Exploring the Development of a Canadian Frostbite Care Network and the Future of Frostbite Care in Canada Using a Qualitative Approach.

Introduction: The Canadian Frostbite Collaborative project is exploring frostbite patient care needs and current practices in Canada to inform the development of a Canadian frostbite care network (CFCN) as a national quality improvement initiative.

Methods: Using a quantitative and qualitative approach, this study aimed to define the landscape of current frostbite practices, challenges, and interest in future work.

Results: Current frostbite care practices were initially assessed through semistructured phone interviews of Canadian healthcare providers.

Clubroot resistance QTL are modulated by nitrogen input in Brassica napus.

Nitrogen levels can modulate the effectiveness of clubroot resistance in an isolate- and host-specific manner. While the same QTL were detected under high and low nitrogen, their effects were altered. Clubroot, caused by Plasmodiophora brassicae, is one of the most damaging diseases of oilseed rape and is known to be affected by nitrogen fertilization.

Improved Efficiency and Reliability of NGS Amplicon Sequencing Data Analysis for Genetic Diagnostic Procedures Using AGSA Software.

Screening for mutations in women with familial risk of breast or ovarian cancer is an ideal situation for high-throughput sequencing, providing large amounts of low cost data. However, 454, Roche, and Ion Torrent, Thermo Fisher, technologies produce homopolymer-associated indel errors, complicating their use in routine diagnostics. We developed software, named AGSA, which helps to detect false positive mutations in homopolymeric sequences.

DNA repair genes implicated in triple negative familial non-BRCA1/2 breast cancer predisposition.

Among breast cancers, 10 to 15% of cases would be due to hereditary risk. In these familial cases, mutations in BRCA1 and BRCA2 are found in only 15% to 20%, meaning that new susceptibility genes remain to be found. Triple-negative breast cancers represent 15% of all breast cancers, and are generally aggressive tumours without targeted therapies available.

Chest CT scan screening for lung cancer in asbestos occupational exposure: a systematic review and meta-analysis.

Objective: Lung cancer is the most frequent malignant asbestos-related pathology and remains the most fatal cancer of industrialized countries. In heavy smokers, early detection of lung cancer with chest CT scan leads to a 20% mortality reduction. However, the use of CT scan screening for early detection of lung cancer in asbestos-exposed workers requires further investigation.

Joint scintigraphy in rabbits with 99mtc-N-[3-(triethylammonio)propyl]-15ane-N5, a new radiodiagnostic agent for articular cartilage imaging.

Unlabelled: The aim of this study was to investigate joint scintigraphy in rabbits with 99mTc-N-[3-(triethylammonio)propyl]-15ane-N5 (NTP 15-5), a new radiopharmaceutical that specifically localizes in cartilaginous tissues.

Methods: Scans obtained after intravenous injection of the 99mTc-labeled compound in normal and arthropathy-induced rabbits were compared with those of the bone-imaging agent 99mTc-methylene diphosphonate (99mTc-MDP).

Results: The radioactive uptake of 99mTc-NTP 15-5 was detected in cartilaginous tissues 5 min after injection and was stable for 2 h.

Disposition in rats of N-pyridinium-propyl-cyclam, N-triethylammonium-propyl-cyclam, and N-[Triethylammonium]-3-propyl-[15]ane-N5, potential cartilage imaging agents.

Quaternary ammonium compounds are known to highly concentrate in articular cartilages after i.v. administration.

New quaternary ammonium oxicam derivatives targeted toward cartilage: synthesis, pharmacokinetic studies, and antiinflammatory potency.

Analogues of nonsteroidal antiinflammatory drugs (NSAIDs) oxicams, in which the active group was linked to a quaternary ammonium function [(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1, 1-dioxide-3-carboxamido)2-methylpyridinium iodide or piroxicam-N(+) and [3-(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1, 1-dioxide-3-carboxamido)propyl]trimethylammonium iodide or propoxicam-N(+)] were synthesized. Compounds were labeled with tritium for piroxicam-N(+) and carbon-14 for propoxicam-N(+). Pharmacokinetic studies conducted on rats showed that these molecules were able to highly concentrate in joint cartilages but their bioavailability by the oral way was low.

Syntheses, biochemical and biological evaluation of staurosporine analogues from the microbial metabolite rebeccamycin.

The indolocarbazole antibiotics staurosporine and rebeccamycin (1) are potent antitumor drugs targeting protein kinase C and topoisomerase I, respectively. To obtain staurosporine analogues from rebeccamycin, different structural modifications were performed: coupling of the sugar moiety to the second indole nitrogen, dechlorination and then reduction of the imide function to amide. The newly synthesized compounds (3-6) were tested for their abilities to bind to DNA and to inhibit topoisomerase I and protein kinase C.

Syntheses and biological evaluation of indolocarbazoles, analogues of rebeccamycin, modified at the imide heterocycle.

A series of 10 indolocarbazole derivatives, analogues to the antitumor antibiotic rebeccamycin, bearing modifications at the imide heterocycle were synthesized. They bear an N-methyl imide, N-methyl amide, or anhydride function instead of the original imide. Their inhibitory potencies toward topoisomerase I were examined using a DNA relaxation assay and by analyzing the drug-induced cleavage of 32P-labeled DNA.

Syntheses and biological activities (topoisomerase inhibition and antitumor and antimicrobial properties) of rebeccamycin analogues bearing modified sugar moieties and substituted on the imide nitrogen with a methyl group.

As a part of studies on structure-activity relationships, several potential topoisomerase I inhibitors were prepared. Different analogues of the antitumor antibiotic rebeccamycin substituted on the imide nitrogen with a methyl group were synthesized. These compounds bore either the sugar residue of rebeccamycin, with or without the chlorine atoms on the indole moieties, or modified sugar residues (galactopyranosyl, glucopyranosyl, or fucopyranosyl) linked to the aglycone via a beta- or alpha-N-glycosidic bond.

Synthesis and biological evaluation of monoindolyl and indolocarbazolyl oxazolones and imidazolones.

Eight compounds structurally related to protein kinase C inhibitor MDL 27032 and substituted with indole moieties were synthesized. Their activities towards protein kinase C (PKC) and protein kinase A (PKA) were determined. Their effect on PKC-mediated contraction of rat tracheal smooth muscle, their antiproliferative activity on two murine tumor cell lines, melanoma B16 and leukemia P388 and their antimicrobial activity on a gram-positive bacterium Bacillus cereus were also examined.

Structure-activity relationships in a series of substituted indolocarbazoles: topoisomerase I and protein kinase C inhibition and antitumoral and antimicrobial properties.

A series of compounds structurally related to staurosporine, rebeccamycin, and corresponding aglycones was synthesized, and their activities toward protein kinase C and topoisomerases I and II were tested together with their in vitro antitumor efficiency against murine B16 melanoma and P388 leukemia cells. Their antimicrobial activities were also examined against a Gram-negative bacterium (Escherichia coli), a yeast (Candida albicans), and three Gram-positive bacteria (Bacillus cereus, Streptomyces chartreusis, and Streptomyces griseus). To avoid side effects expected with protein kinase C inhibitors, we introduced substitution on the maleimide nitrogen and/or a sugar moiety linked to one of the indole nitrogens to obtain specific inhibitors of topoisomerase I with minimal activities on protein kinase C.

Inhibitory effect of ursolic acid on B16 proliferation through cell cycle arrest.

The effects of ursolic acid on the proliferation of B16, a mouse melanoma cell line, were studied. During investigations of the anti-proliferative effects of this triterpene, we observed that MTT colorimetric and colony forming assays show that ursolic acid is a potent inhibitor of B16 cell growth. Cell cycle analysis was performed by propidium iodide staining and flow cytometry technique.

Subcellular distribution of a new fluorinated, biocompatible, non-ionic telomeric carrier: a study in cultured B16 melanoma and rat skin fibroblasts.

Tris-hydroxymethyl-amino-methane telomers bearing a fluorinated end have recently been proposed as potential drug carriers. Using ion microscopy, we have investigated the cell uptake and subcellular distribution of a perfluorinated telomere, called F-TAC, in two cell lines, malignant murine B16 melanoma and normal rat skin fibroblasts. Single layer cell cultures on gold plates were incubated with F-TAC at different concentrations.

In vitro uptake of technetium-99m-teboroxime in carcinoma cell lines and normal cells: comparison with technetium-99m-sestamibi and thallium-201.

Since 201Tl, 99mTc-sestamibi and 99mTc-teboroxime concentrate in cardiac cells through different mechanisms, we compared their uptake in cultured normal cells and carcinoma cell lines in order to define their possible use for tumor evaluation in vivo. Four lines of normal cells from animals, including myocytes from newborn rats, and four lines of human carcinoma cell lines were incubated for 1 hr with 37 kBq of either tracer. Results, expressed in percent of the total activity taken up by 1 million cells, showed a 9% difference between the uptake of teboroxime by normal and carcinoma lines (24.

In vitro binding of oxime acetylcholinesterase reactivators to proteoglycans synthesized by cultured chondrocytes and fibroblasts.

The incorporation of the 14C-labelled acetylcholinesterase reactivators 1-(methyl-imidazolium)-3 (4-carbaldoxime-pyridinium) propane dibromide (pyrimidoxime) and N,N'-trimethylene bis(pyridinium-4-aldoxime) dibromide (TMB4) into cultured chondrocytes and fibroblasts was measured and their binding to macromolecules synthesized by these cells studied. The results showed that these drugs concentrated slowly and poorly into these cells, but bound firmly to high molecular mass materials in the culture supernatants. The chromatographic properties of these macromolecules on Sepharose CL-2B in non-dissociative or dissociative conditions were similar to those of the proteoglycans synthesized by these cells.

Biodistribution and metabolism in rats and mice of bucromarone.

The metabolism and disposition of bucromarone, labeled with 14C on the chromone group, has been investigated in C3H mice and Wistar rats. In separate experiments, animals received 4.4 mmol/kg, iv or po, [14C]bucromarone hydrochloride or succinate.

[Antigenicity of ribosomal proteins from a malignant mouse cell line. Preliminary results].

An original immunological two-dimensional technique with two different gels permits the protein analysis of 80 S cytoplasmic ribosomal murine particles and of their 60 S and 40 S subunits. The diagrams isolate and characterize a definite number of specific polypeptidic structures from each ribosomal particle.