Antagonist activity of the antipsychotic drug lithium chloride and the antileukemic drug imatinib mesylate during glioblastoma treatment in vitro

Objectives: Glioblastoma (GBM), the most common primary tumour of the central nervous system, is characterised by a high malignancy and poor prognosis. The aims of this study were to investigate whether the combination of imatinib mesylate (IM) and lithium chloride (LiCl) exhibited a synergistic effect in treatment and to determine whether midkine (MK) affected the fate of this treatment in vitro.

Methods: Monolayer and spheroid cultures of the T98G human GBM cell line were treated with an IM and LiCl combination for 72 h. The cell proliferation index, apoptotic index, cell cycle distribution, apoptotic and anti-apoptotic protein levels, and cAMP level as well as the cellular morphology and ultrastructure were evaluated.

Results: All applications inhibited cell proliferation and induced apoptosis. The most substantial decreases in cell proliferation and the caspase-3, epidermal growth factor receptor (EGFR), platelet derived growth factor receptor-alpha (PDGFR-α), multidrug resistance protein-1 (MRP-1), aquaporin-4 (AQP-4) and cAMP levels were induced by the LiCl treatment, which exhibited more pronounced effects compared with the combination treatment. LiCl was less effective in decreasing the MK and B cell lymphoma-2 (Bcl-2) levels compared with the combination treatment. The most substantial decrease in the p170 levels was identified following the combination treatment, whereas IM induced the second greatest decrease. LiCl alone had no effect on the p170 levels. IM induced the most substantial decrease in the phospho-glycogen synthase kinase 3-beta (p-GSK-3β)/glycogen synthase kinase 3-beta (GSK-3β) ratio, and LiCl induced the second most substantial decrease. Both LiCl and the combination treatment induced G2 + M arrest, whereas IM induced G0 + G1 arrest after 72 h of exposure. An apoptotic appearance and autophagic vacuoles were commonly identified in the LiCl, combination and IM groups, respectively.

Conclusions: The combination of IM and LiCl exhibited an antagonist effect, and MK had a role at this antagonism.     

Validity and suitability of the Bayley-III Low Motor/Vision version: A comparative study among young children with and without motor and/or visual impairments

The aim of the present study was to examine the validity of the Bayley-III Low Motor/Vision version, and its suitability for children with motor and/or visual impairment(s). This version contains accommodated items, that is, adaptations to minimize impairment bias, without altering what the test measures. We hypothesized that the accommodations would not affect the item scores of children without impairment, and that children with impairment(s) would benefit from the accommodations. We tested 41 children without impairment and 63 children with impairment with both the standard Bayley-III and the Low Motor/Vision versions, in randomly counterbalanced order. The test administrators filled in an evaluation form. Results showed that the accommodations did not affect the test scores of children without impairment and did improve the test scores of children with impairment on the Cognition scale, while no improvement was found for the other scales. The test administrators indicated that the vast majority of the children with impairment had been able to show their abilities on the test and that the accommodations were beneficial in 29 out of these 52 cases. For some children, the accommodated instrument appeared to be unsuitable because the impairment was too severe. The conclusion is that the accommodations improve the validity of the Bayley-III when used with children with mild to moderate motor and/or visual impairment, especially with regard to the Cognition scale.     

Versatile magnetic microdiscs for the radio enhancement and mechanical disruption of glioblastoma cancer cells

This study describes the use of highly versatile, lithographically defined magnetic microdiscs. Gold covered magnetic microdiscs are used in both radiosensitizing cancer cells, acting as intracellular emitters of secondary electrons during radiotherapy, and as well as inducing mechanical damage by exerting a mechanical torque when exposed to a rotating magnetic field. This study reveals that lithographically defined microdiscs with a uniform size of 2 microns in diameter highly increase the DNA damage and reduce the glioblastoma colony formation potential compared to conventional radiation therapy. Furthermore, the addition of mechanical disruption mediated by the magnetic component of the discs increased the efficiency of brain cancer cell killing.

First study demonstrating the use of physically engineered magnetic particles that display two functionalities for cancer treatment.     

Protective effects of thymoquinone on experimental testicular ischaemia–reperfusion injury: an apoptotic,proliferative and biochemical study

The objective of this study was to examine the effects of thymoquinone (TQ), which has antioxidant properties in the experimental testicular I/R model in rats in terms of its anti‐apoptotic, proliferative and biochemical attributes. In our study, 24 male rats were divided into three groups: control group, I/R group and I/R+TQ group. Testicular torsion was created by rotating the left testis 720° in a clockwise direction. The ischaemia period was 4 h, and an orchiectomy was performed after 4 h of detorsion. Spermatogenesis and the mean seminiferous tubule diameter were significantly decreased in the I/R groups compared to the control group. Furthermore, TQ‐treated animals displayed an improved histological appearance in the I/R group. It was also observed that treatment with TQ increased the activity of PCNA, which decreased as a result of I/R, and this treatment also reduced the number of TUNEL‐positive cells. The I/R+TQ group showed a decrease in malondialdehyde levels and an increase in the activities of superoxide dismutase, catalase and glutathione peroxidase in comparison with the I/R group. It could be concluded that cytoprotective effects of TQ on the I/R testicles are via reduction of apoptosis, oxidative stress and lipid peroxidation.     

Effect of intravenous zoledronic acid infusion on electrocardiographic parameters in patients with osteoporosis

Summary

We evaluated the effects of zoledronic acid (ZA) therapy on electrocardiographic (ECG) parameters for the first time in the literature. Measurements were performed on ECGs obtained before and after ZA infusion on the same day as well as 1 month after the infusion. ZA infusion did not have any short- or long-term effect on any parameter that might be associated with the tendency for atrial fibrillation or ventricular arrhythmias.

Introduction

The aim of the present study was to evaluate the early and late effects of ZA therapy on ECG parameters which might be associated with the tendency for atrial and ventricular arrhythmias.

Methods

Consecutive patients with osteoporosis who were admitted to our clinic between December 2013 and December 2014 and who were scheduled to receive ZA infusion constituted our study population. Twelve-lead surface ECGs were obtained from all patients before and after ZA infusion on the same day as well as 1 month after the infusion. All ECG parameters were measured and compared with each other for each patient.

Results

Data of 100 patients were used in the analysis (9 male; 70.5 ± 11.6 years of age). There were no significant differences between repeated measurements regarding pmax, pmin, and p dispersion values. QT max and QT min values were significantly increased after infusion; however, there were no significant changes in QT dispersion, Tp-e interval, and Tp-e dispersion values.

Conclusions

ZA infusion did not affect P wave dispersion both at the immediate post-infusion period and 1 month after infusion. QT values were significantly increased early after ZA infusion; however, there were no significant differences in parameters reflecting disparity of ventricular recovery times and transmural dispersion of ventricular repolarization. Based on these observations, it may be suggested that ZA infusion did not have any short- or long-term effect on any parameter that might be associated with the tendency for atrial fibrillation or ventricular arrhythmias.

     

Effect of long-term <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection on growth of children: a cohort study

Background

The effects of Helicobacter pylori (H. pylori) infection on growth are a controversial issue. We investigated the effects of long-term H. pylori infection on height and weight in children.

Methods

A total of 200 children of 7-18 years old suffering from dyspeptic complaints were classified into two groups: H. pylori positive and negative groups, respectively. Whether the infection was impoved was followed up while performing urea breath test, and according to exposure time to the infection, the children were further divided into group 1 (≤1.5 months), group 2 (>1.5-≤6 months) and group 3 (>6 months). Antropometric measurements were obtained and repeated every six months.

Results

Mean growth velocity scores in the H. pylori positive and negative groups were 0.49±3.85 [95% confidence interval (CI): -0.21-1.18] and 1.98±4.42 (95% CI: 1-2.96), respectively. The difference between both groups was statistically significant (P=0.012). Mean growth velocity scores in groups 1, 2 and 3 were 0.96±3.84, 0.16±4.51 and -0.85±3.09, respectively. Mean growth velocity scores of group 3 were significantly lower than those of groups 0 and 1 (P=0.005 and P=0.041). The mean weight scores in group 3 were similar to those in group 2, but the scores in group 3 were significantly lower than those in group 1 (-1.75±1.05, -1.21±1.37 and -0.88±1.49, respectively).

Conclusion

As the duration of exposure is prolonged in children with H. pylori infection, the negative effect of the infection on both height and weight is evident.