Human preadipocyte proliferation and differentiation

Obesity represents a major health, social and economic burden to many developing and Westernized communities, with the prevalence increasing at a rate exceeding almost all other medical conditions. Despite major recent advances in our understanding of adipose tissue metabolism and dynamics, we still have limited insight into the regulation of adipose tissue mass in humans. Any significant increase in adipose tissue mass requires proliferation and differentiation of precursor cells (preadipocytes) present in the stromo-vascular compartment of adipose tissue. These processes are very complex and an increasing number of growth factors and hormones have been shown to modulate the expression of genes involved in preadipocyte proliferation and differentiation. A number of transcription factors, including the C/EBP family and PP ARy, have been identified as integral to adipose tissue development and preadipocyte differentiation. Together PP ARy and C/EBPa regulate important events in the activation and maintenance of the terminally differentiated phenotype. The ability of PP ARy to increase transcription through its DNA recognition site is dependent on the binding of ligands. This suggests that an endogenous PP ARy ligand may be an important regulator of adipogenesis. Adipose tissue functions as both the major site of energy storage in the body and as an endocrine organ synthesizing and secreting a number of important molecules involved in regulation of energy balance. For optimum functioning therefore, adipose tissue requires extensive vascularization and previous studies have shown that growth of adipose tissue is preceded by development of a microvascular network. This suggests that paracrine interactions between constituent cells in adipose tissue may be involved in both new capillary formation and fat cell growth. To address this hypothesis the work in this project was aimed at (a) further development of a method for inducing preadipocyte differentiation in subcultured human cells; (b) establishing a method for simultaneous isolation and separate culture of both preadipocytes and microvascular endothelial cells from the same adipose tissue biopsies; (c) to determine, using conditioned medium and co-culture techniques, if endothelial cell-derived factors influence the proliferation and/or differentiation of human preadipocytes; and (d) commence characterization of factors that may be responsible for any observed paracrine effects on aspects of human adipogenesis. Major findings of these studies were as follows: (A) Inclusion of either linoleic acid (a long-chain fatty acid reported to be a naturally occurring ligand for PP ARy) or Rosiglitazone (a member of the thiazolidinedione class of insulin-sensitizing drugs and a synthetic PPARy ligand) in differentiation medium had markedly different effects on preadipocyte differentiation. These studies showed that human preadipocytes have the potential to accumulate triacylglycerol irrespective of their stage of biochemical differentiation, and that thiazolidinediones and fatty acids may exert their adipogenic and lipogenic effects via different biochemical pathways. It was concluded that Rosiglitazone is a more potent inducer of human preadipocyte differentiation than linoleic acid. (B) A method for isolation and culture of both endothelial cells and preadipocytes from the same adipose tissue biopsy was developed. Adipose-derived microvascular endothelial cells were found to produce factor/s, which enhance both proliferation and differentiation of human preadipocytes. (C) The adipogenic effects of microvascular endothelial cells can be mimicked by exposure of preadipocytes to members of the Fibroblast Growth Factor family, specifically ~-ECGF and FGF-1. (D) Co-culture of human preadipocytes with endothelial cells or exposure of preadipocytes to either ~-ECGF or FGF-1 were found to 'prime' human preadipocytes, during their proliferative phase of growth, for thiazolidinedione-induced differentiation. (E) FGF -1 was not found to be acting as a ligand for PP ARy in this system. Findings from this project represent a significant step forward in our understanding of factors involved in growth of human adipose tissue and may lead to the development of therapeutic strategies aimed at modifying the process. Such strategies would have potential clinical utility in the treatment of obesity and obesity related disorders such as Type II Diabetes.

Management of co-occurring substance use disorders

Reviewing the breadth of current knowledge on schizophrenia, this handbook provides clear, practical guidelines for effective assessment and treatment in diverse contexts. Leading authorities have contributed 61 concise chapters on all aspects of the disorder and its clinical management. In lieu of exhaustive literature reviews, each chapter summarizes the current state of the science; highlights key points the busy practitioner needs to know; and lists recommended resources, including seminal research studies, invaluable clinical tools, and more. Comprehensive, authoritative, and timely, the volume will enable professionals in any setting to better understand and help their patients or clients with severe mental illness.

Biological monitoring of occupational exposure to polycyclic aromatic hydrocarbons in prebake smelting

In 1984, the International Agency for Research on Cancer determined that working in the primary aluminium production process was associated with exposure to certain polycyclic aromatic hydrocarbons (PAHs) that are probably carcinogenic to humans. Key sources of PAH exposure within the occupational environment of a prebake aluminium smelter are processes associated with use of coal-tar pitch. Despite the potential for exposure via inhalation, ingestion and dermal adsorption, to date occupational exposure limits exist only for airborne contaminants. This study, based at a prebake aluminium smelter in Queensland, Australia, compares exposures of workers who came in contact with PAHs from coal-tar pitch in the smelter’s anode plant (n = 69) and cell-reconstruction area (n = 28), and a non-production control group (n = 17). Literature relevant to PAH exposures in industry and methods of monitoring and assessing occupational hazards associated with these compounds are reviewed, and methods relevant to PAH exposure are discussed in the context of the study site. The study utilises air monitoring of PAHs to quantify exposure via the inhalation route and biological monitoring of 1-hydroxypyrene (1-OHP) in urine of workers to assess total body burden from all routes of entry. Exposures determined for similar exposure groups, sampled over three years, are compared with published occupational PAH exposure limits and/or guidelines. Results of paired personal air monitoring samples and samples collected for 1-OHP in urine monitoring do not correlate. Predictive ability of the benzene-soluble fraction (BSF) in personal air monitoring in relation to the 1-OHP levels in urine is poor (adjusted R2 < 1%) even after adjustment for potential confounders of smoking status and use of personal protective equipment. For static air BSF levels in the anode plant, the median was 0.023 mg/m3 (range 0.002–0.250), almost twice as high as in the cell-reconstruction area (median = 0.013 mg/m3, range 0.003–0.154). In contrast, median BSF personal exposure in the anode plant was 0.036 mg/m3 (range 0.003–0.563), significantly lower than the median measured in the reconstruction area (0.054 mg/m3, range 0.003–0.371) (p = 0.041). The observation that median 1-OHP levels in urine were significantly higher in the anode plant than in the reconstruction area (6.62 µmol/mol creatinine, range 0.09–33.44 and 0.17 µmol/mol creatinine, range 0.001–2.47, respectively) parallels the static air measurements of BSF rather than the personal air monitoring results (p < 0.001). Results of air measurements and biological monitoring show that tasks associated with paste mixing and anode forming in the forming area of the anode plant resulted in higher PAH exposure than tasks in the non-forming areas; median 1-OHP levels in urine from workers in the forming area (14.20 µmol/mol creatinine, range 2.02–33.44) were almost four times higher than those obtained from workers in the non-forming area (4.11 µmol/mol creatinine, range 0.09–26.99; p < 0.001). Results justify use of biological monitoring as an important adjunct to existing measures of PAH exposure in the aluminium industry. Although monitoring of 1-OHP in urine may not be an accurate measure of biological effect on an individual, it is a better indicator of total PAH exposure than BSF in air. In January 2005, interim study results prompted a plant management decision to modify control measures to reduce skin exposure. Comparison of 1-OHP in urine from workers pre- and post-modifications showed substantial downward trends. Exposure via the dermal route was identified as a contributor to overall dose. Reduction in 1-OHP urine concentrations achieved by reducing skin exposure demonstrate the importance of exposure via this alternative pathway. Finally, control measures are recommended to ameliorate risk associated with PAH exposure in the primary aluminium production process, and suggestions for future research include development of methods capable of more specifically monitoring carcinogenic constituents of PAH mixtures, such as benzo[a]pyrene.

Multiple indicators of ambient and personal ultraviolet radiation exposure and risk of non-Hodgkin lymphoma (United States)

Recent epidemiologic studies have suggested that ultraviolet radiation (UV) may protect against non-Hodgkin lymphoma (NHL), but few, if any, have assessed multiple indicators of ambient and personal UV exposure. Using the US Radiologic Technologists study, we examined the association between NHL and self-reported time outdoors in summer, as well as average year-round and seasonal ambient exposures based on satellite estimates for different age periods, and sun susceptibility in participants who had responded to two questionnaires (1994–1998, 2003–2005) and who were cancer-free as of the earlier questionnaire. Using unconditional logistic regression, we estimated the odds ratio (OR) and 95% confidence intervals for 64,103 participants with 137 NHL cases. Self-reported time outdoors in summer was unrelated to risk. Lower risk was somewhat related to higher average year-round and winter ambient exposure for the period closest in time, and prior to, diagnosis (ages 20–39). Relative to 1.0 for the lowest quartile of average year-round ambient UV, the estimated OR for successively higher quartiles was 0.68 (0.42–1.10); 0.82 (0.52–1.29); and 0.64 (0.40–1.03), p-trend = 0.06), for this age period. The lower NHL risk associated with higher year-round average and winter ambient UV provides modest additional support for a protective relationship between UV and NHL.

Vitamin D intake needed to maintain target serum 25-Hydroxyvitamin D concentrations in participants with low sun exposure and dark skin pigmentation is substantially higher than current recommendations

Cutaneous cholecalciferol synthesis has not been considered in making recommendations for vitamin D intake. Our objective was to model the effects of sun exposure, vitamin D intake, and skin reflectance (pigmentation) on serum 25-hydroxyvitamin D (25[OH]D) in young adults with a wide range of skin reflectance and sun exposure. Four cohorts of participants (n = 72 total) were studied for 7-8 wk in the fall, winter, spring, and summer in Davis, CA [38.5° N, 121.7° W, Elev. 49 ft (15 m)]. Skin reflectance was measured using a spectrophotometer, vitamin D intake using food records, and sun exposure using polysulfone dosimeter badges. A multiple regression model (R^sup 2^ = 0.55; P < 0.0001) was developed and used to predict the serum 25(OH)D concentration for participants with low [median for African ancestry (AA)] and high [median for European ancestry (EA)] skin reflectance and with low [20th percentile, ~20 min/d, ~18% body surface area (BSA) exposed] and high (80th percentile, ~90 min/d, ~35% BSA exposed) sun exposure, assuming an intake of 200 IU/d (5 ug/d). Predicted serum 25(OH)D concentrations for AA individuals with low and high sun exposure in the winter were 24 and 42 nmol/L and in the summer were 40 and 60 nmol/L. Corresponding values for EA individuals were 35 and 60 nmol/L in the winter and in the summer were 58 and 85 nmol/L. To achieve 25(OH)D ≥75 nmol/L, we estimate that EA individuals with high sun exposure need 1300 IU/d vitamin D intake in the winter and AA individuals with low sun exposure need 2100-3100 IU/d year-round.

Multiple Health Behavior Changes and Co-variation in a Telephone Counseling Trial

Background Delivering effective multiple health behavior interventions to large numbers of adults with chronic conditions via primary care settings is a public health priority. Purpose Within a 12-month, telephone-delivered diet and physical activity intervention with multiple behavioral outcomes, we examined the extent and co-variation of multiple health behavior change. Methods A cluster-randomized trial with 434 patients with type 2 diabetes or hypertension were recruited from 10 general practices, which were randomized to receive telephone counseling or usual care. Results Those receiving telephone counseling were significantly more likely than those in usual care to make greater reductions in multiple behaviors after adjusting for baseline risk behaviors (OR 2.42; 95%CI 1.43, 4.11). Controlling for baseline risk and group allocation, making changes to either physical activity, fat, vegetable, or fiber intake was associated with making significantly more improvements in other behaviors. Conclusions For patients with chronic conditions, telephone counseling can significantly improve multiple health behaviors, with behavioral changes tending to co-vary.

Workers’ UV exposure and the subsequent impact on skin

Introduction: Excessive exposure to ultraviolet (UV) radiation from sunlight is a causative factor in the development of skin damage and skin cancer. Little research has been undertaken into assessing the sun exposure linking to skin damage inside buildings or behind window glass. This project directly addressed this issue by aiming to assess the role that UV exposure has on skin damage for indoor workers and drivers. Methods: Measurements of personal UV exposure using UV sensitive polymer dosimeters were undertaken of 41 indoor workers and 3 professional drivers. Physical measurements of skin characteristics including skin pigmentation and UV induced skin photoaging were also determined. In addition, demographic information along with phenotypic characteristics, sun exposure and sun protection practice history, and history of skin damage were assessed through a questionnaire. Results: Indoor workers typically received low doses of UV radiation. However, one driver received a high dose (13J/cm2 UVA and 4.99 MED UVB on the arm). Age and years residing in Australia had a positive correlation with UV induced skin pigmentation. The number of major sunburns before 18 years was a risk factor for skin damage in adults. Those participants with fair skin, non-black hair and blue/green /blue-grey eye were more likely to have skin damage related to sun exposure. Conclusions: A person’s age, years residing in Australia, numbers of major sunburn, skin colour, hair colour and eye colour are important factors associated with the development of sun-related skin damage in workers. ‘Real World’ implications: 1. The number of major sunburns before 18 years was a risk factor for skin damage in adults. This clearly confirms the importance of early prevention. To protect the skin from extensive sun exposure for your generation should have significance for further prevention of skin damage. 2. It is unsurprising that age and years residing in Australia were associated with skin damage related UV radiation. Therefore, the general public should reinforce their sun protective measures and check skin regularly. 3. Drivers should take sun protective measures during their working hours between sunrise and sunset.

Effect of cabin ventilation rate on ultrafine particle exposure inside automobiles

We alternately measured on-road and in-vehicle ultrafine (<100 nm) particle (UFP) concentration for 5 passenger vehicles that comprised an age range of 18 years. A range of cabin ventilation settings were assessed during 301 trips through a 4 km road tunnel in Sydney, Australia. Outdoor airflow(ventilation) rates under these settings were quantified on open roads using tracer gas techniques. Significant variability in tunnel trip average median in-cabin/on-road (I/O) UFP ratios was observed (0.08 to ∼1.0). Based on data spanning all test automobiles and ventilation settings, a positive linear relationship was found between outdoor air flow rate and I/O ratio, with the former accounting for a substantial proportion of variation in the latter (R2 ) 0.81). UFP concentrations recorded in cabin during tunnel travel were significantly higher than those reported by comparable studies performed on open roadways. A simple mathematical model afforded the ability to predict tunnel trip average in-cabin UFP concentrations with good accuracy. Our data indicate that under certain conditions, in-cabin UFP exposures incurred during tunnel travel may contribute significantly to daily exposure. The UFP exposure of automobile occupants appears strongly related to their choice of ventilation setting and vehicle.

Exposure to particle number, surface area and PM concentrations in pizzerias

The aim of this work was to quantify exposure to particles emitted by wood-fired ovens in pizzerias. Overall, 15 microenvironments were chosen and analyzed in a 14-month experimental campaign. Particle number concentration and distribution were measured simultaneously using a Condensation Particle Counter (CPC), a Scanning Mobility Particle Sizer (SMPS), an Aerodynamic Particle Sizer (APS). The surface area and mass distributions and concentrations, as well as the estimation of lung deposition surface area and PM1 were evaluated using the SMPS-APS system with dosimetric models, by taking into account the presence of aggregates on the basis of the Idealized Aggregate (IA) theory. The fraction of inhaled particles deposited in the respiratory system and different fractions of particulate matter were also measured by means of a Nanoparticle Surface Area Monitor (NSAM) and a photometer (DustTrak DRX), respectively. In this way, supplementary data were obtained during the monitoring of trends inside the pizzerias. We found that surface area and PM1 particle concentrations in pizzerias can be very high, especially when compared to other critical microenvironments, such as the transport hubs. During pizza cooking under normal ventilation conditions, concentrations were found up to 74, 70 and 23 times higher than background levels for number, surface area and PM1, respectively. A key parameter is the oven shape factor, defined as the ratio between the size of the face opening in respect

Exposure to ultrafine particles and PM2.5 in four Sydney transport modes

Concentrations of ultrafine (<0.1µm) particles (UFPs) and PM2.5 (<2.5µm) were measured whilst commuting along a similar route by train, bus, ferry and automobile in Sydney, Australia. One trip on each transport mode was undertaken during both morning and evening peak hours throughout a working week, for a total of 40 trips. Analyses comprised one-way ANOVA to compare overall (i.e. all trips combined) geometric mean concentrations of both particle fractions measured across transport modes, and assessment of both the correlation between wind speed and individual trip means of UFPs and PM2.5, and the correlation between the two particle fractions. Overall geometric mean concentrations of UFPs and PM2.5 ranged from 2.8 (train) to 8.4 (bus) × 104 particles cm-3 and 22.6 (automobile) to 29.6 (bus) µg m-3, respectively, and a statistically significant difference (p <0.001) between modes was found for both particle fractions. Individual trip geometric mean concentrations were between 9.7 × 103 (train) and 2.2 × 105 (bus) particles cm-3 and 9.5 (train) to 78.7 (train) µg m-3. Estimated commuter exposures were variable, and the highest return trip mean PM2.5 exposure occurred in the ferry mode, whilst the highest UFP exposure occurred during bus trips. The correlation between fractions was generally poor, and in keeping with the duality of particle mass and number emissions in vehicle-dominated urban areas. Wind speed was negatively correlated with, and a generally poor determinant of, UFP and PM2.5 concentrations, suggesting a more significant role for other factors in determining commuter exposure.