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Biomedical subjects

G Kennedy

Publications and source records attributed to G Kennedy.

99 records · Page 6Linked to original sources
PubMedDate not supplied

Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with type 1 diabetes with no clinical vascular disease.

BACKGROUND: Endothelial cell dysfunction is an early feature of vascular disease and oxidative stress may be involved in its pathogenesis. METHODS: Fifty-one children, adolescents and young people with Type 1 diabetes with no clinical diabetic angiopathy, mean age+/-SD of 16+/-4 years, diabetes duration of 8+/-5 years, and HbA(1c) of 8.5+/-1.6%, and 29 age, sex matched normal controls had blood samples assayed for E-selectin, intercellular cell adhesion molecule-1, von Willebrand Factor, red cell superoxide dismutase, plasma thiol and red cell glutathione. RESULTS: E-selectin and ICAM-1 levels were significantly higher in the diabetic patients at 72+/-24 ng/ml and 287+/-57 ng/ml, respectively vs 43+/-16 ng/ml and 248+/-71 ng/ml in the normal controls (p<0.0002 and p<0.013). Von Willebrand Factor levels were not different between the two groups. Superoxide dismutase activity was significantly higher in the diabetic group at 220+/-58 micro/ml vs 175+/-24 micro/ml in the normal controls p<0.001, and those of plasma thiol and red cell glutathione were significantly lower in the diabetic group, at 1267+/-202 micromol/l and 458+/-38 micromol/l, respectively vs 1403+/-278 micromol/l and 487+/-70 micromol/l in the controls p<0.02 and p<0.03. Levels of superoxide dismutase correlated negatively with plasma thiol, age and diabetes duration r=-0.318, p<0.02; r=-0. 328, p<0.02; and r=-0.286, p<0.05, respectively. CONCLUSION: These results confirm evidence of endothelial perturbation in young people with diabetes mellitus, and they also suggest that free radical generation may contribute to this dysfunction. This supports the hypothesis that vascular disease starts early in the course of childhood diabetes, akin to the situation in adults with diabetes.

Adolescent↗
PubMedDate not supplied

Reactions of muconaldehyde isomers with nucleophiles including tri-O-acetylguanosine: formation of 1,2-disubstituted pyrroles from reactions of the (Z,Z)-isomer with primary amines.

(Z,Z)-Muconaldehyde reacts with primary amines, including valine and lysine (epsilon-amino), to afford N-substituted-2-(oxoethyl)pyrroles, which were reduced with sodium borohydride to the more stable N-substituted-2-(hydroxyethyl)pyrroles. The formation of the pyrrole aldehydes was performed in a variety of solvents including aqueous methanol. With tri-O-acetylguanosine, the putative pyrrole aldehyde derived from reaction at NH2 condenses with N-1 (guanine component) to afford a bicyclic adduct: 4,5-dihydro-5-hydroxy-10-beta-D-tri-O- acetylribosylpyrrolo[1',2':3,4]pyrimido[1,2-a]purin-7(10H)-one (5a). This was hydrolyzed to 4,5-dihydro-5-hydroxy-10-beta-D- ribosylpyrrolo[1',2':3,4]pyrimido[1,2-a]purin-7(10H)-one (5b). The structures of 5a and 5b were primarily based on NMR evidence and comparison with 4,5-dihydro-5-hydroxy-9-methylpyrrolo[1',2':3,4]pyrimido[2,1-b] pyrimidin-7-one (7), obtained from reacting (Z,Z)-muconaldehyde with 2-amino-4-hydroxy-6-methylpyrimidine. (E,Z)-Muconaldehyde also reacted with primary amines to give N-substituted-2-(oxoethyl)pyrroles, whereas (E,E)-muconaldehyde gave bis-imines. The results described are discussed in the context of the carcinogenicity of benzene.

Aldehydes↗
PubMedDate not supplied

Mechanisms of formation of adducts from reactions of glycidaldehyde with 2'-deoxyguanosine and/or guanosine.

Convenient synthesis of rac-glycidaldehyde from rac-but-3-ene-1,2-diol and (R)-glycidaldehyde from D-mannitol are described. (R)-Glycidaldehyde (1) reacts with guanosine in water (pH 4-11, faster reaction at higher pH) to give initially 6(S)-hydroxy-7(S)-(hydroxymethyl)-3-(beta-D-ribofuranosyl)-5,6,7- trihydroimidazo[1,2-alpha]purin-9(3H)-one (7a) and 6(S),7(R)-dihydroxy-3-(beta-D-ribofuranosyl)-5,6,7,8- tetrahydropyrimido[1,2- alpha]purin-10(3H)-one (8a). The former decomposes to 7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2- alpha]purine (3a), 5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2-alpha]purine (5a, 1,N2-ethenoguanosine), and formaldehyde, while the latter adduct is relatively stable. The position of the hydroxymethyl group on the imidazo ring of 7-(hydroxymethyl)-5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo-[1,2 - alpha]purine was proved by 13C NMR analysis of adducts derived from [1-15N]guanosine and [amino-15N]guanosine. At longer reaction times, the adduct 7,7'-methylenebis[5,9-dihydro-9-oxo-3-(beta-D-ribofuranosyl)imidazo[1,2- alpha]purine (4a) is formed from guanosine and glycidaldehyde. The structure analysis of this adduct was also aided by 13C NMR analysis of the 15N-labeled adduct derived from [1-15N]guanosine. Analogous adducts were obtained from the reaction between glycidaldehyde and deoxyguanosine. Mechanisms of formation of the adducts from glycidaldehyde and guanosine/deoxyguanosine are proposed and supported by model studies with simple amines. The formaldehyde produced in the reactions described reacts with guanosine to give the known adduct N2-(hydroxymethyl)guanosine (9).

Aldehydes↗
PubMedDate not supplied

Health effects of residential exposure to aluminum plant air pollution.

In this study, the authors evaluated the relative risk of residential exposure to air pollution from an aluminum plant. The authors used government-compiled data to compare hospital admissions in 1997 for selected respiratory diseases for 2 communities in Brazil. One community, Ouro Preto, was located near an aluminum plant, and the other, Diamantina, was located far from any source of industrial air pollution. The relative risk of hospital admissions for selected respiratory diseases was 4.11 (95% confidence interval = 2.96, 5.70). The risk was highest among individuals between 30 and 39 yr of age (relative risk = 11.70; 95% confidence interval = 1.52, 89.96). Admissions per thousand residents were highest for individuals under 10 yr of age and for individuals older than 70 yr of age. The authors assessed exposure with environmental measurements. Dust deposition was collected in the residences of participants (n = 36 in each location), and the dust was analyzed for aluminum, manganese, magnesium, and calcium content. There were significantly different (p < .05) levels of aluminum in the 2 communities; the highest quantities were found near the aluminum plant. Measurements from independent studies indicated that both 24-hr maximum values and annual mean concentrations of suspended particulate matter exceeded the average of international standards in Ouro Preto (i.e., aluminum plant area). These results suggested that exposure to greater air pollution in the aluminum plant area (i.e., Ouro Preto, Brazil) versus the control area resulted in statistically significant health effects in those individuals who resided in Ouro Preto.

Adult↗
PubMedDate not supplied

Airborne manganese particulates and methylcyclopentadienyl manganese tricarbonyl (MMT) at selected outdoor sites in Montreal.

This study aims to assess the atmospheric concentrations of methylcyclopentadienyl manganese tricarbonyl (MMT), respirable manganese (MNR) and total manganese (MnT) in certain specific microenvironments and to provide an estimation of human exposure to MnR. Sampling was carried out in five microenvironments: a gas station, an underground car park, downtown Montreal, near an expressway and near an oil refinery. The samples were collected using Gil-Air portable pumps during three days and were analyzed by instrumental neutron activation analysis (INAA). The mean concentrations of MnR, MnT and MMT were 0.036 microgram m-3, 0.103 microgram m-3 and 0.005 microgram m-3 respectively. The MnR/MnT ratios vary from 25% to 43% (mean 35%) while the MMT/MnT ratios averaged about 5%. Furthermore, the mean concentration of the MnR measured near the expressway (0.053 microgram m-3) is similar to the United States Environmental Protection Agency (U.S. EPA) reference concentration (RfC = 0.05 microgram m-3). The average daily environmental exposure dose to MNR is estimated at 0.010 microgram kg-1 d-1 and its contribution to the multimedia exposure (air, food and water) is low. The overall results show a lack of potential exposure to MMT and substantial concentrations of MnR near an expressway.

Air Pollutants↗