Mol Creatinine Research Articles

Physiology of deep closed circuit rebreather mixed gas diving: vascular gas emboli and biological changes during a week-long liveaboard safari.

Introduction: Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6-8 dives with a maximum of two dives per day at depths ranging from 21 to 122msw with CCR mixed gas diving. Methods: Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-α, IL-6, and neopterin). Results: VGE exhibits a progressive reduction followed by an increase (p < 0.0001) which parallels inflammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09μmol.min-1 (p < 0.001); 199.8 ± 55.9 to 632.7 ± 73.3ng.mg-1 creatinine (p < 0.0001); 2.35 ± 0.54 to 19.5 ± 2.96pg.mL-1 (p < 0.001); and 93.7 ± 11.2 to 299 ± 25.9μmol·mol-1 creatinine (p = 0.005), respectively. The variation after each dive was held constant around 158.3% ± 6.9% (p = 0.021); 151.4% ± 5.7% (p < 0.0001); 176.3% ± 11.9% (p < 0.0001); and 160.1% ± 5.6% (p < 0.001), respectively. Discussion: When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of "first generation" pre-existing micronuclei.

Age-Specific Excretion of Calcium, Oxalate, Citrate, and Glycosaminoglycans and Their Ratios in Healthy Children and Children with Urolithiasis.

We analyzed children with urolithiasis with age- and gender-matched healthy children. Calcium (mmol/mmol creatinine) and the calcium/citrate ratio (mol/mmol) are the only variables that differentiate children before puberty from healthy children (ROC analysis confirmed only calcium/citrate as a significant variable with cut-off value > 0.84). Peri-pubertal children are distinguished from age- and gender-matched healthy children by the following variables: citrate (mmol/mol creatinine), calcium/citrate (mol/mmol), oxalate/glycosaminoglycans (mmol/g), oxalate/citrate ratios (mmol/mmol) and oxalate/(citrate × glycosaminoglycans) (mol oxalate × mol creatinine)/(mol citrate × g glycosaminoglycans). All variables were confirmed by ROC analysis with cut-off values ≤ 327.87, >1.02, >11.24, >0.12 and >0.03, respectively. These results indicate a different risk of urinary stones development before puberty vs. pubertal/postpubertal children and increasing importance (deficiency) of citrate and glycosaminoglycans in such children. J48 classifier confirmed the importance of the oxalate/(citrate × glycosaminoglycans) and the calcium/citrate ratios (Ox/Cit × GAG 0.22 and Cit/GAG 0.612) with the practically applicable classification tree for distinguishing between pubertal/postpubertal children with urolithiasis with age- and gender-matched healthy children.

Disease vulnerability and PAH biomonitoring in urban population exposed to air-borne particulate matter

This study was conducted in urban area of Rawalpindi city with an aim to analyze population exposure to particulate matter (PM) and Polycyclic Aromatic Hydrocarbons (PAHs) in relation to their vulnerability for diseases. Biomonitoring study using serum naphthalene, pyrene and urinary 1-hydroxyprene was also conducted to quantify PAH exposure. The health risks based on self-reported health status was also noted using a questionnaire. Results of HPLC based serum analysis showed that mean concentration of blood naphthalene was 106 μg L-1 which had significant correlation with cigarette smoking (r=0.49; p&lt;0.01). However, pyrene body burden (mean 19.18 μg L-1) appeared to be a significant predictor of urinary 1-hydroxyprene pyrene (69.9 μmol mol-1 creatinine). Among people associated with petroleum related occupations, there was fairly high significant effect of daily work-hours and job duration on serum pyrene levels. Urban population exposed to 6 hour per day or more had significantly high prevalence of physical disorders (OR=2.79, 95% CI=1.28-6.09). Neurasthenic symptoms were found in 65% of the subjects and were associated with years of involvement in job. Ten years or more occupational work at petrol pumps attributed substantial development of neurasthenic effects (OR=2.80, 95% CI=1.23-6.34). We conclude that subjects associating disturbances in physical and neurological behavior with petrol related occupation rated their overall health and functional capacity significantly poorer than that of urban area general population. A direct relationship between exposure to PM with population illness was observed especially during winter. To promote health of occupational groups, reduction in work hours and provision of masks and gloves could be introduced as health interventions.

Exposures and urinary biomonitoring of aliphatic isocyanates in construction metal structure coating.

Isocyanates are highly reactive chemicals used widely in metal structure coating applications in construction. Isocyanates are potent respiratory and skin sensitizers and a leading cause of occupational asthma. At present, there is no cure for isocyanate asthma and no biomarkers of early disease. Exposure reduction is considered the most effective preventive strategy. To date, limited data are available on isocyanate exposures and work practices in construction trades using isocyanates, including metal structure coatings. The primary objectives of this work were: i) to characterize isocyanate inhalation and dermal exposures among painters during metal structure coating tasks in construction; and ii) to assess the adequacy of existing work practices and exposure controls via urinary biomonitoring pre- and post-shift. Exposures to aliphatic isocyanates based on 1,6-hexamethylene diisocyanate (1,6-HDI) and its higher oligomers (biuret, isocyanurate and uretdione) were measured among 30 workers performing painting of bridges and other metal structures in several construction sites in the Northeastern USA. Exposure assessment included simultaneous measurement of personal inhalation exposures (n=20), dermal exposures (n=22) and body burden via urinary biomonitoring pre- and post-shift (n=53). Contextual information was collected about tasks, processes, materials, work practices, personal protective equipment (PPEs) and exposure controls, work histories, and environmental conditions. Breathing zone concentrations were the highest for biuret (median, 18.4μg/m3), followed by 1,6-HDI monomer (median, 3.5μg/m3), isocyanurate (median, 3.4μg/m3) and uretdione (median, 1.7μg/m3). The highest exposures, measured during painting inside an enclosed bridge on a hot summer day, were: 10,288μg/m3 uretdione; 8,240μg/m3 biuret; and 947μg/m3 1,6-HDI. Twenty percent of samples were above the NIOSH ceiling exposure limit for 1,6- HDI (140μg/m3) and 35% of samples were above the UK-HSE ceiling for total isocyanate group (70μg NCO/m3). Isocyanate loading on the gloves was generally high, with a median of 129μg biuret/pair and maximum of 60.8mg biuret/pair. The most frequently used PPEs in the workplace were half-face organic vapor cartridge (OVC) respirators, disposable palmar dip-coated polymer gloves, and cotton coveralls. However, 32% of workers didn't wear any respirator, 47% wore standard clothing with short-sleeve shirts and 14% didn't wear any gloves while performing tasks involving isocyanates. Based on biomonitoring results, 58.4% of urine samples exceeded the biological monitoring guidance value (BMGV) of 1μmol hexamethylene diamine (HDA)/mol creatinine. Post-shift geometric mean HDA normalized to specific gravity increased by 2.5-fold compared to pre-shift (GM, 4.7 vs. 1.9ng/mL; p value, < 0.001), and only 1.4-fold when normalized to creatinine. Exposure and biomonitoring results, coupled with field observations, support the overall conclusions that (i) substantial inhalation and dermal exposures to aliphatic isocyanates occur during industrial coating applications in construction trades; that (ii) the current work practices and exposure controls are not adequately protective. High urinary creatinine values in the majority of workers, coupled with significant cross-shift increases and filed observations, point to the need for further investigations on possible combined effects of heat stress, dehydration, and nutritional deficiencies on kidney toxicity. Implementation of comprehensive exposure control programs and increased awareness are warranted in order to reduce isocyanate exposures and associated health risks among this cohort of construction workers.

Verification of Quantitative Measurement of Urinary Creatinine Enzymatic Method Kit by DIRUI CS-T240 Clinical Chemistry Analyser

Introduction: All urine samples sent for the diagnosis of inborn errors of metabolism (IEM) disorders testing will be first analysed for their creatinine levels. The urine creatinine analysis is applied either for calculation of urine amount needed in other tests or for quantitation of analytes per mol creatinine. Jaffe kinetic-end point method has been the preferred method. We aim to verify the performance of DIRUI enzymatic method reagent kit on DIRUI CS-T240 analyser and compare with Randox Jaffe kinetic-end point method reagent kit on same platform.Method: Precision study, linearity and method comparisons were carried out using three levels of internal quality control (IQC) samples and the measured results were compared against manufacturer’s claims, medical decision limit and biological variation (BV).Results: The within run coefficient variation (CV) were 3.57%, 2.61% and 1.35% for IQC Level 1, 2 and 3 respectively. The total precision and accuracy were 9.59% and 0.27% for Level 1, 3.17% and 0.57% for Level 2, while 2.03% and 3.63% for Level 3. Whereas, the verifica t ion value for CV based on analytical performance specifications (APS) BV desirable for CV and accuracy were 18.2% and 12.2% respectively. These values were compared, and the precision study was acceptable within desirable specification. Linearity met the manufacturer’s claim and range from 0.32 to 21.2mmol/L. The method comparison gave good correlation, r2 of 0.9975 and regression equation, y=0.9852x-0.022 with medical decision limit, 0.53mmol/L. The assessment of acceptability of this new method was acceptable as calculated total error (TEc) &lt; total allowable error (TEa) (APS BV Desirable for TEa = 42.1%).Conclusion: The analytical verification study that we had carried out fulfilled the BV desirable in precision, accuracy and TEa. Therefore, the performances of enzymatic method kit on DIRUI CS-T240 analyser is verified to be fit-for-purpose and can replace the existing method.International Journal of Human and Health Sciences Supplementary Issue: 2019 Page: 53

Genotype and phenotype characterization in a Spanish cohort with isovaleric acidemia.

Isovaleric acidemia (IVA) is a rare disorder of leucine metabolism. We carried out a multicenter study of IVA patients diagnosed by newborn screening (NBS) or symptoms clinics over a period of 28 years in Spain. Evaluated at diagnosis, data included age, detection method, levels of C5 and IVG, enzymatic studies, clinical presentation parameters and genotype in 16 patients. Follow-up data included C5 levels, intellectual quotient and correlation genotype-phenotype. IVA was detected by NBS in 8 patients (prevalence of 1/326 629). Except 1, all the 8 patients identified by NBS were asymptomatic at diagnosis and had isovalerylcarnitine (C5) levels of 1.6-6.4 μM and isovalerylglycine (IVG) levels <1100 mmol per mol creatinine; they remained asymptomatic with a natural protein intake ⩾1.5 g kg-1 per day. Symptomatic patients with chronic intermittent or acute neonatal IVA had C5 levels of 3.9-16.3 μM and IVG levels >3400 mmol per mol creatinine. The percentage of isovalerate incorporation in fibroblasts was 64-80% in patients detected by NBS and 4.9-13% in symptomatic patients. Cognitive function was within normal ranges in all patients but was negatively correlated with IVG at detection (-0.592; P<0.05). The genetic analysis revealed nine novel mutations. The clinical/biochemical phenotype correlated fairly well with the phenotype predicted by the mutations found. In conclusion, although blood C5 levels have traditionally been considered the prognostic marker of choice, urine IVG levels would appear to be a better predictor, as they correlated well with severity of mutations and were associated with a lower incorporation rate of IVA in fibroblasts and a less favorable clinical course.

Firefighters' exposure biomonitoring: Impact of firefighting activities on levels of urinary monohydroxyl metabolites.

The concentrations of six urinary monohydroxyl metabolites (OH-PAHs) of polycyclic aromatic hydrocarbons, namely 1-hydroxynaphthalene, 1-hydroxyacenaphthene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene (1OHPy), and 3-hydroxybenzo[a]pyrene, were assessed in the post-shift urine of wildland firefighters involved in fire combat activities at six Portuguese fire corporations, and compared with those of non-exposed subjects. Overall, median levels of urinary individual and total OH-PAHs (ΣOH-PAHs) suggest an increased exposure to polycyclic aromatic hydrocarbons during firefighting activities with ΣOH-PAH levels in exposed firefighters 1.7-35 times higher than in non-exposed ones. Urinary 1-hydroxynaphthalene and/or 1-hydroxyacenapthene were the predominant compounds, representing 63-98% of ΣOH-PAHs, followed by 2-hydroxyfluorene (1-17%), 1-hydroxyphenanthrene (1-13%), and 1OHPy (0.3-10%). A similar profile was observed when gender discrimination was considered. Participation in fire combat activities promoted an increase of the distribution percentage of 1-hydroxynaphthalene and 1-hydroxyacenaphthene, while contributions of 1-hydroxyphenanthrene and 1OHPy decreased. The detected urinary 1OHPy concentrations (1.73×10-2 to 0.152μmol/mol creatinine in exposed subjects versus 1.21×10-2 to 5.44×10-2μmol/mol creatinine in non-exposed individuals) were lower than the benchmark level (0.5μmol/mol creatinine) proposed by the American Conference of Governmental Industrial Hygienists. This compound, considered the biomarker of exposure to PAHs, was the less abundant one from the six analyzed biomarkers. Thus the inclusion of other metabolites, in addition to 1OHPy, in future studies is suggested to better estimate firefighters' occupational exposure to PAHs. Moreover, strong to moderate Spearman correlations were observed between individual compounds and ΣOH-PAHs corroborating the prevalence of an emission source.

The genetic diversity of cystinuria in a UK population of patients.

To examine the genetic mutations in the first UK cohort of patients with cystinuria with preliminary genotype/phenotype correlation. DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to identify the mutations in 74 patients in a specialist cystinuria clinic in the UK. Patients with type A cystinuria were classified into two groups: Group M patients had at least one missense mutation and Group N patients had two alleles of all other types of mutations including frameshift, splice site, nonsense, deletions and duplications. The levels of urinary dibasic amino acids, age at presentation of disease, number of stone episodes and interventions were compared between patients in the two groups using the Mann-Whitney U-test. In all, 41 patients had type A cystinuria, including one patient with a variant of unknown significance and 23 patients had type B cystinuria, including six patients with variants of unknown significance. One patient had three sequence variants in SLC7A9; however, two are of unknown significance. Three patients had type AB cystinuria. Three had a single mutation in SLC7A9. No identified mutations were found in three patients in either gene. There were a total of 88 mutations in SLC3A1 and 55 mutations in SLC7A9. There were 23 pathogenic mutations identified in our UK cohort of patients not previously published. In patients with type A cystinuria, the presence of a missense mutation correlated to lower levels of urinary lysine (mean [SE] 611.9 [22.65] vs 752.3 [46.39] millimoles per mole of creatinine [mM/MC]; P=0.02), arginine (194.8 [24.83] vs 397.7 [15.32] mM/MC; P<0.001) and ornithine (109.2 [7.40] vs 146.6 [12.7] mM/MC; P=0.02). There was no difference in the levels of urinary cystine (182.1 [8.89] vs 207.2 [19.23] mM/MC; P=0.23). We have characterised the genetic diversity of cystinuria in a UK population including 23 pathogenic mutations not previously published. Patients with at least one missense mutation in SLC3A1 had significantly lower levels of lysine, arginine, and ornithine but not cystine than patients with all other combinations of mutations.

Relevance of urinary 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene to assess exposure to carcinogenic polycyclic aromatic hydrocarbon mixtures in metallurgy workers.

In metallurgy, workers are exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs) in which some compounds are carcinogenic. Biomonitoring of PAH exposure has been performed by measuring urinary 1-hydroxypyrene (1-OHP), a metabolite of pyrene which is not carcinogenic. This study investigated the use of 3-hydroxybenzo(a)pyrene (3-OHBaP), a metabolite of benzo(a)pyrene (BaP) which is the main carcinogenic component in PAHs, to improve carcinogen exposure assessment. We included 129 metallurgy workers routinely exposed to PAHs during working hours. Urinary samples were collected at three sampling times at the beginning and at the end of the working week for 1-OHP and 3-OHBaP analyses. Workers in anode production showed greater exposure to both biomarkers than those in cathode or silicon production, with respectively, 71, 40, and 30% of 3-OHBaP concentrations exceeding the value of 0.4 nmol mol(-1) creatinine. No difference was observed between the 3-OHBaP levels found at the end of the penultimate workday shift and those at the beginning of the last workday shift. Within these plants, the 1-OHP/3-OHBaP ratios varied greatly according to the workers' activity and emission sources. Using linear regression between these two metabolites, the 1-OHP level corresponding to the guidance value for 3-OHBaP ranged from 0.7 to 2.4 µmol mol(-1) creatinine, depending on the industrial sector. This study emphasizes the interest of monitoring urinary 3-OHBaP at the end of the last workday shift when working week exposure is relatively steady, and the irrelevance of a single guideline value for 1-OHP when assessing occupational health risk.

Postmortem Urinary Cortisol Levels in Relation to the Cause of Death

In 239 postmortem cases, we used liquid chromatography/time-of-flight mass spectrometry to measure urinary cortisol concentrations standardized to creatinine, which were then related to causes of death. For comparison, we also analyzed urine samples from 95 living subjects implicated in criminal cases. The median of the postmortem group (18.8 μmol cortisol/mol creatinine) was not significantly different from that of the living group (18.1 μmol cortisol/ mol creatinine), but the highest value in the postmortem group was more than ten times higher than that in the living group (3730 versus 354 μmol cortisol/mol creatinine). Among the postmortem cases, 28% had values exceeding the previously reported upper 95% range for normal living subjects (52.8 μmol cortisol/mol creatinine), as did 12%of the living group. The postmortem cases were divided into subgroups according to cause of death:asphyxiation, blunt force trauma, brain hemorrhage, cardiac-related death, drowning, fire-related death, gun or knife trauma, infection, internal bleeding, ketoacidosis, miscellaneous and poisoning. The median cortisol levels of the ketoacidosisand the infection subgroups (respectively, 152 and 243 μmol cortisol/mol creatinine) were significantly higher than the median of the other subgroups (15.5 μmol cortisol/mol creatinine); however, the spread of data does not allow for any conclusions on an individual case level.

Measurement of 3-hydroxyisovaleric acid in urine from marginally biotin-deficient humans by UPLC-MS/MS

Measurement of 3-hydroxyisovaleric acid (3HIA) in human urine has been shown to be a useful indicator of biotin status for a variety of clinical situations, including pregnancy. The work described herein presents a novel UPLC-MS/MS method for accurate and precise quantitation of urinary 3HIA. This method utilizes sample preparation prior to quantitation that has been simplified compared to the previous GC-MS method. To demonstrate the suitability of the UPLC-MS/MS method for human bio-monitoring, this method was used to measure 3-HIA in 64 human urine samples from eight healthy adults in whom marginal biotin deficiency had been induced experimentally by egg white feeding. 3HIA was detected in all specimens; the mean concentration [±standard deviation (SD)] was 80.6 ± 51 μM prior to inducing biotin deficiency. Mean excretion rate for 3HIA (expressed per mol urinary creatinine) before beginning the biotin-deficient diet was 8.5 ± 3.2 mmol 3HIA per mol creatinine and the mean increased threefold with deficiency. These specimens had been previously analyzed by GC-MS; the two data sets showed strong linear relationship with a correlation coefficient of 0.97. These results provide evidence that this method is suitable for bio-monitoring of biotin status in larger populations.

Benzene Exposure During Tunnelling—Using Biological Monitoring to Assess Control Measures and Working Practice

This paper reports the assessment of worker exposure to high levels of benzene (up to 18 p.p.m. 8 h time weighted average, weekly average) during tunnelling on a contaminated land site (former gas works). Although respiratory and personal protection was used, biological monitoring results indicated that workers had urinary S-phenylmercapturic acid levels in excess of that expected following exposure to the UK workplace exposure limit. Factors such as environmental conditions (high temperature and humidity, confined workspace), respiratory and personal equipment providing insufficient protection, human behaviour (removing protective equipment, using mobile phones), and work practices (12-h shifts, too few and too short breaks, lack of drinking water) were identified as contributing to the exposure. A thorough review of control measures and working practice led to significant improvements, resulting in workers' exposure (as measured by biological monitoring) being kept below the 90th percentile value (8 μmol mol(-1) creatinine, 17 μg g(-1) creatinine) of data from a good cross section of UK industry (N = 2600) despite the continuing high environmental levels.

Otimização e validação de uma metodologia analítica para determinação de 1-hidroxipireno em urina de cortadores de cana-de-açúcar

Este trabalho teve como objetivo otimizar e validar uma metodologia analítica para determinação de 1-hidróxipireno em urina de trabalhadores envolvidos na colheita da cana-de-açúcar. O método utilizado para determinação de 1-hidroxipireno em urina humana utilizado consiste na hidrólise enzimática, extração e clean-up por extração em fase sólida (SPE) e quantificação por cromatografia líquida de alta eficiência com detector de fluorescência (CLAE/Flu). Quatro tipos de cartuchos foram testados para verificação da porcentagem de recuperação. Urina de cortadores de cana-de-açúcar (não-fumantes e de ambos os sexos) foram coletadas no período da safra (n=39) e entressafra (n=34) da cana-de-açúcar. Os melhores resultados de recuperação foram atribuídos aos cartuchos C18. Os mesmos apresentaram recuperação entre 79% e 108%, com coeficiente de variação entre 5% e 10%. O limite de quantificação do método foi de 74 ng de 1-hidroxipireno por litro de urina. A metodologia otimizada e validada foi utilizada para determinação de amostras reais. Os resultados encontrados na urina dos trabalhadores no período da safra variaram de 0,026 a 2,3 μmol de 1-hidroxipireno por mol de creatinina. No período da entressafra os resultados variaram de 0,0023 a 0,38 μmol de 1-hidroxipireno por mol de creatinina.

Otimização e validação de uma metodologia analítica para determinação de 1-hidroxipireno em urina de cortadores de cana-de-açúcar

Este trabalho teve como objetivo otimizar e validar uma metodologia analítica para determinação de 1-hidróxipireno em urina de trabalhadores envolvidos na colheita da cana-de-açúcar. O método utilizado para determinação de 1-hidroxipireno em urina humana utilizado consiste na hidrólise enzimática, extração e clean-up por extração em fase sólida (SPE) e quantificação por cromatografia líquida de alta eficiência com detector de fluorescência (CLAE/Flu). Quatro tipos de cartuchos foram testados para verificação da porcentagem de recuperação. Urina de cortadores de cana-de-açúcar (não-fumantes e de ambos os sexos) foram coletadas no período da safra (n=39) e entressafra (n=34) da cana-de-açúcar. Os melhores resultados de recuperação foram atribuídos aos cartuchos C18. Os mesmos apresentaram recuperação entre 79% e 108%, com coeficiente de variação entre 5% e 10%. O limite de quantificação do método foi de 74 ng de 1-hidroxipireno por litro de urina. A metodologia otimizada e validada foi utilizada para determinação de amostras reais. Os resultados encontrados na urina dos trabalhadores no período da safra variaram de 0,026 a 2,3 μmol de 1-hidroxipireno por mol de creatinina. No período da entressafra os resultados variaram de 0,0023 a 0,38 μmol de 1-hidroxipireno por mol de creatinina. A metodologia validada mostrou-se adequada para determinação de 1-hidroxipireno em urina humana. Os dados obtidos permitem concluir que há forte correlação entre excreção de 1-hidroxipireno e os períodos de safra e entressafra da cana de açúcar.

Association of melamine exposure with urinary stone and oxidative DNA damage in infants

There is evidence in experimental animals for the urolithiasis and carcinogenicity of melamine, but no evidence for melamine in humans. To evaluate any association between melamine-contaminated powdered formula (MCPF) feeding and urolithiasis, and further the MCPF feeding and oxidative damage to DNA in infants. A cross-sectional study was carried out to assess urolithiasis and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in four groups of infants according to the type of feeding: (1) Infants receiving over 90% of their intake as MCPF. (2) Infants receiving 50-90% of their intake as MCPF. (3) Infants receiving less than 50% of their intake as MCPF. (4) Infants receiving over 90% of their intake as imported milk powdered formula free of melamine contamination. Groups 1 to 3 are the observation groups, and Group 4 is the reference group. There is a significant correlation between urolithiasis and percentage of MCPF intake. The mean urinary 8-OHdG concentrations for Groups 1, 2, 3, and 4 were: 2.03 +/- 0.52, 1.67 +/- 0.28, 1.90 +/- 0.39, and 1.85 +/- 0.47 micromoles per mole of creatinine, respectively. There were no significant differences in the mean urinary 8-OHdG concentrations among the observation and control groups. There were also no correlation between mean urinary 8-OHdG excretions and percentage of MCPF intake. Our data suggested that melamine exposure were associated with urolithiasis, but it might not cause any increase in oxidative damage of DNA in infants.

A Survey of Occupational Exposure to 4,4′-methylene-bis (2-chloroaniline) (MbOCA) in the UK

The main objective of the study was to gather information about the current controls and levels of exposure to 4,4'-methylene-bis (2-chloroaniline) (MbOCA) in a representative cross section of workplaces that use it to manufacture polyurethane elastomers. The study also aimed to investigate whether controls and guidance could be improved and to investigate exposure to isocyanates in these workplaces using biological monitoring. An occupational hygienist and a field scientist visited the two UK suppliers and 20 out of the 25 workplaces known to be using MbOCA in the UK during 2005 and 2006. They collected air samples, surface wipes, gloves, and urine samples and made observations to assess exposure and the adequacy of controls. All samples were analysed for MbOCA and urine samples were additionally analysed for isocyanate metabolites. A statistical analysis was made of the results. Only 2.5% of the 80 personal inhalation exposures to MbOCA exceeded the workplace exposure limit of 5 microg m(-3) 8-h time-weighted average and 84% were below the limit of detection (LOD). Surface samples (n = 334) were collected from MbOCA users and suppliers and 60% had detectable levels of MbOCA ranging from 0.019 to 400 microg cm(-2). The highest levels were around a hopper, ovens, and the weighing and pouring areas. MbOCA was also detected in 8 of the 75 samples collected from areas not likely to be in contact with MbOCA. At the two suppliers, samples (n = 28) were collected from the outside surfaces of recently imported kegs, pallets, and the floor around kegs. Six samples had detectable levels and four of these (0.2, 0.8, 1, and 6 microg cm(-2)) were from the floor and pallets in both suppliers. The other two positive results were found on the outside rim (18 microg cm(-2)) and side (23 microg cm(-2)) of a keg at one supplier indicating contamination by the manufacturer. Urine samples (n = 79) were collected and 49% were below the LOD for MbOCA and only three samples had levels of MbOCA that exceeded the biological monitoring guidance value (BMGV) of 15 micromol mol(-1) creatinine. The highest urinary MbOCA concentrations were in samples from workers casting and moulding. The 90th percentile of the urine MbOCA results was 8.6 micromol MbOCA per mol creatinine. Urine samples were also analysed for the diamine metabolites of toluene diisocyanate and hexamethylene diisocyanate and 33% had detectable levels with 22 and 13% of results, respectively, above the BMGV for isocyanates (1 micromol isocyanate-derived diamine per mol creatinine). The maximum urinary concentration of toluene diamine and hexane diamine were 15.6 and 10.1 micromol mol(-1) creatinine, respectively. The survey found that the measures used to control exposure to MbOCA could be improved. Although air levels of MbOCA were generally low, there was evidence of spread of surface contamination and poor maintenance of controls such as local exhaust ventilation. A BMGV based on the 90th percentile of data from workplaces with good control would be less than the 90% value of 8.6 micromol mol(-1) creatinine found in this study and suggests that the current BMGV of 15 micromol mol(-1) creatinine is no longer acting as a stimulus to reduce exposure. The metabolites of isocyanates found in urine samples in this study could arise from inhalation exposure to isocyanates or from dermal exposure to either isocyanates or their diamine breakdown product and need further investigation.

Urinary D-Lactate Excretion in Infants Receiving Lactobacillus johnsonii with Formula

Background/Aims: Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects. This study aimed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii (La1®). Methods: In the framework of a double-blind, randomized controlled trial enrolling 71 infants aged 4–5 months, morning urine samples were collected before and 4 weeks after being fed formulas with or without La1 (1 × 10⁸/g powder) or being breastfed. Urinary D- and L-lactate concentrations were assayed by enzymatic, fluorimetric methods and excretion was normalized per mol creatinine. Results: At baseline, no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found. After 4 weeks, D-lactate excretion did not differ between the two formula groups, but was higher in both formula groups than in breastfed infants. In all infants receiving La1, urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method. Urinary L-lactate also did not vary over time or among groups. Conclusions: Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis.

Pteridine Pathway in Patients with Degenerative Diseases During Short Time Treatment with Low Dose of Meloxicam, as a Non-steroidal Anti-inflammatory Drug

Abstract The profiles of unconjugated pteridines such as neopterin and biopterin and of tryptophan metabolism change in many pathologic conditions such as rheumatoid arthritis, malignancies and autoimmune diseases and are related to the release of pro-inflammatory cytokines. However, studies on potential effects of drugs are very limited. This study investigates whether meloxicam, a non-steroidal anti-inflammatory drug, may cause any alteration of the pteridine pathway and tryptophan metabolism in 22 patients who admitted to the Physical and Rehabilitation Medicine outpatient clinic in the Hacettepe University Hospital and suffering from various musculoskeletal pain conditions without systemic inflammation. Urine concentrations of neopterin, biopterin and xanthopterin, and serum concentrations of neopterin, tryptophan, and kynurenine, and the activity of dihydropteridine reductase were measured at the beginning of the therapy and after a 15 days treatment with meloxicam. Average urine concentrations (± S.E.M.) of pterins before therapy (neopterin: 263 ± 15.6 μmol/mol creatinine, biopterin: 72.4 ± 13.4 μmol/mol creatinine, and xanthopterin: 675 ± 93.0 μmol/mol creatinine) were not changed during meloxicam therapy (neopterin: 230 ± 30.7 μmol/mol creatinine = 88% of baseline, biopterin 115 ± 26.5 μmol /mol creatinine = 159% of baseline, and xanthopterin 684 ± 88.0 μmol/mol creatinine = 101% of baseline; all differences not significant). The activity of dihydropteridine reductase was 6.02 ± 0.21 nmol/cytochrome C reduced/min/5 mm disc before and 6.28 ± 0.18 nmol/cytochrome C reduced/min/5 mm after treatment (= 104% of baseline; p = 0.088). Serum concentrations of neopterin 6.04 ± 0.33 nmol/L before treatment increased to 6.89 ± 0.48 nmol/L after treatment (= 114% of baseline; p &lt;0.05, paired rank test). Likewise serum kynurenine concentrations increased from 1.52 ± 0.13 μmol/L to 1.87 ± 0.14 μmol/L after treatment (= 123% of baseline; p &lt;0.01). There was a significant correlation between neopterin and kynurenine concentrations which corresponds with their common background of production, namely immune activation. However, also the mean tryptophan concentration in pretreatment samples 51.4 ± 3.34 increased to 59.3 ± 3.34 μmol/L post-treatment (= 115% of baseline; p &lt;0.05). The change of kyn/trp was minor (at baseline: 30.4 ± 2.01, post-treatment: 32.2 ± 2.47 μmol/mmol; = 106% of baseline, not significant). Our findings show an influence of meloxicam treatment on neopterin and tryptophan metabolism in patients. However, significant differences were only found in serum but not in urine of patients. In serum, all marker concentrations increased including tryptophan and kynurenine.

Preliminary Evidence on the Direction of Effects Between Day-to-Day Changes in Cellular Immune Activation, Fatigue and Mood in a Patient with Prior Breast Cancer: A Time-Series Analysis Approach

Abstract This study on a patient with prior breast cancer investigated the cause-effect relations between immune system activation, fatigue and mood under real-life conditions. The 60-year old woman (primary diagnosis 5 years ago, relapse one year ago, currently no signs of recurrence) collected her entire urine for 31 days in 12 hour intervals for the determination of immune activation marker neopterin and creatinine concentrations by HPLC. This study used only the daytime urinary neopterin concentrations (from approx. 8 a.m. to 8 p.m.) and cross-correlated them with daily data from mood (3-Skalen-EWL) and fatigue (VAS) questionnaires which the patient filled in for 31 days. Serial dependencies were controlled for by applying moving average smoothing. When averaged over the whole observation period, daily fatigue, daily mood and daily urinary neopterin (average 173 μmol per mol creatinine) were within normal limits. Cross-correlational analyses revealed that increases in urinary neopterin significantly preceded increases in fatigue by 24 hours (lag 1: r = +0.424; p &lt;0.05). The opposite direction of effects, however, existed between mood and neopterin, i.e., decreases in mood preceded increases in neopterin by 96 hours (lag 4: r = −0.697; p &lt;0.05). The results in this patient suggest a disturbed stress system activity where negative emotions are associated with increases instead of decreases in the degree of cellular immune activation and where cellular immune activation may trigger central nervous system symptoms such as fatigue. Despite some restrictions in data quality this study shows the feasibility of gathering evidence on naturally occurring psychoimmunological cause-effect relations based on extensive serial data collection and time series analysis.

Inter- and intra-individual variations in normal urinary glycine betaine excretion

Objectives: To establish whether normal human subjects excrete glycine betaine at a constant rate. Design and methods: Urine was collected from ten normal healthy male subjects for 14 days, during which fluid intake was systematically varied from < 800 mL to > 3 L per day. Glycine betaine, sorbitol and creatinine excretions were estimated per day and as millimole per mol creatinine. Results: The intrasubject SD of urine glycine betaine was 3.5 mmol/mol creatinine, and the intersubject SD 5.8 mmol/mol creatinine. The intrasubject SD of plasma glycine betaine was 10.2 mol/L and the intersubject SD 14.2 mol/L. Water load had little effect on glycine betaine excretion and plasma glycine betaine. After 12 years, excretions and plasma concentrations tended to parallel the initial results. Conclusions: Normal subjects have consistent individual glycine betaine excretions that are not strongly influenced by urine volume. Abnormal excretions, or significant changes in excretion, can be interpreted as indicating a pathological process.