IR-B
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In this work, we investigate the mode of binding of all nine hydrogen-bonded structures of the adenine...thymine base pair. The planar H-bonded structures were optimized at the MP2/cc-pVTZ level, and the respective interaction energies, corrected for the basis set superposition error, were determined with the aug-cc-pVDZ basis set. The energy components were obtained from the DFT-SAPT procedure using the aug-cc-pVDZ basis set. The charge-transfer character of the single structures was estimated using NBO characteristics. It was established that dipole-dipole interaction itself cannot explain the preferred structure of the pair. Of the various energy components, first-order electrostatic energy plays the most important role. Second-order energy (the sum of induction and dispersion energies) amounts to about 56% of the electrostatic energy. The delta(HF) term covering among others the charge-transfer energy is rather large. The importance of delta(HF) is reflected by the NBO characteristics and especially by the NBO charge-transfer energy. The sum of the second-order energy and the delta(HF) term is only slightly smaller than the electrostatic energy (75-77%), which reflects the importance of the nonelectrostatic terms even in the case of strong H-bonded complexes. The WC structure, which exists in DNA, represents the seventh local minimum, while the three most stable structures utilize the N9-H proton donor group of the five-membered ring.
- MeSH
- adenin chemie MeSH
- algoritmy MeSH
- biofyzika metody MeSH
- DNA chemie MeSH
- financování organizované MeSH
- konformace nukleové kyseliny MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- párování bází MeSH
- přenos energie MeSH
- spektrofotometrie infračervená metody MeSH
- statická elektřina MeSH
- thymin chemie MeSH
- vodíková vazba MeSH
Cíl studie: Porovnat výsledky embryotransferů po IVF prováděných 2. den kultivace oproti 4. dni kultivace embrya (standardní kultivace versus prodloužená kultivace). Typ studie: Retrospektivní analýza. Název a sídlo pracoviště: Centrum asistované reprodukce Apolinář, Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze. Metodika: Porovnali jsme pregnancy rate (PR) a implantation rate (IR) po transferech embryí z IVF a IVF/ICSI, za období srpen 2004 až červenec 2008 u skupiny žen, kde byla transferována 2 embrya. Věk žen byl do 35 let (22–35 let, průměrný věk 30,4 let, medián 31,1 let). Všechny transfery byly provedeny týmž lékařem. Na základě morfologických kritérií byla embrya hodnocena stupněm A jako top kvalita embrya a stupněm B střední kvalita embrya. Skupina transferů 2. den byla porovnána se skupinou transferů 4. den. Výsledky: 2. den kultivace bylo provedeno 83 embryotransferů (ET), přičemž 42 ET s embryi s hodnocením A+A mělo PR 69 %. 30 ET s embryi A+B, PR 53,3 %. 11 ET s embryi B+B, PR 36,4 %. IR bylo 50,0 %, 40,0 % a 22,7 %. 4. den kultivace bylo provedeno 100 ET, přičemž 46 ET s embryi s hodnocením A+A, PR 54,3 %. 39 ET s embryi A+B, PR 48,7 %. 15 ET s embryi B+B, PR 26,6 %. IR bylo 45,6 %, 34,6 % a 13,3 %. Závěr: Oproti očekávání, v našem souboru PR a IR dosáhly lepších hodnot ve skupině, kde ET byl 2. den (po standardní kultivaci), oproti ET 4. den (po prodloužené kultivaci). Rozdíl mezi ET provedeným 2. a 4. den není však statisticky významný (p>0,05). Proto analýzy uzavíráme tak, že v našem souboru se výsledky otěhotnění po standardní a prodloužené kultivaci neliší. Nezávisle na dni ET byla prognóza embryí stupně A signifikantně vyšší (p<0,05) než u embryí hodnocených stupněm B.
Objective: Compare the effectiveness of the IVF extended embryo culture day 4 versus day 2. Design: Retrospective analysis. Setting: Assisted Reproduction centre Apolinar, Department of Obstetrics and Gynecology, 1st Faculty of Medicine, Charles University and General Faculty Hospital in Prague. Methods: We compared pregnancy rate (PR) and implantation rate (IR) of all IVF and IVF/ICSI embryo transfers (ET) performed between August 2004 and July 2008, in which 2 embryos were transfered. All transfers were done by the same physician. Maternal age was ? 35 years (from 22 to 35 years, mean 30.4 years, median 31.1 years). The group of embryos evaluated and transfered on the day 2 was compared with the embryos evaluated and transfered on the day 4. Based on the evaluation, each embryo was assigned to one of the following categories: Grade A (top quality embryo) or grade B (medium quality embryo). Results: On the day 2, ET of A+A embryos led to PR 69.0%; A+B 53.3% and B+B 36.4% (IR 50.0%, 40.0% and 22.7%), where number of transfers was 42, 30 and 11 in every group. On the day 4, ET of A+A embryos led to PR 54.3%, A+B 48.7%, B+B 26.6% (IR 45.6%, 34.6%, 13.3%), where number of transfers was 46.39 and 15 in every group. Conclusion: In our group, we found no statistical significant difference (p<0.05) in PR between day 2 and day 4 embryotransfers. Results of the day 2 transfers have a trend to be better than results of day 4 transfers. Regardless of the transfer day, the prognosis of grade A embryos was significantly better (p<0.05) than for grade B embryos.
- Klíčová slova
- prodloužená kultivace, embryotransfer den 4, embryotransfer den 2,
- MeSH
- dospělí MeSH
- fertilizace in vitro MeSH
- implantace embrya MeSH
- kultivace embrya MeSH
- lidé MeSH
- mladý dospělý MeSH
- přenos embrya MeSH
- těhotenství MeSH
- úhrn těhotenství na počet žen v reprodukčním věku MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
New intravenous conjugates of amphotericin B (AMB) with poly(ethylene glycols) (PEG) (M=5000, 10,000, 20,000) have been synthesized and characterised. The intermediate PEGs possess a 1,4-disubstituted benzene ring with aldehyde group at the end of the chain. The benzene ring is connected with PEG at its 4-position (with respect to the aldehyde group) by various functional groups (ether, amide, ester). Reaction of terminal aldehyde group of the substituted PEGs with AMB gave conjugates containing a pH-sensitive imine linkage, which can be presumed to exhibit antimycotic effect at sites with lowered pH value. All types of the conjugates are relatively stable in phosphate buffer at physiological conditions of pH 7.4 (37 degrees C), less than 5 mol% AMB being split off from them within 24 h. For a model medium of afflicted tissue was used a phosphate buffer (pH 5.5, 37 degrees C), in which controlled release of AMB from the conjugates takes place. The imine linkage is split to give free AMB with half-lives of 2-45 min. The rate of acid catalysed hydrolysis depends upon substitution of the benzene ring; however, it does not depend on molecular weights of the PEGs used. The conjugates with ester linkage undergo enzymatic splitting in human blood plasma and/or blood serum at pH 7.4 (37 degrees C) with half-lives of 2-5 h depending on molecular weights of the PEGs used (M = 5000, 10,000, 20,000). At first, the splitting of ester linkage produces the relatively stable pro-drug, that is, 4-carboxybenzylideniminoamphotericin B, which is decomposed to AMB and 4-formylbenzoic acid in a goal-directed manner only at pH 7 (t1/2 = 2 min, pH 5.5, 37 degrees C). A goal-directed release of AMB is only achieved by acid catalysed hydrolysis of imine linkage, either from the polymeric conjugate or from the pro-drug released thereof. The LD50 values determined in vivo (mouse) are 20.7 mg/kg and 40.5 mg/kg for the conjugates with ester linkage (M = 10,000 and 5000, respectively), which means that they are ca. 6-11 times less toxic than free AMB.
- MeSH
- amfotericin B chemická syntéza chemie MeSH
- financování organizované MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- hydrolýza MeSH
- koncentrace vodíkových iontů MeSH
- krev MeSH
- lidé MeSH
- myši MeSH
- polyethylenglykoly chemická syntéza chemie MeSH
- spektrofotometrie infračervená MeSH
- spektrofotometrie ultrafialová MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
Cíl: Zhodnoceni efektu brachyterapie (Iridium - 192) v kombinaci se zavedením kovového stentu V prospektivní randomizované studii. Materiál a metodika: Celkem bylo ošetřeno 76 nemocných. Etiologie stenózy byla u všech ověřena histologický. 38 pacientů s inoperabilní maligní stenózou žlučových cest (skupina A) bylo léčeno perkutánní implantací stentu (Wallstent, spirální Z stent) a následnou brachyterapií (Ir-192, průměrná dávka 30 Gy). 38 nemocných (skupina B) mělo zavedeno jen Wallstent bez následného ozařování. Výsledky: Průměrná délka života nemocných (skupina A) byla 291,2, resp. (skupina B) 195,1 dnů. Ze statistického hodnocení jsme vyřadili pacienty, kteří zemřeli do jednoho měsíce. Závěr: Kombinace perkutánního zavedení stentu a následné rádioterapie statisticky významně prodlužuje délku života u nemocných s maligní stenózou žlučových cest léčenou zavedením kovového stentu. Nejvýraznější rozdíl jsme zaznamenali u nemocných s cholangiokarcinomem (339,8 A versus 298 B).
Objective: Evaluation of the effect of brachytherapy (Iridium-192) combined with insertion of a metal stent in a prospective randomized study. Material and methods: A total of 76 patients were treated. The etiology of stenosis was in all confirmed by histological examination. 38 patients with an inoperable malignant stenosis of the biliary pathways (group A) was treated by percutaneous implantation of a stent (Wallstent, spiral Z stent) and subsequent brachytherapy (Ir-192, mean dose 30 Gy). 38 patients (group B) had a Wallstent only without subsequent irradiation. Results: The mean survival time of patients (group A) was 291.2 days and 195.1 days (group B). From the statistical evaluation patients who died within one month were eliminated. Conclusion: A combination of percutaneous insertion of a stent and subsequent radiotherapy prolongs significantly the life span of patients with malignant stenosis of the biliary pathways treated by insertion of a metal stent. The most marked difference was recorded in patients with cholangiocarcinoma (339.8 A vs. 298 B).
Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.
- MeSH
- alkoholismus * farmakoterapie patofyziologie MeSH
- aminokyseliny MeSH
- bicyklické sloučeniny heterocyklické * farmakologie MeSH
- biologické markery MeSH
- evokované potenciály účinky léků MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech * MeSH
- prefrontální mozková kůra * účinky léků patofyziologie metabolismus MeSH
- psilocybin * farmakologie MeSH
- receptory metabotropního glutamátu MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Léčba kontinuální subkutánní infuzí inzulínu (CSU) inzulínovou pumpou je v současné době metodou léčby, která nejvíce napodobuje fyziologickou sekreci inzulínu. Glykémie při léčbě inzulínovou pumpou jsou blíže normálním, než je možné dosáhnout konvenční injekční inzulínovou léčbou. Po zavedení inzulínové pumpy obvykle klesá denní dávka inzulínu, zlepšuje se kompenzace diabetů (klesá HBAlc). Nejčastější indikací k léčbě inzulínovou pumpou bývá neuspokojivá kompenzace diabetů. Často bývá inzulínová pum¬pa využívána u špatné kompenzovaných pacientů s tzv. dawn fenoménem, při častých těžkých hypoglykémiích a u pacientů s progredujícími orgánovými komplikacemi diabetů.
Diabetes control through subcutaneous insulin infusion (CSU) is currently the therapeutic option that most closely mimics physiologic insulin secretion and provides for glycemia levels close to normál even where standard injection insulin therapy fails. Following CSU installation, the mean daily dose of insulin usually decreases and diabetes control improves (HBAlc falls). Most patients háve the CSU installed because of poor diabetes control. The most frequent indications are the "dawn phenomenon", severe hypoglycemia, and progression of diabetic complications.
- Klíčová slova
- Humalog, Levemir, H-Tron plus V-100, AccuChek Spirit, AccuChek D-tron, Minimed 508c, Minimed Paradigm 511, Minimed Paradigm 712, Minimed Paradigm 722RT, Animas IR 1000, Animas IR 1200, DANA II, Medronic Minimed Paradigm 712 - Bolus Vizard, Medronic Minimed Paradigm 722 - Bolus Vizard, Animas IR 1200 - ez Bolus, Medronic Minimed Paradigm 511 - Bolus Vizard,
- MeSH
- diabetes mellitus farmakoterapie MeSH
- inzulin aplikace a dávkování terapeutické užití MeSH
- inzulinové infuzní systémy klasifikace škodlivé účinky využití MeSH
- lidé MeSH
- výběr pacientů MeSH
- Check Tag
- lidé MeSH
OBJECTIVE: The aim of the study was to discover the interrelation between the severity of gastroesophageal reflux disease (GERD) symptoms, acid exposure time (AET), excessive daytime sleepiness (EDS) and the level of active blood plasma ghrelin in the patients with undifferentiated connective tissue disease (UCTD). PATIENTS AND METHODS: Materials and methods: The study included 120 patients with GERD. All the patients were divided in two groups: Group I - GERD was not accompanied by the signs of connective tissue disease (n=45) and Group II - GERD developed on the background of UCTD syndrome (n=75). Daily transnasal pH monitoring was performed to determine the nature of pathological refluxes. EDS was detected by The Epworth Sleepiness Scale. Active ghrelin in blood plasma samples was determined by ELISA. RESULTS: Results: 80% of the patients of Group II and 35.48% of Group I suffered from EDS (p<0.05). The mean daily AET index was 5.48±0.4% in Group II and 6±0.2% in Group I, in the night hours mostly when patients were in the upright position. This phenomenon contributed to a deterioration of sleep quality and the appearance of EDS and was supported by a connection between AET and EDS (r=+0.827 for Group I and r=+0.768 for Group II). The mean De Meester index was higher in the patients of Group II (23.01±2.24 in Group I vs 31.08±2.4 in Group II; p<0.05). CONCLUSION: Conclusions: GERD manifestations are strongly related to the level to AET and intensity of EDS. The EDS symptoms depend on circulating ghrelin level.
- MeSH
- gastroezofageální reflux * komplikace MeSH
- ghrelin MeSH
- lidé MeSH
- nediferencované onemocnění pojivové tkáně * MeSH
- poruchy nadměrné spavosti * etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
studie byla zaměřena na stanovení exprese membránových cytokinových receptorů na kryostatových tkáňových řezech s použitím vysoce citlivého systému s biotin-streptavidinem. Byly použity monoklonální protilátky proti cytokinovým receptorům vybrané ze 6. mezinárodního workshopu o lidských leukocytámích diferenciačních antigenech: CD25 (IL.2Ra), CD95 (FAS antigen), CD116 (GM-CSFR), CD117 (SCFR), CD120a (TNFR I), CD120b (TNFR H), CD121a (IL-IR I), CDwl23 (IL3R), CD124 (IL.4R), CD126 (DL-GR), CD127 (IL-TR), CDwl28 (IL-8R), CD130 (gp 130), CD131 (IL-3Rβ), CD132 (IL.2Ry), CD134 (OX-40), CD135 (FLT3/FLK2). Patologické tkáně (uzliny a sleziny) byly odebrány 12 pacientům s diagnózami: folikulárního non-Hodgkinova lymfomu, periferního T non Hodgkinova lymfomu, B-lymfomu, myelomu, Hodgkinovy choroby, dva případy B-lymfomu bohatého na T lymfocyty, autoimunitní hemolytické anémie, rudimentární granulomatózní lymfadenitidy, dva případy idiopatické trombocytopenické purpury a lymfedému. Z výsledků vyplývá, že imunohistologická metoda využívající při průkazu cytokinových receptorů nativních zmrazených tkání, monoklonálních protilátek a vizualizačního systému s biotin-streptavidinem je mimořádně vhodnou detekční metodou pro přesnější lokalizaci cytokinových receptorů ve tkáních.
We have studied tissue expression of the cytokine receptors using a high sensitivitity biotin-streptayidm system on cryostat sections. We used a panel of monoclonal antibodies from the 6th International Workshop on Human Leukocyte Differentiation Antigens, namely CD25 (IL-2Rα), CD95 (FAS antigen), CD116 (GM CSFR), CD117 (SCFR), CD120a (TNFR I), CD120b (TNFR II), CD121a (IL-IR I), CDwl23 (IL.3R), CD124 (n.-4R), CD126 (IL-6R), CD127 (IL-7R), CDwl28 (IL-8R), CD130 (gpll30), CD131 (IL-SR), CD132 (IL-2Ry), CD134 (OC-40), CD135 (FLT3/FLK2). Examined tissues (lymph nodes and spleens) were obtained from 12 patients with folicular non-Hodgkin's lymphoma, periferal T non-Hodgkin's lymphoma, B lymphoma, myeloma, Hodgkin's disease, two cases of T cell rich B-lymphoma, autoimmune haemolytic anemia and two cases of rudimentary trombocytopenic purpura. Our results indicate that immunohistological technology using native tissues on cryostat sections, monoclonal antibodies and the visualisation with biotin-streptavidin is a particularly suitable supplementary staining procedure for detection of the cytokine receptors in tissues.
A significant drawback of the exogenous administration of insulin to diabetics is the non-physiological profile of insulin action resulting in the insufficient suppression of hepatic glucose production, which is the main contributing factor to diabetic hyperglycemia under fasting conditions and the basis of the challenge to restore a more physiological glucose profile in diabetes. The insulin receptor (IR) exists in two alternatively spliced variants, IR-A and IR-B, with different tissue distribution. While peripheral tissues contain different proportions of both isoforms, hepatic cells almost exclusively contain IR-B. In this respect, IR-B-selective insulin analogs would be of great interest for their potential to restore more natural metabolic homeostasis in diabetes. Recent advances in the structural biology of insulin and IR have provided new clues for understanding the interaction of both proteins. This article discusses and offers some structural perspectives for the design of specific insulin analogs with a preferential binding to IR-B.
- Publikační typ
- časopisecké články MeSH
