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.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia

KLF4/GKLF normally functions in differentiating epithelial cells, but also acts as a transforming oncogene in vitro. To examine the role of this zinc finger protein in skin, we expressed the wild-type human allele from inducible and constitutive promoters. When induced in basal keratinocytes, KLF4 rapidly abolished the distinctive properties of basal and parabasal epithelial cells. KLF4 caused a transitory apoptotic response and the skin progressed through phases of hyperplasia and dysplasia. By 6 weeks, lesions exhibited nuclear KLF4 and other morphologic and molecular similarities to squamous cell carcinoma in situ. p53 determined the patch size sufficient to establish lesions, as induction in a mosaic pattern produced skin lesions only when p53 was deficient. Compared with p53 wild-type animals, p53 hemizygous animals had early onset of lesions and a pronounced fibrovascular response that included outgrowth of subcutaneous sarcoma. A KLF4-estrogen receptor fusion protein showed tamoxifen-dependent nuclear localization and conditional transformation in vitro. The results suggest that KLF4 can function in the nucleus to induce squamous epithelial dysplasia, and indicate roles for p53 and epithelial-mesenchymal signaling in these early neoplastic lesions.     

The education that we have and the one we want: a perspective on discourses

This research has the purpose of gaining more understanding about the actions and policies put in place in order to ensure the training of professionals that work in the services of the State Health Care System, considering the direct and intrinsic relation between the education and its final quality. Broken down into 3 perspectives, here labeled as voices, we have tried to identify, by means of the discourses on social control in the area of health, the system's administration, and education represented by the schools of nursing, what are the criticisms and propositions concerning the theme of professional training for the State Health Care System. The text deals with the terms used in the context of professional training, as well as a critical reflection about the new tendencies and paradigms that are on the agenda in current debates and discussions.     

Methyl parathion interaction with human and bovine serum albumin

Methyl parathion (MP; O,O-dimethyl O-p-nitrophenyl phosphorothioate) is an organophosphorous compound still largely used in agriculture and fish hatcheries. This pesticide is not quite selective and is potentially toxic for both vertebrates and invertebrates. Its mechanism of acute toxicity is the inhibition of the enzyme acetylcholinesterase in nervous tissue. Binding of pesticides to plasma proteins is one of many factors that influence their distribution and elimination. The free concentration available for toxic action can be effectively reduced for pesticides with high binding to plasma proteins, although the affinity of pesticides to plasma proteins is often lower than for the enzyme targets. Several different transport proteins exist in blood plasma, but albumin only is able to bind a wide diversity of xenobiotics reversibly with high affinity. It was already known that parathion (ethyl parathion) exhibits a high affinity to human and bovine serum albumins. We studied interactions of methyl parathion with these albumins by using fluorescence quenching techniques. We selectively excited the fluorescence of tryptophan residues with a 290 nm wavelength light, and observed quenching by titrating human and bovine serum albumin solutions with methyl parathion. Stern-Volmer graphs were plotted and quenching constants were estimated. Our results pointed to the formation of complexes of methyl parathion with albumins. Association constants at 25 degrees C were 3.07 x 10(4) (1.2 x 10(3))M(-1) for human serum albumin, and 1.96 x 10(4) (+/- 4.5 x 10(2))M(-1) for bovine serum albumin. At 37 degrees C, they were 1.08 x 10(4) (+/- 2.0 x 10(2))M(-1) for human serum albumin, and 8.16 x 10(3) (+/- 1.9 x 10(2))M(-1) for bovine serum albumin. Results also suggest that the primary binding site for methyl parathion on albumin is close to tryptophan residues 214 of human serum albumin and 212 of bovine serum albumin.     

Periodontal disease in pregnancy and low birth weight

OBJECTIVE: Recently, it has been suggested that periodontal disease during pregnancy could have a causal relationship with low weight at birth. Our objective was to evaluate the influence of periodontal disease during pregnancy on the birth weight of newborn infants. METHODS: Mothers who gave birth to low-birth-weight infants were randomly selected (Group 1 - G1; n=13). Immediately after inclusion of each mother in group 1, the mother of the next term newborn with birth weight of > 2,500 g (Group 2 - G2; n=13) was included as control. Mothers were examined by a periodontist who was not informed of the group the child belonged to. A probe was used to measure attachment loss of the alveolar bone. The extension index (EI) and severity index (SI) of the periodontal disease were determined. RESULTS: Both groups of mothers were similar in terms of maternal age, parity, color of skin, height, nutrition, smoking, drinking, socioeconomic status, prenatal examinations, premature rupture of membranes, chorioamnionitis, bacteriuria, placenta previa, abruptio placentae, previous hypertensive disease, preeclampsia, and heart disease. The characteristics of the newborns were: birth weight - G1 = 1,804 -/+ 675 g x G2 = 3,030 -/+ 516 g; gestational age - G1 = 33 -/+ 5 weeks x G2 = 39 -/+ 2 weeks; length of stay in the neonatal intensive care unit (NICU) - G1 = 128 days x G2 = 0 days. Average EI: G1 = 89.788 -/+ 18.355 x G2 = 72.420 -/+ 20.717; p=0.033. Average SI: G1 = 1.377 -/+ 0.626 x G2 = 0.754 -/+ 0.413 (OR=18.3; CI95%: 2.5-133.3; p = 0.006). After adjustment for risk factors for low birth weight, such as smoking, maternal height, bacteriuria, and previous hypertension, the odds ratio for SI dropped to 7.2 (CI95% = 0.4-125.4; P = 0.176). CONCLUSION: The multivariate analysis indicated a marked association between periodontal disease measured by SI score and low birth weight. Our data suggested that periodontal disease during pregnancy may be a risk factor for low weight at birth.     

Comparative study of phenolic compounds in different Brazilian rice (Oryza sativa L.) genotypes

This study was conducted to evaluate the natural variability of total, extractable and non-extractable phenolics in pigmented and non-pigmented rice genotypes (Oryza sativa L.) and to estimate whether the contents and distribution of these compounds are typical for genotypes from indica and japonica subspecies. Twenty-one samples of commercial as well as new genotypes of brown rice, including seven pigmented genotypes were obtained from two Agronomic Institutes in South Brazil. Free and conjugated phenolics were extracted with ethanol, while bound phenolics were released by alkaline hydrolysis. Total phenolics were estimated in both fractions by the Folin–Ciocalteau method. Genotypes from japonica and indica non-pigmented subspecies were not statistically distinguishable from each other, but differences in phenolic contents were associated with pericarp color. Despite individual differences, total phenolics were four times higher in pigmented than in non-pigmented genotypes (4246 and 1073 mg ferulic acid equiv. kg^?1, respectively). These high amounts were mostly due to the presence of extractable (free and conjugated) phenolics, which comprised up to 81% of total phenolics for pigmented genotypes. Non-extractable (bound) phenolics comprised 40% of total phenolics of non-pigmented rice genotypes while pigmented genotypes presented greater absolute amounts, but their contribution on total phenolics was small.