Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. Part 1: Oral route

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM‐202 and 203) and two precipitated (NM‐200 and ‐201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver, spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)‐modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose‐dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells. Environ. Mol. Mutagen. 56:218–227, 2015. © 2014 Wiley Periodicals, Inc.     

Gatekeeper for coronary angiography: reply

We thank Geluk and Zijlstra for their kind words as well astheir considerations and proposals. The latter hits right intothe heart of the issue: should one stick to the ‘anatomic’paradigm urging us to detect and treat coronary stenoses andcalcifications rather than follow     

Cost-effectiveness analysis of screening for abdominal aortic aneurysms based on five year results from a randomised hospital based mass screening trial.

BACKGROUND: The aim of this study was to estimate the cost effectiveness of screening for abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: All 12,639 men born in the years 1921-1933 (aged 64-73) living in Viborg County, Denmark, were randomly allocated either to receive an invitation to abdominal ultrasound scanning for AAA or to be controls. Costs for screening and surveillance were assessed prospectively. Diagnosis Related Group (DRG) costs from 1999 were used concerning admissions with uncomplicated and complicated operations. Admissions for AAA surgery were retrospectively classified according to complications in patient records. RESULTS: Mean follow-up time was 52 months. 76.6% of invited men attended screening, and 191 (4.0%) had an AAA. As previously reported, the cumulative 5-year AAA-specific mortality in the invited group was significantly reduced by 67% compared to the control group (P = 0.003). The costs were estimated to be Euro 11.23 per scan. The costs per life-year saved were Euro 9057 (Euro 5872-20,063) after 5 years, and were expected to decrease to Euro 2708 (Euro 1758-6031) after 10 years and to Euro 1825 (Euro 1185-4063) after 15 years. CONCLUSION: Screening of 64-73 years old males in Denmark seems cost effective.     

Changes in the levels of neuropeptide Y-LI in the external jugular vein in connection with vasoconstriction following subarachnoid haemorrhage in man

Summary NPY is a putative neurotransmitter mainly co-localized with noradrenaline in sympathetic fibers which innervate the cerebral vasculature. The origin of most of the perivascular NPY fibers seems to be in the superior cervical ganglion. To investigate involvement of Neuropeptide Y (NPY) mechanisms in subarachnoid haemorrhage (SAH), twenty patients with SAH were investigated. NPY-LI (-like immunoreactivity) levels in the external jugular vein were assessed using radioimmunoassay in blood samples collected postoperatively (or after SAH in non-surgical patients) on days 1, 2, 3, 5, 7 and 9. These levels were compared with the clinical course and blood flow velocity changes monitored with ultrasonic Doppler equipment from both middle cerebral arteries (MCA) and both internal carotid arteries (ICA).Compared to NPY-LI levels in 14 controls (mean 116±3 pmol/ l), increased levels (up to 253 pmol/l) and a close relationship between velocities and NPY-LI levels were found in a subpopulation of the SAH patients. When comparing the mean haemodynamic index (V MCA/ipsilateral V ICA) and mean NPY-LI levels in each of the 20 patients, a correlation of r=0.75, p=0.0001 was found. Increased NPY-LI were found (131±8 pmol/l) when simultaneous Doppler velocity recordings showed vasoconstriction (Haemodynamic index >5) compared with samples taken when the haemodynamic index was <5, p<0.05. When MCA velocity exceeded 120 cm/sec, increased levels were found (129±9 pmol/l) compared with the conditions when MCA velocity was less than 120 cm/sec (113±5 pmol/ l), p=0.06. The results indicate a possible NPY involvement in cerebral vasoconstriction after SAH.     

Ileal release of glucagon-like peptide-1 (GLP-1)

There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II,N=6), and during endogenous stimulation by intraduodenal essential amino acid perfusion,N=6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P<0.01), and endogenously stimulated output by 68%, respectively (P<0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80–100% (allP<0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein, Decreased acid output is associated with release of GLP-1, but not PYY. These findings support the hypothesis that the distal small intestine may participate in the late postprandial inhibitory regulation of gastric secretory function in humans and that GLP-1 may be an intermediary factor.     

Progesterone Receptor Levels Independently Predict Survival in Endometrial Adenocarcinoma

Estrogen receptor (ER) and progesterone receptor (PR) contents were determined by biochemical (dextran charcoal-coated (DCC) assay) and immunohistochemical (ICA) methods in biopsies from 145 primary endometrial adenocarcinomas and those with eligible receptor measurements were analyzed with respect to correlations to cancer-specific survival in a multivariate analysis including histopathological characteristics. Median patient follow-up time was 67 months with 18 cancer deaths. The PR-DCC and ER-DCC values were dichotomized according to levels previously found by us to correspond to the best agreement between receptor status as determined by the DCC and ICA methods (130 fmol/mg cytosol protein for ER, 114 fmol/mg for PR). Using these thresholds, we found by multivariate analysis that “high” PR-DCC levels (>114 fmol/mg) correlated significantly (P= 0.004) with survival, independent of stage risk group (Ia + b vs Ic-IV). Patient age and histologic grade were prognostic factors in a univariate setting, but these parameters were eliminated in the multivariate model. While the PR-ICA scores also correlated significantly and independently with survival, the predictive effect of PR-ICA positivity alone could not be statistically evaluated due to the number of cases with eligible ICA values. However, we suggest that owing to a close correlation between DCC and ICA results, PR-ICA status may provide significant prognostic information when DCC measurements are not available.     

The anterior cruciate ligament does play a role in controlling axial rotation in the knee

This study deals with the influence of peroperative ligament tension on total tibial rotation at different knee flexion angles. Fourteen human cadaver knees with a mean age of 56 years (range 42–84 years) were examined. The cadaver knees were subjected to internal/external (i/e) rotational torque of 6 Nm, at 10, 30, 50, 70 and 90 deg of knee flexion. The mean total i/e rotation with the anterior cruciate ligament (ACL) intact at 10 deg of knee flexion was 30.4 deg and after removing the ACL, 33.1 deg. At 10 and 30 deg of knee flexion, the increase in i/e rotation was significant, while there was no significant difference in mean values at greater knee flexion. Ligament reconstruction with a tension of 5 N at 30 deg of knee flexion using either the over the top or through the femoral condyle reconstructive procedure restored normal tibial rotation. With increased graft tension the knee motion was increasingly restricted at low angles of knee flexion. Our results indicate that the ACL does play a role in limiting axial rotation, and even minor tensioning forces introduced in any of the two ACL reconstructions used produced restricted knee motion.     

Ultrasonographic diagnosis of renal stones

To illucidate the diagnostic accuracy of ultrasound in the detection of renal stones we performed a blind comparative study of ultrasonography and i.v. urography. In 92 kidneys with 58 stones, 10 stones smaller than 6 mm were overlooked by ultrasound, whereas all stones 6 mm or larger were correctly detected. In one case of uric acid stone disease i.v. urography was inconclusive in determining the true nature of a renal pelvic filling defect, whereas ultrasound correctly diagnosed a stone. We conclude that ultrasonography has a place in diagnosis and control of renal stones.