Aquaporin expression and cell volume regulation in the SV40 immortalized rat submandibular acinar cell line

The amount of aquaporins present and the cellular ability to perform regulatory volume changes are likely to be important for fluid secretions from exocrine glands. In this work these phenomena were studied in an SV40 immortalized rat submandibular acinar cell line. The regulatory cell volume characteristics have not previously been determined in these cells. Cell volume regulation following hyposmotic exposure and aquaporin induction was examined with Coulter counter methodology, radioactive efflux studies, fura-2 fluorescence, and polymerase chain reaction and Western blot techniques. Cell volume regulation was inhibited by the K⁺ channel antagonists quinine and BaCl₂ and the Cl⁻ channel blocker 5-nitro-2-(3-phenypropylamino)benzoic acid. A concomitant increase in cellular ³H-taurine release and Ca²⁺ concentration was also observed. Chelation of both intra- and extracellular Ca²⁺ with EGTA and the Ca²⁺ ionophore A23187 did not, however, affect cell volume regulation. Aquaporin 5 (AQP5) mRNA and protein levels were upregulated in hyperosmotic conditions and downregulated upon return to isosmotic solutions, but were reduced by the mitogen-activated ERK-activating kinase (MEK) inhibitor U0126. A 24-h MEK inhibition also diminished hyposmotically induced cell swelling and cell volume regulation. In conclusion, it was determined that regulatory volume changes in this immortalized cell line are due to KCl and taurine efflux. In conditions that increased AQP5 levels, the cells showed a faster cell swelling and a more complete volume recovery following hyposmotic exposure. This response could be overturned by MEK inhibition.     

Consumer Acceptance and Market Potential of Iodine-Biofortified Fruit and Vegetables in Germany

Biofortification of food crops with iodine is a novel approach to preventing iodine deficiency in humans. The present study analyses the consumer target groups and the market potential of iodine-biofortified fruit and vegetables in Germany. For this purpose, an online survey of 1016 German fruit and vegetable consumers was conducted to investigate the acceptance of different product categories as well as relevant criteria for the market launch. The results show that iodine-biofortified fruit and vegetables are particularly attractive to consumers who purchase at farmers’ markets, organic food shops, and farm stores. Out of this group, 39% of consumers rate such iodine-rich foods as very appealing. They attach importance to food that naturally contains iodine and prefer produce from integrated domestic cultivation. With their focus on sustainability and naturalness, this group of consumers clearly differs from typical users of dietary supplements, who are primarily concerned with health benefits. However, overall about 85% of respondents would prefer biofortified fruits and vegetables to supplements to improve their iodine supply. The greatest market potential for iodine-biofortified fruit and vegetables is to be expected in supermarkets, as this is the preferred food shopping location for most consumers. A total of 28% of those who buy here rate the biofortified foods presented as very appealing. Nevertheless, a successful market launch requires that the benefits of the new products are communicated according to the potential consumer group needs.     

The assessment of views on ageing: a review of self-report measures and innovative extensions

This is a review of existing self-report measures for assessing views on ageing. It provides an overview of instruments, for which basic psychometric properties are available and describes them according to the purposes for which they are suitable. Literature search resulted in the inclusion of 89 instruments which were categorised along eight dimensions. The majority of measures focus on explicit cognitions about people’s own age and ageing or other (older) people. A substantial amount of tools account for the multidimensionality and multidirectionality of views on ageing, i.e. the idea that ageing is accompanied by both gains and losses in several different domains. To some extent, measures reflect that ageing is a long-term process and that views on ageing are malleable, rather than just stable traits. Cluster analysis revealed heterogeneity in instruments regarding the dimensions of Ecosystem, Balance, Stability, Dynamics, and Complexity. It becomes apparent, however, that approaches to measure views on ageing should be extended to more specifically target the implicit level as well as affective, physiological, and behavioural manifestations. Additionally, means for capturing views on ageing on the societal level and tools with a distinct time reference are needed. This is particularly important when one wants to account for the lifelong dynamics of views on ageing.     

Rebound pain and postoperative pain profile following brachial plexus block compared to general anaesthesia—An observational study

Background

Regional anaesthesia has the benefit of reducing the need for systemic analgesia and therefore, potentially reducing undesired side effects. With the end of the sensory nerve block however, many patients report severe pain that requires therapy with opioids and often compromise the initial opioid sparing effect. This study aimed to characterise the postoperative pain profile and the phenomenon of rebound pain after axillary brachial plexus anaesthesia (RA) compared to general anaesthesia (GA).

Design

Single-centre observational, stratified cohort study.

Setting

The study was conducted at University Hospital Marburg from May 2020 until September 2022.

Participants

One hundred thirty-two patients receiving elective hand and forearm surgery were enrolled in this study.

Interventions

Group RA received ultrasound-guided brachial plexus anaesthesia via the axillary approach with 30 mL of prilocaine 1% and 10 mL ropivacaine 0.2%. Group GA received balanced or total intravenous general anaesthesia.

Main Outcome Measures

Primary endpoint were integrated pain scores (IPS) within 24 h postoperatively. Secondary endpoints were pain scores (NRS 0–10), morphine equivalents, patient satisfaction, quality of recovery and opioid-related side effects.

Results

One hundred thirty-two patients were analysed of which 66 patients received brachial plexus block and 66 patients received general anaesthesia. Following RA significantly lower IPS were seen directly after surgery (p < .001) and during the post-anaesthesia care unit interval (p < .001) but equalised after 3 h at the ward. No overshoot in pain scores or increased opioid consumption could be detected. Patient satisfaction and postoperative recovery were comparable between both groups.

Conclusion

The IPS and NRS was initially lower in the RA group, increased with fading of the block until equal to the GA group and equal thereafter. Although various definitions of rebound pain were met during this phase, the opioid sparing effect of regional anaesthesia was not counteracted by it. The incidence of episodes with uncontrolled, severe pain did not differ between groups. We found no clinical implications of rebound pain in this setting, since the RA group did not show higher pain scores than the GA group at any time point. Trial Registration: German Clinical Trials Register (DRKS00021764).     

Effects of intra-articular corticosteroids and anti-TNF therapy on neutrophil activation in rheumatoid arthritis

OBJECTIVE: The pro-inflammatory calcium-binding protein S100A12 has been recently ascribed to the novel group of damage associated molecular pattern (DAMP) molecules. Serum levels of S100A12 reflect neutrophil activation during synovial inflammation. The aim of this project was to analyse the effect of intra-articular corticosteroids or systemic anti-TNF treatment on synovial expression and serum levels of S100A12 in rheumatoid arthritis (RA). METHODS: Serum and synovial tissue was obtained from 19 RA patients prior to and 2 weeks after intra-articular corticosteroid therapy. Serum was collected for 34 other patients, and in 14 of these patients synovial tissue was additionally obtained prior to and after 8 weeks of infliximab treatment. The expression of S100A12 was analysed by immunohistochemistry on frozen sections. Levels of S100A12 in serum were determined by ELISA. RESULTS: S100A12 serum levels were elevated in patients with active RA prior to therapy and decreased significantly in patients who responded to treatment in both patient groups, but not in non-responders. The synovial expression of S100A12 was reduced 2 weeks after successful intra-articular corticosteroid treatment. A similar decrease in local expression was found after 8 weeks of successful infliximab treatment. CONCLUSIONS: Successful treatment of RA leads to downregulation of the DAMP protein S100A12. Expression and secretion of S100A12 is rapidly diminished after therapy with intra-articular corticosteroids or infliximab. Taking these findings together, decreasing serum concentrations of S100A12 could reflect alleviated synovial neutrophil activation during successful anti-inflammatory therapy in RA.     

Synovial macrophages as a biomarker of response to therapeutic intervention in rheumatoid arthritis: standardization and consistency across centers

Successive studies from one academic center (Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands) have consistently suggested that synovial tissue expression of sublining macrophages may be a biomarker of clinical response to therapeutic intervention in rheumatoid arthritis (RA) clinical trials. A proof-of-concept, randomized clinical trial was completed at a second academic center (St. Vincent's University Hospital, Dublin, Ireland), and the relationship between the change in disease activity and the change in sublining macrophages in distinct treatment cohorts was determined. The preliminary findings were not conclusive, but appeared to support a role for sublining CD68+ macrophages as a biomarker of clinical response to therapeutic intervention in cohorts of patients with RA.     

Anti-tumor necrosis factor therapy increases synovial osteoprotegerin expression in rheumatoid arthritis

OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF)-blocking agents, including etanercept and infliximab, has resulted in reductions in the radiographic progression of RA. However, the exact mechanism by which this protection occurs has not been determined. In order to add to such knowledge, we investigated the effect of anti-TNF therapy on the expression of osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in synovial tissue. METHODS: The expression of OPG and RANKL in synovial biopsy specimens was evaluated by immunohistochemistry. Serial synovial biopsy specimens were obtained from 18 patients with RA, before and after treatment with etanercept (9 patients) or infliximab (9 patients). Biopsy specimens were evaluated by double-blind semiquantitative analysis and image analysis. The in vitro effect of TNF antagonists on the RANKL/OPG expression in osteoblasts and endothelial cells was evaluated by Western blotting. Statistical analysis was performed using Wilcoxon's signed rank test, followed by the Bonferroni correction for multiple comparisons of paired samples. The results of in vitro experiments were evaluated by one-way analysis of variance, with Tukey's post hoc test. RESULTS: Treatment with both infliximab and etanercept increased the expression of OPG in synovial tissue. After 8 weeks of treatment, neither infliximab nor etanercept influenced RANKL expression. In both groups of patients, the RANKL:OPG ratio decreased following therapy. In vitro, both of the TNF antagonists mimicked the in vivo effect, inducing a decrease in the RANKL:OPG ratio in TNF-primed osteoblasts and endothelial cells. CONCLUSION: Therapy with TNF antagonists in RA modulates the OPG/RANKL system, a potential mechanism that could explain the retardation of radiographic damage observed following anti-TNF therapy.     

Intrapartal care documented in a Swedish maternity unit and considered in relation to World Health Organization recommendations for care in normal birth

OBJECTIVES: To describe documented intrapartal care in relation to the World Health Organization (WHO) recommendations for care in normal birth, and to compare intrapartal care for pregnant women at low and high risk in a conventional maternity unit. DESIGN: Retrospective examination of 212 consecutive childbirth records using an audit instrument developed from WHO's recommendations. SETTING: A conventional maternity unit in Western Sweden. FINDINGS: Practices that are demonstrably useful and should be encouraged were mostly documented, except for physical assessments, such as pulse and temperature and emotional aspects. Vaginal examinations were carried out more often than recommended, and fetal heart rates were seldom monitored intermittently. Practices classified as harmful, practices with insufficient evidence and practices frequently used inappropriately, were used to a large extent. There were high rates of interventions regardless of the women's risk level. The interventions were carried out without a rational documented indication. According to the documentation, only two-thirds of the women were in active labour on admission to the labour ward. CONCLUSION AND IMPLICATIONS FOR PRACTICE: The recommendations from WHO were only partly adhered to. The instrument is considered useful for systematic audit of documented intrapartal care, and may help to identify areas in need of improvement. Improvements suggested by this study were as follows: inclusion of emotional aspects in the documentation, differentiation in cardiotocographic (CTG) surveillance for women at low and high risk, documentation of explicit indications for interventions and guidelines for admission to the maternity unit.     

Correlations of obstetric anal sphincter injury (OASIS) grade,specific symptoms of anal incontinence,and measurements by endoanal and transperineal ultrasound

PurposeThe aim of the study was to investigate the association between the initial grade of obstetrical anal sphincter injury (OASIS), and Wexner score parameters, with ultrasonographic findings by endoanal ultrasound (EAUS, golden standard) and transperineal ultrasound (TPUS) 6 months post-partum.MethodsFifty-nine women after primary repair of OASIS were included at Helsingborg Hospital, Sweden, 2016–2017. Six months post-partum the women filled in a questionnaire regarding symptoms of anal incontinence by the Wexner score and were scanned with EAUS and TPUS (resting state and contracting state) for classification of the residual defect by a modified Starck score.ResultsCorrelations were found between the OASIS grade and residual defects; length (r_s = 0.41, P = 0.003), depth (r_s = 0.38, P = 0.006) and angle (r_s = 0.40, P = 0.004) of the external anal sphincter (EAS) measured with TPUS in resting state. Using EAUS, correlation between OASIS grade and EAS depth (r_s = 0.35, P = 0.007) and angle (r_s = 0.37, P = 0.004) were similar, but there was no correlation with length (r_s = 0.20, P = 0.14). Between incontinence to gas and the angle of the residual defect in the IAS using TPUS in resting state, correlation was moderate (r_s = 0.42, P = 0.003). Regarding incontinence to liquid stool, measurements by TPUS in resting state of EAS residual defect depth (r_s = 0.46, P < 0.001) and angle (r_s = 0.44, P = 0.001) also correlated moderately. Both corresponding correlations using EAUS were weaker.ConclusionDefects measured with EAUS and TPUS six months post-partum correlated to initial OASIS grade and symptoms of anal incontinence. Specific symptoms correlated with specific anatomical defects, and TPUS was not an inferior method to EAUS.