The effects of a single administration of etifoxine on several psychological tests

The effects of etifoxine on healthy Ss was measured employing perceptual, psychophysiological and motor tests, in addition to which a personality inventory was given. All Ss took both drug and placebo with an interval of one week according to a balanced design. The same experimental procedure was used on both occasions under double blind conditions. The difference between the two sessions was tested for significance. Analyses of covariance were carried out with respect to the personality factors psychoticism, extraversion and neuroticism. The drug had depressant effects on performance in perceptual tests, particularly flicker fusion, and it also affected habituation to tones of both the evoked cortical potential and the GSR in the same direction. The drug seemed completely inactive with respect to motor performance. There was a distinct interaction between drug-effect and personality factors. Ss whose scores indicated a low level of cortical arousal were less affected by the drug than others.We are indebted to Hoechst Pharmaceuticals Ltd. for the support of this investigation.     

Cauda equina syndrome with multiple lumbar diverticula complicating long-standing ankylosing spondylitis

A patient with cauda equina syndrome complicating long-standing inactive ankylosing spondylitis is described. The first neurological symptoms started 15 years after the onset of ankylosing spondylitis. Over a follow-up period of 12 years the cauda equina syndrome showed a slowly progressive but disabling course leading to sensory disturbances in the lumbar and sacral dermatomes, weakness and wasting of the muscles innervated by these nerve roots, sphincter disturbances, and impotence. Magnetic resonance imaging, computed tomography, and lumbar myelography showed enlargement of the dural sac with multiple lubar diverticula eroding the lumbosacral vertebrae. The pathophysiology of the cauda equina syndrome in ankylosing spondylits is unclear. Surgical treatment seems justified only in patients with a short history of neurological symptoms. Correspondence to: R. Schröder     

Different mutations in the COL4A5 collagen gene in two patients with different features of Alport syndrome.

Alport syndrome is a hereditary renal disease in which progressive renal failure is often accompanied by sensorineural deafness and ocular abnormalities. Recently, mutations were detected in the type IV collagen alpha 5 chain gene in Alport syndrome patients. We searched for mutations in this gene in 18 unrelated patients, and in two patients abnormalities were detected. In the gene of patient BB we identified a complex deletion, which included the exons encoding the non-collagenous domain and part of the collagenous region. This patient showed early onset nephritis (end-stage renal disease at 17 years) with deafness. Within a year after receiving a kidney from an unrelated donor, he developed an antiglomerular basement membrane nephritis. In patient WJ a point-mutation was detected, changing a tryptophane into a serine in the non-collagenous domain. His clinical features are milder (renal failure at 33 years, no hearing loss), and a recent renal allograft did not provoke antiglomerular basement membrane disease. These initial data suggest that differences in the extent of disruption of the non-collagenous domain may correlate with the severity and/or heterogeneity of Alport syndrome and with the development of nephritis in renal allografts.     

Pyruvate kinase-catalyzed ATP-formation in human red blood cell membranes

Summary Previous studies on the linkage between enzymatically catalyzed ATP-generating reactions in the red blood cell membrane and the sodium and potassium transport in the control of overall glycolysis of human erythrocytes were controversial. In this study a significant amount of pyruvate kinase activity is shown to be localized within the membrane. Membrane fragments produce 20.5mol of ATP per 10¹⁰ membranes per hour from phosphoenolpyruvate and ADP. The kinetics of the membrane-localized pyruvate kinase do not differ from those of the enzyme from hemolysates. The results clearly document the presence of the second ATP-generating enzyme of glycolysis, pyruvate kinase, in human red blood cell membranes. The main fraction of the enzyme is deeply hidden in the lipid layers of the membrane. It can be demasked by mechanical desintegration of membranes at high levels of activity. It is suggested that the amount of the membrane-localized fraction of pyruvate kinase is related to the clinical severity of the hemolytic process in pyruvate kinase deficiency.Supported by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, Schr 86/13     

The morphology of the bone marrow of the mouse

For an investigation on the morphology of the cells of the bone marrow of the mouse, use was made of 2 stains: MAY-GRUNWALD-GIEMSA (MGG) and methyl-green-pyronine-stilbene (MPS). The results are reported, and are compared with each other and with those obtained with the LENDRUM stain. To compare results in the same cell, its coordinates were determined with a computer-controlled scanning microscope after staining with the first method, and the preparation was then destained and restained for evaluation of the second method. The advantages and disadvantages of the stains are discussed, and it is concluded that for the evaluation of the morphology of the eosinophilic leukocyte, the MPS stain seems to be superior.     

Possible role of prostaglandins in the regulation of coronary blood flow

Summary Prostaglandins may represent one group of local chemical factors that control coronary perfusion and adapt it to the metabolic demands of the heart. Present study summarizes the current knowledge in this field with particular reference to prostacyclin (PGI₂). The major biosynthetic pathways and their modification by drugs are briefly outlined. The sources and fates of cardiac prostaglandins are described and possible mechanisms of action discussed in both physiological and pathophysiological (myocardial ischemia) situations. Attention is focussed on the interplay between catecholamines, adenosine and PGI₂. A model is presented, based on the hypothesis that adenosine from myocardial metabolism and PGI₂ from vascular sites are acting in concert to antagonize sympathetic metabolic and vasoconstrictory influences and to maintain an adequate blood supply to the heart.

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Zusammenfassung Prostaglandine können als eine Gruppe chemischer Substanzen angesehen werden, die lokal entstehen und die koronare Perfusion an die Stoffwechselerfordernisse des Herzens anpassen. Vorliegende Arbeit gibt eine Zusammenfassung des heutigen Wissensstandes auf diesem Gebiet unter besonderer Berücksichtigung von Prostacyclin (PGI₂). Neben Biosynthese und Metabolismus sowie ihrer Beeinflussung durch Pharmaka werden kardiale und koronare Wirkungen von PGI₂ beschrieben und mögliche Wirkungsmechanismen der Substanz unter physiologischen und pathophysiologischen (myokardiale Ischämie) Bedingungen diskutiert. Im Mittelpunkt stehen Wechselwirkungen zwischen PGI₂, Adenosin und Katecholaminen und ihre möglichen Konsequenzen für die Regulation des koronaren Tonus. Hierzu wird ein Modell vorgestellt, bei dem die direkt-vasokonstriktorischen und stoffwechselsteigernden Katecholaminwirkungen durch Bildung von PGI₂ im Gefäßbereich und Adenosin im Herzmuskelstoffwechsel funktionell antagonisiert werden.

     

Effects of 3-isobutyl-1-methylxanthine on neonatal pancreatic islets maintained in tissue culture

The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) promoted the formation of monolayers in cultured pancreatic islets isolated from neonatal rats. Immunofluorescence with specific antisera to insulin and glucagon revealed B-cells and A-cells in these monolayers. Glucose-mediated insulin release was increased by raising the glucose concentration from 5 to 10 mmoles/l. Addition of IBMX (0.1 mmoles/l) to medium containing 10 moles/l glucose produced a further increase in insulin release. Recovery of total insulin, i.e. intracellular insulin plus insulin secreted, was also increased by approximately 50% after 8 days of culture. The B-cells showed a marked biosynthetic response to an acute glucose challenge after prior culture with 10 mmoles/l glucose. Although both unstimulated (1.5 mmoles/l glucose) and stimulated rates (1.5 mmoles/l glucose) of [3H]leucine incorporation into (pro)insulin were significantly higher following culture in 10 mmoles/l glucose plus IBMX (0.1 mmoles/l) than after prior culture with 10 mmoles/l glucose alone, the percentage of (pro)insulin synthesized in relation to total protein synthesis was only increased at the low concentration of glucose. These studies demonstrate that monolayer cultures of neonatal B-cells can be readily produced by IBMX and maintained in a functional state, as defined by their secretory and biosynthetic response. It is suggested that the phosphodiesterase inhibitor exerts a sensitizing effect on the responsiveness of the B-cell to glucose. Moreover, the culture system employed in the present study may prove to be useful for further studies of various agents affecting the B-cell function.