Passive transverse mechanical properties of skeletal muscle under in vivo compression.

The objective of the present study is to determine the passive transverse mechanical properties of skeletal muscle. Compression experiments were performed on four rat tibialis anterior muscles. To assess the stress- and strain-distributions in the muscle during the experiment, a plane stress model of the cross section was developed for each muscle.

Optimisation of oil red O staining permits combination with immunofluorescence and automated quantification of lipids.

The objective of the present study was to develop a stain permitting automated quantification of myocellular lipid depositions in skeletal muscle sections together with immunolocalisation of other myocellular constituents by fluorescence microscopy. Lipid droplets were detected in skeletal muscle by oil red O (ORO). Conventional ORO was modified to diminish background staining, prevent crystallisation of ORO and to optimise lipid retention in cryosections.

In situ assessment of shortening and lengthening contractile properties of hind limb ankle flexors in intact mice.

The availability of animal models with disrupted genes has increased the need for small-scale measurement devices. Recently, we developed an experimental device to assess in situ mechanical properties of isometric contractions of intact muscle complexes of the mouse. Although this apparatus provides valuable information on muscle mechanical performance, it is not appropriate for determining contractile properties during shortening and lengthening contractions.

GLUT-4 expression is not consistently higher in type-1 than in type-2 fibres of rat and human vastus lateralis muscles; an immunohistochemical study.

In whole muscle homogenates, the glucose transporter-4 (GLUT-4) content is reported to be higher in muscles consisting predominantly of oxidative (type-1) muscle fibres than in muscles consisting predominantly of glycolytic (type-2) fibres. From these findings, it has been deduced that in rat muscle, oxidative fibres have an intrinsically higher level of GLUT-4 protein than glycolytic fibres. No data is available concerning human muscle.

Extracellular concentrations of taurine, glutamate, and aspartate in the cerebral cortex of rats at the asymptomatic stage of thioacetamide-induced hepatic failure: modulation by ketamine anesthesia.

Subclinical hepatic encephalopathy (SHE) was produced in rats by two intraperitoneal injections of TAA at 24 h intervals and the animals were examined 21 days later. Concentrations of the neuroactive amino acids taurine (Tau), glutamate (Glu) and aspartate (Asp), were measured in the cerebral cortical microdialysates of thioacetamide (TAA)-treated and untreated control rats. During microdialysis some animals were awake while others were anesthetized with ketamine plus xylazine.

Modifications of the behavioral profile of non-competitive NMDA receptor antagonists, memantine, amantadine and (+)MK-801 after chronic administration.

Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists show antiparkinsonian-like activity in animal models, and possess neuroprotective properties. However they also induce a number of behavioral side effects in rodents at higher doses; these include learning impairment, hyperlocomotion, and ataxia. The present study focused on the possible development of tolerance, or sensitization, to any of these effects after sustained administration, either by repeated injection or continuous infusion.

Controlled lengthening or shortening contraction-induced damage is followed by fiber hypertrophy in rat skeletal muscle.

To study the hypothesis that more severe damage, caused by controlled lengthening (L) contractions, results in greater myofiber hypertrophy compared to increase in fiber size followed shortening (S) contractions, tibialis anterior muscles of anesthesized male Wistar rats were subjected to 240 either L or S contractions. The highest increase in muscle beta-glucuronidase activity, an indicator of muscle damage, was observed in L (7.1-fold) 4 days and in S (2.

Dopamine release in the prefrontal cortex in response to memantine following sub-chronic NMDA receptor blockade with memantine: a microdialysis study in rats.

Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist which blocks the NMDA receptor with moderate-affinity in a use- and voltage dependent manner. In clinical practice it is used chronically in the treatment of dementia and does not induce psychotomimetic effects as, high affinity, uncompetitive antagonists. Thus, it was of interest to determine dopamine (DA) and metabolite (DOPAC - dihydroxyphenylacetic acid and HVA - homovanillic acid) concentrations in the prefrontal cortex (PFC) in response to 14 days administration of memantine (20 mg/kg/day).

Brain distribution of an uncompetitive NMDA receptor antagonist; comparison to its in vitro potency in electrophysiological studies.

Although the concentration of drugs in brain homogenates is relatively easy to determine, such data are sometimes misleading due to accumulation in intracellular compartments. This is apparent for uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists where concentrations assessed in this manner are much higher than those sufficient to block the NMDA channel from the extracellular space. The aim of the present study was to determine whether free brain concentrations (extracellular fluid - ECF) of a new uncompetitive NMDA receptor antagonist MRZ 2/579 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride) following administration of doses effective in animal models are sufficient to block NMDA receptors based on its potency in vitro.

Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists.

Behavioral changes have previously been reported following administrations of uncompetitive NMDA receptor antagonists memantine, amantadine and MK-801 for 14 days, at the doses that produce plasma levels comparable to those seen in patients (20, 100 and 0.31 mg/kg/day respectively). Using the same doses, the effect on receptor binding (autoradiography) was studied in rats.

The role of probenecid-sensitive organic acid transport in the pharmacokinetics of N-methyl-D-aspartate receptor antagonists acting at the glycine(B)-site: microdialysis and maximum electroshock seizures studies.

The purpose of the present study was to determine whether the probenecid-sensitive organic acid transporter is responsible for the short duration of action of a new group of N-methyl-D-aspartate receptor glycine(B)-site antagonists, MRZ 2/570, 2/571, and 2/576. A prolongation of their anticonvulsant activity from 60 to 180 to 240 min, was found in mice after pretreatment with probenecid (200 mg/kg i.p.

Brain penetration and in vivo recovery of NMDA receptor antagonists amantadine and memantine: a quantitative microdialysis study.

Purpose: To determine free brain concentrations of the clinically used uncompetitive NMDA antagonists memantine and amantadine using microdialysis corrected for in vivo recovery in relations to serum, CSF and brain tissue levels and their in vitro potency at NMDA receptors.

Methods: Microdialysis corrected for in vivo recovery was used to determine brain ECF concentrations after steady-state administration of either memantine or amantadine. Additionally CSF, serum, and brain tissue were analyzed.

Amino-alkyl-cyclohexanes are novel uncompetitive NMDA receptor antagonists with strong voltage-dependency and fast blocking kinetics: in vitro and in vivo characterization.

The present study characterized the in vitro NMDA receptor antagonistic properties of novel amino-alkyl-cyclohexane derivatives and compared these effects with their ability to block excitotoxicity in vitro and MES-induced convulsions in vivo. The 36 amino-alkyl-cyclohexanes tested displaced [3H]-(+)-MK-801 binding to rat cortical membranes with K(i)s between 1.5 and 143 microM.

Enzyme activity of rat tibialis anterior muscle differs between treatment with triamcinolone and prednisolone and nutritional deprivation.

The maximal activity of a selection of enzymes involved in muscle carbohydrate handling, citric acid cycle and fatty acyl beta-oxidation were studied after treatment with the fluorinated corticosteroid triamcinolone and compared to a similar treatment of the non-fluorinated corticosteroid prednisolone in an equipotent anti-inflammatory dose. Furthermore, because triamcinolone causes loss of body mass and muscle wasting, the effects of triamcinolone were investigated relative to a control group, with the same loss of body mass, due to nutritional deprivation. The study was performed in male Wistar rats in the following treatment groups: TR, triamcinolone treatment (0.

Modulation of NMDA receptors by glycine--introduction to some basic aspects and recent developments.

Glycine is a co-agonist at NMDA receptors and it's presence is a prerequisite for channel activation by glutamate or NMDA. Physiological concentrations reduce one form of NMDA receptor-desensitization. Interactions between the glycineB site and other domains of the NMDA receptor are complex and include the glutamate, Mg2+ and polyamines sites.

Inhibition of reinforcing effects of morphine and naloxone-precipitated opioid withdrawal by novel glycine site and uncompetitive NMDA receptor antagonists.

The glycine site (MRZ 2/570 and L-701,324), and uncompetitive (MRZ 2/579) NMDA receptor antagonists inhibited morphine-produced behaviors related to drug-abuse. The expression of morphine dependence was blocked by pretreatment with all three compounds (3-7.5 mg/kg); the effects of glycine/NMDA antagonists were not dose-dependent.

The disruption of myofibre structures in rat skeletal muscle after forced lengthening contractions.

Specific antibodies against structural proteins (actin, desmin, dystrophin, fibronectin) of muscle fibres were used to study the effect of forced lengthening contractions on muscle microarchitecture. Tibialis anterior (TA) muscle of male Wistar rats were subjected to 240 forced lengthening contractions. At consecutive time points (0, and 6 h, 2, 4, and 7 days) after stimulation, the TA muscle was excised for biochemical and histological assays.

Acute and sustained effects of isometric and lengthening muscle contractions on high-energy phosphates and glycogen metabolism in rat tibialis anterior muscle.

Previous studies have shown that lengthening contractions, in contrast to isometric contractions, readily result in sustained malfunctioning of the exercised muscles. The present study was performed to investigate whether an exercise period with many (240) lengthening contractions (LC) results in alterations in muscle high-energy phosphates and inosine monophosphate (IMP) content, different from muscles performing a few (60) lengthening or a few (60) or many (240) isometric contractions (IC). Moreover, we sought for a possible cause(s) of the inability to replenish muscle glycogen stores following LC.

Contraction failure of skeletal muscle of rats recovering from critical illness.

1. Most patients recovering from critical illness experience enhanced fatiguability. Previously we have shown that zymosan-induced critical illness in rats is attended by a decreased mitochondrial content (maximal aerobic capacity) in skeletal muscle.

Structural muscle damage and muscle strength after incremental number of isometric and forced lengthening contractions.

Exercise-induced muscle damage is characterized by histological changes, like Z-line streaming, inflammatory response and decreased muscle function reflected in a prolonged decline in maximal isometric muscle strength after eccentric work. It is assumed that force decrement is mainly related to the amount of structural damage. However, the relationship between number of eccentric contractions, magnitude of structural damage and force decrement is not very well documented.

Microdialysis studies with amantadine and memantine on pharmacokinetics and effects on dopamine turnover.

Amantadine and memantine are in clinical use for the treatment of neurodegenerative diseases such as M. Parkinson and dementia syndrome. In order to contribute to the understanding of the interaction of these uncompetitive NMDA-antagonists with the dopaminergic system in the striatum, the pharmacokinetics and the effects of amantadine and memantine on the dopaminergic system were examined in a microdialysis study in anaesthetized rats.

The use of intracerebral microdialysis to determine changes in blood-brain barrier transport characteristics.

The aim of this study was to determine whether changes in the transport of drugs into the brain could be determined by in vivo intracerebral microdialysis. Atenolol was used as a model drug to determine blood-brain barrier (BBB) transport characteristics. In rats, unilateral opening of the blood-brain barrier was achieved by infusion of hyperosmolar mannitol (25%, w/v) into the left internal carotid artery.

Overtraining--what do lactate curves tell us?

In a cyclist, competing at national and international level, submaximal lactate concentrations were initially interpreted as improved endurance capacity. However, 2 weeks later, a test in which maximal lactate was measured showed that maximal lactate was decreased as well. Together with the complaints of deteriorating performance and subjective complaints of irritability and sleep disturbances, overtraining was diagnosed.