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Biomedical subjects

A Nardone

Publications and source records attributed to A Nardone.

At least 55 records · Page 3Linked to original sources

[Acute cholecystitis and gallbladder neoplasms: the experience of 2215 cases].

The authors have retrospectively analysed 2215 surgical procedures for gallbladder stones. The global incidence of gallbladder neoplasm has been 5%. This rate rises to 11% considering female patients over 60 years old. In this group, a gallbladder carcinoma was contemporary present in 17.4% of acute cholecystitis. Cholecystectomy may be suggested in every patients with gallstones, even asymptomatic, particularly if some risk factors are present.

Acute Disease↗

Medium-latency stretch reflexes of foot and leg muscles analysed by cooling the lower limb in standing humans.

1. In standing subjects, an ankle-dorsiflexing perturbation of the supporting surface evokes a short-latency response (SLR) and a medium-latency response (MLR) to stretch in both soleus (Sol) and flexor digitorum brevis (FDB) muscles. The SLR is the counterpart of the monosynaptic reflex, whilst the MLR might be either mediated by Ia fibres, the delay being due to a long-loop central circuit, or by fibres of slower conduction velocity. Since small afferents are slowed more than large ones by low temperature, a greater latency increment for the MLR than the SLR induced by cooling of the limb would point to a peripheral origin of the MLR. 2. In nine subjects, one limb was cooled by circulating water in a tube wrapped around it for about 120 min. Perturbations were delivered to the same limb prior to and during cooling, and after rewarming. EMG was recorded by surface electrodes from the Sol and FDB muscles. 3. The mean increase in latency of MLRs was significantly greater than that of SLRs in both muscles. On average, the Sol SLR increased from 42.4 to 47.0 ms and the Sol MLR from 72.0 to 82.3 ms. The FDB SLR increased from 58.1 to 66.5 ms and the FDB MLR from 94.9 to 110.5 ms. The mean difference (MLR minus SLR) increased from 29.6 to 35.2 ms for Sol, and from 36.8 to 43.9 ms for FDB at the end of cooling. After 30 min of rewarming, the responses of both muscles recovered towards control values. 4. The greater latency increment of the MLRs than of the SLRs favours the hypothesis of a slower conduction velocity of the responsible afferent fibres. The most likely candidate fibres are the spindle group II afferents.

Adult↗

Human stance stability improves with the repetition of the task: effect of foot position and visual condition.

The effects of repetition of quiet stance trials on body sway, recorded through a stabilometric platform, were studied in 12 normal subjects. With feet together, both with eyes open (EO) and closed (EC), a progressive shift forward of the centre of foot pressure (CFP) occurred with repetition. In addition, with EC, but not with EO, a significant progressive reduction in sway area (SA) and sway path (SP) occurred. With feet 10 cm apart, initial SA and SP values were significantly smaller than with feet together, regardless of the visual condition, but repetition of trials induced no significant effects on either position of CFP or body sway under either visual condition. Results indicate the occurrence of a learning phenomenon in this simple postural task, whereby the body shifts towards a 'safer' position with a minimum energy expenditure due to reduced corrections of sway. Forward leaning and decrease in sway are two independently-occurring processes, each possibly due to a better central integration of proprioceptive input with repetition of trials.

Adolescent↗

Inhibition of endosomal acidification in normal cells mimics the derangements of cellular insulin and insulin-receptor metabolism observed in non-insulin-dependent diabetes mellitus.

Dissociation of the insulin-insulin receptor complex plays a crucial role in the processing of both insulin and the insulin receptor, and the acidification of endocytic vesicles may be the mechanism by which internalized insulin is dissociated from its receptor and properly sorted and processed. Internalized insulin-insulin receptor complexes are abnormally processed in cells from patients with non-insulin-dependent diabetes mellitus (NIDDM). Accordingly, to further investigate the mechanisms of the derangements observed in NIDDM cells, we examined the effects of the ionophore monensin, which inhibits endosomal acidification, on the cellular processing of insulin and insulin receptor in monocytes from control subjects (n = 12) and NIDDM patients (n = 14). This study confirms that monocytes from NIDDM patients, compared with cells from normal controls, had reduced binding (P < .01), internalization (P < .01), and degradation (P < .01) of insulin. In addition, the release of intracellular radioactivity was slower (P < .01), and recycling of the insulin receptor was inhibited (P < .01). Moreover, these defects were associated with a significant (P < .01) decrease of dissociation of the internalized insulin-insulin receptor complex. In cells from normal controls, incubation with monensin decreased insulin binding (P < .01), but not insulin internalization. High-performance liquid chromatography (HPLC) analysis of intracellular radioactivity showed that after monensin intracellular intact insulin significantly increased (P < .01), thus suggesting a decrease of intracellular insulin degradation. Moreover, insulin receptor recycling was completely disrupted. All of these derangements were associated with a significant decrease (P < .01) of dissociation of insulin-insulin receptor complexes. On the contrary, in diabetic monocytes, monensin had no significant additional effect on NIDDM-linked alterations. Comparison of the results obtained in cells from NIDDM patients to those found in monensin-treated normal cells demonstrates that NIDDM and monensin gave rise to a superimposable impairment of dissociation of the intracellular insulin-insulin receptor complex, associated with similar abnormal sorting and processing of insulin and its receptor. The only defect present in NIDDM cells but not in monensin-treated cells is the decrease of insulin internalization, which thus seems independent of the action of monensin on the processing of internalized insulin-insulin receptor complex. These results suggest that the impairment of dissociation of the insulin-insulin receptor complex may play a crucial role in the subsequent altered processing of insulin and insulin receptor. Moreover, they raise the question as to a possible similar alteration of the same intracellular mechanism by NIDDM and monensin, and point out that the derangements found in cells from NIDDM patients could be localized within the endosomal apparatus and consist mainly of a defective acidification of its interior.

Chromatography, High Pressure Liquid↗

Fatigue effects on body balance.

Body sway variables (sway area and sway path) were recorded by a dynamometric platform in 13 young subjects, standing quiet with feet together, with eyes open (EO) and eyes closed (EC), prior to and following two types of physical exercise (treadmill walking and cycle ergometer pedalling). Each exercise was performed under both fatiguing (above anaerobic threshold) and non-fatiguing conditions. Following fatiguing treadmill exercise, we observed a significant increase in body sway with respect to pre-exercise values. The increase was present under both visual conditions, affected both sway area and sway path and lasted until about 15 min from the end of the exercise. The Romberg quotient (the ratio of EC/EO of sway area, or sway path) significantly increased after the fatiguing exercise with respect to the non-fatiguing exercise. The mean position of the centre of foot pressure (CFP) was unchanged after the exercise. Fatigue induced an increase in the median frequency of oscillation of the centre of foot pressure, independent of the amplitude of sway. Non-fatiguing treadmill exercise induced no significant changes in sway or in its frequency content. Following fatiguing cycle ergometer exercise, a negligible increase or a decrease (under eyes closed condition) in body sway were observed. Non-fatiguing cycling exercise induced no significant changes or a decrease in sway. Control experiments showed that simple repetition of successive stance trials (without intercalated exercise) was able by itself to induce a decrease in sway. By taking this effect into account, both types of cycling exercises revealed a mild capacity to increase sway. We concluded that body sway increased after strenuous physical exercise, but was little affected by exercise performed below the estimated anaerobic threshold. The effects of fatigue on sway were short-lasting and of moderate extent, and therefore were not liable to seriously threaten body equilibrium.

Adolescent↗

Surveillance of sexual behaviour among homosexual men in a central London health authority.

OBJECTIVE: To establish a surveillance mechanism of high risk sexual behaviour among homosexual and bisexual men living, socialising and using services in a central London health authority. DESIGN: Baseline survey for a system of repeatable behavioural surveillance using a self-completed questionnaire delivered by healthcare providers. SETTING: Genitourinary medicine clinics, gay bars, clubs, community groups and a cruising ground in the defined geographical area of a central London health authority. PARTICIPANTS: Five hundred and fifty three homosexual and bisexual men. MAIN OUTCOME MEASURES: Self-reported behaviours including unprotected anal intercourse (UAI), HIV status of unprotected anal intercourse partners, uptake of HIV testing and use of condoms at first time of anal intercourse. RESULTS: Five hundred and sixty questionnaires were returned (response rate 76%) from 553 men. A third (35%) of men surveyed had had UAI in the previous year. Nearly a fifth (19%) of the sample had had UAI with one or more partners of a discordant or unknown HIV status. A total of 343 (63%) men had had an HIV test. The proportion of men using condoms on the occasion of first anal intercourse has risen from 6% before 1980 to 88% after 1993. CONCLUSIONS: We have demonstrated that a surveillance programme to monitor high risk sexual behaviour among homosexual men can be easily established. The results can be employed to assess progress towards risk reduction targets and also inform future policy development. Our baseline data demonstrate that a large proportion of homosexual men are continuing to engage in high risk sexual behaviour, although there is some evidence of improvement in condom use at first anal intercourse over time. There is a need for continuing health promotion with evaluation among homosexual men.

Adolescent↗

Composition of colostrum from dairy heifers exposed to high air temperatures during late pregnancy and the early postpartum period.

This study examined the effects of heat stress on composition of colostrum from primiparous cows during late pregnancy and the early postpartum period. Two groups of 6 Holstein heifers were utilized. During the last 3 wk of pregnancy and during the first 36 h after calving, one group was exposed to thermal comfort (temperature-humidity index = 65); the other group was exposed to high air temperatures (temperature-humidity index = 82 from 0900 to 2000 h and temperature-humidity index = 76 from 2100 to 0800 h). Heifers under heat stress had higher rectal temperatures and respiratory rates; lower plasma triiodothyronine and glucose; higher plasma nonesterified fatty acids and beta-hydroxybutyrate; lower intakes of dry matter, net energy for lactation, and crude protein; higher water intakes; and lower body condition scores. The decline of plasma immunoglobulins (Ig) over the final 2 wk of pregnancy was less pronounced for heifers under heat stress. For the first four milkings, colostrum of cows exposed to high air temperatures had lower mean concentrations of IgG and IgA; lower mean percentages of total protein, casein, lactalbumin, fat, and lactose; lower contents (grams per liter) of short- and medium-chain fatty acids; lower energy; lower titratable acidity; and higher pH. Thus, high air temperatures during late pregnancy and the early postpartum period markedly affected the composition of colostrum from primiparous dairy cows.

3-Hydroxybutyric Acid↗

Different effect of height on latency of leg and foot short- and medium- latency EMG responses to perturbation of stance in humans.

In standing humans, platform perturbations evoked short- (SLR) and medium-latency responses (MLR) in soleus (Sol), tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles. The latency of all responses significantly increased with subjects' height. The slope of the regression lines for the MLRs versus height was significantly steeper than that for the SLRs. The conduction velocity of the afferent fibres mediating the FDB MLR, calculated on the basis of the regression, was 17.5 m/s. These findings indicate that the MLRs are transmitted through afferent fibres slower than those mediating the SLRs. While the latter fibres are spindle group Ia afferents, the former are suggested to be group II fibres.

Adolescent↗

Unilateral displacement of lower limb evokes bilateral EMG responses in leg and foot muscles in standing humans.

During upright stance, foot dorsiflexion induced by the movement of a supporting platform elicits a short- (SLR) and a medium-latency response (MLR) in both the soleus and the flexor digitorum brevis muscles; foot plantarflexion elicits a MLR in the tibialis anterior. The SLR is the counterpart of the stretch reflex, but no general agreement exists about the origin of the MLR, though recent results suggest that it is transmitted through group II afferent fibres. Animal studies have shown that group II fibres impinge on interneurones projecting contralaterally as well as ipsilaterally, whereas group I fibres impinge on interneurones which project mainly ipsilaterally. Therefore, we compared the changes in amplitude and latency of the SLRs and MLRs in the right and left limb during postural perturbations induced while subjects maintained both feet on the platform (both-on condition) or while they maintained only one foot on the platform and the other on firm ground (one-on condition). Under the both-on condition, the pattern of EMG responses described above occurred bilaterally. Under the one-on condition, both SLRs and MLRs occurred in the displaced leg. However, whereas the SLRs did not change in amplitude compared with the both-on condition, the MLRs decreased in amplitude to about 50%. MLRs were also present in the non-displaced leg. They were not preceded by any SLR but showed a further decrease in size with respect to the corresponding responses in the perturbed leg. Latency of the MLRs of the perturbed leg increased by about 5 ms passing from the both-on to the one-on condition. In the latter condition, a further increase of 5 ms was observed in the nonperturbed leg with respect to the displaced one. The occurrence of the MLRs but not of the SLRs in the contralateral non-displaced leg is in keeping with the notion that crossed neural pathways fed by spindle group II afferent fibres subserve the MLRs. The changes in latency of the MLRs under the one-on condition compared with both-on give a cue about the synaptic delays along the neural circuit and the time taken by the afferent impulses to cross the spinal cord.

Adult↗

Effects of selenium and vitamin E administration during a late stage of pregnancy on colostrum and milk production in dairy cows, and on passive immunity and growth of their offspring.

OBJECTIVE: To determine effects of selenium (Se) and vitamin E (VE) administration in late pregnancy on Se status, plasma immunoglobulin concentrations, and colostrum and milk production of dairy cows, and on Se status, passive immunity, and growth of their offspring. ANIMALS: 25 Holstein cows and their offspring. PROCEDURE: 3 and 1.5 weeks before calving, sodium selenite (5 mg/100 kg of body weight) and d,l-alpha-tocopheryl acetate (25 IU/100 kg) were administered to 13 cows. The other 12 cows were not treated. Se status was assessed by measurement of glutathione peroxidase activity of erythrocytes (GSH-Px-E). RESULTS: The 13 treated cows had higher (P < 0.01) GSH-Px-E values at calving and during the first 12 weeks of lactation. Changes in plasma immunoglobulin concentrations before or after calving did not differ between the 2 groups of cows. During the first 36 hours after calving (4 milkings), treated cows produced 22% more colostrum than did their nontreated counterparts (P < 0.005). Percentages of colostral immunoglobulins did not differ between the 2 groups. During the first 12 weeks of lactation, treated cows produced 10% more milk than did nontreated cows (P < 0.005). GSH-Px-E values at birth and 28 days of life were significantly higher in calves from treated cows. Plasma immunoglobulin concentrations and body weight during the first 56 days after birth did not differ between calves born to treated or nontreated cows. CONCLUSIONS AND CLINICAL RELEVANCE: Cows given Se and VE in late pregnancy produce large quantities of colostrum and milk. Colostrum produced from cows given Se and VE is suitable to feed newborn calves and to be stored for later use. Improvement of Se status in calves born to cows given Se and VE in late pregnancy is not beneficial to passive immunity and growth.

Animals↗

Time course of 'set'-related changes in muscle responses to stance perturbation in humans.

1. In standing subjects, toe-down rotation of a supporting platform elicits a medium-latency response (MLR) in tibialis anterior (TA) muscle and a long-latency response (LLR) in soleus (Sol). Toe-up rotation induces a short-latency response (SLR) in Sol and a LLR in TA. When subjects steadily hold onto a stable frame, all responses are decreased, except Sol SLR. The aim of this investigation was to assess whether the response modulation is dependent on information from the hand touching the frame, or whether it anticipates the holding task. 2. The time course of the changes in response amplitude was studied in a time interval centred around the act of holding, performed in a reaction-time mode. Subjects kept their extended arm close to the frame in front of them and brought the hand in contact with the frame in response to a visual go-signal. The platform was moved at different intervals prior to or after the go-signal. Surface EMGs of Sol, TA and deltoid (Delt) were recorded. 3. TA MLR began to decrease when the platform was displaced at an interval of 140 ms after the go-signal, about 200 ms before subjects touched the frame and 120 ms before termination of Delt EMG. Four hundred milliseconds after the go-signal the response reached and maintained maximal inhibition, similar to that occurring under the stationary holding condition. The time course of inhibition of Sol LLR and TA LLR was similar to that of TA MLR, except that LLRs began to decrease at an earlier interval. Due to the different response latency from the onset of the perturbations, the beginning of inhibition of both MLRs and LLRs occurred almost simultaneously. 4. The changes in amplitude of leg muscle responses are not triggered by the go-signal, contact with the frame, or arm motion, suggesting that the modulation is related to the transition to a new, stabilized postural 'set'. The similar extent and parallel time course of MLR and LLR suppression, possibly transmitted through different pathways, points to the spinal cord as the site of action. The lack of depression of the monosynaptic SLR suggests an effect at premotoneuronal level. On the basis of selectivity, latency and time course of the effect, we favour the hypothesis that a monoaminergic pathway from the brainstem is involved.

Adult↗

Selective depression of medium-latency leg and foot muscle responses to stretch by an alpha 2-agonist in humans.

1. In standing humans, toe-up rotation of a platform induces a short-latency (SLR) and a medium-latency response (MLR) in both soleus (Sol) and flexor digitorum brevis (FDB) muscles. Toe-down rotation evokes a MLR in the tibialis anterior (TA). The SLR is the counterpart of the monosynaptic stretch reflex, but the origin of the MLR is still debated. By means of tizanidine (an alpha 2-adrenergic receptor agonist) we tested the hypothesis that the MLR is relayed by group II afferent fibres, since animal data indicate that tizanidine or stimulation of monoaminergic brainstem centres decrease the excitability of spinal interneurones supplied by those fibres. In addition, we compared the effect of the drug on these responses with that induced by stabilization of posture. 2. Eight subjects received tizanidine (150 micrograms kg-1 orally) or placebo, in a single-blind design. Platform rotations were delivered prior to administration and for 3 h afterwards. Both TA- and FDB-MLRs decreased in size, starting from about 1 h after tizanidine administration. Sol-SLR was unaffected. Response latencies were unchanged. Placebo induced no changes in any response. In each subject, the extent of TA-MLR depression induced by holding onto a frame and by tizanidine was superimposable. 3. The selective effect of tizanidine on MLR supports the notion that it is relayed through group II afferent fibres. The similar effects of holding and tizanidine on the response suggests that it is modulated by monoaminergic centres.

Adrenergic alpha-Agonists↗

Early and late stretch responses of human foot muscles induced by perturbation of stance.

In eight subjects standing on a movable platform, surface EMG activity was recorded from the foot muscles extensor digitorum brevis (EDB) and flexor digitorum brevis (FDB) and from the leg muscles soleus (Sol) and tibialis anterior (TA) during perturbations of upright stance. Perturbations inducing foot dorsiflexion (upward tilt and backward translation) evoked a short-latency response (SLR) and a medium-latency response (MLR) to stretch in the physiological extensors FDB and Sol, and a long-latency response (LLR) in the physiological flexors EDB and TA. Perturbations inducing plantar-flexion (downward tilt and forward translation) evoked the MLR in EDB and TA, and the LLR in FDB and Sol. The latency of the FDB and Sol SLR was compared to that of the H and T reflexes evoked in the same muscles by electrical or mechanical stimulation, respectively. In both muscles, the T reflex and the SLR followed the H reflex at delays accounted for by the different stimulation mode, indicating that the SLR induced in both muscles by upward tilt and backward translation was a true autogenetic stretch reflex from spindle primaries. The time interval between the onset of SLR and of MLR was significantly greater for the FDB than the Sol muscle, suggesting that MLR is a spinal reflex travelling through slower peripheral afferent pathways than SLR. From these latency differences and from the distance between the muscles, we calculated in four subjects the conduction velocity of the afferent fibres presumably responsible for the MLR in FDB. This was about 29 m/s. LLRs were evoked in TA and EDB during upward tilt and backward translation, and in Sol and FDB during downward tilt, but not forward translation. LLRs did not adhere to a proximal-to-distal pattern, since these could appear earlier in the foot than in the leg muscles. All responses were modulated by perturbation type (tilt vs translation) and body posture (normal stance vs forward leaning). Both the large amplitude of the foot muscle responses and their temporal pattern indicate that the muscles acting on the toes play a major role in stabilising posture. Their action increases in amplitude and extends in time the foot-ground reaction force, thereby improving the efficiency of the superimposed action of the leg muscle responses.

Adult↗

Influence of aging on leg muscle reflex responses to stance perturbation.

The effect of age on latency and amplitude of leg muscle responses to stance perturbations was studied in 75 control subjects. They stood upright on a platform and were displaced by toe-up (upward tilt) and toe-down (downward tilt) platform rotations. Perturbations were induced during free and supported stance (holding on to a stable structure). Surface electromyograms (EMG) of the soleus (Sol) and tibialis anterior (TA) were recorded and latency and area of responses were measured. Body sway variables during stance with open or closed eyes were also recorded. Upward tilt evoked a short-latency response (SLR) in Sol and a long-latency response (LLR) in TA. Downward tilt evoked a medium-latency response (MLR) in TA and a LLR in Sol. This pattern of EMG responses was similar in both young and elderly subjects, although there were some differences in latency and amplitude. There was a significant relationship between latency of all responses and age. Slope of the regression lines of TA LLR, TA MLR, and Sol LLR was steeper than that of Sol SLR. Area of Sol SLR was unrelated to age, but a positive trend was identified in the other responses, significant for TA LLR. Under supported-stance condition, amplitude of TA MLR, TA LLR, and Sol LLR was decreased to a similar extent in both young and elderly subjects. There was a weak relationship between age and most body sway variables. A significant relationship was found between most sway variables and latency of Sol SLR and LLR, chiefly with eyes closed. Neither TA MLR nor LLR were significantly correlated with sway variables, but a trend was present for TA MLR with eyes closed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cytosolic 5'-nucleotidase/nucleoside phosphotransferase: a nucleoside analog activating enzyme?

Nucleoside phosphotransferase acting on inosine and deoxyinosine has been partially purified from cultured Chinese hamster lung fibroblasts (V79). The activity is associated with a cytosolic 5'-nucleotidase acting on IMP and deoxyIMP. The transfer of the phosphate group from IMP to inosine catalyzed by this enzyme was activated by ATP and 2,3-bisphosphoglycerate. Inosine, deoxyinosine, guanosine, deoxyguanosine, and the nucleoside analogs 2',3'-dideoxyinosine and 8-azaguanosine are substrates, while adenosine and deoxyadenosine are not. IMP, deoxyIMP, GMP, and deoxyGMP are the best phosphate donors. The cytosolic 5'-nucleotidase/phosphotransferase substrate, 8-azaguanosine, was found to be very toxic for cultured fibroblasts (LD50 = 0.32 microM). Mutants resistant to either 8-azaguanosine and the correspondent base 8-azaguanine were isolated and characterized. Our results indicated that the 8-azaguanosine-resistant cells were lacking both cytosolic 5'-nucleotidase and hypoxanthine-guanine phosphoribosyltransferase, while 8-azaguanine resistant cells were lacking only the latter enzyme. Despite this observation, both mutants displayed 8-azaguanosine resistance, thus indicating that cytosolic 5'-nucleotidase is not essential for the activation of this nucleoside analog.

5'-Nucleotidase↗

The limits of equilibrium in young and elderly normal subjects and in parkinsonians.

Body sway was studied at various body inclinations, voluntarily maintained for about 1 min, in young and elderly normals and in idiopathic parkinsonians. They stood on a dynamometric platform, whose output gave the instantaneous centre of foot pressure (CFP), its mean value and body sway area, with eyes open (EO) or closed (EC). Subjects held the normal upright stance, or the maximum possible inclined posture (body straight, rotated at the ankle joints) in forward or backward direction, or intermediate postures. EMG was recorded from tibialis anterior (TA), soleus (Sol), extensor digitorum brevis (EDB) and flexor digitorum brevis (FDB). The cross-correlation function between the profile of the EMG envelope and the profile of the shift of CFP along the sagittal plane was calculated. In young subjects standing with EO, the maximum extent of antero-posterior (A-P) displacement of CFP was about 60% of foot length. EC reduced this value to about 50%. In the elderly normals, the maximum A-P displacement was about 40% (EO) and 30% (EC). In both groups, sway area was minimal during normal stance with EO and increased progressively when the subjects leant forward or backward. With EC, sway area further increased during normal stance and the rate of increase in relation to inclination augmented markedly. Sol was tonically active during normal stance. Forward leaning increased Sol EMG and induced activity in FDB. TA and EDB were active during backward leaning. The peak of the cross-correlation function between Sol EMG and instantaneous CFP was higher during normal stance than forward inclination, while the reverse was true for FDB. This suggests a role of FDB in the fine-tuning of postural adjustment during forward leaning, and a weight-supporting role of Sol. During backward inclination, TA but not EDB was cross-correlated with CFP. In the parkinsonians, maximum A-P displacement of CFP was just about 30% of foot length (EO; about 20% with EC); its extent was inversely correlated with the severity of the disease. The relationship between sway area and A-P displacement was similar to the elderly, both with EO and EC, within the common range of inclination. In the patients affected by the long-term syndrome, A-P displacement was further reduced while sway area increase at the critical postures was often absent. In all patients, the relationship between muscle activity and body inclination was comparable to normal.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Effect of propionyl-L-carnitine in a rat model of peripheral arteriopathy: a functional, histologic, and NMR spectroscopic study.

Propionyl-L-carnitine (PLC) has been shown to exert beneficial effects in experimental models of peripheral arterial diseases, such as ergotamine-induced tail gangrene and bilateral femoral arteries occlusion in rats. These models, however, present some drawbacks. The present study was performed to determine whether repeated oral administration of PLC improves the functional, histologic, and metabolic parameters in rats with long-lasting chemically induced peripheral arteriopathy. Peripheral arteriopathy was induced by injecting Na laurate in both the femoral arteries of rats. The walking capacity of the animals (treadmill test) was evaluated at different times and up to 5 weeks after Na laurate injection. Histological examination of vessels and muscles was performed at the end of the experimental period (5 weeks). In separate experiments the level of high-energy phosphates was determined with 31P NMR methodology in the leg muscles. Injection of Na laurate impaired (p < 0.05) the walking capacity of rats, caused thickening of the intima and marked narrowing of the vasal lumen, and reduced the ATP and PCr levels in muscles by 42% and 25%, respectively. PLC given orally for 7 days at 30, 60, 120, and 250 mg/kg dose-dependently decreased the severity of walking capacity impairment by 19%, 41%, 64%, and 71%, respectively. Long-term administration (4 weeks) of PLC (60 and 250 mg/kg os) caused a significant improvement of walking capacity throughout the entire period. The improvement persisted 1 week after discontinuation of the treatment. The severity of the vascular and muscular damages was markedly reduced, particularly in animals treated with the highest dose. Alterations in ATP and PCr levels were significantly (p < 0.05) diminished by PLC (120 mg/kg os) administered daily for 15 days starting 24 hours after Na laurate injection, or for 11 days starting 4 days after Na laurate. The dextro-isomer of the compound was completely inactive, and L-carnitine improved motor performance to a much lesser degree than an identical dose of PLC. It is suggested that the activity of PLC is linked to its metabolic effects on fatty acid oxidation, with consequent preservation of high-energy phosphate levels.

Animals↗

Application of an epithelial liver cell line, metabolically competent, for mutation studies of promutagens.

Recently numerous attempts have been made to reduce the use of vertebrate animals in laboratory experiments to evaluate general and acute toxicity, mutagenesis and teratogenesis of new drugs or chemicals. One common approach is to use established, proliferating cell lines that preserve differentiated functions such as the competence to metabolize xenobiotics. To this end a continuous Chinese hamster epithelial liver cell line (CHEL cells) was established, cultured as used for mutagenesis studies. Structurally different promutagens, such as 7,12-dimethylbenz[a]anthracene (7,12-DMBA), benzo[a]pyrene (B(a)P), aflatoxin B1 (AB1) and cyclophosphamide (CP), were used in order to check and validate the test system. anti-Chrysene-1,2-diol 3,4-epoxide (CDE) and mitomycin C (MMC) were taken as representatives of direct mutagens. The genetic change induced by the mutagens was quantified by measuring mutation frequencies at the HGPRT locus. Several parameters, such as mutant expression time for each chemical, cell density for selection of mutants and enzymatic characterization for HGPRT phenotype, were examined to establish the optimal assay conditions. All promutagens analyzed significantly affected either the cloning efficiency and/or the mutant frequency of CHEL cells after 24 h of exposure. In addition, various enzyme activities involved in the metabolism of the promutagens were determined in CHEL cells, under the experimental conditions of chemical exposure used in the mutagenesis assay. The enzyme activities were compared with those found in uninduced Chinese hamster liver.

Animals↗