• MeSH
• Oligonucleotides, Antisense * chemical synthesis   chemistry   metabolism   MeSH
• Chemical Phenomena MeSH
• Nucleic Acid Hybridization * MeSH
• Organophosphonates chemistry   MeSH
• Chemistry Techniques, Synthetic methods   MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

• Publication type
• Abstracts MeSH

In spite of the impressing cytotoxicity of thapsigargin (Tg), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces the clinical potential is the limited access to Tg and its derivatives and cost-inefficient syntheses with unacceptably low yields. Laser trilobum, which contains a structurally related sesquiterpene lactone, trilobolide (Tb), is successfully cultivated. Here, we report scalable isolation of Tb from L. trilobum and a transformation of Tb to 8-O-(12-aminododecanoyl)-8-O-debutanoylthapsigargin in seven steps. The use of cultivated L. trilobum offers an unlimited source of the active principle in mipsagargin.

• MeSH
• Apiaceae chemistry   metabolism   MeSH
• Butyrates chemistry   isolation & purification   MeSH
• Furans chemistry   isolation & purification   MeSH
• Antineoplastic Agents, Phytogenic chemistry   isolation & purification   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Neoplasms drug therapy   pathology   MeSH
• Fruit chemistry   metabolism   MeSH
• Carbon Dioxide chemistry   MeSH
• Plant Extracts chemistry   MeSH
• Sarcoplasmic Reticulum Calcium-Transporting ATPases antagonists & inhibitors   metabolism   MeSH
• Chromatography, Supercritical Fluid methods   MeSH
• Chemistry Techniques, Synthetic * MeSH
• Thapsigargin analogs & derivatives   isolation & purification   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Zeolites are one of the most important heterogeneous catalysts, with a high number of large-scale industrial applications. While the synthesis of new zeolites remain rather limited, introduction of germanium has substantially increased our ability to not only direct the synthesis of zeolites but also to convert them into new materials post-synthetically. The smaller Ge-O-Ge angles (vs. Si-O-Si) and lability of the Ge-O bonds in aqueous solutions account for this behaviour. This Minireview discusses critical aspects of germanosilicate synthesis and their post-synthesis transformations to porous materials.

• Publication type
• Journal Article MeSH
• Review MeSH

Penicillin G acylase from Achromobacter sp. (NPGA) was studied in the enzymatic synthesis of β-lactam antibiotics by kinetically controlled N-acylation. When compared with penicillin acylase of Escherichia coli (PGA), the NPGA was significantly more efficient at syntheses of ampicillin and amoxicillin (higher S/H ratio and product accumulation) in the whole range of substrate concentrations. The degree of conversion of 6-aminopenicillanic acid to amoxicillin and ampicillin (160 mM 6-APA, 350 mM acyl donor methylester[Symbol: see text]HCl, pH 6.3, 25 °C, reaction time of 200 min) with immobilized NPGA equaled 96.9 % and 91.1 %, respectively. The enzyme was highly thermostable with maximum activity at 60 °C (pH 8.0) and 65 °C (pH 6.0). Activity half-life at 60 °C (pH 8.0) and at 60 °C (pH 6.0) was 24 min and 6.9 h, respectively. Immobilized NPGA exhibited long operational stability with half-life of about 2,000 cycles for synthesis of amoxicillin at conversion conditions used in large-scale processes (230 mM 6-APA, 340 mM D-4-hydroxyphenylglycine methylester[Symbol: see text]HCl, 27.5 °C, pH 6.25). We discuss our results with literature data available for related penicillin acylases in terms of their industrial potential.

• MeSH
• Achromobacter enzymology   MeSH
• Amoxicillin metabolism   MeSH
• Ampicillin metabolism   MeSH
• Anti-Bacterial Agents metabolism   MeSH
• beta-Lactams metabolism   MeSH
• Biotransformation MeSH
• Enzymes, Immobilized chemistry   metabolism   MeSH
• Hydrogen-Ion Concentration MeSH
• Penicillanic Acid analogs & derivatives   metabolism   MeSH
• Penicillin Amidase chemistry   isolation & purification   metabolism   MeSH
• Enzyme Stability MeSH
• Temperature MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Scientific evidence regularly guides policy decisions1, with behavioural science increasingly part of this process2. In April 2020, an influential paper3 proposed 19 policy recommendations ('claims') detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to behavioural interventions also had strong empirical support, as did appealing to social consensus or bipartisan agreement. Targeted language in messaging yielded mixed effects and there were no effects for highlighting individual benefits or protecting others. No available evidence existed to assess any distinct differences in effects between using the terms 'physical distancing' and 'social distancing'. Analysis of 463 papers containing data showed generally large samples; 418 involved human participants with a mean of 16,848 (median of 1,699). That statistical power underscored improved suitability of behavioural science research for informing policy decisions. Furthermore, by implementing a standardized approach to evidence selection and synthesis, we amplify broader implications for advancing scientific evidence in policy formulation and prioritization.

• MeSH
• Behavioral Sciences * methods   trends   MeSH
• COVID-19 * epidemiology   ethnology   prevention & control   MeSH
• Communication MeSH
• Culture MeSH
• Evidence-Based Practice * methods   MeSH
• Humans MeSH
• Pandemics * prevention & control   MeSH
• Social Norms MeSH
• Public Health methods   trends   MeSH
• Leadership MeSH
• Policy Making * MeSH
• Health Policy * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

An high-performance liquid chromatography (HPLC) method for identification of quaternary and non-quaternary compounds (parent compounds, intermediates, by-products, and products) within the synthesis of the acetylcholinesterase reactivator HI-6, the most promising antidote of nerve agent poisonings, is described. This HPLC method could be of high interest as a quick purity control for those who are interested in development of new acetylcholinesterase reactivators as well as for those who are interested in the synthesis of HI-6 in laboratory or in large-scale production. An HPLC method for quaternary compounds without using common ion-pairing reagents was developed, too.

• MeSH
• Catalysis MeSH
• Oximes chemical synthesis   chemistry   MeSH
• Pyridinium Compounds chemical synthesis   chemistry   MeSH
• Cholinesterase Reactivators chemical synthesis   chemistry   MeSH
• Chromatography, High Pressure Liquid methods   MeSH
• Publication type
• Journal Article MeSH

Nearly monodispersed superparamagnetic maghemite nanoparticles (15-20nm) were prepared by a one-step thermal decomposition of iron(II) acetate in air at 400 degrees C. The presented synthetic route is simple, cost effective and allows to prepare the high-quality superparamagnetic particles in a large scale. The as-prepared particles were exploited for the development of magnetic nanocomposites with the possible applicability in medicine and biochemistry. For the purposes of the MRI diagnostics, the maghemite particles were simply dispersed in the bentonite matrix. The resulting nanocomposite represents very effective and cheap oral negative contrast agent for MRI of the gastrointestinal tract and reveals excellent contrast properties, fully comparable with those obtained for commercial contrast material. The results of the clinical research of this maghemite-bentonite contrast agent for imaging of the small bowel are discussed. For biochemical applications, the primary functionalization of the prepared maghemite nanoparticles with chitosan was performed. In this way, a highly efficient magnetic carrier for protein immobilization was obtained as demonstrated by conjugating thermostable raffinose-modified trypsin (RMT) using glutaraldehyde. The covalent conjugation resulted in a further increase in trypsin thermostability (T(50)=61 degrees C) and elimination of its autolysis. Consequently, the immobilization of RMT allowed fast in-solution digestion of proteins and their identification by MALDI-TOF mass spectrometry.

• MeSH
• X-Ray Diffraction MeSH
• Enzymes, Immobilized MeSH
• Financing, Organized MeSH
• Gastrointestinal Tract pathology   MeSH
• Contrast Media MeSH
• Magnetic Resonance Imaging MeSH
• Microscopy, Electron, Scanning MeSH
• Microscopy, Electron, Transmission MeSH
• Trypsin MeSH
• Ferric Compounds MeSH

The metal complex copper diethyldithiocarbamate (CuET) induces cancer cell death by inhibiting protein degradation and induces proteotoxic stress, making CuET a promising cancer therapeutic. However, no clinical formulation of CuET exists to date as the drug is insoluble in water and exhibits poor bioavailability. To develop a scalable formulation, nanoliposomal (LP) CuET was synthesized using ethanol injection as a facile one-step method that is suitable for large-scale manufacturing. The nanoparticles are monodispersed, colloidally stable, and approximately 100 nm in diameter with an encapsulation efficiency of over 80%. LP-CuET demonstrates excellent stability in plasma, minimal size change, and little drug release after six-month storage at various temperatures. Additionally, melanoma cell lines exhibit significant sensitivity to LP-CuET and cellular uptake occurs predominantly through endocytosis in YUMM 1.7 cancer cells. Intracellular drug delivery is mediated by vesicle acidification with more nanoparticles being internalized by melanoma cells compared with RAW 264.7 macrophages. Additionally, the nanoparticles preferentially accumulate in YUMM 1.7 tumors where they induce cancer cell death in vivo. The development and characterization of a stable and scalable CuET formulation illustrated in this study fulfils the requirements needed for a potent clinical grade formulation.

• Publication type
• Journal Article MeSH

Autor prezentuje výsledky velké, observační multicentrické studie, která si dala za cíl sledovat účinnost a bezpečnost celecoxibu v léčbě osteoartrózy a revmatoidní artritidy v podmínkách běžné klinické praxe v České republice. Do souboru bylo zařazeno 1818 pacientů s převažující diagnózou osteoartrózy (73,1 %). Délka sledování byla 3 měsíce. Dávkování celecoxibu bylo podle doporučení v SPC, tzn. 200 mg u osteoartrózy a 200–400 mg celecoxibu denně u revmatoidní artritidy. Spokojenost s léčbou (body 1–3 na 10 bodové škále) vyjádřilo 82,5 % pacientů. Své přání pokračovat v léčbě celecoxibem vyjádřilo 88,8%pacientů. Průměrná denní dávka celecoxibu uOA byla 204,25mgdenně a v průběhu léčby se nezvyšovala. Průměrná dávka celecoxibu u RA byly 314 mg a v průběhu studie se snižovala. Snášenlivost byla hodnocena pacienty 92,8 % jako velmi dobrá a pouze u 2,6 % jako špatná. Nežádoucí účinky ve vztahu k léku se vyskytly ve 23 případech (1,3 %) u 20 pacientů vedly k ukončení léčby. Nebyly zaznamenány závažné NÚ. Tato observační studie potvrdila dobrý poměr účinnost/toxicita celecoxibu v klinické praxi při léčbě bolesti a zánětu u OA a RA.

The author presents outcomes of large, observational, multicentric study following efficacy and safety of celecoxib in osteoarthritis (OA) and rheumatoid arthritis (RA) patients in clinical practice in Czech republic. The group has been followed for 3 months and consisted of 1818 patients with a majority of OA (73,1%). Doses of celecoxib were 200 mg and 200–400 mg in OA and RA respectively. Eighty-two and half per cent of patients were satisfied with this treatment (1–3 on 10 point scale) and 88.8% patients wanted to continue in celecoxib using. Average daily dose of celecoxib was 204.25 mg in OA and 317 mg in RA and did not increase during the study. Tolerance, as assessed by patients, was very good in 92.8% and bad in 2.6%. Drug induced adverse events were found in 23 (1.3%) and led to treatment termination in 20 patients. There were no serious adverse drug reactions in this study. This observational study confirms good efficacy/toxicity ratio of celecoxib to reduce pain and inflammation in OA and RA in clinical practice.

• Keywords
• CELECOXIB,
• MeSH
• Anti-Inflammatory Agents, Non-Steroidal administration & dosage   MeSH
• Gastrointestinal Tract adverse effects   MeSH
• Cyclooxygenase Inhibitors administration & dosage   adverse effects   MeSH
• Humans MeSH
• Osteoarthritis drug therapy   MeSH
• Arthritis, Rheumatoid drug therapy   MeSH
• Check Tag
• Humans MeSH