We have measured concentrations of 26 serum amino acids in 46 subjects (aged 17-75 years), with the following neurological diseases: amyotrophic lateral sclerosis, n=7; peripheral neuropathy, n=5; muscular dystrophy, n=7; mitochondriopathy, n=3; metabolic myopathy (others), n=2; inflammatory myopathy, n=4; mononeuropathy, n=3; controls (patients with symptoms suggesting neuromuscular system dysfunction without objective evidence of neuromuscular disease), n=15, before and after prolonged muscular effort. Tests were done on a bicycle ergometer at the individual aerobic/anaerobic threshold determined for each subject in preliminary tests. Using a stepwise multiple linear regression model, age emerged as a significant negative predictor (P<0.05) of the post/before ratio of the levels of five amino acids. We conclude that an increase in recovery time and a reduction in training capacity with aging could be linked to these changes. The cause is assumed to be principally a reduction in glycogen storage in muscle with increasing age; this situation could possibly be improved by consumption of carbohydrate before or during exercise, or also during rehabilitation exercise or training in neuromuscular or other diseases.

Journal Article↗

PubMedDate not supplied

Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle biopsies and rat muscles.

Carnosine has possible functional effects on skeletal muscle contractility, along with membrane-protective, antioxidant effects. We determined tissue free carnosine concentrations in skeletal muscles from patients with neuromuscular diseases and in skeletal and heart muscles from rats of various ages. The effects of age, gender and diagnostic category on free carnosine levels in patients with neuromuscular diseases were analyzed by a stepwise multiple linear regression model. The age of the patients emerged as a significant negative predictor of carnosine concentrations (R=-0.40, P<0.05). Free carnosine concentrations in rat skeletal muscles also showed a significant negative correlation with the ages of the rats (male rats: R=-0.49, P<0.05; female rats: R=-0.56, P<0.05). Only the diagnostic category amyotrophic lateral sclerosis (ALS) emerged as a significant negative predictor compared to the control group in the stepwise regression model, this was confirmed by Wilcoxon Signed Rank Test (P<0.05). We conclude that the age-related decline in muscle mass, strength and function is associated with decreased tissue concentrations of the putative membrane-protective antioxidant carnosine. In addition we found decreased carnosine tissue concentrations in ALS. The reduction in carnosine content might be caused by progressive denervation processes.

Journal Article↗

PubMedDate not supplied

Active head turning and correlated cerebral potentials. Experimental and clinical aspects.

Fast voluntary horizontal head movements (n = 400, maximum acceleration 8,500 deg/sec2) were recorded together with surface EEG over pre- and post-central regions in 30 healthy volunteers while they were gazing at a head-fixed target in darkness. Artifacts of mechanical, myogenic and oculomotor origin could be precluded. Selective averaging of the fastest movements revealed a biphasic cortical potential. Median latency of its onset was 123.5 msec, of its first peak 189 msec, of the second peak 373 msec, with amplitudes ranging around 5.7 microV. Similar recordings in patients with uni- or bilateral vestibular nerve lesions demonstrated that strong stimulation of the joint vestibular and somatosensory (neck afferent) input facilitated characteristically related EEG activity: side differences of vestibular input could be measured on this level of the CNS, i.e. measured on the cortical level as additional information to the commonly used vestibulo-oculomotor response; patients with early, bilateral loss of vestibular functions showed a specific long-term adaptation of their related EEC activity. We conclude that clinical studies of this kind might aid in diagnosis of vertigo and related phenomena.

Adult↗

PubMedDate not supplied

[The nervous system and old age].

Considering the topic "Nervous System and Old age" from an aspect of clinical care and assistance, one must take into account primary changes in the nervous system in terms of physiological changes due to old age, on the one hand, and the differentiation from pathological changes manifested at an earlier time, on the other. The latter task is frequently especially difficult, for the transitions are fluid here. The diverse nervous systems are affected by physiological changes due to old age in different ways. Details of these changes and, above all, their functional meaning are examined comprehensively. Nevertheless, the question of primary changes in the nervous system due to old age is still problematic; a so-called "age--factor" has not precisely described thus far. One must proceed on the assumption that the changes which are known to us are essentially sequelae and that we can make conclusions about the dynamics of the process of aging solely from this data. The differentiation between physiological and pathological changes in the nervous system in old age has eminent practical significance for rehabilitation and above all for prevention, and mastery of aging, which is often experienced not only as a "failure" on the part of different somatic systems, but also as personal fate. These questions become evident especially upon examining the various models of medical care for the aged.

Aged↗

PubMedDate not supplied

Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1.

The volatile anesthetic agent enflurane undergoes oxidative metabolism in human liver, yielding both inorganic and organic fluoride metabolites. Numerous studies conducted in animals indicate that the enzyme cytochrome P-450 2E1 is a major catalyst for the defluorination reaction. However, the P-450 enzyme catalyzing enflurane metabolism in humans has not been identified. Therefore, experiments were conducted to determine whether hepatic P-450 2E1 is a catalyst for the reaction in humans, and whether other constitutive or inducible isoforms might also be involved. Purified human liver P-450 2E1, reconstituted with cytochrome b5 and P-450 reductase, catalyzed enflurane defluorination at a rate of 9.3 nmol F-/nmol P-450/30 min, in contrast to a mean liver microsomal rate of 2.0 nmol F-/nmol P-450/30 min. The microsomal rate of defluorination for individual human livers correlated significantly with the microsomal content of P-450 2E1 protein (r = 0.92), the rate of p-nitrophenol hydroxylation (r = 0.86), and the rate of chlorzoxazone 6-hydroxylation (r = 0.90). In addition, specific anti-P-450 2E1 IgG, at a concentration of 10 mg IgG/nmol P-450 inhibited the microsomal reaction by 80%. Finally, a series of P-450 isoform-specific chemical inhibitors of oxidative metabolism--furafylline (1A2), sulfaphenazole (2C9/10), quinidine (2D6), troleandomycin (3A3/4), and diethyldithiocarbamate (2E1)--were screened for their ability to block human microsomal enflurane defluorination. Only diethyldithiocarbamate, a mechanism-based inhibitor of P-450 2E1, inhibited the reaction; this occurred to a degree comparable to the effect of anti-P-450 2E1 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗