Disruption of rat forebrain development by glucocorticoids: critical perinatal periods for effects on neural cell acquisition and on cell signaling cascades mediating noradrenergic and cholinergic neurotransmitter/neurotrophic responses.

Glucocorticoids are the consensus treatment for the prevention of respiratory distress in preterm infants, but there is evidence for increased incidence of neurodevelopmental disorders as a result of their administration. We administered dexamethasone (Dex) to developing rats at doses below or within the range of those used clinically, evaluating the effects on forebrain development with exposure in three different stages: gestational days 17-19, postnatal days 1-3, or postnatal days 7-9. At 24 h after the last dose, we evaluated biomarkers of neural cell acquisition and growth, synaptic development, neurotransmitter receptor expression, and synaptic signaling mediated by adenylyl cyclase (AC). Dex impaired the acquisition of neural cells, with a peak effect when given in the immediate postnatal period. In association with this defect, Dex also elicited biphasic effects on cholinergic presynaptic development, promoting synaptic maturation at a dose (0.05 mg/kg) well below those used therapeutically, whereas the effect was diminished or lost when doses were increased to 0.2 or 0.8 mg/kg. Dex given postnatally also disrupted the expression of adrenergic receptors known to participate in neurotrophic modeling of the developing brain and evoked massive induction of AC activity. As a consequence, disparate receptor inputs all produced cyclic AMP overproduction, a likely contributor to disrupted patterns of cell replication, differentiation, and apoptosis. Superimposed on the heterologous AC induction, Dex impaired specific receptor-mediated cholinergic and adrenergic signals. These results indicate that, during a critical developmental period, Dex administration leads to widespread interference with forebrain development, likely contributing to eventual, adverse neurobehavioral outcomes.     

Treatment of proximal hypospadias with a tubularized island flap urethroplasty and the onlay technique: a comparative study

BACKGROUND/PURPOSE: The onlay island flap urethroplasty was first described in the repair of mid and distal penile hypospadias. Since then, this technique has been increasingly used in more severe cases of hypospadias, because of the complications of tubularized flaps, mainly megaurethra and proximal anastomotic strictures. The aim of this study was to compare the morbidity of these 2 techniques. METHODS: Between April 1994 and December 1998, 80 patients underwent surgical treatment for hypospadias. A tubularized island flap (Ducketttechnique) was performed in 42 cases, and the onlay island flap technique was used in 38 patients. The authors retrospectively compared the complication rate and type of these 2 procedures. RESULTS: Altogether, fistula was the most frequent complication without any significant difference between the 2 groups (21.4% for Duckett technique and 18.4% for onlay repair; P > .05). However, the anastomotic stricture was much more common in the tubularized flap group (7.14% v 2.63%; P < .05). Moreover, a megaurethra was found only in the Duckett technique group (4.7%). There was no case of chordee recurrence, but 6 patients (15.7%) treated with the onlay technique required urethrolysis including dissection of the chord behind the urethral plate, and in the other 3 patients of the same group (7.9%), a dorsal Nesbit plication also was necessary. In all these cases, the urethroplasty included an island cutaneous flap to provide ventral coverage to the neourethra. CONCLUSIONS: The authors conclude that both techniques present similar complications. However, proximal strictures and megaurethra are more common after the Duckett technique. This procedure is of choice in patients with scrotal hypospadias. Conversely, the onlay repair should be completed with other procedures (urethrolysis, dorsal Nesbit plication) to obtain good results in patients with severe degree of chordee.     

2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxyadenosine adducts resulting from the reaction of tetrahydrofuran with DNA bases

A recent study showed that tetrahydrofuran (THF), a widely used solvent, is carcinogenic in experimental animals. Despite its carcinogenic activity, there is a paucity of information regarding cellular toxicity, biomolecular damage, and genotoxicity induced by THF. We describe here the structural characterization of adducts produced by the reaction of oxidized THF with 2'-deoxyguanosine (dGuo-THF 1 and dGuo-THF 2), 2'-deoxyadenosine (dAdo-THF), and 2'-deoxycytidine (dCyd-THF). Adducts were isolated from in vitro reactions by reverse-phase HPLC and fully characterized on the basis of spectroscopic measurements. The stable derivatives obtained by the reduction of adducts with NaBH(4) (the case of dGuo-THF 1, dCyd-THF, and dAdo-THF) and the stable adduct dGuo-THF 2 were used as standards for optimization of chromatographic separations for adduct detection in DNA through HPLC/ESI/MS-MS. Using this methodology, we successfully detected the four adducts in calf thymus DNA reacted with oxidized THF. The present study also provides evidence that rat liver microsomal monooxigenases oxidize THF to the reactive electrophilic compounds that are able to damage the DNA molecule, as indicated by a significant increase in adduct dGuo-THF 1 level when NADPH was added to the THF/microsomes/dGuo incubation mixtures. Our data point to DNA-THF adducts as possible contributing factors to the toxicological effects of THF exposure.     

Abortion in democratic Spain: the parliamentary political agenda 1979-2004

Since Spain's transition to democracy, abortion has been a public policy issue both inside and outside parliament. This paper describes the history of abortion law reform in Spain from 1979 to 2004 and analyses the discourse on abortion of members of the Spanish parliament by sex and political allegiance. The analysis is based on a retrospective study of the frequency of legislative initiatives and the prevalence of different arguments and positions in debates on abortion found through a systematic search of the parliamentary database. Little time was given to abortion in the parliamentary agenda compared to other women's issues such as violence against women. There were 229 bills and other parliamentary initiatives in that period, 60% initiated and led by pro-choice women. 143 female and 72 male parliamentarians took part in the debates. The inclusion of socio-economic grounds for legal abortion (64%), and making abortion on request legal in the first 12 weeks of pregnancy (60%) were the most frequent forms of law reform proposed, based most often on pro-women's rights arguments. Male and female members of anti-choice parties and most male members of other parties argued for fetal rights. Pro-choice parties tabled more bills than anti-choice parties but till now all reforms proposed since 1985 have been voted down.     

Effect of Surface Tooling Techniques of Medical Titanium Implants on Bacterial Biofilm Formation In Vitro

The aim of this study was to assess the biofilm formation of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli on titanium implants with CAD-CAM tooling techniques. Twenty specimens of titanium were studied: Titanium grade 2 tooled with a Planmeca CAD-CAM milling device (TiGrade 2), Ti₆Al₄V grade 5 as it comes from CAD-DMLS device (computer aided design-direct metal laser sintering device) (TiGrade 5), Ti₆Al₄V grade 23 as it comes from a CAD-CAM milling device (TiGrade 23), and CAD-DMLS TiGrade 5 polished with an abrasive disc (TiGrade 5 polished). Bacterial adhesion on the implants was completed with and without saliva treatment to mimic both extraoral and intraoral surgical methods of implant placement. Five specimens/implant types were used in the bacterial adhesion experiments. Autoclaved implant specimens were placed in petri plates and immersed in saliva solution for 30 min at room temperature and then washed 3× with 1× PBS. Bacterial suspensions of each strain were made and added to the specimens after saliva treatment. Biofilm was allowed to form for 24 h at 37 °C and the adhered bacteria was calculated. Tooling techniques had an insignificant effect on the bacterial adhesion by all the bacterial strains studied. However, there was a significant difference in biofilm formation between the saliva-treated and non-saliva-treated implants. Saliva contamination enhanced S. mutans, S. aureus, and E. faecalis adhesion in all material types studied. S. aureus was found to be the most adherent strain in the saliva-treated group, whereas E. coli was the most adherent strain in the non-saliva-treated group. In conclusion, CAD-CAM tooling techniques have little effect on bacterial adhesion. Saliva coating enhances the biofilm formation; therefore, saliva contamination of the implant must be minimized during implant placement. Further extensive studies are needed to evaluate the effects of surface treatments of the titanium implant on soft tissue response and to prevent the factors causing implant infection and failure.     

Birth prevalence and characteristics of congenital toxoplasmosis in Sergipe,North‐east Brazil

Objectives To estimate, by neonatal screening, the birth prevalence of congenital toxoplasmosis among live‐born infants in Sergipe state, Brazil, and to investigate the clinical features of affected infants. Methods Dried blood spot specimens obtained from 15 204 neonates were assayed for the presence of anti‐T. gondii IgM antibodies. Duplicate retesting was done in infants with positive and borderline results. Confirmatory testing in peripheral blood samples consisted of testing for anti‐T. gondii IgG and IgM in infants and mothers. Those with possible congenital toxoplasmosis were evaluated and followed up to a median age of 20 months. Congenital infection was confirmed in the presence of persisting anti‐T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1 year. Results Fifty‐three infants had detectable IgM in dried blood spot specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed follow‐up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis, resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.4–8.0]. Four infants (67%) showed signs of congenital toxoplasmosis in their first year of life; three (75%) had retinochoroidal scars, and one had cerebral calcifications. Two infants remained asymptomatic until 20 months of age. Conclusions The birth prevalence of congenital toxoplasmosis is high in the Brazilian state of Sergipe, with most of the infants showing ocular lesions. Preventive measures are strongly warranted.