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Biomedical subjects

P N Shek

Publications and source records attributed to P N Shek.

At least 19 recordsLinked to original sources
PubMed1995

Exercise-induced changes in the expression of surface adhesion molecules on circulating granulocytes and lymphocytes subpopulations.

This study examined the relationship between exercise-induced changes in the concentration of circulating immunocompetent cells and their surface expression of adhesion molecules: L-selectin (CD62L) and three beta 2-integrins [LFA-1(CD11a/CD18), Mac-1 (CD11b/CD18), and p150/95(CD11c/CD18)]. Eight young male volunteers exercised on a cycle ergometer for 60 min at 60% maximal oxygen uptake. Peripheral blood samples, collected every 30 min throughout exercise and during the 2-h recovery period, were used for flow-cytometric analysis. The experimental results were compared with control data obtained ever 60 min at corresponding times of the nonexercise day. The exercise regimen induced a granulocytosis and a lymphocytosis, mainly due to an elevation of CD8+ and CD16+ cells. During recovery, a further granulocytosis occurred but accompanied by a lymphopenia. The increased CD8+ cell-count during exercise was characterized by a selective mobilization of the CD62L- and CD11ahigh cells, i.e. primed CD8+ cells. A postexercise suppression of CD4+ cell-count was derived only from CD62L+ cells. The CD11b+ and CD11c+ lymphocytes also increased during exercise, largely attributable to an increase in CD16+ cells which co-expressed CD11b and CD11c molecules. The CD62L surface density of granulocytes increased significantly during recovery. This resulted from a selective influx of CD62Lhigh granulocytes into the circulation. There were no significant changes in per-cell density of the three beta 2-integrins on granulocytes and lymphocytes throughout the experimental period. These results suggest that the cell-surface expression of CD62L (and CD11a) molecules is associated with the differential mobilization of CD8+ cells during exercise, the postexercise suppression of CD4+ cell-counts and the granulocytosis following exercise.

Adult↗
PubMed1995

Exercise, aging and immune function.

Aging leads to a diminution of resting immune function, increasing the risk of infection, tumor development and auto-immune diseases. The production of interleukin-2 is decreased, sometimes with a decrease of total T cell count, and often with changes in T cell subsets and proliferative responses to mitogens. However, natural killer cell activity remains unchanged. In theory, moderate exercise should help to reverse the adverse effects of aging upon the immune system. However, there have been relatively few studies comparing the immune responses of young and older individuals to acute exercise and to training. A single bout of moderate exercise seems to be well tolerated by the elderly. The NK cell response is much as in younger individuals, but perhaps because of a low initial proliferative capacity, older subjects show less stimulation of lymphocyte proliferation by moderate activity and less suppression with exhausting exercise. Perhaps because resting immune function is less than in the young, moderate training programs seem to stimulate immune function to a greater extent than in young subjects. The proliferative response of the T cells is enhanced in elderly rodents whereas in young animals it is suppressed. Moreover, the resting NK cell activity of elderly human subjects seems to be increased by training. Nevertheless, the therapeutic use of exercise must be cautious in the elderly, since aging also enhances susceptibility to over-training.

Aging↗
PubMed1995

Cancer, immune function, and physical activity.

Despite the problems of interpreting epidemiological studies and the difficulty in developing appropriate animal models, there is growing evidence that moderate habitual physical activity can protect against certain types of neoplasm, particularly tumors of the colon and the female reproductive tract. Exercise programs also appear to have a beneficial influence on clinical course, at least in the early stages of the disease. Recent demonstration of exercise-induced changes in the activity of macrophages, natural killer cells, lymphokine activated killer cells, neutrophils, and regulating cytokines suggest that immuno-modulation may contribute to the protective value of exercise. Depression of immune function, such as in HIV infection and in old age, is associated with an enhanced susceptibility to tumors; but the sites of tumorigenesis in HIV infection are not those that gain protection from physical activity. Further research is thus needed before it can be asserted that favorable exercise-induced changes in immune function have a material influence on the risks posed by various types of cancer.

Aged↗
PubMed1995

Liposomal alpha-tocopherol alleviates the progression of paraquat-induced lung damage.

The present study was carried out to investigate the efficacy of liposome-associated alpha-tocopherol in treating pulmonary damage caused by paraquat exposure. alpha-Tocopherol liposomes (8 mg alpha-tocopherol/kg body weight) or plain liposomes were intratracheally instilled into the lungs of rats 24 h after paraquat treatment (20 mg/kg, ip); treated animals were killed 8, 24 or 48 h after administration of the liposomal preparations. Lungs of animals exposed to paraquat were extensively damaged as evidenced by an increase in lung weight and decreases in pulmonary angiotensin converting enzyme and alkaline phosphatase activities. Also, paraquat treatment resulted in a significant reduction in glutathione (GSH) concentration in the lung and an elevation in microsomal lipid peroxidation levels, as measured by the formation of diene conjugates. Treatment of paraquat-injected rats with plain liposomes did not significantly alter paraquat-induced changes of all parameters examined. On the other hand, treatment of rats with alpha-tocopherol liposomes, 24 h after paraquat administration, resulted in a significant increase in pulmonary alpha-tocopherol concentrations as well as a reduction in paraquat-induced changes in lipid peroxidation, GSH concentration, and lung angiotensin converting enzyme and alkaline phosphatase activities. The results of the present study suggest that alpha-tocopherol, administered directly to the lung in a liposomal form, may serve as a potentially effective pharmacological agent in the treatment of paraquat-induced lung injury.

Alkaline Phosphatase↗
PubMed1994

Differential expression of interleukin-2 receptor alpha and beta chains in relation to natural killer cell subsets and aerobic fitness.

Immunophenotyping by dual parameter flow cytometry was used to compare the expression of interleukin-2 receptor alpha and beta chains on lymphocyte subsets in the peripheral blood of 7 trained and 6 untrained volunteers (respective VO2max 57.0 +/- 6.1 and 39.0 +/- 4.5 ml.kg-1.min-1). Venous blood samples were collected at least 36 h after the most recent exercise session. The trained subjects had higher circulating counts (10(9).l-1) of total leukocytes (5.80 +/- 0.83 vs. 4.63 +/- 0.21, p < 0.05), granulocytes (3.14 +/- 0.72 vs. 1.90 +/- 0.30, p < 0.05), and NK cells (CD16+, 0.32 +/- 0.14 vs. 0.16 +/- 0.05, p < 0.05; CD56+, 0.41 +/- 0.14 vs. 0.21 +/- 0.03, p < 0.01), but lower lymphocyte counts than their sedentary peers (1.90 +/- 0.22 vs. 2.26 +/- 0.25, p < 0.05). Counts for T cells (CD3+) and B cells (CD19+), and the CD4+/CD8+ ratio did not differ between the two subject groups. The p55-IL-2 receptor alpha expression (CD25+: 0.63 +/- 0.11 vs. 0.69 +/- 0.17) was unrelated to training, but the p70-75-IL-2 receptor beta expression was higher in the active group (p70/Mik-beta 1+: 0.42 +/- 0.09 vs. 0.20 +/- 0.06, p < 0.001; p75/TU27+: 0.36 +/- 0.08 vs. 0.17 +/- 0.07, p < 0.005). Beta chain co-expression was also higher on NK cell subsets (p < 0.001) in trained than in sedentary subjects. Aerobic power was strongly correlated with IL-2R beta expression (r = 0.914, p < 0.001 for Mik-beta 1; r = 0.884, p < 0.005 for TU27).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Exercise and training: influences on cytotoxicity, interleukin-1, interleukin-2 and receptor structures.

Exercise responses are discussed with particular reference to the functional system involving interleukin-1, interleukin 2 and cytotoxicity. Prolonged endurance exercise causes an increase in plasma levels of interleukin-1, possibly as a response to muscle injuries, but plasma interleukin-2 levels generally fall. The latter change probably reflects stronger binding, consequent upon increased expression of p70-75 receptors for IL-2, and changes in the distribution or activity of target cells; IL-1 secretion may enhance the responsiveness of peripheral blood mononuclear cells, but prostaglandin secretion decreases their IL-2 production. Moderate exercise increases the cytolytic action of NK cells, but there is a prolonged fall of cytolytic activity after exhausting or psychologically stressful exercise; again these responses probably reflect altered IL-2 levels or receptor expression. Appropriately graded training reduces the adverse immune reactions associated with challenging exercise. Cross-sectional comparison and training experiments both show an increased expression of p70-75 IL-2 receptors on the NK cells of active individuals. Moreover, moderate training reduces the exercise-induced suppression of IL-2 production. However, training that is pursued to the level of staleness, nutrient deficiency or muscle damage has a negative impact upon both the production of interleukins and the leukocyte response. Coaches must thus gauge training programs to optimize not only physiological function but also immune responses.

Cytotoxicity, Immunologic↗
PubMed1994

Incorporation of alpha-tocopherol in liposomes promotes the retention of liposome-encapsulated glutathione in the rat lung.

The present study was undertaken to investigate whether alpha-tocopherol incorporated in liposomes could improve the retention of entrapped glutathione (GSH) in the lung following intratracheal instillation in rats. Rats were treated with a single dose of [3H]GSH entrapped in liposomes with or without 30 mol% alpha-tocopherol and killed 0, 24 or 48 h later. The retention of GSH in the lung was assessed by measuring the recovery of either 3H-label or GSH in the lung. Animals instilled with free [3H]GSH were found to retain only 2% of the administered dose at 24 h after treatment and no detectable radioactivity at 48 h. Liposome encapsulation altered the pulmonary retention of GSH with 18 and 10% of radioactivity remaining in the lung at 24 and 48 h post-treatment, respectively. The instillation of GSH encapsulated in alpha-tocopherol-containing liposomes resulted in the highest level of GSH retention in the lung, namely 37 and 30% of the administered GSH dose at 24 and 48 h, respectively. Results from Sepharose 4B column chromatography revealed that lung homogenates, obtained from rats instilled with GSH entrapped in alpha-tocopherol-containing liposomes, 24 and 48 h earlier, contained 2 eluted GSH-related components--one associated with the liposomal lipid marker in the void volume and the other as free GSH tripeptide, suggesting a slow sustained release effect mediated by the liposomal formulation. The same liposome preparation containing both alpha-tocopherol and GSH also conferred better protection against FeADP-induced lipid peroxidation than liposomes containing either alpha-tocopherol or GSH alone, indicative of a potentially effective antioxidant formulation for treating oxidative lung injury.

Animals↗
PubMed1994

Unilamellar liposomes modulate secretion of tumor necrosis factor by lipopolysaccharide-stimulated macrophages.

Liposomal encapsulation of antimicrobial agents has been used to improve drug delivery, particularly against intracellular pathogens. The effect of unilamellar liposomes on macrophage activation in response to Escherichia coli lipopolysaccharide was examined. Liposomes caused a dose- and time-dependent inhibition of tumor necrosis factor release by lipopolysaccharide-treated cells. The accumulation of tumor necrosis factor mRNA transcripts was unaffected, suggesting a posttranscriptional mechanism for this effect. However, induction of macrophage procoagulant activity was unaffected by liposomes, indicating a selective rather than a global inhibition. These data suggest that liposomes used for drug delivery may modulate the host response to infection.

Animals↗
PubMed1994

Potential impact of physical activity and sport on the immune system--a brief review.

Description is given of methods that can evaluate the main functional elements of the immune system. Acute responses to exercise depend on the intensity and duration of the required activity relative to the individual's fitness level. Moderate endurance exercise causes either no change or an enhancement of such indices as total leucocyte count, granulocyte, monocyte, lymphocyte and natural killer cell count, total T cell count, helper:suppressor cell ratio, cell proliferation in response to mitogens, serum immunoglobulin levels, and in vitro immunoglobulin production. However, exhausting exercise tends to produce adverse changes in these same indices, particularly if the physical activity is accompanied by environmental or competitive stress. Moderate, appropriately graded training reduces reactions to any given absolute intensity of exercise. When pursuing a more demanding training regimen, it is important that the exerciser optimize immune responses. If athletic preparation is pursued to the level of staleness and/or muscle damage, it can have substantial negative implications for many aspects of immune function, including resistance to acute infections, HIV infections, ageing, cancer and other conditions influenced by the immune system.

Antibody Formation↗
PubMed1994

Infection in athletes.

Coaches and athletic team physicians have provided anecdotal information and case studies to support their beliefs that athletes may be unusually prone to illness during strenuous training or competition. Many athletes, in contrast, believe that physical activity improves their resistance to infectious disease. However, it is generally agreed that the stress of competition may make athletes temporarily more susceptible to infectious illness. A review of the literature shows that upper respiratory tract infections and skin infections are more prevalent in top level athletes than in the general population, particularly during periods of intensive training. Exercise induced changes occur in both the innate and adaptive components of the immune system; however, the relative importance of each component is unknown. Strenuous exertion and contact sports may compromise host defence both by reducing physical protection and by impairing immunosurveillance. Skin lacerations, vigorous sweating and maceration of the dermis impair the defence normally provided by the skin surface. In addition, adverse changes in soluble and cellular components of the immune system can increase susceptibility to infection. Persistence with strenuous training during an infectious illness can have deleterious effects; not only is athletic performance impaired, but the severity of the disease process can be augmented.

Exercise↗
PubMed1994

Exercise and the immune system. Natural killer cells, interleukins and related responses.

The main methods for the evaluation of natural killer (NK, CD16+ CD56+) cells, interleukins and related subsets of lymphocytes are briefly described. Moderate endurance exercise causes either no change or an increase in lymphocyte and NK cell counts, total T cell (CD3+) count, the ratio of T helper (CD3+ CD4+) to T suppressor (CD3+ CD8+) cells, mitogen-induced lymphocyte proliferation, serum immunoglobulin levels and in vitro immunoglobulin production. Plasma levels of interleukin-1 increase but interleukin-2 (IL-2) levels generally fall. Decreases in plasma IL-2 levels reflect increased expression of beta (CD122) receptors for IL-2, and thus increased binding of IL-2, changes in cell distribution or a lesser production of IL-2 by peripheral blood mononuclear cells. Exercise to exhaustion induces adverse changes in many of these indices of immune function, particularly if the physical activity is accompanied by psychological or environmental stress. Moderate, appropriately graded training reduces the adverse reactions initially associated with a given bout of exhausting exercise, and cross-sectional comparisons show an increased expression of beta IL-2 receptors on the peripheral blood mononuclear cells of trained individuals. However, excessive training, nutrient deficiency and/or muscle damage has adverse consequences for both the production of interleukins and the response of the immune system to these cytokines.

Exercise↗
PubMed1994

Liposomes in pulmonary applications: physicochemical considerations, pulmonary distribution and antioxidant delivery.

The application of liposomes for improved drug delivery to the lung is promising. Liposome-mediated pulmonary drug delivery promotes an increase in drug retention-time in the lung and more importantly, a reduction in extrapulmonary side-effects, invariably resulting in enhanced therapeutic efficacies. The engineering of an effective liposomal drug formulation for inhalation therapy must take into consideration the leakage problem associated with the nebulization process; vesicle stability and release kinetics within the pulmonary milieu; and, the altered pharmacokinetics of the entrapped drug. The delivery of liposome-entrapped antioxidants via the tracheobronchial route has been found to be very useful in increasing the half-times of the administered agents, thus providing a sustained release effect for prolonged drug action. The entrapment in liposomes of alpha-tocopherol, an extremely insoluble but highly effective antioxidant, has been shown to be very effective in ameliorating oxidant-induced injuries in the lung. The use of bifunctional liposomes containing two antioxidants have been determined to provide excellent resistance to an oxidative challenge and appears to hold promise for improved clinical applications in antioxidant therapy.

Animals↗
PubMed1994

Infectious diseases in athletes: new interest for an old problem.

Interest in infectious disease among athletes has been greatly stimulated over the past decade by the development of modern automated systems that can enumerate specific elements of the immune system. Research has confirmed earlier clinical and animal studies in showing that either a single bout of exhausting exercise or persistent over-training can increase susceptibility to upper respiratory and other viral infections, although resistance to bacterial infections is apparently unaltered. Such findings do not seem a non-specific response to cooling and drying of the tracheal mucosa. Rather, heavy exercise has a depressant effect upon the T cell/interleukin/NK cell system which may persist for a week or more. In contrast, moderate training enhances immune defences. Given the negative impact of acute viral infections upon both competitive performance and morale, plus the occasional incident of sudden death associated with viral myocarditis, it is important that sports physicians minimize the incidence of viral infections in the athletes for whom they are responsible. Potential tactics include maintenance of immunization schedules, minimizing of exposure to infection, avoidance of over-training, maintenance of an adequate diet, and reduction of psychological and environmental stress. In top athletes, the regular monitoring of immune status may also be warranted, with the possible administration of immunoglobulins and prostaglandin inhibitors as required.

Communicable Diseases↗
PubMed1993

Pulmonary uptake of liposome-associated alpha-tocopherol following intratracheal instillation in rats.

This study examined the uptake and subcellular distribution of alpha-tocopherol in the lung following intratracheal instillation of liposome-associated alpha-tocopherol in rats. The liposomal suspension was composed of dipalmitoylphosphatidylcholine (DPPC) and alpha-tocopherol (molar ratio 7:3), labelled with [3H]alpha-tocopherol and [14C]cholesterol. Following intratracheal administration of the liposomal preparation (2 mg alpha-tocopherol/animal), the recovery of [3H]alpha-tocopherol in the lung was maximal (87% of initial dose) 1 h after treatment; thereafter, alpha-tocopherol levels remained relatively high (no less than 73% of initial dose) for the rest of the 72-h experimental period. This treatment effect/resulted in a 16-fold increase in pulmonary total alpha-tocopherol concentration 72 h post-instillation. No radioactivity was detected in the blood, liver, kidney, pancreas, spleen and heart of animals during the 72-h experimental period. [3H]alpha-Tocopherol was recovered largely from cytosolic (45%) and nuclear (36%) fractions of lung and to a lesser extent, from microsomal (11%) and mitochondrial (9%) fractions. Chromatographic analysis of the subcellular fractions revealed that [3H]alpha-tocopherol was co-eluted with 14C-labelled liposomal lipids. Our in-vitro study, involving the incubation of Fe(3+)-ADP (a pro-oxidant) with mitochondrial or microsomal fractions isolated from lung tissues of animals treated with liposome-associated alpha-tocopherol, provided evidence that alpha-tocopherol levels present in the membranes of these subcellular fractions were sufficient to protect against oxidant-induced lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

Distribution of free and liposome-encapsulated cefoxitin in experimental intra-abdominal sepsis in rats.

The distributions of radiolabelled free cefoxitin (FC) and liposome-encapsulated cefoxitin (LC) were compared in an animal model of intra-abdominal sepsis. Intraperitoneally administered LC was initially retained in the peritoneal cavity with subsequent preferential drug targeting to the liver (14% injected LC) and spleen (6% injected LC) by 3 h post-injection. Differing patterns of liposomal drug and lipid retention indicated that drug release from the liposome complex occurred within the peritoneum, liver and spleen. Intraperitoneal FC was rapidly taken up into the systemic circulation, with peak recovery in the blood (9% injected FC) and liver (5% injected FC) at 1 h post-injection. FC was also rapidly eliminated; 7% of the injected drug was recovered in the kidney 1 h post-injection. A negligible amount of FC was recovered in the spleen and very little FC or LC was found in the lungs of treated animals. Unlike FC, LC was found to provide a sustained bactericidal drug level (> 40 micrograms mL-1) in the peritoneal fluid for up to 5 h post-injection. LC also achieved significantly higher drug levels, compared with FC, within the liver at 3 and 5 h post-injection. Since severe intra-abdominal sepsis is often characterized by the presence of intraphagocytic bacteria in hepatic and splenic reticuloendothelial systems, the enhanced delivery of liposome-encapsulated anti-microbial agents, such as cefoxitin, to the liver and spleen may provide a more effective treatment for the septic condition.

Abdomen↗
PubMed1992

Protective effect of liposome-associated alpha-tocopherol against paraquat-induced acute lung toxicity.

The present study was undertaken to investigate whether alpha-tocopherol, entrapped in liposomes and delivered directly to the lung, could protect against paraquat-induced lung damage in the rat. Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or DPPC/alpha-tocopherol liposomes were administered intratracheally to animals 24 hr prior to an intraperitoneal injection of paraquat (20 mg/kg); rats were killed 24 or 48 hr after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were damaged extensively as evidenced by an increase in lung weight and a significant reduction in lung angiotensin-converting enzyme (ACE) activity and cytochrome P450 concentration. Furthermore, paraquat treatment resulted in a significant decrease in reduced glutathione (GSH) concentrations and a marked elevation in microsomal lipid peroxidation levels as measured by the formation of diene conjugates. Pretreatment of rats with DPPC liposomes alone did not alter significantly the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with DPPC/alpha-tocopherol liposomes 24 hr prior to paraquat challenge resulted in a significant increase in pulmonary alpha-tocopherol concentrations and antagonized paraquat-induced changes in lipid peroxidation, GSH/GSSG ratio, lung ACE activity and cytochrome P450 concentrations. Results of this study suggested that alpha-tocopherol, delivered directly to the lung in a liposomal formulation 24 hr prior to paraquat administration, confers protection against paraquat-induced lung damage.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Nitrofurantoin-induced pulmonary toxicity. In vivo evidence for oxidative stress-mediated mechanisms.

The present study was carried out to examine whether nitrofurantoin-induced pulmonary toxicity in normal rats was mediated via oxidant stress mechanisms. The relative importance of the cellular antioxidant enzymes in nitrofurantoin toxicity was also assessed. For this, the pulmonary toxicity induced by nitrofurantoin in rats was evaluated at various time intervals after a single subcutaneous injection. Data from this study showed that nitrofurantoin (200 mg/kg, s.c.) resulted in transient but measurable lung damage as evidenced by the increases in wet lung weight/body weight ratio and decreases in lung angiotensin converting enzyme activity. A transient decrease in GSH concentrations with a concurrent increase in GSSG concentrations as well as an increase in lipid peroxidation levels (measured by the formation of diene conjugates and thiobarbituric acid reactants) were also evident in lungs of nitrofurantoin-treated rats. In addition, nitrofurantoin did not alter the pulmonary superoxide dismutase and glutathione peroxidase activities, but it did produce transient decreases in catalase and glutathione reductase activities. These data indicate that impairment of the ability of the lung to detoxify reactive oxygen species may play an important role in the development of nitrofurantoin-induced pulmonary toxicity. The results of the present study suggest that nitrofurantoin can damage the lungs of rats, probably through oxidative stress-mediated mechanisms. Also, our data have provided in vivo evidence for substantiating lipid peroxidation as a possible cause of lung damage.

Animals↗