Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene : new aspects to be considered

Technical dinitrotoluene (DNT) is a mixture of 2,4- and 2,6-DNT. In humans, industrial or environmental exposure can occur orally, by inhalation, or by skin contact. The classification of DNT as an 'animal carcinogen' is based on the formation of malignant tumors in kidneys, liver, and mammary glands of rats and mice. Clear signs of toxic nephropathy were found in rats dosed with DNT, and the concept was derived of an interrelation between renal toxicity and carcinogenicity. Recent data point to the carcinogenicity of DNT on the urinary tract of exposed humans. Between 1984 and 1997, 6 cases of urothelial cancer and 14 cases of renal cell cancer were diagnosed in a group of 500 underground mining workers in the copper mining industry of the former GDR and having high exposures to explosives containing technical DNT. The incidences of both urothelial and renal cell tumors in this group were 4.5 and 14.3 times higher, respectively, than anticipated on the basis of the cancer registers of the GDR. The genotyping of all identified tumor patients for the polymorphic enzymes NAT2, GSTM1, and GSTT1 identified the urothelial tumor cases as exclusively 'slow acetylates'. A group of 161 miners highly exposed to DNT was investigated for signs of subclinical renal damage. The exposures were categorized semi-quantitatively into 'low', 'medium', 'high', and 'very high'. A straight dose-dependence of the excretion of urinary biomarker proteins with the ranking of exposure was seen. Biomarker excretion (alpha1-microglobulin, glutathione S-transferases alpha and pi) indicated that DNT-induced damage was directed toward the tubular system. New data on DNT-exposed humans appear consistent with the concept of cancer initiation by DNT isomers and the subsequent promotion of renal carcinogenesis by selective damage to the proximal tubule. The differential pathways of metabolic activation of DNT appear to apply to the proximal tubule of the kidney and to the urothelium of the renal pelvis and lower urinary tract as target tissues of carcinogenicity.

Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins α 1-microglobulin and glutathione-S-transferase α (GST α) as biomarkers for damage of the proximal tubule and glutathione-S-transferase π (GST π) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers α 1-microglobulin, GST α, and GST π consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

Identification of theta-class glutathione S-transferase in liver cytosol of the marmoset monkey

The presence of theta-class glutathione S-transferase (GST) in marmoset monkey liver cytosol was investigated. An anti-peptide antibody targeted against the C-terminus of rGSTT1 reacted with a single band in marmoset liver cytosol that corresponded to a molecular weight of 28 kDa. The intensity of the immunoreactive band was not affected by treatment of marmoset monkeys with 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbitone, rifampicin or clofibric acid. Similarly, activity towards methyl chloride (MC) was unaffected by these treatments. However, GST activity towards 1,2-epoxy3-(p- nitrophenoxy)-propane (EPNP) was increased in marmosets treated with phenobarbitone (2.6-fold) and rifampicin (2.6-fold), activity towards dichloromethane (DCM) was increased by 50% after treatment of marmosets with clofibric acid, and activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was raised slightly (30-42% increases) after treatment with phenobarbitone, rifampicin or clofibric acid. Compared with humans, marmoset liver cytosol GST activity towards DCM was 18-fold higher, activity towards MC was 7 times higher and activity towards CDNB was 4 times higher. Further, EPNP activity was clearly detectable in marmoset liver cytosol samples, but was undetectable in human samples. Immunoreactive marmoset GST was partially purified by affinity chromatography using hexylglutathione-Sepharose and Orange A resin. The interaction of immunoreactive marmoset GST was similar to that found previously for rat and human GSTT1, suggesting that this protein is also a theta class GST. However, unlike rat GSTT1, the marmoset enzyme was not the major catalyst of EPNP conjugation. Instead, immunoreactivity was closely associated with activity towards MC. In conclusion, these results provide evidence for the presence of theta-class GST in the marmoset monkey orthologous to rGSTT1 and hGSTT1.

Triphasic pattern in the ex vivo response of human proliferative phase endometrium to oestrogens

The aim of this study was to evaluate the ex vivo oestrogen responsiveness of human proliferative phase endometrium using short-term explant cultures. The effects of oestrogen (17beta-E2) on proliferation and the expression of oestrogen-responsive genes known to be involved in regulating endometrial function were evaluated. Three distinct response patterns could be distinguished: (1) the menstrual (M) phase pattern (cycle days 2-5), which is characterised by a complete lack in the proliferative response to 17beta-E2, while an increased expression of AR (2.6-fold, P<0.01), PR (2.7-fold, P<0.01) and COX-2 (3.5-fold, P<0.01) at the mRNA level was observed and a similar upregulation was also found for AR, PR and COX-2 at the protein level; (2) the early proliferative (EP) phase pattern (cycle days 6-10) with 17beta-E2 enhanced proliferation in the stroma (1.7-fold, P<0.05), whereas the expression of AR, PR and COX-2 were not affected at the mRNA and protein levels and ER-a mRNA and protein levels were significantly reduced by 17beta-E2; (3) the late proliferative (LP) phase pattern (cycle days 11-14), which is characterised by a moderate stimulation of proliferation (1.4-fold, P<0.05) and PR mRNA expression (1.7-fold, P<0.01) by 17beta-E2. In conclusion, three distinct response patterns to 17beta-E2 could be identified with respect to proliferation and the expression of known oestrogen-responsive genes in human proliferative phase endometrium explant cultures.

A rapid and cost-effective method of producing recombinant proBNP and NT-proBNP variants in Escherichia coli for immunoassay of heart failure

The measurements of plasma natriuretic peptides (NT-proBNP, proBNP and BNP) are used to diagnose heart failure but these are expensive to produce. We describe a rapid, cheap and facile production of proteins for immunoassays of heart failure. DNA encoding N-terminally His-tagged NT-proBNP and proBNP were cloned into the pJexpress404 vector. ProBNP and NT-proBNP peptides were expressed in Escherichia coli, purified and refolded in vitro. The analytical performance of these peptides were comparable with commercial analytes (NT-proBNP EC50 for the recombinant is 2.6 ng/ml and for the commercial material is 5.3 ng/ml) and the EC50 for recombinant and commercial proBNP, are 3.6 and 5.7 ng/ml respectively). Total yield of purified refolded NT-proBNP peptide was 1.75 mg/l and proBNP was 0.088 mg/l. This approach may also be useful in expressing other protein analytes for immunoassay applications. To develop a cost effective protein expression method in E. coli to obtain high yields of NT-proBNP (1.75 mg/l) and proBNP (0.088 mg/l) peptides for immunoassay use.

Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-2011

BACKGROUND The incidence of skin cancer, both melanoma and keratinocyte cancers (KC) is rising throughout the world, specifically squamous cell carcinomas(SCC) and basal cell carcinoma(BCC), being the most common of all cancers. OBJECTIVE To determine trends in incidence of Melanoma, BCC and SCC among 1.7 million members of Maccabi Healthcare Services from 2006 to 2011. METHODS Data on newly diagnosed Melanoma, SCC and BCC cases was collected from the MHS Cancer Registry and based on histology reports from the centralized pathology lab. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating Average Annual Percentage Change(AAPC). RESULTS During the six year study period, a total of 16,079 subjects were diagnosed with at least one BCC, 4,767 with SCC and 1,264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100,000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among males and primarily affected the elderly. BCC rates were stable throughout the study period(AAPC -0.7%, 95%CI -4.5% to 3.2%) while SCC incidence increased significantly(AAPC 15.5%, 95%CI: 2.6% to 30.0%). In contrast, melanoma rates continuously decreased with a significant AAPC of -3.0%, 95%CI (-4.5 to -0.1). CONCLUSIONS Previously unreported, the incidence of KC in Israel is high. The disparities in incidence trends between SCC, BCC and melanoma allude to their different etiologies. These findings underscore the importance of continuous monitoring, education and prevention programs in a growing high risk population.

Diverse urban plantings managed with sufficient resource availability can increase plant productivity and arthropod diversity

Buildings structures and surfaces are explicitly being used to grow plants, and these “urban plantings” are generally designed for aesthetic value. Urban plantings also have the potential to contribute significant “ecological values” by increasing urban habitat for animals such as arthropods and by increasing plant productivity. In this study, we evaluated how the provision of these additional ecological values is affected by plant species richness; the availability of essential resources for plants, such as water, light, space; and soil characteristics. We sampled 33 plantings located on the exterior of three buildings in the urban center of Brisbane, Australia (subtropical climatic region) over 2, 6 week sampling periods characterized by different temperature and rainfall conditions. Plant cover was estimated as a surrogate for productivity as destructive sampling of biomass was not possible. We measured weekly light levels (photosynthetically active radiation), plant CO2 assimilation, soil CO2 efflux, and arthropod diversity. Differences in plant cover were best explained by a three-way interaction of plant species richness, management water regime and sampling period. As the richness of plant species increased in a planter, productivity and total arthropod richness also increased significantly—likely due to greater habitat heterogeneity and quality. Overall we found urban plantings can provide additional ecological values if essential resources are maintained within a planter such as water, light and soil temperature. Diverse urban plantings that are managed with these principles in mind can contribute to the attraction of diverse arthropod communities, and lead to increased plant productivity within a dense urban context.

Echology: Making sense of data - reflections on resilient ecologies of partnership [Abstract]

The Echology: Making Sense of Data initiative seeks to break new ground in arts practice by asking artists to innovate with respect to a) the possible forms of data representation in public art and b) the artist's role in engaging publics on environmental sustainability in new urban developments. Initiated by ANAT and Carbon Arts in 2011, Echology has seen three artists selected by National competition in 2012 for Lend Lease sites across Australia. In 2013 commissioning of one of these works, the Mussel Choir by Natalie Jeremijenko, began in Melbourne's Victoria Harbour development. This emerging practice of data - driven and environmentally engaged public artwork presents multiple challenges to established systems of public arts production and management, at the same time as offering up new avenues for artists to forge new modes of collaboration. The experience of Echology and in particular, the Mussel Choir is examined here to reveal opportunities for expansion of this practice through identification of the factors that lead to a resilient 'ecology of part nership' between stakeholders that include science and technology researchers, education providers, city administrators, and urban developers.

Teacher education for high-poverty schools : keeping the bar high

For some time now, there has been a focus, both in Australia and internationally, on quality teaching as a fundamental component that affects the educational outcomes of all students. The question of how teacher education programs in Australia prepare effective teachers to work across all school settings-including low-SES schools-has been elevated to national prominence by data from the 20 12 Programme for International Student Assessment (PIS A), which revealed a fall in Australian students' world ranking across Mathematics, Reading and Science. Education is commonly acknowledged as a "foundation capability" that improves a person's life chances, including employment prospects, and it is widely understood to be a "route out of disadvantage" (McLachlan, Gilfillan, and Gordon 20 13). The Australian Bureau of Statistics 201 1- 12 data suggest that around 2.6 million (11.8%) Australians currently live under the poverty line (Phillips et a!. 2012, 8). According to the Organisation for Economic Cooperation and Development (OECD), despite the significant effects teachers have on student performance, disadvantaged schools are not always staffed with the highest quality teachers (see Darling-Hammond, 2006).

Pyrene based conjugated materials: synthesis, characterization and electroluminescent properties

In this work, three novel pyrene cored small conjugated molecules, namely 1,3,6,8-tetrakis(6-(octyloxy)naphthalene-2-yl)pyrene (PY-1), 1,3,6,8-tetrakis((E)-2-(6-(n-octyloxy)naphthalene-2-yl)vinyl)pyrene (PY-2) and 1,3,6,8-tetrakis((6-(n-octyloxy)naphthalene-2-yl)ethynyl)pyrene (PY-3) have been synthesized by Suzuki, heck and Sonogashira organometallic coupling reactions, respectively. The effects of single, double and triple bonds on their optical, electrochemical, and thermal properties are studied in detail. These are all materials fluorescent and they have been used in organic light-emitting diodes (OLEDs) and their electroluminescent properties have been studied.

Predictors of chronic bronchitis in South African adults

SETTING National household survey of adults in South Africa, a middle income country. OBJECTIVE To determine the prevalence and predictors of chronic bronchitis. DESIGN A stratified national probability sample of households was selected. All adults in the selected households were interviewed. Chronic bronchitis was defined as chronic productive cough. Socio-demographic predictors were wealth, education, race, age and urban residence. Personal and exposure variables included history of tuberculosis, domestic exposure to smoky fuels, occupational exposures, smoking and body mass index. RESULTS The overall prevalence of chronic bronchitis was 2.3% in men and 2.8% in women. The strongest predictor of chronic bronchitis was a history of tuberculosis (men, odds ratio [OR] 4.9; 95% confidence interval [CI] 2.6-9.2; women, OR 6.6; 95% CI 3.7-11.9). Other risk factors were smoking, occupational exposure (in men), domestic exposure to smoky fuel (in women) and (in univariate analysis only) being underweight. Wealth and particularly education were protective. CONCLUSION The pattern of chronic bronchitis in South Africa suggests a combination of risk factors that includes not only smoking but also tuberculosis, occupational exposures in men and domestic fuel exposure in women. Control of these risk factors requires public health action across a broad front. The protective role of education requires elucidation.

Wireless Power Transfer (WPT) for electric vehicles (EVs) - present and future trends

100 year old gasoline engine technology vehicles have now become one of the major contributors of greenhouse gases. Plug-in Electric Vehicles (PEVs) have been proposed to achieve environmental friendly transportation. Even though the PEV usage is currently increasing, a technology breakthrough would be required to overcome battery related drawbacks. Although battery technology is evolving, drawbacks inherited with batteries such as; cost, size, weight, slower charging characteristic and low energy density would still be dominating constrains for development of EVs. Furthermore, PEVs have not been accepted as preferred choice by many consumers due to charging related issues. To address battery related limitations, the concept of dynamic Wireless Power Transfer (WPT) enabled EVs have been proposed in which EV is being charged while it is in motion. WPT enabled infrastructure has to be employed to achieve dynamic EV charging concept. The weight of the battery pack can be reduced as the required energy storage is lower if the vehicle can be powered wirelessly while driving. Stationary WPT charging where EV is charged wirelessly when it is stopped, is simpler than dynamic WPT in terms of design complexity. However, stationary WPT does not increase vehicle range compared to wired-PEVs. State-of-art WPT technology for future transportation is discussed in this chapter. Analysis of the WPT system and its performance indices are introduced. Modelling the WPT system using different methods such as equivalent circuit theory, two port network theory and coupled mode theory is described illustrating their own merits in Sect. 2.3. Both stationary and dynamic WPT for EV applications are illustrated in Sect. 2.4. Design challenges and optimization directions are analysed in Sect. 2.5. Adaptive tuning techniques such as adaptive impedance matching and frequency tuning are also discussed. A case study for optimizing resonator design is presented in Sect. 2.6. Achievements by the research community is introduced highlighting directions for future research.

Retinal tissue thickness is reduced in diabetic peripheral neuropathy

Aim Retinal tissue integrity in relation to diabetic neuropathy is not known. The aim of this study was to investigate retinal tissue thickness in relation to diabetic peripheral neuropathy (DPN) with and without diabetic retinopathy (DR). Methods Full retinal thickness at the parafoveal and perifoveal macula and neuro-retinal thickness around the optic nerve head (ONH) and at the macula was examined using spectral domain optical coherence tomography. The eye on the hand-dominant side of 85 individuals with type 1 diabetes and 66 individuals with type 2 diabetes, with or without DR and DPN, were compared to the eyes (n=45) of age-matched non-diabetic controls. Diabetic neuropathy was defined as Neuropathy Disability Score (NDS) ≥3 on a scale of 0-10. A general linear model was used to examine the relationship between diabetic neuropathy and foveal, parafoveal and perifoveal retinal thickness and neuro-retinal thickness, in relation to DR status, age, gender, HbA1c levels and duration of diabetes. A p-value of <0.05 was considered statistically significant. Results Perifoveal retinal thickness is reduced with increasing severity of neuropathy, especially in the inferior hemisphere (p=0.004); this effect was not related to age (p=0.088). For every unit increase in NDS score, the inferior perifoveal retinal thickness reduced by 1.64 μm. Neuro-retinal thickness around the ONH decreased with increasing severity of neuropathy (p<0.014 for average and hemisphere thicknesses); for every unit increase in NDS, neuro-retinal thickness around the ONH reduced by 1.23 μm. Retinal thickness in the parafovea was increased in the absence of DR (p<0.017 for average and hemisphere thicknesses). Neuro-retinal thickness at the macula was inversely related to age alone (p<0.001). All retinal parameters, except the inferior perifovea, reduced with advancing age (p<0.007 for all). Conclusions Diabetic neuropathy is associated with changes in full retinal thickness and neuro-retinal layers. This may represent a second threat to vision integrity, in addition to the better-characterised retinopathy. This study provides new knowledge about the anatomical aspects of the retinal tissue in relation to neuropathy and retinopathy.

Estimating the burden of disease attributable to unsafe water and lack of sanitation and hygiene in South Africa in 2000

Objectives To estimate the burden of disease attributable to unsafe water, sanitation and hygiene (WSH) by age group for South Africa in 2000. Design World Health Organization comparative risk assessment methodology was used to estimate the disease burden attributable to an exposure by comparing the observed risk factor distribution with a theoretical lowest possible population distribution. A scenario-based approach was applied for estimating diarrhoeal disease burden from unsafe WSH. Six exposure scenarios were defined based on the type of water and sanitation infrastructure and environmental faecal-oral pathogen load. For ‘intestinal parasites’ and schistosomiasis, the burden was assumed to be 100% attributable to exposure to unsafe WSH. Setting South Africa. Outcome measures Disease burden from diarrhoeal diseases, intestinal parasites and schistosomiasis, measured by deaths and disability-adjusted life years (DALYs). Results 13 434 deaths were attributable to unsafe WSH accounting for 2.6% (95% uncertainty interval 2.4 - 2.7%) of all deaths in South Africa in 2000. The burden was especially high in children under 5 years, accounting for 9.3% of total deaths in this age group and 7.4% of burden of disease. Overall, the burden due to unsafe WSH was equivalent to 2.6% (95% uncertainty interval 2.5 - 2.7%) of the total disease burden for South Africa, ranking this risk factor seventh for the country. Conclusions Unsafe WSH remains an important risk factor for disease in South Africa, especially in children under 5. High priority needs to be given to the provision of safe and sustainable sanitation and water facilities and to promoting safe hygiene behaviours, particularly among children.

Risk factors for oesophageal, lung, oral and laryngeal cancers in black South Africans

The authors used data collected from 1995 to 1999, from an on-going cancer case–control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5–4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6–204.6) for lung cancer in women, and 23.9 (95% CI 9.5–60.3) for lung cancer and 23.6 (95% CI 4.6–121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7–46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1–7.5) in men working in ‘potentially noxious’ industries. ‘Frequent’ alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0–2.9, for women and odds ratio=1.8, 95% CI 1.2–2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8–7.9 in males and odds ratio=4.8, 95% CI 3.2–6.1 in females). The above results are broadly in line with international findings.