Evidence for phosphate adducts in DNA from mice treated with 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

The weakly alkylating capacity of phosphotriesters (PTE) has been used for the determination of adducts to phosphate groups in DNA by specific transfer to the strongly nucleophilic compound cob(I)alamin [Cbl(I)]. When enzymatically degraded liver DNA from mice treated with 1-(N-methyl-N-nitrosamino)-4-(3-[3H]pyridyl)-4-oxobutane ([3H]NNK) was added to Cbl(I), a 4-(3-[3H]pyridyl)-4-hydroxy-1-butyl-cobalamin ([3H]PHB-Cbl) complex was formed and determined by HPLC and liquid scintillation counting. The PHB-Cbl formed was compared with a synthetic standard verified by LC/MS and 1H NMR and corresponds to phosphate adducts formed from the pyridyloxobutylating species from NNK and from the pyridylhydroxybutylating species from NNAL, NNK being to a large extent converted to NNAL in vivo. It was concluded that about 22% of the total level of pyridyl (oxo or hydroxy) butyl adducts to DNA was bound to phosphate groups.     

Detection and characterization of a novel functional polymorphism in the GSTT1 gene

A novel functional polymorphism in the GSTT1 gene associated with the non-conjugator phenotype has been identified. Sequencing of GSTT1 cDNA revealed a single nucleotide substitution, 310A>C, that altered the amino acid residue 104 from threonine to proline (T104P). Modelling studies of GSTT1 have suggested that residue 104 is located in the middle of alpha-helix 4. Introduction of an alpha-helix-disrupting proline most likely distorts the conformation of the protein. Individuals that lacked GSTT1 activity and carried the variant allele, tentatively denoted GSTT1*B, had no detectable GSTT1 immunoreactive protein. An allele-specific polymerase chain reaction method was developed to determine the frequency of the GSTT1*B allele. In 497 ethnic Swedes, the frequency of the active GSTT1*A allele was 0.65 [95% confidence interval (CI) 0.62-0.68] whereas the frequencies of the non-functional alleles GSTT1*O and the novel GSTT1*B allele were 0.34 (CI 0.31-0.37) and 0.01 (CI 0.01-0.02), respectively. In 100 Swedish Saamis, the GSTT1*B allele appeared to be slightly more common with a frequency of 0.03 (CI 0.01-0.07). The GSTT1 enzyme activity was measured in erythrocytes using methyl chloride as substrate. Individuals with the GSTT1*A/*A genotype had a two-fold higher GSTT1 activity compared to individuals with the GSTT1*A/*B genotype and subjects with the GSTT1*O/*B genotype totally lacked GSTT1 activity, indicating a strict gene-dose effect. By combining the analyses for the novel single nucleotide polymorphism with analyses for the deletion polymorphism, the accuracy in predicting all three GSTT1 conjugator phenotypes was improved from 96% to 99%.     

Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study

Topical butyrate has been shown to be effective in the treatment of ulcerative colitis (UC). Butyrate is derived from colonic fermentation of dietary fiber, and our aim was to study whether UC patients could safely increase the fecal butyrate level by dietary means. We enrolled 22 patients with quiescent UC (mean age, 44 years; 45% women; median time from last relapse, 1 year) in a controlled pilot trial lasting 3 months. The patients were instructed to add 60 g oat bran (corresponding to 20 g dietary fiber) to the daily diet, mainly as bread slices. Fecal short-chain fatty acids (SCFAs) including butyrate, disease activity, and gastrointestinal symptoms were recorded every 4 weeks. During the oat bran intervention the fecal butyrate concentration increased by 36% at 4 weeks (from 11 +/- 2 (mean +/- SEM) to 15 +/- 2 micromol/g feces) (p < 0.01). The mean butyrate concentration over the entire test period was 14 +/- 1 micromol/g feces (p < 0.05). Remaining fecal SCFA levels were unchanged. No patient showed signs of colitis relapse. Unlike controls, the patients showed no increase in gastrointestinal complaints during the trial. Yet patients reporting abdominal pain and reflux complaints at entry showed significant improvement at 12 weeks that returned to baseline 3 months later. This pilot study shows that patients with quiescent UC can safely take a diet rich in oat bran specifically to increase the fecal butyrate level. This may have clinical implications and warrants studies of the long-term benefits of using oat bran in the maintenance therapy in UC.     

Combinations of indigestible carbohydrates affect short-chain fatty acid formation in the hindgut of rats

The fermentability and pattern of short-chain fatty acids (SCFA) formed in the hindgut of rats given various combinations of dietary fibers (DF) and resistant starch (RS) were investigated. Highly fermentable indigestible carbohydrates, i.e., guar gum (GG), pectin (Pec) and high amylose cornstarch (HAS), and a DF with a relatively high resistance to fermentation, i.e., wheat bran (WB), were included. The substrates were studied individually or as mixtures (GG + Pec, GG + WB and HAS + WB, 1:1, wt/wt indigestible carbohydrate basis) at a total concentration of 100 g indigestible carbohydrates/kg diet and fed to rats for 13 d. Rats fed Pec had a high proportion of acetic acid in the cecum (76 +/- 2% of total SCFA), whereas those fed GG had the highest proportion of propionic acid (31 +/- 4%, P <0.0005). Rats fed GG and Pec had low proportions of butyric acid (6 +/- 1 and 10 +/- 1%, respectively), whereas those fed both had a higher proportion of butyric acid (15 +/- 3%, P < 0.05). Consequently, the cecal butyric acid pool was twice as high in rats fed the GG + Pec mixture (44 +/- 9 micro mol) as in those fed the individual components (19 +/- 2 and 21 +/- 3 micro mol, respectively, P < 0.05). Rats fed HAS with WB had a greater fecal excretion of SCFA (184 +/- 19 micro mol/d) than those fed the individual components (77 +/- 10 and 116 +/- 12 micro mol/d in rats fed HAS and WB, respectively P < 0.05), suggesting that incorporation of WB delayed the site of fermentation of HAS to the distal part of the hindgut. In conclusion, the combination of indigestible carbohydrates may affect both SCFA patterns and the site of SCFA release in the rat hindgut.     

Knowledge of osteoporosis in a Swedish municipality--a prospective study

BACKGROUND: As a part of the Vadstena Osteoporosis Prevention Project, the knowledge of osteoporosis was examined before the intervention program started, after 5 and 10 years. METHODS: At baseline (in 1989) 15% of the population in two Swedish municipalities was randomly invited to the study. The participants in the study group were invited for examination by forearm bone densitometry and a questionnaire concerning lifestyle and risk factors for osteoporosis and also knowledge of osteoporosis, while the subjects in the control group were examined only by questionnaire. Follow-ups were made in 1994 and in 1999. Meanwhile education about osteoporosis was given to the study group, to the public, and to various professionals in the study community. RESULTS: There was a difference in the level of knowledge between the groups prior to the intervention. The rate of increment did not differ significantly between the groups for the study period. Previous participants had 0.58 higher score than new participants in the study group in 1994 (P = 0.031) and 0.76 higher score in 1999 (P < 0.001) regarding the total number of correct answers. The women in the study group had 0.63 higher score than the men in 1994 (P = 0.016) and 1.03 higher score in 1999 (P < 0.001) regarding the total number of correct answers. CONCLUSION: There was no significant effect of a general intervention program concerning the knowledge of osteoporosis in participants in the intervention area compared to the control area.     

Activity level and balance in subjects with mild Alzheimer's disease

To clarify if Alzheimer's disease has an impact on activity level and postural control, we examined 17 elderly diagnosed with mild Alzheimer's disease (MMSE scores 21-29) and 18 age- and gender-matched healthy controls (MMSE scores 27-30) using the Frenchay Activities Index, Bergs Balance Scale, Timed Up & Go and Walking in a Figure of Eight. Mild AD subjects were less active and had lower scores on Bergs Balance Scale, performed Timed Up & Go in longer time and took more steps outside the Figure of Eight, as compared to healthy elderly. This study shows that motor performance is affected already at mild stages of Alzheimer's disease and also that functional performance other than gait may also be impaired.     

Does thrombin activatable fibrinolysis inhibitor (TAFI) contribute to impairment of fibrinolysis in patients with preeclampsia and/or intrauterine fetal growth retardation?

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a relatively recently described glycoprotein (MM 55 KDa) that can be converted into its active form by the thrombin/thrombomodulin complex and potentially inhibits fibrinolysis. Since it represents a link between coagulation and fibrinolysis, TAFI can be expected to play a part in various clinical conditions associated with a thrombotic tendency. Preeclampsia (PE) and intrauterine fetal growth retardation (IUFGR) are fairly common complications of pregnancy that are characterized by hemostatic abnormalities. TAFI antigen and its influence on hemostasis was investigated in 46 women with PE and/or IUFGR and in 16 normal pregnancies. We found a significant decrease of TAFI antigen in the patient group. Using the recently described method Overall Hemostatic Potential (OHP) in plasma we measured clot lysis time (CLT) and overall fibrinolytic potential (OFP). We found that CLT is prolonged and OFP decreased in patients with PE and/or IUFGR. Since OFP did not increase after addition of the specific inhibitor of TAFI (potato tuber carboxypeptidase inhibitor), it seems that TAFI does not contribute to the impairment of fibrinolysis in these patients. Since serum albumin was decreased together with presence of proteinuria and aminotransferases were increased in the patients, it seems that one explanation for the decrease in TAFI could be reduced hepatic synthesis and an increased loss in urine. It an be speculated that this mechanism can prevent more serious thrombotic complications in patients with PE and/or IUFGR.     

Musculoskeletal symptom survey among mason tenders

BACKGROUND: Low back pain (LBP) constitutes a major problem in construction. The magnitude and musculoskeletal injury characteristics in certain construction trades have been studied extensively. Musculoskeletal research targeting mason tenders is limited. High physical demands of the job primarily contribute to an increased risk of LBP experienced by these laborers. METHODS: A symptom survey was conducted to determine the magnitude and musculoskeletal injury characteristics among the mason tenders, and to identify work-related activities perceived by them as contributing to their disorders. RESULTS: The findings revealed that 82% of the mason tenders experienced at least one musculoskeletal symptom in the last year. LBP was the most frequently reported symptom (65%). Due to LBP, 12% of the laborers missed work and 18% of them visited a physician. Bending or twisting the back, working in the same position or in pain, and heavy lifting they perceived as the most problematic work-related activities. The vast majority of the laborers requested job-safety training. CONCLUSIONS: The mason tenders experienced high prevalence of LBP. To address the problem a model for primary prevention of LBP was developed and implemented in the trade. The model incorporated ergonomic principles, hazard recognition, and problem solving in the training curriculum for the union instructors teaching apprentices the trade-specific skills.     

Exposure and nasal inflammation in workers heating polyurethane

OBJECTIVE: To test the hypothesis that exposure to thermal-degradation products of polyurethane (PUR), particularly isocyanates, induced nasal inflammation. METHODS: Thirty-eight workers -14 with a history of work-related nasal symptoms (WRS/Nose), and 15 referents without such history - exposed to sprayed and heated PUR glue, were studied with regard to biomarkers of isocyanate exposure [4,4'-diphenylmethane diisocyanate (4,4'-methylenediphenyl diisocyanate; MDI) and 2,4- and 2,6-toluene diisocyanate (TDI), determined as 4,4'-diphenylmethane (U-MDX) and 2,4- and 2,6-toluene (U-2,4 and U-2,6-TDX) diamine in hydrolysed urine and nasal lavage fluid (NAL)], inflammation [albumin; eosinophilic cationic protein (ECP); myeloperoxidase (MPO) and cells in NAL], serum IgG specific for MDI (S-IgG-MDI) and TDI (S-IgG-TDI), and nose symptoms. Nine unexposed office workers were also examined. RESULTS: The exposure to sprayed and heated PUR glue, especially when heated by gun, was associated with the presence of biomarkers of isocyanate exposure in urine; after work the levels [median (range)] in all workers were: U-MDX 0.32 (相似文献