Evaluation of the mutagenic potential of urban air pollution in São Paulo, Southeastern Brazil, using the Tradescantia stamen-hair assay

We used a short‐term bioassay—the Tradescantia stamen‐hair assay (TSH)—to evaluate the toxicity of ambient particles with an aerodynamic diameter less than 10 μm sampled in the metropolitan region of São Paulo, Brazil. Two exposure locations were selected: downtown São Paulo and Caucaia do Alto (mean PM₁₀ levels of 64 and 14 μg/m³, respectively). The experiment was conducted July 11–August 15, 2002, and toxicity was assessed with the Tradescantia stamen‐hair assay (TSH) employing clone KU‐20 of Tradescantia. Four experimental groups were defined: inflorescences collected from plants cultivated in Caucaia, inflorescences collected from plants cultivated in São Paulo (to establish the baseline level of mutations in stamen hairs at both sites), inflorescences collected from plants cultivated in Caucaia and brought to São Paulo and maintained in chambers that received ambient air, and inflorescences collected from plants cultivated in Caucaia and brought to São Paulo and maintained in chambers that received air passed through a particle filter. The frequency of mutations observed in Caucaia was significantly lower than that in the remaining groups. Flower cuttings brought from Caucaia and receiving ambient air of São Paulo showed a rate of mutations similar to that of plants cultivated in São Paulo. Filtering particles from the air reduced the rate of mutation but not sufficiently to reach the level of that in Caucaia. The frequency of mutations observed in São Paulo was significantly associated with PM₁₀ levels on the fifth day before the opening of the flowers (r = 0.47, p = 0.025). Our results indicate that urban particles play a significant role in the development of pollution‐dependent mutations. © 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 578–584, 2004.     

Effects of deltamethrin on functions of rat liver mitochondria and on native and synthetic model membranes

Deltamethrin (DTM) is a synthetic pyrethroid insecticide used wideworld in agriculture, home pest control, protection of foodstuff, and disease vector control. It has widespread applications in Brazilian agriculture. The effects of DTM on mitochondrial respiratory parameters and on the organization of artificial and native membranes are described. DTM (200 nmol mg(-1) protein) on isolated liver mitochondria decreased oxygen consumption of both, state III and state IV, as well as the inner mitochondrial membrane potential (Deltapsi). Analysis of segments of the respiratory chain suggested that the DTM inhibition site is located between complex II and complex III. Mitochondrial swelling, energized or driven by the K+ diffusion potential using valinomycin, were partially inhibited by DTM (200 nmol mg(-1) protein). Fluorescence polarization of DPH and DPH-PA, probing the core and outer regions, respectively, of dimyristoylphosphatidylcholine (DMPC) and native mitochondrial membranes, indicated that DTM shifts the midpoint phase transition to lower values, besides broadening the phase transition. DTM decreased the lipid order of DMPC bilayers, at temperatures lower than the transition temperature and also caused a disordering effect on native membranes. However at temperatures above the transition temperature, the pesticide increased the rigidity of the membrane. These results suggest that DTM causes perturbations in lipid-lipid and lipid-protein interactions, interferes in transport mechanisms operating at the membrane level, and causes alterations of membrane permeability and mitochondrial enzyme activities. These effects could be associated with the toxicity of deltamethrin.     

Adjuvant activity of Mycobacterium bovis BCG expressing CRM197 on the immune response induced by BCG expressing tetanus toxin fragment C

In order to develop a combined recombinant Mycobacterium bovis BCG (rBCG) vaccine against diphtheria, pertussis and tetanus (DPT), we have constructed different strains of rBCG expressing tetanus toxin fragment C (FC), driven by the up-regulated M. fortuitum beta-lactamase promoter, pBlaF*. Tetanus toxin FC was expressed in comparable levels in native form or in fusion with the beta-lactamase exportation signal sequence; however, in both constructs it was localized to the cytosol. Immunization of mice with rBCG-FC or its combination with rBCG expressing CRM197, induced anti-tetanus toxin antibodies with a Th2 immunoglobulin profile. Administration of a subimmunizing dose of the diphtheria-tetanus toxoid vaccine showed that rBCG-FC primed mice for production of an intense humoral response. Interestingly, the combination of rBCG-FC and rBCG-CRM197 reduced the time required for maturation of the immune response and increased anti-tetanus toxin antibody levels, suggesting adjuvant properties for rBCG-CRM197; this combination induced 75% protection in mice challenged with 100 minimum lethal doses (MLD) of tetanus toxin. Antisera from guinea pigs immunized with this combination were shown to neutralize tetanus toxin and diphtheria toxin. Our results suggest reciprocal adjuvant effects of rBCG-FC and rBCG-CRM197, which may contribute to induction of a more effective immune response against both diseases.     

Diffusion imaging may predict reversible brain lesions in eclampsia and severe preeclampsia: initial experience

OBJECTIVE: The purpose of this study was to validate diffusion-weighted magnetic resonance imaging in the prediction of the evolutive course of brain edema and to establish its pathophysiologic presence in patients with eclampsia/severe preeclampsia. STUDY DESIGN: Seventeen patients with a clinical diagnosis of severe eclampsia/preeclampsia and T2 hyperintense brain lesions on routine magnetic resonance imaging were evaluated at hospital admission and 8 weeks later. RESULTS: Brain edema was reversible in 13 patients and irreversible in 4 patients, as indicated on follow-up magnetic resonance imaging. Sixteen of 17 patients were differentiated accurately into reversible and irreversible groups on the basis of diffusion imaging on hospital admission. Diffusion-weighted magnetic resonance imaging demonstrated a significant increase in water mobility in abnormal regions compared with normal-appearing brains in patients in the reversible group (1.34+/-0.10 mm(2) vs 0.79+/-0.08 mm(2)/s x 10(-3), P<.001). In the irreversible group, restricted water diffusion was present, which was consistent with cytotoxic edema and early brain infarction in 3 of 4 patients. CONCLUSION: Diffusion-weighted magnetic resonance imaging can predict successfully the evolutive course of brain edema in an acute setting in these patients. Our findings indicate that brain edema is vasogenic, although ischemic/cytotoxic edema was observed less commonly.     

A new dominant branchiogenic-deafness syndrome with internal auditory canal hypoplasia and abnormal extremities

Two sibs from one Lebanese family presented with congenital hearing loss, meatal atresia, preauricular tags and pits, branchial cysts or fistulae, strabismus, difficulty in opening the mouth wide enough, abnormal fifth fingers, somewhat short stature, and learning disability and patchy skin depigmentation in one. Temporal bone abnormalities identified on computed tomography included atresia of the external auditory canal with reduction in size of the middle ear, malformed ossicles, and unilateral internal auditory canal hypoplasia. Hand radiographs showed pointed phalanges of the 5th fingers with osseous erosions. Their father, his sister, and his half-brother had unilateral auricular pits and/or branchial cysts. Results of all laboratory investigations including sequencing of the EYA1 gene were normal. Differential diagnosis is discussed and the possibility of the report of a new autosomal dominant type of branchiogenic-deafness syndrome with variable expressivity is raised.     

Diagnoses,clinical classification,and proposed treatment of spontaneous early exposure of submerged implants

Spontaneous early exposure of implants can become a serious complication during the initial healing phase. These early perforations and partial exposure of the coverscrews are a foci for plaque accumulation which, if left untreated, may result in inflammation, damage to the periimplant mucosa, and possible bone loss. Sometimes, these exposures are so small so as not to be clinically visible. This article presents methods of diagnoses of perforated mucosa around submerged implants. In addition, an easy-to-use classification of the spontaneous early exposure is proposed. Treatment modalities to prevent or intercept mucositis during the initial healing phase, when early exposures occur, are suggested.     

Hydrocephalus due to idiopathic stenosis of the foramina of Magendie and Luschka. Report of three cases

Idiopathic stenosis of the foramina of Magendie and Luschka is a rare cause of obstructive hydrocephalus involving the four ventricles. Like other causes of noncommunicating hydrocephalus, it can be treated with endoscopic third ventriculostomy (ETV). Three patients who were 21, 53, and 68 years of age presented with either headaches (isolated or associated with raised intracranial pressure) or vertigo, or a combination of gait disorders, sphincter disorders, and disorders of higher functions. In each case, magnetic resonance (MR) imaging demonstrated hydrocephalus involving the four ventricles (mean transverse diameter of third ventricle 14.15 mm; mean sagittal diameter of fourth ventricle 23.13 mm; and mean ventricular volume 123.92 ml) with no signs of a Chiari Type I malformation (normal posterior fossa dimensions, no herniation of cerebellar tonsils). The diagnosis of obstruction was confirmed using ventriculography (in two patients) and/or MR flow images (in two patients). All patients presented with marked dilation of the foramen of Luschka that herniated into the cisterna pontis. All patients were treated using ETV. No complications were observed. All three patients became asymptomatic during the weeks following the surgical procedure and remained stable at a mean follow-up interval of 36 months. Postoperative MR images demonstrated regression of the hydrocephalus (mean transverse diameter of third ventricle 7.01 mm; mean sagittal diameter of fourth ventricle 16.6 mm; and mean ventricular volume 79.95 ml), resolution of dilation of the foramen of Luschka, and good patency of the ventriculostomy (flow sequences). These results confirm the existence of hydrocephalus caused by idiopathic fourth ventricle outflow obstruction without an associated Chiari Type I malformation, and the efficacy of ETV for this rare indication.     

Mechanisms involved in methylmercuric chloride (MeHgCl)-induced suppression of human neutrophil apoptosis

We have previously demonstrated that concentrations of 1-10 microM of methylmercuric chloride (MeHgCl) that are cytotoxic to monocytes-macrophages can curiously inhibit neutrophil apoptosis by a yet unknown mechanism. In the present study, we demonstrate that, as with the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), a classical inhibitor of neutrophil apoptosis, treatment of cells with 5 microM MeHgCl induces de novo protein synthesis and prevents the loss of expression of the antiapoptotic Mcl-1 protein. The expression of the cytoskeletal proteins gelsolin, paxillin and vinculin was similar in MeHgCl- or GM-CSF-induced suppression of apoptosis. However, MeHgCl prevents the degradation of vimentin differently than GM-CSF. Apoptosis was further confirmed by flow cytometry (FITC annexin-V), and by monitoring CD16 cell surface expression. Curiously, unlike GM-CSF, MeHgCl did not prevent CD16 shedding. We conclude that, like GM-CSF, MeHgCl can delay neutrophil apoptosis by inducing de novo protein synthesis and by preventing the loss of the antiapoptotic Mcl-1 protein. However, unlike GM-CSF, MeHgCl induces an atypical degradation of vimentin without preventing CD16 shedding.