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Yiğit Kılıç,1 Abdullah Özer,1 Tolga Tatar,1 Mustafa Hakan Zor,1 Mehmet Kirişçi,2 Hakan Kartal,3 Ali Doğan Dursun,4 Deniz Billur,5 Mustafa Arslan,6 Ayşegül Küçük7 1Department of Cardiovascular Surgery, Gazi University Medical Faculty, Ankara, 2Department of Cardiovascular Surgery, Kahramanmaras Sutcu Imam Medical Faculty, Kahramanmaras, 3Department of Cardiovascular Surgery, Ardahan State Hospital, Ardahan, 4Department of Physiology, Ankara University Medical Faculty, 5Department of Histology and Embryology, Ankara University Medical Faculty, 6Department of Anaesthesiology and Reanimation, Gazi University Medical Faculty, Ankara, 7Department of Physiology, Dumlupinar University Medical Faculty, Kütahya, Turkey Introduction: Many structural and functional damages are observed in cells and tissues after reperfusion of previously viable ischemic tissues. Acute ischemia reperfusion (I/R) injury of lower extremities occurs especially when a temporary cross-clamp is applied to the abdominal aorta during aortic surgery. Research regarding the treatment of I/R injury has been increasing day-by-day. In this study, we aimed to investigate the effect of picroside II on skeletal muscle of rats experiencing simulated I/R.Materials and methods: Twenty-four male Wistar albino rats weighing between 210 and 300 g were used in this study. Rats were randomly divided into 4 groups of 6 rats each (control, I/R, control + picroside II, and I/R + picroside II). The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R group. The clamp was removed after 120 minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg kg–1) was administered intraperitoneally to the animals in control + picroside II and I/R + picroside II groups. At the end of the study, skeletal muscle tissue was obtained for the determination of total oxidant status (TOS) and total antioxidant status (TAS) levels. Apoptosis was evaluated by TUNEL experiment.Results: TOS levels were significantly higher in I/R group than that of control and I/R + picroside II groups (P=0.014, P=0.005, respectively). TAS levels were significantly higher in I/R group than that of control and I/R + picroside II groups (P=0.007 P=0.005, respectively). TUNEL assay revealed that picroside II reduced cell necrosis.Conclusion: The results of this study demonstrated that picroside II plays a critical role to prevent I/R injury. Even though our results were found to be satisfactory, it should be encouraging to those who want to conduct future research on this topic. Keywords: ischemia reperfusion, picroside II, hind limb skeletal muscle, TOS, TAS

Faruk Metin Çomu,1 Yiğit Kılıç,2 Abdullah Özer,2 Mehmet Kirişçi,3 Ali Doğan Dursun,4 Tolga Tatar,2 Mustafa Hakan Zor,2 Hakan Kartal,2 Ayşegül Küçük,5 Hakan Boyunağa,6 Mustafa Arslan71Department of Physiology, Kirikkale University Medical Faculty, Kirikkale, 2Department of Cardiovascular Surgery, Gazi University Medical Faculty, Ankara, 3Department of Cardiovascular Surgery, Necip Fazil State Hospital, Kahramanmaras, 4Department of Physiology, Ankara University Medical Faculty, Ankara, 5Department of Physiology, Dumlupinar University Medical Faculty, Kütahya, 6Department of Biochemistry, Kirikkale University Medical Faculty, Kirikkale, 7Department of Anaesthesiology and Reanimation, Gazi University Medical Faculty, Ankara, TurkeyBackground: Ischemia reperfusion injury (I/R) in hind limb is a frequent and important clinical phenomenon. Many structural and functional damages are observed in cells and tissues in these kinds of injuries. In this study, we aimed to evaluate the effect of picroside II on lipid peroxidation and erythrocyte deformability during I/R in rats.Methods: Rats were randomly divided into four groups – each containing six animals (sham, I/R, sham + picroside II, and I/R + picroside II). The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R groups. The clamp was removed after 120 minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg·kg-1) was administered intraperitoneally to the animals in the appropriate groups (sham + picroside II, I/R + picroside II groups). All rats were euthanized by intraperitoneal administration of ketamine (100 mg·kg-1) and taking blood from the abdominal aorta. Erythrocytes were extracted from heparinized complete blood samples. Buffer (PT) and then erythrocytes (PE) were passed through the filtration system and the changes in pressure were measured to investigate the role of serum malondialdehyde and nitric oxide (NO) in lipid peroxidation and erythrocyte deformability index.Results: Deformability index was significantly increased in the I/R group compared to groups sham, sham + picroside-II, and I/R + picroside-II (P

OBJECTIVE: Advanced age, dilated right atrium, increased preoperative pulmonary artery pressure, increased right atrial pressure, technique of operation, and poor ventricular function were reported to be risk factors for postoperative arrhythmia. Aim of this study is to determine the risk factor for postoperative arrhythmia after Fontan operation with regard to ventricle dominancy and hemodynamic parameters. METHODS: In this retrospective study, the data of the patients including age, weight, dominant ventricle, type of cardiac anomaly, previous operations, duration of cardiopulmonary bypass (CPB), duration of aortic clamping, cardiac rhythm, pulmonary artery pressure, the Nakata Index, systemic atrioventricular (AV) valve insufficiency were obtained from the hospital records, the echocardiographic files, and cardiac catheterization records. Patients were assigned to dominant left ventricle or dominant right ventricle groups. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Arrhythmia was observed in 21 (52.5%) patients in the postoperative period. No postoperative arrhythmia was observed in patients with a right atrial pressure of <5 mmHg, whereas postoperative arrhythmias were observed in patients with a right atrial pressure of >=5 mmHg (p<0.05). When the effects of preoperative and postoperative pulmonary artery pressures on postoperative arrhythmia were evaluated, postoperative arrhythmia was determined in only 2 (12.5%) of 8 patients with a preoperative mean pulmonary artery pressure of <=9 mmHg, whereas postoperative arrhythmia was observed in 19 (59.3%) of 32 patients with a preoperative pulmonary artery pressure of >=10 mmHg. A preoperative mean pulmonary artery pressure of >10 mmHg increased the risk of postoperative arrhythmia (p<0.02). Postoperative arrhythmia was determined in 8 (53%) of 15 patients with a dominant right ventricle, and in 13 (52%) of 25 patients with a dominant left ventricle (p>0.05). CONCLUSION: While a preoperative mean pulmonary artery pressure of >10 mmHg and a preoperative right atrial pressure of >5 mmHg were the risk factors for postoperative arrhythmia in patients undergoing Fontan procedure, the right or left ventricular dominance was not a risk factor. [ABSTRACT FROM AUTHOR]

Objective: We examined the fate of intact vertical vein during long-term follow-up and its effects on ventricular functions. Methods: Eighty one patients with all types of total anomalous pulmonary venous connection (TAPVC) were operated. Thirty-one patients with supracardiac type TAPVC were examined in our retrospective cohort study. Groups were evaluated with respect to left ventricle area, volume, end-systolic, end diastolic diameter, early and late term mortality and properties of pulmonary hypertensive crisis. Vertical vein was left open in 14 patients and it was ligated in 17 patients. Wilcoxon rank and Mann- Whitney U tests were used to compare variables between groups. Results: After mean follow up of 48±36 months, vertical vein closed spontaneously in 3 patients. Two of them were closed surgically due to elevated shunt flow and there was spontaneous closure in one patient who had the highest pulmonary artery pressure amongst others postoperatively. Preoperative left ventricular area, volume, end-systolic diameter and end-diastolic diameter values of the patients increased from 3.5± 0.9 mm(2)-2.9±0.9 mm(3)-14±5 mm-8±4.5 mm to 8±3.3 mm(2)-16±8.7 mm(3)-27±6.7 mm-17±4.8 mm at the postoperative period in Group 1, and from 6.8±3.5 mm(2)-8.4±8.7 mm(3)-15±6.4 mm-9±5.3 mm to 7.4±5.2 mm(2)-16±1.7 mm(3)-21.7±5 mm-13.5±4.1 mm in Group 2, respectively (p=0.02, p=0.039, p=0.054, and p=0.07, respectively). Conclusion: Vertical vein remains intact in most of the patients and may be closed spontaneously in patients with elevated pulmonary resistance. Intact vertical vein both decompresses the left ventricular cavity in patients with decreased left ventricular compliance until the ventricular muscle adapts to new workload and improves ventricular functions on long term follow up. Therefore, we conclude that vertical vein should be left open in selected patients. [ABSTRACT FROM AUTHOR]

Poor survival and lack of treatment response in glioblastoma (GBM) is attributed to the persistence of glioma stem cells (GSCs). To identify novel therapeutic approaches, we performed CRISPR/Cas9 knockout screens and discovered TGFβ activated kinase (TAK1) as a selective survival factor in a significant fraction of GSCs. Loss of TAK1 kinase activity results in RIPK1-dependent apoptosis via Caspase-8/FADD complex activation, dependent on autocrine TNFα ligand production and constitutive TNFR signaling. We identify a transcriptional signature associated with immune activation and the mesenchymal GBM subtype to be a characteristic of cancer cells sensitive to TAK1 perturbation and employ this signature to accurately predict sensitivity to the TAK1 kinase inhibitor HS-276. In addition, exposure to pro-inflammatory cytokines IFNγ and TNFα can sensitize resistant GSCs to TAK1 inhibition. Our findings reveal dependency on TAK1 kinase activity as a novel vulnerability in immune-activated cancers, including mesenchymal GBMs that can be exploited therapeutically., (© 2024. The Author(s).)

Background: A potentially fatal complication of sepsis is septic acute kidney injury. Stem cell therapy is a potential new method of treating sepsis and has been applied to treat some human diseases., Objectives: This study investigated the effects of secretome-MSCs on NGAL, CRP, NF-κB, and MMP-9 proteins, and histopathology in mice with septic AKI., Methods: A post-test-only group design was conducted in 30 Balb/C male mice, which were randomly assigned to five groups: the control group was intraperitoneally injected with 0.5 ml of 0.9 % NaCl, the septic AKI, and the treatment groups (T1, T2, and T3) were intraperitoneally injected with 0.5 ml of 0.9 % NaCl and 0.3 mg/kg BW LPS single dose for three days. Three-day treatments of 150, 300, and 600 µl secretome-MSCs were administered intraperitoneally into the treatment groups. Furthermore, kidney and blood samples were collected for biochemical and histopathological analyses., Results: The T1, T2, and T3 groups had lower expression of NF-κB and MMP-9 and significantly lower CRP and NGAL levels than that of septic AKI group. T1 (1.21 ± 0.19), T2 (0.75 ± 0.22), and T3 (0.38 ± 0.14) groups demonstrated lower average scores for inflammation, necrosis, hemorrhage, and degeneration compared to septic AKI group (2.17 ± 0.13)., Conclusions: Administration of 600 µl/20 g BW secretome-MSCs suppresses NF-κB and MMP-9 expression and reduces CRP and NGAL levels. Meanwhile, the 150 and 300 µl/20 g BW doses also indicated a greater improvement in renal tissue damage of mice with septic AKI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Posttranslational modifications of histones (PTMs) are associated with specific chromatin and gene expression states 1,2 . Although studies in Drosophila melanogaster have revealed phenotypic associations between chromatin-modifying enzymes and their histone substrates, comparable studies in mammalian models do not exist 3-5 . Here, we use CRISPR base editing in mouse embryonic stem cells (mESCs) to address the regulatory role of lysine 27 of histone H3 (H3K27), a substrate for Polycomb repressive complex 2 (PRC2)-mediated methylation and CBP/EP300-mediated acetylation 6,7 . By generating pan-H3K27R (pK27R) mutant mESCs, where all 28 alleles of H3.1, H3.2 and H3.3 have been mutated, we demonstrate similarity in transcription patterns of genes and differentiation to PRC2-null mutants. Moreover, H3K27 acetylation is not essential for gene derepression linked to loss of H3K27 methylation, or de novo activation of genes during cell-fate transition to epiblast-like cells (EpiLCs). In conclusion, our results show that H3K27 is an essential substrate for PRC2 in mESCs, whereas other PTMs in addition to H3K27 acetylation are likely involved in mediating CBP/EP300 function. Our work demonstrates the feasibility of large-scale multicopy gene editing to interrogate histone PTM function in mammalian cells., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Condyloma acuminata (CA) is one of the sexually transmitted infections caused by human papillomavirus (HPV). Condyloma acuminata patients are usually coinfected with human immunodeficiency virus (HIV), particularly those with low CD4+ levels. Chemical cautery and cryosurgery are therapeutic modalities for CA, aiming to remove lesions and prevent recurrence, especially in patients with HIV., Objective: To compare the efficacy of chemical cautery to cryosurgery on CD4+ status of HIV patients with CA., Methods: A cross-sectional retrospective study was conducted in patients with CA visiting the Dermatology and Venereology outpatient clinic and the voluntary counseling and testing (VCT) clinic of Dr. Moewardi Hospital Surakarta, Indonesia from January 2018 to December 2020. The data were taken from the medical records of patients. These subjects were grouped into CA with HIV and without HIV. The data were statistically analyzed with t -tests followed by multivariate regression tests, and a p-value of <0.05 was considered significant., Results: Seventy-eight patients with CA were included in the study, comprising 41 subjects with HIV infection and 37 subjects without HIV infection. The subjects were predominantly male (68%). Of all the subjects, 70.5% received chemical cautery, and the remaining had cryosurgery. Multivariate regression tests obtained no significant differences in CD4+ levels between chemical cautery and cryosurgery (p=0.138 vs p=0.907)., Conclusion: Either chemical cautery or cryosurgery is effective in improving the clinical condition of patients with CA. Although chemical cautery results in a higher level of CD4+ than cryosurgery, statistically both therapies have no significant difference regarding CD4+ status., Competing Interests: The authors report that there are no conflicts of interest in this research., (© 2021 Mawardi et al.)

Deciphering the mechanisms that control the pluripotent ground state is key for understanding embryonic development. Nonetheless, the epigenetic regulation of ground-state mouse embryonic stem cells (mESCs) is not fully understood. Here, we identify the epigenetic protein MPP8 as being essential for ground-state pluripotency. Its depletion leads to cell cycle arrest and spontaneous differentiation. MPP8 has been suggested to repress LINE1 elements by recruiting the human silencing hub (HUSH) complex to H3K9me3-rich regions. Unexpectedly, we find that LINE1 elements are efficiently repressed by MPP8 lacking the chromodomain, while the unannotated C-terminus is essential for its function. Moreover, we show that SETDB1 recruits MPP8 to its genomic target loci, whereas transcriptional repression of LINE1 elements is maintained without retaining H3K9me3 levels. Taken together, our findings demonstrate that MPP8 protects the DNA-hypomethylated pluripotent ground state through its association with the HUSH core complex, however, independently of detectable chromatin binding and maintenance of H3K9me3.

Femoral artery is the most common vascular access site used for angiographic interventions. Various complications such as hematoma, bleeding, dissection, arteriovenous fistula and pseudoaneurysm have been described following iatrogenic puncture. However, angiosarcoma formation at the access site is very uncommon and it poses a diagnostic dilemma due to its resemblance to organized hematoma. A 75-year-old patient who had undergone coronary angiography has suffered from an angiosarcoma and its vascular complications due to local invasion at the puncture site. Although the tumor was completely excised and flow was re-established, he was lost 17 months later because of multiple metastases and their complications. Presence of a persistent mass with vascular complaints should raise suspicion for this rare and aggressive type of tumor.

The Polycomb repressive complex 2 (PRC2) catalyzes H3K27 methylation across the genome, which impacts transcriptional regulation and is critical for establishment of cell identity. Because of its essential function during development and in cancer, understanding the delineation of genome-wide H3K27 methylation patterns has been the focus of intense investigation. PRC2 methylation activity is abundant and dispersed throughout the genome, but the highest activity is specifically directed to a subset of target sites that are stably occupied by the complex and highly enriched for H3K27me3. Here, we show, by systematically knocking out single and multiple non-core subunits of the PRC2 complex in mouse embryonic stem cells, that they each contribute to directing PRC2 activity to target sites. Furthermore, combined knockout of six non-core subunits reveals that, while dispensable for global H3K27 methylation levels, the non-core PRC2 subunits are collectively required for focusing H3K27me3 activity to specific sites in the genome., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tet1 , Tet2 , and Tet3 encode DNA demethylases that play critical roles during stem cell differentiation and reprogramming to pluripotency. Although all three genes are transcribed in pluripotent cells, little is known about the expression of the corresponding proteins. Here, we tagged all the endogenous Tet family alleles using CRISPR/Cas9, and characterised TET protein expression in distinct pluripotent cell culture conditions. Whereas TET1 is abundantly expressed in both naïve and primed pluripotent cells, TET2 expression is restricted to the naïve state. Moreover, TET2 is expressed heterogeneously in embryonic stem cells (ESCs) cultured in serum/leukemia inhibitory factor, with expression correlating with naïve pluripotency markers. FACS-sorting of ESCs carrying a Tet2 Flag-IRES-EGFP reporter demonstrated that TET2-negative cells have lost the ability to form undifferentiated ESC colonies. We further show that TET2 binds to the transcription factor NANOG. We hypothesize that TET2 and NANOG co-localise on chromatin to regulate enhancers associated with naïve pluripotency genes., (© 2019 Pantier et al.)

The aim of this study was to adapt the rapid assessment method (RAM) and International Osteoporosis Foundation Food Frequency Questionnaire (IOF FFQ) tools, used for the assessment of daily calcium intake in university students, and to compare the data obtained using 24-h recall (24-HR) data. There was a moderate positive correlation between the RAM and IOF., Purpose/introduction: Calcium is an essential mineral that plays vital roles in metabolism and it is very important to accurately assess the amount of calcium intake on the diet. It was aimed to assess the daily calcium intake of university students by two different food frequency questionnaires (FFQs) developed specifically for evaluating calcium intake, and 24-h recall method., Method: The study was conducted with a total of 183 female university students aged 18-31. In the study, a questionnaire including sociodemographic information, a calcium calculator, IOF FFQ, prepared in seven different languages, and RAM was applied. In addition, 1-day food consumption records were obtained using 24-HR method., Results: The daily average calcium intakes of individuals according to two different food frequency questionnaires (RAM FFQ and IOF FFQ) and 24-h food consumption records are respectively 1594.2 ± 810.9, 897.9 ± 368.4, and 605.6 ± 278.3 mg. When the daily average calcium intake was compared with the other two methods, RAM was found to be statistically higher (p < 0.001). There was a moderate positive correlation between the RAM and IOF FFQ methods (Pearson r = 0.528, p < 0.01) and the intra-class correlation coefficient between these two methods was found to be significant and moderate (ICC r = 0.452, p < 0.01)., Conclusion: In terms of protecting and improving health, it is important to make suggestions using fast and short tools to ensure adequate calcium intake from young age. It is thought that FFQs are the most appropriate methods in assessing daily calcium intake for this study group because it is observed that the list of foods and the amount of portions in FFQs reduce the problem of remembering at 24-h method to a great extent.

Pollen, pit powder, and gemmule extract of the date palm are rich in flavonoids. Antioxidant characteristics of the flavonoids have a significant effect on prevention and treatment of infertility. The aim of the present study was to review studies investigating the effects of pollen, pit powder, and gemmule extract of the date palm on male infertility. Articles that were published about the topic between 2005 and 2016 were reviewed from different databases in Turkish and English. The search engines used included PubMed, Science Direct, Clinical Key, Google Scholar, Springer, Dergipark, Ulakbim, and Akademik Dizin. The studies found that pollen, pit powder, and gemmule extract of the date palm created positive changes in hormone levels that have a role in male fertility and increased sperm motility and quality, spermatogenesis, and weights of testes and epididymis. Date palm pollen, pit powder, and gemmule extract have a high antioxidant capacity because of phenolic formations in the composition. Such characteristics have a positive effect on prevention and treatment of male infertility. Furthermore, gonadotropic and steroidal compounds within date palm pollen play a role in treatment of male infertility. The limited number of studies conducted on this topic indicates that more research is needed.

Background: Cerium oxide is the oxide form of cerium, which has protective effects in ischemia reperfusion (I/R) injury. The purpose of our study was to look into the effects of this rare-earth metal on erythrocyte deformability in rat lower extremity I/R injury model., Materials and Methods: We used 24 Wistar albino rats as subjects in our study. They were divided into 4 groups; randomized control group (group C; n = 6), cerium oxide group 0.5 mg.kg-1, intraperitoneal (group CO; n = 6), I/R group (group I/R; n = 6) and I/R group with cerium oxide 0.5 mg.kg-1 intraperitoneally (group I/R-CO; n = 6). Erythrocyte packs were prepared from heparinized blood samples and deformability measurements were performed., Results: We obtained similar results from the control and I/R-CO groups (p = 0.158). The results in I/R group were evidently higher than those of the control, CO, and IR-CO groups (p < 0.0001, p < 0.0001, p = 0.001, respectively)., Conclusion: We detected unfavorable effects of I/R on erythrocyte deformability, which may impair blood flow and hence tissue perfusion in infrarenal rat aorta. We also found that cerium oxide had beneficial effects by reversing undesirable effects of I/R. Further studies with larger volume are required to support our promising results (Fig. 1, Ref. 24).

Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency.

Purpose: It was aimed to determine the prevalence of high disordered eating tendencies and its relationship with food addiction, emotional eating and self esteem in participants at 18 and 33 years age group., Methods: This study was planned as a cross-sectional study and conducted with 1359 young adult volunteers (M = 386, F = 973) with an average age of 22.4 ± 2.84 years. Eating Attitudes Test-26 (EAT-26), Yale Food Addiction Scale (YFAS), Emotional Appetite Questionnaire (EMAQ) and Rosenberg Self-Esteem Scale (RSES) were used. EAT-26 score above 20 was considered as eating disorders risk cutoff., Results: Participants with disordered eating tendencies have higher rates (22.4%) of food addiction compared to participants without high disordered eating tendencies (7.2%). There is no difference for EMAQ and YFAS scores; however, there is a significant difference for RSES and EAT-26 scores according to gender. A positive association of EAT-26 with YFAS and EMAQ-negative scores and a negative association of EAT-26 with RSES and EMAQ-positive were found., Discussion: There is association among EAT-26, YFAS, and Rosenberg Self-Esteem Scale, and Emotional Appetite Questionnaire scores. This study provides information for future studies about high disordered eating tendencies, food addiction and mood that are thought to be important in young adults., Level of Evidence: Level V (cross-sectional descriptive study).

The aim of the study was to examine the relationships among food addiction, eating attitudes, emotional appetite, and self-esteem of young adults aged 18-30 years by using a structural model. This cross-sectional study was conducted with 1,058 volunteers (male = 307, female = 751). The hypothesis that self-esteem of young adults influences their eating attitudes was supported in the study (β = -0.081, p < .05). Another hypothesis was also supported, so self-esteem had a positive effect on food addiction (β = 0.280, p < .05). Furthermore, eating attitude has mediating effects on the relationships between self-esteem and food addiction and between emotional appetite and food addiction. Individuals' eating attitude, food addiction, emotional appetite, and self-esteem scores were found to be related to each other. This article provides valuable data for studies of disordered eating attitudes, emotional state, and food addiction that are thought to be important for young adults in the future.

Objectives: Migraine is a headache disorder affecting approximately 12% of the population, predominantly female individuals. Migraine has been associated with vascular events such as stroke and cardiovascular disease. The close connection between these vascular disorders and atherosclerosis is well known. Carotid artery intima-media thickness (CAIMT) is a marker for detection of subclinical atherosclerosis. The present study is an analysis of the presence of subclinical atherosclerosis in migraine patients., Methods: CAIMT was evaluated in 25 female migraine patients and 27 female controls using innovative ultrasound (US) radiofrequency (RF) data technology. Mann-Whitney U test was used to compare measurements in patient and control groups., Results: There was a statistically significant difference between mean CAIMT of migraine patients and control group (p<0.005): mean CAIMT was 701±114 µm in migraine patients and 400±64 µm in control group., Conclusion: Migraine patients are more prone to atherosclerosis compared to healthy individuals. CAIMT measurement with sonography can be utilized in follow-up to detect subclinical atherosclerosis.

Background: The aim of this study was to evaluate the histological and immunohistochemical effects of levosimendan on liver injury induced by myocardial ischemia and reperfusion (I/R) in a rat model., Methods: Twenty-four male Wistar Albino rats were randomly divided into the four groups: Group C (Control, n = 6), Group I/R (n = 6), Group BI (I/R group treated with levosimendan before ischemia, n = 6), and Group AI (I/R group treated with levosimendan after ischemia, n = 6). Myocardial I/R was induced by ligation of the left anterior descending coronary artery for 30 min followed by two hours of reperfusion in I/R and I/R+Levosimendan groups. At the end of the study, liver tissue samples were obtained for histopathological and immunohistochemical examination., Results: Masson Trichrome staining revealed significant hepatocyte degeneration and necrosis most marked in portal acinus Zone 3, especially around the central veins in Group I/R. Histopathological changes in Group AI were more similar to the changes in Group I/R. Milder hepatocellular degeneration was found in Group BI, when compared to groups I/R and AI. Immunohistochemical score was found to be significantly higher in Group I/R compared to groups C, BI and AI (p < 0.0001). The scores in groups BI and AI were found to be similar (p = 0.068)., Conclusion: Levosimendan ameliorates liver injury induced by myocardial IR, especially when administered before induction of ischemia (Fig. 9, Ref. 37).

Purpose: The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model., Materials and Methods: Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses., Results: Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL., Conclusions: These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the effect of dexmedetomidine (100 µg/kg-ip) on liver injury-induced myocardial ischemia and reperfusion (IR) in rats., Materials and Methods: Twenty-four Wistar Albino rats were separated into four groups. There were four experimental groups (Group C (Control; n = 6), Group IR (ischemia-reperfusion, n = 6), Group D (Dexmedetomidine; n = 6) that underwent left thoracotomy and received ip dexmedetomidine without IR administered via 100 µg/kg ip route 30 minutes before ligating the left coronary artery, and Group IR-D (IR-Dexmedetomidine; n = 6). A small plastic snare was threaded through the ligature and placed in contact with the heart. To produce IR, a branch of the left coronary artery was occluded for 30 min followed by two hours of reperfusion. However, after the above procedure, the coronary artery was not occluded or reperfused in the control rats. At the end of the study, liver tissue was obtained for histochemical and immunohistochemical determination.Some part of tissue samples were stained with Masson-trichrome for the evaluation of ultrastructural changes and inducible nitric oxide synthase (iNOS) expression was evaluated in other part of samples for immunohistochemical examination., Results: Histopathological changes were detected in Group IR when compared with Group C. iNOS expression was found to be increased and stronger particularly in the vascular wall, perisinusoidal space and hepatocytes around vena centralis in this group compared to the control group. Perivascular oedema was detected to be decreased in Group IR-D compared to Group IR. It was also observed that the impairment in the radial arrangement of hepatocytes significantly recovered in Group IR-D. The immunoreactivity was found to be significantly decreased in the assessment of iNOS expression in the same group when compared with Group IR., Conclusion: Administration of dexmedetomidine ameliorates liver injury induced by myocardial ischemia and reperfusion (Fig. 8, Ref. 33).

Eps8 is involved in both cell signalling and receptor trafficking. It is a known phosphorylation substrate for two proteins involved in the fibroblast growth factor receptor (FGFR) signalling pathway: the receptor itself and Src. Here we report a differential proteomic analysis of Eps8 aimed to identify specific FGFR and Src family kinase dependent phosphosites and co-associated phosphodependent binding partners. This study reveals a total of 22 Eps8 pTyr and pSer/Thr phosphorylation sites, including those that are dependent on Src family and FGFR kinase activity. Peptide affinity purification of proteins that bind to a selection of the pTyr phosphosites has identified a range of novel Eps8 binding partners including members of the intracellular vesicle trafficking machinery (clathrin and AP-2), proteins which have been shown to regulate activated receptor trafficking (NBR1 and Vav2), and proteins involved in receptor signalling (IRS4 and Shp2). Collectively this study significantly extends the understanding of Eps8 post-translational modification by regulated phosphorylation, identifies novel Eps8 binding partners implicated in receptor trafficking and signalling, and confirms the functions of Eps8 at the nexus of receptor signalling and vesicular trafficking.

Fibroblast growth factor receptors (FGFRs) mediate a wide spectrum of cellular responses that are crucial for development and wound healing. However, aberrant FGFR activity leads to cancer. Activated growth factor receptors undergo stimulated endocytosis, but can continue to signal along the endocytic pathway. Endocytic trafficking controls the duration and intensity of signalling, and growth factor receptor signalling can lead to modifications of trafficking pathways. We have developed live-cell imaging methods for studying FGFR dynamics to investigate mechanisms that coordinate the interplay between receptor trafficking and signal transduction. Activated FGFR enters the cell following recruitment to pre-formed clathrin-coated pits (CCPs). However, FGFR activation stimulates clathrin-mediated endocytosis; FGF treatment increases the number of CCPs, including those undergoing endocytosis, and this effect is mediated by Src and its phosphorylation target Eps8. Eps8 interacts with the clathrin-mediated endocytosis machinery and depletion of Eps8 inhibits FGFR trafficking and immediate Erk signalling. Once internalized, FGFR passes through peripheral early endosomes en route to recycling and degredative compartments, through an Src- and Eps8-dependent mechanism. Thus Eps8 functions as a key coordinator in the interplay between FGFR signalling and trafficking. This work provides the first detailed mechanistic analysis of growth factor receptor clustering at the cell surface through signal transduction and endocytic trafficking. As we have characterised the Src target Eps8 as a key regulator of FGFR signalling and trafficking, and identified the early endocytic system as the site of Eps8-mediated effects, this work provides novel mechanistic insight into the reciprocal regulation of growth factor receptor signalling and trafficking.

Aim: Ischemia reperfusion injury (I/R) in lower extremity is a frequent and important clinical phenomenon. The protective effect of iloprost on local and distant organ injury due to I/R has been well documented but its effect on erythrocyte deformability needs further investigation. Our aim was to investigate the effect of iloprost on erythrocyte deformability in the infrarenal aorta of rats undergoing I/R., Materials and Methods: Our study was conducted with 18 Wistar albino rats. Rats were divided into the 3 groups; the randomized control group (group C; n=6), I/R group without iloprost (group I/R; n=6) and I/R group with iloprost - 10 mcg.kg-1, 30 min infusion (group I/R-I; n=6). Packs of erythrocytes were prepared from heparinized blood samples and deformability measurements were done., Results: The comparisons of the control and I/R-I groups revealed similar results (p=0.951). The values of the IR group were significantly higher than those of the control and IR-I groups (p=0.006, p=0.011, respectively)., Conclusion: In our study, we detected the unfavourable effects of I/R on erythrocyte deformability, which may lead to disturbance in blood flow and hence tissue perfusion in the infrarenal rat aorta. We also found that Iloprost had beneficial effects by reversing the undesirable effects of I/R (Fig. 1, Ref. 15).

Blunt cardiac injury may result in traumatic ventricular septal defect (VSD) in the pediatric population, but presence of postinfarction VSD with accompanying coronary artery thrombosis has not been reported in the literature thus far. We present a seven-year-old patient who underwent surgery for posttraumatic VSD closure and bypass grafting of thrombotic left anterior descending coronary artery (LAD) occlusion following blunt chest trauma. A high index of suspicion and early use of the appropriate imaging studies are essential for diagnosis and surgical treatment of this condition.

Coarctation of the abdominal aorta is a rare pathology. Stenosis of visceral and renal arteries may present together with coarctation, which requires specific operation techniques. We present the case of a patient with coarctation of the abdominal aorta associated with stenosis of the celiac trunk, the superior mesenteric and the right renal arteries. Distal aortic perfusion by extracorporeal circulation and selective right renal perfusion techniques were used during the operation to protect the spinal cord and kidney against hypoperfusion and ischemia.

Background: There is debate on the timing and outcome of coronary artery bypass surgery in patients with coincident malignancy. In this study, we compared the outcome of coronary artery bypass graft (CABG) in such patients with those without malignancy., Methods: The patients were selected from those who had undergone coronary artery bypass surgery in the last decade. The study group (group I) included the patients with malignancy in remission. The control group comprised those patients who were selected randomly from those without any malignancy. The patients were retospectively examined with regard to preoperative, operative, and postoperative data from personal files, computerized recording system, and operation reports., Results: Group I included 48 patients (age 48 to 69; 29 male) while group II included 50 patients (age = 38 to 73; 35 male). In group I, comorbidity rates were: renal dysfunction in 12 (25%), obstructive lung disease 10 (21%), congestive failure in four (8%) patients. The malignancy rates were: lung in 15 (31%), breast in 10 (21%), stomach in five (10%), colon in four (8%), renal in one (2%), Hodgkin's lyphoma in three (6%), leukemia in two (4%), ovarian in three (6%), and prostate in five (10%) patients. In group II, the comorbidity rates were: diabetes mellitus 18 (36%), renal dysfunction in five (10%) and obstructive lung disease in 13 (26%) patients. In group I, chemotherapy and radiotherapy were performed in 38 and 34 patients, respectively. In groups I and II, the CABG was elective in 47 (98%) and in 45 patients (90%); the off-pump surgery was performed in 27 (56%) and 12 (24%) patients, respectively. The total duration of bypass was 37 +/- 6 minutes and 44 +/- 5 minutes; the duration of aortic clamp was 26 +/- 4 and 29 +/- 7 minutes, respectively, in groups I and II. Posoperative complication rates were: infection in 12 (25%), bleeding in eight (17%), acute renal insufficiency in eight (17%), prolonged air escape in five (10%), and prolonged entubation in 17 (35%) patients in group I and atrial fibrillation in 11 (22%) patients in group II. Mortality rates in both groups were two (4%)., Conclusion: CABG in patients with comorbid malignancy is as safe as the other patients. In patients with full remission of malignancy, the surgeons should be encouraged about the safety of CABG.

Background and Aim: Adult patients with complex forms of descending aortic disease remain a surgical challenge and have a high risk of postoperative mortality and morbidity. Surgical management may be complicated when there is an associated cardiac defect, necessitating repair, or a hostile anatomy exists. We present our experience with extra-anatomic bypass through posterior pericardial route at the same stage with intracardiac/ascending aortic aneurysm repair., Methods: Patients that underwent one-stage surgery with posterior pericardial bypass between ascending and descending aorta during 2003-2007 were reviewed. Data from early and mid-term follow-up, including mortality, perioperative blood loss, graft-related complications, patency, and persistent hypertension, were noted., Results: Six male patients with a mean age of 20.8 +/- 0.7 years were operated for coarctation of the aorta associated with additional pathologies (three cases of ascending aortic aneurysm-one with associated aortic valve insufficiency, one case of isolated aortic valve regurgitation, two cases of mitral valve regurgitation). No early or mid-term mortality was observed during follow-up of a mean of 21.6 +/- 10.0 months. No late graft-related complications or reoperations were observed with patent grafts. Systolic blood pressure decreased after surgery by an average of 43 mmHg., Conclusions: Coarctation of the aorta with concomitant cardiac lesions can be repaired simultaneously through sternotomy and posterior pericardial approach, when patients present in adulthood, to minimize morbidity and mortality.

Extensive calcification of mitral apparatus may preclude optimal valve repair, thus requiring debridement. We performed mitral valve replacement in a 55-year-old woman with a modified bileaflet preservation technique to avoid complications related to extensive debridement. Posterior transposition of the anterior leaflet as a buttress over the posterior ventricular wall provided extra support for the weakened tissues and covered the decalcified areas, which protected against debris embolism. This technique is safe and reproducible, especially for elderly patients who have complex calcification that requires extensive debridement, enables better preservation of ventricular function, and avoids disruption of the mechanical left ventricular wall.

Background: This study set out to document the early electrophysiological and immunohistochemical changes that occur in the retina of experimentally induced diabetic rats., Methods: Diabetes was induced in rats by intraperitoneal injection of 60 mg/kg of streptozotocin (STZ). Electroretinogram readings were taken monthly under either short-duration or long-duration stimuli for up to 3 months after STZ. Oscillatory potentials (OP) and the amplitudes and implicit times of a- and b-waves were analysed, and b-wave amplitudes were analysed using a Naka-Rushton fit. Scotopic a-waves were analysed with photoreceptor models, and Rmp3 (the maximum a-wave amplitude) and S (sensitivity) were calculated. Three months after STZ injection, immunohistochemistry for glial fibrillary acidic protein was performed on the retinas of the STZ-treated rats and age-matched controls., Results: The implicit OP times were significantly longer in the diabetic rats as compared with the controls, and this difference was noted as early as 1 month following STZ treatment. Other electrophysiological parameters, such as OP amplitudes, a- and b-wave amplitude as well as the implicit times, did not differ from controls at this stage. The sacrificed STZ-treated rats also demonstrated marked enhancement of glial fibrillary acidic protein immunoreactivity, suggesting that at least in experimentally induced diabetic retinopathy there is increased Müller cell reactivity., Conclusion: The results of this study indicated that functional alterations in the retina develop rapidly after the onset of diabetes. Analysis of each electroretinogram component may be useful in further investigating the development mechanisms of diabetic retinopathy.

Congenital left ventricular aneurysm is an uncommon cardiac malformation. A 9-year-old boy with complaints of dyspnea and palpitation was diagnosed with a left ventricular aneurysm originating from the left ventricle free wall. Aneurysm resection and endoventricular patch repair was performed. Postoperative follow-up was uncomplicated and follow-up echocardiographs showed normal left ventricular contractility.

Cor triatriatum sinister is a rare cardiac anomaly. It is characterized by the presence of a fibromuscular membrane in the left atrium, thus forming a proximal chamber receiving the pulmonary veins and a distal chamber communicating with the mitral valve and the left atrial appendage. This rare pathology tends to coexist with a persistent left superior vena cava, whereas the presence of an anomalous systemic venous return is unusual. In this article, we report successful treatment of a patient with cor triatriatum sinister who has an additional systemic venous return anomaly.