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Biomedical subjects

J M O'Connor

Publications and source records attributed to J M O'Connor.

At least 19 recordsLinked to original sources
PubMed2001

No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status.

OBJECTIVE: To investigate the effects of increasing Cu intakes, above the usual dietary intake, on biomarkers of bone metabolism in healthy young adult females (aged 21-28 y) over a 4 week period. DESIGN: A double-blind, placebo-controlled randomised repeat crossover Cu supplementation trial. SETTING: The study was conducted at the Royal Veterinary and Agricultural University (RVAU), Copenhagen, Denmark. SUBJECTS: Sixteen healthy young adult females aged 20-28 y were recruited from among students at the RVAU. INTERVENTION: During the 4 week intervention periods in this randomised, crossover trial (3x4 weeks with a minimum 3 week wash-out period), each subject received, in addition to their usual diet, either 3 or 6 mg elemental Cu/day as CuSO4 or a matching placebo. On the last 3 days of each dietary period 24 h urines were collected. In addition, blood was collected on the last day of each dietary period. RESULTS: Serum Cu and erythrocyte superoxide dismutase (but not caeruloplasmin protein concentration or activity (putative indices of Cu status)) were significantly increased (P<0.05) after daily Cu supplementation with 3 and 6 mg/day for 4 weeks. Serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline (Pyr)/Cr or deoxypyridinoline (Dpyr)/Cr excretion, or daily urinary Pyr or Dpyr excretion (biomarkers of bone resorption) were unaffected by Cu supplementation. CONCLUSION: Copper supplementation of the usual diet in healthy young adult females, while apparently improving Cu status, had no effect on biochemical markers of bone formation or bone resorption over 4 week periods. SPONSORSHIP: Funding from the European Commission.

Adult↗
PubMed2001

Trace elements and DNA damage.

A number of studies (mainly in vitro and in vivo animal models) have examined the interaction of trace elements with DNA. Normal dietary levels of various trace elements are required to prevent the occurrence of oxidative damage, and deficiency may increase susceptibility. Conversely, overload of some trace elements, including copper and iron, has been demonstrated to result in adverse effects. However, under normal physiological conditions, such overloads are unlikely to occur.

Antioxidants↗
PubMed2000

An investigation of the biological activity of bullrout (Notesthes robusta) venom.

Bullrout envenomation is known to cause intense pain. Crude bullrout venom and venom fractions were assessed for protease, hyaluronidase, phospholipase and hemolytic activities, reactivity with stonefish antivenom, lethality to brine shrimp and ability to elicit pain in human subjects. Compared with venom obtained from frozen specimens, live fish venom-milking techniques rendered greater venom potency and improved storage characteristics. Although mild proteolytic and hemolytic activity was observed, crude venom demonstrated no hyaluronidase or phospholipase A2 activity, did not affect brine shrimp, or show antigenicity with stonefish antivenom. A single venom protein isolated from bullrout venom is attributed with causing pain in human subjects. The sensations elicited by this novel algesic protein are consistent with chemical stimulation of polymodal nociceptors.

Animals↗
PubMed2000

Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project).

The oxidative modification of low-density lipoprotein cholesterol (LDL) has been implicated in the pathogenesis of atherosclerosis. Copper (Cu) is essential for antioxidant enzymes in vivo and animal studies show that Cu deficiency is accompanied by increased atherogenesis and LDL susceptibility to oxidation. Nevertheless, Cu has been proposed as a pro-oxidant in vivo and is routinely used to induce lipid peroxidation in vitro. Given the dual role of Cu as an in vivo antioxidant and an in vitro pro-oxidant, a multicenter European study (FOODCUE) was instigated to provide data on the biological effects of increased dietary Cu. Four centers, Northern Ireland (coordinator), England, Denmark, and France, using different experimental protocols, examined the effect of Cu supplementation (3 or 6 mg/d) on top of normal Cu dietary intakes or Cu-controlled diets (0.7/1.6/6.0 mg/d), on Cu-mediated and peroxynitrite-initiated LDL oxidation in apparently healthy volunteers. Each center coordinated its own supplementation regimen and all samples were subsequently transported to Northern Ireland where lipid peroxidation analysis was completed. The results from all centers showed that dietary Cu supplementation had no effect on Cu- or peroxynitrite-induced LDL susceptibility to oxidation. These data show that high intakes (up to 6 mg Cu) for extended periods do not promote LDL susceptibility to in vitro-induced oxidation.

Adult↗
PubMed2000

Response of putative indices of copper status to copper supplementation in human subjects.

No sensitive functional index is currently available to assess Cu status in healthy human populations. This study evaluated the effect of Cu supplementation on putative indices of Cu status in twelve women and twelve men, aged between 22 and 45 years, who participated in a double-blind placebo controlled crossover study. The study consisted of three 6-week supplementation regimens of 3 mg CuSO4, 3 mg Cu-glycine chelate and 6 mg Cu-glycine chelate, each separated by placebo periods of equal length. Women had significantly higher caeruloplasmin oxidase activity (P < 0.001), caeruloplasmin protein concentration (P < 0.05), and serum diamine oxidase activity (P < 0.01) at baseline than men. Erythrocyte and leucocyte superoxide dismutase activity, leucocyte cytochrome c oxidase activity, and erythrocyte glutathione peroxidase activity did not respond to Cu supplementation. Platelet cytochrome c oxidase activity was significantly higher (P < 0.01), after supplementation with 6 mg Cu-glycine chelate in the total group and in women but did not change in men. Caeruloplasmin oxidase activity was significantly higher (P < 0.05), in men after supplementation with 3 mg Cu-glycine chelate, while caeruloplasmin protein concentration was significantly lower in men after supplementation with 6 mg Cu-glycine chelate (P < 0.05). Serum diamine oxidase activity was significantly higher after all supplementation regimens in the total group and in both men and women (P < 0.01). These results indicate that serum diamine oxidase activity is sensitive to changes in dietary Cu intakes and may also have the potential to evaluate changes in Cu status in healthy adult human subjects.

Adult↗
PubMed1999

Use of a DNA toolbox for the characterization of mutation scanning methods. I: construction of the toolbox and evaluation of heteroduplex analysis.

A systematic characterization of the effects of important physical parameters on the sensitivity and specificity of methods in searching for unknown base changes (mutations or single nucleotide polymorphisms) over a relatively long DNA segment has not been previously reported. To this end, we have constructed a set of molecules of varying G+C content (40, 50, and 60% GC) having all possible base changes at a particular location - the "DNA toolbox". Exhaustive confirmatory sequencing demonstrated that there were no other base changes in any of the clones. Using this set of clones as polymerase chain reaction (PCR) templates, amplicons of various lengths with the same base mutated to all other bases were generated. The behavior of these constructs in manual and automated heteroduplex analysis was analyzed as a function of the size and overall base content of the fragment, the nature and location of the base change. Our results show that in heteroduplex analysis, the nature of the mismatched base pair is the overriding determinant for the ability to detect the mutation, regardless of fragment length, GC content, or the location of the mutation.

DNA, Viral↗
PubMed1999

Use of DNA toolbox for the characterization of mutation scanning methods. II: evaluation of single-strand conformation polymorphism analysis.

Single-strand conformation polymorphism (SSCP) is one of the most commonly used methods for searching for unknown base changes (mutations). In order to characterize systematically the effects of important physical parameters on the sensitivity and specificity of SSCP, we used the DNA toolbox constructed as described in the companion paper [2]. Using this set of DNA molecules as polymerase chain reaction (PCR) templates, amplicons of various lengths with the same base, mutated to all other bases, were generated. The behavior of these constructs in manual and automated SSCP was analyzed as a function of the size, overall base content of the fragment, nature and location of the base change, and the temperature and pH of electrophoresis. Our results demonstrate that all of these variables interact to determine the rate of detection of single-base changes, with the GC content being the predominant determinant of detection sensitivity.

DNA↗
PubMed1999

No effect of copper supplementation on biochemical markers of bone metabolism in healthy adults.

The influence of Cu supplementation of the usual diet for 6 weeks on biochemical markers of bone turnover and on putative indices of Cu status was investigated in healthy adults (twelve male and twelve female) aged 22-46 years, who participated in a double-blind placebo-controlled repeated crossover study. The study consisted of three 6-week supplementation regimens of 3 mg CuSO4, 3 mg Cu-glycine chelate (CuGC), and 6 mg CuGC, each separated by placebo periods of equal length. During baseline and on the last day of each dietary period, fasting morning first-void urine and fasting blood serum, plasma and erythrocytes were collected. The habitual dietary Cu intakes in males and females were approximately 1.4 and 1.1 mg/d respectively. Females had significantly higher (50%) plasma caeruloplasmin (Cp) protein concentrations than males at baseline. Cu supplementation had no effect on erythrocyte superoxide dismutase (SOD, EC 1.15.1.1) activity or plasma Cp protein (putative indices of Cu status) in the total group. Similarly, serum osteocalcin (a marker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline: Cr or deoxypyridinoline: Cr excretion (markers of bone resorption) were unaffected in either the total group or in males and females separately, by any Cu supplementation regimen. It is concluded that Cu supplementation of the usual diet in healthy adult males and females had no effect on biochemical markers of bone formation or bone resorption over 6-week periods.

Adult↗
PubMed1993

Time-varying conjugation of 7,12-dimethylbenz[a]anthracene metabolites in rainbow trout (Oncorhynchus mykiss).

Sexually immature rainbow trout were dosed via gavage with 7,12-[14C]dimethylbenz[a]anthracene (DMBA) in order to study hepatic metabolite formation over time and at single and multiple doses. beta-Glucuronidase and aryl sulfatase hydrolyses of bile extracts and subsequent high-pressure liquid chromatography analysis demonstrated significant levels of sulfate conjugates formed after 12 hr of exposure to a single dose. By 72 hr, glucuronide conjugates had increased and after three doses of [14C]DMBA, glucuronides exceeded the amount of sulfates by almost an order of magnitude. Of the metabolites that could be tentatively identified, the majority were oxidative derivatives of the aromatic rings 3-OH DMBA and 3,4-trans-OHDMBA, the latter of which is mutagenic and a precursor to the proposed ultimate carcinogen of DMBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Biological markers of macrophage activation: applications for fish phagocytes.

The immune defence mechanisms of fish seem to be related and similarly competent to those of mammals. Because of this, there is an increased interest in the immune responses of fish as models for higher vertebrates in immunological/immunotoxicological studies. Macrophages (M phi), phagocytic cells of the mammalian and teleost immune system which reside in tissues, represent a quiescent population of cells. However, upon stimulation, alterations in the physiology of these resident M phi occur which can be defined in terms of activation. This study was undertaken to determine whether biological markers used to assess mammalian M phi activation are applicable for use with fish M phi. Cells were recovered from the peritoneal cavity of non-injected and Aeromonas salmonicida-injected fish, and differences between resident and elicited M phi were evaluated with respect to protein content, phagocytic competence, enzyme activities and hydrogen peroxide production. Results demonstrate that biological markers used to assess mammalian M phi activation, with the exception of acid phosphatase activity, can be used to characterize the activation state of trout M phi, and that the activation process in both fish and mammals may occur by similar mechanism(s).

Aeromonas↗
PubMed1992

Evaluation of four deoxyribonucleic acid (DNA) extraction protocols for DNA yield and variation in restriction fragment length polymorphism (RFLP) sizes under varying gel conditions.

This study originated from discussions and recommendations of the Technical Working Group on DNA Analysis Methods (TWGDAM). Four bloodstain deoxyribonucleic acid (DNA) extraction protocols and five semen stain DNA extraction protocols were evaluated. Nine laboratories participated in the extraction of DNA from 20 bloodstains and 20 semen stains using each protocol. All blood and semen stains originated from a single donor and were prepared under uniform conditions to permit the direct comparison of DNA yields and restriction fragment lengths. The extracted DNA from approximately 600 bloodstains and 700 semen stains was quantified by yield gel analysis and a slot blot hybridization technique. The extracted DNA was digested and restriction fragment length polymorphism (RFLP) patterns were generated using three single-locus probes. The RFLP sizing data produced from the blood and semen stains were evaluated with respect to (1) DNA extraction method, (2) gel length, (3) agarose type, (4) presence or absence of ethidium bromide in the gel, and (5) fragment sizes obtained from DNA isolated directly from the donor's liquid blood. This study demonstrates conclusively that high-molecular-weight DNA can be isolated using either organic or nonorganic DNA extraction protocols and that the resulting RFLP sizes are highly reproducible regardless of gel length, agarose type, or presence/absence of ethidium bromide.

Autoradiography↗
PubMed1991

Comparison of patients with and without emotional/behavioral deterioration during the first year after traumatic brain injury.

The records of 34 patients who showed evidence of emotional deterioration 6 months or more following traumatic brain injury were compared with a group of patients matched for severity of initial neuropsychiatric impairment who did not show deterioration. The deterioration group was more likely to have been involved in assaults and less likely to have been involved in a motor vehicle accident than the improvement group. The deterioration group was also more likely to have a prior history of alcohol abuse and to have sustained a skull fracture with left parietal lobe injury than the improvement group. Agitation, hostility, apathy, lability of mood, emotional withdrawal, and depression were the symptoms most likely to worsen over time. This deterioration may have been due to premorbid personality characteristics or to the nature of long-term neuronal response to injury.

Adult↗
PubMed1990

Pharmacokinetics of sulphadimethoxine in channel catfish (Ictalurus punctatus).

1. Plasma clearance, bioavailability, tissue disposition and elimination of 14C-sulphadimethoxine (SDM) were studied in channel catfish (Ictalurus punctatus) after intravenous (i.v.) and oral dosing (per os; p.o.) at 40 mg/kg body weight. 2. Analysis of blood SDM concentrations over time for intravascularly administered SDM showed that disposition and elimination were best described by a two-compartment pharmacokinetic model; estimated half-lives for SDM in blood were 0.09 and 12.6 h for the distribution and elimination phases, respectively. 3. SDM was found primarily in muscle tissue immediately after oral administration; however, clearance from muscle was rapid, with a half-life of 13.1 h. 4. With time, SDM-derived radioactivity became concentrated in the bile and was eliminated slowly (t 1/2 = 115.5 h). 5. Binding of SDM in channel catfish plasma was low (18%) and was non-specific and dose-independent. 6. With the exception of the initial, rapid clearance of SDM from blood, the pharmacokinetic parameters describing SDM distribution and elimination in channel catfish were similar to values reported for other vertebrate species; the rapid distribution of SDM from blood to the tissues in the catfish may be related to species differences in the plasma binding of SDM.

Administration, Oral↗
PubMed1988

Sulfadimethoxine pharmacokinetics and metabolism in the channel catfish (Ictalurus punctatus).

The pharmacokinetics of sulfadimethoxine (SDM) blood clearance, gastrointestinal absorption and tissue distribution and elimination were determined in channel catfish (Ictalurus punctatus) after intravenous and oral dosing using radiolabelled SDM. Blood clearance of SDM in catfish was rapid compared to mammals when the drug was given iv. Results from in vitro equilibrium dialysis studies suggest that this is due to a lower binding of SDM to plasma proteins in fish (18.4%) compared to mammalian species (60-88%). Results from oral dose studies indicated that SDM is readily absorbed from the gastrointestinal tract in channel catfish and distributes rapidly to body tissues, primarily the muscle. With time, concentrations of SDM in muscle decrease and the drug accumulates in the bile, primarily as the N-acetyl-metabolite.

Acetylation↗