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.

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.

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.

Clinical validation of ineffective breathing pattern, ineffective airway clearance, and impaired gas exchange.

PURPOSE: To describe the clinical validation of symptoms or defining characteristics of three respiratory diagnoses. The contributing factors or etiologies of the diagnoses were identified and the degree of importance of 30 nursing interventions, 15 direct care and 15 teaching, was rated for each diagnosis and each patient. Three nursing diagnoses--ineffective breathing pattern (IBP), ineffective airway clearance (IAC), and impaired gas exchange (IGE)--were among the most frequently used, yet no reported clinical studies validated the defining characteristics of these diagnoses. This study answers the research questions: What are the defining characteristics of IBP, IAC, and IGE? What are the etiologies of IBP, IAC, AND IGE? What are the most important interventions for IBP, IAC, and IGE? DESIGN: Standardized clinical validation using a convenience sample of 76 people hospitalized with medical and surgical diagnoses, in one U.S. city, and identified as having one of the three diagnoses. Data were collected in 1992-1993. METHODS: A literature-based concept analysis generated 37 possible defining characteristics for the three diagnoses which were included in the instrument. The nurse experts conducted a health history and physical examination of each patients and decided (a) whether the 37 defining characteristics were present or absent, (b) the degree of importance of each possible defining characteristic for making one or more of the diagnoses, (c) the etiologies, and (d) which of the 30 nursing interventions were important for each diagnosis and patient. FINDINGS: For each diagnosis, many of the 37 possible defining characteristics were judged as present but few reached the criterion of .50 as important for making one of the diagnoses. Two of the possible defining characteristics reached this criterion for IBP, seven for IAC, and two for IGE. In contrast to the defining characteristics approved by NANDA, the subjective cues of "expresses fatigue" and "expresses anxiety" were judged as important for making one or more of the diagnoses. CONCLUSIONS: Clinical validation methods allow discriminating among defining characteristics. Data that are present are not necessarily characteristic of a diagnosis, and the subjective cues of expresses fatigue or anxiety may be important for making these diagnoses.

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.

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.

Cervical and scalp recorded short latency somatosensory evoked potentials in response to epidural spinal cord stimulation in patients with peripheral vascular disease.

Somatosensory evoked potential (SEP) studies were performed in 14 patients with peripheral vascular disease who received epidural spinal cord stimulation (SCS) for chronic pain relief of the lower limbs. Signals were amplified and filtered between 20-2000 Hz and 200-2000 Hz to better identify activities in the high frequency range. In 7 patients bit-colour maps were also computed. In all the patients a homogeneous short-latency scalp evoked potential with a prevalent diphasic shape (P1-N1) was recorded. In all our scalp records, even with the wide bandpass, small short-latency positive deflections were observed on the descending front of the first major positive wave and they were better defined as a series of up to 6 wavelets, preceding the major negative scalp wave in the tracings filtered through the narrow bandpass. They appeared in an interval ranging from 5.5 to 15.6 msec. Bit-colour maps showed consistent positive fields, with a maximum at the vertex, starting mainly at about 5.5 msec; in 3 patients, a prominent positivity between 8.5 and 10.5 msec was recorded followed by smaller components preceding the major positive-negative (P1-N1) complex. More synchronous volleys during direct SCS produced clear short-latency SEPs. Although they were of larger amplitude, we regarded them as corresponding to those described by previous authors obtained by stimulation of nerves of the lower limbs, and probably arising from subcortical structures.

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.

Sensory neural conduction of median nerve from digits and palm stimulation in carpal tunnel syndrome.

The median sensory nerve conduction between ring finger and wrist is a suitable parameter for early detection of carpal tunnel syndrome (CTS), although shorter segments of median nerve have also been proposed for the same goal. In order to assess the relative diagnostic value of the sensory nerve conduction velocity (SNCV) of the third palmar branch versus the SNCV of the second palmar branch, generally performed until now, we studied 62 patients with typical signs and symptoms of CTS. The following parameters were evaluated by surface recording: orthodromic SNCVs in digit-wrist segments for median (index = M2, third = M3 and ring = M4 fingers), ulnar (fourth = U4 finger) and radial (thumb = R1) nerves; SNCVs in palm-wrist segments by surface bipolar stimulation at each metacarpo-phalangeal interspace (second = P2 and third = P3 for the median nerve and fourth = P4 for the ulnar nerve); and distal motor latencies of the median and ulnar nerves. No responses at the wrist were recorded in 22.6% of patients after digital stimulation of M4, whereas the SNCV of P3, the palmar nerve branch arising from digital nerves of the medial side of M3 and the lateral side of M4, was measurable in 93.5% of patients. As significantly expressed (P < 0.001) by the increased ratio of the mean values of P2 and P3 in CTS patients, the SNCV of P3 decreased more frequently and to a greater extent than the SNCV of P2.

Diagnosis of thoracic outlet syndrome. Relative value of electrophysiological studies.

The diagnostic utility of various electrophysiological techniques was evaluated in patients with thoracic outlet compression syndrome (TOCS). Our results suggest that in true neurogenic TOCS, there is no standard electrophysiological picture, but that this evolves with the severity of the syndrome. The first changes observed are electromyographic, followed by changes in F-wave and SEPs, followed finally by changes in nerve conduction parameters. EMG study was certainly more informative, showing neurogenic damage not only in limbs with neurological signs but also in about 1/4 of limbs with only subjective symptoms. The study of F-wave and SEPs does not seem to be particularly helpful, however, in view of the peculiar changes found in these patients, SEPs may be a useful complement to EMG. Nerve conduction studies were of little utility since changes in these parameters are only found in patients with long-standing anomalies and severe atrophy.

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.

[Chronic progressive obliterating arteriopathy and muscle fatigue: the role of frequency analysis of the electromyographic signal]. / Arteriopatia obliterante cronica progressiva e fatica muscolare: ruolo dell'analisi in frequenza del segnale elettromiografico.

Clinical evaluation of patients with peripheral arterial disease (PAD) is mainly based on Fontaine's classification, in which pain is the most important element. The use of objective techniques can allow a more precise evaluation, since pain is always subjective. In PAD patients, pain is frequently associated with early fatigue. Peripheral muscle fatigue can be easily assessed by a particular electromyographical method, based on the frequency analysis of the signal. In PAD patients, this method can provide objective information on muscular performance, with possible uses in medicine, surgery, rehabilitation and occupational medicine.

Brain excitability and long latency muscular arm responses: non-invasive evaluation in healthy and parkinsonian subjects.

Thirty healthy and 35 volunteers affected by Parkinson's disease (PD) were examined. Long latency responses (LLRs) and short latency somatosensory evoked potentials (SEPs) after median nerve stimulation were respectively recorded from forearm flexor muscles, and from 19 scalp electrodes, during relaxation (condition 1), light and maximal muscle contraction (conditions 2 and 3). Linear interpolation of SEPs was performed to produce isopotential colour maps. Latencies and amplitudes of the V1-V2 component in LLR, as well as of parietal, central and frontal scalp SEPs were analysed in the 3 experimental conditions. Highly significant inverse correlation matched the frontal SEP to the LLR V2 component amplitudes, both in healthy and in PD subjects. However, the V2 component--which in the former group was reliably identifiable only in condition 3--was presented in conditions 1 and 2 in a high percentage of PD subjects who also showed an abnormally reduced frontal SEP during complete relaxation. Excitability changes of brain motor areas induced by a sensory input were tested as follows: the motor cortex was transcranially stimulated (TCS) by magnetic pulses with an intensity 10% below (A) or above (B) the threshold for twitch elicitation during complete relaxation of forearm muscles; TCS was randomly preceded (range 14-32 msec) by a shock to the median or ulnar nerve at the elbow with identical characteristics as for LLR elicitation. An initial epoch of 'inhibition' followed by a peak of 'facilitation' of the amplitude of motor responses to TCS was observed when conditioning stimuli to the median nerve preceded TCS by 14-20 and by 24-32 msec, respectively. Contrary to normals, conditioning stimulation of the median nerve did not significantly influence the excitability threshold to TCS in those parkinsonians with depressed frontal N30.

[Maps of somatosensory evoked potentials from the arm in patients with neoplasms and post-traumatic brain lesions]. / Mappe dei potenziali evocati somatosensoriali (PES) dall'arto superiore in pazienti affetti da neoplasia e lesioni post-traumatiche cerebrali.

Short-latency somatosensory evoked potentials by the stimulation of the median nerve at the wrist, were recorded in six patients (four with cerebral tumors and two with post-trauma lesions). The electrodes were placed on the scalp following the 10-20 International System. A reference electrode was placed on earlobe contralateral to the site of the stimulation. Eleven normal subjects were used as control (mean age 64.4 +/- 12.05). We used the Brain-Surveyor-Basis Trade system which allowed us to elaborate the results by coloured mapping through linear interpolation of signal amplitudes. The following parameters were investigated: peak latencies of the N13, N20, P22, N30 waves; amplitudes of the post-rolandic P14-N20, N20-P25, pre-rolandic P22-N30 components and the central conduction time N13-N20 (CCT). The evaluation of latencies was not significant in determining the lesion site. On the contrary, the evaluation of amplitudes revealed expressive asymmetry, though it did not define the nature of alteration (increase or decrease due to lesion), and the correlation between these variations and the site of the lesion. The authors discussed the possibility that amplitude abnormalities in patients with tumors were related either to the tumors and/or drug effects.

Electrophysiologic evaluation of local steroid injection in carpal tunnel syndrome.

Extensive sensory and motor nerve conduction studies were performed in a series of patients with electrophysiologically proven, idiopathic carpal tunnel syndrome who were treated by a single steroid injection (40 mg of triamcinolone acetonide). Electrophysiologic studies, which included evaluation of median, ulnar, and radial orthodromic sensory action potentials, median and ulnar motor action potentials, and electromyography of two intrinsic muscles of the hand, were done before and at 45 days and six months after the treatment. By the end of the follow-up period, the symptoms had remitted completely in 11 hands (35%), 18 (58%) benefitted from partial relief, and two did not improve. In addition to the relief of symptoms, abnormalities of motor nerve conduction improved in 65% of cases, and abnormalities of sensory nerve conduction improved in 73% of all the individual digital branches of the median nerve examined. Recovery of function of the median nerve continued for a long period, even after the pharmacologic effect of the steroid agent had presumably ceased.

'Excitability changes of muscular responses to magnetic brain stimulation in patients with central motor disorders.

The 'excitability' and 'conductivity' of motor pathways during transcranial stimulation (TCS) have been investigated in 49 patients affected by multiple sclerosis (34), amyotrophic lateral sclerosis (7), spino-cerebellar ataxia (3), primary lateral sclerosis (4) and brain metastasis (1). Hyper-reflexia, spasticity and weakness were correlated with the central motor conduction time (CCT) and with the threshold intensity of TCS required to produce a motor evoked potential (MEP). MEPs to magnetic TCS were recorded from hand and foot muscles during relaxation, contraction and after tendon vibration. Thresholds and CCTs of the patients were compared with those of 30 healthy controls. Increased threshold was found in 37 out of 49 patients (75.5%). Prolongation of the CCT was found in 38 out of 63 clinically affected upper limbs (60.3%) and in 56 out of 77 clinically affected lower limbs (72.7%). Absent motor responses to maximal TCS were found in 20 out of 98 lower limbs (20.4%). Excluding ALS patients (in whom there was a lower threshold for MEP elicitation), a significant linear correlation was found between prolonged CCT and increased threshold. While MEPs with prolonged CCTs have elevated TCS threshold, it is important to note that an elevated threshold was found in 14 out of 49 patients (28.5%) despite unchanged CCT. Spasticity and/or hyper-reflexia were more frequently associated with increased threshold than with prolonged CCT, while weakness was correlated equally well with both these parameters. In this respect magnetic TCS proves to represent a new tool for the detection of abnormal 'excitability' of the central motor tracts.

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.

[Memory changes in herpes virus encephalitis: report of a case]. / Alterazione della memoria nell'encefalite da herpes virus: a proposito di un caso.

A case of Herpes Simplex Encephalitis with a benign course was present in a 66-year-old patient. A year after the acute phase of the illness, the patient continued to suffer from inability to fix verbal material in memory. During the acute phase, cerebral NMR revealed a large evolving lesion in the right temporal region, and an old lesion located in the same region of the opposite hemisphere. From the medical history, we learned that the patient, 35 years earlier, suffered a similar episode, including a short-term memory deficit. In the following study, we will discuss this case report in relation to data found in the literature dealing with memory deficit, caused by mono and bilateral, temporal lesions.