Do diethyl phthalate (DEP) and di-2-ethylhexyl phthalate (DEHP) influence the metabolic syndrome parameters? Pilot study.

The study objective was to determine if the healthy participants were exposed to diethyl phthalate (DEP) and di (2-ethylhexyl) phthalate (DEHP) and if this exposure could be linked to the development of metabolic syndrome. The study included 103 healthy volunteers of similar age with normal BMI values, waist circumference, total cholesterol, HDL, LDL, and triglycerides. DEP and DEHP were measured in the morning urine samples to detect monoethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Two phthalate groups and a control group were formed. Both MEP group and control group had similar results. The correlations between MEP and the measured parameters were insignificant. The correlation between the MEHP group and the age was significantly negative, but between the MHEP group and the waist circumference the correlation was significantly positive. Lipids and lipoproteins were within the reference values and equal in both groups. The significant negative correlation was observed only between MEHP and HDL. Our population is exposed to DEP and DEHP. There was only a significant correlation between DEHP and the observed metabolic syndrome components. Its negative impact was higher as the participants were younger.

The relationship between the vitamin serum 25(OH)D and the B12 concentrations in obese women.

BACKGROUND: In obesity, low levels of vitamin D (VD) and vitamin B12 (VB12) may be the result of different pathophysiological mechanisms, but the possible association between them has not been defined yet. The aim of this cross-sectional analysis was to investigate the possible relationship between serum 25-hydroxyvitamin D (25(OH)D) and VB12 levels in middle aged women. METHODS: In 80 women, we indirectly evaluated body composition and body volumes [extracellular fluid volume (ECV) and total body water (TBW)] by anthropometric and bioelectrical impedance analysis. Vitamin D and VB12 status was assessed by laboratory measurement [serum 25(OH)D levels by electrochemiluminescent immunoassay; VB12 by chemiluminescent microparticle immunoassay]. RESULTS: Obese women were mostly VD deficient [25(OH)D below 50 nmol/L; 40/50, 80%]. Also, among obese we observed presence of VB12 deficiency [VB12 below 148 pmol/L; 13/50, 26%) and marginal depletion of VB12 level (marginal VB12 status 148-221 pmol/L; 20/50, 40%). All anthropometric indicators of obesity, ECV and TBW were significantly associated with both, 25(OH)D and VB12 (P<0.001) levels. In univariate regression analysis serum level of 25(OH)D was significantly associated with VB12 levels (R2=0.170, P<0.001). In regression models, 25(OH)D was significantly associated with VB12 level, independently of fat mass and extracellular fluid volume. CONCLUSIONS: Obesity may negatively affect VB12 level, indirectly, by reducing 25(OH)D level in middle aged women.

Estimation of in vivo and in vitro exposure to bisphenol A as food contaminant.

The goal of this cross-sectional study was to examine the occurrence of bisphenol A (BPA) in the morning spot urine taken from 145 female volunteers of various ages. Total urine BPA concentration was detected in 38.6% samples in the 0.92-70.96 µg/g Cr range. The majority of BPA + women belonged to the 25 + body mass index (BMI) group (54.5% were overweight and 43.4% were obese women). Occurrence of BPA in the urine samples was higher at 40 + ages. The maximum BPA concentration of 70.96 µg/g Cr was detected in the urine sample of an obese woman. It is known that BPA is highly toxic in vitro. In this study BPA impaired significantly the growth of all investigated cell lines, i.e. the EC50 values were reached at very low concentrations, in the range from 3.24 to 34.85 µg/mL. The obtained in vivo results suggest that a higher exposure to BPA could contribute to weight problems in women and the absence of the BPA in vitro selective toxicity studies indicates to its general toxic mode of action and raises awareness of the health risks associated with its ubiquitous presence in the environment.

The influence of hyperprolactinemia on coagulation parameters in females with prolactinomas.

INTRODUCTION: Currently there is little information on the effects of prolactin (PRL) on the coagulation and fibrinolytic systems. OBJECTIVE: The aim of this study was to evaluate the effects of hypeprolactinemia on the parameters of the hemostatic system and activation of the coagulation system. METHODS: We studied PRL levels, body mass index (BMI), values of activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), D-dimer level, von Willebrand factor antigen (vWFAg) and fibrinogen in 15 young female patients with microprolactinomas before and after therapy and in 15 healthy female controls. RESULTS: As expected, pretreatment PRL levels were significantly higher in patients than in controls (140.90 +/- 42.87 vs. 12.53 +/- 4.05 ng/ml; p < 0.001). PT, although still in the normal range, was prolonged in patients with hyperprolactinemia as compared to the control group (13.53 +/- 1.39 vs. 12.65 +/- 0.53 s; p = 0.03) and normalized after therapy (12.69 +/- 0.65 vs. 12.65 +/- 0.53 s; p = 0.88). TT, although in normal range, was significantly shorter in the hypeprolactinemic patients than in the controls (14.34 +/- 4.52 vs. 17.21 +/- 1.35 s; p < 0.025) and after treatment remained significantly shorter than in the controls (15.17 +/- 1.55 vs. 17.21 +/- 1.35 s; p < 0.0001). D-dimer values before treatment in the patients with hyperproplactinemia were above the normal range (239.47 +/- 107.93 vs. 131.27 +/- 50.64 ng/ml, p = 0.002) and decreased to normal values after therapy (239.47 +/- 107.93 vs. 146.60 +/- 39.15 ng/ml; p < 0.001). D-dimer levels correlated with PRL (r = 0.30) and the change in serum D-dimer values significantly correlated with the change in PRL levels during therapy (r = 0.62). aPTT, vWFAg and fibrinogen were similar in patients and controls. CONCLUSION: In our study, increased thrombin generation that resulted in elevated D-dimer levels may be one of the contributing factors to the prethrombotic state in patients with hyperprolactinemia.

Changes of serum VEGF concentration after intravitreal injection of Avastin in treatment of diabetic retinopathy.

PURPOSE: Avastin (bevacizumab) intravitreal injections are widely used for treatment of diabetic retinopathy. The aim of our study was to analyze effect of 1.25 mg of intravitreal Avastin on serum concentration of vascular endothelial growth factor (VEGF) in diabetic patients. METHODS: Participants were 10 diabetic patients on insulin therapy, without any other eye or systemic disease, and no kidney disfunction. Both eyes of diabetic patients were injected simultaneously with 1.25 mg of intravitreal Avastin, as a first step in treatment of nonproliferative diabetic retinopathy with clinically significant macular edema (4 patients), and of proliferative diabetic retinopathy (6 patients). Fluorescein angiography was performed prior to and laser therapy followed 1 month after Avastin treatment. VEGF concentration in patients serum was measured by ELISA technique: on the day of the Avastin administration, and 1, 7, and 28 days after intravitreal injection. RESULTS: In all analyzed participants, 24 hours after Avastin treatment, serum levels of VEGF were lower then basal (preinjection value). Maximal reduction of serum VEGF was noted on the 7th postoperative day. Twenty-eight days after, VEGF level in serum was raised, without completely reaching basal preoperative concentrations in most patients. CONCLUSIONS: Intravitreal injections of anti-VEGF drugs have an effect on decreasing systemic VEGF values. Rhythm of changes in serum VEGF concentrations and lowest detected concentration on the seventh postinjection day are according to pharmacokinetics of Avastin in serum and vitreous, reported by similar studies. The small number of patients involved in this pilot study implicates the need for further studies.

[Bone metabolism during substitution therapy of primary hypothyroidism].

INTRODUCTION: The relation between thyroid hormones and bone metabolism markers in hyperthyroidism is well known. Earlier studies indicate the possibility of bone metabolism acceleration during the excessive replacement therapy with l-thyroxin in hypothyroid patients especially in one with other risk factors for bone metabolism impairment. This study evaluated the effect of physiological l-thyroxine treatment on bone metabolism in patient with primary hypothyroidism. MATERIAL AND METHODS: In the study group of 30 hypothyroid patients individual thyroxine replacement was performed targeting euthyroid status. Bone and calcium metabolism parameters (osteocalcin-OC, alkaline phosphates-ALP, C-terminal cross-linking telopeptide type l-CL, parathormone-PTH, Ca, ionized Ca, P), thyroid hormone levels (T3, T4, TSH) were measured before treatment and when euthyroid status was achieved. RESULTS AND DISCUSSION: A significant treatment effect was observed for bone formation and resorption parameters before and during the therapy; OC (p = 0.000024), CL (p = 0.002648). Ionized calcium levels also showed significantly higher values in euthyroid status confirming bone metabolism acceleration during the l-thyroxine therapy (p = 0.020). Thus, calcium metabolism hormone regulators were not significantly different before and after the therapy; PTH (p = 0.27). Thyroid hormone levels showed significant correlation with bone metabolism parameters before the therapy whereas this correlation was not found during therapy because of different individual l-thyroxine doses. CONCLUSION: It can be concluded that physiological doses of l-thyroxine therapy accelerate bone metabolism in hypothyroid patients. Thus, the argument against bone loss during physiological substitution is highly specific mutual correlation between bone formation and resorption parameters. These assumptions require further investigations in long-term prospective studies in patients on replacement l-thyroxine therapy.

Evolving hypopituitarism as a consequence of traumatic brain injury (TBI) in childhood - call for attention.

Hypopituitarism is a common complication of TBI in long-term survivors, more frequent than previously realized. It may be partial or complete, sometimes very subtle without visible lesions in hypothalamo-pituitary region and is diagnosed only by biochemical means. Neuroendocrine abnormalities caused by TBI may have significant implications for the recovery and rehabilitation of these patients. The subjects at risk are those who have suffered moderate to severe trauma, although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. We describe a patient with hypopituitarism thought to be idiopathic due to mild head trauma which caused diabetes insipidus in childhood, gradual failure of pituitary hormones during the period of growth and development, and metabolic (dyslipidemia), physical (obesity), and cognitive impairments in the adult period.

[Hashimoto's hypothyroidism associated with insulin resistance in type 2 diabetes].

INTRODUCTION Thyroid peroxidase activity inhibiting immunoglobulins (anti-TPO Ab) is a sign of autoimmune process in the thyroid gland. Association of hyperthyroidism and diabetes mellitus has been classically described. However, hypometabolic state, as a consequence of hypothyroidism, is not frequently linked with the biological activity of insulin. CASE DESCRIPTION A 51-year old man was admitted to the Clinic with unregulated diabetes, untreated for 5 yrs. Insulin therapy was introduced one year before, with 96 units on admission. He had bowel movements every three days. BH 176cm, BW 120kg, a puffy face and swollen body. Fundus examination did not show specific diabetic leasions. Hepatic steatosis was present on ultrasound examination. Occlusion of coronary arteries and superficial femoral artreries was present on angiography, and stenosis of carotid artreies on doppler duplex examination. HbA1c 14.7%. TSH 85.7 mlU/l, FT4 1.6 pmol/l, FT3 1.4. Anti TPO Ab >600 IU/ml, triglycerides 2.26 mmol/l, HDL 1.15, cholesterolemia 10.0. Levothyroxine substitution was introduced starting with 25 mgr, gradually increasing up to 75 mgr. The need for insulin gradually decreased and finally it was switched to glibenclamide 5mg +0+2.5 mg. On discharge his FBG was 7.0 mmol/l. HOMA -B 52.3, HOMA-R 9.8. DISCUSSION We can conclude that in our patient secondary obesity caused deterioration of diabetes. After introduction of substitution therapy with levothyroxine, decrease of insulin resistance and of cholesterol level was established. The duration of undiagnosed hypothyroidism can be a matter of speculation. However, the beneficial effect of normalized metabolism on atherosclerotic process will be obvious in the future.

[Effects of alendronate on the markers of bone metabolic activity in postmenopausal women with osteoporosis].

INTRODUCTION: Bisphosphonates are synthetic compounds used in treatment of osteoporosis and inhibition of bone resorption. MATERIAL AND METHODS: The research included a group of 30 postmenopausal women with osteoporosis, treated with alendronate (70 mg per week--Fosamax tablets in combination with calcium and active vitamin D--Alpha D3 0.25mcg). The control group included 20 women with osteoporosis treated with hormone substitution therapy (HST), calcitonin and deca duraboline. Bone metabolic activity, was evaluated using osteocalcin for bone formation and cross-laps for bone resorption. Blood samples were taken before therapy and 6-8 weeks after. RESULTS: The serum levels of osteocalcin and cross-laps during application of alendronate were statistically significantly lower comparing to those in pre-therapy. The serum levels of osteocalcin and cross-laps during the therapy applied in the control group were statistically insignificantly lower than values in pre-therapy. Osteocalcin has a tendency of decreasing in both groups, and it was slightly more evident in alendronate group. Cross-laps demontrated the same tendency of decreasing in both groups, and it was more evident in alendronate group. DISCUSSION: Our results have shown the efficacy of alendronate in preventing bone loss, which was highly statistically significant. They have also shown its suppressive effect on bone formation and resorption, but the effects were statistically less significant. CONCLUSION: Alendronate significantly reduces the level of bone resorption in postmenopausal women with osteoporosis. Its effects on bone formation are less expressed Alendronate's effects on bone metabolism become evident not later than 6-8 weeks after therapy application. Parameters of bone metabolic activity are very useful diagnostic means in evaluation of alendronate effect on bone metabolic activity and in the prognosis of bone mass loss.