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  • 1
    ISSN: 1432-0738
    Keywords: Diisopropylfluorophosphate ; Acute and Chronic Poisoning ; Therapy with Obidoxime ; Reactivation of Cholinesterase in Various Tissues ; Diisopropylphosphorofluoridat ; Akute und subchronische Vergiftung ; Therapie mit Obidoxim ; Reaktivierbarkeit der ChE verschiedener Gewebe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An Meerschweinchen wurde der zeitliche Verlauf der ChE-Hemmung in Erythrocyten, Ventrikelmuskulatur und Gehirn bei subchronischer und akuter DFP-Vergiftung untersucht und die Reaktivierbarkeit der ChE dieser Gewebe nach subcutaner Injektion von Obidoxim geprüft. Bei beiden Vergiftungsarten ergaben sich Unterschiede hinsichtlich des Ausma\es und des zeitlichen Verlaufes der ChE-Hemmung zwischen den drei Geweben. Während der subchronischen Vergiftung durchläuft die ChE-Hemmung bei den Erythrocyten ein Maximum, bei der Ventrikelmuskulatur und dem Gehirn hingegen stellt sie sich kumulativ auf einen Endwert ein. — Die ChE des Gehirns werden durch Obidoxim weder bei der subchronischen noch bei der akuten Vergiftung reaktiviert. Die Reaktivierbarkeit der Erythrocyten-ChE ist bei beiden Vergiftungsarten wesentlich besser als die der ChE in der Ventrikelmuskulatur. Letztere können durch Obidoxim nur innerhalb eines kürzeren Zeitraumes reaktiviert werden als die der Erythrocyten.
    Notes: Summary The time course of inhibition of cholinesterase (ChE) was studied in erythrocytes, ventricular muscle and brain of guinea pigs during chronic and acute poisoning with DFP. The reactivation of ChE in these tissues following subcutaneous injection of obidoxime was also tested. In both kinds of poisoning, considerable differences in degree and time course of ChE-inhibition were observed in the three types of tissue studied. Whereas the ChE-inhibition in erythrocytes achieved a maximum and then subsided, there was a cumulative increase of inhibition leading to a maximal value which was maintained in both ventricular muscle and brain. The ChE of the brain could not be reactivated by obidoxime in either chronic or acute poisoning. In both types of poisoning, the reactivation of ChE in erythrocytes was substantially better than in cardiac muscle. The reactivation by obidoxime in the latter tissue was of shorter duration than in erythrocytes.
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  • 2
    ISSN: 1432-0738
    Keywords: Specific and Non-Specific Cholinesterases ; Guinea Pig Tissues ; Diisopropylfluorophosphate ; Obidoxime ; Reactivation ; Ageing ; Spezifische und unspezifische Cholinesterasen ; Meerschweinchengewebe ; Diisopropylfluorophosphat ; Obidoxim ; Reaktivierung ; Alterung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wird über Versuche berichtet, die Cholinesterasen von Erythrocyten und Plasma und von Homogenaten aus Großhirn und Herzventrikel des Meerschweinchens als spezifische oder unspezifische Cholinesterasen (ChEs) zu charakterisieren. Der relative Gehalt an spezifischen und unspezifischen ChEs kann durch die Verwendung der Substrate Acetylcholin, Acetyl-/gb-methylcholin und Buturyleholin annäherungsweise ermittelt werden. Der Gehalt an unspezifischen ChEs sinkt in der Reihenfolge Plasma, Herzventrikel, Großhirn. Bei der Bestimmung der Inaktivierung, Reaktivierung und Alterungsgeschwindigkeit der verschiedenen ChEs lassen sich folgende Unterschiede nachweisen: 1. Die spezifischen ChEs von Erythrocyten und Großhirn werden durch Obidoxim verschieden stark gehemmt. 2. Die unspezifischen ChEs von Plasma und Herzventrikel können gegenüber denen des Großhirns durch ihre verschiedenen k2-Werte hei der Inaktivierung mit DFP eindeutig unterschieden werden. 3. Gemessen an der Reaktivierbarkeit mit Obidoxim altert die DFP-inaktivierte spezifische ChE des Großhirns langsamer als die der Erythrocyten. 4. Die Reaktivierbarkeit der phosphorylierten unspezifischen ChEs in Plasma, Herzventrikel und Großhirn und ihre Alterungs-Halbwertszeiten hängen von der verwendeten Obidoximkonzentration ab.
    Notes: Abstract Studies were made to characterize the cholinesterases from erythrocytes, plasma and homogenates of cardiac ventricular muscle and brain of guinea pigs as specific or non-specific cholinesterases (ChEs). The relative content of both can be estimated using the substrates acetylcholine, acetyl-β-methylcholine and butyrylcholine. The content of non-specific ChE was found to decrease in the sequence: plasma cardiac-ventricular-muscle brain. The inactivation, reactivation and ageing-rate of the various ChEs were determined and yielded the following differences: 1. The specific ChEs from erythrocytes and brain were inhibited to different degrees by obidoxime. 2. The non-specific ChEs from plasma and cardiac ventricular muscle could be clearly differentiated from that of brain by means of their different k2-values upon inactivation with DFP. 3. The specific ChE of brain once inactivated by DFP was found to age more slowly than that of erythrocytes, taking the reactivation by obidoxime as indicator. 4. The reactivation of the phosphorylated non-specific ChEs and the half-life of the ageing processes were found to be dependent on the obidoxime concentration used.
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  • 3
    ISSN: 1432-0738
    Keywords: Cadmium ; Carbonic anhydrase ; Hemoglobin ; Blood ; Testes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die bei Säugetieren durch Cadmium (Cd) hervorgerufenen Hodenschäden beruhen angeblich auf einer Hemmung der Carboanhydratase (CAH). Da Cd dosisabhängig die Hodendurchblutung beeinflußt, könnte jedoch durch eine Verminderung der Zahl CAH-reicher Erythrocyten eine Hemmung der CAH im Hoden vorgetäuscht werden. Wir bestimmten deshalb CAH-Aktivitäten und Hämoglobin (Hb)-Gehalt im Blut und im Hoden von unbehandelten und Cd-behandelten Sprague-Dawley-Ratten. Entsprechende Untersuchungen wurden an Ratten-Hoden durchgeführt, die vorher über die a. testicularis perfundiert worden waren. Die Ratten erhielten Cd intraperitoneal als CdCl2 jeweils in Einzeldosen von 1,5, 3,0 und 5,0 mg Cd2+/kg Körpergewicht. 1. Die Untersuchungen an perfundierten Hoden zeigten deutlich, daß die im Hodengewebe bestimmten CAH-Aktivitäten nicht einer Hoden-CAH sondern vielmehr der Erythrocyten-CAH zuzuordnen sind. 2. Bei den Cd-behandelten Ratten beobachteten wir kurze Zeit (0,25–1,0 h) nach der Cd-Zufuhr zunächst reversible Durchblutungsänderungen. Sie bestanden in Abhängigkeit von der Cd-Dosis sowohl in einer vorübergehenden Abnahme (1,5 mg Cd2+/kg) als auch in einer Zunahme (3,0 bzw. 5,0 mg Cd2+/kg) des Hb-Gehaltes im Hoden. 3. Unabhängig von diesen geringfügigen Durchblutungsänderungen kam es später (14–24 h nach 1,5 mg Cd2+/kg, 7–14 h nach 3,0 mg Cd2+/kg und 1–3 h nach 5,0 mg Cd2+/kg) zu den bekannten hämorrhagischen Hodenveränderungen mit einer starken Zunahme des Hb-Gehaltes und der CAH-Aktivität. 4. Anhand der Korrelationen zwischen CAH-Aktivität und Hb-Gehalt im Blut und im Hoden konnte eine Hemmung der CAH als primäre Ursache der Cd induzierten Hodenschäden ausgeschlossen werden.
    Notes: Abstract The cadmium-induced (Cd) damage of mammalian testes is thought to be correlated with an inhibition of carbonic anhydrase (CAH) by Cd. Since Cd causes dose-dependent changes in blood flow of the testes, an inhibition of CAH in the testes could be simulated by a decrease of CAH-rich erythrocytes. Therefore, CAH activities and hemoglobin (Hb) content were determined in blood and testes of untreated and Cd-treated Sprague-Dawley rats as well as in testes perfused via the testicular artery. Cd was intraperitoneally applied as CdCl2 in single doses of 1.5, 3.0, and 5.0 mg Cd2+/kg b.w., respectively. 1. The experiments on perfused testes clearly demonstrated that the CAH activities originate from erythrocytes rather than from a tissue located enzyme. 2. The alterations in blood circulation occurring shortly (0.25–1.0 h) after the Cd administration were characterized by a dose-dependent, transient decrease (1.5 mg Cd2+/kg) as well as an increase (3.0 and 5.0 mg Cd2+, respectively) of the Hb content in the testes. 3. Independent of these minor alterations in a later state (14–24 h after 1.5 mg Cd2+/kg, 7–14 h after 3.0 mg Cd2+/kg, and 1–3 after 5.0 mg Cd2+/kg), Cd induced the well known hemorrhagic alterations of the testes with a high increase of Hb content and CAH activity. 4. By means of the correlations between CAH activities and Hb content in blood and testes an inhibition of the CAH by Cd as the primary cause for the tissue damage of the testes could largely be excluded.
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  • 4
    ISSN: 1432-0738
    Keywords: Aluminum ; Toxicokinetics ; Rat ; Parenterals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxicokinetics of aluminum (Al) in male Wistar rats was studied after single intragastric (IG) doses of 1000 and 12000 μg Al/kg and intravenous (IV) doses of 10, 100, 1000, and 12000 μg Al/kg. Serial blood samples, daily samples of urine and feces as well as brain, liver, kidney, spleen, quadriceps muscle, and femur samples were collected. Al was measured by atomic absorption spectrometry. Al blood profiles after IV doses were adequately described by a two-compartment open model. Al toxicokinetics was dose dependent and appeared to plateau at 12000 μg/kg. At IV doses between 10 and 1000 μg/kg the terminal half-life of elimination from whole blood (t1/2β) increased from 29.9±7.8 to 209.3±32.6 min, and the total body clearance (CL) decreased from 2.45±0.64 to 0.28±0.03 ml min−1 kg−1. Following an IV bolus of 10 and 100 μg/kg the administered Al was recovered completely from urine (94.4%±9.9% and 98.5%±3.2%). Twenty-nine days after the IV dose of 1000 μg/kg daily renal excretion decreased to baseline values while only 55.1%±8.0% of the dose was excreted. Nineteen days after the single IV dose of 1000 μg/kg Al accumulated in liver (28.1±7.7 versus 1.7±0.5 μg/g of control rats) and spleen (72.5±21.1 versus 〈0.4 μg/g). After the single 1000 μg/kg IG dose no absorption of Al was detectable. The IG dose of 12000 μg/kg resulted in a maximum blood Al level of 47.9±12.4 μg/l after 50 min. The blood concentration time curve fitted a one-compartment open model with a half-life of absorption of 28.2±3.6 min and a t1/2β of 81.2±20.2 min. Cumulative renal Al excretion was 0.18%±0.10% of the dose and oral bioavailability was 0.02%. Seventeen days after the 12000 μg/kg IG dose the Al content in femur samples was increased (2.7±1.3 versus 0.6±0.4 μg/g). In no case was fecal elimination of incorporated Al observed.
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  • 5
    ISSN: 1432-1076
    Keywords: Selenium ; Supplementation ; Platelets ; Glutathione peroxidase ; Glutathione S-transferase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A low Se intake in dietetically treated patients with phenylketonuria (PKU) or maple syrup urine disease (MSUD) leads to a marked reduction of the platelet glutathione peroxidase activity (GSHPx). The mean value amounted to 2.0 U/1011 platelets with t-butyl hydroperoxide (t-BOOH) (2.2 U/1011 with H2O2) in patients and 5.8 U/1011 with t-BOOH (5.4 U/1011 with H2O2) in the control children. After Se supplementation with yeast rich in Se (dose: 135 μg Se/m2) the GSHPx activities rapidly increased. They reached a plateau after 2–3 weeks and remained there during the following 15–20 weeks of supplementation. After the cessation of supplementation there was a slow decrease, the values reached a low plateau after 24 weeks. In addition platelet glutathione S-transferase (GSHTf) was estimated with 1-chloro-2,4-dinitrobenzene. No significant difference between the values in healthy and dietetically treated patients in a low or normal Se state was observed. GSHTf did not exhibit peroxidase activity and did not show a compensatory increase when Se dependent GSHPx activity was low. The patients do not reveal clinical signs of disturbed platelet function. GSHPx may act in platelets via lipoxygenase on the prostaglandin pathway. The physiologic consequence of altered arachidonate metabolism, when GSHPx is deficient in platelets, remains to be elucidated.
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  • 6
    ISSN: 1432-1076
    Keywords: Zinc ; Hair ; North Rhine-Westphalia ; Atomic absorption spectrophotometry ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hair zinc levels were estimated by atomic absorption spectrophotometry in 474 children, aged 3–7 years, from 11 kindergartens in a highly industrialized and polluted area (Duisburg) and 8 kindergartens in a rural area of North Rhine-Westphalia. The mean hair zinc level amounted to 118 μg/g, increasing between the 4th and 7th year of life. At all ages the values from the urban toddlers were lower than from rural toddlers, and in both regions they were higher in winter than in summer. Children with frequent upper respiratory tract infections (〉6 infections/year) showed significantly lower zinc hair values, independent of their age. Low hair zinc values (below 70 μg/g) were frequently found, raising the question as to whether this is a normal, age-related phenomenon, or whether it indicates a suboptimal zinc status of young children from North Rhine-Westphalia.
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  • 7
    ISSN: 1432-1076
    Keywords: Selenium ; Supplementation ; Plasma ; Glutathione peroxidase ; Glutathione S-transferase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The plasma glutathione peroxidase (GSHPx) activity was measured in normal adults and children and in patients with reduced selenium state because of dietary treatment of metabolic diseases (phenylketonuria or maple-syrup-urine disease) before and after selenium supplementation. Besides GSHPx (measured with t-butyl hydroperoxide, cumene hydroperoxide and hydrogen peroxide as acceptor substrates) the activity of glutathione S-transferase was estimated in plasma. Plasma GSHPx activity in healthy children was significantly lower than in healthy adults. In 11 dietetically treated patients with phenylketonuria or maple-syrup-urine disease the plasma GSHPx was reduced to about 17% of the values of healthy children of the same age. No glutathione S-transferase activity could be found in plasma of children in normal or reduced Se state. During administration of yeast rich in Se (200μg Se/d) for 90 days 2 healthy adults showed no significant change of plasma GSHPx activity. During Se supplementation (75–100μg Se/d) for 120–163 days 5 dietetically treated patients with PKU or MSUD exhibited a significant increase of plasma GSHPx activity within 2 days. The values reached a plateau after 1 to 3 weeks of supplementation and remained at this level within the following 4 to 5 months. Therefore, the activity of plasma glutathione peroxidase can be used as an indicator of short-term changes of selenium intake in selenium deficient individuals.
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  • 8
    ISSN: 1432-0738
    Keywords: Cholinesterases of Cod ; Characterization of Their Properties ; Inactivation by Paraoxon and Tabun ; Phosphorylating Constantsin vitro andin vivo ; Cholinesterasen beim Dorsch ; Charakterisierung ihrer Eigenschaften ; Inaktivierung durch Paraoxon und Tabun ; Phosphorylierungskonstantenin vitro undin vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Untersuchungen wurden im Zusammenhang mit einer möglichen Kontamination der Ostsee durch versenkte Tabunmunition durchgeführt. — Mittels verschiedener Substrate konnte festgestellt werden, daß die meisten Gewebe von Gadus callarias (Gehirn ≫ Herz ≧ Muskulatur ≫ Kiemen) ausschließlich Acetylcholinesterase (AChE, E.C.3.1.1.7.), die Leber auch Butyrylcholinesterase (E.C.3.1.1.8.) enthalten. Erythrocyten und Serum sind frei von beiden Cholinesterasetypen. Die Eigenschaften der AChE des Gehirns wurden durch Bestimmung des Substratoptimums (1 · 10−3M ACh), der Substrathemmung (I 50 bei 2 · 10−2M ACh), der Michaelis-Konstanten (K m = 1 · 10−4M ACh), der pH- und Temperaturabhängigkeit (maximale Aktivität bei pH 8,5 bzw. 37 °C) charakterisiert. Die spezifische Aktivität der AChE in Gehirn und Muskulatur hängt praktisch nicht vom Körpergewicht ab. Die Exposition (0,5 bis 24 Std) lebender Fische in Meerwasser mit Paraoxonund Tabunkonzentrationen zwischen 1 · 10−8 und 1 · 10−6M ergab: Beide Organophosphate werden offenbar schnell resorbiert. Die AChE in Gehirn und Muskulatur wird durch Paraoxon mit exponentiellem Zeitverlauf gleich schnell inaktiviert. Die bimolekulare Geschwindigkeitskonstante (k 2) unterscheidet sich kaum von derin vitro gemessenen. Die Reaktionskinetik von Tabun wird wahrscheinlich durch die Hydrolyse im Meerwasser verfälscht. Durch Tabun wird die AChE der Muskulatur schwächer inaktiviert als die des Gehirns. Die Fische sterben, wenn die Aktivität der Gehirn-AChE durch Paraoxon oder Tabun auf 5% gesenkt worden ist. Trotz der extrem langsamen Reaktionsgeschwindigkeit der Gehirn-AChE mit beiden Organophosphaten lassen sich mit Hilfe der AChE-Inaktivierung Konzentrationen zwischen 3. 10−8 und 1 · 10−7M = 0,005 bis 0,015 ppm Paraoxon oder Tabun bei 3- bis 6stündiger Exposition nachweisen.
    Notes: Abstract The investigations presented in this paper were carried out in connection with possible contamination of the Baltic Sea by dumped tabun ammunition. By means of different substrates it was possible to demonstrate that most tissues of Gadus callarias (cod), (brain 〉 myocardium ≧ skeletal muscle ≫ gills) contain only acetyleholinesterase (AChE, E.C.3.1.1.7.), whereas the liver also contains some butyrylcholinesterase (E.C.3.1.1.8.). Neither type of cholinesterase can be detected in erythrocytes and serum. The properties of the AChE of brain were characterized by determination of the substrate optimum (1 · 10−3M ACh), the substrate inhibition (I50 at 2·10−2M ACh), the Michaelis constant (Km = 1 · 10−4M ACh), and the dependence on pH and temperature (maximal activity at pH 8.5 and 37°C). The specific activity of AChE of brain or skeletal muscle is practically independent of the body weight. Exposure of living fish to concentrations of paraoxon or tabun between 1 · 10−8 M and 1 · 10−6M in sea water for 0.5 to 24 h yielded the following results: Both organophosphates were absorbed rapidly. Paraoxon inactivates the AChE of brain and of skeletal muscle with an exponential activity course at similar rates. The bimolecular rate constant (k 2) hardly differs from the one measured in vitro (k 2 in vivo 1.15 · 104M−1min−1,in vitro 1.6 · 104M−1min−1). Thein vitro reaction of tabun was probably falsified by its hydrolysis in sea water (k 2 for AChE of brain is approximately 8 · 103M−1min−1). The AChE of muscle was inactivated to a lesser degree by tabun than was cerebral AChE. The fish died when the activity of the AChE of the brain was lowered to a 5 % level by paraoxon or tabun. In spite of the extremely slow rate of reaction of cerebral AChE with either organophosphate it was possible to detect concentrations of 3 · 10−8 - 1· 10−7M ( 0.005 to 0.015 ppm. of paraoxon and tabun) by means of the AChE inactivation after 3 to 6 h of exposure.
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  • 9
    ISSN: 1591-9528
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 10
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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