[Show abstract][Hide abstract] ABSTRACT: Background
Metabolic syndrome (MetS) is a clustering of cardiovascular risk factors, which is associated with diabetes mellitus and cardiovascular disease. Lifestyle interventions applied to people with MetS has considerable beneficial effects on disease preventive outcomes. This study aimed to examine the effects of 1-year of yoga exercise on the cardiovascular risk factors including central obesity, hypertension, dyslipidemia and hyperglycemia in middle-aged and older Hong Kong Chinese adults with MetS.
Adults diagnosed with MetS using National Cholesterol Education Program criteria (n = 182; mean ± SD age = 56 ± 9.1) were randomly assigned to a 1-year yoga intervention group or control group. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol were examined at baseline, midway, and on completion of the study. Physical activity level and caloric intake were assessed and included in the covariate analyses.
A reduction of the number of diagnostic components for MetS was found to be associated with the yoga intervention. Waist circumference was significantly improved after the 1-year yoga intervention. A trend towards a decrease in systolic blood pressure was observed following yoga intervention.
These results suggest that yoga exercise improves the cardiovascular risk factors including central obesity and blood pressure in middle-aged and older adults with MetS. These findings support the complementary beneficial role of yoga in managing MetS.
[Show abstract][Hide abstract] ABSTRACT: Regular intake of green tea (Camellia sinensis) lowers DNA damage in humans, but molecular mechanisms of genoprotection are not clear. Protection could be via direct antioxidant effects of tea catechins, but, paradoxically, catechins have pro-oxidant activity in vitro, and it is hypothesized that mechanisms relate to redox-sensitive cytoprotective adaptations. We investigated this hypothesis, focusing particularly on effects on the DNA repair enzyme human oxoguanine glycosylase 1 (hOGG1), and heme oxygenase-1, a protein that has antioxidant and anti-inflammatory effects. A randomized, placebo-controlled, human supplementation study of crossover design was performed. Subjects (n = 16) took a single dose (200 mL of 1.5%, w/v) and 7-days of (2 × 200 mL 1%, w/v per day) green tea (with water as control treatment). Lymphocytic DNA damage was ∼30% (p < 0.001) lower at 60 and 120 min after the single dose and in fasting samples collected after 7-day tea supplementation. Lymphocytic hOGG1 activity was higher (p < 0.0001) at 60 and 120 min after tea ingestion. Significant increases (p < 0.0005) were seen in hOGG1 activity and heme oxygenase-1 after 7 days. Results indicate that molecular triggering of redox-sensitive cytoprotective adaptations and posttranslational changes affecting hOGG1 occur in vivo in response to both a single dose and regular intake of green tea, and contribute to the observed genoprotective effects of green tea.
[Show abstract][Hide abstract] ABSTRACT: There are a multitude of antioxidants in foods, especially in foods of plant origin. Higher intake of antioxidant-rich foods is clearly associated with better health and functional longevity. The specific agents and mechanisms responsible are not yet clear, but there is convincing evidence that including more plant-based, antioxidant-rich foods, herbs, and beverages in the diet is effective in promoting health and lowering risk of various age-related diseases. The content of some individual antioxidants, such as vitamin C, in food can be measured, but it is not feasible to attempt to measure each antioxidant separately, and methods have been developed to assess the "total antioxidant content" of foods. One of the most widely used methods is the ferric reducing/antioxidant power (FRAP) assay, which is relatively simple, quick, sensitive, and inexpensive to perform. There are many published studies that have used the FRAP assay, and these have generated a very large database of total antioxidant content of foods that can help guide food choices for increased antioxidant intake. The FRAP assay has also been used to assess the bioavailability of antioxidants in foods and to investigate the effects of growing conditions, storage, processing, and cooking method on the total antioxidant content of food. The test can be employed as a quality control check device, and to detect adulteration of food. Furthermore, in a modified form (FRASC), the assay can measure ascorbic acid content almost simultaneously with the total antioxidant content of the sample. In this chapter, basic concepts of oxidation and the role of antioxidants, as well as the types and action of different antioxidants in foods will be reviewed briefly, and the underpinning concepts and evidence for health benefits of increased intake of dietary antioxidants will be discussed, with some focus on vitamin C, and also in the context of our evolutionary development. The basic concepts and limitations of measuring "total antioxidant content" of food will be presented. The FRAP assay and the modified version FRASC will be described, and the total antioxidant content (as the FRAP value) of a range of foods will be presented. Finally, issues of bioavailability and redox balance will be discussed in relation to the biological significance and molecular action of antioxidants in foods, some caution and caveats are presented about overcoming biological barriers to absorption of antioxidant phytochemicals, and research needs to further our understanding in the important area of food, antioxidants, and health will be highlighted.
Advances in food and nutrition research 02/2014; 71:1-53. DOI:10.1016/B978-0-12-800270-4.00001-8
[Show abstract][Hide abstract] ABSTRACT: Doxorubicin is an effective chemotherapeutic agent used to treat malignancies but it causes cardiomyopathy. This study examined the cellular effects of desacyl ghrelin on myocardial fibrosis and apoptosis in a doxorubicin cardiomyopathy experimental model. Adult C57BL/6 mice received an intraperitoneal injection of doxorubicin to induce cardiomyopathy, followed by 4-day treatment of saline (control) or desacyl ghrelin with or without [D-Lys3]-GHRP-6 (a growth hormone secretagogue receptor or GHSR1a antagonist). Ventricular structural and functional parameters were evaluated by transthoracic echocardiography. Molecular and cellular measurements were performed in ventricular muscle to examine myocardial fibrosis and apoptosis. Cardiac dysfunction was induced by doxorubicin as indicated by significant decreases in ventricular fractional shortening and ejection fraction. This doxorubicin-induced cardiac dysfunction was prevented by the treatment of desacyl ghrelin no matter with or without the presence of [D-Lys3]-GHRP-6. Doxorubicin induced fibrosis (accumulated collagen deposition and increased CTGF), activated apoptosis (increased TUNEL index, apoptotic DNA fragmentation and caspase-3 activity and decreased Bcl-2/Bax ratio), and suppressed phosphorylation status of prosurvival signals (ERK1/2 and Akt) in ventricular muscles. All these molecular and cellular alterations induced by doxorubicin were not found in the animals treated with desacyl ghrelin. Notably, the changes of the major markers of apoptosis, fibrosis and Akt phosphorylation were found to be similar in the animals following the treatment of desacyl ghrelin with and without GHSR antagonist [D-Lys3]-GHRP-6. These findings clearly demonstrate that desacyl ghrelin protects the cardiomyocytes against the doxorubicin-induced cardiomyopathy by preventing the activation of cardiac fibrosis and apoptosis.
[Show abstract][Hide abstract] ABSTRACT: Regular intake of green tea associates with lower DNA damage and increased resistance of DNA to oxidant challenge. However, in vitro pro-oxidant effects of green tea have been reported. Both effects could be mediated by hydrogen peroxide (H2O2) which is generated by autoxidation of tea catechins. In large amounts, H2O2 is genotoxic, but low concentrations could activate the redox-sensitive antioxidant response element (ARE) via the Keap-1/Nrf2 redox switch, inducing genoprotective adaptations. Our objective was to test this hypothesis.
Peripheral lymphocytes from healthy volunteers were incubated for 30 minutes at 37°C in freshly prepared tea solutions (0.005, 0.01, 0.05%w/v (7, 14, 71 µmol/l total catechins) in phosphate buffered saline (PBS), with PBS as control) in the presence and absence of catalase (CAT). H2O2 in tea was measured colorimetrically. Oxidation-induced DNA lesions were measured by the Fpg-assisted comet assay.
H2O2 concentrations in 0.005, 0.01, and 0.05% green tea after 30 minutes at 37°C were, respectively, ∼3, ∼7, and ∼52 µmol/l. Cells incubated in 0.005 and 0.01% tea showed less (P < 0.001) DNA damage compared to control cells. Cells treated with 0.05% green tea showed ∼50% (P < 0.001) more DNA damage. The presence of CAT prevented this damage, but did not remove the genoprotective effects of low-dose tea. No significant changes in expression of ARE-associated genes (HMOX1, NRF2, KEAP1, BACH1, and hOGG1) were seen in cells treated with tea or tea + CAT.
Genoprotection by low-dose green tea could be due to direct antioxidant protection by green tea polyphenols, or to H2O2-independent signalling pathways.
Redox report: communications in free radical research 07/2013; 18(4):150-154. DOI:10.1179/1351000213Y.0000000051 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fruits can be defined as the edible, usually sweet and fleshy form of the ripened ovary of a seed-bearing plant; they include apples, citrus fruits, kiwifruit, berries, red and green capsicum, banana, avocado and tomatoes. There is a huge variety of phytochemicals in fruits, many of which have antioxidant properties. These include ascorbic acid (vitamin C), vitamin E, the carotenoid family, which includes lycopene, lutein and zeaxanthin, and the flavonoid ‘superfamily’, which encompasses polyphenolic subfamilies such as the anthocyanins and catechins. This chapter focuses on the antioxidant content of different fruits, the factors that affect this, the bioaccessibility, absorption and systemic distribution (‘bioavailability’) of fruit antioxidants, and how these can be modulated. The possible effects of higher intake or improved bioavailability of antioxidants on human health are also discussed briefly from the perspective of human evolution and dietary requirements and biological restrictions on antioxidant bioavailability.
Bioactives in Fruit, 06/2013: pages 35-58; , ISBN: 9780470674970
[Show abstract][Hide abstract] ABSTRACT: Allantoin in human plasma is a specific biomarker of oxidative stress. We describe a sensitive method to measure plasma allantoin using isocratic liquid chromatography and mass spectrometry (LC-MS/MS).
Direct injection of deproteinized plasma into the LC-MS/MS system was performed. The method was technically evaluated. Results on 200 healthy and 35 Type 2 diabetic Chinese subjects were compared.
Dose-response of allantoin was linear to at least 21 pmol (20 μmol/l in plasma); LOD was 0.16 pmol; recovery 99.2-100.2% at 1-5 μmol/l; accuracy, 98.5-100.8%; within-day and between-day CVs (n=6), <4.0% (at 5.00-40 μmol/l) and <2.0% (at 1-5 μmol/l), respectively. Plasma allantoin in diabetic patients was ~8-fold higher than in healthy subjects; mean(SD): 8.82(7.26) and 1.08(0.86) μmol/l, respectively (p<0.0001). Allantoin was slightly higher in healthy men than in age- and BMI-matched women: 1.21(0.99) μmol/l, n=88 compared to 0.97(0.74) μmol/l, n=112; p<0.001. No association with age was seen. Gender difference was also seen in the diabetes patients: men, n=14, 11.57(8.57) μmol/l; women, n=21, 6.99(5.75) μmol/l, p<0.05.
Based on 95th percentiles of the healthy subjects, plasma allantoin >2.2 μmol/l in women and >3.1 μmol/l in men indicates increased oxidative stress. Allantoin in diabetes subjects is clearly and markedly increased. The method will facilitate future studies of oxidative stress in human biomonitoring studies.
Clinica chimica acta; international journal of clinical chemistry 06/2013; 424. DOI:10.1016/j.cca.2013.06.015 · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The comet assay is widely used in human biomonitoring to measure DNA damage as a marker of exposure to genotoxic agents or to investigate genoprotective effects. Studies often involve small numbers of subjects, and design may be sub-optimal in other respects. In addition, comet assay protocols in use in different laboratories vary significantly. In spite of these difficulties, it is appropriate to carry out a pooled analysis of all available comet assay biomonitoring data, in order to establish baseline parameters of DNA damage, and to investigate associations between comet assay measurements and factors such as sex, age, smoking status, nutrition, lifestyle, etc. With this as its major objective, the ComNet project has recruited almost 100 research groups willing to share datasets. Here we provide a background to this project, discussing the history of the comet assay and practical issues that can critically affect its performance. We survey its diverse applications in biomonitoring studies, including environmental and occupational exposure to genotoxic agents, genoprotection by dietary and other factors, DNA damage associated with various diseases, and intrinsic factors that affect DNA damage levels in humans. We examine in depth the quality of data from a random selection of studies, from an epidemiological and statistical point of view.
Mutation Research/Reviews in Mutation Research 01/2013; 753:24-40. DOI:10.1016/j.mrrev.2013.10.001 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Green tea (Camellia sinensis) catechin profiles in plasma and urine following single dosing and regular ingestion of green tea are not clear. We performed a placebo-controlled intervention study with sixteen healthy volunteers to determine changes in total and free catechins after a single dose and following 1 week of twice-daily green tea. Blood and urine samples were collected before (fasting) and after (60 and 120 min for blood; 90 and 180 min for urine) drinking 200 ml of 1·5 % (w/v) green tea or water (n 8 each), and fasting samples were again collected after 7 d of 150 ml of 1 % (w/v) supplemental green tea or water twice daily. After a 4-week washout, subjects were crossed onto the other treatment and procedures repeated. Plasma results at 1 h post-ingestion showed elevated (P < 0·05) mean epigallocatechin gallate (EGCG; 310 (sd 117) nmol/l; all in free form), epigallocatechin (EGC; 192 (sd 67) nmol/l; 30 % free) and epicatechin gallate (ECG; 134 (sd 51) nmol/l; 75 % free). Fasting plasma after 7 d of regular intake showed increased (P < 0·05) EGCG (80 v. 15 nmol/l at baseline) and ECG (120 v. 40 nmol/l), with ≥ 90 % of both in their conjugated forms. Total EGC was < 10 nmol/l. Post-ingestion conjugation and renal loss of EGC and epicatechin were rapid and high, but were negligible for EGCG and ECG. In the green tea consumed, the content was EGCG >EGC >ECG, and the acute plasma response mirrored this. However, after chronic consumption there was almost no EGC found in fasting plasma, some EGCG was present, but a rather high level of ECG was maintained.
The British journal of nutrition 10/2012; 109(12):1-9. DOI:10.1017/S0007114512004370 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heme oxygenase-1 (HMOX-1) is activated by oxidative stress, and gene responsiveness is reportedly determined by the number of dinucleotide (GT(n)) repeats in its highly polymorphic promoter region. "Short" (S; GT(n)<25) alleles reportedly associate with higher response, lower oxidative stress, lower risk of type 2 diabetes mellitus (type 2DM), and better glycemic control and outcome, but data are conflicting. We investigated GT(n) in type 2DM subjects (all ethnic Chinese) in relation to basal glycemic control, oxidative stress, and outcome during up to 9 years' follow-up. Fasting blood from 418 type 2 DM subjects was collected at entry for GT(n) genotyping, glycated hemoglobin, glucose, lipids, and biomarkers of oxidative stress and antioxidants. A subset (n=368) was followed for up to 9 years for incident complications or death. GT(n) genotype distribution was 128, 182, and 108 for, respectively, S/S, S/L, and L/L. No significant differences in glycemic control, lipids, or oxidative stress were seen across genotypes. During follow-up, 168/368 subjects developed complications. No association was seen with GT(n). No difference in plasma HO-1 was seen between genotypes in a small substudy (S/S n=21 vs L/L n=23). Glycated hemoglobin and lymphocytic DNA damage was higher (p<0.05) at entry in the incident complications group. No other significant differences were seen in oxidative stress or antioxidants. Data do not support the postulated link between HMOX-1 microsatellite polymorphism and type 2 DM or the putative beneficial effect of the S allele on glycemic control, oxidative stress, or outcome in type 2 DM patients, at least in this particular population.
Free Radical Biology and Medicine 04/2012; 53(1):60-3. DOI:10.1016/j.freeradbiomed.2012.04.017 · 5.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A commonly held belief is that higher intake of antioxidants will promote better health through enhanced antioxidant status and lowered oxidative stress. However, the benefits of antioxidant-rich foods have not been reproduced in supplementation trials with pure antioxidants. This has driven research and commercial interest in foods, including traditional foods and their components, with enhanced antioxidant content and improved antioxidant bioavailability, which in many cases is very low. In this paper, evidence for the health benefits of antioxidant-rich foods and methods to increase the antioxidant content and bioavailability of food antioxidants are reviewed briefly, and the concept that increased food antioxidant content/intake per se is beneficial is examined from a cautionary perspective, considering issues of low bioavailability, rapid catabolism, biotransformation and the paradoxical pro-oxidant effects of dietary antioxidants.
International Journal of Food Sciences and Nutrition 03/2012; 63 Suppl 1(S1):62-70. DOI:10.3109/09637486.2011.621934 · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Electronic Health Records (EHR) form a valuable resource in the healthcare enterprise because clinical evidence can be provided to identify potential complications and support decisions on early intervention. Simple string matching, the common search algorithm, is not able to map a query to the similar health records in the database with respect to the medical concepts. A novel ontological vector model supported by the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) is proposed in this paper to project the disease terms of a health record to a feature space so that each health record can be characterized using a feature vector, giving a fingerprint of the record. The similarity between the query and database health records was measured by similarity measures of their feature vectors and string matching score respectively. Three types of similarity measures were considered in this study, namely, Euclidean distance (ED), direction cosine (DC) and modified direction cosine (mDC). Medical history and carotid ultrasonic imaging findings were collected from 47 subjects in Hong Kong. The dataset formed 1081 pairs of health records and ROC analysis was used to evaluate and compare the accuracy of the ontological vector model and simple string matching against the agreement of the presence or absence of carotid plaques identified by carotid ultrasound between two subjects. It was found that the score generated by simple string matching was a random rater but the ontological vector model was not. In other words, the degree of health record similarity based on the ontological vector model is associated with the agreement of atherosclerosis between two patients. The vector model using feature terms at the SNOMED-CT level 4 gave the best performance. The performance of mDC was very close to that of ED and DC but the properties of mDC make it more suitable for the retrieval of similar health records. It was also shown that the ontological vector model was enhanced by the support vector classifier approach.
[Show abstract][Hide abstract] ABSTRACT: The comet assay measures DNA damage in individual cells (usually lymphocytes) and is widely used in biomonitoring studies. Lymphocytes are harvested and are usually cryopreserved for batch testing. We investigated cell loss during harvesting, cryopreservation, thawing, and washing of human peripheral lymphocytes and compared DNA damage, using the Fpg-assisted comet assay for oxidation-induced DNA lesions, in freshly harvested cells and cells that were thawed and tested after cryopreservation of 2-3 days and 4 weeks. Lymphocyte numbers were measured in fresh venous blood and after the steps of harvesting, cryopreservation, and washing. Results showed that >50% of lymphocytes in whole blood were harvested, but ∼60% were lost during washing. Loss during washing was not different (P>0.05) between fresh cells and cells thawed and washed after 2-3 days or 4 weeks cryopreservation. No change in DNA damage was seen after cryopreservation and thawing: mean (SD) % DNA in comet tail was 11.2 (1.53) in freshly harvested cells, 12.9 (1.39) in 2-3 days cryopreserved cells, and 12.9 (2.0) in cells tested after 4 weeks cryopreservation (P>0.05). Results indicate that there is no predominant loss of more highly damaged cells during cryopreservation and thawing and there is no induction of oxidation-induced DNA lesions in cryopreserved cells stored for up to 4 weeks.
Biopreservation and Biobanking 12/2011; 9(4):343-7. DOI:10.1089/bio.2011.0024 · 1.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An HPLC method with photodiode array detection was used for the quantification of 11 synthetic dyes in
87 snack food products commonly consumed by children in Hong Kong, China. Dietary exposure to synthetic
colours was estimated using food-frequency questionnaire data obtained from 142 primary school children aged 8–9 years in three districts of Hong Kong. Dietary exposure to synthetic colours for an average primary school student was considerably lower than the threshold for acceptable daily intake (ADI) for their ages, except for sunset yellow FCF. Data obtained showed that the average daily intake of sunset yellow FCF (E110) was 51% over the ADI threshold in 9-year-old boys. The higher intakes of sunset yellow FCF were mainly due to the high consumption of soft drinks and desserts such as jellies, which have high concentrations of this synthetic colour additive.
Food Additives and Contaminants: Part B Surveillance 09/2011; 4(3):162-167. DOI:10.1080/19393210.2011.585246 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies have suggested that Lingzhi (Ganoderma lucidum) has antioxidant effects and possibly beneficial effects on blood pressure, plasma lipids and glucose, but these have not been confirmed in subjects with mild hypertension or hyperlipidaemia. The objective of the present study was to assess the cardiovascular, metabolic, antioxidant and immunomodulatory responses to therapy with Lingzhi in patients with borderline elevations of blood pressure and/or cholesterol in a controlled cross-over trial. A total of twenty-six patients received 1·44 g Lingzhi daily or matching placebo for 12 weeks in a randomised, double-blind, cross-over study with placebo-controlled run-in and cross-over periods. Body weight, blood pressure, metabolic parameters, urine catecholamines and cortisol, antioxidant status and lymphocyte subsets were measured after each period. Lingzhi was well tolerated and data from twenty-three evaluable subjects showed no changes in BMI or blood pressure when treated with Lingzhi or placebo. Plasma insulin and homeostasis model assessment-insulin resistance were lower after treatment with Lingzhi than after placebo. TAG decreased and HDL-cholesterol increased with Lingzhi but not with placebo in the first treatment period, but significant carry-over effects prevented complete analysis of these parameters. Urine catecholamines and cortisol, plasma antioxidant status and blood lymphocyte subsets showed no significant differences across treatments. Results indicate that Lingzhi might have mild antidiabetic effects and potentially improve the dyslipidaemia of diabetes, as shown previously in some animal studies. Further studies are desirable in patients with hyperglycaemia.
The British journal of nutrition 08/2011; 107(7):1017-27. DOI:10.1017/S0007114511003795 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The underlying mechanisms of adaptation from staying physically active are not completely revealed. This study examined the effects of 8 and 20 weeks of habitual voluntary exercise on the susceptibility of lymphocytes to oxidant-induced DNA damage, antioxidant enzyme activities in cardiac and skeletal muscles, and circulatory antioxidant profile. Forty young adult rats were randomly assigned to sedentary control and exercise groups for an experimental period of 8 or 20 weeks. Animals assigned to exercise groups were subjected to 24 h daily free access to an in-cage running wheel with circumference of 1.19 m. A magnetic digital counter was attached to the running wheel to record daily exercise distance run by the animals. Control rats were housed in cages without a running wheel, located next to the exercised animals. Body weight and food intake were recorded weekly. After the experimental periods of 8 and 20 weeks, blood, left ventricle, soleus and plantaris muscles were collected for analysis. No significant difference was found in plasma total antioxidant capacity between exercised and control animals in the 8 and 20 week groups according to our ferric reducing/antioxidant power (FRAP) analysis. However, modified FRAP for ascorbic acid (FRASC) analysis indicated that plasma ascorbic acid content was significantly increased by 46 and 34% in 8 and 20 week exercise groups, respectively, when compared with the corresponding control groups. Superoxide dismutase (SOD) activity was significantly elevated by 39% in erythrocytes of animals exercised for 8 weeks relative to control animals. In the 20 week exercise group, Glutathione peroxidase (GPx) activity in ventricle and plantaris was significantly upregulated by 477 and 290%, respectively, relative to control values. As demonstrated by comet assay, the oxidant-induced DNA damage was significantly reduced by 21 and 45% in lymphocytes of animals exercised for 8 and 20 weeks, respectively, when compared with the corresponding control lymphocytes. Our qRT-PCR analysis showed that the transcript expression of SOD2 was significantly elevated by 939% in lymphocytes of animals exercised for 8 weeks relative to control animals. Increased expressions of SOD2 (by 19%), catalase (25%), APEX nuclease (multifunctional DNA repair enzyme) 1 (APEX1; 46%), Protein kinase, DNA-activated, catalytic polypeptide (Prkdc; 9%) and O-6-methylguanine-DNA methyltransferase (Mgmt; 26%) were found in lymphocytes of animals exercised for 20 weeks relative to control rats. These results demonstrate that habitual exercise confers increased resistance of lymphocytes to oxidant-induced DNA damage, and this protective effect is possibly attributed to the regular exercise-induced elevated expression of antioxidant and DNA repairing enzymes.
[Show abstract][Hide abstract] ABSTRACT: Non-technical summary A pressure ulcer, also known as a pressure sore, bedsore or decubitus ulcer, results from localized ulcerated tissue breakdown caused by sustained, unrelieved mechanical pressure in the body–support interface such as with a bed, wheelchair and orthoses/prostheses. Pressure ulcers are common in the wheelchair bound or bedridden frail elderly patients with neuromuscular disorder and orthoses/prostheses clients. Pressure ulcers represent a significant health problem as they impose a heavy burden on sufferers, with negative psychological, physical, social and financial consequences. Most importantly, there are currently no effective therapies for preventing and treating pressure ulcers. In the present study, our data demonstrate that pharmacological inhibition of caspase is effective in alleviating muscle damage induced by prolonged moderate compression. These findings suggest that regimens targeting caspase/apoptosis inhibition might be of use to prevent or treat pressure ulcers.
Abstract There are currently no effective therapies for treating pressure-induced deep tissue injury. This study tested the efficacy of pharmacological inhibition of caspase in preventing muscle damage following sustained moderate compression. Adult Sprague–Dawley rats were subjected to prolonged moderate compression. Static pressure of 100 mmHg compression was applied to an area of 1.5 cm2 in the tibialis region of the right limb of the rats for 6 h each day for two consecutive days. The left uncompressed limb served as intra-animal control. Rats were randomized to receive either vehicle (DMSO) as control treatment (n= 8) or 6 mg kg−1 of caspase inhibitor (z-VAD-fmk; n= 8) prior to the 6 h compression on the two consecutive days. Muscle tissues directly underneath the compression region of the compressed limb and the same region of control limb were harvested after the compression procedure. Histological examination and biochemical/molecular measurement of apoptosis and autophagy were performed. Caspase inhibition was effective in alleviating the compression-induced pathohistology of muscle. The increases in caspase-3 protease activity, TUNEL index, apoptotic DNA fragmentation and pro-apoptotic factors (Bax, p53 and EndoG) and the decreases in anti-apoptotic factors (XIAP and HSP70) observed in compressed muscle of DMSO-treated animals were not found in animals treated with caspase inhibitor. The mRNA content of autophagic factors (Beclin-1, Atg5 and Atg12) and the protein content of LC3, FoxO3 and phospho-FoxO3 that were down-regulated in compressed muscle of DMSO-treated animals were all maintained at their basal level in the caspase inhibitor treated animals. Our data provide evidence that caspase inhibition attenuates compression-induced muscle apoptosis and maintains the basal autophagy level. These findings demonstrate that pharmacological inhibition of caspase/apoptosis is effective in alleviating muscle damage as induced by prolonged compression.
The Journal of Physiology 05/2011; 589(Pt 13):3349-69. DOI:10.1113/jphysiol.2011.209619 · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new approach for assigning bioactivity to individual components in extracts from natural products is presented and validated. 60 mixtures were created according to a uniform design from 12 chemical components of which 7 possessed antioxidant activity. The synthetic mixtures were characterized by chromatographic profiling and their antioxidant power was assessed by use of the Ferric Reducing Antioxidant Power (FRAP) assay. 40 of the prepared mixtures were used as a training set to create a cross validated partial least squares (PLS) regression model with the FRAP measurement as response. The remaining 20 mixtures were used as an independent external validation set. The bioactive signature was singled out from the multi-component PLS model using target projection (TP). In addition to excellent prediction performance of antioxidant strength from the bioactive signature, our approach, called Quantitative Pattern-Activity Relationship (QPAR), was able to rank 6 of the 7 bioactive components according to individual bioactive strength. The ratios of bioactive capacity of the two most active components to the two least active components were close to 100 to 1. This explains why one of the two least bioactive components was not detected.