Glutamine deficiency shifts the asthmatic state toward neutrophilic airway inflammation.

BACKGROUND: The administration of L-glutamine (Gln) suppresses allergic airway inflammation via the rapid upregulation of MAPK phosphatase (MKP)-1, which functions as a negative regulator of inflammation by deactivating p38 and JNK mitogen-activated protein kinases (MAPKs). However, the role of endogenous Gln remains to be elucidated. Therefore, we investigated the mechanism by which endogenous Gln regulates MKP-1 induction and allergic airway inflammation in an ovalbumin-based murine asthma model. METHODS: We depleted endogenous Gln levels using L-γ-glutamyl-p-nitroanilide (GPNA), an inhibitor of the Gln transporter ASCT2 and glutamine synthetase small interfering siRNA. Lentivirus expressing MKP-1 was injected to achieve overexpression of MKP-1. Asthmatic phenotypes were assessed using our previously developed ovalbumin-based murine model, which is suitable for examining sequential asthmatic events, including neutrophil infiltration. Gln levels were analyzed using a Gln assay kit. RESULTS: GPNA or glutamine synthetase siRNA successfully depleted endogenous Gln levels. Importantly, homeostatic MKP-1 induction did not occur at all, which resulted in prolonged p38 MAPK and cytosolic phospholipase A2 (cPLA2 ) phosphorylation in Gln-deficient mice. Gln deficiency augmented all examined asthmatic reactions, but it exhibited a strong bias toward increasing the neutrophil count, which was not observed in MKP-1-overexpressing lungs. This neutrophilia was inhibited by a cPLA2 inhibitor and a leukotriene B4 inhibitor but not by dexamethasone. CONCLUSION: Gln deficiency leads to the impairment of MKP-1 induction and activation of p38 MAPK and cPLA2 , resulting in the augmentation of neutrophilic, more so than eosinophilic, airway inflammation.

Family Avoidance of Communication about Cancer: A Dyadic Examination.

PURPOSE: This study aimed to examine the following questions: to what extent do patients and caregivers perceive their family members to be avoidant of communication regarding patient's cancer, and to what extent do these perceptions interrelate; and how do such perceptions influence their own and each other's communication behaviors, communication outcome, mental health, and quality of life. MATERIALS AND METHODS: A national survey was performed with 990 patient-caregiver dyads (participation rate, 76.2%). To examine the dyadic interaction, we developed linked patient and family member questionnaires, including the Family Avoidance of Communication about Cancer (FACC) scale. RESULTS: The mean scores (standard deviations) of patient- and caregiver-perceived FACC were low at 10.9 (15.5) and 15.5 (17.5), respectively (p < 0.001), and concordance was low, a well (Spearman's rho, 0.23). Patient-perceived FACC was associated with lower levels of disclosure and behaviors of holding back communication, as well as lower levels of mental health outcome and quality of life. The same was true for caregivers (all p < 0.05). Patient-perceived FACC was associated with caregiver holding back, caregiver's depression level, and caregiver quality of life (all p < 0.05). Both patient- and caregiver-perceived FACC were independently associated with communication difficulty within the family. CONCLUSION: Future research would benefit from the measurement of FACC from both patients and caregivers, and promote family intervention to enhance openness to communication, which would be helpful for improving mental health and quality of life for both patients and caregivers.

Declining hepatitis A antibody seroprevalence in the Korean military personnel.

We retrospectively analyzed serological test results for anti-hepatitis A virus immunoglobulin G (anti-HAV IgG) of sera collected from 779 military personnel during January 2001 to May 2008. The overall seroprevalence of anti-HAV IgG of the subjects was 17.5% (95% confidence interval [CI], 14.8-20.1%). When adjusted to the age-specific distribution of the army population, the age-adjusted seroprevalence was 14.6% (95% CI, 13.0-16.3%). All subjects who were 40 years and over had anti-HAV IgG. Meanwhile, the seroprevalence of anti-HAV IgG for those 24 years and younger was 4.7%. This low prevalence rate among young military personnel calls for stricter adherence to vaccination policies and stronger requirements for military HAV vaccination programs.

Facial wrinkles as a predictor of decreased renal function.

AIMS: Oxidative stress generated either by exogenous or endogenous sources can lead to progressive organ damage and skin ageing over a long period of time. Moreover, some dermatological signs are independent of chronological ageing, and may reflect the long-term redox state of internal organs. Therefore, we hypothesized that there might be an association between facial wrinkles and decreased renal function, an oxidative stress-related disease. METHODS: A cross-sectional study was carried out in a Korean population of 264 adults aged 30 years and older. Facial wrinkle scores in the crow's-foot area were estimated using a standardized form of visual assessment. As an index of renal function, we determined estimated glomerular filtration rate (eGFR). Lipid hydroperoxide (LPO) assay was performed to measure the levels of oxidative stress. RESULTS: After adjusting for possible confounders, lower eGFRs and higher LPO levels were found in those with severe facial wrinkles. CONCLUSION: We conclude that severe facial wrinkles might be used as a predictive marker of decreased renal function, independently of age, gender and other established risk factors.

[Mercuric chloride induces apoptosis in MDCK cells].

OBJECTIVES: Mercury is a hazardous organ-specific environmental contaminant. It exists in a wide variety of physical and chemical states, each of which has unique characteristics for the target organ specificity. Exposure to mercury vapor and to organic mercury compounds specifically affects the CNS, while the kidney is the target organ for inorganic Hg compounds. METHODS: In this study, mercury chloride (HgCl2) was studied in a renal derived cell system, i.e., the tubular epithelial Madin-Darby canine kidney (MDCK) cell line, which has specific sensitivity to the toxic effect of mercury. MDCK cells were cultured for 6-24 hr in vitro in various concentrations (0.1-100 M) of HgCl2, and the markers of apoptosis or cell death were assayed, including DNA fragmentation, caspase-3 activity andwestern blotting of cytochrome c. The influence of the metal on cell proliferation and viability were evaluated by the conventional MTT test. RESULTS: The cell viability was decreased in a time and concentration dependent fashion: decreases were noted at 6, 12 and 24 hr after HgCl2 exposure. The increases of DNA fragmentation were also observed in the concentrations from 0.1 to 10 M of HgCl2 at 6 hr after exposure. However, we could not observe DNA fragmentation in the concentrations more than 25 M because the cells rapidly proceeded to necrotic cell death. The activation of caspase-3 was also observed at 6 hr exposure in the HgCl2 concentrations from 0.1 to 10 M. The release of cytochrome c from the mitochondria into the cytosol, which is an initiator of the activation of the caspase cascade, was also observed in the HgCl2-treated MDCK cells. CONCLUSIONS: These results suggest that the activation of caspase-3 was involved in HgCl2-induced apoptosis. The release of cytochrome c from the mitochondria into the cytosol was also observed in the HgCl2-treated MDCK cells. These findings indicate that in MDCK cells, HgCl2 is a potent inducer of apoptosis via cytochrome c release from the mitochondria.