Exploring the role of moral injury outcomes in intimate relationship functioning among U.S. combat veterans.

OBJECTIVE: Moral injury entails psychological, social, and possible spiritual issues that might interfere with veterans' functioning in romantic or intimate relationships. To date, research has not examined the contribution of moral injury outcomes in this core functional domain in many veterans' lives. METHOD: In total, 65 combat veterans who were engaging in a peer-led intervention for moral injury in a Veteran Service Organization completed the Expressions of Moral Injury Scale, posttraumatic stress disorder (PTSD) checklist for DSM-5, and the romantic relationship subscale of the Inventory of Psychosocial Functioning Scale. RESULTS: Bivariate analyses revealed that moral injury and PTSD symptoms were each associated with worse relationship functioning among the veterans. When including moral injury and PTSD symptoms as predictors in a multivariate analysis, only moral injury was uniquely linked with poorer relationship functioning. CONCLUSIONS: Overall, these findings suggest that moral injury could play a pernicious role in many veterans' issues in relationship problems with their spouses or partners. Future research needs to examine the potential utility of addressing moral injury among veterans who are struggling to meet demands for intimacy and connection in their intimate or romantic relationships. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Papiloma Conjuntival: revisión bibliográfica / Conjunctival Papilloma: a literature review

Objetivo: El objetivo de la realización del presente artículo de revisión bibliográfica es analizar las características del Papiloma conjuntival como: el pronóstico, prevalencia, relación con el VPH, diagnóstico, tratamiento e importancia que representa la presencia del mismo. Métodos: El siguiente artículo se realizó mediante la búsqueda de artículos científicos en español e inglés, mismos que fueron obtenidos a través de base de datos como Scopus, PubMed y Google Academic. Se hizo usó de la plataforma virtual de la biblioteca católica de Cuenca utilizando comandos de búsqueda avanzada (""), AND, OR. Finalmente se incluyeron 15 artículos dentro de la revisión bibliográfica. Para el trabajo conjunto de los colaboradores se hizo uso de la plataforma Google Drive. Resultados: Papiloma conjuntival es un tumor de células escamosas benigno de la conjuntiva con una tendencia mínima a la malignidad. Estos tumores están relacionados con el VPH específicamente los tipos VI y XI. Para obtener un diagnóstico es importante realizar una anamnesis y un examen oftalmológico exhaustivo, una biopsia posterior a la extirpación de la lesión, la tomografía de coherencia óptica de alta definición (HR-OCT), y la biomicroscopia ultrasónica (UBM). El MSP, ha elaborado una iniciativa denominada "Programa Ampliado de Inmunizaciones (PAI)", mismo que consiste en el proceso de vacunación de la población femenina de 9, 10 y 11 años pertenecientes a escuelas públicas y privadas. Conclusiones: Es importante que las instituciones educativas fomenten más la salud ocular porque al momento de que existe un contagio de VPH hay riesgo de tener papiloma conjuntival y las personas desconocen este medio de transmisión. Además, se debe promover la vacunación en niños porque cualquier género es propenso a adquirir el VPH

Objective: The aim of this literature review article is to analyze the characteristics of: conjunctival papilloma such as prognosis, prevalence, relationship with HPV, diagnosis, treatment and importance of its presence. Methods: The following article was carried out by searching scientific articles in Spanish and English, which were obtained through databases such as Scopus, PubMed and Google Academic. We used the virtual platform of the Catholic Library of Cuenca using advanced search commands (""), AND, OR. Finally, 15 articles were included in the biliographic review. For the joint work of the collaborators, use was made of the Google Drive platform. Results: Conjunctival papilloma is a benign squamous cell tumor of the conjunctiva with a minimal tendency to malignancy. These tumors are related to HPV specifically types VI and XI. To obtain a diagnosis it is important to perform a thorough anamnesis and ophthalmologic examination, a biopsy after removal of the lesion, high-definition optical coherence tomography (HR-OCT), and ultrasonic biomicroscopy (UBM). The MSP has developed an initiative called "Expanded Program of Immunizations (PAI)", same that consists of the vaccination process of the female population of 9, 10 and 11 years old belonging to public and private schools. Conclusions: It is important that educational institutions promote more eye health because when there is an HPV infection there is a risk of having conjunctival papilloma and people are unaware of this means of transmission. In addition, vaccination should be promoted in children because any gender is prone to acquire HPV.

Examining the outcomes and acceptability of a peer-led spiritual intervention for moral injury in a veteran service organization.

The purpose of this proof-of-concept study was to examine the outcomes and acceptability of a spiritual intervention for moral injury led by veteran peers in a Veteran Service Organization (VSO), called "Heroes to Heroes." From baseline to 1-year follow-up, 101 veterans who participated in the intervention completed the evaluation surveys at four time points assessing psychological outcomes (moral injury, posttraumatic stress disorder [PTSD] symptoms, and life satisfaction), spiritual outcomes (spiritual struggles and spiritual transcendence), and their perceived helpfulness of the program. In addition, we conducted four focus groups with six to eight alumni to more fully understand veterans' views and experiences of the program. Focusing on the longitudinal surveys, latent growth modeling analyses revealed veterans generally improved across the psychological and spiritual outcomes in the study. Specifically, veterans reported steady decreases in moral injury outcomes, PTSD symptoms, and spiritual struggles along with increased life satisfaction and spiritual transcendence over the 1-year period. An inductive content analysis of veterans' responses to open-ended items in the surveys and focus group interviews revealed four possible mechanisms or facilitators of these outcomes: (a) social connectivity and belonging (e.g., shared vulnerability and camaraderie); (b) behavioral engagement in core aspects of their spirituality (e.g., sacred practices and visiting sacred places); (c) spiritual transformation and growth (e.g., closeness with God and divine forgiveness); and (d) appreciation for diversity (e.g., religious and military). Overall, these findings affirm the potential effectiveness and acceptability of the VSO's peer-led spiritual intervention for promoting the holistic healing among veterans who are contending with emotional and spiritual wounds of war. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Seroprevalence and risk factors associated with hepatitis C: a cross-sectional study of persons who inject drugs in Puerto Rico, 2018.

BACKGROUND: People Who Inject Drugs (PWID) are at a higher risk of acquiring bloodborne infections. We aimed to estimate the seroprevalence of the Hepatitis C Virus (HCV) in PWID and identify correlates and risk factors using data from the Puerto Rico National HIV Behavioral Surveillance System, PWID cycle 5, conducted in 2018. METHODS: A total of 502 San Juan Metropolitan Statistical Area participants were recruited through the Respondent Driven Sampling method. Sociodemographic, health-related, and behavioral characteristics were assessed. Testing for HCV antibodies was completed after the face-to-face survey. Descriptive and logistic regression analyses were performed. RESULTS: Overall seroprevalence of HCV was 76.5% (95% CI: 70.8-81.4%). A significantly (p < 0.05) higher HCV seroprevalence was observed among PWID with the following characteristics: heterosexuals (78.5%), high school graduates (81.3%), tested for sexually transmitted infections (STI) in the past 12 months (86.1%), frequent speedball injection (79.4%), and knowing the HCV serostatus of the last sharing partner (95.4%). Adjusted logistic regression models showed that having completed high school and reported STI testing in the past 12 months were significantly associated with HCV infection (ORa = 2.23; 95% CI: 1.06-4.69; ORa = 2.14; 95% CI: 1.06-4.30, respectively). CONCLUSIONS: We report a high seroprevalence of HCV infection in PWID. Social health disparities and potential missed opportunities validate the continuing call for local action for public health and prevention strategies.

Chaplain Training in Evidence-Based Practices to Promote Mental Health and Improve Care for Suicidality in Veterans and Service Members.

OBJECTIVE: Chaplains are key care providers in a comprehensive approach to suicide prevention, which is a priority area for the U.S. Department of Veterans Affairs (VA) and the Department of Defense (DoD). In a cohort of 87 VA and military chaplains who completed the Mental Health Integration for Chaplain Services (MHICS) training-an intensive, specialty education in evidence-based psychosocial and collaborative approaches to mental health care-we assessed chaplains' self-perceptions, intervention behaviors, and use of evidence-based practices, including Acceptance and Commitment Therapy (ACT), Problem-Solving Therapy (PST), and Motivational Interviewing (MI), in providing care for suicidality. METHOD: Chaplains responded to a battery of items Pre- and Post-training and provided deidentified case examples describing their use of evidence-based practices in spiritual care for service members and veterans (SM/V) on various levels of a suicide prevention continuum. RESULTS: Post-training, chaplains reported increased abilities to provide care and mobilize collaborative resources. Over the course of MHICS, 87% of chaplains used one or more evidence-based practices with a SM/V at risk for suicide or acutely suicidal. Fifty-six percent of chaplains reported intervening with an acutely suicidal SM/V by using principles from ACT, 36% PST, and 48% MI. With persons at risk for suicide, 81% used principles from ACT, 66% PST, and 71% MI. Cases exemplified diverse evidence-based practice applications. CONCLUSIONS: Findings indicate chaplains trained in evidence-based practices report effective application in caring for SM/V who are suicidal, thus offering a valuable resource to meet needs in a priority area for VA and DoD.HIGHLIGHTSChaplains provide essential care for SM/V who are at risk for suicide or acutely suicidalTraining helps chaplains mobilize interdisciplinary and community resources in suicide careEvidence-based practices can effectively integrate within the scope of chaplaincy practice for suicide care.

TNF-α Plus IL-1ß Induces Opposite Regulation of Cx43 Hemichannels and Gap Junctions in Mesangial Cells through a RhoA/ROCK-Dependent Pathway.

Connexin 43 (Cx43) is expressed in kidney tissue where it forms hemichannels and gap junction channels. However, the possible functional relationship between these membrane channels and their role in damaged renal cells remains unknown. Here, analysis of ethidium uptake and thiobarbituric acid reactive species revealed that treatment with TNF-α plus IL-1ß increases Cx43 hemichannel activity and oxidative stress in MES-13 cells (a cell line derived from mesangial cells), and in primary mesangial cells. The latter was also accompanied by a reduction in gap junctional communication, whereas Western blotting assays showed a progressive increase in phosphorylated MYPT (a target of RhoA/ROCK) and Cx43 upon TNF-α/IL-1ß treatment. Additionally, inhibition of RhoA/ROCK strongly antagonized the TNF-α/IL-1ß-induced activation of Cx43 hemichannels and reduction in gap junctional coupling. We propose that activation of Cx43 hemichannels and inhibition of cell-cell coupling during pro-inflammatory conditions could contribute to oxidative stress and damage of mesangial cells via the RhoA/ROCK pathway.

Excessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons.

Non-cell-autonomous mechanisms contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), in which astrocytes release unidentified factors that are toxic to motoneurons (MNs). We report here that mouse and patient iPSC-derived astrocytes with diverse ALS/FTD-linked mutations (SOD1, TARDBP, and C9ORF72) display elevated levels of intracellular inorganic polyphosphate (polyP), a ubiquitous, negatively charged biopolymer. PolyP levels are also increased in astrocyte-conditioned media (ACM) from ALS/FTD astrocytes. ACM-mediated MN death is prevented by degrading or neutralizing polyP in ALS/FTD astrocytes or ACM. Studies further reveal that postmortem familial and sporadic ALS spinal cord sections display enriched polyP staining signals and that ALS cerebrospinal fluid (CSF) exhibits increased polyP concentrations. Our in vitro results establish excessive astrocyte-derived polyP as a critical factor in non-cell-autonomous MN degeneration and a potential therapeutic target for ALS/FTD. The CSF data indicate that polyP might serve as a new biomarker for ALS/FTD.

Collaborative spiritual care for moral injury in the veterans Affairs Healthcare System (VA): Results from a national survey of VA chaplains.

The psychospiritual nature of moral injury invites consideration regarding how chaplains understand the construct and provide care. To identify how chaplains in the VA Healthcare System conceptualize moral injury, we conducted an anonymous online survey (N = 361; 45% response rate). Chaplains responded to a battery of items and provided free-text definitions of moral injury that generally aligned with key elements in the existing literature, though with different emphases. Over 90% of chaplain respondents indicated that they encounter moral injury in their chaplaincy care, and a similar proportion agreed that chaplains and mental health professionals should collaborate in providing care for moral injury. Over one-third of chaplain respondents reported offering or planning to offer a moral injury group. Separately, nearly one-quarter indicated present or planned collaboration with mental health to provide groups that in some manner address moral injury. Previous training in evidence-based and collaborative care approaches appears to contribute to the likelihood of providing integrated psychosocial-spiritual care. Results and future directions are discussed, including a description of moral injury that may be helpful to understand present areas of emphasis in VA chaplains' care for moral injury.

Cambios en la capacidad física y algunas variables fisiológicas en pacientes con insuficiencia cardiaca a las 6 y 12 semanas de un programa de rehabilitación cardiaca / Changes in physical capacity and some physiological variables in patients with cardiac insufficiency at 6 and 12 weeks of a cardiac rehabilitation program

Resumen Introducción: La insuficiencia cardiaca es un estado fisiopatológico y clínico en el cual el corazón es incapaz de aportar sangre de acuerdo con los requerimientos metabólicos periféricos, repercutiendo directamente sobre la capacidad aeróbica. La rehabilitación cardiaca durante 12 semanas tiene beneficios claros principalmente sobre la capacidad aeróbica, pero son pocos los estudios que detallan dichos cambios en el transcurso del proceso de intervención. Objetivo: Determinar los cambios en la capacidad aeróbica y algunas variables fisiológicas en pacientes con insuficiencia cardiaca, a las 6 y 12 semanas de su rehabilitación cardiaca. Método: Estudio de tipo descriptivo longitudinal. La muestra se constituyó por 23 pacientes vinculados a un programa de rehabilitación cardiaca, donde realizaron prueba de esfuerzo en tres momentos (inicio y semanas 6 y 12). Las variables cuantitativas se compararon en tres momentos utilizando la prueba de medidas repetidas hasta tres colas, teniendo en cuenta la homogeneidad y la igualdad de varianzas. La significación estadística fue de 0.05. Resultados: El consumo de oxígeno mostró un aumento de 3,6 ml/kg/min durante la rehabilitación, encontrando diferencias estadísticamente significativas en los tres momentos de medición, pero se evidenció un mayor incremento entre las semanas 1 y 6 (p = 0.00), cuando se registró un cambio de 2,2 ml/kg/min. La medición de la presión arterial sistólica/diastólica inicial y final mostró una disminución (p < 0.05). Conclusiones: En pacientes con insuficiencia cardiaca, el consumo de oxígeno obtuvo un incremento progresivo a lo largo de las 12 semanas de rehabilitación cardiaca, observándose su mayor incremento en las primeras 6 semanas de intervención.

Abstract Introduction: Heart failure is a pathological and clinical state in which the heart is unable to provide blood according to peripheral metabolic requirements having a direct impact on aerobic capacity. Cardiac rehabilitation for 12 weeks has clear benefits mainly on aerobic capacity, but few studies detail such changes over the course of the intervention process. Objective: To determine changes in aerobic capacity and some physiological variables in patients with cardiac insufficiency, at 6 and 12 weeks after cardiac rehabilitation. Method: Longitudinal descriptive type study. The sample was made up of 23 patients linked to a cardiac rehabilitation program, where they performed stress testing at three times (start, weeks 6 and 12). Quantitative variables were compared in 3 moments using the repeated measurement test up to 3 tails, taking into account the homogeneity and equality of variances. The statistical significance was 0.05. Results: Oxygen consumption showed an increase of 3.6 ml/kg/min during rehabilitation, finding statistically significant differences in the three measurement moments but there was a greater increase between week 1 and 6 (p = 0.00) where a change of 2.2 ml/kg/min was recorded. Measurement of initial and final systolic/diastolic blood pressure showed a decrease (p < 0.05). Conclusions: In patients with heart failure, oxygen consumption achieved a progressive increase over 12 weeks of cardiac rehabilitation, with its largest increase seen in the first 6 weeks of intervention.

A physiologic rise in cytoplasmic calcium ion signal increases pannexin1 channel activity via a C-terminus phosphorylation by CaMKII.

Pannexin1 (Panx1) channels are ubiquitously expressed in vertebrate cells and are widely accepted as adenosine triphosphate (ATP)-releasing membrane channels. Activation of Panx1 has been associated with phosphorylation in a specific tyrosine residue or cleavage of its C-terminal domains. In the present work, we identified a residue (S394) as a putative phosphorylation site by Ca2+/calmodulin-dependent kinase II (CaMKII). In HeLa cells transfected with rat Panx1 (rPanx1), membrane stretch (MS)-induced activation-measured by changes in DAPI uptake rate-was drastically reduced by either knockdown of Piezo1 or pharmacological inhibition of calmodulin or CaMKII. By site-directed mutagenesis we generated rPanx1S394A-EGFP (enhanced green fluorescent protein), which lost its sensitivity to MS, and rPanx1S394D-EGFP, mimicking phosphorylation, which shows high DAPI uptake rate without MS stimulation or cleavage of the C terminus. Using whole-cell patch-clamp and outside-out excised patch configurations, we found that rPanx1-EGFP and rPanx1S394D-EGFP channels showed current at all voltages between ±100 mV, similar single channel currents with outward rectification, and unitary conductance (∼30 to 70 pS). However, using cell-attached configuration we found that rPanx1S394D-EGFP channels show increased spontaneous unitary events independent of MS stimulation. In silico studies revealed that phosphorylation of S394 caused conformational changes in the selectivity filter and increased the average volume of lateral tunnels, allowing ATP to be released via these conduits and DAPI uptake directly from the channel mouth to the cytoplasmic space. These results could explain one possible mechanism for activation of rPanx1 upon increase in cytoplasmic Ca2+ signal elicited by diverse physiological conditions in which the C-terminal domain is not cleaved.

Long-term effects of stress resilience: Hippocampal neuroinflammation and behavioral approach in male rats.

Resilience to stress is the ability to quickly adapt to adversity. There is evidence that exposure to prolonged stress triggers neuroinflammation what produces individual differences in stress vulnerability. However, the relationship between stress resilience, neuroinflammation, and depressive-like behaviors remains unknown. The aim of this study was to analyze the long-term effects of social defeat stress (SDS) on neuroinflammation in the hippocampus and depressive-like behaviors. Male rats were subjected to the SDS paradigm. Social interaction was analyzed 1 and 2 weeks after ending the SDS to determine which animals were susceptible or resilient to stress. Neuroinflammation markers glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and elevated membrane permeability in astrocytes and microglia, as well as depressive-like behaviors in the sucrose preference test and forced swim test were evaluated in all rats. One week after SDS, resilient rats increased their sucrose preference, and time spent in the floating behavior decreased in the forced swim test compared to susceptible rats. Surprisingly, resilient rats became susceptible to stress, and presented neuroinflammation 2 weeks after SDS. These findings suggest that SDS-induced hippocampal neuroinflammation persists in post-stress stages, regardless of whether rats were initially resilient or not. Our study opens a new approach to understanding the neurobiology of stress resilience.

The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway.

In the adult hypothalamus, the neuronal precursor role is attributed to the radial glia-like cells that line the third-ventricle (3V) wall called tanycytes. Under nutritional cues, including hypercaloric diets, tanycytes proliferate and differentiate into mature neurons that moderate body weight, suggesting that hypothalamic neurogenesis is an adaptive mechanism in response to metabolic changes. Previous studies have shown that the tanycyte glucosensing mechanism depends on connexin-43 hemichannels (Cx43 HCs), purine release, and increased intracellular free calcium ion concentration [(Ca2+ )i ] mediated by purinergic P2Y receptors. Since, Fibroblast Growth Factor 2 (FGF2) causes similar purinergic events in other cell types, we hypothesize that this pathway can be also activated by FGF2 in tanycytes to promote their proliferation. Here, we used bromodeoxyuridine (BrdU) incorporation to evaluate if FGF2-induced tanycyte cell division is sensitive to Cx43 HC inhibition in vitro and in vivo. Immunocytochemical analyses showed that cultured tanycytes maintain the expression of in situ markers. After FGF2 exposure, tanycytic Cx43 HCs opened, enabling release of ATP to the extracellular milieu. Moreover, application of external ATP was enough to induce their cell division, which could be suppressed by Cx43 HC or P2Y1-receptor inhibitors. Similarly, in vivo experiments performed on rats by continuous infusion of FGF2 and a Cx43 HC inhibitor into the 3V, demonstrated that FGF2-induced ß-tanycyte proliferation is sensitive to Cx43 HC blockade. Thus, FGF2 induced Cx43 HC opening, triggered purinergic signaling, and increased ß-tanycytes proliferation, highlighting some of the molecular mechanisms involved in the cell division response of tanycyte. This article has an Editorial Highlight see https://doi.org/10.1111/jnc.15218.

Stretch-Induced Activation of Pannexin 1 Channels Can Be Prevented by PKA-Dependent Phosphorylation.

Pannexin 1 channels located in the cell membrane are permeable to ions, metabolites, and signaling molecules. While the activity of these channels is known to be modulated by phosphorylation on T198, T308, and S206, the possible involvement of other putative phosphorylation sites remains unknown. Here, we describe that the activity of Panx1 channels induced by mechanical stretch is reduced by adenosine via a PKA-dependent pathway. The mechanical stretch-induced activity-measured by changes in DAPI uptake-of Panx1 channels expressed in HeLa cell transfectants was inhibited by adenosine or cAMP analogs that permeate the cell membrane. Moreover, inhibition of PKA but not PKC, p38 MAPK, Akt, or PKG prevented the effects of cAMP analogs, suggesting the involvement of Panx1 phosphorylation by PKA. Accordingly, alanine substitution of T302 or S328, two putative PKA phosphorylation sites, prevented the inhibitory effect of cAMP analogs. Moreover, phosphomimetic mutation of either T302 or S328 to aspartate prevented the mechanical stretch-induced activation of Panx1 channels. A molecular dynamics simulation revealed that T302 and S328 are located in the water-lipid interphase near the lateral tunnel of the intracellular region, suggesting that their phosphorylation could promote conformational changes in lateral tunnels. Thus, Panx1 phosphorylation via PKA could be modulated by G protein-coupled receptors associated with the Gs subunit.

Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation.

Denervation of skeletal muscles induces severe muscle atrophy, which is preceded by cellular alterations such as increased plasma membrane permeability, reduced resting membrane potential and accelerated protein catabolism. The factors that induce these changes remain unknown. Conversely, functional recovery following denervation depends on successful reinnervation. Here, we show that activation of nicotinic acetylcholine receptors (nAChRs) by quantal release of acetylcholine (ACh) from motoneurons is sufficient to prevent changes induced by denervation. Using in vitro assays, ACh and non-hydrolysable ACh analogs repressed the expression of connexin43 and connexin45 hemichannels, which promote muscle atrophy. In co-culture studies, connexin43/45 hemichannel knockout or knockdown increased innervation of muscle fibers by dorsal root ganglion neurons. Our results show that ACh released by motoneurons exerts a hitherto unknown function independent of myofiber contraction. nAChRs and connexin hemichannels are potential molecular targets for therapeutic intervention in a variety of pathological conditions with reduced synaptic neuromuscular transmission.

Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity Reactions.

Mast cells (MCs) release pro-inflammatory mediators through a process called degranulation response. The latter may be induced by several conditions, including antigen recognition through immunoglobulin E (IgE) or "cross-linking," classically associated with Type I hypersensitivity reactions. Early in this reaction, Ca2+ influx and subsequent increase of intracellular free Ca2+ concentration are essential for MC degranulation. Several membrane channels that mediate Ca2+ influx have been proposed, but their role remains elusive. Here, we evaluated the possible contribution of pannexin-1 channels (Panx1 Chs), well-known as ATP-releasing channels, in the increase of intracellular Ca2+ triggered during cross-linking reaction of MCs. The contribution of Panx1 Chs in the degranulation response was evaluated in MCs from wild type (WT) and Panx1 knock out (Panx1-/-) mice after anti-ovalbumin (OVA) IgE sensitization. Notably, the degranulation response (toluidine blue and histamine release) was absent in Panx1-/- MCs. Moreover, WT MCs showed a rapid and transient increase in Ca2+ signal followed by a sustained increase after antigen stimulation. However, the sustained increase in Ca2+ signal triggered by OVA was absent in Panx1-/- MCs. Furthermore, OVA stimulation increased the membrane permeability assessed by dye uptake, a prevented response by Panx1 Ch but not by connexin hemichannel blockers and without effect on Panx1-/- MCs. Interestingly, the increase in membrane permeability of WT MCs was also prevented by suramin, a P2 purinergic inhibitor, suggesting that Panx1 Chs act as ATP-releasing channels impermeable to Ca2+. Accordingly, stimulation with exogenous ATP restored the degranulation response and sustained increase in Ca2+ signal of OVA stimulated Panx1-/- MCs. Moreover, opening of Panx1 Chs in Panx1 transfected HeLa cells increased dye uptake and ATP release but did not promote Ca2+ influx, confirming that Panx1 Chs permeable to ATP are not permeable to Ca2+. These data strongly suggest that during antigen recognition, Panx1 Chs contribute to the sustained Ca2+ signal increase via release of ATP that activates P2 receptors, playing a critical role in the sequential events that leads to degranulation response during Type I hypersensitivity reactions.

Angiotensin II-Induced Mesangial Cell Damaged Is Preceded by Cell Membrane Permeabilization Due to Upregulation of Non-Selective Channels.

Connexin43 (Cx43), pannexin1 (Panx1) and P2X7 receptor (P2X7R) are expressed in kidneys and are known to constitute a feedforward mechanism leading to inflammation in other tissues. However, the possible functional relationship between these membrane channels and their role in damaged renal cells remain unknown. In the present work, we found that MES-13 cells, from a cell line derived from mesangial cells, stimulated with angiotensin II (AngII) developed oxidative stress (OS, thiobarbituric acid reactive species (TBARS) and generated pro-inflammatory cytokines (ELISA; IL-1ß and TNF-α). The membrane permeability increased progressively several hours before the latter outcome, which was a response prevented by Losartan, indicating the involvement of AT1 receptors. Western blot analysis showed that the amount of phosphorylated MYPT (a substrate of RhoA/ROCK) and Cx43 increased progressively and in parallel in cells treated with AngII, a response followed by an increase in the amount in Panx1 and P2X7R. Greater membrane permeability was partially explained by opening of Cx43 hemichannels (Cx43 HCs) and Panx1 channels (Panx1 Chs), as well as P2X7Rs activation by extracellular ATP, which was presumably released via Cx HCs and Panx1 Chs. Additionally, inhibition of RhoA/ROCK blocked the progressive increase in membrane permeability, and the remaining response was explained by the other non-selective channels. The rise of activity in the RhoA/ROCK-dependent pathway, as well as in Cx HCs, P2X7R, and to a minor extent in Panx1 Chs led to higher amounts of TBARS and pro-inflammatory cytokines. We propose that AngII-induced mesangial cell damage could be effectively inhibited by concomitantly inhibiting the RhoA/ROCK-dependent pathway and one or more non-selective channel(s) activated through this pathway.

Inhibition of glial hemichannels by boldine treatment reduces neuronal suffering in a murine model of Alzheimer's disease.

The contribution of reactive gliosis to the pathological phenotype of Alzheimer's disease (AD) opened the way for therapeutic strategies targeting glial cells instead of neurons. In such context, connexin hemichannels were proposed recently as potential targets since neuronal suffering is alleviated when connexin expression is genetically suppressed in astrocytes of a murine model of AD. Here, we show that boldine, an alkaloid from the boldo tree, inhibited hemichannel activity in astrocytes and microglia without affecting gap junctional communication in culture and acute hippocampal slices. Long-term oral administration of boldine in AD mice prevented the increase in glial hemichannel activity, astrocytic Ca2+ signal, ATP and glutamate release and alleviated hippocampal neuronal suffering. These findings highlight the important pathological role of hemichannels in AD mice. The neuroprotective effect of boldine treatment might provide the basis for future pharmacological strategies that target glial hemichannels to reduce neuronal damage in neurodegenerative diseases.

Invaginación colocolónica en adulto por pólipo adenomatoso: una causa excepcional de una entidad poco frecuente / Adult colocolonic intussusception due to adenomatous polyp: An exceptional cause of a rare entity

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Neural progenitor cells isolated from the subventricular zone present hemichannel activity and form functional gap junctions with glial cells.

The postnatal subventricular zone (SVZ) lining the walls of the lateral ventricles contains neural progenitor cells (NPCs) that generate new olfactory bulb interneurons. Communication via gap junctions between cells in the SVZ is involved in NPC proliferation and in neuroblast migration towards the olfactory bulb. SVZ NPCs can be expanded in vitro in the form of neurospheres that can be used for transplantation purposes after brain injury. We have previously reported that neurosphere-derived NPCs form heterocellular gap junctions with host glial cells when they are implanted after mechanical injury. To analyze functionality of NPC-glial cell gap junctions we performed dye coupling experiments in co-cultures of SVZ NPCs with astrocytes or microglia. Neurosphere-derived cells expressed mRNA for at least the hemichannel/gap junction channel proteins connexin 26 (Cx26), Cx43, Cx45 and pannexin 1 (Panx1). Dye coupling experiments revealed that gap junctional communication occurred among neurosphere cells (incidence of coupling: 100%). Moreover, hemichannel activity was also detected in neurosphere cells as evaluated in time-lapse measurements of ethidium bromide uptake. Heterocellular coupling between NPCs and glial cells was evidenced in co-cultures of neurospheres with astrocytes (incidence of coupling: 91.0 ± 4.7%) or with microglia (incidence of coupling: 71.9 ± 6.7%). Dye coupling in neurospheres and in co-cultures was inhibited by octanol, a gap junction blocker. Altogether, these results suggest the existence of functional hemichannels and gap junction channels in postnatal SVZ neurospheres. In addition, they demonstrate that SVZ-derived NPCs can establish functional gap junctions with astrocytes or microglia. Therefore, cell-cell communication via gap junctions and hemichannels with host glial cells might subserve a role in the functional integration of NPCs after implantation in the damaged brain.