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Biomedical subjects

R Häcker

Publications and source records attributed to R Häcker.

At least 19 recordsLinked to original sources
PubMed2002

Enhanced conditioned inhibitory avoidance by a combined extract of Zingiber officinale and Ginkgo biloba.

Previous work has shown that intragastric administration of Zingicomb, a preparation consisting of Zingiber officinale and Ginkgo biloba extracts, has anxiolytic-like properties. The aim of the present study was to assess the effects of acute treatment with this preparation on inhibitory avoidance learning. The influence of pre-trial administered Zingicomb (ZC) on inhibitory avoidance conditioning was investigated in adult male Wistar rats, with a one-trial step-through avoidance task. The animals were treated intragastrically with either vehicle, 0.5, 1, 10 or 100 mg/kg ZC 60 min prior to the acquisition trial. When tested 24 h after training, rats which had received 10 mg/kg ZC exhibited significantly longer step-through latencies than vehicle treated animals. This result, thus, demonstrates the beneficial effects of Zingicomb on conditioned inhibitory avoidance. Unlike conventional anxiolytic drugs, such as the benzodiazepines, which tend to have amnesic properties, this phytopharmacon is a potent anxiolytic agent which, additionally, can facilitate performance on a learning task, indicating promising clinical applications.

Administration, Oral↗
PubMed1998

Dissociation between anxiolytic and hypomnestic effects for combined extracts of zingiber officinale and ginkgo biloba, as opposed to diazepam.

Previous work has shown that Zingicomb (ZC), a combination preparation of zingiber officinale and ginkgo biloba, exerts anxiolytic-like effects in the elevated plus-maze (EPM), possibly related to 5-HT antagonistic properties of its components. The first experiment of this study was performed to gauge the specificity of the anxiolytic action of ZC with respect to the mixture ratio of the single components in the combination preparation. Two different combinations of zingiber officinale and ginkgo biloba extracts (ratio of components: 1:1 or 1:2.5) were compared with the standard ratio adjusted for ZC (2.5:1). Each combination was administered intragastrically (I.G.) in five doses (0.01 to 10 mg/kg) before the rats were tested on the EPM. Zingicomb at 1 mg/kg elevated the time spent on the open arms, scanning of the open arms and excursions into the ends of the open arms, whereas the two other combinations (1:1 and 1:2.5) did not influence rats' behavior on the EPM in the entire dose range tested. With regard to the memory-disrupting effects of anxiolytics, particularly of diazepam (DZP), a second experiment was performed to compare the effects of ZC (0.5, 1, 10 mg/kg, I.G.) and DZP (1 or 5 mg/kg, I.P.) on the performance of rats in two different learning tasks. Rats were treated with DZP or ZC prior to the learning trial of a one-trial step-through inhibitory avoidance task. Retention testing 24 h later showed impaired retention for rats injected with DZP at 5 mg/kg but not for animals that had received ZC prior to training. In a further experiment, rats were treated once daily with DZP or ZC prior to the training trials in a water maze. Injections of DZP at 5 mg/kg impaired place and cue learning, whereas the treatment with ZC did not influence the navigation performance in the maze. The present results indicate that the anxiolytic-like effects of ZC are specific in that only the mixture ratio of zingiber officinale and ginkgo biloba adjusted for the phytopharmacon was active in the EPM. Furthermore, ZC did not interfere negatively with the performance on an inhibitory avoidance and a water maze task, as opposed to DZP. This finding is interesting with regard to other studies that have revealed a similar dissociation between anxiolytic and memory-disrupting effects for chemically defined 5-HT antagonists, especially for those acting at 5-HT3 receptors.

Animals↗
PubMed1997

Increased neostriatal dopamine activity after intraperitoneal or intranasal administration of L-DOPA: on the role of benserazide pretreatment.

L-DOPA provides the most potent medication to treat Parkinson's disease, and such systemic treatment is usually combined with a peripheral amino acid decarboxylase inhibitor to amplify its central effectiveness. Since L-DOPA can lose its efficacy or can lead to adverse effects with prolonged application, current pharmacokinetic and dynamic research is aimed at improving the drug's applicability. In a previous study, performed with in vivo microdialysis in the anesthetized rat, we have shown that intranasal L-DOPA administration (without prior decarboxylase inhibition) can increase extracellular dopamine levels in the neostriatum. Using similar experimental conditions in the present experiment, we tested the neurochemical effects of L-DOPA treatment in combination with the peripheral amino acid decarboxylase inhibitor benserazide. In accordance with other data, it was found that the combination of i.p. benserazide and i.p. L-DOPA led to pronounced increases of extracellular levels of dopamine, dihydroxyplenylacetic acid and homovanillic acid in the neostriatum, whereas i.p. L-DOPA alone only moderately increased dopamine, but strongly increased the metabolite levels. Furthermore, increased dopamine levels, and weaker increases of dihydroxyplenylacetic acid and homovanillic acid were observed after i.p. benserazide followed by intranasal L-DOPA. Finally, we found that i.p. benserazide alone can lead to pronounced increases in neostriatal dopamine and moderate increases of dihydroxyplenylacetic acid levels, whereas it did not affect homovanillic acid. Thus, not only the combination of L-DOPA (i.p. or intranasal) with the presumed peripheral L-DOPA decarboxylase inhibitor benserazide, but also each component alone can affect dopamine activity in the brain. Especially the findings with benserazide treatment might be of relevance for understanding the mechanisms of current L-DOPA therapy, since they indicate that part of the treatment's actions may possibly be determined by central dopaminergic effects of the accompanying amino acid decarboxylase inhibitor.

Administration, Intranasal↗
PubMed1997

Intranasal administration of the dopaminergic agonists L-DOPA, amphetamine, and cocaine increases dopamine activity in the neostriatum: a microdialysis study in the rat.

The effectiveness of intranasal drug administration to stimulate central neuronal systems is well known from drug addiction and has also been considered as an alternative pharmacokinetic approach to treat brain disorders such as Parkinson's disease. In the present study, the possible neurochemical effects of intranasal administration of the psychostimulants cocaine and amphetamine and of the antiparkinsonian drug L-DOPA were analyzed. By using in vivo microdialysis in the urethane-anesthetized rat, it was found that unilateral intranasal administration of either of the psychostimulants led to huge and rapid increases of extracellular dopamine levels in the neostriatum followed by decreases of its metabolites dihydroxyphenylacetic acid and homovanillic acid. Furthermore, intranasal administration of L-DOPA, but not of the saline vehicle, also led to increased extracellular levels of neostriatal dopamine and to increases of its metabolites. Because the effect of intranasal L-DOPA on neostriatal dopamine was observed only ipsilaterally but not contralaterally to the side of intranasal drug administration, it can be hypothesized that L-DOPA was not effective via passage through the circulation but may have acted through a neuronal or an extraneuronal route. These data provide neurochemical evidence that the intranasal route may not only be efficient in drug abuse, but may also be useful to target the brain therapeutically, as in the case of neurodegenerative brain disorders.

Administration, Intranasal↗
PubMed1996

Parenteral application of NADH in Parkinson's disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis.

Exogenous application of levodopa is conventionally used to equalize the striatal dopamine deficit in idiopathic Parkinson's disease (PD). The stimulation of endogenous biosynthesis of levodopa via activation of tyrosine hydroxylase (TH) has been proposed as new therapeutic concept in PD. This may be achieved by exogenous supply with the reduced coenzyme nicotinamide adenine dinucleotide (NADH). Aim of this open prospective study was to investigate (1) the efficacy of a new developed, parenteral application form of NADH on Parkinsonian symptoms and (2) the influence of bioavailability of levodopa. 15 patients, suffering from idiopathic PD (11 male, 4 female, age: 61.40[mean] +/- 10.27[SD] range: 44-74 years, Hoehn and Yahr stage: 3.03 +/- 0.69, range 2-4) received intravenous infusions of NADH (10 mg a' 30 min) over a period of 7 days in addition to conventional Parkinsonian pharmacotherapy. Parkinsonian symptoms were scored before (day 1) and after NADH treatment (day 8). Levodopa plasma levels were estimated over a period of four hours on the day before and on the first day of NADH application by HPLC. Parkinsonian patients showed a significant response, evaluated by the Unified Parkinson's Disease Rating Scale Version 3.0 (p = 0.025; Wilcoxon test). Moreover application of NADH significantly increased bioavailability of plasma levodopa (AUC, p = 0.035; Cmax p = 0.025). In conclusion NADH in used galenic form may be a potent stimulator of endogenous levodopa biosynthesis with clinical benefit for Parkinsonian patients.

Adult↗
PubMed1996

Anxiolytic-like effect of combined extracts of Zingiber officinale and Ginkgo biloba in the elevated plus-maze.

The effects of the known anxiolytic compound diazepam (DZ) on the behavior of rats in the elevated plus-maze were compared with those of zingicomb (ZC) (registered trademark of Mattern et Partner), a combination preparation of standardized extracts of Ginkgo biloba and Zingiber officinale. DZ was administered intraperitoneally (IP) in a reference dosage of 1 mg/kg 30 min before the rats were tested on the elevated plus-maze for 5 min. The treatment with DZ elevated the time spent on the open arms and excursions into the end of the open arms, increased scanning over the edge of an open arm, and decreased risk-assessment from an enclosed arm. ZC was administered intragastrically (IG) in four doses ranging between 0.5 and 100 mg/kg 60 min prior to plus-maze testing. The treatment with 0.5 mg/kg ZC elevated the time spent on the open arms and excursions into the end of the open arms; at the high dosage of 100 mg/kg, ZC led to fewer excursions to and less scanning of the open arms. Injection of 1 or 10 mg/kg ZC had no significant effect on the behavior in the maze. These data provide evidence that ZC has anxiolytic effects in the elevated plus-maze comparable to those of DZ, but that in high dosage the phytopharmacon may also have anxiogenic properties. The anxiolytic-like effects of ZC are discussed with regard to the known antiserotonergic action of ginger and Ginkgo biloba.

Animals↗
PubMed1995

Blockade of lithium chloride-induced conditioned place aversion as a test for antiemetic agents: comparison of metoclopramide with combined extracts of Zingiber officinale and Ginkgo biloba.

The present study tests the hypothesis that the blockade of lithium chloride-induced conditioned place aversion might be a suitable model to assess antiemetic properties of drugs, especially in species that do not vomit, like rats. The effects of the known antiemetic compound metoclopramide were compared with those of zingicomb, a combination preparation of extracts of Ginkgo biloba and Zingiber officinale, also presumed to have antiemetic properties. Place conditioning was performed using a conventional three-compartment test procedure. On three successive conditioning trials, rats received an intraperitoneal (i.p.) injection of lithium chloride (125 mg/kg) and were placed into the compartment that they had preferred over three baseline trials. During the test, rats treated with lithium chloride (LiCl) spent less time in the treatment compartment, indicative of a conditioned place aversion (CPA). In the first experiment, metoclopramide (MCP) was administered intragastrically (IG) in doses of 2 or 10 mg/kg 60 min prior to LiCl injection. The pretreatment with 50 and 100 mg/kg zingicomb attenuated the LiCl-produced CPA, whereas a dosage of 10 mg/kg had no effect. These findings suggest that LiCl-induced CPA is a viable procedure with which to assess the antiemetic properties of metoclopramide. Furthermore, the data confirm the hypothesis that the phytopharmacon zingicomb might have antiemetic properties that are comparable to those of metoclopramide.

Animals↗
PubMed1987

[Oxygen supply and oxygen uptake by skeletal muscle in acute arterial circulatory disorders--an experimental study in the dog].

The oxygen supply and the oxygen uptake of the ischemic skeletal muscle were defined in rest and by loading in experimental studies in dog. About 72% of the supplied arterial oxygen was taken up from the ischemic skeletal muscle in rest in opposite to 84.7% by loading. Therewith the authors found an essential higher value as supposed in literature so far. The absolute value of the oxygen uptake of the normally circulated skeletal muscle with 0.14 ml O2/min/100 g is small in contrast to the highly differentiated parenchymatous organs. An adaptation to an anaerobic metabolism is assumed by the authors in case of falling below the critical boundary value of 0.1 ml O2/min/100 g in skeletal muscle.

Animals↗
PubMed1986

[Modification of plasma blood coagulation factor activity by physical stress].

The influence of physical stress (bicycle ergometer and track) on 13 parameters of the plasmatic coagulation system was investigated in trained and untrained test persons. Shortenings of the coagulation times as well as distinct increases of the activity or concentration were observed in the partial thromboplastin time (PTT), the factor VIII activity (VIII:C) and the factor VIII-associated antigen (VIIIR:Ag). The results are discussed with regard to their causes and their clinical importance.

Adult↗
PubMed1986

[pH measurement in tissue--a reliable criterion for the registration of acute arterial circulatory disorder in animal experiments].

An arterial ischemia was carried out step by step in the right pelvic extremity of the dog. The ph level was measured continuously in the lateral vastus of the femoris muscle on both sides by means of a glass-one-rod measuring equipment. The pH value decreased to 6.43 ninety minutes after a total interruption of the arterial circulation. The initial value amounted to 7.20. The tissue-pH-values increase quickly during the following phase of recirculation.

Animals↗
PubMed1984

Adenine nucleotides and glycolysis during liver preservation by simple hypothermic storage.

Adenine nucleotides and glycolytic metabolites were examined during hypothermic storage of porcine livers by different preservation methods. The parameters ATP, ADP, AMP, G6P, F6P, FDP, GAP, 2PG, PEP, Pyr and Lact were investigated. The results indicate a dependence of adenine nucleotides but no dependence of glycolytic metabolites on preservation method. Storage by plasma protein fraction or Collins C2 solution causes a better result in TAN concentration after 6 h than albumin and Ringer storage or Ringer trickle perfusion. Conditioning the organ for a better outcome of preservation aimed at increasing the glycolytic rate is of questionable value.

Adenine Nucleotides↗
PubMed1983

[Reaction of the whole body to auxiliary liver transplantation].

Changes of hemoglobin, hematocrit, blood pressure, blood lactate concentration, and blood pyruvate concentration, as well as in the acid-base balance, the electrolyte metabolism, and the enzyme activities into the serum were investigated in auxiliary liver transplantation in 5 dogs. Transitory hypokalemia and hypoglycemia, a slight controllable acidosis caused by lactate accumulation, as well as a strong short-term increase of the enzyme activities in the serum are an expression of the functioning of the transplanted liver. Hyperkalemia, a massive increase of the blood lactate concentration with uncontrollable acidosis, a therapy-resistant depression in blood pressure, and a slow continuous increase of the enzyme activities in the serum are symptoms of the irreversible ischemic damage of the transplanted liver. The avoidance of an irreversible ischemic damage during the preservation, the maintenance of a normal blood pressure after the transplantation, as well as the compensation of acidosis, hypoglycemia, and hypokalemia are of decisive importance for a successful liver transplantation.

Acid-Base Equilibrium↗
PubMed1982

[Adenine nucleotides and metabolites of glycolysis in the liver in auxiliary transplantation].

The metabolic state of the liver during preservation as well as in and after auxiliary transplantation was investigated in dogs. The biopsy was carried out by means of TRU-CUT biopsy needle. - The ATP concentration, the storage of energy, the amount of the adenine nucleotides, and the ATP/ADP quotient decrease in the preserved liver. The AMP concentration, the concentration of the hexosemonophosphates and the mass-effective quotient of the phosphofructokinase increase simultaneously. The energy supply is the glycolysis exclusively. A lactate accumulation is avoided by continuous perfusion. - The changeover of the anaerobic to the aerobic energy preparation took place by degrees after the recovery of the liver circulation. The ATP concentration, the ATP/ADP quotient, the storage of energy, and the amount of the adenine nucleotides increase in the transplanted liver. - An irreversible ischemic damage of the liver appears in the metabolic state of the organ by a massive decrease of the ATP concentration below 0.7 mmol/kg, the amount of the adenine nucleotides below 1.8 mmol/kg, and AMP concentration.

Adenine Nucleotides↗
PubMed1982

Plasma vasopressin and oxytocin in response to exercise and during a day-night cycle in man.

Plasma vasopressin (AVP) and oxytocin (OXT) were determined by radioimmunoassay in healthy young men before, during and after a running exercise until exhaustion. In four of the five test subjects (one subject was underloaded) physical load resulted in a marked increase in plasma AVP with peak values of 11.7 to 57.8 pg/ml at exhaustion. Plasma OXT increased in three test subjects with peak values of 4.5 to 23.9 pg/ml. Within 1 h of recovery, both neuropeptides returned to basal plasma levels. The relationship between plasma AVP and osmolality (p less than 0.001) suggests that changes in osmolality play a dominant role in regulating the secretion of AVP. Besides peripheral effects, the increased levels of AVP and/or OXT during and immediately after the exercise, respectively, might induce a favourable action on the brain function. Determination of plasma AVP and OXT during a day-night cycle in the same test subjects reveals increased AVP levels from 02.00 to 08.00 h as compared to the other time periods chosen (18.00--24.00 h, p less than 0.001; 08.00--16.00 h, p = 0.031). In contrast, OXT does not differ between these time periods but decreased from 08.00 to 16.00 h (p less than 0.01). Accordingly, no correlation exists between both neuropeptides suggesting an independent secretion. It is unclear whether the circadian variations shown are able to influence the neuropeptide response to exercise.

Adolescent↗