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Das Problem der Beziehungen zwischen Tuberkulose und Schizophrenie löst sich — vom konstitutionsbiologischen Standpunkt—dahin auf, daß diese beiden Krankheiten gleichsinnige Affinitäten zum leptosomen Habitus haben und so auf dem Weg über die Körperbauform in einer gewissen Korrelation stehen. Damit ist freilich kein direkter Gegenbeweis gegen die AnschauungenLuxemburgers, der ja methodisch ganz anders vorgeht, erbracht. Beide Betrachtungsweisen sind nebeneinander möglich, uns scheint aber, daß unsere Ansicht über das Problem Schizophrenie — Tuberkulose dadurch mehr an Wahrscheinlichkeit gewinnt, daß sie sich auf den empirisch genau bekannten leptosomen Habitus stützt, während das RadikalLuxemburgers ja vorwiegend aus erbtheoretischen Überlegungen abgeleitet ist.

Das tempierte Hypnoticum „Profundol“ (0,5 g) führte in Versuchen an psychiatrischem Krankenmaterial auch bei schweren Schlafstörungen einen ausgiebigen, durchschnittlich 7 Stunden währenden Schlaf herbei. Das Profundol stellt also ein Mittel dar, mit welchem selbst bei jenen schweren und schwierig zu bekämpfenden Formen von Schlafstörung, wie sie die psychiatrisch-klinische Praxis aufweist, ein die ganze Nacht währender, im allgemeinen ruhiger Schlaf erzielt wird, ohne daß weitere Nachhilfe erforderlich wäre. Der Eintritt des Schlafes erfolgte im allgemeinen I Stunde nach Verabfolgung des Mittels. Will man also die gute Wirksamkeit des Profundols an psychiatrischen Kliniken entsprechend ausnützen, so muß die Verabfolgung des Profundols genügend lange Zeit vor der Stunde des gewünschten Schlafeintrittes erfolgen.

Nach Umwandlung in die Methylester wurden gaschromatographische Analysen der Stuhlfettsäuren vorgenommen. Das Fettsäuremuster von zwei Kranken mit einer Steatorrhoe unterschied sich wesentlich von dem beim Gesunden. Es ähnelt weitgehend dem des Nahrungsfettes. Unter Substitution mit Pankreasfermenten trat trotz Normalisierung der Stuhlfettausscheidung keine völlige Angleichung der Stuhlfettsäurenzusammensetzung an die Werte beim Gesunden ein.

Previous study showed inhibition of RhoA and Rho kinase (ROCK) activity with fasudil could alleviate diabetes-induced cardiac dysfunction partially due to improvement of myocardial fibrosis. However, the effect of fasudil on intracellular calcium cycling and actin remodeling, both of which are important to regulate excitation-contract coupling, is still not fully elucidated. In this study, a diabetic cardiomyopathy model was induced by a single intraperitoneal injection of streptozotocin (STZ) in male Sprague Dawley rats. Diabetic rats were treated with fasudil or placebo for 8 weeks. We found that long-term administration of fasudil, a specific Rho kinase inhibitor, significantly ameliorated diabetes-induced contractile dysfunction both at cellular and whole organ levels. Fasudil-treated rats displayed improved diastolic intracellular calcium ([Ca2+]i) removal and rescued expression of protein responsible for [Ca2+]i clearance. Furthermore, our study indicated that fasudil treatment normalized the phosphorylation of the PKCβ2/Akt pathway in the diabetic heart, which might be the underlying mechanism accounting for the protective effect of fasudil on [Ca2+]i clearance. In addition, compared to the diabetes group, fasudil also normalized the G/F-actin ratio by preventing cofilin phosphorylation and promoted F-actin organization, suggesting a beneficial effect on actin remodeling. These findings indicate the protective effect of fasudil against diabetes-induced cardiac dysfunction via modulation of Ca2+ handling and actin remodeling. Overactivation of RhoA/ROCK plays a key role in the development of DCM. Inhibition of ROCK activity with fasudil improved [Ca2+]i removal in diabetic cardiomyocytes. Fasudil normalized the G/F-actin ratio and promoted F-actin organization. ROCK may be an excellent therapeutic target for the treatment of DCM.

A neurogenetic disorder is defined as a clinical disease caused by a defect in one or more genes which affect the differentiation and function of the neuroectoderm and its derivatives. Genetic findings in various neurogenetic disorders are discussed. Huntington disease, spinobulbar muscular atrophy, and the autosomal dominant cerebellar ataxias are examples of autosomal dominant disorders caused by the expansion of trinucleotides (CAG) within disease genes. The CAG expansions appear to result in a gain of gene function. Prenatal, presymptomatic, and differential diagnostic tests are based on the detection of the repeat expansions. Point mutations within disease genes result in many additional neurogenetic disorders. An autosomal dominant form of amyotrophic lateral sclerosis and various types of craniosynostotic syndromes are described. The mutations in the disease genes also appear to result in a gain of gene function. Molecular diagnosis in these disorders is based on the direct examination of the mutated gene by methods such as single-strand conformation polymorphism analysis, denaturing gradient gel electrophoresis, and direct DNA sequencing. In many neurogenetic disorders the disease gene has not yet been identified. Here molecular diagnosis relies on indirect approaches based on methods such as the analysis of linkage and of allelic association. Hereditary forms of dystonia are presented as examples. Common sporadic neurological disorders such as Alzheimer and Parkinson diseases frequently have multifactorial causes. Investigations into the molecular basis and the development of diagnostic tests in these two important diseases are discussed. At present no curative therapies exist in neurogenetic disorders. Gene therapeutic approaches, however, provide promise for a cure in at least some of these diseases. Basic principles of gene therapy are explained and attempts at gene therapy in Alzheimer and Parkinson diseases are described. Finally, some of the many obstacles are summarized that must be overcome before gene therapy becomes feasible in most monogenic neurological diseases.