Diurnal differences in memory and learning in young and adult rats treated with methylphenidate

Methylphenidate (MPH) is a very effective treatment option for children and adolescents with attention-deficit/hyperactivity disorder. Nevertheless, there have been inconsistent reports regarding the effects of MPH on learning and memory. The aim of this study was to evaluate whether the treatment with MPH during the morning differs from that during the night on learning and memory (short and long term) in young and adult male Wistar rats. The animals received once daily intraperitoneal injection of either MPH (2 mg/kg) or saline (0.9%) for 28 days (either in the morning or at night). The animals underwent two behavioral tasks to evaluate learning and memory: inhibitory avoidance task and continuous multiple trials step-down inhibitory avoidance (CMIA). Young rats treated in the morning showed significant impaired long-term memory for inhibitory avoidance training and facilitated acquisition in the CMIA. Adult rats treated in the night showed impaired long-term retention in the CMIA. We observed similar performances in both tests for young rats treated at night or adult rats treated in the morning. Our results suggest that age and time of treatment can alter the MPH effects in learning and memory.     

Evaluation of brain creatine kinase activity in an animal model of mania induced by ouabain

Bipolar disorder (BD) is a common and severe mood disorder associated with higher rates of suicide and disability. The development of new animal models, and the investigation employing those available have extensively contributed to understand the pathophysiological mechanisms of BD. Intracerebroventricular (i.c.v.) administration of ouabain, a specific Na⁺,K⁺-ATPase inhibitor, has been used as an animal model for BD. It has been demonstrated that Na⁺,K⁺-ATPase is altered in psychiatric disorders, especially BD. Creatine kinase (CK) is important for brain energy homeostasis by exerting several integrated functions. In the present study, we evaluated CK activity in the striatum, prefrontal cortex and hippocampus of rats subjected to i.c.v. administration of ouabain. Adult male Wistar rats received a single i.c.v. administration of ouabain (10⁻² and 10⁻³ M) or vehicle (control group). Locomotor activity was measured using the open field test. CK activity was measured in the brain of rats immediately (1 h) and 7 days after ouabain administration. Our results showed that spontaneous locomotion was increased 1 h after ouabain administration and that hyperlocomotion was also observed 7 days after that. Moreover, CK activity was inhibited immediately after the administration of ouabain in the striatum, hippocampus and prefrontal cortex. Moreover, the enzyme was not affected in the striatum and hippocampus 7 days after ouabain administration. On the other hand, an inhibition in CK activity in the prefrontal cortex was observed. If inhibition of CK also occurs in BD patients, it will be tempting to speculate that the reduction of brain metabolism may be related probably to the pathophysiology of this disease.     

Cortical-evoked potentials reflect speech-in-noise perception in children

Children are known to be particularly vulnerable to the effects of noise on speech perception, and it is commonly acknowledged that failure of central auditory processes can lead to these difficulties with speech-in-noise (SIN) perception. However, little is known about the mechanistic relationship between central processes and the perception of SIN. Our aims were twofold: to examine the effects of noise on the central encoding of speech through measurement of cortical event-related potentials and to examine the relationship between cortical processing and behavioral indices of SIN perception. We recorded cortical responses to the speech syllable [da] in quiet and multi-talker babble noise in 32 children with a broad range of SIN perception. Outcomes suggest inordinate effects of noise on auditory function in the bottom SIN perceivers compared with the top perceivers. The cortical amplitudes in the top SIN group remained stable between conditions, whereas amplitudes increased significantly in the bottom SIN group, suggesting a developmental central processing impairment in the bottom perceivers that may contribute to difficulties in encoding and perceiving speech in challenging listening environments.     

Prevalence of Medication Nonadherence to Co-medication Compared to Immunosuppressants in Heart Transplant Recipients: Findings From the International Cross-sectional BRIGHT Study

Purpose

To assess and compare the prevalence of medication nonadherence (MNA) (implementation and persistence) to immunosuppressants and co-medications in heart transplant recipients.

Radiolabeling of trastuzumab with 177Lu via DOTA,a new radiopharmaceutical for radioimmunotherapy of breast cancer

AimTrastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical.Material and MethodsTrastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line.ResultsThe radiochemical purity of the complex was 96±0.9%. The stabilities in phosphate buffer and in human blood serum at 96 h postpreparation were 93±1.2% and 85±3.5%, respectively. The immunoreactivity of the complex was 89±1.4%. At a concentration of 1 nM, the complex killed 70±3% of MCF7 cells. At 1.9 nM, 90±5% of the cells were killed.ConclusionsThe results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against breast cancer.     

From the Cover: A strategy for blood biomarker amplification and localization using ultrasound

Blood biomarkers have significant potential applications in early detection and management of various diseases, including cancer. Most biomarkers are present in low concentrations in blood and are difficult to discriminate from noise. Furthermore, blood measurements of a biomarker do not provide information about the location(s) where it is produced. We hypothesize a previously undescribed strategy to increase the concentration of biomarkers in blood as well as localize the source of biomarker signal using ultrasound energy directly applied to tumor cells. We test and validate our hypothesis in cell culture experiments and mouse tumor xenograft models using the human colon cancer cell line LS174T, while measuring the biomarker carcinoembryonic antigen (CEA) before and after the use of ultrasound to liberate the biomarker from the tumor cells. The results demonstrate that the application of low-frequency ultrasound to tumor cells causes a significant release of tumor biomarker, which can be measured in the blood. Furthermore, we establish that this release is specific to the direct application of the ultrasound to the tumor, enabling a method for localization of biomarker production. This work shows that it is possible to use ultrasound to amplify and localize the source of CEA levels in blood of tumor-bearing mice and will allow for a previously undescribed way to determine the presence and localization of disease more accurately using a relatively simple and noninvasive strategy.