Biomedical subjects

A Ameri

Publications and source records attributed to A Ameri.

At least 37 records · Page 2Linked to original sources

PubMed1998

Effects of the Aconitum alkaloid mesaconitine in rat hippocampal slices and the involvement of alpha- and beta-adrenoceptors.

1 The effects of mesaconitine, the main alkaloid contained in Aconiti tuber, were investigated by use of extracellular recordings of stimulus-evoked population spikes and field excitatory postsynaptic potentials (e.p.s.ps) in the CA1 region of rat hippocampal slices. 2 At a concentration of 10 nM, mesaconitine evoked excitations, which were manifested as an increase in the amplitude of the orthodromic spike and the appearance of multiple spikes following the first postsynaptic spike, without affecting the magnitude of paired-pulse facilitation. The increase in spike amplitude was persistent and was not reversed by up to 90 min of washout. At concentrations of 30 and 100 nM, the alkaloid produced a biphasic effect, that is an excitation followed by an inhibition without having any effect upon the field e.p.s.p. At concentrations above 100 nM, mesaconitine suppressed the orthodromic population spike and the field e.p.s.p. 3 The excitatory effect was also observed when electrical stimulation was stopped completely during the application of mesaconitine (10 nM) and during the first 15 min of washout. 4 The enhancement of the population spike and the appearance of multiple spikes induced by mesaconitine (10-100 nM) were blocked by pretreatment with the beta-adrenoceptor antagonists propranolol (1 microM) and timolol (1 microM), whereas the inhibitory effect was blocked by the alpha-adrenoceptor antagonists yohimbine (1 microM) and phentolamine (10 microM). However, when the beta-adrenoceptor antagonist timolol was added 10 min after the application of mesaconitine, it failed to block the long-lasting enhancement of the spike amplitude and the appearance of multiple population spikes. 5 Application of the selective beta-adrenoceptor agonist isoprenaline (500 nM) to the hippocampal slices induced an increase in the amplitude of the orthodromic population spike and elicited 2-3 additional spikes. Mesaconitine (10 nM) did not further potentiate this enhancement of the spike amplitude when added after a 15 min pretreatment with isoprenaline. 6 Perfusion of forskolin, which directly activates adenylate cyclase, enhanced the population spike. Mesaconitine had no additional effect when applied after pretreatment with forskolin. 7 It is concluded that the excitatory effects evoked by lower concentrations of the plant alkaloid mesaconitine are mediated by stimulation of beta-adrenoceptors and the consequent activation of intracellular processes which lead to the long-lasting changes in excitability.

Aconitine↗

PubMed1998

Effects of the Aconitum alkaloid songorine on synaptic transmission and paired-pulse facilitation of CA1 pyramidal cells in rat hippocampal slices.

1. The present study investigated the electrophysiological effects of songorine (1 100 microM), an alkaloid occurring in plants of the Aconitum genus, in rat hippocampal slices. 2. Songorine (10-100 microM) evoked a concentration-dependent increase in the amplitude of the orthodromic population spike and in the slope of the field e.p.s.p. The enhancement was long-lasting and was not reversed by up to 90 min of washout. Songorine failed to affect size and shape of the presynaptic fiber spike which represents the compound action potential of the Schaffer collaterals. This indicates that enhancement of the synaptic response is no consequence of an increased afferent excitability. 3. The antidromically evoked population spike was not affected by songorine at concentrations up to 100 microM suggesting that the enhancement of the orthodromic population spike and of the field e.p.s.p. was not due to an increase in pyramidal cell excitability. 4 The input-output curve for the postsynaptic population spike was shifted to the left implying that a presynaptic fiber spike of the same size elicited a larger postsynaptic response, indicating a decrease in threshold for generation of the population spike. 5. The songorine-evoked increase in excitability was not affected by the NMDA receptor antagonist, D-AP5. However, the effect of songorine was completely abolished by the selective dopamine D2 receptor antagonist sulpiride (0.1 microM) as well as by haloperidol (10 microM) and was mimicked by application of the dopamine releaser, amantadine (100 mM). In contrast, the selective D1 receptor antagonist, SCH23390, did not block the action of songorine. 6. The results indicate that the plant alkaloid songorine enhances excitatory synaptic transmission which may be due to an agonistic action at D2 receptors.

Alkaloids↗

PubMed1998

Frequency of the 20210 G-->A mutation in the 3'-untranslated region of the prothrombin gene in 35 cases of cerebral venous thrombosis.

BACKGROUND AND PURPOSE: A novel sequence variation in the 3'-untranslated region of the prothrombin (factor II) gene (nucleotide 20210 G-->A) has been recently described as a risk factor for deep vein thrombosis and pulmonary embolism. It is found in approximately 1% to 4% of healthy subjects. We studied the frequency of this factor II variant in patients with cerebral venous thrombosis. METHODS: The 20210A allele of the prothrombin gene was studied after DNA extraction, polymerase chain reaction amplification, and HindIII digestion in 35 patients with magnetic resonance imaging or angiographically confirmed cerebral venous thrombosis (23 women and 12 men, aged 11 to 71 years). RESULTS: Two patients (5.7%) had the 20210A allele of the prothrombin gene. Both had other risk factors for thrombosis (use of oral contraceptives and of intrathecal steroids). CONCLUSIONS: The 20210A allele of the prothrombin gene in association with other prothrombic factors may increase the risk of cerebral venous thrombosis, but case-control studies will be necessary to clarify these associations.

Adolescent↗

PubMed1998

Intermediate syndrome with delayed distal polyneuropathy from ethyl parathion poisoning.

An acute poisoning in a 44-y-old female who ingested 50 ml of ethyl parathion concentrate (25 g) is described. She was treated by gastric lavage, administration of pralidoxime and atropine, and mechanical ventilation. As signs of intoxication disappeared at day 3, treatment was discontinued. The patient had a relapse of acute cholinergic crisis at day 4, and the same treatment was applied again. The acute poisoning phase was followed by an intermediate syndrome and delayed distal polyneuropathy. The clinical course of this severe ethyl parathion poisoning was favorable after 40 d.

Acute Disease↗

PubMed1997

Inhibition of rat hippocampal excitability by the Aconitum alkaloid, 1-benzoylnapelline, but not by napelline.

The effects of the two structurally related Aconitum alkaloids, 1-benzoylnapelline and napelline, were investigated by extracellular recording of the stimulus-evoked population spike in the CA1 region of rat hippocampal slices in vitro. 1-Benzoylnapelline (1-100 microM) exerted a depressant action on the orthodromic as well as on the antidromic population spike. Napelline failed to evoke a significant effect at concentrations up to 100 microM. The inhibitory action induced by 1-benzoylnapelline was enhanced when the frequency of electrical stimulation was increased. In contrast, reversal of the inhibitory effect was accelerated when stimulation frequency was decreased. The activity-dependent mode of action of 1-benzoylnapelline raised the question of whether the drug is effective to suppress epileptiform activity. The results obtained from experiments on epileptiform hippocampal slices revealed a reduction of the burst duration and of the number of spikes in the burst as well as attenuation of the amplitude of the population spikes. These data support the conclusion that 1-benzoylnapelline, in contrast to the structurally related compound, napelline, has an activity-dependent inhibitory action on central neurons.

Aconitine↗

PubMed1997

Structure-dependent differences in the effects of the Aconitum alkaloids lappaconitine, N-desacetyllappaconitine and lappaconidine in rat hippocampal slices.

Lappaconitine, a C19 diterpenoid alkaloid from Aconitum sinomontanum has been reported to possess analgesic and antiinflammatory properties in vivo and to inhibit neuronal activity in brain slices. In the present study the effect of lappaconitine has been compared with the effects of its main metabolite N-desacetyllappaconitine and the structurally related alkaloid lappaconidine. For comparison of drug effects population spikes and field excitatory postsynaptic potentials (EPSPs) evoked by stimulation of stratum radiatum or the alveus were studied in normal rat hippocampal slices and in slices treated with low Mg2+-medium. At concentrations of 3-100 microM, both lappaconitine and N-desacetyllappaconitine inhibited population spikes elicited by stratum radiatum and alvear stimulation as well as the field EPSP recorded in CA1 stratum radiatum. The drug-induced depression of field potential responses was increased with rising stimulus frequency, indicating an activity-dependent mode of action. The effect of N-desacetyllappaconitine on each parameter investigated was significantly stronger than the effect of lappaconitine. Despite the structural relationship, lappaconidine failed to affect neuronal excitability in concentration below 100 microM, and an increase in stimulus frequency did not potentiate its effect. Moreover, lappaconitine and N-desacetyllappaconitine suppressed epileptiform activity induced by bicuculline or by omission of Mg2+ from the bathing medium.

Aconitine↗

PubMed1997

Inhibition of rat hippocampal excitability by the plant alkaloid 3-acetylaconitine mediated by interaction with voltage-dependent sodium channels.

The effects of the Aconitum alkaloid 3-acetylaconitine on neuronal activity were investigated in the slice preparation and on cultivated neurons of rat hippocampus by extracellular and patch-clamp recordings, respectively. 3-Acetylaconitine (0.01-1 microM) diminished the orthodromic and antidromic population spike in a concentration-dependent manner. The inhibitory action of the drug was preceded by a transiently enhanced excitability. The latency of onset of the inhibition was accelerated by increased stimulation frequency, whereas recovery during washout of the alkaloid was accelerated by decreased stimulation frequency. Moreover, the inhibitory effect of 3-acetylaconitine was evaluated in two different models of epileptiform activity induced either by blockade of GABA receptors by bicuculline (10 microM) or by a nominal Mg(2+)-free bathing medium. In accordance with the activity-dependent mode of action, this compound abolished the synaptically evoked population spikes in the presence of bicuculline or nominal Mg(2+)-free bathing medium, respectively. Whole-cell patch-clamp recordings revealed an interaction of 3-acetylaconitine with the voltage-dependent sodium channel. At a concentration of 1 microM, 3-acetylaconitine did not affect the peak amplitude of the sodium current, but shifted the current-voltage relationship in the hyperpolarized direction such that sodium currents were already activated at the resting potential.

Aconitine↗

PubMed1997

Electrophysiological actions of the plant alkaloid 6-benzoylheteratisine in rat hippocampal slices.

The effects of the Aconitum alkaloid 6-benzoylheteratisine on neuronal activity was investigated in the in vitro slice preparation of rat hippocampus by extracellular recording of the stimulus-evoked population spike. 6-Benzoylheteratisine (0.01-10 microM) depressed the orthodromic and antidromic population spike in a concentration-dependent manner. The action of the drug was activity-dependent. The latency of onset of the inhibition was accelerated when the frequency of electrical stimulation had been increased. Furthermore, the effect of 6-benzoylheteratisine was evaluated in two different models of epileptiform activity induced either by blockade of GABA receptors by bicuculline (10 microM) or by a nominal Mg2+-free bathing medium. Due to the activity-dependent mode of action, this drug effectively reduced the number and the size of the synaptically evoked population spikes in the presence of bicuculline or nominal Mg2+-free bathing medium, respectively.

Aconitine↗

PubMed1997

Calcium-dependent, sustained enhancement of excitability during washout of aconitine in rat hippocampal slices.

Extracellular recording of the stimulus-evoked population spike was performed in the CA1 area of rat hippocampal slices in order to investigate delayed effects of the plant alkaloids aconitine and veratridine. Veratridine (1 microM and 10 microM) suppressed the orthodromic and antidromic population spike. After washout of the drug, only a partial recovery was obtained. Aconitine (1 microM) exerted the same inhibitory action as veratridine. However, after washout, the spike amplitude was enhanced compared with the control. This enhancement of the spike amplitude was dependent on the concentration of aconitine and was maintained during the observation period of at least 2 h. Lowering the Ca2+ concentration of the bathing medium from 2.5 mM to 1.25 mM during application of aconitine attenuated recovery and prevented the enhancement observed during washout of the drug. Application of aconitine in the presence of CdCl2 as well as in the presence of inhibitors of protein kinase C and Ca2+/calmodulin-dependent protein kinase II prevented the increase in spike amplitude during washout with standard artificial cerebrospinal fluid. In contrast, the N-methyl-D-aspartate (NMDA) receptor antagonists D-AP5 and MK-801 as well as the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione were ineffective in abolishing the aconitine-induced enhancement. These data support the conclusion that different modes of action are involved in the effects of aconitine but not veratridine. It is concluded that the aconitine-induced increase in neuronal activity is mediated by intracellular Ca2+-dependent mechanisms leading to an activation of Ca2+-dependent protein kinases. This effect is independent of Ca2+ entrance through NMDA and non-NMDA receptors.

2-Amino-5-phosphonovalerate↗

PubMed1997

Effects of the alkaloids 6-benzoylheteratisine and heteratisine on neuronal activity in rat hippocampal slices.

Alkaloids of different Aconitum species are employed as analgesics in traditional Chinese folk medicine. The present study was designed in order to investigate the effects of the structurally related alkaloids 6-benzoylheteratisine and heteratisine on neuronal activity in rat hippocampus. Experiments were performed as extracellular recordings of stimulus evoked population spikes in rat hippocampal slices. 6-Benzoylheteratisine (0.01-10 microM) inhibited the ortho- and antidromic population spike as well as the field EPSP in a concentration- and frequency-dependent manner. Heteratisine (1-100 microM) was a less potent inhibitor. It exerted a depression of the orthodromic spike, but failed to affect the antidromic population spike. 6-Benzoylheteratisine (10 microM) diminished epileptiform activity induced by bicuculline. In hippocampal neurons, this compound reduced the peak amplitude of the sodium current. There was no effect of heteratisine on the sodium current in concentrations up to 100 microM. It is concluded that the frequency-dependent action of 6-benzoylheteratisine suggests an inhibition of neuronal activity which underlies epileptiform burst discharges. The predominant effect is a suppression of neuronal activity due to a blockade of sodium channels.

Aconitine↗

PubMed1997

Treatment of recurrent malignant supratentorial gliomas with the association of carboplatin and etoposide: a phase II study.

Thirty one patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea for malignant supratentorial gliomas received a combination of carboplatin (CBDCA) and etoposide (VP16) at tumor progression. Carboplatin and etoposide (CE) were given, each at a dose of 100 mg/m2/day from day 1 to 3. The response was evaluated at each course and a minimum of three course was required to definite stable patient. Tolerance was evaluated in 31 patients. None had renal or auditory toxicity. Side effects consisted of grade III hematologic toxicity in 6 patients (19%), and grade III hepatic toxicity in one patient. No grade IV WHO toxicity was observed. All 31 patients could be evaluated for therapeutic response. A partial response was noted in 4 patients during 13, 34 +, 35 + and 51 + weeks. Ten patients had stable disease after a minimum of 3 courses (19 to 37 weeks). The rate of partial response (PR) and stabilisation (S) was 45% (14/31). The median time to tumor progression (MTTP) for responding and stable patients was 28 weeks. The median survival time (ST) for the entire group was 45 weeks and over 51 weeks for PR and S patients.

Adult↗

PubMed1997

Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human platelets.

(+)-Kavain, a 4-methoxy-alpha-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), respectively. Exogenously applied AA (100 mumol/l) provoked a 90% aggregation of platelets, the release of 14 pmol ATP, and the formation of either 220 pg TXA2 or 43 pg PGE2, each parameter being related to 10(6) platelets. An application of (+)-kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA2 and PGE2 with IC50 values of 78, 115, 71, and 86 mumol/l, respectively. The similarity of the IC50 values suggest an inhibition of COX by (+)-kavain as primary target, thus suppressing the generation of TXA2 which induces aggregation of platelets and exocytosis of ATP by its binding on TXA2-receptors.

Arachidonic Acids↗

PubMed1997

Bicuculline-induced epileptiform activity in rat hippocampal slices: suppression by Aconitum alkaloids.

Alkaloids of Aconitum spec. (Ranunculaceae) are employed in traditional Chinese folk medicine as analgesics. The present study was designed in order to investigate the effects of the structurally related alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine on experimentally induced epileptiform activity. Experiments were performed as extracellular recordings of stimulus evoked population spikes in rat hippocampal slices. Epileptiform activity was induced by bicuculline. All three alkaloids exerted an inhibitory action on excitability of hippocampal pyramidal cells in a frequency-dependent manner. The onset of inhibition was accelerated by increasing the frequency of electrical stimulation. Aconitine (1 microM) evoked a complete suppression of both normal and epileptiform activity, whereas lappaconitine (10 microM) and 6-benzoylheteratisine (10 microM) selectively diminished the epileptiform afterdischarges and the duration of the bursts, but spared the normal activity. The present findings suggest that the structurally related Aconitum alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine possess an anticonvulsive potential. The predominant effect of these alkaloids is to suppress the spread of seizure activity, and they may therefore tend to distort epileptic events. However, despite their similar structure, they exert qualitatively and quantitatively different inhibitory effects.

Aconitine↗

PubMed1997

Relaxation of evoked contractile activity of isolated guinea-pig ileum by (+/-)-kavain.

Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-kavain (400 microM). However, (+/-)-kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-kavain may act in a non-specific musculotropic way on the smooth muscle membrane.

Animals↗

PubMed1996

Anticonvulsive action of (+/-)-kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites.

Kava pyrones are constituents of the intoxicating pepper (Piper methysticum Forst), which has been shown to be anticonvulsive. The question of how the excitability of neurons is affected was investigated by determining the interaction of (+/-)-kavain with epitopes (site 1, site 2) of voltage-dependent Na+ channels and the action of (+/-)-kavain on 4-aminopyridine-stimulated synaptosomes as model of repetitive firing neurons. [3H]Saxitoxin and [3H]batrachotoxin were used for radioligand-binding assays performed with synaptosomal membranes. Gultamate released from 4-aminopyridine-stimulated cerebrocortical synaptosomes and the cytosolic concentrations of Na+ and Ca2+ ([Na+]i, [Ca+]i) were detected fluorometrically by using an enzyme-linked assay, sodium-binding benzofuranisophthalate (SBFI) and Fura-2, respectively. (+/-)-Kavain failed to compete with [3H]saxitoxin up to 400 mumol/l but dose-dependently suppressed binding of [3H]batrachotoxin with an IC50 value of 88 mumol/l (Ki = 72 mumol/l) although displacement of [3H]batrachotoxin was restricted to 33% of control at 400 mumol/l (+/-)-kavain. In stimulated synaptosomes, 5 mmol/l 4-aminopyridine provoked an increase in [Na+]i and [Ca2+]i by 9 mmol/l Na+ and 235 nmol/l Ca2+. Comparable to the reduction in [3H]batrachotoxin binding, 400 mumol/l (+/-)-kavain suppressed the increase in [Na+]i and [Ca2+]i to 38 and 29% of control, respectively. Consistent with the increase in [Na+]i and [Ca2+]i, 5 mmol/l 4-aminopyridine provoked glutamate release (rate: 38 pmol/s*mg protein) which was dose-dependently diminished to 60% of control by 400 mumol/l (+/-)-kavain. KCl depolarization (40 mmol/l) provoked an increase in [Ca2+]i and glutamate release almost identical to the responses elicited by 4-aminopyridine but 400 mumol/l (+/-)-kavain suppressed only the rate of glutamate release by 9% of control. The data suggest an interaction of (+/-)-kavain with voltage-dependent Na+ and Ca2+ channels, thereby suppressing the 4-aminopyridine-induced increase in [Na+]i, [Ca2+]i and the release of endogenous glutamate.

4-Aminopyridine↗

PubMed1996

Inhibition of neuronal activity in rat hippocampal slices by Aconitum alkaloids.

The structurally related Aconitum alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine inhibited the orthodromic and antidromic population spike in hippocampal CA1 area in a frequency-dependent manner. Aconitine (1 microM) completely suppressed epileptiform activity induced by omission of Mg2+ as well as normal neuronal activity, whereas lappaconitine (10 microM) and 6-benzoylheteratisine (10 microM) diminished epileptiform activity by sparing normal neuronal activity.

Aconitine↗

PubMed1996

Age-dependent differences in sensitivity to aconitine of rat hippocampal slices.

The effect of aconitine, a plant alkaloid known to bind at site 2 of the sodium channel, was investigated on neuronal excitability in hippocampal slices of adult and juvenile rats. Aconitine (0.01-1 microM) diminished the extracellularly recorded population spike in a concentration-dependent manner. At each concentration, the inhibitory action of aconitine was significantly stronger and was obtained after a shorter latency in slices of juvenile rats (20-25 days) as compared with slices of adult rats (45-50 days). When maximal inhibition was achieved, a prolonged application of aconitine evoked an increase in spike amplitude of up to 15% in slices of juvenile but not of adult rats. The latency of recovery from the aconitine-induced inhibition was also significantly shorter in slices of juvenile rats. This effect was concentration-dependent and significantly stronger in slices of juvenile rats. These observations indicate that juvenile hippocampi have a higher susceptibility to the effect of aconitine, but also provide a partial protective mechanism.

Aconitine↗

PubMed1996

Aconitine inhibits epileptiform activity in rat hippocampal slices.

The effect of aconitine, an alkaloid neurotoxin known to bind at site 2 of the sodium channel, was investigated on epileptiform activity in hippocampal slices by use of extracellular recordings in CA1 pyramidal cell layer. Epileptiform activity was induced by bicuculline, picrotoxin, penicillin, pentylenetetrazol or by omission of magnesium from the bathing medium, respectively. In every case aconitine (0.1 and 1 microM) blocked the multiple population spikes representing the epileptiform activity. The onset of inhibition was shorter by use of an increased concentration of the epileptogenic drug. Epileptiform activity evoked by pentylenetetrazol and low magnesium was first increased by aconitine followed by a rapid inhibition, while the bicuculline-, picrotoxin-, and penicillin-induced epileptiform discharges were immediately abolished.

Aconitine↗