Biomedical subjects

J M Allen

Publications and source records attributed to J M Allen.

At least 37 records · Page 2Linked to original sources

PubMed2000

Perfluorochemical liquid enhances adeno-associated virus-mediated transgene expression in lungs.

Use of adeno-associated virus (AAV) vectors for lung gene therapy is limited, in part, by low levels of AAV-mediated transgene expression in lungs. Generally, less than 1% of total airway and alveolar epithelial cells express transgene activity following vector administration. A means of improving AAV vector delivery could potentially enhance AAV-mediated gene expression in lungs. We have previously demonstrated that use of perfluorochemical (PFC) liquids improved overall levels of adenovirus vector-mediated gene expression as well as distribution of expression in lungs of spontaneously breathing rodents. To evaluate whether use of PFC liquids might similarly enhance AAV-mediated expression, spontaneously breathing rodents received intratracheal instillation of the AAV vectors CWRAP and ARAP4 (2-5 x 10(8) FFU/animal) with or without 10 cc/kg body wt PFC liquid (FC-75, ACROS). Animals were sacrificed 4 weeks later and lungs assessed for overall and in situ alkaline phosphatase (AP) expression. Animals receiving vector alone exhibited scattered sparse in situ activity, predominantly in alveolar epithelium. In contrast, animals receiving vector with FC-75 exhibited increased and more widespread AP expression as well as up to a 26-fold increase in AP activity. These results demonstrate that use of the PFC liquid FC-75 improves overall and in situ AAV-mediated gene expression in rodent lungs.

Animals↗

PubMed2000

Delayed onset muscle soreness: effect of an ischaemic block upon mechanical allodynia in humans.

The current study, for which ethical approval was obtained, was designed to assess the extent to which the tenderness or mechanical allodynia observed in delayed onset muscle soreness (DOMS) might be mediated by large diameter myelinated nerve fibres. Healthy human volunteers were recruited and randomly allocated to one of three groups: Normal-Control, Ischaemic-Control, and Test-DOMS (total n=21; n=7 in each group). In the Normal-Control group, subjects attended on a single occasion for assessment of mechanical pain threshold (MPT) at standardized sites over the biceps brachii using a pressure algometer for a period of 20 min. In both remaining groups, ischaemia was induced in subjects' non-dominant upper limbs by elevation of the limb, followed by application of a sphygmomanometer cuff at a pressure of 250 mmHg. Throughout the period of the block (20-40 min), sharp/blunt sensation was assessed at regular intervals. MPT was assessed upon inflation of the cuff and reassessed at 10 min intervals until deflation. In the two ischaemic block groups, current level of pain was also monitored using a computerized visual analogue scale (VAS) at the beginning and end of the procedure. Subjects in the Test-DOMS group attended 48 h prior to ischaemic block for induction of DOMS using a standardized regime of eccentric exercise, but thereafter were treated in exactly the same manner as the Ischaemic-Control group. Results showed a significant (P<0.05; ANOVA) increase in MPT in the Test-DOMS group by the 20 min point, corresponding to a 'normalization' of MPT; loss of the ability to distinguish between sharp/blunt sensation accompanied such changes. Parallel increases in reported pain were seen in both groups undergoing ischaemic block, indicating that the procedure did not alter nociception. While not definitive, these results suggest that altered processing of activity in large diameter (myelinated) afferents might underlie the mechanical allodynia observed in DOMS; thus, this is an area which warrants further investigation.

Adolescent↗

PubMed2000

Study of the effects of various transcutaneous electrical nerve stimulation (TENS) parameters upon the RIII nociceptive and H-reflexes in humans.

Despite over two decades of clinical use, the neurophysiological and anti-nociceptive effects of transcutaneous electrical nerve stimulation (TENS) have yet to be definitively described. The current study was designed to examine the effect of TENS on the RIII nociceptive reflex elicited in healthy human subjects; the H-reflex was measured concomitantly to monitor changes in alpha-motoneuron excitability. Following approval from the university's ethical committee, 50 healthy human volunteers (25 male and 25 female) participated in the study. The subjects ranged in age from 18 to 30 years (mean 22, SD 3). Subjects were randomly allocated equally to a control group or one of four TENS groups. In the TENS groups, stimulation was applied for a total of 15 min over the sural nerve in the left leg. Ipsilateral RIII and H-reflexes were recorded five times during the 45 min experimental period. In addition, subjects also rated pain associated with the RIII reflex using a computerized visual analogue scale (VAS). Statistical analysis using two-way repeated-measures ANOVA showed no differences between groups for H-reflex, RIII reflex nor VAS data. These results suggest that TENS does not significantly affect either of the two reflexes, at least using the parameters and application time in the current study.

Adolescent↗

PubMed2000

Managing delayed-onset muscle soreness: lack of effect of selected oral systemic analgesics.

OBJECTIVE: To investigate the efficacy of commonly available analgesics in the management of delayed-onset muscle soreness over an 11-day period. DESIGN: Double-blind, placebo-controlled randomized trial. SETTING: University laboratory. PARTICIPANTS: Sixty healthy volunteers (30 men, 30 women) with no current arm pain or pathology completed the experimental procedure. INTERVENTIONS: Subjects were randomly allocated to one of five experimental groups: control; placebo; aspirin (900 mg); codeine (60 mg); and paracetamol (1000 mg) (n = 12 in all groups). Delayed soreness was induced in the nondominant elbow flexors using a standardized exercise protocol of repeated eccentric contractions. MAIN OUTCOME MEASURES: Pain (visual analogue scale; McGill pain questionnaire [MPQ]), range of extension, flexion and resting angle (universal goniometer), and mechanical pain threshold (pressure algometer). Measurements were taken before and after drug administration each day, except for the MPQ, which was completed on the first and third days of the experiment. RESULTS: Analysis of results using repeated-measures analysis of variance and relevant post hoc tests provided no evidence of the effectiveness of any of the preparations. CONCLUSION: There is no beneficial effect from the medications, at least at the doses stated, in the management of delayed-onset muscle soreness.

Acetaminophen↗

PubMed2000

Effect of acupuncture upon experimentally induced ischemic pain: a sham-controlled single-blind study.

OBJECTIVE: To investigate the hypoalgesic effect of true and sham acupuncture upon experimentally induced ischemic pain. DESIGN: Human volunteers (n = 60) were required to attend two sessions for pain induction using a submaximal effort tourniquet technique; on the first occasion, baseline pain scores were recorded and on the second, 48 hours later, subjects were randomly allocated to one of five groups: Control, Treatment Groups 1 or 2, or Placebo Groups 1 or 2. SUBJECTS: Healthy human volunteers. INTERVENTION: In all the Treatment and Placebo Groups, subjects received some form of needle acupuncture 15 minutes before, and 5 minutes during, the pain induction procedure on the second day. Treatment Group 1 received acupuncture on acupuncture points situated distal to the tourniquet, whereas Treatment Group 2 received acupuncture on acupuncture points situated proximal to the tourniquet. In Placebo Groups 1 and 2, subjects received 'sham' acupuncture either on nonacupuncture points (Placebo Group 1) or on acupuncture points (Placebo Group 2) using (standardized) minimal levels of stimulation. A licensed acupuncturist who was not involved in data collection and analyses carried out all treatments. OUTCOME MEASURES: Pain was assessed using a computerized visual analog scale (VAS) and a McGill Pain Questionnaire (MPQ). RESULTS: Analysis of VAS scores using ANOVA revealed no significant differences between groups (e.g., VAS sum of differences data (mean +/- SEM): Treatment Group 1: 90+/-47, Treatment Group 2: 187+/-56, Placebo Group 1: 152+/-40, Placebo Group 2: 121+/-42, CONTROLS: 46+/-24, p>0.05). Analysis of MPQ percentage difference scores using one-way ANOVA revealed some isolated effects in the subjective descriptors and the Pain Rating Index, both for Treatment Group 2 and Placebo Group 2, proving them superior to any of the other groups. CONCLUSION: The results of the study provide no convincing evidence for a superior hypoalgesic effect of acupuncture compared with "sham" procedures on this model of experimental pain.

Acupuncture Therapy↗

PubMed2000

Repeat transduction in the mouse lung by using adeno-associated virus vectors with different serotypes.

Vectors derived from adeno-associated virus type 2 (AAV2) promote gene transfer and expression in the lung; however, we have found that while gene expression can persist for at least 8 months in mice, it was reduced dramatically in rabbits over a period of 2 months. The efficiency and persistence of AAV2-mediated gene expression in the human lung have yet to be determined, but it seems likely that readministration will be necessary over the lifetime of an individual. Unfortunately, we have found that transduction by a second administration of an AAV2 vector is blocked, presumably due to neutralizing antibodies generated in response to the primary vector exposure. Here, we have explored the use of AAV2 vectors pseudotyped with capsid proteins from AAV serotypes 2, 3, and 6 for readministration in the mouse lung. We found that an AAV6 vector transduced airway epithelial and alveolar cells in the lung at rates that were at least as high as those of AAV2 pseudotype vectors, while transduction rates mediated by AAV3 were much lower. AAV6 pseudotype vector transduction was unaffected by prior administration of an AAV2 or AAV3 vector, and transduction by an AAV2 pseudotype vector was unaffected by prior AAV6 vector administration, showing that cross-reactive neutralizing antibodies against AAV2 and AAV6 are not generated in mice. Interestingly, while prior administration of an AAV2 vector completely blocked transduction by a second AAV2 pseudotype vector, prior administration of an AAV6 vector only partially inhibited transduction by a second administration of an AAV6 pseudotype vector. Analysis of sera obtained from mice and humans showed that AAV6 is less immunogenic than AAV2, which helps explain this finding. These results support the development of AAV6 vectors for lung gene therapy both alone and in combination with AAV2 vectors.

Alkaline Phosphatase↗

PubMed2000

The experience of pet ownership as a meaningful occupation.

This qualitative study examined the experience of pet ownership in the everyday lives of seven men with human immuno-deficiency virus or acquired immune deficiency syndrome. Interviews and field observations were analyzed using a grounded theory approach. The findings demonstrate that the experience of pet ownership is both typical of any pet owner and yet profoundly impacted by the illness of the owners. The results of this preliminary study indicate pet ownership can be a highly valued occupation for some, and thus has implications for occupational therapy intervention.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Endocytosis and vesicular trafficking of immune complexes and activation of phospholipase D by the human high-affinity IgG receptor requires distinct phosphoinositide 3-kinase activities.

FcgammaRI, the human high-affinity IgG receptor, is responsible for the internalization of immune complexes and their subsequent targetting to the lysosomes for degradation. We show here that aggregation of FcgammaRI by surface immune complexes in interferon-gamma-primed U937 cells causes the transient appearance of swollen vacuolar structures, probably swollen late endosomes, which disappear as the immune complexes are degraded. Wortmannin and LY294002, specific inhibitors of phosphoinositide 3-kinases (PI 3-kinases), delay the disappearance of these structures and also correspondingly inhibit degradation of FcgammaRI-mediated immune complexes. In addition these inhibitors delay the initial phase of FcgammaRI-mediated endocytosis of immune complexes and block the activity of FcgammaRI-stimulated phospholipase D, an enzyme that has previously been implicated in membrane-trafficking events. p85 is the regulatory subunit of PI 3-kinase. A p85-dependent PI 3-kinase was shown to be involved in the initial phase of FcgammaRI-mediated endocytosis, but not in the trafficking of immune complexes for degradation or the activation of phospholipase D. The results presented here show a role for a p85-independent PI 3-kinase in regulating the trafficking of FcgammaRI-mediated immune complexes, either directly or as a result of the activation of phospholipase D, and a distinct role for a p85-dependent PI 3-kinase isoform in the initial phases of FcgammaRI-mediated internalization of immune complexes.

Androstadienes↗

PubMed1999

Persistent, therapeutically relevant levels of human granulocyte colony-stimulating factor in mice after systemic delivery of adeno-associated virus vectors.

Adeno-associated virus (AAV) vectors have been shown to preferentially transduce hepatocytes after systemic administration in adult mice and to provide long-term expression of introduced genes. One application of this technology would be for the production of granulocyte colony-stimulating factor (G-CSF), which increases mature neutrophil numbers in humans and in animals, and has therapeutic effects in disorders featuring chronic neutropenia, including cyclic, severe congenital, and idiopathic neutropenia, and glycogen storage disease type Ib. We have treated mice by tail vein injection of AAV vectors encoding human G-CSF, and have detected high G-CSF levels and marked elevation of neutrophil counts for at least 5 months. A therapeutically relevant amount of G-CSF production was obtained when the liver-specific mouse albumin promoter-enhancer was used to drive G-CSF expression. In mice receiving higher amounts of vector, plasma levels of human G-CSF gradually increased over 3 weeks to high concentrations, whereas for lower amounts human G-CSF remained at initial, low levels. The previously observed effect of gamma irradiation, to increase AAV transduction rates, was diminished when large amounts of vector were used. Absolute neutrophil counts increased 10- to 50-fold for the period of observation to levels that would be therapeutic in the treatment of cyclic neutropenia. In conclusion, gene therapy with AAV vectors synthesizing G-CSF shows promise for the treatment of disorders featuring neutropenia.

Animals↗

PubMed1999

Management of nonspecific low back pain by physiotherapists in Britain and Ireland. A descriptive questionnaire of current clinical practice.

STUDY DESIGN: A descriptive questionnaire of chartered physiotherapists. OBJECTIVE: To investigate current physiotherapeutic management of low back pain throughout Britain and Ireland. SUMMARY OF BACKGROUND DATA: Physiotherapists play a key role in low back pain management. Although clinical guidelines for best practice have been developed recently, there has been no large-scale attempt to describe current physiotherapeutic treatment approaches within Britain or Ireland. METHODS: After semi-structured interviews (n = 6) and two pilot studies (n = 77) were done, postal questionnaires were distributed to four regional cluster samples of the membership of two physiotherapy professional organizations (n = 2654). After two mailings, a random sample of 90 nonresponders were followed up. Data were analyzed using the Statistical Package for the Social Sciences (SPSS Ltd., Woking, Surrey, UK), and precision of the survey estimates was assessed by calculation of sampling errors and intraclass correlation coefficients for cluster sampling. RESULTS: Results were received from 1548 therapists (total response rate, 58.3%); of these, 813 reported that they were practicing in settings in which they treated patients with low back pain. Analysis of the results indicated the overall popularity of the Maitland mobilization and McKenzie approaches among physiotherapists. Although exercise per se was mentioned frequently by respondents, a marked difference in opinion among therapists regarding the optimal type of exercise for low back pain was obvious. Little evidence was demonstrated of the use of manipulation, fitness programs, or multidisciplinary efforts involving behavioral and physical aspects of treatment. Commonly used methods of electrotherapy were interferential therapy, ultrasound, pulsed short-wave diathermy, and transcutaneous electrical nerve stimulation. CONCLUSIONS: The results of this study emphasize the need to evaluate further and improve the dissemination of findings regarding the effectiveness of specific physiotherapy approaches for low back pain management.

Adult↗

PubMed1999

Nicotinamide-inhibited vasoconstriction: lack of dependence on agonist signalling pathways.

Previously, we have shown that nicotinamide inhibits both high [K+]- and phenylephrine-induced constrictions in a dose-dependent manner in rat tail arteries. We have now investigated the effect of nicotinamide on intracellular signalling pathways in vascular smooth muscle. Nicotinamide (8.2 mM) reduced the response to phenylephrine- and [Arg8]vasopressin-induced constrictions by means of 72.9+/-6.9 and 51.8+/-5.7%, respectively. It also blocked phenylephrine-induced constrictions in the absence of a functional endothelium (P < 0.0136). In addition, pre-treatment of the artery with nifedipine (10 mM) also failed to inhibit nicotinamide's activity (P < 0.0178). Moreover, nicotinamide significantly reduced the sensitivity to phenylephrine in Ca2+-free Krebs' solution (P < 0.0152). Continuous perfusion of maximal concentrations of ryanodine or thapsigargin significantly inhibited the response to phenylephrine; the addition of nicotinamide (8.2 mM) caused a significant additional inhibition when compared to the effect of ryanodine (P < 0.0006) or thapsigargin (P<0.037) alone. In addition, beta-escin (0.02%) permeabilisation and Ca2+ (2.5 mM)-mediated constriction was also significantly attenuated by nicotinamide (P < 0.0001). However, phorbol ester-induced constriction was not attenuated by nicotinamide. This would suggest that nicotinamide directly inhibits vascular smooth muscle cell contraction and is unlikely to act via blockage of external Ca2+ entry or release of Ca2+ from intracellular stores.

Animals↗

PubMed1999

Comparative analgesic effects of H-wave therapy and transcutaneous electrical nerve stimulation on pain threshold in humans.

OBJECTIVE: To assess the comparative analgesic efficacy of H-wave therapy (HWT) and transcutaneous electrical nerve stimulation (TENS) using a mechanical model of pain threshold measurement. STUDY DESIGN: Forty-eight healthy human volunteers (24 women, 24 men) were recruited and randomly assigned into one of six experimental groups; control, HWT (placebo, 2Hz, or 60Hz), or TENS (placebo or 110Hz). For each subject, mechanical pain threshold (MPT) measurements were recorded at three standardized recording points marked on the dorsal web space of the dominant hand. Two MPT measurements were recorded at each point at the following time intervals: before treatment was initiated (baseline), after each of three consecutive 10-minute periods of stimulation (HWT or TENS), and at four intervals within 30 minutes after stimulation. In the control and placebo groups MPT measurements were recorded at similar time intervals. RESULTS: Difference scores, calculated from patients' baseline values, were analyzed by ANOVA for each of the three recording points. Although results showed a significant increase in MPT levels in all three stimulation groups when compared with their relative placebo (indicating a hypoalgesic effect), no differences were observed between the different modalities or HWT frequencies. Significant hypoalgesia continued for 5 minutes after stimulation. CONCLUSION: The findings showed that HWT and TENS provided localized hypoalgesia during stimulation and for up to 5 minutes after it. No frequency- or modality-specific effects were observed between the groups.

Adult↗

PubMed1999

Delayed onset muscle soreness: lack of effect of therapeutic ultrasound in humans.

OBJECTIVE: To investigate the effects of two dosages of pulsed ultrasound therapy (1 MHz, spatial averaged peak intensity 0.8 W/cm2, mark space ratio of 1:4) on acute-stage delayed onset muscle soreness (DOMS). DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING: Laboratory of a university physiotherapy department. PARTICIPANTS: Forty-eight healthy volunteers (24 men, 24 women) with no arm pathology or pain at the time of the study. INTERVENTIONS: Subjects were randomly allocated to one of four treatment groups: control, placebo (sham insonation), low-dosage pulsed ultrasound (mean dosage 172.8 J), or high-dosage pulsed ultrasound (mean dosage 345.6 J). DOMS was induced in the nondominant elbow flexors in a standardized fashion through repeated eccentric exercise until exhaustion. MAIN OUTCOME MEASURES: Elbow extension, flexion, and resting angles (universal goniometer), pain (visual analogue scale), mechanical pain threshold/tenderness (pressure algometer), and a McGill pain questionnaire. Measurements were taken before and after treatment each day except for the McGill pain questionnaire, which was completed at the end of the trial. RESULTS: Significant differences were seen between groups in relation to range of flexion (p = .0032), with the control group losing least range of flexion. There were no other significant differences between the groups. CONCLUSION: No convincing evidence was found to support the use of pulsed ultrasound therapy in the management of DOMS at the parameters discussed here.

Adult↗

PubMed1999

Biosynthesis of straight-chain ester volatiles in red delicious and granny smith apples using deuterium-labeled precursors.

Biosynthesis of straight-chain ester volatiles by Granny Smith and Red Delicious apples was investigated using deuterium-labeled fatty acids, C-6 aldehydes, and alcohols. Perdeuterated saturated and monounsaturated fatty acids were metabolized to hexyl-d(11), hexanoate-d(11), heptanoate-d(13), and octanoate-d(15) esters, whereas perdeuterated linoleic acid produced only hexyl-d(11) and hexanoate-d(11) esters. Exposure of fruit to vapors of deuterated 3Z-hexenal, 2E-hexenal, and hexanal identified the following biosynthetic processes: (1) isomerization between 3E, 3Z, and 2E-hexenals; (2) reduction to 3E, 3Z, and 2E-hexenyl esters; (3) reduction to hexanol and hexyl esters; (4) oxidation to hexanoic acid and formation of hexanoate esters; (5) beta-oxidation of hexanoic acid leading to butyl and butanoate esters; and (6) alpha-oxidation of hexanoic acid leading to pentyl and pentanoate esters. Unsaturated straight-chain ester volatiles appear to arise only by the lipoxygenase pathway and may be useful indicators of lipoxygenase activity in fruit.

Chromatography, Gas↗

PubMed1999

Differentiation-dependent switch in protein kinase C isoenzyme activation by FcgammaRI, the human high-affinity receptor for immunoglobulin G.

Aggregation of receptors for the constant region (Fc) of immunoglobulin G on myeloid cells results in endocytosis or phagocytosis and cellular activation. Previous work has shown, using the cell line U937, that the high-affinity immunoglobulin G receptor, FcgammaRI, activates alternate intracellular signalling pathways depending on the cell differentiation state, which results in a marked change in the nature of calcium transients within the cell. Here, we show that protein kinase C (PKC) is activated in both interferon-gamma (IFN-gamma) -primed and dibutyryl cyclic AMP (dbcAMP) -differentiated cells but that the nature of the particular isoenzymes recruited differs. Thus, in IFN-gamma-primed U937 cells, FcgammaRI aggregation results in an increase of PKC activity which is essentially calcium independent resulting from the translocation to the membrane of the novel PKCs, delta and epsilon, together with the atypical PKC zeta. However, in cells differentiated to a more macrophage phenotype, all PKC enzyme activity after receptor aggregation is calcium dependent. Consistent with this finding, the isoenzymes translocated to the nuclear-free membrane fraction are the conventional PKCs alpha, beta and gamma; results consistent with our previous finding that FcgammaRI couples to phospholipase C in such dbcAMP-differentiated cells. Thus, the nature of PKC isoenzyme activated following FcgammaRI aggregation is defined by differentiation. The calcium dependence of the PKC isoenzyme is consistent with the duration of calcium transients previously reported in the two differentiation states.

Blotting, Western↗

PubMed1999

The human high-affinity immunoglobulin G receptor activates SH2-containing inositol phosphatase (SHIP).

On cytokine-primed U937 cells, aggregation of the human high-affinity immunoglobulin receptor, FcgammaRI, initiates signal transduction cascades which lead to the release of calcium from intracellular stores and no significant calcium influx. In these cells, aggregation of FcgammaRI results in no significant increase in inositol trisphosphate production, but rather phospholipase D is activated. Here we show that, in interferon-gamma (IFN-gamma)-primed cells, the SH2 containing inositol 5' phosphatase, SHIP, is constitutively associated with the membrane fraction. Following aggregation of FcgammaRI, SHIP is rapidly and transiently tyrosine phosphorylated and becomes associated with the adapter molecule Shc. Shc also becomes tyrosine phosphorylated and translocates from the cytoplasm to the membrane fraction concomitant with the association between Shc and SHIP. Further, SHIP and Shc appear to be recruited to membrane-associated immune complexes following FcgammaRI aggregation. As no immunoreceptor inhibitory motif has been demonstrated to associate with FcgammaRI, these data suggest that SHIP may be recruited to the receptor through an SH2 domain interaction with Shc.

Adaptor Proteins, Signal Transducing↗

PubMed1999

FcgammaRI activation of phospholipase Cgamma1 and protein kinase C in dibutyryl cAMP-differentiated U937 cells is dependent solely on the tyrosine-kinase activated form of phosphatidylinositol-3-kinase.

The human high affinity receptor for immunoglobulin G, FcgammaRI, in dibutyryl cyclic AMP (dbcAMP)-differentiated U937 cells, is coupled to the activation of phospholipase C (PLC) and the conventional protein kinase C (PKC) isoforms, alpha, beta, and gamma. Here we demonstrate that aggregation of FcgammaRI activates the tyrosine-kinase regulated form of phosphatidylinositol-3-kinase (PI-3-kinase) and that an increase of phosphatidylinositol trisphosphate (PIP3) is essential for the activation and translocation of PLCgamma1 in these cells. In addition, activation of the PKC isoforms was ablated by specific inhibitors of PI3-kinase or by overexpression of a dominant negative p85 subunit of PI3-kinase. The findings reported here demonstrate that PLCgamma1 and PKC activation by FcgammaRI are downstream of PI3-kinase, and that in contrast to cytokine primed cells, only the tyrosine-kinase activated isoform of PI3-kinase is coupled to FcgammaRI in dbcAMP-differentiated cells.

Bucladesine↗

PubMed1999

Effect of cholesterol feeding on DNA damage in male and female Syrian hamsters.

Cholesterol oxides are cytotoxic and have been implicated in many disease processes; however, it has been proposed that cholesterol oxides result from cholesterol acting as a sacrificial antioxidant. In this study, the effect of dietary cholesterol on DNA damage, assessed by the alkaline comet assay, was examined in male and female Syrian hamsters. Animals were fed ad libitum a modified AIN-76 diet (control) or a diet with 0.5% cholesterol for 10 weeks. Following the 10-week feeding period, there was no significant difference in body weight between cholesterol-fed and control animals. Cholesterol feeding resulted in significant liver hypertrophy, and increased plasma total and HDL cholesterol in both male and female animals compared with controls. There was no difference in liver cell DNA damage levels as measured by the comet assay. Heart cells from cholesterol-fed hamsters, however, showed a significant decrease in tail DNA (p = 0.050) indicating decreased damage compared with controls and a possible protective effect of cholesterol against DNA damage.

Animals↗