GSK-3β in cerebrospinal fluid of schizophrenia patients

Summary. Cerebrospinal fluid contains proteins and metabolites of brain origin and was extensively studied in psychiatry in the 1970s with few definitive results. We have recently found 40% reduced protein levels of GSK-3 in schizophrenia in postmortem prefrontal cortex, but our attempt to develop a diagnostic marker using peripheral lymphocyte GSK-3 was not successful. In this study we aimed to find whether the reduction in brain GSK-3 is reflected in CSF of schizophrenia patients. We report a significant reduction in CSF GSK-3 protein levels in six schizophrenia patients compared to seventeen healthy subjects. Our results corroborate other studies in which CSF protein levels reflect the alteration found in these proteins in schizophrenia patients postmortem brain.     

Glycogen synthase kinase (GSK)-3beta levels and activity in a neurodevelopmental rat model of schizophrenia

We have previously reported reduced GSK-3beta protein levels and GSK-3 total (alpha + beta isoforms) activity in postmortem frontal cortex of schizophrenic patients. We now studied whether GSK-3beta is altered in the frontal cortex of rats with the neonatal excitotoxic hippocampal lesion used as a model of schizophrenia. Rats were infused with ibotenic acid (or artificial CSF in controls) bilaterally into the ventral hippocampus (VH) at postnatal day 7, then killed at postnatal day 35 (pre-puberty) or 56 (post-puberty). GSK-3beta protein levels were reduced in the frontal cortex of the lesioned rats as compared to sham animals; post-hoc comparisons revealed that the reduction was statistically significant at a pre-pubertal age. Total GSK-3 (alpha + beta) activity was not different between lesioned and sham rats at any age. These results demonstrate that reduced frontal cortical GSK-3beta levels may occur as a result of neonatal hippocampal damage and suggest that this animal model may be utilized to study the mechanism of GSK-3 reduction in schizophrenia, a disorder in which postmortem changes in GSK-3 were found.     

Low GSK-3 activity in frontal cortex of schizophrenic patients

Glycogen synthase kinase-3 (GSK-3) (EC 2.7.1.37) is a protein kinase highly abundant in brain and involved in signal transduction cascades of multiple cellular processes, particularly neurodevelopment. Two forms of the enzyme, GSK-3alpha and -3beta have been previously identified. We have previously reported reduced GSK-3beta protein levels in postmortem frontal cortex of schizophrenic patients. In an attempt to explore whether reduction of GSK-3beta levels is brain region specific we examined it in occipital cortex. In order to find out if the reduction in frontal cortex is reflected in altered activity we measured GSK-3 enzymatic activity in this brain region. Western-blot analysis of GSK-3beta was carried out in postmortem occipital cortex of 15 schizophrenic, 15 bipolar, and 15 unipolar patients, and 15 normal controls. GSK-3 activity was measured by quantitating the phosphorylation of the specific substrate phospho-CREB in the frontal cortex specimens. GSK-3beta levels in occipital cortex did not differ between the four diagnostic groups. GSK-3 activity in the frontal cortex of schizophrenic patients was 45% lower than that of normal controls (0.196+/-0.082 and 0.357+/-0.084 pmol/mg proteinxmin, respectively; Kruskal-Wallis analysis: chi-square=8.27, df=3, p=0.04). The other two diagnostic groups showed no difference from the control group. Our results are consistent with the notion that schizophrenia involves neurodevelopmental pathology.     

Spontaneous early exposure of submerged endosseous implants resulting in crestal bone loss: a clinical evaluation between stage I and stage II surgery

Spontaneous early exposure of submerged implants during the osseointegration healing phase may be a harmful factor that results in early crestal bone loss around the implants. The objective of this study was to assess the effect of spontaneous early exposure on crestal bone loss around submerged implants, with special attention given to the relationship between the degree of exposure and the amount of peri-implant bone loss. Crestal bone level relative to the shoulder of the implant was measured at the time of placement and at the time of exposure 4 to 5 months later. During the period between stage I and stage II surgery, implant sites were observed, and each implant site in which spontaneous early exposure was detected was recorded. Perforations were classified according to the degree of implant exposure from Class 0 (no perforation) to Class IV (complete exposure). Measurements from 206 implants in 64 patients produced 85 groups valid for statistical comparison; each of these contained at least 2 lesions of different types. There was a statistically significant difference between bone loss associated with intact mucosa (Class 0) and Class I, Class II, and Class III lesions, and between Class I and II lesions. There were no significant differences between Class I and III and between Class II and III. In Class II and III lesions, there was more bone loss associated with the buccal aspect of the implants. Of the 115 perforated sites, 10 were associated with bone loss exceeding 2 mm, 2 presented 3 to 4 mm bone loss, 1 showed more than 4 mm, and 1 displayed more than 5 mm. In view of the clinical implications that spontaneous early exposure may have on the success of osseointegration, prematurely partially exposed implants should be exposed as soon as possible after the perforation is observed.     

Spatial distribution of abnormal EEG activity in Creutzfeldt-Jakob disease

ObjectivesElectroencephalogram (EEG) pattern in Creutzfeldt-Jakob disease (CJD) is characterized by diffuse abnormal activity, although lateralization to one hemisphere has been described in the first stages of the disease. This study aimed to determine whether abnormal EEG activity predominantly occurs in anterior versus posterior brain regions.MethodsAs part of a prospective study, the demographics, clinical features and MRI findings of genetic E200K CJD patients were collected. EEG was performed and the recordings reviewed for the typical periodic sharp wave complex (PSWC) and non-specific slow activity. Data were analyzed using the qEEG tool, and the activity in anterior and posterior regions of the brain compared.ResultsEleven genetic E200K CJD patients were included in the study (67% women). The average age was 59.1 ± 8.4 SD years and the average disease duration was 2.4 ± 2.1 months. EEG showed the classic PSWC pattern in 5/11 (45%) of the patients, and slow activity was seen in 9/11 (82%). EEG was normal in 2 patients. PSWC activity was diffuse in 2/5 patients and unilateral in 3/5 patients; slow activity was diffuse in 9 patients. Quantitative analysis of PSWC and slow activity showed no significant difference between anterior and posterior distribution.ConclusionThe abnormal EEG activity in CJD is diffuse with no clear spatial predominance in anterior or posterior brain regions.     

Mental health status among younger generation around Chernobyl

Introduction

In order to improve our understanding of how to approach the younger generation around Chernobyl, we screened mental health status among young adults born after the accident living in the Gomel region, Belarus.

Material and methods

We enrolled 697 medical students who were born after the accident. Participants were asked to answer self-administered questionnaires including the General Health Questionnaire (GHQ-12).

Results

GHQ-12 scores were 1.80 ±2.28 (mean ± SD) among all 697 subjects. When logistic regression analysis was performed with confounding factors, “economic situation” and “association of diseases and/or poor health condition with radiation exposure” were significantly associated with poor mental status.

Conclusions

Our findings suggest that anxiety about radiation exposure among highly educated medical students in the Gomel region, although they were born after the accident, affects their poor mental health status.     

The effect of meal-feeding and food restriction on body composition, food utilization and intestinal adaptation in light-breed chicks

The effects of feeding meals, in amounts equivalent to ad lib, intake or to 75% and 50% restriction by intubation, were studied in chicks. Growth estimated by body-weight gain and shank length was improved by tube feeding in the 50%-restricted chicks. Tube feeding increased energy retention at all feeding levels and nitrogen retention in the restricted chicks only. Body fat was increased in the full-fed chicks by intubation and decreased in the 50%-restricted chicks only. Crop and gizzard weights were increased by food restriction and by intubation. Tube-feeding increased the weight of the small intestine at all feeding levels. The activities of the digestive enzymes were lower in the pancreas and higher in the small intestine of the tube-fed chicks than in the voluntarily-fed ones at all feeding levels. It is suggested that synthesis, secretion and stability of the different pancreatic enzymes could be affected diversely by feeding regimens.