Raman spectroscopy as a detection and analysis tool for in vitro specific targeting of pancreatic cancer cells by EGF-conjugated, single-walled carbon nanotubes

Single-walled carbon nanotubes (SWCNTs) were covalently linked to epidermal growth factor (EGF) proteins through an esterification process that was found to be responsible for the docking of SWCNTs on the human pancreatic cancer cells (PANC-1) surface, thus providing a mechanism for the enhanced delivery and internalization of the nanotubes. Micro Raman spectroscopy and enzyme-linked immunosorbent assay were used to evaluate the delivery process and kinetics of the SWCNTs. In vitro studies indicated that the delivery kinetics of SWCNT-EGF conjugates, at a concentration of 85 μg ml(-1), to the PANC-1 cell surfaces was significant in the first 30 min of incubation, but reached a plateau with time in accordance with the establishment of equilibrium between the association and the dissociation of EGF with the cell receptors. SWCNT-EGF conjugates could act as strong thermal ablation agents and could induce higher percentages of cellular death compared with the nontargeted SWCNTs alone.     

Temporal scaling properties and spatial synchronization of spontaneous blood oxygenation level‐dependent (BOLD) signal fluctuations in rat sensorimotor network at different levels of isoflurane anesthesia

Spontaneous fluctuations in the blood oxygenation level‐dependent (BOLD) MRI signal during the resting state are increasingly being studied in healthy and diseased brain in humans and animal models. Yet, the relationship between functional brain status and the characteristics of spontaneous BOLD fluctuations remains poorly understood. In order to obtain more insights into this relationship and, in particular, the effects of anesthesia thereupon, we investigated the spatial and temporal correlations of spontaneous BOLD fluctuations in somatosensory and motor regions of rat brain at different inhalation levels of the frequently applied anesthetic isoflurane. We found that the temporal scaling, characterized by the Hurst exponent (H), showed persistent behavior (H > 0.5) at 0.5–1.0% isoflurane. Furthermore, low‐pass‐filtered spontaneous BOLD oscillations were correlated significantly in bilateral somatosensory and bilateral motor cortices, reflective of interhemispheric functional connectivity. Under 2.9% isoflurane anesthesia, the temporal scaling characteristics approached those of Gaussian white noise (H = 0.5), the relative amplitude of BOLD low‐frequency fluctuations declined, and cross‐correlations of these oscillations between functionally connected regions decreased significantly. Loss of interhemispheric functional connectivity at 2.9% isoflurane anesthesia was stronger between bilateral motor regions than between bilateral somatosensory regions, which points to distinct effects of anesthesia on differentially organized neuronal networks. Although we cannot completely rule out a possible contribution from hemodynamic signals with a non‐neuronal origin, our results emphasize that spatiotemporal characteristics of spontaneous BOLD fluctuations are related to the brain's specific functional status and network organization, and demonstrate that these are largely preserved under light to mild anesthesia with isoflurane. Copyright © 2010 John Wiley & Sons, Ltd.     

Preventive effects of letrozole in the model of premenopausal mammary carcinogenesis

Single - agent therapy with aromatase inhibitors has no established role in premenopausal women with breast cancer. In this study, tumor suppressive effects of letrozole in the prevention of N-methyl-N-nitrosourea - induced mammary carcinogenesis in female Sprague-Dawley rats were evaluated. Letrozole was dietary administered in two concentrations - 1 mg/1 kg (LETRO 1), and 10 mg/1 kg (LETRO 10). Letrozole suppressed incidence of mammary gland cancer by 93 % (P<0.00002) in the group LETRO 1 in comparison with control animals. Total suppression of mammary carcinogenesis was observed in the group LETRO 10. In the groups with letrozole, uterine and vaginal atrophy was found at the end of experiment. In letrozole - treated animals in comparison with untreated animals, increased plasmatic triacylglycerol concentrations (P<0.0001) were observed, but total cholesterol and cholesterol of low- and high- density lipoprotein fractions were not significantly changed. An increase in body weight gain and food intake was found in the groups LETRO 1 and LETRO 10 compared with the control group (P<0.0001). The present study points to high tumor suppressive effects of letrozole in premenopausal model of mammary carcinogenesis in female rats.     

Metabolic Effects of Pioglitazone in Chemically-Induced Mammary Carcinogenesis in Rats

In this paper, the effect of peroral antidiabetic pioglitazone, a thiazolidinedione derivate, on selected parameters of carbohydrate and lipid metabolism in N-methyl-N-nitrosourea-induced mammary carcinogenesis in female Sprague-Dawley rats was evaluated. Pioglitazone was administered in the diet at two concentrations (10?ppm and 100?ppm), the chemoprevention was initiated 12?days before carcinogenesis induction and lasted until the termination of the experiment. The experiment was terminated 17?weeks after carcinogenesis induction, selected organs and tissues were removed and weighed and basic metabolic and hormonal parameters were determined. Pioglitazone increased glycemia (without exceeding normal values) and glycogen concentration in both liver and heart muscle without altering insulinemia and increased triacylglycerol concentration in liver, these changes were more prominent in group with higher dose. Pioglitazone also reduced corticosterone serum concentration and attenuated lipid peroxidation. Pioglitazone and other glitazones may be useful in alleviation of unfavourable metabolic changes in cancer patients.     

A validation study of the Italian Short-Form Leeds Dyspepsia Questionnaire

Assessment of symptoms should be one of the main outcome measures in dyspepsia clinical trials. This requires a reliable, valid and responsive questionnaire that measures the frequency and severity of dyspeptic symptoms. The Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) has been proven to fulfil these criteria in its original version in the English language. The aim of the study was to assess the internal consistency, reliability, validity and responsiveness of the Italian version of the SF-LDQ in primary and secondary care. Unselected primary and secondary care patients completed the Italian version of the SF-LDQ. Test–retest reliability was assessed after 2 days. Validity was measured by comparison with diagnosis made by physicians. Responsiveness was determined before and after treatment for endoscopically proven disease. The SF-LDQ was administered to 311 patients in primary care and 179 in secondary care patients. Internal consistency, as judged by the Cronbach’s α, was 0.90. Pearson’s correlation coefficient for test–retest reliability was 0.92. The SF-LDQ had a sensitivity of 80% and a specificity of 82%. A highly significant response to change was also observed (p = 0.001). The Italian SF-LDQ is a reliable, valid and responsive self-completed outcome measure for quantifying the frequency and severity of dyspeptic symptoms.