Expression of uteroglobin in a murine model of allergic rhinitis

CONCLUSION: We observed for the first time the expression of Uteroglobin (UGB) in the nasal mucosa of mice. The results of our study suggest that UGB may play an important role in the regulation of inflammation in allergic rhinitis (AR) as well as in the lower airway allergic inflammations. OBJECTIVES: Uteroglobin is a protein secreted by epithelial lining of organs communicating with the external environment. Reports of its immunomodulatory effects in allergic disease have been made, but the true physiological role still remains to be elucidated. In this study we tried to observe the expression of UGB in the nasal mucosa of mice and determine its role in AR. MATERIALS AND METHODS: Thirty BALB-c mice at 3 weeks of age (10 mice/group) were sensitized systemically by intraperitoneal ovalbumin injection and locally by ovalbumin inhalation. Control group were sensitized with PBS. Treatment group had intraperitoneal dexamethasone injection 1 hour before the initial sensitization while control and AR group were injected with PBS. Symptom scores, eosinophil counts, immunohistochemical staining as well as UGB mRNA expression in the nasal mucosa and lung tissue were analyzed. RESULTS: The symptom scores and eosinophil counts between control and treatment group was significantly different from the AR group (P<0.01). On immunohistochemical staining, UGB was localized in the epithelium and submucosal gland of the nasal mucosa as well as in the epithelium of respiratory bronchioles. UGB mRNA expression of the nasal mucosa and lung tissue was decreased in the AR group compared to the control group (P=0.022). In the treatment group UGB expression was increased compared to the AR group (P=0.016). The results of IHC and mRNA expression in the lung tissue correlated with the results in the nasal mucosa.     

Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation

Connexin 43 (Cx43) mediates osteocyte communication with other cells and with the extracellular milieu and regulates osteoblastic cell signaling and gene expression. We now report that mice lacking Cx43 in osteoblasts/osteocytes or only in osteocytes (Cx43(ΔOt) mice) exhibit increased osteocyte apoptosis, endocortical resorption, and periosteal bone formation, resulting in higher marrow cavity and total tissue areas measured at the femoral mid-diaphysis. Blockade of resorption reversed the increased marrow cavity but not total tissue area, demonstrating that endocortical resorption and periosteal apposition are independently regulated. Anatomical mapping of apoptotic osteocytes, osteocytic protein expression, and resorption and formation suggests that Cx43 controls osteoclast and osteoblast activity by regulating osteoprotegerin and sclerostin levels, respectively, in osteocytes located in specific areas of the cortex. Whereas empty lacunae and living osteocytes lacking osteoprotegerin were distributed throughout cortical bone in Cx43(ΔOt) mice, apoptotic osteocytes were preferentially located in areas containing osteoclasts, suggesting that osteoclast recruitment requires active signaling from dying osteocytes. Furthermore, Cx43 deletion in cultured osteocytic cells resulted in increased apoptosis and decreased osteoprotegerin expression. Thus, Cx43 is essential in a cell-autonomous fashion in vivo and in vitro for osteocyte survival and for controlling the expression of osteocytic genes that affect osteoclast and osteoblast function.     

Histological and immunological features of non-eosinophilic nasal polyps

OBJECTIVE: The aim of this study was to investigate the histoimmunological features of non-eosinophilic nasal polyps (NPs). METHODS: Thirty patients with chronic rhinosinusitis and NPs were included in this study. NPs were grouped into eosinophilic and non-eosinophilic types according to the amount of eosinophils in the NPs. The amount of serum total IgE and peripheral blood eosinophils were measured. Basement membrane (BM) thickness was measured, along with the expression of chemokine receptor 5 (CCR5) and chemokine receptor 3 (CCR3) in NP lymphocytes. RESULTS: Non-eosinophilic NPs comprised 66.7% of the total NPs included in this study. The amount of eosinophils in NPs was related to eosinophilia of the peripheral blood, but not to elevated serum IgE. BM was significantly thinner in non-eosinophilic than in eosinophilic NPs. Lymphocytes expressing CCR5 or CCR3 were less frequently found in non-eosinophilic than in eosinophilic NPs. CONCLUSION: Histoimmunological characteristics of non-eosinophilic NPs differ from those of eosinophilic NPs; non-eosinophilic NPs may be featured by thinner BM and fewer CCR5- and CCR3-positive lymphocytes.     

Defining incidence and outcome of contrast-induced nephropathy among trauma: is it overhyped?

Contrast-induced nephropathy (CIN) in trauma patients is uncommon and the incidence is unknown. We studied the incidence of CIN and its outcome. A retrospective chart review of trauma patients 16 years of age and older who were admitted to our Level I trauma center during 2005 was performed. Patients who received the intravenous contrast CT scan and had their serum creatinine (Cr) monitored at admission and at 48 to 72 hours were identified. CIN was defined as a 0.5-mg/dL rise of serum Cr or a 25 per cent increase from the baseline if the baseline Cr was abnormal. We excluded patients transferred from an outside facility, patients without repeated serum Cr measurements, patients who had cardiac arrest or persistent hypotension, and patients who had received N-acetylcysteine (Mucomyst) before their CT scan. We compared CIN and non-CIN groups. During 2005, 543 fit our study criteria, of whom 19 (3.5%) had CIN. CIN (vs non-CIN) had a higher baseline serum Cr (1.48 + 0.23 vs 1.06 + 0.02, P < 0.001), a longer intensive care unit stay (17 vs 5 days, P < 0.001), and a longer hospital stay (19 vs 8 days, P < 0.001); the mortality rate was not different (10 vs 4%, P = 0.2). We found elevated baseline serum Cr (OR, 1.92; 95% CI, 1.13 to 3.27; P = 0.016) to be associated with increased risk for CIN. All but two serum Cr levels peaked within 48 hours; all returned to baseline. One patient with an underlying congenital kidney disease required temporary dialysis. CIN incidence in trauma is low and the clinical course is benign.     

Factors Associated With Withdrawal From Dialysis Therapy in Incident Hemodialysis Patients Aged 80 Years or Older

ObjectivesAmong kidney disease patients ≥80 years progressing to end-stage renal disease, there is growing interest in conservative nondialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis.Study designHistorical cohort study.Setting and participantsWe examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007 to 2011.MeasuresWe identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence rates and subdistribution hazard ratios for withdrawal from dialysis as well as 4 other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients ≥80 years old was assessed using logistic regression analysis.ResultsAmong 17,296 patients aged ≥80 years, 10% of patients withdrew from dialysis. Duration from the last hemodialysis treatment to death was 10 [interquartile range 6-16] days in patients with available data. Withdrawal from dialysis was the second and third most common cause of death among patients aged ≥80 years and <80 years, respectively. Among patients ≥80 years, minorities were much less likely than non-Hispanic whites to stop dialysis. Other factors associated with higher odds of dialysis withdrawal included having a central venous catheter compared to an arteriovenous fistula at dialysis start, dementia, living in mid-west regions, and less favorable markers associated with malnutrition-inflammation-cachexia syndrome such as higher white blood cell counts and lower body mass index, albumin, and normalized protein catabolic rate.Conclusion/ImplicationsAmong very-elderly incident hemodialysis patients, dialysis therapy withdrawal exhibits wide variations across age, race and ethnicity, regions, cognitive status, dialysis vascular access, and nutritional status. Further studies examining implications of withdrawal from dialysis in older patients are warranted