Cellular responses to protein accumulation involve autophagy and lysosomal enzyme activation

Protein oligomerization and aggregation are key events in age-related neurodegenerative disorders, causing neuronal disturbances including microtubule destabilization, transport failure and loss of synaptic integrity that precede cell death. The abnormal buildup of proteins can overload digestive systems and this, in turn, activates lysosomes in different disease states and stimulates the inducible class of lysosomal protein degradation, macroautophagy. These responses were studied in a hippocampal slice model well known for amyloidogenic species, tau aggregates, and ubiquitinated proteins in response to chloroquine-mediated disruption of degradative processes. Chloroquine was found to cause a pronounced appearance of prelysosomal autophagic vacuoles in pyramidal neurons. The vacuoles and dense bodies were concentrated in the basal pole of neurons and in dystrophic neurites. In hippocampal slice cultures treated with Abeta(142), ultrastructural changes were also induced. Autophagic responses may be an attempt to compensate for protein accumulation, however, they were not sufficient to prevent axonopathy indicated by swellings, transport deficits, and reduced expression of synaptic components. Additional chloroquine effects included activation of cathepsin D and other lysosomal hydrolases. Abeta(142) produced similar lysosomal activation, and the effects of Abeta(142) and chloroquine were not additive, suggesting a common mechanism. Activated levels of cathepsin D were enhanced with the lysosomal modulator Z-Phe-Ala-diazomethylketone (PADK). PADK-mediated lysosomal enhancement corresponded with the restoration of synaptic markers, in association with stabilization of microtubules and transport capability. To show that PADK can modulate the lysosomal system in vivo, IP injections were administered over a 5-day period, resulting in a dose-dependent increase in lysosomal hydrolases. The findings indicate that degradative responses can be modulated to promote synaptic maintenance.     

Information management: considering adolescents' regulation of parental knowledge

Employing Goffman's [(1959). The presentation of self in everyday life. New York: Doubleday and Company] notion of impression management, adolescents' conveyance of information about their whereabouts and activities to parents was assessed employing two methodologies. First, a two-wave panel design with a sample of 121 adolescents was used to test a model of information management incorporating two forms of information regulation (lying and willingness to disclose), adolescents' perception of their parents' knowledge about their activities, and adolescent misconduct. Path analysis was used to examine the model for two forms of misconduct as outcomes: substance use and antisocial behaviours. Fit indices indicate the path models were all good fits to the data. Second, 96 participants' responses to semi-structured questions were analyzed using a qualitative analytic technique. Findings reveal adolescents withhold or divulge information in coordination with their parents, employ impression management techniques, and try to balance safety issues with preservation of the parent-adolescent relationship.     

Gamma-glutamyl transferase (GGT) as an independent predictive factor of sustained virologic response in patients with hepatitis C treated with interferon-alpha and ribavirin

BACKGROUND: Recently, gamma-glutamyl transferase (GGT) has been investigated as a predictive factor for therapy response in hepatitis C patients, but so far its value in pretreatment screening has not been established. Therefore, this study aimed at evaluating GGT as an independent predictive factor for the response to treatment with interferon-alpha and ribavirin in hepatitis C virus (HCV)-infected patients. METHODS: Naive chronic hepatitis C patients undergoing a 6-month follow-up after interferon-alpha and ribavirin therapy had their sustained virologic response (SVR) analyzed according to age, sex, body mass index, GGT levels, genotype, and liver histology by use of a multivariate logistic regression model. RESULTS: Of the 211 patients studied with a mean age of 48+/-10 years, 125 (59%) were males. Overweight was detected in 47% of patients. Genotype 1 was detected in 141 (75%) of the 187 patients tested. Cirrhosis was present in 67 (32%). A high pretreatment GGT level was observed in 134 (63%). SVR was obtained in 84 (40%) patients. In the final logistic regression model, the variables independently associated with SVR were GGT (P<0.001), genotype (P<0.001), and liver histology (P<0.001). CONCLUSION: A normal GGT level is an independent predictive factor for SVR in HCV-infected patients and should be considered for pretreatment screening.     

Use of intraoperative lymphoscintigraphy in doubtful cases of sentinel node detection

Lymphoscintigraphy is a widely accepted method used to detect selectively the sentinel node in malignant melanoma. This is the case report of a patient who was operated on for an inguinal melanoma and who was referred to the Nuclear Medicine Section for preoperative lymphoscintigraphy. There were technical problems for sentinel node detection due to the proximity of injection points. We aimed to know the possibility to perform an intraoperative lymphoscintigraphy as a valid and useful technique in cases as this one.     

Mammography of ductal carcinoma in situ of the breast: review of 909 cases with radiographic-pathologic correlations

We retrospectively analysed mammographies of 909 ductal carcinoma in situ (DCIS) (1980-1999) and compared our results to those of literature. Microcalcifications were present in 75% of the cases, and soft-tissue abnormalities in 27% cases with association with calcifications in 14% of cases. Palpable masses were found in 12% of the cases and nipple discharge was present in 12% of the cases. The radiographic-pathologic correlation allowed to suspect the DCIS "aggressiveness" on radiologic signs. Granular, linear, branching and/or galactophoric topography of the microcalcifications were correlated with necrosis, grade 3, comedocarcinoma type. A number of microcalcifications higher than 20 was correlated with necrosis and grade 3. Mammographic size was correlated to histologic size. Masses were correlated with grade 1. A diagnosis strategy can be proposed with a multidisciplinar approach.     

Orthodontic extrusion anchored in osseointegrated implants: a case report

Rapid orthodontic extrusion is indicated for cases involving biological space invasion of the periodontal ligament in which the surgical increase of the clinical crown can compromise esthetics or the support of the adjacent teeth. This article presents the case report of a tooth with radicular perforation 1.0 mm below the bone crest. A procedure to restore the biological distances was necessary. Rapid orthodontic extrusion of the affected tooth, with anchorage in the adjacent osseointegrated implants, was selected.     

Hormonal cryptorchidism therapy: systematic review with metanalysis of randomized clinical trials

The importance of cryptorchidism treatment concerns the possibility of diminishing risk of malignant degeneration and improving fertility. Success rates of hormonal treatment vary: 0–55% with human chorionic gonadotropin (hCG) and 9–78% with gonadotropin-releasing hormone (GnRH). Due to uncertainties regarding the effectiveness of this treatment, a systematic review and meta-analysis of randomized controlled trials (RCTs) on hormonal cryptorchidism treatment was done using the methodology of Cochrane Collaboration. Two studies compared hCG with GnRH, with a testicular descent rate of 25% vs. 18%, respectively. Nine trials compared intranasal LHRH with placebo, with complete testicular descent rates of 19% vs. 5%. Two other studies comparing doses and administration intervals could not be pooled together due to heterogeneity. With the information analyzed until the present, the evidence for the use of hCG vs. GnRH shows advantages for hCG, and this review also shows that there is evidence that luteinizing hormone releasing hormone (LHRH) is more effective than placebo. But because this evidence is based on few trials, with small sample sizes and moderated risk of bias, this treatment cannot be recommended for everyone, and there is no evidence that supports hCGs use in larger doses and larger intervals. Results from this systematic review are important for developing better RCTs that may decrease the uncertainty of cryptorchidism treatment.