Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Identifying Risk Drinking in Expectant Fathers

Abstract: Background: Identification of risk drinking in expectant fathers may be helpful as an important part of efforts to minimize maternal alcohol use, and as an opportunity to inform them about a problematic practice during a critical developmental stage for the couple. The purpose of this study was to evaluate the T‐ACE screening questionnaire, which asks about t olerance to alcohol, being a nnoyed by other's comments about drinking, attempts to c ut down, and having a drink first thing in the morning (“ e ye‐opener”), in the male partners of pregnant women who themselves were T‐ACE positive. Methods: Two hundred fifty‐four male partners were asked to complete the T‐ACE embedded in a health survey, the Alcohol Use Disorders Identification Test (AUDIT), and other questions about their alcohol use in the past 30 days when their pregnant partners had a median gestation of 11.5 weeks (T₁). After delivery, male partners again completed the T‐ACE and quantity‐frequency questions (T₂). The predictive ability of the T‐ACE and AUDIT was compared, using risk drinking (>4 drinks/day or >14 drinks/week) as the criterion standard. Results: A substantial minority of male partners had risk drinking, 31 percent at T₁ and 25 percent at T₂. Although the AUDIT was better than the T‐ACE as an independent predictor of risk drinking, the latter was most accurate when the tolerance threshold exceeded 2 drinks, the same established for pregnant women. The sensitivity (T₁ = 84.6%, T₂ = 82.8%) and specificity (T₁ = 43.8%, T₂ = 51.1%) of the T‐ACE at this threshold compared favorably with those of the AUDIT at the standard cut point of 8. Conclusions: The T‐ACE may be a practical way for clinicians to identify risk drinking in both pregnant women and expectant fathers. (BIRTH 33:2 June 2006)     

Youth Tobacco Access and Possession Policy Interventions: Effects on Observed and Perceived Tobacco Use

This study evaluated the effects of tobacco Purchase, Use and Possession (PUP) laws on student perceptions of adolescent tobacco use within towns and schools. Twenty‐four towns were randomly assigned into two conditions, the experimental condition (E PUP) involved efforts to increase both PUP law enforcement and reduce minors' access to commercial sources of tobacco, whereas the control condition (C) focused only on efforts to reduce minors' access to commercial sources of tobacco. A hierarchical linear modeling analytical approach was selected due to the multilevel data and nested design. The present study found that over time, youth in the experimental PUP condition observed less youth tobacco usage at school and in their town, and perceived lower rates of tobacco among their peers at school and among friends than youth in the control condition. The findings suggest that PUP law enforcement might be used to strengthen community norms against youth tobacco use.     

LYSOSOMAL IRON ACCUMULATION AND TUBULAR DAMAGE IN RAT PUROMYCIN NEPHROSIS AND AGEING

1. Energy dispersive X-ray spectrometry was used to examine the relationship between proteinuria and increased urinary iron excretion, and structural and functional damage in puromycin nephrosis. 2. After 11–12 days rats treated with puromycin (10 mg/100g, i.v.i.) had greater proteinuria (211.6 ± 35.7 mg/day, mean ± s.e.m.) and urinary iron excretion (15.4 ± 2.2 μg/day) than salinetreated controls (14.5 ± 1.4 mg/day and 1.1 ± 0.2 μg/day, respectively, both P<0.001). 3. On day 13, mean lysosomal iron concentration of proximal tubular cells (306.6 ± 64.5 vs 11.9 ± 8.6 mg%, P<0.001), and proximal tubular cell damage assessed semi-quantitively (1.17 ± 0.10 vs 0.62 ± 0.10, P<0.001) were higher and creatinine clearance (0.15 ± 0.01 vs 0.29 ± 0.02 mL/min perg kidney weight, P<0.001) lower than in control rats. 4. At days 35, 60 and 360 there were no differences in any of the measured parameters between rats treated with puromycin or saline, and in both groups proteinuria, tissue damage and lysosomal iron concentration increased with time. 5. Lysosomal iron accumulation was the only independent predictor of both functional and structural damage. 6. In conclusion, the apparent association between proteinuria and tubulo-interstitial damage in puromycin nephrosis, and with ageing, is best explained by factors associated with accumulation of iron within lysosomes of proximal tubule cells.     

Effects of the angiotensin II type 1 receptor antagonist telmisartan on monocyte adhesion and activation in patients with essential hypertension.

Circulating monocytes from hypertensive patients show elevated secretion patterns of pro-inflammatory cytokines, an increased expression of adhesion molecules, and an increased adhesion to vascular endothelial cells. We tested the hypothesis that telmisartan, an angiotensin II type 1 (AT(1)) receptor antagonist, reduces the activation of circulating monocytes from hypertensive patients and diminishes the monocyte-endothelial cell adhesion. Monocytes of 20 hypertensive patients and 20 normotensive controls were isolated by density gradient centrifugation and Dynabeads, and the monocyte adhesion to human aortic endothelial cell monolayers was measured by adhesion assays. To characterize monocyte activation we assessed the expression of activity-related cell surface markers that are also involved in monocyte adhesion to endothelial cells, such as CD11a/b and CD54, as well as the chemokine receptors CCR1, CCR2 and CCR5 before and after telmisartan therapy using flow cytometry. Spontaneous adhesion of monocytes from hypertensive patients and the adhesion after stimulation with angiotensin II were significantly increased compared with those in normotensive controls (p<0.05). Treatment of hypertensive patients with the AT(1) receptor antagonist telmisartan significantly diminished the adhesion of circulating monocytes to human endothelial cells (p=0.02) despite the increase in the expressions of CD11b, CD54 and CCR5 after telmisartan therapy. Reducing monocyte adhesion may be a novel beneficial effect of the AT(1) receptor antagonist telmisartan helping to prevent vascular alterations in hypertension. The mechanism of action remains to be elucidated, since reduction in monocyte adhesion was not attributable to changes in adhesion molecule expression.