Quality of recovery after day care surgery with app-controlled remote monitoring: study protocol for a randomized controlled trial.

BACKGROUND: The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient's recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient's recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring. METHODS: This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery. The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions. The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery. DISCUSSION: This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period. TRIAL REGISTRATION: The 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial' is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial', is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772).

Serious adverse events attributed to remifentanil patient-controlled analgesia during labour in The Netherlands.

BACKGROUND: During labour, remifentanil patient-controlled analgesia is used as an alternative to neuraxial analgesia. Remifentanil is associated with hypoventilation and respiratory depression but the frequency of serious maternal and neonatal adverse events is unknown. The aim of this study was to estimate the number of serious adverse events attributed to the use of remifentanil patient-controlled analgesia during labour in The Netherlands and to investigate the circumstances (e.g. monitoring, practice deviations) of these events and the subsequent management. METHODS: In a nationwide survey among obstetricians, anaesthetists and clinical midwives the frequency of serious adverse events was assessed. A questionnaire was sent by email to all 61 Dutch hospitals in which remifentanil patient-controlled analgesia is, or has been, available for labour analgesia. All reported cases were assessed independently by two expert teams. RESULTS: We received information from all hospitals. After independent assessments, 17 cases of single maternal desaturation; 10 maternal cases of apnoea, bradycardia and/or cardiac arrest; and two neonatal cases of respiratory depression, over a period of more than 10 years of remifentanil patient-controlled analgesia use, were identified as a serious adverse event. All serious adverse events were resolved without irreversible damage. CONCLUSIONS: The risk of a potentially life-threatening serious adverse event attributed to remifentanil patient-controlled analgesia seems to be low. All patients recovered without deficit. Adherence to strict monitoring and the attendance of trained healthcare providers is required to safely use remifentanil for labour analgesia.

Peri-operative management of patients with type-2 diabetes mellitus undergoing non-cardiac surgery using liraglutide, glucose-insulin-potassium infusion or intravenous insulin bolus regimens: a randomised controlled trial.

In this open-label multicentre randomised controlled trial, we investigated three peri-operative treatment strategies to lower glucose and reduce the need for rescue insulin in patients aged 18-75 years with type-2 diabetes mellitus undergoing non-cardiac surgery. Patients were randomly allocated using a web-based randomisation program to premedication with liraglutide (liraglutide group), glucose-insulin-potassium infusion (insulin infusion group) or insulin bolus regimen (insulin bolus group), targeting a glucose < 8.0 mmol.l-1 . The primary outcome was the between group difference in median glucose levels 1 h after surgery. We analysed 150 patients (liraglutide group n = 44, insulin infusion group n = 53, insulin bolus group n = 53) according to the intention-to-treat principle. Median (IQR [range]) plasma glucose 1 h postoperatively was lower in the liraglutide group compared with the insulin infusion and insulin bolus groups (6.6 (5.6-7.7 [4.2-13.5]) mmol.l-1 vs. 7.5 (6.4-8.3 [3.9-16.6]) mmol.l-1 (p = 0.026) and 7.6 (6.4-8.9 [4.7-13.2]) mmol.l-1 ) p = 0.006, respectively). The incidence of hypoglycaemia and postoperative complications did not differ between the groups. Six patients had pre-operative nausea in the liraglutide group, of which two had severe nausea, compared with no patients in the insulin infusion and insulin bolus groups (p = 0.007). The pre-operative administration of liraglutide stabilised peri-operative plasma glucose levels and reduced peri-operative insulin requirements, at the expense of increased pre-operative nausea rates.

Factors associated with time to achieve an undetectable HIV RNA viral load after start of antiretroviral treatment in HIV-1-infected pregnant women.

OBJECTIVE: To identify factors associated with the time to viral suppression in women starting antiretroviral treatment (ART) during pregnancy. Knowledge on duration of viral load (VL) decline could help deciding the timing of treatment initiation. METHODS: Highly active antiretroviral treatment (HAART)-naive pregnant women over 18 years of age who started treatment during pregnancy were included. The time to viral suppression was calculated and compared between subgroups. RESULTS: A total of 227 pregnancies matched our inclusion criteria. In 84.6% of these an undetectable VL was reached at the time of delivery. The median time to undetectable VL after initiation of treatment was 60 days (12-168 days). Only baseline VL <10,000 copies/mL showed an independent association with time to viral suppression in multivariate Cox regression analysis, with a mean time to reach a VL <50 HIV-1 copies/mL of 49 days (95% CI 44-53). No difference in time to undetectable VL was found between protease inhibitor and non-nucleoside reverse transcriptase inhibitor-based regimens. Integrase inhibitors were not part of any treatment regimen. CONCLUSION: Our results suggest that in patients with baseline HIV RNA <10,000 copies/mL ART initiation might be postponed up to the twentieth week of pregnancy, thus minimising the risk of possible drug-related teratogenicity and toxicity.

Labour pain with remifentanil patient-controlled analgesia versus epidural analgesia: a randomised equivalence trial.

OBJECTIVE: To distinguish satisfaction with pain relief using remifentanil patient-controlled analgesia (RPCA) compared with epidural analgesia (EA) in low-risk labouring women. DESIGN: Randomised controlled equivalence trial. SETTING: Eighteen midwifery practices and six hospitals in the Netherlands. POPULATION: A total of 408 pregnant women at low risk for obstetric complications initially under the care of primary-care midwives. METHODS: Women randomised before active labour to receive analgesia with RPCA or EA, if requested. MAIN OUTCOME MEASURES: Primary outcome was satisfaction with pain relief measured hourly using a visual analogue scale and summed as area under the curve (AUC). Secondary outcomes were overall satisfaction with pain relief, pain intensity scores during labour, mode of delivery, and maternal and neonatal outcomes. RESULTS: We randomised 418 women, of whom 409 could be followed for the primary endpoint. Analgesia was received by 46% (94/203) in the remifentanil group and 37% (76/206) in the epidural group. The AUC for satisfaction with pain relief was 32 in the remifentanil group and 31 in the epidural group (mean difference -0.50; 95% CI -6.8 to 5.9). Among women who actually received analgesia, these values were 23 and 35, respectively (mean difference -12; 95% CI -22 to -1.5). Secondary outcomes were comparable. CONCLUSIONS: In low-risk labouring women, we could not demonstrate equivalence between a strategy with RPCA to EA with respect to satisfaction with pain relief assessed during the total duration of labour. However, once applied satisfaction was higher in women who received epidural analgesia. TWEETABLE ABSTRACT: Satisfaction with pain relief is higher in women receiving epidural analgesia compared with Remifentanil PCA.

Different brain responses during empathy in autism spectrum disorders versus conduct disorder and callous-unemotional traits.

BACKGROUND: Deficits in empathy are reported in autism spectrum disorders (ASD) and also underlie antisocial behavior of individuals with conduct disorder and callous-unemotional traits (CD/CU+). Many studies suggest that individuals with ASD are typically impaired in cognitive aspects of empathy, and individuals with CD/CU+ typically in affective aspects. In the current study, we compared the neural correlates of cognitive and affective aspects of empathy between youth with ASD and youth with CD/CU+. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess boys with ASD (N = 23), boys with CD/CU+ (N = 23), and typically developing (TD) boys (N = 33), aged 15-19 years. Angry and fearful faces were presented and participants were asked to either infer the emotional state from the face (other-task; emotion recognition) or to judge their own emotional response to the face (self-task; emotional resonance). RESULTS: During emotion recognition, boys with ASD showed reduced responses compared to the other groups in the ventromedial prefrontal cortex (vmPFC). During emotional resonance, the CD/CU+ and ASD groups showed reduced amygdala responses compared to the TD controls, boys with ASD showed reduced responses in bilateral hippocampus, and the CD/CU+ boys showed reduced responses in the inferior frontal gyrus (IFG) and anterior insula (AI). CONCLUSION: Results suggest differential abnormal brain responses associated with specific aspects of empathic functioning in ASD and CD/CU+. Decreased amygdala responses in ASD and CD/CU+ might point to impaired emotion processing in both disorders, whereas reduced vmPFC responses suggest problems in processing cognitive aspects of empathy in ASD. Reduced IFG/AI responses, finally, suggest decreased emotional resonance in CD/CU+.

Glucocorticoids can affect Pseudomonas aeruginosa (ATCC 27853) internalization and intracellular calcium concentration in cystic fibrosis bronchial epithelial cells.

BACKGROUND AND OBJECTIVE: Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated. METHODS: We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide. RESULTS: GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration. CONCLUSION: These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.

N-acetylcysteine and azithromycin affect the innate immune response in cystic fibrosis bronchial epithelial cells in vitro.

BACKGROUND AND OBJECTIVE: We have previously reported that N-acetylcysteine (NAC), ambroxol and azithromycin (AZM) (partially) correct the chloride efflux dysfunction in cystic fibrosis bronchial epithelial (CFBE) cells with the ΔF508 homozygous mutation in vitro. METHODS: In the present paper, we further investigated possible immunomodulatory effects of these drugs on the regulation of the innate immune system by studying the expression of the cytosolic NOD-like receptors NLRC1 and NLRC2, and interleukin (IL)-6 production in CFBE cells. RESULTS: Under basal conditions, PCR and Western Blot data indicate that the NLRC2 receptor has a reduced expression in CF cells as compared to non-CF (16HBE) cells, but that the NLRC1 expression is the same in both cell lines. AZM significantly upregulated NLRC1 and NLRC2 while NAC upregulated only NLRC2 receptor expression in CF cells. Reduced basal IL-6 production was found in CF cells as compared to non-CF cells. MDP (an NLRC2 agonist), NAC and AZM, but not Tri-DAP (an NLRC1 agonist), increased IL-6 production in CF cells, indicating that in CF cells IL-6 upregulation is independent of NLRC1, but involves the activation of NLRC2. CONCLUSION: Overall, the results indicate that NAC and AZM not only can correct the chloride efflux dysfunction but also have a weakly strengthening effect on the innate immune system.

Pharmacological treatment of the basic defect in cystic fibrosis.

Cystic fibrosis (CF) is a genetic disease due to a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel in epithelial cells. There are about 1900 mutations, divided in several groups, for example, stop mutations, mutations affecting the permeability of the channel, and mutations in which the mutated CFTR is recognized as abnormal and destroyed. Pharmacological treatment has become possible for stop mutations (about 10% of the patients), and for a rare mutation affecting channel permeability. For the majority of patients, however, that have a mutation in which the mutated CFTR is destroyed on its way to the cell membrane, research is still in progress, although a number of compounds have been identified that (at least partly) corrects the error in chloride transport.

X-ray microanalysis in the scanning electron microscope.

X-ray microanalysis conducted using the scanning electron microscope is a technique that allows the determination of chemical elements in bulk or semi-thick specimens. The lowest concentration of an element that can be detected is in the order of a few mmol/kg or a few hundred parts per million, and the smallest amount is in the order of 10(-18) g. The spatial resolution of the analysis depends on the thickness of the specimen. For biological specimen analysis, care must be taken to prevent displacement/loss of the element of interest (usually ions). Protocols are presented for the processing of frozen-hydrated and freeze-dried specimens, as well as for the analysis of small volumes of fluid, cell cultures, and other specimens. Aspects of qualitative and quantitative analysis are covered, including limitations of the technique.

Isolation and culture of primary human nasal epithelial cells from anesthetized nasal epithelia.

CONCLUSION: Using a local anesthetic agent before obtaining nasal biopsies by nasal brushing makes the sampling procedure smooth, avoids lacrimation, nasal itching/irritation, and/or sneezing and provides enough viable cells to establish primary cultures. OBJECTIVES: To examine the use of local anesthesia to avoid the irritation experienced by the subject when nasal biopsies are obtained by nasal brushing in order to culture viable nasal epithelial cells. METHODS: Nasal epithelial cells were collected from the mid-part of the inferior turbinate of healthy volunteers by brushing with interdental brushes, after spraying a topical anesthetic on the nasal mucosa. Immunocytochemistry was performed to assess the purity of epithelial cells. RESULTS: Cell samples ranging from 1.16 × 10(5) to 3.06 × 10(5) cells/per sample were obtained. Of 11 samples, 7 formed confluent cultures, while the remaining 4 samples showed only patches of epithelial cells. Neither fungal nor bacterial contamination posed a problem. Immunocytochemistry of the cytospin slides confirmed the presence of epithelial cells in the cultures. No adverse effects were experienced by the volunteers.

Modulation of ENaC, CFTR, and iNOS expression in bronchial epithelial cells after stimulation with Staphylococcus epidermidis (94B080) and Staphylococcus aureus (90B083).

Bacteria affect the respiratory epithelium, which is covered by airway surface liquid (ASL) and mucus. Ion concentrations in the ASL are determined by the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na(+) channel (ENaC). Neonatal sepsis is a major risk factor for subsequent pulmonary disease in preterm newborns. Predominating are coagulase-negative staphylococci (e.g., Staphylococccus epidermidis and Staphylococccus aureus). The aim of this study was to investigate modulation of CFTR, ENaC, mucins, proinflammatory cytokines, and inducible nitric oxide synthase (iNOS) in respiratory epithelial cells after S. epidermidis 94B080 and S. aureus 90B083 exposure. Bronchial epithelial cells were incubated with S. epidermidis 94B080 and S. aureus 90B083 (neonatal blood isolates) for 1-36 h. Expression of CFTR, ENaC, iNOS, and mucins was analyzed by real-time PCR and Western blotting. Release of cytokines was analyzed by ELISA, and production of NO by the Griess assay. Expression of CFTR significantly decreased after 36 h incubation with S. epidermidis and more prominently with S. aureus, whereas S. epidermidis caused a significant increase in the expression of ß- and γ-ENaC. Expression of iNOS increased, but NO was not detected. Both staphylococci caused a decrease in the intracellular Ca(2+) concentration. S. aureus induced increased secretion of IL-6, IL-8, and transforming nuclear factor (TNF)-α in a time-dependent manner as compared with S. epidermidis. In conclusion, expression of ENaC, CFTR, and iNOS is modulated by exposure to S. aureus 90B083 and S. epidermidis 94B080. S. aureus is more potent in causing release of IL-6, IL-8, and TNF-α by bronchial epithelial cells as compared with S. epidermidis. The mRNA expression for the mucus proteins MUC2, MUC5AC, and MUC5B could not be measured, neither in the presence nor in the absence of bacteria.

The effect of ambroxol on chloride transport, CFTR and ENaC in cystic fibrosis airway epithelial cells.

Ambroxol, a mucokinetic anti-inflammatory drug, has been used for treatment of cystic fibrosis (CF). The respiratory epithelium is covered by the airway surface liquid (ASL), the thickness and composition of which is determined by Cl(-) efflux via the cystic fibrosis transmembrane conductance regulator (CFTR) and Na(+) influx via the epithelial Na(+) channel (ENaC). In cells expressing wt-CFTR, ambroxol increased the Cl(-) conductance, but not the bicarbonate conductance of the CFTR channels. We investigated whether treatment with ambroxol enhances chloride transport and/or CFTR and ENaC expression in CF airway epithelial cells (CFBE) cells. CFBE cells were treated with 100 µM ambroxol for 2, 4 or 8 h. mRNA expression for CFTR and ENaC subunits was analysed by real-time polymerase chain reaction (RT-PCR); protein expression was measured by Western blot. The effect of ambroxol on Cl(-) transport was measured by Cl(-) efflux measurements with a fluorescent chloride probe. Ambroxol significantly stimulated Cl(-) efflux from CFBE cells (a sixfold increase after 8 h treatment), and enhanced the expression of the mRNA of CFTR and α-ENaC, and of the CFTR protein. No significant difference was observed in ß-ENaC after exposure to ambroxol, whereas mRNA expression of γ-ENaC was reduced. No significant effects of ambroxol on the ENaC subunits were observed by Western blot. Ambroxol did not significantly affect the intracellular Ca(2+) concentration. Upregulation of CFTR and enhanced Cl(-) efflux after ambroxol treatment should promote transepithelial ion and water transport, which may improve hydration of the mucus, and therefore be beneficial to CF-patients.

The effect of NO-donors on chloride efflux, intracellular Ca(2+) concentration and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells.

Since previous studies showed that the endogenous bronchodilator, S-nitrosglutathione (GSNO), caused a marked increase in CFTR-mediated chloride (Cl(-)) efflux and improved the trafficking of CFTR to the plasma membrane, and that also the nitric oxide (NO)-donor GEA3162 had a similar, but smaller, effect on Cl(-) efflux, it was investigated whether the NO-donor properties of GSNO were relevant for its effect on Cl(-) efflux from airway epithelial cells. Hence, the effect of a number of other NO-donors, sodium nitroprusside (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), diethylenetriamine/nitric oxide adduct (DETA-NO), and diethylenetriamine/nitric oxide adduct (DEA-NONOate) on Cl(-) efflux from CFBE (∆F508/∆F508-CFTR) airway epithelial cells was tested. Cl(-) efflux was determined using the fluorescent N-(ethoxycarbonylmethyl)-6-methoxyquinoliniu bromide (MQAE)-technique. Possible changes in the intracellular Ca(2+) concentration were tested by the fluorescent fluo-4 method in a confocal microscope system. Like previously with GSNO, after 4 h incubation with the NO-donor, an increased Cl(-) efflux was found (in the order SNAP>DETA-NO>SNP). The effect of DEA-NONOate on Cl(-) efflux was not significant, and the compound may have (unspecific) deleterious effects on the cells. Again, as with GSNO, after a short (5 min) incubation, SNP had no significant effect on Cl(-) efflux. None of the NO-donors that had a significant effect on Cl(-) efflux caused significant changes in the intracellular Ca(2+) concentration. After 4 h preincubation, SNP caused a significant increase in the mRNA expression of CFTR. SNAP and DEA-NONOate decreased the mRNA expression of all ENaC subunits significantly. DETA-NO caused a significant decrease only in α-ENaC expression. After a short preincubation, none of the NO-donors had a significant effect, neither on the expression of CFTR, nor on that of the ENaC subunits in the presence and absence of L-cysteine. It can be concluded that the effect of GSNO on Cl(-) efflux is, at least in part, due to its properties as an NO-donor, and the effect is likely to be mediated by CFTR, not by Ca(2+)-activated Cl(-) channels.

Increased plasma norepinephrine concentration in psychotic depression.

OBJECTIVE: We previously found psychotic depression (PSDEP) to have positively correlating plasma norepinephrine (NE) and vasopressin (AVP) concentrations. Since central noradrenergic activity and plasma NE concentration are highly correlated, this suggests an increased noradrenergic activation of the hypothalamus-pituitary-adrenal axis. We hypothesize the increased release of NE in PSDEP to be an associated mechanism. METHODS: To test this hypothesis we analyzed the relation between plasma NE and PSDEP in a comparison with non-psychotically depressed patients. Potentially confounding variables were, among others, melancholia and two better validated subcategories in the field of melancholia and endogenous depression, three global dimensions of psychopathology - Emotional Dysregulation, Retardation and Anxiety - smoking habit, and different types of psychotropic and particularly antidepressant treatment. The data from nine patients with PSDEP and 69 patients with non-PSDEP were reanalysed. RESULTS: Analysis of covariance controlling for the effects of tricyclic antidepressant treatment (≥100 mg) and smoking habit showed that PSDEP had an increased concentration of plasma NE. The previously found correlation between plasma NE and AVP was still present after correcting for the effects of confounding variables. CONCLUSIONS: The results suggest an increased activity of the sympathetic nervous system in PSDEP that may act as a specific mechanism for increased vasopressinergic activation. This supports the view of PSDEP as a distinct subcategory of major depression.

The effect of S-nitrosoglutathione and L-cysteine on chloride efflux from cystic fibrosis airway epithelial cells.

The endogenous bronchodilator, S-nitrosoglutathione (GSNO), has been proposed as a possible pharmacological remedy that reverses the ΔF508-CFTR (cystic fibrosis transmembrane conductance regulator) maturation defect and increases CFTR-mediated chloride efflux in cultured cystic fibrosis airway epithelial cells (CFBE41o(-)). It has also been reported that L-cysteine enhanced S-nitrosothiol uptake and increased the intracellular S-nitrosothiol levels, likely through transnitrosation chemistry. The present study investigated whether L-cysteine augmented the effect of GSNO on chloride efflux from CF airway epithelial cells. Treatment with 10 µM GSNO combined with 20 µM L-cysteine resulted in increased chloride efflux from CFBE41o(-) cells after 5 minutes exposure compared to the control efflux rate and to the efflux rate in the presence of L-cysteine alone as measured using the fluorescent dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE). Chloride efflux rates from these cells after 4h exposure to GSNO and L-cysteine were not different from control. Treatment with 10 µM GSNO alone increased chloride efflux from CFBE41o(-) cells after 4h but not at shorter incubation times. GSNO with or without L-cysteine did not alter epithelial tight junction integrity. In conclusion, a combination of GSNO with L-cysteine led to significant increase in chloride efflux in CFBE41o(-) cells but the effect was transient and not sustained beyond minutes.

Evidence of vasopressinergic-noradrenergic mechanisms in depression with above-normal plasma vasopressin concentration with and without psychotic features.

Previous studies in the field of melancholic or endogenous depression have resulted in support for a subcategory of depression with above-normal plasma vasopressin (AVP) concentration (ANA). Since an analogous animal model with increased release of above-normal plasma vasopressin exhibits reduced Sympathetic-Nervous-System activity, the present study investigated the plasma norepinephrine concentration and the correlation between plasma norepinephrine and AVP in this ANA depression. As psychotic-melancholic patients may have increased plasma norepinephrine concentration, and noradrenergic activation may stimulate AVP release, potentially confounding effects of psychotic features were also investigated. The data set of the same depressed patient sample that was used before, but limited to those with complete hormonal data (n = 75), was re-analysed. ANA depression (n = 14) had negatively correlating AVP and norepinephrine concentrations. A very small subcategory of ANA depression with psychotic features (n = 3) had high plasma norepinephrine concentration, suggesting that this could be an independent subcategory. This was supported by the combination of relatively low above-normal plasma AVP concentrations with the highest severity scores for depression in this subcategory, which does not correspond with the positive correlation between AVP concentration and severity in non-psychotic ANA depression. The results further support the validity of ANA depression and the analogy with the High Anxiety Behaviour animal model of depression. Further investigations are needed to replicate these findings and to search for genetic and traumatic factors involved.

Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia.

The lantibiotic duramycin (Moli1901, Lancovutide) has been suggested as a drug of choice in the treatment for cystic fibrosis (CF). It has been proposed that duramycin may stimulate chloride secretion through Ca²(+) -activated Cl⁻ channels (CaCC). We investigated whether duramycin exhibited any effect on Cl⁻ efflux and intracellular Ca²(+) concentration ([Ca²(+)](i)) in CF and non-CF epithelial cells. Duramycin did stimulate Cl⁻ efflux from CF bronchial epithelial cells (CFBE) in a narrow concentration range (around 1 µM). However, 100 and 250 µM of duramycin inhibited Cl⁻ efflux from CFBE cells. An inhibitor of the CF transmembrane conductance regulator (CFTR(inh)₋172) and a blocker of the capacitative Ca²(+) entry, gadolinium chloride, inhibited the duramycin-induced Cl⁻ efflux. No effect on Cl⁻ efflux was observed in non-CF human bronchial epithelial cells (16HBE), human airway submucosal gland cell line, human pancreatic epithelial cells, CF airway submucosal gland epithelial cells, and CF pancreatic cells. The [Ca²(+)](i) was increased by 3 µM duramycin in 16HBE cells, but decreased after 1, and 3 µM of duramycin in CFBE cells. The results suggest that the mechanism responsible for the stimulation of Cl⁻ efflux by duramycin is mainly related to unspecific changes of the cell membrane or its components rather than to effects on CaCC.