Prevalence of childhood hypertension and hypertension phenotypes by weight status and waist circumference: the Healthy Growth Study.

PURPOSE: The aim of the present study was to report for the first time the prevalence of hypertension and its phenotypes in obese children and in children with central obesity in a large sample of Greek children. METHODS: A regionally representative sample of 2263 schoolchildren (50.3% boys) (9-13 years) having full data on blood pressure assessment, physical examination, anthropometric, and physical activity participated in a cross-sectional study in Greece. RESULTS: Prevalence of stage 1 and 2 hypertension, of isolated systolic hypertension (ISH) and of combined systolic or diastolic hypertension, was significantly higher for obese children and children on the 3rd tertile of waist circumference in the total sample, as well as in each gender separately. ISH was the most prevalent phenotype reaching 24.3% in obese children and 17.5% in children on the highest tertile of waist circumference. Obese children and children on the highest tertile of waist circumference had 6.31 times and 3.94 times, respectively, higher likelihood to have abnormal systolic or diastolic blood pressure (SBP or DBP) than their normal-weight counterparts. CONCLUSIONS: Prevalence of hypertension and especially ISH in obese children and in children with central obesity in Greece are among the highest reported in Europe. Future public health initiatives should aim to prevent or tackle several underlying factors related to childhood hypertension, focusing primarily on children with excess body weight.

Maternal fetal loss history and increased acute leukemia subtype risk in subsequent offspring: a systematic review and meta-analysis.

PURPOSE: History of fetal loss including miscarriage and stillbirth has been inconsistently associated with childhood (0-14 years) leukemia in subsequent offspring. A quantitative synthesis of the inconclusive literature by leukemia subtype was therefore conducted. METHODS: Eligible studies (N = 32) were identified through the screening of over 3500 publications. Random-effects meta-analyses were conducted on the association of miscarriage/stillbirth history with overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150 cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia. Sensitivity and subgroup analyses by age and ALL subtype, as well as meta-regression were undertaken. RESULTS: Fetal loss history was associated with increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04-1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in sensitivity analyses. Notably, stillbirth history was significantly linked to ALL risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL and AML with previous miscarriage reached marginal significance. The association of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60). CONCLUSIONS: In this meta-analysis involving >50,000 children, we found noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia type; namely, of stillbirth with ALL and miscarriage history with infant ALL. Elucidation of plausible underlying mechanisms may provide insight into leukemia pathogenesis and indicate monitoring interventions prior to and during pregnancy.

A HEALth Promotion and STRESS Management Program (HEAL-STRESS study) for prehypertensive and hypertensive patients: a quasi-experimental study in Greece.

Current hypertension guidelines advocate strategies encouraging healthy lifestyle behaviours. So far, there is a paucity of studies for the efficacy of such multifaceted programmes. The aim of this study is to investigate the efficacy of an 8-week health-promotion programme for lowering blood pressure (BP) in prehypertensive and hypertensive patients in the community. This was a quasi-experimental study using wait-list controls of 548 patients. The intervention group was administered with an 8-week health-promotion intervention. Measurements included home BP, smoking, body mass index (BMI), perceived stress, depression, anxiety and Health Locus of Control. After adjusting for confounders, the intervention group had a significant reduction in both systolic BP (SBP; mean -2.62 mm Hg, 95% confidence interval (CI): -1.29 to -3.96) and diastolic BP (DBP; mean -1.0, 95% CI: -0.93 to -1.9) compared with controls. In all, 14.9% of patients in the intervention group had >10 mm Hg reduction in SBP vs 4.4% in the control group (P<0.001, numbers needed to treat (NNT)=10). With regards to DBP, 21.7% of patients in the intervention group had >5 mm Hg reduction vs 12.5% in the control group (P=0.01, NNT=11). In terms of effect size, moderate-to-large improvements of BMI, perceived stress, anxiety, depression, external and chance Health Locus of Control were recorded. Changes in SBP and DBP were attributed to BMI and depressive symptom reductions, respectively. Comprehensive non-pharmaceutical programmes for BP management are strongly encouraged. Their long-term benefits on cardiovascular morbidity and mortality remain to be established by future research.

The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene.

BACKGROUND: Nonclassical congenital adrenal hyperplasia (NC-CAH) is caused by mutations of the CYP21A2 gene. The clinical manifestations and hormonal derangements of NC-CAH are quite variable. OBJECTIVES: (i) To define the phenotype and its relation to genotype according to gender and age and (ii) to evaluate the validity of currently applied hormonal criteria for establishing the diagnosis of NC-CAH. PATIENTS AND METHODS: The clinical, hormonal and molecular data of 280 subjects (235 female) with NC-CAH and a median age of 17·6 years were analysed. CYP21A2 genotyping was performed in all subjects. RESULTS: The majority of females aged less than 8 years presented with premature pubarche (88·3%), while those older than 8 presented with a polycystic ovary-like phenotype (63·2%). A total of 7·7% of the females and 51·1% of the males were asymptomatic at the time of diagnosis. In the total group, 50·4% of the subjects were compound heterozygotes for one classical (C) and one nonclassical (NC) mutation, while 46% of the alleles studied carried the p.V281L mutation. Basal 17OHP values were below 6 nm (2 ng/ml) in 2·1% of the subjects with NC-CAH, but none had peak 17OHP values post-ACTH lower than 30 nm (10 ng/ml). CONCLUSIONS: NC-CAH has a variable phenotype depending on the age, gender and the presence of a classical mutation. A peak cut-off value of 17OHP post-ACTH lower than 30 nm excludes the diagnosis of NC-CAH, whereas basal 17OHP <6 nm may represent a false-negative result. A significant number of patients harboured a classical mutation, a finding which requires genotyping of the partner for genetic counselling.

Revised Healthy Lifestyle-Diet Index and associations with obesity and iron deficiency in schoolchildren: The Healthy Growth Study.

BACKGROUND: The Healthy Lifestyle-Diet Index (HLD-index), previously developed to assess the degree of adherence to dietary and lifestyle guidelines for primary schoolchildren, was revised according to updated recommendations. Τhe association of the revised HLD-index (R-HLD-index) with obesity and iron deficiency (ID) was also examined. METHODS: A representative sample of 2660 primary schoolchildren from Greece (9-13 years old) participating in the 'Healthy Growth Study' was examined. Twelve components related to dietary and lifestyle patterns were used to develop the R-HLD-index. Scores from 0 up to 4 were assigned to each one of these components, giving a total score ranging from 0 to 48. The associations between the R-HLD-index, obesity and ID were examined via logistic regression analysis. RESULTS: The total score of the R-HLD-index calculated for each one of the study participants was found to range between 2 and 32 units, with higher scores being indicative of a healthier lifestyle and better diet quality. After adjusting for potential confounders, logistic regression analysis showed that an increase in the R-HLD-index score by one unit was associated with 6% lower odds for obesity. However, no significant association was observed between the R-HLD-index score and ID. CONCLUSIONS: The R-HLD-index may be a useful tool for public health policy makers and healthcare professionals when assessing diet quality and lifestyle patterns of primary schoolchildren. Identification of children with lower scores in the R-HLD-index and its individual components could guide tailored made interventions targeting specific children and behaviors.

Identification of lifestyle patterns, including sleep deprivation, associated with insulin resistance in children: the Healthy Growth Study.

BACKGROUND/OBJECTIVES: Although diet, physical activity (PA), sedentary behavior and sleep deprivation are factors that have been individually associated with insulin resistance (IR) in childhood, the combined effect of these lifestyle behaviors has not been examined yet. The current study aimed to examine the association of lifestyle patterns with IR, combining all these indices, in children. SUBJECTS/METHODS: Socio-economic, demographic, anthropometric (body weight, height and waist circumference), biochemical (plasma glucose and serum insulin), clinical (pubertal stage) and lifestyle (dietary intake, PA level and sleeping habits) data were collected from a representative sample of 2026 children (50.1% girls) aged 9-13 years in Greece. Homeostasis model assessment (HOMA-IR) was calculated, and principal component analysis was used to identify lifestyle patterns, combining all these lifestyle indices. RESULTS: In multivariable regression analyses, the lifestyle pattern characterized by more screen time, shorter sleep duration and higher consumption of sugared beverages was positively associated with HOMA-IR (ß=0.043; P=0.040), whereas the pattern characterized by more time spent on moderate-to-vigorous PA (MVPA) and more frequent eating occasions was inversely associated with HOMA-IR (ß=-0.061; P=0.003). In logistic regression analyses, children with 72.2 min/day of MVPA and 5.05 eating occasions/day and children with 141.8 min/day of MVPA and 5.22 eating occasions/day were less likely of being insulin resistant based on HOMA-IR, compared with children with 20.0 min/day of MVPA and 4.09 eating occasions/day. CONCLUSIONS: A lifestyle pattern of >72 min of MVPA and 5 eating occasions/day was associated with reduced likelihood of IR in children.

Stress management can facilitate weight loss in Greek overweight and obese women: a pilot study.

BACKGROUND: Stress and negative emotions have been shown to be critical factors in inducing overeating as a form of maladaptive coping in obese people. METHODS: The present study aimed to evaluate the efficacy of an 8-week stress management programme that includes progressive muscle relaxation (PMR) and diaphragmatic breathing on weight loss and eating behaviour in a sample of overweight and obese women who started a weight-loss programme. A total of 34 women with a mean (SD) body mass index of 38.17 (7.19) kg m(-) ² and mean (SD) age 47.35 (11.64) years were recruited from the outpatients Obesity Clinic of a public hospital in Athens. Participants were randomly assigned into a Stress Management (SM) and a control group. Anthropometric measurements were taken before and after the intervention, and the participants completed the following questionnaires: Dutch Eating Behaviour Questionnaire (DEBQ), Eating Attitudes Test (Eat-26), Health Locus of Control (HLC) and Perceived Stress Scale (PSS) before and after the intervention. RESULTS: The findings indicated a significant improvement in weight loss in the SM group [4.44 (0.83) kg] after intervention compared to the control group [1.38 (0.78) kg] (P < 0.05). A higher restrained eating behaviour was observed in the SM group after intervention compared to the control group, although there was no significant difference in perceived stress levels. CONCLUSIONS: The intervention group showed greater weight reduction, possibly because of the stress management programme, and a greater dietary restraint was demonstrated by them compared to the control group. It is likely that stress management could facilitate weight loss in obese women; however, more studies are needed to confirm this hypothesis.

The double burden of obesity and iron deficiency on children and adolescents in Greece: the Healthy Growth Study.

BACKGROUND: Some small cohort studies have noted that obesity co-exists with lower serum iron levels. The present study aimed to examine the association between being overweight and iron deficiency (ID) in a large cohort of Greek children and adolescents. METHODS: A representative sample of 2492 primary schoolchildren aged 9-13 years old was examined. Anthropometric, biochemical, clinical, dietary intake and physical activity data were collected. RESULTS: The prevalence of ID and iron deficiency anaemia (IDA) was higher in obese boys and girls compared to their normal-weight peers (P < 0.05). Serum ferritin was higher in obese compared to normal-weight boys (P = 0.024) and higher in obese compared to normal-weight and overweight girls (P = 0.001). By contrast, a negative association was found between transferrin saturation and adiposity in both boys and girls (P = 0.001 and P = 0.005). Furthermore, obese girls had significantly higher fibre intake than normal-weight girls (P = 0.048) and also overweight and obese boys and girls recorded significantly fewer pedometer steps than their normal-weight peers (P < 0.001). Finally, obesity more than doubled the likelihood of ID in both boys (odds ratio = 2.83; 95% confidence inteval = 1.65-4.85) and girls (odds ratio = 2.03; 95% confidence interval = 1.08-3.81) after controlling for certain lifestyle and clinical indices as potential confounders. CONCLUSIONS: The present study shows that obese children and adolescents were at greater risk for ID and IDA than their normal-weight peers. Low grade inflammation induced by excessive adiposity may be a reason for the observed low iron levels. This is also strengthened by the elevated serum ferritin levels, comprising an acute phase protein that is plausibly increased in inflammation.

Hypovitaminosis D associations with adverse metabolic parameters are accentuated in patients with Type 2 diabetes mellitus: a body mass index-independent role of adiponectin?

BACKGROUND: Hypovitaminosis D has been associated with an increased prevalence of Type 2 diabetes mellitus (DMT2) and metabolic syndrome manifestations. The purpose of this study was to examine the association between 25-hydroxy-vitamin D (25-OH-VitD) levels and indices of insulin resistance (IR), including adipocytokines, in a Saudi population with or without DMT2. SUBJECTS AND METHODS: A total of 266 subjects (153 DMT2 and 113 healthy controls) aged 26-80 yr were randomly selected from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort). Subjects were assessed clinically, anthropometry was performed, morning blood chemistries, including fasting glucose (FG), triglycerides, total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol were obtained. Homeostasis model assessment of IR (HOMA-IR) was calculated, and serum 25-OH-VitD, leptin, adiponectin, resistin, insulin, high sensitivity CRP (hsCRP), and tumor necrosis factor α concentrations were measured using specific assays. RESULTS: In DMT2 subjects, negative correlations between 25-OH-vitD and body mass index (BMI), FG, insulin, HOMA-IR, cholesterol, LDL-C, and hsCRP were observed, while a positive correlation between 25-OH-VitD and adiponectin was detected. The later remained significant after controlling for BMI. Interestingly, only weak and nonsignificant associations between 25-OH-VitD and metabolic parameters were observed in the control group, whereas, when the entire population was examined, negative correlations were evident primarily between 25-OH-VitD and FG, HOMA-IR, total cholesterol, LDL-C. These associations remained significant after controlling for BMI. CONCLUSIONS: These results suggest that hypovitaminosis D associations with metabolic disturbances are accentuated in DMT2. The BMIindependent positive correlation between 25-OH-VitD and adiponectin suggests a potential role for this adipocytokine as a link between 25-OH-VitD and IR in patients with DMT2.

The effect of CRH and its inhibitor, antalarmin, on in vitro growth of preantral mouse follicles, early embryo development, and steroidogenesis.

In vitro growth systems of preantral follicles allow studying the effect of various endocrine, paracrine, and autocrine factors on follicular growth and oocyte maturation. CRH is a 41-amino-acid neuropeptide responsible for endocrine, autonomic, immunological, and behavioral responses of mammals to stress and has two receptors, CRH receptor type 1 (CRH-R1) and CRH-R2. Antalarmin, a CRH-R1 antagonist, has been used to elucidate the role of CRH in stress, inflammation, and reproduction. The present study describes in vitro growth of mouse preantral follicles, early embryo development, and steroidogenesis in the presence of CRH and its antagonist antalarmin. We cultured 732 follicles in control media, 1306 in CRH 10(-7) mol/liter, and 1202 in CRH 10(-7) plus antalarmin 10(-6) mol/liter. The culture medium was assayed on alternate days for 17ß-estradiol, progesterone, and ß-human chorionic gonadotropin. Total RNA was extracted from preantral follicles as well as early preimplantation embryos and was assessed by real-time RT-PCR for the expression of CRH-R1 and CRH-R2 mRNAs. Hormone analysis showed that the CRH group had lower levels of 17ß-estradiol, progesterone, and ß-human chorionic gonadotropin as the culture progressed, in comparison with the other two groups. RT-PCR demonstrated the presence of CRH-R1 and CRH-R2 in all stages of preantral follicle culture. Morula/blastocyst-stage embryos expressed only CRH-R1. In conclusion, CRH has an inhibitory effect on in vitro fertilized oocytes, resulting from cultured preantral follicles at all stages of preimplantation embryo development. Furthermore, the presence of CRH in the culture medium inhibits steroidogenesis by preantral mouse follicles cultured in vitro.

Neck circumference: a useful screening tool of cardiovascular risk in children.

OBJECTIVE: Early identification of cardiovascular risk factors consists an essential target for public health. The current study aims to examine the association between neck circumference and several cardiovascular risk factors and to compare it with well-established anthropometric indices. METHODS: Demographic, anthropometric (body weight and height, waist, hip and neck circumference [WC, HC and NC, respectively]), biochemical (total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, triglycerides [TG], fasting plasma glucose and serum insulin), clinical (pubertal stage, systolic and diastolic blood pressure [SBP and DBP, respectively]) and lifestyle (dietary intake, physical activity level) data were collected from 324 children (51.5% boys; 48.5% girls) aged 9-13 in Greece. Body mass index z-score (BMI z-score), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and fasting glucose to insulin ratio (FGIR) were calculated. RESULTS: All indices (BMI z-score, NC, WC, HC, WHR and WHtR) were correlated with SBP, HDL and insulin-related indices (insulin, HOMA-IR, QUICKI and FGIR) and all indices except WHR with TG. LDL was correlated with BMI z-score, WC, WHR and WHtR, whereas DBP was correlated with BMI z-score, WC, HC and WHtR. In multivariate analysis, HDL, TG, SBP, insulin, HOMA-IR, QUICKI and FGIR were associated with all anthropometric indices; DBP with WC, HC, NC and WHtR; LDL with BMI z-score, WC, HC and WHtR. CONCLUSIONS: NC is associated with most cardiovascular disease risk factors. These associations are comparable with those observed for BMI z-score, WC, HC, WHR and WHtR. NC could be a simple, alternative screening tool of cardiovascular risk in children.

Biological agents in paediatric inflammatory bowel disease: a clinical observation study from Greece.

OBJECTIVES: Biological agents have contributed significantly in controlling inflammatory bowel disease during the last 15 years. This study aimed at recording and evaluating paediatric data regarding the efficacy and safety of infliximab and adalimumab during the last decade. PATIENTS AND METHODS: A total of 31 patients (43% males) with a mean age of 13.5 +/- 3.0 years were included and the majority (74%) had Crohn's disease (CD). Failure of previous treatment and steroid dependency were the main reasons for initiating anti-TNF-alpha therapy. Mean age at the first infusion was 11.0 +/- 2.8 years, while the mean disease duration at the introduction of infliximab was 2.6 +/- 2.7 years. The number of infusions per patient ranged from 1-25 (median 7, IQR: 4-13). RESULTS: Initial response was achieved in 82.8% of patients. After one year of treatment the estimated rate of remission was 53%. The rate of surgery-free disease at 12, 36 and 60 months, after the first dose of infliximab, was 89.6%, 89.6% and 74.7% respectively. The incidence of serious anaphylaxis was 4/268 infusions (1.5%) or 4/31 patients (12.3%). At three months after the first infusion only 2 children were on steroids. Adalimumab was administered to 5 patients for a mean duration of 7.4 months, as a second option after infliximab failure or infusion reaction. Two out of five patients failed to achieve remission with adalimumab and these two patients were also infliximab failures. CONCLUSION: Biological agents are valuable and safe options for children with refractory IBD. The results, so far, have been satisfactory, although, long-term outcomes remain yet to be determined.

The immediate and long-term impact of physical and/or emotional stress from motor vehicle accidents on circulating stress hormones and adipo-cytokines in children and adolescents.

Motor vehicle accidents (MVA) represent a complex physical and emotional stressor. Consequent short- and/or long-term alterations on the circulating concentrations of stress hormones and adipo-cytokines may have potential health implications. Fifty-nine children and adolescents, aged 7-18 years, were evaluated within 24 h after hospitalization for a MVA, and 1 and 6 months later; 40 children served as controls. We examined longitudinally the effects of physical injury-associated (PI) group vs. emotional-only stress (ES) group on circulating cortisol, catecholamine, interleukin (IL)-6, leptin and adiponectin concentrations. Within 24 h after the accident, serum cortisol concentration was greater than the controls in the PI but not the ES group (p = 0.02), while serum IL-6 concentration was greater in both trauma groups than in the controls (p = 0.004 for PI, p = 0.04 for ES). Adiponectin concentration was lower in the PI than the ES (p = 0.031) and the control (p = 0.019) groups and this was mainly attributed to females. The catecholamine and leptin concentrations were similar in the three groups. At the 1 and 6 month evaluations, cortisol and IL-6 concentrations in both trauma groups became normal. Adiponectin concentration in females, however, remained low 1 and 6 months after the accident (p = 0.03 for month six). In conclusion, circulating IL-6 concentration was influenced equally by the physical and emotional stress shortly after the trauma. Physical but not emotional-only stress lowered the circulating adiponectin concentrations in females and this effect persisted for at least 6 months.

Selective effects of CPAP on sleep apnoea-associated manifestations.

BACKGROUND: Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy. MATERIALS AND METHODS: Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese controls were monitored in the sleep laboratory for four consecutive nights. Objective measures of daytime sleepiness and performance, serial 24 h plasma measures of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), TNF receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using the same protocol after 3 months of CPAP. RESULTS: At baseline, IL-6, TNF-r1, and insulin resistance were highest in OSA patients, intermediate in obese controls, and lowest in non-obese controls (P < 0.05). Visceral fat was significantly greater in sleep apnoeics than obese controls and predicted insulin resistance and IL-6 levels, whereas OSA predicted TNF-r1 levels (P < 0.05). CPAP decreased daytime sleepiness and blood pressure (P < 0.05), but did not affect fasting glucose or insulin or around the clock adiponectin, IL-6, TNF-alpha, or TNF-r1 levels. CONCLUSIONS: In obese sleep apnoeics, visceral fat is strongly associated with insulin resistance and inflammation. CPAP decreases sleepiness and moderates hypertension but does not affect visceral adiposity, insulin resistance, hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk factors for cardiovascular disease and diabetes.

Changes in free radical generation and antioxidant capacity during ultramarathon foot race.

BACKGROUND: Exhaustive exercise has been implicated in the generation of reactive oxygen species, resulting in oxidative stress. We studied the effect of a long-distance, endurance exercise on oxidative stress parameters in athletes who participated in the ultramarathon race Spartathlon (246 km). MATERIALS AND METHODS: This study included 18 runners (16 men and 2 women) aged 42.8 +/- 1.4 years. Blood samples were obtained 24 h before (prerace), at the end (postrace) and 48 h after the end of the race (48 h postrace). We measured oxidative stress indices, including red cell glutathione, malonyldialdehyde and 8-iso-prostaglandin F(2a), as well as the total antioxidant capacity. RESULTS: 8-Iso-prostaglandin F(2a) level increased significantly at the end of the race, compared to prerace levels (up to 914.7 +/- 61.4 pg mL(-1) from 197.6 +/- 8.4 pg mL(-1)), and remained 2.5-fold increased over the baseline 48 h after the race (532.0 +/- 54.2 pg mL(-1), P < 0.000). The total antioxidant capacity of the athletes increased from a baseline of 289.6 +/- 9.0 micromol L(-1) to 358.7 +/- 11.0 micromol L(-1) immediately after the race and remained elevated 48 h later (350.6 +/- 7.6 micromol L(-1)) (P < 0.001). CONCLUSIONS: Prolonged exercise induces a marked response of oxidative stress biomarkers, which in part is compensated by serum ability to scavenge free radicals. Whether these changes have long-term negative effects in the organism needs further investigation.

Melanoma risk in association with serum leptin levels and lifestyle parameters: a case-control study.

BACKGROUND: Solar radiation has been identified as a principal factor for the causation of melanoma, whereas changing lifestyle patterns associated with obesity and diabetes might also contribute to the increasing incidence of the malignancy. No study has investigated the role of leptin, a hormone whose levels increase in obesity and which has also been related to cancer. PATIENTS AND METHODS: Fifty-five patients with incident melanomas and 165 age- and gender-matched healthy controls were interviewed on the basis of a questionnaire that covers phenotypic features, sociodemographic and medical history variables, lifestyle habits and frequency of consumption of major food groups. Anthropometrical measures were also recorded and blood samples were obtained for determination of serum leptin levels. Adjusted odds ratios (ORs) for melanoma risk were derived through multiple logistic regression analyses. RESULTS: An excess melanoma risk was observed for sun sensitive individuals and those with high circulating levels of leptin (OR: 1.56, 95% confidence interval 1.07-2.28, P = 0.02), after controlling for obesity indices, diabetes mellitus and education. Increased physical exercise, lower alcohol consumption and plant food consumption seem to play a protective role against melanoma development. CONCLUSIONS: Melanoma risk was found to be positively associated with serum leptin levels and inversely with healthy lifestyle factors. The findings need to be confirmed in prospective studies.

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation.

Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropin-releasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer.

The role of corticotropin-releasing hormone in blastocyst implantation and early fetal immunotolerance.

During blastocyst implantation, the maternal endometrial response to the invading semi-allograft has characteristics of an acute, aseptic inflammatory response. However, once implanted, the embryo suppresses this response and prevents rejection. Simultaneously, the mother's immune system prevents a graft VS. host reaction deriving from the fetal immune system. We have shown that embryonic trophoblast and maternal decidua cells, i.e., cells located in the interface between the fetal placenta and the maternal endometrium, produce corticotropin-releasing hormone (CRH) and express Fas ligand. CRH may play a crucial role in the implantation and the anti-rejection process that protects the fetus from the maternal immune system, primarily by killing activated T cells through the Fas-FasL interaction. In experimental animals, type 1 CRH receptor (CRH-R1) blockade by antalarmin, a specific type 1 CRH receptor antagonist, decreased implantation sites by approximately 70%. CRH is also involved in controlled trophoblast invasion, by downregulating the synthesis of the carcinoembryonic antigen-related cell adhesion molecule 1 by extravillous trophoblast cells. IN VITRO findings showed that CRH-R1 blockade by antalarmin increased trophoblast invasion by approximately 60%. Defective uterine CRH/CRH-R1 system during early pregnancy may be implicated in the pathophysiology of recurrent miscarriage, placenta accreta, and preeclampsia.

Circulating adiponectin levels in relation to melanoma: a case-control study.

AIM: Melanoma, a malignancy with steadily increasing prevalence, has been associated not only with sun exposure but also with phenotypic characteristics including obesity. Adiponectin, an adipocyte secreted endogenous insulin sensitizer, has been found to play a protective role in several obesity related cancers but has not yet been studied in relation to melanoma. We investigated the association of circulating adiponectin levels with melanoma in Greece, a country with rather low incidence of the disease and high annual sunshine levels. METHODS: In the context of a case-control study, we studied over a 22-month period 55 patients with incident, histologically confirmed melanoma cases and 165 healthy controls matched for gender and age. RESULTS: After controlling for the possible confounding effect of education, body mass index and waist-to-hip ratio in multiple logistic regression analyses, sun sensitive skin type was significantly and positively associated with melanoma risk (OR: 2.48, 95% Confidence Interval: 1.22-5.10, p: 0.01). On the contrary, there was a sizeable, though non-significant, inverse association of serum adiponectin levels with the disease (OR: 0.75, 95% Confidence Interval: 0.52-1.10, p: 0.14). CONCLUSION: A protective role of adiponectin in the development of melanoma cannot be excluded given the presented empirical evidence (25% reduction per one SD of adiponectin) and the direct anti-neoplastic features of the hormone. The results are intriguing enough to point to the need for further investigation.