Functional central nervous system myelin repair in an adult mouse model of demyelination caused by proteolipid protein overexpression

Two types of interventions to remyelinate the adult demyelinated central nervous system were investigated in heterozygous transgenic mice overexpressing the proteolipid protein gene. 1) A cocktail of trophic factors, “TS1,” was directed toward the activation of the endogenous pool of neural progenitors to increase the number of myelinating oligodendrocytes (OL) in the brain. 2) A combinatorial approach in which OL progenitors were coinjected with TS1 into the corpus callosum of wild‐type and He4e transgenic mice that displayed hindlimb paralysis. The levels of locomotor ability in these mice were evaluated after a single treatment. The data showed that a single administration of either one of the interventions had similar therapeutic effects, alleviating the symptoms of demyelination and leading to the recovery of hindlimb function. Histological and immunofluorescent examination of brain sections showed extensive remyelination that was sufficient to reverse hindlimb paralysis in transgenic mice. When the interventions were administered prior to hindlimb paralysis, He4e mice were able to walk up to 1 year of age without paralysis. © 2010 Wiley‐Liss, Inc.     

Nerve growth factor increases the sensitivity to zinc toxicity and induces cell cycle arrest in PC12 cells

Zinc is a basic trace element that plays important roles in brain and, consequently, its homeostasis needs to be critically controlled. High zinc concentrations in the interneuron synaptic space may induce neuronal death through mechanisms still partially solved. Undifferentiated pheochromocytoma (PC12) cells have been used to study zinc toxicity. As these cells can be differentiated into neuronal-like cells, the results obtained from differentiated cultures are more useful to understand zinc toxicity in neurons. In this paper, we show by flow cytometry that nerve growth factor (NGF) induces PC12 cells differentiation characterized by cell cycle arrest in the G1/G0 phase, similarly to that observed in serum-deprived cultures. Zinc induces cell death in NGF-differentiated PC12 cultures with an EC₅₀ value of 143 ± 14 μM, which reveals a higher sensitivity with respect to undifferentiated PC12 cultures (EC₅₀, 308 ± 32 μM) and a similar response to that obtained in hippocampal neurons (134 ± 12 μM). Thus, the differentiation process appeared responsible for such increase in sensitivity. To further support this tenet, when the NGF differentiation was impaired in presence of 10 μM MK-801, a selective blocker of the N-methyl-d-aspartate (NMDA) receptor that plays a role in the differentiation process, the higher sensitivity to zinc was reverted to an EC₅₀ value of 241 ± 26 μM. Flow cytometry experiments showed that NGF-differentiated PC12 cells in presence of zinc were positive for propidium iodide but not for annexin-V labeling. These results, together with data from fluorescent labeling of nuclear fragmentation, caspase-3 activation, and reactive oxygen species generation, support the view that zinc toxicity in NGF-differentiated PC12 cells takes place mainly through a necrotic process.     

Fungal infection by Paracoccidioides brasiliensis mimicking bone tumor

Paracoccidioides brasiliensis infection causes a systemic mycosis originally described in Latin America but with current reports of worldwide distribution. The clinical presentation of paracoccidiodomycosis as an isolated long-bone lesion in children is quite unusual. This article describes a 10-year-old male with a lytic femoral bone lesion caused by P. brasiliensis infection that was first suspected of being of neoplasic etiology. The text also emphasizes the importance of including endemic fungal infections in the differential diagnosis of bone lesions.     

A comparison of the Fujita classification of awake and drug-induced sleep endoscopy patients

Only a few studies have compared the outcomes of patients kept awake during endoscopic examination and subjects submitted to drug-induced sleep endoscopy.ObjectiveThis study aimed to compare the endoscopic findings of patients submitted to outpatient endoscopy and endoscopic examination with sedation by propofol based on the Fujita Classification.MethodThis cross-sectional cohort study enrolled 34 patients. The subjects underwent ENT examination, nasal endoscopy with Müller's maneuver, and drug-induced sleep endoscopy with propofol. The Fujita Classification was used to compare the two modes of endoscopic examination. The examinations were correlated to patient clinical data such as BMI, age, and OSAS severity.ResultsThere was no agreement between the two modes of endoscopic examination, whether for the group in general or for the analyzed subgroups.ConclusionThere was no agreement between the endoscopic findings of endoscopic examinations done with the patient awake or in drug-induced sleep.     

Migration and HIV risk: life histories of Mexican-born men living with HIV in North Carolina

Latino men in the Southeastern USA are disproportionately affected by HIV, but little is known about how the migration process influences HIV-related risk. In North Carolina, a relatively new immigrant destination, Latino men are predominantly young and from Mexico. We conducted 31 iterative life history interviews with 15 Mexican-born men living with HIV. We used holistic content narrative analysis methods to examine HIV vulnerability in the context of migration and to identify important turning points. Major themes included the prominence of traumatic early-life experiences, migration as an ongoing process rather than a finite event, and HIV diagnosis as a final turning point in migration trajectories. Findings provide a nuanced understanding of HIV vulnerability throughout the migration process and have implications including the need for bi-national HIV-prevention approaches, improved outreach around early testing and linkage to care, and attention to mental health.     

In vitro penetration of bleaching agents into the pulp chamber

AIM: To investigate pulp chamber penetration of bleaching agents in teeth following restorative procedures. METHODOLOGY: Bovine lateral incisors were sectioned 3 mm apical to the cemento-enamel junction and the coronal pulpal tissue was removed. Teeth were divided into six groups (n = 10): G1, G2 and G3 were not submitted to any restorative procedure, while G4, G5 and G6 were submitted to Class V preparations and restored with composite resin. Acetate buffer was placed in the pulp chamber and treatment agents were applied for 60 min at 37 degrees C as follows: G1 and G4, immersion into distilled water; G2 and G5, 10% carbamide peroxide (CP) exposure; G3 and G6, 35% CP bleaching. The buffer solution was removed and transferred to a glass tube where leuco crystal violet and horseradish peroxidase were added, producing a blue solution. The optical density of the blue solution was determined spectrophotometrically at 596 nm. A standard curve made with known amounts of hydrogen peroxide was used to convert the optical density values of the coloured samples into microgram equivalents of hydrogen peroxide. Data were submitted to anova and Tukey's test (5%). RESULTS: Amounts of hydrogen peroxide found in the pulp chamber of G2 and G5 specimens (0.1833 +/- 0.2003 micro g) were significantly lower (P = 0.001) when compared to G3 and G6 specimens (0.4604 +/- 0.3981 micro g). Restored teeth held significantly higher (P = 0.001) hydrogen peroxide concentrations in the pulp chamber than intact teeth. CONCLUSION: Higher concentrations of the bleaching agent produced higher levels of hydrogen peroxide in the pulp chamber, especially in restored teeth.