Ocular manifestations in classic homocystinuria

ABSTRACT

Background

Classic homocystinuria (HCU), or cystathionine beta-synthase (CBS) deficiency, is a rare inborn error of methionine metabolism. Main clinical features may include skeletal and vascular manifestations, developmental delay, intellectual disability and eye disorders.     

Influence of indigenous microbiota on experimental toxoplasmosis in conventional and germ‐free mice

Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii, causes a severe innate pro‐inflammatory response. The indigenous intestinal microbiota promotes host animal homoeostasis and may protect the host against pathogens. Germ‐free (GF) animals provide an important tool for the study of interactions between host and microbiota. In this study, we assessed the role of indigenous microorganisms in disease development utilizing a murine toxoplasmosis model, which includes conventional (CV) and GF NIH Swiss mice. CV and GF mice orally inoculated with T. gondii had similar survival curves. However, disease developed differently in the two animal groups. In CV mice, intestinal permeability increased and levels of intestinal pro‐inflammatory cytokines were altered. In GF animals, there were discrete epithelial degenerative changes and mucosal oedema, but the liver and lungs displayed significant lesions. We conclude that, despite similar survival curves, CV animals succumb to an exaggerated inflammatory response, whereas GF mice fail to produce an adequate systemic response.     

Surface modification of a biodegradable composite by UV laser ablation: in vitro biological performance

Melt blends of chitosan and biodegradable aliphatic polyester have been physically and biologically studied, presenting great potential for biomedical applications. Structurally, poly(butylene succinate)–chitosan (PBS/Cht) composite scaffolds are covered by a thin PBS layer, preventing the desired interaction of cells/tissues with the chitosan particules. In the present work, a selective and controlled ablation of this skin layer was induced by UV laser processing. X‐ray photoelectron spectroscopy (XPS) and time‐of‐flight secondary ion mass spectrometry (ToF–SIMS) data demonstrated an increment of chitosan components and others resulting from the laser ablation process. The biological activity (i.e. cell viability and proliferation) on the inner regions of the composite scaffolds is not significantly different from those of the external layer, despite the observed differences in surface roughness (determined by interferometric optical profilometry) and wettability (water contact angle). However, the morphology of human osteoblastic cells was found to be considerably different in the case of laser‐processed samples, since the cells tend to aggregate in multilayer columnar structures, preferring the PBS surface and avoiding the chitosan‐rich areas. Thus, UV laser ablation can be considered a model technique for the physical surface modification of biomaterials without detrimental effects on cellular activity. Copyright © 2010 John Wiley & Sons, Ltd.     

BITE FORCE EVALUATION IN SUBJECTS WITH CLEFT LIP AND PALATE

The purpose of this study was to evaluate the masticatory function of subjects with cleft lip and palate by analyzing the bite force developed by these individuals. Bite force was evaluated in a group of 27 individuals with repaired unilateral cleft lip and palate (14 males and 13 females – aged 18-26 years) and compared to the data achieved from a group of 20 noncleft subjects (10 males and 10 females – aged 18-26 years). Measurement was achieved on three positions within the dental arch (incisors, right molars and left molars), three times at each position considering the highest value for each one. Statistical analysis was performed by ANOVA and Mann-Whitney test (α = 5%). There was a significant deficit in bite force in male individuals with cleft lip and palate compared to the male control group (p=0.02, p=0.004, p=0.003 for incisors, right and left molars, respectively). For the female group, the difference was not statistically significant (p=0.79, p=0.06, p=0.47). In the group of individuals with clefts, 92.6% were under orthodontic treatment, which could be a reason for the present findings, since it can decrease the bite force more remarkably in males than in females. In conclusion, the bite force is significantly reduced in men when comparing the cleft group to the noncleft group. In females, this reduction was not significant in the same way. However, the main reason for this reduction and for the different behavior between genders should be further investigated.     

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry.

Pleomorphic adenoma is the most common benign tumor of the salivary glands. It has marked histological diversity with epithelial, myoepithelial and mesenchymal-type cells arranged in a variety of architectural and differentiation patterns. Pleomorphic adenoma gene 1 (PLAG1), shown to be consistently rearranged in pleomorphic adenomas, is activated by chromosomal translocations involving 8q12, the chromosome region that is most frequently affected in these tumors. In this study, we evaluated PLAG1 involvement in salivary gland tumorigenesis by determining the frequency of its alterations in a selected group of 20 salivary gland tumors: 16 pleomorphic adenomas and four carcinomas ex-pleomorphic adenoma, having in common the presence of karyotypic chromosome 8 deviations, either structural, with 8q12 rearrangements, or numerical, with gain of chromosome 8. PLAG1 status was analyzed using in situ hybridization techniques, on metaphase cells, by fluorescence detection and/or interphase cells in paraffin sections, by chromogenic detection. Except for one pleomorphic adenoma case (5%) that lacked PLAG1 involvement, 17 tumors (85%), (14 pleomorphic adenomas and three carcinomas ex-pleomorphic adenoma) showed intragenic rearrangements of PLAG1 and the remaining two cases (10%), (one pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma), had chromosome trisomy 8 only. To further investigate the role of PLAG1 on pleomorphic adenomas tumorigenesis, as well as the putative morphogenesis mechanism, we attempted to identify the cell types (epithelial vs myoepithelial) carrying 8q12/PLAG1 abnormalities by a combined phenotypic/genotypic analysis in four cases (three pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma) characterized by 8q12 translocations and PLAG1 rearrangement. In these cases, both cells populations carried PLAG1 rearrangements. This finding further supports the pluripotent single-cell theory, which postulates that the tumor-initiated, modified myoepithelial cell, evolves into the varied somatic cell phenotypes present in pleomorphic adenoma, and reinforces the role of PLAG1 on the tumorigenesis of benign and malignant pleomorphic adenoma.     

New effects in the electrochemistry of carbon dioxide on platinum by the application of potential perturbations

The electroformation and electrooxidation of carbon dioxide adsorbates were studied on polycrystalline and preferentially oriented platinum surfaces by the application of medium frequency potential perturbations in saturated carbon dioxide aqueous sulphuric acid solutions. Preferentially oriented platinum surfaces were obtained by the application of fast symmetric square wave potential programmes to polycrystalline electrodes based on well-known methodology. Two new electrochemical characteristics for the electrochemistry of carbon dioxide were observed after the application of the medium frequency routines, that is, an extended adsorption potential domain for the formation of carbon dioxide adsorbates, and novel voltammetric features for the two anodic stripping peaks. These effects upon carbon dioxide electrochemistry are dependent on the morphology of the platinum electrode surface and adsorption potentials.     

Effect of p-mercuribenzoate on the subestimation of angiotensin-converting enzyme measurement during chick retina development

The time course of dipeptidase activity and the effect of p-mercuribenzoate (PCMB) on the subestimation of the fluorometric determination of angiotensin-converting enzyme (ACE, EC 3.4.15.1) during development was studied. ACE and dipeptidase activities were measured fluorometrically in homogenates of the developing chick retina using Hip-His-Leu and His-Leu as substrates, respectively, both either in the presence or in the absence of 1 mM PCMB. ACE activity was inhibited by captopril (IC50 1.7 nM), MK 422 (IC50 4.8 nM), BPP9a (IC50 0.25 microM) and BPP5a (IC50 1.2 microM), thus suggesting that avian retinal ACE catalytically resembles the mammalian enzyme. Dipeptidase activity varied 3.4-fold throughout development, leading to a large and variable (28-83%) subestimation of ACE activity during chick retina ontogenesis. PCMB (1 mM) inhibited 67-94% dipeptidase activity during development, thus greatly reducing any subestimation of ACE activity determination during the development of the chick retina.