Monoamine receptors in the amygdaloid complex of the tree shrew (Tupaia belangeri)

Although it is well known that the mammalian amygdala comprises a heterogeneous complex of cytoarchitectonically and histochemically distinct nuclei, the association of these nuclei with different monoamine systems has not been described in detail. We therefore investigated the pattern of receptors for monoamines in the amygdala of the tree shrew (Tupaia belangeri). Binding sites for the α₂-adrenoceptor ligand (³H) rauwolscine, the α₁-adrenoceptor ligand (³H) prazosin, the β-adrenoceptor ligand (¹²⁵I) iodocyanopindolol, and the serotonin_1A-receptor ligand (³H) 8-hydroxy-2 (di-n-propylamino) tertralin were visualized by in vitro autoradiography, and anatomically localized by comparing the autoradiograms to Nissl- and acetylcholinesterase-stained sections. To characterize binding of the radioligands pharmacologically, displacement experiments with different specific competitors were performed. Whereas the highest number of α₂-adrenergic binding sites was detected in the medial and the central nucleus as well as in the intercalated nueclei, the majority of serotonin_1A binding sites was found in the magnocellular basal nucleus and the accessory basal nucleus, demonstrating a clear difference in the anatomy of the α₂-adrenergic and the serotonin_1A receptor systems. In contrast, the pattern of α₁-adrenoceptor binding partially overlaps with that of both former receptor types. While the number of α-adrenergic and serotonin_1A binding sites is relatively high in the tree shrew amygdala, there is only a low number of β-adrenergic binding sites in most nuclei. However, in the cortical nuclei, moderate to high numbers of binding sites for all radioligands are present. Therefore, according to our data on the tree shrew amygdala, which is anatomically similar to the amygdala of cats and primates, α₂-adrenoceptors cover primarily the medial part of the amygdaloid formation and serotonin_1A-receptors predominantly occupy the basal nuclei, whereas α₁-adrenoceptors are present in both parts of the formation. © 1994 Wiley-Liss, Inc.     

Update Nephrologie?Renoprotektion durch Antihypertensiva: Teil I

Zusammenfassung. Inzidenz und Prävalenz einer terminalen, dialysepflichtigen Niereninsuffizienz auf dem Boden einer diabetischen Nephropathie und Hypertonie nehmen weltweit zu. Die Höhe des Blutdrucks stellt einen besonderen Risikofaktor dar. Zur primären und sekundären Prävention einer diabetischen Nephropathie, vor allem aber zur Progressionsverzögerung einer chronischen Nierenerkrankung ist deshalb die Blutdrucksenkung von außerordentlicher Bedeutung. Seit dem Working Group Report on Hypertension and Diabetes 1964 wurde bei Patienten mit einem Diabetes mellitus und/oder Niereninsuffizienz als Zielblutdruck 130/80 mmHg empfohlen; bei Patienten mit einer Proteinurie > 1 g/d und Niereninsuffizienz unabhängig von deren Ätiologie sollte der Blutdruck 125/75 mmHg betragen. Auf der Grundlage der vorliegenden Studien sind ACE-Hemmer bzw. AT1-Rezeptorblocker eine obligatorische Komponente der Therapie, da sie neben der antihypertensiven Wirkung blutdruckunabhängig renoprotektive Effekte aufweisen. Insbesondere bei Patienten mit chronischer Niereninsuffizienz ist in den meisten Fällen eine Mehrfachkombination von Antihypertensiva erforderlich; die Kombination eines ACE-Hemmers mit einem Kalziumblocker ist häufig notwendig. Ziele dieser antihypertensiven Therapie sind neben der Senkung des Blutdrucks die Rückbildung der Proteinurie und die Verzögerung bzw. Stopp der Progression des chronischen Nierenfunktionsverlustes. Abstract. Diabetes has become the most common single cause of end-stage renal disease in many countries. The coexistence of diabetes mellitus and hypertension dramatically increases the risk of developing target organ complications including renal disease. There are good arguments that ESRD in the patient with diabetes is largely preventable with the interventions currently available. For type 2 diabetes the UK Prospective Diabetes Study Group Trial clearly documented that the frequency of microangiographic sequelae can be diminished by glycaemic control and even more impressively by intensified antihypertensive treatment. An analysis of recent randomized long-term clinical trials that evaluated the rate of decline in renal function demonstrated that the lower the blood pressure within the range of normotensive values, the greater the preservation of renal function. Since the 1994 Working Group Report on Hypertension and Diabetes suggested a goal blood pressure of 130/80 mmHg should be achieved in patients with diabetes and/or renal insufficiency; lower bllod pressure levels, i. e. less than 125/75 mmHg are recommended for patients with proteinuria > 1 g/d and renal insufficiency regardless of etiology. Antihypertensive regimens should include an ACE inhibitor or an AT1-receptor blocker in order to provide maximum renal benefits in diabetic and non-diabetic renal diseases. Such low blood pressure are virtually impossible to achieve with monotherapy. In most cases the combination of two and more antihypertensive drugs is necessary. The purpose of this report is to update the previous recommendations with a focus on level of blood pressure control, proteinuria reductionn and retarding the progression of renal disease.     

Functional Topography of the Myelin-associated Glycoprotein. I. Mapping of Domains by Electron Microscopy

The functional topography of the myelin-associated glycoprotein (MAG) was investigated by electron microscopic analysis of rotary-shadowed molecules of a MAG fragment (MAG 90) comprising the five immunoglobulin-like domains of the extracellular part of the molecule. MAG 90 molecules appeared as rod-like structures (18.5±1.2 nm long and 4.0±0.8 nm wide) with a globular domain at one end. Antibodies directed against the amino- and carboxy-terminus of MAG 90 interacted with the non-globular terminal region, indicating that the molecule is bent in the globular region with the amino- and carboxy-terminal arms in close apposition to each other. An antibody which interferes with the binding of MAG to neurons interacted predominantly with the globular domain of MAG 90. The fibril-forming collagen types I, III and V bound mainly to the non-globular terminal region of MAG 90, whereas the majority of heparin molecules interacted with the globular region of the molecule. The L2/HNK-1 carbohydrate structure was localized at the non-globular region in the protein fragment comprising the fourth and fifth immunoglobulin-like domains.     

The mouse neural plate as starting material for studying neuronal differentiation in vitro

Summary Tissue from the mouse neural plate and neural tube was studied, by light and electron microscopy, as starting material for tissue culture.In vivo, up to embryonic day 9 (E 9, stage Th 14; Theiler 1972) all neuroepithelial cells of the neural plate were mitotically active. As judged from their light microscopic or ultrastructural appearance, they could hardly be distinguished from one another or from neuroepithelial cells of more mature embryos. The earliest few immature neurons in the mesencephalic anlage were discernible on day 9 1/2 (stage Th 15) in the prospective intermediate layer of the neural tube, concomitantly with the development of processes containing neurotubules and vesicles which were oriented in parallel to the basal lamina. For tissue culture, explants of the mesencephalic anlage of embryonic days 8 (Th 12/13), 9 1/2 (Th 15), and 11 (Th 18) were kept in vitro and their development was compared with each other and with the corresponding developmental stage in vivo in the initial phase of culture (e.g., E 8, day of explanation, kept in vitro for 2 days, E 10 in vivo being the stage for comparison). The study demonstrated that further in vitro development proceeded in an accelerated manner, independent of the developmental stage of the embryo from which the tissue was explanted. In vitro, proliferation of the explanted neuronal progenitor cells stopped in all explants within 24 h of culture as revealed by autoradiographic and electron microscopic techniques. Cytoplasmic transformation was observed corresponding to that found in vivo, but always greatly accelerated. Earliest axons had formed after 24 h in vitro; synapses with clear vesicles and dense core vesicles were observed after at least 3 days in culture in all explants regardless of age at the time of explantation (E 8 or E 11).The present ultrastructural results indicate that prospective neurons within the neuroepithelium of the neural plate and early neural tube were immediately able to develop into neurons without the complete sequence of mitotic events normally occurring under in vivo conditions.