Search

To determine the frequency of NOD2 gene c.3019-3020insC (rs5743293) and c.2104CT (rs2066844) allelic variants in the patients with Crohn's disease (CD), colorectal cancer (CRC) and in the control groups and to study the association of these mutations with the onset time of the diseases, gender and surgical interventions.The diagnoses of CD and CRC were established based on standard clinical examination and laboratory tests. Molecular genetic study of a frameshift 3020insC mutations of NOD2 gene were performed in 54 patients with CD; missense R702W mutations of the NOD2 gene - in 41 CD patients and 38 healthy controls. In CRC group, 3020insC mutation was tested in 48 patients, R702W mutation - in 40 patients and 40 healthy controls. PCR-RFLP technique was used to identify the mutations.The frequency of the minor allele (M) of 3020insC mutation of NOD2 gene in the patients with CD was significantly higher than in the control group (р = 0.01). The age at CD onset in females carrying 3020insC mutation was significantly lower (22.5 ± 1.6 years) when compared with females without the mutation (32.7 ± 2.5 years) (p = 0.002). There was no significant difference in the allele frequencies and genotype distributions of R702W mutation in the patients with CD in comparison with the controls. The mean age at CD onset in the patients carrying R702W mutation was significantly lower (28.4 ± 1.4 years) compared with the patients without the mutation (39.4 ± 2.8 years) (p 0.01). Surgical interventions for CD was required in 40.0% of 3020insC mutation carriers. Among patients with CRC, only 4.2% carried 3020insC mutation and 20.0% R702W mutation. Our study suggests that R702W and 3020insC mutations are not associated with the risk of CRC in Ukrainian patients. There was no statistically significant difference in mean age at CRC onset in patients with/without R702W mutation. Only one patient with CRC had two mutations.The earlier age at CD onset was associated with 3020insC mutation, but only in female patients. The association between R702W mutation and the earlier age of CD onset was found. Patients with 3020insC mutation showed a trend to a higher frequency of surgical interventions for CD.

Мета роботи. Дослідження гострої токсичності та протизапальної (антиексудативної) активності спиртових екстрактів трави сну білого (Pulsatila alba). Матеріали і методи. Дослідження гострої токсичності проведено на 78 безпородних білих щурах обох статей масою 190–220 г, яким вводили тестовані спиртові екстракти трави сну білого (Pulsatila alba) одноразово внутрішньошлунково за допомогою металевого зонда в дозах 5000, 10 000 та 15 000 мг/кг. Для вивчення антиексудативної активності використовували карагенінову модель запального набряку задньої лапи білих щурів (42 тварини). Досліджувані екстракти вводили внутрішньошлунково в дозі 2 мл/кг. Як препарати порівняння використовували диклофенак натрію та кеторолаку трометаміну. Результати й обговорення. Результати вивчення гострої токсичності екстрактів трави сну білого (Pulsatila alba) свідчать про відсутність будь-яких токсичних проявів при внутрішньошлунковому введенні в дозах 5000, 10 000 та 15 000 мг/кг на білих щурах, що дозволяє віднести їх до VI класу токсичності (відносно нешкідливі речовини). Спиртові екстракти трави сну білого проявляють протизапальну активність на карагеніновій моделі запального набряку лапи білого щура і фармакологічний ефект залежить від концентрації етанолу та співвідношення сировина:екстрагент. Найкращу антиексудативну активність проявляє 70 % спиртовий екстракт (1:20), показник пригнічення запальної реакції якого становив 27 %, що дещо поступається референс-препаратам (нижче на 10 та 17 % відносно кеторолаку трометаміну та диклофенаку натрію, відповідно) та є хорошим показником для рослинних протизапальних засобів. Висновки. Досліджено гостру токсичність та протизапальну дію спиртових екстрактів трави сну білого (Pulsatila alba) і встановлено, що 70 % спиртовий екстракт (1:20) є відносно нешкідливою речовиною (VI клас токсичності) та проявляє виразну протизапальну активність (показник пригнічення запальної реакції - 27 %) на карагеніновій моделі запального набряку лапи білого щура при внутрішньошлунковому введенні.

The new aggregate data analyses revealed the earlier missing role played by the cerebellum long-term electrical stimulation in the absence epilepsy. Neurophysiologic data gained by authors favor that cerebellar serial deep brain stimulation (DBS) (100 Hz) causes the transformation of penicillin-induced cortical focal discharges into prolonged 3,5-3,75 sec oscillations resembling spike-wave discharges (SWD) in cats. Such SWDs were not organized in the form of bursts and persisted continuously after stimulation. Therefore the appearance of prolonged periods of SWD is regarded as a tonic cerebellar influence upon pacemaker of SWD and might be caused by the long-lasting DBS-induced increase of GABA-ergic extrasynaptic inhibition in forebrain networks. At the same time, cerebellar DBS high-frequency (100 Hz) suppressed bursts of SWD observed during the phase of stimulation. Different types of cerebellar DBS upon epileptic activity emphasized the absence seizure facilitation discussed with the reviewed data on optogenetic stimulation, neuronal activity of cerebellar structures, and functional magnetic resonance imaging data.

Development and introduction in medical practice sedative meals on the base of complex phytopoliextracts from the domestic medical plants permitted for medical application is highly actual because of incrised incidence of abnormal psychology disorders determined by socioeconomical problems, global informative boom, ecological problems, worsening of life quality. The aim of a study – determination of the sedative phytopoliextraction complex chronic toxicity parameters in experiments after oral administration to laboratory rats. Standardized phytopoliextraction сomplex which is composed of extracts of medical plants (Valeriana officinalis L., Crataégus, Melissa officinalis L., Hypericum, Mentha piperita L., Húmulus lúpulus, Viburnum). It was determined that phytopoliextraction complex is non-toxic compound – LD50 drug after a single oral administration to mice is > 5.0 ml/kg, to rats > 10.0 ml/kg. A two-month administration of a phytopolietextraction complex in an effective and sub-toxic dose (1 ml/kg and 5 ml/kg, respectively) does not exert a toxic effect on the general state of the behavior and the increase in the weight of the animals. Phytopolietextraction complex in the subtotoxic dose does not change the functional state of the CNS in male rats, but in the effective state it increases the research activity. At the same time, it exerts a certain stimulating effect on females, due to the content of ethyl alcohol, and in a sub-toxic dose has a hypoglycemic effect largely due to the presence of ethyl alcohol. Thus, futher experiments have to be provided to learn other chronic toxicity parametres like local localirritating action, embrio- and gonadotoxicity.

Aim.Obtaining the mathematical equations for calculating the size of the parts to which different morphological organs of medicinal plants are to be chopped in order to achieve a required degree of extraction of biologically active compounds when they are extracted simultaneously. Methods.Looking at the increasing trends of the level of psychopathological disorders, it is expedient to develop and introduce into medical practice sedatives which is based on complex phytopolyextracts, obtained from medicinal vegetable raw materials permitted for medical use. Modern data about the chemical ingredients, pharmacological effect, application in world medical practice allow us to positively evaluate the trends of using the medicinal vegetable raw materials for the preparation of phytopolyextracts of sedative meditinal. Growing requirements for the quality of medicinal products of plant origin are a prerequisite for the development of advanced methodologies for the production of phytopolyextracts. Result.The results of research into the development of a methodology for the analytical calculation of the particle size of plant raw materials of various morphological organs to simultaneously achieve a given degree of extraction of organic acids and other biologically active substances during joint extraction are presented. Conclusions.The obtained mathematical equations describe the dynamics of extraction of organic acids from medicinal vegetable raw materials. Solving the system of obtained mathematical equations allows to calculate the size to which the vegetable raw materials of different morphological organs should be grinded in order to simultaneously achieve a given degree of extraction with joint extraction the mixture of medicinal vegetable raw materials. The obtained results represent the benefits from research of joint extraction of medicinal vegetable raw materials to obtain natural biologically active substances for the manufacture of multicomponent phytopreparations

The development of stomatitis is characterized by the appearance of oxidative stress, which is marked by an increase in the intensity of peroxide lipid oxidation processes, resulting in metabolic disturbance in oral mucosa. As a result, toxic substances accumulate and endogenic toxicity develops. Thus, correction of pathological processes in the oral mucosa with antioxidant medication enables to optimize the intensity of inflammation, shorten the period of catabolic phase and accelerate the regeneration. Extract of Geranium palustre herb as a dental film was used to reduce the intensity of processes of lipid peroxidation and endogenous intoxication. This treatment method enables to release an active substance from the drug locally and to provide optimal therapeutic effect. The efficacy of the experimental medication was studied in the dynamics of experimental ulcerative stomatitis development in rabbits. The experimental model of ulcerative stomatitis in animals was induced with a burn method. For the experiment, the animals were divided into 2 groups: control group, where treatment was not performed, and experimental group, where animals were treated by applying a dental film with Geranium palustre extract. The monitoring was conducted on the 3rd, 5th, 7th and 10th days of the experiment, which are key stages of healing. During these periods, blood was taken under anesthesia from the auricular vein of each experimental animal. Dynamics of prooxidant processes was detected by the level of lipid hydroperoxides and malondialdehyde, and the level of endogenic toxicity by the content of middle molecules. Statistic processing of the obtained results of investigation was performed using personal computer with installed proper software package StatSoft Statistica 10. Reliable difference was considered р

The new aggregate data analyses revealed the earlier missing role of cerebellum long-term electrical stimulation in the absence epilepsy. Neurophysiologic data gained by authors favor that cerebellar serial deep brain stimulation (DBS) (100 Hz) causes the transformation of penicillin-induced cortical focal discharges into prolonged 3,5–3,75 sec oscillations resembling spike-wave discharges (SWD) in cats. Such SWDs were not organized in the form of bursts and persisted continuously after stimulation. Therefore, the appearance of prolonged periods of SWD is regarded as a tonic cerebellar influence upon pacemaker of SWD and might be caused by the long-lasting DBS-induced increase of GABA-ergic extrasynaptic inhibition in the forebrain networks. The absence seizure facilitation caused by cerebellar DBS was discussed with the reviewed data on optogenetic stimulation, neuronal activity of cerebellar structures, and imaging data.

The research is dedicated to in-depth study of neurotrophic and antiepileptic properties of original potential anticonvulsant agents from 4-thiazolidinones – LES-2658 (5-(3-nitro-benzylidene)-2-(thiazol-2-ylimino)-thiazolidin-4-one) and LES-1205 ([2,4-dioxo-5-(thiazol-2-ylcarbamoylmethyl)-thiazolidin-3-yl]-acetic acid ethyl ester), synthesized at the Department of Pharmaceutical, Organic and Bioorganic Chemistry of Danylo Halytsky Lviv National Medical University, Ukraine. Studying of sleep - wakefulness cycle characteristics in animals with chronic epileptic syndrome in conditions of 4-thiazolidinones derivatives LES-2658 and LES-1205 use was performed. The kindling syndrome was induced in Wistar rats via daily pentylenetetrazol (PTZ) (30 mg/kg, i.p.) administrations during three weeks and sleep - wakefulness cycle was studied under conditions of LES-2658 and LES-1205 administrations at doses 25.0and 100.0 mg/kg i.p.. Total wakefulness, non - rapid eye movement sleep, rapid eye movement sleep, falling asleep latency, REM - onset latency and also number of REM sleep episodes have been determined by behavioral characteristics of experimental animals. It was established that 4-thiazolidinone derivatives Les-1205 and Les-2658 reduce REM sleep fragmentation and increase its duration in PTZ-kindled rats. Les-1205 compound at dose 100.0 mg/kg show a clear correcting influence on kindling - induced sleep disturbances.

Peroxisome proliferator-activated receptors (PPARs) play an important role in numerous chronic diseases such as diabetes, obesity, atherosclerosis and cancer, and PPAR modulators are among the approved drugs and drug-candidates for their treatment. The aim of this study was to elucidate the involvement of PPARs in the mechanism of cytotoxic and pro-apoptotic action of novel anticancer 4-thiazolidinone derivatives (Les-2194, Les-3377, Les-3640) and approved 4-thiazolidinones (Rosiglitazone, Pioglitazone) towards the human squamous carcinoma (SCC-15) cell line. Experiments with 4-thiazaolidinone derivatives and PPAR-specific siRNA were conducted and PPARα, PPARβ and PPARγ mRNA expression was studied. Moreover, after PPARα, PPARβ and PPARγ siRNA gene silencing, cell viability, cell metabolism and caspase-3 activity were measured. The results showed a decrease of mRNA expression of the studied PPARs in SCC-15 cells treated with 10 and 50 μM Les-2194, Les-3377 and Les-3640. PPARγ knockdown protected the cells from the cytotoxic effect of the tested compounds (50 μM). It was established that novel anticancer 4-thiazolidinone derivatives act mainly through the PPARγ pathway in SCC-15 cells. Our results suggest that all studied compounds act as PPARs agonists. Interestingly, silencing of PPARγ gene increases the expression of PPARα, PPARβ mRNA in SCC-15 cells. The anticancer potential of new studied compounds was more expressed as compared to Rosiglitazone and Pioglitazone.

4-Thiazolidinones are a known class of prospective drug-like molecules, especially in the design of new anticancer agents. Two of the most prominent subtypes of these compounds are 5-ene-2-amino(amino)-4-thiazolidinones and thiopyrano[2,3-d]thiazoles. The latter are considered to be cyclic mimetics of biologically active 5-ene-4-thiazolidinones with similar pharmacological profiles. Therefore, the aim of this study was to evaluate the impact of 4-thiazolidinone-based compounds on cytotoxicity, the apoptotic process, and metabolism in the human squamous carcinoma (SCC-15) cell line. The SCC-15 cells were cultured in phenol red-free DMEM/F12 medium supplemented with 10% FBS, hydrocortisone, and exposed to rising concentrations (1 nM–100 μM) of the studied compounds for 6, 24 and 48 h. Afterwards, reactive oxygen species (ROS) formation, cell viability, caspase-3 activity, and cell metabolism were measured. The obtained results showed that all of the studied compounds in a wide range of concentrations (1 nM–100 μM) increased DCF fluorescence which suggests a stimulation of ROS production. Nevertheless, these new compounds showed cytotoxic and proapoptotic properties only at high (10–100 μM) concentrations. Our studies are the first to be carried out on these compounds and require further investigation to clarify the mechanism of action of their anticancer potential.

Introduction. The article presents the results of biochemical studies of enzymes, intermediate and final products of prooxidant-peroxidic processes in periodontal diseases against the background of urolithiasis in the dynamics of treatment and in the aspect of the presenting of comparison of two drug regimens: standard common and developed pathogenetic. The presented data represent a fragment of the scientific and practical research performed to improve the periodontal care in patients with urolithiasis. The aim of the study – to analyze the biochemical studies performed in patients with comorbid pathology after combined pharmacotherapy. The biomaterial was studied in 60 patients with inflammatory periodontal diseases on the background of urolithiasis. Two different pharmacotherapeutic regimens were used to treat patients. Research M ethods . A series of biochemical studies was carried out to objectify the results. According to the obtained data, the application of the developed treatment regimen in patients with comorbid pathology provided normalization of the antioxidant protection system in catalase parameters from 1.99±0.14 at the beginning of treatment to 1.66±0.04 after treatment and superoxidedismutase from 1.40±0, 12 to 2.10±0.07, as well as a decrease in the levels of intermediate and final products of peroxidation. Results and D iscussion. The analysis of the results of the observation showed high efficiency of combined pharmacotherapy. Conclusions. Thus, according to the resulted biochemical indicators, application of standard and developed treatment regimens ensured the normalization of the activity of the enzymatic level of the antioxidant system and reduced the intensity of the oxidative processes. An analysis of the results of the studies suggests a higher efficiency of the combined pharmacotherapy, since antioxidant protection indicators in patients treated under the developed scheme, normalized faster than when administered under the traditional generally accepted protocol.

Heart rate variability (HRV ) parameters and hematological indices in rats under hypobaric hypoxia duringtreatment by a thiazolidine derivative substance Les-589 (potassium salt of 3-(5-phenylpropeniliden rhodamine-3-yl)-propanoic acid) were studied. Hypobaric hypoxia was developed in altitude chamber for 1 hour under conditionsidentical height of 6000 m above sea level, 45 minutes after injection of Les-589. Thiotriazolin was applied as areference drug.After one day after exposure to hypoxia, according to blood parameters and hematological indices, adaptiveresponse develops by the type of insufficient adaptation. The effect of the prior administration of Les-589, similar tothe effect of a reference drug Thiotriazolin, in the time of post-hypoxic period developed reactions of an increasedactivation, which indicates a favorable course of adaptation.Considering the parameters of HRV was found that prior administration of Les-589 within studied terms of posthypoxicperiod leads to earlier and more effective recovery of various links of regulatory systems, compared withhypoxia. This is consistent with an estimated type of adaptation processes, based on hematological parametersand indices.