New Myrtenal-Adamantane Conjugates Alleviate Alzheimer's-Type Dementia in Rat Model.

Alzheimer's disease (AD) is a neurodegenerative disease associated with memory impairment and other central nervous system (CNS) symptoms. Two myrtenal-adamantane conjugates (MACs) showed excellent CNS potential against Alzheimer's models. Adamantane is a common pharmacophore for drug design, and myrtenal (M) demonstrated neuroprotective effects in our previous studies. The aim of this study is to evaluate the MACs' neuroprotective properties in dementia. METHODS: Scopolamine (Scop) was applied intraperitoneally in Wistar rats for 11 days, simultaneously with MACs or M as a referent, respectively. Brain acetylcholine esterase (AChE) activity, noradrenaline and serotonin levels, and oxidative brain status determination followed behavioral tests on memory abilities. Molecular descriptors and docking analyses for AChE activity center affinity were performed. RESULTS: M derivatives have favorable physicochemical parameters to enter the CNS. Both MACs restored memory damaged by Scop, showing significant AChE-inhibitory activity in the cortex, in contrast to M, supported by the modeling analysis. Moderate antioxidant properties were manifested by glutathione elevation and catalase activity modulation. MACs also altered noradrenaline and serotonin content in the hippocampus. CONCLUSION: For the first time, neuroprotective properties of two MACs in a rat dementia model were observed. They were stronger than the natural M effects, which makes the substances promising candidates for AD treatment

ЛЕЧЕНИЕ РАКА ПРЯМОЙ КИШКИ И РЕКТОСИГМОИДНОГО ОТДЕЛА ТОЛСТОЙ КИШКИ, ОСЛОЖНЕННЫХ ОПУХОЛЕВЫМ КРОВОТЕЧЕНИЕМ, МЕТОДОМ РЕНТГЕН-ЭНДОВАСКУЛЯРНОГО ГЕМОСТАЗА

Short-term treatment outcomes of X-ray endovascular hemostasis in patients with rectosigmoid and rectal cancer complicated by bleeding were presented. Patients were divided into two groups. Group I (study group) consisted of 16 patients who underwent x-ray-endovascular hemostasis. Group II (control group) included 17 patients who received conservative methods of hemostasis. After hemostasis, patients with rectal cancer from both groups received preoperative radiotherapy followed by radical surgery. Patients with rectosigmoid cancer underwent surgery alone. The components derived from donated blood were used in a significantly larger volume in patients from the control group than in patients from the study group (p<0.01), with the same median estimated blood loss. Recurrence of bleeding was observed on 13.3 ± 1.6 days in 100 % of control group patients. There was no evidence of bleeding recurrence in the study group patients. The relative risk reduction of bleeding was 100 % in Group I patients. Thus, the method of X-ray-endovascular hemostasis allows intraluminal tumor bleeding completely to be stopped avoiding repeated blood transfusions.Представлены ближайшие результаты рентген-эндоваскулярного гемостаза пациентов, страдающих злокачественными новообразованиями ректосигмоидного отдела толстой кишки и прямой кишки, осложненных кровотечением. Пациенты были распределены на основную (n=16, проводился рентгенэндоваскулярный гемостаз) и контрольную группу (n=17, проводились консервативные методы гемостаза). После гемостаза больным раком прямой кишки в сравниваемых группах проводилась предоперационная лучевая терапия с последующей радикальной операцией, при раке ректосигмоидного отдела – оперативное лечение. При одинаковой медиане кровопотери в основной группе использовалось значимо меньшее количество и объем продуктов донорской крови, чем в контрольной (p<0,01). Кроме того, во всех случаях в контрольной группе на 13,3 ± 1,6 сут противоопухолевого лечения отмечался рецидив кровотечения. В основной группе рецидивов кровотечения не наблюдалось. Снижение относительного риска развития кровотечения при проведении предоперационной лучевой терапии в основной группе составило 100 %. Таким образом, метод рентген-эндоваскулярного гемостаза позволяет достоверно остановить внутрипросветное толстокишечное опухолевое кровотечение, дает возможность стабилизировать пациента, не прибегая к повторным гемотрансфузиям

Multi-layer structures for protection against infrared laser radiation

Práce je zaměřená na studium metod ochrany lidského těla před účinkem záření vysoce výkonných laserů pomocí vícevrstvých struktur. Nejdříve byla zvolena základní struktura a dále byly navrženy tři metody ochrany - ''vzduchová bariéra'', gelová vrstva, aktivní ochrana. V experimentální části byl zkoušen vliv metod a jejich parametrů. Také byla snaha o optimalizaci a kombinaci jednotlivých metod. Všechny metody prokázaly svou účinnost za podmínek navrženého experimentu a v kombinaci vybraných metod je účinnost ochrany efektivnější. Na závěr byla provedena diskuze o výsledcích experimentu a možnost uplatnění metod v praxi

STUDY OF MONGOLIAN NATIONAL CLOTHING'S SHAPE SOLUTION

56 s., 4 s. příl. :obr., tab., grafy +CD ROMTato bakalářská práce se zabývá studiem historie a specifiky národního mongolského oděvu. Na základě této studie je navržen novodobý oděv s využitím tradičních prvků. Analytická část zahrnuje studium informací o hodnocení somatotypu mongolských mužů a národních norem pro označování velikostí oděvu. Praktická část zahrnuje měření vybraného somatotypu a test dynamiky oděvu. Práce končí vytvořením technické dokumentace k navrženému oděvu

TREATMENT OF RECTAL AND RECTOSIGMOID CANCER COMPLICATED BY TUMOR BLEEDING USING THE METHOD OF X-RAY-ENDOVASCULAR HEMOSTASIS

Short-term treatment outcomes of X-ray endovascular hemostasis in patients with rectosigmoid and rectal cancer complicated by bleeding were presented. Patients were divided into two groups. Group I (study group) consisted of 16 patients who underwent x-ray-endovascular hemostasis. Group II (control group) included 17 patients who received conservative methods of hemostasis. After hemostasis, patients with rectal cancer from both groups received preoperative radiotherapy followed by radical surgery. Patients with rectosigmoid cancer underwent surgery alone. The components derived from donated blood were used in a significantly larger volume in patients from the control group than in patients from the study group (p<0.01), with the same median estimated blood loss. Recurrence of bleeding was observed on 13.3 ± 1.6 days in 100 % of control group patients. There was no evidence of bleeding recurrence in the study group patients. The relative risk reduction of bleeding was 100 % in Group I patients. Thus, the method of X-ray-endovascular hemostasis allows intraluminal tumor bleeding completely to be stopped avoiding repeated blood transfusions

Novel Multitarget Hydroxamic Acids with a Natural Origin CAP Group against Alzheimer’s Disease: Synthesis, Docking and Biological Evaluation

Hydroxamic acids are one of the most promising and actively studied classes of chemical compounds in medicinal chemistry. In this study, we describe the directed synthesis and effects of HDAC6 inhibitors. Fragments of adamantane and natural terpenes camphane and fenchane, combined with linkers of various nature with an amide group, were used as the CAP groups. Accordingly, 11 original target compounds were developed, synthesized, and exposed to in vitro and in vivo biological evaluations, including in silico methods. In silico studies showed that all synthesized compounds were drug-like and could penetrate through the blood–brain barrier. According to the in vitro testing, hydroxamic acids 15 and 25, which effectively inhibited HDAC6 and exhibited anti-aggregation properties against β-amyloid peptides, were chosen as the most promising substances to study their neuroprotective activities in vivo. All in vivo studies were performed using 5xFAD transgenic mice simulating Alzheimer’s disease. In these animals, the Novel Object Recognition and Morris Water Maze Test showed that the formation of hippocampus-dependent long-term episodic and spatial memory was deteriorated. Hydroxamic acid 15 restored normal memory functions to the level observed in control wild-type animals. Notably, this effect was precisely associated with the ability to restore lost cognitive functions, but not with the effect on motor and exploratory activities or on the level of anxiety in animals. Conclusively, hydroxamic acid 15 containing an adamantane fragment linked by an amide bond to a hydrocarbon linker is a possible potential multitarget agent against Alzheimer’s disease