Age-related changes in the regulation of autophagic proteolysis in rat isolated hepatocytes.

During intervals between meals, autophagy is a major source of nutrients and may remove damaged organelles and membranes. Age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release from liver cells of 2-, 6-, 12-, 18-, and 24-month-old male Sprague-Dawley rats fed ad libitum, and incubated in vitro with added amino acids and 10(-7) M of insulin or glucagon. The maximum rate of proteolysis and its maximum inhibition by amino acids were reached at 6 months and declined thereafter. In contrast, the rate of protein degradation in the presence of high concentrations of amino acids was not affected by aging. The inhibitor effect of insulin was additive to that of amino acids and was not altered significantly by age. The conclusion is that altered regulation of autophagic proteolysis decreases susceptibility of older cells to lysosomal degradation, and it may lead to the accumulation of altered organelles and membranes.

Age-related changes in the autophagic proteolysis of rat isolated liver cells: effects of antiaging dietary restrictions.

Autophagy is a process that sequesters and degrades organelles and macromolecular constituents of cytoplasm for cellular restructuring and repair and as a source of nutrients for metabolic use in early starvation. The effects of two antiaging dietary regimens (initiated in rats at the age of 2 months), namely, 40% dietary restriction (DR) and every-other-day ad-libitum feeding, that exhibited different effects on metabolism and similar effects on longevity on the age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release in the incubation medium from isolated liver cells of male albino Sprague-Dawley rats aged 2, 6, 12, 18, 24, and 27 months. (The liver cells were incubated in vitro with added amino acids and 10(-7) M insulin or glucagon.) Age-matched male albino Sprague-Dawley rats fed ad libitum served as a control. Results show that in ad-libitum-fed rats, after a transient increase by age 6 months, autophagic proteolysis and regulation by amino acid exhibit a dramatic age-related decline, and that the age-related changes are prevented by dietary antiaging intervention. A comparison shows that the protective effects of DR and every-other-day ad-libitum feeding are partially different in 24-month-old rats (but the beneficial effects of the two diets on regulation of autophagic proteolysis are always similar). With regard to endocrine regulation, results confirm that the liver cell response to glucagon (but not to insulin) declines with increasing age, and they show that antiaging DRs significantly improve the effects of glucagon (and have no effect on the response to insulin). The interactions of age by diet, glucagon (and in older rats, insulin), and amino acids are significant. It is concluded that DR significantly improves the susceptibility of liver cells to lysosomal degradation, and it prevents decline with increasing age. It is suggested that improved liver autophagy and lysosomal degradation might be part of the antiaging mechanisms of DR.

The age-related accumulation of protein carbonyl in rat liver correlates with the age-related decline in liver proteolytic activities.

Increases of protein carbonyl in animal tissues have been associated with the aging process. So far, the accumulation of oxidized proteins, highly susceptible to proteolysis, has been attributed to age-related changes in proteasomal alkaline proteases. Carbonyl in protein was monitored in six different tissues of male Sprague-Dawley rats fed ad libitum up to the age of 27 months, and of 24 and 27-month-old rats subjected to anti-aging diet restriction (every-other-day feeding ad libitum). Alkaline protease activities and liver lysosomal proteolysis were studied. The levels of protein carbonyl were significantly different in different tissues, and quite stable throughout life; accumulation was restricted to liver tissue very late in life, between ages 24 and 27 months; was fully prevented by diet restriction; was not accompanied by any diet-restriction-sensitive decline of alkaline protease activity; and was accompanied by a dramatic age-related decline in lysosomal proteolysis that was partially prevented by anti-aging diet restriction. No correlation was found between levels of alkaline protease activity and levels of protein carbonyl in the different tissues from younger animals. It is concluded that the process of autophagy, a well-known mechanism for cell maintenance, may deserve more interest in aging studies.

Age-dependent accumulation of dolichol in rat liver: is tissue dolichol a biomarker of aging?

Dolichols are long hydrophobic molecules broadly distributed in all tissues and cellular membranes of eukariotic cells. Dolichol affects membrane structure and fluidity, membrane-associated protein activities, and membrane sensitivity to oxidative stress. Reports have shown that dolichols exhibit a remarkable (6- to 30-fold) age-related increase in the tissues of adult and mature rats and of old flies, mice, and humans. In our longitudinal study, the age-related accumulation of dolichol was monitored in the liver tissue of male Sprague Dawley rats fed ad libitum up to age of 27 months. In addition 24-month-old rats subjected to different regimens of anti-aging diet restriction (40% calorie restriction or every-other-day feeding ad libitum) were tested. A parallel study of the accumulation of carbonyl in liver protein (a proposed biomarker of aging) was made. In addition, the age-related decline of liver autophagy/proteolysis was studied in isolated liver cells, in view of the essential role of this function in liver membrane maintenance. Results show that an age-dependent accumulation of dolichol can be observed in the liver of the rats fed ad libitum but not in the liver of 24-month-old food-restricted rats, that accumulation of dolichol precedes the accumulation of altered liver proteins, and that dolichol accumulation is accompanied by a decline in liver autophagy. It is concluded that dolichol accumulation satisfies the proposed primary and secondary applicable criteria and the desirable features required to be qualified as a biomarker of aging.

Sex differences in surface EMG interference pattern power spectrum.

Sex differences in the spectral parameters of the surface electromyogram (EMG) power spectrum were studied during voluntary muscle contractions of different strength with rest in between. The influence of two different types of leads (unipolar and bipolar) on the values of the spectral parameters was also investigated under the same experimental conditions. The subjects were 15 healthy female and 15 healthy male volunteers. The relationship between the amplitude (root mean square) of the EMG and the force developed was not linear. The mean values of the median power frequency were lower in women than in men. With both types of lead, the increase in force was accompanied by a progressive increase in median power frequency in male and female subjects. The significant differences in spectral parameters observed in the two sexes are probably correlated with anatomic differences.

Single fibre motor evoked potentials to brain, spinal roots and nerve stimulation. Comparisons of the 'central' and 'peripheral' response jitter to magnetic and electric stimuli.

Single fibre motor evoked potentials to magnetic and electric non-invasive stimulation of brain, spinal cord and peripheral nerve were recorded in 8 healthy volunteers. The 'central motor jitter' and the 'peripheral motor jitter' were respectively calculated and a comparison between the magnetic and electric modalities was made. The highest degree of latency variability was observed for both magnetic and electric central motor jitter, whilst the peripheral motor jitter to nerve stimulation was as low as the neuromuscular one (range 16-60 microsecond). The magnetic 'central motor jitter' (range 94-1024 microsecond) was much larger than the electric one (range 55-280 microsecond), which was in the order of jitter calculated on H-reflex studies; moreover, the former was organized in a bi- or trimodal distribution. On the contrary, no significant differences were observed between the two modalities when the jitter to nerve stimulation was taken into account. Possible contributions of corticocortical circuitries containing several synaptic interruptions during magnetic as opposed to electric transcranial stimulation, is discussed.

Charcot-Marie-Tooth disease: study of a large kinship with an intermediate form.

A clinical, genetic, electrophysiological and ultrastructural study of a large kinship with peroneal muscular atrophy is reported. There was a noteworthy homogeneity in the phenotype as well as in the electrophysiological characteristics encountered in 15 affected members aged between 7 and 72 years. The symptoms appeared first in the second decade of life and stabilized by the fourth decade. There was no evidence of linkage of the neuropathy gene to the Duffy blood group locus on chromosome 1. The electrophysiological data in this family as well as the ultrastructural findings confirm that there is heterogeneity in hereditary motor and sensory neuropathy type I, and support the concept of an intermediate form of Charcot-Marie-Tooth disease.

Diagnostic specificity of sensory and motor nerve conduction variables in early detection of carpal tunnel syndrome.

In the carpal tunnel syndrome (CTS) sensory nerve conduction is more sensitive than motor conduction. However, 8%-25% of the sensory distal latencies in symptomatic hands may still be normal. A systematic study was made of the median, ulnar and radial orthodromic nerve conduction velocities (SNCV) stimulating each of the fingers separately. Four SNCVs from the median nerve, two SNCVs from the ulnar nerve and one from the radial nerve were obtained, and the ratio of the median to radial SNCV and the ratios of the median and ulnar SNCVs were estimated. The significance of these parameters in the diagnosis of the CTS was studied, and a rapid technique for the screening of nerve entrapment in the initial stages of the disease is proposed. Three hundred and seventy-five symptomatic hands were examined. Seventy-five hands showed normal distal latency, in which cases, however, the SNCV of the ring finger was always outside the normal range, while the SNCVs of the thumb, index and middle fingers were abnormal in 64%, 80% and 92% of cases respectively. The amplitudes of the sensory responses were the least sensitive of the parameters studied. Our results suggest that a study of the median nerve digital branch to the ring finger may be of value in providing an easily performed and rapid technique for screening an early median nerve entrapment at the wrist.

Hemofiltration: an alternative to dialysis.

Continuous arteriovenous hemofiltration (CAVH) is a relatively new procedure designed to relieve fluid overload. It has proved useful in many patients whose ability to maintain fluid homeostasis is compromised. Burn victims, patients with acute renal failure, patients with pulmonary edema, and trauma patients have all received benefit from CAVH. CAVH is an extracorporeal circuit in which blood is propelled by the force of the patient's blood pressure through a filter, ultrafiltered, and returned to the patient. CAVH removes fluid and solutes more slowly than hemodialysis, eliminating the danger of rapid fluid and electrolyte shifts. There are several ways to perform the procedure but all require intense and sophisticated medical and nursing care. Strong knowledge of fluid, electrolyte, and acid/base balance, hemodynamics, and assessment skills is required. The ability to intervene quickly and appropriately if trouble arises is a necessity. The dynamics of the treatment are discussed in detail in this article. How to deliver a safe and efficient treatment, troubleshooting guidelines, and suggestions for accurate documentation are also included.

An electromyographic evaluation of motor complications in thoracic herpes zoster.

Motor complications in thoracic herpes zoster were evaluated in 52 patients by electromyographic examination of the paraspinal muscles. At the initial EMG examination, abnormal findings were observed in 18 patients (35%). In 8 patients the myomers involved coincided in location with affected dermatomes, while in 10 patients, in addition to the involvement of myomers corresponding to affected dermatomes, there also appeared an involvement of one or more contiguous myomers not corresponding to affected dermatomes. Our study demonstrated that motor involvement in thoracic HZ is much more common than previously suggested and its incidence (35%) appears to be greater than that reported in both cervical and lumbosacral HZ.

Accuracy of interpreting human responses.

Nurse managers who advocate continuous quality improvement should be examining system-level policies, procedures and attitudes to determine whether they support or detract from accuracy of nurses' interpretations of human responses. A study discusses the relationship of accuracy of nurses' diagnoses to continuous quality improvement and demonstrates why nurse managers should focus on accuracy in system-level decisions. Four guidelines, which emphasize quality of interventions and outcomes, are given.

Short latency somatosensory evoked potentials in Charcot-Marie-Tooth disease. A family with an intermediate form.

9 patients with Charcot-Marie-Tooth Disease (CMTD) of intermediate type (PMA type II, 10), all from the same family, presented with a significant increase of the interpeak N9-N13 latency. This increase is already present in the pre-symptomatic phase of the disease and there is no significant difference between the various patients of different ages and clinical severity, indicating that the lesions appears very early and tends to establish itself equally early. Similar behaviour is also seen in the distal conduction velocity along the sensitive fibres, while the more proximal areas seem to be relatively spared. The authors interpret these data as an expression of a distal central peripheral sensory neuropathy. In contrast, the lesion of the peripheral motor fibres, particularly in the legs, has a different and more severe pattern of evolution. Alterations in central conduction time (N13-N20) were not seen in any of the 9 patients studied.

Cervical myelopathy secondary to ossification of the posterior longitudinal ligament (a case report).

A case of ossification of the posterior longitudinal ligament, documented by spinal X-ray, myelography and CT scanning of the spinal cord is reported. The patient underwent decompressive laminectomy by posterior approach, which was successful. The case is discussed in the light of recent published data.

Automatic analysis of surface EMG (preliminary findings in healthy subjects and in patients with neurogenic motor diseases).

Supramaximal electrical stimulation of a motor nerve produces a full contraction of a muscle and the corresponding compound action potential can be recorded. Recent studies appear to support the view that all the motor units are activated during voluntary maximal contraction, at least in the tibialis anterior muscle. The compound action potential and the EMG interference pattern in the tibialis anterior are regarded as two different manifestations of the activation of all the motor units. A method has been developed which compares these EMG activities, by automatic analysis, in order to obtain useful parameters for clinical applications.

Differences between surface EMG in male and female subjects evidenced by automatic analysis.

40 healthy volunteers (20 males and 20 females) have been studied by an automatic analysis of their surface EMG. The power density spectrum (PDS) of the electromyographic signal, derived from the tibialis anterior muscle, was used to evaluate the RMS values of the EMG developed during maximal voluntary (Vc) and evoked (Vm) contractions. The ratios between Vc, calculated over each of 5 frequency bands (5-15, 20-40, 45-70, 75-110, 115-160 Hz), and the total Vc have also been calculated. No significant differences emerge in the Vm values for males and females, whereas the Vc values for female subjects are found to be significantly reduced (P less than 0.001) with respect to the corresponding values for males. Significant differences have also been found concerning the percentage distribution of power in the above mentioned frequency bands for men and women (P less than 0.001). It can thus, be hypothesized that there are two different modalities of motor unit recruitment and that different sociological and cultural traditions may be more important in producing these differences than sexually determined physiological differences.

Non-invasive evaluation of central motor tract excitability changes following peripheral nerve stimulation in healthy humans.

The interval between muscle stretch and the onset of the long latency electromyographic responses (LLRs) has been theoretically fragmented into an afferent time (AT), taken at the peak of wave N20 of somatosensory evoked potentials and an efferent time (ET), calculated by means of magnetic transcranial stimulation (TCS), the two being separated by a cortical interval (CI). If this were the case, the afferent input should progressively 'energize' the sensorimotor cortex during the CI and change the excitability of cortico-spinal tracts. To investigate this, motor evoked potentials (MEPs) from thumb flexor muscles were recorded, whilst a conditioning stimulation of median or ulnar nerve randomly preceded (10-48 msec intervals) magnetic brain TCS. Nerve stimulation was adjusted to motor threshold and amplitudes of conditioned and test MEPs at different nerve-TCS interstimulus intervals were evaluated. Conditioned MEPs were significantly attenuated with nerve-TCS intervals between 16 and 20 msec for elbow and 20 and 22 msec for wrist stimulation. This was followed by MEP potentiation with nerve-TCS intervals corresponding to the sum of AT + CI (mean 23.2 msec, range 21.7-24.8). The onset latency of facilitated conditioned MEPs was about 1 msec briefer than that of test MEPs, but invariably longer than the latency of MEPs facilitated by a voluntary contraction. This protocol did not demonstrate amplitude facilitation of the segmental H reflex, corroborating the idea that the facilitated part of the conditioning nerve-TCS curve receives a transcortical loop contribution.