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Biomedical subjects

R Mercer

Publications and source records attributed to R Mercer.

At least 19 recordsLinked to original sources

Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron.

Single-walled carbon nanotubes (SWCNT), nano-cylinders with an extremely small diameter (1-2 nm) and high aspect ratio, have unique physico-chemical, electronic and mechanical properties and may exhibit unusual interactions with cells and tissues, thus necessitating studies of their toxicity and health effects. Manufactured SWCNT usually contain significant amounts of iron that may act as a catalyst of oxidative stress. Because macrophages are the primary responders to different particles that initiate and propagate inflammatory reactions and oxidative stress, we utilized two types of SWCNT: (1) iron-rich (non-purified) SWCNT (26 wt.% of iron) and (2) iron-stripped (purified) SWCNT (0.23 wt.% of iron) to study their interactions with RAW 264.7 macrophages. Ultrasonication resulted in predominantly well-dispersed and separated SWCNT strands as evidenced by scanning electron microscopy. Neither purified nor non-purified SWCNT were able to generate intracellular production of superoxide radicals or nitric oxide in RAW 264.7 macrophages as documented by flow-cytometry and fluorescence microscopy. SWCNT with different iron content displayed different redox activity in a cell-free model system as revealed by EPR-detectable formation of ascorbate radicals resulting from ascorbate oxidation. In the presence of zymosan-stimulated RAW 264.7 macrophages, non-purified iron-rich SWCNT were more effective in generating hydroxyl radicals (documented by EPR spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide, DMPO) than purified SWCNT. Similarly, EPR spin-trapping experiments in the presence of zymosan-stimulated RAW 264.7 macrophages showed that non-purified SWCNT more effectively converted superoxide radicals generated by xanthine oxidase/xanthine into hydroxyl radicals as compared to purified SWCNT. Iron-rich SWCNT caused significant loss of intracellular low molecular weight thiols (GSH) and accumulation of lipid hydroperoxides in both zymosan-and PMA-stimulated RAW 264.7 macrophages. Catalase was able to partially protect macrophages against SWCNT induced elevation of biomarkers of oxidative stress (enhancement of lipid peroxidation and GSH depletion). Thus, the presence of iron in SWCNT may be important in determining redox-dependent responses of macrophages.

Animals↗

Social deprivation and childhood injuries in North and West Belfast.

Injuries in childhood represent a major public health concern. North and West Belfast is an area in which a high rate of emergency department attendance due to injury has been observed, and in which social deprivation is widespread. We carried out a cross sectional survey of 479 injuries in children aged 0-12 years presenting to four emergency departments serving North and West Belfast. Injury rates were compared between the most deprived and least deprived areas, selected on the basis of Noble Economic Deprivation scores. A significant correlation between economic deprivation and injury rate was demonstrated (r = 2.14, p < or = 0.001). Children living within the most deprived areas were particularly likely to be involved in road traffic accidents (relative risk RR = 3.25, p = 0.002). We conclude that children living within the most deprived areas of North and West Belfast are at greater risk of injury than those in less deprived areas. Specific causes of injury, for example burns and scalds, high falls, and motor vehicle accidents are particularly associated with deprivation. Targeting should be taken into account when injury prevention strategies are being developed.

Child↗

The need for youth-oriented policies and programmes on responsible sexuality in Argentina.

Since the mid-1990s, several provincial bills have been passed in Argentina mandating the creation of programmes for family planning and sexual health services and education. A National Plan for Integrated Health Care for Adolescents was also passed but resources and actual programmes remain limited. The policy process has been fraught with difficulties, owing to a strong alliance between the State and the Catholic church. Provision of contraceptives to adolescents has been one of the most contentious issues, as adolescents are legally minors and need parental permission to use family planning. NGOs are working with young people to help them to voice their perspectives and demands. The Programme for Responsible Sexuality was launched by the Province of Buenos Aires in 1999, in response to concrete demands on the part of poor communities for sexual and reproductive health services, including for young people. This Programme came to an abrupt end with the change of governor in that same year, illustrating the complexity of the policy-making process. These experiences demonstrate the urgency to develop strategies and set up task forces for effective advocacy of health and social programmes, and to make political leaders more aware of the social costs of refusing to support these.

Adolescent↗

Relationship of numbing to alexithymia, apathy, and depression.

The present study assessed the relationship between numbing and three associated conditions of alexithymia, apathy, and depression, utilizing data collected on 353 Vietnam combat veterans diagnosed with Posttraumatic Stress Disorder from in- and out-patient settings and an outreach center at various Department of Veterans Affairs Medical centers. All subjects completed four self-report measures: the Glover Numbing Scale, the Beck Depression Inventory, the Apathy Evaluation Scale, and the Toronto Alexithymia Scale-20. The correlation matrix indicated that scores on the four measures were moderately to highly correlated. Principal components analysis with a varimax rotation indicated a five-factor solution that provided evidence for the factorial validity of each of the constructs assessed. Results of the factor analysis of items from the four measures were consistent with numbing being a separate and distinct construct from alexithymia, apathy, and depression. In general, results indicated that all constructs measured were separate and distinct from one another.

Affective Symptoms↗

Determination of blood folate using acid extraction and internally standardized gas chromatography-mass spectrometry detection.

Whole blood folate level is a superior indicator of folate nutritional status than serum/plasma level. Problems with and lack of confidence in results of current whole blood folate assays have limited its popularity for assessing folate nutritional status. Here, an acid extraction GCMS detection method that measures total folate whole blood is presented. Folates are released from the matrix of whole blood and cleaved to para-aminobenzoic acid (pABA) by acid hydrolysis in the presence of [(13)C(6)]pABA as internal standard (IS). The hydrolysate is passed over a C18 resin to remove heme. The pABA isotopomers are ethyl esterified, isolated on C18 resin, and trifluoroacetylated. Following normal-phase HPLC separation, the isotopomers are silylated to their tBDMS derivatives. The abundance of these derivatives are measured at m/z 324 for [(13)C(6)]pABA as IS and m/z 318 for pABA from whole blood folate. Our method uses readily available chemicals and our results agree well with those using Lactobacillus casei, the current gold standard reference assay. The presence of folate analogs (methotrexate) or antibacterials (sulfonamines) does not affect our method. This feature makes it useful in monitoring folate status of patients undergoing chemotherapy. Before using our method, pABA supplements must be discontinued for a few days.

Acids↗

Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene.

Previous studies have suggested that alveolar Na,K-ATPases play an important role in active Na+ transport and lung edema clearance. We reasoned that overexpression of Na,K-ATPase subunit genes could increase Na,K-ATPase function in lung epithelial cells and edema clearance in rat lungs. To test this hypothesis we produced replication deficient human type 5 adenoviruses containing cDNAs for the rat alpha1 and beta1 Na,K-ATPase subunits (adMRCMValpha1 and adMRCMVbeta1, respectively). As compared to controls, adMRCMVbeta1 increased beta1 subunit expression and Na,K-ATPase function by 2. 5-fold in alveolar type 2 epithelial cells and rat airway epithelial cell monolayers. No change in Na,K-ATPase function was noted after infection with adMRCMValpha1. Rat lungs infected with adMRCMVbeta1, but not adMRCMValpha1, had increased beta1 protein levels and lung liquid clearance 7 d after tracheal instillation. Alveolar epithelial permeability to Na+ and mannitol was mildly increased in animals infected with adMRCMVbeta1 and a similar Escherichia coli lacZ-expressing virus. Our data shows, for the first time, that transfer of the beta1 Na,K-ATPase subunit gene augments Na,K-ATPase function in epithelial cells and liquid clearance in rat lungs. Conceivably, overexpression of Na,K-ATPases could be used as a strategy to augment lung liquid clearance in patients with pulmonary edema.

Adenoviruses, Human↗

Microfibril-associated glycoprotein binds to the carboxyl-terminal domain of tropoelastin and is a substrate for transglutaminase.

Microfibril-associated glycoprotein (MAGP) is an integral component of microfibrillar structures that play a critical role in the organization of elastic fibers in the extracellular matrix. To study possible molecular interactions between MAGP and other elastic fiber components, we have generated native MAGP using a baculovirus expression system and tested its ability to associate with tropoelastin and fibrillin. MAGP produced by SF9 cells underwent processing similar to the mammalian protein, including correct cleavage of the signal peptide and sulfation of tyrosine residues. When tested in solid-phase binding assays, native MAGP specifically bound to tropoelastin but not fibrillin-1. Binding to tropoelastin was divalent cation-independent and was completely blocked by reduction and alkylation of either protein. Antibody inhibition studies indicated that the carboxyl terminus of tropoelastin mediated its interaction with MAGP. In addition to binding to elastin, MAGP was also a substrate for transglutaminase, which might explain its propensity to form high molecular weight aggregates that cannot be dissociated with reduction or denaturation. Together, the results of this study provide new insights into the functional relationship between microfibrillar proteins and have important implications for understanding elastic fiber assembly.

Amino Acid Sequence↗

Suspected acute myopathy of pigs.

Following sudden exposure to extreme cold, a group of 15-week-old pigs exhibited strange nervous signs which included arching the back, a high stepping gait, violent tremors of the whole body and screaming. The animals lowered themselves and once sitting, the tremors and screaming stopped. But if forced to rise, these signs recurred. When the pigs returned to a warmer environment, they rapidly recovered. An acute clinical myopathy caused by a marginal vitamin E deficiency was suspected. Other stress-induced factors, such as circulatory collapse caused by movement from a warm to a cold environment, were also thought to have contributed towards the myopathy.

Acute Disease↗

Abnormal electrical stimulus of an intra-aortic balloon pump with concurrent support with continuous veno-venous hemodialysis.

Malfunction of electronic medical support apparatus utilized in the ICU usually causes system failure. We report several occurrences of a potentially dangerous interaction between a continuous veno-venous hemodialysis (CVVHD) system and an intra-aortic balloon pump (IABP) counterpulsation device in four patients requiring both systems. The patients had acute renal failure in the face of multi-organ failure and were dependent upon the balloon pump for pressure support. Electrical interference created by the roller pump action of the CVVHD system was identified by the balloon pump as cardiac in origin, and it responded by inflation and deflation. As the blood pump rate was reduced, the interference reduced to the point of complete cessation when the blood pump was shut down. Whereas one patient transiently had a significant drop of mean arterial pressure (from 70 +/- 4 to 40 +/- 2 mm Hg) the other observed occurrences had no clinically significant sequelae. Electrocardiogram (ECG) tracings identified the abnormal stimulus and systematic review identified as potential sources for the creation of this interference static electricity buildup, piezoelectric properties of the polyvinyl chloride tubing, and, possibly but less likely, radiofrequency interference. A newer generation ECG cable and advanced cardiac rhythm recognition software (CardioSync) have been introduced with the Datascope System 98, and the ECG interference, although still occasionally present, does not cause erratic inflation and deflation of the intra-aortic balloon pump. Interference between different electrical support systems may occur, and we suggest that the systems be tested for compatibility before combined use and that older equipment be more rigorously tested for potential clinically significant interference.

Aged↗