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At least 469 records · Page 26Linked to original sources
PubMed1996

Enhanced fast synaptic transmission and a delayed depolarization induced by transient potassium current blockade in rat hippocampal slice as studied by optical recording.

In hippocampal neurons, a slowly inactivating aminopyridine-sensitive transient potassium current, D-current, influences the time course of action potential repolarization and therefore activity-dependent Ca2+ entry. We used high-speed optical recording techniques to study the effects of selectively inhibiting D-current with 4-AP (40 microM) on transmission at the Schaffer collateral (CA3)-CA1 synapse in rat hippocampal slices stained with the voltage-sensitive dye RH-155. We observed that addition of 4-AP to the bathing solution resulted in (1) augmentation of a fast component of the optical signal corresponding to the postsynaptic EPSP and action potential, and (2) the appearance of a delayed depolarization of CA1 neurons and other adjacent cells. 4-AP appeared to alter the presynaptic action potential and the dynamics of synaptic transmission to both reduce the sensitivity of the postsynaptic EPSP and action potential to omega-toxin calcium channel blockers (omega-conotoxin GVIA and omega-agatoxin IVA) and the Ca(2+)-dependent potassium channel blocker charybdotoxin, and to increase sensitivity to the dihydropyridine nifedipine, the NMDA receptor blocker aminophosphonopentanoic acid, and the intracellular Ca2+ release inhibitor thapsigargin. The delayed depolarization induced by 4-AP was inhibited in hyperosmotic extracellular solution, suggesting that enhanced transmitter release resulted in increased accumulation of K+ in the extracellular space. Because 4-AP is a convulsant at concentrations similar to those used here, we suggest that the 4-AP-targeted channel(s) carrying D-current may contribute to the hyperexcitability associated with epilepsy.

4-Aminopyridine↗
PubMed2002

Strain-rate sensitivity of the rabbit MCL diminishes at traumatic loading rates.

This study was performed to determine whether the viscoelastic behavior of ligaments persists at high rates of loading, such as those associated with sports-related trauma or motor vehicle accidents. Medial collateral ligaments (MCLs) from 22 skeletally mature New Zealand White rabbits were tensile tested quasi-statically and via two impact conditions at displacement rates of 0.17 mm/s (n=22), 640+/-160 mm/s (n=10) and 2500+/-270 mm/s (n=12) (corresponding to strain rates of approximately 1.0%/s, 3660%/s and 14,000%/s, respectively). Despite dramatic increases in displacement rate, only a modest strain-rate effect was observed when the specimens tested quasi-statically were compared to those tested via impact (24% and 37% increases in stiffness and failure load, respectively). There were no differences in the structural (e.g. 145+/-30 and 136+/-29 N/mm stiffness values, respectively) or failure properties (e.g. 434+/-91 and 443+/-154 N failure load values, respectively) of the two impact-tested groups. Our findings suggest that the rabbit MCL is not viscoelastic at loading rates approximating those associated with high-energy trauma.

Animals↗
PubMed1994

Selective inactivation of viruses in the presence of human platelets: UV sensitization with psoralen derivatives.

Inactivation of viruses in blood products requires that the method employed display selectivity in its action for viral elements while not affecting the biological entity of interest. Several methods have been developed for the treatment of human plasma or products derived from human plasma. An effective technique for the treatment of the cellular components of blood has been lacking, in part due to the inability to develop agents capable of selectively targeting viral agents in the milieu of cellular material. In this paper, we examine the behavior of a group of viral sensitizers designed to be added to cellular samples and be activated upon exposure to UVA light. Upon activation, these agents are capable of disrupting nucleic acids of the virus in a manner that renders them inactive for proliferation. The selectivity observed in this inactivation is determined by the chemical structure of the sensitizer, which can be varied to increase viral killing capacity while diminishing collateral damage to cellular and protein constituents.

Adenosine Diphosphate↗
PubMed1975

The sensitivity of Renshaw cells to velocity of sinusoidal stretches of the triceps surae muscle.

1. The electrical activity of Renshaw cells monosynaptically excited by ventral root stimulation and disynaptically excited by electric stimulation of the group I afferents in the GS nerve has been recorded and their response to individual sinusoidal stretches of the deefferented GS muscle tested for different amplitudes and durations of the stimulus. 2. The experimental data indicate that the Rensahw cell responses are not only length dependent but also rate dependent. This finding indicates that the same Renshaw cells receive recurrent collaterals of both tonic and phasic motoneurons. 3. The observation that the discharge of Renshaw cells is particularly sensitive to the velocity of stretch suggests that the recurrent collaterals of large phasic motoneurons, which are recruited during high velocity stretches, exert a stronger excitatory action on Renshaw cells than do axon collaterals of the smaller tonic motoneurons, which are selectively stimulated during low velocity stretches.

Action Potentials↗
PubMed1996

Occlusive arterial disease of the upper extremity: colour Doppler as a screening technique and for assessment of distal circulation.

A prospective study was performed to evaluate the sensitivity of colour Doppler flow imaging (CDFI) in the detection of occlusive arterial disease in the upper limb (using angiography as the standard) and to quantify the severity of the disease. Twenty-one ischaemic and 15 healthy limbs were studied by intra-arterial digital subtraction angiograms (IADSA) and CDFI. Selective subclavian digital subtraction angiograms were performed by the percutaneous transfemoral route. CDFI was performed from the brachial artery superiorly to the subclavian artery origin. Special attention was paid to the study of spectral waveforms and peak systolic velocities at various levels. In each subject, IADSA and CDFI were performed by different radiologists without knowledge of the results of the other investigation. In normal limbs, all arteries demonstrated a characteristic sharp triphasic spectral pattern with mean peak systolic velocity of 105, 80 and 57 cm/s for the subclavian, axillary and brachial arteries, respectively. In ischaemic limbs, reduction in peak systolic value and broadening of the spectral trace with filling in of the spectral window were noted. More characteristic was the finding of a loss of diastolic flow reversal, which was the earliest sign of significant arterial stenosis. The pattern of diastolic blood flow correlated well with the degree of collateral formation and distal vascular runoff. In conclusion, CDFI has a high sensitivity and specificity in the detection of significant arterial stenosis and is thus an ideal, inexpensive screening procedure. Analysis of the diastolic wave-form distal to the stenosis is an indicator of the degree of collateral circulation and distal runoff and thus acts as a prognostic indicator, guiding further investigation and management.

Angiography, Digital Subtraction↗
PubMed1999

Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus.

Ca2+ released from presynaptic and postsynaptic intracellular stores plays important roles in activity-dependent synaptic plasticity, including long-term depression (LTD) of synaptic strength. At Schaffer collateral-CA1 synapses in the hippocampus, presynaptic ryanodine receptor-gated stores appear to mobilize some of the Ca2+ necessary to induce LTD. Cyclic ADP-ribose (cADPR) has recently been proposed as an endogenous activator of ryanodine receptors in sea urchin eggs and several mammalian cell types. Here, we provide evidence that cADPR-mediated signaling pathways play a key role in inducing LTD. We show that biochemical production of cGMP increases cADPR concentration in hippocampal slices in vitro, and that blockade of cGMP-dependent protein kinase, cADPR receptors, or ryanodine-sensitive Ca2+ stores each prevent the induction of LTD at Schaffer collateral-CA1 synapses. A lack of effect of postsynaptic infusion of either cADPR antagonist indicates a probable presynaptic site of action.

ADP-ribosyl Cyclase↗
PubMed1990

Comparison between ultrasonographic signs and the degree of portal hypertension in patients with cirrhosis.

The sensitivity of ultrasonography (US) for the diagnosis of portal hypertension was assessed in 48 patients with known cirrhosis. These results were compared to the hemodynamic values obtained on the same day by hepatic vein catheterization. The sensitivity of US in detecting portal hypertension was about 40% considering either a greater than 13 mm diameter of the portal vein, or the lack of mild caliber variation of the superior mesenteric vein. The sensitivity was more than 80% considering the presence of portosystemic venous collaterals. Presence of numerous portosystemic shunts was significantly associated with high hepatic venous pressure gradients which reflected the severity of portal hypertension.

Female↗
PubMed2000

Potassium channel openers and blockers in coronary artery disease. Comparison to betablockers and calcium antagonists.

Potassium channel openers and blockers, which belong to a novel class of vasodilator drugs and to the class of specific bradycardic substances, are potential new antianginal drugs. Experimental findings in vivo suggest that bimakalim is a new substance characterized as ATP-sensitive K+ channel openers, since it exerts preferential vasodilation of the collateral circulation of the coronary vasculature and both leads to increase blood flow to ischemic areas and to attenuate the ST segment elevation caused by regional ischemia in the canine heart. Opening of KATP increases the conductivity of potassium ions which results in hyperpolarization of smooth muscle membranes, thus producing vasodilation. Tedisamil is a new bradycardic agent proven to exert antiischemic and antiarrhythmic effects by blockade of the cellular cardiac repolarization K+ currents as well as of multiple neuronal and vascular K+ currents (Ito, Ik, and K+ATP). Using right heart catheterization and exercise tolerance tests, we investigated the hemodynamic, antiischemic and neurohumoral effects of bimakalim and tedisamil in patients with angiographically proven coronary artery disease, stable angina pectoris and reproducible ST segment depression during exercise. In 50 patients with coronary artery disease, the hemodynamic and antiischemic effects of a single oral dose bimakalim of 0.1 mg, 0.3 mg and 0.6 mg were compared to placebo. In a dose-finding baseline-controlled study, a comparable collective was examined for the effects of acute i.v. administration of tedisamil 0.1, 0.2, 0.3 and 0.4 mg/kg bw. A subgroup of 8 patients receiving 0.3 mg/kg bw tedisamil i.v. was compared with a similar group of 14 patients who had received esmolol (i.v. bolus of 500 micrograms/kg, maintenance dose 200 micrograms/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intra-individual comparison. Furthermore, in 48 patients, short-term (6 days) effects of tedisamil, 2 times 100 mg orally, were compared to 2 times 50 mg atenolol treatment. With a single oral dose of bimakalim antianginal and/or antiischemic effects were lacking, increased doses, however, induced changes in hemodynamics typical of vasodilation, i.e., a significant decrease in systolic blood pressure and a secondary chronotropic response. In contrast to bimakalim, tedisamil produced antiischemic effects and was found to have favorable hemodynamic, neurohumoral and antiischemic effects in comparison to the betablocker esmolol and atenolol in patients with coronary artery disease. Tedisamil induced a dose-dependent decrease in both heart rate and the index of myocardial oxygen consumption associated with an improvement in ST segment depression. Tedisamil as well as esmolol and atenolol showed almost equipotent antiischemic effects at the doses administered. Compared with gallopamil, both tedisamil and esmolol were superior in their effects on myocardial oxygen consumption and ST segment depression, whereas plasma lactate concentrations were more reduced by tedisamil and gallopamil.

Adrenergic beta-Antagonists↗
PubMed1988

Quantitative correlation between tetanus-induced decreases in extracellular calcium and LTP.

Decreases in the extracellular calcium concentration ([Ca2+]o), induced by tetanization of the Schaffer collaterals in rat hippocampal slices, were measured by means of Ca2+-sensitive microelectrodes. The amount of long term potentiation (LTP) of the evoked field potentials, induced by this tetanus, was determined. A positive correlation was found between the amplitude of the tetanus induced decrease in [Ca2+]o and the amount of LTP that was elicited. The N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-phosphonovalerate decreased both the tetanus-induced decreases in [Ca2+]o and the amount of LTP that was induced. We conclude that the amount of Ca2+ that enters the cell during a tetanus is of major importance in the induction process of LTP.

2-Amino-5-phosphonovalerate↗
PubMed2006

Comparison of plain MRI and MR arthrography in the evaluation of lateral ligamentous injury of the ankle joint.

BACKGROUND: The purpose of this study was to determine the efficacy of plain magnetic resonance imaging (MRI) and magnetic resonance (MR) arthrography for detecting collateral ligamentous injury of the ankle joint. METHODS: Fifty patients (October 2001 to November 2003) suffering from ankle disability who underwent plain MRI and MR arthrographic studies were enrolled in this study. The diagnostic criteria for ligament disruption on plain MRI included nonvisualization, disruption, waviness of the ligament, or coexistent avulsion fracture. The MR arthrographic findings of ligament disruption were based on leakage of gadolinium contrast medium anterior to the anterior talofibular (ATaF) ligament following ATaF ligament disruption, and the contrast medium filling into the common peroneal tendon sheath after calcaneofibular (CF) ligament disruption. The 2 modalities were interpreted respectively and blindly. RESULTS: Seventeen patients received surgical intervention. There were 14 patients who had a torn ATaF ligament and 6 patients who suffered from CF ligament disruption proved by surgery. Limited detection of preoperative plain MRI survey, which showed 12 patients had torn ATaF and 2 patients had torn CF ligament, was noted. However, most patients with ligamentous injury were correctly diagnosed by MR arthrography preoperatively (only 1 case of CF injury was missed). The plain MRI alone had a higher incidence of false negative and false positive detection. MR arthrography was also valuable for evaluating the coexisting intra-articular pathologies of the ankle joint. CONCLUSION: For evaluating ankle disability, using plain MRI alone is not adequate for correctly detecting lateral collateral ligamentous injury of the ankle joint. MR arthrography improves the sensitivity and the accuracy for ATaF and CF ligament injuries. It also helps in assessing coexisting pathologic lesions of ankle joints, especially impingement syndromes and osteochondral lesions, and provides more information for therapeutic decision making.

Adolescent↗
PubMed2004

Effective strategies for recruiting families ascertained through alcoholic probands.

BACKGROUND: Recruiting a large number of participants meeting strict inclusion criteria can be challenging, particularly when selecting for a condition associated with a social stigma such as alcoholism, when participation involves collection of medical specimens and sensitive information, and when the participation of family members or other collaterals is required. Developing and implementing a successful recruitment plan depends upon identifying the most effective recruitment strategies given the available resources. METHODS: Several strategies for recruiting subjects for a large family study on the genetics of alcoholism were evaluated over a two-year period with regard to participant yield, time and cost expenditure. RESULTS: Overall effectiveness of a recruitment strategy was determined based on a composite of yield, cost and time expenditure. The most effective recruitment strategies were direct mail, press release, the Internet and treatment center collaborations. CONCLUSION: Results provide insight into successful strategies for recruiting large numbers of participants and their family members selected for a condition associated with a social stigma.

Alcoholism↗
PubMed1980

Compensatory increase of responses to nerve stimulation of the partially denervated rat urinary bladder.

The rat urinary bladder was deprived of half of its innervation by removing the pelvic ganglion on one side. The motor response of such a partially denervated bladder to stimulation of the pelvic nerve on the other side were examined 1 week, 1 month and 2 months postoperatively. On all three occasions the increase in pressure of the operated bladder was larger than that of the control bladder; the enlargement was most marked 2 months after operation. The responses were further enlarged by eserine, and markedly reduced by atropine. The present results combined with those of previous investigations, showing a rapid recovery in the activity of the acetylcholine forming enzyme from a reduced level and a transient supersensitivity to chemical stimuli after unilateral removal of the pelvic ganglion, suggest that the enlarged responses to nerve stimulation 1 week postoperatively are mainly due to sensitization, while those observed at the later stages are due to collateral sprouting from the cholinergic nerve fibres of the intact pelvic nerve.

Adrenergic Fibers↗
PubMed1994

Pulmonary gas trapping differences among animal species in response to intravenous infusion of perfluorocarbon emulsions.

In animals, increased lung volume and a concomitant failure of lungs to collapse normally upon autopsy can occur following intravenous injection of higher vapor pressure perfluorocarbons (PFCs) administered as emulsions. Responses vary considerably depending on the PFC, dose and animal model. The study objective was to examine animal species differences with respect to this apparent pulmonary gas trapping (PGT) phenomenon which has not been observed in human clinical trials. A dose-related increase in postmortem lung volume following treatment with either a concentrated perflubron emulsion or Fluosol was observed. It was most pronounced in pigs, rabbits and monkeys, and essentially nonexistent in mice and dogs. No clear effects on arterial blood gases were seen in most species, but PaO2 levels were reduced transiently in monkeys given the highest PFC doses. Reversibility of pulmonary effects occurred more rapidly with perflubron emulsions than with Fluosol. Vacuolated mononuclear cells, reflecting the presence of PFC particles in the lung, and alveolar distention varied between species, but no lesions or edema were observed. Species differences in collateral ventilation, airway morphology and pulmonary intravascular macrophages may influence their sensitivity and contribute to the interspecies differences in response to intravenously administered PFC emulsions.

Animals↗
PubMed1996

L-deprenyl (selegiline) decreases excitatory synaptic transmission in the rat hippocampus via a dopaminergic mechanism.

The effect of L-deprenyl (selegiline) on the excitatory synaptic transmission was characterized in the CA1 neurons of rat hippocampal slices by using a intracellular recording technique. Superfusion of L-deprenyl (0.1-10 microM) reversibly decreased the EPSP, which was evoked by orthodromic stimulation of the Schaffer collateral-commissural afferent pathway in a concentration-dependent manner. The sensitivity of postsynaptic neurons to the glutamate receptor agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or N-methyl-D-aspartate, was not affected by L-deprenyl (1 microM) pretreatment. In addition, L-deprenyl (1 microM) clearly increased the magnitude of paired-pulse facilitation regardless of the interstimulus intervals of 20 to 300 msec used. The ability of L-deprenyl to decrease the EPSP amplitude was not observed in the dopamine-depleted rats. Pargyline and 4-phenylpyridine, the monoamine oxidase type B inhibitors, mimicked the depressant effect of L-deprenyl on the EPSP. Moreover, the reduction of L-deprenyl (1 microM) on the EPSP amplitude was specifically antagonized by sulpiride (0.01-0.1 microM), a selective dopamine D2 receptor antagonist. However, the dopamine D1 receptor antagonist, SKF-83566 (1-10 microM), did not significantly affect L-deprenyl's action. These results indicate that the monoamine oxidase type B inhibitory ability leading to an increase of the dopaminergic tonus in the hippocampus is involved in the L-deprenyl-induced depression of excitatory synaptic transmission in the CA1 region of the rat hippocampus. Moreover, application of L-deprenyl (1 and 10 microM) also reversibly suppressed the epileptiform activity evoked by picrotoxin.

Animals↗
PubMedDate not supplied

[Sequelae of diathermocoagulation of cerebellar arteries and veins in normal rabbits and rabbits sensitized to brain antigen].

Electrocauterization of an artery or a vein on the surface of the posterior lobe of the cerebellum may cause no focal changes in the bed of the occluded vessel, or result in varying severity and extension of lesion of the posterior cerebellar lobe. In occluding an artery a focus of complete necrosis or oedema is formed in its bed, while in occluding avein a focus of oedema is formed that may be accompanied by erythrocytic extravasation. In the group of animals sensitized with brain antigens a tendency towards oedema enhancement, and a vascular permeability increase is noted, neuronal changes are more frequent at a distance from the occluded vessel's basin. However, the importance of sensitization is, as a rule, masked by individual peculiarities of the collateral supply or venous return in the bed of the occluded vessel.

Animals↗
PubMed1982

Selective cytotoxicity of haloethylnitrosoureas in a carcinoma cell line resistant to bifunctional nitrogen mustards.

A Walker 256 rat carcinoma cell line (WR) has been shown to be resistant to a broad spectrum of bifunctional nitrogen mustards (NM) in cell culture. The parent cell line (WS) from which the WR cells were selected retains marked sensitivity to this class of drugs. Karyotype analysis showed that the parent WS had a chromosome content which was significantly higher than the WR. A number of chromosome marker bands were also distinguishable, indicative of distinct nuclear structural differences. A lack of collateral resistance to haloethylnitrosoureas was demonstrated for the WR cell line. In some cases the sensitivity of the WR to nitrosoureas was greater than that of WS. In addition, the WR could be sensitized to NM by a concomitant addition of a water-soluble carbamoylating agent, N,N'-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea, which possessed no intrinsic alkylating activity. Since NM and nitrosoureas differ pharmacologically, mainly by the latter's potential to carbamoylate, this reaction would appear to be critical to the cytotoxic properties of nitrosoureas against WR cells. Heretofore, carbamoylation has been considered of little importance to the antitumor properties of nitrosoureas. Moreover, 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) has been reported as possessing only minimal carbamoylating potential, as measured in vitro by a lysine assay. While remaining an accurate assay for the modification of the psi-amino groups of lysine, it is possible that the quantitative lysine assay may not predict the physiological carbamoylating potential of ACNU in the Walker cells, since marked cytotoxicity was achieved in both WR and WS by ACNU.

Animals↗
PubMed1992

[The recent development and the present status of K+ channel opener].

The development of vasodilator drugs that open the K+ channels in blood vessels has been of great academic and practical interest. The discoveries of the ATP-sensitive K+ channel and the glibenclamide-sensitive K+ channel have promoted these interests. In relation to this channel, the cardioprotective effectiveness of a K+ channel opener (Aprikalim) in doses that did not change haemodynamics or collateral blood flow were demonstrated in infarct dog heart. The effects were antagonized by glibenclamide. Thus, ATP-sensitive K+ channels seem to play an important role in this effect. Clinical evaluations of the K+ channel openers are reviewed. The hypotensive effects of the drugs are well-recognized. At present, however, the clinical usefulness of K+ channel openers has not been accepted widely, because of their side-effects including reflex tachycardia, edema, flushing and headache. An approach to reduce these side-effects is critical if these K+ channel openers are to be used as good hypotensive drugs. The K+ channel opener nicorandil has been evaluated as a highly effective antianginal drug. It seems likely that the clinical benefits of nicorandil result from both its K+ channel opening properties and its ability to stimulate smooth muscle guanylate cyclase. Clinical data on the pure-selective K+ channel opener cromakalim (lemakalim) as an antianginal drug is limited. However, on the basis of the vasodilator profile of this drug, it is expected to be useful for this purpose. The application of K+ channel openers to treat other disorders such as bladder instability is limited because of its hypotensive action.

Animals↗
PubMed2003

Anesthetic sensitivities to propofol and halothane in mice lacking the R-type (Cav2.3) Ca2+ channel.

UNLABELLED: Because inhibition of voltage-dependent Ca(2+) channels can be a mechanism underlying general anesthesia, we examined sensitivities to propofol and halothane in mice lacking the R-type (Ca(v)2.3) channel widely expressed in neurons. Sleep time after propofol injection (26 mg/kg IV) and halothane MAC(RR) and MAC (50% effective concentrations for the loss of the righting reflex and for the tail pinch/withdrawal response, respectively) were determined. Significantly shorter propofol-induced sleep time (291.6 +/- 16.8 s versus 344.4 +/- 12.1 s) and larger halothane MAC(RR) (1.11% +/- 0.04% versus 0.98% +/- 0.03%) were observed in Ca(v)2.3 channel knockouts (Ca(v)2.3(-/-)) than in wild-type (Ca(v)2.3(+/+)) litter mates. To investigate the basis of the decreased anesthetic sensitivities in vivo, field excitatory postsynaptic potentials and population spikes (PSs) were recorded from Schaffer collateral CA1 synapses in hippocampal slices. Propofol (10-30 micro M) inhibited PSs by potentiating gamma-aminobutyric acid-ergic inhibition, and this potentiation was markedly smaller at 30 micro M in Ca(v)2.3(-/-) mice, possibly accounting for the decreased propofol sensitivity in vivo. Halothane (1.4%-2.2%) inhibited field excitatory postsynaptic potentials similarly in both genotypes, whereas 1%-2% halothane depressed PSs more in Ca(v)2.3(-/-) mice, suggesting the postsynaptic role of the R-type channel in the propagation of excitation and other mechanisms underlying the increased halothane MAC(RR) in Ca(v)2.3(-/-) mice. IMPLICATIONS: Because inhibition of neuronal Ca(2+) currents can be a mechanism underlying general anesthesia, we examined anesthetic sensitivities in mice lacking the R-type (Ca(v)2.3) Ca(2+) channels both in vivo and in hippocampal slices. Decreased sensitivities in mutant mice imply a possibility that agents blocking this channel may increase the requirements of anesthetics/hypnotics.

Anesthetics, Inhalation↗