Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention.

Endocrine Disrupting Chemicals (EDCs) are a global problem for environmental and human health. They are defined as "an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action". It is estimated that there are about 1000 chemicals with endocrine-acting properties. EDCs comprise pesticides, fungicides, industrial chemicals, plasticizers, nonylphenols, metals, pharmaceutical agents and phytoestrogens. Human exposure to EDCs mainly occurs by ingestion and to some extent by inhalation and dermal uptake. Most EDCs are lipophilic and bioaccumulate in the adipose tissue, thus they have a very long half-life in the body. It is difficult to assess the full impact of human exposure to EDCs because adverse effects develop latently and manifest at later ages, and in some people do not present. Timing of exposure is of importance. Developing fetus and neonates are the most vulnerable to endocrine disruption. EDCs may interfere with synthesis, action and metabolism of sex steroid hormones that in turn cause developmental and fertility problems, infertility and hormone-sensitive cancers in women and men. Some EDCs exert obesogenic effects that result in disturbance in energy homeostasis. Interference with hypothalamo-pituitary-thyroid and adrenal axes has also been reported. In this review, potential EDCs, their effects and mechanisms of action, epidemiological studies to analyze their effects on human health, bio-detection and chemical identification methods, difficulties in extrapolating experimental findings and studying endocrine disruptors in humans and recommendations for endocrinologists, individuals and policy makers will be discussed in view of the relevant literature.

Are increased carotid artery pulsatility and resistance indexes early signs of vascular abnormalities in young obese males?

PURPOSE: To provide insight into the factors by which obesity in itself may directly lead to early arterial damage, we aimed to determine early sonographic markers of obesity-related vascular dysfunction in young obese males. METHODS: Thirty-five young obese males and 23 age-matched healthy male volunteers were recruited into the study. Common carotid artery pulsatility index and resistance index were calculated from blood flow velocities curves obtained by pulsed Doppler ultrasonography. RESULTS: The mean pulsatility index, resistance index, body mass index, waist circumference, systolic and diastolic blood pressure, homeostasis model assessment for insulin resistance, plasma fasting glucose, insulin, C-peptide, triglycerides, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein were statistically higher in obese subjects than in healthy controls. CONCLUSIONS: Our results suggest that depressed vessel compliance and increased vascular resistance are features of young, obese, normotensive subjects independently of and in addition to cardiovascular risk factors. As changes in arterial wall properties may be incipient in young obese subjects, future studies will be required to demonstrate whether early intervention such as diet and exercise in this population can improve vascular functions.

Therapeutical potential of autologous peripheral blood mononuclear cell transplantation in patients with type 2 diabetic critical limb ischemia.

AIM: The aim was to evaluate the therapeutic effectiveness of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood mononuclear cells (PBMNCs) in critical limb ischemia (CLI) of type 2 diabetic patients. METHOD: Forty diabetic patients with CLI were enrolled and randomized to treatment and control groups. In the treatment group, the patients received subcutaneous injections of recombinant human G-CSF (30 MU/day) for 5 days to mobilize stem cells. PBMNCs were collected and transplanted by multiple intramuscular injections of 1 ml in 1-1.5-cm depth into ischemic limbs. RESULTS: At the end of 12 weeks of follow-up, the baseline and end point results in transplant group were as follows: Fontaine score improved from 3.8±03 to 3±0.5 (P=.0001), ankle brachial pressure index increased from 0.68±0.24 to 0.87±024 (P=.001), transcutaneous oxygen increased from 33±14 mmHg to 44±10 mmHg (P=.0001), and 6-min walking distance improved from 280±82 m to 338±98 m (P=.0001). Pain score decreased from 8.2±1.3 to 5.63±1.6 (P=.001), and the number of patients with limb ulcers was reduced from 9/20 (45%) to 3/20 (15%) (P=.031). In the control group, Fontaine score, 6-min walking distance, and pain score were improved; ankle brachial pressure index and transcutaneous oxygen pressure were not improved. The number of patients with limb ulcers did not change in the control group. There are improvement in amputation rates, collateral vessel development, and number of limb ulcers healed. CONCLUSIONS: These results indicate that the autologous transplantation of G-CSF that mobilized PBMNCs in CLI diabetic patients is safe and effective in patient compliant reduction and improved perfusion.

Increased iron and oxidative stress are separately related to cognitive decline in elderly.

AIM: The aim of this study is to examine the relation between body iron, oxidative stress and cognitive function in elderly. METHODS: Eighty-seven elderly residents from nursing homes were the subjects of our study. Cognitive status was screened by the Mini-Mental State Examination (MMSE). Of the 87 eligible subjects, 46 patients who obtained 24 or fewer points on the MMSE scale were considered as subjects with cognitive dysfunction. The control group consisted of 41 subjects who obtained more than 24 points on the MMSE. Routine biochemical analyses, parameters of iron metabolism, malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were determined in all subjects. RESULTS: There were statistically significant increases in serum iron, transferrin saturation, ferritin and MDA levels; whereas there was a statistically significant decrease in serum GSH-Px enzyme activity and serum sodium levels in subjects with cognitive dysfunction. A significant negative correlation was found between serum iron, transferrin saturation, ferritin and MMSE score. There was a negative correlation between MMSE score and serum MDA; however, a positive significant correlation was found between MMSE score and both GSH-Px enzyme activity and serum sodium. CONCLUSION: Our study provides evidence of increased markers of iron deposition and oxidative stress in patients with cognitive dysfunction. It seems likely that these markers negatively affect the MMSE score. Interestingly, we did not find any correlation between the markers of iron deposition and oxidative stress. Future studies will be required to demonstrate whether diminishing iron and oxidative stress will enhance MMSE score and thereby ameliorate cognitive impairment.

The vasoactive intestinal polypeptide (VIP) levels at the patients with ankylosing spondylitis and its association with inflammation markers.

Vasoactive intestinal polypeptide (VIP) is a neuropeptide from secretin/glukagon family. Recently, the importance of VIP is becoming more evident, and it is thought that VIP is playing an important regulatory role between neuroendocrine-immune-gastrointestinal systems. In this study, we have tried to evaluate the potential role of VIP in patients with ankylosing spondylitis (AS). In this study, 40 patients (30 male and 10 female) with AS and 40 healthy controls were included. X-ray examinations and scoring of sacroiliac joints of the patients with AS were done according to 1984 Modified New York Criteria for AS. All patients have been assessed with Bath Ankylosing Spondylitis Disease Activity Index. Platelet counts were significantly higher in study group (P < 0.05) in contrast to levels of the hemoglobin. The mean VIP levels were 4.2 ± 1.8 (pg/mL) for study group and 2.8 ± 0.8 (pg/mL) for controls. These results were statistically significant (P < 0.05). There was not any correlation between plasma VIP levels with CRP, ESR, Hb, BASDAI results and radiological scoring of the patients (P > 0.05) in contrast to our expectations. However, platelet counts and VIP levels were correlated significantly (P = 0.03). Our data demonstrate that VIP tended to be high in patients with AS when compared with healthy subjects and correlated with platelet counts significantly, for the first time at the literature. According to this study, VIP may have potential role in the pathogenesis of AS, and it is a potential candidate for many kinds of therapies.

High frequency of MEFV gene mutations in patients with myeloid neoplasm.

We aimed to investigate the rate of MEFV, the gene mutated in familial Mediterranean fever, mutations in patients with myeloid neoplasm and to determine if known mutations of MEFV cause a tendency for myeloid neoplasms. The frequency of the five most common MEFV gene mutations (M694V, M680I, V726A, E148Q and M694I) was determined in 26 patients with myeloid neoplasm. We identified 1 homozygous (E148Q/E148Q), 1 compound heterozygous (M694V/E148Q) and 5 heterozygous MEFV gene mutations; none had their own and/or family history compatible with familial Mediterranean fever. The mean overall mutation rate was 0.269. We found a high frequency of carriers in patients with myelodysplastic syndrome (66.6%), polycythemia vera (33.3%) and acute myeloid leukemia (28.6%). However, there was no MEFV gene mutation in patients with chronic myeloid leukemia. In conclusion, this study reports for the first time a possibly high prevalence of MEFV gene mutations in patients with myeloid neoplasm, especially myelodysplastic syndrome, polycythemia vera and acute myeloid leukemia. Our findings could open new perspectives for MEFV gene mutations in myeloid neoplasms and its association with tumor promotion. Further research is needed to determine the actual role of MEFV gene mutations in these malignancies.

Relationship between anaemia and cognitive functions in elderly people.

BACKGROUND: The primary goal of the present study was to investigate the effects of anaemia on the cognitive functions and daily living activities in elderly people. METHODS: This sectional study was performed using 180 elderly people. Face-to-face interviews and questionnaires were conducted to evaluate daily activities. To evaluate cognitive functions we used the Folstein's Mini-Mental State Examination (MMSE). RESULTS: The mean age of the anaemic group and the nonanaemic group were 76.0+/-11.7 and 72.5+/-15.2 years, respectively. The average haemoglobin level among the anaemic population was 10.4 g/dL compared with 13.6 g/dL among the nonanaemic population; a statistically significant difference. There was more impairment in functional status (Katz ADL) (6.8+/-4.3 vs 9.3+/-3.7) and cognition (MMSE) (17.9+/-6.4 vs 21.7+/-6.7) in anaemic than nonanaemic groups, respectively. Albumin and body mass index were lower and the percentage of two or more comorbidities was higher in anaemic group compared to the nonanaemic group, which was a statistically significant variation. The anaemic group was more dependent in terms of bathing, dressing, toileting and transferring. CONCLUSION: In the elderly anaemic group, the dependency for daily activities that require physical effort was higher compared to the nonanaemic group. The MMSE score in the elderly anaemic group was lower than subjects who had normal haemoglobin levels. We conclude that anaemia may impair cognitive functions and some daily living activities in the elderly.

Albumin, hemoglobin, body mass index, cognitive and functional performance in elderly persons living in nursing homes.

The aim of this study is to produce the relation between cognitive and functional performance and some biochemical parameters in elderly population. So, we searched for the correlation between the activities of daily living (ADL), mini-mental state examination (MMSE) and body weight, age, hemoglobin, albumin, serum sodium level of 180 elderly people in five nursing homes. Face-to-face interviews and questionnaires were applied to evaluate ADL. To evaluate the cognitive function we used the MMSE. The average age of 180 people contacted was 71.5+/-5.1 (+/-S.D.), ranging 65-91 years; 112 of them were women (62.2%), 68 were men (37.8%). Of these elderly people, 25% had no medically diagnosed illnesses, whereas 17 of them (9.4%) were bedridden. There was a positive correlation between ADL and hemoglobin, albumin, body weight, cognitive function parameters and a negative one with age and serum sodium. There was a positive correlation between cognitive functions and hemoglobin, body weight, ADL and a negative one with serum sodium. Hemoglobin concentrations indicating anemia were observed in 30% of subjects, 3.9% of them had hyponatremia and 26.7% displayed a hypernatremia. There was a positive correlation between cognitive and physical function scores and hemoglobin, albumin levels in elderly patients. These results suggest that restoration of hemoglobin and albumin levels could improve cognitive and physical functional status in the elderly population.

Risk assessment study of the pressure ulcers in intensive care unit patients.

In this research, we studied the incidence of pressure ulcer and risk factors and screening of the patients for pressure ulcers at intensive care unit on the first day of admission in 142 patients. All patients were evaluated according to National Pressure Ulcer Advisory Panel during the ICU period strictly. Pressure ulcer risk evaluation was performed according to Norton Scale. Nutritional state was evaluated according to nutritional risk screening 2002. Age, hospitalization period, mean arterial pressure, pressure ulcer degree, hemoglobin and albumin levels, body mass index, APACHE-II scores and comorbidities were evaluated. In the following parameters, first value represents PU (+) cases, and second value represents PU (-) cases. On the admittance: 14 (9.8%) patients had PU (prevalence). NRS-2002: 5.4+/-1.9 and 4.3+/-2.1 (p<0.05), Norton score: 8.4+/-4.7 and 13.9+/-4.6 (p<0.05), albumin 2.7+/-0.7 g/dl and 3.2+/-0.8 g/dl (p<0.05). MAP and hemoglobin levels were not different (p>0.05). Mean pressure ulcer degree was 2.15. On the discharge: first values represent new developed PU (+) patients and second values represent PU (-) cases. 25 (17.6%) patients had PU. Incidence was 7.8%. NRS-2002: 6.4 and 3.6 (p<0.05), Norton score: 7.1 and 14.4 (p<0.05), albumin 2.2 g/dl and 3.0 g/dl (p<0.05). MAP 55.15+/-24.10 mm Hg and 79.76+/-18.12 mm Hg (p<0.05), APACHE-II score 22.3+/-4.2 and 18.2+/-6.2 (p<0.05). Hospitalization period: 18.3+/-10.3 days and 6.6+/-4.3 days (p<0.05) respectively. BMI and hemoglobin levels were not different (p>0.05). Two or more co morbidity, neurophyschiatric disorders, infections and medications were more prevalent in PU (+) group (p<0.05). Results of this study show us the PU incidence of ICU patients may be low if we perform PU screening all patients at the admission and put into practice NPUAP strictly. Age, low Norton score, hospitalization period, high APACHE-II score, hypotension, malnutrition and hypoalbuminemia were significant in patients with PU; however, BMI and hemoglobin were not significant. The studies focusing on the relation between the effect of optimization of these parameters from the first day of admittance and pressure ulcer are required.

Increased asymmetric dimethylarginine levels in young men with familial Mediterranean fever (FMF): is it early evidence of interaction between inflammation and endothelial dysfunction in FMF?

OBJECTIVE: Unlike in many other chronic inflammatory rheumatic diseases, studies investigating endothelial dysfunction and atherosclerosis in familial Mediterranean fever (FMF) are limited, and the results are controversial. Asymmetric dimethylarginine (ADMA) is considered an indicator for endothelial dysfunction and a sensitive marker for cardiovascular risk. There have been no reports on serum ADMA levels in patients with FMF. METHODS: We aimed (1) to determine serum ADMA concentrations in 38 young male patients with FMF and 23 age- and body mass index-matched healthy volunteers; (2) to evaluate its correlations with MEFV mutations, C-reactive protein (CRP) levels, and lipid profile; and (3) to compare effects of colchicine on circulating ADMA concentrations. RESULTS: In patients with FMF, ADMA and CRP levels were higher than in healthy controls. The mean levels of ADMA and CRP were higher during acute attacks than in attack-free periods. Patients taking colchicine had lower serum ADMA levels than non-colchicine users. There was a positive strong correlation between ADMA and CRP in patients with FMF. Stepwise linear regression analysis in patients with FMF revealed that age and CRP levels were independently associated with serum ADMA levels. CONCLUSION: Our data imply that higher serum ADMA levels in FMF may indicate inflammation-related "endothelial dysfunction." It seems likely that regular use of colchicine is effective in preventing the development of and reversing not only amyloidosis but also endothelial dysfunction in patients with FMF.

Analyses of subjects with hypokalemic metabolic alkolosis, Gitelman's and Bartter's syndrome.

The two most common forms of inherited normotensive hypokalemic metabolic alkalosis are Bartter's and Gitelman's syndromes. Bartter's is mostly seen in children, while Gittelman's is mostly seen in adolescents and adults. We analyze three subjects of adult-onset Gitelman's and Bartter's syndrome. The patients applied to our hospital due to severe hypokalemia with little clinical expression (paresthesia, cramp, polyuria, polydipsia, and/or weakness). All had normal blood pressure, hypokalemia, hyperreninemic hyperaldosteronism, and a decrease in the fractional chloride reabsorption. Key elements in differential diagnosis of chronic hypokalemia are blood pressure assessment, acid base equilibrium, serum calcium concentration, and 24-hour urine potassium and calcium excretion.

Familial Mediterranean fever attacks do not alter functional and morphologic tissue Doppler echocardiographic parameters.

The aim of this study is to investigate the tissue Doppler echocardiographic (TDE) characteristics of acute familial Mediterranean fever (FMF) attack on young Turkish males. Thirty-four young males with FMF were investigated utilizing echocardiography both before and after FMF attacks. Echocardiographic findings were assessed by two cardiologist utilizing Vingmed system V echocardiography machine and a 2.5 MHz probe by two-dimensional and color Doppler examination, as well as tissue Doppler parameters. The incidence of pericardial effusion was found to be 23.3% during acute FMF attack. There was no significant difference between the patients in attack-free period and attack period with respect to TDE measurements. TDE measurements did not differ between the patients with and without pericardial effusion. There was no correlation between pericardial effusion and disease duration, family history, and physical findings. In conclusion, our results suggest preserved systolic and diastolic ventricular functions in attack period. Pericardial effusion is not associated with impaired TDE parameters.

Herpes zoster ophthalmicus and syndrome of inappropriate antidiuretic hormone secretion.

The syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a common consequence of neurologic and pulmonary infections as well as drug intake and many other clinical situations. This report describes SIADH that developed in an elderly woman with single dermatomal herpes varicella zoster ophthalmicus without evidence of varicella zoster encephalitis or dissemination. A 76-year-old woman was admitted to our department for evaluation of left facial pain, confusion and disorientation. Further investigation revealed hyponatremia 112 mEq/L, low serum osmolality, high urine osmolality, normal renal function, normal adrenal and thyroid hormones, and high plasma vasopressin 40 pg/mL. These results indicate that the hyponatremia in this case was due to SIADH and that SIADH was caused by an increased release of vasopressin probably because of the antiviral drug (acyclovir) or infection of varicella zoster virus (VZV) in a single dermatome.

Causes of gynaecomastia in young adult males and factors associated with idiopathic gynaecomastia.

Gynaecomastia is a common clinical condition. Persistent pubertal or late onset idiopathic gynaecomastia is the leading cause of gynaecomastia in different series. The aim of this study was the assessment of the prevalence and characteristics of different causes of gynaecomastia in young adult males, and evaluation of the factors associated with idiopathic gynaecomastia. Fifty-three male patients (mean age 22.04 +/- 2.22, range 19-29), who had been admitted to our outpatient clinics with gynaecomastia as the main presenting symptom were enrolled in the study. Patients were evaluated with breast palpation, breast ultrasonography, anthropometric measurements and sex steroid levels. Secondary causes of gynaecomastia were ruled out. Thirty age-matched healthy individuals were also studied as healthy control group. Idiopathic gynaecomastia was diagnosed in 31 of 53 patients (58%), with 17 (32%) persistent pubertal and 14 (24%) late onset course. Other causes of gynaecomastia were hypogonadism in 13 cases (25%), hyperprolactinaemia in five (9%), chronic liver disease in two (4%), and drug induced (prolonged use of H2 antagonists) in two (4%). Patients with idiopathic gynaecomastia, either pubertal or late onset, were compared with the healthy control group in order to find out associated factors. Anthropometric measurements revealed a significant increase in body weight and body mass index (BMI) in the patient group compared with healthy controls (72.4 +/- 13.3 vs. 63.6 +/- 7.9 kg, p = 0.0086 and 25.2 +/- 4.0 vs. 21.5 +/- 2.7 kg/m2, p = 0.0001). Total skin fold thickness (SFT) of four different regions were also higher in the patient group (50.9 +/- 22.1 vs. 32.6 +/- 10.2 mm, p = 0.0006) indicating a higher body fat percentage. Total serum testosterone (4.76 +/- 1.31 vs. 5.70 +/- 1.06 microg/mL, p = 0.0038) and luteinizing hormone (LH) (4.80 +/- 1.92 vs. 7.32 +/- 1.90 mIU/mL, p < 0.0001) levels were significantly lower in the patient group while oestradiol levels were similar. There was a significant correlation between total testosterone and LH levels (r = 0.27, p = 0.0445). Total testosterone and LH levels were negatively correlated with BMI and total SFT. As a result most common form of gynaecomastia is idiopathic gynaecomastia either as persistent pubertal or late onset forms in young adult males. Idiopathic gynaecomastia is closely correlated with generalized obesity, reduced LH and testosterone levels which may be the result of increased conversion of testosterone to oestradiol in increased adipose tissue mass.