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Introduction: Lung cancer is one of the main causes of death worldwide. 80% as NSCLC and the majority is inoperable. In surgical stages surgery is the best option being the only possibility of cure. Objectives: To characterize the universe of patients with Surgical stage lung cancer of our Unit in a 4-year period (2001/2004); to evaluate the prognostic role of tumour markers. To compare this series with a previous one of our Unit. Methodology: Retrospective analysis. Demographic data, diagnostic method, tumour marker profile and survival. Results: In the period 2001/04 493 cases of lung cancer were diagnosed, 446 of which were NSCLC; 83 had a surgical stage. Male:Female 71:12; mean age 65.9 years; PS 0/1/2/3 - 36/38/5/4; 56 ex or current smokers. Diagnosis made by: TTNA 30, thoracotomy 23, bronchial biopsy 13, bronchial lavage 9, bronchial brushing 8; Histology type: Adenocarcinoma 34, Scamous Ca 22, NSCLC 13, Neuroendocrine tumour 8, Bronchial-alveolar 5, Large Cells Ca 1; Staging ...

The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3-c][1,2,6]thiadiazine 2,2-dioxides was achieved following the silylation method. Lipase-mediated methodology was employed for deprotection of the acyclic moieties. The antiviral effects were determined against a broad spectrum of viruses, including cytomegalovirus (CMV) and varicella zoster virus (VZV). Only minor antiviral activity against VZV was observed for those acyclonucleosides carrying a benzyl group.

... 12. (3S)2,5diethoxy3isopropyl3,6dihydropyrazine was prepared from glycine and Lvaline, by treatment of cyclo[(2S)val gly] with triethyloxonium tetrafluorborate. See Rose, JE, Leeson, PD;Gani, DJ Chem. Soc. ... See Rose, JE, Leeson, PD; Gani, D. J. Chem. Soc. Perkin Trans. ...

We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and carboplatin on a 3-week (trial A) versus a 4-week (trial B) schedule in patients with advanced/metastatic non-small cell lung cancer. Chemotherapy-naive patients in trial A received gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin area under the curve of 5 on day 1, every 3 weeks. In trial B, patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and carboplatin area under the curve of 6 on day 1, every 4 weeks. Thirty patients were enrolled in trial A and 28 in trial B. Patients received a total of 142 cycles in trial A and 134 in trial B. Despite more frequent treatment delays (82 cycles in trial B and 20 cycles in trial A), and dose reductions/omissions (mainly on day 15), gemcitabine mean dose intensities of both schedules were similar. The principal dose-limiting toxicity was grade 3/4 thrombocytopenia. Objective response rates were 40% in trial A and 68% in trial B (no complete response). Gemcitabine and carboplatin administered on days 1 and 8 every 3 weeks is associated with lower myelotoxicity than that of a 4-week schedule, although both schedules were active against non-small cell lung cancer. Semin Oncol 28 (suppl 10):10-14.

Glycogen synthase kinase (GSK-3beta) plays a crucial role in Alzheimer's disease (AD). Its inhibition is a valid approach to the treatment of AD. In this initial letter, some thienyl and phenyl alpha-halomethyl ketones are described as new non-ATP competitive inhibitors of GSK-3beta. They are considered as lead compounds for designing and synthesizing new series, to carry out SAR studies, clear up the mechanism of action, and, in general, evaluate their therapeutical usefulness.

Rough lipopolysaccharide (RLPS) antigens were prepared from cultures of Brucella abortus RB51, B. ovis, and B. canis. The preparations were standardized by weight and tested with sera from cattle immunized with B. abortus RB51, sheep infected with B. ovis, and dogs infected with B. canis. Populations of unexposed animals of each species were also tested. The tests used were the indirect enzyme immunoassay (IELISA) using RLPS and the fluorescence polarization assay (FPA) using RLPS core fractions, labeled with fluorescein isothiocyanate. The IELISA using B. abortus RB51 RLPS antigen resulted in sensitivity and specificity values of 94.8% and 97.3%, respectively, when testing bovine sera, 98.5% and 97.8% when testing ovine sera, and 95.8% and 100% when testing dog sera. The IELISA using B. ovis RLPS antigen gave sensitivity and specificity values of 80.5% and 91.7%, respectively with bovine sera, 98.9% and 93.8% with sheep sera, and 70.8% and 79.8% with dog sera. The IELISA using B. canis RLPS antigen resulted in sensitivity and specificity values of 97.0% and 97.4%, respectively, with bovine sera, 96.2% and 96.3% with sheep sera, and 95.8% and 98.8% with dog sera. Labeling RLPS core from B. ovis and B. canis with fluorescein was not successful. B. abortus RB51 core labeled with fluorescein resulted in sensitivity and specificity values of 93.5% and 99.8%, respectively, with bovine sera and 78.1% and 99.0% with sheep sera. It was not possible to test the dog sera in the FPA.

A new family of 1,2,4-thiadiazolidinone derivatives containing the N-benzylpiperidine fragment has been synthesised. The acetylcholinesterase (AChE) inhibitory activity of all compounds was measured using Ellman's method and some of them turned out to be as potent as tacrine. Furthermore, compound 13 was as active as tacrine in reversing the blockade induced by tubocurarine at rat neuromuscular junction. Additionally, receptor binding studies provided new lead compounds for further development of alpha2-adrenergic and sigma-receptor antagonists. Molecular dynamic simulation using X-ray crystal structure of AChE from Torpedo californica was used to explain the possible binding mode of these new compounds.

From an in-house library of compounds, five phenothiazines and one dibenzothiadiazepine were selected to be tested in neuroprotective and cholinergic assays. Three of them, derived from the N-alkylphenothiazine, the N-acylaminophenothiazine, and the 1,4,5-dibenzo[b,f]thiadiazepine system, protected human neuroblastoma cells against oxidative stress generated by both exogenous and mitochondrial free radicals. They could also penetrate the CNS, according to an in vitro blood-brain barrier model, and an N-acylaminophenothiazine derivative behaved as a selective inhibitor of butyrylcholinesterase. Free radical capture and/or promotion of antioxidant protein biosynthesis are mechanisms that can be implicated in their neuroprotective actions. Due to their excellent pharmacological properties and the fact that they were not biologically explored in the past, one N-acylaminophenothiazine and one 1,4,5-dibenzo[b,f]thiadiazepine have been selected to develop two new series that are currently in progress.

ABSTRACT Glucose fatty acid monoesters were produced in a stirred-tank reactor in combination with a membrane-pervaporation sepn. unit for the regeneration of the solvent Et methylketone (EMK) on a preparative scale. Yields up to 79% (169g product) were achieved in the synthesis of 6-O-stearoyl-D-glucose in a mainly solid phase system in the presence of a small amt. of EMK maintaining a catalytic liq. phase as well as forming a suitable azeotropic mixt. with the reaction water. High residual activity was found using lipase B from Candida antarctica under reduced pressure at 60°. EMK could be easily removed from the reaction mixt. and is regarded as biocompatible in the prepn. of food additives. [on SciFinder(R)]

... NEW MACROCYCLES CONTAINING A 1,3-BIS(1H-PYRAZOL-1-YL)PROPANE UNIT Marta Fierros, Maria Isabel Rodriguez-Franco, Klar Navarro, and Santiago Conde* Instituto de Qufmica ... 2. Izatt, RM; Bradshaw, JS; Nielsen, SA; Lamb, JD; Christensen, JJ; Sen, S. Chem. Rev. ...

New acetylcholinesterase inhibitors were synthetized via a lipase-mediated regioselective amidation using Candida antarctica lipase B as a biocatalyst in the key step. The new compounds have two different structural fragments: a N-benzylpiperidine moiety to anchor the enzyme active site and a dicarboxylic aminoacid to act as a biological carrier. Some analogues of N-benzylpiperazine were also synthesised and studied but they did not display AChE inhibitor activity. A preliminary structure activity relationship study was performed employing some computational techniques as similarity indices and electrostatic potential maps.