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  • 1
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    Doxycycline in Macrophage Polarization [Immunology] (2014)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2014-03-22
    Description: Macrophages occur along a continuum of functional states between M1-type polarized macrophages with antiangiogenic and antitumor activity and M2-type polarized macrophages, which have been implicated to promote angiogenesis and tumor growth. Proangiogenic M2-type macrophages promote various pathologic conditions, including choroidal neovascularization in models of neovascular age-related macular degeneration, or certain cancers, such as glioblastoma multiforme. Thus, a potential novel therapeutic approach to target pathological angiogenesis in these conditions would be to inhibit the polarization of macrophages toward the proangiogenic M2-type. However, no pharmacological inhibitors of M2-type macrophage polarization have been identified yet. Here we performed an unbiased pharmacological and small chemical screen to identify drugs that inhibit proangiogenic M2-type macrophage polarization and block pathologic macrophage-driven neovascularization. We identified the well tolerated and commonly used antibiotic doxycycline as a potent inhibitor of M2-type polarization of macrophages. Doxycycline inhibited, in a dose-dependent manner, M2-type polarization of human and bone marrow-derived mouse macrophages without affecting cell viability. Furthermore, doxycycline inhibited M2-type macrophage polarization and subsequent neovascularization in vivo in a laser injury model of choroidal neovascularization. Thus, doxycycline could be used to enhance current antiangiogenic treatment approaches in various conditions that are promoted by proangiogenic M2-type macrophages, including neovascular age-related macular degeneration and certain cancers.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 2
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    Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF-A levels [Research Communications] (2014)
    The Federation of American Societies for Experimental Biology (FASEB)
    Details
    Publication Date: 2014-05-02
    Description: Patients with nonexudative ("dry") age-related macular degeneration (AMD) frequently also develop neovascular ("wet") AMD, suggesting a common pathomechanism. Increased vascular endothelial growth factor A (VEGF-A) has been implicated in the pathogenesis of choroidal neovascularization (CNV) in neovascular AMD, while its role in nonexudative AMD that manifests with progressive retinal pigment epithelium (RPE) and photoreceptor degeneration is not well defined. Mice with overall increased VEGF-A levels develop progressive morphological features of both forms of AMD, suggesting that an increase in VEGF-A has a direct age-dependent adverse effect on RPE and photoreceptor function independently of its CNV-promoting proangiogenic effect. Here we provide evidence for this hypothesis and show that morphological RPE abnormalities and retinal thinning in mice with increased VEGF-A levels correlate with progressive age-dependent attenuation of visual function with abnormal electroretinograms and reduced retinal rhodopsin levels. Retinoid profiling revealed a progressive reduction of 11- cis and all- trans retinal in the retinas of these mice, consistent with an impaired retinoid transport between the RPE and photoreceptors. These findings suggest that increased VEGF-A leads to an age-dependent RPE and retinal dysfunction that occurs also at sites where no CNV lesions form. The data support a central role of increased VEGF-A not only in the pathogenesis of neovascular but also of nonexudative AMD.—Ablonczy, Z., Dahrouj, M., Marneros, A. G. Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF-A levels.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
    Published by The Federation of American Societies for Experimental Biology (FASEB)
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    PAPER CURRENT
  • 3
    Electronic Resource
    Electronic Resource
    Prognostic value of initial subtype in schizophrenic disorders
    Amsterdam : Elsevier
    Schizophrenia Research 12 (1994), S. 145-157 
    Details
    ISSN: 0920-9964
    Keywords: (Schizophrenia) ; DSM-III-R ; ICD-10 ; Long-term outcome ; Positive vs. negative symptoms ; Schizophrenic subtype
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0920-9964(94)90072-8
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  • 4
    Electronic Resource
    Electronic Resource
    Validity of the negative/positive dichotomy for schizophrenic disorders under long-term conditions
    Amsterdam : Elsevier
    Schizophrenia Research 7 (1992), S. 117-123 
    Details
    ISSN: 0920-9964
    Keywords: (Schzophrenia) ; Longitudinal stability ; Negative symptom ; Positive symptom
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0920-9964(92)90041-3
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  • 5
    Electronic Resource
    Electronic Resource
    Was ist Zyklothymia? (1997)
    Springer
    Der Nervenarzt 68 (1997), S. 531-544 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Zyklothymia ; Bipolare Störung ; Nosologie ; Geschichte ; Überblick ; Key words Cyclothymic disorder ; Bipolar disorder ; History ; Nosology ; Review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The term ’’cyclothymia’’ is being used with different meanings. DSM-IV and ICD-10 define ’’cyclothymia’’ or ’’cyclothymic disorder’’ as a long lasting, subaffective disorder with frequent shifts between hypomanic and (sub)depressive states. In the tradition of Kurt Schneider cyclothymia was understood as a synonym for manic-depressive illness exclusively, while different personality typologies speak of a ’’cyclothymic’’ typus. Historically, the term was first used by the German psychiatrist Ewald Hecker in 1877. The definitions of DSM-IV and ICD-10 seem to be satisfactory in respect to reliability, but the nosological position of ’’cyclothymic disorder’’ is unclear. We review results concerning clinical symptomatology, comorbidity, biological parameters, personality (including the question of creativity), psycho- and pharmacotherapy as well as clinical course, which leave many questions open. Nevertheless, results in family studies support the idea that at least a fraction of ’’cyclothymia’’ is a mild or subcinical form of bipolar disorders. Until further research, which is urgently needed, we suggest that the term ’’cyclothymia’’ should be only used according to the guidelines of DSM-IV and ICD-10.
    Notes: Zusammenfassung Der Begriff „Zyklothymie” wird mit verschiedenen Bedeutungen verwandt. DSM-IV und ICD-10 verstehen unter der „Zyklothymia” bzw. der „zyklothymen Störung” lang dauernde „subaffektive” Störungen mit häufi-gen Schwankungen zwischen hypomanischer und (sub)depressiver Stimmung. In der Tradition Kurt Schneiders wird auch heute noch der Begriff „Zyklothymie” als Synonym für „manisch-depressive Erkrankung” gebraucht. Schließlich erscheint v.a. in der Tradition E. Kretschmers in verschiedenen Persönlichkeitstypologien das Adjektiv „zyklothym”, um einen bestimmten Persönlichkeitstypus zu kennzeichnen. Geschichtlich wurde der Begriff 1877 von Hecker einge-führt. Die operationalisierten Definitionen der „Zyklothymia” von DSM-IV und ICD-10 scheinen eine ausreichende Reliabilität zu haben, die nosologische Position dieser Diagnose ist aber weiterhin unklar. Die besprochenen Ergebnisse zur Epidemiologie, zur klinischen Symptomatik, zu Komorbidität, biologischen Markern, der Persönlichkeit (einschließlich der Frage der Kreativität), der Psycho- und Pharmakotherapie und zum Verlauf sind als lückenhaft zu bewerten. Die Ergebnisse Familienuntersuchungen stützen, daß zumindest ein Teil der „zyklothymen Störungen” als milde oder subklinische Verlaufsform von bipolaren Störungen zu sehen ist. Wir plädieren dafür, bis zum Vorliegen weiterführender, dringend notwendiger Forschungsergebnisse den Begriff „Zyklothymia” einheitlich im Sinne der operationalisierten Diagnostiksysteme zu verwenden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050158
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  • 6
    Electronic Resource
    Electronic Resource
    Akute Alkoholwirkung und chronische Alkoholabhängigkeit als Determinanten von Gewaltdelinquenz (2000)
    Springer
    Der Nervenarzt 71 (2000), S. 715-721 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Alkohol ; Alkoholabhängigkeit ; Kriminalität ; Gewalt ; Key words Alcohol intoxication ; Dependency ; Violent crime
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary To study the influence of alcohol and psychosocial variables on delinquent behavior, we coded data from the psychiatric evaluation of 254 defendants using a standardized score sheet, analyzing correlations between acute intoxication at the time of the crime (ICD 10: F10.0), diagnosis of alcohol dependency according to ICD 10 (F10.2), psychobiographical variables, criminal history, and parameters relating to the index offence. We found that 64.6% of all defendants studied were intoxicated when committing the crime and 25.6% suffered from alcohol dependency. Alcohol intoxication correlated to occurrence of violent crime, cruelty in committing the index offence, and earlier convictions. Logistic regression, with demographic and psychosocial variables entered as covariables, revealed acute alcohol intoxication but not alcohol dependency as a predictor of violent crime (odds ratio 2.3, P=0.02). Alcohol intoxication and dependency were also independent predictors of earlier convictions (intoxication, odds ratio 4.4, P=0.0001; dependency, odds ratio 3.6, P=0.003). Our findings support the hypothesis that acute alcohol intoxication, not dependency, influences violent crime in a direct manner. However, alcohol dependency predicts criminal recidivism.
    Notes: Zusammenfassung Wir untersuchten die Bedeutung von akuter Alkoholisierung zum Tatzeitpunkt (ICD-10: F10.0) und chronischer Abhängigkeitserkrankung (ICD-10: F10.2) für das delinquente Verhalten bei 254 begutachteten Straftätern. 64,6% der untersuchten Täter waren zum Tatzeitpunkt alkoholisiert, 25,6% waren alkoholabhängig. Alkoholisierung zum Tatzeitpunkt korrelierte mit der Begehung eines Gewaltdelikts, rücksichtsloser Ausführung der Tat sowie mit früheren Verurteilungen. Bei Kontrolle demographischer und psychosozialer Faktoren durch logistische Regression erwies sich akute Alkoholisierung, nicht aber Alkoholabhängigkeit, als signifikanter Prädiktor eines Gewaltdelikts (Odds Ratio 2,3; p=0,02). Sowohl akute Alkoholisierung als auch Alkoholabhängigkeit sagten unabhängig voneinander und hochsignifikant das Vorliegen von Vorstrafen voraus (Alkoholisierung: Odds Ratio 4,3; p=0,0001; Abhängigkeit: Odds Ratio 3,6; p=0,003). Unsere Befunde stützen die Hypothese, dass die akute Alkoholisierung zum Tatzeitpunkt einen direkten Einfluss auf die Gewaltsamkeit der begangenen Tat hat. Alkoholabhängigkeit hingegen erscheint mit der Chronifizierung kriminellen Verhaltens assoziiert zu sein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050655
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  • 7
    Electronic Resource
    Electronic Resource
    Komorbidität bei psychiatrischen Krankheiten Einige theoretische Überlegungen (2000)
    Springer
    Der Nervenarzt 71 (2000), S. 525-534 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Komorbidität ; Psychiatrische Störungen ; Diagnose ; Key words Comorbidity ; Mental disorders ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract During the last 10 years, comorbidity has become an important topic in psychiatric research, leading to a growing number of publications. We discuss the theoretical and historical background of this development and present definitions and models for the phenomenon. Methodological difficulties have to be stated: considering its clinical consequences, we conclude that (1) comorbidity is an inevitable methodological consequence of the diagnostic strategies and continued diversification of DSM-IV and ICD-10, (2) there is little doubt of its relevance in the clinical context, and (3) the diagnostic strategies of DSM-IV and ICD-10 concerning comorbidity are difficult to follow in clinical reality.
    Notes: Zusammenfassung Komorbidität ist in den letzten 10 Jahren zu einem wichtigen Thema in der Psychiatrie geworden, was sich auch in der Zahl der entsprechenden Publikationen widerspiegelt. Theoretische und geschichtliche Hintergründe dieser Entwicklung werden diskutiert, außerdem werden verschiedene Definitionen und Modelle für das Phänomen “Komorbidität” dargestellt. Es gibt zahlreiche methodische Schwierigkeiten zu konstatieren. Ausgehend von der klinischen Bedeutung der Komorbidität wird in der abschließenden Diskussion festgestellt, dass (1) Komorbidität eine zwangsläufige methodische Konsequenz der Diagnosestrategie und der immer weitergehenden Diversifizierung von ICD-10 und DSM-IV ist, dass (2) Komorbiditätsphänomene unzweifelhaft klinisch bedeutsam sind, dass aber (3) die in ICD-10 und DSM-IV vorgegebenen Diagnosestrategien hinsichtlich Komorbidität in der Praxis kaum zu realisieren sind.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050019
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  • 8
    Electronic Resource
    Electronic Resource
    Subtypes in schizophrenic disorders: frequencies in long-term course and premorbid features (1993)
    Springer
    Social psychiatry and psychiatric epidemiology 28 (1993), S. 164-171 
    Details
    ISSN: 1433-9285
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The subclassification of schizophrenic disorders according to four diagnostic systems (DSM-III-R, ICD-10, the positive vs. negative dichtomy and Schneider's first rank symptoms) was compared over the long-term course of the disease in 148 narrowly defined schizophrenic patients. A total of 595 episodes were classified over a mean observation period of 23 years (range 10–50 years). Initially, paranoid/positive subtypes predominated, while later in the course episodes fulfilling the symptomatological criteria of residual/negative subtypes became more frequent. Disorganised/hebephrenic and catatonic subtypes were found to be rare. Some premorbid features were investigated as non-symptomatological validators for subclassification. Significant differences were found with regard to age at onset. Patients whose first episode was paranoid or positive had the highest age at onset. Patients with initial disorganised/hebephrenic or “residual” episodes had the most unfavourable premorbid social adjustment, even when the influence of age at onset was discounted. The diagnostic systems investigated showed similarities and differences as a result of the underlying concepts. Methodological implications are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00797318
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  • 9
    Electronic Resource
    Electronic Resource
    Long-term outcome of schizoaffective and schizophrenic disorders: a comparative study (1989)
    Springer
    European archives of psychiatry and clinical neuroscience 238 (1989), S. 135-139 
    Details
    ISSN: 1433-8491
    Keywords: Long-term outcome ; Prediction ; Schizophrenia ; Schizoaffective disorders ; Social consequences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A significantly higher proportion of schizophrenic than schizoaffective patients were found to experience negative social consequences of their illness. Schizophrenic males are more likely to have an unfavourable social prognosis than are schizophrenic females or schizoaffective patients of either gender. Schizophrenic males are, however, equally disadvantaged in regard to social consequences independently of other premorbid and sociodemographic factors. Unfavourable social consequences in male schizophrenics and favourable ones in female schizoaffectives can be predicted with high probability. Some social consequences can be predicted with relatively high probability for male schizoaffectives, while no prognosis can be made for female schizophrenics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00451000
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  • 10
    Electronic Resource
    Electronic Resource
    Early auditory evoked potentials (EAEP) in vertebral basilar insufficiency (1979)
    Springer
    European archives of psychiatry and clinical neuroscience 227 (1979), S. 367-376 
    Details
    ISSN: 1433-8491
    Keywords: Early auditory evoked potentials ; Vertebral-basilar insufficiency ; Frühe akustisch evozierte Potentiale ; Vertebro-basiläre Insuffizienz
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach akustischer Reizung mit einem kurzen Tonimpuls (tone pip) lassen sich in den ersten 10 ms das Summenaktionspotential des N. acusticus (I) und weitere 6 Wellen (II–VII) ableiten. 7 Komponenten wurden bei 40 Normalpersonen und 5 Komponenten (I–V) bei 12 Patienten mit typischen Symptomen einer vertebro-basilären Insuffizienz einer genauen Analyse unterzogen. Veränderungen der frühen akustisch evozierten Potentiale (FAEP) lassen eine topische Zuordnung gefäßbedingter Schädigungen dorso-lateraler Hirnstammanteile zu. Es handelt sich um eine nicht-invasive Untersuchungsmethode, die durch Verlaufskontrollen prognostische Aussagen ermöglicht.
    Notes: Summary Stimulation with a short tone pip elicits an acoustic nerve compound action potential (I) and different waves (II–VII) in the initial 10 ms. Seven waves have been studied in 40 control subjects and five waves in 12 patients with vertebral-basilar insufficiency. Abnormalities of the different waves were observed at levels such as cochlea and/or acoustic nerve, medulla, caudal pons, rostral pons, and midbrain. The recording of early auditory evoked potentials (EAEP) is a noninvasive method of confirming impairment of the auditory pathway caused by a reduced vascular supply of vertebral and basilar arteries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00344821
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