No description available.

Suicide continues to claim hundreds of thousands of lives worldwide each year, in spite of the significant progress of research efforts aimed at understanding the complexity of this tragic behaviour. Data accumulated over the last decades suggest a certain biological predisposition to suicidal behaviour. Among the possible biological risk factors, cholesterol has frequently been cited. Several lines of evidence support the relationship between altered lipid metabolism, particularly low levels of serum cholesterol, and suicidal behaviour, yet the possible mechanisms governing the relationship remain to be elucidated. Three separate strategies were employed in order to explore the link between lipid metabolism and suicidal behaviour, each one from a novel perspective on this issue. The first approach aimed to substantiate the existing evidence of an association between low serum cholesterol and suicidality by examining psychiatric data, suicidality and related behavioural characteristics in a sample of Smith-Lemli-Opitz syndrome heterozygotes---a clinically normal population with altered cholesterol metabolism due to an inherited partial deficiency in the 7-dehydrocholesterol reductase enzyme---compared with controls. The second approach consisted in measuring the lipid profile in brain tissue from suicide completers, in order to address whether there are alterations in cholesterol and/or fatty acids in the brain. The final approach involved the use of exploratory gene expression studies to identify novel candidate genes and proteins that may be involved in mediating the link between lipid metabolism and suicidality. The results of these studies will be presented and discussed.

Zugl.: Kairo, Univ., Diss., 2004

Texte remanié de: Habilitationsschrift--St Gallen--Universität, 1998. / Bibliogr. p. 313-322.

No description available.

O presente estudo é focalizado na avaliação dos achados do sistema nervoso central através de imagens obtidas através de ressonância nuclear magnética (RNM) em pacientes com a Síndrome de Opitz G/BBB. A síndrome de Opitz G/BBB (OMIM; 145410; 300000) é uma síndrome de anomalias congênitas múltiplas que comprometem a linha média, clinica e geneticamente heterogênea, com uma forma ligada ao cromossomo X mapeada em Xp22.3 e uma outra forma supostamente autossômica dominante mapeada em 22q11 cujo gene nunca foi identificado; no entanto, ambas são reconhecidas como uma condição única. Esta síndrome de anomalias da linha média se caracteriza principalmente por hipertelorismo, bico de viúva, ponte nasal larga, hipospádia, fissura de lábio/palato, e anomalias laringo-traqueo-esofágicas. Neste estudo avaliamos 19 pacientes do sexo masculino, brasileiros, sem etnia específica, com idades variando entre 5 e 38 anos, diagnosticados previamente como portadores de síndrome de Opitz G/BBB, selecionados dos arquivos da Seção de Genética Clinica, Divisão de Sindromologia, HRAC-USP Bauru. Destes pacientes, 6 tinham avaliação prévia por estudos de genética molecular gentilmente realizados pelas Dras. Chiara Migliore (Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", Trieste, Italy) e Germana Meroni (CBM - Cluster in Biomedicine, AREA Science Park, Trieste, Italy). Os estudos por imagem através de RNM foram realizados em todos os pacientes. Atenção especial foi dedicada a 3 pacientes que mostravam fenótipos clínicos distintos dos demais dentro do espectro da síndrome de Opitz G/BBB: dois pacientes apresentavam ptose, pescoço alado, e anomalias da cintura escapular, enquanto que o terceiro apresentava retardo mental grave e microcefalia associado a graves alterações encefálicas na avaliação por imagem, tais como atrofia cortical generalizada e grande anomalia de Dandy-Walker. Os principais achados por imagem da amostra total são representados por cisterna magna ampla (15 indivíduos = 78,95%), dilatação do 4º ventrículo (14 = 73,68%), hipoplasia do vermis cerebelar (8 = 42,10%), hemisférios cerebelares anômalos e cavum septum vergae (3 = 15,79% cada condição); atrofia de córtex cerebral, alargamento do III ventrículo, aumento da cisterna pré-pontina, hipoplasia de corpo caloso e persistência de septo pelúcido contam, cada um, com dois pacientes acometidos (10,53%). Aparentemente não havia correlação entre o fenótipo clínico e os achados por imagem, existindo grande variabilidade de paciente para paciente, que se estendiam desde discretas alterações da linha média até grave malformação de Dandy-Walker. As alterações comportamentais e cognitivas usualmente descritas na literatura como achados principais em pacientes com hipoplasia do vermis cerebelar e/ou hipoplasia cerebelar não foram reconhecidas como achados marcantes nos pacientes do presente trabalho. A alta frequência de anomalias cerebelares em pacientes com a síndrome de Opitz G/BBB nos leva a recomendação para a reformulação do aconselhamento genético, abordagem e manejo destes pacientes. / The present survey focused on the evaluation of the central nervous system images findings in patients with the Opitz G/BBB syndrome obtained through magnetic nuclear resonance imaging (MRI). The Opitz G/BBB syndrome (OMIM; 145410; 300000) is a midline congenital malformation syndrome, clinical and genetically heterogeneous with an X-linked form mapped on Xp22.3 and a not well defined autosomal dominant form purportedly on 22q11, however they are recognized as one entity. This multiple congenital midline malformation syndrome is mainly characterized by hypertelorism, widows peak, broad nasal bridge, hypospadias, cleft lip/palate, and laryngo-tracheo-esophageal abnormalities. In the present study we have evaluated nineteen male patients of Brazilian extraction, with no preferential ethnic background, with age span ranging from 5 to 38 years old and previously diagnosed with the OS were selected from the files of the Section of Clinical Genetics, Division of Syndromology, HRAC-USP Bauru. From these patients, six had previous evaluation through molecular analysis graciously performed by Chiara Migliore (Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", Trieste, Italy) and Germana Meroni (CBM - Cluster in Biomedicine, AREA Science Park, Trieste, Italy). Imaging studies through MRI were performed in all patients. Special attention was given to 3 out the 19 patients who showed unique phenotypes within the OS spectrum: 2 of them presented ptosis, pterigium colli, and abnormal scapular girdle as deviant signs and they presented mild/moderate cerebellar anomalies, and the 3rd presented severe mental retardation and microcephaly associated to generalized severe imaging findings mainly represented by generalized cortical atrophy and huge Dandy-Walker anomaly. Main MRI findings of the whole sample included wide cisterna magna (15 = 78,95%), enlarged 4th ventricle (14 = 73,68%), cerebellar vermis hypoplasia (8 = 42,10%); abnormal cerebellar hemispheres and cavum septum vergae (3 = 15,79% each one); cerebral cortical atrophy, enlarged III ventricle, enlarged prepontine cisterna, calosal hypoplasia and cavum septum pellucidum counts, each one, two patients (10,53%). Apparently there is no correlation between the clinical phenotype and the imaging findings, and there is a wide variability from patients to patients, ranging from mild midline anomalies to severe Dandy Walker anomaly. Behavioral and severe cognitive deficits usually reported in the pertinent literature as main findings associated to cerebellar vermis hypoplasia and/or cerebellar hypoplasia were not recognized as a remarkable finding in the present series. The high frequency of cerebellar anomalies in the OS patients led us to recommend a reformulation in the genetic counseling approach to these patients.

O presente estudo é focalizado na avaliação dos achados do sistema nervoso central através de imagens obtidas através de ressonância nuclear magnética (RNM) em pacientes com a Síndrome de Opitz G/BBB. A síndrome de Opitz G/BBB (OMIM; 145410; 300000) é uma síndrome de anomalias congênitas múltiplas que comprometem a linha média, clinica e geneticamente heterogênea, com uma forma ligada ao cromossomo X mapeada em Xp22.3 e uma outra forma supostamente autossômica dominante mapeada em 22q11 cujo gene nunca foi identificado; no entanto, ambas são reconhecidas como uma condição única. Esta síndrome de anomalias da linha média se caracteriza principalmente por hipertelorismo, bico de viúva, ponte nasal larga, hipospádia, fissura de lábio/palato, e anomalias laringo-traqueo-esofágicas. Neste estudo avaliamos 19 pacientes do sexo masculino, brasileiros, sem etnia específica, com idades variando entre 5 e 38 anos, diagnosticados previamente como portadores de síndrome de Opitz G/BBB, selecionados dos arquivos da Seção de Genética Clinica, Divisão de Sindromologia, HRAC-USP Bauru. Destes pacientes, 6 tinham avaliação prévia por estudos de genética molecular gentilmente realizados pelas Dras. Chiara Migliore (Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", Trieste, Italy) e Germana Meroni (CBM - Cluster in Biomedicine, AREA Science Park, Trieste, Italy). Os estudos por imagem através de RNM foram realizados em todos os pacientes. Atenção especial foi dedicada a 3 pacientes que mostravam fenótipos clínicos distintos dos demais dentro do espectro da síndrome de Opitz G/BBB: dois pacientes apresentavam ptose, pescoço alado, e anomalias da cintura escapular, enquanto que o terceiro apresentava retardo mental grave e microcefalia associado a graves alterações encefálicas na avaliação por imagem, tais como atrofia cortical generalizada e grande anomalia de Dandy-Walker. Os principais achados por imagem da amostra total são representados por cisterna magna ampla (15 indivíduos = 78,95%), dilatação do 4º ventrículo (14 = 73,68%), hipoplasia do vermis cerebelar (8 = 42,10%), hemisférios cerebelares anômalos e cavum septum vergae (3 = 15,79% cada condição); atrofia de córtex cerebral, alargamento do III ventrículo, aumento da cisterna pré-pontina, hipoplasia de corpo caloso e persistência de septo pelúcido contam, cada um, com dois pacientes acometidos (10,53%). Aparentemente não havia correlação entre o fenótipo clínico e os achados por imagem, existindo grande variabilidade de paciente para paciente, que se estendiam desde discretas alterações da linha média até grave malformação de Dandy-Walker. As alterações comportamentais e cognitivas usualmente descritas na literatura como achados principais em pacientes com hipoplasia do vermis cerebelar e/ou hipoplasia cerebelar não foram reconhecidas como achados marcantes nos pacientes do presente trabalho. A alta frequência de anomalias cerebelares em pacientes com a síndrome de Opitz G/BBB nos leva a recomendação para a reformulação do aconselhamento genético, abordagem e manejo destes pacientes. / The present survey focused on the evaluation of the central nervous system images findings in patients with the Opitz G/BBB syndrome obtained through magnetic nuclear resonance imaging (MRI). The Opitz G/BBB syndrome (OMIM; 145410; 300000) is a midline congenital malformation syndrome, clinical and genetically heterogeneous with an X-linked form mapped on Xp22.3 and a not well defined autosomal dominant form purportedly on 22q11, however they are recognized as one entity. This multiple congenital midline malformation syndrome is mainly characterized by hypertelorism, widows peak, broad nasal bridge, hypospadias, cleft lip/palate, and laryngo-tracheo-esophageal abnormalities. In the present study we have evaluated nineteen male patients of Brazilian extraction, with no preferential ethnic background, with age span ranging from 5 to 38 years old and previously diagnosed with the OS were selected from the files of the Section of Clinical Genetics, Division of Syndromology, HRAC-USP Bauru. From these patients, six had previous evaluation through molecular analysis graciously performed by Chiara Migliore (Institute for Maternal and Child Health - IRCCS \"Burlo Garofolo\", Trieste, Italy) and Germana Meroni (CBM - Cluster in Biomedicine, AREA Science Park, Trieste, Italy). Imaging studies through MRI were performed in all patients. Special attention was given to 3 out the 19 patients who showed unique phenotypes within the OS spectrum: 2 of them presented ptosis, pterigium colli, and abnormal scapular girdle as deviant signs and they presented mild/moderate cerebellar anomalies, and the 3rd presented severe mental retardation and microcephaly associated to generalized severe imaging findings mainly represented by generalized cortical atrophy and huge Dandy-Walker anomaly. Main MRI findings of the whole sample included wide cisterna magna (15 = 78,95%), enlarged 4th ventricle (14 = 73,68%), cerebellar vermis hypoplasia (8 = 42,10%); abnormal cerebellar hemispheres and cavum septum vergae (3 = 15,79% each one); cerebral cortical atrophy, enlarged III ventricle, enlarged prepontine cisterna, calosal hypoplasia and cavum septum pellucidum counts, each one, two patients (10,53%). Apparently there is no correlation between the clinical phenotype and the imaging findings, and there is a wide variability from patients to patients, ranging from mild midline anomalies to severe Dandy Walker anomaly. Behavioral and severe cognitive deficits usually reported in the pertinent literature as main findings associated to cerebellar vermis hypoplasia and/or cerebellar hypoplasia were not recognized as a remarkable finding in the present series. The high frequency of cerebellar anomalies in the OS patients led us to recommend a reformulation in the genetic counseling approach to these patients.

The aim of this thesis was the development of a voltammetric method for the determination of 7-dehydrocholesterol as a biomarker of congenital disease Smith-Lemli-Opitz syndrome. The concentration of 7-dehydrocholesterol in plasma will increase hundred-fold to hundreds to thousands µmol L-1 in patients suffering from Smith-Lemli-Opitz syndrome. The determination of 7-dehydrocholesterol was carried out in artifical serum in this work, which was prepared to mimic the conditions of postnatal diagnosis of Smith-Lemli-Opitz syndrome. 7-dehydrocholestrol provides a well developed voltammetric signal at approximately +0.8 V vs. Ag/AgNO3 in acetonitrile. Differential pulse voltammetry with optimized parameters was used for the determination of 7-dehydrocholesterol. The presence of protein in artificial serum (human serum albumin) resulted in an unacceptably high detection limit of the method (178 µmol L-1 in artificial serum). Therefore, human serum albumin was eliminated from the artificial serum samples by precipitating it with acetonitrile and subsequently centrifuging the resulting suspension. At the same time, the ratio of aqueous and organic components in the studied medium was also adjusted with acetonitrile to achieve an optimal voltammetric response of 7-dehydrocholestrol. With regard to the...

Im Jahr der Wiederkehr des 350. Todestages von Heinrich Schütz können die „Denkmäler der Tonkunst in Dresden“ leider kein neues Werk des Dresdner Hofkapellmeisters vorlegen, aber dafür eines aus seinem unmittelbaren Umfeld: Die „10 Opitzianischen Lieder“ aus der „Aelbianischen Musenlust“ von Constantin Christian Dedekind. Diese großangelegte Sammlung von 157 Liedern aus dem Jahr 1657 vereinigt Texte der damals bekanntesten deutschen Dichter: u.a. von Martin Opitz, Paul Fleming, Johann Rist, Andreas Tscherning, Simon Dach, David Schirmer, Mit den meisten stand Heinrich Schütz auf der Suche nach gut vertonbaren deutschen Texten in Verbindung. Dedekind lernte Schütz 1647 kennen, wurde von diesem 1654 als Sänger in die „Hofcantorey“ aufgenommen, war Schüler und Schwiegersohn von Christoph Bernhard und wurde 1671 von Schütz gebeten, ihm bei dessen letztem großem Motettenwerk, dem „Schwanengesang“, bei der Instrumentierung zu helfen. 1624 hatte Martin Opitz das „Buch von der deutschen Poeterey“, ein Standardwerk der Barockepoche, veröffentlicht als einen wesentlichen Beitrag zur Schaffung einer deutschen Nationalliteratur. 1627 übertrug er eine der frühesten italienischen Opern, die „Dafne“ von Ottavio Rinunccini von 1597, für Schütz ins Deutsche, für eine Festaufführung in Torgau.So ist die „Aelbianische Musenlust“ eng mit dem Elbtal bei Dresden verbunden, zeigt doch der Titelkupfer die bekanntesten Felsen der Sächsischen Schweiz.