PubMed HealthSearch

PubMed · 7440084

Factors affecting spasticity.

Abstract

Although the basic rhythm of stepping, walking, and running is present in the spinal cord, it is not manifest in patients with lesions of the spinal cord, on account of spasticity. Spasticity is an over-reaction to every kind of input. Every response is followed by an after-discharge. This affects the muscles which have reacted, and it spreads to involve many other muscles, more ipsilaterally than contralaterally. In the normal this is prevented by the corticospinal tract, by Renshaw inhibition, and by inhibition of the input to the spinal cord. Anything that reduces the input that finally reaches motor neurons reduces general excitability; it reduces spasticity permanently, allowing normal movements to occur.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P W Nathan. 1980. Factors affecting spasticity.. https://doi.org/10.3109/09638288009163951

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Interaction of human serum albumin with the electrophilic metabolite 1-O-gemfibrozil-beta-D-glucuronide.

Acyl glucuronides are electrophilic metabolites that are readily hydrolyzed, undergo intramolecular rearrangement, and bind covalently to endogenous proteins. Gemfibrozil is a fibrate lipid-lowering agent that is extensively metabolized to an acyl glucuronide conjugate in humans. The aims of this study were to examine the interactions of 1-O-gemfibrozil-beta-D-glucuronide with human serum albumin. The degradation of 1-O-gemfibrozil-beta-D-glucuronide (approximately 200 microM) was examined in vitro during incubations at 37 degrees C with phosphate buffer (pH 7.4 or 9.0), solutions of human serum albumin (pH 7.4), or fresh human plasma (pH 7.4). The effects of diazepam, oxyphenbutazone, and gemfibrozil on the degradation of 1-O-gemfibrozil-beta-D-glucuronide, and its reversible binding to albumin were also studied. A pilot in vivo study was performed on two patient volunteers administered 1 g/day p.o. gemfibrozil. 1-O-Gemfibrozil-beta-D-glucuronide was unstable, with degradation half-lives in buffer of 4.1 hr and 44 hr at pH 9.0 and 7.4, respectively; and 8.5 hr and 5.5 hr in pH 7.4 solutions of human serum albumin or fresh plasma, respectively. Degradation was dependent on pH and the presence of albumin, which seemed to accelerate the intramolecular rearrangement and hydrolysis of the conjugate. 1-O-Gemfibrozil-beta-D-glucuronide was highly reversibly bound to albumin, with a mean unbound fraction of 0.028, and its degradation seemed to be related to the degree of reversible binding. Hydrolysis and covalent binding were associated with the site II binding domain on albumin, because only diazepam inhibited these reactions. However, intramolecular rearrangement was increased when binding to the site I domain was inhibited. Covalent binding was also detected in vivo to human plasma proteins. The half-life of the gemfibrozil-protein adducts was 2.5-3 days. Albumin plays an important role in the disposition of acyl glucuronides by acting as: i) a transporter protein; ii) a potential catalyst for their degradation and, therefore, clearance; and iii) a target for covalent adduct formation.

Diazepam

The value of sleep nasendoscopy in the evaluation of patients with suspected sleep-related breathing disorders.

Fifty patients with sleep-related breathing disorders were tested with nocturnal polysomnography and with nasendoscopic diurnal polysomnography after diazepam administration, and various indices of breathing disorders were examined, and the results obtained in the two sleep studies compared. There were no significant differences between the two sleep studies in either the type of apnoea or the indices of breathing disorder except for the longest duration of apnoea. There was a significant difference in the duration of REM sleep between the two sleep studies, but no significant difference in the duration of each stage of non-REM sleep. We speculate that nasendoscopic diurnal polysomnography with diazepam can be used as a substitute for nocturnal polysomnography in the clinical study of non-REM sleep stage but it is not sufficient in evaluating REM sleep stage, in patients with sleep-related breathing disorders without pathological obesity or abnormal respiratory function.

Diazepam

Influence of the carrier on the intrinsic rate of dissolution of diazepam in interactive mixtures.

The use of interactive mixtures of drugs adhering to the surface of carriers can promote drug dissolution. The mechanism of dissolution of such mixtures has been studied using the rotating-disc method under conditions eliminating secondary influences such as carrier surface characteristics and drug particle aggregation. Levich plots were used to characterize the dissolution behaviour. Diazepam-compactrol interactive mixtures had initial dissolution rates similar to that of pure diazepam owing to the deposition of a continuous layer of diazepam on the disc surface from the interactive mixture. Linear Levich plots were produced at all drug loadings and the presence of compactrol in the disc slightly enhanced dissolution rates. Dissolution rates for diazepam-emcompress interactive mixtures were lower than those of pure diazepam. The Levich plots for these systems were non-linear with increasing negative curvature as the diazepam loading decreased. The rate of dissolution of diazepam in the lactose interactive mixture was markedly higher than that of pure diazepam, but high diazepam loadings in the lactose mixtures inhibited diazepam dissolution. Rapid carrier dissolution caused surface retraction of the disc, enhancing the dissolution rate. The Levich plots showed an upward curvature due to turbulence. Linear Levich plots for diazepam and other benzodiazepines and for diazepam-compactrol interactive mixtures showed that their dissolution in pH 5 phosphate buffer was diffusion-controlled. The Levich plots for diazepam-emcompress interactive mixtures were indicative of some interfacial control during dissolution, but the hypothesis of common ion precipitation of dissolved carrier, calcium phosphate, onto the disc surface did not fully explain this effect.

Diazepam