Macropinocytosis of Extracellular Glutathione Ameliorates Tumor Necrosis Factor α Release in Activated Macrophages

A number of inflammatory lung diseases have abnormally low glutathione (GSH) levels in the airway fluids. Lung macrophages are common mediators of inflammation, make up the majority of cells that are found in the airway epithelial lining fluid (ELF), and are commonly elevated in many lung diseases. Several animal models with altered ELF GSH levels are associated with similar alterations in the intracellular GSH levels of bronchoalveolar lavage (BAL) cells. The possible mechanisms and outcomes for this association between ELF GSH levels and intracellular BAL cell GSH are unknown. To investigate these issues, macrophages were grown in media supplemented with 500 µM GSH. GSH supplementation resulted in a 2–3 fold increase in macrophage intracellular GSH levels. The increase in macrophage intracellular GSH levels was associated with a significant reduction in NF-κB nuclear translocation and tumor necrosis factor α (TNFα) release upon LPS stimulation. Furthermore, co-treatment of macrophages with GSH and inhibitors of GSH breakdown or synthesis did not block GSH accumulation. In contrast, treatment with cytochalasin D, an inhibitor of actin dependent endocytosis, and amiloride, an inhibitor of macropinocytosis blocked, at least in part, GSH uptake. Furthermore, using two cigarette smoke exposure paradigms that result in two different GSH levels in the ELF and thus in the BAL cells resulted in modulation of cytokine release when stimulated with LPS ex vivo. These data suggest that macrophages are able to utilize extracellular GSH which can then modulate inflammatory signaling in response to proinflammatory stimuli. This data also suggests the lung can modulate inflammatory responses triggered by proinflammatory stimuli by altering ELF GSH levels and may help explain the dysregulated inflammation associated with lung diseases that have low ELF GSH levels

Strategi Komunikasi dalam Mempertahankan Hubungan Pacaran dengan Perbedaan Agama

Strategi komunikasi dalam menjalani pacaran beda agama memang sangat diperlukan, mengingat tingkat toleransi yang diberikan kepada pasangan jauh lebih besar daripada pacaran seiman. Didukung pula oleh ‘equity theory\u27 atau teori keseimbangan, bahwa dalam hubungan sangat diperlukan adanya keseimbangan agar hubungan tersebut dapat bertahan. Keseimbangan disini tidak selalu berupa materi, tetapi dapat juga berupa perhatian, pengorbanan, dan pembagian tugas dalam hubungan. Jika keseimbangan tidak tercapai, maka keutuhan hubungan tersebut akan terancam (DeVito, 2007 p.244). Strategi komunikasi kemudian menjadi topik yang menarik, bagaimana mahasiswa Univeristas Katolik Widya Mandala Surabaya dalam mempertahankan hubungan pacaran mereka yang beda agama. Penelitian ini dilakukan dengan wawancara mendalam kepada narasumber berdasarkan pada tujuh strategi komunikasi yang disampaikan oleh DeVito dalam bukunya yang berjudul ‘The Interpersonal Communication Book,\u27 yaitu be nice, communicate, be open, give assurance, share joint activities, be positive, dan focus on improving yourself. Ketujuh strategi komunikasi antarpersonal tersebut akan diaplikasikan pada pola komunikasi antarpersonal mahasiswa Universitas Katolik Widya Mandala Surabaya dalam mempertahankan hubungan pacaran beda agama

Hypertonic saline increases lung epithelial lining fluid glutathione and thiocyanate: two protective CFTR-dependent thiols against oxidative injury

<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis is a debilitating lung disease due to mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) and is associated with chronic infections resulting in elevated myeloperoxidase activity and generation of hypochlorous acid (HOCl). CFTR mutations lead to decreased levels of glutathione (GSH) and thiocyanate (SCN) in the epithelial lining fluid (ELF). Hypertonic saline is used to improve lung function however the mechanism is uncertain.</p> <p>Methods</p> <p>In the present study, the effect of GSH and SCN on HOCl-mediated cell injury and their changes in the ELF after hypertonic saline nebulization in wild type (WT) and CFTR KO mice was examined. CFTR sufficient and deficient lung cells were assessed for GSH, SCN and corresponding sensitivity towards HOCl-mediated injury, in vitro.</p> <p>Results</p> <p>CFTR (-) cells had lower extracellular levels of both GSH and SCN and were more sensitive to HOCl-mediated injury. In vivo, hypertonic saline increased ELF GSH in the WT and to a lesser extent in the CFTR KO mice but only SCN in the WT ELF. Finally, potential protective effects of GSH and SCN at concentrations found in the ELF against HOCl toxicity were examined in vitro.</p> <p>Conclusions</p> <p>While the concentrations of GSH and SCN associated with the WT ELF protect against HOCl toxicity, those found in the CFTR KO mice were less sufficient to inhibit cell injury. These data suggests that CFTR has important roles in exporting GSH and SCN which are protective against oxidants and that hypertonic saline treatment may have beneficial effects by increasing their levels in the lung.</p

Strategi Komunikasi dalam Mempertahankan Hubungan Pacaran dengan Perbedaan Agama

Strategi komunikasi dalam menjalani pacaran beda agama memang sangat diperlukan, mengingat tingkat toleransi yang diberikan kepada pasangan jauh lebih besar daripada pacaran seiman. Didukung pula oleh ‘equity theory’ atau teori keseimbangan, bahwa dalam hubungan sangat diperlukan adanya keseimbangan agar hubungan tersebut dapat bertahan. Keseimbangan disini tidak selalu berupa materi, tetapi dapat juga berupa perhatian, pengorbanan, dan pembagian tugas dalam hubungan. Jika keseimbangan tidak tercapai, maka keutuhan hubungan tersebut akan terancam (DeVito, 2007 p.244). Strategi komunikasi kemudian menjadi topik yang menarik, bagaimana mahasiswa Univeristas Katolik Widya Mandala Surabaya dalam mempertahankan hubungan pacaran mereka yang beda agama. Penelitian ini dilakukan dengan wawancara mendalam kepada narasumber berdasarkan pada tujuh strategi komunikasi yang disampaikan oleh DeVito dalam bukunya yang berjudul ‘The Interpersonal Communication Book,’ yaitu be nice, communicate, be open, give assurance, share joint activities, be positive, dan focus on improving yourself. Ketujuh strategi komunikasi antarpersonal tersebut akan diaplikasikan pada pola komunikasi antarpersonal mahasiswa Universitas Katolik Widya Mandala Surabaya dalam mempertahankan hubungan pacaran beda agama

Infant Hedonic/Anhedonic Processing Index (HAPI-Infant): Assessing Infant Anhedonia and Its Prospective Association with Adolescent Depressive Symptoms

Background Anhedonia, an impairment in the motivation for or experience of pleasure, is a well-established transdiagnostic harbinger and core symptom of mental illness. Given increasing recognition of early life origins of mental illness, we posit that anhedonia should, and could, be recognized earlier if appropriate tools were available. However, reliable diagnostic instruments prior to childhood do not currently exist. Methods We developed an assessment instrument for anhedonia/reward processing in infancy, the Infant Hedonic/Anhedonic Processing Index (HAPI-Infant). Exploratory factor and psychometric analyses were conducted using data from 6- and 12-month-old infants from two cohorts (N = 188, N = 212). Then, associations were assessed between infant anhedonia and adolescent self-report of depressive symptoms. Results The HAPI-Infant (47-items), exhibited excellent psychometric properties. Higher anhedonia scores at 6 (r = 0.23, p \u3c .01) and 12 months (r = 0.19, p \u3c .05) predicted elevated adolescent depressive symptoms, and these associations were stronger than for established infant risk indicators such as negative affectivity. Subsequent analyses supported the validity of short (27-item) and very short (12-item) versions of this measure. Limitations The primary limitations of this study are that the HAPI-Infant awaits additional tests of generalizability and of its ability to predict clinical diagnosis of depression. Conclusions The HAPI-Infant is a novel, psychometrically strong diagnostic tool suitable for recognizing anhedonia during the first year of life with strong predictive value for later depressive symptoms. In view of the emerging recognition of increasing prevalence of affective disorders in children and adolescents, the importance of the HAPI-Infant in diagnosing anhedonia is encouraging. Early recognition of anhedonia could target high-risk individuals for intervention and perhaps prevention of mental health disorders

Experiences of COVID-19-Related Racism and Impact on Depression Trajectories Among Racially/Ethnically Minoritized Adolescents

Purpose In 2020, racially/ethnically minoritized (REMD) youth faced the “dual pandemics” of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic). Methods A community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean age = 16, standard deviation = 2.7, and identified as Latinx/Hispanic (48%), Multiethnic (34%), Asian American (12%), and Black (6%). Results REMD adolescents\u27 depressive symptoms were elevated during the COVID-19 pandemic compared to pre-pandemic levels, and increases were more pronounced over time for those who endorsed exposure to COVID-19-era-related racism. In general, Asian American participants endorsed racism experiences at the highest rates compared to others, including being called names (42%), people acting suspicious around them (33%), and being verbally threatened (17%). Additionally, more than half of Black and Asian American participants reported worry about experiencing racism related to the COVID-19 pandemic, even if they had not experienced it to date. Discussion REMD adolescents are at increased risk for depressive symptoms related to converging stressors stemming from the COVID-19 pandemic and pandemic-related racism, which has the potential to widen racial/ethnic mental health disparities faced by the REMD youth

Measuring Novel Antecedents of Mental Illness: The Questionnaire of Unpredictability in Childhood

Increasing evidence indicates that, in addition to poverty, maternal depression, and other well-established factors, unpredictability of maternal and environmental signals early in life influences trajectories of brain development, determining risk for subsequent mental illness. However, whereas most risk factors for later vulnerability to mental illness are readily measured using existing, clinically available tools, there are no similar measures for assessing early-life unpredictability. Here we validate the Questionnaire of Unpredictability in Childhood (QUIC) and examine its associations with mental health in the context of other indicators of childhood adversity (e.g., traumatic life events, socioeconomic status, and parenting quality). The QUIC was initially validated through administration to a cohort of adult females (N = 116) and then further refined in two additional independent cohorts (male Veterans, N = 95, and male and female adolescents, N = 175). The QUIC demonstrated excellent internal (α = 0.89) and test–retest reliability (r = 92). Scores on the QUIC were positively correlated with other prospective indicators of exposures to unpredictable maternal inputs in infancy and childhood (unpredictable maternal mood and sensory signals), and accuracy of recall also was confirmed with prospective data. Importantly, the QUIC predicted symptoms of anxiety, depression, and anhedonia in the three study cohorts, and these effects persisted after adjusting for other previously established risk factors. The QUIC, a reliable and valid self-report assessment of exposure to unpredictability in the social, emotional, and physical domains during early life, is a brief, comprehensive, and promising instrument for predicting risk for mental illness