Identification of An mtDNA Setpoint Associated with Highest Levels of CD44 Positivity and Chemoresistance in HGC-27 and MKN-45 Gastric Cancer Cell Lines.

OBJECTIVE: Cancer stem cells (CSCs) have important roles in survival and chemoresistance. These cells are commonly recognized with CD44 and CD24 markers. In this study, we aimed to analyze the effects of mtDNA content on cell surface positivity for anti-CD24 and anti-CD44 antibodies and chemoresistance level in AGS, HGC-27 and MKN-45 gastric cancer (GC) cell lines and to determine a setpoint for mtDNA copy for each cell line. MATERIALS AND METHODS: In this experimental study, we initially decreased mtDNA levels in AGS, HGC-27 and MKN-45 by EtBr treatment. This depletion was confirmed with quantitative polymerase chain reaction (qPCR). Changes in cell surface positivity for anti-CD24 and anti-CD44 antibodies in control and mtDNA-depleted AGS, HGC-27 and MKN-45 were then analyzed with flow cytometry. Changes in chemoresistance (5-FU and cisplatin) were analyzed for all cell lines. The relationship between mtDNA content and cell surface positivity for CD24 and CD44 markers was examined. RESULTS: The highest CD44 positivity was found in HGC-27 and MKN-45 ρlow cells which had 33-40% mtDNA content of control cells, however, CD24 positivity decreased with mtDNA depletion in all cell lines. The highest chemoresistance levels were found in all ρlow cells. mtDNA-recovered (i.e. reverted) HGC-27 and MKN-45 cells partially maintained their increased chemoresistance while reverted AGS cells did not maintain an increased level of chemoresistance. CONCLUSION: mtDNA depletion triggers chemoresistance in cancer cell lines and is correlated with increase and decrease of CD44 and CD24 positivity respectively in HGC-27 and MKN-45 GC cell lines. A mtDNA content above or below the identified setpoint (33-40% of that in control cells), results in the decrease of CD44 positivity and chemoresistance levels.

Mitochondrial depletion in CD4+ and CD19+ peripheral lymphocytes in early stage Alzheimer's disease.

Alzheimer's disease (AD) may be associated with mitochondrial defects. The aim of the present study was to investigate changes in mitochondrial abundance in peripheral lymphocytes of early and late stage AD patients. We analysed levels of mitochondrial DNA (mtDNA) and mean fluorescence intensity (MFI) of the mitochondria-specific antibody 113-1 in CD4+, CD8+, CD19+ and CD56+ peripheral lymphocytes of early and late stage AD by quantitative real-time PCR and flow cytometry, respectively. In early stage AD, the levels of mtDNA were significantly decreased in CD4+, CD19+ and CD56+ peripheral lymphocytes while the MFI of 113-1 staining was significantly decreased in CD4+ and CD19+ cells. Thus, CD4+ and CD19+ peripheral lymphocytes of early stage AD patients exhibit mitochondrial depletion, as seen both at the level of DNA and protein.

The molecular aspects of chordoma.

Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial-mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas.

Impact of COPD exacerbation on cerebral blood flow.

We aimed to investigate the impact of chronic obstructive pulmonary disease (COPD) exacerbation on cerebral blood flow (CBF). In 21 COPD patients - in both exacerbation and stable phases -Doppler ultrasonographies of internal carotid artery (ICA) and vertebral artery (VA) were performed. There were significant differences in total, anterior and posterior CBF, ICA and VA flow volumes in exacerbated COPD compared to stable COPD. Total CBF was correlated with cross-sectional areas of left and right ICA, whereas independent predictor of total CBF was cross-sectional area of right ICA. Increased CBF might indicate cerebral autoregulation-mediated vasodilatation to overcome COPD exacerbation induced hypoxia.

Low-power holmium:YAG laser urethrotomy for urethral stricture disease: comparison of outcomes with the cold-knife technique.

In this prospective randomized clinical trial, we aimed to evaluate the safety and efficacy of endourethrotomy with holmium:yttrium-aluminium-garnet (HO:YAG) laser and compare the outcomes with the conventional cold-knife urethrotomy. Fifty-one male patients with single, iatrogenic, annular strictures of the urethra were randomly divided into two groups; 21 patients who underwent direct-vision endoscopic urethrotomy with Ho:YAG laser (15 W; 1,200-1,400 mJ; 8-12 Hz) at 12 o'clock position (laser group) and 30 patients who underwent direct-vision endoscopic urethrotomy with cold-knife incision at 12 o'clock position (cold-knife group). The results obtained were analyzed and compared at 3 months, 6 months, 9 months, and 12 months postoperatively by clinical evaluation, uroflowmetry, and retrograde urethrographies. Variables were compared among groups using Fisher's exact and Mann Whitney U tests. There were no differences between two groups in terms of patient age, preoperative Qmax value, stricture location, and length. Operative time was shorter in laser group (16.4 ± 8.04 minutes) when compared with cold-knife group (23.8 ± 5.47 minutes) (p<0.001). Recurrence-free rate at 3 months was similar between two groups (p=0.122). However, recurrence-free rates at 6 months, 9 months, and 12 months were significantly higher in laser group when compared with cold-knife group (p values were 0.045, 0.027, and 0.04, respectively). No intra- or postoperative complications were encountered. Use of Ho:YAG laser in the management of urethral stricture disease is a safe and effective method. In addition, it provides shorter operative time and lower recurrence rate when compared with the conventional technique.

Impact of passive smoking on uterine, umbilical, and fetal middle cerebral artery blood flows.

PURPOSE: The aim of this study was to evaluate the influence of passive maternal smoking on blood flow velocities in arteries of the fetal-placental-maternal circulation. MATERIALS AND METHODS: A total of 79 pregnant women in their third trimester, including 33 passive smokers, 23 active smokers, and 23 nonsmoking controls, were enrolled in the study. Fetal biophysical indices were evaluated with B-mode scanning, whereas blood flow waveforms of uterine, umbilical, and fetal middle cerebral (MCA) arteries were analyzed with Doppler ultrasonography. RESULTS: There were significant differences among active smokers vs. passive smokers vs. controls with regard to the presence of a uterine artery diastolic notch (39.1% vs. 18.2% vs. 4.3%; P = 0.012); ratio of peak systolic/end-diastolic velocity of fetal MCA [3.73 ± 1.27 vs. 4.26 ± 1.20 vs. 5.00 ± 2.15, analysis of variance (ANOVA) P = 0.026]; resistance index of fetal MCA (0.74 ± 0.08 vs. 0.75 ± 0.07 vs. 0.80 ± 0.09; ANOVA P = 0.014); ratio of fetal MCA/umbilical artery resistance index (1.27 ± 0.20 vs. 1.24 ± 0.14 vs. 1.39 ± 0.21; ANOVA P = 0.011); and ratio of fetal MCA/umbilical artery pulsatility index (1.56 ± 0.44 vs. 1.63 ± 0.43 vs. 1.97 ± 0.54; ANOVA P = 0.046). CONCLUSION: Effects of passive maternal smoking on the fetal-placental-maternal unit were comparable to those with active maternal smoking as determined by the means of increased resistance in the maternal vasculature and adaptive changes of cerebroplacental circulation for maintaining fetal cerebral circulation.

Pain perception during shock wave lithotripsy: does it correlate with patient and stone characteristics?

BACKGROUND: To investigate the correlation of various clinical parameters [number of shock wave lithotripsy (SWL) sessions, body mass index, patient age, gender, and stone characteristics] with pain perception during the SWL procedure. METHODS: A total of 88 patients who underwent 165 SWL sessions for renal or ureteral stones in our institution were included in the study. The degree of pain perception during the procedure was evaluated with a 10-point visual analog scale. RESULTS: A significant p value was reached when the cut-off value for stone burden was taken as 100 mm(2). Mean pain scores during the SWL procedures were affected by gender and the number of SWL sessions. However, they were not affected by laterality, patient age, body mass index, and location of stones. CONCLUSION: Our results suggest that patient comfort is better during the first SWL session than in the following sessions for renal or ureteral stones with a stone burden of less than 100 mm(2). In addition, severity of pain during SWL treatment may be better tolerated in males than in females.

Comparison of the analgesic effects of dexketoprofen and diclofenac during shockwave lithotripsy: a randomized, double-blind clinical trial.

BACKGROUND AND PURPOSE: This prospective, randomized, and double-blind clinical study aimed to assess the analgesic efficacy of single-dose intramuscular (IM) injection of dexketoprofen (group DE) compared with single-dose IM injection of diclofenac (group DI) in patients who were undergoing shockwave lithotripsy (SWL). PATIENTS AND METHODS: A total of 70 men with single renal or ureteral stones were randomly separated into two groups. The 40 men in group DI received 75 mg IM diclofenac sodium and 30 men in Group DE received 50 mg IM dexketoprofen trometamol 30 minutes before SWL. A 10-point visual analog scale was used to evaluate pain. RESULTS: The age, body mass index, and mean stone burden were comparable between the two groups (P > 0.05). The mean visual analog scale score for group DE was statistically lower compared with the score for group DI (P = 0.02). In 34 (85%) of the 40 men in group DI, the SWL procedure was performed with no, minor, or tolerable pain. In group DE, however, 28 (93.3%) of 30 patients evaluated the pain severity as no, minor, or tolerable (p = 0.01). No major/minor adverse effects were observed in group DI, whereas in one patient in group DE, dyspepsia after injection was noticed (P = 0.423). CONCLUSIONS: The severity of SWL-related pain was significantly better tolerated with dexketoprofen trometamol. During an SWL procedure, the analgesic efficacy of dexketoprofen was greater than that of diclofenac sodium. Although statistically insignificant, a little increased risk for gastric irritation was noticed with dexketoprofen.

Protective value of a folkloric medicinal plant extract against mortality and hemorrhage in a life-threatening renal trauma model.

OBJECTIVES: To compare the efficacy of a folkloric medicinal plant extract (Ankaferd Blood Stopper [ABS]) with that of oxidized cellulose (Surgicel) in a life-threatening renal injury model. ABS is a mixture of 5 plants that has historically been used in Turkish traditional medicine. It has been approved by the Ministry of Health to manage external hemorrhage and dental surgery bleeding in Turkey. METHODS: Twenty-two Wistar albino rats underwent partial nephrectomy after intravenous heparin anticoagulation (2000 U/kg). The cut surface received 1 of 3 therapies, namely no treatment, Surgicel (Johnson & Johnson, New Brunswick, NJ) or ABS (Trend Teknoloji Iaç AS, Istanbul, Turkey). Blood pressure was continually monitored. Survival time, total blood loss, and mean arterial pressure were recorded for 60 minute or until death. Rats that were alive (mean arterial pressure>or=20 mm Hg) at the end of 60 minutes were sacrificed with blood withdrawal with the help of catheters. RESULTS: All animals that received no treatment died within 60 minutes of follow-up. One of 7 in the Surgicel group, and 5 of 7 animals in the ABS group, survived. Mean survival times for the Surgicel and ABS groups were 42.7 and 53.4 minutes, respectively. Rats in the ABS and Surgicel groups survived significantly longer than rats in the control group (P<.05). There were no significant differences between the ABS and the Surgicel groups in survival (P=.128). CONCLUSIONS: ABS is as effective as Surgicel in achieving hemostasis and lengthening survival time following partial nephrectomy in an experimental rat model.

Bilateral invasive papillary carcinoma of the breast.

Papillary carcinoma, a rare malignant tumor of the breast, accounts for only 1-2% of breast tumors. It predominantly affects elderly women in the sixth decade to the eighth decade of life. The incidence of bilateral papillary carcinomas is very low, with only one case reported in the literature. However, there has been no report of a case of bilateral invasive papillary carcinoma. A case of bilateral invasive papillary carcinoma of the breasts, along with mammography and ultrasound findings, is reported here.