Shreaya; Stutzmann, Grace E

    2014-09-15

    Calcium ions are versatile and universal biological signaling factors that regulate numerous cellular processes ranging from cell fertilization, to neuronal plasticity that underlies learning and memory, to cell death. For these functions to be properly executed, calcium signaling requires precise regulation, and failure of this regulation may tip the scales from a signal for life to a signal for death. Disruptions in calcium channel function can generate complex multi-system disorders collectively referred to as "calciumopathies" that can target essentially any cell type or organ. In this review, we focus on the multifaceted involvement of calcium signaling in the pathophysiology of Alzheimer's disease (AD), and summarize the various therapeutic options currently available to combat this disease. Detailing the series of disappointing AD clinical trial results on cognitive outcomes, we emphasize the urgency to design alternative therapeutic strategies if synaptic and memory functions are to be preserved. One such approach is to target early calcium channelopathies centrally linked to AD pathogenesis. © 2013 Published by Elsevier B.V.

  9. Effects of interpersonal violence-related post-traumatic stress disorder (PTSD) on mother and child diurnal cortisol rhythm and cortisol reactivity to a laboratory stressor involving separation.

    Science.gov (United States)

    Cordero, Maria I; Moser, Dominik A; Manini, Aurelia; Suardi, Francesca; Sancho-Rossignol, Ana; Torrisi, Raffaella; Rossier, Michel F; Ansermet, François; Dayer, Alexandre G; Rusconi-Serpa, Sandra; Schechter, Daniel S

    2017-04-01

    Women who have experienced interpersonal violence (IPV) are at a higher risk to develop posttraumatic stress disorder (PTSD), with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and impaired social behavior. Previously, we had reported impaired maternal sensitivity and increased difficulty in identifying emotions (i.e. alexithymia) among IPV-PTSD mothers. One of the aims of the present study was to examine maternal IPV-PTSD salivary cortisol levels diurnally and reactive to their child's distress in relation to maternal alexithymia. Given that mother-child interaction during infancy and early childhood has important long-term consequences on the stress response system, toddlers' cortisol levels were assessed during the day and in response to a laboratory stressor. Mothers collected their own and their 12-48month-old toddlers' salivary samples at home three times: 30min after waking up, between 2-3pm and at bedtime. Moreover, mother-child dyads participated in a 120-min laboratory session, consisting of 3 phases: baseline, stress situation (involving mother-child separation and exposure to novelty) and a 60-min regulation phase. Compared to non-PTSD controls, IPV-PTSD mothers - but not their toddlers, had lower morning cortisol and higher bedtime cortisol levels. As expected, IPV-PTSD mothers and their children showed blunted cortisol reactivity to the laboratory stressor. Maternal cortisol levels were negatively correlated to difficulty in identifying emotions. Our data highlights PTSD-IPV-related alterations in the HPA system and its relevance to maternal behavior. Toddlers of IPV-PTSD mothers also showed an altered pattern of cortisol reactivity to stress that potentially may predispose them to later psychological disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. SKA2 Methylation is Involved in Cortisol Stress Reactivity and Predicts the Development of Post-Traumatic Stress Disorder (PTSD) After Military Deployment.

    Science.gov (United States)

    Boks, Marco P; Rutten, Bart P F; Geuze, Elbert; Houtepen, Lotte C; Vermetten, Eric; Kaminsky, Zachary; Vinkers, Christiaan H

    2016-04-01

    Genomic variation in the SKA2 gene has recently been identified as a promising suicide biomarker. In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD). Increased SKA2 methylation was significantly associated with lower cortisol stress reactivity in 85 healthy individuals exposed to the Trier Social Stress Test (B=-173.40, t=-2.324, p-value=0.023). Next, we observed that longitudinal decreases in SKA2 methylation after deployment were associated with the emergence of post-deployment PTSD symptoms in a Dutch military cohort (N=93; B=-0.054, t=-3.706, p-value=3.66 × 10(-4)). In contrast, exposure to traumatic stress during deployment by itself resulted in longitudinal increases in SKA2 methylation (B=0.037, t=4.173, p-value=6.98 × 10(-5)). Using pre-deployment SKA2 methylation levels and childhood trauma exposure, we found that the previously published suicide prediction rule significantly predicted post-deployment PTSD symptoms (AUC=0.66, 95% CI: 0.53-0.79) with an optimal sensitivity of 0.81 and specificity of 0.91. Permutation analysis using random methylation loci supported these findings. Together, these data establish the importance of SKA2 for cortisol stress responsivity and the development of PTSD and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD.

  11. [Pharmacological study on blood pressure in rats with bone disorders].

    Science.gov (United States)

    Shamoto, T

    1989-12-01

    To evaluate the relationship between the elevation of blood pressure and altered bone metabolism, the changes of systolic blood pressure in six experimental models for bone disorders were investigated. Rats used were either parathyroidectomized, ovariectomized, fed with a calcium-deficient diet, fed with a vitamin D-deficient diet, treated with HEBP (1-Hydroxyethylidene-1, 1-bisphosphonate) or treated with streptozotocin. Hypertension developed in 5-week-old male rats fed with a calcium-deficient diet for 2 weeks, which evoked hypocalcemia and nutritional hyperparathyroidism. The blood pressure returned to normal when fed with a normal calcium diet. In parathyroidectomized rats receiving a normal calcium diet, the blood pressure did not rise, though the plasma calcium level decreased to an extent similar to the rats fed with the calcium-deficient diet. These findings seem to indicate that hyperparathyroidism, but not hypocalcemia, was involved in the elevation of blood pressure in rats fed with a calcium-deficient diet. Hypertension was not observed in rats fed with a vitamin D-deficient diet or treated with streptozotocin. These rats showed not only an increase in parathyroid hormone (PTH) but also a decrease in 1,25 (OH)2 D3. These results may suggest that the presence of 1,25 (OH)2D3 as well as the enhanced parathyroid function is necessary for the development of hypertension. The elevated blood pressure was reduced by a calcium antagonist, nifedipine, or by calcium supplementation, but not by an inhibitor of angiotensin-converting enzyme, captopril, or by calcitonin. This may indicate that hypertension due to nutritional hyperparathyroidism responds to the calcium antagonist nifedipine and to calcium supplementation, but does not depend on renin or salt. Furthermore, an acute hypotensive effect by human PTH (1-34) was not observed in the hypertension of calcium-deficient rats, suggesting the difference between acute and chronic effects of PTH. The hypertension

  12. Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study.

    Science.gov (United States)

    Gonzalez, Suzanne; Xu, Chun; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Contreras, Salvador A; Contreras, Javier; Dassori, Albana; Leach, Robin J; Flores, Deborah; Jerez, Alvaro; Raventós, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

    2013-03-01

      Through recent genome-wide association studies (GWASs), several groups have reported significant association between variants in the calcium channel, voltage-dependent, L-type, alpha 1C subunit (CACNA1C) and bipolar disorder (BP) in European and European-American cohorts. We performed a family-based association study to determine whether CACNA1C is associated with BP in the Latino population.   This study included 913 individuals from 215 Latino pedigrees recruited from the USA, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single-nucleotide polymorphisms (SNPs) that spanned a 602.9-kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family-Based Association Test (version 2.0.3) and Haploview (version 4.2) software.   An eight-locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15).   Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  13. Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study

    Science.gov (United States)

    Gonzalez, Suzanne; Xu, Chun; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Contreras, Salvador A; Contreras, Javier; Dassori, Albana; Leach, Robin J; Flores, Deborah; Jerez, Alvaro; Raventós, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

    2013-01-01

    Objectives Through recent genome-wide association studies (GWAS), several groups have reported significant association between variants in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) and bipolar disorder (BP) in European and European-American cohorts. We performed a family-based association study to determine whether CACNA1C is associated with BP in the Latino population. Methods This study consisted of 913 individuals from 215 Latino pedigrees recruited from the United States, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single-nucleotide polymorphisms (SNPs) that spanned a 602.9 kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family-Based Association Test (version 2.0.3) and Haploview (version 4.2) software. Results An eight-locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). Conclusions Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population. PMID:23437964

  14. Calcium ion currents mediating oocyte maturation events

    Directory of Open Access Journals (Sweden)

    Tosti Elisabetta

    2006-05-01

    Full Text Available Abstract During maturation, the last phase of oogenesis, the oocyte undergoes several changes which prepare it to be ovulated and fertilized. Immature oocytes are arrested in the first meiotic process prophase, that is morphologically identified by a germinal vesicle. The removal of the first meiotic block marks the initiation of maturation. Although a large number of molecules are involved in complex sequences of events, there is evidence that a calcium increase plays a pivotal role in meiosis re-initiation. It is well established that, during this process, calcium is released from the intracellular stores, whereas less is known on the role of external calcium entering the cell through the plasma membrane ion channels. This review is focused on the functional role of calcium currents during oocyte maturation in all the species, from invertebrates to mammals. The emerging role of specific L-type calcium channels will be discussed.

  15. Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage.

    Directory of Open Access Journals (Sweden)

    Mingqiang Ren

    Full Text Available Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19(+ IgM(- CD43(+ immunophenotype was seen both in primary tumors and two cell lines derived from these tumors. In all primary tumors, subpopulations of these CD19(+ IgM(- CD43(+ were also either B220(+ or B220(-, suggesting a block in differentiation at the pro-B cell stage. The B220(- phenotype was retained in one of the cell lines while the other was B220(+. When the two cell lines were transplanted into syngeneic mice, all animals developed the same B-lymphoblastic leukemia within 2-weeks. Thus, the murine model described here closely mimics the human disease with bilineage myeloid and B-cell leukemia/lymphoma which provides a representative model to investigate therapeutic intervention and a better understanding of the etiology of the disease.

  16. Antiatherogenic properties of calcium antagonists. State of the art.

    Science.gov (United States)

    Weinstein, D B; Heider, J G

    1989-04-17

    Atherosclerosis is an arterial disease characterized by localized accumulation of collagen, elastin, lipids, and calcium at sites associated with macrophage infiltration and altered smooth muscle metabolism. Studies in several types of animal models, especially cholesterol-fed rabbits, have shown that calcium competitors, calcium chelators, anticalcifying agents, and calcium antagonists can reduce the accumulation of atherogenic lesion components and decrease the progression of lesions. Although there are some conflicting data in the animal model studies, it is now apparent that several classes of calcium antagonists inhibit the progression of early arterial lesions induced by cholesterol-feeding in animals. The dihydropyridine class of calcium antagonists may be more potent as anti-atherosclerotic agents than the other classes. Mechanisms involving regulation of endothelial cell, smooth muscle cell, and macrophage metabolism may be responsible for the effects of calcium antagonists on early lesion progression. Recent studies in cell culture-model systems suggest that calcium antagonists may significantly alter activities that regulate lipoprotein-derived cholesterol accumulation by arterial wall cells. Some of these activities are independent of calcium flux across voltage-operated calcium channels. Thus, calcium antagonists may reduce the progression of atherogenic lesions by a combination of decreasing calcium accumulation within arterial wall cells and by altering calcium channel-independent metabolic activities, which affect lesion development.

  17. Inhibition of Intermediate-Conductance Calcium-Activated K Channel (KCa3.1) and Fibroblast Mitogenesis by α-Linolenic Acid and Alterations of Channel Expression in the Lysosomal Storage Disorders, Fabry Disease, and Niemann Pick C

    Science.gov (United States)

    Oliván-Viguera, Aida; Lozano-Gerona, Javier; López de Frutos, Laura; Cebolla, Jorge J.; Irún, Pilar; Abarca-Lachen, Edgar; García-Malinis, Ana J.; García-Otín, Ángel Luis; Gilaberte, Yolanda; Giraldo, Pilar; Köhler, Ralf

    2017-01-01

    The calcium/calmodulin-gated KCa3.1 channel regulates normal and abnormal mitogenesis by controlling K+-efflux, cell volume, and membrane hyperpolarization-driven calcium-entry. Recent studies suggest modulation of KCa3.1 by omega-3 fatty acids as negative modulators and impaired KCa3.1 functions in the inherited lysosomal storage disorder (LSD), Fabry disease (FD). In the first part of present study, we characterize KCa3.1 in murine and human fibroblasts and test the impact of omega-3 fatty acids on fibroblast proliferation. In the second, we study whether KCa3.1 is altered in the LSDs, FD, and Niemann-Pick disease type C (NPC). Our patch-clamp and mRNA-expression studies on murine and human fibroblasts show functional expression of KCa3.1. KCa currents display the typical pharmacological fingerprint of KCa3.1: Ca2+-activation, potentiation by the positive-gating modulators, SKA-31 and SKA-121, and inhibition by TRAM-34, Senicapoc (ICA-17043), and the negative-gating modulator, 13b. Considering modulation by omega-3 fatty acids we found that α-linolenic acid (α-LA) and docosahexanenoic acid (DHA) inhibit KCa3.1 currents and strongly reduce fibroblast growth. The α-LA-rich linseed oil and γ-LA-rich borage oil at 0.5% produce channel inhibition while α-LA/γ-LA-low oils has no anti-proliferative effect. Concerning KCa3.1 in LSD, mRNA expression studies, and patch-clamp on primary fibroblasts from FD and NPC patients reveal lower KCa3.1-gene expression and membrane expression than in control fibroblasts. In conclusion, the omega-3 fatty acid, α-LA, and α-LA/γ-LA-rich plant oils, inhibit fibroblast KCa3.1 channels and mitogenesis. Reduced fibroblast KCa3.1 functions are a feature and possible biomarker of cell dysfunction in FD and NPC and supports the concept that biased lipid metabolism is capable of negatively modulating KCa3.1 expression. PMID:28197106

  18. Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications.

    Science.gov (United States)

    Salanova Villanueva, Laura; Sánchez González, Carmen; Sánchez Tomero, José Antonio; Aguilera, Abelardo; Ortega Junco, Esther

    2016-01-01

    Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

  19. Integumentary loss of calcium.

    Science.gov (United States)

    Chu, J Y; Margen, S; Calloway, D H; Costa, F M

    1979-08-01

    Integumentary calcium loss was studied in 16 healthy young men. The daily loss by the 16 ambulatory but relatively sedentary young men in 52 determinations of 6-day periods each was 8.7 +/- 1.9 mg/m2 per day (average 15.8 mg/man per day). The amount lost was not influenced by calcium intake (0.1 to 2.3 g/day). In contrast to urinary calcium excretion, which is directly related to protein intake, there was no significant change in integumentary calcium loss with varying protein intakes (1 to 96 g nitrogen per day). No compensatory relationship between urinary and integumentary calcium excretion was noted. During strenuous exercise calcium loss increased to an average of 25 mg in 40 min. There was no compensatory decrease in urinary excretion on the day of strenuous exercise. It was also noted that integumentary calcium loss was not affected by general calcium balance.

  20. Calcium and Mitosis

    Science.gov (United States)

    Hepler, P.

    1983-01-01

    Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

  1. Calcium and Mitosis

    Science.gov (United States)

    Hepler, P.

    1983-01-01

    Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

  2. Use of genetically-encoded calcium indicators for live cell calcium imaging and localization in virus-infected cells.

    Science.gov (United States)

    Perry, Jacob L; Ramachandran, Nina K; Utama, Budi; Hyser, Joseph M

    2015-11-15

    Calcium signaling is a ubiquitous and versatile process involved in nearly every cellular process, and exploitation of host calcium signals is a common strategy used by viruses to facilitate replication and cause disease. Small molecule fluorescent calcium dyes have been used by many to examine changes in host cell calcium signaling and calcium channel activation during virus infections, but disadvantages of these dyes, including poor loading and poor long-term retention, complicate analysis of calcium imaging in virus-infected cells due to changes in cell physiology and membrane integrity. The recent expansion of genetically-encoded calcium indicators (GECIs), including blue and red-shifted color variants and variants with calcium affinities appropriate for calcium storage organelles like the endoplasmic reticulum (ER), make the use of GECIs an attractive alternative for calcium imaging in the context of virus infections. Here we describe the development and testing of cell lines stably expressing both green cytoplasmic (GCaMP5G and GCaMP6s) and red ER-targeted (RCEPIAer) GECIs. Using three viruses (rotavirus, poliovirus and respiratory syncytial virus) previously shown to disrupt host calcium homeostasis, we show the GECI cell lines can be used to detect simultaneous cytoplasmic and ER calcium signals. Further, we demonstrate the GECI expression has sufficient stability to enable long-term confocal imaging of both cytoplasmic and ER calcium during the course of virus infections.

  3. Practical recommendations for calcium channel antagonist poisoning

    NARCIS (Netherlands)

    Rietjens, S J; de Lange, D W; Donker, D W; Meulenbelt, J

    Calcium channel antagonists (CCAs) are widely used for different cardiovascular disorders. At therapeutic doses, CCAs have a favourable side effect profile. However, in overdose, CCAs can cause serious complications, such as severe hypotension and bradycardia. Patients in whom a moderate to severe

  4. Calcium - Function and effects

    NARCIS (Netherlands)

    Liang, Jianfen; He, Yifan; Gao, Qian; Wang, Xuan; Nout, M.J.R.

    2016-01-01

    Rice is the primary food source for more than half of the world population. Levels of calcium contents and inhibitor - phytic acid are summarized in this chapter. Phytic acid has a very strong chelating ability and it is the main inhibit factor for calcium in rice products. Calcium contents in br

  5. Calcium en cardioplegie

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Meijler, F.L.

    1985-01-01

    Coronary perfusion with a calcium-free solution, followed by reperfusion with a calcium containing solution, may result in acute myocardial cell death and in irreversible loss of the e1ectrical and mechanical activity of the heart. This phenomenon is known as the calcium paradox. A number of cardiop

  6. Vitamin D, calcium homeostasis and aging

    Science.gov (United States)

    Veldurthy, Vaishali; Wei, Ran; Oz, Leyla; Dhawan, Puneet; Jeon, Yong Heui; Christakos, Sylvia

    2016-01-01

    Osteoporosis is characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Evidence is accumulating for an important role of calcium deficiency as the process of aging is associated with disturbed calcium balance. Vitamin D is the principal factor that maintains calcium homeostasis. Increasing evidence indicates that the reason for disturbed calcium balance with age is inadequate vitamin D levels in the elderly. In this article, an overview of our current understanding of vitamin D, its metabolism, and mechanisms involved in vitamin D-mediated maintenance of calcium homeostasis is presented. In addition, mechanisms involved in age-related dysregulation of 1,25(OH)2D3 action, recommended daily doses of vitamin D and calcium, and the use of vitamin D analogs for the treatment of osteoporosis (which remains controversial) are reviewed. Elucidation of the molecular pathways of vitamin D action and modifications that occur with aging will be an active area of future research that has the potential to reveal new therapeutic strategies to maintain calcium balance. PMID:27790378

  7. Voltage-Activated Calcium Channels as Functional Markers of Mature Neurons in Human Olfactory Neuroepithelial Cells: Implications for the Study of Neurodevelopment in Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Héctor Solís-Chagoyán

    2016-06-01

    Full Text Available In adulthood, differentiation of precursor cells into neurons continues in several brain structures as well as in the olfactory neuroepithelium. Isolated precursors allow the study of the neurodevelopmental process in vitro. The aim of this work was to determine whether the expression of functional Voltage-Activated Ca2+ Channels (VACC is dependent on the neurodevelopmental stage in neuronal cells obtained from the human olfactory epithelium of a single healthy donor. The presence of channel-forming proteins in Olfactory Sensory Neurons (OSN was demonstrated by immunofluorescent labeling, and VACC functioning was assessed by microfluorometry and the patch-clamp technique. VACC were immunodetected only in OSN. Mature neurons responded to forskolin with a five-fold increase in Ca2+. By contrast, in precursor cells, a subtle response was observed. The involvement of VACC in the precursors’ response was discarded for the absence of transmembrane inward Ca2+ movement evoked by step depolarizations. Data suggest differential expression of VACC in neuronal cells depending on their developmental stage and also that the expression of these channels is acquired by OSN during maturation, to enable specialized functions such as ion movement triggered by membrane depolarization. The results support that VACC in OSN could be considered as a functional marker to study neurodevelopment.

  8. CCN3 and calcium signaling

    Directory of Open Access Journals (Sweden)

    Li Chang Long

    2003-08-01

    Full Text Available Abstract The CCN family of genes consists presently of six members in human (CCN1-6 also known as Cyr61 (Cystein rich 61, CTGF (Connective Tissue Growth Factor, NOV (Nephroblastoma Overexpressed gene, WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins. Results obtained over the past decade have indicated that CCN proteins are matricellular proteins, which are involved in the regulation of various cellular functions, such as proliferation, differentiation, survival, adhesion and migration. The CCN proteins have recently emerged as regulatory factors involved in both internal and external cell signaling. CCN3 was reported to physically interact with fibulin-1C, integrins, Notch and S100A4. Considering that, the conformation and biological activity of these proteins are dependent upon calcium binding, we hypothesized that CCN3 might be involved in signaling pathways mediated by calcium ions. In this article, we review the data showing that CCN3 regulates the levels of intracellular calcium and discuss potential models that may account for the biological effects of CCN3.

  9. The E646D-ATP13A4 mutation associated with autism reveals a defect in calcium regulation.

    Science.gov (United States)

    Vallipuram, Janaki; Grenville, Jeffrey; Crawford, Dorota A

    2010-03-01

    ATP13A4 is a member of the subfamily of P5-type ATPases. P5-type ATPases are the least studied of the P-type ATPase subfamilies with no ion specificities assigned to them. In order to elucidate ATP13A4 function, we studied the protein's subcellular localization and tested whether it is involved in calcium regulation. The intracellular calcium concentration was measured in COS-7 cells over-expressing mouse ATP13A4 using ratiometric calcium imaging with fura-2 AM as a calcium indicator. The results of this study show that ATP13A4 is localized to the endoplasmic reticulum (ER). Furthermore, we demonstrate that over-expression of ATP13A4 in COS-7 cells caused a significant increase in the intracellular calcium level. Interestingly, over-expression of the sequence variant containing a substitution of aspartic acid for a glutamic acid (E646D), previously found in patients with autism spectrum disorder (ASD), did not increase the free cellular calcium likely due to the mutation. In this study, we also describe the expression of ATP13A4 during mouse embryonic development. Quantitative real-time PCR revealed that ATP13A4 was highly expressed at embryonic days 15-17, when neurogenesis takes place. The present study is the first to provide further insights into the biological role of a P5-type ATPase. Our results demonstrate that ATP13A4 may be involved in calcium regulation and that its expression is developmentally regulated. Overall, this study provides support for the hypothesis that ATP13A4 may play a vital role in the developing nervous system and its impairment can contribute to the symptoms seen in ASD.

  10. FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats.

    Science.gov (United States)

    Xu, Jingjing; Wang, Rui; Liu, Yuan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2017-08-14

    Exposure to stressful events induces depressive-like symptoms and increases susceptibility to depression. However, the molecular mechanisms are not fully understood. Studies reported that FK506 binding protein51 (FKBP5), the co-chaperone protein of glucocorticoid receptors (GR), plays a crucial role. Further, miR-124a and miR-18a are involved in the regulation of FKBP5/GR function. However, few studies have referred to effects of early life stress on depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a in the basolateral amygdala (BLA) from adolescence to adulthood. This study aimed to examine the dynamic alternations of depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a expressions in the BLA of chronic unpredictable mild stress (CUMS) rats and dexamethasone administration rats during the adolescent period. Meanwhile, the GR antagonist, RU486, was used as a means of intervention. We found that CUMS and dexamethasone administration in the adolescent period induced permanent depressive-like behaviours and memory impairment, decreased GR expression, and increased FKBP5 and miR-124a expression in the BLA of both adolescent and adult rats. However, increased miR-18a expression in the BLA was found only in adolescent rats. Depressive-like behaviours were positively correlated with the level of miR-124a, whereas GR levels were negatively correlated with those in both adolescent and adult rats. Our results suggested FKBP5/GR and miR-124a in the BLA were associated with susceptibility to depressive disorder in the presence of stressful experiences in early life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.

    Science.gov (United States)

    Egorova, Polina; Popugaeva, Elena; Bezprozvanny, Ilya

    2015-04-01

    Neurodegenerative disorders, such as spinocerebellar ataxias (SCAs) and Alzheimer's disease (AD) represent a huge scientific and medical question, but the molecular mechanisms of these diseases are still not clear. There is increasing evidence that neuronal calcium signaling is abnormal in many neurodegenerative disorders. Abnormal neuronal calcium release from the endoplasmic reticulum may result in disturbances of cell homeostasis, synaptic dysfunction, and eventual cell death. Neuronal loss is observed in most cases of neurodegenerative diseases. Recent experimental evidence supporting the role of neuronal calcium signaling in the pathogenesis of SCAs and AD is discussed in this review.

  12. Phase-based treatment of a complex severely mentally ill case involving complex posttraumatic stress disorder and psychosis related to dandy walker syndrome

    NARCIS (Netherlands)

    Mauritz, M.W.; Sande, R. van der; Goossens, P.J.J.; Achterberg, T. van; Draijer, N.

    2014-01-01

    For patients with comorbid complex posttraumatic stress disorder (PTSD) and psychotic disorder, trauma-focused therapy may be difficult to endure. Phase-based treatment including (a) stabilization, (b) trauma-focused therapy, and (c) integration of personality with recovery of connection appears to

  13. Apatite Formation from Amorphous Calcium Phosphate and Mixed Amorphous Calcium Phosphate/Amorphous Calcium Carbonate.

    Science.gov (United States)

    Ibsen, Casper J S; Chernyshov, Dmitry; Birkedal, Henrik

    2016-08-22

    Crystallization from amorphous phases is an emerging pathway for making advanced materials. Biology has made use of amorphous precursor phases for eons and used them to produce structures with remarkable properties. Herein, we show how the design of the amorphous phase greatly influences the nanocrystals formed therefrom. We investigate the transformation of mixed amorphous calcium phosphate/amorphous calcium carbonate phases into bone-like nanocrystalline apatite using in situ synchrotron X-ray diffraction and IR spectroscopy. The speciation of phosphate was controlled by pH to favor HPO4 (2-) . In a carbonate free system, the reaction produces anisotropic apatite crystallites with large aspect ratios. The first formed crystallites are highly calcium deficient and hydrogen phosphate rich, consistent with thin octacalcium phosphate (OCP)-like needles. During growth, the crystallites become increasingly stoichiometric, which indicates that the crystallites grow through addition of near-stoichiometric apatite to the OCP-like initial crystals through a process that involves either crystallite fusion/aggregation or Ostwald ripening. The mixed amorphous phases were found to be more stable against phase transformations, hence, the crystallization was inhibited. The resulting crystallites were smaller and less anisotropic. This is rationalized by the idea that a local phosphate-depletion zone formed around the growing crystal until it was surrounded by amorphous calcium carbonate, which stopped the crystallization.

  14. Calcium Channel Blockers and Esophageal Sclerosis: Should We Expect Exacerbation of Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Charalampos Seretis

    2012-01-01

    Full Text Available Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

  15. G Protein-induced Trafficking of Voltage-dependent Calcium Channels

    National Research Council Canada - National Science Library

    Eugene Tombler; Nory Jun Cabanilla; Paul Carman; Natasha Permaul; John J. Hall; Ryan W. Richman; Jessica Lee; Jennifer Rodriguez; Dan P. Felsenfeld; Robert F. Hennigan; María A. Diversé-Pierluissi

    2006-01-01

    .... Here we report a novel mechanism for G protein-mediated modulation of neuronal voltage-dependent calcium channels that involves the destabilization and subsequent removal of calcium channels from the plasma membrane...

  16. Dysbalance of astrocyte calcium under hyperammonemic conditions.

    Directory of Open Access Journals (Sweden)

    Nicole Haack

    Full Text Available Increased brain ammonium (NH4(+/NH3 plays a central role in the manifestation of hepatic encephalopathy (HE, a complex syndrome associated with neurological and psychiatric alterations, which is primarily a disorder of astrocytes. Here, we analysed the influence of NH4(+/NH3 on the calcium concentration of astrocytes in situ and studied the underlying mechanisms of NH4(+/NH3-evoked calcium changes, employing fluorescence imaging with Fura-2 in acute tissue slices derived from different regions of the mouse brain. In the hippocampal stratum radiatum, perfusion with 5 mM NH4(+/NH3 for 30 minutes caused a transient calcium increase in about 40% of astrocytes lasting about 10 minutes. Furthermore, the vast majority of astrocytes (∼ 90% experienced a persistent calcium increase by ∼ 50 nM. This persistent increase was already evoked at concentrations of 1-2 mM NH4(+/NH3, developed within 10-20 minutes and was maintained as long as the NH4(+/NH3 was present. Qualitatively similar changes were observed in astrocytes of different neocortical regions as well as in cerebellar Bergmann glia. Inhibition of glutamine synthetase resulted in significantly larger calcium increases in response to NH4(+/NH3, indicating that glutamine accumulation was not a primary cause. Calcium increases were not mimicked by changes in intracellular pH. Pharmacological inhibition of voltage-gated sodium channels, sodium-potassium-chloride-cotransporters (NKCC, the reverse mode of sodium/calcium exchange (NCX, AMPA- or mGluR5-receptors did not dampen NH4(+/NH3-induced calcium increases. They were, however, significantly reduced by inhibition of NMDA receptors and depletion of intracellular calcium stores. Taken together, our measurements show that sustained exposure to NH4(+/NH3 causes a sustained increase in intracellular calcium in astrocytes in situ, which is partly dependent on NMDA receptor activation and on release of calcium from intracellular stores. Our study

  17. Immunogenicity of P/Q-type calcium channel in small cell lung cancer: investigation of alpha1 subunit polyglutamine expansion.

    Science.gov (United States)

    Black, J L; Nelson, T R; Snow, K; Lennon, V A

    1999-12-01

    The ectopic expression of neuronal P/Q-type voltage-gated calcium channels in small cell lung carcinoma (SCLC) is thought to induce antisynaptic autoimmunity in the paraneoplastic Lambert-Eaton myasthenic syndrome. The gene CACNL1A4, encoding the principal (alpha1A) subunit of this calcium channel, is mutated in several inherited neurological disorders. One of these disorders (spinocerebellar ataxia, type 6, or SCA-6) involves the expansion of a trinucleotide (CAG) repeat unit. We hypothesized that a somatic CAG repeat instability of this gene in neoplastic cells might generate a non-self epitope capable of initiating autoimmunity to P/Q-type calcium channels. We therefore analyzed the CACNL1A4 gene in SCLC lines established from metastases derived from seven individual patients (four associated with Lambert-Eaton myasthenic syndrome, one associated with myasthenia gravis, and two not associated with neurological autoimmunity). We compared their CAG repeat numbers (determined by polymerase chain reaction (PCR) amplification followed by separation of products on a 6% polyacrylamide/8M urea gel) to published norms and to DNA from a patient with SCA-6. The number of CAG repeats in SCLC DNA fell within a normal range whether or not the neoplasm was complicated by neurological autoimmunity. Therefore, it is unlikely that somatically unstable CAG repeat units in the gene encoding the P/Q-type voltage-gated calcium channel account for this tumor protein's immunogenicity in the Lambert-Eaton myasthenic syndrome.

  18. Common proteomic changes in the hippocampus in schizophrenia and bipolar disorder and particular evidence for involvement of cornu ammonis regions 2 and 3.

    LENUS (Irish Health Repository)

    2011-05-01

    The hippocampus is strongly implicated in schizophrenia and, to a lesser degree, bipolar disorder. Proteomic investigations of the different regions of the hippocampus may help us to clarify the basis and the disease specificity of the changes.

  19. TMJ Disorders

    Science.gov (United States)

    ... that the conditions fall into three main categories: Myofascial pain involves discomfort or pain in the muscles ... exist with TMJ disorders, such as chronic fatigue syndrome, sleep disturbances or fibromyalgia, a painful condition that ...

  20. Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

    Directory of Open Access Journals (Sweden)

    Conall M O'Seaghdha

    Full Text Available Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12, rs10491003 upstream of GATA3 (P = 4.8E-09 and rs7481584 in CARS (P = 1.2E-10 implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11, also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10 are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

  1. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2005-04-01

    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

  2. Therapeutic Strategies for Mitochondrial Dysfunction and Oxidative Stress in Age-Related Metabolic Disorders.

    Science.gov (United States)

    Bhatti, J S; Kumar, S; Vijayan, M; Bhatti, G K; Reddy, P H

    2017-01-01

    Mitochondria are complex, intercellular organelles present in the cells and are involved in multiple roles including ATP formation, free radicals generation and scavenging, calcium homeostasis, cellular differentiation, and cell death. Many studies depicted the involvement of mitochondrial dysfunction and oxidative damage in aging and pathogenesis of age-related metabolic disorders and neurodegenerative diseases. Remarkable advancements have been made in understanding the structure, function, and physiology of mitochondria in metabolic disorders such as diabetes, obesity, cardiovascular diseases, and stroke. Further, much progress has been done in the improvement of therapeutic strategies, including lifestyle interventions, pharmacological, and mitochondria-targeted therapeutic approaches. These strategies were mainly focused to reduce the mitochondrial dysfunction caused by oxidative stress and to retain the mitochondrial health in various diseases. In this chapter, we have highlighted the involvement of mitochondrial dysfunction in the pathophysiology of various disorders and recent progress in the development of mitochondria-targeted molecules as therapeutic measures for metabolic disorders.

  3. Calcium is important forus.

    Institute of Scientific and Technical Information of China (English)

    高利平

    2005-01-01

    Calcium is important for our health.We must have it in our diet to stay well.A good place to get it is from dairy products like milk, cheese and ice cream.One pound of cheese has fifty times the calcium we should have every day.Other foods have less.For example,a pound of beans also has calcium.But it has only three times the amount we ought to have daily.

  4. 腹膜透析患者钙磷代谢紊乱临床分析%A Clinical Analysis of the Disorders of Calcium and Phosphorus Metabolism Peritoneal Dialysis Patients

    Institute of Scientific and Technical Information of China (English)

    仉超; 王莹莹; 张艳玲; 唐晓红; 秦敏

    2011-01-01

    Objective To investigate the effects of physiological calcium dialysate on the calcium and phosphorus metabolism in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods We retrospectively analyzed the clinical data of 60 patients having undergone CAPD in West China Hospital of Sichuan University between January 2008 and December 2009. The patients were divided into two groups with 30 in each by calcium concentration of the dialysate: the physiological calcium dialysate group ( 1.25 mmol/L) and the standard calcium dialysate group (1.75 mmol/L). The metabolism indexes of calcium and phosphorus for the two group of patients were compared.Results Levels of Serum phosphate, calcium-phosphate product and immoreactive parathyroid hormone (iPTH) of all the patients in both groups before and after treatment showed no significant differences (P>0. 05). Sertm calcium increased significantly in patients treated with standard calcium dialysate (P < 0. 05), while it did not change significantly in patients treated with physiological calcium dialysate (P>0. 05). Conclusions Dialysate with different concentrations of calcium provides different influence on the metabolism of calcium and phosphorus. Changing calcium concentration to 1. 25 mmol/L in the dialysate can lower the calcium load for patients with hypercalcium and/or hyperphosphate with low bone turnover, providing treatment space for clinical doctors to use binders containing both calcium and phosphorus.%目的 探讨生理钙透析液对持续性不卧床腹膜透析(CAPD)患者钙磷代谢的影响.方法 回顾性分析2008年1月-2009年12月腹膜透析患者的钙磷指标,资料齐全的患者中使用钙浓度为1.25 mmol/L的腹膜透析液(生理钙组)的患者有30例,使用钙浓度为1.75 mmol/L的透析液(标准钙组)患者30例.对两组患者钙磷代谢指标进行比较.结果 治疗前后两组的血磷、钙磷乘积和全段甲状旁腺素

  5. Effects of extracellular calcium on calcium transport during hyperthermia of tumor cells.

    Science.gov (United States)

    Anghileri, L J; Marcha, C; Crone-Escanyé, M C; Robert, J

    1985-08-01

    The effects of different concentrations of extracellular ion calcium on the transport of calcium by tumor cells have been studied by means of the uptake of radiocalcium. Tumor cells incubated at 45 degrees C take up 4-10 times the amount of radioactivity incorporated by cells incubated at 37 degrees C. The difference is still greater (up to 100 times) for the intracellular incorporation as assessed by elimination of the membrane-bound calcium by EGTA treatment. The possible mechanisms involved in this differential behavior are discussed.

  6. Effects of Exterior Abscisic Acid on Calcium Distribution of Mesophyll Cells and Calcium Concentration of Guard Cells in Maize Seedlings

    Institute of Scientific and Technical Information of China (English)

    GUO Xiu-lin; MA Yuan-yuan; LIU Zi-hui; LIU Bin-hui

    2008-01-01

    In this study, the direct effects of exterior abscisic acid (ABA) on both calcium distribution of mesophyll cells and cytosolic calcium concentration of guard cells were examined. The distribution of Ca2+ localization were observed with calcium antimonate precipitate-electromicroscopic-cyto-chemical methods after treated with ABA and pretreated with ethylene glycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA), verapamil (Vp), and trifluoperazine (TFP). The laser scanning confocal microscopy was used to measure the cytosolic calcium concentrations of guard cells under different treatments. The results showed that the cytosolic Ca2+ concentration of mesophyll cells was induced to increase by ABA, but to decrease in both outside cell and the vacuoles within 10 min after treatments. The cytosolic calcium concentration of guard cells was increased gradually with the lag in treatment time. However, both EGTA and TFP could inverse those effects, indicating that the increase of cytosolic calcium induced by exterior ABA was mainly caused by calcium influx. The results also showed that calmodulin could influence both the calcium distribution of mesophyll cells and calcium concentration of guard cells. It shows that calmodulin participates in the process of ABA signal transduction, but the mechanism is not known as yet. The changes both calcium distribution of mesophyll cells and calcium concentration of guard cells further proved that the variations of cytosolic Ca2+ concentration induced by ABA were involved in the stomatal movements of maize seedlings.

  7. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibi...

  8. Extracellular calcium sensing and extracellular calcium signaling

    Science.gov (United States)

    Brown, E. M.; MacLeod, R. J.; O'Malley, B. W. (Principal Investigator)

    2001-01-01

    The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others

  9. Genetic screening of Congenital Short Bowel Syndrome patients confirms CLMP as the major gene involved in the recessive form of this disorder

    NARCIS (Netherlands)

    Alves, Maria M.; Halim, Danny; Maroofian, Reza; de Graaf, Bianca M.; Rooman, Raoul; van der Werf, Christine S.; Van de Vijver, Els; Mehrjardi, Mohammad Y. V.; Aflatoonian, Majid; Chioza, Barry A.; Baple, Emma L.; Dehghani, Mohammadreza; Crosby, Andrew H.; Hofstra, Robert M. W.

    2016-01-01

    Congenital short bowel syndrome (CSBS) is an intestinal pediatric disorder, where patients are born with a dramatic shortened small intestine. Pathogenic variants in CLMP were recently identified to cause an autosomal recessive form of the disease. However, due to the rare nature of CSBS, only a sma

  10. Glucocorticoids specifically enhance L-type calcium current amplitude and affect calcium channel subunit expression in the mouse hippocampus.

    NARCIS (Netherlands)

    Chameau, P.J.P.; Qin, Y.J.; Smit, G.; Joëls, M.

    2007-01-01

    Previous studies have shown that corticosterone enhances whole cell calcium currents in CA1 pyramidal neurons, through a pathway involving binding of glucocorticoid receptor homodimers to the DNA. We examined whether glucocorticoids show selectivity for L- over N-type of calcium currents. Moreover,

  11. Oyster shell calcium induced parotid swelling

    Directory of Open Access Journals (Sweden)

    Muthiah Palaniappan

    2014-01-01

    Full Text Available A 59 year old female consumer was started on therapy with oyster shell calcium in combination with vitamin D3 and she presented with swelling below the ear, after two doses. She stopped the drug by herself and the swelling disappeared in one day. She started the drug one day after recovery and again she developed the swelling. She was advised to stop the drug with a suggestion to take lemon to enhance parotid secretion and the swelling subsided. Calcium plays major role in salivary secretion and studies have shown reduced parotid secretion in rats, deficient of vitamin D. But in humans involvement of calcium and vitamin D3 in parotid secretion is unknown. However, the patient had no history of reaction though she had previously taken vitamin D3 with calcium carbonate which was not from oyster shell. Hence, we ruled out vitamin D3 in this reaction and suspecting oyster shell calcium as a culprit. This adverse drug reaction (ADR was assessed using World Health Organization (WHO causality assessment, Naranjo′s and Hartwig severity scales. As per WHO causality assessment scale, the ADR was classified as "certain". This reaction was analyzed as per Naranjo′s algorithm and was classified as probable. According to Hartwig′s severity scale the reaction was rated as mild. Our case is an example of a mild but rare adverse effect of oyster shell calcium carbonate which is widely used.

  12. Abnormal calcium homeostasis in peripheral neuropathies

    OpenAIRE

    2009-01-01

    Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The cent...

  13. Genes involved in pruning and inflammation are enriched in a large mega-sample of patients affected by Schizophrenia and Bipolar Disorder and controls.

    Science.gov (United States)

    Calabrò, Marco; Marco, Calabrò; Drago, Antonio; Antonio, Drago; Sidoti, Antonina; Antonina, Sidoti; Serretti, Alessandro; Alessandro, Serretti; Crisafulli, Concetta; Concetta, Crisafulli

    2015-08-30

    A molecular pathway analysis has been performed in order to complement previous genetic investigations on Schizophrenia. 4486 Schizophrenic patients and 4477 controls served as the investigation sample. 3521 Bipolar patients and 3195 controls served as replication sample. A molecular pathway associated with the neuronal pruning activity was found to be enriched in subjects with Schizophrenia compared to controls. HLA-C and HLA-DRA had more SNPs associated with both Schizophrenia and Bipolar Disorder than expected by chance.

  14. Calcium channels, neuromuscular synaptic transmission and neurological diseases.

    Science.gov (United States)

    Urbano, Francisco J; Pagani, Mario R; Uchitel, Osvaldo D

    2008-09-15

    Voltage-dependent calcium channels are essential in neuronal signaling and synaptic transmission, and their functional alterations underlie numerous human disorders whether monogenic (e.g., ataxia, migraine, etc.) or autoimmune. We review recent work on Ca(V)2.1 or P/Q channelopathies, mostly using neuromuscular junction preparations, and focus specially on the functional hierarchy among the calcium channels recruited to mediate neurotransmitter release when Ca(V)2.1 channels are mutated or depleted. In either case, synaptic transmission is greatly compromised; evidently, none of the reported functional replacements with other calcium channels compensates fully.

  15. RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders.

    Directory of Open Access Journals (Sweden)

    Mingyan Lin

    Full Text Available Genome-wide expression analysis using next generation sequencing (RNA-Seq provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs, pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ, bipolar disorder (BD and autism spectrum disorders (ASD that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients.

  16. Phase-based treatment of a complex severely mentally ill case involving complex posttraumatic stress disorder and psychosis related to Dandy Walker syndrome.

    Science.gov (United States)

    Mauritz, Maria W; van de Sande, Roland; Goossens, Peter J J; van Achterberg, Theo; Draijer, Nel

    2014-01-01

    For patients with comorbid complex posttraumatic stress disorder (PTSD) and psychotic disorder, trauma-focused therapy may be difficult to endure. Phase-based treatment including (a) stabilization, (b) trauma-focused therapy, and (c) integration of personality with recovery of connection appears to be the treatment of choice. The objective of this article is to describe and evaluate the therapeutic process of a single case from a holistic perspective. We present a case report of a 47-year-old woman treated for severe complex PTSD resulting from repeated sexual and physical abuse in early childhood and moderate psychotic symptoms stemming from Dandy Walker Syndrome with hydrocephalus. The patient was treated with quetiapine (600-1,000 mg) and citalopram (40 mg). Stabilization consisted of intensive psychiatric nursing care in the home and stabilizing group treatment for complex PTSD. After stabilization, the following symptom domains showed improvement: self-regulation, self-esteem, assertiveness, avoidance of social activities, and negative cognitions. However, intrusions and arousal persisted and were therefore subsequently treated with prolonged imaginary exposure that also included narrative writing assignments and a final closing ritual. This intensive multidisciplinary, phase-based approach proved effective: All symptoms of complex PTSD were in full remission. Social integration and recovery were promoted with the reduction of polypharmacy and the provision of social skills training and lifestyle training. The present case shows a phase-based treatment approach with multidisciplinary collaborative care to be effective for the treatment of a case of complex PTSD with comorbid psychotic disorder stemming from severe neurological impairment. Replication of this promising approach is therefore called for.

  17. Calcium and Vitamin D

    Science.gov (United States)

    ... Pizza, cheese, frozen 1 serving 115 mg Pudding, chocolate, prepared with 2% milk 4 oz 160 mg ... Treatment Medication and Treatment Adherence Calcium/Vitamin D Nutrition Overall Health Fractures/Fall Prevention Exercise/Safe Movement ...

  18. Stoichiometry of Calcium Medicines

    Science.gov (United States)

    Pinto, Gabriel

    2005-01-01

    The topic of calcium supplement and its effects on human lives is presented in the way of questions to the students. It enables the students to realize the relevance of chemistry outside the classroom surrounding.

  19. Get Enough Calcium

    Science.gov (United States)

    ... Resources You may also be interested in: Calcium: Shopping list Menopause: Questions for ... A Federal Government website managed by the U.S. Department of Health and Human Services healthfinder.gov is ...

  20. Stoichiometry of Calcium Medicines

    Science.gov (United States)

    Pinto, Gabriel

    2005-01-01

    The topic of calcium supplement and its effects on human lives is presented in the way of questions to the students. It enables the students to realize the relevance of chemistry outside the classroom surrounding.

  1. Calcium and Your Child

    Science.gov (United States)

    ... for dinner. Create mini-pizzas by topping whole-wheat English muffins or bagels with pizza sauce, low- ... Minerals Do I Need to Drink Milk? Lactose Intolerance Becoming a Vegetarian Soy Foods and Health Calcium ...

  2. Calcium and Calcium-Base Alloys

    Science.gov (United States)

    1949-01-01

    should be satisfactory, because the electrolytic process for •(!>: A. H. Everts and G. D. Baglev’, " Physical «nrt m<„.+„4 i «_ of Calcium«, Electrochem...Rev. Metalurgie , 3j2, (1), 129 (1935). 10 ^sm^mssss^ma^^ extension between two known loads, is preferable to the value of 3,700,000 p.B.i. obtained

  3. Diagnosis of calcium and phosphorus metabolism disorder in chronic renal failure and treatment with integrative traditional Chinese and western medicine%慢性肾衰竭钙磷代谢紊乱的诊断及中西医结合治疗

    Institute of Scientific and Technical Information of China (English)

    李伟; 周乐

    2013-01-01

    钙磷代谢紊乱及其骨病是慢性肾衰竭特别是透析患者的重要并发症之一。长期骨矿物质代谢异常会引起全身血管钙化,与心血管事件的发生及死亡密切相关。2009年改善全球肾脏病预后组织(KDIGO)发布了慢性肾脏病矿物质及骨代谢紊乱(CKD-MBD)的诊断、评估、预防和治疗的临床实践指南,2013年KDIGO新发布的《CKD评估与管理临床实践指南》又针对CKD骨代谢疾病提出了新的观点。治疗的重点是降低高血磷和维持血钙,控制甲状旁腺激素在目标范围。中医治疗慢性肾衰竭钙磷代谢紊乱有独到之处,通过辩证施治,同时结合必要的西药治疗,可显著改善患者的临床生化指标及自觉症状,改善预后。%Calcium and phosphorus metabolism disorder and bone disease are important complications in patients with chronic renal failure especially undergoing dialysis.Long-term metabolism disorder of bone mineral content can cause systemic vascular calcification,which is closely associated with cardiovascular events and mortality.In 2009,Kidney Disease:Improving Global Outcomes (KDIGO) published the mineral and bone disorder of chronic kidney disease (CKD)guidelines.In 201 3,KDIGO proposed some new perspectives about CKD metabolic bone diseases in “Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease”.The treatment for these complications mainly aims to decrease the high blood phosphate,maintain the level of blood calcium,and keep parathyroid hormone (PTH)within defined levels.It is unique for traditional Chinese medicine to treat the calcium and phosphorus metabolism disorder through dialectical therapy and integration with western medicine necessary, which can significantly improve the clinical symptoms,biochemical indices,and the prognosis.

  4. Role of a circadian-relevant gene NR1D1 in brain development: possible involvement in the pathophysiology of autism spectrum disorders

    Science.gov (United States)

    Goto, Masahide; Mizuno, Makoto; Matsumoto, Ayumi; Yang, Zhiliang; Jimbo, Eriko F.; Tabata, Hidenori; Yamagata, Takanori; Nagata, Koh-ichi

    2017-01-01

    In our previous study, we screened autism spectrum disorder (ASD) patients with and without sleep disorders for mutations in the coding regions of circadian-relevant genes, and detected mutations in several clock genes including NR1D1. Here, we further screened ASD patients for NR1D1 mutations and identified three novel mutations including a de novo heterozygous one c.1499 G > A (p.R500H). We then analyzed the role of Nr1d1 in the development of the cerebral cortex in mice. Acute knockdown of mouse Nr1d1 with in utero electroporation caused abnormal positioning of cortical neurons during corticogenesis. This aberrant phenotype was rescued by wild type Nr1d1, but not by the c.1499 G > A mutant. Time-lapse imaging revealed characteristic abnormal migration phenotypes in Nr1d1-deficient cortical neurons. When Nr1d1 was knocked down, axon extension and dendritic arbor formation of cortical neurons were also suppressed while proliferation of neuronal progenitors and stem cells at the ventricular zone was not affected. Taken together, Nr1d1 was found to play a pivotal role in corticogenesis via regulation of excitatory neuron migration and synaptic network formation. These results suggest that functional defects in NR1D1 may be related to ASD etiology and pathophysiology. PMID:28262759

  5. Discrete-State Stochastic Models of Calcium-Regulated Calcium Influx and Subspace Dynamics Are Not Well-Approximated by ODEs That Neglect Concentration Fluctuations

    Directory of Open Access Journals (Sweden)

    Seth H. Weinberg

    2012-01-01

    Full Text Available Cardiac myocyte calcium signaling is often modeled using deterministic ordinary differential equations (ODEs and mass-action kinetics. However, spatially restricted “domains” associated with calcium influx are small enough (e.g., 10−17 liters that local signaling may involve 1–100 calcium ions. Is it appropriate to model the dynamics of subspace calcium using deterministic ODEs or, alternatively, do we require stochastic descriptions that account for the fundamentally discrete nature of these local calcium signals? To address this question, we constructed a minimal Markov model of a calcium-regulated calcium channel and associated subspace. We compared the expected value of fluctuating subspace calcium concentration (a result that accounts for the small subspace volume with the corresponding deterministic model (an approximation that assumes large system size. When subspace calcium did not regulate calcium influx, the deterministic and stochastic descriptions agreed. However, when calcium binding altered channel activity in the model, the continuous deterministic description often deviated significantly from the discrete stochastic model, unless the subspace volume is unrealistically large and/or the kinetics of the calcium binding are sufficiently fast. This principle was also demonstrated using a physiologically realistic model of calmodulin regulation of L-type calcium channels introduced by Yue and coworkers.

  6. Follow up of low calcium dialysate and lanthanum carbonate in peritoneal dialysis patients with calcium and phosphorus metabolism disorder%腹膜透析钙磷代谢紊乱患者使用低钙腹膜透析液及碳酸镧的随访分析

    Institute of Scientific and Technical Information of China (English)

    夏阳阳; 万骋; 张庆燕; 汤天凤; 张苗

    2016-01-01

    目的:调查腹膜透析患者血钙(Ca)、血磷(P)及甲状旁腺激素的情况,并观察使用低钙腹膜透析液结合药物治疗高 Ca、高 P 及甲状旁腺功能亢进(甲旁亢)的效果。方法统计2010年以后在南京鼓楼医院规律随访一直使用普通钙腹膜透析液(钙离子浓度为1.75 mmol·L -1)1年以上时间的腹膜透析患者血 Ca、血 P 及全段甲状旁腺激素(iPTH)水平。根据患者血Ca、血 P 及 iPTH 水平挑选120例高 Ca、高 P、甲旁亢患者,随机平均分为 A、B 两组,A 组改用低钙腹膜透析液(钙离子浓度为1.25 mmol·L -1),B 组改用低钙腹膜透析液的同时加用碳酸镧降磷治疗。结果6个月后,A 组与之前比较,血 Ca 降低,血P、iPTH 升高(P <0.05),B 组与之前比较血 Ca、血 P、iPTH 降低(P <0.05),半年后 B 组与 A 组比较血 Ca、血 P、iPTH 降低(P<0.05)。结论对于出现高 Ca、高 P 及高 iPTH 的患者建议使用低钙腹膜透析液,同时必须使用碳酸镧加强降磷治疗。%Objective To investigate blood calcium,phosphate and intact parathyroid hormone(iPTH)in peritoneal dialysis patients treated at The Affiliated Drum Tower Hospital of Nanjing University Medical School,and to observe the efficacy of high blood calcium, phosphate and iPTH by using low calcium dialysate with medicine.Methods We investigated blood calcium,phosphate and iPTH in peritoneal dialysis patients who were regularly followed up at least one year using regular calcium dialysate (calcium concentration was 1.75mmol/L).One hundred and twenty patients with high calcium phosphorus and iPTH were selected,who were randomized into group A,and group B.Group A with sixty patients changed to low calcium dialysate (calcium concentration was 1.25 mmol·L -1 ), while group B with sixty patients changed to low calcium dialysate and used lanthanum carbonate at the same time.Results After six

  7. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    NARCIS (Netherlands)

    Jonge, H.J. de; Gans, R.O.; Huls, G.A.

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate ab

  8. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    NARCIS (Netherlands)

    Jonge, H.J. de; Gans, R.O.; Huls, G.A.

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate ab

  9. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    NARCIS (Netherlands)

    Jonge, H.J. de; Gans, R.O.; Huls, G.A.

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate

  10. Posttraumatic Stress Disorder and Social Support in Female Victims of Sexual Assault: The Impact of Spousal Involvement on the Efficacy of Cognitive-Behavioral Therapy

    Science.gov (United States)

    Billette, Valerie; Guay, Stephane; Marchand, Andre

    2008-01-01

    The goal of this study is to enhance the efficacy of CBT with victims of sexual assault suffering from PTSD by getting the spouse involved. Thus, in addition to attempting to reduce PTSD symptoms, the therapy focuses on improving the support offered by the spouse and favors management of the impact of the traumatic event within the couple. A…

  11. SKA2 Methylation is Involved in Cortisol Stress Reactivity and Predicts the Development of Post-Traumatic Stress Disorder (PTSD) after Military Deployment

    NARCIS (Netherlands)

    Boks, Marco P.; Rutten, Bart P F; Geuze, Elbert; Houtepen, Lotte C.; Vermetten, Eric; Kaminsky, Zachary; Vinkers, Christiaan H.

    2016-01-01

    Genomic variation in the SKA2 gene has recently been identified as a promising suicide biomarker. In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic s

  12. Lipid Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs disease, involve lipids. Lipids are fats or fat-like substances. They ...

  13. Salivary miRNA profiles identify children with autism spectrum disorder, correlate with adaptive behavior, and implicate ASD candidate genes involved in neurodevelopment.

    Science.gov (United States)

    Hicks, Steven D; Ignacio, Cherry; Gentile, Karen; Middleton, Frank A

    2016-04-22

    Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that lacks adequate screening tools, often delaying diagnosis and therapeutic interventions. Despite a substantial genetic component, no single gene variant accounts for >1 % of ASD incidence. Epigenetic mechanisms that include microRNAs (miRNAs) may contribute to the ASD phenotype by altering networks of neurodevelopmental genes. The extracellular availability of miRNAs allows for painless, noninvasive collection from biofluids. In this study, we investigated the potential for saliva-based miRNAs to serve as diagnostic screening tools and evaluated their potential functional importance. Salivary miRNA was purified from 24 ASD subjects and 21 age- and gender-matched control subjects. The ASD group included individuals with mild ASD (DSM-5 criteria and Autism Diagnostic Observation Schedule) and no history of neurologic disorder, pre-term birth, or known chromosomal abnormality. All subjects completed a thorough neurodevelopmental assessment with the Vineland Adaptive Behavior Scales at the time of saliva collection. A total of 246 miRNAs were detected and quantified in at least half the samples by RNA-Seq and used to perform between-group comparisons with non-parametric testing, multivariate logistic regression and classification analyses, as well as Monte-Carlo Cross-Validation (MCCV). The top miRNAs were examined for correlations with measures of adaptive behavior. Functional enrichment analysis of the highest confidence mRNA targets of the top differentially expressed miRNAs was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), as well as the Simons Foundation Autism Database (AutDB) of ASD candidate genes. Fourteen miRNAs were differentially expressed in ASD subjects compared to controls (p ASD demonstrated differential expression of 14 miRNAs that are expressed in the developing brain, impact mRNAs related to brain development, and correlate with

  14. OSTEOPOROSIS IN CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

    Directory of Open Access Journals (Sweden)

    S A Vladimirov

    2013-01-01

    Full Text Available Objective: to study the incidence of osteoporosis (OP in patients with calcium pyrophosphate crystal deposition disease (CPCDD. Subjects and methods. Eighty patients with CPCDD were examined. Bone mineral density (BMD of the forearm, lumbar spine, and femoral neck was determined by dual-energy X-ray absorptiometry. Laboratory diagnosis involved determination of the blood levels of C-reactive protein, parathyroid hormone, calcium, magnesium, and phosphorus and the daily urinary excretion of calcium and phosphates. Results. The patients with OP were significantly older than those with normal BMD and osteopenia. Forearm bones were the most common isolated location of OP and osteopenia. Injuries in the history, traumatic fractures, and the intake of diuretics were somewhat more common in the patients diagnosed with OP. The incidence of hyperparathyroidism did not differ significantly in the groups.

  15. Rare mutations of CACNB2 found in autism spectrum disease-affected families alter calcium channel function.

    Directory of Open Access Journals (Sweden)

    Alexandra F S Breitenkamp

    Full Text Available Autism Spectrum Disorders (ASD are complex neurodevelopmental diseases clinically defined by dysfunction of social interaction. Dysregulation of cellular calcium homeostasis might be involved in ASD pathogenesis, and genes coding for the L-type calcium channel subunits CaV1.2 (CACNA1C and CaVβ2 (CACNB2 were recently identified as risk loci for psychiatric diseases. Here, we present three rare missense mutations of CACNB2 (G167S, S197F, and F240L found in ASD-affected families, two of them described here for the first time (G167S and F240L. All these mutations affect highly conserved regions while being absent in a sample of ethnically matched controls. We suggest the mutations to be of physiological relevance since they modulate whole-cell Ba2+ currents through calcium channels when expressed in a recombinant system (HEK-293 cells. Two mutations displayed significantly decelerated time-dependent inactivation as well as increased sensitivity of voltage-dependent inactivation. In contrast, the third mutation (F240L showed significantly accelerated time-dependent inactivation. By altering the kinetic parameters, the mutations are reminiscent of the CACNA1C mutation causing Timothy Syndrome, a Mendelian disease presenting with ASD. In conclusion, the results of our first-time biophysical characterization of these three rare CACNB2 missense mutations identified in ASD patients support the hypothesis that calcium channel dysfunction may contribute to autism.

  16. Direct and Indirect Psychosocial Outcomes for Children with Autism Spectrum Disorder and their Parents Following a Parent-involved Social Skills Group Intervention.

    Science.gov (United States)

    Weiss, Jonathan A; Viecili, Michelle A; Sloman, Leon; Lunsky, Yona

    2013-11-01

    This study examined the direct and indirect outcomes of a social skills group intervention for children with high functioning autism spectrum disorders and their parents. Thirty-five children and their parents participated in the program evaluation. Children and parents completed measures of child social skills and problem behaviors. Children reported on their self-concept, and parents reported on their psychological acceptance and empowerment. Results indicate significant increases in overall child social skills according to parent and child report, in child general self-worth, and in parent service empowerment and psychological acceptance. While past program evaluations of social skills groups highlight changes in social competence, taking a broader perspective on the types of positive outcomes suggests potential benefits for both child and parent.

  17. Elemental calcium intake associated with calcium acetate/calcium carbonate in the treatment of hyperphosphatemia

    OpenAIRE

    Wilson, Rosamund J; Copley, J Brian

    2017-01-01

    Background Calcium-based and non-calcium-based phosphate binders have similar efficacy in the treatment of hyperphosphatemia; however, calcium-based binders may be associated with hypercalcemia, vascular calcification, and adynamic bone disease. Scope A post hoc analysis was carried out of data from a 16-week, Phase IV study of patients with end-stage renal disease (ESRD) who switched to lanthanum carbonate monotherapy from baseline calcium acetate/calcium carbonate monotherapy. Of the intent...

  18. Molecular neurobiological clues to the pathogenesis of bipolar disorder.

    Science.gov (United States)

    Harrison, Paul J

    2016-02-01

    Bipolar disorder is a serious psychiatric disorder, with a high heritability and unknown pathogenesis. Recent genome-wide association studies have identified the first loci, implicating genes such as CACNA1C and ANK3. The genes highlight several pathways, notably calcium signalling, as being of importance. Molecular studies suggest that the risk variants impact on gene regulation and expression. Preliminary studies using reprogrammed patient-derived cells report alterations in the transcriptome and in cellular adhesion and differentiation. Mouse models show that genes involved in circadian biology, acting via dopaminergic effects, reproduce aspects of the bipolar phenotype. These findings together represent significant advances in identification of the genetic and molecular basis of bipolar disorder, yet we are still far from an integrated, evidence-based understanding of its aetiopathogenesis.

  19. Information flow through calcium binding proteins

    Science.gov (United States)

    Bak, Ji Hyun; Bialek, William

    2013-03-01

    Calcium signaling is a ubiquitous mode of biological communication, which regulates a great variety of vital processes in living systems. Such a signal typically begins with an elementary event, in which calcium ions bind to a protein, inducing a change in the protein's structure. Information can only be lost, from what was conveyed through this initial event, as the signal is further transduced through the downstream networks. In the present work we analyze and optimize the information flow in the calcium binding process. We explicitly calculate the mutual information between the calcium concentration and the states of the protein, using a simple model for allosteric regulation in a dimeric protein. The optimal solution depends on the dynamic range of the input as well as on the timescale of signal integration. According to our result, the optimizing strategy involves allowing the calcium-binding protein to be ``activated'' by a partial occupation of its sites, and tuning independently the strengths of cooperative interactions in the binding and unbinding processes.

  20. Calcium's Role in Mechanotransduction during Muscle Development

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    Tatiana Benavides Damm

    2014-01-01

    Full Text Available Mechanotransduction is a process where cells sense their surroundings and convert the physical forces in their environment into an appropriate response. Calcium plays a crucial role in the translation of such forces to biochemical signals that control various biological processes fundamental in muscle development. The mechanical stimulation of muscle cells may for example result from stretch, electric and magnetic stimulation, shear stress, and altered gravity exposure. The response, mainly involving changes in intracellular calcium concentration then leads to a cascade of events by the activation of downstream signaling pathways. The key calcium-dependent pathways described here include the nuclear factor of activated T cells (NFAT and mitogen-activated protein kinase (MAPK activation. The subsequent effects in cellular homeostasis consist of cytoskeletal remodeling, cell cycle progression, growth, differentiation, and apoptosis, all necessary for healthy muscle development, repair, and regeneration. A deregulation from the normal process due to disuse, trauma, or disease can result in a clinical condition such as muscle atrophy, which entails a significant loss of muscle mass. In order to develop therapies against such diseased states, we need to better understand the relevance of calcium signaling and the downstream responses to mechanical forces in skeletal muscle. The purpose of this review is to discuss in detail how diverse mechanical stimuli cause changes in calcium homeostasis by affecting membrane channels and the intracellular stores, which in turn regulate multiple pathways that impart these effects and control the fate of muscle tissue.

  1. LncRNA pathway involved in premature preterm rupture of membrane (PPROM: an epigenomic approach to study the pathogenesis of reproductive disorders.

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    Xiucui Luo

    Full Text Available Preterm birth (PTB is a live birth delivered before 37 weeks of gestation (GW. About one-third of PTBs result from the preterm premature rupture of membranes (PPROM. Up to the present, the pathogenic mechanisms underlying PPROM are not clearly understood. Here, we investigated the differential expression of long chain non-coding RNAs (lncRNAs in placentas of PTBs with PPROM, and their possible involvement in the pathogenic pathways leading to PPROM. A total number of 1954, 776, and 1050 lncRNAs were identified with a microarray from placentas of PPROM (group A, which were compared to full-term birth (FTB (group B, PTB (group C, and premature rupture of membrane (PROM (group D at full-term, respectively. Instead of investigating the individual pathogenic role of each lncRNA involved in the molecular mechanism underlying PPROM, we have focused on investigating the metabolic pathways and their functions to explore what is the likely association and how they are possibly involved in the development of PPROM. Six groups, including up-regulation and down-regulation in the comparisons of A vs. B, A vs. C, and A vs. D, of pathways were analyzed. Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs. C, 18 up-regulated and 15 down-regulated in A vs. D, and 33 up-regulated and 7 down-regulated in A vs. B. Functional analysis showed pathways of infection and inflammatory response, ECM-receptor interactions, apoptosis, actin cytoskeleton, and smooth muscle contraction are the major pathogenic mechanisms involved in the development of PPROM. Characterization of these pathways through identification of lncRNAs opened new avenues for further investigating the epigenomic mechanisms of lncRNAs in PPROM as well as PTB.

  2. The Roles of Intrinsic Disorder-Based Liquid-Liquid Phase Transitions in the "Dr. Jekyll-Mr. Hyde" Behavior of Proteins Involved in Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration.

    Science.gov (United States)

    Uversky, Vladimir N

    2017-10-05

    Pathological developments leading to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are associated with misbehavior of several key proteins, such as SOD1 (superoxide dismutase 1), TARDBP/TDP-43, FUS, C9orf72, and dipeptide repeat proteins generated as a result of the translation of the intronic hexanucleotide expansions in the C9orf72 gene, PFN1 (profilin 1), GLE1 (GLE1, RNA export mediator), PURA (purine rich element binding protein A), FLCN (folliculin), RBM45 (RNA binding motif protein 45), SS18L1/CREST, HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1), HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1), ATXN2 (ataxin 2), MAPT (microtubule associated protein tau), and TIA1 (TIA1 cytotoxic granule associated RNA binding protein). Although these proteins are structurally and functionally different and have rather different pathological functions, they all possess some levels of intrinsic disorder and are either directly engaged in or are at least related to the physiological liquid-liquid phase transitions (LLPTs) leading to the formation of various proteinaceous membrane-less organelles (PMLOs), both normal and pathological. This review describes the normal and pathological functions of these ALS- and FTLD-related proteins, describes their major structural properties, glances at their intrinsic disorder status, and analyzes the involvement of these proteins in the formation of normal and pathological PMLOs, with the ultimate goal of better understanding the roles of LLPTs and intrinsic disorder in the "Dr. Jekyll-Mr. Hyde" behavior of those proteins.

  3. The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings O envolvimento do cortex orbitofrontal em transtornos psiquiátricos: uma atualização dos achados de neuroimagens

    Directory of Open Access Journals (Sweden)

    Andrea Parolin Jackowski

    2012-06-01

    Full Text Available OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC in the pathophysiology of the most prevalent psychiatric disorders (PD. METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was done up to July 2011. DISCUSSION: Structural and functional OFC abnormalities have been reported in many PD, namely schizophrenia, mood disorders, anxiety disorders, personality disorders and drug addiction. Structural magnetic resonance imaging studies have reported reduced OFC volume in patients with schizophrenia, mood disorders, PTSD, panic disorder, cluster B personality disorders and drug addiction. Furthermore, functional magnetic resonance imaging studies using cognitive paradigms have shown impaired OFC activity in all PD listed above. CONCLUSION: Neuroimaging studies have observed an important OFC involvement in a number of PD. However, future studies are clearly needed to characterize the specific role of OFC on each PD as well as understanding its role in both normal and pathological behavior, mood regulation and cognitive functioning.OBJETIVO: Relatar estudos de neuroimagens estruturais e funcionais explorando o papel potencial do córtex orbitofrontal (COF na fisiopatologia dos transtornos psiquiátricos (TP mais prevalentes. MÉTODO: Foi realizada uma revisão não sistemática da literatura no MEDLINE, usando como parâmetros os seguintes termos: "córtex orbitofrontal", "esquizofrenia", "transtorno bipolar", "depressão maior", "transtornos ansiosos", "transtornos de personalidade" e "dependência a drogas". A pesquisa eletrônica foi feita até julho de 2011. DISCUSSÃO: Foram relatadas anormalidades estruturais e funcionais do COF em muitos

  4. Differential involvement of L- and T-type Ca(2+) channels, store-operated calcium channel (TRPC) and Rho-kinase signaling pathway(s) in PGF2α-induced contractions in myometrium of non-pregnant and pregnant buffaloes (Bubalus bubalis).

    Science.gov (United States)

    Sharma, Abhishek; Nakade, Udayraj P; Jaitley, Pooja; Sharma, Vipin; Choudhury, Soumen; Garg, Satish Kumar

    2017-09-12

    This study unravels the differential involvement of calcium signaling pathway(s) in PGF2α-induced contractions in myometrium of non-pregnant and pregnant buffaloes. Compared to the myometrium of pregnant animals, myometrium of non-pregnant buffaloes was more sensitive to PGF2α-induced contractile effect as manifested by the changes in mean integral tension (MIT) and tonicity. However, phasic contraction was significantly more in myometrium of pregnant animals. The uterotonic effect of PGF2α was dependent on extracellular Ca(2+) and its influx through nifedipine-sensitive L-type Ca(2+) channels both in non-pregnant and pregnant animals, but T-type Ca(2+) channels play an additional role during pregnancy. Entry of extracellular Ca(2+) is triggered by enhanced functional involvement of Pyr3-sensitive TRPC3 channels and Rho-kinase pathways to regulate uterotonic action of PGF2α in myometrium of non-pregnant buffaloes while these are down-regulated during pregnancy as there was significantly reduced expression of Rho-A proteins in myometrium of pregnant buffaloes and down-regulation of these pathways facilitate uterine quiescence. Intracellular Ca(2+) plays minor role in myometrium of both the non-pregnant and pregnant buffaloes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Two years changes in the development of caudate nucleus are involved in restricted repetitive behaviors in 2-5-year-old children with autism spectrum disorder.

    Science.gov (United States)

    Qiu, Ting; Chang, Chen; Li, Yun; Qian, Lu; Xiao, Chao Yong; Xiao, Ting; Xiao, Xiang; Xiao, Yun Hua; Chu, Kang Kang; Lewis, Mark H; Ke, Xiaoyan

    2016-06-01

    Caudate nucleus volume is enlarged in autism spectrum disorder (ASD) and is associated with restricted and repetitive behaviors (RRBs). However, the trajectory of caudate nucleus volume in RRBs of young children remains unclear. Caudate nucleus volume was measured in 36 children with ASD and 18 matched 2-3-year-old subjects with developmentally delayed (DD) at baseline (Time 1) and at 2-year follow-up (Time 2). The differential growth rate in caudate nucleus volume was calculated. Further, the relationships between the development of caudate nucleus volume and RRBs were analyzed. Our results showed that caudate nucleus volume was significantly larger in the ASD group at both time points and the magnitude of enlargement was greater at Time 2. The rate of caudate nucleus growth during this 2-year interval was faster in children with ASD than DD. Right caudate nucleus volume growth was negatively correlated with RRBs. Findings from this study suggest developmental abnormalities of caudate nucleus volume in ASD. Longitudinal MRI studies are needed to explore the correlation between atypical growth patterns of caudate nucleus and phenotype of RRBs.

  6. Two years changes in the development of caudate nucleus are involved in restricted repetitive behaviors in 2–5-year-old children with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Ting Qiu

    2016-06-01

    Full Text Available Caudate nucleus volume is enlarged in autism spectrum disorder (ASD and is associated with restricted and repetitive behaviors (RRBs. However, the trajectory of caudate nucleus volume in RRBs of young children remains unclear. Caudate nucleus volume was measured in 36 children with ASD and 18 matched 2–3-year-old subjects with developmentally delayed (DD at baseline (Time 1 and at 2-year follow-up (Time 2. The differential growth rate in caudate nucleus volume was calculated. Further, the relationships between the development of caudate nucleus volume and RRBs were analyzed. Our results showed that caudate nucleus volume was significantly larger in the ASD group at both time points and the magnitude of enlargement was greater at Time 2. The rate of caudate nucleus growth during this 2-year interval was faster in children with ASD than DD. Right caudate nucleus volume growth was negatively correlated with RRBs. Findings from this study suggest developmental abnormalities of caudate nucleus volume in ASD. Longitudinal MRI studies are needed to explore the correlation between atypical growth patterns of caudate nucleus and phenotype of RRBs.

  7. Non-coding RNAs at the Gnas and Snrpn-Ube3a imprinted gene loci and their involvement in hereditary disorders.

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    Antonius ePlagge

    2012-11-01

    Full Text Available Non-coding RNAs (ncRNAs have long been recognized at imprinted gene loci and provided early paradigms, to investigate their functions and molecular mechanisms of action. The characteristic feature of imprinted genes, their monoallelic, parental-origin-dependent expression, is achieved through complex epigenetic regulation, which is modulated by ncRNAs. This minireview focuses on two imprinted gene clusters, in which changes in ncRNA expression contribute to human disorders. At the GNAS locus loss of NESP RNA can cause autosomal dominant Pseudohypoparathyroidism type 1b (AD-PHP-Ib, while at the SNRPN-UBE3A locus a long ncRNA and processed snoRNAs play a role in Angelman-Syndrome (AS and Prader-Willi-Syndrome (PWS. The ncRNAs silence overlapping protein-coding transcripts in sense or anti-sense orientation through changes in histone modifications as well as DNA methylation at CpG-rich sequence motifs. Their epigenetic modulatory functions are required in early development in the pre-implantation embryo or already in the parental germ cells. However, it remains unclear whether the sequence homology-carrying ncRNA itself is required, or whether the process of its transcription through other promoters causes the silencing effect.

  8. Mathematical learning disabilities and attention deficit and/or hyperactivity disorder: A study of the cognitive processes involved in arithmetic problem solving.

    Science.gov (United States)

    Iglesias-Sarmiento, Valentín; Deaño, Manuel; Alfonso, Sonia; Conde, Ángeles

    2017-02-01

    The purpose of this study was to examine the contribution of cognitive functioning to arithmetic problem solving and to explore the cognitive profiles of children with attention deficit and/or hyperactivity disorder (ADHD) and with mathematical learning disabilities (MLD). The sample was made up of a total of 90 students of 4th, 5th, and 6th grade organized in three: ADHD (n=30), MLD (n=30) and typically achieving control (TA; n=30) group. Assessment was conducted in two sessions in which the PASS processes and arithmetic problem solving were evaluated. The ADHD group's performance in planning and attention was worse than that of the control group. Children with MLD obtained poorer results than the control group in planning and simultaneous and successive processing. Executive processes predicted arithmetic problem solving in the ADHD group whereas simultaneous processing was the unique predictor in the MLD sample. Children with ADHD and with MLD showed characteristic cognitive profiles. Groups' problem-solving performance can be predicted from their cognitive functioning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Inositol trisphosphate and calcium signalling

    Science.gov (United States)

    Berridge, Michael J.

    1993-01-01

    Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals. It operates through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle. This family of intracellular calcium channels displays the regenerative process of calcium-induced calcium release responsible for the complex spatiotemporal patterns of calcium waves and oscillations. Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling.

  10. Calcium and Calcium Supplements: Achieving the Right Balance

    Science.gov (United States)

    ... bone mass, which is a risk factor for osteoporosis. Many Americans don't get enough calcium in their diets. Children and adolescent girls are at particular risk, but so are adults age 50 and older. How much calcium you ...

  11. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    Science.gov (United States)

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

    The gravimetric determination of calcium as calcium carbonate is described. This experiment is suitable for undergraduate quantitative analysis laboratories. It is less expensive than determination of chloride as silver chloride. (BB)

  12. Study on calcium homeostasis disorders of adriamycin resistant human breast cancer cells MCF-7/ADM and its mechanism%耐阿霉素人乳腺癌细胞MCF-7/ADM钙稳态失调及其机制研究

    Institute of Scientific and Technical Information of China (English)

    蔡燕飞; 陈蕴; 朱瑞宇; 马鑫; 姚晓强; 金坚

    2013-01-01

    目的 探讨耐阿霉素人乳腺癌细胞MCF-7/ADM钙稳态失调及其机制.方法 转染指示钙离子质粒GECO1.2,检测野生型和耐药型细胞中的[Ca2+]含量;通过Western blot检测瞬时受体电位离子通道(transient receptor potential channel)蛋白TRPC1、TRPC3、TRPC4、TRPC5和TRPC6在两种细胞中的表达情况;运用钙离子通道抑制剂2-APB(100μmol·L-1)抑制耐药细胞中高表达的TRPC5活性后,检测耐药细胞中的[Ca2+]含量.结果 耐药细胞中的[Ca2+]含量明显上调,并检测到TRPC5蛋白在耐药细胞中发生高表达,其活性被抑制后,耐药细胞中的[Ca2+]浓度发生下调.结论 与野生型细胞相比,耐药细胞中钙稳态失调,其原因可能是由于耐药细胞中TRPC5表达上调引起耐药细胞中[Ca2+]内流所致.提示钙稳态失调与肿瘤细胞的耐药发生有着密切关系.%Aim To investigate the calcium homeostasis disorders of adriamycin-resistant human breast cancer cells MCF-7/ADM and its mechanism. Methods Detect the ( [ Ca2+ ] ) content of wild-type and drug-resistant cells by the transformation of calcium indicator plasmid GEC01.2; Detect the expression of transient receptor potential ion channel protein TRPC1 , TRPC3 , TRPC4 , TRPC5 and TRPC6 in these two cells by Western blot; Suppress the TRPC5 activity with calcium channel inhibitor 2-APB (100 μmol · L-1 ), and then detect the ( [ Ca2+] ) content in the drug-resistant cells. Results The result shows that the significantly up-regulation of ( [ Ca2+ ] ) content in resistant cells,and the TRPC5 protein shows over-expression, but the ( [ Ca2+] ) concentration became to decrease after the inhibition of its activity. Conclusion Compared with the wild-type cells, the calcium in resistant cells became homeostasis disorder, maybe the underlying mechanism is the up-regulation of TRPC5 caused [ Ca2+ ] entry into the resistant cells. This study suggests that there must be a close relationship between calcium homeostasis

  13. Calcium Signaling and Meiotic Exit at Fertilization in Xenopus Egg

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    Alexander A. Tokmakov

    2014-10-01

    Full Text Available Calcium is a universal messenger that mediates egg activation at fertilization in all sexually reproducing species studied. However, signaling pathways leading to calcium generation and the mechanisms of calcium-induced exit from meiotic arrest vary substantially among species. Here, we review the pathways of calcium signaling and the mechanisms of meiotic exit at fertilization in the eggs of the established developmental model, African clawed frog, Xenopus laevis. We also discuss calcium involvement in the early fertilization-induced events in Xenopus egg, such as membrane depolarization, the increase in intracellular pH, cortical granule exocytosis, cortical contraction, contraction wave, cortical rotation, reformation of the nuclear envelope, sperm chromatin decondensation and sister chromatid segregation.

  14. Calcium Signaling and Meiotic Exit at Fertilization in Xenopus Egg

    Science.gov (United States)

    Tokmakov, Alexander A.; Stefanov, Vasily E.; Iwasaki, Tetsushi; Sato, Ken-Ichi; Fukami, Yasuo

    2014-01-01

    Calcium is a universal messenger that mediates egg activation at fertilization in all sexually reproducing species studied. However, signaling pathways leading to calcium generation and the mechanisms of calcium-induced exit from meiotic arrest vary substantially among species. Here, we review the pathways of calcium signaling and the mechanisms of meiotic exit at fertilization in the eggs of the established developmental model, African clawed frog, Xenopus laevis. We also discuss calcium involvement in the early fertilization-induced events in Xenopus egg, such as membrane depolarization, the increase in intracellular pH, cortical granule exocytosis, cortical contraction, contraction wave, cortical rotation, reformation of the nuclear envelope, sperm chromatin decondensation and sister chromatid segregation. PMID:25322156

  15. Indirect Effects of the Fast Track Intervention on Conduct Disorder Symptoms and Callous-Unemotional Traits: Distinct Pathways Involving Discipline and Warmth.

    Science.gov (United States)

    Pasalich, Dave S; Witkiewitz, Katie; McMahon, Robert J; Pinderhughes, Ellen E

    2016-04-01

    Little is known about intervening processes that explain how prevention programs improve particular youth antisocial outcomes. We examined whether parental harsh discipline and warmth in childhood differentially account for Fast Track intervention effects on conduct disorder (CD) symptoms and callous-unemotional (CU) traits in early adolescence. Participants included 891 high-risk kindergarteners (69% male; 51% African American) from urban and rural United States communities who were randomized into either the Fast Track intervention (n = 445) or non-intervention control (n = 446) groups. The 10-year intervention included parent management training and other services (e.g., social skills training, universal classroom curriculum) targeting various risk factors for the development of conduct problems. Harsh discipline (Grades 1 to 3) and warmth (Grades 1 and 2) were measured using parent responses to vignettes and direct observations of parent-child interaction, respectively. Parents reported on children's CD symptoms in Grade 6 and CU traits in Grade 7. Results demonstrated indirect effects of the Fast Track intervention on reducing risk for youth antisocial outcomes. That is, Fast Track was associated with lower scores on harsh discipline, which in turn predicted decreased levels of CD symptoms. In addition, Fast Track was associated with higher scores on warmth, which in turn predicted reduced levels of CU traits. Our findings inform developmental and intervention models of youth antisocial behavior by providing evidence for the differential role of harsh discipline and warmth in accounting for indirect effects of Fast Track on CD symptoms versus CU traits, respectively.

  16. Stress among Parents of Children with and without Autism Spectrum Disorder: A Comparison Involving Physiological Indicators and Parent Self-Reports.

    Science.gov (United States)

    Padden, Ciara; James, Jack E

    2017-01-01

    Parents of children with Autism Spectrum Disorder (ASD) have been reported as experiencing higher levels of stress and poorer physical health than parents of typically developing children. However, most of the relevant literature has been based on parental self-reports of stress and health. While research on physiological outcomes has grown in recent years, gaps still exist in our understanding of the physiological effects, if any, of stress related to parenting a child with ASD. The present study compared parent-reported stress, anxiety, and depression, as well as selected physiological measures of stress (i.e., cortisol, alpha-amylase, and ambulatory blood pressure and heart rate) between matched groups of parents of children with (N = 38) and without (N = 38) ASD. Participants completed questionnaires, collected saliva samples for the purpose of measuring cortisol and alpha-amylase, and wore an ambulatory blood pressure monitor for 24 h. Parents of children with ASD reported significantly higher levels of parental distress, anxiety, and depression than parents of typically developing children. Parent-reported distress, anxiety, depression, and health were not correlated with physiological measures. With the exception that parents of children with ASD had significantly lower cortisol levels 30 min after waking, no other significant group differences were found for physiological measures. Parents of children with ASD reported significantly higher use of a number of adaptive coping strategies (e.g., emotional support) in comparison to parents of typically developing children. Results are discussed in the context of implications for future research directions, stress research, and practical implications for parental support.

  17. Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in experiments involving computer-assisted self-infusion of ethanol (CASE).

    Science.gov (United States)

    Zimmermann, Ulrich S; Mick, Inge; Laucht, Manfred; Vitvitskiy, Victor; Plawecki, Martin H; Mann, Karl F; O'Connor, Sean

    2009-03-01

    Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration.

  18. Behandling af uraemisk osteodystrofi med laegemidler, som påvirker calcium-fosfor-omsaetningen

    DEFF Research Database (Denmark)

    Vestergaard, Peter; Eiken, Pia A

    2012-01-01

    This review discusses the mineral bone disorders in patients with chronic kidney disease. We focus on the management of these conditions by administration of calcium, vitamin D (ergocalciferol and cholecalciferol), vitamin D receptor activators (calcitriol, alphacalcidiol), phosphate binders...

  19. influence of foliar applications of calcium chloride and borax on fruit ...

    African Journals Online (AJOL)

    Dr. A Rab

    2011-12-16

    Dec 16, 2011 ... plants results in high cracking incidence (Li et al., 2001). Similarly, the cracked ... the calcium related physiological disorders (Fallahi et al.,. 1997). Boron is ... All nutrient solutions were prepared from AnalaR Grade chemicals.

  20. Amnestic disorders

    NARCIS (Netherlands)

    Kessels, R.P.C.; Savage, G.

    2015-01-01

    Amnestic disorders may involve deficits in the encoding or storage of information in memory, or in retrieval of information from memory. Etiologies vary and include traumatic brain injury, neurodegenerative disease, and psychiatric illness. Different forms of amnesia can be distinguished: anterograd

  1. Calcium-regulated in vivo protein phosphorylation in Zea mays L. root tips

    Science.gov (United States)

    Raghothama, K. G.; Reddy, A. S.; Friedmann, M.; Poovaiah, B. W.

    1987-01-01

    Calcium dependent protein phosphorylation was studied in corn (Zea mays L.) root tips. Prior to in vivo protein phosphorylation experiments, the effect of calcium, ethyleneglycol-bis-(beta-aminoethyl ether)-N-N' -tetraacetic acid (EGTA) and calcium ionophore (A-23187) on phosphorus uptake was studied. Calcium increased phosphorus uptake, whereas EGTA and A-23187 decreased it. Consequently, phosphorus concentration in the media was adjusted so as to attain similar uptake in different treatments. Phosphoproteins were analyzed by two-dimensional gel electrophoresis. Distinct changes in phosphorylation were observed following altered calcium levels. Calcium depletion in root tips with EGTA and A-23187 decreased protein phosphorylation. However, replenishment of calcium following EGTA and ionophore pretreatment enhanced phosphorylation of proteins. Preloading of the root tips with 32P in the presence of EGTA and A-23187 followed by a ten minute calcium treatment, resulted in increased phosphorylation indicating the involvement of calcium, calcium and calmodulin-dependent kinases. Calmodulin antagonist W-7 was effective in inhibiting calcium-promoted phosphorylation. These studies suggest a physiological role for calcium-dependent phosphorylation in calcium-mediated processes in plants.

  2. Protein ligand-tethered synthetic calcium indicator for localization control and spatiotemporal calcium imaging in plant cells.

    Science.gov (United States)

    Takaoka, Yousuke; Shigenaga, Miyuki; Imai, Masaki; Nukadzuka, Yuuki; Ishimaru, Yasuhiro; Saito, Kei; Yokoyama, Ryusuke; Nishitani, Kazuhiko; Ueda, Minoru

    2016-01-01

    In plant biology, calcium ions are involved in a variety of intriguing biological phenomena as a secondary messenger. However, most conventional calcium indicators are not applicable for plant cells because of the difficulty with their localization control in plant cells. We here introduce a method to monitor spatiotemporal Ca(2+) dynamics in living plant cells based on linking the synthetic calcium indicator Calcium Green-1 to a natural product-based protein ligand. In a proof-of-concept study using cultured BY-2 cells overexpressing the target protein for the ligand, the ligand-tethered probe accumulated in the cytosol and nucleus, and enabled real-time monitoring of the cytosolic and nucleus Ca(2+) dynamics under the physiological condition. The present strategy using ligand-tethered fluorescent sensors may be successfully applied to reveal the spatiotemporal dynamics of calcium ions in living plant cells.

  3. Calcium, vitamin D and bone

    OpenAIRE

    Borg, Andrew A.

    2012-01-01

    Calcium, protein and vitamin D are the main nutrients relevant to bone health. This short article discusses the importance of vitamin D and its relation to calcium homeostasis. The various causes, clinical manifestations and treatment are outlined.

  4. Parental Involvement

    OpenAIRE

    Ezra S Simon

    2008-01-01

    This study was conducted in Ghana to investigate, (1) factors that predict parental involvement, (2) the relationship between parental home and school involvement and the educational achievement of adolescents, (3) the relationship between parental authoritativeness and the educational achievement of adolescent students, (4) parental involvement serving as a mediator between their authoritativeness and the educational achievement of the students, and (5) whether parental involvement decreases...

  5. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma

    2006-01-01

    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to

  6. Calcium channel blockers in cardiovascular pharmacotherapy.

    Science.gov (United States)

    Godfraind, Theophile

    2014-11-01

    This paper summarizes the pharmacological properties of calcium channel blockers (CCBs), their established therapeutic uses for cardiovascular disorders and the current improvement of their clinical effects through drug combinations. Their identification resulted from study of small molecules including coronary dilators, which were named calcium antagonists. Further experiments showed that they reduced contraction of arteries by inhibiting calcium entry and by interacting with binding sites identified on voltage-dependent calcium channels. This led to the denomination calcium channel blockers. In short-term studies, by decreasing total peripheral resistance, CCBs lower arterial pressure. By unloading the heart and increasing coronary blood flow, CCBs improve myocardial oxygenation. In long-term treatment, the decrease in blood pressure is more pronounced in hypertensive than in normotensive patients. A controversy on the safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by the National Heart, Lung, and Blood Institute. There are two main types of CCBs: dihydopyridine and non-dihydropyridine; the first type is vascular selective. Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic angina. Non-dihydropyridines have the same indications plus antiarrythmic effects in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order to reach recommended blood pressure goals, there is a recent therapeutic move by combination of CCBs with other antihypertensive agents particularly with inhibitors acting at the level of the renin-angiotensin system. They are also combined with statins. Prevention of dementia has been reported in hypertensive patients treated with nitrendipine, opening a way for further studies on CCBs' beneficial effect in cognitive deterioration associated with aging.

  7. The complex nature of calcium cation interactions with phospholipid bilayers

    Science.gov (United States)

    Melcrová, Adéla; Pokorna, Sarka; Pullanchery, Saranya; Kohagen, Miriam; Jurkiewicz, Piotr; Hof, Martin; Jungwirth, Pavel; Cremer, Paul S.; Cwiklik, Lukasz

    2016-01-01

    Understanding interactions of calcium with lipid membranes at the molecular level is of great importance in light of their involvement in calcium signaling, association of proteins with cellular membranes, and membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers are used to characterize local binding sites of calcium in zwitterionic and anionic model lipid assemblies, while dynamic light scattering and zeta potential measurements are employed for macroscopic characterization of lipid vesicles in calcium-containing environments. To gain additional atomic-level information, the experiments are complemented by molecular simulations that utilize an accurate force field for calcium ions with scaled charges effectively accounting for electronic polarization effects. We demonstrate that lipid membranes have substantial calcium-binding capacity, with several types of binding sites present. Significantly, the binding mode depends on calcium concentration with important implications for calcium buffering, synaptic plasticity, and protein-membrane association. PMID:27905555

  8. High Blood Calcium (Hypercalcemia)

    Science.gov (United States)

    ... as well as kidney function and levels of calcium in your urine. Your provider may do other tests to further assess your condition, such as checking your blood levels of phosphorus (a mineral). Imaging studies also may be helpful, such as bone ...

  9. Calcium carbonate overdose

    Science.gov (United States)

    Calcium carbonate is not very poisonous. Recovery is quite likely. But, long-term overuse is more serious than a single overdose, because it can cause kidney damage. Few people die from an antacid overdose. Keep all medicines in child-proof bottles and out ...

  10. Solar Imagery - Chromosphere - Calcium

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset consists of full-disk images of the sun in Calcium (Ca) II K wavelength (393.4 nm). Ca II K imagery reveal magnetic structures of the sun from about 500...

  11. Extracellular Calcium and Magnesium

    African Journals Online (AJOL)

    i cellular and neuronal metabolism and functions. The objective of ... as having preeclampsia or eclampsia, in the same age range. ... Booking status Number (n) ("/o) Number (n) (%). Booked 7 ... is influx of calcium ions into the cell leacling to.

  12. Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

    Science.gov (United States)

    Petropoulos, Sophie; Guillemin, Claire; Ergaz, Zivanit; Dimov, Sergiy; Suderman, Matthew; Weinstein-Fudim, Liza; Ornoy, Asher; Szyf, Moshe

    2015-06-01

    Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

  13. Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

    Science.gov (United States)

    Betz, N. A.; Westhoff, B. A.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB-c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS-18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS-18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18-induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10-fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression.

  14. Calcium aluminate in alumina

    Science.gov (United States)

    Altay, Arzu

    The properties of ceramic materials are determined not only by the composition and structure of the phases present, but also by the distribution of impurities, intergranular films and second phases. The phase distribution and microstructure both depend on the fabrication techniques, the raw materials used, the phase-equilibrium relations, grain growth and sintering processes. In this dissertation research, various approaches have been employed to understand fundamental phenomena such as grain growth, impurity segregation, second-phase formation and crystallization. The materials system chosen was alumina intentionally doped with calcium. Atomic-scale structural analyses of grain boundaries in alumina were carried on the processed samples. It was found that above certain calcium concentrations, CA6 precipitated as a second phase at all sintering temperatures. The results also showed that abnormal grain growth can occur after precipitation and it is not only related to the calcium level, but it is also temperature dependent. In order to understand the formation mechanism of CA6 precipitates in calcium doped alumina samples, several studies have been carried out using either bulk materials or thin films The crystallization of CA2 and CA6 powders has been studied. Chemical processing techniques were used to synthesize the powders. It was observed that CA2 powders crystallized directly, however CA6 powders crystallized through gamma-Al 2O3 solid solution. The results of energy-loss near-edge spectrometry confirmed that gamma-Al2O3 can dissolve calcium. Calcium aluminate/alumina reaction couples have also been investigated. All reaction couples were heat treated following deposition. It was found that gamma-Al2O3 was formed at the interface as a result of the interfacial reaction between the film and the substrate. gamma-Al 2O3 at the interface was stable at much higher temperatures compared to the bulk gamma-Al2O3 formed prior to the CA6 crystallization. In order to

  15. Vitamin D-Dependent Calcium Binding Protein: Immunocytochemical Localization in Chick Kidney

    Science.gov (United States)

    Roth, Jurgen; Thorens, Bernard; Hunziker, Willi; Norman, Anthony W.; Orci, L.

    1981-10-01

    A vitamin D-dependent calcium binding protein in the chick kidney that was detected by immunocytochemical techniques was localized exclusively in the distal convoluted tubule, the initial collecting tubule, and the early part of the collecting tubule. The intercalated (mitochondria-rich) cells in these tubular segments were negative for the calcium binding protein. Subcellularly, the protein was found in the cytosol and the nucleus of the tubular cells. The results suggest a role for vitamin D-dependent calcium binding protein in intracellular calcium metabolism rather than a direct involvement in membrane-mediated calcium reabsorption in the avian kidney.

  16. Antenatal calcium intake in Malaysia.

    Science.gov (United States)

    Mahdy, Zaleha Abdullah; Basri, Hashimah; Md Isa, Zaleha; Ahmad, Shuhaila; Shamsuddin, Khadijah; Mohd Amin, Rahmah

    2014-04-01

    To determine the adequacy of antenatal calcium intake in Malaysia, and the influencing factors. A cross-sectional study was conducted among postnatal women who delivered in two tertiary hospitals. Data were collected from antenatal cards, hospital documents and diet recall on daily milk and calcium intake during pregnancy. SPSS version 19.0 was used for statistical analyses. A total of 150 women were studied. The total daily calcium intake was 834 ± 43 mg (mean ± standard error of the mean), but the calcium intake distribution curve was skewed to the right with a median intake of 725 mg daily. When calcium intake from milk and calcium supplements was excluded, the daily dietary calcium intake was only 478 ± 25 mg. Even with inclusion of milk and calcium supplements, more than a third (n=55 or 36.7%) of the women consumed less than 600 mg calcium in their daily diet. The adequacy of daily calcium intake was not influenced by maternal age, ethnicity, income or maternal job or educational status as well as parity. The daily dietary calcium intake of the Malaysian antenatal population is far from adequate without the addition of calcium supplements and milk. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  17. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

    Risnes, H.; Fjellerup, Jan Søren; Henriksen, Ulrik Birk

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...

  18. The relationship between calcium and the metabolism of plasma membrane phospholipids in hemolysis induced by brown spider venom phospholipase-D toxin.

    Science.gov (United States)

    Chaves-Moreira, Daniele; Souza, Fernanda N; Fogaça, Rosalvo T H; Mangili, Oldemir C; Gremski, Waldemiro; Senff-Ribeiro, Andrea; Chaim, Olga M; Veiga, Silvio S

    2011-09-01

    Brown spider venom phospholipase-D belongs to a family of toxins characterized as potent bioactive agents. These toxins have been involved in numerous aspects of cell pathophysiology including inflammatory response, platelet aggregation, endothelial cell hyperactivation, renal disorders, and hemolysis. The molecular mechanism by which these toxins cause hemolysis is under investigation; literature data have suggested that enzyme catalysis is necessary for the biological activities triggered by the toxin. However, the way by which phospholipase-D activity is directly related with human hemolysis has not been determined. To evaluate how brown spider venom phospholipase-D activity causes hemolysis, we examined the impact of recombinant phospholipase-D on human red blood cells. Using six different purified recombinant phospholipase-D molecules obtained from a cDNA venom gland library, we demonstrated that there is a correlation of hemolytic effect and phospholipase-D activity. Studying recombinant phospholipase-D, a potent hemolytic and phospholipase-D recombinant toxin (LiRecDT1), we determined that the toxin degrades synthetic sphingomyelin (SM), lysophosphatidylcholine (LPC), and lyso-platelet-activating factor. Additionally, we determined that the toxin degrades phospholipids in a detergent extract of human erythrocytes, as well as phospholipids from ghosts of human red blood cells. The products of the degradation of synthetic SM and LPC following recombinant phospholipase-D treatments caused hemolysis of human erythrocytes. This hemolysis, dependent on products of metabolism of phospholipids, is also dependent on calcium ion concentration because the percentage of hemolysis increased with an increase in the dose of calcium in the medium. Recombinant phospholipase-D treatment of human erythrocytes stimulated an influx of calcium into the cells that was detected by a calcium-sensitive fluorescent probe (Fluo-4). This calcium influx was shown to be channel

  19. Spectroscopic study of the inhibition of calcium oxalate calculi by Larrea tridentata

    Science.gov (United States)

    Pinales, Luis Alonso

    The causes of urolithiasis include such influences as diet, metabolic disorders, and genetic factors which have been documented as sources that aggravate urinary calculi depositions and aggregations, and, implicitly, as causes of urolithiasis. This study endeavors to detail the scientific mechanisms involved in calcium oxalate calculi formation, and, more importantly, their inhibition under growth conditions imposed by the traditional medicinal approach using the herbal extract, Larrea tridentata. The calculi were synthesized without and with Larrea tridentata infusion by employing the single diffusion gel technique. A visible decrease in calcium oxalate crystal growth with increasing amounts of Larrea tridentata herbal infusion was observed in photomicrographs, as well as a color change from white-transparent for pure crystals to light orange-brown for crystals with inhibitor. Analysis of the samples, which includes Raman, infrared absorption, scanning electron microscopy (SEM), and X-ray powder diffraction (XRD) techniques, demonstrate an overall transition in morphology of the crystals from monohydrate without herbal extract to dihydrate with inhibitor. Furthermore, the resulting data from Raman and infrared absorption support the possibilities of the influences, in this complex process, of NDGA and its derivative compounds from Larrea tridentata, and of the bonding of the magnesium of the inhibitor with the oxalate ion on the surface of the calculi crystals. This assumption corroborates well with the micrographs obtained under higher magnification, which show that the separated small crystallites consist of darker brownish cores, which we attribute to the dominance of growth inhibition by NDGA, surrounded by light transparent thin shells, which possibly correspond to passivation of the crystals by magnesium oxalate. The SEM results reveal the transformation from the dominant monoclinic structure of the calcium oxalate crystals grown alone to the tetragonal

  20. Bioceramics of calcium orthophosphates.

    Science.gov (United States)

    Dorozhkin, Sergey V

    2010-03-01

    A strong interest in use of ceramics for biomedical applications appeared in the late 1960's. Used initially as alternatives to metals in order to increase a biocompatibility of implants, bioceramics have become a diverse class of biomaterials, presently including three basic types: relatively bioinert ceramics, bioactive (or surface reactive) and bioresorbable ones. Furthermore, any type of bioceramics could be porous to provide tissue ingrowth. This review is devoted to bioceramics prepared from calcium orthophosphates, which belong to the categories of bioresorbable and bioactive compounds. During the past 30-40 years, there have been a number of major advances in this field. Namely, after the initial work on development of bioceramics that was tolerated in the physiological environment, emphasis was shifted towards the use of bioceramics that interacted with bones by forming a direct chemical bond. By the structural and compositional control, it became possible to choose whether the bioceramics of calcium orthophosphates was biologically stable once incorporated within the skeletal structure or whether it was resorbed over time. At the turn of the millennium, a new concept of calcium orthophosphate bioceramics, which is able to regenerate bone tissues, has been developed. Current biomedical applications of calcium orthophosphate bioceramics include replacements for hips, knees, teeth, tendons and ligaments, as well as repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jawbone, spinal fusion and bone fillers after tumor surgery. Potential future applications of calcium orthophosphate bioceramics will include drug-delivery systems, as well as they will become effective carriers of growth factors, bioactive peptides and/or various types of cells for tissue engineering purposes.

  1. Ionized calcium and cyclic AMP in plasma and urine. Biochemical evaluation in calcium metabolic disease.

    Science.gov (United States)

    Thode, J

    1990-01-01

    Measurement of ionized calcium and cAMP in plasma and urine are used as sensitive parameters for the evaluation of calcium disorders. Ionized calcium is accepted as the biologically active form of calcium in the extracellular fluid, while urine cAMP provides an in vivo receptor assay for the biologically active parathyroid hormone. When urine is included as part of the calcium metabolic investigation it usually requires 24 h urine collection with a variety of different laboratory tests. Ionized calcium and cAMP are described in the literature in terms of several derived quantities, nomenclatures, and units which are rather unsystematic. The author developed reliable techniques and proposed systematic names and symbols and reference values for these quantities. Due to the lack of guidelines for the collection of urines in calcium metabolic evaluation, the author presented a simplified protocol (4 h standardized urine collection). In clinical investigation plasma and urine cAMP have been used to differentiate idiopathic hypoparathyroidism from pseudohypoparathyroidism (PsHP) based on the results of i.v. injection of parathyroid hormone (PTH). Nephrogenous cAMP has also been used for the detection of primary and secondary hyperparathyroidism with a high nosographic sensitivity (90%) (Broadus). The author showed that measurement of cAMP after i.v. PTH was a reliable and sensitive test to establish the diagnosis of PsHP, and that the urinary cAMP was useful for the diagnosis of secondary hyperparathyroidism in patients with jejunoileal bypass, but could not confirm the high nosographic sensitivity for the diagnosis of primary hyperparathyroidism. Further data are needed for proper conclusion. Although pursued vigorously the research into idiopathic stone formation using different protocols has not prevented stone recurrence nor indicated where further progress might be made. For the evaluation of recurrent calcium disease, the author proposed a simplified 4 h

  2. The complex nature of calcium cation interactions with phospholipid bilayers

    OpenAIRE

    Adéla Melcrová; Sarka Pokorna; Saranya Pullanchery; Miriam Kohagen; Piotr Jurkiewicz; Martin Hof; Pavel Jungwirth; Cremer, Paul S.; Lukasz Cwiklik

    2016-01-01

    Understanding interactions of calcium with lipid membranes at the molecular level is of great importance in light of their involvement in calcium signaling, association of proteins with cellular membranes, and membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers ar...

  3. Glucocorticoids specifically enhance L-type calcium current amplitude and affect calcium channel subunit expression in the mouse hippocampus.

    Science.gov (United States)

    Chameau, Pascal; Qin, Yongjun; Spijker, Sabine; Smit, August Benjamin; Smit, Guus; Joëls, Marian

    2007-01-01

    Previous studies have shown that corticosterone enhances whole cell calcium currents in CA1 pyramidal neurons, through a pathway involving binding of glucocorticoid receptor homodimers to the DNA. We examined whether glucocorticoids show selectivity for L- over N-type of calcium currents. Moreover, we addressed the putative gene targets that eventually lead to the enhanced calcium currents. Electrophysiological recordings were performed in nucleated patches that allow excellent voltage control. Calcium currents in these patches almost exclusively involve N- and L-type channels. We found that L- but not N-type calcium currents were largely enhanced after treatment with a high dose of corticosterone sufficient to activate glucocorticoid receptors. Voltage dependency and kinetic properties of the currents were unaffected by the hormone. Nonstationary noise analysis suggests that the increased current is not caused by a larger unitary conductance, but rather to a doubling of the number of functional channels. Quantitative real-time PCR revealed that transcripts of the Ca(v)1 subunits encoding for the N- or L-type calcium channels are not upregulated in the mouse CA1 area; instead, a strong, direct, and consistent upregulation of the beta4 subunit was observed. This indicates that the corticosteroid-induced increase in number of L-type calcium channels is not caused by a simple transcriptional regulation of the pore-forming subunit of the channels.

  4. Intermittent Explosive Disorder

    Directory of Open Access Journals (Sweden)

    Lut Tamam

    2011-09-01

    Full Text Available Intermittent explosive disorder is an impulse control disorder characterized by the occurrence of discrete episodes of failure to resist aggressive impulses that result in violent assault or destruction of property. Though the prevalence intermittent explosive disorder has been reported to be relatively rare in frontier studies on the field, it is now common opinion that intermittent explosive disorder is far more common than previously thought especially in clinical psychiatry settings. Etiological studies displayed the role of both psychosocial factors like childhood traumas and biological factors like dysfunctional neurotransmitter systems and genetics. In differential diagnosis of the disorder, disorders involving agression as a symptom such as alcohol and drug intoxication, antisocial and borderline personality disorders, personality changes due to general medical conditions and behavioral disorder should be considered. A combination of pharmacological and psychotherapeutic approaches are suggested in the treatment of the disorder. This article briefly reviews the historical background, diagnostic criteria, epidemiology, etiology and treatment of intermittent explosive disorder.

  5. Calcium Biofortification: Three Pronged Molecular Approaches for Dissecting Complex Trait of Calcium Nutrition in Finger Millet (Eleusine coracana) for Devising Strategies of Enrichment of Food Crops

    Science.gov (United States)

    Sharma, Divya; Jamra, Gautam; Singh, Uma M.; Sood, Salej; Kumar, Anil

    2017-01-01

    Calcium is an essential macronutrient for plants and animals and plays an indispensable role in structure and signaling. Low dietary intake of calcium in humans has been epidemiologically linked to various diseases which can have serious health consequences over time. Major staple food-grains are poor source of calcium, however, finger millet [Eleusine coracana (L.) Gaertn.], an orphan crop has an immense potential as a nutritional security crop due to its exceptionally high calcium content. Understanding the existing genetic variation as well as molecular mechanisms underlying the uptake, transport, accumulation of calcium ions (Ca2+) in grains is of utmost importance for development of calcium bio-fortified crops. In this review, we have discussed molecular mechanisms involved in calcium accumulation and transport thoroughly, emphasized the role of molecular breeding, functional genomics and transgenic approaches to understand the intricate mechanism of calcium nutrition in finger millet. The objective is to provide a comprehensive up to date account of molecular mechanisms regulating calcium nutrition and highlight the significance of bio-fortification through identification of potential candidate genes and regulatory elements from finger millet to alleviate calcium malnutrition. Hence, finger millet could be used as a model system for explaining the mechanism of elevated calcium (Ca2+) accumulation in its grains and could pave way for development of nutraceuticals or designer crops. PMID:28144246

  6. Calcium Biofortification: Three Pronged Molecular Approaches for Dissecting Complex Trait of Calcium Nutrition in Finger Millet (Eleusine coracana) for Devising Strategies of Enrichment of Food Crops.

    Science.gov (United States)

    Sharma, Divya; Jamra, Gautam; Singh, Uma M; Sood, Salej; Kumar, Anil

    2016-01-01

    Calcium is an essential macronutrient for plants and animals and plays an indispensable role in structure and signaling. Low dietary intake of calcium in humans has been epidemiologically linked to various diseases which can have serious health consequences over time. Major staple food-grains are poor source of calcium, however, finger millet [Eleusine coracana (L.) Gaertn.], an orphan crop has an immense potential as a nutritional security crop due to its exceptionally high calcium content. Understanding the existing genetic variation as well as molecular mechanisms underlying the uptake, transport, accumulation of calcium ions (Ca(2+)) in grains is of utmost importance for development of calcium bio-fortified crops. In this review, we have discussed molecular mechanisms involved in calcium accumulation and transport thoroughly, emphasized the role of molecular breeding, functional genomics and transgenic approaches to understand the intricate mechanism of calcium nutrition in finger millet. The objective is to provide a comprehensive up to date account of molecular mechanisms regulating calcium nutrition and highlight the significance of bio-fortification through identification of potential candidate genes and regulatory elements from finger millet to alleviate calcium malnutrition. Hence, finger millet could be used as a model system for explaining the mechanism of elevated calcium (Ca(2+)) accumulation in its grains and could pave way for development of nutraceuticals or designer crops.

  7. Nanostructure of Calcium Silicate Hydrates in Cements

    KAUST Repository

    Skinner, L. B.

    2010-05-11

    Calcium silicate hydrate (CSH) is the major volume phase in the matrix of Portland cement concrete. Total x-ray scattering measurements with synchrotron x rays on synthetic CSH(I) shows nanocrystalline ordering with a particle diameter of 3.5(5) nm, similar to a size-broadened 1.1 nm tobermorite crystal structure. The CSH component in hydrated tricalcium silicate is found to be similar to CSH(I). Only a slight bend and additional disorder within the CaO sheets is required to explain its nanocrystalline structure. © 2010 The American Physical Society.

  8. Calcium signaling in taste cells.

    Science.gov (United States)

    Medler, Kathryn F

    2015-09-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

  9. Concurrent imaging of synaptic vesicle recycling and calcium dynamics.

    Directory of Open Access Journals (Sweden)

    Haiyan eLi

    2011-11-01

    Full Text Available Synaptic transmission involves the calcium-dependent release of neurotransmitter from synaptic vesicles. Genetically encoded optical probes emitting different wavelengths of fluorescent light in response to neuronal activity offer a powerful approach to understand the spatial and temporal relationship of calcium dynamics to the release of neurotransmitter in defined neuronal populations. To simultaneously image synaptic vesicle recycling and changes in cytosolic calcium, we developed a red-shifted reporter of vesicle recycling based on a vesicular glutamate transporter, VGLUT1-mOrange2 (VGLUT1-mOr2, and a presynaptically-localized green calcium indicator, synaptophysin-GCaMP3 (SyGCaMP3 with a large dynamic range. The fluorescence of VGLUT1-mOr2 is quenched by the low pH of synaptic vesicles. Exocytosis upon electrical stimulation exposes the luminal mOr2 to the neutral extracellular pH and relieves fluorescence quenching. Re-acidification of the vesicle upon endocytosis again reduces fluorescence intensity. Changes in fluorescence intensity thus monitor synaptic vesicle exo- and endocytosis, as demonstrated previously for the green VGLUT1-pHluorin. To monitor changes in calcium, we fused the synaptic vesicle protein synaptophysin to the recently improved calcium indicator GCaMP3. SyGCaMP3 is targeted to presynaptic varicosities, and exhibits changes in fluorescence in response to electrical stimulation consistent with changes in calcium concentration. Using real-time imaging of both reporters expressed in the same synapses, we determine the time course of changes in VGLUT1 recycling in relation to changes in presynaptic calcium concentration. Inhibition of P/Q- and N-type calcium channels reduces calcium levels, as well as the rate of synaptic vesicle exocytosis and the fraction of vesicles released.

  10. Microdamage induced calcium efflux from bone matrix activates intracellular calcium signaling in osteoblasts via L-type and T-type voltage-gated calcium channels.

    Science.gov (United States)

    Jung, Hyungjin; Best, Makenzie; Akkus, Ozan

    2015-07-01

    Mechanisms by which bone microdamage triggers repair response are not completely understood. It has been shown that calcium efflux ([Ca(2+)]E) occurs from regions of bone undergoing microdamage. Such efflux has also been shown to trigger intracellular calcium signaling ([Ca(2+)]I) in MC3T3-E1 cells local to damaged regions. Voltage-gated calcium channels (VGCCs) are implicated in the entry of [Ca(2+)]E to the cytoplasm. We investigated the involvement of VGCC in the extracellular calcium induced intracellular calcium response (ECIICR). MC3T3-E1 cells were subjected to one dimensional calcium efflux from their basal aspect which results in an increase in [Ca(2+)]I. This increase was concomitant with membrane depolarization and it was significantly reduced in the presence of Bepridil, a non-selective VGCC inhibitor. To identify specific type(s) of VGCC in ECIICR, the cells were treated with selective inhibitors for different types of VGCC. Significant changes in the peak intensity and the number of [Ca(2+)]I oscillations were observed when L-type and T-type specific VGCC inhibitors (Verapamil and NNC55-0396, respectively) were used. So as to confirm the involvement of L- and T-type VGCC in the context of microdamage, cells were seeded on devitalized notched bone specimen, which were loaded to induce microdamage in the presence and absence of Verapamil and NNC55-0396. The results showed significant decrease in [Ca(2+)]I activity of cells in the microdamaged regions of bone when L- and T-type blockers were applied. This study demonstrated that extracellular calcium increase in association with damage depolarizes the cell membrane and the calcium ions enter the cell cytoplasm by L- and T-type VGCCs.

  11. Tongue Disorders

    Science.gov (United States)

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  12. Mental Disorders

    Science.gov (United States)

    Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, post- ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play a ...

  13. Synthesis of calcium superoxide

    Science.gov (United States)

    Rewick, R. T.; Blucher, W. G.; Estacio, P. L.

    1972-01-01

    Efforts to prepare Ca(O2) sub 2 from reactions of calcium compounds with 100% O3 and with O(D-1) atoms generated by photolysis of O3 at 2537 A are described. Samples of Ca(OH) sub 2, CaO, CaO2, Ca metal, and mixtures containing suspected impurities to promote reaction have been treated with excess O3 under static and flow conditions in the presence and absence of UV irradiation. Studies with KO2 suggest that the superoxide anion is stable to radiation at 2537 A but reacts with oxygen atoms generated by the photolysis of O3 to form KO3. Calcium superoxide is expected to behave in an analogous.

  14. DISTILLATION OF CALCIUM

    Science.gov (United States)

    Barton, J.

    1954-07-27

    This invention relates to an improvement in the process for the purification of caicium or magnesium containing an alkali metal as impurity, which comprises distiiling a batch of the mixture in two stages, the first stage distillation being carried out in the presence of an inert gas at an absolute pressure substantially greater than the vapor pressure of calcium or maguesium at the temperature of distillation, but less than the vaper pressure at that temperature of the alkali metal impurity so that only the alkali metal is vaporized and condensed on a condensing surface. A second stage distilso that substantially only the calcium or magnesium distills under its own vapor pressure only and condenses in solid form on a lower condensing surface.

  15. Comparative impact of voltage-gated calcium channels and NMDA receptors on mitochondria-mediated neuronal injury.

    Science.gov (United States)

    Stanika, Ruslan I; Villanueva, Idalis; Kazanina, Galina; Andrews, S Brian; Pivovarova, Natalia B

    2012-05-09

    Glutamate excitotoxicity, a major component of many neurodegenerative disorders, is characterized by excessive calcium influx selectively through NMDARs. However, there is a substantial uncertainty concerning why other known routes of significant calcium entry, in particular, VGCCs, are not similarly toxic. Here, we report that in the majority of neurons in rat hippocampal and cortical cultures, maximal L-type VGCC activation induces much lower calcium loading than toxic NMDAR activation. Consequently, few depolarization-activated neurons exhibit calcium deregulation and cell death. Activation of alternative routes of calcium entry induced neuronal death in proportion to the degree of calcium loading. In a small subset of neurons, depolarization evoked stronger calcium elevations, approaching those induced by toxic NMDA. These neurons were characterized by elevated expression of VGCCs and enhanced voltage-gated calcium currents, mitochondrial dysfunction and cell death. Preventing VGCC-dependent mitochondrial calcium loading resulted in stronger cytoplasmic calcium elevations, whereas inhibiting mitochondrial calcium clearance accelerated mitochondrial depolarization. Both observations further implicate mitochondrial dysfunction in VGCC-mediated cell death. Results indicate that neuronal vulnerability tracks the extent of calcium loading but does not appear to depend explicitly on the route of calcium entry.

  16. Calcium renal lithiasis: metabolic diagnosis and medical treatment

    Directory of Open Access Journals (Sweden)

    Miguel Angel Arrabal-Polo

    Full Text Available Calcium renal lithiasis is a frequent condition that affects the worldwide population and has a high recurrence rate. Different metabolic changes may trigger the onset of calcium stone disorders, such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and others. There are also other very prevalent disorders that are associated with calcium calculi, such as arterial hypertension, obesity and loss of bone mineral density. A correct diagnosis needs to be obtained through examining the serum and urinary parameters of mineral metabolism in order to carry out adequate prevention and treatment of this condition. Once the metabolic diagnosis is known, it is possible to establish dietary and pharmacological treatment that may enable monitoring of the disease and prevent recurrence of stone formation. Some advances in treating this pathological condition have been made, and these include use of sodium alendronate in patients with calcium renal lithiasis and osteopenia/osteoporosis, or use of a combination of a thiazide with a bisphosphonate. In summary, calcium renal lithiasis often requires multidrug treatment with strict control and follow-up of patients.

  17. Calcium renal lithiasis: metabolic diagnosis and medical treatment.

    Science.gov (United States)

    Arrabal-Polo, Miguel Angel; Arrabal-Martin, Miguel; Garrido-Gomez, Juan

    2013-01-01

    Calcium renal lithiasis is a frequent condition that affects the worldwide population and has a high recurrence rate. Different metabolic changes may trigger the onset of calcium stone disorders, such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and others. There are also other very prevalent disorders that are associated with calcium calculi, such as arterial hypertension, obesity and loss of bone mineral density. A correct diagnosis needs to be obtained through examining the serum and urinary parameters of mineral metabolism in order to carry out adequate prevention and treatment of this condition. Once the metabolic diagnosis is known, it is possible to establish dietary and pharmacological treatment that may enable monitoring of the disease and prevent recurrence of stone formation. Some advances in treating this pathological condition have been made, and these include use of sodium alendronate in patients with calcium renal lithiasis and osteopenia/osteoporosis, or use of a combination of a thiazide with a bisphosphonate. In summary, calcium renal lithiasis often requires multidrug treatment with strict control and follow-up of patients.

  18. Functional Characterization of a Tomato Calcium-dependent Protein Kinase Gene, LeCPK2, Involved in Heat (Light) Stress%番茄钙依赖性蛋白激酶基因LeCPK2在热(光)胁迫中的功能鉴定

    Institute of Scientific and Technical Information of China (English)

    畅文军; 付桂; 陈鑫; 朱家红; 张治礼

    2011-01-01

    Calcium-dependent protein kinases (CDPKs) may function as calcium sensors and play important roles in the regulation of plant growth and development and in plant responses to biotic and abiotic stresses. LeCPK2 (GenBank accession No.: GQ205414) is the third CDPK gene isolated from tomato and is observed to play roles in the response to heat stress in our previous studies. To further characterize the role of Le CPK2 in heat stress, we isolated the LeCPK2 promoter by in silico cloning and investigated the physiological roles of LeCPK2 under heat stress using LeCPK2 overexpression tobacco plants. Bioinformatic analysis showed that the promoter region of LeCPK2 contained five cis-regulatory elements responsive to heat stress, which was in accord with our previous experimental results. The wild-type tobacco plants stressed by high temperature were observed to be sensitive to light and thus exhibited obvious wilt of leaves. However, the strong light would not harm the healthy wild-type plants untreated by heat. Contrarily, the Le CPK2 overexpression plants would not be harmed by high temperature and following strong light stress. A1l the results suggested that the tomato Le CPK2 may be an excellent heat (light)-tolerant gene, which was involved in the response to heat stress and can effectively protect plants from the harms of heat (light) stress. Our studies will lay a foundation for the discovery of the genetic roles and for the development and application of LeCPK2.%钙依赖性蛋白激酶(calcium-dependent protein kinases,CDPKs or CPKs)作为一类钙感知蛋白在植物的生长发育和胁迫应答中起着重要的作用.LeCPK2 (GenBank accession No.:GQ205414)是我们从番茄中分离的第3个CDPK基因,前期研究表明LeCPK2可能在植物热胁迫应答中发挥作用.为了进一步研究其在热胁迫中的功能,我们通过电子克隆的方法分离了LeCPK2的启动子序列,并通过LeCPK2过表达烟草分析其在高温胁迫中的潜在的功

  19. The contribution of the sodium-calcium exchanger (NCX) and plasma membrane Ca(2+) ATPase (PMCA) to cerebellar synapse function.

    Science.gov (United States)

    Roome, Chris J; Empson, Ruth M

    2013-01-01

    The cerebellum, a part of the brain critically involved in motor learning and sensory adaptation, expresses high levels of the sodium-calcium exchanger (NCX) and the plasma membrane calcium ATPase (PMCA). Both these transporters control calcium dynamics at a variety of synapses, and here, we draw upon the available literature to discuss how NCX and PMCA work together to shape pre-synaptic calcium dynamics at cerebellar synapses.

  20. Models of calcium signalling

    CERN Document Server

    Dupont, Geneviève; Kirk, Vivien; Sneyd, James

    2016-01-01

    This book discusses the ways in which mathematical, computational, and modelling methods can be used to help understand the dynamics of intracellular calcium. The concentration of free intracellular calcium is vital for controlling a wide range of cellular processes, and is thus of great physiological importance. However, because of the complex ways in which the calcium concentration varies, it is also of great mathematical interest.This book presents the general modelling theory as well as a large number of specific case examples, to show how mathematical modelling can interact with experimental approaches, in an interdisciplinary and multifaceted approach to the study of an important physiological control mechanism. Geneviève Dupont is FNRS Research Director at the Unit of Theoretical Chronobiology of the Université Libre de Bruxelles;Martin Falcke is head of the Mathematical Cell Physiology group at the Max Delbrück Center for Molecular Medicine, Berlin;Vivien Kirk is an Associate Professor in the Depar...

  1. A novel mutation in the calcium-sensing receptor gene in an Irish pedigree showing familial hypocalciuric hypercalcemia: a case report.

    LENUS (Irish Health Repository)

    Elamin, Wael F

    2010-01-01

    Familial hypocalciuric hypercalcemia is a rare autosomal dominant disorder characterized by asymptomatic and non-progressive hypercalcemia due to mutations of the calcium-sensing receptor gene. Disorders of calcium metabolism are very common in the elderly, and they can coexist with familial hypocalciuric hypercalcemia in affected families.

  2. G protein-induced trafficking of voltage-dependent calcium channels.

    Science.gov (United States)

    Tombler, Eugene; Cabanilla, Nory Jun; Carman, Paul; Permaul, Natasha; Hall, John J; Richman, Ryan W; Lee, Jessica; Rodriguez, Jennifer; Felsenfeld, Dan P; Hennigan, Robert F; Diversé-Pierluissi, María A

    2006-01-20

    Calcium channels are well known targets for inhibition by G protein-coupled receptors, and multiple forms of inhibition have been described. Here we report a novel mechanism for G protein-mediated modulation of neuronal voltage-dependent calcium channels that involves the destabilization and subsequent removal of calcium channels from the plasma membrane. Imaging experiments in living sensory neurons show that, within seconds of receptor activation, calcium channels are cleared from the membrane and sequestered in clathrin-coated vesicles. Disruption of the L1-CAM-ankyrin B complex with the calcium channel mimics transmitter-induced trafficking of the channels, reduces calcium influx, and decreases exocytosis. Our results suggest that G protein-induced removal of plasma membrane calcium channels is a consequence of disrupting channel-cytoskeleton interactions and might represent a novel mechanism of presynaptic inhibition.

  3. Joint involvement in Ochronosis

    OpenAIRE

    Biehl, Christoph; Thormann, U.; Madera, N.; Heiß, C

    2016-01-01

    Introduction: Ochronosis is a metabolic disorder that is usually associated with the typical brown-black colored urine and retention of phenol complexes in sclera and skin. Kidney and heart are also checked, the disease can also cause damage in these organs. The disease is less associated with degenerative changes in the joints of the limbs and the spine. Methods: We report on the progress of a patient with documented family history on alcaptonuria and joint involvement. In the age of 69 ...

  4. Calcium signalling and calcium channels: evolution and general principles.

    Science.gov (United States)

    Verkhratsky, Alexei; Parpura, Vladimir

    2014-09-15

    Calcium as a divalent cation was selected early in evolution as a signaling molecule to be used by both prokaryotes and eukaryotes. Its low cytosolic concentration likely reflects the initial concentration of this ion in the primordial soup/ocean as unicellular organisms were formed. As the concentration of calcium in the ocean subsequently increased, so did the diversity of homeostatic molecules handling calcium. This includes the plasma membrane channels that allowed the calcium entry, as well as extrusion mechanisms, i.e., exchangers and pumps. Further diversification occurred with the evolution of intracellular organelles, in particular the endoplasmic reticulum and mitochondria, which also contain channels, exchanger(s) and pumps to handle the homeostasis of calcium ions. Calcium signalling system, based around coordinated interactions of the above molecular entities, can be activated by the opening of voltage-gated channels, neurotransmitters, second messengers and/or mechanical stimulation, and as such is all-pervading pathway in physiology and pathophysiology of organisms.

  5. Elemental calcium intake associated with calcium acetate/calcium carbonate in the treatment of hyperphosphatemia

    Science.gov (United States)

    Wilson, Rosamund J; Copley, J Brian

    2017-01-01

    Background Calcium-based and non-calcium-based phosphate binders have similar efficacy in the treatment of hyperphosphatemia; however, calcium-based binders may be associated with hypercalcemia, vascular calcification, and adynamic bone disease. Scope A post hoc analysis was carried out of data from a 16-week, Phase IV study of patients with end-stage renal disease (ESRD) who switched to lanthanum carbonate monotherapy from baseline calcium acetate/calcium carbonate monotherapy. Of the intent-to-treat population (N=2520), 752 patients with recorded dose data for calcium acetate (n=551)/calcium carbonate (n=201) at baseline and lanthanum carbonate at week 16 were studied. Elemental calcium intake, serum phosphate, corrected serum calcium, and serum intact parathyroid hormone levels were analyzed. Findings Of the 551 patients with calcium acetate dose data, 271 (49.2%) had an elemental calcium intake of at least 1.5 g/day at baseline, and 142 (25.8%) had an intake of at least 2.0 g/day. Mean (95% confidence interval [CI]) serum phosphate levels were 6.1 (5.89, 6.21) mg/dL at baseline and 6.2 (6.04, 6.38) mg/dL at 16 weeks; mean (95% CI) corrected serum calcium levels were 9.3 (9.16, 9.44) mg/dL and 9.2 (9.06, 9.34) mg/dL, respectively. Of the 201 patients with calcium carbonate dose data, 117 (58.2%) had an elemental calcium intake of at least 1.5 g/day, and 76 (37.8%) had an intake of at least 2.0 g/day. Mean (95% CI) serum phosphate levels were 5.8 (5.52, 6.06) mg/dL at baseline and 5.8 (5.53, 6.05) mg/dL at week 16; mean (95% CI) corrected serum calcium levels were 9.7 (9.15, 10.25) mg/dL and 9.2 (9.06, 9.34) mg/dL, respectively. Conclusion Calcium acetate/calcium carbonate phosphate binders, taken to control serum phosphate levels, may result in high levels of elemental calcium intake. This may lead to complications related to calcium balance. PMID:28182142

  6. The Effect of Continuous Quality Improvement(CQI) on Disorders of Calcium and Phosphorus Metabolism Management in Continuous Ambulatory Peritoneal Dialysis(CAPD) Patients%持续质量改进对老年腹膜透析患者钙磷代谢紊乱的作用

    Institute of Scientific and Technical Information of China (English)

    郑设锋; 刘金女; 卢蝉; 毛红; 孙维文; 赵瑞育; 赵章健; 陈法东; 缪初升; 宋瑞芳

    2012-01-01

    Objective: To evaluate the effect of continuous quality improvement CQI ) on management of calcium and phos-phorus metabolism disorders in elderly patients undergoing peritoneal dialysis . Methods: With the use of PDCA four - step( plan, do, check and act), we designed and carried out treatments to improve calcium and phosphorus metabolism in ederly patients undergoing peritoneal dialysis. Results :45 elderly patients dialyzed for more than 3 months participated in the study. The overall incidence of calcium and phosphorus metabolism disorders got down from 82. 22% to 42. 22% after CQI. In details, the level of serum calcium reduced from ( 2. 71 ± 0. 25 )mmol/L to( 2. 52 ± 0. 31 )mmol/L in hypercalcemia group( P 3个月的老年患者参与了此项研究.经9个月CQI,各种钙磷代谢紊乱总发生率由82.22%降至42.22%(P<0.05).其中高钙血症组血钙由(2.71±0.25)mmol/L降至(2.52±0.31)mmol/L(P<0.05),低钙血症组血钙由(1.78±0.42)mmol/L升至(2.11±0.24)mmol/L(P<0.05),血磷水平由(2.13±0.62)mmol/L降至(1.67±0.53)mmol/L(P<0.05),钙磷乘积由(80.22±16.61)mg2/dl2降至(54.58±15.93)mg2/dl2(P<0.05),继发性甲状旁腺功能亢进患者的血清全段甲状旁腺素(iPTH)由(488.12±227.31)pg/ml降至(290.3±171.15)pg/ml(P<0.01),血清碱性磷酸酶水平由(108.75±35.31)U/L降至(88.75±38.14)U/L(P<0.05).有残肾功能较无残肾功能组,虽KT/V差异不大,在CQI后纠正高磷血症、高钙血症、甲状旁腺功能亢进上差异均有统计学意义(P<0.05).结论:持续质量改进措施显著改善了老年腹膜透析患者的钙磷代谢紊乱.

  7. Endoplasmic reticulum-mitochondria calcium signaling in hepatic metabolic diseases.

    Science.gov (United States)

    Rieusset, Jennifer

    2017-06-01

    The liver plays a central role in glucose homeostasis, and both metabolic inflexibility and insulin resistance predispose to the development of hepatic metabolic diseases. Mitochondria and endoplasmic reticulum (ER), which play a key role in the control of hepatic metabolism, also interact at contact points defined as mitochondria-associated membranes (MAM), in order to exchange metabolites and calcium (Ca(2+)) and regulate cellular homeostasis and signaling. Here, we overview the role of the liver in the control of glucose homeostasis, mainly focusing on the independent involvement of mitochondria, ER and Ca(2+) signaling in both healthy and pathological contexts. Then we focus on recent data highlighting MAM as important hubs for hormone and nutrient signaling in the liver, thus adapting mitochondria physiology and cellular metabolism to energy availability. Lastly, we discuss how chronic ER-mitochondria miscommunication could participate to hepatic metabolic diseases, pointing MAM interface as a potential therapeutic target for metabolic disorders. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Neuronal calcium sensor-1 deletion in the mouse decreases motivation and dopamine release in the nucleus accumbens.

    Science.gov (United States)

    Ng, Enoch; Varaschin, Rafael K; Su, Ping; Browne, Caleb J; Hermainski, Joanna; Le Foll, Bernard; Pongs, Olaf; Liu, Fang; Trudeau, Louis-Eric; Roder, John C; Wong, Albert H C

    2016-03-15

    Calcium sensors detect intracellular calcium changes and interact with downstream targets to regulate many functions. Neuronal Calcium Sensor-1 (NCS-1) or Frequenin is widely expressed in the nervous system, and involved in neurotransmission, synaptic plasticity and learning. NCS-1 interacts with and regulates dopamine D2 receptor (D2R) internalization and is implicated in disorders like schizophrenia and substance abuse. However, the role of NCS-1 in behaviors dependent on dopamine signaling in the striatum, where D2R is most highly expressed, is unknown. We show that Ncs-1 deletion in the mouse decreases willingness to work for food. Moreover, Ncs-1 knockout mice have significantly lower activity-dependent dopamine release in the nucleus accumbens core in acute slice recordings. In contrast, food preference, responding for conditioned reinforcement, ability to represent changes in reward value, and locomotor response to amphetamine are not impaired. These studies identify novel roles for NCS-1 in regulating activity-dependent striatal dopamine release and aspects of motivated behavior.

  9. A novel Toxoplasma gondii calcium-dependent protein kinase

    Directory of Open Access Journals (Sweden)

    Tzen M.

    2007-06-01

    Full Text Available Toxoplasma gondii is an obligate intracellular parasite that infects all types of cells in humans. A family of calcium-dependent protein kinases (CDPKs, previously identified as important in the development of plants and protists, was recently shown to play a role in the infectivity of apicomplexans, and in motility and host cell invasion in particular. We report here the isolation of a new calcium-dependent protein kinase gene from the human toxoplasmosis parasite, Toxoplasma gondii. The gene consists of 12 exons. The encoded protein, TgCDPK4, consists of the four characteristic domains of members of the CDPK family and is most similar to PfCDPK2 from Plasmodium falciparum. We measured TgCDPK4 activity, induced by calcium influx, using a kinase assay. A calcium chelator (EGTA inhibited this activity. These findings provide evidence of signal transduction involving members of the CDPK family in T. gondii.

  10. Effect of inhibitors on macroscopical oxidation kinetics of calcium sulfite

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yi; WANG Li-dong; WANG Xiao-ming; LI Qiang-wei; XU Pei-yao

    2005-01-01

    In the presence of inhibitors, the macroscopical oxidation kinetics of calcium sulfite, the main byproduct in wet limestone scrubbing, was studied for the first time by adding different inhibitors and varying pH, concentration of calcium sulfite, oxygen partial pressure, concentration of inhibitors and temperature. The mathematical model about the general oxidation reaction was established,which was controlled by three steps involving dissolution of calcium sulfite, mass transfer of oxygen and chemical reaction in the solution.It was concluded that the general reaction was controlled by mass transfer of oxygen under uncatalyzed conditions, while it was controlled by dissolution of calcium sulfite after adding three kinds of inhibitors. Thus, the theory was provided for investigating the mechanism and oxidation kinetics of sulfite. The beneficial references were also supplied for design of oxidation technics in the wet limestone scrubbing.

  11. 1α,25-(OH)2D3影响体外培养OB增殖分化的钙离子通道机制%Calcium channel mechanism involved in proliferation and differentiation of osteoblasts affected by 1α,25-(OH)2D3 in vitro

    Institute of Scientific and Technical Information of China (English)

    顾建红; 蒋杉杉; 王世涛; 闫汶; 王怡; 刘宗平

    2011-01-01

    为研究1α,25-(OH)2D3影响体外培养成骨细胞(Osteoblasts,OB)增殖分化是否存在L-型钙离子通道机制。在体外培养SD大鼠0B基础上,添加不同浓度的1α,,25-(OH)2D。(0、10^-9、10、10^-7mol/I。)或和10mol/OB硝苯地平(NIF)作用24、48、72h。采用MTT法测定0B增殖率,PNPP法测定碱性磷酸酶(AI。P)活性。结果显示,1α,25-(OH)2D。卉13量依赖性地抑制oB增殖、促进ALP活性;10^-8mol/LNIF单独作用亦能抑制OB增殖、促进ALP活性;并且在培养早期(24、48h)能消除10mol/L 1α,25-(OH)2D3对OB增殖的抑制效应及对ALP活性的促进效应。结果表明,1α,,25-(0H)2D3能够抑制0B增殖、促进其分化;并且此过程涉及L-型钙离子通道机制。%To study whether L-type calcium channel mechanism is involved in proliferation and differentiation of oste- oblasts fOB) affected by 1α,, 25-(OH)2D3 in vitro, different concentrations of 1α,, 25-dihydroxyvitamin D3 or and nifedipine (NIF) were added into the culture after 80% cell fusion. 24,48 and 72 h after cultured, the proliferation and the alkaline phosphatase (ALP) activity of OB were evaluated. The results showed that,1α,, 25-(OH)2 D3 inhibi- ted the proliferation and induced ALP activity dose dependently. Similarly, 10 8 mol/L NIF inhibited OB proliferation and induced ALP activity alone. At the same time,10-8 mol/L NIF eliminated the inhibitory effect on OB prolifera- tion and the promotion effect on ALP activity induced by 1α,, 25- ( OH )2 D3. It was concluded that, 1α, 25- ( OH ) 2 D3 could inhibit proliferation and induce differentiation of OB,and this process involves l.-type calcium channel mechanism.

  12. Calcium – how and why?

    Indian Academy of Sciences (India)

    J K Jaiswal

    2001-09-01

    Calcium is among the most commonly used ions, in a multitude of biological functions, so much so that it is impossible to imagine life without calcium. In this article I have attempted to address the question as to how calcium has achieved this status with a brief mention of the history of calcium research in biology. It appears that during the origin and early evolution of life the Ca2+ ion was given a unique opportunity to be used in several biological processes because of its unusual physical and chemical properties.

  13. Calcium Phosphate Biomaterials: An Update

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Current calcium phosphate (CaP) biomaterials for bone repair, substitution, augmentation and regeneration include hydroxyapatite ( HA ) from synthetic or biologic origin, beta-tricalcium phosphate ( β-TCP ) , biphasic calcium phosphate (BCP), and are available as granules, porous blocks, components of composites (CaP/polymer) cements, and as coatings on orthopedic and dental implants. Experimental calcium phosphate biomaterials include CO3- and F-substituted apatites, Mg-and Zn-substituted β-TCP, calcium phosphate glasses. This paper is a brief review of the different types of CaP biomaterials and their properties such as bioactivity, osteoconductivity, osteoinductivity.

  14. Cardiovascular Effects of Calcium Supplements

    Directory of Open Access Journals (Sweden)

    Ian R. Reid

    2013-07-01

    Full Text Available Calcium supplements reduce bone turnover and slow the rate of bone loss. However, few studies have demonstrated reduced fracture incidence with calcium supplements, and meta-analyses show only a 10% decrease in fractures, which is of borderline statistical and clinical significance. Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27%–31% increase in risk of myocardial infarction, and a 12%–20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and are consistent across the trials. Co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, vascular cells, blood coagulation and calcium-sensing receptors. Thus, the non-skeletal risks of calcium supplements appear to outweigh any skeletal benefits, and are they appear to be unnecessary for the efficacy of other osteoporosis treatments.

  15. Calcium signaling mediates cold sensing in insect tissues.

    Science.gov (United States)

    Teets, Nicholas M; Yi, Shu-Xia; Lee, Richard E; Denlinger, David L

    2013-05-28

    The ability to rapidly respond to changes in temperature is a critical adaptation for insects and other ectotherms living in thermally variable environments. In a process called rapid cold hardening (RCH), insects significantly enhance cold tolerance following brief (i.e., minutes to hours) exposure to nonlethal chilling. Although the ecological relevance of RCH is well-established, the underlying physiological mechanisms that trigger RCH are poorly understood. RCH can be elicited in isolated tissues ex vivo, suggesting cold-sensing and downstream hardening pathways are governed by brain-independent signaling mechanisms. We previously provided preliminary evidence that calcium is involved in RCH, and here we firmly establish that calcium signaling mediates cold sensing in insect tissues. In tracheal cells of the freeze-tolerant goldenrod gall fly, Eurosta solidaginis, chilling to 0 °C evoked a 40% increase in intracellular calcium concentration as determined by live-cell confocal imaging. Downstream of calcium entry, RCH conditions significantly increased the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) while reducing phosphorylation of the inhibitory Thr306 residue. Pharmacological inhibitors of calcium entry, calmodulin activation, and CaMKII activity all prevented ex vivo RCH in midgut and salivary gland tissues, indicating that calcium signaling is required for RCH to occur. Similar results were obtained for a freeze-intolerant species, adults of the flesh fly, Sarcophaga bullata, suggesting that calcium-mediated cold sensing is a general feature of insects. Our results imply that insect tissues use calcium signaling to instantly detect decreases in temperature and trigger downstream cold-hardening mechanisms.

  16. C2-domain containing calcium sensors in neuroendocrine secretion.

    Science.gov (United States)

    Pinheiro, Paulo S; Houy, Sébastien; Sørensen, Jakob B

    2016-12-01

    The molecular mechanisms for calcium-triggered membrane fusion have long been sought for, and detailed models now exist that account for at least some of the functions of the many proteins involved in the process. Key players in the fusion reaction are a group of proteins that, upon binding to calcium, trigger the merger of cargo-filled vesicles with the plasma membrane. Low-affinity, fast-kinetics calcium sensors of the synaptotagmin family - especially synaptotagmin-1 and synaptotagmin-2 - are the main calcium sensors for fast exocytosis triggering in many cell types. Their functions extend beyond fusion triggering itself, having been implicated in the calcium-dependent vesicle recruitment during activity, docking of vesicles to the plasma membrane and priming, and even in post-fusion steps, such as fusion pore expansion and endocytosis. Furthermore, synaptotagmin diversity imparts distinct properties to the release process itself. Other calcium-sensing proteins such as Munc13s and protein kinase C play important, but more indirect roles in calcium-triggered exocytosis. Because of their higher affinity, but intrinsic slower kinetics, they operate on longer temporal and spatial scales to organize assembly of the release machinery. Finally, the high-affinity synaptotagmin-7 and Doc2 (Double C2-domain) proteins are able to trigger membrane fusion in vitro, but cellular measurements in different systems show that they may participate in either fusion or vesicle priming. Here, we summarize the properties and possible interplay of (some of) the major C2-domain containing calcium sensors in calcium-triggered exocytosis. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases".

  17. Short-range intercellular calcium signaling in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R

    2005-01-01

    to osteoclasts as well. We demonstrated that paracrine action of ATP was responsible for the wave propagation, but now the purinergic P2X7 receptor was involved. Thus, the studies demonstrate that calcium signals can be propagated not only among osteoblasts, but also between osteoblasts and osteoclasts...... different mechanisms for this propagation. One mechanism involves the secretion of a nucleotide, possibly ATP, acting in an autocrine action to purinergic P2Y2 receptors on the neighboring cells, leading to intracellular IP3 generation and subsequent release of calcium from intracellular stores. The other...

  18. Calcium measurement methods

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-09-01

    Full Text Available Rightly stressed by prof. Wolfgang Walz in the Preface to the series Neuromethods series, the “careful application of methods is probably the most important step in the process of scientific inquiry”. Thus, I strongly suggest to all those interested in calcium signaling and especially to the new-comers in the hot topic of neuroscience (which has so much space even in science-society debate for its implications in legal issues and in the judge-decision process to take profit from this so well edited book. I am saying this since prof. Verkhratsky and prof. Petersen......

  19. Community involvement

    Directory of Open Access Journals (Sweden)

    Editorial Office

    1979-09-01

    Full Text Available Community involvement is the main theme of Health Year. Governments have a responsibility for the health of their people, and in this country under the present 3-tier system of government, the responsibility for the rendering of health services is divided between central, provincial and local government. However, under our democratic system, all people have the right to, and it is indeed their duty, to participate individually and collectively in the planning and implementation of services to meet their health needs. Ultimately, through involvement of individuals, families and communities, greater self-reliance is achieved leading to greater responsibility being assumed by people for their own health.

  20. Solid-state characterization of amorphous and mesomorphous calcium ketoprofen.

    Science.gov (United States)

    Atassi, Faraj; Mao, Chen; Masadeh, Ahmad S; Byrn, Stephen R

    2010-09-01

    This article is concerned with exploring the application of pair distribution in pharmaceutical analysis. The solid-state characterization of amorphous and mesomorphous (liquid crystalline) calcium ketoprofen is used as an example and the structures of the amorphous and mesomorphous phases of calcium ketoprofen are compared to that of the crystalline phase. An approach to calculating the optimal experimental parameters in pair distribution function (PDF) analysis as well as a suggested method to help assign the many different peaks in a PDF diagram of an organic material are discussed. The studied salts were analyzed by X-ray powder diffraction (XRPD), single crystal X-ray diffraction, Raman spectroscopy, polarized light microscopy (PLM), solid-state NMR (SSNMR), variable-temperature SSNMR, and PDF. Raman and SSNMR were useful techniques in identifying and differentiating the crystalline phase from the other two phases but failed, alone, to differentiate between the amorphous and mesomorphous phases. The absence of significant changes in chemical shifts in SSNMR and peak shifts in Raman spectra suggested that the differences in the molecular environment of the major chemical groups in the amorphous and mesomorphous phases were minimal. However, the broadening of the Raman and SSNMR peaks in the noncrystalline phases indicated an increase in the disorder in these systems. PDF analysis of the disordered phases revealed that upon dehydration or quench cooling where the system transformed from crystalline to become disordered, the calcium-calcium and calcium-oxygen (oxygen of the carboxylic acid) distances remained intact meanwhile the rest of the molecule became disordered. The preliminary results from variable-temperature SSNMR showed two different T(1) relaxation time profiles for the amorphous and mesomorphous phases. This was consistent with the hypothesis that part of the molecule remained ordered while the rest of the molecule became disordered and the amorphous

  1. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pantothenate, calcium chloride double salt..., calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may... information required by the Act, the following: (1) The name of the additive “calcium chloride double salt of...

  2. Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille

    2013-01-01

    BACKGROUND: Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation...... offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium...

  3. Comorbidity of bipolar disorder and eating disorders.

    Science.gov (United States)

    Álvarez Ruiz, Eva M; Gutiérrez-Rojas, Luis

    2015-01-01

    The comorbidity of bipolar disorder and eating disorders has not been studied in depth. In addition, clinical implications involved in the appearance of both disorders are very important. A systematic literature review of MEDLINE published up to September 2013 was performed, analyzing all the articles that studied the comorbidity of both conditions (bipolar disorder and eating disorders) and others research that studied the efficacy of pharmacological treatment and psychotherapy to improve these illnesses. In this review we found a high comorbidity of bipolar disorder and eating disorders, especially of bulimia nervosa and binge eating disorder. Studies show that lithium and topiramate are 2 of the more effective pharmacological agents in the treatment of both disorders. There are a lot of studies that show evidence of comorbidity of bipolar disorder and eating disorders. However, further research is needed on assessment and treatment when these conditions co-exist, as well as study into the biopsychological aspects to determine the comorbid aetiology. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

  4. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

    ... in Balance › Vitamin D, Calcium, and Bone Health Vitamin D, Calcium, and Bone Health March 2012 Download ... also helps keep your bones strong. Why are vitamin D and calcium important to bone health? Vitamin ...

  5. Calcium, vitamin D, and your bones

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000490.htm Calcium, vitamin D, and your bones To use the sharing ... and maintain strong bones. How Much Calcium and Vitamin D do I Need? Amounts of calcium are ...

  6. Carboxylic Acid Ionophores as Probes of the Role of Calcium in Biological Systems

    Science.gov (United States)

    Reed, P. W.

    1983-01-01

    The biological effects of calcium ionophores are described, focusing on arachidonic acid oxygenation, and the formation of a number of oxygenated metabolites of arachidonic acid. These metabolites are involved in a number of bodily functions, and their production may be regulated by calcium.

  7. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual

    OpenAIRE

    Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward; Wysolmerski, John

    2013-01-01

    To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate ...

  8. Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR gene.

    Directory of Open Access Journals (Sweden)

    Karen Kapur

    2010-07-01

    Full Text Available Calcium has a pivotal role in biological functions, and serum calcium levels have been associated with numerous disorders of bone and mineral metabolism, as well as with cardiovascular mortality. Here we report results from a genome-wide association study of serum calcium, integrating data from four independent cohorts including a total of 12,865 individuals of European and Indian Asian descent. Our meta-analysis shows that serum calcium is associated with SNPs in or near the calcium-sensing receptor (CASR gene on 3q13. The top hit with a p-value of 6.3 x 10(-37 is rs1801725, a missense variant, explaining 1.26% of the variance in serum calcium. This SNP had the strongest association in individuals of European descent, while for individuals of Indian Asian descent the top hit was rs17251221 (p = 1.1 x 10(-21, a SNP in strong linkage disequilibrium with rs1801725. The strongest locus in CASR was shown to replicate in an independent Icelandic cohort of 4,126 individuals (p = 1.02 x 10(-4. This genome-wide meta-analysis shows that common CASR variants modulate serum calcium levels in the adult general population, which confirms previous results in some candidate gene studies of the CASR locus. This study highlights the key role of CASR in calcium regulation.

  9. 21 CFR 184.1191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the...

  10. Evolution of the Calcium Paradigm: The Relation between Vitamin D, Serum Calcium and Calcium Absorption

    Directory of Open Access Journals (Sweden)

    Borje E. Christopher Nordin

    2010-09-01

    Full Text Available Osteoporosis is the index disease for calcium deficiency, just as rickets/osteomalacia is the index disease for vitamin D deficiency, but there is considerable overlap between them. The common explanation for this overlap is that hypovitaminosis D causes malabsorption of calcium which then causes secondary hyperparathyroidism and is effectively the same thing as calcium deficiency. This paradigm is incorrect. Hypovitaminosis D causes secondary hyperparathyroidism at serum calcidiol levels lower than 60 nmol/L long before it causes malabsorption of calcium because serum calcitriol (which controls calcium absorption is maintained until serum calcidiol falls below 20 nmol/L. This secondary hyperparathyroidism, probably due to loss of a “calcaemic” action of vitamin D on bone first described in 1957, destroys bone and explains why vitamin D insufficiency is a risk factor for osteoporosis. Vitamin D thus plays a central role in the maintenance of the serum (ionised calcium, which is more important to the organism than the preservation of the skeleton. Bone is sacrificed when absorbed dietary calcium does not match excretion through the skin, kidneys and bowel which is why calcium deficiency causes osteoporosis in experimental animals and, by implication, in humans.

  11. Inflammatory mediators alter the astrocyte transcriptome and calcium signaling elicited by multiple G-protein-coupled receptors.

    Science.gov (United States)

    Hamby, Mary E; Coppola, Giovanni; Ao, Yan; Geschwind, Daniel H; Khakh, Baljit S; Sofroniew, Michael V

    2012-10-17

    Inflammation features in CNS disorders such as stroke, trauma, neurodegeneration, infection, and autoimmunity in which astrocytes play critical roles. To elucidate how inflammatory mediators alter astrocyte functions, we examined effects of transforming growth factor-β1 (TGF-β1), lipopolysaccharide (LPS), and interferon-gamma (IFNγ), alone and in combination, on purified, mouse primary cortical astrocyte cultures. We used microarrays to conduct whole-genome expression profiling, and measured calcium signaling, which is implicated in mediating dynamic astrocyte functions. Combinatorial exposure to TGF-β1, LPS, and IFNγ significantly modulated astrocyte expression of >6800 gene probes, including >380 synergistic changes not predicted by summing individual treatment effects. Bioinformatic analyses revealed significantly and markedly upregulated molecular networks and pathways associated in particular with immune signaling and regulation of cell injury, death, growth, and proliferation. Highly regulated genes included chemokines, growth factors, enzymes, channels, transporters, and intercellular and intracellular signal transducers. Notably, numerous genes for G-protein-coupled receptors (GPCRs) and G-protein effectors involved in calcium signaling were significantly regulated, mostly down (for example, Cxcr4, Adra2a, Ednra, P2ry1, Gnao1, Gng7), but some up (for example, P2ry14, P2ry6, Ccrl2, Gnb4). We tested selected cases and found that changes in GPCR gene expression were accompanied by significant, parallel changes in astrocyte calcium signaling evoked by corresponding GPCR-specific ligands. These findings identify pronounced changes in the astrocyte transcriptome induced by TGF-β1, LPS, and IFNγ, and show that these inflammatory stimuli upregulate astrocyte molecular networks associated with immune- and injury-related functions and significantly alter astrocyte calcium signaling stimulated by multiple GPCRs.

  12. Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure

    Science.gov (United States)

    Lu, Luyao; Xia, Ling; Ye, Xuesong; Cheng, Heping

    2010-06-01

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion-reaction equations presented by Izu et al (2001 Biophys. J. 80 103-20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca2+ pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca2+ leak in the form of Ca2+ quarks, increase the probability of occurrence of spontaneous Ca2+ waves even with smaller SR Ca2+ stores, accelerate Ca2+ wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca2+ wave model under HF conditions provides a new view of Ca2+ dynamics that could not be mimicked by adjusting traditional parameters involved in Ca2+ release units and other ion channels, and contributes to understanding the underlying mechanism of HF.

  13. Bipolar disorder

    Science.gov (United States)

    Manic depression; Bipolar affective disorder; Mood disorder - bipolar; Manic depressive disorder ... Fatigue or lack of energy Feelings of worthlessness, hopelessness, or guilt Loss of pleasure in activities once ...

  14. Hypercalcemic Disorders in Children

    DEFF Research Database (Denmark)

    Stokes, Victoria J; Nielsen, Morten F; Hannan, Fadil M

    2017-01-01

    , and familial isolated primary hyperparathyroidism, and less commonly, as part of inherited complex syndromic disorders such as multiple endocrine neoplasia (MEN). Advances in identifying the genetic causes have resulted in increased understanding of the underlying biological pathways and improvements......Hypercalcemia is defined as a serum calcium concentration that is greater than 2 standard deviations above the normal mean, which in children may vary with age and sex, reflecting changes in the normal physiology at each developmental stage. Hypercalcemic disorders in children may present......-independent hypercalcemia in children include hypervitaminosis; granulomatous disorders and endocrinopathies. Congenital syndromes associated with PTH-independent hypercalcemia include idiopathic infantile hypercalcemia (IIH); William's syndrome; and inborn errors of metabolism. PTH-dependent hypercalcemia is usually...

  15. New Role of P/Q-type Voltage-gated Calcium Channels

    DEFF Research Database (Denmark)

    Hansen, Pernille B L

    2015-01-01

    Voltage-gated calcium channels are important for the depolarization-evoked contraction of vascular smooth muscle cells (SMCs), with L-type channels being the classical channel involved in this mechanism. However, it has been demonstrated that the CaV2.1 subunit, which encodes a neuronal isoform...... of the voltage-gated calcium channels (P/Q-type), is also expressed and contributes functionally to contraction of renal blood vessels in both mice and humans. Furthermore, preglomerular vascular SMCs and aortic SMCs coexpress L-, P-, and Q-type calcium channels within the same cell. Calcium channel blockers...... are widely used as pharmacological treatments. However, calcium channel antagonists vary in their selectivity for the various calcium channel subtypes, and the functional contribution from P/Q-type channels as compared with L-type should be considered. Confirming the presence of P/Q-type voltage...

  16. A toxin from the spider Phoneutria nigriventer that blocks calcium channels coupled to exocytosis

    Science.gov (United States)

    Guatimosim, C; Romano-Silva, M A; Cruz, J S; Beirão, P S L; Kalapothakis, E; Moraes-Santos, T; Cordeiro, M N; Diniz, C R; Gomez, M V; Prado, M A M

    1997-01-01

    The aim of the present experiments was to investigate the pharmacological action of a toxin from the spider Phoneutria nigriventer, Tx3-3, on the function of calcium channels that control exocytosis of synaptic vesicles. Tx3-3, in confirmation of previous work, diminished the intracellular calcium increase induced by membrane depolarization with KCl (25 mM) in rat cerebrocortical synaptosomes. The toxin was very potent (IC50 0.9 nM) at inhibiting calcium channels that regulate calcium entry in synaptosomes. In addition, Tx3-3 blocked the exocytosis of synaptic vesicles, as measured with the fluorescent dye FM1-43. Using ω-toxins that interact selectively with distinct neuronal calcium channels, we investigated whether the target of Tx3-3 overlaps with known channels that mediate exocytosis. The results indicate that the main population of voltage-sensitive calcium channels altered by Tx3-3 can also be inhibited by ω-agatoxin IVA, an antagonist of P/Q calcium channels. ω-conotoxin GVIA, which inhibits N type calcium channels did not decrease significantly the entry of calcium or exocytosis of synaptic vesicles in depolarized synaptosomes. It is concluded that Tx3-3 potently inhibits ω-agatoxin IVA-sensitive calcium channels, which are involved in controlling exocytosis in rat brain cortical synaptosomes. PMID:9351520

  17. The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia

    Science.gov (United States)

    Nikawa, Takeshi; Choi, Inho; Haruna, Marie; Hirasaka, Katsuya; Maita Ohno, Ayako; Kondo Teshima, Shigetada

    Overloaded mitochondrial calcium concentration contributes to progression of mitochondrial dysfunction in aged muscle, leading to sarcopenia. Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. Recently, it has been reported that UCP3 is associated with calcium uptake into mitochondria. However, the mechanisms by which UCP3 regulates mitochondrial calcium uptake are not well understood. Here we report that UCP3 interacts with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that is localized in mitochondria, which is involved in cellular responses to calcium ion. The hydrophilic sequences within the loop 2, matrix-localized hydrophilic domain of mouse UCP3 are necessary for binding to Hax-1 of the C-terminal domain in adjacent to mitochondrial innermembrane. Interestingly, these proteins interaction occur the calcium-dependent manner. Indeed, overexpression of UCP3 significantly enhanced calcium uptake into mitochondria on Hax-1 endogenously expressing C2C12 myoblasts. In addition, Hax-1 knock-down enhanced calcium uptake into mitochondria on both UCP3 and Hax-1 endogenously expressing C2C12 myotubes, but not myoblasts. Finally, the dissociation of UCP3 and Hax-1 enhances calcium uptake into mitochondria in aged muscle. These studies identify a novel UCP3-Hax-1 complex regulates the influx of calcium ion into mitochondria in muscle. Thus, the efficacy of UCP3-Hax-1 in mitochondrial calcium regulation may provide a novel therapeutic approach against mitochondrial dysfunction-related disease containing sarcopenia.

  18. Ryanodine Receptors Selectively Interact with L Type Calcium Channels in Mouse Taste Cells.

    Directory of Open Access Journals (Sweden)

    Michelle R Rebello

    Full Text Available WE REPORTED THAT RYANODINE RECEPTORS ARE EXPRESSED IN TWO DIFFERENT TYPES OF MAMMALIAN PERIPHERAL TASTE RECEPTOR CELLS: Type II and Type III cells. Type II cells lack voltage-gated calcium channels (VGCCs and chemical synapses. In these cells, ryanodine receptors contribute to the taste-evoked calcium signals that are initiated by opening inositol trisphosphate receptors located on internal calcium stores. In Type III cells that do have VGCCs and chemical synapses, ryanodine receptors contribute to the depolarization-dependent calcium influx.The goal of this study was to establish if there was selectivity in the type of VGCC that is associated with the ryanodine receptor in the Type III taste cells or if the ryanodine receptor opens irrespective of the calcium channels involved. We also wished to determine if the ryanodine receptors and VGCCs require a physical linkage to interact or are simply functionally associated with each other. Using calcium imaging and pharmacological inhibitors, we found that ryanodine receptors are selectively associated with L type VGCCs but likely not through a physical linkage.Taste cells are able to undergo calcium induced calcium release through ryanodine receptors to increase the initial calcium influx signal and provide a larger calcium response than would otherwise occur when L type channels are activated in Type III taste cells.

  19. Physiological Disorders in Closed, Controlled Environment Crops

    Science.gov (United States)

    Wheeler, Raymond M.; Morrow, Robert C.

    2010-01-01

    This slide presentation reviews some of the physiological disorders that affect crops grown in closed controlled environments. A physiological disorder is understood to be a problem resulting from the influence of environmental and horticultural factors on plan development other than a problem caused by a pathogen or some other abiotic cause. The topics that are addressed are: (1) Calcium-Related Disorders (2) Oedema (Intumescence) (3) Long-Photoperiod Injury (4) Light Spectral Quality Effects (5) Super-Elevated CO2 Injuries (6) Ethylene (7) Other Disorders (8) Considerations for Closed Space Environments. Views of plant with the disorders are shown.

  20. Musculoskeletal involvement in sarcoidosis*, **

    Science.gov (United States)

    Nessrine, Akasbi; Zahra, Abourazzak Fatima; Taoufik, Harzy

    2014-01-01

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management. PMID:24831403

  1. Musculoskeletal involvement in sarcoidosis

    Directory of Open Access Journals (Sweden)

    Akasbi Nessrine

    2014-04-01

    Full Text Available Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis, and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management.

  2. 44gSc from metal calcium targets for PET

    DEFF Research Database (Denmark)

    Severin, Gregory; Gagnon, K.; Engle, J. W.

    2012-01-01

    A low-cost and efficient method for producing pre-clinical scale quantities of 44gSc is presented. Production involves proton irradiation of natural unenriched calcium metal followed by rapid separation of radioscandium from the target using hydroxmate functionalized resin.© 2012 American Institu...

  3. Calcium binding protein-mediated regulation of voltage-gated calcium channels linked to human diseases

    Institute of Scientific and Technical Information of China (English)

    Nasrin NFJATBAKHSH; Zhong-ping FENG

    2011-01-01

    Calcium ion entry through voltage-gated calcium channels is essential for cellular signalling in a wide variety of cells and multiple physiological processes. Perturbations of voltage-gated calcium channel function can lead to pathophysiological consequences. Calcium binding proteins serve as calcium sensors and regulate the calcium channel properties via feedback mechanisms. This review highlights the current evidences of calcium binding protein-mediated channel regulation in human diseases.

  4. Dietary magnesium, not calcium, prevents vascular calcification in a mouse model for pseudoxanthoma elasticum

    OpenAIRE

    Gorgels, Theo; Waarsing, Jan; Wolf, Anneke; Brink, Jacoline; Loves, Willem; Bergen, Arthur

    2010-01-01

    textabstractPseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic calcification of connective tissue in skin, Bruch's membrane of the eye, and walls of blood vessels. PXE is caused by mutations in the ABCC6 gene, but the exact etiology is still unknown. While observations on patients suggest that high calcium intake worsens the clinical symptoms, the patient organization PXE International has published the dietary advice to increase calcium intake in combination with...

  5. Connections between connexins, calcium, and cataracts in the lens.

    Science.gov (United States)

    Gao, Junyuan; Sun, Xiurong; Martinez-Wittinghan, Francisco J; Gong, Xiaohua; White, Thomas W; Mathias, Richard T

    2004-10-01

    There is a good deal of evidence that the lens generates an internal micro circulatory system, which brings metabolites, like glucose, and antioxidants, like ascorbate, into the lens along the extracellular spaces between cells. Calcium also ought to be carried into the lens by this system. If so, the only path for Ca2+ to get out of the lens is to move down its electrochemical gradient into fiber cells, and then move by electrodiffusion from cell to cell through gap junctions to surface cells, where Ca-ATPase activity and Na/Ca exchange can transport it back into the aqueous or vitreous humors. The purpose of the present study was to test this calcium circulation hypothesis by studying calcium homeostasis in connexin (Cx46) knockout and (Cx46 for Cx50) knockin mouse lenses, which have different degrees of gap junction coupling. To measure intracellular calcium, FURA2 was injected into fiber cells, and the gradient in calcium concentration from center to surface was mapped in each type of lens. In wild-type lenses the coupling conductance of the mature fibers was approximately 0.5 S/cm2 of cell to cell contact, and the best fit to the calcium concentration data varied from 700 nM in the center to 300 nM at the surface. In the knockin lenses, the coupling conductance was approximately 1.0 S/cm2 and calcium varied from approximately 500 nM at the center to 300 nM at the surface. Thus, when the coupling conductance doubled, the concentration gradient halved, as predicted by the model. In knockout lenses, the coupling conductance was zero, hence the efflux path was knocked out and calcium accumulated to approximately 2 microM in central fibers. Knockout lenses also had a dense central cataract that extended from the center to about half the radius. Others have previously shown that this cataract involves activation of a calcium-dependent protease, Lp82. We can now expand on this finding to provide a hypothesis on each step that leads to cataract formation: knockout of

  6. Clindamycin and taste disorders

    NARCIS (Netherlands)

    de Groot, Mark C H; van Puijenbroek, Eugène P

    2007-01-01

    AIMS: Topical use of clindamycin has been associated with taste disorders in the literature, but little is known about the nature of this adverse drug reaction. The aim of this article was to describe reports of clindamycin-induced taste disorders and to analyse the factors involved. METHODS: The ad

  7. Schizophrenia as a semiotic disorder.

    Science.gov (United States)

    Harrod, J B

    1986-01-01

    Lanin-Kettering and Harrow (1985) argue the traditional position that schizophrenia is a thought disorder. Chaika and Lambe (1985) counter that it is a speech disorder at the syntactic-discursive level, and not a thought disorder. On the basis of state-of-the-art research in linguistics, it is suggested that the symptoms of schizophrenia are evidence of neither a thought disorder nor a syntactic-discursive disorder but a semiotic disorder. Semiotic structures have the form of saying something about something to someone and involve speech act, reference, pragmatics, and interpretation. Therefore, it appears that schizophrenic disorder is located in this structure.

  8. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  9. Conversion Disorder

    Science.gov (United States)

    ... Recent significant stress or emotional trauma Being female — women are much more likely to develop conversion disorder Having a mental health condition, such as mood or anxiety disorders, dissociative disorder or certain personality disorders Having ...

  10. Conduct disorder

    Science.gov (United States)

    ... Conduct disorder is often linked to attention-deficit disorder . Conduct disorder also can be an early sign of ... child or teen has a history of conduct disorder behaviors. A physical examination and blood tests can help ...

  11. Psychotic Disorders

    Science.gov (United States)

    Psychotic disorders are severe mental disorders that cause abnormal thinking and perceptions. People with psychoses lose touch ... is not there. Schizophrenia is one type of psychotic disorder. People with bipolar disorder may also have ...

  12. The ER mitochondria calcium cycle and ER stress response as therapeutic targets in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Vedrana eTadic

    2014-05-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Although the etiology remains unclear, disturbances in calcium homoeostasis and protein folding are essential features of neurodegeneration in this disorder. Here, we review recent research findings on the interaction between endoplasmic reticulum (ER and mitochondria, and its effect on calcium signaling and oxidative stress. We further provide insights into studies, providing evidence that structures of the ER mitochondria calcium cycle (ERMCC serve as a promising targets for therapeutic approaches for treatment of ALS.

  13. Gelation and biocompatibility of injectable alginate-calcium phosphate gels for bone regeneration

    NARCIS (Netherlands)

    Cardoso, D.A.; Beucken, J.J.J.P van den; Both, L.L.; Bender, J.; Jansen, J.A.; Leeuwenburgh, S.C.G.

    2014-01-01

    An emerging approach toward development of injectable, self-setting, and fully biodegradable bone substitutes involves the combination of injectable hydrogel matrices with a dispersed phase consisting of nanosized calcium phosphate particles. Here, novel injectable composites for bone regeneration h

  14. Huntington's Disease: Calcium Dyshomeostasis and Pathology Models.

    Science.gov (United States)

    Kolobkova, Y A; Vigont, V A; Shalygin, A V; Kaznacheyeva, E V

    2017-01-01

    Huntington's disease (HD) is a severe inherited neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and mental impairment. At the molecular level, HD is caused by a mutation in the first exon of the gene encoding the huntingtin protein. The mutation results in an expanded polyglutamine tract at the N-terminus of the huntingtin protein, causing the neurodegenerative pathology. Calcium dyshomeostasis is believed to be one of the main causes of the disease, which underlies the great interest in the problem among experts in molecular physiology. Recent studies have focused on the development of animal and insect HD models, as well as patient-specific induced pluripotent stem cells (HD-iPSCs), to simulate the disease's progression. Despite a sesquicentennial history of HD studies, the issues of diagnosis and manifestation of the disease have remained topical. The present review addresses these issues.

  15. 21 CFR 184.1187 - Calcium alginate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium alginate. 184.1187 Section 184.1187 Food... Specific Substances Affirmed as GRAS § 184.1187 Calcium alginate. (a) Calcium alginate (CAS Reg. No. 9005.... Calcium alginate is prepared by the neutralization of purified alginic acid with appropriate pH...

  16. Calcium phosphates for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Canillas, M.; Pena, P.; Aza, A.H. de; Rodriguez, M.A.

    2017-07-01

    The history of calcium phosphates in the medicine field starts in 1769 when the first evidence of its existence in the bone tissue is discovered. Since then, the interest for calcium phosphates has increased among the scientific community. Their study has been developed in parallel with new advances in materials sciences, medicine or tissue engineering areas. Bone tissue engineering is the field where calcium phosphates have had a great importance. While the first bioceramics are selected according to bioinert, biocompatibility and mechanical properties with the aim to replace bone tissue damaged, calcium phosphates open the way to the bone tissue regeneration challenge. Nowadays, they are present in the majority of commercial products directed to repair or regenerate damaged bone tissue. Finally, in the last few decades, they have been suggested and studied as drug delivering devices and as vehicles of DNA and RNA for the future generation therapies. (Author)

  17. Calcium-sensing beyond neurotransmitters

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Han, Weiping

    2009-01-01

    synaptotagmins are located in brain and endocrine cells, and some of these synaptotagmins bind to phospholipids and calcium at levels that trigger regulated exocytosis of SVs and LDCVs. This led to the proposed synaptotagmin-calcium-sensor paradigm, that is, members of the synaptotagmin family function...... as calcium sensors for the regulated exocytosis of neurotransmitters, neuropeptides and hormones. Here, we provide an overview of the synaptotagmin family, and review the recent mouse genetic studies aimed at understanding the functions of synaptotagmins in neurotransmission and endocrine-hormone secretion......Neurotransmitters, neuropeptides and hormones are released through the regulated exocytosis of SVs (synaptic vesicles) and LDCVs (large dense-core vesicles), a process that is controlled by calcium. Synaptotagmins are a family of type 1 membrane proteins that share a common domain structure. Most...

  18. The role of childhood trauma in bipolar disorders.

    Science.gov (United States)

    Aas, Monica; Henry, Chantal; Andreassen, Ole A; Bellivier, Frank; Melle, Ingrid; Etain, Bruno

    2016-12-01

    This review will discuss the role of childhood trauma in bipolar disorders. Relevant studies were identified via Medline (PubMed) and PsycINFO databases published up to and including July 2015. This review contributes to a new understanding of the negative consequences of early life stress, as well as setting childhood trauma in a biological context of susceptibility and discussing novel long-term pathophysiological consequences in bipolar disorders. Childhood traumatic events are risk factors for developing bipolar disorders, in addition to a more severe clinical presentation over time (primarily an earlier age at onset and an increased risk of suicide attempt and substance misuse). Childhood trauma leads to alterations of affect regulation, impulse control, and cognitive functioning that might decrease the ability to cope with later stressors. Childhood trauma interacts with several genes belonging to several different biological pathways [Hypothalamic-pituitary-adrenal (HPA) axis, serotonergic transmission, neuroplasticity, immunity, calcium signaling, and circadian rhythms] to decrease the age at the onset of the disorder or increase the risk of suicide. Epigenetic factors may also be involved in the neurobiological consequences of childhood trauma in bipolar disorder. Biological sequelae such as chronic inflammation, sleep disturbance, or telomere shortening are potential mediators of the negative effects of childhood trauma in bipolar disorders, in particular with regard to physical health. The main clinical implication is to systematically assess childhood trauma in patients with bipolar disorders, or at least in those with a severe or instable course. The challenge for the next years will be to fill the gap between clinical and fundamental research and routine practice, since recommendations for managing this specific population are lacking. In particular, little is known on which psychotherapies should be provided or which targets therapists should focus

  19. Simultaneous spectrophotometric estimation of atorvastatin calcium and ezetimibe in tablets

    Directory of Open Access Journals (Sweden)

    Sonawane S

    2007-01-01

    Full Text Available A simple, accurate, economical and reproducible procedure for simultaneous estimation of atorvastatin calcium and ezetimibe in their tablet dosage form has been developed using, Q-absorbance equation. The method involves, the absorbance measurement at 235.5 nm (iso-absorptive point and 246.0 nm (λmax of atorvastatin calcium, in methanol. Both the drugs, obey Beer-Lambert′s law in the concentration range of 5-25 μg/ml. The results of analysis have been validated statistically and by recovery studies.

  20. Improved preparation and cooperative calcium contraction of glycerinated Vorticella.

    Science.gov (United States)

    Asai, H; Ochiai, T; Fukui, K; Watanabe, M;