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Metal-based coordination compounds have been used throughout the history of human medicine to treat various diseases, including cancer. Since the discovery of cisplatin in 1965, a great number of metal coordination complexes, such as platinum, ruthenium, gold or copper have been designed, synthesized and tested in order to develop clinically effective and safe drugs. Currently, many reviews cover applications of cytostatic metal complexes pointing out the most promising examples of platinum- and non-platinum-based compounds in preclinical and clinical trials. However, recent comprehensive reviews covering chemical and biological aspects of metal-based coordination compounds in cancer therapy are still rare. In this review we wish to provide an overview of the coordination chemistry of current and novel cytostatic compounds, including an outline of their design and rationale of synthesis, and summarize bio-chemical reactivity and physicochemical properties of candidate metal complexes.
- MeSH
- antitumorózní látky * farmakologie terapeutické užití MeSH
- cisplatina dějiny farmakologie terapeutické užití MeSH
- galium dějiny farmakologie terapeutické užití MeSH
- genomika metody trendy MeSH
- individualizovaná medicína metody trendy využití MeSH
- kobalt dějiny farmakologie terapeutické užití MeSH
- komplexní sloučeniny * farmakologie terapeutické užití MeSH
- lidé MeSH
- měď farmakologie terapeutické užití MeSH
- metabolomika metody trendy MeSH
- mezioborová komunikace MeSH
- proteomika metody trendy MeSH
- sloučeniny ruthenia dějiny farmakologie terapeutické užití MeSH
- sloučeniny železa dějiny farmakologie terapeutické užití MeSH
- sloučeniny zlata dějiny farmakologie terapeutické užití MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Improved knowledge of genome composition, especially of its repetitive component, generates important information for both theoretical and applied research. The olive repetitive component is made up of two main classes of sequences: tandem repeats and retrotransposons (REs). In this study, we provide characterization of a sample of 254 unique full-length long terminal repeat (LTR) REs. In the sample, Ty1-Copia elements were more numerous than Ty3-Gypsy elements. Mapping a large set of Illumina whole-genome shotgun reads onto the identified retroelement set revealed that Gypsy elements are more redundant than Copia elements. The insertion time of intact retroelements was estimated based on sister LTR's divergence. Although some elements inserted relatively recently, the mean insertion age of the isolated retroelements is around 18 million yrs. Gypsy and Copia retroelements showed different waves of transposition, with Gypsy elements especially active between 10 and 25 million yrs ago and nearly inactive in the last 7 million yrs. The occurrence of numerous solo-LTRs related to isolated full-length retroelements was ascertained for two Gypsy elements and one Copia element. Overall, the results reported in this study show that RE activity (both retrotransposition and DNA loss) has impacted the olive genome structure in more ancient times than in other angiosperms.
OBJECTIVE: Among elderly individuals with dementia, the use of antipsychotics has been associated with serious adverse events including ischemic stroke and death. Multiple medications can interact with antipsychotics and increase the risk of such adverse events. The purpose of this retrospective, longitudinal cohort study was to estimate the prevalence of potential antipsychotic drug interactions and their effect on increasing the risk of death among cognitively impaired elderly individuals treated with antipsychotics. METHODS: We conducted a retrospective longitudinal cohort study in 59 nursing homes of 7 European Union countries and Israel. The study was conducted during the years 2009 to 2011. Participants were cognitively impaired individuals aged 65 years or older residing in the participating nursing homes and being treated with antipsychotics (N = 604). Risk of death associated with potential antipsychotic drug interactions was the main outcome. The inter-Resident Assessment Instrument for Long Term Care Facilities (interRAI LTCF) was used to assess participants. Follow-up time was 12 months. RESULTS: The prevalence of potential antipsychotic drug interactions was 46.0%. Antipsychotic drug interactions were associated with higher mortality (incidence rate of 0.26 per person-year in the antipsychotic drug-interaction group versus 0.17 per person year in the no antipsychotic drug-interaction group). After adjusting for potential confounders, risk of death was higher in the group of residents with potential antipsychotic drug interactions relative to those unexposed to such interactions (hazard ratio = 1.71; 95% CI, 1.15-2.54). CONCLUSIONS: Part of the observed excess risk of death associated with the use of antipsychotic medications in elderly individuals with cognitive impairment may be attributable to antipsychotic drug interactions. Antipsychotics should be used with extreme caution especially among those individuals receiving concomitant cardiovascular or psychotropic medications.
- MeSH
- Alzheimerova nemoc farmakoterapie mortalita MeSH
- antipsychotika škodlivé účinky terapeutické užití MeSH
- domovy pro seniory * MeSH
- kognitivní dysfunkce farmakoterapie mortalita MeSH
- kohortové studie MeSH
- lékové interakce * MeSH
- lidé MeSH
- longitudinální studie MeSH
- pečovatelské domovy * MeSH
- retrospektivní studie MeSH
- riziko MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Izrael MeSH
We studied a natural infection of the oligochaete Branchiura sowerbyi Beddard, 1892 with the Raabeia-type actinosporean stage of Myxobolus lentisuturalis Dyková, Fiala et Nie, 2002 which infected goldfish Carassius auratus auratus (L.) in Italy, using molecular analysis of the SSU rRNA gene. The existence of intraoligochaete development shows that this parasite follows the life-cycle pattern described by Wolf and Markiw (1984) for Myxobolus cerebralis. Histological examinations of the goldfish infected by M. lentisuturalis showed at low magnification the presence of two bilateral crescent-shaped masses in the dorsal epaxial muscle. These lesions were not circumscribed, presented irregular edges and infiltrated the underlying bundles of skeletal muscle and interstitial tissue. At higher magnification, disappearance of muscle fibres and substitution of the muscle tissue with Myxobolus spores and plasmodia were observed.
This study sought to characterize the soluble free and bound phenolic compounds from shaddock (Citrus maxima) peels and investigate their effect on 3-hydroxy-methyl-3-glutaryl coenzyme A reductase (HMG-CoA reductase) and glutathione-linked enzymes in colon (Caco-2) cells. The radicals scavenging ability and the protective ability of the phenolic extracts against pro-oxidant induced oxidative damage in Caco-2 cells and rat colon homogenates were also investigated. The free phenolics were extracted with 80% acetone (v/v), while bound phenolics were extracted from the alkaline (NaOH) and acid (HCl) hydrolyzed residue with ethyl acetate. HPLC fingerprinting revealed the presence of gallic acid, catechin, chlorogenic acid, caffeic acid, ellagic acid, epicatechin, rutin, quercitrin and quercetin in the extracts. The results revealed that the extracts inhibited HMG-CoA reductase activity and increased the activities of glutathione reductase and glutathione peroxidase in Caco-2 cells. The extracts inhibited peroxyl radical induced oxidation of membrane lipids in Caco-2 cells and malondialdehyde production in rat colon homogenates. Furthermore, the phenolic extracts scavenged radicals [2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl (OH)] and chelated Fe2+ in a concentration-dependent manner. This study showed that shaddock peels could serve as a dietary means or nutraceutical source for protecting the colon from degeneration.
- MeSH
- Citrus chemie MeSH
- fenoly metabolismus MeSH
- glutathionreduktasa metabolismus účinky léků MeSH
- hydroxymethylglutaryl-CoA-reduktasy metabolismus účinky léků MeSH
- kolon * enzymologie metabolismus účinky léků MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- rostlinné extrakty MeSH
- scavengery volných radikálů metabolismus MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
BACKGROUND: The presence of single-nucleotide polymorphisms (SNPs) within the 3'-untranslated regions of genes could affect the binding between a microRNA (miRNA) and its target, with consequences on gene expression regulation. Considering the important role of miRNAs in carcinogenesis, it is hypothesized here that these SNPs could also affect the individual risk of colorectal cancer (CRC). METHODS: To test this hypothesis, a list was developed of 140 somatically mutated genes deduced from previous works on the mutome of the CRC. A further selection was conducted of SNPs within target sites for miRNAs that are expressed only in the colorectum (the colorectal microRNAome) and having adequate population frequencies. This yielded 12 SNPs that were genotyped in a case-control association study on 717 colorectal cases and 1171 controls from the Czech Republic. RESULTS: Statistically significant associations were found between the risk of CRC and the variant alleles of KIAA0182 (rs709805) (odds ratio = 1.57; 95% confidence interval = 1.06-2.78, for the variant homozygotes) and NUP210 genes (rs354476) (odds ratio = 1.36; 95% confidence interval = 1.02-1.82, for the variant homozygotes). CONCLUSIONS: The results support the study hypothesis and highlight the importance of SNPs within miRNA-dependent regulatory regions. Further studies on the role exerted by NUP210 and KIAA0182 in colorectal carcinogenesis are warranted.
- MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- haplotypy MeSH
- hodnocení rizik MeSH
- jednonukleotidový polymorfismus * MeSH
- kolorektální nádory genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- logistické modely MeSH
- mikro RNA analýza MeSH
- multivariační analýza MeSH
- mutace * MeSH
- odds ratio MeSH
- rizikové faktory MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- vazebná nerovnováha MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Solanum melongena L., also known as eggplant, is a widely consumed vegetable and it is well-known for its beneficial antioxidant properties, due to phenolic compounds. In this work, the influence of different cooking procedures on the content of chlorogenic acid was evaluated on eggplant samples of different geographic origin by high-performance liquid chromatography (HPLC). An easy and quick extraction procedure with 50% methanol as the extraction solvent was optimized for the first time by means of a design-of-experiment and applied to heat treated samples of eggplant. The antioxidant capacity of eggplant extracts was also evaluated by using the ABTS assay and it was correlated with the data obtained by the HPLC method. The content of chlorogenic acid was different in each heat-treated eggplant sample and it depended on the temperature applied during the cooking procedure. In particular, an increase of chlorogenic acid content with rising temperature was observed. Conversely, a very high temperature (250 °C) caused a decrease of chlorogenic acid amount. The influence of storage on the content of chlorogenic acid was also monitored. While the level of chlorogenic acid in fresh samples decreased during four weeks of storage, an increase in its content in heat treated eggplant was observed within the same period. Multivariate data analysis was used to classify eggplant samples into different groups, according to the country of origin and heat treatment procedure. This study provides new insights to preserve the antioxidant properties of eggplant phenolics during different thermal and storage treatments in order to highlight their health promoting effects.
- Publikační typ
- časopisecké články MeSH
Accurate identification and analysis of signs of trauma on human bone is one of the mainstays of forensic pathology. However, when a forensic pathologist has to deal with charred remains, the task become extremely difficult, because tissues are subjected to severe morphological alterations and their assessment can be critically distorted. We analyzed 38 individuals with peri-mortem skull fractures due to falls from height (17 cases), traffic accidents (16 cases), gunshots wounds (5 cases), of which we had the demographic and clinical data and the autopsy report with the description and photographic records of the fracture lines. After autopsy, the bodies were cremated in gas furnaces and the analysis of cremated cranial remains was conducted in order to verify if it was possible to reconstruct the original peri-mortem fractures and verify differences between known peri-mortem and post-mortem fractures. After 90 min and exposure to temperatures up to 1280 °C, in less than a third of cases (11-29%) the original peri-mortem fracture pattern could be found and reconstructed. The edges and the surface of the fractures can preserve their proper morphology, or they can be affected by post-mortem heat-induced fractures and deformations. Interestingly whenever peri-mortem fracture margins showed the evidence of yellow/brownish colouration, a matte appearance was observed, much different from post-mortem fractures, which may provide further food for thought for the identification of peri-mortem fractures after the cremation process.
- MeSH
- fraktury lebky etiologie patologie MeSH
- kremace * MeSH
- lidé MeSH
- pitva MeSH
- posmrtné změny * MeSH
- soudní patologie metody MeSH
- tělesné pozůstatky patologie MeSH
- vysoká teplota * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
