Biomedical subjects

M A Lynch

Publications and source records attributed to M A Lynch.

161 records · Page 9Linked to original sources

PubMedDate not supplied

Regulation of intracellular Ca2+ concentration by interleukin-1beta in rat cortical synaptosomes: an age-related study.

The pro-inflammatory cytokine interleukin-1beta (IL-1beta) is released by cells during injury and stress, and increased neuronal expression of IL-1beta is a feature of age-related neurodegeneration. We have recently reported that IL-1beta has a biphasic effect on the K+-induced rise in intracellular Ca2+ concentration ([Ca2+]i) in cortical synaptosomes, exerting an inhibitory effect on the K+-induced rise in [Ca2+]i at lower (3.5 ng/mL) concentrations and a stimulatory effect on the K+-induced rise in [Ca2+]i at higher (100 ng/mL) concentrations. In the present study, we observed that the K+-induced rise in [Ca2+]i was inhibited to a similar extent by the lower concentration of IL-1beta in cortical synaptosomes prepared from young (3-month-old), middle-aged (12-month-old) and aged (24-month-old) rats. In contrast, cortical synaptosomes prepared from the aged rats exhibited an increased susceptibility to the higher concentration of IL-1beta, resulting in a marked elevation in [Ca2+]i. We propose that the age-related increase in neuronal concentration of IL-1beta promotes a dramatic elevation in [Ca2+]i following membrane depolarization, thereby altering Ca2+ homeostasis and exacerbating neuronal vulnerability to excitotoxicity.

Aging↗

PubMedDate not supplied

Age-related changes in LTP and antioxidant defenses are reversed by an alpha-lipoic acid-enriched diet.

Among the age-related changes identified in rat hippocampus are impairments in LTP and glutamate release. These deficits have been coupled with decreased arachidonic acid concentration. In this study we compared LTP and glutamate release in groups of aged and young rats fed for 8 weeks on a control diet or on a diet enriched in alpha-lipoic acid. Dietary supplementation in aged rats restored hippocampal arachidonic acid concentration to levels observed in tissue prepared from young rats. We observed that aged rats that received the experimental diet sustained LTP in perforant path-granule cell synapses in a manner indistinguishable from young rats whereas the age-related impairment in glutamate release was reversed in synaptosomes prepared from dentate gyrus obtained from these rats. The evidence presented supports the hypothesis that the alpha-lipoic acid-enriched diet has antioxidant properties, because the age-related increase in superoxide dismutase activity and decrease in alpha-tocopherol concentration were reversed. The finding that the age-related increase in interleukin-1 (IL-1)beta concentration was also reversed suggests a possible role for this cytokine in ageing.

Aging↗

PubMedDate not supplied

Possible association of alcohol tolerance with increased synaptic Ca2+ sensitivity.

The inhibitory effect of ethanol on neurotransmitter release has been suggested to be due to either reduced Ca2+ entry or increased removal of free intracellular Ca2+ from the synapse. The use of the Ca2+ ionophore, A23187, to allow direct access of external Ca2+ to the presynaptic interior should help to determine which of these two factors is the more important, as ethanol should inhibit A23187-induced release of transmitter only if increased Ca2+ removal from the synapse is important. Here we show in rat striatal slices that, although 3H-dopamine release evoked by depolarization with 40 mM K+ is inhibited by 50 mM ethanol, the release evoked by A23187 is enhanced by the presence of ethanol in vitro. The results suggest that ethanol reduces depolarization-induced transmitter release by reducing Ca2+ entry to the presynaptic terminal. However, for brain slices taken from rats made tolerant to ethanol, 3H-dopamine release in the absence of ethanol showed altered characteristics; both K+ depolarization and A23187 released a significantly greater fraction of 3H-dopamine from these slices than from controls. Thus tolerance to the inhibitory effect of ethanol on release may develop by a mechanism involving increased sensitivity of the terminal to Ca2+ entry.

Alcoholism↗

PubMedDate not supplied

Long-term potentiation in aged rats is restored when the age-related decrease in polyunsaturated fatty acid concentration is reversed.

Several age-related changes have been identified in rat hippocampus; among these are deficits in glutamate release and long-term potentiation in dentate gyrus. These deficits correlate with a decrease in the concentration of arachidonic acid in hippocampus. In this study, the effects of dietary supplementation for 8 weeks with omega -6 or omega -3 fatty acids were assessed in groups of aged and young rats. The data presented indicate that dietary supplementation in aged rats restored the concentrations of arachidonic acid and docosahexanoic acid in hippocampal preparations to those observed in tissue prepared from young rats. In parallel, aged rats which received the experimental diets sustained long-term potentiation in a manner indistinguishable from young rats. The evidence presented supports the view that an age-related increase in reactive oxygen species production is linked with the decrease in polyunsaturated fatty acids and that a diet enriched in eicosapentanoic acid has antioxidant properties which may play a key role in reversal of the observed age-related deficits.

Aging↗

PubMedDate not supplied

Providing health care for refugee children and unaccompanied minors.

The health of refugee children must be considered beyond ensuring access to health care to include issues such as housing and education. Refugees require support in using services, and their culture and religious background must be taken into account. Asylum seeking children have the same rights to health as any other children, yet non-eligibility for welfare foods may have implications for their nutrition. Providing for 15-18 year olds presents particular problems. It is important to arrange access to appropriate care for unfamiliar diseases and to recognize emotional health problems, particularly when they are related to past experiences of violence.

Adolescent↗

PubMedDate not supplied

Training in the Morris water maze occludes the synergism between ACPD and arachidonic acid on glutamate release in synaptosomes prepared from rat hippocampus.

We report here that release of glutamate, inositol phospholipid metabolism, and protein kinase C (PKC) activity are increased in synaptosomes prepared from hippocampi of rats that had been trained in a spatial learning task. In hippocampi obtained from animals that were untrained, activation of the metabotropic glutamate receptor by the specific agonist trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD) increased release of glutamate but only in the presence of a low concentration of arachidonic acid. A similar interaction between arachidonic acid and ACPD was observed on inositol phospholipid turnover and on PKC activity. However, the synergistic effect of arachidonic acid and ACPD on glutamate release was occluded in hippocampal synaptosomes prepared from trained rats. Occlusion of the effect on inositol phospholipid turnover and PKC activation was also observed. These data suggest that the molecular changes that underlie spatial learning may include activation of metabotropic glutamate receptors in the presence of arachidonic acid and that the interaction between arachidonic acid and ACPD triggers the presynaptic changes that accompany learning.

Animals↗

PubMedDate not supplied

The availability of advice regarding infant feeding to immigrants of Vietnamese origin: a survey of families and health visitors.

Since their arrival in Britain most Vietnamese mothers have abandoned traditional infant feeding practices for 'modern' methods which are unsatisfactory and expensive. Health staff are not perceived as a source of information or support. This paper emphasizes the need for culturally sensitive initiatives to reverse this trend.

Adult↗

PubMedDate not supplied

Interleukin-1 induces lipid peroxidation and membrane changes in rat hippocampus: An age-related study.

BACKGROUND: The proinflammatory cytokine, interleukin-1, is traditionally associated with the immune response but recent evidence indicates that it plays a role in neuronal function. Its expression is increased in neurodegenerative conditions and preliminary evidence suggests that it is also increased with increasing age. Receptors for interleukin-1 are differentially distributed in the brain with a high density in the hippocampus, where interleukin-1beta exerts inhibitory effects on release and calcium channel function. OBJECTIVE: The aim of this study was to investigate the possibility that interleukin-1 might lead to age-related changes in membrane composition. METHODS: Lipid peroxidation was assessed in the presence or absence of interleukin-1beta in hippocampal tissue prepared from 4- and 22-month-old rats. These data were analysed in parallel with age-related changes in arachidonic acid and interleukin-1beta concentrations in the hippocampus. RESULTS: We report that interleukin-1beta increased lipid peroxidation in hippocampal tissue prepared from 4- but not 22-month-old rats, and that this effect was inhibited by alpha-tocopherol. The attenuated response to interleukin-1beta in tissue prepared from aged rats correlated with increased expression of endogenous interleukin-1beta. Thus, using an ELISA, we have demonstrated an age-related increase in the concentration of interleukin-1beta, which is accompanied by an age-related decrease in membrane arachidonic acid. CONCLUSION: We propose that increased interleukin-1beta expression impacts on membrane composition and therefore contributes to age-related impairments in neuronal function.

Aging↗

PubMedDate not supplied

Evaluation of meniscus tears of the knee by radionuclide imaging.

We compare the accuracy of radionuclide imaging of the knee with Tc99m-pyrophosphate with arthrography for the evaluation of meniscus tears in young athletes with clinically suspected knee injury. All patients had arthroscopy which was used as the standard against which the other two diagnostic procedures were compared. Radionuclide scintigraphy and arthrography were comparable in their ability to detect tears of the medial meniscus. Scintigraphy was superior for the detection of tears of the lateral meniscus and of both menisci.

Arthroscopy↗

PubMedDate not supplied

An in vivo strain gage study of elongation of the anterior cruciate ligament.

The purpose of this paper is to study the load-elongation characteristics of a Grade II sprain of the anterior cruciate ligament (ACL) at the time of local anesthesia arthroscopy. The data may be used to increase diagnostic and prognostic accuracy when evaluating Grade II ACL sprains and to structure properly a rehabilitation program following ACL injury. This report is based on the data from two in vivo strain gage studies of Grade II ACL sprains. Following instrumentation of the ligament, several events common to physical examination and rehabilitation programs were tested. The Lachman test produced greater elongation of the anteromedial fibers than did the anterior drawer or pivot shift test. A fairly high force of 80 pounds may be required by the examiner's hands to test satisfactorily the anteromedial fibers in the acutely injured large athlete. The proper order for a rehabilitation program should be crutch walking, cycling, walking, slow running, and faster running. Patients should be cautioned to run on a perfectly level surface. Cycling produced 7% as much elongation as an 80 pound Lachman test, and the one leg half squat 21% as much. Quadriceps rehabilitation can be done more safely using these exercises. Quadriceps exercises by knee extension against a 20 pound weight boot in the range of full extension to 22 degrees flexion created peak elongation of the anteromedial fibers ranging from 87 to 121% of that produced by an 80 pound Lachman test. We recommend that quadriceps exercises and testing by knee extension through a full range of motion not be done during the first year following ACL injury or reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Local↗

PubMedDate not supplied

Exercise-related stress reaction of the sacroiliac joint. An unusual cause of low back pain in athletes.

Low back pain, secondary to a variety of musculoskeletal injuries, is common in individuals engaged in athletics. Sports-related stress reactions of the pars interarticularis are not uncommon. Stress reactions of the sacroiliac joint, on the other hand, are considered very rare. The limitations of plain radiographs and the ability of bone scintigraphy to detect stress lesions in athletes is well documented. In this paper we describe four young athletes with stress reactions of the sacroiliac region. We consider these to be uncommon but not rare, and probably self-limiting. Accurate diagnosis is important, however, to exclude more important causes of low back pain that require therapy. This type of injury also results in abnormal stresses to the lower extremities which can result in an independent and more serious injury. All sacroiliac stress reactions were unsuspected and were diagnosed only by bone scintigraphy after plain radiographs were noncontributory.

Adolescent↗

PubMedDate not supplied

Acute ligamentous diastasis of the ankle without fracture. Evaluation by radionuclide imaging.

Diastasis of the ankle syndesmosis without fracture is an uncommon injury. We present the results of bone scintigraphy as well as stress radiographs of the ankle performed on 27 athletes with suspected acute diastasis of the ankle without fracture. Scintigraphy is a reliable procedure to guide initial management of those patients in whom stress radiographs of the ankle cannot be obtained because of pain or swelling, or in whom the radiographs were considered unreliable. Scintigraphy correctly identified all 20 patients with positive stress tests (sensitivity = 100%). Two of seven patients with negative stress tests had positive scans (specificity = 71%), for an accuracy of 93%. We feel that scintigraphy is of value in a small subset of patients with suspected acute diastasis of the ankle syndesmosis on whom stress radiographs cannot be performed, or are considered inadequate in the immediate postinjury period.

Ankle Injuries↗

PubMedDate not supplied

Analysis of the mechanisms underlying the age-related impairment in long-term potentiation in the rat.

The process of ageing is common to all organisms but despite its universality, understanding of the cellular and molecular changes which accompany ageing is poor. With the increase in the ageing population, the need for systematic study of the process becomes a priority but the development of a systematic approach to the problem requires the development of a testable theory of ageing. While several theories of ageing have been proposed /336/, between which there is at least some overlap, no generally-accepted theory has been identified. In relation to the brain, four interrelated theories of ageing have received significant attention; these are (1) the membrane hypothesis, (2) the free radical hypothesis, (3) the calcium hypothesis and (4) the glucocorticoid theory. The overlap between these hypotheses is such that a causal relationship between them is very likely with age-related changes in membrane composition triggered by changes in free radical production, while changes in membrane composition are likely to account for changes in membrane function including age-related changes in calcium homeostasis. The glucocorticoid theory could equally well be termed the stress hypothesis of ageing, which in the hippocampus at least, might trigger age-related changes in free radical production. This review is not intended to be a balanced appraisal of each theory but emphasizes aspects of the membrane hypothesis of ageing and discusses some relevant aspects of the other hypotheses. Attention is focussed on analysis of the biochemical changes which might underlie age-related changes in hippocampal function, particularly maintenance of long-term potentiation (LTP), and these changes are discussed in the context of the four hypotheses of ageing.

Aging↗

PubMedDate not supplied