Measurement of the reaction enthalpy of CO2 in aqueous solutions with thermographic and gravimetric methods.

In this work, a new concept for the approximate determination of the reaction enthalpy of the reaction between CO2 and monoethanolamine (MEA) in aqueous solution was developed. For this purpose, a CO2 gas stream was flowed into aqueous MEA solutions with different concentrations of 1 wt%, 2.5 wt% and 7.5 wt%. The weight difference ∆T, which is based on the increase in CO2 bound by the MEA over time, was documented using a thermographic camera. The mass difference ∆m, which is also based on the increase in CO2 bound by the MEA over time, was determined using a balance. By determining ∆T and ∆m, an approximate calculation of the reaction enthalpy is possible. The deviation from the values from the data known from the literature was less than 5% in all experiments.

New combined absorption/1H NMR method for qualitative and quantitative analysis of PET degradation products.

Poly(ethylene terephthalate) (PET) is a very valuable and beneficial material for industrial purposes, with various different applications. Due to the high annual production volume of over 50 million tons worldwide and the indiscriminate disposal by consumers, the polymers accumulate in the environment, causing negative effects on various ecosystems. Biodegradation via suitable enzymes represents a promising approach to combat the plastic waste issue so validated methods are required to measure the efficiency and efficacy of these enzymes. PETase and MHETase from Ideonella sakaiensis are suitable enzymes needed in combination to completely degrade PET into its environmentally friendly monomers. In this project, we compare and combine a previously described bulk absorbance measurement method with a newly established 1H NMR analysis method of the PET degradation products mono(2-hydroxyethyl) terephthalic acid, bis(2-hydroxyethyl) terephthalic acid and terephthalic acid. Both were optimized regarding different solvents, pH values and drying processes. The accuracy of the measurements can be confirmed with sensitivity limits of 2.5-5 µM for the absorption method and 5-10 µM for the 1H NMR analysis. The combination of the described methods therefore allows a quantitative analysis by using bulk absorption coupled with a qualitative analysis through 1H NMR. The methods established in our work can potentially contribute to the development of suitable recycling strategies of PET using recombinant enzymes.

p-Phenylene Diisothiocyanate-Based Covalent Immobilization of ß-d-Galactosidase and Determination of Enzyme Activity by Cleavage of X-Gal and ONPG on Solid Support.

Herein, we present the immobilization of a technical grade ß-d-galactosidase on amino-functionalized microtiter plates. Afterward, we transferred the results to a resin-based approach. For the covalent binding of the enzyme, an amino-functionalized microtiter plate was prefunctionalized with 1,4-phenylendiisothiocyanate. The cleavage of the substrate 5-bromo-4-chloro-3-indoxyl-ß-d-galactopyranoside (X-Gal) produces a deep blue dye, which was quantified in a microtiter plate reader at 595 nm. The maximum reaction rates and the Michaelis-Menten constant were calculated. In addition, the unwanted blue precipitate formed during the experiments could be minimized by optimizing the experiments. When transferring the immobilization method to Rink amide resin, o-nitrophenyl-ß-d-galactopyranoside was used as the substrate and the measurement was carried out in a photometer at 420 nm.

Dataset for density/temperature correlation of tetramethylammonium hydroxide solutions of various concentrations.

Densities for various Tetramethylammonium hydroxide (TMAH) solutions at different temperatures have been determined based on Archimedes' principle using a hydrostatic balance and a vitreous body with a defined volume. Due to the toxicity of the compound, these data are important especially in the field of wet processing techniques for the automated dosage of TMAH.

Synergy of R-(-)carvone and cyclohexenone-based carbasugar precursors with antibiotics to enhance antibiotic potency and inhibit biofilm formation.

The widespread use of antibiotics in recent decades has been a major factor in the emergence of antibiotic resistances. Antibiotic-resistant pathogens pose increasing challenges to healthcare systems in both developing and developed countries. To counteract this, the development of new antibiotics or adjuvants to combat existing resistance to antibiotics is crucial. Glycomimetics, for example carbasugars, offer high potential as adjuvants, as they can inhibit metabolic pathways or biofilm formation due to their similarity to natural substrates. Here, we demonstrate the synthesis of carbasugar precursors (CSPs) and their application as biofilm inhibitors for E. coli and MRSA, as well as their synergistic effect in combination with antibiotics to circumvent biofilm-induced antibiotic resistances. This results in a biofilm reduction of up to 70% for the CSP rac-7 and a reduction in bacterial viability of MRSA by approximately 45% when combined with the otherwise ineffective antibiotic mixture of penicillin and streptomycin.

Like Visiting an Old Friend: Fischer Glycosylation in the Twenty-First Century: Modern Methods and Techniques.

Fischer glycosylation is typically the chemical reaction of a monosaccharide and an alcohol in presence of an acidic catalyst to afford glycosides in pyranosidic and furanosidic forms. This reaction is still applied today for the synthesis of specialized glycosides, and optimization and modification of the method have continued since its discovery by Emil Fischer in the 1890s. This review presents advancements in Fischer glycosylation described in literature of the past 15 years and its implementation in modern chemical methods.

Current Synthetic Approaches to the Synthesis of Carbasugars from Non-Carbohydrate Sources.

Carbasugars are a group of carbohydrate derivatives in which the ring oxygen is replaced by a methylene group, producing a molecule with a nearly identical structure but highly different behavior. Over time, this definition has been extended to include other unsaturated cyclohexenols and carba-, di-, and polysaccharides. Such molecules can be found in bacterial strains and the human body, acting as neurotransmitters (e.g., inositol trisphosphate). In science, there are a wide range of research areas that are affected by, and involve, carbasugars, such as studies on enzyme inhibition, lectin-binding, and even HIV and cancer treatment. In this review article, different methods for synthesizing carbasugars, their derivatives, and similar cyclohexanes presenting comparable characteristics are summarized and evaluated, utilizing diverse starting materials and synthetic procedures.

Do it yourself! - Initial experiences with self-synthesized CsTFA for RNA-SIP analyses.

Cesium trifluoroacetate (CsTFA) is a gradient medium for isopycnic centrifugation in RNA-based Stable Isotope Probing (RNA-SIP), an important means to link the structure and function of microbial communities. We report a protocol to easily synthesize CsTFA from cesium carbonate (Cs2CO3) and trifluoroacetic acid (TFA) and show that self-synthesized CsTFA performs similarly to commercial CsTFA in the separation of isotopically labelled and unlabelled bacterial RNA.

Methacryloyl-GlcNAc Derivatives Copolymerized with Dimethacrylamide as a Novel Antibacterial and Biocompatible Coating.

Improving medical implants with functional polymer coatings is an effective way to further improve the level of medical care. Antibacterial and biofilm-preventing properties are particularly desirable in the area of wound healing, since there is a generally high risk of infection, often with a chronic course in the case of biofilm formation. To prevent this we here report a polymeric design of polymer-bound N-acetyl-glucosamine-oligoethylene glycol residues that mimic a cationic, antibacterial, and biocompatible chitosan surface. The combination of easy to use, crosslinkable, thin, potentially 3D-printable polymethacrylate layering with antibacterial and biocompatible functional components will be particularly advantageous in the medical field to support a wide range of implants as well as wound dressings. Different polymers containing a N-acetylglucosamine-methacryloyl residue with oligoethylene glycol linkers and a methacryloyl benzophenone crosslinker were synthesized by free radical polymerization. The functional monomers and corresponding polymers were characterized by 1H, 13C NMR, and infrared (IR) spectroscopy. The polymers showed no cytotoxic or antiadhesive effects on fibroblasts as demonstrated by extract and direct contact cell culture methods. Biofilm formation was reduced by up to 70% and antibacterial growth by 1.2 log, particularly for the 5% GlcNAc-4EG polymer, as observed for Escherichia coli and Staphylococcus aureus as clinically relevant Gram-negative and Gram-positive model pathogens.

Systematic synthesis and characterization of a series of different bromoalkylglycosides by Fischer glycosylation.

In order to investigate the possibilities of Fischer glycosylation towards the synthesis of bromoalkylglycosides we performed a variety of different reactions resulting in a small library of 16 different glycosides. Using standardized reaction conditions we could gain a broad range of results from small to higher yields. Finally we randomly selected three reactions and performed them with higher amounts of bromoalcohol resulting in significantly better yields, showing the optimization potential of these basic research work.

Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: A systematic review.

BACKGROUND: The recently established association between higher levels of DNA-incorporated thioguanine nucleotides and lower relapse risk in childhood acute lymphoblastic leukaemia (ALL) calls for reassessment of prolonged 6-thioguanine (6TG) treatment, while avoiding the risk of hepatotoxicity. OBJECTIVES: To assess the incidence of hepatotoxicity in patients treated with 6TG, and to explore if a safe dose of continuous 6TG can be established. DATA SOURCES: Databases, conference proceedings, and reference lists of included studies were systematically searched for 6TG and synonyms from 1998-2018. METHODS: We included studies of patients with ALL or inflammatory bowel disorder (IBD) treated with 6TG, excluding studies with 6TG as part of an intensive chemotherapy regimen. We uploaded a protocol to PROSPERO (registration number CRD42018089424). Database and manual searches yielded 1823 unique records. Of these, 395 full-texts were screened for eligibility. Finally, 134 reports representing 42 studies were included. RESULTS AND CONCLUSIONS: We included data from 42 studies of ALL and IBD patients; four randomised controlled trials (RCTs) including 3,993 patients, 20 observational studies including 796 patients, and 18 case reports including 60 patients. Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9-25% of the ALL patients in two of the four included RCTs using 6TG doses of 40-60 mg/m2/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. In IBD patients treated with 6TG doses of approximately 23 mg/m2/day, NRH occurred in 14% of patients. At a 6TG dose of approximately 12 mg/m2/day, NRH was reported in 6% of IBD patients, which is similar to the background incidence. According to this review, doses at or below 12 mg/m2/day are rarely associated with notable hepatotoxicity and can probably be considered safe.

Effect of hospital-admission volume on outcomes following acute non-variceal upper gastrointestinal bleeding.

INTRODUCTION: Treatment-requiring acute non-variceal upper gastrointestinal bleeding (NVUGIB) is a common, potentially life-threatening emergency. This study investigated whether hospital admittance volume of patients with NVUGIB was associated with reduced mortality, reduced lasting failure of haemostatic procedures defined as rate of re-endoscopy with repeated haemostasis intervention (ReWHI), transfusion requirements and conversion to surgery. METHODS: Data on Danish nationwide admissions of patients with acute NVUGIB from 2011-2013 were analysed to estimate 30-day mortality, re-bleeding (ReWHI), transfusion rates and rates of conversion to surgery. Data were analysed by regression modelling while controlling for confounders including age, admission haemoglobin, the American College of Anesthesiologists score, comorbidities and the Forrest classification. RESULTS: A total of 3,537 patients with acute non-variceal upper gastrointestinal bleeding were included in the study. The hospital admission volume of patients with NVUGIB was positively associated with a significant increase in ReWHI with an odds ratio of 1.27; p = 1.91 × 10-6. There was no significant association between admission volume and conversion to surgery, 30-day mortality or transfusion rates. CONCLUSIONS: A positive association between admission volumes of patients with NVUGIB and ReWHI was identified. No association between admission volumes and 30-day mortality or other failure of haemostasis events could be identified. FUNDING: none. TRIAL REGISTRATION: not applicable.

Multivalent Carbohydrate-Functionalized Polymer Nanocrystals.

Nanoparticles with a covalently bound shell of carbohydrate or sulfate groups, respectively, and a polyethylene core were generated by Ni(II)-catalyzed aqueous copolymerization of ethylene with comonomers undec-10-en-1-yl sulfate, undec-10-en-1-yl ß-d-glucoside or undec-10-en-1-yl α-d-mannoside, respectively. Via remote substituents of the catalyst, the degree of branching and consequently degree of crystallinity of the polyethylene core of the glyconanoparticles could be controlled. This in turn impacts particle shapes, from spherical to anisotropic platelets, as observed by cryo-transmission electron microscopy. Enzyme-linked lectin assays revealed the mannose-decorated nanocrystals to be efficient multivalent ligands for concavalin A.

Traumatic bicycle handlebar hernia in children: a systematic review.

INTRODUCTION: This is a systematic review of existing literature on the diagnostic modalities and treatment of traumatic abdominal wall hernia caused by bicycle handlebar injury in children. 
METHODS: A systematic literature search was conducted covering incidents involving children below 17 years of age. Data were extracted regarding gender, age, diagnostic modality, timing of surgery, location of hernia, associated injuries, management and recurrence of hernia.
 RESULTS: A total of 62 cases of handlebar hernia were included in the systematic review. CT scan was the most frequently used final diagnostic modality (52%) followed by ultrasonography (13%), explorative laparotomy (5%) and diagnostic laparoscopy (5%). Coexisting intraabdominal injuries were present in 57% of all hernias located in the upper abdomen. Open surgical repair was the preferred treatment of choice (85%). Laparoscopic suturing was performed in one study. Six cases of handlebar hernia were treated conservatively. No cases of recurrence of hernia were reported in any of the cases. 
CONCLUSIONS: Traumatic abdominal wall hernia can be visualized by ultrasonography, but CT scan is often used as the final diagnostic modality because of the risk of associated intra-abdominal injuries. Open surgical repair in layers or laparoscopic suturing during diagnostic laparoscopy may be appropriate in managing traumatic abdominal wall hernias in children. Non-surgical management has been described, but available data do not support a general recommendation for a non-surgical approach.

[Traumatic bicycle handlebar hernia in a child].

Traumatic abdominal wall hernia in children caused by a bicycle handlebar is a rare injury. This is a case report of a 15-year-old boy with a traumatic hernia in the right groin, where a physical examination revealed a small bulge in the right inguinal region, and an ultrasonography confirmed the diagnosis. The condition was initially treated conservatively. However, the patient had surgery performed three days later because of pain. Surgical repair with open layered closure is the preferred method. Laparoscopic sutured repair may also be performed, especially if diagnostic laparoscopy is performed anyway.

Highly reactive, liquid diacrylamides via synergistic combination of spatially arranged curing moieties.

Six polymerizable N,N'-diacylamides containing spatially arranged N-acryl, N-allyl and/or N-alkyl groups were prepared via two-step syntheses and characterized by 1H/13C NMR-spectra, refractive index (RI) and viscosity measurements. Photo DSC measurements on activated samples provided reactivity parameters ∆Hp, Rp,max and tmax, while FTIR spectra before and after curing elucidated the underlying polymerization mechanism. Mechanical testing of the obtained polymers exhibited gradual differences in network densities, depending on the intramolecular arrangement and number of functional groups. Overall, a general building principle for highly reactive, liquid diacrylamides via synergistic combination of optimally arranged functional groups could be identified. The highest possible level of intramolecular synergism was found for low viscous N,N'-diacryloyl-N,N'-diallyl-1,4-but-2-enediamine.

Real-Time NMR Studies of Oxyamine Ligations of Reducing Carbohydrates under Equilibrium Conditions.

Ligation reactions at the anomeric center of carbohydrates have gained increasing importance in the field of glycobiology. Oxyamines are frequently used in labeling, immobilization, and bioconjugation of reducing carbohydrates. Herein, we present a systematic investigation of these ligation reactions under aqueous conditions. A series of four unprotected monosaccharides (glucose, N-acetylglucosamine, mannose, and 2-deoxyglucose) and one disaccharide (N,N'-diacetylchitobiose) was reacted with three primary and one secondary oxyamine. We monitored the concentrations of the starting materials and products by 1 H NMR spectroscopy and determined reaction times and equilibrium yields. Our experiments show that the outcome of the ligation reaction is not only dependent on the sugar and oxyamine used but also strongly on the reaction conditions. In the case of glucose, lowering the pH from 6 to 3 led to steadily increasing reaction rates, whereas the yields were decreasing at the same time. Variation of the temperature did not only influence the product ratio in equilibrium but can also have a strong impact on the equilibrium yield. In the case of reactions of a primary oxyamine, increased temperatures led to a higher proportion of acyclic products. Reaction of the secondary oxyamine with glucose unexpectedly led to lower yields at higher temperatures.

Studies toward the synthesis of linear triazole linked pseudo oligosaccharides and the use of ferrocene as analytical probe.

Three different building blocks have been synthesised and used for the synthesis of linear triazole linked pseudo oligosaccharides with copper(I)-catalysed cycloaddition (CuAAC). Ethynylferrocene has been used as analytical probe to improve the UV/Vis properties and HPLC methods have been used and optimised for the analysis of the pseudo oligosaccharides. The smallest ones have been isolated and characterised by analytical HPLC, NMR, ESI-MS and elemental analysis.

Carbohydrate-based Cu(I) stabilizing ligands and their use in the synthesis of carbohydrate-ferrocene conjugates.

A series of carbohydrate-ferrocene conjugates have been synthesized by copper(I)-catalyzed cycloaddition of carbohydrate-azides and ethynylferrocene (CuAAC). Newly carbohydrate-based tris-triazoles have been used as Cu(I) stabilizing ligands and showed at least comparable, in some cases even better results compared to the use of tris-(benzyltriazolylmethyl)amine (TBTA).

Carba-sugars activate the glmS-riboswitch of Staphylococcus aureus.

The glmS-riboswitch is unique among riboswitch families as it represents a metabolite-dependent ribozyme that undergoes self-cleavage upon recognition of glucosamin-6-phosphate. The glmS-riboswitch is located in the 5'-untranslated region of bacterial genes involved in cell wall biosynthesis. Therefore, this riboswitch represents a promising target for developing new antibiotics. We describe the metabolite-dependent glmS-riboswitch of pathologically relevant and vancomycin-resistant Staphylococcus aureus and the discovery and synthesis of a carba-sugar with potency similar to that of the native metabolite glucosamine-6-phosphate in modulating riboswitch activity. This compound represents a valuable lead structure for the development of antibiotics with a novel mode of action.