Efthymios Deligeoroglou

Impact of Maternal Diabetes on Epigenetic Modifications Leading to Diseases in the Offspring

Gestational diabetes, occurring during the hyperglycemic period of pregnancy in maternal life, is a pathologic state that increases the incidence of complications in both mother and fetus. Offspring thus exposed to an adverse fetal and early postnatal environment may manifest increased susceptibility to a number of chronic diseases later in life. Compelling evidence for the role of epigenetic transmission in these complications has come from comparison of siblings born before and after the development of maternal diabetes, exposure to this intrauterine diabetic environment being shown to cause alterations in fetal growth patterns which predispose these infants to developing overweight and obesity later in life. Diabetes of the offspring is also mainly the consequence of exposure to the diabetic intrauterine environment, in addition to genetic susceptibility. Since obesity and diabetes are known to increase the risk of cardiovascular disease, cardiovascular sequelae in the offspring of diabetic mothers are virtually inevitable. Research data also suggest that exposure to a diabetic intrauterine environment during pregnancy is associated with an increase in dyslipidemia, subclinical vascular inflammation, and endothelial dysfunction processes in the offspring, all of which are linked with development of cardiovascular disease later in life. The main underlying mechanisms involve persistent hyperglycemia hyperinsulinemia and leptin resistance.

The oxytocin-oxytocin receptor system and its antagonists as tocolytic agents.

Oxytocin, a hormone involved in numerous physiologic processes, plays a central role in the mechanisms of parturition and lactation. It acts through its receptor, which belongs to the G-protein-coupled receptor superfamily, while Gq/phospholipase C (PLC)/inositol 1,4,5-triphosphate (InsP3) is the main pathway via which it exerts its action in the myometrium. Changes in receptor levels, receptor desensitization, and locally produced oxytocin are factors that influence the effect of oxytocin on uterine contractility in labor. Activation of oxytocin receptor causes myometrial contractions by increasing intracellular Ca+2 and production of prostaglandins. Since oxytocin induces contractions, the inhibition of its action has been a target in the management of preterm labor. Atosiban is today the only oxytocin receptor antagonist that is available as a tocolytic. However, the quest for oxytocin receptor antagonists with a better pharmacological profile has led to the synthesis of peptide and nonpeptide molecules such as barusiban, retosiban, L-368,899, and SSR-126768A. Many of these oxytocin receptor antagonists are used only as pharmacological tools, while others have tocolytic action. In this paper, we summarize the action of oxytocin and its receptor and we present an overview of the clinical and experimental data of oxytocin antagonists and their tocolytic action.

Prostaglandins: PGF2α, PGE2, 6-keto-PGF1α and TXB2 serum levels in dysmenorrheic adolescents before, during and after treatment with oral contraceptives

Ten adolescents with primary dysmenorrhea (PD) were treated with the oral contraceptive (OC) Lyndiol 2.5 mg (R) for one cycle. The levels of PGF2 alpha, PGE2 and the metabolites of PGI2 and TXA2: 6-keto-PGF1 alpha and TXB2 were tested by a radioimmunoassay method during the 1st and 23rd day of the pre-treatment cycle (PrTC), the 23rd day of treatment (TC) and the 1st day of the post-treatment cycle (PoTC). The ratios PGF2 alpha/PGE2 and TXB2/6-keto-PGF1 alpha were also tested and compared during the above-mentioned days. Analytical comparison was made, for each Prostaglandin (PG) separately, between the 1st day of the PrTC and PoTC as well as the 23rd day of the PrTC and TC, respectively. All PG levels during TC and PoTC were found significantly lower, compared to those of the PrTC respectively. With regard to the ratios mentioned above, no statistically significant differences were found on the same days and cycles as previously stated. The reduction of the PG levels in PD patients after treatment with oral contraceptives, together with an improvement of the clinical findings of the disease, support the theory that oral contraceptives can be used for the treatment of PD cases, especially for those adolescents who also desire a contraceptive method.

Osteoprotegerin as a Marker of Atherosclerosis in Diabetic Patients

Atherosclerosis is the principal cause of cardiovascular disease (CVD) and has many risk factors, among which is diabetes. Osteoprotegerin (OPG) is a soluble glycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various inflammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL) is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients.

Vulvovaginitis during Childhood and Adolescence

STUDY OBJECTIVE To evaluate cases of vulvovaginitis treated in our institutions. DESIGN Follow-up of 1,778 cases of vulvovaginitis to investigate the prevalence of various pathogens involved in the disease. SETTING Divisions of pediatric and adolescent gynecology, university hospitals of Crete and Athens, Greece. PARTICIPANTS Girls 1-18 years old seen at the clinics of the above institutions. INTERVENTIONS None. MAIN OUTCOME MEASURES Vaginal culture, cytology, and vaginoscopy. RESULTS Vulvovaginitis was encountered in 61.8% of the gynecological problems seen during childhood and adolescence. Infections were usually located in both the vulva and the vagina (56.9%). The main symptoms were vaginal discharge (53%), erythema (33%), and pruritus (27%). Candida spp (23.0%), beta-hemolytic Streptococci group B (15.0%), and Enterococci spp (10.0%) were the most frequent pathogens involved in the disease. CONCLUSIONS Vulvovaginitis is a common disease during childhood and adolescence. Effective treatment, reassurance, and appropriate consultation based on the prevention of relapses are the most important steps for the management of the disease.

High normal thyroid-stimulating hormone is associated with arterial stiffness in healthy postmenopausal women.

Objective: Apart from the effects of a dysfunctional thyroid gland on the cardiovascular system, thyroid function within the reference range may have an impact on the vasculature. The present study aimed to evaluate the association between thyroid function and markers of arterial structure and function in euthyroid postmenopausal women. Methods: The present cross-sectional study recruited 106 healthy postmenopausal women with a mean age of 55.0 years and thyroid-stimulating hormone (TSH) levels within the laboratory reference range (0.4–4.5 &mgr;IU/ml). Anthropometric and biochemical measures as well as blood pressure were determined in each individual. Vascular structure and function were assessed by intima–media thickness, pulse wave velocity (PWV), augmentation index and flow-mediated dilation, respectively. We evaluated the associations between arterial markers and serum TSH, free triiodothyronine, free thyroxin, as well as serum thyroid peroxidase and thyroglobulin autoantibodies. Results: Mean levels of PWV increased linearly across increasing TSH quartiles (P value = 0.014). Individuals with serum TSH greater than 2.5 &mgr;IU/ml had significantly higher values of PWV when compared with individuals with TSH levels below 2.5 &mgr;IU/ml (9.68 ± 1.97 vs. 8.54 ± 1.83 m/s; P = 0.030). In multivariate analysis, age, insulin resistance and TSH above 2.5 &mgr;IU/ml were the only significant predictors of PWV (TSH, &bgr;-coefficient = 0.222; P = 0.014). No associations were found between the remaining markers and levels of thyroid hormones, whereas thyroid antibodies were not associated with any of the arterial markers. Conclusion: Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH. The upper limit of normal TSH in postmenopausal women may need re-evaluation with respect to the effects on the vasculature.

Treatment of polycystic ovarian disease during adolescence with ethinylestradiol/cyproterone acetate versus a d-tr-6-lhrh analog

OBJECTIVE: This study was undertaken to compare the clinical and endocrinological results of two kinds of treatment on adolescents with polycystic ovarian disease (PCOD). METHOD: Forty‐five adolescents with PCOD were randomly allocated into two groups, treated either with ethinylestradiol (EE)/ cyproterone acetate (group A) or the GnRH analog D‐Tr‐6‐LHRH (group B). RESULT: No significant changes were detected on the body mass index and waist‐hip circumference. A significant improvement of hirsutism was noticed in both groups of patients. A normal menstrual period was recorded in group A adolescents while all group B patients became amenorrheic. A favorable decrease of ovarian volume was detected in both groups. LH/FSH ratio and Δ4‐androstenedione serum levels were found significantly reduced in both groups in comparison to pre‐treatment levels. The comparison between the two groups, after 6 months, showed significantly lower values of LH/FSH ratio in group B cases. CONCLUSION: Both forms of treatment are safe and effective to a various degree for the management of PCOD adolescents.

Study of association of IRS-1 and IRS-2 genes polymorphisms with clinical and metabolic features in women with polycystic ovary syndrome. Is there an impact?

Objective. Insulin receptor substrate (IRS) proteins are critical to signal transduction in insulin target tissues. The present study was undertaken to determine whether IRS-1 Gly972Arg and IRS-2 Gly1057Asp influence hormonal and metabolic characteristics in Greek patients with polycystic ovary syndrome (PCOS) and controls. Material and methods. One hundred and eighty-three women with PCOS and 88 healthy volunteers were enrolled. Venous blood samples were obtained for genetic study and hormonal profile, glucose, and insulin assays, on days 3 to 7 from cycling patients. DNA was extracted by whole blood samples for genotyping and detection of IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms. Results. Fifty-six women with PCOS (30.60%), whereas 12 women in the control group (13.64%) carried the IRS-1 polymorphism (p = 0.0026). No statistically significant differences in genotypes or allele frequencies for IRS-2 polymorphism were observed between controls and PCOS women. No significant differences in any clinical or hormonal measures between subjects on the basis of genotype were observed, except the increased levels of fasting glucose that exhibit the carriers of the Asp allele of the IRS-2 polymorphism. Conclusions. Only the IRS-1 polymorphism is associated with increased susceptibility to PCOS in a Greek population. These loci should not be considered as major contributors to the hormonal and metabolic phenotype of PCOS.

Ultrasound imaging to evaluate Creatsas vaginoplasty

Objective: To present a new imaging technique for the evaluation of the functional effectiveness of Creatsas vaginoplasty. Method: Eighteen women with Mayer–Rokitansky–Küster–Hauser syndrome underwent a transabdominal and transperineal ultrasound examination 4 weeks and 6 months after the surgical creation of a neovagina, and then yearly, with a condom filled with water as a distending and imaging medium. The functional length and width of the neovagina and its axis deviation were assessed, as well as the postoperative quality of the womens sexual life. Results: A functional vagina 10 to 12 cm in length and 4 to 5 cm in width was observed; its axis deviation, which was similar to the anatomic deviation, was easily determined; and 94.5% of the women reported a satisfactory while 5.5% reported an adequate sexual life. Conclusion: This new imaging technique is a simple and effective alternative for the evaluation of the postoperative effectiveness of colpopoiesis.

Laparoscopic Gonadectomy in a Patient With Testicular Feminization Syndrome

A laparoscopic technique is reported as an operative approach for gonadectomy in a case of testicular feminization syndrome. A 17-year-old phenotypic female presented with primary amenorrhea and was evaluated through a diagnostic protocol that included clinical, cytogenetic, and hormonal examinations. The findings supported the diagnosis of testicular feminization syndrome. The left gonad was found at the internal opening of the inguinal canal and removed laparoscopically. No gonad was found at the contralateral side. No complications occurred during the operation and the patient left the hospital the same day. A long-term hormonal replacement treatment was initiated postoperatively.