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Hradec Kralove, Czech Republic

University of Hradec Králové was founded on June 21, 2000 by renaming the University College of Education , which itself traces its roots back to 1959. It is attended by around 8,500 students.It belongs to one of the most important education and research institutions in the Eastern Bohemia.The current rector of the university is prof. RNDr. Josef Hynek, MBA, Ph.D. Wikipedia.

Pohanka M.,University of Hradec Kralove
International Journal of Molecular Sciences

Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is an important part of the cholinergic nerve system in the brain. Moreover, it is associated with a cholinergic anti-inflammatory pathway in the termination of the parasympathetic nervous system. Antagonists of α7 nAChR are a wide group represented by conotoxin and bungarotoxin. Even Alzheimer's disease drug memantine acting as an antagonist in its side pathway belongs in this group. Agonists of α7 nAChR are suitable for treatment of multiple cognitive dysfunctions such as Alzheimer's disease or schizophrenia. Inflammation or even sepsis can be ameliorated by the agonistic acting compounds. Preparations RG3487, SEN34625/WYE-103914, SEN12333, ABT-107, Clozapine, GTS-21, CNI-1493, and AR-R17779 are representative examples of the novel compounds with affinity toward the α7 nAChR. Pharmacological, toxicological, and medicinal significance of α7 nAChR are discussed throughout this paper. © 2012 by the authors; licensee MDPI, Basel, Switzerland. Source

Pohanka M.,University of Hradec Kralove | Pohanka M.,Karel Englis College, Brno
Current Medicinal Chemistry

Alzheimer's disease (AD) is a neurodegenerative disorder with no known cure and rapid rise in incidence. The predominant cognitive impairment is currently treated using cognitive enhancers like cholinesterase inhibitors. The two molecular hallmarks of AD are amyloid plaques created from an amyloid precursor protein and hyperphosphorylated tau protein that is deposited as neurofibrillary tangles inside neurons. A number of pathological mechanisms follow or precede these formations. Alteration in mitochondrial function and deposition of heavy metals are reported. The disease progression is enhanced by oxidative stress. However, the role of oxidative stress is not universally accepted. The current review covers and discusses the basic evidence and role of oxidative stress in AD development. © 2014 Bentham Science Publishers. Source

Pohanka M.,University of Hradec Kralove
Analytical Letters

Acetylcholinesterase and butyrylcholinesterase are the only two known cholinesterases. Acetylcholinesterase plays an important part in cholinergic system. It terminates neurotransmission by hydrolysis of transmitter acetylcholine. The role of butyrylcholinesterase is not well understood. It is able to detoxify several compounds such as cocaine, succinylcholine, and so forth. The current review is focused on the application of cholinesterases in biorecognition. Cholinesterases are important markers in the body. Butyrylcholinesterase activity in plasma can serve as a liver function test or specific marker for sensitivity to myorelaxants or liver carcinoma. Both cholinesterases can serve as markers of poisoning by some neurotoxic compounds. Nerve agents (sarin, soman, tabun, VX), some Alzheimer disease drugs (galantamine, huperzine, donepezil, rivastigmine), pesticides (carbofuran, trichlorfon, paraoxon, malaoxon), and natural toxins (aflatoxin, pyridostigmine) can act as inhibitors of butyrylcholinesterase and/or acetylcholinesterase. Devices filled with immobilized cholinesterases can be used for the assay of the aforementioned toxins. In this review, methods for examination of cholinesterases activity in the body and in analytical devices are described. Applications, types of diagnosis, and assays are described as well. © 2013 Copyright Taylor and Francis Group, LLC. Source

Smolej L.,University of Hradec Kralove
Expert Opinion on Investigational Drugs

Introduction: Management of refractory chronic lymphocytic leukemia (CLL) represents a major challenge because of the poor prognosis and limited treatment options. While corticosteroids have been used to treat CLL since 1940s, their benefit has never been conclusively proved. Recently, several groups reported use of high-dose corticosteroids (methylprednisolone or dexamethasone) either alone or combined with chemotherapy and/or monoclonal antibodies in relapsed/refractory CLL. Areas covered: While efficacy of high-dose corticosteroids is excellent including responses in patients with bulky lymphadenopathy or those considered ultra high-risk CLL because of deletion and/or mutation of p53 gene, the duration of response is still unsatisfactory. Combination with monoclonal antibodies seems to improve therapeutic efficacy but no randomized trials have been conducted. For the purpose of this review, a search for terms, high-dose corticosteroids/methylprednisolone/dexamethasone, and chronic lymphocytic leukemia has been performed in PubMed and database of abstracts from American Society of Hematology Meetings. Expert opinion: High-dose corticosteroids appear to play an important role in the management of highly pretreated relapsed/refractory CLL including patients with massive lymphadenopathy. Myelosuppression is usually limited but infectious toxicity, including increased risk of invasive fungal infections, represents the most dreaded side effects. This therapeutic approach should be further tested within large prospective trials, to optimize efficacy and safety. © 2012 Informa UK, Ltd. Source

Summary: The aim of this study was to assess the relationships between both a marker of bone formation and a marker of bone turnover and age, sex, and pubertal stage in a group (n =439) of healthy children and adolescents. These reference data should be instrumental in interpretation of results. Introduction: The skeletal system has high metabolic activity. In children, bone markers may be useful in diagnostics and treatment management of skeletal diseases but there could be difficulties with interpretation of results. Compared with adults, children have elevated bone marker levels due to high skeletal growth velocity and rapid bone turnover. Thus, valid age- and sex-specific reference data should be obtained for each pediatric population living in a particular climate and with a similar lifestyle. The aim of this study was to assess the relationships between both a marker of bone formation (procollagen type I N-terminal propeptide [PINP]) and a marker of bone turnover (osteocalcin [OC]) and age, sex, and pubertal stage in a group of healthy children and adolescents. Methods: Four hundred thirty-nine healthy Caucasian children participated. Their height, weight, and pubertal stage were recorded. Fasting PINP and OC weremeasured using a morning blood sample. Results: The highest levels of PINP were observed during the first year of life. There is no OC postnatal peak, but levels are higher than the adult reference interval throughout childhood. OC peaks with the pubertal growth spurt at second-third Tanner stage of breast development in girls and at second-third Tanner stage of genital development in boys. PINP peaks during second-third Tanner stage of breast development in girls and at third Tanner stage of genital development in boys. Conclusion: This study provides reference data for OC and PINP in healthy Caucasian children from a Central European population. © International Osteoporosis Foundation and National Osteoporosis Foundation 2013. Source

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