Investigation of the miR-637 and miR-523-5p as candidate biomarkers in breast cancer.

OBJECTIVES: The distinction of benign lesions from malign tumors is crucial for the diagnosis and treatment of breast cancers. BACKGROUND: The aim of this study was to investigate the use of miRNAs as plasma biomarkers for the discrimination of malign and benign breast tumors. METHODS: Whole blood samples obtained from 40 individuals in 3 groups designated as invasive ductal carcinoma group, fibroadenoma group and healthy controls were included in this study. The expression levels of 372 miRNAs were determined using RT-PCR.  Results: The comparison of fibroadenoma group with healthy controls revealed an upregulation of thirty miRNAs and downregulation of twenty-nine miRNAs. The comparison of invasive ductal carcinoma (IDC) group with controls has shown that eight miRNAs were upregulated while eleven miRNAs were downregulated. When comparing IDC and fibroadenoma groups, 15 miRNAs were found to be upregulated, while 10 miRNAs were downregulated. Further analysis of these miRNAs aimed to determine their power in distinguishing  IDCs from fibroadenomas. Among the miRNAs analyzed, seven miRNAs have shown sufficient discriminative power, of which three miRNAs, namely miR-637, miR-523-5p and miR-490-3p, have shown a significantly high discriminative power. CONCLUSIONS: Circulating miR-637 and miR-523-5p combination maybe used to discriminate between invasive ductal carcinomas and fibroadenomas. (Tab. 9, Fig. 4, Ref. 30).

Role of mir-33a, mir-203b, mir361-3p, and mir-424 in hepatocellular carcinoma

Background/aim: Hepatocellular carcinoma (HCC) is one of the most aggressive cancer types. MicroRNAs (miRNAs) are small noncoding regulatory RNAs that function posttranscriptionally. miRNA deregulation was observed in the development and progression of HCC. In this study, we aimed to investigate the expression levels of four miRNAs (mir-33a, mir-203b, mir361-3p, and mir-424) in HCC patients in comparison to healthy individuals. Materials and methods: Venous blood samples were collected from both HCC patients and healthy individuals. In order to determine the relative expression levels of mir-33a, mir-203b, mir361-3p, and hsa-mir-424 in HCC patients, probe-based quantitative real time PCR (qRT-PCR) was performed. The cycle threshold (Ct) results were analyzed according to the 2−∆∆Ct method and statistical analyses were performed by SPSS Statistics version 15 for Windows. Results: qRT-PCR analysis revealed that the expression levels of mir-33a (fold change: 7.3 and P < 0.001), mir-203b (fold change: 4.6 and P < 0.001), and mir361-3p (fold change: 5.1 and P < 0.001)were downregulated compared to healthy individuals and mir-424 did not show any significant change between HCC patients and controls. Conclusion: Our results indicated that mir-33a, mir-203b, and mir-361-3p may significantly contribute to tumor pathogenesis in HCC and have potential to be used as a noninvasive biomarker for cancer therapy.

Effects of Different Crystalloid Fluids on Renal Tissue in an Experimental Model of Hemorrhagic Shock.

Objective: The type of fluid that should be used in uncontrollable hemorrhages remains an area of research. This study was designed to compare the effects of resuscitation with Ringer's lactate (RL) solution versus a normal saline (NS) solution on hemodynamics, renal tissue histopathology, coagulation, and apoptosis in a rat model of hemorrhagic shock. Methods: The study employed groups designated as the control, hemorrhage, NS, and RL groups. Heart rate, mean arterial pressure, and respiratory rate were monitored. Annexin A5 values were assayed, rotational thromboelastometry analysis was performed, and excised kidney tissue samples were histopathologically analyzed. Results: Blood pressure levels were found to be significantly higher in the control group than those measured in the other groups. While the clotting time (CT) and clot formation time (CFT) in the hemorrhage group were significantly longer than those in the control and RL groups, the CT and CFT measured in the control group were significantly shorter compared to the RL group. The mean Annexin A5 level was in the hemorrhage group, which was significantly higher compared to the other groups. In the renal histopathological evaluation, the scores of proximal tubular injury, distal renal tubular injury, and interstitial renal tubular injury were found to be significantly lower in the control group compared to the other groups. Conclusion: This study demonstrated that NS or RL can be used safely to improve the hemodynamic symptoms resulting from hemorrhagic shock as a means to reduce apoptosis, and to decrease findings in favor of coagulopathy in bedside coagulation tests during the early stages of hemorrhagic shock until the time of starting a blood transfusion.

Quantification of cell-free circulating mitochondrial DNA copy number variation in hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma is the most common primary malignant liver tumor. Mitochondrial DNA copy number has been shown to be associated with various malignancies. However, there has not been any study on the absolute quantification of mtDNA copy number in hepatocellular carcinoma. The aim of this study was to develop a new method for absolute quantification of mtDNA copy number and to relatively quantify the variations in the mtDNA copy number in hepatocellular carcinoma patients in comparison with healthy individuals. METHODS: Venous blood samples were collected from both hepatocellular carcinoma patients (34) and healthy individuals (34). Circulating cell-free DNAs were isolated and the relative quantification of mtDNA copy number variation was determined using quantitative polymerase chain reaction and digital polymerase chain reaction. RESULTS: It was found that the relative mtDNA copy number was significantly decreased in hepatocellular carcinoma patients in comparison with the control group (p<0.05). The median (range) and average of relative mtDNA/ß-actin gene of the patients were determined as 42.8 cp/µL (11.1-88.5) and 45.1 cp/µL, respectively, while the median (range) and average relative mtDNA/ß-actin gene of the control group were determined as 102.8 cp/µL (55.1-291.8) and 138.7 cp/µL, respectively (p<0.05). When quantitative polymerase chain reaction and digital polymerase chain reaction were compared, mtDNA/ß-actin gene copy number ratio of digital polymerase chain reaction results was found to be 1.76-fold more than that of quantitative polymerase chain reaction results. CONCLUSION: Circulating mtDNA copy number was decreased in hepatocellular carcinoma patients in comparison with healthy individuals, and we suggest that it can be used as a noninvasive biomarker for hepatocellular carcinoma diagnosis in the future.

The role of the serum exosomal and endometrial microRNAs in recurrent implantation failure.

OBJECTIVE: It has been identified that endometrium specific microRNAs have different expression levels in endometrial tissues and maternal serum during endometrial cycle. The aim of this study was to analyze microRNA expression levels in recurrent implantation failure patients and healthy controls endometrial samples for enlightening the aetiopathogenesis of the disease. The second aim was to search for a potential noninvasive molecular biomarker in early diagnosis and treatment of Recurrent Implantation Failure (RIF) patients. METHODS: Endometrium and serum samples in two different phases (PP; proliferative phase and SP; secretory phase) from the same cases (RIF; n = 12 and Control; n = 8) were obtained. The expression levels of the microRNA by RT-qPCR method were measured. The expression levels of the healthy controls and study group were compared. Lastly performed target genes analysis of significantly dysregulated miRNA by target analyze databases for obtained related biological pathways. RESULTS: This study showed that has-miR-145, has-miR-23b, has-miR-31 and has-miR-30b were significantly up-regulated in PP and down-regulated in SP endometrium samples. In serum samples, has-miR-145 and hsa-miR-23b were significantly down-regulated in both of PP and SP. Target gene and pathway analysis for dysregulated miRNAs identified important, validated and predicted genes for the implantation process. CONCLUSIONS: This study is the first study to obtain endometrium and serum samples in two different phases from the same cases and measure the candidate miRNAs expression. Our finding suggests that expression level of four candidate miRNAs may be involved in RIF development in women. Furthermore, these miRNAs can be potential biomarker for early diagnosis of RIF patients.

Can miRNA Expression Levels Predict Treatment Resistance to Serotonin Reuptake Inhibitors in Patients with Obsessive-Compulsive Disorder?

Background: Obsessive-compulsive disorder is a psychiatric disorder with different clinical manifestations caused by the interaction of genetic and environmental factors. Recently, it has been shown that microRNAs play a role in the pathogenesis of some psychiatric diseases. We aimed to compare the expression levels of microRNAs between obsessive-compulsive disorder patients and healthy controls and investigate the association between miRNA expression levels and treatment resistance. Methods: Twelve miRNA expression levels in venous blood of 100 obsessive-compulsive disorder patients and 50 healthy controls were detected by real-time polymerase chain reaction. Patients were assessed using the Hamilton Depression Rating Scale, Yale-Brown Obsessive-Compulsive Scale, and Yale-Brown Obsessive-Compulsive Symptom Checklist. Each patient was scheduled for a monthly follow-up for a minimum 6-month-period after serotonin receptor inhibitor treatments were initiated. Results: We found that miR-26a-5p (P < .001), miR-21-3p (P < .001), miR-219a-1-3p (P = .016), miR-106b-5p (P = .039), miR-6740-5p (P = .020), miR-320a (P = .001), miR-22-3p, and miR-16b-5p (P = .010) expression levels were statistically higher in obsessive-compulsive disorder patients than healthy controls; miR-135a-5p (P < .001) and miR-129-6b-5p (P < .001) expression levels were statistically lower. Also, it was determined that increased miR-106b-5p levels were associated with treatment-resistance (P = .020) and there was a negative correlation between miR-374b-3p and disease severity (P = .042). Conclusion: In obsessive-compulsive disorder, there may be a potential value in the relationship between various miRNA expression levels and treatment resistance and disease severity, and future studies may be beneficial.

Transcriptomic analysis of asymptomatic and symptomatic severe Turkish patients in SARS-CoV-2 infection.

Objective: Coronavirus disease 2019 (COVID-19), leading to mild infection (MI), acute respiratory distress syndrome or death in different persons. Although the basis of these variabilities has not been fully elucidated, some possible findings have been encountered. In the present study, we aimed to reveal genes with different expression profiles by next-generation sequencing of RNA isolated from blood taken from infected patients to reveal molecular causes of different response. Methods: Two healthy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative control individuals (NCI), two SARS-CoV-2-positive patients who have MI, and two patients who have critical infection (CI) were included in the study. Total RNA was extracted from blood samples and sequenced. Raw RNA-Seq data were analyzed on Galaxy platform for the identification of differentially expressed genes and their pathway involvements. Results: We found that 199 and 521 genes were downregulated in whole blood of COVID-19-positive CI patients compared to NCI and MI patients, respectively. We identified 21 gene ontology pathways commonly downregulated in CI patients compared to both NCI and MI, mostly associated with innate and adaptive immune responses. Three hundred and fifty-four and 600 genes were found to be upregulated compared to NCI and MI, respectively. Upregulated six pathways included genes that function in inflammatory response and inflammatory cytokine release. Conclusion: The transcriptional profile of CI patients deviates more significantly from that of MI in terms of the number of differentially expressed genes, implying that genotypic differences may account for the severity of SARS-CoV-2 infection and inflammatory responses through differential regulation of gene expression. Therefore, further studies that involve whole genome analysis coupled with differential expression analysis are required in order to determine the dynamics of genotype - gene expression profile associations.

Comparison of MED 12 gene mutation and microRNA-124 expression in leiomyoma and myometrium of Turkish patients.

OBJECTIVES: It is believed that there are still unclear areas in the formation mechanism of leiomyomas. In our study, it was aimed to investigate the formation mechanisms of leiomyomas due to local MED 12 gene exon 2 mutation and local microRNA-124 expression in a Turkish population. MATERIAL AND METHODS: Thirty patients who underwent hysterectomy for leiomyoma uteri at Gaziantep University between January 2013 and January 2016 were included in our study. In the pathology specimens of these patients, the patient's myometrium tissue and her own leiomyoma tissue were analysed via quantitative Realtime PCR in association with MED 12 exon 2 mutation and microRNA-124 expression. RESULTS: The average age of the 30 patients included in our study is 46.67 ± 5.42 and 13 patients had single leiomyoma; 17 patients had more than one leiomyoma. There were significantly higher c.130G> T (p.G44C) mutation and c.131G> A (p.G44A) mutation of MED 12 gene exon in leiomyoma tissues than healthy myometrium tissues of same patients. There was a 3.7-fold decrease in the expression of microRNA-124 in leiomyoma tissues compared to intact eutopic myometrium tissues, but this difference was not statistically significant. CONCLUSIONS: In recent studies, it has been suggested that MED 12 gene may play an active role in the formation of fibroids. MED12 and ß-catenin / Wnt pathway were emphasized, and alternative genetic pathways are sought in fibroid formation. Also, tumour suppressor and oncogenesis effects of microRNAs have been demonstrated in many different studies. Since it is involved in the Wnt pathway, microRNA-124 has been blamed by some previous studies for the formation of fibroids. This study demonstrates that MED12 exon 2 mutations and probably microRNA-124 gene expressions might contribute to uterine leiomyoma pathology.

The effects of exogenous melatonin on peripheral nerve regeneration and collagen formation in rats.

BACKGROUND: Peripheral nerve damage that requires surgical repair does not result in complete recovery because of collagen scar formation, ischemia, free oxygen radical damage, and other factors. To date, the best treatment method has not yet been determined. In this study, we designed an experimental peripheral nerve injury model, and researched the possible effects of melatonin hormone, based on evidence of its strong antioxidant and cell-protective effects via mimicking the effects of calcium channel blockers. MATERIALS AND METHODS: We randomized 24 healthy female albino rats into three groups: the pinealectomy group, melatonin group, and control group. In the pinealectomy group, craniotomy, pinealectomy, sciatic nerve transection, and coaptation were performed, and 0.9% NaCl was injected intraperitoneally. In the melatonin group, craniotomy (without pinealectomy), sciatic nerve dissection, and coaptation were performed, and melatonin was injected intraperitoneally, instead of NaCl. In the control group, craniotomy (without pinealectomy), sciatic nerve dissection and coaptation, and intraperitoneal NaCl injection were performed. In each group, nerve recovery was evaluated histologically, functionally, and electrophysiologically. Functional and electrophysiologic evaluations were conducted before surgery and at 4 and 12 wk. RESULTS: At 4 wk, no significant difference was observed between the groups. However, at 12 wk, significant electrophysiologic and functional improvement was observed only in the melatonin group. CONCLUSIONS: Melatonin seems to have a beneficial effect on nerve recovery. However, this effect is not effective at physiologic doses. Future comparative studies with melatonin versus other nerve-regenerating agents are necessary to determine the clinical utility of melatonin hormone.

Effect of Ramadan fasting on maternal oxidative stress during the second trimester: a preliminary study.

AIM: To evaluate whether fasting during Ramadan has any significant effects on maternal oxidative stress or fetal health in healthy, pregnant women with an uncomplicated, second-trimester, singleton pregnancy. METHODS: During the month of Ramadan, 1-29 September 2008, 42 fasting and 30 non-fasting pregnant women were enrolled in this prospective controlled study. Total antioxidant status (TAS), total oxidant status (TOS) and the oxidative stress index (OSI) were measured from maternal serum samples taken on a fasting day during Ramadan. The two groups underwent routine follow-up examinations. At the end of the pregnancy, maternal complications, birth weight and maternal weight gain during the entire pregnancy were noted. To evaluate whether the duration of fasting days (≥10 or ≥15 days) had any significant effects on maternal oxidative stress, pregnant women who observed Ramadan for more than nine days or those who fasted for more than 14 days were compared with the control group in terms of TAS, TOS and OSI. RESULTS: No significant differences were observed between the groups studied in terms of TAS, TOS, OSI, maternal age, gestational age, parity, birth weight or weight gain during the pregnancy. The TAS level was evaluated as significantly higher (P = 0.027) in the ≥10 fasting days group compared to the non-fasting control group, while there were no significant differences between the groups with respect to TOS and OSI. CONCLUSION: Maternal fasting during Ramadan during the second trimester does not have a significant effect on maternal oxidative stress, fetal development or fetal birth weight.

Measurement of the placental total antioxidant status in preeclamptic women using a novel automated method.

AIM: We aimed to measure the levels of total antioxidant status (TAS) in placental samples from preeclamptic pregnant women and evaluate the relation of placental TAS, total oxidant status (TOS) and oxidative stress index (OSI) with fetomaternal compartments using the more recently designated Erel method. MATERIAL AND METHODS: Thirty four preeclamptic and 27 normotensive pregnant women were enrolled in this prospective controlled study. Subjects were selected from women attending the Obstetrics and Gynecology Department of Gaziantep University. TAS, TOS, OSI were measured from placental, maternal and cord blood samples using a novel automated method. Statistical analyses were performed with SPSS for Windows version 13.0 (SPSS Inc., Chicago, IL, USA). RESULTS: The TAS level of the placenta was evaluated as significantly lower (P<0.001) in preeclamptic women compared to normotensive women. In preeclamptic pregnancies, while the placental TAS level was not correlated with placental TOS level, the TAS levels of maternal plasma (P<0.001; r=0.584) and cord plasma (P<0.005; r=0.529) were significantly correlated with the TOS level of the placenta. CONCLUSION: Our results support the concept that placental defective response to an oxidant stimulus plays a central role in the etiopathogenesis of preeclampsia by using the novel automated Erel method.

Homocysteine, folic acid and vitamin B12 levels in maternal and umbilical cord plasma and homocysteine levels in placenta in pregnant women with pre-eclampsia.

AIM: The aim of this study was to evaluate maternal and fetal serum levels of homocysteine, folic acid, vitamin B12 and placental tissue levels of homocysteine and their association with severity of pre-eclampsia. MATERIAL & METHODS: A case-control study, performed by a single center, included 26 pregnant women with mild pre-eclampsia, 26 pregnant women with severe pre-eclampsia and 26 healthy pregnant women. Maternal blood was collected before delivery and fetal blood was collected from the umbilical cord at delivery. Placental tissue samples were obtained after delivery of placenta. Homocysteine, folic acid, vitamin B12 levels in serum and homocysteine levels in placental tissue homogenates were analyzed by immunochemiluminescent assay. RESULTS: Homocysteine levels in both maternal and fetal serum were significantly higher in the severe pre-eclampsia group compared to mild pre-eclampsia and control groups. However, homocysteine levels in both maternal and fetal serum were not significantly different between mild pre-eclampsia and control groups. No significant differences were observed in folic acid and vitamin B12 levels in both maternal and fetal serum between the groups. Homocysteine levels in placental tissue homogenates were too low to be measured in the three groups (<2 µmol/l). CONCLUSION: Maternal and fetal serum homocysteine levels were found to be significantly higher in severe pre-eclampsia group compared to mild pre-eclampsia and control groups suggesting that elevated serum levels of homocysteine might be associated with severity of pre-eclampsia. On the other hand it seems like elevated serum homocysteine levels were not associated with deficiency of folic acid and vitamin B12.

A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms.

Cerebral cavernous malformation (CCM) is a vascular lesion of the central nervous system that may lead to distinct symptoms among patients including cerebral hemorrhages, epileptic seizures, focal neurologic deficits, and/or headaches. Disease-related mutations were identified previously in one of the three CCM genes: CCM1, CCM2, and CCM3. However, the rate of these mutations in sporadic cases is relatively low, and new studies report that mutations in CCM genes may not be sufficient to initiate the lesions. Despite the growing body of research on CCM, the underlying molecular mechanism has remained largely elusive. In order to provide a novel insight considering the specific manifested symptoms, CCM patients were classified into two groups (as Epilepsy and Hemorrhage). Since the studied patients experience various symptoms, we hypothesized that the underlying cause for the disease may also differ between those groups. To this end, the respective transcriptomes were compared to the transcriptomes of the control brain tissues and among each other. This resulted into the identification of the differentially expressed coding genes and the delineation of the corresponding differential expression profile for each comparison. Notably, some of those differentially expressed genes were previously implicated in epilepsy, cell structure formation, and cell metabolism. However, no CCM1-3 gene deregulation was detected. Interestingly, we observed that when compared to the normal controls, the expression of some identified genes was only significantly altered either in Epilepsy (EGLN1, ELAVL4, and NFE2l2) or Hemorrhage (USP22, EYA1, SIX1, OAS3, SRMS) groups. To the best of our knowledge, this is the first such effort focusing on CCM patients with epileptic and hemorrhagic symptoms with the purpose of uncovering the potential CCM-related genes. It is also the first report that presents a gene expression dataset on Turkish CCM patients. The results suggest that the new candidate genes should be explored to further elucidate the CCM pathology. Overall, this work constitutes a step towards the identification of novel potential genetic targets for the development of possible future therapies.

Investigation of Scavenger Receptor Class B Type I gene variants in patients with coronary heart disease with a history of early myocardial infarction.

OBJECTIVE: The scavenger receptor class B type 1 (SR-BI, SCARB1), which is a high-density lipoprotein (HDL) receptor that mediates selective cholesteryl ester uptake, plays an important role in reverse cholesterol transport. This study investigated the distribution of polymorphic variants of the SR-BI gene in patients with coronary heart disease (CHD) with a history of early myocardial infarction (MI) at an early age and their effects on their serum lipid levels. METHODS: SR-BI rs5888(T>C), rs4238001(C>T), and rs10846744(G>C) were analyzed in 100 male patients with CHD with a history of MI (MI+) who were younger than 50 years and 89 male control subjects without MI history (MI-) using real-time polymerase chain reaction (PCR) and mutant-allele-specific PCR techniques. RESULTS: SR-BI rs4238001 common-CC genotype was found to be more frequent in patients with MI+ than in control subjects (MI-; odds ratio 4.046, p<0.001). The rs10846744 rare-C allele showed a significant association with increased total cholesterol (p=0.014) and triglyceride (p=0.009) levels in the MI+ CHD group. Logistic regression analysis confirmed that there may be an association between the rs4238001-CC genotype (p=0.002), smoking (p=0.026), and MI+ CHD in the presence of other risk factors associated with CHD, whereas haplotype analysis confirmed that patients with MI+ CHD (rs5888-C, rs10846744-G, and rs4238001-C alleles) and CCC (rs5888-C, rs10846744-C, and rs4238001-C alleles) haplotypes were highly frequent (p<0.01 and p=0.027, respectively). CONCLUSION: These results indicated that SR-BI gene variants show different distribution in patients with MI+ CHD compared with that in MI- control subjects, and these variants may have effects in favor of dyslipidemia.

SARS-CoV-2 Presence in the Saliva, Tears, and Cerumen of COVID-19 Patients.

OBJECTIVES/HYPOTHESIS: The emergence of a new coronavirus strain (SARS-CoV-2) in December 2019 from China led to a global pandemic. The lack of herd immunity against this virus and the possibility of viral spread from asymptomatic individuals is still a major challenge for the prevention of viral transmission. The aim of this study was to evaluate the presence of the virus in different bodily secretions as a potential source of viral spread among patients infected with SARS-CoV-2. STUDY DESIGN: Cross Sectional Study. METHODS: The study included 38 COVID-19 patients with a positive real-time polymerase chain reaction (RT-PCR) test result for SARS-CoV-2, obtained from the combined nasopharyngeal-oropharyngeal swab samples. Saliva, tear, and cerumen samples were taken from the patients within 72 hours of the first RT-PCR test. SARS-CoV-2 N1 and N2 gene regions were studied with single-step RT-PCR in all samples. RESULTS: Among the studied samples, the highest positivity rate was in saliva (76.3%) followed by tears (55.3%) and cerumen (39.5%). Viral load in saliva was also significantly higher compared to tears and cerumen (P < .001), while there was no significant difference between tears and cerumen. Higher viral load in combined nasopharyngeal-oropharyngeal swab samples was associated with higher viral load in tears, but not in saliva or cerumen. Half of the saliva, tear, and cerumen samples obtained from asymptomatic patients contained SARS-CoV-2 genome. CONCLUSIONS: The virus was detected in the saliva, tears, and cerumen samples of both symptomatic and asymptomatic patients. The potential role of these bodily fluids on viral spread needs to be studied. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1677-E1682, 2021.

Examination of the expression levels of MACC1, Filamin A and FBXW7 genes in colorectal cancer patients.

OBJECTIVE: Colorectal cancer (CRC) is the third most common type of cancer observed in cancer-related mortality because it has a high metastasis ratio. This study aims to investigate the expression levels of several genes, including metastasis-related colon cancer 1 (MACC1), Filamin A (FLNA), F-box/WD repeat-containing protein 7 (FBXW7), which has an important role in cell signaling, migration and adhesion through the remodeling of the cell skeleton. METHODS: In this study, 21 patients with a precise diagnosis of CRC and 21 controls were included. Gene expressions were examined using the RT-PCR technique. To define the relationship of the genes with metastasis, blood samples were collected from all patients with colon/rectal cancer diagnosis without metastasis at six months before and after the medication with Xelox. RESULTS: Our findings showed that no significant difference was observed in the pre-treatment values compared to the control group, whereas FLNA (p=0.001) expression was observed to be significantly increased following treatment with Xelox. CONCLUSION: To our knowledge, our study is the first study to investigate the effects of Xelox treatment on the expression levels of MACC1, FBXW7 and FLNA genes in non-metastatic colorectal cancer patients in Turkey.

Effects of ECE-1b rs213045 and rs2038089 polymorphisms on the development of contrast-induced acute kidney injury in patients with acute coronary syndrome.

OBJECTIVE: Endothelin-1 (ET-1) promotes the progression and induction of sclerotic renal changes in end-stage kidney disease. Membrane-bound endothelin-converting enzyme 1 (ECE-1) is involved in the production of ET-1. The aim of this study was to assess the effects of ECE-1b rs213045 and rs2038089 polymorphisms, which have been shown to be involved in the development of atherosclerosis, hypertension, and nephropathy, on the development of contrast-induced acute kidney injury (CI-AKI) in patients with acute coronary syndrome. METHODS: Our study included 38 patients with CI-AKI (CI-AKI[+]) and 55 patients without CI-AKI (CI-AKI[-]) who had coronary syndrome. The ECE-1b polymorphisms rs213045 and rs2038089 were assessed using real-time PCR. Serum ET-1 levels were measured by ELISA. RESULTS: The distributions of ECE-1b rs213045 and rs2038089 polymorphisms were similar between the two groups. Additionally, the serum ET-1 level did not different between the groups and was not associated with the ECE-1b polymorphisms. Peri-procedural low systolic blood pressure (SBP) was identified as a risk factor for CI-AKI development. CONCLUSION: Our findings indicate that ECE-1b rs213045 and rs2038089 polymorphisms are not associated with CI-AKI development and that peri-procedural low SBP is a risk factor for CI-AKI. However, variations in ECE-1b rs2038089 may contribute to the development of CI-AKI.

The risk of hepatotoxicity during long-term and low-dose flutamide treatment in hirsutism.

OBJECTIVE: Flutamide is an effective drug in treatment of hirsutism. Hepatotoxicity occasionally may occur with therapeutic doses (750-1500 mg/day), 3 months after initiation of treatment. Monitoring of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels is recommended to obviate serious hepatotoxicity. MATERIALS AND METHODS: Two hundred and fourteen patients with mean age of 20.9+/-2.34 years suffering from hirsutism were included in the study. Of these 214 women, 117 had diagnosis of polycystic ovarian syndrome (PCOS), and 97 had diagnosis of idiopathic hirsutism. Thirty age-matched (mean age 20.3+/-2.0 years) normal women without signs of hirsutism and with normal menstrual cycle served as control group. Hirsutism was assessed using modified Ferriman-Gallwey method at the beginning and at the end of the treatment. Serum levels of luteinizing hormone (LH), follicle stimulant hormone (FSH), prolactin (PRL), estradiol (E2), androstenodion (A), testosterone (T), dehydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-P), sex hormone binding protein (SHBG), and ACTH were measured. Pelvic ultrasonography was performed for diagnosis of PCOS. Fifty-seven patients with PCOS (group 1) were given flutamide 125 mg/day + oral contraceptive. Sixty patients with PCOS (group 2) were given flutamide 250 mg/day + oral contraceptive. Forty-seven patients with IH (group 3) were given flutamide 125 mg/day alone, and 50 patients with IH (group 4) were given flutamide 250 mg alone. Thirty women in control group (group 5) were given placebo only. ALT and AST levels were measured in the beginning of the treatment, and repeated after 3, 6, 9 and 12 months. RESULTS: No incidence of increase in AST or ALT levels (>or= 45 U/L) was observed in any of the groups. No evidence of hepatotoxicity in any of the 214 hyperandrogenic women was observed on low-dose flutamide for 1 year. CONCLUSION: We conclude that flutamide in a dosage of 125 or 250 mg daily is a safe drug in the long-term treatment of hirsutism. The follow-up of patients receiving flutamide can be done by monitoring AST or ALT levels for hepatotoxicity.

Effects of progesterone on total brain tissue adenosine deaminase activity in experimental epilepsy.

Single seizure and epilepsy is one of the most commonly encountered neurologic disorders in elderly individuals, arising as a result of complex and often multiple acquired underlying pathologies. Adenosine, acting at A1 receptors, exhibits anticonvulsant effects in experimental epilepsy and inhibits progression to status epilepticus. Adenosine deaminase is the enzyme for the regulation of adenosine levels. Therefore any change in adenosine deaminase levels will reflect to adenosine levels. Adenosine deaminase levels were decreased in the groups that were given progesterone. Progesterone may have an antiseizure effect with the additional finding decreased levels of adenosine deaminase that would have resulted in increased adenosine levels that exerts anticonvulsant effect via GABA-A receptors. Further studies are needed to evaluate the role of progesterone effects on adenosine deaminase levels and its mechanism(s) in the pathogenesis.

Antiepileptogenic effects of glutathione against increased brain ADA in PTZ-induced epilepsy.

Adenosine has been shown to play a significant role as a modulator of neuronal activity in convulsive disorders, acting as an endogenous anticonvulsant agent. Any change in adenosine deaminase (ADA) levels will reflect to adenosine levels. In the present study, we have investigated the effect of glutathione on brain tissue ADA levels due to seizures induced by convulsive and subconvulsive dose of pentylenetetrazol (PTZ) in mice. ADA levels due to seizures induced by convulsive and subconvulsive pentylenetetrazol were measured using the Giusti method. ADA levels were higher in the experimental epilepsy groups than in the control and sham groups. ADA levels significantly decreased in the glutathione groups, which may have antiseizure effects. Decreased levels of ADA would be due to increased adenosine levels, protecting against oxidative stress.