Search Results - (Author, Cooperation:Kuschinsky)

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: The hydroxyl radical is a very reactive oxygen species that damages biomolecules in the brain and in other tissues. The possible pharmacological intervention to prevent hydroxyl radical formation was studied in vivo using the microdialysis technique in brains of nonanesthetized rats. Hydroxyl radicals form stable adducts [mainly 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-DHBA)] via an aromatic hydroxylation reaction with salicylic acid. 2,3-DHBA was separated and quantified by HPLC and electrochemical detection. Microdialysis probes were implanted into the striatum 1 day before measurement of levels of hydroxyl radicals. The next day, the probes were first perfused for 120 min with a modified Ringer's solution containing 5 mM salicylic acid, to obtain stable baselines. Afterward, the perfusion solution was switched to another solution that in addition contained 50 mM glutamate, to stimulate radical formation. Twenty minutes later, α-phenyl-tert-butylnitrone (PBN; 100 mg/kg), selegiline (10 mg/kg), or saline was administered intraperitoneally. The glutamate perfusion produced marked two- to 2.5-fold increases in 2,3-DHBA content. Treatment with PBN significantly antagonized the rise of 2,3-DHBA level, indicating that PBN is a direct radical scavenger not only in vitro but also in vivo. Acute treatment with selegiline failed to reduce significantly the glutamate-induced radical formation. The acute experiments presented here do not support the suggestion that the neuroprotective effects of selegiline described in the literature are due to a potential hydroxyl radical scavenging property of the drug.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

G-protein-coupled receptors (GPCRs) are the largest group of cell surface molecules involved in signal transduction and are receptors for a wide variety of stimuli ranging from light, calcium and odourants to biogenic amines and peptides. It is assumed that systematic genomic data-mining has identified the overwhelming majority of all remaining GPCRs in the genome. Here we report the cloning of a novel orphan GPCR which was identified in a search for erythropoietin-induced genes in the brain as a strongly up-regulated gene. This unknown gene coded for a protein which had a seven-transmembrane topology and key features typical of GPCRs of the A family but a low overall identity to all known GPCRs. The protein, coded ee3, has an unusually high evolutionary conservation and is expressed in neurons in diverse areas of the CNS with relation to integrative functions or motor tasks. A yeast two-hybrid screen for interacting proteins revealed binding to the microtubule-associated protein (MAP) 1b. Coupling to MAP1a has been described for another cognate GPCR, the 5-hydroxytryptamine (5HT) 2a receptor. Surprisingly, we found complete colocalization of ee3 and the 5HT2a receptor. The interaction with MAP1b proved to be critical for the stability or folding of ee3 as in mice lacking MAP1b the ee3 protein was undetectable by immunohistochemistry, although messenger RNA levels remained unchanged. We propose that ee3 is a highly interesting new orphan GPCR with potential connections to erythropoietin and 5HT2a receptor signalling.

Electronic Resource

0006-3002

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Chemistry and Pharmacology

Medicine

Physics

Electronic Resource

0006-3002

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Chemistry and Pharmacology

Medicine

Physics

Electronic Resource

1436-6215

Springer Online Journal Archives 1860-2000

Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition

Medicine

Electronic Resource

1435-1463

Morphine ; conditioned effects ; hyperkinesia ; stereotyped behaviour

Springer Online Journal Archives 1860-2000

Medicine

Summary Morphine (15 mg/kg i.p.) produces a biphasic effect: hypokinesia, followed by hyperkinesia and stereotyped behaviour. After repeated administration, the signs of the second phase more and more predominate. In the following study, it was evaluated, to which degree “classical” pharmacodynamic tolerance to hypokinesia or, alternatively, conditioning phenomena contribute to this shift. In particular, it was studied whether not only hyperkinesia but also stereotypies could occur as conditioned responses either in the presence or in absence of morphine. Rats were conditioned 8 times with morphine (15 mg/ kg i.p.) in the presence of various, defined conditioned stimuli (auditory, olfactory and tactile), another group was “pseudoconditioned”, i.e. they were exposed to the same treatment schedule of morphine and stimuli, but with no positive association between drug and stimuli, a third group (“naive rats”) was treated with saline instead of morphine, but exposed to the same stimuli as both other groups. All groups were tested for conditioned responses in the presence of the conditioned stimuli. One series of experiments was performed with saline after a break of 2 days after the end of the conditioning period, a second series was tested with saline after a break of 7 days, a third series with morphine (15 mg/kg i.p.) after a break of 2 days, a fourth series with the same dose of morphine after a break of 7 days. The results showed that when morphine was used after a break of 2 days, “classical” pharmacodynamic tolerance, but not conditioning phenomena could explain the shift in behaviour, whereas under the three other protocols described, some conditioned behavioural effects could be observed, either in presence or in absence of morphine, at least in part of the parameters used (locomotor activation, decrease in hypokinesia, sniffing, gnawing, rearing, but not in licking). Accordingly, development of pharmacodynamic tolerance and, to a lesser degree, conditioning contribute to the shift in behaviour after repeated administration of morphine. The conditioned effects could not be attributed to any alteration in striatal or mesolimbic dopamine turnover.

Electronic Resource

1435-1463

Keywords: Chronic nicotine ; local cerebral glucose utilization ; 3-O-methylglucose ; autoradiography.

Springer Online Journal Archives 1860-2000

Medicine

Summary. Acute and chronic infusion of nicotine is known to result in a distinct increase in local cerebral glucose utilization (LCGU) in several brain structures. The present study addresses the question whether this increase in LCGU is paralleled by a local change in glucose transport in rat brain. Nicotine was infused either acutely for 3 hours or chronically by osmotic minipumps for one week. Local rate constants for glucose transport were measured in brain cryosections using the 3-O-[14C]methylglucose method. Local rate constants K1 and k2 were lower in part of the brain structures during acute (−10% to −20%) and in nearly all structures during chronic (−39% to −41%) nicotine. The finding of a decreased glucose transport during chronic nicotine was confirmed by additional experiments of 3-O-[14C]methylglucose transfer in an epithelial cell culture. It is concluded that acute and chronic nicotine infusion results in decreased glucose transport although LCGU is either unchanged or increased.

Electronic Resource

1420-9071

Springer Online Journal Archives 1860-2000

Biology

Medicine

Summary After two-stage nephrectomy in rats the potassium concentration in the red blood corpuscles (RBC) decreases from 10.6 ± 0.3 to 5.5 ± 0.3 mEq per 100 ml of RBC within 48 h. The decrease is accompanied by a much smaller increase in the plasma potassium concentration; the hyperkaliemia in nephrectomized rats is less pronounced than in nephrectomized dogs or anuric humans. Na+ in RBC increases by about 44% after nephrectomy; while there is only a very slight decrease of Na+ in plasma. Plasma chlorides drop from 10.92 ± 0.08 mEq/100 ml of plasma to 6.00 ± 0.81 mEq % within 48 h after nephrectomy. RBC chlorides tend to increase again after an initial drop from 5.22 ± 0.07 to 3.82 ± 0.90 mEq% within the first 8 h.

Electronic Resource

1420-9071

Springer Online Journal Archives 1860-2000

Biology

Medicine

Summary A method has been described which allows the continuous recording of the blood pressure of small laboratory animals (mice and rats) on the smoked drum.

Electronic Resource

1420-9071

Springer Online Journal Archives 1860-2000

Biology

Medicine

Summary Δ 5-Pregnen-3,20-dione-N,N'-ethylpyrrolidine-bisguanylhydrazone and Δ5-pregnen-3β-hydroxy-20-one-N,N'-ethyl-pyrrolidine-monoguanylhydrazone inhibit the activity of the ionic pump of cold-stored erythrocytes of guinea-pigs. The contractile force of isolated guinea-pig auricles is decreased by the mono-derivate and increased by the bis-derivate in spite of the similar action upon the pumping mechanism.

Electronic Resource

1420-9071

Springer Online Journal Archives 1860-2000

Biology

Medicine

Zusammenfassung Nach Hemmung der Dopaminsynthese beschleunigte Morphin bei Ratten die Abnahme der Dopaminkonzentration im Corpus striatum. Dieser Effekt, der durch Naloxon gehemmt wurde, lässt sich durch eine Erhöhung des Dopamin-Umsatzes im Corpus striatum unter Einfluss von Morphin erklären.

Electronic Resource

1437-2320

Capillary density ; cerebrovascular resistance ; local cerebral blood flow ; local cerebral glucose utilization ; neuronal activity ; uncoupling of cerebral metabolism and blood flow

Springer Online Journal Archives 1860-2000

Medicine

Abstract Functional activity, metabolism and blood flow are locally heterogeneous in the brain, but tightly coupled. This adjustment occurs in two different ways: 1. Shortterm, dynamic coupling mediated by local vasoactive factors that ensure second-to-second regulation. 2. Long-term, static coupling apparently mediated by capillary density and developed in response to local functional and metabolic activity. Recognizing these two mechanisms permits one to distinguish apparent from real uncoupling. It allows the conclusion that there is no indication of an uncoupling of metabolism and blood flow during physiological conditions.

Electronic Resource

1432-1459

Springer Online Journal Archives 1860-2000

Medicine

Zusammenfassung 1. Es wird eine Apparatur (Modifikation des von Spiegel angegebenen Modells) beschrieben, mit welcher der Tonus beider Kniestrecker beim Kaninchen gleichzeitig bzw. kurz hintereinander gemessen werden kann. Bei steigender Belastung ergibt sich eine Spannungskurve. 2. Der Verlauf der Spannungskurve des linken und rechten Kniestreckers ist normalerweise gleich. Auch nach einseitiger Exstirpation des Bauchgrenzstranges ist kein Unterschied festzustellen. 3. Nach Entfernung des Bauchgrenzstranges tritt eine humorale Regulation von seiten der Nebennieren nicht in Kraft; denn auch nach Nebennierenexstirpation ist der Tonus der normalen und sympathektomierten Seite derselbe. Auch eine Adrenalininfusion hat keinen Einfluß auf den Tonus des ruhenden Muskels. 4. Ergotaminvergiftung hat keine Wirkung auf den Tonus des Kniestreckers (sowohl an der normalen wie an der operierten Seite). 5. Durch Hyperventilation ließ sich bei Kaninchen keine nachweisliche Tonusveränderung erzielen.

Electronic Resource

1432-1238

Local cerebral blood flow ; Autoradiography ; Hemorrhagic hypovolemia ; Hemorrhagic shock

Springer Online Journal Archives 1860-2000

Medicine

Abstract Objective Of the animal models of human hemorrhagic shock, the volume-controlled hemorrhage model appears to come closer to the clinical situation than the commonly used pressure-controlled model, since the volumecontrolled model allows regulatory adjustment of blood pressure. The effects of volume-controlled hemorrhage on local cerebral blood flow (LCBF) of conscious animasl are not known. The present study investigates specific reaction patterns of LCBF in comparison to mean cerebral blood flow (CBF) during graded volume-controlled hemorrhagic shock in conscious rats. Methods Conscious, spontaneously breathing, and minimally restrained rats were subjected to different degrees of volume-controlled hemorrhage (taking either 25, 30, 35, or 40 ml arterial blood/kg body weight (b.w.). Thirty minutes after the completion of blood taking, LCBF was determined during hemorrhagic hypovolemia using the autoradiographic iodo (14C) antipyrine method. A group of untreated rats (no hemorrhage) served as controls. LCBF was determined in 34 defined brain structures and mean CBF was calculated. Results During less severe hemorrhage (25 and 30 ml/kg b.w.) mean CBF was significantly higher than in the control group (+19% and +25%). During severe hemorrhage (35 and 40 ml/kg b.w.) mean CBF remained unchanged compared to the control values, although significant increases in LCBF could be detected in many of the brain structures analyzed (maximum +44%). The mean coefficient of variation of CBF was increased, indicating a larger heterogeneity of LCBF values at shed blood volumes of 35 and 40 ml/kg b.w. Conclusions A comprehensive and novel description of the local distribution of CBF during graded volume-controlled hemorrhage in conscious rats shows unexpected increases in LCBF and mean CBF. This “hypovolemic cerebral hyperemia” might be caused by endogenous hemodilution, thus maintaining the blood supply to the brain during hypovolemic shock.

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Zusammenfassung Die Veränderungen der Natrium-, Kalium- und Chlorid-Konzentration in Plasma und Erythrocyten nach der Nephrektomie wurden bei mehreren Gruppen von verschieden alten und verschieden ernährten Ratten untersucht. Nach der Nephrektomie steigt in der Regel der Plasma-Kalium-Spiegel an, während der Plasma-Chlorid-Spiegel innerhalb von 72 Std um etwa 20% fällt. In den Erythrocyten verändert sich die Natrium-Konzentration nicht, die Kalium-Konzentration sinkt langsam, innerhalb von 72 Std um 12% ab (die Chlorid-Konzentration verändert sich nicht). Der Hämoglobingehalt des Blutes sinkt innerhalb von 48 Std um etwa 11% ab. Verschiedene Ernährungsformen haben auf diese Veränderungen wenig Einfluß. Nach der Nephrektomie steigt bei jungen Ratten der Plasma-Kalium-Spiegel schneller und sinkt der Chlorid-Plasma-Spiegel schneller ab als bei ausgewachsenen Tieren; die Kalium-Konzentration in den Erythrocyten sinkt bei jungen Ratten nach der Nephrektomie nicht ab. Behandlung mit massiven Dosen von Alkalien nach der Nephrektomie verlängert die Überlcbenszeit, verlangsamt das Ansteigen der Plasma-Kalium-Konzentration und beschleunigt das Absinken der Plasma-Chlorid-Konzentration.

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Zusammenfassung Am isolierten Papillarmuskel und Vorhof der Katze haben Val5-Hypertensin II und Val5-Hypertensin Hamid eine positiv inotrope Wirkung, die auf molarer Basis berechnet fast so stark wie die kontraktionssteigernde Wirkung von Noradrenalin ist. Im Gegensatz zum Noradrenalineffekt nimmt die Frequenz des spontanschlagenden Vorhofpräparates dabei nur geringgradig zu. Die positiv inotrope Wirkung der genannten Hypertensine läßt sich durch das Sympathicolyticum 1-(3,4-Dichlorphenyl)-2-(isopropylamino)-äthanol hemmen. Das mit intracellulären Mikroelektroden gemessene Membranpotential und Aktionspotential des Papillarmuskels zeigt unter Val5-Hypertensin II keine Veränderungen.

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Zusammenfassung Im Muskel des NN-losen Tieres zerfällt bei gleicher Arbeitsleistung mehr Phosphagen als im normalen. Dieser vermehrte Zerfall beruht auf verminderter Milchsäurebildung (analog der Monojodessigsäurewirkung). Da die Tätigkeit des Muskels durch Adrenalin wieder in Gang kommt, ist anzunehmen, daß Adrenalin bei dem Ablauf der chemischen Prozesse im Muskel eine physiologisch wichtige Rolle spielt; ohne Adrenalin scheint das Glykogen blockiert zu sein.

Electronic Resource