Quantifying Cancer Cell Receptors with Paired-Agent Fluorescent Imaging: a Novel Method to Account for Tissue Optical Property Effects.

Dynamic fluorescence imaging approaches can be used to estimate the concentration of cell surface receptorsin vivo. Kinetic models are used to generate the final estimation by taking the targeted imaging agent concentration as a function of time. However, tissue absorption and scattering properties cause the final readout signal to be on a different scale than the real fluorescent agent concentration. In paired-agent imaging approaches, simultaneous injection of a suitable control imaging agent with a targeted one can account for non-specific uptake and retention of the targeted agent. Additionally, the signal from the control agent can be a normalizing factor to correct for tissue optical property differences. In this study, the kinetic model used for paired-agent imaging analysis (i.e., simplified reference tissue model) is modified and tested in simulation and experimental data in a way that accounts for the scaling correction within the kinetic model fit to the data to ultimately extract an estimate of the targeted biomarker concentration

Correcting for Targeted and Control Agent Signal Differences in Paired-Agent Molecular Imaging of Cancer Cell-Surface Receptors

Paired-agent kinetic modeling protocols provide one means of estimating cancer cell-surface receptors with in vivo molecular imaging. The protocols employ the coadministration of a control imaging agent with one or more targeted imaging agent to account for the nonspecific uptake and retention of the targeted agent. These methods require the targeted and control agent data be converted to equivalent units of concentration, typically requiring specialized equipment and calibration, and/or complex algorithms that raise the barrier to adoption. This work evaluates a kinetic model capable of correcting for targeted and control agent signal differences. This approach was compared with an existing simplified paired-agent model (SPAM), and modified SPAM that accounts for signal differences by early time point normalization of targeted and control signals (SPAMPN). The scaling factor model (SPAMSF) outperformed both SPAM and SPAMPN in terms of accuracy and precision when the scale differences between targeted and imaging agent signals (α) were not equal to 1, and it matched the performance of SPAM for α  =  1. This model could have wide-reaching implications for quantitative cancer receptor imaging using any imaging modalities, or combinations of imaging modalities, capable of concurrent detection of at least two distinct imaging agents (e.g., SPECT, optical, and PET/MR)

Role of endogenous oxytocin in cardiac ischemic preconditioning

Background: The aim of the present study is to assess the role of endogenous oxytocin (OT) in cardioprotective effects of ischemic preconditioning (IPC) in anesthetized rat. Materials and methods: Animals were divided into five groups: 1) ischemia-reperfusion (IR); (n= 6), hearts were subjected to 25 min regional ischemia and 60 min reperfusion, 2) OT; (n= 6), oxytocin was administered (0.03. μg/kg i.p) 10 min prior to ischemia, 3) IPC; (n= 7), IPC was induced via a 5 min regional ischemia followed by 5 min of reperfusion before IR, 4) IPC. +. ATO (Atosiban); (n= 6), atosiban (1.5. μg/kg i.p) was used as OT receptor selective antagonist in the beginning of IPC and 5) IR. +. ATO; (n= 6), atosiban was injected 10 min prior to ischemia-reperfusion. Results: In our experiment, Infarct size was decreased significantly in OT and IPC groups compared to IR (23 ± 1.5% and 19 ± 0.6% vs 45 ± 2.9% in IR group, P < 0.05). Administration of atosiban in IPC. +. ATO group increased infarct size to 39 ± 0.9% in comparison with OT and IPC groups (P<0.05). The use of OT and IPC prior to ischemia significantly declined ventricular arrhythmias severity in compared to IR group (1.2±0.4 and 1 ±0.5 respectively, vs 4±0.4 in IR group, P<0.05). Blockade of OT receptor by atosiban abolished the cardiopreconditioning effects of IPC. Conclusion: This study shows that, in part, the cardioprotective effects of IPC can be induced by endogenous OT. © 2010 Elsevier B.V

Concurrent infections of hepatitis C and HIV in hepatitis B patients in the north-east of Iran

Co-infection of HBV, HCV and HIV is common because of shared routes of viral transmission with increased risk of morbidity and mortality. Anti-HCV and HIV antibodies of168 HBV patients were assayed. Co-infection of HCV in HBV patients was seen in four cases (2.4%). Simultaneous infection of HIV in HBV patents was seen in three cases (1.8%).There was no simultaneous co-infection of HCV, HIV and HBV. It is recommended that all patients are screened for possible co-infections before initiating treatment

Osteoclast-like giant-cell tumor of the parotid with salivary duct carcinoma: Case report and cytologic, histologic, and immunohistochemical findings

Primary giant-cell tumor of the salivary gland is a rare lesion with an incompletely characterized histogenesis. To the best of our knowledge, only 16 cases have been previously documented in the English-language literature. We report a new case, which occurred in a 75-year-old man who presented with a parotid mass and cervical lymphadenopathy. The patient underwent a left total parotidectomy and cervical lymph node dissection. As far as we know, ours is the only reported case of a primary giant-cell tumor of the salivary gland in which the patient presented with lymph node metastasis. Because so little is known about giant-cell tumor of the salivary gland, we use the occasion of this case report to describe the cytologic, histologic, and immunohistochemical characteristics that we observed

Diagnostic accuracy of fine needle aspiration cytology versus concurrent core needle biopsy in evaluation of intrathoracic lesions: A retrospective comparative study

Background: Transthoracic fine needle aspiration (FNA) cytology and core needle biopsy (CNB) are two commonly used approaches for the diagnosis of suspected neoplastic intrathoracic lesions. This study compared the diagnostic accuracy of FNA cytology and concurrent CNB in the evaluation of intrathoracic lesions. Materials and Methods: We studied FNA cytology and concurrent CNB specimens of 127 patients retrospectively, using hematoxylin and eosin (H&E), immunohistochemistry, and, on certain occasions cytochemistry. Information regarding additional tissue tests was derived from the electronic archives of the Department of Pathology and Laboratory Medicine as well as patient records. Diagnostic accuracy was calculated for each test. Results: Of 127 cases, 22 were inconclusive and excluded from the study. The remaining 105 were categorized into 73 (69.5) malignant lesions and 32 (30.5) benign lesions. FNA and CNB findings were in complete agreement in 63 cases (60). The accuracy and confidence intervals (CIs) of FNA and CNB for malignant tumors were 86.3 (CI: 79.3-90.7) and 93.2 (CI: 87.3-96.0) respectively. For epithelial malignant neoplasms, a definitive diagnosis was made in 44.8 of cases by FNA and 80.6 by CNB. The diagnostic accuracy of CNB for nonepithelial malignant neoplasms was 83.3 compared with 50 for FNA. Of the 32 benign cases, we made specific diagnoses in 16 with diagnostic accuracy of 81.3 and 6.3 for CNB and FNA, respectively. Conclusions: Our findings suggest that FNA is comparable to CNB in the diagnosis of malignant epithelial lesions whereas diagnostic accuracy of CNB for nonepithlial malignant neoplasms is superior to that for FNA. Further, for histological typing of tumors and examining tumor origin, immunohistochemical work up plays an important role

Effect of chronic lithium administration on endothelium-dependent relaxation of rat corpus cavernosum: The role of nitric oxide and cyclooxygenase pathways

OBJECTIVE: To verify the effect of chronic lithium administration on the endothelium-dependent relaxation of rat corpus cavernosum, as lithium is a major drug for treating bipolar disorder and some studies showed that lithium might cause erectile dysfunction in such patients, by a mechanism as yet unknown. MATERIALS AND METHODS: LiCl (600 mg/L) was dissolved in drinking water and Sprague-Dawley rats received the solution for 30 days; control rats received tap water. After 30 days corporeal strips were prepared from both groups, mounted under tension in oxygenated organ baths, and pre-contracted with phenylephrine (7.5 μm). After equilibration, the strips were relaxed by acetylcholine (10 nm to 1 mm) in the presence or absence of indomethacin (a cyclooxygenase inhibitor; 20 μm). Furthermore, the relaxant responses to sodium nitroprusside (1 nm to 1 mm), a nitric oxide (NO) donor, were investigated in both groups. NADPH-diaphorase histochemistry was used to identify NO synthase within cavernosal tissue strips of both groups. RESULTS: The acetylcholine-dependent relaxation was significantly lower in lithium-treated rats than in controls. Although indomethacin decreased significantly the relaxant responses to acetylcholine in controls, it increased the relaxant responses in lithium-treated rats. NADPH-diaphorase staining was greater in the chronic lithium-treated than in control preparations. Sodium nitroprusside produced similar relaxation in both groups. CONCLUSION: Chronic lithium administration can impair the endothelium-dependent relaxation of rat corpus cavernosum; NO availability might decrease after lithium administration and the cyclooxygenase pathways might have a role in this effect. © 2006 The Authors

2C-B: A New Psychoactive Phenylethylamine Recently Discovered in Ecstasy Tablets Sold on the Swiss Black Market

This study sought to identify, by means of several analytical methods (GC-MS, HPLC-DAD, CE-DAD, FTIR, and NMR), 4-bromo-2,5-dimethoxyphenethylamine (2C-B), which was found in two sets of tablets obtained from the Swiss black market. Unequivocal identification of 2C-B was only achieved by a combination of mass spectrometric and NMR analysis. Quantitation of 2C-B was performed by HPLC-DAD and CE-DAD. The amounts of 2C-B found in the tablets (3-8 mg) were in the range of the minimum quantity required to induce the effects characteristic of this dru