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61.
Clinical Rheumatology - A progressively growing number of rheumatologists have integrated musculoskeletal ultrasound (MSUS) as a prized tool in their daily clinical practice over the past two... 相似文献
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Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma 总被引:1,自引:0,他引:1
Heider U von Metzler I Kaiser M Rosche M Sterz J Rötzer S Rademacher J Jakob C Fleissner C Kuckelkorn U Kloetzel PM Sezer O 《European journal of haematology》2008,80(2):133-142
Objectives: Mantle cell lymphoma (MCL) is an incurable B cell lymphoma, and novel treatment strategies are urgently needed. We evaluated the effects of combined treatment with the proteasome inhibitor bortezomib and the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) on MCL. Bortezomib acts by targeting the proteasome, and – among other mechanisms – results in a reduced nuclear factor-kappa B (NF-κB) activity. HDACi promote histone acetylation, and also interfere with NF-κB signaling.
Methods: Human MCL cell lines (JeKo-1, Granta-519 and Hbl-2) were exposed to bortezomib and/or SAHA. Cell viability and apoptosis were quantified by the MTT and annexin-V assay, respectively. Reactive oxygen species (ROS) were analyzed using the fluorophore H2 DCFDA. In addition, activated caspases, proteasome- and NF-κB activity were quantified.
Results: Combined incubation with bortezomib and SAHA resulted in synergistic cytotoxic effects, as indicated by combination index values <1 using the median effect method of Chou and Talalay. The combination of both inhibitors led to a strong increase in apoptosis as compared to single agents and was accompanied by enhanced ROS generation, while each agent alone only modestly induced ROS. The free radical scavenger N -acetyl- l -cysteine blocked the ROS generation and reduced the apoptosis significantly. In addition, coexposure of bortezomib and SAHA led to increased caspase-3, -8 and -9 activity, marked reduction of proteasome activity and decrease of NF-κB activity.
Conclusions: This is the first report giving evidence that SAHA and bortezomib synergistically induce apoptosis in MCL cells. These data build the framework for clinical trials using combined proteasome and histone deacetylase inhibition in the treatment of MCL. 相似文献
Methods: Human MCL cell lines (JeKo-1, Granta-519 and Hbl-2) were exposed to bortezomib and/or SAHA. Cell viability and apoptosis were quantified by the MTT and annexin-V assay, respectively. Reactive oxygen species (ROS) were analyzed using the fluorophore H
Results: Combined incubation with bortezomib and SAHA resulted in synergistic cytotoxic effects, as indicated by combination index values <1 using the median effect method of Chou and Talalay. The combination of both inhibitors led to a strong increase in apoptosis as compared to single agents and was accompanied by enhanced ROS generation, while each agent alone only modestly induced ROS. The free radical scavenger N -acetyl- l -cysteine blocked the ROS generation and reduced the apoptosis significantly. In addition, coexposure of bortezomib and SAHA led to increased caspase-3, -8 and -9 activity, marked reduction of proteasome activity and decrease of NF-κB activity.
Conclusions: This is the first report giving evidence that SAHA and bortezomib synergistically induce apoptosis in MCL cells. These data build the framework for clinical trials using combined proteasome and histone deacetylase inhibition in the treatment of MCL. 相似文献
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Yesim Salik Sengul Nergis Kaya Gamze Yalcinkaya Muge Kirmizi Orhan Kalemci 《Explore (New York, N.Y.)》2021,17(4):334-339
ContextPatients who have suffered from persistent symptoms often undergo lumbar spinal surgery (LSS). Motor imagery should be added to postoperative home exercises to reduce patient complaints.ObjectiveThe aim of this study was to compare the effects of home exercise plus motor imagery and only home exercise in patients undergoing LSS.DesignA randomized controlled study.SettingsThis study was designed by researchers at Dokuz Eylul University.ParticipantsThirty-seven patients undergoing LSS were randomized to motor imagery group (n = 19) and control group (n = 18).Main outcome measuresPain was measured by Visual Analogue Scale, disability related to low back pain by Oswestry Disability Index, pain-related fear by Tampa Scale of Kinesiophobia, depression by Beck Depression Inventory, quality of life by World Health Organization Quality of Life Scale-Short Form (WHOQOL-BREF). All assessments were repeated in the preoperative period, three weeks after and six weeks after the surgery.InterventionsMotor imagery group underwent home exercise plus motor imagery program applied by voice recording. Control group underwent only home exercise program. Exercise program compliance was monitored by exercise diary and telephone calls once every week.ResultsThere was a significant improvement in pain at rest and during activity, disability, kinesiophobia, depression, physical health and psychological sub-parameters of WHOQOL-BREF between preoperative period, and the third week and sixth week in both groups (p < 0.05). When comparing groups for gain scores, there was a more significant improvement in pain during activity in motor imagery group (p < 0.05). Motor imagery should be addressed as an effective treatment after LSS. 相似文献
66.
H. Nursun ?zcan Berna O?uz Mithat Halilo?lu Diclehan Orhan Mu?turay Kar?aalt?ncaba 《Diagnostic and interventional radiology (Ankara, Turkey)》2015,21(4):355-360
Fatty liver can present as focal, diffuse, heterogeneous, and multinodular forms. Being familiar with various patterns of steatosis can enable correct diagnosis. In patients with equivocal findings on ultrasonography, magnetic resonance imaging can be used as a problem solving tool. New techniques are promising for diagnosis and follow-up. We review imaging patterns of steatosis and new quantitative methods such as proton density fat fraction and magnetic resonance elastography for diagnosis of nonalcoholic fatty liver disease in children.Nonalcoholic fatty liver disease (NAFLD) is as widely encountered in children as in adults, with an estimated prevalence of 9.6% (1). It occurs due to accumulation of triglyceride in hepatocytes without alcohol ingestion. Nonalcoholic steatohepatitis (NASH) was first defined in children in 1983 (2). NAFLD includes a broad range of clinicopathologic features ranging from simple steatosis (fat with inflammation and/or fibrosis), steatohepatitis/NASH to cirrhosis. Some other diseases of liver can also cause hepatic steatosis including hepatitis B and C, Wilson’s disease, α-1-antitrypsin deficiency, autoimmune hepatitis, drug-induced liver injury (valproate, methotrexate, tetracycline, amiodarone, and prednisone), and total parenteral nutrition (3). Furthermore, fatty liver is a risk factor for cirrhosis, diabetes, and cardiovascular disease.In clinical practice, the diagnosis of NAFLD is made by increased serum ALT and/or presence of enlarged echogenic liver in ultrasonography. Being overweight or obese, and/or insulin resistance are highly indicative but not absolutely necessary for diagnosing NAFLD (4). The gold standard for diagnosis is liver biopsy, which additionally provides semi-quantitative analysis of NASH damage in children (5). It is an expensive, invasive procedure with a risk of morbidity (0.06%–0.35%) and mortality (0.01%–0.1%) (6).The evaluation of liver fat in children via noninvasive imaging modalities is needed to avoid complications of biopsy and for follow-up. Main imaging modalities for the assessment of pediatric NAFLD are ultrasonography (US) and magnetic resonance imaging (MRI). Computed tomography is the other imaging method for liver fat assessment, but ionizing radiation is a major drawback in children (7). Assessment of fat accumulation may cause diagnostic dilemmas and confusion due to manifestations with unusual structural patterns and imaging appearance of the liver. This article reviews the histopathology of pediatric NAFLD, radiologic evaluation and different structural patterns of childhood NAFLD/NASH on US and MRI. We also discuss diagnostic pitfalls and briefly review new imaging techniques. 相似文献
67.
Nihat?KarakoyunluEmail author Goksel?Goktug Nevzat?Can??ener Kursad?Zengin Ismail?Nalbant Ufuk?Ozturk Ugur?Ozok Abdurrahim?Imamoglu 《Urological research》2015,43(3):283-287
The aim of the study was to compare percutaneous nephrolithotomy (PCNL) and staged retrograde flexible ureteroscopy (FURS) methods used in the treatment of kidney stones of 2 cm or more in diameter. The study comprised a total of 60 patients with a diagnosis of kidney pelvic stones more than 2 cm in diameter, for whom surgery was planned between January 2013 and January 2014. The patients were randomly allocated to two groups as staged retrograde FURS (Group A) and PCNL (Group B). Comparison of the groups was made with respect to operating time, number of procedures, total treatment time, length of hospital stay, stone-free rates and complications according to the Clavien–Dindo classification. In Group A, the total operating time of multiple sessions was 114.46 min. In Group B, a single session of PCNL was applied to all patients and the mean operating time was 86.8 min (p = 0.014). Mean total treatment time was 2.01 weeks in Group A and 1 week in Group B (p < 0.01). The mean total hospitalization time was 3.66 days in Group A and 3.13 days in Group B (p = 0.037). At the end of the sessions, clinically insignificant residual fragments were observed in ten patients of Group A and one patient of Group B (p = 0.03). No statistically significant difference was determined between the groups in terms of stone-free rates or complications. Although current technology with FURS is effective on large kidney stones, it has no superiority to PCNL due to the need for multiple sessions and long treatment time. 相似文献
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Burc Aydin Nil Hocaoglu Serap Cilaker Micili Bekir Ugur Ergur Sule Kalkan 《Cardiovascular toxicology》2016,16(4):374-380
The aim of this study was to investigate the efficacy of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as an antidotal treatment for the in vivo cardiovascular effects of amitriptyline poisoning. Experiments were carried out on 33 Wistar rats. To evaluate cardiovascular effects of HPBCD, rats were infused with dextrose or HPBCD. In the poisoning model, amitriptyline (0.94 mg/kg/min) was infused until the mean arterial blood pressure (MAP) dropped to 50 % of the baseline. Following amitriptyline infusion, dextrose, low-dose HPBCD (4.19 mg/kg/min), or high-dose HPBCD (16.76 mg/kg/min) was infused, and MAP, heart rate (HR), and electrocardiogram were recorded for 60 min. Hearts were examined for tissue damage and apoptosis. HPBCD infusion alone did not yield significant difference for MAP, HR, QRS duration, QT interval, and cardiac tissue damage when compared to dextrose (p > 0.05). In the poisoning model, MAP and HR decreased, while QRS duration and QT interval prolonged significantly following amitriptyline infusion (p < 0.0167). Dextrose, low-dose HPBCD, and high-dose HPBCD infusion similarly corrected MAP, HR, QRS duration, and QT interval values at the end-experiment time point (p > 0.05). Histological scores for tissue damage and apoptosis showed no significant difference between the groups (p > 0.05). Based on our results, HPBCD did not show cardiovascular toxicity, while it was not more effective than dextrose for the treatment of amitriptyline poisoning. Further antidotal studies of cyclodextrins with higher doses and/or binding affinities are needed for poisonings. 相似文献
70.
Jonathan M. Tobis Orhan Nalcioglu Warren D. Johnston Anthony Seibert Werner Roeck Uri Elkayam Walter L. Henry 《American heart journal》1983,105(6):946-952
Left ventriculograms were obtained with the use of 10 ml of contrast media by passing fluoroscopic video images through a video image processor. The low concentration of dye in the left ventricle was enhanced by the technique of mask mode subtraction, and the images were postprocessed to increase visibility by manipulation of the gray scale and contrast levels. These digital subtraction angiograms were compared to standard cineangiograms by means of 40 ml of contrast media. Of 30 patients studied, six (20%) had runs of ventricular tachycardia during the cineangiogram and had to be excluded. In the remaining 24 patients, there was a good correlation between the two techniques for left ventricular end-diastolic volume (r = 0.77, end-systolic volume (r = 0.95), and ejection fraction (r = 0.97). Spatial resolution in the digital studies was adequate to appreciate wall motion abnormalities that were visualized on the cineangiograms. Left ventricular end-diastolic pressure (LVEDP) did not change after the 10 ml injection, but the mean LVEDP rose 6.0 mm Hg after the 40 ml cineangiograms (p < 0.01). Digital subtraction angiography can be used to obtain left ventriculograms with one-fourth the amount of contrast media and one-fourth the x-ray exposure compared to standard cineangiograms. This technology will permit multiple left ventriculograms to be obtained which, in turn, will allow intervention studies to be performed in the catheterization laboratory. 相似文献