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  • Amiloride  (4)
  • pharmacokinetics  (4)
  • Battered child syndrome  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 1111 (1992), S. 159-164 
    ISSN: 0005-2736
    Keywords: (Colon) ; (Coprodeum) ; (Hen intestine) ; Amiloride ; Current-voltage relationship ; Expression ; Oocyte ; Sodium ion channel
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    International journal of legal medicine 94 (1985), S. 93-101 
    ISSN: 1437-1596
    Keywords: Infant skull fractures ; Biomechanical fragility ; Battered child syndrome ; Schädelfraktur, Säuglinge ; Biomechanische Fragilität ; Kindesmißhandlung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung In Fortführung früherer experimenteller, postmortaler Schädelbruchverletzungen von Säuglingen nach Stürzen aus 82 cm Höhe wurden weitere 35 Sturzversuche durchgeführt, so daß insgesamt Ergebnisse von 50 Fällen vorliegen. Bei je 5 Sturzversuchen auf harten Untergrund — (Steinkachelboden, Teppichboden und Linol-Schaumstoff) — waren in allen Fällen Kalottenfrakturen entstanden. Bei den 35 Sturzvorgängen auf weich gepolsterten Untergrund — (Schaumstoffmatte, Kamelhaardecke) — traten bei 5 Fällen gleichartige Frakturen auf, die im Os parietale lokalisiert waren. In dieser Region besteht bis zum späten Säuglingsalter wegen primärer Einschichtigkeit der Ossifikation, noch fehlender Diploe und Vaskularisation eine besondere Prädilektionszone für Bruchverletzungen nach stumpfer Gewalt, insbesondere bei Sturz auf den Kopf. Diese Untersuchungsergebnisse haben somit bestätigt, daß nach angeblichen Sturzvorgängen aus Wickeltischhöhe die Annahme der Unversehrtheit des Säuglingsschädels nicht berechtig ist.
    Notes: Summary Following previous experiments on postmortem skull fractures of infants, falls from 82-cm heights onto stone (A), carpet (B) and foam-backed linoleum (C), 35 further falling tests were carried out onto softly cushioned ground. In 10 cases a 2-cm thick foam rubber mat (D) was chosen and in 25 further cases a double-folded (8-cm-thick) camel hair blanket (E). Hence the results of altogether 50 tests could be evaluated. In test groups A–C on a relatively hard surface, skull fractures of the parietale were observed in every case; in test group D this fracture was seen in one case and in test group E in four cases. Measurements along the fracture fissures showed bone thicknesses of 0.1–0.4 mm. The fracture injuries originated in paper-thin single-layer bone areas without diploe, which can also be considered the preferred regions for skull fractures of older infants following falls from low heights. These results indicate that it is no longer possible to assume that the skull of infants is not damaged after falls from table height.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    International journal of legal medicine 92 (1984), S. 87-94 
    ISSN: 1437-1596
    Keywords: Infant skull fractures, experimental study ; Battered child syndrome ; Schädelfraktur, Säuglinge ; Sturzhöhe ; Kindesmißhandlung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Nach pädiatrischen Untersuchungen sollen Stürze aus Standhöhe zu Schädelfrakturen des Säuglings führen können und meist symptomlos bleiben. Fast jeder Säugling hat einen oder mehrere Stürze aus „niedriger Höhe“, z. B. aus dem Kinderwagen, vom Wickeltisch, von der Treppe etc., erlitten. Unter den forensischen Aspekten der Aufsichtspflichtverletzung, der Kindesmißhandlung bzw. der Kindestötung stellt sich für den Rechtsmediziner oft die Frage, ob Schädelbrüche beim Säugling tatsächlich bei angeblich geringen Fallhöhen entstehen können. In 3 Testserien (à 5) ist der Sturz aus 0,82 m im freien Fall 1) auf Stein-Kachelboden, 2) auf Teppichboden, 3) auf Linol-Schaumstoffboden erfolgt. Nach den Obduktionsbefunden sind in allen Fällen Schädelbrüche entstanden, unabhängig von der Beschaffenheit des Bodens. In 3 Fällen haben die Bruchlinien die Schädelnähte überschritten. Fazit: 1. Bei Stürzen aus Wickeltischhöhe ist prinzipiell mit Brüchen des Säuglingsschädels zu rechnen. 2. Bei dem Verdacht einer Kindesmißhandlung bleibt letztlich der Gesamtaspekt entscheidend.
    Notes: Summary According to pediatric statements, falls from a standing position may cause skull fractures in infants without specific symptoms. Nearly every infant has at some time fallen from the changing table or the baby carriage, etc. From the forensic aspect it is the duty of experts to discuss the “battered child syndrome.” Evidence given by the defendants concerning the height of the fall are unreliable. Experimental test series concerned with the stumbling height (82 cm in free fall) and three various types of floor—stone, carpet, and foam-backed linoleum—were carried out. In each case skull fractures were seen. In three cases the fractures crossed the sutures. Conclusions: (1) Each fall of an infant from the height of a table may cause a skull fracture, which may lead to death; (2) when child mishandling is suspected, all circumstances must be taken into consideration.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2013
    Keywords: Key wordsXenopus oocytes ; Guinea-pig colon ; Na+ channel ; Single-channel analysis ; Amiloride ; Benzamil ; cAMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Guinea-pig distal colonic mRNA injection into Xenopus laevis oocytes resulted in expression of functional active epithelial Na+ channels in the oocyte plasma membrane. Poly(A)+ RNA was extracted from distal colonic mucosa of animals fed either a high-salt (HS) or a low-salt (LS) diet. The electrophysiological properties of the expressed amiloride-sensitive Na+ conductances were investigated by conventional two-electrode voltage-clamp and patch-clamp measurements. Injection of poly(A)+ RNA from HS-fed animals [from hereon referred to as HS-poly(A)+ RNA] into oocytes induced the expression of amiloride-sensitive Na+ conductances. On the other hand, oocytes injected with poly(A)+ RNA from LS-fed animals [LS-poly(A)+ RNA] expressed a markedly larger amount of amiloride-blockable Na+ conductances. LS-poly(A)+ RNA-induced conductances were completely inhibitable by amiloride with a K i of 77 nM, and were also blocked by benzamil with a K i of 1.8 nM. 5-(N-Ethyl-N-isopropyl)-amiloride (EIPA), even in high doses (25 μM), had no detectable effect on the Na+ conductances. Expressed amiloride-sensitive Na+ channels could be further activated by cAMP leading to nearly doubled clamp currents. When Na+ was replaced by K+, amiloride (1 μM) showed no effect on the clamp current. Single-channel analysis revealed slow gating behaviour, open probabilities (P o) between 0.4 and 0.9, and slope conductances of 3.8 pS for Na+ and 5.6 pS for Li+. The expressed channels showed to be highly selective for Na+ over K+ with a permeability ratio P Na/P K 〉 20. Amiloride (500 nM) reduced channel P o to values 〈 0.05. All these features make the guinea-pig distal colon of LS-fed animals an interesting mRNA source for the expression of highly amiloride-sensitive Na+ channels in Xenopus oocytes, which could provide new insights in the regulatory mechanism of these channels.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 585-587 
    ISSN: 1432-1041
    Keywords: Flumazenil ; benzodiazepine ; absorption ; disposition ; elderly volunteers ; pharmacokinetics ; aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open design, randomised, two-way cross-over study, a single 2 mg i.v. dose and a single 30 mg oral dose of flumazenil were each administered to a group of healthy young (n=6) and elderly (n=12) volunteers (male: female 2/1). Plasma samples were collected at intervals and intact drug was assayed. Both the IV and oral doses of flumazenil were very well tolerated by both age groups and no severe or unexpected adverse effects were observed. The main complaints were dizziness and headache, mainly after oral dosing, probably due to the higher Cmax and AUC following this route of administration. After 2 mg i. v. the disposition parameters in the two age groups (elderly/young) were very similar: volume of distribution (Vss): 0.88/0.901·kg−1; total body clearance (ClPL): 0.86/0.99 l·min−1; terminal elimination half-life (t1/2β): 1.02/0.91 h. After the 30 mg oral dose the mean Cmax of 87.6 ng·ml−1 (elderly) and 78.4 ng·ml−1 (young) were generally reached within 0.5 to 1 h. In 26% (elderly) and 23% (young), the absolute bioavailability of flumazenil was very similar. It is concluded that the absorption and disposition paramters of flumazenil were not significantly affected by aging.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 43 (1992), S. 209-210 
    ISSN: 1432-1041
    Keywords: Moxonidine ; Hydrochlorothiazide ; pharmacokinetics ; drug interaction ; steady-state ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 213-219 
    ISSN: 1432-1041
    Keywords: thiamine ; plasma level ; pharmacokinetics ; nonlinear renal elimination ; assay for clinical use
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A sensitive assay for thiamine suitable for clinical use has been developed. It is based on precolumn oxidation of thiamine to thiochrome followed by HPLC-separation and fluorescence detection. The assay is applicable to various biological materials, including human plasma. The minimum amount detectable was 5 fmol, minimum plasma concentration 0.5 nmol/l and minimum sample volume 0.3 ml plasma. Each chromatographic run took 3 min. Inter- and intra-assay relative standard deviations (RSD) were 8.3% and 6.3%, respectively, at a stock plasma concentration of 10.8 nmol/l. At 38.8 nmol/l, interassay RSD was reduced to 3.4%. The recovery of 5 nmol/l added thiamine was 102 (SD±17)%, that of 30 nmol/l was 94±5%. Plasma levels in 91 volunteers ranged from 6.6 to 43 nmol/l, showing a log normal distribution with a median of 11.6 nmol/l. Thiamine kinetics were studied in plasma and urine from 8 men after intravenous and oral doses of 50, 100 and 200 mg thiamine hydrochloride. In all individuals, nonlinear renal elimination kinetics were demonstrated by plotting the fractional amount of thiamine excreted unchanged in urine against the corresponding area under the plasma concentration — time curve.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 38 (1990), S. 237-242 
    ISSN: 1432-1041
    Keywords: cyclosporin A ; diltiazem ; pharmacokinetics ; kidney transplantation ; drug metabolism ; cytochrome P-450 ; drug interactions ; human liver microsomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous reports have indicated that administration of the calcium antagonist diltiazem results in major changes in the pharmacokinetics of cyclosporin A (CyA). A new clinical trial was undertaken in 22 renal transplant patients receiving a constant dose of cyclosporin to further explore this interaction. Coadministration of diltiazem for one week produced an increase in the blood concentration of CyA and its metabolites 17 and 18 in almost all patients, but no increase in CyA metabolites 1 and 21. The mean whole blood CyA trough level determined by HPLC rose from 117 ng·ml−1 to 170 ng·ml−1 after one week on diltiazem, and the mean trough level of metabolite 17 rose similarly from 184 ng·ml−1 before to 336 ng·ml−1. Based on experiments with microsomes from human liver the effect of diltiazem was due to noncompetitve inhibition of CyA-metabolism by diltiazem, and the increased concentration of metabolite 17 might have been due to stronger inhibition of its secondary metabolism steps.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2013
    Keywords: Key words Cystic fibrosis ; Human nasal epithelium ; Primary culture ; Epithelial Na+ channel ; Amiloride ; Phenamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Transepithelial short-circuit current (I SC), potential (V T) and resistance (R T) of confluent monolayers of human nasal epithelium cultured from patients with and without cystic fibrosis (CF) were measured. In our Ussing chamber experiments with monolayers derived from non-CF and CF patients neither I SC (non-CF: 14.1 ± 1.0 μA/cm2, n = 77; CF: 16.7 ± 1.5 μA/cm2, n = 42), nor R T (non-CF: 288 ± 15 Ω· cm2; CF: 325 ± 20 Ω· cm2) showed any significant differences, only V T showed moderate but significant different values (non-CF: –3.6 ± 0.4 mV; CF: –5.6 ± 0.7 mV, respectively). Total I SC in CF cells was nearly completely inhibited by amiloride (92 ± 9.6%), while in non-CF tissue amiloride-insensitive conductances mediated a considerable amount of the I SC (36.3 ± 6.1%), indicating a lower activity of amiloride-sensitive Na+ conductances in non-CF cells. In both tissues the amiloride-sensitive I SC could also be blocked by the amiloride analogues benzamil, phenamil and 5-(N-ethyl-N-isopropyl)2’,4’-amiloride (EIPA) with different affinities. However, amiloride had a significant lower affinity in CF tissue (half-maximal blocker concentration, K 1/2 = 586 ± 59 nM) compared with non-CF tissue (K 1/2 = 294 ± 22 nM). Astonishingly, phenamil, a blocker which irreversibly blocks all epithelial Na+ channels hitherto described, inhibited the Na+ conductances of human nasal epithelium in a completely reversible way, but nevertheless with high affinity (non-CF: K 1/2 = 12.5 ± 1.2 nM; CF: K 1/2 = 17.1 ± 1.1 nM). Even in high doses none of these blockers had any effect on intracellular Ca2+ concentration as measured with Fura-2. From these findings, we conclude that the epithelial Na+ conductances of human CF nasal epithelium show modified regulation or are functionally different from those of other tissues.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of comparative physiology 163 (1993), S. 153-159 
    ISSN: 1432-136X
    Keywords: Na+ channels ; Amiloride ; Benzamil ; Noise analysis ; Leech, Hirudo medicinalis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The dorsal skin of the leech Hirudo medicinalis was used for electrophysiological measurements performed in Ussing chambers. The leech skin is a tight epithelium (transepithelial resistance = 10.5±0.5 kΩ· cm-2) with an initial short-circuit current of 29.0±2.9 μA·cm-2. Removal of Na+ from the apical bath medium reduced short-circuit current about 55%. Ouabain (50μmol·l-1) added to the basolateral solution, depressed the short-circuit current completely. The Na+ current saturated at a concentration of 90 mmol Na+·l-1 in the apical solution (K M=11.2±1.8 mmol·l-1). Amiloride (100 μmol·l-1) on the apical side inhibited ca. 40% of the Na+ current and indicated the presence of Na+ channels. The dependence of Na+ current on the amiloride concentration followed Michaclis-Menten kinetics (K i=2.9±0.4 μmol·l-1). The amiloride analogue benzamil had a higher affinity to the Na+ channel (K i=0.7±0.2 μmol·l-1). Thus, Na+ channels in leech integument are less sensitive to amiloride than channels known from vertebrate epithelia. With 20 mmol Na+·l-1 in the mucosal solution the tissue showed an optimum amiloride-inhibitable current, and the amiloride-sensitive current under this condition was 86.8±2.3% of total short-circuit current. Higher Na+ concentrations lead to a decrease in amiloride-blockade short-circuit current. Sitmulation of the tissue with cyclic adenosine monophosphate (100 μmol·l-1) and isobutylmethylxanthine (1 mmol·l-1) nearly doubled short-circuit current and increased amiloride-sensitive Na+ currents by 50%. By current fluctuation analysis we estimated single Na+ channel current (2.7±0.9 pA) and Na+ channel density (3.6±0.6 channels·μm-2) under control conditions. After cyclic adenosine monophosphate stimulation Na+ channel density increased to 5.4±1.1 channels·μm-2, whereas single Na+ channel current showed no significant change (1.9±0.2 pA). These data present a detailed investigation of an invertebrate epithelial Na+ channel, and show the similarities and differences to vertebrate Na+ channels. Whereas the channel properties are different from the classical vertebrate Na+ channel, the regulation by cyclic adenosine monophosphate seems similar. Stimulation of Na+ uptake by cyclic adenosine monophosphate is mediated by an increasing number of Na+ channels.
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