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Ian Martin

Publications and source records attributed to Ian Martin.

15 recordsLinked to original sources
PubMed2006

Distinct genetic influences on locomotor senescence in Drosophila revealed by a series of metrical analyses.

Decline of locomotor function is a prominent feature of aging in most species. We previously described a series of metrical analyses for quantifying functional declines associated with aging. Here, we have applied these metrics to elucidate differences in the nature of locomotor senescence between Drosophila cohorts from four different genetic backgrounds (Canton-S, Oregon-R, Samarkand and Lausanne-S) and two long-lived mutant strains, Indy(206) and chico(1). These analyses demonstrate that senescence of locomotor function in Oregon-R and Canton-S proceeds more rapidly than in Samarkand and Lausanne-S flies. Our analyses also show that while chico(1) and Indy mutants both exhibit attenuated locomotor declines, the impact of chico loss of function on locomotor senescence is substantially greater. Our studies illustrate how important differences in functional senescence characteristics can be unveiled by in-depth analysis on functional senescence data sets.

Aging↗
PubMed2006

Oxidative damage and age-related functional declines.

Most organisms experience progressive declines in physiological function as they age. Since this senescence of function is thought to underlie the decrease in quality of life in addition to the increase in susceptibility to disease and death associated with aging, identifying the mechanisms involved would be highly beneficial. One of the leading mechanistic theories for aging is the oxidative damage hypothesis. A number of studies in a variety of species support a strong link between oxidative damage and life span determination. The role of oxidative damage in functional senescence has also been investigated, albeit not as comprehensively. Here, we review these investigations. Several studies show that the age-related loss of a number of functions is associated with an accrual of oxidative damage in the tissues mediating those functions. Additionally, treatments that increase the accumulation of oxidative damage with age frequently exacerbate functional losses. Moreover, treatments that reduce the accumulation of oxidative damage often attenuate or delay the loss of function associated with aging. These data provide the foundation for a link between oxidative damage and functional senescence, thereby supporting the oxidative damage hypothesis of aging within the context of age-related functional decline.

Aging↗
PubMed2006

Modeling human exposures to air pollution control (APC) residues released from landfills in England and Wales.

Human exposures to air pollution control (APC) residues released from 6 landfills were modeled and assessed. Following a qualitative risk characterisation, direct and indirect exposures were quantified. Site-specific air dispersion modeling was conducted for PM(10), PCDDs/PCDFs, Pb, Cd, As and Cr(VI) concentrations at the closest residential points of exposure for 4 landfill sites accepting, in total, 75% w/w of the APC residues disposed of in 2000-2001 (UK). Inhalation risks, assessed by reference to air quality standards at residential exposure points, were assessed as insignificant. Preliminary modeling suggested that indirect exposures from PCDDs/PCDFs at the 95th percentile level for the site where APC deposition rates were highest could potentially exceed the tolerable daily soil intake (TDSI) but this warrants further study given the model limitations. These results offer an initial screen of the significance of potential risks from APC disposal, which is of value in addressing concerns about the uncertainty of potential risks to human health from bulk APC disposal at strategic locations.

Air Pollutants↗
PubMed2006

Laparoscopic vs open living donor nephrectomy: a contemporary series from one centre.

OBJECTIVE: To report our experience of laparoscopic living donor nephrectomy (LDN) vs open donor nephrectomy (ODN), as LDN offers potential advantages to the donor and has become a routine procedure for live kidney procurement worldwide. PATIENTS AND METHODS: Between February 2000 and August 2005 we performed 183 donor-recipient operations at our institution (ODN, 83; LDN, 100). We prospectively collected information on all donors and recipients for the same period to audit our experience with the first 100 LDNs. Patients made their operative choice after discussions that included unit experience and published information. We present our findings with the emphasis on donor operative details and early recipient graft outcome. RESULTS: Donor and recipient age, gender, body mass index, human leukocyte antigen mismatches, and vascular anastomotic times did not differ significantly between the groups. There were two conversions to an open operation in the LND group; neither affected recipient-graft outcome. The mean (sd) operative duration was 178 (38) min for the LDN and 159 (34) min for the ODN (P < 0.05). The mean (sd) hospital stay was 4.7 (1.2) days in the LND group and 6.8 (1.5) days in the ODN group (P < 0.05). There was one case of delayed graft function in both groups. Serum creatinine levels at 1, 6 and 12 months after transplantation did not differ significantly between the groups. CONCLUSIONS: Our contemporaneous series shows the safe introduction of a laparoscopic living-donor programme without compromising donor patient safety or allograft outcome.

Adult↗
PubMed2005

Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in Drosophila.

Age-related behavioral declines are common manifestations of aging in animals. Negative geotaxis, an innate escape response during which flies ascend the wall of a cylinder after being tapped to its bottom, is one of the behaviors that senesces in Drosophila. Many laboratories, including ours, have used a variety of negative geotaxis assays based on the performance of single flies. To circumvent limitations of single-fly assays, we developed a new method for assessing negative geotaxis called rapid iterative negative geotaxis (RING). In RING assays, digital photography is used to document negative geotaxis in multiple groups of animals simultaneously. We show that performance in RING assays is not influenced by the density of flies being tested, the time of day, or repeated testing. We used the RING assay to demonstrate that negative geotaxis declines with the age of animals as previously shown in single fly studies and that senescence of negative geotaxis is sensitive to genetic background. Finally, we used RING assays to show that long-lived Indy and chico mutants exhibit delayed senescence of negative geotaxis. Our results demonstrate that RING is a powerful method for assessing negative geotaxis that should facilitate the search for manipulations that influence behavioral aging in Drosophila.

Aging↗
PubMed2005

Functional senescence in Drosophila melanogaster.

The fruit fly Drosophila melanogaster is one of the principal model organisms used for studying the biology of aging. Flies are well suited for such studies for a number of reasons. Flies develop to adulthood quickly, have a relatively short life span, and are inexpensive to house. Most of the fly genome has been sequenced, powerful genetic tools are available to manipulate it, and most fly genes have obvious homologues in mammals. While the majority of aging studies in flies have focused on regulation of life span, the fly is emerging as a powerful model system for investigating the biology that underlies age-related functional decline. Key to the use of flies in this way is the striking number of parallels between functional senescence in Drosophila and humans. Here, we review age-related functional declines in Drosophila, human correlates of these age-related declines, and common mechanisms that influence longevity and specific aspects of functional senescence in flies.

Aging↗
PubMed2005

A proposed set of descriptors for functional senescence data.

Declines in function are common manifestations of aging in many phyla. Because functional senescence is thought to drive the increasing risk of death with age, understanding functional senescence is important for understanding aging. Experimental investigation of functional senescence requires one to quantitative and compare age-dependent declines in function between cohorts. Such quantitation and comparison is often difficult due to complexities in functional senescence data sets. Here, we discuss issues related to describing and contrasting age-related declines in function. We parameterized functional senescence data in simple ways to generate descriptors for (1) rate of functional decline, (2) time to onset of functional decline, and (3) total function. To illustrate how these descriptors can be used, we analyzed a hypothetical data set and one of our previously published data sets. We conclude that no one descriptor sufficiently characterizes functional senescence. Useful distinctions between functional senescence in different cohorts can be made, however, when multiple descriptors are used in an integrated fashion [corrected]

Aging↗
PubMed2004

Nitroxides scavenge myeloperoxidase-catalyzed thiyl radicals in model systems and in cells.

Nitroxide radicals possess important antioxidant activity in live tissues because of their ability to scavenge reactive radicals. Despite the fact that, in cells, damaging free radicals are primarily quenched by glutathione (GSH) with subsequent formation of harmful glutathionyl radical (GS(*)), interactions of nitroxide radicals with GS(*) and thiols have not been studied in detail. In addition, intracellular metabolic pathways leading to the formation of secondary amines from nitroxides are unknown. Here we report that GS(*) radicals react efficiently and irreversibly with nitroxides to produce secondary amines. We developed a sensitive method for the detection of GS(*) based on their specific interaction with Ac-Tempo, a nonfluorescent conjugate of fluorogenic acridine with paramagnetic nitroxide Tempo, and used it to characterize interactions between nitroxide and thiyl radicals generated through phenoxyl radical recycling by peroxidase. During reaction of Ac-Tempo with GS(*), Tempo EPR signals decayed and acridine fluorescence concurrently increased. DMPO and PBN, spin traps for GS(*), inhibited this interaction. Using combined HPLC and mass spectrometry, we determined that 90% of the Ac-Tempo was converted into fluorescent acridine (Ac)-piperidine; GSH was primarily oxidized into sulfonic acid. In myeloperoxidase-rich HL-60 cells, Ac-piperidine fluorescence was observed upon stimulation of GS(*) generation by H(2)O(2) and phenol. Development of fluorescence was prevented by preincubation of cells with the thiol-blocking reagent N-ethylmaleimide as well as with peroxidase inhibitiors. Furthermore, Ac-Tempo preserved intracellular GSH and protected cells from phenol/GS(*) toxicity, suggesting a new mechanism for the free-radical scavenging activity of nitroxides in live cells.

Acridines↗
PubMed2004

Glutathione propagates oxidative stress triggered by myeloperoxidase in HL-60 cells. Evidence for glutathionyl radical-induced peroxidation of phospholipids and cytotoxicity.

Glutathione acts as a universal scavenger of free radicals at the expense of the formation of the glutathionyl radicals (GS*). Here we demonstrated that GS* radicals specifically interact with a reporter molecule, paramagnetic and non-fluorescent 4-((9-acridinecarbonyl)-amino)-2,2,6,6-tetramethylpiperidine-1-oxyl (Ac-Tempo), and convert it into a non-paramagnetic fluorescent product, identified as 4-((9-acridinecarbonyl)amino)-2,2,6,6-tetramethylpiperidine (Ac-piperidine). Horseradish peroxidase-, myeloperoxidase-, and cyclooxygenasecatalyzed oxidation of phenol in the presence of H2O2 and GSH caused the generation of phenoxyl radicals and GS* radicals, of which only the latter reacted with Ac-Tempo. Oxidation of several other phenolic compounds (e.g. etoposide and tyrosine) was accompanied by the formation of GS* radicals along with a characteristic fluorescence response from Ac-Tempo. In myeloperoxidase-rich HL-60 cells treated with H2O2 and phenol, fluorescence microscopic imaging of Ac-Tempo revealed the production of GS* radicals. A thiol-blocking reagent, N-ethylmaleimide, as well as myeloperoxidase inhibitors (succinyl acetone and azide), blocked formation of fluorescent acridine-piperidine. H2O2/phenolinduced peroxidation of major classes of phospholipids in HL-60 cells was completely inhibited by Ac-Tempo, indicating that GS* radicals were responsible for phospholipid peroxidation. Thus, GSH, commonly viewed as a universal free radical scavenger and major intracellular antioxidant, acts as a pro-oxidant during myeloperoxidase-catalyzed metabolism of phenol in HL-60 cells.

Cell Survival↗
PubMed2004

Ascorbate as a "redox sensor" and protector against irradiation-induced oxidative stress in 32D CL 3 hematopoietic cells and subclones overexpressing human manganese superoxide dismutase.

PURPOSE: To determine whether increased expression of manganese superoxide dismutase (MnSOD) protects cells from irradiation by preventing the production of reactive oxygen species (ROS), a new approach to detecting free radical intermediates using ascorbate as an endogenous spin trap was used. MATERIALS AND METHODS: Cells from the 32D cl 3 hematopoietic cell line or a subclone overexpressing MnSOD (2C6) were incubated with dehydroascorbate for 30 min and irradiated to doses from 0 to 50 Gy. Radical intermediates reacting with spin traps or ascorbate were measured by electron spin resonance spectroscopy. Results were compared to irradiation-induced changes in thiol levels, irradiation survival curves, and accumulation of 8-OHdG as a measurement of DNA oxidative damage. RESULTS: Manganese superoxide dismutase-overexpressing 2C6 cells maintained higher levels of ascorbate (5.4 +/- 0.5 and 2.6 +/- 0.5 nmol/10(6) cells, respectively) and thiols (14.0 +/- 0.1 and 11.1 +/- 0.2 nmol/10(6) cells) compared to 32D cl 3 parent cells. Cells overexpressing MnSOD produced lower levels of ROS than did the parental 32D cl 3 cells, as evidenced by lower expenditure of ascorbate and GSH after irradiation. Increased ascorbate levels protected both 32D cl 3 and 2C6 cells from irradiation killing, as demonstrated by an increased shoulder on survival curves and decreased DNA 8-OHdG accumulation. CONCLUSIONS: Manganese superoxide dismutase overexpression protects 2C6 cells from irradiation damage by scavenging ROS that readily interact with major endogenous antioxidants--ascorbate and GSH--in nontransfected hematopoietic 32D cl 3 cells.

Animals↗
PubMed2004

Arachidonic acid-induced carbon-centered radicals and phospholipid peroxidation in cyclo-oxygenase-2-transfected PC12 cells.

Cyclo-oxygenase-2 (COX-2) is believed to induce neuronal oxidative stress via production of radicals. While oxygen radicals are not directly involved in COX-2-catalytic cycle, superoxide anion radicals have been repeatedly reported to play a critical role in COX-2-associated oxidative stress. To resolve the controversy, we characterized production of free radicals in PC12 cells in which COX-2 expression was manipulated either genetically or by direct protein transfection and compared them with those generated by a recombinant COX-2 in a cell-free system. Using spin-traps alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone, 5,5-dimethyl-1-pyrroline-N-oxide and 4-((9-acridinecarbonyl) amino)-2,2,6,6- tetramethylpiperidine-1-oxyl (Ac-Tempo), we observed arachidonic acid (AA)-dependent production of carbon-centered radicals by heme-reconstituted recombinant COX-2. No oxygen radicals or thiyl radicals have been detected. COX-2 also catalyzed AA-dependent one-electron co-oxidation of ascorbate to ascorbate radicals. Next, we used two different approaches of COX-2 expression in cells, PCXII cells which express isopropyl-1-thio-beta-D-galactopyranoside inducible COX-2, and PC12 cells transfected with COX-2 using a protein delivery reagent, Chariot. In both models, COX-2-dependent AA-induced generation of carbon-centered radicals was documented using spin-traps and Ac-Tempo. No oxygen radical formation was detected in COX-2-transfected cells by either spin-traps or fluorogenic probe, dihydroethidium. In the presence of ascorbate, AA-induced COX-2-dependent ascorbate radicals were detected. AA caused a significant and selective oxidation of one of the major phospholipids, phosphatidylserine (PS). PS was not a direct substrate for COX-2 but was co-oxidized in the presence of AA. The radical generation and PS oxidation were inhibited by COX-2 inhibitors, niflumic acid, nimesulide, or NS-398. Thus, COX-2 generated carbon-centered radicals but not oxygen radicals or thiyl radicals are responsible for oxidative stress in AA-challenged PC12 cells overexpressing COX-2.

Animals↗
PubMed2002

Laparoscopic repair of ventral incisional hernia.

BACKGROUND: Laparoscopic repair of ventral incisional hernias was first reported in 1993. Since then, there have been sporadic case reports and small series published about this procedure, but it has not been widely adopted. Newer types of composite prosthetic mesh may reduce the potential problem of bowel adhesion. METHODS: Thirty cases of laparoscopic ventral incisional hernia repairs (carried out by two surgeons or their senior registrars) have been retrospectively reviewed and reported in this article. The data were obtained from patient records and subsequent phone surveys. RESULTS: Thirty patients between 29 and 82 years (mean: 58 years) underwent this procedure. There were 14 men and 16 women. The average weight of the patients was 81 kg. The hernias were up to 6 or 7 cm in diameter. Mesh was used in 28 cases (polypropylene in 25 cases, expanded polytetrafluoroethylene in two cases and composite mesh in one case). Most meshes were laid intraperitoneally and fixed into position with laparoscopic spiral tacks. Twenty-nine cases were completed laparoscopically. One operation (3.3%) was converted to an open procedure because of severe bowel adherence to the hernia sac. The mean operating time was 52 min for laparoscopic ventral incisional hernia repairs only. All but two patients tolerated an oral diet within 24 h. The postoperative hospital stay ranged from 0 to 11 days, with 17 patients (57%) staying overnight and eight patients (27%) staying another day. Over 80% of the patients returned to house duties within a week. There was no mortality, and minor complications occurred in four patients (14%). One patient had a small bowel obstruction treated successfully by repeat laparoscopy with division of fibrinous adhesions to polypropylene mesh on day four. Follow up ranged from 1 to 69 months (mean: 12 months). One patient did not attend follow-up appointments. There were three cases of hernia recurrence (10%). CONCLUSION: The results suggest that laparoscopic repair of ventral incisional hernias is a safe, effective and technically feasible operation for small- to medium-sized hernias allowing shorter hospital stay, early recovery and resumption of normal activities. However, recurrence rates are comparable to open mesh hernioplasty especially for larger hernias.

Adult↗
PubMedDate not supplied

Methamphetamine use among marginalized youth in British Columbia.

BACKGROUND: Crystal methamphetamine (MA) is a powerful, highly addictive central nervous stimulant that can cause serious health consequences including neurotoxicity, paranoia, psychosis, depression, violence, and death. The objective of this study is to assess the prevalence and characteristics of MA use among two marginalized populations of youth (less than 30 years of age) in British Columbia. METHODS: A self-administered questionnaire was administered to a convenience sample of Vancouver street-involved youth (SY) and Lesbian/Gay/Bisexual/Transgender/Questioning (LGBTQ) centre youth in Vancouver and Victoria. Items measured include: participants' demographic characteristics; illicit substance use, including details of MA use; attempts at recovery and treatment; and potential consequences of MA use. RESULTS: One hundred and eighty of the 200 questionnaires distributed were completed. Sixty-seven percent of the SY and 24% of the LGBTQ youth reported ever having used MA. Of these: 43% had used within the last week; 46-57% used multiple times per day in their lifetime; they spent a maximum of 7-9 consecutive days awake; they began use in their middle to late teens; and half had sought help for a substance use disorder. SY who used MA within the last week were more likely to also use marijuana, cigarettes, heroin, ecstasy, and ketamine. Previous use of MA was associated with reports of auditory hallucinations. CONCLUSION: The current study demonstrates a high prevalence of MA use in two marginalized populations of youth. Use in sexual minorities, resulting psychopathology, and concurrent substance use all have important implications in delivery of service, prevention, and subsequent research.

Adolescent↗