Kinetics of the anionic polymerization of ϵ-caprolactone with K+ · (dibenzo-18-crown-6 ether) counterion. Propagation via macroions and macroion pairs

Following our earlier work on the polymerization of lactones involving crowned cations, kinetics of the anionic polymerization of ?-caprolactone (?CL) with K⁺ · (dibenzo-18-crown-6 ether) (K⁺DB18C6) counterion was studied calorimetrically in THF solution in the temperature range from 0 to 20°C. Dissociation constants of CH₃(CH₂)₅O^?K⁺DB18C6, modelling the active centers, were determined conductometrically: K_D (20°C) = 7,7 · 10^?5 mol · dm^?3, ΔH = 9,3 ± 0,2 kJ · mol^?1, ΔS = ?47 ± 2J · mol^?1 · K^?1. From kinetic measurements and from measurements of the dissociation constant of CH₃(CH₂)₅O^? K⁺DB18C6, rate constants of propagation via macroions and via macroion pairs were determined. Activation parameters for propagation via these species are equal to: ΔH = 39,2 ± 0,2 kJ · mol^?1, ΔS = ?63 ± 1 J · mol^?1 · K^?1, ΔH = 13,7 ± 0,1 kJ · mol^?1, ΔS = ?185 ± 2 J · mol^?1 · K^?1. At 20°C, k = 3,50 · 10² dm³ · mol^?1 · s^?1 and k = 5,2 dm³ · mol^?1 · s^?1. Due to the large difference of ΔH^≠ for propagation via macroions and macroion pairs (vide supra), the isokinetic point (k = k) would appear at ?65°C.     

Functional and morphological aspects of Helicobacter pylori-induced gastric cancer in Mongolian gerbils

BACKGROUND: Helicobacter pylori infection of Mongolian gerbils is an established model of gastric carcinogenesis, but gastric secretory aspects of this carcinogenesis have not been studied. METHODS: The effects of single intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) CFU/ml) or vehicle (saline) were examined at 1, 2, 4, 6, 9, 12 and 30 weeks from inoculation. Gastric morphology, the presence of H. pylori using the rapid urease test, the density of H. pylori and 16S rRNA and the plasma gastrin and somatostatin were determined. RESULTS: H. pylori was detected in gastric mucosa in all infected animals. Basal gastric acid in gerbils was reduced by about 50% after H. pylori inoculation. Early lesions seen at 4 weeks after H. pylori inoculation consisted of chronic gastritis with thickened mucosal folds, oedema, congestion and mucosal lymphocytic infiltration. Adenomatous hyperplasia with cellular atypia with increased mitotic activity and the formation of apoptotic bodies and visible erosions and ulcerations were observed at 12-30 weeks after inoculation. The atypical gastric glands were situated 'back-to-back', suggesting gastric pre-cancer. The gastric blood flow in H. pylori-infected gerbils was significantly lower than that in the controls. Six- to seven-fold increase in plasma gastrin levels combined with significant fall in gastric somatostatin contents and the intraepithelial neoplasia were noticed in gerbils at all tested periods. CONCLUSION: H. pylori-infection in gerbils resulted in gastric pre-cancer associated with functional changes, such as suppression of gastric secretion and impairment of both gastric mucosal microcirculation and the gastrin-somatostatin link.     

Transfer of chemicals to a secondary container,from the introduction of new labelling regulation to COVID-19 lockdown: A retrospective analysis of exposure calls to the Poison Control Centre of Rome,Italy, 2017–2020

The transfer of a chemical product from its original container to an unlabelled secondary container by consumers is a potential health hazard that may result in unintentional exposures and intoxications. The aim of this study was to describe the pattern of prevalence of exposures to transferred products in Italy from year 2017, when the new European labelling regulation for chemicals became fully operative, to 2020, year of the coronavirus 19 disease first outbreak. Calls to the Poison Control Centre (PCC) of Policlinico Umberto I Hospital - Sapienza University of Rome were analysed retrospectively for characteristics, clinical presentation and circumstances related to the event. We registered 198 cases of interest. There was a reduction in cases from 2017 (4.9%) to 2019 (2.2%), followed by an increased prevalence in 2020 (4.2%) mainly due to the months “post-lockdown.” The transferred product was very frequently diluted, and an empty drinking bottle was usually used as secondary container. Exposures were mostly of minor severity, and no deaths occurred. The study highlights the importance of PCCs data in the evaluation of the hazard communication to users through labels and advises for public campaigns to promote safe behaviours during future lockdowns to prevent exposures at a later period.     

Protein Requirements in Critical Illness: Do We Really Know Why to Give So Much?

The protein and energy requirements of critically ill patients treated in intensive care units (ICUs) have been actively discussed recently. Currently published clinical recommendations and reviews suggest significant increases of protein provision to 2–2.5 g/kg/d in some populations of ICU patients. However, a detailed analysis of the main sources of these recommendations reveals a number of serious contradictions, as well as an absence of obvious evidence supporting the allotment of high doses of protein. We went through these recommendations and reviewed cited articles and other studies, and we have separated our arguments against excessive protein provision into sections.     

Evidence of 5‐lipoxygenase overexpression in the skin of patients with systemic sclerosis: A newly identified pathway to skin inflammation in systemic sclerosis

Objective

Leukotrienes are a family of arachidonic acid derivatives with potent proinflammatory and profibrotic properties, and 5‐lipoxygenase (5‐LOX) catalyzes two key steps in the leukotriene biosynthetic pathway. Since inflammatory cell infiltrates and excessive fibrosis are hallmarks of systemic sclerosis (SSc) skin lesions, we undertook the present study to investigate the expression of 5‐LOX in skin biopsy specimens from patients with SSc.

Methods

Expression of 5‐LOX in skin sections from 10 SSc patients and 8 healthy controls was examined by in situ hybridization with specific riboprobes and by immunohistochemistry analysis with 5‐LOX monoclonal antibodies. Synthesis of 5‐LOX by cultured dermal fibroblasts from 7 patients with SSc and 4 controls was measured by fluorescence‐activated cell sorter analysis. In addition, concentrations of leukotriene B₄ (LTB₄) and LTE₄ in fibroblast supernatants after stimulation were determined using enzyme immunoassays.

Results

Expression of 5‐LOX was found in all skin sections from SSc patients as well as from controls. However, the number and percentage of 5‐LOX–positive cells were significantly higher in SSc skin sections compared with control sections. Expression of 5‐LOX was seen in cells within perivascular inflammatory infiltrates as well as in fibroblasts throughout the skin. The experiments with cultured skin fibroblasts revealed that 5‐LOX was constitutively expressed in these cells, which resulted in the production of leukotrienes after cell stimulation. Whereas no difference was found for LTE₄, SSc fibroblasts produced significantly higher amounts of LTB₄ after stimulation, compared with healthy control fibroblasts.

Conclusion

The results of this study suggest that the 5‐LOX pathway may be of significance in the pathogenesis of SSc and may represent a target for new treatment strategies.