Marija Andjelkovic

Induction of mitochondrial apoptotic pathway by raloxifene and estrogen in human endometrial stromal ThESC cell line

Introduction Endometrial hyperplasia is a condition that occurs as a result of hormonal imbalance between estrogen and progesterone. Morphological disturbance of endometrial cells occurs consequently leading towards endometrial cancer. In therapy of endometrial hyperplasia SERMs are used to supress effects of locally high estrogen level in uterus. There is strong evidence suggesting that estrogen could be involved in cell death – apoptosis. There are no experimental data demstrating the direct apoptotic effect of both raloxifene and estrogen on the ThESC cell line. The aim of our study wa sto investigate both cytotoxic and apototic mechanism of raloxifene and estrogen – induced death in the ThESC cell line. Material and methods In order to determine their cytotoxic and apoptotic effects, various doses of raloxifene and estrogen were applied to the ThESC cell line for 24 h. After the treatment MTT assay, FACS analysis and immunofluoroscence method were conducted. Results The results of this study for the first time demonstrated the cytotoxic and apoptotic effects of raloxifene and estrogen on human endometrial stromal cell line suggesting the involvement of the inner, mitochondrial apoptotic pathway. Conclusions Our results demonstrated apoptotic effects of investigated drugs in the ThESC cell line through increasing the Bax/Bcl-2 ratio and activation of caspase 3.

Older Hypertensive Patients’ Adherence to Healthy Lifestyle Behaviors

Abstract Non-pharmacological treatment including diet, body weight reduction, smoking cessation and physical activity, is very important part of hypertension treatment. The objective of this study was to investigate the adherence to healthy lifestyle behavior in the representative sample of the older hypertensive patients, and to investigate factors associated with adherence in the studied older population. The study was conducted on random sample of 362 long term hypertensive (> five years) patients older than 65 years of age, at Health Care Center of Kragujevac. Adherence was assessed using the structured questionnaire for the analysis of the implementation of both hypertension and diabetes guidelines in the primary care. Both bivariate and multivariate analyses were conducted. Nearly 35% of examined patients were highly adherent; they exercised regularly, avoided smoking for at least five years and consumed special healthy diet prescribed for hypertension. Another 35.6% of the cases reported exercising regularly, 39.5% followed the recommended diet for the hypertension, while 23.4% of the patients have still consumed cigarettes. Multivariate logistic regression demonstrated that received counseling on healthy lifestyle behaviors by physicians and lack of education predicted high adherence to healthy lifestyle behavior. In order to improve adherence of elderly hypertensive patients to healthy lifestyle, strengthening patient-physician relationships through efforts to enhance communication may be a promising strategy to enhance patients’ engagement in healthy lifestyle behaviors for hypertension. Such an improvement could be achieved through the education of both the physicians and patients.

Enhanced cytotoxicity and apoptosis by raloxifene in combination with estrogen and methotrexate in human endometrial stromal cells

Endometrial hyperplasia is a condition that may lead to the development of endometrial carcinoma. Initially, changes of the endometrium are caused by the estrogens hyperstimulation that may lead to the development of an irregular bleeding and the infertility problems. Therapy of endometrial hyperplasia is limited to medical and surgical approaches. During the past decade, the new types of drugs were developed for the treatment of the endometrial hyperplasia. Here, for the first time, we investigated the cytotoxic effects of the various combinations of estrogen, raloxifene, and methotrexate in human ThESC cell line as a possible potential treatment of the endometrial hyperplasia. Our aim was to investigate and to determine the most efficient combination of investigated drugs in ThESC cells during 24‐hr period using MTT assay, FACS analysis, and immunofluorescence staining. Our results demonstrated that the combination of raloxifene with methotrexate efficiently induced both the cytotoxicity and apoptosis in ThESC cells when compared to their single effect, as well as to the effect of combined treatment of raloxifene with estrogen. The application of the low doses of methotrexate combined with raloxifene offers all advantages of a potential beneficial antitumor match in cancer chemoprevention and therapy.

Cushing’s syndrome diagnosed after delivery: a case report

IntroductionDuring normal pregnancy there are significant changes in hypothalamic-pituitary-adrenal axis, with increased levels of plasma cortisol and adrenocorticotropic hormone which sometimes reach values observed in patients with Cushing’s syndrome. Cushing’s syndrome (CS) is rarely encountered during pregnancy, but is associated with serious maternal and fetal complications.Case presentationA 31-year-old female was admitted to our institution four weeks after delivery. Physical examination revealed moon face, purple striae throughout the abdomen, bruising over the legs, a dorsocervical fat pad and hirsutism. She delivered a eutrophic preterm newborn at 34 weeks gestation, without any maternal or fetal complications during delivery. Imaging showed a mass in the right suprarenal gland with a normal pituitary. After four weeks the patient underwent a right adrenalectomy. The mass was eventually identified as an adrenocortical adenoma.ConclusionIn our case the diagnosis of CS was established only after pregnancy, which enabled the development of numerous adverse consequences secondary to increased plasma cortisol. If CS is recognized during pregnancy, treatment and its timing could be carefully chosen according to the patient’s individual characteristics.

Gallbladder emptying in patients with major depression: a case series.

INTRODUCTION Although several adverse effects of antidepressants on the gastrointestinal tract have been described (bleeding, constipation, dolichocolon), their influence on gallbladder motility was not investigated.The aim of our study was to investigate the effects of selected antidepressants on gallbladder emptying in patients with major depression. METHODS The study was set up as an open clinical trial, with the same intervention (ingestion of test meal provoking gallbladder emptying) undertaken in 112 patients with major depression. There were 30 patients not taking antidepressants (the control group), 25 patients taking amitriptyline, 30 patients taking maprotiline, and 27 patients taking fluoxetine. The volume of gallbladder in the study patients was measured by ultrasonography before the test meal, and 15, 30, 45 and 60 min after the meal. RESULTS 1 h after ingestion of the study meal, the amitriptyline group showed incomplete gallbladder emptying (F=10.829, df=3, p=0.000; mean residual volume 11.0±6.1 mL), while in the control, maprotiline and fluoxetine groups emptying of gallbladder was complete (mean residual volumes 5.0±3.3 mL, 5.6±3.7 mL and 5.7±2.3 mL, respectively). DISCUSSION In patients with cholecystitis, it would be wise to use antidepressants which do not impair gallbladder emptying, like maprotiline or fluoxetine, and to avoid amitriptyline.