Specificity of the anti-glycolytic activity of 3-bromopyruvate confirmed by FDG uptake in a rat model of breast cancer

Summary   Purpose: To evaluate the anti-glycolytic effects of 3-BrPA on rats bearing RMT mammary tumors, by determining FDG uptake after intravenous administration of the therapeutic dose. Materials and Methods: Sixteen rats bearing RMT tumors were treated either with 15 mM 3-BrPA in 2.5 ml of PBS or with 2.5 ml of PBS. After treatment, all rats received FDG and were sacrificed 1 h later. Results: 3-BrPA treatment significantly decreased FDG uptake in tumors by 77% (p = 0.002). FDG uptake did not significantly decrease in normal tissues after treatment. Conclusion: Our study showed that 3-BrPA exhibits a strong anti-glycolytic effect on RMT cells implanted in rats. Buijs and Vossen contributed equally to this work.     

Tau protein, phosphorylated tau protein, and beta-amyloid 42 levels in patients with neurodegenerative diseases complicated by cognitive deficits A non-randomized, concurrent, case-control investigation

BACKGROUND： The differential diagnosis of many neurodegenerative disorders depends primarily on clinical symptoms together with imaging methods. Recently, increased importance has been placed on the use of biomarkers for diagnosing various neurodegenerative disorders. OBJECTIVE： To assess the feasibility of tau-protein, phosphorylated tau-protein, beta-amyloid 42 （Aβ42）, and 14-3-3 protein as biomarkers for diagnosing several neurodegenerative diseases complicated by cognitive deficits. DESIGN, TIME AND SETTING： A non-randomized, concurrent, case-control investigation was performed in three medical centers in the Czech Republic （Department of Neurology at the University Hospital in Hradec Kralove, Department of Neurology at the 2rd Medical Faculty, and the University Hospital Motol） between October 2000 and November 2006. PARTICIPANTS： Eighteen patients with probable AIzheimer＇s disease, 4 patients with Creutzfeldt-Jakob disease, 10 patients with frontotemporal dementia, 9 patients with clinically isolated syndrome suggestive of multiple sclerosis, and 7 patients with multiple sclerosis, as well as 38 race-, nationality-, and age-matched cognitively intact controls, were included in the study. Diagnoses were established based on the following criteria： the criteria for Alzheimer＇s disease proposed by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer＇s Disease and Related Disorders Association, WHO criteria for Creutzfeldt-Jakob disease, Neary criteria for frontotemporal dementia, and McDonald＇s criteria for multiple sclerosis. All included patients were confirmed to suffer from various degrees of dementia. METHODS： Enzyme-linked immunosorbent assay was used to measure concentrations of tau-protein, phosphorylated tau-protein, and Aβ42 in cerebrospinal fluid （CSF） samples collected by standard lumbar puncture from each patient. Moreover, 14-3-3 protein was assessed by Western blot in CSF of Creutzfeldt-Jakob disease patients. Cognitive status was assessed using the Mini Mental Scale Examination （MMSE） in all subjects. MAIN OUTCOME MEASURES： Establishment of biomarkers with greatest specificity and sensitivity for the investigated disorders according to Receiver Operating Characteristic curves, which were based on values from patients and controls; correlation between concentrations of given biomarkers and demographic parameters, diagnosis, duration of disease, and level of cognitive deficit. RESULTS： Increased concentrations of total tau protein and phosphorylated tau protein, and decreased levels of Aβ42, in CSF of Alzheimer＇s disease patients reached the required sensitivity/specificity ratio of 80% or greater. A marked elevation in CSF concentrations of total tau protein showed even greater sensitivity than 14-3-3 protein in Creutzfeldt-Jakob disease. There was no association between selected biomarkers and frontotemporal dementia or multiple sclerosis. Phosphorylated tau-protein was the only biomarker that noticeably correlated with MMSE scores for Alzheimer＇s disease.CONCLUSION： Levels of total tau protein, phosphorylated tau protein, and A!342 in the CSF could differentiate patients with Alzheimer＇s disease and Creutzfeldt-Jakob disease from healthy controls and patients with other neurodegenerative disorders. The diversity of absolute values demonstrates the necessity to establish a specific standard for each laboratory.     

Psychometric properties of the Persian version of the Questionnaire of Cognitive Schema Activation in Sexual Context (QCSASC) in unsuccessful sexual situations

The aim of this study was to translate and adapt to Persian, and to assess psychometric properties of the Questionnaire of Cognitive Schema Activation in Sexual Context (QCSASC). A total of 265 Iranian participants (121 women and 144 men) were recruited for this study. A principal component analysis (PCA) with varimax rotation and subsequent confirmatory factor analysis revealed a best fitting five-factor structure similar to the original QCSASC: Incompetence, Undesirability, Abandon/Rejection, Powerless/Helpless, and Difference. However, in the Iranian sample, the original Self-Depreciation dimension was included in the Incompetence and Undesirability factors. An Abandon/Rejection dimension was also evident, and may be explained by cultural, social, and religious factors in the Iranian culture. Additionally, reliability analysis has supported the internal consistency (adequate Cronbach's alpha values) and temporal stability (test–retest reliability) of the QCSASC in an Iranian sample. The findings suggest the adequacy of the Persian version of the QCSASC to assess cognitive schemas in sexual context among Iranian men and women.     

Molecular and cellular biomarkers for field cancerization and multistep process in head and neck tumorigenesis

Summary One way to explain the development of head and neck cancer is through the theories of field cancerization, i.e., the exposure of an entire field of tissue to repeated carcinogenic insult, and multistep process, i.e., development of multiple cancers in a predisposed field through a series of recognizable states. Recent molecular genetic studies of histologically normal and prealignant epithelia of high-risk subjects and studies of malignant tumors in aerodigestive tract epithelia have identified a continuum of accumulated specific genetic alterations that possibly occur during the clonal evolution of tumors, namely, during the multistep process. Second primary or multiple primary tumors arise in the same fields as independent clones, with similar but unique molecular genetic and/or cellular alterations. Consequently, the assessment of these genetic and phenotypic alterations has been integrated into clinical chemoprevention trials in an effort to identify biomarkers that are also risk predictors and intermediate end points. This review covers candidate biomarkers of the processes of field cancerization and multistep tumor development in aerodigestive tract epithelia, including general and specific genetic markers, proliferation markers, and squamous differentiation markers.     

Interconvertibility of asbestos fibre count concentrations recorded by three most frequent methods.

Simultaneous airborne chrysotile asbestos fibre samples were collected with three types of instruments, namely, the konimeter, the thermal precipitator and the membrane filter, in four asbestos plants (textile manufacturing, asbestos cement production, mining, milling). Linear regression analyses were performed of the membrane filter on the konimeter and thermal precipitator count concentrations, respectively. Sampling was performed at 24-35 locations in each of the processes studied. In order to linearize the relationships and to stabilize the sample variances the data were transformed using the transformation ln(x+1) for both the predictor and the response variables. Eight linear regression equations were developed. The slope coefficients of regressions differed significantly (P < 0.05 or < 0.01) between all the asbestos processes except for the differences of coefficients in mining and milling (P > 0.05). It is concluded that no single conversion factor can be used to reliably convert the konimeter or thermal precipitator to membrane filter asbestos fibre concentrations; a separate conversion factor must be derived for each technological process. In this case the confidence limits of estimates are acceptable for practical occupational hygiene purposes.     

Cellular and molecular interactions between MC3T3-E1 pre-osteoblasts and nanostructured titanium produced by high-pressure torsion

Ultra-fine surface features are commonly used to modulate cellular activity on a variety of materials. The continuing challenge for materials in contact with bone is the development of a material with both favorable surface and bulk properties to modulate not only the cell-substrate interactions, but also to ensure the long-term stability of the implant. In a combined approach involving material sciences and cell and molecular biology, the nature and mechanism of cell-substrate interaction, in particular, the molecular machinery controlling cell response to the surface of the nanostructured titanium based material produced by the high pressure torsion (HPT) process is assessed. The degree of pre-osteoblast attachment and rate of growth, which are regulated through the activity and interaction of proteins present in the extracellular matrix and associated with cytoskeleton and focal adhesion, are notably increased on the HPT-processed titanium substrates. The improved cell activity is attributed to the nanostructured feature of these substrates consisting of ultra-fine crystals (<50 nm) and a distinct surface oxide layer which provide higher degree of surface wettability. These findings demonstrate the advantages of HPT-processed titanium over the conventional and coated titanium implants, as both mechanical properties and cellular response are improved.     

Spontaneous Tumor Regression in a Syngeneic Rat Model of Liver Cancer: Implications for Survival Studies

PurposeTo characterize tumor growth of N1S1 cells implanted into the liver of Sprague–Dawley rats to determine if this model could be used for survival studies. These results were compared with tumor growth after implantation with McA-RH7777 cells.Materials and MethodsN1S1 or McA-RH7777 cells were implanted into the liver of Sprague–Dawley rats (n = 20 and n = 12, respectively) using ultrasound (US) guidance, and tumor growth was followed by using US. Serum profiles of 19 cytokines were compared in naive versus tumor-bearing rats.ResultsBoth types of tumors were visible on US 1 week after tumor implantation, but the mean tumor volume of N1S1 tumors was larger compared to McA-RH7777 tumors (231 mm³ vs 82.3 mm³, respectively). Tumor volumes in both groups continued to increase, reaching means of 289 mm³ and 160 mm³ in N1S1 and McA-RH7777 groups, respectively, 2 weeks after tumor implantation. By week 3, tumor volumes had decreased considerably, and six tumors (50%) in the McA-RH7777 had spontaneously regressed, versus two (10%) in the N1S1 group. Tumor volumes continued to decrease over the following 3 weeks, and complete tumor regression of all tumors was seen 5 weeks and 6 weeks after tumor implantation in the McA-RH7777 and N1S1 groups, respectively. In an N1S1-implanted rat, multiple cytokines that have been shown to correlate with the ability of the tumor to survive in a hostile environment were increased by as much as 50%, whereas the average increase in cytokine levels was 90%. These findings suggest that the net cytokine environment favors an antitumor immune response. A similar trend was observed in a rat with a McA-RH7777 tumor, and the increase in cytokine levels was considerably more pronounced, with an average increase of 320%.ConclusionsThe model of N1S1 cell implantation in the liver of Sprague–Dawley rats is not ideal for survival studies and should only be used with great caution in short-term studies that involve cancer therapies.     

Lung function in textile workers.

Acute changes in ventilatory function during a workshift with exposure to hemp, flax, and cotton dust were measured on Mondays in a group of 61 textile workers, all working on carding machines. In addition, single-breath diffusing capacity (DLCOSB) was measured before dust exposure on Monday in 30 of the 61 workers. Large acute reductions during dust exposure were recorded in maximum expiratory flow rate at 50% VC (MEF50%), ranging from 38 to 22%. Acute reductions of FEV1-0 were considerably smaller, ranging from 17 to 9%. There was a statistically significant increase in residual volume (RV) with very small and insignificant changes in total lung capacity (TLC). Although preshift FEV1-0 and FVC were decreased, DLCOSB was within normal limits. Plethysmographic measurements in six healthy volunteers exposed to hemp-dust extract confirmed the results obtained in textile workers, that is, that TLC does not change significantly during dust-induced airway constriction and that maximum expiratory flow rate at 50% VC (MEF50%) is a more sensitive test than FEV1-0 in detecting acute ventilatory changes caused by the dust extract.