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  • 1
    Electronic Resource
    Electronic Resource
    In field-stimulated guinea-pig atria an AT"1-receptor mediated increase of noradrenaline release by angiotensin II is seen only in the presence of prejunctional autoinhibition
    Amsterdam : Elsevier
    Regulatory Peptides 53 (1994), S. 145 
    Details
    ISSN: 0167-0115
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0167-0115(94)90630-0
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  • 2
    Electronic Resource
    Electronic Resource
    A meta-analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori-associated gastric or duodenal ulcer (2001)
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 15 (2001), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To compare the effectiveness of Helicobacter pylori eradication in curing peptic ulcer disease in trials involving both gastric ulcer and duodenal ulcer.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Twenty-four relevant randomized controlled trials and randomized comparative trials met the predefined selection criteria. Only proton pump inhibitor-based eradication trials were considered for the evaluation of eradication efficacy and ulcer healing. For the determination of relapse rates, all trials independent of the eradication therapy regimen were considered.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Data from 2102 patients were analysed comparing gastric ulcer with duodenal ulcer. No statistical differences between gastric ulcer and duodenal ulcer patients were found with regard to eradication rates (summarized odds ratio, 1.23; 95% confidence interval, 0.98–1.55) or ulcer relapse rates, whether in successfully H. pylori eradicated patients (summarized odds ratio, 0.69; 95% confidence interval, 0.26–1.84) or unsuccessfully H. pylori eradicated patients (summarized odds ratio, 1.48; 95% confidence interval, 0.85–2.56). Owing to heterogeneity, healing rates were not comparable.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:The eradication of H. pylori infection cures both gastric and duodenal ulcer, and the cure rates are similar. This suggests that H. pylori is the key factor in peptic ulcer disease independent of the ulcer site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2001.01109.x
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of the local anesthetics brufacain and lidocaine on transmembrane action potentials, refractory period, and reactivation of the sodium system in guinea pig heart muscle (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 297 (1977), S. 153-161 
    Details
    ISSN: 1432-1912
    Keywords: Lidocaine ; Brufacain ; Cardiac transmembrane action potential ; Refractory period ; Na+ system reactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lidocaine (3 · 10−5 and 10−4 M) and equimolar concentrations of brufacian dose-dependently reduced the depolarization velocity (dV/dtmax) and the force of contraction of guinea pig atria and papillary muscles. Repolarization time was increased in atria but reduced in papillary muscles. The maximum effects on action potential parameters were identical but developed with brufacain more slowly than with lidocaine. In papillary muscles lidocaine (3 · 10−5 M) prolonged the functional refractory period. No such effect but even a shortening was observed with brufacain. As brufacain reduced the duration of the action potential (AP) more than the functional refractory period, the “relative refractory period” (in percent of AP duration) was slightly prolonged. The half-time of the recovery of the Na+ system was increased three to five times the control value after lidocaine but only doubled after brufacain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499925
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of simple indoles, noradrenaline, nicotine, and tyramine on action potential and contractility of the isolated guinea-pig papillary muscle (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 299 (1977), S. 259-265 
    Details
    ISSN: 1432-1912
    Keywords: Noradrenaline ; Indole derivatives ; Papillary muscle ; Action potential ; Contractility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Simultaneous recordings of both the transmembrane action potential and the contractions were made in isolated electrically driven papillary muscles of the guinea pig in order to compare the effects of 6-methoxyindole (6-MOI), 3-methylindole (3-MI) and 5-methylindole (5-MI) with those of noradrenaline (1.2 · 10−6 M), nicotine (2 · 10−5 M), and tyramine (5.8 · 10−6 M). 2. Noradrenaline, nicotine, tyramine and 6-MOI (5.4 · 10−4 M) enhanced the contractility whilst 3-MI (3.8 and 7.8 · 10−4 M) and 5-MI (1.9 and 3.8 · 10−4 M) had only irregular effects. The active compounds shortened the time-to-peak tension and increased the rate of relaxation. 3. The duration of the action potential was prolonged by noradrenaline, nicotine, and tyramine, but shortened by 3-MI, 5-MI, and 6-MOI. 4. The results showed that the effect of drugs on the action potential are not necessarily linked to those on contractility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500318
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  • 5
    Electronic Resource
    Electronic Resource
    Caerulein and morphine in a model of visceral pain (1982)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 319 (1982), S. 161-167 
    Details
    ISSN: 1432-1912
    Keywords: Renal colic ; Visceral pain ; Nociception ; Caerulein ; Morphine ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In pentobarbital-anaesthetized rats (60 mg/kg, i.p.) renal pelvis distension with a pressure of 80 cm H2O caused a decline in mean arterial blood pressure. This pressure response, which disappeared rapidly after cessation of the distension, was used to study the effects of analgesic drugs known to be effective in renal colic pain in man. Morphine (0.75 and 1 mg/kg, s.c.) and the decapeptide caerulein (1.6, 4 and 8 μg/kg, s.c.) abolished the pressure response. The effects of the largest doses lasted for at least 30 min. Ineffective in this respect were (a) desulphated caerulein (40 μg/kg, s.c.) and (b) additional doses of pentobarbital (20 and 40 mg/kg, s.c.). This shows (a) the importance of the sulphated tyrosine (known from previous studies on central effects) and (b) the missing influence of the depth of anaesthesia. Naloxone (0.5 mg/kg, s.c.) abolished the effect of morphine (1 mg/kg, s.c.) but failed to influence that of caerulein (8 μg/kg, s.c.). Even a fourfold dose of naloxone (2 mg/kg, s.c.) did not weaken the effect of caerulein. Naloxone, per se, was ineffective. These results suggest different mechanisms of the present effects of morphine and caerulein. It appears that renal pelvis distension in the anaesthetized rat can serve as a model of renal colic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00503931
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  • 6
    Electronic Resource
    Electronic Resource
    Lack of direct antiarrhythmic electrophysiological effects of salicylate on isolated guinea-pig myocardium (1983)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 323 (1983), S. 343-349 
    Details
    ISSN: 1432-1912
    Keywords: Na-salicylate ; 2,4-Dinitrophenol ; Oxidative phosphorylation ; Guinea pig ; Action potential
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1) Conventional microelectrode techniques were used to study the influence of Na-salicylate, Na-benzoate, Na-2,6-dihydroxybenzoate and 2,4-dinitrophenol (2,4-DNP) on the action potential (AP) of guinea-pig papillary muscles and atria. 2) In papillary muscles, Na-salicylate (0.19–1.87 mmol/l) concentration-dependently shortened the AP duration and the functional refractory period. The AP amplitude decreased slightly with the largest concentration, while the resting potential and the maximum depolarisation velocity (V max) were not affected. A concentration-dependent negative inotropic effect was also seen. All drug effects were reversible after washout. 3) In atria, 6.24 mmol/l Na-salicylate induced a slight shortening of the AP duration, a decrease of the AP amplitude and V max, but no decrease of the contractile force. 4) The effects of the uncoupling agent, 2,4-DNP (10 μmol/l), were similar to those of the largest concentration of Na-salicylate in papillary muscles and in atria. 5) Na-benzoate and Na-2,6-dihydroxybenzoate had no significant influence on AP duration, AP amplitude, resting potential, V max, refractory period or force of contraction of either papillary muscles or atria. 6) These results suggest that Na-salicylate exerts its effects on isolated guinea-pig myocardium by uncoupling the oxidative phosphorylation, whereas two other possible mechamisms of action, namely an increase of membrane surface charge and an inhibition of prostaglandin synthesis, seem to be of minor importance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00512474
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of TRIS (hydroxymethyl-)aminomethane in healthy subjects and in patients with metabolic acidosis (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 257-264 
    Details
    ISSN: 1432-1041
    Keywords: TRIS buffer ; metabolic acidosis ; pharmacokinetics ; cellular uptake ; renal excretion ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To investigate the pharmacokinetics of TRIS, an infusion of the buffer was given to 6 healthy volunteers (121 mg/kg=1 mmol/kg; pH 7.4) and to 20 patients suffering from metabolic acidosis (109–376 mg/kg; pH 10.9). The drug exhibited two-compartment characteristics in volunteers (t0.5,β=5.6 h) and patients with intact renal function (t0.5,β=16.3–45.6 h). The final volume of distribution (Vβ) indicated uptake into tissues, but equilibration between body compartments was slow. Mainly unchanged TRIS was eliminated by the kidney; 82% of the administered dose was recovered from 24 h-urine of healthy subjects. In the patients a linear correlation between creatinine-clearance and TRIS-clearance was observed, the latter always being somewhat greater than the former. Only insignificant amounts of the drug were found in bile and gastric juice. In anuric patients the plasma concentration of TRIS declined monoexponentially, with a half-life between 10 and 58 h. Haemodialysis or haemofiltration did not influence this process. From the data it seems questionable whether cellular uptake of TRIS is an important factor in the therapy of intracellular acidosis, but the possibility of drug accumulation must be borne in mind if repeated doses are given to the same patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545225
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  • 8
    Electronic Resource
    Electronic Resource
    Significance of acid base status, respiration, Na+-and K+-concentrations and plasma glucose for acute toxicity of TRIS (hydroxymethyl-)aminomethane in rats (1982)
    Springer
    Archives of toxicology 51 (1982), S. 139-149 
    Details
    ISSN: 1432-0738
    Keywords: TRIS-Buffer ; Alkalosis ; Respiration ; Hypoglycaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanism of acute toxicity of TRIS-buffer was investigated in pentobarbital-anaesthetized Wistar-rats. An infusion of 0.5 mmol/kg · min TRIS, either pH 10.9 or pH 7.4, was tolerated for 60–70 min before death. TRIS concentration in plasma increased linearly to 53.7±9.09 mmol/l after 60 min (¯x±sx), indicating slow uptake of the drug into tissues. Blood pressure, heart rate, ECG and Na+- and K+-concentrations in plasma and erythrocytes were not influenced by TRIS. A small rise of plasma osmolarity by 39±4.7 mosmol/l after 30 min seemed unimportant for toxicity. With alkaline TRIS a metabolic alkalosis developed and the compensatory arrest of ventilation caused a sudden drop of arterial pO2 to 48±9 mm Hg after 50 min. A similar, though more gradual, decline of pO2 was observed with neutralized TRIS without concomitant changes of acid-base status. Artificially ventilated rats, with constant arterial pO2, tolerated an infusion of neutralized TRIS for at least 90 min. With TRIS of either pH plasma glucose concentration was nearly halved after 30 min. Addition of glucose (50 mg/ml) to the infusion neither prevented this effect nor increased the survival time. From these results we conclude that the main lethal action of TRIS is a depression of ventilation that, in the case of neutralized TRIS, may be related to an intracellular alkalosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00302754
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  • 9
    Electronic Resource
    Electronic Resource
    Field stimulation-induced noradrenaline release from guineapig atria is modulated by prejunctional α2-adrenoceptors and protein kinase C (1993)
    Springer
    Basic research in cardiology 88 (1993), S. 545-556 
    Details
    ISSN: 1435-1803
    Keywords: Guinea-pig atrium ; noradrenaline release ; α2-adrenoceptors ; protein kinase C ; phorbol esters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Guinea-pig left atria were loaded with 10 μCi 7-[3H]noradrenaline, and noradrenaline release from sympathetic nerve endings was then elicited by refractory period field stimulation. When one pulse of 0.2 ms duration was applied during each refractory period, the resulting transmitter release was halved by 3×10−7 mol/l of the α2-adrenoceptor agonist clonidine and increased about 2.5-fold by either 3×10−7 mol/l of the α2-adrenoceptor antagonist idazoxan, 5×10−3 mol/l of the potassium channel blocker tetraethylammonium chloride (TEA) or 3×10−7 mol/l phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C (PKC). Phorbol-12-myristate-13-acetate-4-O-methylether, a compound which does not stimulate PKC, was ineffective. The stimulatory effect of PMA was antagonized by 7×10−5 mol/l of the PKC inhibitor polymyxin B. No significant transmitter release was observed when either PMA or TEA was applied together with 10−7 mol/l of the sodium channel blocker tetrodotoxin. Combinations of either idazoxan and TEA or PMA and TEA caused greater increased of the noradrenaline release than any individual drug given alone. Thus, different mechanisms of action seem to mediate the increase of noradrenaline release by action potential prolongation on the one hand and activation of PKC or inhibition of α2-adrenoceptors on the other hand. In contrast, the effects of idazoxan and PMA were not additive which suggests a common mechanism of action. In atria pretreated for 10 min with 10−4 mol/l N-ethylmaleimide, an alkylating agent which inactivates Gi-proteins, neither idazoxan nor PMA caused a significant increase of the stimulation-induced transmitter release, while TEA was still effective. When a train of four pulses, lasting 0.05 ms each, was applied during each refractory period, the resulting transmitter release was not modified by idazoxan or PMA, but was significantly increased by TEA. From these results, a scheme is proposed which, links the regulation of noradrenaline release by prejunctional α2-adrenoceptors and protein kinase C via an influence on a common inhibitory Gi-protein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00788873
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  • 10
    Electronic Resource
    Electronic Resource
    Influence of phorbol esters on stimulation-induced noradrenaline release and contractile force of isolated guinea-pig atria (1991)
    Springer
    Basic research in cardiology 86 (1991), S. 283-290 
    Details
    ISSN: 1435-1803
    Keywords: phorbolesters ; isolatedatrium ; nradrenalineefflux ; contractileforce ; protein kinase C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phorbol-12,13-dibutyrate (PDB) and phorbol-12-myristate-13-acetate (PMA) increased the field-stimulation-induced efflux of radioactivity from guinea-pig atria preloaded with 7-[3H]-noradrenaline. The efflux was more than doubled by 10−7 mol/l of either compound. Phorbol-12-myristate-13-acetate-4-O-methylether (PME), which has no effect on the protein kinase C (PKC), did not modify the stimulation-induced efflux of radioactivity, while a slight reduction was seen with 70 μM of the PKC inhibitor polymyxin B. In the presence of polymyxin B, the effects of PMA and PDB were greatly attenuated. In addition, PDB had a concentration-dependent negative inotropic effect (EC50 7,0 × 10−10 mol/l). Pretreatment with polymyxin B shifted the concentration-response curve for PDB to the right (EC50 4,6 × 10−9 mol/l). No negative inotropic effect was seen with PMA or PME. The results suggest that all effects of the phorbol esters were mediated by a stimulation of PKC. The different lipophilicity of PMA and PDB or a different influence on the various isozymes of PKC may account for the diverging postjunctional effects of the two compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02190608
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