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Biomedical subjects

D Reinhardt

Publications and source records attributed to D Reinhardt.

At least 181 records · Page 10Linked to original sources
PubMed1981

Influence of preseasonal treatment with L-tyrosine-adsorbed allergoids on IgE-mediated histamine release from basophils of children suffering from allergic diseases.

In 10 children suffering from allergic pollinosis and/or asthma, a preseasonal hyposensitization scheme with 3 weekly injections of a glutaraldehyde-modified, tyrosine-adsorbed grass-pollen allergen reduced the histamine release from basophils in response to increasing concentrations of antigen. The decrease in histamine release which occurred 1 week after the injection course was even maintained during the pollen season. The inhibition was only obtained when basophils were incubated with the serum of patients, but not with the serum of normals, indicating that blocking antibodies may have occurred. In contrast to what has been observed in the treated patients' group, 5 patients, who were not included in the hyposensitization scheme, showed identical histamine release curves during the whole investigation period. Specific IgE did not increase after the treatment course and shows the same behaviour as the untreated patients. Thus, as treatment with glutaraldehyde modified, tyrosine-adsorbed allergoids is safe to administer, requires only 3 injections, reduces histamine release from basophils by production of "blocking" antibodies, it appears to be a useful tool in the hyposensitization treatment.

Adsorption↗
PubMed1981

[Isoniacid intoxication: correlation between blood level and coagulation status? (author's transl)].

In a 1,10 year old boy intoxication by isoniazid (INH) produced an initial fall of prothrombin and a prolonged fall of the clotting factor VII. The rest of the coagulation factors as well as the inhibitor activity remained uninfluenced. Since the decrease of the liver-dependent clotting factors occurred immediately after ingestion the apparently rare INH induced liver injury is considered as dose-dependent. On the other hand, however, since the serum half-life of INH amounted to 2,98 hours whereas the decrease of factor VII persisted over 46 hours and there appears to be no correlation between liver injury and INH plasma levels. This discrepancy may be attributable to the fact that only the acetylated intermediates of INH may have a hepatotoxic potential.

Blood Coagulation Disorders↗
PubMed1981

Pharmacolinetic and pharmacodynamic data analysis of theophylline for three different drug forms.

Theophylline, which is widely used in asthmatics, should be maintained within narrow plasma limits to achieve maximum therapeutic benefit with minimum adverse effects. For the evaluation of drug input schemes it is essential to know the pharmacokinetic parameters and their variation for different dosage forms. Apart from absorption and elimination rates, an appropriate dosage schedule is determined by the extent of bioavailability. The objectives of the study presented here are the assessment of bioavailability, the estimation of pharmacokinetic parameters, and the investigation of the relationship between plasma drug levels and cardiac side effects. Additionally, it was checked whether drug levels in saliva could be used for monitoring drug levels in plasma. The time course of theophylline in plasma and saliva was measured in twelve healthy volunteers on different drug forms: intravenous injection as well as oral application of a fast and a slow release form of theophylline. Pharmacokinetic parameters were estimated using a three-compartment model for the distribution of theophylline. The extent of bioavailability was estimated via the area under the curves and by numerical evaluation of the invasion function. By simultaneous measurements of heart rate and c-AMP levels the drug response was monitored. The results show the following: i) The slow and fast release dosage forms do not differ with respect to extent of bioavailability, whereas bioavailability rates are slower for the sustained release form. ii) Apart from the initial phase (less than or equal to 1 h) plasma and saliva drug levels run approximately parallel. However, the mean concentration ratio has a large variance. iii) The time courses of heart rate are closely related to the time courses of drug level. iv) When the sustained release form is used for a long-term therapy, it is possible to evaluate dosage schedules and dosage regimens that reduce cardiac side effects caused by the fast release form. This was shown by computer simulation carried out on the basis of pharmacokinetic parameters that were estimated from the experimental curves.

Administration, Oral↗
PubMed1980

Comparison of the effects of theophylline, prednisolone and sleep withdrawal on airway obstruction and urinary cyclic AMP/cyclic GMP excretion of asthmatic children with and without nocturnal asthma.

Asthmatic children suffering from nocturnal asthmatic paroxysms showed not only a reduced peak exspiratory flow rate (PEER) but also a diminished excretion of cyclic AMP (cAMP) at night. In contrast, in asthmatic children without nocturnal asthmatic attacks, neither in PEFR nor in cAMP excretion did a circadian rhythm occur. Prednisolone, theophylline, and sleep withdrawal were able to reestablish normal airway function and cAMP excretion in those patients with nocturnal bronchoconstriction. Cyclic GMP (cGMP), which has been suggested as a mediator for cholinergic mechanisms, shows the exact opposite behavior of that of cAMP. In children suffering from nocturnal asthmatic attacks, cGMP increases during the night, whereas under sleep withdrawal it decreases. Hence we propose that a reduced responsiveness of beta-adrenergic receptors as well as an increased cholinergic activity are due to nocturnal asthmatic attacks. Therapeutic interventions taking the form of increasing cAMP or decreasing cGMP levels may thus be most helpful in treating nocturnal asthma.

Adolescent↗
PubMed1979

Hypothermia-induced potentiation of histamine H2-receptor-mediated relaxation and cyclic AMP increase in the isolated mesenteric artery of the rabbit.

On helically cut strips of the rabbit's mesenteric artery, a temperature decrease from 42 degrees C to 25 degrees C reduced the contractile responses to histamine. Metiamide shifted the dose-response curve of the histamine-induced contraction towards higher values at 25 degrees C, but not at 42 degrees C. Furthermore, on arterial strips contracted by phenylephrine histamine evoked a dose-dependent relaxation at 25 degrees C whereas at 42 degrees C only slight relaxing responses to histamine occurred. Metiamide was capable of preventing the relaxation induced by histamine in a competitive manner. At 25 degrees C the relaxation as produced by histamine was accompanied by increases in cyclic AMP which occurred prior to the relaxing effects. Metiamide abolished the cyclic AMP increase in response to histamine. At 42 degrees C histamine was unable to elevate the cyclic AMP content. Thus, it is concluded that a cyclic AMP-mediated relaxation due to stimulation of H2-receptors counteracts the histamine-induced contraction and reduces the contractile responses to histamine at low temperatures. In addition, clear-cut evidence exists from the present study that also on artery smooth muscle the H2-receptor-mediated responses are closely associated to cyclic AMP.

Animals↗
PubMed1979

Relationship between histamine-induced changes of cyclic AMP and mechanical activity on smooth muscle preparations of the guinea-pig ileum and the rabbit mesenteric artery.

On guinea-pig ileum and rabbit mesenteric artery contracted by high potassium (100 mM) histamine produced relaxations which were inhibited by the H2-receptor antagonist metiamide. These results are thus indicative for the role of H2-receptors in mediating relaxation and for H1-receptors in mediating contraction on smooth muscle. Time course studies for the relaxing and cyclic AMP responses to histamine showed that the cyclic AMP increase preceded the H2-receptor mediated relaxation. The cyclic AMP increase in response to histamine was prevented by metiamide, but remained unaffected by mepyramine on both the guinea-pig ileum and the rabbit mesenteric artery. In addition, dose-response curves obtained on the mesenteric artery demonstrated that the H2-receptor mediated depressor responses coincided with cyclic AMP increases. Thus, these results gave clear-cut evidence that cyclic AMP is an intracellular metabolic event only implicit in the H2-receptor mediated relaxation, but not in the H1-receptor mediated contraction on smooth muscle preparations.

Animals↗
PubMed1979

[Oral desensitization in childhood (author's transl)].

1) There is some evidence that orally administered allergens are absorbed. 2) 75% of the children considered oral desensitization to be effective. 3) As judged by bronchial flow resistance after provocation, oral and subcutaneous desensitization appear to be equally effective in reducing bronchial hypersensitivity. The reduction in hypersensitivity after oral desensitization was of the same magnitude as that induced by 1 capsule of DNCG. Reduced bronchial hypersensitivity was also observed in children who had received sympatomatic anti-asthma treatment over periods of 1-3 years.

Administration, Oral↗
PubMed1978

The role of cyclic AMP in temperature-dependent changes of contractile force and sensitivity ot isoprenaline and papaverine in guinea-pig atria.

Right and left guinea-pig atria responded to decreasing temperatures (42-27 degrees C) with elevation for force of contraction and concomitant increases in cAMP. When atria were rapidly cooled from 42 to 27 degrees C the increase in cAMP occurred prior to the onset of the inotropic responses. Papaverine (3 X 10(-5) M) potentiated the effects of temperature on cAMP and force of contraction on left atria driven at 0.5 Hz. On right atria beating spontaneously at frequencies above 2 Hz papaverine only potentiated the effect of decreasing temperatures on the response of cAMP but not on that of force of contraction. Time course studies of the effects of isoprenaline (3 X 10(-8) M) on right atria at 27 degrees C showed large inotropic responses to isoprenaline which were accompanied by increases in cAMP. At 42 degrees C the responses of force of contraction and cAMP to isoprenaline occurred faster and were only short-lasting. As with the time courses for isoprenaline, dose-response curves for the effect of isoprenaline and papaverine on cAMP content and force of contraction also appeared to be shifted towards higher levels at hypothemia. However, pD2 values reflected increases in affinity for inotropic, but not for the cAMP responses to isoprenaline and papaverine at hypothermia. These results show that cyclic AMP is involved in the inotropic responses to hypothermia, but not in the supersensitivity of heart to isoprenaline and papaverine as observed at low temperatures.

Animals↗
PubMed1977

[The mechanism of action of histamine on the myocardium and the smooth vascular muscles].

Histamine-H1-receptors are only present in the left atrium of guinea-pig hearts, whereas the ventricular myocardium contains histamine-H2-receptors exclusively. Although the stimulation of both receptor types causes positive intropic effects, only the H2-receptor response is closely associated with increases of cyclic AMP. H1- as well as H2-receptors are present in the rabbit mesenteric artery. Cyclic AMP serves as a messenger for H2-receptor mediated relaxation only and not for H1-receptor mediated contraction. Thus, the different effects on the cyclic AMP-system must also be considered in H1- and H2-receptor differentiation.

Animals↗
PubMed1977

Effect of papaverine on the frequency-force relationship in guinea-pig left atria.

Contractile responses of guinea-pig atria to papaverine were analyzed under different stimulation frequencies. Atria, driven at 2 Hz, showed positive inotropic responses to papaverine which were maximal within 10-15 min. These responses were maintained for 60 min in the presence of low concentrations of papaverine (up to 10(-5) M), but reversed into marked negative inotropic effects under the influence of higher concentrations. The well-known frequency-force relationship was reversed by papaverine. At low stimulation rates papaverine elicited positive inotropic responses, which gradually decreased with increasing frequencies until strong cardiodepression occurred. A frequency-force curve obtained in the presence of both the Ca2+-antagonistic drug D 600 and the inhibitor of the phosphodiesterase theophylline was similar to that obtained under the influence of papaverine. Theophylline alone evoked positive inotropic effects at all frequencies studied and left the character of the ascending staircase unchanged. In contrast, D 600 was ineffective at low, but cardiodepressive at high stimulation frequencies. In the presence of D 600 or papaverine high external Ca2+ could not restore a normal frequency-force relationship. The reversal of the frequency-force relationship as produced by D 600 and papaverine could not be obtained by lowering of the external Ca2+. The present results show that papaverine is able to evoke marked positive inotropic effects at low stimulation frequencies by inhibition of phosphodiesterase. At high frequencies, however, these effects are masked by negative inotropic responses due to the inhibitory action of papaverine on Ca2+-exchange of the cardiac muscle cell.

Animals↗
PubMed1977

H1 - and H2-receptor mediated responses to histamine on contractility and cyclic AMP of atrial and papillary muscles from guinea-pig hearts.

On guinea-pig heart we investigated whether cyclic AMP serves as a messenger for H1 - and/or H2-mediated responses to histamine. (1) On papillary muscle histamine elicited positive inotropic responses which were antagonized by burimamide but not by promethazine. The stimulation of H2-receptors was not only associated with an increase in contractility but also with an increase in cAMP. As shown by the time course of effects for 10(-5) M histamine, the maximal increase in cAMP preceded the maximum in contractility. The mechanical and biochemical responses to histamine were potentiated by the phosphodiesterase inhibitor papaverine, but antagonized by burimamide. (2) On the left guinea-pig atrium containing H1-receptors the inotropic response to histamine (10(-5) M) was not accompanied by increases in cAMP at stimulation frequencies of 0.5 and 2 Hz, respectively. In addition, in the presence of papaverine (3 X 10 (-5) M) no change in the cyclic AMP level occurred after application of histamine. Papaverine by itself, however, concomitantly increased contractility and cyclic AMP at a stimulation frequency of 0.5 Hz. In contrast, at 2 Hz papaverine increased only cAMP leaving the contractility unchanged. At this frequency the well-known Ca2+-antagonistic effect comes into prominence, thus masking the positive inotropic effect attributable to the inhibition of the phosphodiesterase. (3) On the right guinea-pig atrium the mediation of the positive chronotropic response to histamine by H2-receptors which is partly involved in the inotropic effect via the frequency-force relationship does not lead to a concomitant increase in cAMP. Also, in the presence of papaverine, histamine had no influence on the cAMP. However, papaverine potentiated the cardioacceleration produced by histamine. Although it is very likely that the cAMP in the sinus node rises, we were not able to detect an increase in cAMP in the whole atrial tissue. From the present results the conclusion can be drawn that the mediation of the inotropic effect due to stimulation of H2-receptors by histamine is associated with an increase of cyclic AMP, whereas that of H1-receptors is not. The view that cAMP may be the second messenger in the chronotropic action of histamine needs further elucidation by experiments on sino-atrial cells.

Animals↗