Ondřej Bradáč

Comparison of the electronic properties, and thermodynamic and kinetic parameters of the aquation of selected platinum(II) derivatives with their anticancer IC50 indexes

AbstractThree potential anticancer agents {trans-[PtCl2(NH3)(thiazole)], cis-[PtCl2(NH3)(piperidine)], and PtCl2(NH3)(cyclohexylamine) (JM118)} were explored and compared with cisplatin and the inactive [PtCl(dien)]+ complex. Basic electronic properties, bonding and stabilization energies were determined, and thermodynamic and kinetic parameters for the aquation reaction were estimated at the B3LYP/6-311++G(2df,2pd) level of theory. Since the aquation process represents activation of these agents, the obtained rate constants were compared with the experimental IC50 values for several tumor cells. Despite the fact that the processes in which these drugs are involved and the way in which they affect cells are very complex, some correlations can be deduced. FigureAquation energy profile for the family of cisplatin derivatives (JM118)

Recognition of Facial Emotional Expression in Amnestic Mild Cognitive Impairment

We examined whether recognition of facial emotional expression would be affected in amnestic mild cognitive impairment (aMCI). A total of 50 elderly persons met the initial inclusion criteria; 10 were subsequently excluded (Geriatric Depression Score > 5). 22 subjects were classified with aMCI based on published criteria (single domain aMCI [SD-aMCI], n = 10; multiple domain aMCI [MD-aMCI], n = 12); 18 subjects were cognitively normal. All underwent standard neurological and neuropsychological evaluations as well as tests of facial emotion recognition (FER) and famous faces identification (FFI). Among normal controls, FFI was negatively correlated with Mini-Mental Status Examination scores and positively correlated with executive function. Among patients with aMCI, FER was correlated with attention/speed of processing. No other correlations were significant. In a multinomial logistic regression model adjusted for age, gender, and education, a poorer score on FER, but not on FFI, was associated with greater odds of being classified as MD-aMCI (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.05-13.91; p = 0.042). This association was not explained by memory or global cognitive score. There was no association between FER or FFI and SD-aMCI (OR, 1.13; 95% CI, 0.36-3.57; p = 0.836). Therefore, FER, but not FFI, may be impaired in MD-aMCI. This implies that in MD-aMCI, the tasks of FER and FFI may involve segregated neurocognitive networks.

Melatonin and cortisol secretion profile in patients with pineal cyst before and after pineal cyst resection

A pineal cyst is a benign affection of the human pineal gland on the borderline between pathology and normality. Only a small percentage of patients present with symptoms and a surgical treatment is indicated in highly selected cases. A melatonin secretion in patients with a pineal cyst before and after a pineal cyst resection has not been studied yet and the effect of surgery on human metabolism is unknown. The present study examined melatonin, cortisol and blood glucose secretion profiles perioperatively in a surgical group of 4 patients. The control group was represented by 3 asymptomatic patients with a pineal cyst. For each patient, 24-h circadian secretion curves of melatonin, cortisol and glycemia were acquired. An analysis of melatonin profiles showed an expected diurnal pattern with the night peak in patients before the surgery and in the control group. In contrast, melatonin levels in patients after the surgery were at their minimum throughout the whole 24-h period. The cortisol secretion was substantially increased in patients after the surgery. Blood glucose sampling showed no statistically significant differences. Clinical results demonstrated statistically significant headache relief measured by Visual Analogue Scale in patients after the surgery. Despite the small number of examined patients, we can conclude that patients with a pineal cyst preserved the physiological secretion of the hormone melatonin while patients who underwent the pineal cyst resection experienced a loss of endogenous pineal melatonin production, which equated with pinealectomy. Surprisingly, cortisol secretion substantially increased in patients after the surgery.

Magnetic resonance imaging and histology correlation in Cushing's disease

INTRODUCTION We continuously look for new techniques to improve the radicality of resection and to eliminate the negative effects of surgery. One of the methods that has been implemented in the perioperative management of Cushings disease was the combination of three magnetic resonance imaging (MRI) sequences: SE, SPGR and fSPGR. MATERIAL AND METHODS We enrolled 41 patients (11 males, 30 females) diagnosed with Cushings disease. A 3D tumour model with a navigation console was developed using each SPGR, fSPGR and SE sequence. The largest model was then used. In all cases, a standard four-handed, bi-nostril endoscopic endonasal technique was used. Endocrinological follow-up evaluation using morning cortisol sampling was performed for 6-34 months in our study. RESULTS In total, 36 patients (88%) were disease-free following surgery. Our results indicate we achieved 100% sensitivity of MR. Overall, the conformity of at least one donor site, as compared with the places designated on MR, was in 78% of patients. We searched the place of compliance in individual locations. There is a consensus in individual locations in 63 of the 123 cases (or 56%). The correlation gamma function at a 5% significance level was then 0.27. DISCUSSION The combination of MR sequences (SE, SPGR, fSPGR), neuronavigation system and iMRI led to increased sensitivity of up to 100%. Specificity reached 56% in our study. CONCLUSION We found a high success rate in surgical procedure in terms of the correlation between MR findings and histology, which leads to remission of Cushings disease.

Safety and Efficacy of Endovascular Treatment of Previously Clipped Aneurysms: A Systematic Review and Meta-Analysis

BACKGROUND/OBJECTIVE The safety and efficacy of endovascular treatment of previously clipped aneurysms have not been well-established. We conducted a systematic review of the literature to evaluate the outcomes of endovascular treatment of previously clipped aneurysms. METHODS A systematic search of MEDLINE, Embase, Scopus, and the Web of Science was performed for studies published until October 2017. We included studies with ≥2 patients that described endovascular treatment of previously clipped aneurysms. A random-effects meta-analysis was used to pool the following outcomes: technical success, aneurysm occlusion/recurrence/rebleed, ischemic/thrombotic/thromboembolic events, neurologic/procedure-related morbidity/mortality, and favorable neurologic outcomes. We performed subgroup analyses by aneurysm rupture status on presentation to the endovascular procedure, treatment timing, and by aneurysm location (anterior vs. posterior circulation). RESULTS In total, 27 studies with 271 patients were included. Overall complete occlusion was 76.1% (95% confidence interval [CI] 0.676-0.836) and technical success was 97.9% (95% CI 0.958-0.993). Combined procedure-related morbidity/mortality was 4.5% (95% CI 0.024-0.073). There were no statistically significant differences in any of the safety and efficacy outcomes by aneurysm location. Overall long-term favorable neurologic outcome was 78.5% (95% CI 0.732-0.834). All included studies are retrospective. CONCLUSIONS Our meta-analysis demonstrated that endovascular treatment is acceptably safe and effective. It is important to point out that the complication rate of treatment of these aneurysms is not negligible. These findings should be considered when deciding the best therapeutic strategy. Our findings may suggest that endovascular treatment of previously clipped aneurysms should only be considered in circumstances in which conservative management seems to be unsafe.

Computational fluid dynamics of intracranial aneurysms and its potential contribution in clinical practice from a neurosurgeon’s perspective

Computational fluid dynamics have developed in the area of cerebrovascular dis eases in recent years, especial ly in the research of intracranial aneurysms. The goal of most studies is to understand the pathophysiology of the initiation, growth and rupture of brain aneurysms and determine those risk hemodynamic parameters that lead to such proces ses. In our paper, we sum marize the cur rent state of art computational fluid dynamics especial ly from a surgical point of view of intracranial aneurysms and we focus on its pos sible contribution in clinical practice.