Genotoxicity studies on professional hair colorists exposed to oxidation hair dyes

The cytogenic repercussions of occupational exposure to oxidation hair dyes were assessed by using three assays in professional hair colorists. The assays were sister chromatid exchanges (SCE) in circulating lymphocytes to evaluate the interchange of DNA replication products at apparently homologous chromosomal loci, single cell gel electrophoretic (SCGE) assay to detect the presence of DNA strand breaks/alkali-labile damage, and the Ames assay using Salmonella typhimurium strain TA98 to detect the urine mutagenicity. The ability of these assays to detect genetic damage caused by oxidation hair dyes in man compared with closely matched controls produced the following findings. (i) The SCE assay could not detect the mutagenic effect in lymphocytes of exposed subjects from whom complete data were obtained. However, subjects (controls and exposed) with a history of smoking had slightly increased SCEs than the non-smokers in both groups. (ii) The extent of DNA migration (SCGE assay) did not distinguish between the samples in either the exposed or control subjects. Like the SCE results, the exposed and control smoker subjects showed a greater proportion of damaged lymphocytes with apparent migration of DNA. (iii) No clear differences in the mutagenic activity of the urine samples were observed between the exposed and control subjects. But, pooling exposed and controls together, a positive and significant variation in the urinary mutagenic effect was observed with the number of cigarettes smoked per day.     

Chromosomal aberrations, sister-chromatid exchanges, cells with high frequency of SCE, micronuclei and comet assay parameters in 1, 3-butadiene-exposed workers

The association of occupational exposure to 1,3-butadiene (BD) and induction of cytogenetic damage in peripheral lymphocytes was studied in 19 male workers from a monomer production unit and 19 control subjects from a heat production unit. The exposure to BD was measured by passive personal monitors. The following biomarkers were used: chromosomal aberrations (CA), sister chromatid exchanges (SCE), cells with a high frequency of SCE (HFC), micronuclei, comet assay parameters like tail length (TL) and percentage of DNA in tail [T (%)] and polymorphisms of GSTM1 and GSTT1 genotypes. BD exposure with a median value of 0.53 mg/m3 (range: 0.024-23.0) significantly increased (a) the percentage of cells with chromosomal aberrations in exposed vs. control groups (3.11% vs. 2.03%, P<0.01), (b) the frequency of SCE per cell (6.96 vs. 4.87, P<0.001), and (c) the percentage of HFC (19.9% vs. 4.1%, P<0.001). BD exposure had no significant effects on formation of micronuclei and on comet assay parameters. Effect of smoking was observed only for HFC in BD-exposed group. GSTM1 genotype affected chromosomal aberrations in exposed group, while GSTT1 genotype affected chromosomal aberrations in controls. No effect of GSTM1 or GSTT1 genotypes was observed on any other biomarkers used.     

Urinary mutagenicity as a biomarker in workers exposed to benzidine: correlation with urinary metabolites and urothelial DNA adducts

Urinary mutagenicity has been used in occupational and epidemiological studies for over two decades as a cost-effective, general biomarker of exposure to genotoxic agents. However, few studies have compared urinary mutagenicity to additional biomarkers determined among low- and high-exposed groups. To address this issue, we evaluated the relationship between urinary mutagenicity and other types of biomarkers in a cross-sectional study involving 15 workers exposed to the urinary bladder carcinogen benzidine (BZ, high exposure), 15 workers exposed to BZ-dyes (low exposure), and 13 unexposed controls in Ahmedabad, India. Urinary organics were extracted by C18/methanol and evaluated for mutagenicity in the presence of S9 in the Salmonella strain YG1024, which is a frameshift strain that overproduces acetyltransferase. The results were compared to biomarker data reported recently from the same urine samples (Rothman et al., Proc. Natl Acad. Sci. USA, 93, 5084-5089, 1996) that included a metabolite biomarker (the sum of the urinary levels of BZ + N-acetylbenzidine + N,N'-diacetylbenzidine) and a DNA adduct biomarker [a presumptive N-(3'-phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine (C8dG-ABZ) DNA adduct in exfoliated urothelial cells]. The mean +/- SE urinary mutagenicity (revertants/micromol of creatinine) of the low-exposure (BZ-dye) workers was 8.2 +/- 2.4, which was significantly different from the mean of the controls (2.8 +/- 0.7, P = 0.04) as was that of the mean of the high-exposure (BZ) workers (123.2 +/- 26.1, P < 0.0001). Urinary mutagenicity showed strong, positive correlations with urinary metabolites (r = 0.88, P < 0.0001) and the level of the presumptive C8dG-ABZ urothelial DNA adduct (r = 0.59, P = 0.0006). A strong association was found between tobacco use (bidi smoking) and urinary mutagenicity among the controls (r = 0.68, P = 0.01) but not among the exposed workers (r = 0.18, P = 0.11). This study confirms the ability of a biomarker such as urinary mutagenicity to detect low-dose exposures, identify additional genotoxic exposures among the controls, and correlate strongly with urinary metabolites and DNA adducts in the target tissue (urinary bladder epithelia) in humans.     

Exposure to glycols and their renal effects in motor servicing workers

Ten car mechanics frequently exposed to glycol-based cooling liquids were followed during a workshift. Airborne ethylene and propylene glycol concentrations in the car mechanics' environment were measured. The car mechanics gave urine samples after the workshift and their excretion of ethylene glycol, propylene glycol, oxalic acid, calcium and ammonia was analysed and compared to that of unexposed office workers. Urinary succinate dehydrogenase activity and glycosaminoglycans were also measured in both groups. Airborne ethylene and propylene glycol concentrations in the car mechanics' environment were negligible. Urinary ethylene glycol excretion in exposed workers was significantly higher than that in unexposed workers, but propylene glycol excretion was at the same levels as in controls. In the exposed group, the excretion of the end metabolite of ethylene glycol, oxalic acid (47 +/- 11 mmol/mol creatinine, mean +/- SD, n = 10) differed slightly from that of controls (36 +/- 14 mmol/mol creatinine, mean +/- SD, n = 10). Urinary excretion of ammonia was higher among exposed workers than office workers. The excretion of calcium did not differ from that of controls. A marginally decreased urinary succinate dehydrogenase activity was found in the exposed men. The excretion of glycosaminoglycans was significantly lower in exposed workers. Therefore, it seems that ethylene glycol is absorbed by skin contact. The internal body burden is associated with oxaluria and increased ammoniagenesis typical of chronic acidosis.     

Distribution and role of aspartate in the nervous system of the chaetognath Sagitta

Forty-nine female workers in the shoemaking industry, exposed to a solvent mixture containing benzene and twenty-seven non-exposed controls, were investigated. Concentrations of benzene and toluene in the working atmosphere, as well as benzene and toluene in blood and phenols in pre- and post-shift urine as parameters of biological monitoring, were determined. In order to assess hematotoxic risk, a complete blood cell count with differential, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, reticulocytes, serum iron, alkaline phosphatase in neutrophils and red blood cell glycerol lysis time were determined in all subjects. Benzene concentrations in the workplace atmosphere at the shoemaking factory ranged from 1.9 to 14.8 ppm (median = 5.9). Significant difference in benzene in blood (p = 0.005) and phenol in post-shift urine (p = 0.003) between exposed workers and controls confirmed exposure to benzene. Hemoglobin level (p = 0.02) and mean corpuscular hemoglobin concentration (p = 0.0002) in the shoe workers were lower, and band neutrophils (p = 0.005) and mean corpuscular volume (p = 0.03) higher, than in controls. Red blood cell glycerol lysis time was significantly higher (p = 0.000001) in shoe workers (X +/- SD = 41.6 +/- 8.9) than in controls (X +/- SD = 31.1 +/- 6.5) and showed a significant correlation with exposure biomarkers. The results confirm that benzene exposure below 15 ppm may produce qualitative abnormalities, particularly macroerythrocytosis and increased red cell glycerol resistance, in the absence of an overt quantitative decrease in circulating blood cells. Increased resistance to the hemolytic action of glycerol is a potentially useful biological monitoring procedure in medical surveillance of benzene exposed workers. The results of this study suggest that potential threshold concentration for hematologic effects of benzene is lower than 15 ppm.     

Mechanism of pyocyanin- and 1-hydroxyphenazine-induced lung neutrophilia in sheep airways

Pyocyanin (Pyo) and 1-hydroxyphenazine (1-HP) are extracellular products of Pseudomonas aeruginosa. To test whether these products were capable of producing an inflammatory response in the airways, combinations of Pyo and 1-HP at concentrations of 10(-4) and 10(-5) M were instilled into sheep airways, and indexes of inflammation were assessed by bronchoalveolar lavage (BAL) 24 h later. Challenge with the phenazines caused a significant dose-dependent increase in the number of cells and neutrophils recovered by BAL. Control challenges produced no such changes. The lung neutrophilia was accompanied by an increased concentration of albumin in BAL. The increases in BAL neutrophils and albumin could be blocked by treating the sheep with the 5-lipoxygenase inhibitor zileuton. Neither 1-HP nor Pyo was chemotactic to neutrophils when tested in vitro, but when alveolar macrophages (AM) were cultured in vitro in the presence of both Pyo and 1-HP (1 microM), the supernatants caused neutrophil chemotaxis. Analysis of AM culture supernatants incubated with the combination of pigments showed significant increases in leukotriene B4 and interleukin-8, and blocking these mediators separately or together reduced AM supernatant-induced neutrophil chemotaxis. We conclude that local instillation of Pyo and 1-HP can initiate an inflammatory response in the airways of sheep in vivo. This effect can be explained, in part, by the release of chemotactic factors produced by AM.     

Sister-chromatid exchanges and cell-cycle kinetics in the lymphocytes of workers occupationally exposed to a chemical mixture in the tyre industry

Cytogenetic studies of clinically healthy workers employed in the rubber industry showed an increase in chromosome aberrations (CAs), sister-chromatid exchanges (SCEs) and a decrease in proliferation indices (PIs). The aim of the present study was to establish, using the SCE and PI tests, genotoxic effects of hazardous chemicals in the rubber industry. An increase in mean SCEs in the lymphocytes of vulcanizers as compared to controls was observed. Since the PI in the exposed group was insignificantly decreased as compared to the controls, it could be concluded that the SCE test is the most sensitive cytogenetic test for the detection of a genotoxic effect of chemicals in the rubber industry. There was no evidence in the present study that the genotoxic effect of chemicals in the rubber industry was enhanced by cigarette smoking.     

Sister chromatid exchange studies for monitoring DNA damage in lymphocytes of malignant lymphoma patients under cytostatic therapy

Sister chromatid exchange (SCE) frequencies were studied in lymphocytes from 45 patients with malignant lymphoma. Fifteen patients were untreated when studied. The mean SCE frequency for these patients was 8.70 +/- 0.99 per mitosis. The mean score for 35 controls was 4.37 +/- 1.19. SCE mean scores were significantly higher in the untreated patients than in the controls (p < 0.001). Nine patients were treated with radiotherapy alone. The mean SCE frequency (6.80 +/- 0.87) they demonstrated was significantly lower (p < 0.01) than that found in untreated patients. Twelve patients received cyclophosphamide 1 month before the study was started. They demonstrated a mean SCE frequency (12.00 +/- 1.31) significantly higher (p < 0.05) than that found in patients who had received regimens that did not contain cyclophosphamide (9.72 +/- 1.32). From these findings we suggest that untreated patients with malignant lymphoma have elevated SCE frequencies, which may be further increased by chemotherapeutic agents.     

Biomonitoring of United States Army soldiers serving in Kuwait in 1991

Biomarkers of polycyclic aromatic hydrocarbon (PAH) exposure and genetic biomarkers of potential cancer susceptibility were determined in a group of United States Army soldiers who were deployed to Kuwait and Saudi Arabia in 1991 in the aftermath of the Persian Gulf War. Because hundreds of oil well fires were still burning, there was concern that ground troops stationed in Kuwait might be exposed to high levels of PAHs and other toxicants. The United States Army Environmental Hygiene Agency monitored air and soil for ambient PAHs. In addition, a group of 61 soldiers was involved in the biomonitoring study reported here. These soldiers kept diaries of daily activities and provided blood and urine samples in Germany (June) before deployment to Kuwait, after 8 weeks in Kuwait (August), and 1 month after the return to Germany (October). Here we present data for PAH-DNA adducts measured by immunoassay in blood cell DNA samples obtained at all three sampling times from 22 soldiers and bulky aromatic adducts measured by 32P-postlabeling in blood cell DNA samples from 20 of the same soldiers. Urinary 1-hydroxypyrene-glucuronide levels were determined by synchronous fluorescence spectrometry in a matched set of samples from 33 soldiers. Contrary to expectations, environmental monitoring showed low ambient PAH levels in the areas where these soldiers were working in Kuwait. For both DNA adduct assays, levels were the lowest in Kuwait in August and increased significantly after the soldiers returned to Germany (October). Urinary 1-hydroxypyrene-glucuronide levels were also lowest in Kuwait and highest in Germany, but the differences were not statistically significant. The PAH-exposure biomarker levels were not significantly influenced by polymorphic variations of CYP1A1 (MspI) and glutathione S-transferases M1 and T1. Overall, the data suggest that this group of soldiers was not exposed to elevated levels of PAHs while deployed in Kuwait.     

Cytogenetic investigations on patients with oral submucous fibrosis

Lymphocyte cultures were set up from venous blood samples collected from 23 patients of submucous fibrosis (SMF) and 10 normal controls. Slides, thus prepared, were processed and screened for G-, C-banding and sister chromatid exchange (SCE) frequency analysis. No gross chromosomal anomalies except that a few breaks and gaps were observed to be randomly distributed throughout the genome. However, a proportionate increase in SCE frequency in SMF patients as compared to the normal control individuals was observed. An attempt has been made to correlate the period of betel leaves, nuts, quid and tobacco chewing with the incidence of chromosomal anomalies and increase in SCE frequency and its sexwise distribution in these patients.     

Control of biologic hazards

Spontaneous and diepoxybutane (DEB)-induced sister-chromatid exchanges (SCEs) were examined in whole-blood lymphocyte cultures of 3 men and 4 women. A strong increase in mean number of SCEs per cell with increasing DEB concentrations (0, 2, and 4 microM) was observed in cultures of all subjects, but 3 of the donors were clearly more sensitive than the others. The SCE measurements were repeated 2-6 times per donor over a period of 55 months to assess the stability of the individual SCE response. The results showed that SCE induction by DEB was steady in the individuals during the follow-up at each DEB dose, with no significant differences among the repeated experiments. At 4 microM DEB, the DEB-sensitive and -resistant donors could be reliably be differentiated from each other in all trials. As DEB-sensitivity has been suggested to be due to the lack of glutathione S-transferase (GST) T1, the donors were genotyped for the presence of GSTT1 and GSTM1 genes. The 3 individuals found to be DEB-sensitive were all of the GSTT1 null genotype, whereas the 4 DEB-resistant donors were GSTT1 positive, which supported the role of the GSTT1 gene in determining DEB-sensitivity. Three of the DEB-resistant and none of the DEB-sensitive had the GSTM1 null genotype. Thus, the lack of the GSTM1 gene was not associated with the DEB-sensitivity trait. In conclusion, the present findings show that individual SCE responses to treatment of cultured human lymphocytes with DEB can reliably be reproduced in repeated trials. The results confirm that the GSTT1 gene but not the GSTM1 gene is important in determining individual sensitivity to the in vitro genotoxicity of DEB.     

Initial effects of the grounding of the tanker Braer on health in Shetland. The Shetland Health Study Group

OBJECTIVE: To determine if the oil spillage from the tanker Braer had any immediate health effects on the exposed resident population. DESIGN: Cohort study with a comparison against controls, exposure status being assigned on the basis of geographical location. SETTING: Rural Shetland. SUBJECTS: All those resident on or after 5 January 1993 (day 0) within 4.5 km of the site of tanker's grounding. Controls matched for sex and age were drawn from a general practice list 95 km distant. OUTCOME MEASURES: Demographic details; smoking and alcohol consumption; perception of health and reported presence or absence of specific symptoms; peak expiratory flow; results of haematology, liver and renal function tests, and blood and urine toxicology. RESULTS: Of subjects contacted, 420 (66%) exposed people and 92 (68%) controls were studied; 56 non-attenders were surveyed. Principal health effects arose on days 1 and 2 and were headache, throat irritation, and itchy eyes. No significant differences between those exposed and controls were found for any of the biological markers. Toxicological studies did not show any exposures that are known to affect human health. CONCLUSIONS: The study confirmed the anecdotal reports of certain acute symptoms. No evidence of pulmonary, haematological, renal, or hepatic damage was detected at the population level. Toxicological samples from exposed people did not find levels known to affect human health. Further studies are required to ascertain whether there have been any long term effects on the population.     

Sensory epithelium of the vomeronasal organ express TrkA-like and epidermal growth factor receptor in adulthood. An immunohistochemical study in the horse

This study was undertaken to compare the genotoxic effects of arsenite in cultured human lymphocytes and lymphoblastoid cell lines from a group of normal human volunteers. The goal was to determine whether, as found with other genotoxins, subgroups might exist which showed relative high or low sensitivity to induction of sister chromatid exchanges (SCEs) by this metal. Primary lymphoblast cultures were established by treatment with phytohemagglutinin (PHA-L). Lymphoblastoid cell lines were established by transformation with Epstein-Barr virus. Cultures were exposed for 40 h to sodium arsenite (AsIII) and SCEs assayed by 5-bromo-2'-deoxyuridine incorporation and staining by fluorescence plus Giemsa. SCEs were increased by arsenite in a dose-dependent manner over the concentration range of 10(-7)-10(-5) M. SCEs could not be scored above 10(-5) M because of cytotoxicity. Comparison of SCE frequency in primary lymphocyte cultures among individuals showed substantial variation in sensitivity to arsenite, with some showing no significant effect while others showed a 2-3-fold increase in SCE frequency. In one lymphoblastoid cell line especially sensitive to arsenite, arsenic acid (AsV) or dimethylarsinic acid (DMA) at concentrations up to 10(-5) M did not increase the SCE frequency suggesting that AsIII is the active form of arsenic. When pooled data from the primary lymphocytes was compared to that obtained with the lymphoblastoid cells, the slopes of the dose-response curves for ASIII-induced SCEs were similar. The sensitivity of the majority of the individual primary lymphocyte cultures to SCE induction by arsenite was correlated with the sensitivity of the lymphoblastoid cultures established from the same individual. However, in three individuals no correlation was found. Individual lymphoblastoid cell lines retained their As sensitivity after cryopreservation and subsequent revival. Whether the genotoxic response to As is genetically controlled or the result of phenotypic selection is being explored in these stable lymphoblastoid cell lines.     

Using 3'' untranslated sequences to identify differentially expressed genes in Leishmania

Because garbage collectors work in the street, they are exposed to polycyclic aromatic hydrocarbons (PAHs) in motor vehicle exhaust gas as they work. Urinary 1-hydroxypyrene (1-OH-pyrene) began to be used as a biological monitoring index for human exposure to high concentrations of PAHs. The objective of this study was to examine the applicability of urinary 1-OH-pyrene as a biological monitoring index for human low-level PAH exposure, such as the PAH exposure experienced while working in the street. The subjects were fifteen male garbage collectors. We measured individual exposure to PAHs, urinary 1-OH-pyrene concentrations and urinary cotinine concentrations. Individual air samplers were attached to the collar of the clothing of five workers to capture PAHs. Urine samples were collected before work, around noon and after finishing the day's work. In all, five PAH samples and 45 urine samples were collected. As control data, we analyzed the urinary 1-OH-pyrene and urinary cotinine levels of six smoking and four non-smoking control subjects who were not occupationally exposed to PAHs. The benzo[a]pyrene level in the air sampled for 5-6 h was 2.5-10.5 ng/m3, and the pyrene level as 10.3-70.3 ng/m3. These levels were similar to those in the vicinity of streets in Japan. A positive correlation between total PAH levels and the pyrene levels was observed. The average urinary 1-OH-pyrene level of the smokers was 0.21 +/- 0.13 mumol/mol creatinine, vs. 0.15 +/- 0.11 mumol/mol creatinine in the non-smokers. The urinary 1-OH-pyrene level obtained in this study was slightly higher than in the control group. No correlation was found between pyrene exposure and the urinary 1-OH-pyrene level of the five workers who wore the personal samplers. A significant positive correlation was observed between the urinary 1-OH-pyrene level and urinary cotinine level of the smokers. A significant positive correlation was also observed between the urinary 1-OH-pyrene and urinary cotinine levels of the control group smokers. In conclusion, urinary 1-OH-pyrene is not applicable for biological monitoring of extremely low levels of exposure to PAHs, as in the case of working in the street. Caution is required to exclude the effects of smoking when evaluating PAH exposure.     

Using analog baselines to assess the effects of naltrexone on self-injurious behavior

Healthy male and female human volunteers were exposed to 50 ppm or 100 ppm trichloroethylene (Tri) by inhalation for 4 h. Blood and urine samples were taken at various times before, during, and after the exposure period for analysis of glutathione (GSH), related thiols and disulfides, and GSH-derived metabolites of Tri. The GSH conjugate of Tri, S-(1,2-dichlorovinyl)glutathione (DCVG), was found in the blood of all subjects from 30 min after the start of the 4-h exposure to Tri to 1 to 8 h after the end of the exposure period, depending on the dose of Tri and the sex of the subject. Male subjects exposed to 100 ppm Tri exhibited a maximal content of DCVG in the blood at 2 h after the start of the exposure of 46.1 +/- 14.2 nmol/ml (n = 8), whereas female subjects exposed to 100 ppm Tri exhibited a maximal content of DCVG in the blood at 4 h after the start of the exposure of only 13.4 /- 6.6 nmol/ml (n = 8). Pharmacokinetic analysis of blood DCVG concentrations showed that the area under the curve value was 3.4-fold greater in males than in females, while the t1/2 values for systemic clearance of DCVG were similar in the two sexes. Analysis of the distribution of individual values indicated a possible sorting, irrespective of gender, into a high- and a low-activity population, which suggests the possibility of a polymorphism. The mercapturates N-acetyl-1,2-DCVC and N-acetyl-2,2-DCVC were only observed in the urine of 1 male subject exposed to 100 ppm Tri. Higher contents of glutamate were generally found in the blood of females, but no marked differences between sexes were observed in contents of cyst(e)ine or GSH or in GSH redox status in the blood. Urinary GSH output exhibited a diurnal variation with no apparent sex- or Tri exposure-dependent differences. These results provide direct, in vivo evidence of GSH conjugation of Tri in humans exposed to Tri and demonstrate markedly higher amounts of DCVG formation in males, suggesting that their potential risk to Tri-induced renal toxicity may be greater than that of females.     

Effects of a safe person on induced distress following a biological challenge in panic disorder with agoraphobia.

This study examined the effect of having a safe person present on artificially induced anxiety following a biological challenge among panic-disordered patients. Anxiety symptoms were induced using a 5.5% CO?-inhalation procedure. Panic patients underwent the inhalation procedure either in the presence or absence of their safe person. Nonanxious controls underwent the procedure without a safe person. Panic patients exposed to CO? without their safe person present reported greater distress, a greater number of catastrophic cognitions, and a greater level of physiological arousal than did panic patients exposed with their safe person. The latter group did not differ from controls on most measures at postexposure. The attenuation of self-reported anxiety and catastrophic cognitions is consistent with the safety-signal theory and the cognitive model of panic, respectively. The results, however, are inconsistent with a biological model of panic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Determination of N,N',N"-triethylenthiophosphoramide in biological samples using capillary gas chromatography

A sensitive assay for the determination of N,N',N"-triethylenthiophosphoramide (thioTEPA) in microvolumes of human plasma and urine has been developed. ThioTEPA was analysed using gas chromatography with selective nitrogen-phosphorus detection, after extraction with ethyl acetate from the biological matrix. Diphenylamine is the internal standard. The limit of quantitation was 0.1 ng/ml, using only 100 microl of sample; recoveries ranged between 85 and 100% and both accuracy and precision were less than 10%. Using a flame ionisation nitrogen-phosphorus detector, the assay was not linear over the concentration range of 2-1000 ng/ml for plasma and 10-1000 ng/ml for urine. Linearity was accomplished in the range of 1-1000 ng/ml for plasma and urine when a thermionic nitrogen/phosphorous detector was used. The stability of thioTEPA in plasma proved to be satisfactory over a period of 3 months, when kept at -20 degrees C, whereas it was stable in urine for at least 1 month at -80 degrees C. ThioTEPA plasma concentrations of two patients treated with thioTEPA are presented demonstrating the applicability of the assay.     

Urinary measurement of transforming growth factor-beta and type IV collagen as new markers of renal injury: application in diabetic nephropathy

Urinary samples were concentrated rapidly and efficiently and were used to develop several protein assays that may be of value in monitoring individuals with progressive renal disorders. Transforming growth factor-beta1 (TGF-11) and retinol binding protein (RBP) were measured with modification of commercially available methods used to assay serum specimens; type 3 collagen (T3C) was measured with a new immunonephelometric assay. The precision characteristics of these assays are comparable with those reported for microalbuminuria. The clinical utility of measuring a panel of these markers was demonstrated in urine samples from 16 control subjects and from 46 individuals with insulin-dependent diabetes mellitus (IDDM) with various albumin excretion rates (AERs). TGF-beta1 and T3C were used as markers of cytokine expression and of the renal fibrogenic process, whereas RBP excretion served as a marker of tubular injury or dysfunction. Compared with controls, T3C excretion was significantly increased in 18 normoalbuminuric and further increased in 13 microalbuminuric (AER 20 < or = 200 microg/min) IDDM subjects. RBP excretion was increased in macroalbuminuric IDDM subjects (AER >200 microg/min, overt nephropathy). Significant correlations were also found between AER and RBP in all but macroalbuminuric individuals, whereas TGF-beta1 correlated with T3C excretion in controls and in normoalbuminuric diabetic subjects. Urinary RBP but not AER was an excellent predictor of diabetic nephropathy as defined by serum creatinine (P = 0.0001). This underscores the importance of an early tubulopathy in the subsequent development of glomerulopathy and overt nephropathy. The data suggest that longitudinal monitoring of a panel of urinary markers such as that used in the current study may better define their relevance in progressive glomerulosclerosis and may also provide greater insight into the mechanisms underlying such process.     

Chromosome breaks and sister chromatid exchanges in albinos in Nigeria

The prevalence of squamous cell carcinoma of the skin in albinos reaches approximately 90% in patients over 20 years of age in the vicinity of Enugu, Nigeria. Chromosome breaks and sister chromatid exchanges (SCE) were evaluated in tyrosinase-positive oculocutaneous albinos and pigmented controls of Ibo extraction who were life-long residents of Nigeria. No difference in the frequency of chromosomal breaks in 14 albinos compared to 6 pigmented controls, and no differences in the frequency of SCE in 9 albinos compared to 3 controls could be detected. Increased chromosomal abnormalities in lymphocytes do not appear to be assoicated with albinism or fulminating skin cancer present in albinos in the tropics.     

Longitudinal relationships between family routines and biological profiles among youth with asthma.

Objective: To investigate whether longitudinal trajectories of inflammatory markers of asthma can be predicted by levels of family routines in youth with asthma. Design: Family routines were assessed through parent questionnaires and peripheral blood samples obtained from youth every 6 months throughout the 18-month study period. Longitudinal relationships were evaluated using hierarchical linear modeling. Main Outcome Measures: Mitogen-stimulated production of cytokines implicated in asthma, specifically IL-4, IL-5, and IL-13. Results: Youth with more family routines in their home environment showed decreases in IL-13 (but not IL-4 or IL-5) over the course of the study period. In turn, within-person analyses indicated that at times when stimulated production of IL-13 was high, asthma symptoms were also high, pointing to the clinical relevance of changes in IL-13 over time. A variety of child and parent psychosocial as well as child behavioral characteristics could not explain these effects. However, medication use eliminated the relationship between family routines and stimulated production of IL-13. Conclusion: Our study suggests that family routines predict asthma outcomes at the biological level, possibly through influencing medication use. Considering daily family behaviors when treating asthma may help improve both biological and clinical profiles in youth with asthma. (PsycINFO Database Record (c) 2010 APA, all rights reserved)