Stress Perception and Coping Strategies of Students on Both Sides of the EU's Eastern Border during the COVID-19 Pandemic.

The aim of the study was to compare the perception of stress and the characteristic coping-strategies among students in the context of the different anti-pandemic measures taken in Belarus, Poland, and the Russian exclave of Kaliningrad. A cross-sectional online survey using standardized questionnaires (Perceived Stress Scale-PSS-10 and Brief-COPE-Mini-COPE inventory) was conducted among 3113 students of seven universities in three neighboring regions on both sides of the eastern border of the EU. The groups that are the most prone to stress are the Polish and Russians students. Among the students from Belarus, 122 (13.7%) have high levels of stress symptoms. Among the respondents from Poland-238 (19.4%), and 191 (19.2%) from Kaliningrad have high levels of stress, respectively. The different approaches of the authorities to the COVID-19 pandemic diversified the choice of students' stress coping strategies. The behavior of the students from Kaliningrad and Poland was similar. The Belarusian students used active coping strategies less often, while an avoidance-focused style, and denial were more frequent. The neglect of restrictive anti-pandemic measures by the Belarusian students was manifested by a higher incidence of disease and minimal use of vaccinations.

Influence of substituents in aryl groups on the structure, thermal transitions and electrorheological properties of zinc bis(diarylphosphate) hybrid polymers.

The structures and thermal properties of three new hybrid one-dimensional (1D) polymers based on zinc bis(diarylphosphate)s containing p-substituted phenyl rings are reported. The crystal structures of Zn[O2P(p-OC6H4NO2)2]2 (1), Zn[O2P(p-OC6H4OMe)2]2 (2) and Zn[O2P(p-OC6H4CO2Et)2]2 (3) differ from that of their unsubstituted analogue, Zn[O2P(OPh)2]2 (ZnDPhP). Compounds 1 and 3 consist of tetrahedrally coordinated zinc cations connected by double bridges of phosphate groups (2+2 bridging mode) and form polymeric chains that are packed in a distorted hexagonal lattice with six closest neighbours. In compound 2 zinc cations are linked by alternating single and triple phosphate bridges (3+1 bridging mode) and the resulting chains, having only four closest neighbors, are packed in a distorted tetragonal manner. DFT computations revealed that the 2+2 bridging mode, even at the highest energy conformation, is more stable than the 3+1 one. Simultaneous Thermal Analysis, Raman spectroscopy and powder XRD (PXRD) studies show that pyrolysis of the studied hybrid polymers begins above 260 °C, leading to a mixture of zinc condensed phosphates and carbonaceous deposits that may have electron-conducting properties. DSC and PXRD studies provide evidence that crystalline domains in 2 and 3 rearrange and/or disappear at a much lower temperature (ca. 150 °C) leading to an isotropic liquid (in the case of 3) or an amorphous solid material (in the case of 2). Electrorheological measurements indicate that 1-3 are polarized in an external electric field, and the type of electrorheological effect depends on the type of functional group attached to the phenyl ring; this feature can be utilized in designing new electrorheological devices.

Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner.

Resveratrol, as a polyphenolic compound that can be isolated from plants, and also a component of red wine has broad beneficial pharmacological properties. The aim was to investigate the role of nitric oxide and potassium channels in resveratrol-induced relaxation of human gastric smooth muscle. Gastric tissues were obtained from patients who underwent sleeve gastrectomy for severe obesity (n = 10 aged 21-48; BMI 48.21 ± 1.14). The mechanical activity from the muscle strips was detected under isometric conditions as the response to increasing concentrations of resveratrol before and after different pharmacological treatments. Resveratrol caused an observable, dose-dependent gastric muscle relaxation. The maximal response caused by the highest concentration of resveratrol was 83.49 ± 2.85% (p < 0.0001) of the control. Preincubation with L-NNA, L-NAME, or ODQ did not prevent the resveratrol-induced relaxation. Apamin, glibenclamide, 4AP or tamoxifen, did not inhibit the relaxing effect of resveratrol, as well. In turn, blocking BKCa by TEA, iberiotoxin, or charybdotoxin resulted in inhibition of resveratrol-induced relaxation (91.08 ± 2.07, p < 0.05; 95.60 ± 1.52, p < 0.01 and 89.58 ± 1.98, p < 0.05, respectively). This study provides the first observation that the relaxant effects of resveratrol in human gastric muscle strips occur directly through BKCa channels and independently of nitric oxide signaling pathways. Furthermore, there is considerable potential for further extensive clinical studies with resveratrol as an effective new drug or health supplement to treat gastrointestinal dyspepsia and other gastric hypermotility disorders.

Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies.

OBJECTIVE: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. DESIGN: This was a controlled and prospective ex vivo study. SETTING: The work was conducted as a collaboration between 4 academic departments. MATERIALS AND METHODS: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. RESULTS: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). LIMITATIONS: These results require now to be placed into a firm clinical context. CONCLUSIONS: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

Quercetin relaxes human gastric smooth muscles directly through ATP-sensitive potassium channels and not depending on the nitric oxide pathway.

BACKGROUND: Quercetin has recently become a remarkably popular subject of research due to its broad beneficial pharmacological properties. The goal of our study was to observe its effects on contractility of human gastric smooth muscles in reference to the NO pathway and direct influence of potassium channels. METHODS: Tissues were obtained from patients undergoing sleeve gastrectomy due to morbid obesity (n = 10 aged 24-56; BMI 47.16 ± 1.84). The following parameters were evaluated in the recordings: area under the curve (AUC), average baseline muscle tone, and relative change in muscle contraction. KEY RESULTS: Quercetin induced noticeable, dose-dependent relaxation of the carbachol treated gastric strips. The substantial effect was noted at concentrations higher than 10-7  mol/L and maximal at 10-4  mol/L (81.82 ± 3.32%; n = 10; p < 0.0001) of the control. Neither NOS blockers nor guanylyl cyclase blockers had inhibitory effects on the relaxation of strips induced by examined polyphenol. Glibenclamide inhibited the relaxing effect of quercetin, significant at concentrations higher than 5⋅10-5  mol/L. Preincubation with charybdotoxin or apamin extended the relaxing effect of quercetin (from 10-6  mol/L). Tamoxifen, in turn, significantly increased muscle relaxation at all quercetin concentrations. CONCLUSIONS & INFERENCES: In conclusion, the current study was the first to show that quercetin-induced relaxation of human gastric smooth muscle occurs directly through K+ATP channels and independently to NO pathways. The present results suggest that quercetin is a potential nutraceutical in the treatment of functional gastrointestinal dyspepsia and other minor gastric muscle motility disturbance.

Intraoperative Peritoneal Interleukin-6 Concentration Changes in Relation to the High-Mobility Group Protein B1 and Heat Shock Protein 70 Levels in Children Undergoing Cholecystectomy.

The aim was the evaluation of IL-6 concentration in peritoneal lavage fluid of children which underwent cholecystectomy to ascertain if there is a difference in early inflammatory response depending on the type of surgical approach (open vs. laparoscopy). The analysis of high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70) was performed to find out if the source of IL-6 was related to tissue damage. IL-6 concentration in peritoneal lavage fluid samples, obtained at the beginning and at the end of the laparoscopic (N = 23) and open cholecystectomy (N = 14), was tested with a routinely used electrochemiluminescence assay. The concentrations of HMGB1 and HSP70 were analyzed with the use of an ELISA method. Statistical analysis was performed using the STATISTICA PL release 12.5 Program. The differences were assessed using the Mann-Whitney U test and Wilcoxon matched pairs test. Correlations were studied by using the Spearman correlation test. Our results demonstrated significant peritoneal lavage fluid IL-6 concentration growth measured at the end of the cholecystectomy as compared to the beginning, regardless of the type of the procedure. IL-6 growth during open cholecystectomy was greater compared to laparoscopic cholecystectomy (62.51-fold vs. 3.19-fold). IL-6 concentration did not correlate with HMGB1 and HSP70, which indicate that the significant growth of this cytokine was not related to mechanical tissue damage due to surgical procedure. A clinical significance of the study could be related to the fact that the evaluation of IL-6 concentration in peritoneal lavage fluid may be useful to assess an early local inflammatory response.

The effects of extended nitric oxide release on responses of the human non-pregnant myometrium to endothelin-1 or vasopressin.

BACKGROUND: Uterotonic mediators: endothelin-1 (ET-1), arginine vasopressin (AVP), and nitric oxide (NO) play important roles in the regulation of uterine contractility. We hypothesize that NO affects both ET-1 or AVP. Therefore, this study investigated the involvement of extended exogenous NO release in the regulation of responses of the human non-pregnant myometrium to ET-1 and AVP. METHODS: Specimens were obtained from 10 premenopausal women, undergoing hysterectomy for benign gynecological disorders. Responses of the myometrial strips to ET-1 or AVP in the absence and presence of an exogenous NO donor (diethylenetriamine; DETA/NO; 10-4 mol/L) were recorded under isometric conditions. To inhibit endogenous NO, a competitive inhibitor of NO synthase, L-NG-nitroarginine (L-NNA) was added to the organ bath. RESULTS: ET-1 enhanced the spontaneous contractile activity of the myometrium more powerfully (p < 0.01) than AVP. Preincubation with exogenous NO weakened ET-1- or AVP-induced increases in this contractile activity (p < 0.05). However, unexpected results were obtained after preincubation with L-NNA and with DETA/NO then added. Both ET-1 and AVP induced augmented contractile effects in almost all concentrations compared with the responses to these peptides alone or after NOS synthase inhibition (both p < 0.01). CONCLUSIONS: This study demonstrated for the first time that extended incubation with a NO donor influences the uterine muscle response evoked by ET-1 and AVP. Both endogenous and exogenous NO is involved in the control of the uterine responses to ET-1 or AVP of non-pregnant myometrium. Furthermore, both peptides stimulate increased uterine contractility when the local imbalance between the constrictive and relaxing mediators takes place.

Assessment of Socio-Health Determinants of Dental Check-Ups Among Students of Selected Polish, Belarusian and Ukrainian Universities.

PURPOSE: Systematic dental check-ups play a vital role in maintaining good oral health. When oral examinations are performed as regularly as recommended, the dentist may be the first health care provider to diagnose a health problem in its early stages. The aim of the study was to identify and assess determinants of dental check-up among students of Suwalki (Poland), Grodno (Belarus) or Lviv (Ukraine) universities taking sociodemographic variables into account. MATERIALS AND METHODS: Data were collected from 2013 to 2016 among freshman students of Polish (n = 1245), Belarusian (n = 1012) and Ukrainian universities (n = 688). The study was performed with the diagnostic survey method, using a questionnaire designed by the authors. In order to identify the determinants of dental check-ups, logistic regression analysis was applied. RESULTS: A majority of students visited a dentist for a check-up at least once a year (32.7% twice a year; 41.0% once a year). Women from Belarus (OR 1.690; 95% CI: 1.256-2.273) or Poland (OR 1.832; 95% CI: 1.374-2.442) underwent dental check-ups with a higher frequency, as did students whose financial situation was very good or good (Belarus: OR 1.574; 95% CI: 1.184-2.093 or Poland OR 1.604; 95% CI: 1.227-2.096). Variables related to students' health behaviours, i.e. smoking, alcohol consumption or drug use, were not statistically significant. CONCLUSIONS: The frequency of stomatological control examinations among students from Polish, Belarusian or Ukrainian universities is high. The frequency of dental examination among students is conditioned by sociodemographic factors. Regular check-ups at the dentist are more prevalent for women and those students from Polish or Belarusian universities who rated their financial situation as good or very good. In Belarusian or Ukrainian respondents, maintaining healthy eating habits was a positive predictor of dental check-up attendance, while in Polish students self-evaluation of health was a negative one.

Congenital vesicouterine fistulas-A PRISMA-compliant systematic review.

AIMS: Vesicouterine fistulas (VUFs) are infrequent abnormal connections between the bladder and the uterine cavity or cervical canal, being mainly sequelae of repeat Cesarean sections. Exceedingly rare are congenital VUFs. This is a systematic review of available world data aimed to characterize congenital VUFs and better understand the mechanism(s) of their formation. METHODS: The PubMed® database via MEDLINE® search engine was explored from its inception to March 2018. Relevant studies were identified using selected Medical Subject Heading-based terms. This was further supplemented by cross-referencing and handsearching. Retrieved literature was evaluated in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, guidelines. RESULTS: A total of 6561 articles were identified of which 10 were analyzed. Three VUFs accompanied broader syndromes of congenital defects. A lack of patency at the level of the vagina was present in all assessed cases. Unilateral renal agenesis was confirmed in four of eight (50%) verified patients. Hence, unilateral kidney agenesis was related to a lesser degree (P = 0.0186) than vaginal atresia to VUF. The principal features of these fistulas were as follows: partial or complete vaginal atresia resulting in primary amenorrhea, menouria present since menarche, and urinary continence. CONCLUSIONS: This review provides the first systematic evidence that congenital VUFs are chiefly associated with concomitant vaginal atresia. The symptomatology of such VUFs is consistent with that of type I acquired fistulas.

The effect of the release of exogenous nitric oxide on the responses of the pregnant human myometrium to oxytocin.

OBJECTIVE: Introduction: Currently there is insufficient evidence to support the routine administration of nitric oxide donors in the treatment of threatened preterm labor. An understanding of the role that nitric oxide plays in the management of threatened preterm labor may lead to more effective treatment and prevention. The aim of our study was to examine the involvement of exogenous nitric oxide release in regulating responses of the human pregnant myometrium to oxytocin. PATIENTS AND METHODS: Material and methods: Biopsies of human myometrial tissue during pregnancy were obtained from 8 pregnant women, aged 21-35 years. The responses of the specimens to oxytocin in the absence and presence of a DETA/NO were recorded under isometric conditions. Preincubation with exogenous nitric oxide significantly (p<0.001) attenuated the contractile response of the uterine strips to oxytocin in concentrations higher than 10-8 mol/L. RESULTS: Results: The inhibition of nitric oxide synthesis alone or in combination with DETA/NO incubation did not significantly change the oxytocin contractile effect in the concentration-response curve. Moreover, there was no significant variation in the mean value for log EC50 for oxytocin between the group with oxytocin alone and other groups. CONCLUSION: Conclusions: We present evidence in support of the hypothesis that continuous nitric oxide supply to the human pregnant myometrium environment attenuates its response to oxytocin but only when endogenous production of nitric oxide is not impaired.

The sources of calcium for noradrenaline-induced contraction in the human thoracic internal artery.

The aim of the present study was to examine the contribution of intracellular and extracellular calcium sources in contraction caused by noradrenaline (NA) of the human internal thoracic artery (ITA) in vitro. Distal segments of ITA were obtained from 20 patients (aged 38-73, at the time of routine coronary artery surgical revascularization (CABG)). Contractile responses to 10-6 mol/L NA in the physiological salt solution and in Ca2+-free solution without and after incubation with 10-6 mol/L thapsigargin (TSG) were recorded under isometric conditions. Responses of ITA rings to 1 µM NA without incubation with TSG accounted (% of reaction to 80 mM KCl) 224.70 ± 14.06% in PSS solution, 141.30 ± 8.66% in Ca2+-free solution, and 80.03 ± 1.71% after PSS restoration and were statistically significantly different (p < 0.0001, one-way ANOVA). Responses of ITA rings to 1 µM NA with 1 µM TSG accounted (% of reaction to 80 mM KCl) 114.50 ± 2.79% in Ca2+-free solution and 36.70 ± 2.38% after PSS restoration. Responses in Ca2+-free solution and after PSS restoration without and with TSG were statistically significantly different (p = 0.0257 and p < 0.0001, respectively-t test). ITA contraction is caused by calcium derived not only from the SR and the extracellular matrix. The delivery of calcium to the space surrounding tissue does not immediately deliver calcium to the myofilaments.

Altered uterine contractility in response to ß-adrenoceptor agonists in ovarian cancer.

We aimed to prospectively examine ß-adrenoceptor-mediated uterine contractility in women suffering from gynecological malignancies. Myometrial specimens were obtained from non-pregnant women undergoing hysterectomy for benign gynecological disorders, and ovarian, endometrial, synchronous ovarian-endometrial, and cervical cancer. Contractions of myometrial strips in an organ bath before and after cumulative dosages of ß2- and ß3-adrenoceptor agonists with preincubation of propranolol, SR 59230A, and butoxamine were studied. All agonists induced a dose-dependent attenuation for uterine contractility in endometrial or cervical cancer, similar to that observed in the reference group. Contradictory effects were observed for ovarian cancer alone or in combination with endometrial cancer. CL 316243 or ritodrine abolished the relaxation, whereas BRL 37344 increased the uterine contractility in ovarian cancer. Moreover, ß-adrenoceptor antagonists caused varied effects for ß2- or ß3-adrenoceptor agonists. Our experiments demonstrate that ovarian cancer, alone or as synchronous ovarian-endometrial cancer, substantially alters uterine contractility in response to ß-adrenoceptor agonists.

Levels of vitamin C In the blood plasma patients treated with coronary artery bypass grafting increases significantly after surgery.

One strong risk factor of coronary artery disease (CAD), which affects the levels of vitamin C in the blood is cigarette smoking. The supplementary effects of coronary artery bypass grafting (CABG) is smoking cessation by patients. Therefore, the aim of this study was to examine the level of vitamin C in the blood plasma one day before and one month after CABG. Human blood were collected from 20 patients (men); 1day before and 1 month after CABG. All patients were smoker and after CABG they declared their not smoking. The concentration of vitamin C in the blood plasma was assayed by FIA method with spectrophotometric detection. The mean value of the vitamin C concentration 1day before CABG was 12.36±2.84µmol/L (mean±SD), 1 month after CABG 40.07±10.95µmol/L (mean±SD). The average increase in the concentration of vitamin C was 3.27±0.73 times (mean±SD) and showed significant positive correlations (Pearson r=0.657, p=0.002). It should be consider incorporating the recommendations of preoperative smoking cessation for at least one month prior to CABG and/or additional supplementation. In addition it would be relevant to monitor the level of vitamin C in the patients' blood in the preoperative period.

Beta-adrenoceptors in obstetrics and gynecology.

One hundred and twenty years after the description of extracts from the adrenal medulla, the use of beta-blockers and beta-agonists evolved from antianginal drugs and tocolytics to ligand-directed signaling. Beta-blockers in the fields of obstetrics and gynecology have so far been limited to the consideration of continuing treatment of disorders of the cardiovascular system and other dysfunctions that started before pregnancy. Studies in recent years have shown that beta-adrenoceptor signaling might be crucial in carcinogenesis and metastasis, apoptosis and anoikis. On the other hand, the use of beta-adrenoceptor agonists in tocolysis is, as yet, the primary method for inhibiting premature uterine contractions. Unfortunately, the efficacy of current pharmacological treatment for the management of preterm labor is regularly questioned. Moreover, studies related to non-pregnant myometrium performed to date indicate that the rhythmic contractions of the uterus are required for menstruation and have an important role in human reproduction. In turn, abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. The benefits of the use of beta2-adrenoceptor agonists in dysmenorrhea are still unclear and should be balanced against a wide range of adverse effects recognized with this class of medication. The ideal tocolytic agent is one which is effective for the pregnant or non-pregnant woman but has no side effects on either the woman or the baby. Looking to the future with both caution and hope, the potential metamorphosis of beta3-adrenoceptor agonists from experimental tools into therapeutic drugs for tocolysis warrants attention.

Levels of l-ascorbic acid and cadmium in the saphenous vein of patients with coronary artery disease are negatively correlated.

BACKGROUND: The aim of this study was the simultaneous determination of levels of cadmium and l-ascorbic Acid (AA) in human saphenous vein (SV) used in coronary artery bypass grafting (CABG) and check whether there is a relationship between these levels. METHODS: Human SV were collected from 40 patients (20 men and 20 women; age, 40-75 years) at the time of routine coronary artery surgical revascularization. The concentration of cadmium in the tissue was determined according to the GF AAS-atomic absorption method. The concentration of AA was assayed in supernatant by FIA method with spectrophotometric detection. RESULTS: AA concentration (mean±SD); men: 98,7±13,18µg/g tissue, women: 96,06±11,98µg/g tissue. Cadmium concentration(mean±SD); men: 309±103,71ng/g tissue, women: 348,5±255,71ng/g tissue. Correlations among concentrations of AA and cadmium were insignificant negative in the group of men (Pearson r=-0,1504, p=0,5269) and in the group women (Pearson r=-0339, p=0144). CONCLUSIONS: Negative correlations among concentrations of AA and cadmium in human SV obtained in our study may indicate a protective effect of this vitamin in relation to toxic cadmium.

Cu(II) complexation does not affect oxytocin action on pregnant human myometrium in vitro.

OBJECTIVE: Copper may influence the in vivo and in vitro uterine activity. Recent evidence shows that cupric ions can easily form complexes with oligopeptides like oxytocin (OXT). The high complex stability in vitro suggests a possibility of complex formation in vivo. STUDY DESIGN: In vitro isometric contractions were recorded in uterine tissues from pregnant women undergoing caesarean sections and the effect of OXT and the Cu-OXT complex on isolated human pregnant myometrium was investigated. RESULTS: In the concentration range from 10(-14) to 10(-6)M of OXT alone, pre-formed Cu-OXT complex, and OXT following sample preincubation with Cu(II) salt, nosignificant differences were observed for the following parameters of pregnant uterine smooth muscle contraction: the area under the curve, frequency and amplitude of contraction. CONCLUSION: The binding of Cu(2+) ions does not abolish the ability of OXT to interact with oxytocin receptors and stimulate myometrial contraction in vitro.

Potassium induced contraction of the internal thoracic artery in vitro is time related: the potential consequences in the analysis of the mechanism of the spasm after coronary artery bypass grafting and in the analysis of the results of in vitro studies.

The aim of the present study was to examine how, under in vitro conditions, the human left internal thoracic artery (LITA) reacts to contractile agonist:potassium chloride (KCL) as a function of time, as well as to examine whether a change in the LITA reactivity can correlate with the occurrence of the refractory vascular spasm (RVS). Distal segments of LITA obtained from 33 patients aged 38-73, at the time of routine coronary artery surgical revascularization (CABG). Contractile response to 80 mmol K(+) was recorded under isometric conditions. In 16 (48,5 %) LITA segments, contractile reaction to K(+) after experiments ranging 1-10 h were registered. No contractile response even after 10 h of incubation was observed in 17 (51.5 %) LITA segments. Between 120 and 300 min after the beginning of the experiment, the reaction was maximum and amounted up to 300 % control reaction, then decreased. First, with respect to in vitro research isolated by LITA rings, while analyzing the results of the research, one should take into consideration the possibility that during the research, the functional state of the tissues changes and in particular its sensitivity to depolarization of the cell membrane. Second, the change in the sensitivity to depolarization of the cell membrane of the smooth muscles' LITA might be the potential mechanism causing the occurrence of the postoperative spasm after the CABG treatment.

[Levonorgestrel-releasing intrauterine system Mirena® (Bayer) for the prevention and treatment of endometrial adenocarcinoma and the incidence of other malignancies in women]. / Wplyw systemu wewnatrzmacicznego uwalniajacego lewonorgestrel Mirena® (Bayer) na prewencje i leczenie raka gruczlowego blony sluzowej macicy oraz na inne nowotwory zlosliwe u kobiet.

The use of hormone-releasing intrauterine devices has been on the increase for the last three decades. To date, evidence of their long-term efficiency is available. The aim of the present paper was to briefly review beneficial prophylactic effects of the levonorgestrel-releasing intrauterine system on the incidence of a variety of malignancies in women. Such an influence is of a particular importance in the light of the currently observed increased prevalence of endometrial and cervical adenocarcinomas. Low-dose releasing intrauterine systems are also available, but the hard evidence-based medical data have been derived primarily for Mirena® (Bayer) device, which topically releases from 20 to 14 pg of levonorgestrel daily. Consequently the risk of developing endometrial carcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk To a lesser extent, the intrauterine system decreases the risk for cervical adenocarcinoma and squamous cell carcinoma, as well as ovarian, pancreas, and lung carcinomas. In one population-based study Mirena® increased the risk for breast carcinoma by approximately 20%, whereas a number of other studies failed to demonstrate such a hazard. In the recent decades of the increased predominance of insulin resistance and obesity and an occurrence of hormone-dependent carcinomas at earlier age, a broad application of levonorgestrel-releasing intrauterine systems may become a particularly important component of primary prevention of malignancies in women. Both obese and overweight patients seem perfect candidates for such a hormonal intervention.

Differences in the effects of beta2- and beta3-adrenoceptor agonists on spontaneous contractions of human nonpregnant myometrium.

OBJECTIVE: This study aimed to compare the relaxant properties of BRL 37344 with p2-adrenoceptors agonist ritodrine on the contractility of human nonpregnant myometrium. MATERIAL AND METHODS: The activity of myometrial strips mounted in an organ bath was recorded under isometric conditions using force transducers with digital output. Contractility before and after cumulative additions of both uterorelaxants and with preincubation with beta-adrenoceptor antagonists bupranolol, propranolol, and butoxamine were studied. RESULTS: Both BRL 37344 (10(-10)-10(-4) mol/L) and ritodrine (10(-10)-10(-5) mol/L) decreased the area under curve, or AUC, value (log/C50 -6.45 +/- 0.18 and -8.71 +/- 0.35, respectively), and the degree of inhibition of spontaneous contractile activity was similar (< 30%). However BRL 37344 decreased the mean frequency of contractions, whereas ritodrine decreased the mean amplitude of contractions. The inhibition of contractions by BRL 37,344 was partially antagonized by bupranolol and propranolol, but not with butoxamine. The inhibition by ritodrine was counteracted by all these antagonists. CONCLUSIONS: The effects of BRL37344 and ritodrine on human nonpregnant myometrium are quantitatively similar in respect to the inhibition of spontaneous contractility yet are also distinct due to their substantially different influences on contraction parameters. Our data indicate that beta3-adrenoceptor activation is not the sole effect of BRL 37,344 on this tissue.