Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube.

Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage-dependent channels for Na+ , K+ and Ca2+ , but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10-9  M/L to 1.4 × 10-6  M/L) produced concentration-dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10-8  M/L, r = 0.580, P < 0.05) (F = 2.980, df1  = 6, df2  = 28, P < 0.05). Paroxetine (from 1.2 × 10-9  M/L to 5.1 × 10-5  M/L) produced concentration-dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10-8  M/L, r = 0.500, P < 0.05) (F = 2.350, df1  = 9, df2  = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.

Calcitonin Gene-Related Peptide Receptor Blocker Inhibits Spontaneous Activity of Human Ureter.

Calcitonin gene-related peptide (CGRP) is present in nerve fibers that innervate the human ureter and may have important influence on the motility of this organ. The aim of our study was to investigate whether CGRP could affect the motility of an isolated human ureter. The tension and intraluminal pressure of the isolated ureteral segments were recorded and registered on a personal computer. Both phasic and tonic contractions of the isolated preparations were measured as area under the tension or pressure recordings. CGRP and CGRP fragment 8-37 were separately added to the organ baths in a cumulative way, thereby gradually increasing their concentration in the baths' solution. Alpha-CGRP did not affect either phasic, spontaneous activity or tone of isolated ureteral segments, as measured by both tension and intraluminal pressure. On the other hand, CGRP 8-37 caused concentration-dependent inhibition of spontaneous contractions of the isolated ureteral segments.

Angiotensin Receptor Blocker Losartan Inhibits Spontaneous Motility of Isolated Human Ureter.

BACKGROUND AND OBJECTIVES: Ureteral motility is essential for elimination of intraluminal stones, and it may be adversely affected by cardiovascular drugs that a patient is taking chronically. The aim of our study was to test whether ACE inhibitors and an angiotensin receptor blocker may influence spontaneous contractions of isolated human ureter. METHODS: Both phasic and tonic contractions of the isolated ureteral segments taken from 10 patients were measured as changes of the longitudinal tension or pressure recordings. Captopril, enalapril and losartan were separately added to the organ baths cumulatively. RESULTS: While enalapril (2.7 × 10-7-3.9 × 10-4 M) and captopril (6.1 × 10-7-2.7 × 10-3 M) did not affect either spontaneous activity or tone of isolated ureteral segments, losartan (2.9 × 10-7-4.2 × 10-4 M) caused concentration-dependent inhibition of spontaneous contractions of the segments (50 % effective concentration (EC50) = 13.46 ± 1.80 × 10-6 M; F = 10.72, r = 0.79, p < 0.001). CONCLUSIONS: Due to differences in molecular mechanism of action, angiotensin receptor blocker losartan does and ACE inhibitors captopril and enalapril do not inhibit spontaneous contractions of isolated human ureter.

Gestational choriocarcinoma of the cervix.

Choriocarcinoma is the most aggressive, malignant form of gestational trophoblastic disease and has varying incidence, increasing in patients older than 40 years. It usually develops after a malignant alteration in a molar pregnancy, but rarely after an abortion or normal or ectopic pregnancies. The most common localization is the uterus, but it can also be found rarely in the ovaries, fallopian tubes, vagina, vulva, cervix or pelvic region. A 38-year-old multiparous woman, with no complications in three previous labors and four miscarriages, presented to her gynecologist one year after the last miscarriage complaining of abnormal vaginal bleeding. Clinical examinations showed normal ultrasound and histopathology findings. Blood analysis demonstrated moderate anemia and low elevated serum b-human chorionic gonadotropin. Due to profuse hemorrhage and anemia after the curettage, the medical council decided that a total hysterectomy should be performed. Macroscopic examination of the post-operative material showed regular morphology of the uterus, fallopian tubes and ovaries. However, a whitish brown lesion with a maximum diameter of 22 mm was noted in a longitudinal section of the cervix. Using standard histopathology and immunohistochemical analysis, a cervical gestational choriocarcinoma was diagnosed. Knowledge of the characteristics of the choriocarcinoma is very important for accurate diagnosis and treatment, especially when the tumor is localized on the rare locations and where a high level of serum b-human chorionic gonadotropin is absent.

Population pharmacokinetics of carvedilol in patients with congestive heart failure.

The aim of this study was to derive population pharmacokinetic (PK) model for clearance (CL) of carvedilol in adult patients with chronic heart failure (CHF). Medication and demographic data were obtained from 52 Caucasian patients with CHF taking carvedilol. Population PK analysis was performed by nonlinear mixed-effects modeling (NONMEM) to estimate and identify different factors that could affect carvedilol CL. A total of 55 plasma concentrations were collected from 52 patients with mean age of 63.02 ± 11.95 years and total body weight (TBW) of 77.96 ± 13.46 kg. Total daily doses of carvedilol in the target population had wide range of variability (6.25-50 mg), followed by high variability of drug plasma concentrations (1-59.07 ng/mL). The typical mean value for carvedilol CL, estimated by the base model, in the target population was 43.8 L/h. The TBW, concomitant therapy with digoxin, and tobacco using were determinants of a derived population model. The final regression model for the CL of carvedilol is: [Formula: see text] Our results suggest that the TBW, concomitant therapy with digoxin, and tobacco using are the main subjects of carvedilol PK variability.

Dystocia as a cause of untimely cesarean section.

BACKGROUND/AIM: One of the most frequent indications for cesarean section is dystocia. It is impossible to predict, difficult to identify and coincident with the rapid expiry of the expected time, so it is important to point out some mistakes in expecting vaginal delivery. The aim of this study was to examine the frequency and the length of dystocia-related cesarean delivery, as well as the vitality of the newborn immediately after birth. METHODS: A prospective 3-year study was conducted including a total number of 6470 deliveries regardless of whether they were completed using cesarean section after an unsuccessful attempt of spontaneous vaginal delivery or not. The Apgar score, a proved useful tool for the assessment of the vitality of newborn children in the first minute, was used. RESULTS: On the basis of the established indications, 653 (10.10%) of deliveries were completed using cesarean section. Dystocia was the third most common indication for cesarean section (16.38%). Deliveries in which dystocia was established as a diagnosis lasted much longer (p = 0.030) which resulted in weaker vitality of newborn children (p = 0.000) compared to the deliveries ended by spontaneous vaginal delivery. CONCLUSION: This study shows that deliveries caused by dystocia last much longer and newborn children are of weaker vitality compared to other deliveries caused not by dystocia. Decisions concerning cesarean section must be made in a timely fashion.

Ovarian endometroid adenocarcinoma in pregnancy.

BACKGROUND: Ovarian cancer is very rare in pregnancy. It is mainly of epithelial origin, low grade and low malignant potential. CASE REPORT: We presented a patient in which ultrasound confirmed the presence of clearly limited tumor in the left ovary when she was eight weeks pregnant. The results of 4D Color Doppler showed a central type of tumor vascularisation with resistance index (IR) less than 0.5. The Consultancy Board in Gynecology of the Institute for Oncology and Radiology of Serbia decided to remove the patient's left adnexa and intensively monitor the pregnancy period. The operation (Adnexectomia lateralis sinistra) was performed at 18th week of gestation. Histopathological analysis showed adenocarcinoma invasivum, endometroid well-differentiated type (histological grade I, nuclear grade 2). In 37th week of gestation, the patient gave birth to a male child by cesarean section. In the next 3 years the patient had no subjective interference, laboratory tests and ultrasonographic findings were normal. CONCLUSION: Ovarian cancer in pregnancy is usually asymptomatic and diagnosed during routine clinical and ultrasound examination. The color Doppler technique have particular importance in the diagnosis of pathological blood supply in tumors and in indication of malignant ovarian mass.

[Breech presentation at term: caesarean section or vaginal delivery?].

INTRODUCTION: Term breech presentation occurs in 3-4% of all deliveries. Most obstetricians are completely sure how to end delivery when the foetus is in breech presentation, by caesarean section as the only option. OBJECTIVE: The main goal of the paper was to present the method of delivery for term breech presentation analyzed at the Hospital of Gynaecology and Obstetrics and Clinical Centre in Kragujevac, and parameters that influenced the decision on the method of choice to perform delivery with the foetus in breech position. METHODS: During a three-year prospective study, the course and outcome of all term breech deliveries were under followup. The study involved only deliveries in breech presentation, with a trial of labour ending by vaginal delivery, while elective caesarean section due to breech presentation of the foetus was not included in the study. The following parameters were compared: body mass, newborn's first minute Apgar score and head circumference, gestational maturity, gestational age, delivery duration, maternal level of education and maternal parity. RESULTS: Of total 6,470 deliveries, 653 (10.10%) were finalized by caesarean section. Of these, there were 202 (3.12%) term breech presentations, of which 72 (35.64%) women had caesarean and 130 (64.36%) vaginal delivery. A difference was detected in newborn's body mass and head circumference, delivery duration, maternal level of education and parity between pregnancies terminated surgically in comparison to vaginal delivery, while pregnancy duration, maternal age, first minute Apgar score, and most significantly, perinatal morbidity did not show any difference regardless of the method of delivery for term breech presentation. CONCLUSION: With respect of all known parameters, vaginal delivery in breech presentation is also accepted.

[Histochemical and immunohistochemical analysis of ruptured atherosclerotic abdominal aortic aneurysm wall].

BACKGROUND/AIM: The main complication of the atherosclerotic abdominal aortic aneurysm (AAA) is her rupture that begins with lesion in intima and rupture. The purpose of this work was to determine immunocytochemical and morphofunctional characteristics of the cells in aortic wall in ruptured atherosclerotic abdominal aortic aneurysm. METHOD: During the course of this study, 20 samples of atherosclerotic AAA were analyzed, all of them obtained during authopsy. The samples were fixed in 4% formalin and embedded in paraffin. Sections of 5 microm thickness were stained histochemically (of Heidenhain azan stain and Periodic acid Schiff--PAS stain) and immunocytochemically using a DAKO LSAB+/HRP technique to identify alpha-smooth muscle actin (alpha-SMA), vimentin, myosin heavy chains (MHC), desmin, S-100 protein, CD45 and CD68 (DAKO specification). RESULTS: The results of our study showed that ruptured atherosclerotic AAA is characterized by a complete absence of endothelial cells, the disruption of basal membrane and internal elastic lamina, as well as a presence of the remains of hypocellular complicated atherosclerotic lesion in intima. On the plaque margins, as well as in the media, smooth muscle cells (SMCs) are present, which express a alpha-SMA and vimentin (but without MHC or desmin expression), as well as leukocyte infiltration, and a large number of foam cells. Some of the foam cells show a CD68- immunoreactivity, while the others show vimentin- and S-100 protein-immunoreactivity. Media is thinned out with a disorganized elastic lamellas, while adventitia is characterized by inflammatory inflitrate (infection). CONCLUSION: Rupture of aneurysm occurs from the primary intimal disruption, which spreads into thinned out media and adventitia. Rupture is caused by unstable atherom, hypocellularity, loss of contractile characteristics of smooth muscle cells in intima and media, neovascularization of the media, as well as by the activity of the macrophages in the lesion.