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Plant extracts and nutraceuticals are the most ancient and widespread form of medication employed by the general population. The pomegranate is a prehistoric, mystical and a highly differentiated fruit. Moreover, pomegranate is found in some medicinal systems as a cure for a variety of illnesses. Pomegranate has been used for a long time for nutraceutical purposes. Current research indicates that the most medicinally useful pomegranate components include ellagitannins, anthocyanins, anthocyanidins, flavonoids, estrogenic flavonols and flavones. Also pomegranate seed oil contains 64-83% punicic acid. Therefore, this review focussed on the effects of punicic acid, particularly those that have been reported such as the anticarcinogenic, antioxidant, antiinflammatory and antidiabetic effects. As nutraceuticals appear to play a major role in the prophylaxis of various diseases, punicic acid could be an important and phytoconstituent among these agents. Nutraceuticals are generally regarded as safe to use with lower incidence of side effects. In spite of all these reports it is obvious that there is a clear need for more clinical studies. [ABSTRACT FROM AUTHOR]

Screening of antibacterial activity and toxicity of 22 aqueous plant extracts from 17 Turkish plants was conducted. Antibacterial activity was performed with six bacteria including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Staphylococcus epidermidis. Extracts of Tussilago farfara leaves, Helichyrsum plicatum flowers, Solanum dulcamara aerial parts and Urtica dioica leaves gave the best inhibitory activity against S. pyogenes, S. aureus and S. epidermidis. Of the 22 plant extracts, 20 extracts displayed toxicity (LC50 was <1000 mg L-1) in the brine shrimp bioassay. For radish seed bioassay, two different determinations (root length and seed germination) were performed with a comparison between two concentrations (50,000 mg L-1 and 10,000 mg L-1). At low concentration (10,000 mg L-1), S. dulcamara aerial parts and Primula vulgaris leaf extracts were observed to inhibit the root length more than the other plant extracts. Also, the most inhibitive plant extract for seed germination was obtained with S. dulcamara aerial parts. [ABSTRACT FROM AUTHOR]

Recent evidences have shown that phenolic structures can exert many biological functions. Ellagic acid (EA), a phenolic compound, has been suggested to have cardioprotective effects. In this study we aimed to investigate the effect of EA on cardiac Ca2+ currents and contractility in rat ventricular myocytes and to elucidate the underlying mechanisms of these changes.All records measured from the freshly isolated ventricular myocytes of rat heart at 36±1 °C by using whole-cell configuration of voltage clamp. Cell shortening was measured by detecting the length of edges with video-based system at 1 Hz frequency of field stimulation. We found that EA dose dependently reduced Ca2+ currents with EC50= 23 nM. EA decreased voltage dependent L-type Ca2+ current density (ICaL) but it didn't affect the inactivation and reactivation parameters. Inhibition of adenylate cyclase (AC) with SQ-22536 (10 μM) and using probucol (antioxidant, 5 μM) had no effect on EA modulation of ICaL. Interestingly, blockage of nitric oxide synthase (NOS) with L-NAME (500 μM) and guanylate cyclase (GC) with ODQ (1 μM) abolished inhibitory effect of EA on ICaL. Moreover, EA dose dependently blunted fractional shorthening of ventricular myocytes.In conclusion, EA affects ionic and mechanical properties of ventricular myocytes starting at nanomolar concentrations. Our findings indicated that EA suppresses ICaL and exerts negative inotropic effects through activation of NOS-GC-cGMP pathway. Accordingly, EA may be useful in pathophysiological conditions whereby these effects might be favorable such as hypertension and ischemic heart diseases. [ABSTRACT FROM PUBLISHER]

Purpose: The use of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) as the first choice of surgical route for patients scheduled to undergo conventional laparoscopy is still being debated. We aimed to evaluate and compare the outcomes of the "vNOTES first" strategy in benign gynecological cases., Methods: All benign gynecological surgeries were initiated using vNOTES during the study period, regardless of the difficulty. Surgical outcomes, short-term patient satisfaction and sexual pain were compared between hysterectomies, adnexal and diagnostic procedures. Visual Analog Score (VAS), Patients Global Impressions of Improvements scale (PGI-I) and Female Sexual Function Index (FSFI) were used to assess the postoperative pain, satisfaction and sexual pain, respectively., Results: A total of 105 vNOTES procedures were performed during the study period: 63 (60.58%) adnexal procedures, 36 (34.62%) hysterectomies, 5 (4.81%) diagnostic procedures and one (0.96%) myomectomy. The median 24th hour VAS scores for adnexal, hysterectomy, and diagnostic procedures were 1.29 ± 1.41, 2.06 ± 2.08, and 2.6 ± 2.41, respectively. The satisfaction rate was 96.19% at the 1st postoperative week and 97.14% at the first month. There was either no change or a slight improvement in the patients' total score on the FSFI/pain domain before and after surgery. There were two conversions (1.9%) from vNOTES to laparoscopy and laparotomy, and two (5.56%) bladder injuries in hysterectomy cases., Conclusion: Implementing the vNOTES technique as an initial approach for all benign gynecological surgeries seems feasible, safe and satisfactory, even in those with a non-prolapsed or enlarged uterus and those that have previously undergone abdominal surgery. The pain scores were found to be low and patients stated a high satisfaction with no or better change in their sexual life., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study was to determine the scope of knowledge, attitudes, and behaviors of pregnant women about the coronavirus disease 2019 (COVID-19) vaccine., Materials and Methods: A total of 886 pregnant women were recruited for the study. A cross-sectional questionnaire was conducted on these selected participants. Data about past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV-2 infection of closely related people, and deaths due to COVID-19 among their relatives were questioned., Results: The rate of vaccination was higher (64.1%) in pregnant women with higher education levels. Informing about the vaccine, especially by health professionals, showed that the rates of vaccination (25%) increased (p<0.001). In addition, a significant increase was observed in vaccination rates with increasing age and financial income (p<0.001)., Conclusion: The main limitation of our study is that the vaccine, which was approved for "emergency use", was just started to be administered to pregnant women during the study. Our findings show that our target audience, low-income, low-education, younger pregnant women should be given more attention than those who apply to the doctor for routine follow-up., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)

Objective: To present coronavirus disease-2019 (COVID-19) related maternal mortality in relation to Delta and Omicron waves and to investigate the role of lung ultrasound (LUS) in estimating mortality., Materials and Methods: This retrospective cohort study was conducted in the obstetrics and gynecology clinic of a tertiary pandemic hospital between March 2020 and January 2022. The hospitalized pregnant women with COVID-19 diagnosis and maternal deaths were studied in relation with Delta and Omicron waves. The relationship between LUS scores of hospitalized patients and maternal mortality was explored., Results: Thousand and sixty-five pregnant women were hospitalized because of COVID-19 infection. Fifty-one (4.79%) of these patients had critical sickness, 96 (9.01%) of them had severe illness, 62 (5.82%) of them were admitted to the intensive care unit and 28 (2.63%) of all hospitalized pregnant women had died. Of the 1.065 patients, 783 (73.5%) were hospitalized before the Delta wave and the maternal mortality rate was 1.28% (10/783), 243 (22.8%) were hospitalized during the Delta wave and the maternal mortality rate was 7% (17/243) [relative risk (RR)=5.478, 95% confidence interval (CI) (2.54-11.8), z=4.342, p<0.001]. During the Omicron wave 39 (3.66%) patients were hospitalized and the maternal mortality rate was 2.56% (1/39). Maternal mortality rates, according to LUS scores, were 0.37% (1/273) for LUS 0, 0.72% (2/277) for LUS 1, 2.58% (10/387) for LUS 2 and 11.72% (15/128) for LUS 3 respectively (LUS 3 vs. others; maternal mortality: RR=8.447, 95% CI (4.11-17.34), z=5.814, p<0.0001). There were no vaccinated patients in the study cohort., Conclusion: The maternal mortality rate was relatively high, particularly during the Delta wave at our referral center. The Delta wave, delayed vaccination and vaccine hesitancy of pregnant women might have important roles in maternal mortality. Higher LUS scores should warn clinicians of an increased risk of maternal death., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by Turkish Society of Obstetrics and Gynecology, Turkish Journal of Obstetrics and Gynecology published by Galenos Publishing House.)

Inhalation anesthetics have been shown to cause neurodevelopmental disorders and neurotoxic effects. In this study, we aimed to investigate the effect of resveratrol on the possible neurotoxic effect of sevoflurane and the brain-derived neurotrophic factor (BDNF) pathway in newborn rats. The animals were divided into four groups: control, sevoflurane, sevoflurane+resveratrol 25 mg/kg, and sevoflurane+resveratrol 50 mg/kg. The groups that received anesthesia were given 3% sevoflurane for 2 h on the postnatal seventh, eighth, and ninth days. Control gas was applied to the control group. The Morris water maze (MWM) test was performed on postnatal 35th day. After performing the open field test on the postnatal 41st day, the animals were dissected, and the hippocampal BDNF levels were determined by Western blot method. In the MWM test, there was a significant decrease in the time spent in the target quadrant in the sevoflurane anesthesia group compared with control group. This reduction was reversed with the resveratrol pretreatment. Sevoflurane exposure significantly decreased hippocampal BDNF levels compared with the control group. The resveratrol 25 mg/kg pretreatment did not reverse this reduction, whereas resveratrol 50 mg/kg ameliorated this impairment. Sevoflurane did not cause any significant difference in the rats' performance in the open field test. However, 50 mg/kg resveratrol pretreatment caused a statistically significant increase in this performance. Our results showed that sevoflurane impaired learning and memory functions in newborn rats and resveratrol reversed this deterioration. Also BDNF might play a role in this beneficial effect of resveratrol.

Aim: To compare the outcome of double ovarian stimulation (DOS) with follicular phase ovarian stimulation (FPS) per started cycle in poor ovarian responders (PORs)., Methods: A total of 204 PORs who underwent ovulation induction for in vitro fertilization, cryopreservation of all embryos available, and frozen embryo transfer cycle were retrospectively analyzed. Of those, 146 received single FPS, and 58 received DOS. All viable embryos were cryopreserved and subsequently transferred within 1-6 months., Results: The number of oocytes collected and the number of mature oocytes per started cycle were higher in the DOS group compared to the FPS group (6.0 ± 1.9 vs. 2.8 ± 1.3 and 4.3 ± 1.3 vs. 2.2 ± 1.2, respectively, p = 0.001). Clinical pregnancy rate and live birth rate per started cycle were also significantly higher in the DOS group than the FPS group (41.4% vs. 16.4% and 36.2% vs. 15.1%, respectively, p < 0.001). The cancellation rate of embryo transfer due to no viable embryo was significantly lower in the DOS group (10.3%) than the FPS group (40.4%) (p = 0.001). In the DOS group, numbers of oocytes (3.2 ± 1.2 vs. 2.7 ± 1.1, p = 0.006), MII oocytes (2.6 ± 1.0 vs. 2.1 ± 0.8, p = 0.001), and cryopreserved blastocysts (1.5 ± 0.8 vs. 1.1 ± 0.7, p = 0.002) were significantly higher in the luteal ovarian stimulation compared to follicular ovarian stimulation., Conclusions: Live birth per started cycle with DOS is superior to FPS in PORs. Luteal phase stimulation contributes to improving pregnancy rates in these patients., (© 2021 Japan Society of Obstetrics and Gynecology.)

The objective of this study was to investigate proliferation, apoptosis, and antiapoptotic molecule expression in endometrial cells of reproductive-aged women with and without type II diabetes mellitus (T2D). In this case-control study, a total of 80 endometrial tissue specimens from reproductive-aged women (35 in the proliferative phase and 45 in the secretory phase) were examined. The age and body mass index (BMI) were matched between the groups. Formalin-fixed and paraffin-embedded endometrial tissue samples were used for immunohistochemistry analysis. The presence of proliferation was evaluated with Ki-67 expression, antiapoptotic function of cells was evaluated with Bcl-2 expression, and apoptosis was evaluated with terminal deoxynucleotidyl transferase (TUNEL) immunoreactivity in both the glandular epithelium and stroma of endometrial tissue samples from women with and without T2D. Ki-67 expression in the glandular epithelium and Bcl-2 expression in both the glandular epithelium and stroma were significantly higher in endometrial tissue samples of women in the T2D group than the control group (p = 0.0008, p = 0.0022, and p = 0.0261, respectively). TUNEL immunoreactivity was significantly lower in the glandular epithelium of women in the T2D group than the control group (p = 0.0001). Glandular Ki-67 expression correlated positively with BMI, use of insulin, and hemoglobin A1c level (p = 0.0034, p = 0.0154, and p = 0.0011, respectively). Glandular Bcl-2 expression correlated positively with BMI and duration of T2D (p = 0.0090 and p = 0.0109, respectively). Stromal Bcl-2 expression correlated positively with duration of T2D (p = 0.0069). TUNEL immunoreactivity in the glandular epithelium correlated negatively with duration of T2D (p = 0.0340) and positively with the use of oral antidiabetic agents (p = 0.0226). Compared to age and BMI-matched controls, women with T2D experienced increased cell proliferation and decreased apoptosis in the glandular epithelium and increased antiapoptotic function in both the glandular epithelium and stromal cells. High BMI values in women with diabetes seemed to contribute to increased cell proliferation and increased antiapoptotic function in the glandular epithelium but not the stromal cells.

Objectives: Aromatherapy has become popular in pain control in recent years compared with other complementary methods. Lavender ( Lavandula angustifolia Miller) is a fragrant essential oil used in aromatherapy for its antibacterial, antifungal, muscle-relaxing, and analgesic effects. The smell of lavender oil, known for its soothing effect on adults, has not been adequately investigated in regards to pain control in premature infants. The purpose of our study was to assign the effect of the scent of lavender oil on pain in preterm infants during heel lancing. Design: A double-blind randomized controlled clinical study. Settings/Location: The study was conducted in a third-level neonatal intensive care unit of Bezmialem Vakif University Hospital from March 2019 to November 2019. It consisted of two groups. Subjects: Sixty-one premature babies (24-37 weeks of gestation) were enrolled in the study. Interventions: Heel stick sampling for metabolic screening was used for both study groups. The interventions were performed by two experienced nurses. Heart rate, oxygen saturation, and the baby's facial expression were recorded by a camera 3 min before the intervention, during the sampling, and 3 min after the procedure. After collecting the data, the head researcher and the assistant researcher separately watched the videos and scored them by using the Premature Infant Pain Profile-Revised (PIPP-R). Outcome measures: The difference of pain scores (PIIP-R) between two groups. Results: There was a statistically significant difference between the two groups in terms of PIPP-R scores during and after the sampling ( p  = 0.008 and p  = 0.03 respectively). The PIPP-R scores at the beginning of the procedure were not found to be significantly different between the groups ( p  > 0.05). Conclusions: Inhalation of lavender scent is effective in pain control in premature infants. It is safe and low cost; it does not interfere with medical care.

Objective: The aim of the study was to determine the effects of age, gender and season on vitamin D status in healthy urban population at reproductive age. Also, we investigated the distribution of population into different groups regarding 25(OH)D levels., Methods: Serum 25(OH)D levels of 21,317 participants: 5,364 men (25.1%) and 15,953 women (74.8%), aged between 18-45 years, applying to two medical centres for check-up located in the same city were retrospectively analyzed. Group I consisted of 14,720 participants (11,257 women and 3,463 men) in the first centre and Group II consisted of 6,597 participants (4,696 women and 1,901 men) in the second centre., Results: The mean 25(OH)D levels did not differ between women and men in both groups: 23.4 (SD = 14.4) and 23.1 (SD = 12.6) in Group I, and 22.6 (SD = 15.9) and 23.1 (SD = 14.3) in Group II, respectively, (p > 0.05). Similar trends exhibiting lower mean 25(OH)D levels at younger ages and higher levels at later ages were observed in both groups; a seasonal variation of 25(OH)D levels was observed in both genders with the highest levels in August and September and the lowest levels from February through April; percentages of women with 25(OH)D level of < 5 ng/ml were significantly higher than of men in Group I (1.4% vs. 0.2%, respectively, p < 0.001) and in Group II (4.1% vs. 1.1%, respectively, p < 0.001)., Conclusion: There is a slight increase in serum 25(OH)D levels from 18 through 45 years of age in healthy population. The seasonal variation of 25(OH)D levels is prominent in both genders with men having slightly lower levels in some months of winter and higher levels in summer as compared to women. The prevalence of women having 25(OH)D levels less than 5 ng/ml is higher than that of men.

Background: Endometriosis is an estrogen-dependent inflammatory disease that often causes infertility and chronic pelvic pain. Although endometriosis is known as a benign disease, it has demonstrated characteristics of malignant neoplasms, including neoangiogenesis, tissue invasion, and cell implantation to distant organs. Octamer-binding protein 4 (Oct-4) is a molecular marker for stem cells that plays an essential role in maintaining pluripotency and self-renewal processes in various types of benign and malignant tissues. CD44 is a multifunctional cell surface adhesion molecule that acts as an integral cell membrane protein and plays a role in cell-cell and cell-matrix interactions. E-cadherin is an epithelial cell-cell adhesion molecule that plays important role in the modulation of cell polarization, cell migration, and cancer metastasis. The aim of this study was to investigate the expression patterns of Oct-4, CD44, and E-cadherin in eutopic and ectopic endometrial tissues from women with endometrioma compared to control endometrial tissues from women without endometrioma., Methods: In the present study, Oct-4, CD44, and E-cadherin expressions were evaluated in eutopic and ectopic endometrial tissue samples from women with endometrioma (n = 32) and compared with those of control endometrial tissue samples from women without endometrioma (n = 30)., Results: Immunohistochemical expression of Oct-4 was significantly higher in the ectopic endometrial tissue samples of women with endometrioma than in the control endometrial tissue samples (p = 0.0002). Conversely, CD44 and E-cadherin expressions were significantly lower in the ectopic endometrial tissue samples of women with endometrioma than in the control endometrial tissue samples (p = 0.0137 and p = 0.0060, respectively). Correlation analysis demonstrated significant correlations between Oct-4 expression and endometrioma cyst diameter (p = 0.0162), rASRM stage (p = 0.0343), and total rASRM score (p = 0.0223). Moreover, CD44 expression was negatively correlated with the presence of peritoneal endometriotic lesions (p = 0.0304) while E-cadherin expression was negatively correlated with the presence of deep infiltrating endometriosis (p = 0.0445)., Conclusions: Increased expression of Oct-4 and decreased expression of adhesion molecules in endometriotic tissues may contribute to the development and progression of endometriosis.

Background: COVID-19 is a novel type of the coronavirus family with an incompletely described clinical course. Little is known about the psychological aspects, particularly for vulnerable populations including pregnant women. Objectives: To understand the attitude, concerns, and knowledge of the non-infected pregnant women toward the COVID-19 outbreak in order to constitute base data for detailed counseling and to develop targeted messages. Patients and methods: This cross-sectional survey research presented analysis of prospectively collected data yielded at a single tertiary "Coronavirus Pandemic Hospital" referral center for a ten days period following the first confirmed death due to the COVID-19 pandemic in Turkey. Non-infected women with a confirmed pregnancy over 30th gestational week were consecutively included. A patient-reported non-validated questionnaire formed by the expert committee that includes 15 specific questions was used. Non-infected, pregnant women over 30th gestational week who applied to the outpatient clinic were consecutively included. A total of 213 women were enrolled, 37 were excluded: 7 for being in the first trimester, 3 were illiterate, and 27 were Syrian refugees having difficulties in translation. Results: A total of 172 pregnant women were included. Overall, four women refused to participate to the survey (1.9%). The mean age was 27.5 ± 5.3 years. Median gestational week and parity were 35 ± 11 weeks and 1 ± 2, respectively. Pregnant women were observed to trust the authorities (65%) and the healthcare staff (92.4%), and their respect was increased (82.5%) during the outbreak. Majority of the women (87.2%) comply with the self-quarantine rules. Half of the women (52%) reported that they felt vulnerable and predominantly were concerned (80%). Approximately one-third of the women constantly keep thinking that they may get infected (35.5%) or they might get infected during/following the delivery or their baby might get infected after being born (42%). Half of the women (50%) were reported that they either had no idea about or think the breastfeeding is not safe during the outbreak. About 45% of the women were confused or had doubts about if the mode of delivery may be affected by the pandemic. Greater part of the participants does not know if COVID-19 might cause birth defects (76%) or preterm birth (64.5%). Counseling flow keys helping pregnant women to overcome misleads, regarding the COVID-19 outbreak is proposed. Conclusions: Non-infected pregnant women with a viable pregnancy at near term were observed to have positive attitude and compliance toward the COVID-19 outbreak and frontline healthcare staff; increased concern and vulnerability; and restricted knowledge about the pregnancy-related outcomes. While the clinical evidence was growing rapidly, this data may guide obstetricians and midwives to perceive what accurate information should be provided to the pregnant women.

Background: The emerging evidence for the asymptomatic carriers of SARS-CoV-2 infection emphasized the critical need for universal screening of pregnant women., Objectives: This study aimed to present the prevalence of overall and asymptomatic SARS-CoV-2 infection rates in pregnant women admitted to the hospital, and assess the diagnostic accuracy of maternal symptoms and lung ultrasound (LUS) findings in detecting the infection., Patients and Methods: This prospective cohort study was conducted at a single tertiary center in Istanbul, Turkey, for a month period starting from 27 April 2020. Women with a confirmed pregnancy regardless of the gestational week admitted to the obstetric unit with any indication were consecutively underwent LUS and PCR testing for SARS-CoV-2., Results: A total of 296 patients were included for the final analysis. The universal screening strategy diagnosed 23 pregnant women (7.77%) with SARS-CoV-2 infection. The rate of symptomatic and asymptomatic patients diagnosed with SARS-CoV-2 was found as 3.72% ( n  = 11) and 4.05% ( n  = 12), respectively. Four of nine women who underwent a second testing for SARS-CoV-2 upon abnormal LUS findings were found positive eventually (17.4%, n  = 4/23). The asymptomatic pregnant women with LUS score of 1 and those with normal LUS findings were considered as likely to be normal. Symptomatic patients with LUS score of 1 and those with score of 2 or 3 were considered as abnormal. On a secondary diagnostic performance analysis, the positive predictive value and the sensitivity were found as 44% and 47.8% for the triage based on maternal symptoms and, 82.3% and 60.9% for the triage based on LUS, respectively., Conclusion: A one-month trial period of universal testing for SARS-CoV-2 infection with RT-PCR in pregnant women who admitted to the hospital showed an overall and asymptomatic infection diagnose rate of 7.77% and 4%, respectively. Using lung ultrasound was found more predictive in detecting the infection than the use of symptomatology solely.

Purpose: This study investigated interobserver agreement in lung ultrasonography (LUS) in pregnant women performed by obstetricians with different levels of expertise, with confirmation by an expert radiologist., Methods: This prospective study was conducted at a tertiary "Coronavirus Pandemic Hospital" in April 2020. Pregnant women suspected to have coronavirus disease 2019 (COVID-19) were included. Two blinded experienced obstetricians performed LUS on pregnant women separately and noted their scores for 14 lung zones. Following a theoretical and hands-on practical course, one experienced obstetrician, two novice obstetric residents, and an experienced radiologist blindly evaluated anonymized and randomized still images and videoclips retrospectively. Weighted Cohen's kappa and Krippendorff's alpha tests were used to assess the interobserver agreement., Results: Fifty-two pregnant women were included, with confirmed COVID-19 diagnosis rate of 82.7%. In total, 336 eligible still images and 115 videoclips were included in the final analysis. The overall weighted Cohen's kappa values ranged from 0.706 to 0.912 for the 14 lung zones. There were only seven instances of major disagreement (>1 point) in the evaluation of 14 lung zones of 52 patients (n=728). The overall agreement between the radiologist and obstetricians for the still images (Krippendorff's α=0.856, 95% confidence interval [CI], 0.797 to 0.915) and videoclips (Krippendorff's α=0.785; 95% CI, 0.709 to 0.861) was good., Conclusion: The interobserver agreement between obstetricians with different levels of experience on still images and videoclips of LUS was good. Following a brief theoretical course, obstetricians' performance of LUS in pregnant women and interpretation of pre-acquired LUS images can be considered consistent.

Backround: HPV causes specific cell-mediated immunity in the cervix. Mononuclear cells such as helper T cells (CD4+), cytotoxic T cells (CD8+), and dendritic cells play a critical role in the initiation of the HPV-specific immune response and destruction of virus-infected cervical epithelial cells. The programmed cell death ligand 1 (PD-L1) gene encodes an immune inhibitory receptor ligand and overexpression of PD-L1 inhibits T-cell activation and cytokine production. The aim of this study was to investigate the expression of PD-L1 in cervical tissue and its correlation with clinicopathological findings., Methods: In this cross-sectional study, a total of 94 women who were referred for colposcopy due to abnormal Papanicolaou (PAP) test results and/or HPV positivity were evaluated. The presence of HR-HPV-DNA was analyzed using type- and gene-specific primers along with commercial real-time polymerase chain reaction. The cervical examination was done with a colposcope. Cervical biopsies were obtained from the areas that were evaluated as abnormal during the colposcopy. Histopathological result of cervical biopsies were defined as no intraepithelial neoplasia (CIN 0), mild CIN (CIN I), and moderate-to-high CIN (CIN II-III). All women were classified into four groups based on their HR-HPV positivity and cervical biopsy results: Group I (controls; n  = 29), HR-HPV (-) CIN 0; Group II ( n  = 21), HR-HPV (+) CIN 0; Group III ( n  = 20), HR-HPV (+) CIN I; and Group IV ( n  = 24), HR-HPV (+) CIN II-III. A semi-quantitative scoring system was used to evaluate the degree of Ki-67, p16, and PD-L1 immunoreactivity in the cervical tissue samples., Results: We found that PD-L1 expression in both mononuclear cells and in cervical epithelial cells gradually increases from the HR-HPV (-), CIN 0 group to the HR-HPV (+), CIN II-III group ( p  = 0.0003 and p  = 0.0394, respectively) and mononuclear PD-L1 expression was correlated with HPV type, initial Pap test results, HPV persistence, and CIN persistence or recurrence ( p  = 0.0180, p  = 0.0109, p  = 0.0042, and p  = 0.0189, respectively). Moreover, mononuclear PD-L1 expression was also correlated with Ki-67 and p16 immunoreactivity ( p  = 0.0432 and p  = 0.0166, respectively). Epithelial PD-L1 expression was only correlated with HPV type and the presence of HPV persistence ( p  = 0.0122 and p  = 0.0292, respectively)., Conclusion: During the initial evaluation of the cervical histology results, the assessment of PD-L1 expression-especially in mononuclear cells in cervical tissue samples-may provide more information on the progression of HR-HPV infection and its persistence., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Introduction: Preeclampsia is a systemic inflammatory disorder and a major cause of maternal and fetal mortality. Fractalkine (CX3CL1) is a member of the chemokine family with multiple functions in the organization of the immune system. It is up-regulated in inflammatory disorders. During inflammation, fractalkine enhances tissue destruction and inflammatory cell invasion. We aimed to investigate the alteration of fractalkine in the placental tissues of pregnant women with preeclampsia and the correlation of this alteration with clinicopathological variables. Materials and methods: Alteration of fractalkine in placental tissue specimens was determined immunohistochemically in 84 pregnant women: 33 women with mild preeclampsia, 19 women with severe preeclampsia, and 30 women with normal pregnancy. Preeclampsia was diagnosed using current guidelines of the American College of Obstetricians and Gynecologists. Results: Pregnant women with mild and severe preeclampsia revealed significantly higher fractalkine expression in syncytiotrophoblast cells than in the normotensive group ( p  = .0051 and .0001, respectively). The expression of fractalkine in preeclampsia was positively correlated with clinical parameters including the presence of intrauterine growth restriction, systolic and diastolic blood pressure, and 24-h urine protein, whereas it was negatively correlated with plasma albumin levels and placental weight. Additionally, the pathological changes in the placenta-including the presence of syncytiotrophoblast basement membrane thickening, increased number of syncytial knots, and vascularization of terminal villi were significantly correlated with fractalkine expression in pregnant women with preeclampsia. Conclusions: Overexpression of fractalkine in pregnant women with preeclampsia, as well as the correlation between fractalkine expression and poor pregnancy outcomes and placental histopathological changes may be associated with the underlying mechanisms of preeclampsia.

Our study aimed to determine the effects of losartan and PD123319 in ischemia-reperfusion (IR) injury in isolated perfused rat heart. The study used 40 male Wistar albino rats that were grouped as Control, IR, and IR treatment groups that received losartan (20 mg/kg), PD123319 (20 mg/kg), and losartan+PD123319. The hearts were attached to Langendorff isolated heart system by employing in situ cannulation method, and cardiodynamic parameters were recorded during the experiment. At the end of experiment, hearts were retained for biochemical analysis and all data were statistically evaluated. A partial recovery of cardiodynamic parameters was observed in all treatment groups. A significant increase in oxidative stress parameters were seen in the IR group, whereas all treatment groups exhibited lower increase. Furthermore, levels of all antioxidant parameters were significantly lower in the IR group, but higher in the treatment groups. Effects on all parameters were much more remarkable in the PD123319 group. Levels of angiotensin II and renin were increased ( P < 0.001) with IR application and decreased ( P < 0.001) with the treatment of both antagonists. In conclusion, treatment of losartan and PD123319 played a cardioprotective role against IR injury, PD123319 being more effective in this protection.

The aim of present study was to evaluate the antidepressant-like activity of ellagic acid (EA) in mice-forced swim test (FST) and tail suspension test (TST) and the possible role of brain-derived neurotrophic factor (BDNF) in EA's antidepressant-like effect. We found that EA and sertraline did not affect the spontaneous locomotor activity of mice. EA produced statistically significant decrease in immobility time as compared to vehicle group in TST. EA at 1 and 5 mg/kg doses did not produce any significant effect in immobility time as compared to vehicle group in FST. But EA produced significantly reduced immobility time at 2.5 mg/kg dose. EA treatment increased hippocampal BDNF level. This study demonstrates that EA is able to produce antidepressant-like effect in both TST and FST in mice. Moreover, the antidepressant-like effects of EA seems to be mediated by increased BDNF level in mice hippocampus.

The increase in cardiovascular disease prevalence with ageing has been attributed to several age-related changes such as changes in the vascular wall elasticity, the coagulation and haemostatic system and endothelial dysfunction, among other causes. There is a 50% increased mortality risk per 10-year increase in age starting at 65 years old. Here, we aimed to discuss pharmacological treatment in acute coronary syndrome (ACS) without persistent ST segment elevation myocardial infarction in the elderly. The main aim of ACS treatment in elderly people is at preventing ischemia, myocardial damage and complications. A meta-analysis suggests that invasive revascularization therapy is probably most useful in older patients. Dual antiplatelet therapy is currently the standard of care post-ACS. Platelet P2Y12 inhibitors are among the most commonly used medications worldwide, due to their established benefits in the treatment and prevention of arterial thrombosis. The main recommendation is to tailor antithrombotic treatment, considering body weight, renal function (Class I, level C) and careful evaluation of life expectancy, comorbidities, risk/benefit profile, quality of life and frailty when invasive strategies are considered (Class IIa, level A) on top of the different recommendations given for a general non ST elevation ACS population. It is obvious that potent P2Y12 inhibitors will continue to play an important role in pharmacological treatment for elderly ACS patients in the future.

Platelet aggregation is a crucial feature in coronary artery thrombus formation and is a major causative factor in both acute coronary syndromes (ACS) and reocclusion after percutaneous coronary interventions (PCI). The glycoprotein (GP) IIb/IIIa (αIIbβ3) integrin receptor is the pivotal mediator of platelet aggregation. In late 1990s, the introduction of GP IIb/IIIa inhibitors (GPI) was associated with a reduction of ischemic complication, and a clear clinical benefit in PCI during ACS, for both non ST-elevation (NSTE) and ST-segment elevation myocardial infarction (STEMI). The currently available GPI (abciximab, eptifibatide and tirofiban) tended to be replaced in the current therapy of STEMI by different agents and this is in part related to the effectiveness and to the potential adverse effects (thrombocytopenia and bleeding). There might be a certain level of variability among these agents and here we have reviewed only abciximab in detail. Interestingly, however, the story may not be entirely different from that of positive inotropic agents in the context of acute ischemia where the potent action to sustain left ventricular function had an arrhythmogenic counterpart to evaluate and take into consideration and therefore therapeutically it will always be necessary to weigh benefits and harms if actions are expected by relatively potent agents., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The most prevalent malignant ovarian neoplasms are epithelial ovarian cancers which is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of survivin and cycline D1 biomarkers in mucinous ovarian neoplasms and their correlations with clinicopathological variables in mucinous ovarian cancers. We analyzed pathological specimens of 98 patients with benign (n = 34), borderline (n = 22) and malignant (n = 42) mucinous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Immunohistochemical analysis revealed that survivin and cyclin D1 expressions were located primarily in the nucleus of ovarian tumor cells and relatively weaker cytoplasmic staining. Survivin expression was significantly higher in malignant tumors (88.1 %) than those found in borderline (18.2 %) and benign tumors (8.8 %) (p < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (100 %) compared to borderline (36.4 %) and benign tumors (5.9 %) (p < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant mucinous tumors. In terms of clinicopathological variables, tumor grade, FIGO stage and lymph node methastasis were associated with the expression of both biomarkers. Whereas age exhibited no different correlations in mucinous ovarian cancers. The expressions of survivin and cycline D1 are positively correlated with the malignant potential of mucinous ovarian neoplasms.

To evaluate the influence of sperm parameters on the outcome of intracytopiasmic sperm injection (ICSI) cycies in poor responaer women under the age of 35 years in a retrospective analysis in a fertility center., Materials and Methods: A total of 432 poor responder women who underwent ICSI cycles were evaluated. The interventions included ICSI and microdissection testicular sperm extraction (m-TESE). Main outcome measures included fertilization, cleavage, clinical pregnancy, and delivery rates., Results: Patients were di- vided into four groups according to the sperm parameters and the source of sperm; testicular spermatozoa obtained from men with azoospermia (group 1; n=26), severe oligoasthenoteratozoospermia (OAT) (group 2; n=35), OAT (group 3; n=104), and normal semen analysis (group 4; n=267). Average age of the women, antral follicle count, FSH level, male age, number of previous ICSI cycles, duration of infertility, and the maximal endometrial thickness were similar among the groups. In group 1, the fertilization rate was lower than those in all other groups. Cleavage, clinical pregnancy, and delivery rates were similar among the groups., Conclusions: Neither sperm parameters nor the source of spermatozoa affects delivery rate through ICSI in poor responder women < 35-years-old.

There is evidence that phenolic structure may have biological functions. Ellagic acid (EA), a phenolic compound, has been suggested to have cardioprotective effects. EA effects were investigated on cardiac Ca currents and contractility in rat ventricular myocytes to elucidate the underlying mechanisms. Freshly isolated ventricular myocytes from rat hearts were used. EA dose-dependently reduced Ca currents (ICaL) with EC50 = 23 nM, whereas it did not affect the inactivation and reactivation parameters. Inhibition of adenylate cyclase by SQ-22536 (10 μM) and probucol (5 μM) had no effect on EA modulation of ICaL. Nitric oxide synthase block by L-NAME (500 μM) and of guanylate cyclase by ODQ (1 μM) abolished EA inhibitory effects on ICaL. Moreover, EA blunted ventricular myocytes' fractional shortening in a concentration-dependent manner. In conclusion, EA affects ionic and mechanical properties of rat ventricular myocytes starting at nanomolar concentrations. EA suppresses ICaL and exerts negative inotropic effects through activation of NOS-GC-cGMP pathways. Thus, EA may be useful in pathophysiological conditions such as hypertension and ischemic heart diseases.

Screening of antibacterial and antitumour activities of 33 different extracts prepared with three types of solvents (water, ethanol and methanol) was conducted. The extracts were obtained from 11 different plant species grown in Turkey: Eryngium campestre L., Alchemilla mollis (Buser) Rothm., Dorycnium pentaphyllum Scop., Coronilla varia L., Onobrychis oxyodonta Boiss., Fritillaria pontica Wahlenb., Asarum europaeum L., Rhinanthus angustifolius C. C. Gmelin, Doronicum orientale Hoffm., Campanula glomerata L. and Campanula olympica Boiss. Antibacterial activity against six bacteria was evaluated: Escherichia coli , Pseudomonas aeruginosa , Klebsiella pneumoniae , Streptococcus pyogenes , Staphylococcus aureus and Staphylococcus epidermidis by using disc diffusion and well diffusion methods. S. aureus and S. epidermidis were most sensitive to the methanolic extract from A. europaeum . S. pyogenes was vulnerable to all used extracts of D. orientale . In addition, ethanolic or methanolic extracts of E. campestre , A. mollis , D. pentaphyllum , C. varia , R. angustifolius , C. glomerata and C. olympica displayed strong antibacterial activity against at least one of the tested gram-negative bacteria. The methanolic extract from R. angustifolius showed a broad-spectrum activity against both gram-positive and gram-negative bacteria. Antitumour activity was evaluated with Agrobacterium-tumefaciens -induced potato disc tumour assay. Best antitumour activity was obtained with the aqueous extract from A. europaeum and methanolic extract from E. campestre (100% and 86% tumour inhibition, respectively).

In recent years, the therapeutic use of non-drug substances such as herbal and medicinal foods is increasing progressively. Of these substances, Punica granatum L., which is an ancient and highly distinctive fruit, has been proposed for treatment of several different illnesses. Ellagic acid (EA) is one of those biological molecules found in pomegranate and may have therapeutic potential in many diseases. EA has been detected not only in pomegranate but also in a wide variety of fruits and nuts such as raspberries, strawberries, walnuts, grapes and black currants, and is becoming an increasingly popular dietary supplement over recent years. Similar to other ellagitannins (ETs), EA is quite stable under physiological conditions in the stomach. EA and ETs as active agents induce vasorelaxation, oxygen free radical scavenging, hypolipidemic, anti-inflammatory and anti-carcinogenic activities in various animal preparations call an attention to the need for designing adequate tests in humans to assess these potentially useful properties in diseased states.

The present study first investigated the mechanisms of vasorelaxation induced by ellagic acid (EA), which is one of the major compounds extracted from the pomegranate in the rat thoracic aorta. Male Wistar rats aged 10 to12 weeks weighing 250-350 g were used for the present study. The animals were killed by decapitation, and thoracic aortas were immediately excised and placed in Krebs solutions, cleaned, and freed from surrounding connective tissue. The isolated arteries were cut into rings (4- to 5-mm long) and placed in 20-mL tissue chambers filled with Krebs solution. Initially, the aortic rings were equilibrated for 60 min until a resting tension of 1.0 gr. After the equilibration period, aortic rings were firstly contracted with phenylephrine to increase tone. Once a stable contraction was achieved, EA (10(-8) to 10(-4)  M) was added cumulatively on aortic rings with or without endothelium into organ bath. To characterize the mechanisms involved in EA-induced vasorelaxant effect, the aortic rings were incubated with each inhibitor added to the bath for 30 min before phenylephrine was added to increase tone. The results of the present study have demonstrated in the rat thoracic aorta that EA causes vasorelaxations, which are partly modulated via endothelium-dependent mechanisms and through inhibition of calcium influx., (Copyright © 2012 John Wiley & Sons, Ltd.)

We investigated both the effect of levosimendan and the role of various potassium channels in carbachol-precontracted tracheal preparations samples obtained from guinea pig. The tracheas were cut into 0.5 cm wide rings and suspended in a 20 ml organ bath. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Levosimendan or cromakalim produced concentration-dependent relaxation responses in guinea pig tracheal rings precontracted by carbachol. Incubation of guinea pig tracheal rings with the ATP-dependent potassium channel (K(ATP)) blocker glibenclamide for 30 min significantly inhibited the relaxant responses to both levosimendan and cromakalim. The large conductance Ca(2+)-activated potassium channel (BK(Ca)) blocker iberiotoxin also caused a significant inhibition on relaxant responses to levosimendan. However, incubation of the tracheal rings with the voltage-dependent potassium channel blocker 4-aminopyridine for 10 min did not cause significant alterations on relaxant responses to levosimendan. The present findings suggested that the relaxant effect induced by levosimendan might be partially due to K(ATP) and BK Ca in isolated guinea pig tracheal rings.

Pseudomonas aeruginosa immobilized multiwalled carbon nanotubes has been used as biosorbent for the solid phase extraction of some heavy metal ions in environmental samples. Cobalt(II), cadmium(II), lead(II), manganese(II), chromium(III) and nickel(II) ions have been selected as analytes for the presented study, due to their important negative and positive roles in human life. In order to investigate quantitative biosorption conditions of the analytes, the influences of pH of the aqueous solution, eluent type, eluent volume, samples volume, etc. were examined. The effects of alkaline, earth alkaline and some transitions metals on the biosorption of analyte ions on P. aeruginosa immobilized multiwalled carbon nanotubes were also investigated. The presented biosorption procedure was applied to the determination of analytes in tomato leaves, bovine liver, boiled wheat, canned fish, black tea, lichen and natural water samples.

Bacillus thuringiensis var. israelensis immobilized on Chromosorb 101 that is a new solid phase extractor has been presented at this work for the preconcentration and separation of cadmium(II), lead(II), manganese(II), chromium(III), nickel(II) and cobalt(II) in environmental samples. The analytical parameters including pH of aqueous solutions, sample volume, eluent types, etc. were investigated for the quantitative recoveries of the analytes. The influences of the some metal ions as concomitant were investigated. Under the optimized conditions, the detection limits by 3sigma for analyte ions were in the range of 0.37-2.85 microg L(-1). The accuracy of the developed procedure was confirmed by IAEA 336 Lichen and NIST SRM 1573a Tomato leaves certified reference materials. The method was also applied successfully to the determination of analytes in microwave digested red wine, rice and canned fish samples and sea water, spring water and urine samples.

Introduction: We investigated both the effect and the role(s) of potassium channels, nitric oxide (NO) and cyclooxygenase (COX) products in the effect of hydrogen peroxide (H(2)O(2)) in human internal thoracic artery (ITA) rings., Materials and Methods: Samples of redundant ITA obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system., Results: H(2)O(2) (10(-7)-10(-4) M) produced concentration-dependent relaxation responses in human ITA precontracted by phenylephrine. The relaxant responses to H(2)O(2) did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human ITA rings with superoxide dismutase (50 U/ml) did not affect the relaxant responses to H(2)O(2), while 1,000 U/ml catalase caused a significant decrease. Incubation of endothelium-intact or endothelium-denuded human ITA rings with voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) significantly inhibited the relaxant responses to H(2)O(2). COX inhibitor indomethacin (10(-5) M) also caused a significant inhibition. Incubation with ATP-dependent potassium channel blocker glibenclamide (10(-6) M) or Ca(2+)-activated potassium channel blocker iberiotoxin (10(-7) M) or NO synthase (NOS) blocker N(omega)-nitro-L: -arginine methyl ester (10(-4) M) did not alter relaxant responses of ITA rings to H(2)O(2)., Conclusion: The findings of the present study suggested that H(2)O(2)-induced relaxation responses in human ITA were neither dependant on the endothelium nor blocked by NOS inhibition but they rather seem to depend on the activation of voltage-dependent potassium channels and COX.

The biosorption of copper(II), lead(II), iron(III) and cobalt(II) on Bacillus sphaericus-loaded Diaion SP-850 resin for preconcentration-separation of them have been investigated. The sorbed analytes on biosorbent were eluted by using 1 mol L(-1) HCl and analytes were determined by flame atomic absorption spectrometry. The influences of analytical parameters including amounts of pH, B. sphaericus, sample volume etc. on the quantitative recoveries of analytes were investigated. The effects of alkaline, earth alkaline ions and some metal ions on the retentions of the analytes on the biosorbent were also examined. Separation and preconcentration of Cu, Pb, Fe and Co ions from real samples was achieved quantitatively. The detection limits by 3 sigma for analyte ions were in the range of 0.20-0.75 microg L(-1) for aqueous samples and in the range of 2.5-9.4 ng g(-1) for solid samples. The validation of the procedure was performed by the analysis of the certified standard reference materials (NRCC-SLRS 4 Riverine Water, SRM 2711 Montana soil and GBW 07605 Tea). The presented method was applied to the determination of analyte ions in green tea, black tea, cultivated mushroom, boiled wheat, rice and soil samples with successfully results.

Objective: We investigated the role of potassium channels in vasodilatory effect of levosimendan in human internal thoracic arteries., Methods: Samples of redundant internal thoracic arteries obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system., Results: Levosimendan (10(-8)-10(-5) M) or cromakalim (10(-8)-10(-5) M) produced concentration-dependent relaxation responses in human internal thoracic arteries precontracted by 10(-6) M phenylephrine. The relaxant responses to levosimendan did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human internal thoracic artery rings with adenosine 3',5'-triphosphate (ATP)-dependent potassium channel blocker glibenclamide (10(-6) M) for 30 min significantly inhibited the relaxant responses to both levosimendan and cromakalim. The Ca2+-activated potassium channel blocker iberiotoxin (10(-7) M) also caused a significant but smaller inhibition on relaxant responses to levosimendan. Incubation of the rings with the voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) for 10 min did not cause significant alterations in relaxant responses to levosimendan., Conclusions: The findings of this study suggested that levosimendan-induced relaxation responses in human internal thoracic arteries were depended on the activation of ATP-dependent and Ca2+-activated potassium channels.

We investigated both the effect of levosimendan and the role of various potassium channels in KCl-precontracted rat small mesenteric arteries. Levosimendan (10(-6)-10(-3) M) or cromakalim (CRO, 10(-7)-10(-4) M) produced concentration-dependent relaxation responses in small mesenteric arteries precontracted by 30 mM KCl. The relaxant responses to levosimendan in KCl-precontracted arteries did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of rat small mesenteric arterial segments with ATP-dependent potassium channel (KATP) blocker glibenclamide (GLI, 10(-6) M) for 30 min significantly inhibited the relaxant responses to both levosimendan and CRO. Neither the Ca(2+)-activated potassium channel (KCa) blocker iberiotoxin (10(-7) M) nor the voltage-dependent potassium channel (KV) blocker 4-aminopyridine (5 mM) incubation for 30 min caused significant alterations in relaxant responses to levosimendan in KCl-precontracted small mesenteric arteries. These findings suggested that levosimendan-induced relaxation responses in isolated rat small mesenteric arteries were neither depended on endothelium nor inhibited by the blockers of KV or KCa but, they rather seem to depend on the activation of KATP.

The aim of this study was to compare the positive inotropic effects of 3 different agents with 3 different mechanisms of actions-levosimendan, rolipram, and dobutamine-on human atrial trabecular muscles. Samples of right atrial appendage (1 cm, 500-1000 mg) were removed and immersed in preoxygenated and modified Tyrode solution. In oxygenated Tyrode solution, preparations were used to investigate the concentration-effect relationship of levosimendan, dobutamine, and rolipram on percentage developed tension (DT), from 10 to 10 M, each concentration for 15 minutes. All 3 agents produced concentration-dependent increments in DT. We found that levosimendan was the most efficacious positive inotropic agent on isolated human atrial trabeculae. Both the sensitivity (pD2) and maximum response (Emax) of human atrial trabeculae to levosimendan (6.711 +/- 0.26 and 23.2 +/- 2.2 mN, respectively) were significantly greater than those of dobutamine (6.663 +/- 0.19 and 17.6 +/- 2.8 mN) and rolipram (6.497 +/- 0.18 and 15.0 +/- 1.0 mN). pD2 and Emax values for dobutamine were significantly higher than those for rolipram. It was suggested that because of its potential to enhance cardiac performance without predisposition to calcium-induced arrhythmias, levosimendan might be more useful as a positive inotropic agent in clinical practice.

The aim of this study was to investigate the effects of indomethacin alone and with phosphodiesterase (PDE) inhibitory agents (rolipram, theophylline) on the isolated trachea preparations from control and ovalbumin sensitized guinea-pigs. Adult male guinea-pigs, weighing 300-350 g, were randomly allocated to 2 experimental groups each consisting of 12 animals. Guinea-pigs were sensitized by i.m. injections of 0.35 ml of a 5% (w/v) ovalbumin/saline solution into each thigh (0.7 ml total) on days 1 and 4. Tissues were first contracted with a submaximal concentration of histamine (10(-6) M). We tested the effects of indomethacin (10(-7)-10(-4) M) on the resting tension and precontracted with histamine on the isolated trachea preparations from control and ovalbumin sensitized guinea-pigs. We also tested the effects of the rolipram, theophylline and isoproterenol isolated trachea preparations precontracted with histamine in indomethacin incubated or non-incubated groups. We found that the relaxant effects of rolipram and theophylline increased, but not of isoproterenol, in the presence of indomethacin in isolated trachea preparations precontracted from control and ovalbumin-sensitized guinea-pigs. In the presence of indomethacin there was no difference in relaxant responses between both groups. Therefore, we concluded that the increased relaxant responses may be due to inhibitor effect of this agent on PDE isoenzymes.

Background: Dobutamina Studio Italiano Multicentrico (Do.S.I.M.) is a prospective, randomized, multicenter interuniversity Italian study aimed at assessing the effects of dobutamine on spontaneous variability of ventricular arrhythmias in sinus rhythm NYHA class III-IV patients with congestive heart failure (CHF)., Methods: Out of 74 pre-hoc estimated CHF patients, 68 (92%) were randomized electively to either being washed out of all active drugs except diuretics (group A) or to continue with the standard regimen including digitalis, diuretics and ACE-inhibitors (group B, standard therapy). In 63 patients, complete Holter data were obtained and are reported here. After 72 hours, in both groups, 48-hour Holter monitoring (Holter 1) was performed. The spontaneous variability of ventricular arrhythmias was assessed by calculating the natural logarithm of the sum of hourly incidences (during 48 consecutive hours) of index events such as the mean heart rate or the various forms of total and either sustained or non-sustained ventricular arrhythmias. The results were then grouped for the first and second 24-hour Holter periods. All patients were submitted to 10 microg/kg/min infusion of dobutamine for 72 hours and 48-hour Holter monitoring (Holter 2) was repeated 24 hours before the end of dobutamine infusion. The incidence of arrhythmia and the distribution of laboratory and echocardiographic variables was also studied in group A and B patients. The data of the two groups along with the intrapatient +/- 95% confidence intervals were pooled, both on and off dobutamine., Results: There was no significant difference between Holter 1 and Holter 2 in the rates of index events in 63 patients with regard to pro-arrhythmic effects. Pro-arrhythmic effects were seen during dobutamine infusion in 21% of cases, an effect which subsided (to 5%) when dobutamine was discontinued. Interestingly, the positive inotropic effects of dobutamine (based on ejection fraction changes) were parallel (22%) to the pro-arrhythmic changes, although they persisted long after dobutamine discontinuation (18%). The pro-arrhythmic effects of dobutamine, both during (5%) as well as after (1%) drug infusion, were unrelated to heart rate changes. The prevalence and incidence of non-sustained ventricular tachycardia due to dobutamine were 47 and 29% respectively., Conclusions: In sinus rhythm patients with severe CHF, dobutamine had chronotropic effects and increased a depressed ejection fraction without significantly increasing arrhythmogenicity.

We investigated the effect of doxazosin on cholinergic and adrenergic agonists responses in detrusor smooth muscle preparations from sham-operated and 2-week partially obstructed rat bladders. Male Wistar albino rats, 200-250 g, were randomly allocated to 4 experimental groups consisting of 12 animals each: sham-operated bladder, sham-operated bladder treated with doxazosin, partially obstructed bladder, and partially obstructed bladder treated with doxazosin. Partial outlet obstruction of the rat was surgically induced. The response to carbachol (10(-7)-10(-4) M), isoproterenol (10(-6)-10(-3) M), and 80 mM KCl were recorded. Carbachol caused concentration-dependent contractile responses in the detrusor smooth muscles from sham-operated and partially obstructed bladder. Isoproterenol produced concentration-dependent relaxation responses in the detrusor strips from all groups. Dose-response curves for carbachol and isoproterenol showed a shift to the left in rat detrusor smooth muscles from partially obstructed bladder when compared with the results obtained in detrusor muscles from sham-operated bladder. These responses were reversed to normal by doxazosin treatment in rat detrusor smooth muscles from partially obstructed bladder. KCl produced contractile responses in rat detrusor smooth muscles from all groups. The contractile responses to KCl were not significantly changed in all groups. We have shown that carbachol and isoproterenol responses were shifted to the left in rat detrusor smooth muscles from partially obstructed bladder and these responses were reversed by doxazosin treatment.

1. The aim of the present study was to investigate the inhibitory effects of adenosine on the contractile force and chronotropic action of isolated right atrial preparations from streptozotocin (STZ)-diabetic rats. 2. The rats were anaesthetized with diethyl ether and STZ (65 mg kg(-1)) was injected intravenously via the tail vein. 3. Adenosine produced concentration-dependent decreases in the force of contraction and a negative chronotropic action of atria both in control and diabetic groups. The inhibition responses to adenosine were significantly higher in diabetic rat atria than control. 4. Dypiridamole incubation caused a significant potentiation of the inhibitory effect of adenosine on contractile force and chronotropic action of atria in the control group, but not in the diabetic group. In the presence of dipyridamole, the inhibitory effects of adenosine on measured parameters in diabetic rats were not significantly different from those in control rats. 5. These results suggested that atria from 6 weeks STZ-diabetic rats exhibited a supersensitivity to the negative inotropic and chronotropic effects of adenosine compared with atria from control rats because of an impairment in adenosine uptake mechanism. Altered sensitivity to effects of adenosine might reflect relatively early changes in the course of diabetes.

1. In the present study, we investigated the effect of GABA and selective GABA agonists and antagonists on neurally induced tracheal contractions in streptozotocin (STZ) diabetic rats. 2. Contractile responses to electrical field stimulation (EFS) in rat tracheal rings were completely abolished by atropine and tetrodotoxin, but were unaffected by the ganglion blocker hexamethonium, indicating that they were mediated via neuronal release of acetylcholine (ACh). 3. Contractions induced by EFS, but not by exogenous ACh, were inhibited by GABA and the selective GABA(B) receptor agonist baclofen, but not by the selective GABA(A) receptor agonist 3-aminopropane sulphonic acid. The inhibitory effects of GABA or baclofen were not affected by the GABA(A) antagonist bicuculline, but were significantly reversed by the GABA(B) antagonist phaclofen. 4. The inhibitory effects of both GABA and baclofen were found to be significantly greater in trachea from control rats compared with tissues from diabetic rats. 5. Non-adrenergic, non-cholinergic relaxation responses elicited by EFS in precontracted tracheal rings from diabetic and control rats were similar in magnitude and were unaffected by GABA or GABA analogues. 6. These results suggest that GABA decreases the response to EFS by directly inhibiting the evoked release of ACh through GABA(B) receptors in rat trachea and that STZ-induced diabetes causes an impairment in the inhibitory effect of GABA on neurally induced contractions in this tissue.

We investigated the effect of nitric oxide (NO) on the responses of isolated tracheas to acetylcholine and to electrical field stimulation in streptozotocin-diabetic and controls rats. The contractile responses to acetylcholine were neither different nor affected by the NO synthase blocker, N(omega)-nitro-L-arginine methyl ester (L-NAME), in the two groups. Diabetic rat tracheas were supersensitive to field stimulation. L-NAME enhanced field stimulation-induced contractions at low frequencies in control rat tracheas, but had no effect in diabetic rat tracheas. After L-NAME treatment, there was no difference in sensitivity to field stimulation between the groups. The relaxation responses to sodium nitroprusside in acetylcholine-precontracted tracheas were not different between the groups. However, diabetic rat trachea was supersensitive to the relaxant effect of sodium nitroprusside on contractile responses to field stimulation. These results suggested that the increase in sensitivity to field stimulation in tracheas from diabetic rats might be due to impairment in the production and/or release of an endogenous NO-like factor.

The aim of the present study was to investigate the relaxant effects of selective III, IV and nonselective phosphodiesterase inhibitors, e.g. amrinone, rolipram and theophylline, respectively, on isolated tracheal preparations in streptozotocin (STZ)-diabetic rats. Six weeks before the experiments, the rats to be made diabetic were anesthetized with diethyl ether and diabetes was then induced by a single intravenous injection of STZ (65 mg kg(-1)) via the tail vein. All drugs produced concentration-dependent relaxations of tracheal preparations precontracted with 10(-6) mol/l carbachol. The responses of phosphodiesterase inhibitors were marked in the diabetic groups compared to the control group, but it was found that only amrinone responses are significantly higher in the diabetic groups., (Copyright 2000 S. Karger AG, Basel)