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).     

Impact of cisplatin administration on protein expression levels in renal cell carcinoma: a proteomic analysis

Renal cell carcinoma (RCC) is the most common renal neoplasm in adults. Considering that chemoresistance is a typical feature of RCC, every effort should be made in order to identify mechanisms of drug resistance. We used two-dimensional gel electrophoresis and mass spectrometry to study changes in protein expression levels that occur in primary resistant LN78 RCC cells when treated with therapeutic concentrations of cisplatin. Expression differences of selected proteins were confirmed by immunoblot. Up-regulation of heat-shock proteins can block apoptosis indirectly by altered protein folding and by direct interaction with apoptosis regulatory proteins. Cyclophilin A and stratifin can modify cell cycle control and enable tumor cells to escape and further proliferate despite DNA damage caused by cisplatin. Increased activity of glycolytic enzymes reflect metabolic adaptations to increased energy requirements as well as converting to alternative energy sources because of cisplatin-induced disturbed mitochondrial oxidation. Changes in cytoskeletal proteins may change the handling of cisplatin by altering transport and increasing cellular efflux of the drug. Repression of vimentin and disturbance of antioxidative mechanisms may represent vulnerable points in tumor cellular defense against cisplatin. The involvement of these proteins in cisplatin resistance and their potential as therapeutic targets requires further evaluation.     

Labour augmentation and fetal outcomes in relation to birth positions: A secondary analysis of an RCT evaluating birth seat births

Objective

the aim of this study was to compare the use of synthetic oxytocin for augmentation, duration of labour and birth and infant outcomes in nulliparous women randomised to birth on a birth seat or any other position.

Study design

a randomised controlled trial in Sweden where 1002 women were randomised to birth on a birth seat (experimental group) or birth in any other position (control group). Data were collected between November 2006 and July 2009. The outcome measurements included synthetic oxytocin augmentation, duration of the second stage of labour and fetal outcome. Analysis was by intention to treat.

Setting

southern Sweden.

Findings

the main findings of this study were that women randomised to the experimental group had a statistically significant shorter second stage of labour than women randomised to the control group. There were no differences between the groups for use of synthetic oxytocin augmentation or for neonatal outcomes.

Conclusions

women allocated to the birth seat had a significantly shorter second stage of labour despite similar numbers of women subjected to synthetic oxytocin augmentation in the study groups. The adverse neonatal outcomes did not differ between groups. The birth seat can be suggested as non-medical intervention used to reduce duration of second stage labour and birth. The birth seat can be suggested as a non-medical intervention that may facilitate reduced duration of the second stage of labour. Furthermore it is recommended that caregivers, both midwives and midwifery students, should learn skills to assist women in using a variety of birth positions.

Trial registration

unique Protocol ID: Dnr 2009/739 (register.clinicaltrials.gov).     

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.     

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.     

AAV8-Mediated In Vivo Overexpression of miR-155 Enhances the Protective Capacity of Genetically Attenuated Malarial Parasites

Malaria, caused by protozoan Plasmodium parasites, remains a prevalent infectious human disease due to the lack of an efficient and safe vaccine. This is directly related to the persisting gaps in our understanding of the parasite''s interactions with the infected host, especially during the clinically silent yet essential liver stage of Plasmodium development. Previously, we and others showed that genetically attenuated parasites (GAP) that arrest in the liver induce sterile immunity, but only upon multiple administrations. Here, we comprehensively studied hepatic gene and miRNA expression in GAP-injected mice, and found both a broad activation of IFNγ-associated pathways and a significant increase of murine microRNA-155 (miR-155), that was especially pronounced in non-parenchymal cells including liver-resident macrophages (Kupffer cells). Remarkably, ectopic upregulation of this miRNA in the liver of mice using robust hepatotropic adeno-associated virus 8 (AAV8) vectors enhanced GAP''s protective capacity substantially. In turn, this AAV8-mediated miR-155 expression permitted a reduction of GAP injections needed to achieve complete protection against infectious parasite challenge from previously three to only one. Our study highlights a crucial role of mammalian miRNAs in Plasmodium liver infection in vivo and concurrently implies their great potential as future immune-augmenting agents in improved vaccination regimes against malaria and other diseases.