Secondhand Smoke Exposure and Maternal Action to Protect Children from Secondhand Smoke: Pre- and Post-Smokefree Legislation in Hong Kong

Background

Smokefree legislation may protect children from secondhand smoke (SHS) in the home from smoking parent(s). We examined the effect of the 2007 smokefree legislation on children’s exposure to SHS in the home and maternal action to protect children from SHS exposure in Hong Kong.

Methods

Families with a smoking father and a non-smoking mother were recruited from public clinics before (2005–2006, n = 333) and after the legislation (2007–2008, n = 742) which led to a major extension of smokefree places in Hong Kong. Main outcomes included children’s SHS exposure in the home, nicotine level in mothers’ and children’s hair and home environment, mothers’ action to protect children from SHS, and their support to the fathers to quit.

Results

Fewer mothers post-legislation reported children’s SHS exposure in the home (87.2% versus 29.3%, p<0.01), which was consistent with their hair nicotine levels (0.36ng/mg versus 0.04ng/mg, p<0.01). More mothers post-legislation in the last month took their children away from cigarette smoke (6.3% versus 92.2%; p<0.01) and advised fathers to quit over 3 times (8.3% versus 33.8%; p<0.01). No significant change was found in the content of smoking cessation advice and the proportion of mothers who took specific action to support the fathers to quit.

Conclusions

SHS exposure in the home decreased and maternal action to protect children from SHS increased after the 2007 smokefree legislation. Maternal support to fathers to quit showed moderate improvement. Cessation services for smokers and specific interventions for smoking families should be expanded together with smokefree legislation.     

Analyses of toxic metals and essential minerals in the hair of arizona children with autism and associated conditions, and their mothers

The objective of this study ws to assess the levels of 39 toxic metals and essential minerals in hair samples of children with autism spectrum disorders and their mothers compared to controls. Inductively coupled plasma-mass spectrometry was used to analyze the elemental content of the hair of children with autism spectrum disorders (n=51), a subset of their mothers (n=29), neurotypical children (n=40), and a subset of their mothers (n=25). All participants were recruited from Arizona. Iodine levels were 45% lower in the children with autism (p=0.005). Autistic children with pica had a 38% lower level of chromium (p=0.002). Autistic children with low muscle tone had very low levels of potassium (−66%, p=0.01) and high zinc (31%, p=0.01). The mothers of young children with autism had especially low levels of lithium (56% lower, p=0.005), and the young children (ages 3–6 yr) with autism also had low lithium (−30% p=0.04). Low iodine levels are consistent with previous reports of abnormal thyroid function, which likely affected development of speech and cognitive skills. Low lithium in the mothers likely caused low levels of lithium in the young children, which could have affected their neurological and immunological development. Further investigations of iodine, lithium, and other elements are warranted.     

Enhanced proinflammatory response of mononuclear cells to in vitro LPS-challenge in patients with ventricular fibrillation in the setting of acute myocardial infarction

Aims. Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death. A potential role of intrinsic, subclinical inflammatory states in patients suffering from ischemia-related VF has not been investigated yet. The aim of the present study was (i) to examine serum levels of proinflammatory markers in VF survivors and (ii) to evaluate basal and lipopolysaccharide (LPS)-stimulated interleukin-8-mRNA (IL-8-mRNA) levels in patients with and without VF complicating AMI. Methods. Twenty-five patients with a history of VF during AMI and a control group of 25 AMI patients without VF were included. Blood samples were taken remote from AMI with a mean of 590 days. Circulating serum levels of IL-8, IL-6, soluble E-selectin (sE-selectin), tissue factor activity (TFA), tissue inhibitor of matrix-metalloproteinase-1 (TIMP-1) and matrix-metalloproteinase-9 (MMP-9) were measured. Mononuclear cells were isolated by density gradient centrifugation. The cells were stimulated with lipopolysaccharide (LPS) from Escherichia coli (700 ng/mL). IL-8-mRNA levels in mononuclear cells were determined by a colorimetric mRNA quantification assay. Results. Serum levels (median; range) of IL-8 (VF: 2.24 pg/mL; <0.10–19.3 pg/mL versus controls: 0.10 pg/mL; <0.10–7.7 pg/mL; p = 0.014), IL-6 (VF: 0.68 pg/mL; <0.05–2.9 pg/mL versus controls: 0.23 pg/mL; <0.05–1.8 pg/mL; p = 0.042) and TIMP-1 (VF: 229 ng/mL; 144–348 ng/mL versus controls: 186 ng/mL; 126–263 ng/mL; p = 0.014) were significantly higher among patients with VF as compared to controls. Baseline IL-8-mRNA concentrations of blood mononuclear cells were significantly higher among patients with VF (257 amol/mL; 52–2672 amol/mL) as compared to patients without VF (37 amol/mL, 3.2–770 amol/mL; p < 0.01). IL-8-mRNA levels after LPS-challenge were significantly higher among patients with VF (3503 amol/mL; 215–13,573 amol/mL) than in patients without VF (1003 amol/mL; 208–3386 amol/mL; p < 0.01). Conclusions. Circulating IL-8, IL-6, and TIMP-1 concentrations as well as IL-8-mRNA expression in mononuclear cells at baseline and after LPS-challenge are increased among patients with a history of VF in the setting of AMI as compared to patients without VF. These findings indicate an enhanced inflammatory response to a proinflammatory stimulus in VF survivors. The magnitude of this increased acute phase reactants may indicate a novel pathway of arrhythmogenesis in patients with AMI.     

Structure of the extracellular hemoglobin of Biomphalaria glabrata

The hemoglobin of Biomphalaria glabrata was purified to homogeneity by gel filtration column followed by anion exchange chromatography. The dissociation products were analyzed by a 5–15% gradient polyacrylamide gel electrophoresis containing sodium dodecyl sulfate (SDS-PAGE) giving a band of 270 kDa and a band of 180 kDa after reduction with β-mercaptoethanol. The same profile was obtained in a 3.5% agarose gel electrophoresis containing SDS (SDS-AGE) but showed additional bands of higher molecular weight. These bands were proposed to be monomers, dimers and trimers, since they showed a good correlation in a plot of R_f versus log M_r. After partial reduction in a two-dimensional SDS-AGE, the proposed monomers and dimers produced two and four bands, respectively, likely indicating one to four chains crosslinked by disulfide bridges. Digestion with four different proteases yielded several equivalent fragments with molecular weights multiples of its minimum molecular weight (17.7 kDa). The circular dichroism spectrum of the protein showed a characteristic high α-helix content (70%). It was proposed that this hemoglobin is a pentamer with a molecular weight of aproximately 1.8×10³ kDa, assembled by five 360-kDa subunits, each formed by two 180-kDa chains linked in pairs by disulfide bridges and each of these chains, in turn, comprised by ten heme binding domains linked in tandem. These data are compared to the published information for other planorbid extracellular hemoglobins.     

G to C transition at position −173 of MIF gene of the recipient is associated with reduced relapse rates after allogeneic stem cell transplantation

Pro-inflammatory and dendritic cell-activating properties of macrophage migration inhibitory factor (MIF) suggest a potentially important role for MIF in alloantigen-specific immune responses after allogeneic stem cell transplantation (allo-SCT). We tested whether MIF −173 G/C gene polymorphism of donor or patient had impacts on the outcomes after allo-SCT. Four hundred and fifty-four donor–patient pairs were genotyped and mortality, relapse, and development of complications were analyzed. Patient but not donor MIF −173*C allele was associated with improved overall survival (OS) (5 years: 60.8% versus 46.3%, p = 0.042) and disease free survival (DFS) (5 years: 55.4% versus 39.5%; p = 0.014) due to a reduction in relapse (day 2000: 22.8% versus 42.0% p = 0.006) but not due to decreased transplantation-related mortality (TRM) (p = 0.44). Multivariate analysis proved patient −173*C allele as an independent factor for reducing relapse after allo-SCT (p = 0.023). Subgroup analysis showed a clear MIF −173*C allele-related reduction in relapse for those patients who did not receive T cell depleted (TCD) SCT (p = 0.01) in contrast to patients receiving TCD SCT (p = 0.20). In summary, patient MIF −173*C allele may be linked to specific, yet unrevealed functions in tumor biology and graft versus leukemia and lymphoma effects and potentially presents a novel prognostic marker for patient-tailored counseling and therapy in allo-SCT.     

Employment Situation of Parents of Long-Term Childhood Cancer Survivors

Background

Taking care of children diagnosed with cancer affects parents’ professional life. The impact in the long-term however, is not clear. We aimed to compare the employment situation of parents of long-term childhood cancer survivors with control parents of the general population, and to identify clinical and socio-demographic factors associated with parental employment.

Methods

As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of survivors aged 5–15 years, who survived ≥5 years after diagnosis. Information on control parents of the general population came from the Swiss Health Survey (restricted to men and women with ≥1 child aged 5–15 years). Employment was categorized as not employed, part-time, and full-time employed. We used generalized ordered logistic regression to determine associations with clinical and socio-demographic factors. Clinical data was available from the Swiss Childhood Cancer Registry.

Results

We included 394 parent-couples of survivors and 3’341 control parents (1’731 mothers; 1’610 fathers). Mothers of survivors were more often not employed (29% versus 22%; p_trend = 0.007). However, no differences between mothers were found in multivariable analysis. Fathers of survivors were more often employed full-time (93% versus 87%; p_trend = 0.002), which remained significant in multivariable analysis. Among parents of survivors, mothers with tertiary education (OR = 2.40, CI:1.14–5.07) were more likely to be employed. Having a migration background (OR = 3.63, CI: 1.71–7.71) increased the likelihood of being full-time employed in mothers of survivors. Less likely to be employed were mothers of survivors diagnosed with lymphoma (OR = 0.31, CI:0.13–0.73) and >2 children (OR = 0.48, CI:0.30–0.75); and fathers of survivors who had had a relapse (OR = 0.13, CI:0.04–0.36).

Conclusion

Employment situation of parents of long-term survivors reflected the more traditional parenting roles. Specific support for parents with low education, additional children, and whose child had a more severe cancer disease could improve their long-term employment situation.     

A Study of Factors Affecting the Efficiency of Electrofusion of Enucleated Eggs and Cells-Donors of Nuclei

We studied the capacity of rabbit oocytes for electrofusion with morula blastomeres and fetal fibroblasts. The morula blastomeres fused with aging ooplasts more readily than the fetal fibroblasts: 92.9 versus 63.0%, p < 0.001. The fetal fibroblasts fused with young enucleated oocytes more efficiently than with the aging ones: 98.4 versus 63.0%, p < 0.001. Serum starvation of the fetal fibroblasts in DMEM medium for 7–14 days reduced their capacity for fusion with young ooplasts, as compared to that after starvation for 0–4 days: 67.2 versus 98.9%, p < 0.01). The increased time of starvation in an impoverished medium reduced the capacity of fetal fibroblasts with aging ooplasts as compared to the fibroblasts cultivated in the full medium and in the impoverished medium for one or two days: 64.5 versus 37.4%, p < 0.01. Hence, the efficiency of the fusion of the oocytes with nuclear donor cells depends on the age of the recipient oocyte, the origin of nuclear donor cells, and the conditions of cultivation.     

Dietary vitamin A intake below the recommended daily intake during pregnancy and the risk of congenital diaphragmatic hernia in the offspring

BACKGROUND

Vitamin A has been related to the etiology of congenital diaphragmatic hernia (CDH). We performed a case‐control study to investigate whether maternal dietary vitamin A intake is related to CDH in the offspring.

METHODS

Thirty‐one pregnancies diagnosed with CDH and 46 control pregnancies were included during the study. After CDH diagnosis and inclusion of controls by risk set sampling, maternal vitamin A intake was investigated with a food frequency questionnaire. Serum retinol and retinol‐binding protein were determined. Univariable and multivariable logistic regression models were used to calculate risk estimates with adjustment for potential confounders.

RESULTS

We found no significant differences in the overall nutrient and vitamin A intake between case and control mothers. After stratification in body mass index (BMI) categories, case mothers with normal weight showed a lower energy adjusted vitamin A intake (685 vs. 843 μg retinol activity equivalents [RAEs] / day; p = 0.04) and a slightly lower serum retinol (1.58 vs. 1.67 μmol/L; p = 0.08) than control mothers. Vitamin A intake <800 μg retinol activity equivalents (recommended daily intake) in normal weight mothers was associated with a significantly increased CDH risk (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.5–34.4; p = 0.01). Associations were not significantly different in underweight and overweight mothers.

CONCLUSIONS

In normal‐weight mothers, dietary vitamin A intake during pregnancy below the recommended daily intake is significantly associated with an increased risk of a child with CDH. This finding supports the retinoid hypothesis in human CDH, but warrants further investigation in larger study populations. Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.     

Inflammation but not oxidative stress is associated with beta-chemokine levels and prevalence of cardiovascular disease in uraemic patients

Inflammation and oxidative stress (SOX) have been reported in patients with chronic renal failure (CRF), but their influence on β-chemokines levels and cardiovascular disease (CVD) prevalence remains unknown. We assessed β-chemokines, SOX markers and high sensitivity C-reactive protein (hs CRP) as a marker of inflammation in 40 uraemic patients, both with as well as without CVD and 20 controls. Compared with the controls, the patients with CVD showed a significant increase in plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), total peroxide (both p < 0.05), macrophage inflammatory protein 1β (MIP-1β) and hs CRP (both p < 0.01). The values of MCP-1 and hs CRP were more elevated in patients with CVD than without CVD (p < 0.01 and p < 0.05; respectively). Both subgroup of CRF patients were lower of regulated upon activation, normal T cell expressed and secreted (RANTES) levels than in the controls (both p < 0.001). The positive relationships were between hs CRP and presence of CVD, MIP-1β (both p < 0.01) and MCP-1 levels (p < 0.05). SOX markers did not show any significant correlation with β-chemokines, hs CRP and presence of CVD. We documented that increased inflammation but not SOX were associated with significant elevation in plasma β-chemokines levels and CVD prevalence in CRF patients not requiring dialysis.     

The significance of episodic rains for reproductive phenology and productivity of trees in semiarid regions of northwestern Venezuela

The semiarid regions of northwestern Venezuela have extremely low and highly unpredictable precipitation, yet these conditions support species with contrasting phenology and leaf longevity. Episodic rains significantly increased leaf water potential (from –5 to –2.5 MPa) in several species and, in some cases, triggered flowering, leading us to hypothesize that the coexistence of species with contrasting phenology is due to differences in their ability to utilize small rainfall events. Irrigation treatments were used to simulate brief rainfall events, and the response of three species (Erythrina velutina [deciduous], Croton heliaster [semideciduous], and Capparis odoratissima [evergreen]) was monitored over a period of 14 months. To partition the effects of water reaching the canopy versus the soil, irrigation was supplied either in the form of mist to the canopy or by minisprinklers near the base of the trees. Nonirrigated trees were used as controls. Productivity (estimated as aboveground litter production) and water potential were enhanced by soil irrigation in two species. However, in the evergreen species canopy irrigation had a greater effect on water relations and productivity than soil irrigation, as indicated by higher predawn water potential, higher total annual flower (40 g m^–2 year^–1) and fruit (5 g m^–2 year^–1) production, and longer leaf longevity (410 days in control trees versus 520 days in canopy-irrigated trees). Canopy irrigation augmented flower and fruit production in all three species. Our findings suggest that reproductive phenology in these species is driven by episodic rains and that evergreen species may sustain productivity by their ability to make use of water deposited on leaf surfaces.     

Determinants of anti-benzo[a]pyrene diol epoxide–DNA adduct formation in lymphomonocytes of the general population

We evaluated determinants of anti-benzo[a]pyrenediolepoxide-(B[a]PDE)–DNA adduct formation (adduct induced by the ultimate carcinogenic metabolite of B[a]P) in lymphomonocytes of subjects environmentally exposed to low doses of polycyclic aromatic hydrocarbons (PAHs) (B[a]P). Our study population consisted of 585 Caucasian subjects, all municipal workers living in North-East Italy and recruited during their periodic check-ups after informed consent. PAH (B[a]P) exposure was assessed by questionnaire. Anti-B[a]PDE–DNA levels were measured by HPLC fluorescence analysis.We found that cigarette smoking (smokers (22%) versus non-smokers, p < 0.0001), dietary intake of PAH-rich meals (≥52 (38%) versus <52 times/year, p < 0.0001), and outdoor exposure (≥4 (19%) versus <4 h/day; p = 0.0115) significantly influenced adduct levels. Indoor exposure significantly increased the frequency of positive subjects (≥0.5 adducts/10⁸ nucleotides; χ² for linear trend, p = 0.051). In linear multiple regression analysis the major determinants of increased DNA adduct levels (ln values) were smoking (t = 6.362, p < 0.0001) and diet (t = 4.035, p < 0.0001). In this statistical analysis, indoor and outdoor exposure like other factors of PAH exposure had no influence. In non-smokers, the influence of diet (p < 0.0001) and high indoor exposure (p = 0.016) on anti-B[a]PDE–DNA adduct formation became more evident, but not that of outdoor exposure, as was confirmed by linear multiple regression analysis (diet, t = 3.997, p < 0.0001 and high indoor exposure, t = 2.522, p = 0.012).This study indicates that anti-B[a]PDE–DNA adducts can be detected in the general population and are modulated by PAH (B[a]P) exposure not only with smoking – information already known from studies with limited number of subjects – but also with dietary habits and high indoor exposure. In non-smokers, these two factors are the principal determinants of DNA adduct formation. The information provided here seems to be important, since DNA adduct formation in surrogate tissue is an index of genotoxic exposure also in target organs (e.g., lung) and their increase may also be predictive of higher risk for PAH-related cancers.     

Inheritance pattern of familial hypercholesterolemia and markers of cardiovascular risk

Studies in children and adults have resulted in conflicting evidence in the quest for the answer to the hypothesis that offspring from hypercholesterolemic mothers might have an increased cardiovascular risk. Previous studies might have suffered from limitations such as cohort size and clinical sampling bias. We therefore explored this hypothesis in large cohorts of both subjects with familial hypercholesterolemia (FH) and unaffected siblings in a wide age range. In three cohorts (cohort 1: n = 1,988, aged 0–18 years; cohort 2: n = 300, 8–30 years; cohort 3: n = 369, 18–60 years), we measured lipid and lipoproteins as well as carotid intima-media thickness (c-IMT) in offspring from FH mothers versus FH fathers. For LDL cholesterol, triglycerides (TGs), and c-IMT, we performed a pooled analysis. No significant differences could be observed in c-IMT, lipid, or lipoprotein levels from offspring of FH mothers versus FH fathers. Pooled analyses showed no significant differences for either LDL cholesterol [mean difference 0.02 (−0.06,0.11) mmol/l, P = 0.60], TGs [mean difference 0.07 (0.00,0.14) mmol/l, P = 0.08], or c-IMT [mean difference −0.00 (−0.01,0.01) mm, P = 0.86]. Our data do not support the hypothesis that cardiovascular risk markers are different between offspring from FH mothers and FH fathers.     

Immunoreactive urinary prostaglandins A and E in neonates, children, and adults

Urinary prostaglandins were measured by radioimmunoassay in neonates (31–35 weeks gestational age), children (4–15 years) and adults (24–36 years). Neonates showed significantly lower levels of both iPGE and iPGA compared to children (p<0.01) and adults (p<0.01). Children also had significantly lower levels than adults (p<0.01). Since urinary prostaglandins reflect intrarenal levels of prostaglandins, the results support other studies that suggest prostaglandins may play a role in controlling renal blood flow in infants.     

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism as a potential risk factor for cardiovascular disease in hemodialyzed patients

Aim: Polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene (A-2518G) has been associated with functional effects. The aim of the present study was to assess the effect of this polymorphism on end-stage renal disease (ESRD) and cardiovascular disease (CVD) in hemodialyzed patients. Methods: A total of 720 patients with ESRD treated with hemodialysis (450 patients with CVD) and 325 healthy control subjects were genotyped for the MCP-1 -2518 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. Results: There was a significant difference in genotype frequencies between entire group of hemodialyzed patients and controls (p < 0.01). The odds ratio for the risk allele was 1.85, 95% CI 1.49–2.32 (p < 0.01). Hemodialyzed patients were divided into subgroups with CVD (n = 450) and without CVD (n = 270). The G allele carriers occurred with significantly higher frequency in patients with CVD (62% vs. 38% in patients without CVD and 36% in controls). The odds ratio for the risk allele for patients with CVD vs. those without CVD was 2.17, 95% CI 1.71–2.79. There was no statistically significant difference in the distribution of MCP-1 genotypes between ESRD patients without CVD and healthy controls. Conclusion: Our results demonstrate for the first time an association between the polymorphism in the regulatory region of the MCP-1 gene and susceptibility to CVD in hemodialyzed patients.     

Tissue estradiol is selectively elevated in receptor positive breast cancers while tumour estrone is reduced independent of receptor status

Previous studies have suggested elevated estrogen production in tumour-bearing breast quadrants as well as in breast cancers versus benign tissue. Using highly sensitive assays, we determined breast cancer tissue estrogen concentrations together with plasma and benign tissue estrogen concentrations in each quadrant obtained from mastectomy specimens (34 postmenopausal and 13 premenopausal women). We detected similar concentrations of each of the three major estrogens estradiol (E₂), estrone (E₁) and E₁S in tumour-bearing versus non-tumour-bearing quadrants. Considering malignant tumours, intratumour E₁ levels were reduced in cancer tissue obtained from pre- as well as postmenopausal women independent of tumour ER status (average ratio E₁ cancer: benign tissue of 0.2 and 0.3, respectively; p < 0.001 for both groups), suggesting intratumour aromatization to be of minor importance. The most striking finding was a significant (4.1–8.6-fold) increased E₂ concentration in ER positive tumours versus normal tissue (p < 0.05 and <0.001 for pre- and postmenopausal patients, respectively), contrasting low E₂ concentrations in ER− tumours (p < 0.01 and <0.001 comparing E₂ levels between ER+ and ER− tumours in pre- and postmenopausals, respectively). A possible explanation to our finding is increased ligand receptor binding capacity for E₂ in receptor positive tumours but alternative factors influencing intratumour estrogen disposition cannot be excluded.     

Serum trace element levels and the complexity of inter-element relations in patients with Parkinson's disease

Trace elements have been postulated to play a role in Parkinson's disease (PD). In order to elucidate whether changes in the serum levels of trace elements reflect the progression of PD, we assessed serum levels of 12 elements (Na, K, Fe, Al, Cu, Zn, Ca, Mg, Mn, Si, P and S) in early PD, severe PD and normal subjects, using inductively coupled plasma atomic emission spectrometry. The concentrations in μmol/ml, the relative mole percentage distribution and inter-element relations were computed. Statistical analysis of these data showed a definite pattern of variation among certain elements in early and severe PD compared to controls. In both early and severe PD serum, Al and S concentrations were significantly decreased (p<0.05) compared to the controls. Fe (p<0.01) and Zn (p<0.05) concentrations were significantly lower in severe PD, while K, Mg, Cu (p<0.01) and P (p<0.05) concentrations were higher in early and severe PD compared to the controls. The data revealed an imbalance in the inter-element relations in both early and severe PD serum compared to controls, as shown by the direct and inverse correlations. These results suggest a disturbance in the element homeostasis during the progression of PD.     

Growth and age structure of the swan mussel Anodonta cygnea (L.) at different depths in lake Mattsee (Salzburg, Austria)

Unionid clams were collected at 1–2 m, 3–4 m and 6–7 m depth in lake Mattsee, a moderately mesotrophic lake, to investigate the effect of depth on clam growth and age structure. No significant differences in age structure of Anodonta cygnea were found (p=0.65). Three and ten years old clams were present at all depths, but in different percentages. Whereas at 1–2 m 13.3% of the collected clams were <4 years old, this percentage was 4.4% at 6–7 m and 7.1% at 3–4 m. A greater percentage (6.7%) of older mussels (9, 10 years) were collected at 6–7 m than at 1–2 m (2.2%). Growth declined with depth. Total length at a given age of clams at 1–2 m and 3–4 m did not differ (p=0.54), whereas differences were significant between clams at 1–2 m and 6–7 m (p<0.05) as well as between 3–4 m and 6–7 m (p<0.05). The Growth constant k was highest at 1–2 m depth.     

Dendritic cells are dysfunctional in patients with operable breast cancer

Background: Dendritic cells (DCs) play a crucial role in presenting antigens to T lymphocytes and inducing cytotoxic T cells. DCs have been studied in patients with breast cancer to define the factors leading to failure of an effective systemic and locoregional anticancer host response. Methods: Purified DCs were obtained from peripheral blood (PB) and lymph nodes (LNs) of women with operable breast cancer, using immunomagnetic bead selection. The stimulatory capacity of DCs in the allogeneic mixed leukocyte reaction (MLR) and autologous T cell proliferation test (purified protein derivative (PPD) as stimulator), the expression of surface markers on DCs and the production of cytokines in vitro by DCs from patients with operable breast cancer and from healthy donors (controls) were studied. Results: 70–75% purified DCs were isolated from PB and LNs. PBDCs and LNDCs from patients with operable breast cancer demonstrated a reduced capacity to stimulate in an MLR, compared with PBDCs from normal donors (p<0.01). Autologous T cell proliferation in patients had a decreased ability to respond to PPD, when compared with controls (p<0.01). However, T cells from patients responded as well as control T lymphocytes in the presence of control DCs. PBDCs and LNDCs from patients expressed low levels of HLA-DR and CD86, and induced decreased interleukin-12 (IL-12) secretion in vitro, compared with DCs from normal donors (p<0.01). Conclusion: These data suggest a defective DC function in patients with operable breast cancer. Switched-off DCs in patients with early breast cancer and decreased IL-12 production may be important factors for progressive tumour growth.     

Chronic maternal stress affects growth, behaviour and hypothalamo-pituitary-adrenal function in juvenile offspring

Maternal stress during pregnancy, particularly that combined with low socioeconomic status (SES), has been linked to an increased risk for impaired behavioural and emotional development and affective disorders in children. In animal models, acute periods of prenatal stress have profound effects on hypothalamo-pituitary-adrenal (HPA) function and behaviour. However, few studies have determined the impact of chronic exposure to stress in animal models. The objective of this study was to determine the effects of chronic maternal stress (CMS) during the 2nd half of pregnancy and nursing on growth, locomotor behaviour and HPA axis function in juvenile guinea pig offspring. Pregnant guinea pigs were exposed to a random combination of variable stressors every other day over the 2nd half of gestation and from postnatal day (pnd) 1 until weaning (pnd25). CMS mothers displayed increased basal salivary cortisol levels in the later stages of pregnancy compared to control mothers (p < 0.05). The male offspring of CMS mothers had a lower bodyweight, which was maintained to weaning (p < 0.01). In open-field testing, CMS male offspring showed a decrease in activity compared to controls (p < 0.05). There was no effect of CMS on bodyweight or activity in female offspring. In contrast, both male and female offspring born to CMS mothers displayed increased (p < 0.05) basal salivary cortisol at pnd25, but a blunted adrenocortical response to exposure to the novel open-field enclosure. In conclusion, CMS leads to modification of growth trajectory, locomotor activity and adrenocortical responses to stress in juvenile offspring. Further, males appear considerably more vulnerable to these effects than females.