Search

The structures and thermal and electrorheological properties of coordination polymers with the formula Zn[O2P(OC6H4R)2]3 [R = OMe, NO2 or C(O)OEt] are reported.

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.

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.

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

Polymorphism of four biologically active 3-(4,5-diaryl-4H-1,2,4-triazole-3-yl)propenoic acid derivatives has been investigated. Traditional solution-based solid-state forms screening revealed three anhydrous forms of 3-[4-phenyl-5-(2-pyridyl)-4H-1,2,4-triazole-3-yl]propenoic acid. Noteworthy, two pairs of concomitant polymorphs were detected for this system. Two other compounds were found to be dimorphic. The molecular and crystal structures of all obtained crystal forms were established by single-crystal X-ray diffraction. The resulting crystal structures were analyzed in terms of molecular conformation, intermolecular interaction patterns, and crystal packing motifs. The experimental studies were supported by extended lattice and interaction energy calculations. It was found that the carboxylic group adopts the anti conformation in all studied forms and is involved in the intramolecular O–H···Ntriazole hydrogen bonding. In consequence, the association modes are dominated by the weak C–H···O, C–H···N hyd...

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 ± 13,18 μg/g tissue, women: 96,06 ± 11,98 μg/g tissue. Cadmium concentration(mean ± SD); men: 309 ± 103,71 ng/g tissue, women: 348,5 ± 255,71 ng/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.

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 Suwałki (Poland), Grodno (Belarus) or Lviv (Ukraine) universities taking sociodemographic variables into account.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.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.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.

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. 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. ET-1 enhanced the spontaneous contractile activity of the myometrium more powerfully (p s< 0.01) than AVP. Preincubation with exogenous NO weakened ET-1- or AVP-induced increases in this contractile activity (p s< 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 s< 0.01). 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.

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 series of new 1,2,4-triazole derivatives with methacrylic acid moiety were synthesized and characterized by NMR and IR spectroscopy as well as X-ray crystallography. The influence of newly synthesized compounds on the inflammation on the level of cytokine production and the proliferation of human peripheral blood mononuclear cells (PBMC) were experimentally evaluated. Obtained triazoles showed antiproliferative activity and diverse effects on cytokine production. Two compounds demonstrated potentially anti-inflammatory activity and comparable effects with ibuprofen.

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.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 (p0.001) attenuated the contractile response of the uterine strips to oxytocin in concentrations higher than 10-8 mol/L.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.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.

Heterocyclic oxime ethers play a significant role in organisms due to their biological activity. Lipophilicity is an important parameter that may affect biological activity of the compounds 1-(benzofuran-2-yl)ethan-1-one oxime and its nine biologically active ethers. The relationship between the structure and lipophilicity parameters (log kw values) of the ten compounds is here described. Reversed phase high performance liquid chromatography (RP-HPLC) method was used having methanol, 2-propanol and acetonitrile as organic modifiers of the mobile phases. Both experimental (log kw) and calculated (log P) parameters showed to be strongly positively correlated. The weakest correlation with all the data was for the log kw methanol. For all of analyzed compounds, log kw values are smaller than 5 (except for analyses carried out in methanol), and this result corresponds to the Lipinski’s rule in the range of lipophilicity. Therefore, in the case of their use as drugs, they will be probably active after oral application.

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); 1 day 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 1 day before CABG was 12.36 ± 2.84 μmol/L (mean ± SD), 1 month after CABG 40.07 ± 10.95 μmol/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.

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.

We aimed to prospectively examine β-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 β2- and β3-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, β-adrenoceptor antagonists caused varied effects for β2- or β3-adrenoceptor agonists. Our experiments demonstrate that ovarian cancer, alone or as synchronous ovarian–endometrial cancer, substantially alters uterine contractility in response to β-adrenoceptor agonists. Electronic supplementary material The online version of this article (doi:10.1007/s12576-016-0500-1) contains supplementary material, which is available to authorized users.

To evaluate the involvement K+ channels in the relaxation induced by exogenous nitric oxide, after preincubation with L-arginine analogue L-NA in the human nonpregnant myometrium. The activity of myometrial strips, obtained from 60 premenopausal hysterectomised women, mounted in an organ bath was recorded under isometric conditions using force transducers with digital output. Concentration-response curves to DEA/NO after inhibition of endogenous NO were constructed in the absence and presence of soluble granulate cyclase and K+ channels’ blockers. The responses were quantified by calculating the area under the curve, the amplitude and frequency of the contractions. The inhibition of NOS results in slight but significant attenuation of the myometrium strips response to DEA/NO. Pre-treatment with both sGC inhibitors after preincubation with L-NA did not counteract the DEA-NOinduced relaxation of the spontaneous contractions of the myometrial strips. Application of blockers of different types of K+ channels to the myometrial strips significantly attenuated relaxing effect of cumulative DEA/NO administration in all cases. The present data indicate that even when endogenous production of NO is inhibited, the DEA/NO induced relaxation of human non-pregnant myometrium without involving the cGMP pathway.

The activity of fungicide agents containing a quinazolinone ring was described using the quantitative structure-activity relationship (QSAR) model by applying it to data taken from literature. The title compounds exhibit two important types of activity against certain fungal pathogens, i.e. activity against yeast and activity against filamentous fungi. A correlation between both antifungal activities (e.g. FA(yst) and FA(ff)) and physicochemical parameters such as the logarithm of the n-octanol/water partition coefficient (log P), the polarizability (P), the global minimum energy (TE), the energy difference between the frontier molecular orbital (DELH) and the molar refractivity (MR), was established using multiple linear regression. The molecular descriptors of the antifungal agents were obtained by quantum chemical calculations combined with molecular modeling calculations. Statistical analysis shows that the antifungal activity depends mainly on the calculated partition coefficients, log P, of the compounds. Bi-parametric models reveal that antifungal activity relates linearly to log P and P.

Nitric oxide (NO) is known to be an important relaxant of contractile activity in various muscles including the human uterine arteries. It has been suggested that NO plays a role in modulation of vascular action of arginin vasopressin (AVP), a strong vasoconstrictor of the human uterine arteries. Therefore, the purposes of this study were to investigate an involvement of endogenous NO in regulation of responses of the human intrauterine arteries to AVP and examine the effect of exogenous NO on contractions of the human intrauterine arteries evoked by AVP. Pretreatment of the artery rings with L-NA, an inhibitor of NO synthase significantly increased the resting force and enhanced the artery responses to AVP. The opposite effect has been observed after administration of 10(-6) mol/L sodium nitroprusside (SNP). Pretreatment of the artery rings with 10(-7) M CTX, a blocker of Ca2+-sensitive potassium channels with large conductance, did not change significantly their responses to ANT. Glibenclamide (1.5 10(-6) mol/L), a blocker of ATP-dependent potassium channels and apamin (10(-8) M), a specific blocker of Ca2+-sensitive potassium channels with small conductance strongly enhanced the maximum responses of the artery rings to AVP. Pretreatment with CTX significantly decreased the relaxation induced by SNP while apamin attenuated the sensitivity to SNP resulted in rightward shift of the concentration-response curve to SNP. In conclusion, this study indicates that: NO plays a role in regulation of both the vascular tone of the human intramyometrial arteries and their response to AVP. Ca2+-sensitive K+ channels with small and large conductance are involved in the SNP-induced relaxation of these arteries. The pathways of this relaxation cannot be sufficiently explained at this moment and need further investigation. (C) 2007 Elsevier Inc. All rights reserved. (Less)

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.

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 Cu2+ ions does not abolish the ability of OXT to interact with oxytocin receptors and stimulate myometrial contraction in vitro.

Immunohistochemical localization and distribution of endothelin (ET-1) and nitric oxide synthase (eNOS) were investigated in precollector and collector lymphangions of lymphatic vessels leaving the ovary and were found in the vascular subovarian plexus (mesovarium) as well as in those emanating from the oviductal isthmus and uterine horn (mesosalpinx and mesometrium, respectively) forming the paraovarian lymphatic plexus in the broad ligament of the uterus during different phases of the estrous cycle in pigs. The polyclonal antibody for ET-1 and the monoclonal antibody for eNOS isoform were used for studies on the light-microscopic level. Immunoreactivities to both ET-1 and eNOS were observed in the endothelial cell cytoplasm of precollector and collector lymphangions and were not demonstrated in smooth muscle cells of the lymphatics examined. In the endothelium, the intensity of immunostaining for ET-1 and eNOS was found to be estrous phase-dependent and differed between precollector and collector lymphangions. In general, immunoreactivity to ET-1 was more intense in the endothelium of shrunken lymphangions, whereas that for eNOS was more intense in lymphangions with the large lumen. These results suggest that ET-1 and eNOS can play a role in mechanisms regulating the vascular contractile activity promoting lymph flow during the estrous cycle in the porcine broad ligament.

2-Phenyl-5-(2,4-dihydroxybenzene)-1,3,4-thiadiazole (4), 2-(2-pyridyl)-2,4-dihydroxybenzene-1,3,4-thiadiazole (5), N(1)-2,4-dihydroxybenzenecarbothio-N(3)-phenyl-benzamidrazone (6) and N(1)-2,4-dihydroxybenzenecarbothio-N(3)-phenyl-2-picoline-amidrazone (7) were prepared and tested for their antimycotic activity. The chemical structures were confirmed by IR, 1H-NMR, EI-MS and elemental analysis. The minimal inhibitory concentration (MIC) values against dermatophytes, yeasts and moulds were determined for the estimation of potential activity in vitro. The strongest fungistatic activity for compound 5 in relation to dermatophytes was found with MIC 0.48-0.99 microg mL(-1).

The role of calcium (Ca(2+)) released from intracellular stores and the entry of extracellular Ca(2+) for vasopressin (AVP)-induced responses in large and small, human, intramyometrial arteries was investigated. There was no statistical difference as revealed by pD(2) values (-log EC(50)), in the sensitivity of large and small vessels to AVP. Nimodipine caused an inhibition of contractions induced by low concentrations (10(-10) mol/l) of AVP in both types of vessels but, at higher concentration (>10(-10) mol/l), whereas responses in small arteries were diminished, in large arteries they remained unchanged. In Ca(2+)-free solution, responses of large and small arteries to potassium and to 10(-10) mol/l AVP were abolished. With 10(-6) mol/l AVP, response in small arteries was completely inhibited, whereas in large arteries it was reduced by approximately 50%. Additional experiments were done on large arteries. Thapsigargin (TSG), which causes depletion of internal Ca(2+) stores, caused a significant reduction in responses. Following treatment with TSG, responses to AVP in Ca(2+)-free solution were almost completely inhibited but arteries responded again when incubated in normal physiological salt solution. The results indicate that in contrast to large arteries, small arteries are highly dependent on extracellular Ca(2+). Response of large arteries showed considerable dependence on Ca(2+) stored internally particularly, for maximum activation.

Nitric oxide (NO), an important endogenous substance, is known to be a strong relaxant of smooth muscle, including myometrium. It has been postulated that the relaxing effect of NO on smooth muscle is achieved by the stimulation of soluble guanylyl cyclase, which leads to an increase in the cyclic guanosine 3',5'-monophosphate (cGMP) levels and hyperpolarization of the cellular membrane. The aim of our study was to investigate the involvement of K+ATP channels in the mechanism of cGMP-independent nitric oxide-induced inhibition of contractile activity of the nonpregnant human myometrium, obtained at hysterectomy. Nitric oxide's influence on contractile activity was recorded in the presence of methylene blue and glybenclamide, blockers of soluble guanylyl cyclase and K+ATP channels, respectively. Nitric oxide, generated by the NO donor DEA/NO, caused a dose-dependent inhibition of the spontaneous contractile activity of human nonpregnant myometrium. Preincubation with methylene blue (5 microM) did not prevent NO-induced relaxation of uterine strips, while 1.5 microM glybenclamide blocked this effect. Our results indicate that nitric oxide relaxes human non-pregnant uterus through K+ATP channels, independent of the cGMP pathway.

This study aimed to compare the relaxant properties of BRL 37344 with p2-adrenoceptors agonist ritodrine on the contractility of human nonpregnant myometrium.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.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.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.

Nitric oxide (NO) is a potent inhibitor of spontaneous contractions of the human non-pregnant myometrium; however, the precise mechanism by which NO causes the myometrial smooth muscles to relax remains unclear. The aim of this study was to determine the influence of methylene blue (MB) on myometrial contractions and the response of the myometrium to DEA/NO in vitro. Concentration-response curves to DEA/NO were constructed in the absence and presence of MB (5x10(-6), 10(-4) and 10(-2) mol/l) and 5x10(-3) mol/l cystamine. Cystamine did not counteract the DEA/NO-induced relaxation of the myometrial strips. MB itself, excluding the lowest concentration, caused noticeable changes in spontaneous activity. The changes involved a concentration-dependent increase in the frequency of contractions, and a decrease in their amplitude. In conclusion, our results confirm that NO relaxes the human myometrium via a cGMP-independent mechanism. The results obtained in the presence of MB may be misleading because of its complex influence on myometrial contractile activity.

The asymmetric unit of the title compound, 2C18H16N4O2·H2O, consists of two organic molecules and one solvent molecule. The symmetry-independent organic molecules have slightly different conformations: the 1,2,4-triazole ring forms dihedral angles of 84.61 (4), 89.68 (5) and 22.38 (6)°, respectively, with the 2-propenecarbocylic, p-tolyl and 4-pyridyl groups in one independent molecule, and 71.35 (4), 82.13 (5) and 24.82 (6)°, respectively, in the second. In the crystal, molecules ralated by the 21 screw axes are assembled via O—H...N and O—H...O hydrogen bonds into infinite chains and these are linked by further O—H...N hydrogen bonds into undulating sheets parallel to the bc plane. Adjacent sheets are connected by weak C—H...O interactions, forming a three-dimensional structure.

Background Copper may influence in vivo and in vitro uterine activity. Recent evidence has shown that cupric ions can easily form complexes with oligopeptides like arginine vasopressin (AVP). The high complex stability in vitro suggests a possibility of complex formation in vivo, in the uterus of intrauterine device users. Methods In vitro isometric contractions were recorded in uterine tissues from nonpregnant premenopausal women undergoing hysterectomy and the effect of Cu-AVP complex on isolated human nonpregnant myometrium was investigated. Results The addition of the Cu(II)-AVP complex to the bath medium led to a concentration-dependent increase of the contractile activity. The activity was somewhat lower for the complex (−log EC 50 of 8.5 ± 0.2, n = 7) than for AVP, but the difference was not statistically significant (p = 0.11). The maximal responses (E max ) of the myometrium strips treated with AVP and the Cu (II)-AVP complex did not differ significantly. To assess the effect of presence of Cu (II) in the medium on tissue response to AVP, myometrium strips were preincubated for 20 min in the medium containing 10 −6 mol/L Cu(II) prior to the administration of AVP. The chosen Cu (II) concentration was below the threshold of effect on the spontaneous contractile activity in our experiments. Conclusion The presence of cupric ions in the bath caused a significant leftward shift in the concentration-response curve to AVP.

The aim of this study was to investigate whether apamin-sensitive K(+)channels play a role in the NO induced relaxation of the human pregnant myometrium. Concentration-response curves for sodium nitroprusside (SNP) (10(-9)-10(-4)M) were constructed in the absence and presence of 10(-8)M apamin and 10(-7)M charybdotoxin (CTX). Preincubation with apamin resulted in a significant attenuation of the relaxation caused by SNP, while pre-treatment with CTX insignificantly decreased the SNP induced relaxation. Our findings suggest that apamin-sensitive K(+)channels exist in the human pregnant myometrium and play a role in modulation of the myometrium response to NO donors

The authors developed a method of measuring the fractal box dimension of the human eyeball movement. They found a fractal property in schizophrenic subjects (n=10) and normal controls (n=10). The value of the fractal box dimension for schizophrenic patients differs from the results obtained in the control group.

There is now considerable evidence for the involvement of K+ channels in nitric oxide (NO) induced relaxation of smooth muscles including the myometrium. In order to assess whether apamin-sensitive K+ channels play a role in NO – induced relaxation of the human uterus, we have studied the effect of specific blockers of these channels on the relaxation of myometrium from non-pregnant women. In vitro isometric contractions were recorded in uterine tissues from non-pregnant premenopausal women who had undergone hysterectomy. Apamin (10 nM) and scyllatoxin (10 nM) did not alter spontaneous myometrial contractions. However, 15-min pretreatment of the myometrium strips with apamin completely inhibited relaxation caused by diethylamine-nitric oxide (DEA/NO). The pretreatment with scyllatoxin significantly reduced (about 2.6 times) maximum relaxation of the strips induced by DEA/NO (p < 0.05). These results strongly suggest that, beside Ca2+ and voltage dependent charybdotoxin-sensitive (CTX-sensitive) K+ channels, apamin-sensitive K+ channels are also present in the human non-pregnant myometrium. These channels offer an additional target in the development of new tocolytic agents.

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.