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Case Reports 2017; 37(8): 535-539 PubMed PMID: 28326748 Citation  Keywords:  Adult, Appendiceal Neoplasms:diagnosis, Carcinoid Tumor:diagnosis, Female, Follow-Up Studies, Humans, Parturition:physiology, Pregnancy, Pregnancy Complications, Neoplastic:diagnosis, Prognosis, Receptors, Somatostatin:metabolism, Treatment Outcome,.   

: Neuroendocrine neoplasms are detected very rarely in pregnant women. The following is a case report of carcinoid tumor of the appendix diagnosed in 28 year-old woman at 25th week of gestation. The woman delivered spontaneously a healthy baby at the 38th week of gestation. She did not require adjuvant therapy with somatostatin analogues. The patient remained in remission. There are not established standards of care due to the very rare incidence of carcinoid tumors in pregnancy. A review of the literature related to management and prognosis in such cases was done....

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Journal Article 2016; 37(Suppl 1): 118-122 PubMed PMID: 28263539 Citation  Keywords:  Acetylcholinesterase:drug effects, Celecoxib:pharmacology, Cholinesterase Inhibitors:pharmacology, Cyclooxygenase 2 Inhibitors:pharmacology, Dithionitrobenzoic Acid, Humans, Molecular Docking Simulation,.   

OBJECTIVES: Celecoxib is a nonsteroidal anti-inflammatory drug inhibiting enzyme cyclooxygenase-2 (COX-2). The drug was introduced in 1990s. In the work presented here, affinity of celecoxib to enzyme acetylcholinesterase (AChE) is inferred.

METHODS: Inhibition of human AChE by celecoxib was tested using standard spectrophotometric Ellman´s method and extrapolation of experimental data by Dixon plot. Interaction between AChE and celecoxib was also predicted by molecular docking using Swiss dock software.

RESULTS: A non-competitive mechanism of inhibition was revealed and equilibrium inhibitory constant equal to 313±40 µmol/l was determined. Comparing to AChE, celecoxib was not proved as an inhibitor of enzyme butyrylcholinesterase (BChE). The lowest ΔG was equal to -7.78 kcal/mol. In this case, celecoxib stacked sulfonamide moiety between TYR 337 and TYR 341 of alfa anionic subsite of active site. Cation-Π interactions appears to be responsible for the inhibition.

CONCLUSIONS: Though the here revealed and characterized inhibition has lower effect in real conditions than inhibition of COX-2, the inhibitory effect would be utilized in the next research and development of new AChE inhibitors.

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Journal Article 2016; 37(Suppl 1): 95-102 PubMed PMID: 28263536 Citation  Keywords:  Antineoplastic Agents, Phytogenic:metabolism, Cytochrome P-450 CYP3A:metabolism, DNA Adducts:metabolism, Ellipticines:metabolism, Humans, Liposomes, Microsomes,.   

OBJECTIVES: Ellipticine is an anticancer agent that functions through multiple mechanisms participating in cell cycle arrest and initiation of apoptosis. This drug forms covalent DNA adducts after its enzymatic activation with cytochrome P450 (CYP), which is one of the most important ellipticine DNA-damaging mechanisms of its cytotoxic effects. The improvements of cancer treatment are the major challenge in oncology research. Nanotransporters (nanoparticles) are promising approaches to target tumor cells, frequently leading to improve drug therapeutic index. Ellipticine has already been prepared in nanoparticle forms. However, since its anticancer efficiency depends on the CYP3A4-mediated metabolism in cancer cells, the aim of our research is to develop nanoparticles containing this enzyme that can be transported to tumor cells, thereby potentiating ellipticine cytotoxicity.

METHODS: The CYP3A4 enzyme encapsulated into two nanoparticle forms, liposomes and microsomes, was tested to activate ellipticine to its reactive species forming covalent DNA adducts. Ellipticine-derived DNA adducts were determined by the 32P-postlabeling method.

RESULTS: The CYP3A4 enzyme both in the liposome and microsome nanoparticle forms was efficient to activate ellipticine to species forming DNA adducts. Two DNA adducts, which are formed from ellipticine metabolites 12-hydroxy- and 13-hydroxyellipticine generated by its oxidation by CYP3A4, were formed by both CYP3A4 nanoparticle systems. A higher effectiveness of CYP3A4 in microsomal than in liposomal nanoparticles to form ellipticine-DNA adducts was found.

CONCLUSION: Further testing in a suitable cancer cell model is encouraged to investigate whether the DNA-damaging effects of ellipticine after its activation by CYP3A4 nanoparticle forms are appropriate for active targeting of this enzyme to specific cancer cells.

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Journal Article 2016; 37(Suppl 1): 84-94 PubMed PMID: 28263535 Citation  Keywords:  Animals, Benzo(a)pyrene:pharmacology, Cytochrome P-450 Enzyme System:metabolism, Endocrine Disruptors:pharmacology, Estradiol:pharmacology, Estrogens:pharmacology, Ethinyl Estradiol:pharmacology, Male, Microsomes, Liver:metabolism, Rats, Rats, Wistar,.   

OBJECTIVES: The term "endocrine disruptor" (ED) is used for compounds that mimic or antagonize the effects of endogenous hormones. Synthetic estrogen 17α-ethinylestradiol (EE2) and a human carcinogen benzo[a]pyrene (BaP) are assigned as exogenous endocrine disruptors and an estrogenic hormone estradiol is a natural endogenous disruptor. Here, the potency of these three disruptors administered to rats individually and in combination to induce expression of cytochrome P450 (CYP) enzymes involved in their own metabolism (CYP1A1, 2C and 3A) in vivo was investigated.

METHODS: Changes in CYP protein expression after exposure of rats to BaP, EE2 or estradiol were analyzed by Western blotting. Using the HPLC method, CYP1A1, 2C and 3A specific activities in hepatic microsomes isolated from exposed rats were analyzed.

RESULTS: Whereas exposure to BaP induces expression of CYP1A1 protein and its marker activity (Sudan I oxidation) in liver, kidney and lung of rats, no significant induction of this CYP and its enzyme activity was produced by EE2 and estradiol. Treatment of BaP in combination with EE2 and/or estradiol decreased the BaP-mediated CYP1A1 induction in liver of exposed rats. BaP also induces CYP2C11 protein in rat liver and kidney, but does not increase its enzyme activity measured as testosterone 16α-hydroxylation. The enzyme activity of another enzyme of the 2C subfamily, CYP2C6, diclofenac 4'-hydroxylation, is even decreased by BaP. The CYP2C11 protein expression and/or its activity are also increased in liver of rats treated with EE2 and estradiol, but its expression is significantly decreased in lung. The CYP2C6 activity is also elevated by treatment of rats with EE2 and estradiol administered individually as well as in their combination. Whereas only a slight increase in CYP3A protein expression was found by BaP in rat liver, its enzyme activity, testosterone 6β-hydroxyalation, increased significantly in this organ. In contrast, no effect or even a decrease in CYP3A expression and its enzyme activity was produced by EE2 and estradiol in rats exposed to these compounds....

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Journal Article 2016; 37(Suppl 1): 78-83 PubMed PMID: 28263534 Citation  Keywords:  Analgesics:toxicity, Animals, Cytotoxins:toxicity, Deer, Heart:drug effects, Ketamine:analogs & derivatives, Kidney:cytology, Liver:cytology, Toxicity Tests:methods, Xylazine:analogs & derivatives,.   

OBJECTIVES: Chemical restraint of wild animals is practiced to accomplish intended procedures such as capture, clinical examination, collection of diagnostic samples, treatment and/or transport. Extra-label use of animal medicinal drugs is often necessary in wildlife because most approved therapeutics do not list wild species on the labelling. Here, we used cellular in vitro models, a cutting-edge tool of biomedical research, to examine cytotoxicity of anaesthetic agents in fallow deer and extrapolate these data for anaesthetic risks in wildlife.

METHODS: We examined the cytotoxic effects of ketamine, xylazine, and ketamine-xylazine, i.e. the Hellabrunn mixture, on liver-, heart- and kidney-derived cell cultures prepared from a fallow deer (Dama dama) specimen. In line with preliminary studies we exposed cells to 10 µM, 50 µM, 100 µM, 1 mM, and 10 mM ketamine or xylazine. The combination of ketamine-xylazine was dosed at 0.025+0.02 mg/ml, 0.05+0.04 mg/ml, 0.75+0.06 mg/ml, 0.1+0.08 mg/ml, and 0.125+0.1 mg/ml per one well containing 10 000 cells. The quantification of cytotoxicity was based on lactate dehydrogenase activity released from damaged cells.

RESULTS: Liver-derived cells show higher sensitivity to the cytotoxic effects of both ketamine and xylazine administered as single drugs when compared with cells cultured from the heart and kidney. The Hellabrunn mixture induced significantly higher cytotoxicity for kidney-derived cells ranging from 16.78% to 35.6%. Single and combined exposures to ketamine and xylazine resulted only in high-dose cytotoxicity in the heart-derived cells.

CONCLUSIONS: Our results indicate that immobilization drugs significantly differ in their cytotoxic effects on cells derived from various organs of the fallow deer.

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Case Reports 2016; 37(Suppl 1): 9-12 PubMed PMID: 28263524 Citation  Keywords:  Adult, Asphyxia:complications, Brain Diseases:etiology, Female, Fetal Diseases, Humans, Infant, Newborn, Infant, Premature, Pregnancy, Sympathetic Nervous System,.   

: The aim of the study was to analyse case report of prenatally unknown asphyxia of the foetus (a preterm newborn from the second pregnancy delivered by urgent caesarean section in 31st gestational week; birth weight 850 grams, birth length 41 cm, value of Apgar score 7/8) with signs of respiratory insufficiency immediately after birth with hypotonicity. The authors present the case of postnatal at the 1st day of life assessed cystic malformation in the brain of premature newborn. They emphasize the importance of detailed prenatal investigation as most important in preventing prenatal asphyxia and consequent complications. Central nervous system and especially white matter of the brain of the newborn is most vulnerable area of the brain. Together with oxidative stress after exceeding of antioxidant capacity belong among main factors that play an important role in the pathogenesis of hypoxic-ischemic encephalopathy.

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Journal Article 2016; 37(suppl 2): 11-17 PubMed PMID: 28233960 Citation  Keywords:  Aged, Aged, 80 and over, Czech Republic, Female, Health Literacy:statistics & numerical data, Humans, Information Seeking Behavior, Male, Qualitative Research,.   

OBJECTIVES: This study aimed to map the selected indicators of health literacy in the senior population via a qualitative survey that focused specifically on its relationship with autonomy in the context of health literacy among seniors.

METHODS: A qualitative survey focused on the selected indicators of health literacy of seniors living in the South Bohemian Region of the Czech Republic (R1-19). The snowball sampling method was intentionally selected. Completed interviews were transcribed and data was reduced, analyzed, and categorized. The identified categories were 1) information comprehension, 2) decision-making in healthcare, and 3) compliance with nonpharmacologic treatment.

RESULTS: The 'information comprehension' category clearly shows that the seniors involved in this study rated the comprehensibility of information provided by medical professionals as being good. An especially positive finding was that seniors do seek information through the internet, print sources, or other media, even though, as one senior (80-year-old woman) said, comprehension of medical information is becoming "more and more complex". The 'decision-making in healthcare' category touched upon opinions regarding informed consent and opinions regarding seniors' own involvement in healthcare. Results from this category suggest that seniors accept informed consent as a routine necessity. Inhibition regarding personal involvement in healthcare was also apparent: "... I come from a family accustomed to not bothering the doctor unnecessarily, so I just stick out my arm..." The last category of 'compliance with nonpharmacologic treatment' clearly shows that respondents are informed regarding lifestyle modifications that would benefit their treatment, although, few respondents had achieved the desired lifestyle changes.

CONCLUSION: Results of this qualitative research show clear health literacy limits among seniors. As shown in this study, age itself could also be a limiting factor of health literacy....

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Journal Article 2016; 37(suppl 2): 25-31 PubMed PMID: 28233957 Citation  Keywords:  Adolescent, Adult, Czech Republic, Female, Health Literacy:statistics & numerical data, Humans, Male, Middle Aged, Patient Acceptance of Health Care:statistics & numerical data, Patient Participation:statistics & numerical data, Qualitative Research, Youn.   

: In this study, the question of health literacy in adult patient population in the Czech Republic is explored in the context of healthcare, particularly in the South Bohemian Region. The study is based on the analysis of qualitative data which were collected during the first half of 2016. The study included 34 adult participants at the age range between 18 and 64 years. The study is focused on the involvement of adult patients in the process of decision making concerning the healthcare provided. The views of this sort of problems were recorded by the technique of semi-structured dialogues. The study results have suggested that adult individuals accept the healthcare provided by doctors or nurses prevailingly with trust. In addition, they have shown that in the sphere of health education, the adults lack the knowledge of the right for information about the individual's health condition and information about the service provided by the health insurance agency. It is regarded as desirable to deal with the topic of health literacy of adult population, particularly in the area of internet counselling and telemedicine, and to develop the space for information sharing between the doctor and nurse on one side and the patient on the other.

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