Detection of gonadotropin-releasing hormone receptor in normal human pituitary cells and pituitary adenomas using immunohistochemistry

Gonadotropin-releasing hormone (GnRH), which is a well-known regulator of gonadotroph function, has recently been considered to be a paracrine factor involved in the control of somatotroph, lactotroph, and corticotroph cells. GnRH action is initiated by binding to a specific cell surface receptor, the gonadotropin-releasing hormone receptor (GnRHR), which is expressed by follicle-stimulating hormone/luteinizing hormone (FSH/LH) cells. Using in situ hybridization techniques, GnRHR messenger ribonucleic acid (mRNA) has recently been detected in normal human anterior pituitary gland and in various pituitary adenomas, including FSH/LH-cell, growth hormone (GH)-cell, adrenocorticotropic hormone (ACTH)-cell, and null-cell adenomas. However, immunohistochemical studies indicating the specific cell distribution of GnRHR in normal pituitary cells have never been reported. The aim of the present investigation was to evaluate the immunohistochemical expression of GnRHR in different types of normal pituitary cells and related tumors. Using double-label immunohistochemical techniques on formalin-fixed and paraffin-embedded tissues and specific antibodies directed against pituitary hormones and GnRHR, we found GnRHR immunoreactivity not only in FSH/LH cells, but also in GH- and thyroid-stimulating hormone (TSH) cells. GnRHR was detected in FSH/LH-cell, GH-cell, mixed GH- and prolactin (PRL)-cell, and alpha-subunit (alpha-SU)/null-cell adenomas. The findings of this study suggest that the interaction between GnRH and GnRHR may play a role in paracrine/autocrine regulation of different types of normal pituitary cells and pituitary adenoma

Clinical, biochemical and molecular characterization of prosaposin deficiency

Prosaposin (PSAP) deficiency is an ultra-rare, fatal infantile lysosomal storage disorder (LSD) caused by variants in the PSAP gene, with 7 subjects reported so far. Here, we provide the clinical, biochemical and molecular characterization of two additional PSAP deficiency cases. Lysoplex, a targeted resequencing approach was utilized to identify the variant in the first patient, while quantification of plasma lysosphingolipids (lysoSLs), assessed by liquid chromatography mass spectrometry (LC-MS/MS) and brain magnetic resonance imaging (MRI), followed by Sanger sequencing allowed to attain diagnosis in the second case. Functional studies were carried out on patients' fibroblast lines to explore the functional impact of variants. The two patients were homozygous for two different truncating PSAP mutations (c.895G>T, p.Glu299*; c.834_835delGA, p.Glu278Aspfs*27). Both variants led to a complete lack of processed transcript. LC-MS/MS and brain MRI analyses consistently provided a distinctive profile in the two children. Quantification of specific plasma lysoSLs revealed elevated levels of globotriaosylsphingosine (lysoGb3) and glucosylsphingosine (GlSph), and accumulation of autophagosomes, due to a decreased autophagic flux, was observed. This report documents the successfully use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement.Prosaposin (PSAP) deficiency is an ultra-rare, fatal infantile lysosomal storage disorder (LSD) caused by variants in the PSAP gene, with seven subjects reported so far. Here, we provide the clinical, biochemical and molecular characterization of two additional PSAP deficiency cases. Lysoplex, a targeted resequencing approach was utilized to identify the variant in the first patient, while quantification of plasma lysosphingolipids (lysoSLs), assessed by liquid chromatography mass spectrometry (LC-MS/MS) and brain magnetic resonance imaging (MRI), followed by Sanger sequencing allowed to attain diagnosis in the second case. Functional studies were carried out on patients' fibroblast lines to explore the functional impact of variants. The two patients were homozygous for two different truncating PSAP mutations (c.895G>T, p.Glu299*; c.834_835delGA, p.Glu278Aspfs*27). Both variants led to a complete lack of processed transcript. LC-MS/MS and brain MRI analyses consistently provided a distinctive profile in the two children. Quantification of specific plasma lysoSLs revealed elevated levels of globotriaosylsphingosine (LysoGb3) and glucosylsphingosine (GlSph), and accumulation of autophagosomes, due to a decreased autophagic flux, was observed. This report documents the successful use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement

Diagnostic work-up and therapeutic options in management of pediatric status epilepticus

BACKGROUND: Status epilepticus (SE) is a life-threatening neurologic disorder comprising prolonged and unremitting crisis, and two or more series of seizures without complete intercritical recovery. DATA SOURCES: We reviewed the literature through a Pubmed/Medline research using key words including status epilepticus, antiepileptic drugs and children, in order to revise and compare international/national protocols and to examine pediatric guidelines in SE management. RESULTS: Neurologic impairment and SE etiology seem to be the most independent risks for mortality. A deep semiologic evaluation is essential to addressing diagnostic work-up. Ematochemical parameters, plasma levels of antiepileptic drugs and clinically oriented toxic/metabolic screening should be mandatory for investigating both causes and effects of SE. Electroencephalography is clearly helpful to characterize focal from generalized SE and to distinguish epileptic events from pseudoseizures, and it is deal to find nonconvulsive SE. Neuroimaging techniques could detect epileptogenic lesions (such as cortical malformations, tumors, demyelinating disorders or strokes) but are common in practice to find negative or controversial results. Pharmacologic management can be essentially arranged in three stages: benzodiazepines for early SE (lasting less than 30 minutes), phenytoin/fosphenytoin, phenobarbital, valproate, levetiracetam or lacosamide for established SE (30-90 minutes), and anesthetics for refractory SE (more than 90 minutes). CONCLUSIONS: Status epilepticus is the most common neurologic emergency in childhood. A systematic diagnostic work-up and a three steps based therapeutic approach is required at this age

La poesia encomiastica latina per Carlo di Borbone

This paper has two main purposes: providing a general overview of theeulogistic production for Charles of Bourbon, highlighting its literarygenres and authors, the most frequently used topics, the models of referenceand, furthermore, the public use of rethoric, the restoration of Classicism,and the influence of Vico and Gravina’s theories in eloquence. In the secondpart the study focuses on some carmina composed for Charles of Bourbonby Alessio Simmaco Mazzocchi, the most distinguished Neapolitanintellectual of the first half of the XVIII century. The study analizes theircontent, the occasion on which they were composed, and their quotationsof ancient authors. Mazzocchi constantly promoted Charles of Bourbon’sreforms. Nevertheless, this aspect of his production and his role as a poetlaureate has never been adequately considered yet

GLUT1 DEFICIENCY: A MILD PHENOTYPE IN A 4 YEARS OLD FEMALE WITH EARLY ONSET ABSENCES AND ATAXIA

Introduction: Glucose (GLUT1) transporter 1 deficiency (OMIM 606777) is a polymorphic syndrome including an epileptic encephalopathy, early onset absences, complex movement disorders and developmental delay. Case report: We present the case of a 4 year old female with episodes of recurrent staring since the age of 3 months and fluctuating ataxic gait when awakening since the age of 2 years and 6 months. Symptoms were exacerbated at awakening and with fasting. Psychomotor development was only mildly impaired. Electroencephalogram evidenced diffuse epileptiform discharges with the prominent involvement of the anterior regions. Seizures have been well controlled with valproic acid. Brain MRI was negative. Lumbar puncture showed a CSF/blood glucose ratio of 0,28.Molecular investigation on SLC2A1 gene revelaed a heterozygosis for the mutation c.274 C>T (p.Arg92Trp). Discussion: GLUT1 deficiency have an expanding phenotype. Our experience evidences that the pattern of GLUT 1 deficiency includes different ranges of clinical severity. This is probably due to differences in the functional impairment of the transporter

A diagnostic algorithm for the evaluation of early onset genetic-metabolic epileptic encephalopathies

Early onset epileptic encephalopathies represent a struggling challenge in neurological clinical practice, mostly in infants and very young children, partly due to an unclear and still debated cathegorization. In this scenario genetic and metabolic epileptic encephalopathies play a central role, with new entries still needing an arrangement. In this Paper we present a brief overview on genes, metabolic disorders and syndromes picturing the pathogenesis of genetic and metabolic epileptic encephalopathies with onset under one year of age. These forms will be classified, according to a combined clinical and genetic-metabolic criterion, into two main groups including seizures as prominent/unique symptom and seizures associated with a syndromic phenotype. Starting from this classification we suggest a possible simplified diagnostic algorithm, discussing main decision making nodes in practical patients management. The aim of the proposed algorithm is to guide through metabolic and molecular-genetic work up and to clarify "where" and "what" to search in biochemical, electroencephalographic and neuroimaging investigations. (C) 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved

A new form of cerebral folate deficiency with severe self-injurious behaviour

[No abstract available