Periodicum Biologorum最新文献

{"title":"Neuropharmacology: Oxime antidotes for organophosphate pesticide and nerve agent poisoning","authors":"Tamara Zorbaz, Z. Kovarik","doi":"10.18054/PB.V121-122I1-2.10623","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10623","url":null,"abstract":"Organophosphate (OP) compounds remain a great threat for humans because they are used as pesticides or misused as chemical warfare nerve agents. Their mechanism of toxicity involves the irreversible inhibition of the acetylcholinesterase (AChE) enzyme important in the control of cholinergic neurotransmission at the periphery and in the brain. An available pharmacological treatment are oxime compounds, that are reactivators of OP-inhibited AChE. However, oximes are not equally effective for every possible OP and they cross the blood-brain barrier (BBB) poorly. Novel oximes are being designed and synthesized at a high rate and scale and their pharmacological efficiency is being addressed mostly with the in vitro reactivation assay. Nevertheless, only few newly synthesized oximes have shown comparable or better pharmacological properties than the ones developed more than 65 years ago beacuse oxime potential to act as efficient antidote in vivo depends on its pharmacokinetic and neuropharmacokinetics profile. This paper provides an overview of all the important aspects that should be accounted for in the search for a centrally active oxime. Furthermore, it lists the most important BBB oxime delivery strategies employed until now, and the available pharmacokinetic data on old and new oximes. NEUROTOXIC ORGANOPHOSPHATES N disorders include different conditions categorized as neurodegenerative, neuroinflammatory, neuropsychiatric, and other diseases, and as such represent one of the major global public health challenges that affect hundreds of millions of peoples worldwide (1). Conditions that originate at the level of the central nervous system (CNS) are difficult to treat both pharmacologically and surgically due to the specific anatomy and physiology of the nervous system. In addition, the nervous system is the target of many toxic compounds such as highly lethal synthetic organophosphorus compounds (OPs) derived from phosphorous, phosphonic, or phosphonic acid. They were primarily developed and used as pesticides; however, they turned out to be toxic for different species, including humans; therefore, many OP pesticides have been banned, e.g., parathion, dichlorvos (2, 3). The incidence of intentional/unintentional OP pesticide poisoning is about 3 million cases per year, while lethal outcomes of poisoning (about 200 000 cases) have mostly been recorded in developing or under-developed countries due to a lack of strict pesticide use regulation and proper medical care (4, 5). In addition, OPs are mostly colourless and odourless TAMARA ZORBAZ*","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48636964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of thyroid volume in healthy young adults of Dalmatia","authors":"T. Zemunik","doi":"10.18054/PB.V121-122I1-2.10268","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10268","url":null,"abstract":"Background and purpose: The aim of this study was to investigate thyroid volume (TV) and its determinants in healthy young adults without present or previous thyroid disease. Materials and methods: The study was performed in a sample of 145 healthy young participants aged 19–29 years, living in an iodine-sufficient area of Dalmatia. Dimensions of the thyroid gland were obtained by ultrasound and used to determine TV. Anthropometric data was collected, and measurements of serum TSH, fT4, Tg, TgAb, and TPOAb levels were determined. Correlations between TV and other continuous variables were determined using the Pearson correlation test, while multivariate linear regression analysis was used to determine the associations of the potential predictors for the TV. Results: TV in men was larger than in women (p = 3.53 × 10–8) and was positively correlated with anthropometric measurements, with the highest correlation coefficient for height (r = 0.53, p = 6.36 × 10–12), then body surface area, BSA (r = 0.48, p = 1.68 × 10–9), weight (r = 0.43, p = 8.28 × 10–8) and body mass index, BMI (r = 0.17, p = 0.04). Age and cigarette smoking did not appear to be significantly associated with TV (p = 0.13 and p = 0.95, respectively). Univariate analysis showed TV correlated with fT4 plasma levels (b = 0.79, p = 1.73 × 10–5), while multivariate analysis showed height and fT4 levels to be important parameters with a significant role in TV. Conclusions: We confirmed previously observed association of TV with sex and anthropometric parameters and reported a significant correlation between TV and fT4 levels. Furthermore, fT4 levels and height were found to be the important parameters for predicting TV.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49649805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATIC as a link between antirheumatic drugs and regulation of energy metabolism in skeletal muscle","authors":"K. Dolinar","doi":"10.18054/PB.V121-122I3-4.10802","DOIUrl":"https://doi.org/10.18054/PB.V121-122I3-4.10802","url":null,"abstract":"Chronic inflammatory rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus, increase the risk of developing insulin resistance, metabolic syndrome, and/or type 2 diabetes. While inflammation is thought to be a major mechanism underlying metabolic dysregulation in rheumatic diseases, antirheumatic drugs that exert direct metabolic effects in addition to suppressing inflammation, might be particularly useful to prevent metabolic complications. Here we review antirheumatic drugs, such as methotrexate, that inhibit ATIC, the final enzyme in the de novo purine biosynthesis, responsible for conversion of ZMP to IMP. Inhibition of ATIC results in accumulation of ZMP, thus promoting activation of AMP-activated protein kinase (AMPK), a major regulator of cellular energy metabolism and one of the most promising targets for the treatment of insulin resistance and type 2 diabetes. We focus especially on ATIC inhibition and AMPK activation in skeletal muscle as this is the largest and one of the most metabolically active tissues with a major role in glucose homeostasis. As an important site of insulin resistance, skeletal muscle is also one of the main target tissues for pharmacological therapy of type 2 diabetes. Finally, we review the metabolic effects of ATIC-inhibiting antirheumatic drugs and discuss whether these drugs might improve systemic glucose homeostasis by inhibiting ATIC and activating AMPK in skeletal muscle.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48803388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crossroads in Life Sciences","authors":"T. Balog","doi":"10.18054/PB.V121-122I1-2.11506","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.11506","url":null,"abstract":"T entire volume of Periodicum biologorum is dedicated to molecular life sciences with two papers written by the Spiridion Brusina Medal laureates and 14 papers as an overview of the scientific topics presented at the HDBMB2019 “Crossroads in Life Sciences” that was held in Lovran, Croatia from 25 to 28 September 2019. We are pleased that Periodicum biologorum will serve as a support to disseminate scientific achievements of this Congress, and we are honoured to give assistance as guest editors. This collaboration between HDBMB and Periodicum biologorum has proven successful in 2016 when an issue was dedicated to the 40th Anniversary of the Croatian Society for Biochemistry and Molecular Biology (HDBMB). We also hope to continue down this road and justify the trust given by the readers.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43410760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in recombinant technology for production of butyrylcholinesterase, a bioscavenger of nerve agent","authors":"T. Čadež, Z. Kovarik","doi":"10.18054/PB.V121-122I1-2.10867","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10867","url":null,"abstract":"Butyrylcholinesterase (BChE) is a serine hydrolase present in plasma and other mammalian tissues. As a target of organophosphorous pesticides and warfare nerve agents, BChE acts as their stoichiometric bioscavenger. However, so far it has been a significant challenge to produce BChE at large scales and low cost. For decades, numerous research efforts have been directed first at isolation from human volunteers and later at production of BChE in eukaryotic and prokaryotic expression systems. In this review we focused on recent studies on recombinant BChE discussing reasons why the efficient, economically sensible expression system for recombinant BChE is hard to develop. We also bring the most recent advancements in the use of expression of human BChE in vivo as an effective prophylactic against organophosphate poisoning.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46241855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tools and databases for solving problems in detection and identification of repetitive DNA sequences","authors":"E. Šatović","doi":"10.18054/PB.V121-122I1-2.10571","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10571","url":null,"abstract":"Genome compartments known to carry out very important biological functions (e.g. centromeres and telomeres) are mostly constituted of repetitive sequences. At the same time, regions of the genomes enriched in repetitive sequences have always presented great technical challenges for sequence alignments and genome assemblies. Fast evolving sequencing technologies and the increasing accessibility of genomic datasets have opened the opportunity to gain new insights into poorly explored genome fractions, built of repetitive DNA. Comprehensive and accurate annotation and characterization of these sequences is therefore an important contribution to the understanding of genomic architecture and function as a whole. In order to attend the emerging needs in repeat analysis and characterization, many bioinformatics tools, databases and pipelines have been generated. This review is intended to draw attention to the problems encountered in the genomic studies of repetitive sequences and to provide an overview of a spectrum of most prominent bioinformatics tools used for gaining better insight into these important genomic components. Some of the described assets are focused on detection of a wide range of repeats while the others are focused on a specific type of repetitive DNA sequences, generated as an answer to specific research interests and needs of the scientific community. REPETITIVE SEQUENCES IN EUKARYOTIC","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45726487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optineurin Dysfunction in Amyotrophic Lateral Sclerosis: Why So Puzzling?","authors":"Nikolina Prtenjaca","doi":"10.18054/PB.V121-122I1-2.10627","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10627","url":null,"abstract":"Mutations in optineurin have been linked to amyotrophic lateral sclerosis (ALS) a decade ago, but its exact role in the neurodegenerative process is still unclear. As a lysine 63 (K63)and methionine (M1)-linked polyubiquitin-binding protein, optineurin has been reported to act as an adaptor in inflammatory signaling pathways mediated via nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 3 (IRF3), as well as in membrane-associated trafficking events including autophagy, maintenance of the Golgi apparatus, and exocytosis. Other studies have demonstrated its role in other processes such as regulation of mitosis, transcription, necroptosis and apoptosis. However, many of the reported effects in cell models have been proven difficult to reproduce in optineurin animal models, demonstrating the challenges of extrapolation between model systems. Knowing that multifunctional proteins present a “nightmare” for researchers, to help navigating through this field, we address the most common controversies, open questions, and artefacts related to optineurin and its role in pathogenesis of ALS and other neurodegenerative diseases.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46083604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of quinoline-arylamidine hybrids on LPS-induced inflammation in RAW 264.7 cells","authors":"A. Peris","doi":"10.18054/PB.V121-122I3-4.11132","DOIUrl":"https://doi.org/10.18054/PB.V121-122I3-4.11132","url":null,"abstract":"Background and purpose: Inflammation is a common pathogenesis in infection, injury, cancer, and many chronic diseases. Macrophages are among the main cells involved in generation of inflammation. The aim of the present study was to investigate the effects of molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible a 2-aminoethanol linker, on the in vitro inflammatory responses to lipopolysaccharides (LPS) induced inflammation in the RAW 264.7 cells. Materials and methods: To determine effects of seven quinoline-arylamidine hybrids on the growth of the murine macrophage-like (RAW 264.7) cells MTT assay was used. Inflammatory reactions in the RAW264.7 cells were induced using E. coli lipopolysaccharides (LPS). Levels of nitric oxide (NO) and malondialdehyde (MDA) were determined by spectrophotometry methods. Intracellular production of reactive oxygen species (ROS) was measured by flow cytometry. Antioxidant capacity of tested compounds was tested by 2,2’-azino-bis(3-ethybenzthiazoline-6-sulfonic acid (ABTS) radical cation method. Results: Tested hybrid compounds differentially influenced proliferation of non-stimulated and LPS-stimulated RAW 264.7 cells. The hybrid compounds have not presented ABTS radical-scavenger activity. In the LPSstimulated RAW 264.7 cells 10 μM compounds slightly decreased production of NO and ROS and significantly modulated LPS-induced lipid peroxidation. Conclusions: Molecular hybrids with 7-chloroquinoline and arylamidine moieties joined through flexible 2-aminoethanol linker markedly decreased accumulation of lipid peroxidation products in the LPS-stimulated RAW 264.7 cells. Further studies are necessary to determine their mechanism of anti-inflammatory action in more details.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46919423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological activity of monoquaternary ammonium compounds based on 3-substituted quinuclidine: A short review","authors":"R. Odžak","doi":"10.18054/PB.V121-122I1-2.10603","DOIUrl":"https://doi.org/10.18054/PB.V121-122I1-2.10603","url":null,"abstract":"Quaternary ammonium compounds (QACs) have a long-known application as antiseptics and disinfectants applied in various industries such as pharmaceutical, agricultural and food industry. Given the alarming number of QACs resistant bacteria, there is an urgent need to develop new QACs with broad-spectrum antimicrobial activities and low tendency to trigger bacterial resistance. One recently proposed approach to develop new QACs is based on quaternization of natural products, which proved to be successful. Quinuclidine is an interesting natural precursor find to be a part of the structure of biologically active cinchona alkaloids. In addition to the well-established medicinal and pharmaceutical potential of 3-substituted quinuclidines, QACs based on 3-substituted quinuclidines, have only recently been shown to exhibit a significant antimicrobial activity. Most importantly, these compounds exhibit low toxicity toward normal human cell lines, which opens up a new chapter in the QACs field ensuring further investigation of possible therapeutic application of 3-substituted quinuclidine based QACs.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45133550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinic acetylcholine receptors: Diversity and physiological importance for neurodegenerative disorders and development of organophosphate antidotes","authors":"A. Zandona, M. Katalinić","doi":"10.18054/PB.V121-122I3-4.10547","DOIUrl":"https://doi.org/10.18054/PB.V121-122I3-4.10547","url":null,"abstract":"The communication between the nervous and other systems in the organism is carried out by the transmission of nerve impulses. Diverse neurotransmitters are released into the synaptic cleft and bind to the specific receptors at the neighbouring cell to transmit the signal further. One of such receptors are nicotinic acetylcholine receptors (nAChR), integrated membrane proteins (ligand-gated ion channels) activated by the binding of a neurotransmitter acetylcholine. nAChR’s main characteristic is their diversity, as they consist of five of the same or mutually different subunits, which contribute to the specific receptors properties and biological activity. During the assembly of a pentameric protein structure, various combinations of subunits are linked together. After the discovery of nAChR’s involvement in various diseases, they became an important therapeutic target, for example in the treatment of neurodegenerative diseases (Alzheimer’s and Parkinson’s) and in the treatment of organophosphorus compound poisoning. This paper presents an overview of current knowledge on nicotinic receptors and an accompanying discussion on diseases, poisonings, potential drugs and treatments is given.","PeriodicalId":19950,"journal":{"name":"Periodicum Biologorum","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49621489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}