Relationship of lead and essential elements in whole blood from school-age children in Nanning,China

ObjectivesThe aim of this study was to investigate blood lead level and its relationship to essential elements (zinc, copper, iron, calcium and magnesium) in school-age children from Nanning, China.MethodsA total of 2457 children aged from 6 to 14 years were enrolled in Nanning, China. The levels of lead (Pb), zinc (Zn), copper (Cu), iron (Fe), calcium (Ca) and magnesium (Mg) were determined by an atomic absorption spectrometer.ResultsThe mean blood lead level (BLL) was 57.21 ± 35.00 μg/L. 188 (7.65%) asymptomatic children had toxic lead level higher than 100 μg/L. The school-age boys had similar lead level among different age groups, while the elder girls had less BLL. The blood Zn and Fe were found to be increased in the boys with elevated BLL, but similar trends were not observed in the girls. Positive correlations between Pb and Fe or Mg (r = 0.112, 0.062, respectively, p < 0.01) and a negative correlation between Pb and Ca (r = −0.047, p < 0.05) were further established in the studied children.ConclusionsLead exposure in school-age children was still prevalent in Nanning. The boys and girls differed in blood levels of lead and other metallic elements. Lead exposure may induce metabolic disorder of other metallic elements in body.     

Counteract of bone marrow of blotchy mice against the increases of plasma copper levels induced by high-fat diets in LDLR−/− mice

BackgroundBone marrow of blotchy mouse (blotchy marrow) reflects the function of transmembrane domain and relevant intramembrane sites of ATP7A in myeloid cells. By chronic infusion of angiotensin II, we previously found that blotchy marrow plays a minor role in regulating plasma copper. Moreover, the recipients of blotchy marrow presented a moderate reduction of plasma lipids and inflammatory mediator production. Little is known about whether these changes are a specific response to angiotensin II or reveal a more general role of ATP7A.Objective and designWe investigated if blotchy marrow reduces plasma lipids and inflammatory mediators induced by high-fat diets. To test this hypothesis, blotchy and control marrows were reconstituted to the recipient mice (irradiated male LDLR−/− mice), followed by high-fat-diet feeding for 4 months. At the end points, plasma metals (copper, zinc and iron), lipid profiling (cholesterol, triglyceride, phospholipids and lipoprotein) and six inflammatory mediators (lymphotacin, MCP3, MCP5, TIMP1, VEGF-A and IP-10) were measured. Parallel experiments were performed using male LDLR−/− mice fed either high-fat diets or chow diets for 4 months.ResultsIn addition to hyperlipidemia and low-grade inflammation, high-fat diets selectively increased plasma copper concentration compared to chow diets in LDLR−/− mice. After high-fat-diet feeding, the recipients with blotchy marrow showed a decrease in plasma copper (p < 0.01) and an increase in plasma iron (p < 0.05). The recipients with blotchy marrow also presented decreases in cholesterol (p < 0.01) and phospholipids (p < 0.05) in plasma. Surprisingly, plasma levels of MCP3 (p < 0.05), MCP5 (p < 0.05), TIMP1 (p < 0.01), VEGF-A (p < 0.01) and IP-10 (p < 0.01) were significantly increased in the recipients with blotchy marrow compared to controls; the increased levels of MCP3, MCP5 and TIMP1 were more than 50%.ConclusionOur studies showed that blotchy marrow counteracts the increased copper levels induced by high-fat diets, indicating that circulating myeloid cells can regulate blood copper levels via ATP7A. Moreover, transplantation of blotchy marrow followed by high-fat diets leads to a decrease in lipid profile and an increase in inflammatory mediator production. Overall, blotchy marrow mediates divergent responses to angiotensin II and high-fat diets in vivo.     

Survival of hepatocellular carcinoma patients is significantly improving: a population-based study from southern Switzerland

BackgroundDuring the last 20 years, relevant diagnostic procedures and advanced treatments have been progressively introduced in the management of hepatocellular carcinoma (HCC).The aim of the present study was to assess up-to-date survival trends for HCC in southern Switzerland, a region with one of the highest incidence rates in the country.MethodsHCCs diagnosed in 1996–2009 were selected by the Ticino Cancer Registry. Cancer-specific survival (CSS) analysis was performed using the Kaplan–Meier method by calendar period: 1996–2000, 2001–2005 and 2006–2009. The log-rank test was used to detect differences in survival curves. Simultaneous assessment of prognostic factors was performed by a multivariate analysis using the Cox proportional-hazards regression model.Results619 HCCs were analysed. There was a significant increase of patients undergoing transarterial chemoembolisation (TACE), whereas patients undergoing curative or palliative supportive treatments remained unchanged (p < 0.0001). No shift to earlier stages was detected. Significant differences in CCS were observed by age-group (p < 0.0001), diagnosis period (p < 0.0001), diagnosis technique (p = 0.0035), Barcelona-Clinic liver cancer stage (p < 0.0001), treatment (p < 0.0001). Multivariate analysis confirmed the independent impact on CSS of factors above mentioned, not including the diagnosis technique. Death risk was higher for patients diagnosed in 1996–2000 (HR: 1.32; 95% CI: 1.03; 1.68) and 2001–2005 (HR: 1.33; 95% CI: 1.05; 1.67) in comparison with 2006–2009 (reference group).ConclusionsThe current population-based report describes a major increase in HCC survival. Simultaneously an increased use of TACE has been detected, probable cofactor of the observed survival increase. Possibly additional efforts could be made to decrease the HCC stage at diagnosis through active surveillance of cirrhotic patients to allow an increase in curative treatments. For sure efforts should be made to comply with a standardised staging system for HCC, particularly for comparative population-based issues.     

Hyperuricemia and metabolic syndrome in children with overweight and obesity

ObjectiveTo study the prevalence of hyperuricemia in children with overweight or obesity and analyze the relation with metabolic syndrome and the diseases that define it.Materials and methodsThis is a cross-sectional prevalence study in 148 children recruited from pediatric endocrinology consultation, with overweight or obesity (12 ± 3 years, 48% boys, BMI 31.8 ± 6.1). We measured BMI, waist-height, waist circumference, blood pressure with standard instrumentation and glucose (fasting and after overload with 75 g), insulin resistance, cholesterol HDL, triglycerides and uric acid.ResultsThe prevalence of hyperuricemia was 53%. Patients with hyperuricemia had greater BMI (33.9 vs 30.6, p = 0.003), plus waist circumference (101.4 vs 91.1 cm, p < 0.001), higher blood pressure: systolic (123.4 vs 111.9 mm Hg, p < 0.001), diastolic (78.2 vs 68.7 mm Hg, p < 0.001). They presented greater blood glucose after overload oral glucose (107.5 vs 100.7 mg/dl, p = 0.03), insulin was higher (29.2 vs 20.7 mg/dl, p = 0.001) as well as HOMA IR (6.5 vs 4.4, p < 0.001) and HDL levels were lower (49.5 vs 54.4 mg/dl, p = 0.02).Uric acid's level which most is the likely diagnosis of metabolic syndrome corresponds to 5.4 mg/dl in our sample (sensitivity: 64% and specificity 62%).ConclusionThe prevalence of hyperuricemia in children with overweight and obesity is high. In the group of patients with obesity and hyperuricemia, we found out that the parameters measured to diagnose with metabolic syndrome were less favorable. Uric acid's level from where there is a higher possibility to see metabolic syndrome is 5.4 mg/dl.     

Evidence that metyrapone in the presence of inflammation modulates cytokine mRNA expression

ObjectiveMetyrapone (MT) has been used clinically to decrease glucocorticoid levels in human and animal studies. However, the potential effects of MT in the presence of inflammation are poorly understood. Thus, the aim of this study was to evaluate the effects of the administration of MT on the mRNA levels of pro-inflammatory cytokines in the presence of inflammation induced by the well-established model of ligature-induced periodontitis in rats.Material and methodsSixty animals were randomly assigned into three experimental groups of 20 rats each: G1-control; G2-periodontal disease (PD) induced by cotton ligature; G3-PD associated with 3 daily doses of MT (50 mg/kg/3 × 3 h). After 30 days, all animals were killed by decapitation. Blood samples were taken and the concentrations of corticosterone and catecholamines measured. Marginal tissues around ligated and non-ligated teeth were harvested and gene expression was assessed by quantitative polymerase chain reaction technique (qPCR). Moreover, the area of interradicular bone loss (ABL) was histometrically determined.ResultsData analysis showed that: (i) ligature placement resulted in a significant ABL, as compared to non-ligated sites of G1 group; (ii) mRNA levels of all the pro-inflammatory factors assessed (INF-γ, TNF-α, IL-1β and IL-6) were increased in the PD group (G2) (p < 0.05) when compared to G1; (iii) there were no significant differences in corticosterone and catecholamine plasmatic levels between the three groups; (iv) MT administration, in the presence of inflammation, induces an increased ABL and significantly increased mRNA levels of all pro-inflammatory cytokines analyzed (p < 0.05).ConclusionWithin the limits of this study, it can be concluded that MT in the presence of inflammation may modulate expression of pro-inflammatory cytokines, regardless of its effect on plasma corticosterone levels.     

Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

AimImbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity.MethodsSixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-β) were measured by enzyme linked immunosorbent assays (ELISA).ResultsSLE patients were found to have significantly higher levels of IL-17 (p < 0.001), IL-6 (p < 0.01), IL-12 (p < 0.001) and IL-10 (p < 0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-β levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p < 0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p < 0.01), IL-6 (p < 0.05), IL-17 (p < 0.001), IL-23 (p < 0.01) and TGF-β (p < 0.5) and lower IFN-γ (p < 0.001) and IL-10 (p < 0.01) than those of healthy subjects.ConclusionOur study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-β1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease.     

The Quételet index revisited in children and adults

BackgroundThe body mass index (BMI) is based on the original concept that body weight increases as a function of height squared. As an indicator of obesity the modern BMI assumption postulates that adiposity also increases as a function of height in states of positive energy balance.ObjectiveTo evaluate the BMI concept across different adiposity magnitudes, in both children and adults.MethodsWe studied 975 individuals who underwent anthropometric evaluation: 474 children and 501 adults. Tetrapolar bioimpedance analysis was used to assess body fat and lean mass.ResultsBMI significantly correlated with percentage of body fat (%BF; children: r = 0.893; adults: r = 0.878) and with total fat mass (children: r = 0.967; adults: r = 0.953). In children, body weight, fat mass, %BF and waist circumference progressively increased as a function of height squared. In adults body weight increased as a function of height squared, but %BF actually decreased with increasing height both in men (r = −0.406; p < 0.001) and women (r = −0.413; p < 0.001). Most of the BMI variance in adults was explained by a positive correlation of total lean mass with height squared (r² = 0.709), and by a negative correlation of BMI with total fat mass (r = −0.193).ConclusionsBody weight increases as a function of height squared. However, adiposity progressively increases as a function of height only in children. BMI is not an ideal indicator of obesity in adults since it is significantly influenced by the lean mass, even in obese individuals.     

Serum and urinary selenium levels in obese children: A cross-sectional study

ObjectiveTo determine serum and urinary selenium (Se) levels in children with and without obesity, and to assess if Se influences the risk of obesity.Subjects and methodsHigh-resolution-continuum source-atomic absorption spectrometry (HR-CS-AAS) was used to determine the content of Se in 80 children (age 6–17; 40 boys, 40 girls). Correlations between variables were tested with the use of Spearman's correlation coefficient. U Mann–Whitney test was applied to assess the difference of Se contents in samples. Measured metabolic risk factors (blood pressure, glucose level, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol), age, gender, and BMI were correlated. Logistic regression models were fitted to identify predictors of obesity interacting with selenium content in serum and urine, separately.ResultsObese children, regardless of gender, had lower Se content. Se level in serum (p = 0.001, OR 0.74, 95%CI 0.62–0.88) and total cholesterol (p = 0.001, OR 1.19, 95%CI 1.08–1.31) were the independent factors significantly influencing the risk of obesity in children. Two separate models were observed for Se in urine: (i) Se level (p < 0. 0001, OR 0.70, 95%CI 0.58–0.84) and glucose level (p < 0.0001, OR 1.22, 95%CI 1.10–1.35), and (ii) Se level (p = 0.002, OR 0.60 95%CI 0.43–0.83) and total cholesterol level (p = 0.003, OR 1.16, 95%CI 1.05–1.28).ConclusionThe current study suggests a possible role of Se in obesity. Further research needs to be performed to check if obese children are an at-risk group for Se deficiency.     

BMI and levels of zinc,copper in hair,serum and urine of Turkish male patients with androgenetic alopecia

ObjectiveMale pattern androgenetic alopecia is characterized by progressive hair loss from the scalp. It is known that imbalances of some trace elements play a role in the pathomechanism of many forms of alopecia. The aim of this study was to evaluate the levels of zinc and copper in hair, serum and urine samples of Turkish males with male pattern androgenetic alopecia and to compare with healthy controls.Material and methods116 males with male pattern androgenetic alopecia and 100 controls were involved in this study.ResultsLevels of zinc and copper in hair were decreased significantly in the patients (p < 0.05), although zinc and copper levels of serum and urine were not different between patients and controls (p > 0.05). Body mass index of patients were higher than control group. In addition, in the group with body mass index of 25 and lower zinc level in hair and urine, copper level in serum were significantly higher (p < 0.05). Body mass index was negatively correlated with hair zinc levels.ConclusionWe thought that decreased zinc and copper levels in hair may play a role in the etiology of male pattern androgenetic alopecia. In addition, obesity by making changes in the balance of the trace elements in hair, serum and urine may play a role in male pattern androgenetic alopecia. Hence, assessing the levels of trace elements in hair of male pattern androgenetic alopecia patients may be more valuable compared to serum and urine for treatment planning.     

Postural stability in young healthy subjects – Impact of reduced base of support,visual deprivation,dual tasking

ObjectiveTo provide normative postural stability data in young subjects.MethodsNinety-six healthy participants (58 W, 28 ± 6y) stood on a force plate during 60 s. We measured effects of support width (feet apart, FA; feet together, FT), vision (eyes open, EO; closed, EC), and cognitive load (single task, ST; dual tasking, DT) on anteroposterior (AP) and medio-lateral (ML) ranges, area and planar velocity of center of pressure (COP) trajectory.ResultsAll variables increased with FT (AP range, +15%; ML, +185%; area, +242%; velocity, +50%, p < 0.0002 for all, MANOVA). Visual deprivation increased COP ranges with added constraints (FT or DT, p = 0.002) and increased velocity in all conditions (FA/ST, +16%; DT, +18%; FT/ST, +29%; DT, +23%, p < 0.0002 for all). Dual tasking reduced COP displacements with FT (AP range, EO, −15%; EC, −11%; ML range, EO, −19%; EC, −13%; area, EO, −40%; EC, −28%, p < 0.0002 for all) and increased velocity in most conditions (FA/EO, +15%; FA/EC, +16%; FT/EO, +7%, p < 0.0002 for all).ConclusionIn young healthy adults, base of support reduction increases COP displacements. Vision particularly affects postural stability with feet together or dual tasking. Dual tasking increases velocity but decreases COP displacements in challenging postural tasks, potentially by enhanced lower limb stiffness.     

The effect of adding zinc to vitamin A on IGF-1, bone age and linear growth in stunted children

A randomized, double-blind, placebo controlled trial of a single dose of 200,000 I.U. of vitamin A with daily zinc supplementation was conducted with children in Mojo village, Surabaya City. Children aged 48 to 60 months were randomized to receive a single dose of 200,000 I.U. of vitamin A plus zinc sulfate (n = 12) or a single dose of 200,000 I.U. of vitamin A (n = 12) plus placebo six days a week for six months. Children were evaluated weekly for nutrient intake and for IGF-1, C-reactive protein levels, gamma globulin levels, serum zinc, serum retinol, bone age and the index height for age at six months.At the end of the study, there was a significant increase in the serum retinol level (p < 0.03), serum zinc level (p < 0.03), IGF-1 hormone (p < 0.04) and Z-score height for age (p < 0.001), bone age (p < 0.01), and gamma globulin level (p < 0.04) and a significant decrease in the amount of infection/inflammation measured by CRP level (p < 0.001). There was also a significant correlation between CRP level and height for age (p < 0.01), and between gamma level and height for age (p < 0.01).These results suggest that combined vitamin A and zinc supplementation reduces the risk of infection and increases linear growth among children, and thus may play a key role in controlling infection and stunted growth for children under five years old.     

A Fraxinus excelsior L. seeds/fruits extract benefits glucose homeostasis and adiposity related markers in elderly overweight/obese subjects: A longitudinal,randomized, crossover,double-blind,placebo-controlled nutritional intervention study

PurposeThe aim of this study was to investigate the potential benefits of an extract obtained from seeds/fruits of an Oleaceae (Fraxinus excelsior L.) on glucose homeostasis and associated metabolic markers in non-diabetic overweight/obese subjects.Materials and methodsThis study was performed in 22 participants (50–80 years-old; BMI 31.0 kg/m²). The design was a longitudinal, randomized, crossover, double-blind, placebo-controlled 7-week nutritional intervention. The participants received daily 3 capsules each containing either 333 mg of an extract from Fraxinus excelsior L. seeds (Glucevia^®) or placebo capsules (control) in a random order for 3 weeks with 1 week of washout between treatments. Moreover, they followed a balanced covert energy-restricted diet (−15% energy). All variables were measured at the beginning and at the end of each period.ResultsCompared to baseline, the administration of 1 g of Glucevia^® for 3 weeks resulted in significantly lower incremental glucose area under the curve (−28.2%; p < 0.01), and significantly lower 2 h blood glucose values (−14%; p < 0.01) following an oral glucose tolerance test. No significant changes were found in the control group (−7.9% AUC, −1.6% 2 h blood glucose). Furthermore, significant differences were found between responses in the control and Glucevia^® groups with respect to serum fructosamine and plasma glucagon levels (p < 0.01 and p < 0.05, respectively). Interestingly, administration of Glucevia^® significantly increased the adiponectin:leptin ratio (p < 0.05) and decreased fat mass (p < 0.01) compared to control (p < 0.05).ConclusionThe administration of an extract from Fraxinus excelsior L. seeds/fruits in combination with a moderate hypocaloric diet may be beneficial in metabolic disturbances linked to impaired glucose tolerance, obesity, insulin resistance and inflammatory status, specifically in older adults.     

Altered cellular redox status,sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH

BackgroundWe have previously shown that high fat (HF) feeding during pregnancy primes the development of non-alcoholic steatohepatits (NASH) in the adult offspring. However, the underlying mechanisms are unclear.AimsSince the endogenous molecular clock can regulate hepatic lipid metabolism, we investigated whether exposure to a HF diet during development could alter hepatic clock gene expression and contribute to NASH onset in later life.MethodsFemale mice were fed either a control (C, 7% kcal fat) or HF (45% kcal fat) diet. Offspring were fed either a C or HF diet resulting in four offspring groups: C/C, C/HF, HF/C and HF/HF. NAFLD progression, cellular redox status, sirtuin expression (Sirt1, Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and clock-controlled genes involved in lipid metabolism (Rev-Erbα, Rev-Erbβ, RORα, and Srebp1c) were measured in offspring livers.ResultsOffspring fed a HF diet developed NAFLD. However HF fed offspring of mothers fed a HF diet developed NASH, coupled with significantly reduced NAD⁺/NADH (p < 0.05, HF/HF vs C/C), Sirt1 (p < 0.001, HF/HF vs C/C), Sirt3 (p < 0.01, HF/HF vs C/C), perturbed clock gene expression, and elevated expression of genes involved lipid metabolism, such as Srebp1c (p < 0.05, C/HF and HF/HF vs C/C).ConclusionOur results suggest that exposure to excess dietary fat during early and post-natal life increases the susceptibility to develop NASH in adulthood, involving altered cellular redox status, reduced sirtuin abundance, and desynchronized clock gene expression.     

Expression of orexin receptors 1 (OX1R) and 2 (OX2R) in the porcine pituitary during the oestrous cycle

Orexin A and B, also termed hypocretin 1 and 2, are associated with the stimulation of food intake and arousal. The biological actions of the hormones are mediated via two distinct G protein-coupled receptors, termed orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). OX1R is selective for orexin A and OX2R binds orexin A and orexin B with similar affinity. The present study analyzed mRNA and protein expressions of OX1R and OX2R in adenohypophysis (AP) and neurohypophysis (NP) of cycling pigs. The tissue samples were harvested on days 2–3, 10–12, 14–16, and 17–19 of the oestrous cycle. Using quantitative real-time PCR higher OX1R gene expression was detected in AP on days 2–3 relative to days 10–12, 14–16 and 17–19 (p < 0.05). In NP the OX1R mRNA level was elevated on days 10–12 compared to the remaining stages (p < 0.05). OX2R gene expression in AP was the lowest on days 10–12 (p < 0.05 compared to days 2–3 and 17–19) and the expression peak occurred on days 17–19 (p < 0.05 vs. the all studied stages). In NP the highest (p < 0.05) expression of OX2R mRNA was noted on days 17–19 in relation to the remaining periods. OX1R protein content in AP was greatest on days 10–12 (p < 0.05), whereas in NP it was greatest on days 2–3 and 14–16 (p < 0.05 vs. days 10–12 and 17–19). In both cases the lowest OX1R protein expression was observed during follicular phase (p < 0.05 in relation to three remaining studied stages). OX2R protein in AP was lower (p < 0.05) on days 2–3 and 14–16 compared to days 10–12 and 17–19. In NP the lowest (p < 0.05) expression of this protein was on days 17–19 and the highest on days 10–12 (p < 0.05 compared to days 2–3 and 17–19). In summary, the present findings provide the first evidence that OX1R and OX2R mRNAs and proteins occur in the pituitary of the pig and indicate the dependence of orexin receptor expression on the endocrine reproductive state.     

Blood lead level and its relationship to essential elements in preschool children from Nanning,China

ObjectiveOur study aimed to assess the distribution of blood lead level and its relationship to essential elements in preschool children in an urban area of China.Design and methodsA total of 6741 children aged 0- to 6-year-old were recruited. Levels of lead, zinc, copper, iron, calcium, and magnesium in whole blood samples were determined using atomic absorption spectrometry.ResultsThe mean blood lead level (BLL) and the prevalence of BLL ≥ 10 μg/dl (5.26 ± 4.08 μg/dl and 6.84%, respectively) increased with age gradually, and there was a gender-difference for blood lead, copper, zinc and iron levels. Compared with the group of children who had BLLs < 5 μg/dl, the groups of 5 ≤ BLLs < 10 μg/dl and 10 ≤ BLLs < 15 μg/dl showed higher blood zinc, iron and magnesium levels, and a lower blood calcium level. A positive correlation of lead with zinc, iron and magnesium, and a negative correlation of lead with calcium were found in the group of children with BLL < 5 μg/dl.ConclusionAge- and gender-differences were found when assessing the BLL and intoxication prevalence in preschool children. Metabolic disorder of essential elements was found even with a low level of lead exposure.     

Trace elements in bipolar disorder

IntroductionTrace elements may play an important role in bipolar disorders. The objective of this study is to determine serum copper and zinc, blood lead and cadmium and urine lead, cadmium and thallium concentrations in patients diagnosed with bipolar disorders and to compare these levels with those of a healthy control group.Materials and methodsA total of 25 patients diagnosed with bipolar disorder and 29 healthy subjects participated in this study. Serum copper and zinc concentrations were measured using flame atomic absorption spectrometry; the blood lead and cadmium concentrations were measured by electrothermal atomization atomic absorption spectrometry with Zeeman background correction; urine lead, cadmium and thallium concentrations were measured by inductively coupled plasma mass spectrometry.ResultsMedian blood and urine lead and cadmium levels were significantly higher among the bipolar patients than among the control group: Blood lead (μg/dL): patient median: 3.00 (IQR: 1.40–4.20); control median (μg/dL): 2.20 (IQR: 0.90–3.00) p = 0.040. Blood cadmium (μg/L): patient median: 0.39 (IQR: 0.10–1.15); control median: 0.10 (IQR: 0.10–0.17) p < 0.001. The median of cadmium (μg/L) in patients who smoked (1.20 IQR: 0.44–2.30) was higher than that in non-smokers (0.12 IQR: 0.10–0.34) p < 0.001. There was a statistically significant increase (p = 0.001) in zinc levels among patients in the manic phase (mean 111.28, SD: 33.36 μg/dL) with respect to the control group (mean 86.07, SD: 12.39 μg/dL).ConclusionsThe results suggest that there could be higher levels of some toxic trace elements in the group of patients with bipolar disorder than in the healthy control group.     

Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries

IntroductionThe epidemiology of chronic myeloid leukemia (CML) in low and middle income countries is limited. As a result, we analyzed a contemporary cohort of patients from low and middle income countries treated with Imatinib through The Glivec^® International Patient Assistance Program (GIPAP).MethodsGeneralized estimating equations (GEE) and Kaplan–Meier estimation were utilized to test for regional variations in age at diagnosis and overall survival among 33,985 patients from 94 countries.ResultsPatients participated from Asia (79.2%), Africa (9.4%), Latin America (8.7%) and Southern/Eastern Europe (2.5%). Sixty-one (61.2%) percent were male. Mean age at diagnosis was 38.5 years (9.4% <20 years and only 4.7% ≥65 years). Using GEE, Asians were youngest (38.3 years), followed by Africans (39.5 years), Southern/Eastern Europeans (41.1 years) and Latin Americans (41.3 years; p < 0.0001). Diagnoses were predominately in chronic stage (78.3%). In 2002, 85.2% of patients had a delay in treatment >1 year; decreasing to 15.5% in 2010 (p < 0.0001). The 3-year overall survival probability was 89.4% (95% CI, 88.9–89.9). In multivariate analysis, risk of death increased among patients 65 years or older at diagnosis (p < 0.0001), time from diagnosis to treatment >1-year (p < 0.0001), diagnoses in the accelerated or blast crisis (p < 0.0001), initial dose of Imatinib >400 mg (p < 0.0001) and among Latin Americans and Africans (p < 0.0001).ConclusionThe GIPAP cohort is the largest series of patients with CML described from low and middle income countries. Differences in age at diagnosis and overall survival exist within and between regions. Additional epidemiological studies should be conducted to assess for possible environmental factors associated with the earlier age at onset.     

Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes

Introduction/objectivesThe role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic.The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls.MethodsPRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n = 8) at delivery and compared to controls (n = 5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n = 5) or nicotinamide (NCT) plus STZ (n = 9) or vehicle (n = 9). Placental whole-genome gene expression and PRL western blots were performed at birth.ResultsIn human placentas, PRL (p < 0.05) and BMP-1 (p < 0.01) gene expressions were increased with a higher amount of cleaved PRL (p < 0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT–STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p < 0.01) and Bmp-1 (p < 0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p < 0.05) and NCT–STZ (p < 0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women.ConclusionsAlterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.     

Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study

BackgroundChromium is an essential mineral that contributes to normal glucose function and lipid metabolism. This study evaluated the effect of chromium picolinate (CrPic) supplementation in patients with type 2 diabetes mellitus (T2DM).MethodsA four month controlled, single blind, randomized trial was performed with 71 patients with poorly controlled (hemoglobin A1c [HbA1c] > 7%) T2DM divided into 2 groups: Control (n = 39, using placebo), and supplemented (n = 32, using 600 μg/day CrPic). All patients received nutritional guidance according to the American Diabetes Association (ADA), and kept using prescribed medications. Fasting and postprandial glucose, HbA1c, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and serum ferritin were evaluated.ResultsCrPic supplementation significantly reduced the fasting glucose concentration (−31.0 mg/dL supplemented group; −14.0 mg/dL control group; p < 0.05, post- vs. pre-treatment, in each group) and postprandial glucose concentration (−37.0 mg/dL in the supplemented group; −11.5 mg/dL in the control group; p < 0.05). HbA1c values were also significantly reduced in both groups (p < 0.001, comparing post- vs. pre-treatment groups). Post-treatment HbA1c values in supplemented patients were significantly lower than those of control patients. HbA1c lowering in the supplemented group (−1.90), and in the control group (−1.00), was also significant, comparing pre- and post-treatment values, for each group (p < 0.001 and p < 0.05, respectively). CrPic increased serum chromium concentrations (p < 0.001), when comparing the supplemented group before and after supplementation. No significant difference in lipid profile was observed in the supplemented group; however, total cholesterol, HDL-c and LDL-c were significantly lowered, comparing pre- and post-treatment period, in the control group (p < 0.05).ConclusionsCrPic supplementation had a beneficial effect on glycemic control in patients with poorly controlled T2DM, without affecting the lipid profile. Additional studies are necessary to investigate the effect of long-term CrPic supplementation.