Renal epithelia can be provoked mechanically to release nucleotides, which subsequently increases the intracellular Ca(2+) concentration [Ca(2+)](i) through activation of purinergic (P2) receptors. Cultured cells often show spontaneous [Ca(2+)](i) oscillations, a feature suggested to involve nucleotide signalling. In this study, fluo-4 loaded Madin-Darby canine kidney (MDCK) cells are used as a model for quantification and characterisation of spontaneous [Ca(2+)](i) increases in renal epithelia. Spontaneous [Ca(2+)](i) increases occurred randomly as single cell events. During an observation period of 1 min, 10.9 +/- 6.7% (n = 23) of the cells showed spontaneous [Ca(2+)](i) increases. Spontaneous adenosine triphosphate (ATP) release from MDCK cells was detected directly by luciferin/luciferase. Scavenging of ATP by apyrase or hexokinase markedly reduced the [Ca(2+)](i) oscillatory activity, whereas inhibition of ecto-ATPases (ARL67156) enhanced the [Ca(2+)](i) oscillatory activity. The association between spontaneous [Ca(2+)](i) increases and nucleotide signalling was further tested in 132-1N1 cells lacking P2 receptors. These cells hardly showed any spontaneous [Ca(2+)](i) increases. Transfection with either hP2Y(6) or hP2Y(2) receptors revealed a striking degree of oscillations. Similar spontaneous [Ca(2+)](i) increases were observed in freshly isolated, perfused mouse medullary thick ascending limb (mTAL). The oscillatory activity was reduced by basolateral apyrase and substantially lower in mTAL from P2Y(2) knock out mice (0.050 +/- 0.020 events per second, n = 8) compared to the wild type (0.147 +/- 0.018 events per second, n = 9). These findings indicate that renal epithelia spontaneously release nucleotides leading to P2-receptor-dependent [Ca(2+)](i) oscillations. Thus, tonic nucleotide release is likely to modify steady state renal function.

Luminal P2 receptors are ubiquitously expressed in transporting epithelia. In steroid-sensitive epithelia (e.g., lung, distal nephron) epithelial Na(+) channel (ENaC)-mediated Na(+) absorption is inhibited via luminal P2 receptors. In distal mouse colon, we have identified that both, a luminal P2Y(2) and a luminal P2Y(4) receptor, stimulate K(+) secretion. In this study, we investigate the effect of luminal adenosine triphosphate/uridine triphosphate (ATP/UTP) on electrogenic Na(+) absorption in distal colonic mucosa of mice treated on a low Na(+) diet for more than 2 weeks. Transepithelial electrical parameters were recorded in an Ussing chamber. Baseline parameters: transepithelial voltage (V (te)): -13.7 +/- 1.9 mV (lumen negative), transepithelial resistance (R (te)): 24.1 +/- 1.8 Omega cm(2), equivalent short circuit current (I (sc)): -563.9 +/- 63.8 microA/cm(2) (n = 21). Amiloride completely inhibited I (sc) to -0.5 +/- 8.5 microA/cm(2). Luminal ATP induced a slowly on-setting and persistent inhibition of the amiloride-sensitive I (sc) by 160.7 +/- 29.7 microA/cm(2) (n = 12, NMRI mice). Luminal ATP and UTP were almost equipotent with IC(50) values of 10 microM and 3 microM respectively. In P2Y(2) knock-out (KO) mice, the effect of luminal UTP on amiloride-sensitve Na(+) absorption was absent. In contrast, in P2Y(4) KO mice the inhibitory effect of luminal UTP on Na(+) absorption remained present. Semiquantitative polymerase chain reaction did not indicate regulation of the P2Y receptors under low Na(+) diet, but it revealed a pronounced axial expression of both receptors with highest abundance in surface epithelia. Thus, luminal P2Y(2) and P2Y(4) receptors and ENaC channels co-localize in surface epithelium. Intriguingly, only the stimulation of the P2Y(2) receptor mediates inhibition of electrogenic Na(+) absorption.

BackgroundMental health (MH) problems have considerable personal and societal implications. Systematic MH screening may raise general practitioners’ (GP) awareness of the current need of treatment in their listed patients. The focus of MH screening has so far been on increasing diagnostic rates and treatment of mental disorders, whereas cessation of MH treatment after normal test results has rarely been studied. This study aims to examine the mental healthcare trajectories after MH screening combined with feedback on both positive and negative screening results to the GP.MethodsThis prospective cohort study is based on data from 11,714 randomly selected individuals aged 30–49 years, who were invited to a preventive health check in Denmark during 2012–2015. A total of 5970 (51%) were included. MH status was assessed using the SF-12 Health Survey Mental Component Summary score, and scores were categorised into poor, moderate, and good MH. ‘Mental healthcare’ within 1 year of follow-up covered the following MH support: psychometric testing by GP, talk therapy by GP, contact to psychologist, contact to psychiatrist, and psychotropic medication.ResultsMH was found to be poor in 9%, moderate in 25%, and good in 66% of participants. After 1 year, mental healthcare was initiated in 29% of the participants with poor MH who did not receive mental healthcare at baseline, and mental healthcare was ceased in 44% of the participants with good MH who received mental healthcare at baseline. Odds ratio (OR) for initiation of mental healthcare was associated with worse MH screening status: poor MH: OR 7.1 (5.4–9.4), moderate MH: OR 2.4 (1.9–3.1), compared to those with good MH. OR for cessation of mental healthcare was associated with better MH screening status: good MH: OR 1.6 (1.1–2.6), moderate MH: OR 1.6 (1.0–2.4), compared to those with poor MH. Initiation and cessation of mental healthcare appeared to be time-related to the MH screening.ConclusionsMH screening combined with feedback on both positive and negative screening results to the GP may contribute to relevant initiation and cessation of mental healthcare.Trial registrationRegistration of the Check Your Health-trial: ClinicalTrials.gov (NCT02028195), 7 March 2014.Electronic supplementary materialThe online version of this article (10.1186/s12875-018-0864-9) contains supplementary material, which is available to authorized users.

IntroductionPoor mental health is an important public health concern, but mental health problems are often under-recognised. Providing feedback to general practitioners (GPs) on their patients’ mental health status may improve the identification of cases in need of mental healthcare.ObjectivesTo investigate the extent of initiation of mental healthcare after identification of poor mental health and to identify factors associated with non-initiation.DesignProspective cohort study with 1-year follow-up.SettingIn a population-based health preventive programme, Check Your Health, we conducted a combined mental and physical health check in Randers Municipality, Denmark, in 2012–2015 in collaboration with local GPs.ParticipantsParticipants were 350 individuals aged 30–49 years old with screen-detected poor mental health who had not received mental healthcare within the past year. The cohort was derived from 14 167 randomly selected individuals of whom 52% (n=7348) participated. Mental health was assessed by the mental component summary score of the 12-item Short-Form Health Survey.OutcomeThe outcome was initiation of mental healthcare. Mental healthcare included psychometric testing by GP, talk therapy by GP, contact with a psychologist, contact with a psychiatrist and psychotropic medication.ResultsWithin 1 year, 22% (95% CI 18 to 27) of individuals with screen-detected poor mental health initiated mental healthcare. Among individuals who initiated mental healthcare within follow-up, one in six had visited their GP once or less in the preceding year. Male sex (OR: 0.49 (95% CI 0.28 to 0.86)) and less impaired mental health (OR: 0.93 (95% CI 0.89 to 0.98)) were associated with non-initiation of mental healthcare. We found no overall association between socioeconomic factors and initiating mental healthcare.ConclusionSystematic provision of mental health test results to GPs may improve the identification of cases in need of mental healthcare, but does not translate into initiation of mental healthcare. Further research should focus on methods to improve initiation of mental healthcare, especially among men.Trial registration numberNCT02028195.

Mental distress is an independent risk factor for illness related impairment. Awareness of mental health (MH) allows prevention, but early detection is not routinely performed in primary care. This cohort study incorporated MH assessment in a health promoting programme. We described the level of poor MH among health check participants, explored the potential for early intervention, and the potential for reducing social inequality in MH. The study was based on 9767 randomly selected citizens aged 30–49 years invited to a health check in Denmark in 2012–14. A total of 4871 (50%) were included; 49% were men. Poor MH was defined as a mental component summary score of ≤ 35.76 in the SF-12 Health Survey. Data was obtained from national health registers and health check. Participants with poor MH (9%) were more socioeconomic disadvantaged and had poorer health than those with better MH. Two thirds of men (64%) and half of women (50%) with poor MH had not received MH care one year before the health check. Among those with (presumably) unrecognized MH problems, the proportion of participants with disadvantaged socioeconomic characteristics was high (43–55%). Four out of five of those with apparently unacknowledged poor MH had seen their GP only once or not at all during the one year before the health check. In conclusion, MH assessment in health check may help identify yet undiscovered MH problems.