Inhibition of cromakalim-activated K<Superscript>+</Superscript> current by ethanol in follicle-enclosed <Emphasis Type="Italic">Xenopus</Emphasis> oocytes

Ethanol has been reported to modulate arterial dilation and insulin secretion. ATP-inhibited K+ channels (K(ATP)) are reported to have regulatory roles during these events. In the present study, the effect of ethanol on K+ currents activated by the K(ATP) channel opener cromakalim was investigated in follicular cells of Xenopus oocytes. The results indicate that ethanol in the concentration range of 10-300 mM (approximately 0.06%-2% v/v) reversibly inhibits the cromakalim-induced K+ currents. The 50% of maximal ethanol effect was obtained at 53 mM. Inhibition of cromakalim-activated K+ current by ethanol was non-competitive. In oocytes treated with the Ca2+-chelator BAPTA, inhibition of cromakalim-induced K+ currents by ethanol was not altered, suggesting that Ca2+-activated second messenger pathways were not involved in the actions of ethanol. Similarly, currents activated by 8-Br-cAMP were also inhibited by ethanol, but the ethanol inhibition of 8-Br-cAMP-activated currents was significantly less than inhibition of cromakalim-activated currents by ethanol. These results indicate that cromakalim-activated K+ currents in follicular cells of Xenopus oocytes were modulated by ethanol.     

Irradiation After Surgically Induced Brain Injury in the Rat: Timing in Relation to Severity of Radiation Damage

The aim of this study was to evaluate how timing of irradiation after brain surgery in rats relates to overall extent of brain radiation damage. Extent of injury was determined according to lipid peroxidation (malondialdehyde; MDA) levels in brain tissue. Thirty female rats were randomly assigned to five equal groups (Groups A-E). Four groups underwent trephination and scalpel hemisection of right frontal lobe. Rats in Groups B and D received 25 Gy cranial irradiation in a LINAC system at 10 and 20 days after surgery, respectively. Twenty-four hours later they were killed and their right frontal lobes were removed for lipid peroxidation determination. Groups A and C were not irradiated; these groups were killed and had their frontal lobes removed on day 11 and day 21 post-surgery, respectively. The remaining six animals (Group E, sham surgery) underwent trephination only, and were killed and had their frontal lobes removed 24 h later. There was a significant difference between the mean MDA levels in the control group and Group D, and between the levels in Group B and Group D (P < 0.05 for both). The difference between the mean for Group A and the mean for Group B was even more significant (P < 0.01). The most striking differences were between the control group and Group B, and between Group B and Group C (P < 0.001 for both). The data from this rat model suggest that, in humans, starting radiotherapy early (1-2 weeks) after debulking of a brain tumor may result in significantly higher levels of tissue damage than if the radiation is started 3 weeks or more postoperatively. Further experimental research is needed to project these findings in rats to human subjects.     

Interferon-alpha2b induction treatment with or without ribavirin in chronic hepatitis C: a multicenter,randomized, controlled trial

We aimed to compare the efficacy of interferon-_2b (IFN) induction treatment in combination with ribavirin to IFN induction alone in chronic hepatitis C. In total, 125 patients (66 male, 59 female, mean age: 48 ± 9, range: 21–70) were enrolled and randomized into two arms: In the first, patients received 5 MU/day of IFN for 4 weeks followed by 3 MU/day for the next 4 weeks. Treatment was continued with 3 MU three times a week IFN for an additional 40 weeks. Ribavirin was administered 1000–1200 mg/day according to the body weight for the entire 48-week period. In the second arm, patients received placebo in addition to IFN. Fifty-nine patients were placed in the ribavirin arm and 66 in placebo arm. All patients were genotype 1. At week 48, 24/66 (36%) from the placebo and 31/59 (52%) from the ribavirin group responded (P < 0.05). However, during the 24-week untreated follow-up period, 13/24 (54%) from the placebo, and 8/31 (26%) from the ribavirin group relapsed (P = 0.002.), resulting in a sustained virologic response (SVR) rate of 17% in the placebo and 39% in the ribavirin group (P = 0.005.) In conclusion, IFN induction treatment in combination with ribavirin is superior to IFN induction treatment alone in genotype 1 patients, and the SVR rate of 39% is encouraging.     

Association of sleep duration with socio‐economic status and behavioural problems among schoolchildren

Aim: In this population‐based study, we aimed to determine the total sleep duration (TSD), its association with socio‐economic status (SES) and behavioural symptoms among schoolchildren. Methods: A cross‐sectional study was performed among schoolchildren in Istanbul. A structured questionnaire evaluating the sleep schedule variables was filled out by their parents. SES was determined according to the Turkish SES scale. Results:  The mean age of 2669 children was 8.2 ± 2.4 years, and 51% of the students were girls. The mean TSD was 10.20 ± 1.04, and the mean bedtime was 21.57 ± 0.56 (both in hours, minutes ± SD). Boys tended to go bed later (p = 0.004) and slept less than girls (p = 0.02). The duration of sleep disruptions increased (p < 0.001), whereas TSD decreased with age (p < 0.001). Multiple linear regression revealed that waking time and TSD decreased significantly (p < 0.05) with higher SES among both girls and boys. Sleep fragmentation was associated with habitual snoring, parasomnias, daytime sleepiness and conduct symptoms. Conclusion: Decreased total sleep duration is more prominent in boys, older children and children among higher socio‐economic status. Insufficient sleep attributed to shortened total sleep duration by age and higher socio‐economic status might have a negative effect on both sleep hygiene and psychological well‐being in schoolchildren.     

The impact of serum oestradiol concentration prior to progesterone administration on live birth rate in single vitrified–warmed blastocyst transfer cycles

Research questionCan serum oestradiol concentrations on the day of progesterone initiation predict live birth rates in single, autologous vitrified–warmed blastocyst transfers following artificial endometrial preparation?DesignThis retrospective study included the first transfers of 468 patients with unexplained or tubal factor infertility who underwent freeze-all cycles using single, top-quality blastocysts after artificial endometrial preparation from January 2015 to January 2018. Patients were stratified into four groups based on serum oestradiol concentration percentiles on the day of progesterone initiation: Group 1 (<25th percentile), Group 2 (25–50th percentile), Group 3 (51–75th percentile) and Group 4 (>75th percentile). The primary outcome was live birth rate. The secondary outcomes were implantation, clinical pregnancy and multiple pregnancy rates. Receiver operating characteristic (ROC) curves were generated to evaluate serum oestradiol concentrations in predicting implantation, clinical pregnancy and live birth.ResultsSimilar live birth rates of 51.6%, 55.1%, 54.9% and 56.4% for Groups 1, 2, 3 and 4, respectively, were found. The groups also showed similar implantation and clinical pregnancy rates. ROC analysis revealed that serum oestradiol concentrations on the day of progesterone initiation were not predictive for implantation (area under the curve [AUC] 0.490, 95% CI 0.445–0.554), clinical pregnancy (AUC 0.507, 95% CI 0.453–0.561) or live birth (AUC 0.514, 95% CI 0.461–0.566).ConclusionsSerum oestradiol concentration monitoring just prior to progesterone administration does not appear to be predictive for live birth rates in good prognosis patients undergoing single, autologous vitrified–warmed blastocyst transfer after artificial endometrial preparation. Therefore, the current practice of monitoring serum oestradiol concentration is not supported by this study.     

DNA methylation or histone modification status in metastasis and angiogenesis-related genes: a new hypothesis on usage of DNMT inhibitors and <Emphasis Type="Italic">S</Emphasis>-adenosylmethionine for genome stability

Metastasis is a leading cause of mortality and morbidity in cancer. This process needs angiogenesis. The biology underlying cancer, metastasis, and angiogenesis has been investigated so as to determine the therapeutic targets. Invasive and metastatic cancer cells have undergone numerous genetic and epigenetic changes, manifested by cytoskeletal changes, loss of adhesion, and expression of proteolytic enzymes that degrade the basement membrane. Additionally, in endothelial cells, some epigenetic modifications occur during the formation of angiogenesis. Researchers have used some methylation inhibitors, histone deacetylase inhibitors, or methylating agents (such as S-adenosylmethionine, SAM) against cancer and angiogenesis. Although they are effective to beat these diseases, each one results in differentiation or changes in genome structure. We review epigenetically modified genes related with angiogenesis and metastasis in cancer and endothelial cells, and suggest a new proposal. This hypothesis has discussed the importance of the usage of DNA methylation inhibitors together with SAM to prevent tumor progression and genome instability or changes resulting in additional diseases.     

Optimal timing and temperature for hyperthermic preconditioning in an animal model of fecal peritonitis.

The impact of immune parameters in the mechanism of hyperthermia is yet to be explained. In this study, the optimal timing and temperature of thermal treatment for reversing the abnormal immunologic parameters obtained in a rat model of peritonitis were planned to be determined. Male Sprague-Dawley rats were grouped as sham, control peritonitis, and thermally treated rats at the time of peritonitis or 4 h prior to induction of peritonitis both at 40 and 42 degrees C. Peritonitis was induced by the cecal ligation and perforation model. Eight hours after the induction of peritonitis, rats were sacrified and samples were taken for measurements of CD4+, CD8+, CD(11b), B cells, NK cells, and tumor necrosis factor alpha (TNFalpha) and thiobarbituric acid-reactive substances (TBARS) levels. CD4+ expression and B cell amount were decreased whereas TNFalpha levels, CD8+ and CD(11b) expression, and NK cell amount were found to be increased in the control peritonitis group when compared to the sham group. Peritonitis induction also increased TBARS levels in liver tissue. Hyperthermic preconditioning at either 40 or 42 degrees C applied 4 h prior to peritonitis induction returned all parameters to their normal levels, which is similar to the results of the sham laparotomy group. The results of TNFalpha values in preconditioned rats were varied according to the temperature that was applied. The levels were increased at 40 degrees C, whereas they showed a decline at 42 degrees C. Hyperthermic preconditioning prevented the oxidative damage in liver as well as TNFalpha elevation, particularly at 42 degrees C. Results from this study suggest that hyperthermic preconditioning 4 h prior to the onset of septic events may improve the adverse outcome in sepsis.     

Evaluation of 99mTc-citrate, 67Gacitrate and 99mTc(V) dimercaptosuccinic acid for the scintigraphic visualization of acute appendicitis

An experimental study was planned to evaluate ^99mTc-citrate, ⁶⁷Gacitrate and ^99mTc(V) dimercaptosuccinic acid (DMSA) as agents for the visualization of acute appendicitis. Appendiceal ligation was performed through a midline incision in 24 rabbits. Twenty-four hours later the animals were divided into three equal groups. The rabbits were injected through the aurical vein with 1 mCi (37 MBq) ^99mTc-citrate in group I, 0.5 mCi (18.5 MBq) ⁶⁷Ga-citrate in group II and 1 mCi (37 MBq) ^99mTc(V) DMSA in group III. After 3 h, static images of the rabbits were obtained with a gamma camera. There were positive images in seven, six and five rabbits in groups I, II and III respectively. The image quality was better in group I than in the other groups. Also, the mean uptake in group I was significantly higher than those of other two groups (P < 0.05). There was no significant difference between groups II and III (P > 0.05). All rabbits had appendicitis confirmed histologically. In conclusion, these results show that 99mTc-citrate is preferable to 67Ga-citrate and ^99mTc(V) DMSA for the differential diagnosis of acute abdominal inflammations such as appendicitis, because of higher concentration ratios, simple and rapid preparation, low cost, excretion mainly through the kidneys and fast blood clearance.