10 research outputs found
Anti-NMDA (N-metil-D-aszparaginsav) receptor enkefalitisz: irodalmi összefoglaló, esetismertetés és kutatási terv
Anti-NMDAR (N-methyl-D-aspartic acid receptor) encephalitis, first described in 2007, is a rare, autoimmune limbic encephalitis. In half of the cases anti-NMDAR antibodies are paraneoplastic manifestations of an underlying tumor (mostly ovarian teratoma). In the early stage of the disease psychiatric symptoms are prominent, therefore 60-70% of the patients are first treated in a psychiatric department. In most of the cases, typical neurological symptoms appear later. Besides the clinical picture and typical symptoms, verifying presence of IgG antibodies in the serum or CSF is necessary to set up the diagnosis. Other diagnostic tools, including laboratory tests, MRI, lumbar puncture or EEG are neither specific, nor sensitive enough. Therapy is based on supportive care, plasma exchange and immune suppression, intensive care administration can be necessary. If there is an underlying tumor, tumor removal is the first-line treatment. The disease can cause fatal complications in the acute phase but with adequate therapy long-term prognosis is good, although rehabilitation can last for months. In the past few years besides the typical clinical picture and illness course an increasing number of case reports described no typical neurological symptoms, only psychiatric symptoms, including psychosis, disorganized behavior, and catatonic symptoms. Immune suppressive treatment was still effective in most of these cases. Such cases present a difficult diagnostic challenge. These patients may receive unnecessary antipsychotic treatment because of the suspected schizophrenia, although they often suffer from serious extrapyramidal side effects. A few years ago there was a hypothesis that a small part of the patients who are treated with therapy-resistant schizophrenia may suffer from anti-NMDAR encephalitis, so they require a different kind of medication. Evidence from the latest publications did not confirm this hypothesis, although the connection between anti-NMDAR antibodies and disorders with psychotic symptoms is still not clear. After reviewing the most important studies regarding the psychiatric aspects of anti-NMDAR encephalitis, we present a case report of a patient with a pure psychiatric manifestation of this disease. We conclude with a short outline of the design and plan of our future study
A PUMA-G receptor élettani és kórélettani szerepe az agyi vérkeringésben. = Role of the PUMA-G receptor in the cerebral circulation.
EredmĂ©nyeink szerint a PUMA-G receptor nem játszik szignifikáns szerepet az agykĂ©rgi vĂ©ráramlás szabályozásában sem Ă©lettani sem pedig kĂłrĂ©lettani körĂĽlmĂ©nyek között. Igazoltuk az epidermális Langerhans-sejtek szerepĂ©t a nikotinsav-okozta flush- reakciĂł a közvetĂttĂ©sĂ©ben, mely adatok egyĂşttal arra utalnak, hogy a Langerhans-sejteknek Ă©lettani/kĂłrĂ©lettani szerepe lehet a bĹ‘r vĂ©ráramlásának szabályozásában. EredmĂ©nyeink szerint a nikotinsav a PUMA-G receptor által közvetĂtett mechanizmussal csökkenti a sebocyták zsĂrtartalmát egĂ©rben, ami felveti a PUMA-G receptor agonisták alkalmazásának lehetĹ‘sĂ©gĂ©t az acne Ă©s seborrhea kezelĂ©sĂ©re. LeĂrtuk, hogy hypoxia Ă©s hypercapnia során az endocannabinoid felszabadulás agykĂ©rgi vĂ©ráramlás-csökkenĂ©st okoz, aminek hátterĂ©ben az excitatorikus glutamáterg neurotranszmissziĂł preszinaptikus gátlását feltĂ©telezzĂĽk. Igazoltuk, hogy az endogĂ©n CO kĂ©pzĹ‘dĂ©s egyrĂ©szt tĂłnusosan gátolja a hypothalamikus nitrogĂ©n monoxid szintetáz (NOS) aktivitást, másrĂ©szt pedig stimulálja a PGE2?felszabadulást Ă©s e kĂ©t Ăşton keresztĂĽl indirekt mĂłdon kĂ©pes befolyásolni a hypothalamus vĂ©ráramlását. Más agyi rĂ©giĂłkban, pl. a parietális agykĂ©regben az endogĂ©n CO NOS-t gátlĂł hatása dominál Ă©s Ăgy vĂ©ráramlás-csökkenĂ©st okoz. MegállapĂtottuk, hogy a neutrális szfingomielináz reaktĂv oxigĂ©n szabadgyökök által közvetĂtett, de NOX2-tĹ‘l fĂĽggetlen mĂłdon csökkenti az a. carotis kontrakciĂłs válaszait. | Our results indicate that the PUMA-G receptor has no significant role in the regulation of the cerebrocortical blood flow under physiological or pathophysiological conditions. We proved that epidermal Langerhans-cells mediate the nicotinic acid induced flush reaction indicating that these cells may play important roles in the regulation of the dermal blood flow. Nicotinic acid inhibits lipogenesis in sebocytes which effect is mediated by the PUMA-G receptor. Therefore, PUMA-G agonists may be beneficial in the treatment of seborrhea and acne. We described that endogenous CO suppresses hypothalamic NOS activity but stimulates PGE2-release at the same time. Both of these effects indirectly influence the hypothalamic circulation. In the parietal cortex CO reduces blood flow via inhibition of NO synthesis. In preliminary experiments we found that neutral sphingomyelinase suppresses the contractile responses of the carotid artery via NOX2-independent generation of reactive oxygen species
Hypersensitivity to Thromboxane Receptor Mediated Cerebral Vasomotion and CBF Oscillations during Acute NO-Deficiency in Rats
), NO-deficiency is often associated with activation of thromboxane receptors (TP). In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. synthesis by ozagrel (10 mg/kg iv.) attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 µM Y-27632.These results suggest that hypersensitivity of the TP-receptor – Rho-kinase signaling pathway contributes to the development of low frequency cerebral vasomotion which may propagate to vasospasm in pathophysiological states associated with NO-deficiency
Weak activation of thromboxane receptors aggravates while inhibition of TXA<sub>2</sub> synthesis attenuates CoBF oscillations developed in the absence of NO.
<p><b>A–C</b>: Original recordings of the cerebrocortical laser-Doppler flux <i>in vivo</i> before (left panels) and after (right panels) administration of the TP-receptor agonist U-46619 (A), the thromboxane synthase inhibitor ozagrel (C) or their vehicle (saline) (B) in rats pretreated by the NO synthase inhibitor L-NAME. <b>D</b>: Quantitative analysis of slow wave oscillations with discrete Fourier transformation. The peak magnitudes of the power spectra are compared before and after treatments in the three experimental groups. Values are mean ± SEM (n = 20, 12 and 14 in Group IIa, IIb, and IIc, respectively) *p<0.05 vs. “Before Treatment”.</p
Baseline physiological parameters in the different in vivo experimental groups.
<p>Values are mean ± SEM (n = 7, 10, 6 and 7 in Groups I, IIa., IIb. and IIc., respectively). No significant difference was found between the experimental groups.</p
NO synthase blockade increases mean arterial pressure (MAP), while decreases heart rate (HR) and cerebrocortical blood flow (CoBF).
<p>Mean ± SEM percentual changes are shown after NO synthase inhibition by 100 mg/kg of L-NAME, compared to the steady state pre-injection values presented on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014477#pone-0014477-t001" target="_blank">Table 1</a> (n = 10, 6 and 7 in the case of MAP and HR, and n = 20, 12 and 14 in the case of CoBF in Groups IIa., IIb. and IIc., respectively).</p
Activation of thromboxane or endothelin receptors induce Rho-kinase dependent vasomotion in NO synthase blocked MCAs.
<p>Quantitative analysis of slow wave oscillations with discrete Fourier transformation in L-NAME treated vessels before and after the administration of the TP-receptor agonist U-46619 (Panel A) or endothelin-1 (Panel B) followed by the Rho-kinase inhibitor Y-27632. Values are mean ± SEM fold changes of the peak magnitudes of the power spectra compared to the baseline. *p<0.05, ***p<0.001 vs. L-NAME, ##<0.01 vs. ET-1 and ###<0.001 vs. U-46619 (n = 10–20).</p