Grey zone amyloid burden affects memory function: the SCIENCe project.

PURPOSE: To determine thresholds for amyloid beta pathology and evaluate associations with longitudinal memory performance with the aim to identify a grey zone of early amyloid beta accumulation and investigate its clinical relevance. METHODS: We included 162 cognitively normal participants with subjective cognitive decline from the SCIENCe cohort (64 ± 8 years, 38% F, MMSE 29 ± 1). Each underwent a dynamic [18F] florbetapir PET scan, a T1-weighted MRI scan and longitudinal memory assessments (RAVLT delayed recall, n = 655 examinations). PET scans were visually assessed as amyloid positive/negative. Additionally, we calculated the mean binding potential (BPND) and standardized uptake value ratio (SUVr50-70) for an a priori defined composite region of interest. We determined six amyloid positivity thresholds using various data-driven methods (resulting thresholds: BPND 0.19/0.23/0.29; SUVr 1.28/1.34/1.43). We used Cohen's kappa to analyse concordance between thresholds and visual assessment. Next, we used quantiles to divide the sample into two to five subgroups of equal numbers (median, tertiles, quartiles, quintiles), and operationalized a grey zone as the range between the thresholds (0.19-0.29 BPND/1.28-1.43 SUVr). We used linear mixed models to determine associations between thresholds and memory slope. RESULTS: As determined by visual assessment, 24% of 162 individuals were amyloid positive. Concordance with visual assessment was comparable but slightly higher for BPND thresholds (range kappa 0.65-0.70 versus 0.60-0.63). All thresholds predicted memory decline (range beta - 0.29 to - 0.21, all p < 0.05). Analyses in subgroups showed memory slopes gradually became steeper with higher amyloid load (all p for trend < 0.05). Participants with a low amyloid burden benefited from a practice effect (i.e. increase in memory), whilst high amyloid burden was associated with memory decline. Memory slopes of individuals in the grey zone were intermediate. CONCLUSION: We provide evidence that not only high but also grey zone amyloid burden subtly impacts memory function. Therefore, in case a binary classification is required, we suggest using a relatively low threshold which includes grey zone amyloid pathology.

The -31 G/C promoter gene polymorphism of surviving in Turkish colorectal cancers patients

Introduction: Survivin (also known as birc5) is the first protein discovered among the apoptosis-regulating gene family referred to as inhibitor of apoptosis proteins (IAPs). It is expressed and controlled during cellular differentiation and development in human beings. Survivin expression has been shown in a number of cancers and has been associated with cancer development. Objective: In our study, we compared with blood samples as our control and normal- tumoural tissue samples, which obtained from the same tissue of 100 cases diagnosed with colorectal cancer, at Department of Pathology, Istanbul University. Methods: The present study employed PCR-RFLP to identify the -31 G/C polymorphism in the promoter region of the survivin gene. Distribution of the survivin polymorphism was compared between control and tumoural tissue samples using the chi-square test. Results: Comparison of all samples revealed that there was significant difference in distribution of survivin promoter -31G/C between control group and tumour and normal tissue of the patient group (p<0.05). When genotypes of the control and tumour tissues were compared according to gender, there was no statistically significant difference in the distribution of survivin promoter -31G/C in females p=0.420 or males p=0.309. Conclusion: A significant difference was seen in distribution of C allele in tumour tissue compared to normal tissue.

Mutation detection in the promoter region of survivin gene on N-methyl-N-nitrosourea induced colon tumor model in experiment.

Survivin (also known as BIRC5) is one of the first reported inhibitors of apoptosis proteins (IAPs), which is an important family of proteins that regulate apoptosis. It is developmentally regulated and expressed during cell differentiation in humans, mice and rat. Survivin is expressed in a series of human cancers and it has been widely accepted that survivin is strongly related to the onset and development of cancer. In the present study, we tried to determine differences in the promoter region of survivin gene in colon tissue samples from N-methyl-N-nitrosourea (MNU) induced rat colon tumor model and control group. Polymerase chain reaction (PCR) - single strand conformation polymorphism (SSCP) analysis was used for this aim. No significant differences were found in the promoter region of survivin gene between the normal and tumor tissues (Tab. 2, Fig. 1, Ref. 16).

The 50 Hz (10 mT) sinusoidal magnetic field: effects on stress-related behavior of rats.

PURPOSE: The purpose of this study was to investigate the behavioral changes induced by 50 Hz, 10 mT flux density Sinusoidal Magnetic Field (MF). MATERIAL AND METHODS: Seventy-six young adult male Wistar albino rats were used in the study. They were separated into two groups: control group (C) n=38; MF group n=38. C animals were left under the same conditions with the MF group for 21 days but with prevented or avoided exposure to MF. Anxiety and stress-related behavioral changes were investigated by elevated plus-maze and hole-board systems. Just before being tested in the maze, each animal was tested by means of the hole-board method in order to separate the directed exploration behavior and locomotion activity changes from anxiety-related behavior. RESULTS: In the hole-board system parameters there were no statistically significant differences between the two groups. There was a statistically significant difference between MF and C groups when the ratio of time spent on open arms to the total time spent on all arms was evaluated (0.12±0.08 and 0.34±0.18 respectively and p <0.01). CONCLUSION: Our results suggest that after 21 days, a continuous exposure to extremely low frequency of magnetic field (50 Hz, 10 mT) has no significant effect on activity and exploration activity but significantly induces stress and anxiety-related behavior in rats (Tab. 2, Fig. 9, Ref. 19).

Tau PET and relative cerebral blood flow in dementia with Lewy bodies: A PET study.

PURPOSE: Alpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. METHODS: Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. RESULTS: Regional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stß = 0.72) and category fluency (stß = 0.69) tests. Lower parietal R1 was related to lower delayed (stß = 0.50) and immediate (stß = 0.48) recall, VOSP number location (stß = 0.70) and fragmented letters (stß = 0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stß = 0.61), all p < 0.05. CONCLUSION: The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.

Hypoglycemic activity of Urtica pilulifera in streptozotocin-diabetic rats.

The hypoglycemic activity of lectin isolated from Urtica pilulifera L. seeds (Urticaceae) was investigated in streptozotocin (STZ) induced diabetic rats. Significant hypoglycemic effect was found at the dose of 100 mg/kg after i.p. administration for 30 days. Blood glucose (BG) level, food and fluid intake, body weight (BW) loss and histopathologic findings of the normal and diabetic animals were evaluated. The group treated with UPSL (U. pilulifera seed lectin) was also compared against glipizide (oral antidiabetic agent, Carlo-Erba) as a standard.