Discrepancies Between Objective and Subjective Outcomes of and Quality of Life During Molding Helmet Therapy for Cranial Deformities.

Positional skull deformities have been on the rise for decades and can be treated with molding helmets in early childhood. Parents often fear later cosmetic stigmatization, but also a reduced quality of life (QoL) during treatment. The aim of this study was to examine therapy results in our patient collection from a new perspective. Cranial vault asymmetry (CVA), cranial vault asymmetry index (CVAI), and cranial index (CI) were compared before and after molding helmet therapy. Correction was defined by a decrease in CVA <3.5 mm and CI <90%. Subjective therapy outcome, side effects and QoL from the parents' perspective were determined using a questionnaire. There were 25 patients included. Differences between pretherapeutic and posttherapeutic CVA, CVAI, and CI were significant (P<0.01). An objective correction according to the defined values was observed in only 12% of cases. However, 76% of parents stated that their child's skull shape was normal after therapy. There were 60 side effects reported in 23 cases. The QoL of 21 children was assessed as unimpaired during helmet therapy. Even though complete normalization was rarely observed, the parameters were significantly different after therapy, and subjective reduction in skull deformity was common.

The effect of activated charcoal on adenine-induced chronic renal failure in rats.

Activated charcoal (AC) is a sorbent that has been shown to remove urinary toxins like urea and indoxyl sulfate. Here, the influence of AC on kidney function of rats with experimental chronic renal failure (CRF) is investigated. CRF was induced in rats by feeding adenine (0.75%) for four weeks. As an intervention, AC was added to the feed at concentrations of 10%, 15% or 20%. Adenine treatment impaired kidney function: it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and vanin-1. Furthermore, it raised plasma concentrations of the uremic toxins indoxyl sulfate, phosphate and uric acid. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activity, total antioxidant capacity and reduced glutathione were adversely affected. Most of these changes were significantly ameliorated by dietary administration of AC at a concentration of 20%, while effects induced by lower doses of dietary AC on adenine nephrotoxicity were not statistically significant. The results suggest that charcoal is a useful sorbent agent in dietary adenine-induced CRF in rats and that its usability as a nephroprotective agent in human kidney disease should be studied.

Oxidative DNA damage in kidneys and heart of hypertensive mice is prevented by blocking angiotensin II and aldosterone receptors.

INTRODUCTION: Recently, we could show that angiotensin II, the reactive peptide of the blood pressure-regulating renin-angiotensin-aldosterone-system, causes the formation of reactive oxygen species and DNA damage in kidneys and hearts of hypertensive mice. To further investigate on the one hand the mechanism of DNA damage caused by angiotensin II, and on the other hand possible intervention strategies against end-organ damage, the effects of substances interfering with the renin-angiotensin-aldosterone-system on angiotensin II-induced genomic damage were studied. METHODS: In C57BL/6-mice, hypertension was induced by infusion of 600 ng/kg • min angiotensin II. The animals were additionally treated with the angiotensin II type 1 receptor blocker candesartan, the mineralocorticoid receptor blocker eplerenone and the antioxidant tempol. DNA damage and the activation of transcription factors were studied by immunohistochemistry and protein expression analysis. RESULTS: Administration of angiotensin II led to a significant increase of blood pressure, decreased only by candesartan. In kidneys and hearts of angiotensin II-treated animals, significant oxidative stress could be detected (1.5-fold over control). The redox-sensitive transcription factors Nrf2 and NF-κB were activated in the kidney by angiotensin II-treatment (4- and 3-fold over control, respectively) and reduced by all interventions. In kidneys and hearts an increase of DNA damage (3- and 2-fold over control, respectively) and of DNA repair (3-fold over control) was found. These effects were ameliorated by all interventions in both organs. Consistently, candesartan and tempol were more effective than eplerenone. CONCLUSION: Angiotensin II-induced DNA damage is caused by angiotensin II type 1 receptor-mediated formation of oxidative stress in vivo. The angiotensin II-mediated physiological increase of aldosterone adds to the DNA-damaging effects. Blocking angiotensin II and mineralocorticoid receptors therefore has beneficial effects on end-organ damage independent of blood pressure normalization.

Angiotensin II-induced hypertension dose-dependently leads to oxidative stress and DNA damage in mouse kidneys and hearts.

OBJECTIVE: Hypertension is associated with an increased cancer mortality and a higher kidney cancer risk. Blood pressure regulating hormones, such as the peptide hormone angiotensin II (AngII), are elevated in hypertension. AngII showed DNA-damaging effects in vitro and in the ex-vivo perfused mouse kidney. Here, the effect of rising doses of AngII was analysed for their genotoxic effects in vivo. METHODS: In C57BL/6-mice equipped with osmotic mini pumps, delivering AngII in four different concentrations between 60 ng/kg per min and 1 µg/kg per min during 28 days, the oxidative and DNA damaging effects of AngII were studied, using immunohistochemistry and mass spectrometry. RESULTS: AngII increased the SBP for up to 38 mmHg over control and adversely affected the kidney function of the mice. In the heart, at the highest dose administered, a significant increase of reactive oxygen species formation (1.4-fold over control) and double-strand breaks could be detected (13-fold over control). In the kidney, a dose-dependent increase of superoxide formation (up to 1.7-fold over control), double-strand breaks (up to 4.7-fold over control) and the mutagenic DNA base modification 7,8-dihydro-8-oxo-guanine (8-oxodG, up to 3.6-fold over control) was observed. Adverse effects already appeared at lower AngII doses, which did not raise the blood pressure. Administration of the radical scavenger tempol significantly decreased oxidative stress (by 20%) in the kidney and DNA double-strand breaks in the kidney by 60% and in the heart by 52%, without being able to lower the blood pressure. CONCLUSION: This study for the first time shows oxidative stress mediated genotoxic effects of AngII in vivo. Furthermore, the increase of 8-oxodG suggests a mutagenic potential of an activated renin-angiotensin-aldosterone system, which is often found in hypertensive patients.