Urban vegetable contamination - The role of adhering particles and their significance for human exposure.

While urban-grown vegetables could help combat future food insecurity, the elevated levels of toxic metals in urban soils need to be met with measures that minimise transfer to crops. This study firstly examines soil/dust particle inclusion in leafy vegetables and its contribution to vegetable metals (As, Ba, Cd, Co, Cr, Cu, Ni, Pb, Sb, and Zn), using vegetable, soil and dust data from an open-field urban farm in southeastern Sweden. Titanium concentrations were used to assess soil/dust adherence. Results showed that vegetables contained 0.05-1.3 wt% of adhering particles (AP) even after washing. With 0.5 % AP, an adult with an average intake of vegetables could ingest approximately 100 mg of particles per day, highlighting leafy vegetables as a major route for soil/dust ingestion. The presence of adhering particles also significantly contributed to the vegetable concentrations of As (9-20 %), Co (17-20 %), Pb (25-29 %), and Cr (33-34 %). Secondly, data from an indoor experiment was used to characterise root metal uptake from 20 urban soils from Sweden, Denmark, Spain, the UK, and the Czech Republic. Combining particle adherence and root uptake data, vegetable metal concentrations were calculated for the 20 urban soils to represent hypothetical field scenarios for these. Subsequently, average daily doses were assessed for vegetable consumers (adults and 3-6 year old children), distinguishing between doses from adhering particles and root uptake. Risks were evaluated from hazard quotients (HQs; average daily doses/tolerable intakes). Lead was found to pose the greatest risk, where particle ingestion often resulted in HQs > 1 across all assessed scenarios. In summary, since washing was shown to remove only a portion of adhering metal-laden soil/dust particles from leafy vegetation, farmers and urban planners need to consider that measures to limit particle deposition are equally important as cultivating in uncontaminated soil.

Future food contaminants: An assessment of the plant uptake of Technology-critical elements versus traditional metal contaminants.

Technology-critical elements (TCEs) include most rare earth elements (REEs), the platinum group elements (PGEs), and Ga, Ge, In, Nb, Ta, Te, and Tl. Despite increasing recognition of their prolific release into the environment, their soil to plant transfer remains largely unknown. This paper provides an approximation of the potential for plant uptake by calculating bioconcentration factors (BCFs), defined as the concentration in edible vegetable tissues relative to that in cultivation soil. Here data were obtained from an indoor cultivation experiment growing lettuce, chard, and carrot on 22 different European urban soils. Values of BCFs were determined from concentrations of TCEs in vegetable samples after digestion with concentrated HNO3, and from concentrations in soil determined after 1) Aqua Regia digestion and, 2) diluted (0.1 M) HNO3 leaching. For comparison, BCFs were also determined for 5 traditional metal contaminants (TMCs; As, Cd, Cu, Pb, and Zn). The main conclusions of the study were that: 1)BCF values for the REEs were consistently low in the studied vegetables;2)the BCFs for Ga and Nb were low as well;3) the BCFs for Tl were high relative to the other measured TCEs and the traditional metal contaminants; and 4) mean BCF values for the investigated TCEs were generally highest in chard and lowest in carrot. These findings provide initial evidence that there are likely to be real and present soil-plant transfer of TCEs, especially in the case of Tl. Improvements in analytical methods and detection limits will allow this to be further investigated in a wider variety of edible plants so that a risk profile may be developed.

Is obesity a risk factor for impaired cognition in young adults with low birth weight?

BACKGROUND: Overweight and obesity are risk factors for cardiovascular disease. There is also an association between body mass index (BMI) and cognitive ability. Since low birth weight is associated with adult metabolic disease, particularly in obese subjects, the question emerges whether obesity has an additional negative effect on cognitive function in subjects with low birth weight. OBJECTIVES: The aim was to analyse whether overweight or obesity influence intellectual performance in young adults with particular focus on those with a low birth weight. METHODS: Data were collected from the Swedish Medical Birth Register on 620,834 males born between 1973 and 1988 and matched to results on intellectual performance and BMI at conscription. RESULTS: The risk for low intellectual performance was higher for those with high BMI compared to those with normal. The highest risk was found among subjects with low birth weight and overweight or obesity in young adulthood (odds ratios, 1.98 [1.73-2.22] and 2.59 [2.00-3.34], respectively). However, subjects with further high birth weight and a high BMI at conscription had no further increased risk. CONCLUSIONS: Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance. A high birth weight increases the risk for obesity, but a high adult BMI does not further increase the risk for subnormal performance.

Topology and structural self-organization in folded proteins.

Topological methods are indispensable in theoretical studies of particle physics, condensed matter physics, and gravity. These powerful techniques have also been applied to biological physics. For example, knowledge of DNA topology is pivotal to the understanding as to how living cells function. Here, the biophysical repertoire of topological methods is extended, with the aim to understand and characterize the global structure of a folded protein. For this, the elementary concept of winding number of a vector field on a plane is utilized to introduce a topological quantity called the folding index of a crystallographic protein. It is observed that in the case of high resolution protein crystals, the folding index, when evaluated over the entire length of the crystallized protein backbone, has a very clear and strong propensity towards integer values. The observation proposes that the way how a protein folds into its biologically active conformation is a structural self-organization process with a topological facet that relates to the concept of solitons. It is proposed that the folding index has a potential to become a useful tool for the global, topological characterization of the folding pathways.

Differences between men and women in the regulation of adipose 11ß-HSD1 and in its association with adiposity and insulin resistance.

This study explored sex differences in 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity and gene expression in isolated adipocytes and adipose tissue (AT), obtained via subcutaneous biopsies from non-diabetic subjects [58 M, 64 F; age 48.3 ± 15.3 years, body mass index (BMI) 27.2 ± 3.9 kg/m²]. Relationships with adiposity and insulin resistance (IR) were addressed. Males exhibited higher 11ß-HSD1 activity in adipocytes than females, but there was no such difference for AT. In both men and women, adipocyte 11ß-HSD1 activity correlated positively with BMI, waist circumference, % body fat, adipocyte size and with serum glucose, triglycerides and low-density lipoprotein:high-density lipoprotein (LDL:HDL) ratio. Positive correlations with insulin, HOMA-IR and haemoglobin A1c (HbA1c) and a negative correlation with HDL-cholesterol were significant only in males. Conversely, 11ß-HSD1 activity in AT correlated with several markers of IR and adiposity in females but not in males, but the opposite pattern was found with respect to 11ß-HSD1 mRNA expression. This study suggests that there are sex differences in 11ß-HSD1 regulation and in its associations with markers of obesity and IR.

Gestational diabetes and offspring body disproportion.

AIM: It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants. METHODS: Birth characteristics of 884,267 infants of non-diabetic mothers and 7817 of mothers with GDM were analysed. LGA was defined as birth weight or birth length >2 standard deviation scores for gestational age. Multiple logistic regression analysis was performed. RESULTS: The odds ratio (OR) for a woman with GDM to give birth to an LGA infant that was heavy alone was four times increased (OR: 3.71, 95% CI: 3.41-4.04). Furthermore, in the population of mothers giving birth to LGA infants, the proportion heavy alone was 68% in the group of women with GDM compared with 64.4% in the group of non-diabetic women. The risks were independent of gender of the foetus. CONCLUSION: Women with GDM have an almost four times higher risk of delivering an LGA infant that is heavy alone. The noted disproportion between weight and length in infants of such mothers may have an impact on the risk of later obesity.

Sex- and depot-specific lipolysis regulation in human adipocytes: interplay between adrenergic stimulation and glucocorticoids.

The purpose of this investigation was to explore interactions between adrenergic stimulation, glucocorticoids, and insulin on the lipolytic rate in isolated human adipocytes from subcutaneous and omental fat depots, and to address possible sex differences. Fat biopsies were obtained from 48 nondiabetic subjects undergoing elective abdominal surgery. Lipolysis rate was measured as glycerol release from isolated cells and proteins involved in lipolysis regulation were assessed by immunoblots. Fasting blood samples were obtained and metabolic and inflammatory variables were analyzed. In women, the rate of 8-bromo-cAMP- and isoprenaline-stimulated lipolysis was approximately 2- and 1.5-fold higher, respectively, in subcutaneous compared to omental adipocytes, whereas there was no difference between the two depots in men. Dexamethasone treatment increased the ability of 8-bromo-cAMP to stimulate lipolysis in the subcutaneous depot in women, but had no consistent effects in fat cells from men. Protein kinase A, Perilipin A, and hormone sensitive lipase content in adipocytes was not affected by adipose depot, sex, or glucocorticoid treatment. In conclusion, catecholamine and glucocorticoid regulation of lipolysis in isolated human adipocytes differs between adipose tissue depots and also between sexes. These findings may be of relevance for the interaction between endogenous stress hormones and adipose tissue function in visceral adiposity and the metabolic syndrome.

Insulin action and signalling in fat and muscle from dexamethasone-treated rats.

Glucocorticoids initiate whole body insulin resistance and the aim of the present study was to investigate effects of dexamethasone on protein expression and insulin signalling in muscle and fat tissue. Rats were injected with dexamethasone (1mg/kg/day, i.p.) or placebo for 11 days before insulin sensitivity was evaluated in vitro in soleus and epitrochlearis muscles and in isolated epididymal adipocytes. Dexamethasone treatment reduced insulin-stimulated glucose uptake and glycogen synthesis by 30-70% in epitrochlearis and soleus, and insulin-stimulated glucose uptake by approximately 40% in adipocytes. 8-bromo-cAMP-stimulated lipolysis was approximately 2-fold higher in adipocytes from dexamethasone-treated rats and insulin was less effective to inhibit cAMP-stimulated lipolysis. A main finding was that dexamethasone decreased expression of PKB and insulin-stimulated Ser(473) and Thr(308) phosphorylation in both muscles and adipocytes. Expression of GSK-3 was not influenced by dexamethasone treatment in muscles or adipocytes and insulin-stimulated GSK-3beta Ser(9) phosphorylation was reduced in muscles only. A novel finding was that glycogen synthase (GS) Ser(7) phosphorylation was higher in both muscles from dexamethasone-treated rats. GS expression decreased (by 50%) in adipocytes only. Basal and insulin-stimulated GS Ser(641) and GS Ser(645,649,653,657) phosphorylation was elevated in epitrochlearis and soleus muscles and GS fractional activity was reduced correspondingly. In conclusion, dexamethasone treatment (1) decreases PKB expression and insulin-stimulated phosphorylation in both muscles and adipocytes, and (2) increases GS phosphorylation (reduces GS fractional activity) in muscles and decreases GS expression in adipocytes. We suggest PKB and GS as major targets for dexamethasone-induced insulin resistance.

Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants.

AIM: To analyse if females born large for gestational age (LGA) have an increased risk to give birth to LGA infants and to study anthropometric characteristics in macrosomic infants of females born LGA. METHODS: The investigation was performed as an intergenerational retrospective study of women born between 1973 and 1983, who delivered their first infant between 1989 and 1999. Birth characteristics of 47,783 females, included in the Swedish Birth Register both as newborns and mothers were analysed. LGA was defined as >2 SD in either birth weight or length for gestational age. The infants were divided into three subgroups: born tall only, born heavy only and born both tall and heavy for gestational age. Multiple logistic and linear regression analyses were performed. RESULTS: Females, born LGA with regard to length or weight, had a two-fold (adjusted OR 1.96, 95% Cl 1.54-2.48) increased risk to give birth to an LGA infant. Females, born LGA concerning weight only, had a 2.6 (adjusted OR 2.63, 95%, 1.85-3.75) fold increased risk of having an LGA offspring heavy only and no elevated risk of giving birth to an offspring that was tall only, compared to females born not LGA. In addition, maternal obesity was associated with a 2.5 (adjusted OR 2.56, 95%, 2.20-2.98) fold increased risk of having an LGA newborn, compared to mothers with normal weight. CONCLUSION: Females, born LGA, have an increased risk to give birth to LGA infants, compared to mothers born not LGA. Maternal overweight increases this risk even further.

Fat cell enlargement is an independent marker of insulin resistance and 'hyperleptinaemia'.

AIMS/HYPOTHESIS: The aim of this study was to explore whether fat cell size in human subcutaneous and omental adipose tissue is independently related to insulin action and adipokine levels. MATERIALS AND METHODS: Fat cells were prepared from abdominal subcutaneous biopsies obtained from 49 type 2 diabetic and 83 non-diabetic subjects and from omental biopsies obtained from 37 non-diabetic subjects. Cell size and insulin action on glucose uptake capacity in vitro were assessed in isolated fat cells. Insulin sensitivity in vivo was assessed with euglycaemic-hyperinsulinaemic clamps. Fasting blood samples were collected and adipokines and NEFA were measured. RESULTS: Negative correlations were found between subcutaneous fat cell size and insulin sensitivity assessed as M-value during clamp and as insulin action on glucose uptake in fat cells in vitro. This was seen in non-diabetic subjects after including age, sex and BMI in the analyses. No such relationship was found in type 2 diabetic subjects. In both groups, subcutaneous fat cell size correlated positively and independently with plasma levels of leptin but not to any of the other assessed adipokines. In non-diabetic subjects, omental fat cell size was independently and negatively correlated with insulin action in subcutaneous, but not omental, fat cells in vitro. CONCLUSIONS/INTERPRETATION: Fat cell enlargement is associated with insulin resistance in non-diabetic individuals independently of BMI. This was not seen in type 2 diabetic subjects, suggesting that after development of type 2 diabetes other factors, not related to fat cell size, become more important for the modulation of insulin resistance.

Lipoprotein lipase activity/mass ratio is higher in omental than in subcutaneous adipose tissue.

BACKGROUND: Lipoprotein lipase (LPL) is important for lipid deposition in adipose tissue (AT) and responds rapidly to changes in the nutritional state. Animal experiments indicate that short-term regulation of LPL is mainly post-translational. Different processing of LPL in different AT depots may play a role in the distribution of lipids in the body. MATERIALS AND METHODS: Lipoprotein lipase mRNA, mass and activity were measured in pieces of omental adipose tissue (OAT) and subcutaneous adipose tissue (SAT) from 15 subjects undergoing gastrointestinal surgery (four male and 11 female subjects, mean age 54 +/- 5 years, BMI 28 +/- 2 kg m(-2)). RESULTS: Lipoprotein lipase activity was higher in OAT than in SAT (18 +/- 2.1 compared with 12 +/- 1.6 mU g(-1), P < 0.01), whereas LPL mass was lower in OAT than in SAT (100 +/- 9 compared with 137 +/- 16 mU g(-1), P < 0.05). Consequently, the specific LPL activity (ratio of activity over mass) was approximately twofold greater in OAT compared with SAT. There was correlation between LPL mRNA and LPL activity in SAT (P < 0.05) and a similar tendency in OAT (P = 0.08). There were strong correlations (P < 0.01) for mRNA abundance as well as for LPL activity between the two depots. In contrast there was no correlation between the LPL mass and LPL mRNA or activity in any of the depots. CONCLUSIONS: These results indicate that long-term regulation, as reflected in the mRNA abundance, is similar in the two types of adipose tissue. The displayed activity reflects the mRNA abundance and the fraction of newly synthesized LPL molecules which the post-translational mechanism allows to become/remain active. This fraction was on average twofold greater in OAT compared with SAT.

Glucocorticoids down-regulate glucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes.

Visceral adiposity is associated with insulin resistance and type 2 diabetes. This study explores the metabolic differences between s.c. and visceral fat depots with respect to effects in vitro of glucocorticoids and insulin on glucose uptake. Adipocytes from human s.c. and omental fat depots were obtained during abdominal surgery in 18 nondiabetic subjects. Cells were isolated, and metabolic studies were performed directly after the biopsies and after a culture period of 24 h with or without dexamethasone. After washing, basal and insulin-stimulated [14C]glucose uptake as well as cellular content of insulin signaling proteins and glucose transporter 4 (GLUT4) was assessed. Omental adipocytes had an approximately 2-fold higher rate of insulin-stimulated glucose uptake compared with s.c. adipocytes (P < 0.01). Dexamethasone treatment markedly inhibited (by approximately 50%; P < 0.05) both basal and insulin-stimulated glucose uptake in omental adipocytes but had no consistent effect in s.c. adipocytes. The cellular content of insulin receptor substrate 1 and phosphatidylinositol 3-kinase did not differ significantly between the depots, but the expression of protein kinase B (PKB) tended to be increased in omental compared with s.c. adipocytes (P = 0.09). Dexamethasone treatment decreased the expression of insulin receptor substrate 1 (by approximately 40%; P < 0.05) and PKB (by approximately 20%; P < 0.05) in omental but not in s.c. adipocytes. In contrast, dexamethasone pretreatment had no effect on insulin-stimulated Ser473 phosphorylation of PKB. GLUT4 expression was approximately 4-fold higher in omental than s.c. adipocytes (P < 0.05). Dexamethasone treatment did not alter the expression of GLUT4. In conclusion, human omental adipocytes display approximately 2-fold higher glucose uptake rate compared with s.c. adipocytes, and this could be explained by a higher GLUT4 expression. A marked suppression is exerted by glucocorticoids on glucose uptake and on the expression of insulin signaling proteins in omental but not in s.c. adipocytes. These findings may be of relevance for the interaction between endogenous glucocorticoids and visceral fat in the development of insulin resistance.

No in vitro effects of fatty acids on glucose uptake, lipolysis or insulin signaling in rat adipocytes.

Elevated plasma levels of free fatty acids (FFA) can produce insulin resistance in skeletal muscle tissue and liver and, together with alterations in beta-cell function, this has been referred to as lipotoxicity. This study explores the effects of FFAs on insulin action in rat adipocytes. Cells were incubated 4 or 24 h with or without an unsaturated FFA, oleate or a saturated FFA, palmitate (0.6 and 1.5 mM, respectively). After the culture period, cells were washed and insulin effects on glucose uptake and lipolysis as well as cellular content of insulin signaling proteins (IRS-1, PI3-kinase, PKB and phosphorylated PKB) and the insulin regulated glucose transporter GLUT4 were measured. No significant differences were found in basal or insulin-stimulated glucose uptake in FFA-treated cells compared to control cells, regardless of fatty acid concentration or incubation period. Moreover, there were no significant alterations in the expression of IRS-1, PI3-kinase, PKB and GLUT4 following FFA exposure. Insulin's ability to stimulate PKB phosphorylation was also left intact. Nor did we find any alterations following FFA exposure in basal or cAMP-stimulated lipolysis or in the ability of insulin to inhibit lipolysis. The results indicate that oleate or palmitate does not directly influence insulin action to stimulate glucose uptake and inhibit lipolysis in rat fat cells. Thus, lipotoxicity does not seem to occur in the fat tissue itself.

Binding of Ikaros to the lambda5 promoter silences transcription through a mechanism that does not require heterochromatin formation.

The Ikaros family of proteins are DNA binding factors required for correct development of B and T lymphocytes. Cytogenetic studies have shown that these proteins form complexes with pericentromeric heterochromatin in B cells, and the colocalization of transcriptionally silent genes with these complexes suggests that Ikaros could silence transcription by recruiting genes to heterochromatin. Here we show that a site in the lambda5 promoter that binds Ikaros and Aiolos is required for silencing of lambda5 expression in activated mature B cells. Analysis of methylation and nuclease accessibility indicates that the silenced lambda5 gene is not heterochromatinized in B cells, despite being associated with pericentromeric heterochromatin clusters. We also found that a promoter mutation, which affects Ikaros-mediated silencing of lambda5 expression, is not rescued in a transgenic line that has the gene integrated into pericentromeric heterochromatin. Our results indicate that the Ikaros proteins initiate silencing of lambda5 expression through a direct effect on the promoter with localization to pericentromeric heterochromatin likely to affect the action of Ikaros on regulatory sequences rather than causing heterochromatinization of the gene.

Transcription factor dosage affects changes in higher order chromatin structure associated with activation of a heterochromatic gene.

The mechanisms of transcriptional activation in heterochromatin were investigated by using FISH to directly visualize changes in chromatin organization during activation of a heterochromatic lambda5 transgene. A DNase I hypersensitive site was shown to relocate the transgene to the outside of the pericentromeric heterochromatin complex in the absence of transcription. Activation of transcription, which is dependent on the transcription factor EBF, occurs in a stochastic manner that resembles telomeric silencing in yeast, with the transcribed gene remaining closely associated with the heterochromatin complex. Reducing the dosage of EBF results in a reduced frequency of localization of the transgene to the outside of the heterochromatin complex and lower levels of transcription. These data provide evidence that transcription factors can initiate changes in higher order chromatin structure during the earliest stages of gene activation.

Root caries and some related factors in 88-year-old carriers and non-carriers of Streptococcus sobrinus in saliva.

The prevalence of caries on exposed root surfaces in 88-year-old subjects with and without salivary levels of Streptococcus sobrinus was studied. Ninety-two individuals were examined with regard to root caries lesions and fillings. The root caries index (RCI) was calculated and related to salivary flow rate and buffer capacity, plaque score and salivary counts of Streptococcus mutans, S. sobrinus and lactobacilli. In 89 subjects with exposed root surfaces, all but 2 harbored mutans streptococci; 51 subjects carried S. mutans only, 35 both S. sobrinus and S. mutans, and 1 S. sobrinus only. The RCI was significantly higher in persons with than those without S. sobrinus (p < 0.05). Subjects with both S. sobrinus and S. mutans had higher counts of total mutans streptococci and lactobacilli than subjects with only S. mutans (p < 0.05). The RCI was significantly correlated to S. sobrinus and S. mutans (p < 0.05). The positive correlation between the RCI and S. sobrinus was still significant when the other tested variables were kept constant, whereas the correlation between the RCI and S. mutans was weaker when S. sobrinus and lactobacilli were kept constant. The D-component of the RCI (DSr%) was significantly correlated to S. sobrinus, S. mutans and lactobacilli, whereas the F-component of the RCI showed no significant correlation to any of the tested variables. A stepwise multiple correlation showed that the variance of DSr% was best explained in the S. sobrinus carriers by S. sobrinus and the salivary buffer effect, and in the non-carriers by S. mutans.

Utilization of dental services in relation to socioeconomic and health factors in the middle-aged and elderly Swedish population.

The aims of this study were to describe the change in reported time since the latest visit to a dentist between the years 1980/81 and 1988/89 and the reported use of dental services in relation to age, dental state, and socioeconomic and health characteristics in a sample of the Swedish population in 1988/89. The studies are based on interviews by Statistics Sweden about the living conditions. In the investigations in 1980/81, 14,964 inhabitants between 16 and 84 years of age participated, and in 1988/89, 13,309 inhabitants. In all age groups there was a significantly higher frequency of reported visits to a dentist last year in 1988/89 than in 1980/81. In the age group 50-64 years old this figure increased from 54% to 75%, and in the age group 65-84 years old it increased from 26% to 39%. In the investigation in 1988/89 about 75% of the dentulous women in all age groups up to 75 years reported visiting a dentist last year. The relative risk for not visiting a dentist last year, adjusted for age, gender, and dental state, was higher in dentulous subjects with low income and education, not married, not native-born, living in rural areas, smoking, and low social and physical activity. The results of the logistic regression analysis showed that, among the elderly, functional ability and general health factors have lower significance for time since last visit to a dentist than socioeconomic, social support, and life-style factors.