The spatio-temporal segregation of GAD forms defines distinct GABA signaling functions in the developing mouse olfactory system and provides novel insights into the origin and migration of GnRH neurons.

GABA (gamma-aminobutyric acid) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 co-expressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually non-overlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia. In contrast GAD67 is expressed in a subregion of the non-sensory epithelium/vomeronasal organ epithelium containing the putative GnRH progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme (FNM) into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant EGAD concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and post-migratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out (KO) embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools. (c) 2014 Wiley Periodicals, Inc. Develop Neurobiol, 2014

Differential Gene Expression in Gonadotropin-Releasing Hormone Neurons of Male and Metestrous Female Mice.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) neurons play a pivotal role in regulation of the hypothalamic-pituitary gonadal axis in a sex-specific manner. We hypothesized that the differences seen in reproductive functions of males and females are associated with a sexually dimorphic gene expression profile of GnRH neurons. METHODS AND RESULTS: We compared the transcriptome of GnRH neurons obtained from intact, metestrous female and male GnRH-GFP transgenic mice. About 1,500 individual GnRH neurons from each sex were sampled with laser capture microdissection followed by whole transcriptome amplification for gene expression profiling. Under stringent selection criteria (fold change >1.6, adjusted p value 0.01), Affymetrix Mouse Genome 430 PM array analysis identified 543 differentially expressed genes. Sexual dimorphism was most apparent in gene clusters associated with synaptic communication, signal transduction, cell adhesion, vesicular transport and cell metabolism. To validate microarray results, 57 genes were selected and 91% of their differential expression was confirmed by real-time PCR. Similarly, 88% of microarray results were confirmed with PCR from independent samples obtained by patch pipette harvesting and pooling of 30 GnRH neurons from each sex. We found significant differences in expression of genes involved in vesicle priming and docking (Syt1, Cplx1), GABAergic (Gabra3, Gabrb3, Gabrg2) and glutamatergic (Gria1, Grin1, Slc17a6) neurotransmission, peptide signaling (Sstr3, Npr2, Cxcr4) and the regulation of intracellular ion homeostasis (Cacna1, Cacnb1, Cacng5, Kcnq2, Kcnc1). CONCLUSION: The striking sexual dimorphism of the GnRH neuron transcriptome we report here contributes to the better understanding the differences in cellular mechanisms of GnRH neurons in the two sexes. (c) 2015 S. Karger AG, Basel

Thromboangitis obliterans agyi manifesztációja

Thromboangiits obliterans (Buerger's disease) is a non-atherosclerotic, segmental inflammatory and obliterative disease affecting small and medium sized arteries and veins. The etiology is still unknown, but it is in close relationship with tobacco use. Symptoms begin under the age of 45 years and the undulating course is typical. Patients usually present with acute and chronic ischemic or infectious acral lesions. Diagnosis is usually based on clinical and angiographic criteria and it is important to exclude autoimmune disease, thrombophilia, diabetes, and proximal embolic sources. Even though Buerger's disease most commonly involves the arteries of the extremities, the pathologic findings sometimes affect the cerebral, coronary and internal thoracic, renal and mesenteric arteries as well. The authors present the history of a patient with known Buerger's disease and acute ischemic stroke. Brain imaging detected acute and chronic ischemic lesions caused by middle cerebral non-atherosclerotic arteriopathy on the symptomatic side. Other etiology was excluded by detailed investigations. Orv. Hetil., 2016, 157(30), 1207-1211

Fabry-betegség – terápiás útmutató

A Fabry-kór a lizoszomális tárolási betegségek csoportjába tartozó, X-kromoszómához kötötten, recesszív módon öröklődő betegség, amely a globotriaozilceramid felhalmozódásához vezet a szervezet legkülönbözőbb szöveteiben. A betegség első tünetei többnyire gyermekkorban jelentkeznek, a progresszió során a betegek súlyos szervi károsodásokkal és korai halálozással számolhatnak. Elsősorban férfiak érintettek, azonban a betegség tüneteit heterozigóta nők esetében is megfigyelhetjük, de náluk a kórkép súlyossága változó, általában enyhébb lefolyású. Az enzimpótló kezelések megjelenése szükségessé tette, hogy részletes diagnosztikus és terápiás protokollt dolgozzunk ki. A jelen dolgozatban megjelenő ajánlásokat egy, a magyarországi Fabry-kóros betegek kezelésében részt vevő orvosokból, a diagnosztika területén dolgozó biológosukból és egyéb szakemberekből álló multidiszciplináris munkacsoport foglalta össze. A munkacsoport áttekintette a korábbi klinikai tanulmányokat, a publikált vizsgálatokat és a közelmúltban megjelent nemzetközi és nemzeti útmutatókat. | Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive and the first symptoms usually present in childhood. Consequences of the disease are disability and premature death. The disease in females could be as severe as in males although women may be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline has been summarized by a Hungarian multi-disciplinary working group consisting of physicians who are involved in diagnosis and care of Fabry patients. Previous clinical studies, published articles, and recently established international treatment guidelines were reviewed by the group

Fabry-betegség - Diagnosztikai útmutató

A Fabry-kór a lizoszomális tárolási betegségek csoportjába tartozó, X-kromoszómához kötötten, recesszív módon öröklődő betegség, amely a globotriaosylceramid felhalmozódásához vezet a szervezet legkülönbözőbb szöveteiben. A betegség első tünetei többnyire gyermekkorban jelentkeznek, a progresszió során a betegek súlyos szervi károsodásokkal és korai halálozással számolhatnak. Elsősorban fiúk és férfiak érintettek, azonban a betegség tüneteit heterozigóta nők esetében is megfigyelhetjük, de náluk a kórkép súlyossága változó, általában enyhébb lefolyású. Az enzimpótló kezelések megjelenése szükségessé tette, hogy részletes diagnosztikus és terápiás protokollt dolgozzunk ki. A jelen dolgozatban megjelenő ajánlásokat egy, a magyarországi Fabry-betegek kezelésében aktívan részt vevő orvosokból, a diagnosztika területén dolgozó biológosukból és egyéb szakemberekből álló multidiszciplináris munkacsoport foglalta össze. A munkacsoport áttekintette a korábbi klinikai tanulmányokat, a publikált vizsgálatokat és a közelmúltban megjelent nemzetközi és nemzeti útmutatókat. | Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive, first symptoms usually present in childhood. Consequencies of the diseases are disability and premature death. The disease in females could be as severe as in males although women may also be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline was established by a Hungarian multi-disciplinary working group, consisting of physicians who are involved in health care of Fabry patients. Previous clinical studies, published materials, and recently established international treatment guidelines were reviewed by the group

A case report of isolated distal upper extremity weakness due to cerebral metastasis involving the hand knob area

Unilateral weakness of an upper extremity is most frequently caused by traumatic nerve injury or compression neuropathy. In rare cases, lesion of the central nervous system may result in syndromes suggesting peripheral nerve damage by the initial examination. Pseudoperipheral hand palsy is the best known of these, most frequently caused by a small lesion in the contralateral motor cortex of the brain. The 'hand knob' area refers to a circumscribed region in the precentral gyrus of the posterior frontal lobe, the lesion of which leads to isolated weakness of the upper extremity mimicking peripheral nerve damage. The etiology of this rare syndrome is almost exclusively related to an embolic infarction.We present the case of a 70-year-old male patient with isolated left sided upper extremity weakness and clumsiness without sensory disturbance suggesting a lesion of the radial nerve. Nerve conduction studies had normal results excluding peripheral nerve damage. Neuroimaging (cranial CT and MRI) detected 3 space occupying lesions, one of them in the right precentral gyrus. An irregularly shaped tumor was found by CT in the left lung with multiple associated lymph node conglomerates. The metastasis from this mucinous tubular adenocarcinoma with solid anaplastic parts to the 'hand knob' area was responsible for the first clinical sign related to the pulmonary malignancy.Pseudoperipheral palsy of the upper extremity is not necessarily the consequence of an embolic stroke. If nerve conduction studies have normal results, neuroimaging - preferably MRI - should be performed, as lesion in the hand-knob area of the precentral gyrus can also be caused by a malignancy

Wernicke-encephalopathia kialakulása fogyasztótabletta használata és kiegyensúlyozatlan diéta következtében [Wernicke's encephalopathy induced by the use of diet pills and unbalanced diet].

A Wernicke-encephalopathia akutan kialakuló, életet veszélyeztető neurológiai kórkép, amely a tiaminhiány következtében alakul ki. A betegséget nagyon gyakran nem diagnosztizálják időben, így megfelelő terápia hiányában a krónikus forma, a Korsakoff-szindróma kialakulásához vagy egyes esetekben halálhoz is vezethet. A tiaminhiány fejlett országokban leggyakrabban krónikus alkoholfogyasztás következtében alakul ki, de az utóbbi időben az alkoholfogyasztással nem összefüggő esetek száma is gyarapodott. A szerzők egy 23 éves nőbeteg esetét mutatják be, akinél drasztikus diéta és fogyasztótabletta használata következtében alakult ki szemmozgászavar, zavartság és ataxia, amelyek hátterében Wernicke-encephalopathia igazolódott. A diagnózist támogatta, hogy a tünetek parenteralis tiaminpótlás hatására napokon belül megszűntek. A szerzők az esetet etiológiai ritkasága és diagnosztikai nehézsége miatt közlik, illetve rámutatnak a legfrissebb ajánlásokra a kórkép diagnosztikáját és terápiáját illetően. Orv. Hetil., 2014, 155(12), 469–474. | Wernicke’s encephalopathy is an acute, potentially life-threatening, neurological syndrome resulting from thiamine deficiency. The disorder is still greatly underdiagnosed and, without prompt treatment, the condition can lead to the chronic form of the disease, Korsakoff’s syndrome or even death. In developed countries Wernicke’s encephalopathy has been associated with alcoholism, but in recent years there has been an increasing number of non-alcoholic cases. Authors report the case of a 23-year-old woman who developed oculomotor dysfunction, encephalopathy and ataxia as a result of an extreme diet and use of diet pills. The diagnosis of Wernicke’s encephalopathy was supported by the resolution of neurological signs after parenteral thiamine replacement. This case is presented because of the rare etiology and diagnostic difficulty, and the latest diagnostic and therapic guidelines are also highlighted. Orv. Hetil., 2014, 155(12), 469–474

Agytörzsi tályog: differenciáldiagnosztikai nehézségek két eset fényében

Brain abscess is a rare and often fatal disease. Bacterial infections of the brain could develop by direct extension of local infections e.g. sinusitis, otomastoiditis, or due to hematogenous spread. Headache, fever and focal neurological deficits are the leading clinical symptoms and signs in brain abscess. Pathogen detection by CSF examination or by microbiological methods from needle aspiration or stereotaxic samples is often unsuccessful. Imaging studies are the keys for the diagnosis. The abscess in contrast enhanced CT scan may be represented as a low density area, which is similar to a subacute ischaemic lesion. Meanwhile, the pyogenic lesion is characterized with MR as a hypointense region on T1 and hyperintense region on T2 and FLAIR images. Diffusion weighted images (DWI) could distinguish between tumours and abscesses. As an empiric treatment, combined intravenous - clindamycine / metronidazole + 3d generation cephalosprin - antibiotic therapy is recommended. In this article we report two cases of brainstem abscess developed in immunocompetent patients. The diagnosis was based partially on the imaging studies and partially on the successful outcome of combined antibiotic treatment

Preserved structural and functional characteristics of common carotid artery in properly treated normoglycemic women with gestational diabetes mellitus

Women with gestational diabetes mellitus (GDM) are at high risk of subsequently developing type 2 diabetes mellitus which is an important cardiovascular risk factor. We have evaluated whether preclinical morphological and functional arterial changes are present in GDM. Diameter, intima-media thickness (IMT), intima-media cross-section area (IMCSA) and elasticity features (compliance, distensibility coefficient, circumferential strain, stiffness index (SI) α and β, incremental elastic modulus) of the common carotid arteries (CCA) were studied in the 3rd trimester in 25 women with GDM, and 17 normal pregnant women matched for age and body mass index using an ultrasonographic vessel wall-movement tracking system and applanation tonometry. Mean IMT, IMCSA and SI α tended to be larger, whereas compliance was smaller in women with GDM but none of these differences were significant. Serum glucose (4.99±0.51 vs. 4.79±0.61 mmol/L, p=0.37) and HbA1c (5.33±0.27 vs. 5.36±0.47 mmol/L, p=0.85) proved normoglycemia in both groups. In conclusion, by the combination of methods we applied in this case control study, neither morphological nor functional characteristics of large elastic arteries differ significantly between well-treated normoglycemic women with GDM and non-diabetic pregnant women in the 3rd trimester