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Dimitrios Botsis - Top 30 Publications

Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives.

Diabetes mellitus, the prevalence of which has increased dramatically worldwide, may put patients at a higher risk of cancer. The aim of our study is the clarification of the possible mechanisms linking diabetes mellitus and gynecological cancer and their epidemiological relationship.

Endocrine, paracrine, and autocrine placental mediators in labor.

Considering that preterm birth accounts for about 6-10% of all births in Western countries and of more than 65% of all perinatal deaths, elucidation of the particularly complicated mechanisms of labor is essential for determination of appropriate and effective therapeutic interventions. Labor in humans results from a complex interplay of fetal and maternal factors, which act upon the uterus to trigger pathways leading gradually to a coordinated cervical ripening and myometrial contractility. Although the exact mechanism of labor still remains uncertain, several components have been identified and described in detail. Based on the major role played by the human placenta in pregnancy and the cascade of labor processes activated via placental mediators exerting endocrine, paracrine, and autocrine actions, this review article has aimed at presenting the role of these mediators in term and preterm labor and the molecular pathways of their actions. Some of the aforementioned mediators are involved in myometrial activation and preparation and others in myometrial stimulation leading to delivery. In the early stages of pregnancy, myometrial molecules, like progesterone, nitric oxide, and relaxin, contribute to the retention of pregnancy. At late stages of gestation, fetal hypothalamus maturation signals act on the placenta causing the production of hormones, including CRH, in an endocrine manner; the signals then enhance paracrinically the production of more hormones, such as estrogens and neuropeptides, that contribute to cervical ripening and uterine contractility. These molecules act directly on the myometrium through specific receptors, while cytokines and multiple growth factors are also produced, additionally contributing to labor. In situations leading to preterm labor, as in maternal stress and fetal infection, cytokines trigger placental signaling sooner, thus leading to preterm birth.

Aberrant expression of collapsin response mediator proteins-1, -2 and -5 in the brain of intrauterine growth restricted rats.

Intrauterine growth restriction (IUGR) has been associated with increased perinatal morbidity, higher incidence of neurodevelopmental defects and increased risk for adult metabolic syndrome manifestations. Altered protein expression profiles associated with IUGR may be informative on the pathological mechanisms of this condition and might reveal potential markers for postnatal complications. We hypothesized that nutrient manipulation of the pregnant rat might influence the expression of important neurodevelopmental proteins in the resultant IUGR offspring. Therefore, we aimed to determine in newborn rat brain tissue the expression of collapsin response mediator proteins (CRMPs)-1, -2 and -5, commonly referred to as dihydropyrimidinase-related proteins (DPYLs) - playing a role in axon guidance, invasive growth and cell migration - and compare it to the corresponding expression in control rats. Two-dimensional electrophoresis and mass spectrometry, as well as Western blot analysis were employed in brain tissue from 24 IUGR newborn rats and 24 controls. With both methods, CRMP-1, CRMP-2 and CRMP-5 were decreased in the brains of the IUGR group as compared to the control group at the time of delivery. In conclusion, IUGR rat offspring are born with a decreased expression of CRMPs, suggesting that these proteins may be implicated in fetal stress-induced programming.

Diagnosing arthrogryposis multiplex congenita: a review.

Arthrogryposis multiplex congenita (AMC) refers either to a syndromic or to a nonsyndromic group of conditions with varied etiology and complex clinical features, including multiple congenital contractures in different body areas. Its etiology still remains unclear but generally any cause that leads to reduced fetal movement may lead to congenital contractures and in severe cases to fetal akinesia deformation sequence (FADS). It affects approximately 1 in 2-3000 live births with an approximately equal gender ratio. There are many known subgroups of AMC differing in signs, symptoms, and causes. The primary diagnosis is made when a lack of mobility and an abnormal position is noted in routine ultrasound scanning. Early diagnosis, prenatal evaluation, and further surveillance via image scanning (ultrasound and MRI) give the opportunity for family counseling concerning neonatal morbidity and mortality and labor or delivery planning. Better understanding of the ultrasound findings and the etiology of this clinical situation offers the opportunity for careful prenatal assessment.

Association of adiponectin and placental growth factor in amniotic fluid with second trimester fetal growth.

We investigated the associations between second trimester amniotic fluid (AF) levels of human adiponectin and placental growth factor (PLGF) in small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) fetuses.

Response to hormonal treatment of young females with primary or very premature ovarian failure.

The aim of this study was to evaluate the impact of hormone treatment (HT) on several endocrinologic, metabolic and bone parameters in young women with primary or very premature ovarian failure. The study included 40 phenotypically females of 14-20 years old with primary or secondary amenorrhoea and female external genitalia. Study subjects were categorised in three groups: Group A included 12 subjects with Turner syndrome, Group B included 19 subjects with Swyer syndrome and Group C included 9 subjects with very premature ovarian failure. HT was administered for 24 months and included conjugated oestrogens and medroxyprogesterone acetate. In all groups, HT provided a beneficial hormonal profile and resulted in safe and adequate serum oestrogens levels. In Group A, no adverse effects on metabolic or coagulation parameters were noted; significant increases in high-density lipoprotein cholesterol (HDL) levels and bone density were observed. Similar positive effects of HT were observed in Group B. Finally, in Group C, no adverse effects of HT were noted, but the favourable increase in HDL was absent; bone density kept significantly increasing until the 12-month evaluation. In conclusion, the administration of HT is remarkably beneficial for young women with primary or very premature ovarian failure.

Seven cases of fetal ovarian cysts.

The role of maternal gut hormones in normal pregnancy: fasting plasma active glucagon-like peptide 1 level is a negative predictor of fetal abdomen circumference and maternal weight change.

Maternal weight in pregnancy contributes to a glycemic environment that affects fetal growth. Gut peptides (glucagon-like peptide 1 (GLP1), glucose-dependent insulinotropic peptide (GIP), ghrelin, and peptide YY (PYY)) have been related to insulin sensitivity and secretion, weight control, and adipose tissue metabolism. This study aimed at examining the associations of gut hormones during pregnancy with maternal glucose homeostasis, maternal weight, and fetal growth.

Serum adiponectin during pregnancy and postpartum in women with gestational diabetes and normal controls.

To investigate changes in serum adiponectin during pregnancy and postpartum and assess its relationship with insulin resistance as measured by homeostasis model assessment (HOMA-IR).

Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined with intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and intrauterine insemination.

To compare the efficacy of letrozole to recombinant FSH for ovarian stimulation combined with IUI in a group of patients that had failed to conceive after clomiphene citrate (CC) and IUI.


Bisphosphonates belong to a class of compounds similar to pyrophosphate. In these compounds the oxygen atom of the pyrophosphate is replaced by a carbon atom resulting in a P-C-P bond. They exert a potent inhibitory effect on osteoclasts and are therefore potent antiresorptive agents. They reduce bone turnover, increase bone mineral density, and decrease fracture risk both at the lumbar spine and the hip. Bisphosphonates have a high affinity for bone surfaces, where they accumulate, mainly at sites of bone remodeling. Due to their selectivity in action, they are usually not associated with systemic side effects. Their main unwanted effect is upper gastrointestinal irritation. Alendronate and risedronate are the two most widely used compounds in the treatment of postmenopausal osteoporosis. They are administered orally either daily or once weekly. Ibandronate is a highly potent newer third-generation bisphosphonate administered once monthly with similar efficacy with respect to bone mineral density and fracture risk. Zoledronate, another potent third-generation bisphosphonate, currently approved for the treatment of malignancy-associated hypercalcemia, is currently undergoing phase III trials for the treatment of postmenopausal osteoporosis as an intravenous (i.v.) infusion once annually.

The fetus that is small for gestational age.

The symmetric small for gestational age (SGA) fetus presents a complex management problem for the obstetrician, but the growth restriction affects morbidity and mortality at all stages of life. The differential diagnosis in symmetric growth aberration includes the constitutionally small fetus, the fetus with pathology, and the cases with incorrect dating of pregnancy. The ultrasonographic examination focuses in the detection of anomalies, signs of intrauterine infection, and serial assessment of fetal growth. Accuracy of fetal biometry may be improved by using individualized fetal growth curves. From the available surveillance tools, the uterine artery Doppler has a value in predicting poor perinatal outcome. Magnetic resonance imaging is also useful in the evaluation of anomalies. Cesarean section is not justified for all symmetric SGA fetuses that may carry a guarded prognosis.

Sonohysterography is superior to transvaginal sonography for the diagnostic approach of irregular uterine bleeding in women of reproductive age.

To evaluate and compare the accuracy of transvaginal sonography (TVS) and sonohysterography (SHG) in the investigation of women of reproductive age presenting with irregular uterine bleeding (IUB).

Proximal tubal occlusion and salpingectomy result in similar improvement in in vitro fertilization outcome in patients with hydrosalpinx.

To evaluate and compare the clinical impact of proximal tubal occlusion and salpingectomy when performed before IVF in patients with hydrosalpinges.

Endogenous sex hormones and risk factors for atherosclerosis in healthy Greek postmenopausal women.

To assess the association between endogenous sex hormones and risk factors for atherosclerosis in healthy postmenopausal women.

Elevated mid-trimester amniotic fluid ADAM-8 concentrations as a potential risk factor for preterm delivery.

To determine during mid-trimester amniocentesis if elevated concentrations of ADAM-8 (A Disintegrin And Metalloprotease 8) and/or cortisol can recognize women at risk for spontaneous preterm delivery.

Increased impedance in the uterine arteries of women with unexplained recurrent pregnancy loss.

The effect of low dose hormone therapy on mammographic breast density.

To evaluate the effect of two standard and one low dose continuous hormone therapy regimens on mammography.

The effect of raloxifene and tibolone on the uterine blood flow and endometrial thickness: a transvaginal Doppler study.

To evaluate and compare the effect of different than classical hormone therapy medications, such as raloxifene and tibolone, on the uterine arteries and endometrium of postmenopausal women using transvaginal ultrasonography.

A 5-year study on the effect of hormone therapy, tibolone and raloxifene on vaginal bleeding and endometrial thickness.

To study the effect of standard and low-dose estrogen-progestin therapy (EPT), tibolone and raloxifene on the incidence of vaginal spotting/bleeding and endometrial thickness over a 5-year period.

Tension-free vaginal tape (TVT) in women with low urethral closure pressure.

Aim of the study was to assess the effectiveness and the complications associated with the use of tension-free vaginal tape (TVT) in women with stress urinary incontinence and low urethral closure pressure (LUCP).

The effect of hormone therapy and raloxifene on serum matrix metalloproteinase-2 and -9 in postmenopausal women.

The aim of the study was to investigate the effect of continuous-combined hormone therapy and raloxifene on the total and active forms of serum matrix metalloproteinase (MMP) -2 and -9.

Concentrations of soluble Fas in maternal serum and amniotic fluid during uncomplicated pregnancies.

To determine, during normal pregnancy, maternal serum (MS) and amniotic fluid (AF) concentrations of soluble Fas (sFas), an apoptosis-suppressing molecule that might play a role in the apoptotic process. Soluble Fas levels might explain existing immunotolerance, fetal well being, and rupture of membranes at term.