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     

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.     

N-cadherin expression in adrenal tumors: upregulation in malignant pheochromocytoma and downregulation in adrenocortical carcinoma

Cell adhesion molecules (CAMs) are important regulators of tumor growth. The aim of the present study was to evaluate the expression pattern of CAMs in adrenal tumors regarding origin (cortex vs medulla) and biologic behavior (benign vs malignant). Eighty-seven adrenal tumors were investigated by immunocytochemistry (ICC) using monoclonal antibodies against N-cadherin (NCAD), E-cadherin (ECAD), neural cell adhesion molecule (NCAM), and CD44. Western blotting was performed on 30 tumors using the same antibodies. Markers for proliferation (Ki-67) and catecholamine synthesis (tyrosine hydroxylase) were also analyzed in tumors by ICC. NCAD was expressed in 12/27 benign pheochromocytomas (BPCs) (12 familial cases), 8/8 malignant pheochromocytomas (MPCs), 28/30 adrenocortical adenomas, and 9/22 adrenocortical carcinomas. ECAD was expressed in 0/27 BPCs, 0/8 MPCs, 0/30 adrenocortical adenomas, and 2/22 adrenocortical carcinomas. NCAM was expressed in 26/27 BPCs, 7/8 MPCs, 21/30 adrenocrotical adenomas, and 17/22 adrenocortical carcinomas. CD44 was expressed in 23/27 BPCs, 6/8 MPCs, 7/30 adrenocortical adenomas, and 4/22 adrenocortical carcinomas. Both cortical and medullary adrenal tumors expressed NCAD, NCAM, and CD44 but were devoid of ECAD. The expression of CD44 and NCAM did not correlate with the malignant potential of tumors. NCAD was upregulated in MPCs, but downregulated in adrenocortical carcinoma. Thus, NCAD appears to be involved in the development of both cortical and medullary adrenal tumors.     

Ultrastructure of the early human implantation in vitro

Four hatched human blastocysts obtained after in-vitro fertilizationand development were placed on monolayer cell cultures of humanendometrial epithelium, and subsequently examined by transmissionelectron microscopy. All four blastocysts became adherent tothe monolayer and three implanted and exhibited outgrowth oftheir trophoblastic cells. During implantation the blastocystsdifferentiated into mural and polar trophoblastic cells, andembryonic cells including endodermal cells. The endometrialcells were displaced and stacked into a multilayer at the peripheryof the implantation sites, allowing the trophoblastic cellsto come in contact with the culture dish. The endometrial cellsdisplayed local exo- or endo-cytosis where they contacted thetrophoblastic cells. The trophoblastic cells were not observedto be phagocytosing endometrial cells. These observations suggestthat human blastocysts portray an intrusive type of implantationduring the initial stages.     

'Vanishing embryo syndrome' in IVF/ICSI

BACKGROUND: In a Danish population-based cohort study assessing the risk of cerebral palsy in children born after IVF, we made some interesting observations regarding 'vanishing co-embryos'. METHODS and RESULTS: All live-born children born in Denmark from 1 January 1995 to 31 December 2000 were included in this analysis. The children conceived by IVF/ICSI (9444) were identified through the IVF Register, the children conceived without IVF/ICSI (395 025) were identified through The Danish Medical Birth Register. Main outcome measure was the incidence of cerebral palsy. Within the IVF/ICSI children we found indications of an increased risk of cerebral palsy in those children resulting from pregnancies, where the number of embryos transferred was higher than the number of children born. CONCLUSIONS: The association between vanishing embryo syndrome and incidence of cerebral palsy following IVF requires further investigation in larger, adequately powered, studies.     

Determination of immunoglobulin A against Gardnerella vaginalis hemolysin,sialidase, and prolidase activities in vaginal fluid: implications for adverse pregnancy outcomes

A nested case-control study of low birth weight and preterm delivery was performed with singleton women. Immunoglobulin A (IgA) against the Gardnerella vaginalis hemolysin (anti-Gvh IgA) and sialidase and prolidase activities were determined in vaginal fluid at 17 weeks of gestation. Sialidase positivity and bacterial vaginosis with high prolidase activity were associated with 2- and 11-fold increased risks for low birth weight, respectively. No woman with bacterial vaginosis plus a strong anti-Gvh IgA response had an adverse outcome.     

Electronic data processing in the Danish Cytogenetic Central Register and EDP problems of registers in general

A brief introduction to the Danish Cytogenetic Central Register (DCCR) is given, and possibilities, principles and problems concerning the establishment and maintenance of a national cytogenetic register are presented.
Various data carrier media for registers in general are discussed, of which the magnetic disc is considered most appropriate. General principles for programs capable of performing insertions, deletions and other modifications in the data base are outlined as well as the principles for the programs in the DCCR.
The individual records should preferably be identified by aid of a central person registration number (CPR) rather than by name. The data should be stored and sorted by this identification in order to facilitate retrieval of a desired record. The structure of the records is discussed with regard to prevention of the occurrence of certain errors as well as the optimization of processing.
Flexibility and economy of space are achieved by using programs able to handle records of unequal length, and problems occurring in connection with this are discussed. The question of how to protect sensitive data is dealt with, and two different methods used in the DCCR are outlined. Programs capable of analyzing karyotypes with the purpose of recognizing various cytogenetic syndromes have been developed for use in the DCCR. Various examples of computing times of typical program runs are presented.     

Use of monoclonal antibodies for the identification of different antigenic domains in apple chlorotic leaf spot virus

Summary Thirteen monoclonal antibodies (Mabs) specific for apple chlorotic leaf spot virus (ACLSV), produced by the somatic cell hybridization technique, were used to investigate the antigenic structure of the virus. Epitope specificity studies showed that these Mabs defined in ACLSV particles seven independent antigenic domains, representing at least eight distinct epitopes. One of them was present only in virions and not in dissociated subunits. It appeared that the interaction between a Mab and the virus could, in some cases, induce conformational changes in the viral particles which enhanced the binding of others. Twenty nine virus isolates differing in geographical origin, primary hosts and symptomatology were tested with these monoclonal antibodies by ELISA. With the exception of two Mabs which did not react with three cherry isolates, and one Mab which did not react with one plum isolate, all of them recognized all ACLSV isolates tested.