Brain trace elements in Pick's disease

The trace element content of the brain of two patients with Pick's disease examined postmortem was studied using instrumental neutron activation analysis. Results showed significant increases in chlorine, iron, manganese, sodium, and phosphorus and significant decreases in chromium, cesium, rubidium, and selenium and in the mean freeze-dried to wet-weight ratio for patients with Pick's disease compared with control patients. Brain zinc content was not elevated in the two patients, a finding that fails to support the hypothesis that elevated zinc levels play a role in the pathogenesis of Pick's disease.     

A human-derived reporter gene for noninvasive imaging in humans: mitochondrial thymidine kinase type 2.

A human-derived intrinsically nonimmunogenic reporter gene was tested for PET imaging of different molecular-genetic processes for potential clinical use. METHODS: The human mitochondrial thymidine kinase type 2 (hTK2) reporter gene truncated at the N terminus (DeltahTK2), alone or fused with green fluorescent protein (GFP), was used for preclinical evaluation in a mouse model. The levels of enzymatic activity of DeltahTK2 and DeltahTK2 GFP proteins were assessed using radiotracer accumulation and prodrug activation assays in vitro and in subcutaneous tumors grown from the corresponding cell lines in nude mice. Kinetic analyses of (124)I-2'-fluoro-2'-deoxy-1-beta-D-beta-arabinofuranosyl-5-iodouracil (FIAU), (18)F-2'-fluoro-2'-deoxy-1-beta-D-beta-arabinofuranosyl-5-ethyluracil (FEAU), or (18)F-9-(4-(18)F-fluoro-3-hydroxymethylbutyl)guanine (FHBG) uptake in tumors and biodistribution studies were performed. RESULTS: DeltahTK2 was successfully expressed in the cytoplasm of transduced cells. A new anti-hTK2 monoclonal antibody 8G2 was developed. The levels of FIAU and FEAU accumulation in cells expressing DeltahTK2 and DeltahTK2 GFP were at least 10-fold higher than in wild-type cells in vitro and about 6 times higher in vivo. We determined that FEAU is a more specific reporter substrate for DeltahTK2 than FIAU, whereas FHBG is not phosphorylated by this enzyme. In addition, we showed that DeltahTK2 transduced cells can be eliminated by treatment with d-arabinofuranosyl-cytosine. CONCLUSION: We have tested a human-derived reporter gene that is likely to be nonimmunogenic and potentially allows for long-term monitoring of different molecular-genetic processes by nuclear imaging techniques in humans. Using (124)I-FIAU, (18)F-FIAU, or (18)F-FEAU, it should be possible to image DeltahTK2 reporter gene expression with PET in preclinical and clinical studies.     

Antihyperglycemic Effect of Trigonella Foenum-Graecum (Fenugreek) Seed Extract in Alloxan-Induced Diabetic Rats and Its Use in Diabetes Mellitus: A Brief Qualitative Phytochemical and Acute Toxicity Test on the Extract

The effects of ethanol extract of Trigonella foenum-graecum (Fenugreek) seeds on the blood glucose levels in alloxan-induced diabetic rats at different doses (2g/kg, 1g/kg, 0.5g/kg and 0.1g/kg) were studied. The hypoglycemic effect of extract was compared with that of the standard antidiabetic drug (glimepiride, 4mg/kg) single dose. The extract showed significant activity against the diabetic state induced by alloxan but the intensity of hypoglycemic effect varied from dose to dose. The most effective dose recognized was 1g/kg but that is still lower than the standard antidiabetic drug. No acute toxicity was observed for ethanol extract of T. foenum-graecum seed when it was administered orally at high dose level (3 g/kg body weight), which is higher than effective antihyperglycemic dose, and closely observed for 24 hrs for any mortality and next 10 days for any delayed toxic effects on gross behavioral activities. Phytochemical group tests were also accomplished and presence of alkaloids, steroids and carbohydrates were recognized in the extract.     

Dietary B vitamin intakes and urinary total arsenic concentration in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort, Bangladesh

Purpose  

The objective of this analysis was to evaluate the effects of dietary B vitamin intakes on creatinine-adjusted urinary total arsenic concentration among individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Araihazar, Bangladesh. Arsenic exposure is a major public health problem in Bangladesh, where nearly 77 million people have been chronically exposed to arsenic through the consumption of naturally contaminated groundwater. Dietary factors influencing the metabolism of ingested arsenic may potentially be important modifiers of the health effects of arsenic in this population.     

Blocking catabolism with eniluracil enhances PET studies of 5-[18F]fluorouracil pharmacokinetics.

Noninvasive methods for measuring the pharmacokinetics of chemotherapeutic drugs such as 5-fluorouracil (FU) are needed for individualized optimization of treatment regimens. PET imaging of [18F]FU (PET/[18F]FU) is potentially useful in this context, but PET/[18F]FU is severely hampered by low tumor uptake of radiolabel and rapid catabolism of FU in vivo. Pretreatment with eniluracil (5-ethynyluracil) prevents catabolism of FU. Hypothesizing that suppression of catabolism would enhance PET/[18F]FU, we examined the effects of eniluracil on the short-term pharmacokinetics of the radiotracer. METHODS: Anesthetized rats bearing a subcutaneous rat colorectal tumor were given eniluracil or placebo and injected intravenously 1 h later with [18F]FU or [3H]FU. In the 18F studies, dynamic PET image sequences were obtained 0-2 h after injection. Tumors were excised and frozen at 2 h and then analyzed for labeled metabolites by high-performance liquid chromatography. Biodistribution of radiolabel was determined by direct tissue assay. RESULTS: Eniluracil improved tumor visualization in PET images. With eniluracil, tumor standardized uptake values ([activity/g]/[injected activity/g body weight]) increased from 0.72 +/- 0.06 (mean +/- SEM; n = 6) to 1.57 +/- 0.20 (n = 12; P < 0.01), and tumor uptake increased by factors of 2 or more relative to plasma (P < 0.05) and bone, liver, and kidney (P < 0.01). Without eniluracil (n = 5), 57% +/- 4% of recovered radiolabel in tumor at 2 h was on catabolites, with the rest divided among FU (2% +/- 1%), anabolites of FU (38% +/- 7%), and unidentified peaks (4% +/- 2%). With eniluracil (n = 8), catabolites, FU, and anabolites comprised 2% +/- 1%, 41% +/- 5%, and 57% +/- 4%, respectively, of the recovered radiolabel in tumors. CONCLUSION: Eniluracil increased tumor accumulation of 18F relative to host tissues and fundamentally changed the biochemical significance of that accumulation. With catabolism suppressed, tumor radioactivity reflected the therapeutically relevant aspect of FU pharmacokinetics--namely, uptake and anabolic activation of the drug. With this approach, it may be feasible to measure the transport and anabolism of [18F]FU in tumors by kinetic modeling and PET. Such information may be useful in predicting and increasing tumor response to FU.     

Evaluation of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-l-arabinofuranosyluracil ([18F]-l-FMAU) as a PET imaging agent for cellular proliferation: comparison with [18F]-d-FMAU and [18F]FLT

PURPOSE: Clevudine (L: -FMAU) an un-natural analogue of thymidine, is in clinical trials for the treatment of hepatitis B virus (HBV). L: -FMAU is phosphorylated by cellular kinases such as thymidine kinase 1 and deoxycytidine kinase, and its triphosphate form inhibits HBV deoxyribonucleic acid synthesis. Thus, L: -FMAU, radiolabeled with an appropriate isotope, may be useful for positron emission tomography (PET) imaging of tumor proliferation. We evaluated [18F]-L-FMAU as a PET imaging agent in tumor-bearing mice and compared the results with those of two other radiotracers, [18F]-d-FMAU and [18F]-FLT. METHODS: Subcutaneous xenografts of the human lung cancer cell lines H441 and H3255 were established in mice. A micro-PET scanner was used to obtain images of the tumor-bearing animals with [18F]-L-FMAU, [18F]-D-FMAU, and [18F]-FLT. RESULTS: At 2 h postinjection, the tumor uptake (% ID/g) of 18F]-L: -FMAU, 18F]-D: -FMAU, and [18F]-FLT in the faster-growing H441 cells was 3.13 +/- 1.11, 7.74 +/- 1.39, and 5.10 +/- 1.45, respectively. The corresponding values for the slower-growing H3255 cells were 1.38 +/- 0.81, 4.49 +/- 1.08, and 0.57 +/- 0.33. Tumor/muscle ratios of accumulation for [18F]-L: -FMAU, [18F]-D: -FMAU, and [18F]-FLT in H441 cells were 4.15 +/- 1.82, 3.37 +/- 1.19, and 12.94 +/- 4.38, respectively, and the corresponding values in H3255 cells were 1.62 +/- 0.50, 1.96 +/- 0.74, and 1.50 +/- 0.90. CONCLUSIONS: [18F]-L: -FMAU may be a useful agent for imaging tumor proliferation in fast-growing human lung cancers by PET.     

Fetal heart rate monitoring based on independent component analysis

In this paper, an algorithm based on independent component analysis (ICA) for extracting the fetal heart rate (FHR) from maternal abdominal electrodes is presented. Three abdominal ECG channels are used to extract the FHR in three steps: first preprocessing procedures such as DC cancellation and low-pass filtering are applied to remove noise. Then the algorithm for multiple unknown source extraction (AMUSE) algorithm is fed to extract the sources from the observation signals include fetal ECG (FECG). Finally, FHR is extracted from FECG. The method is shown to be capable of completely revealing FECG R-peaks from observation leads even with a SNR=-200dB using semi-synthetic data.     

Receptor mediated uptake of a radiolabeled contrast agent sensitive to beta-galactosidase activity

Radiolabeling of the MRI contrast agent 1-[2-(beta-galactopyranosyloxy)propyl]-4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane with (111)In, and its evaluation is reported. Radiolabeling was performed in acetate buffer with 50-78% radiochemical yield. In vitro studies revealed that the asialoglycoprotein receptor-poor cell line MH1C1 has low uptake, while the receptor-rich cell lines BNL-CL2 and Hep G2 have higher uptake. In vivo, the uptake of the compound in receptor-rich organ liver was very high. Blocking the receptor in vivo, reduced liver uptake by 90% suggesting that the compound localizes in receptor-enriched tissues by binding to the asialoglycoprotein receptor.     

Parotidectomy--a prospective study

Preservation of facial nerve is a real challenge in parotidectomy. Total conservative parotidectomy and superficial parotidectomy are the commonly practised operations for parotid diseases. Twelve patients have undergone total conservative parotidectomy and 52 patients have undergone superficial perotidectomy with preservation of integrity and function of the facial nerve and its branches. Fifty-eight patients were suffering from neoplastic conditions of which 46 had pleomorphic adenoma, 7 had muco-epidermoid carcinoma, 3 had carcinoma ex-pleomorphic adenoma, and 2 had adenoid cystic carcinoma. Non-neoplastic conditions were seen in 6 cases of which 3 had chronic parotitis and 3 had congenital parotid fistula. The aim of the study was to observe the efficacy of preservation of facial nerve in parotidectomy done in 64 patients.     

Copper oxide nanostructured thin films processed by SILAR for optoelectronic applications

The lack of high-functioning p-type semiconductor oxide material is one of the critical challenges that face the widespread performance of transparent and flexible electronics. Cu_xO nanostructured thin films are potentially appealing materials for such applications because of their innate p-type semi-conductivity, transparency, non-toxicity, abundant availability, and low-cost fabrication. This review summarizes current research on Cu_xO nanostructured thin films deposited by the SILAR technique. After a brief introduction to the advantages of Cu_xO semiconductor material, diverse approaches for depositing and growing such thin films are discussed. SILAR is one of the simplest deposition techniques in terms of better flexibility of the substrate choice, the capability of large-area fabrication, budget-friendly, deposition of stable and adherent film, low processing temperature for the film fabrication as well as reproducibility. In addition, various fabrication parameters such as types of copper salts, pH of precursors, number of cycles during immersion, annealing of as-deposited films, doping by diverse dopants, and growth temperature affect the rate of fabrication with the structural, electrical, and optical properties of Cu_xO nanostructured thin films, which led the technique unique to study extensively. This review will include the recent progress that has recently been made in different aspects of Cu_xO processed by the SILAR. It will describe the theory, mechanism, and factors affecting SILAR-deposited Cu_xO. Finally, conclusions and perspectives concerning the use of Cu_xO materials in optoelectronic devices will be visualized.

Cu_xO nanostructured thin films are potentially appealing materials for many applications. The deposition technique, SILAR, explored in this paper offers many advantages.