Cofactor metals and antioxidant enzymes in cisplatin-treated rats: effect of antioxidant intervention

We explored the association between the activities of antioxidant enzymes and their metallic cofactors in rats treated with cisplatin. The antioxidant effects of aminoguanidine, and a combination of vitamins E and C were investigated. Plasma platin was significantly lower than liver and kidney. Cisplatin treatment caused significant increase in plasma Se-glutathione peroxidase activity. Activities of Se-glutathione peroxidase, glutathione S-transferase, catalase and Cu,Zn-superoxide dismutase have been found to be significantly decreased in liver and kidney compared to controls. Zn levels in these organs were diminished upon cisplatin treatment, while levels of Cu were unaffected. Interestingly, levels of iron, the cofactor of catalase, were found to be significantly increased in liver and kidney. Intervention with aminoguanidine or vitamins was generally prevented cisplatin-caused changes in the activity of enzymes and in the tissue levels of cofactor metals. These observations suggest that relation between activities of enzymes and levels of cofactor metals is multifactorial.     

Educational quality of YouTube videos on musculoskeletal ultrasound

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...     

Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma

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 H₂DCFDA. 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.     

The effects of the addition of motor imagery to home exercises on pain,disability and psychosocial parameters in patients undergoing lumbar spinal surgery: A randomized controlled trial

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.     

Imaging patterns of fatty liver in pediatric patients

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.