Chemoselective and stereoselective lithium carbenoid mediated cyclopropanation of acyclic allylic alcohols.

The reaction of geraniol with different lithium carbenoids generated from n-BuLi and the corresponding dihaloalkane has been evaluated. The reaction occurs in a chemo and stereoselective manner, which is consistent with a directing effect from the oxygen of the allylic moiety. Furthermore, a set of polyenes containing allylic hydroxyl or ether groups were chemoselectively and stereoselectively converted into the corresponding gem-dimethylcyclopropanes in one single step in moderate to good yields mediated by a lithium carbenoid generated in situ by the reaction of n-BuLi and 2,2-dibromopropane.

Western Canadian Arctic ringed seal organic contaminant trends in relation to sea ice break-up.

The association between changing sea ice conditions and contaminant exposure to Arctic animals interests Inuvialuit harvesters, communities, and researchers. We examined organochlorine contaminant (OC) concentrations in the blubber of 90 male adult ringed seals (Phoca hispida) sampled from the subsistence harvest in Ulukhaktok (formerly Holman), NT, Canada, just prior to break-up of the sea ice (1993-2008). OC blubber concentrations were assessed with respect to year and sea ice break-up date. HCB and age- and blubber-adjusted concentrations of p,p'-DDT and ΣCHB (chlorobornane) significantly decreased over the study period. With respect to the timing of the spring break-up, highly lipophlic OCs, such as p,p'-DDE and PCB 153, were higher during years of early ice clearing (at least 12 days earlier than the mean annual break-up date), whereas no trends were observed for α, ß, and γ isomers of HCH, trans- and cis-chlordane, oxychlordane, or ΣCHB. The higher contaminant concentrations found in earlier break-up years is likely due to earlier and/or increased foraging opportunities. This situation also has potential for enhancing bioaccumulation and biomagnification of contaminants over the long-term if projected changes continue to result in lighter and earlier ice conditions.

Vaccination of mice with chitosan nanogel-associated recombinant NcPDI against challenge infection with Neospora caninum tachyzoites.

The effects of nanogel encapsulation of recombinant NcPDI (recNcPDI) following vaccination of mice by intranasal or intraperitoneal routes and challenge infection with Neospora caninum tachyzoites were investigated. Nanogels were chitosan based, with an alginate or alginate-mannose surface. None of the mice receiving recNcPDI intraperitoneal (i.p.) (without nanogels) survived, whereas intranasal (i.n.) application protected 9 of 10 mice from disease. Association of recNcPDI with nanogels improved survival of i.p. vaccinated mice, but nanogels without recNcPDI gave similar protection levels. When nanogels were inoculated via the i.n. route, 80% of the mice were protected. Association of recNcPDI with the alginate-coated nanogels protected all mice against disease. Quantification of the cerebral parasite burden showed a significant reduction of parasite numbers in most experimental groups vaccinated i.n., except those vaccinated with alginate-mannose nanogels with or without recNcPDI. For i.p. vaccinated groups, no significant differences in cerebral infection densities were measured, but there was a reduction in the groups vaccinated with recNcPDI associated with both types of nanogels. Analysis of the immune responses of infected mice indicated that association of recNcPDI with nanogels altered the patterns of cytokine mRNA expression profiles, but had no major impact on the antibody subtype responses. Nevertheless, this did not necessarily relate to the protection.

Metal removal from soil leachates using DTPA-functionalised maghemite nanoparticles, a potential soil washing technology.

There is significant current interest in the application of magnetic (magnetite or maghemite) nanoparticles functionalised with chelating agents for the environmental remediation of metal contaminated waters and solutions. Whilst there is a body of knowledge about the potential remediation efficacy of such engineered nanoparticles from studies involving synthetic solutions of single metals, there is relatively little data involving mixed-metal solutions and virtually no studies about nanoparticle performance in chemically complex environmental solutions representing those to which a scaled-up nanoremediation process might eventually be applied. Therefore, we investigated the ability of diethylenetriaminepentaacetic acid (DTPA)-functionalised, silica-coated maghemite nanoparticles to extract potentially toxic (Cd, Co, Cu) and "non-toxic" (Ca, Mg) metals from solution (initial [metal] = 10 mg L-1; pH range: 2-8) and to extract a wider range of elements (As, Ca, Cd, Co, Cr, Cu, Mg, Na, Pb, Zn) from leachate obtained from 10 different contaminated soils with variable initial pH, (semi-)metal and dissolved organic carbon (DOC) concentrations. The functionalised nanoparticles could extract the potentially toxic metals with high efficiency (in general >70%) from single metal solutions and with efficiencies that were either unaffected or reduced from the soil leachates. Kd values remained high (>500 L kg-1), even for the soil leachate extractions. Our findings show that DOC and relatively high concentrations of non-toxic elements do not necessarily reduce the efficiency of metal contaminant removal by DTPA-functionalised magnetic nanoparticles and thus demonstrate the remediation potential of such particles when added to chemically complex soil-derived contaminated solutions.

Adsorption of Pb and Zn from binary metal solutions and in the presence of dissolved organic carbon by DTPA-functionalised, silica-coated magnetic nanoparticles.

The ability of diethylenetriaminepentaacetic acid (DTPA)-functionalised, silica-coated magnetic nanoparticles to adsorb Pb and Zn from single and bi-metallic metal solutions and from solutions containing dissolved organic carbon was assessed. In all experiments 10 mL solutions containing 10 mg of nanoparticles were used. For single metal solutions (10 mg L-1 Pb or Zn) at pH 2 to 8, extraction efficiencies were typically >70%. In bi-metallic experiments, examining the effect of a background of either Zn or Pb (0.025 mmol L-1) on the adsorption of variable concentrations (0-0.045 mmol L-1) of the other metal (Pb or Zn, respectively) adsorption was well modelled by linear isotherms (R2 > 0.60; p ≤ 0.001) and Pb was preferentially adsorbed relative to Zn. In dissolved organic carbon experiments, the presence of fulvic acid (0, 2.1 and 21 mg DOC L-1) reduced Pb and Zn adsorption from 0.01, 0.1 and 1.0 mmol L-1 solutions. However, even at 21 mg DOC L-1 fulvic acid, extraction efficiencies from 0.01 to 0.1 mmol L-1 solutions remained >80% (Pb) and >50% (Zn). Decreases in extraction efficiency were significant between initial metal concentrations of 0.1 and 1.0 mmol L-1 indicating that at metal loadings between c. 100 mg kg-1 and 300 mg kg-1 occupancy of adsorption sites began to limit further adsorption. The nanoparticles have the potential to perform effectively as metal adsorbents in systems containing more than one metal and dissolved organic carbon at a range of pH values.

Spatial trends and factors affecting variation of organochlorine contaminants levels in Canadian Arctic beluga (Delphinapterus leucas).

Organochlorine pesticides and PCBs were analysed in blubber from beluga (Delphinapterus leucas), or white whales, collected at 15 sites in the Canadian Arctic between 1993 and 2001. The objective of the study was to define and interpret the spatial trends of major organic contaminants in northern beluga in terms of sources and transport pathways, and the biological factors influencing accumulation. When compared on a lipid weight basis, the concentrations of beta-HCH, cis-CHL and SigmaCHL, cis-nonachlor, heptachlor epoxide and p,p'-DDT were significantly higher in males than females at all five sites in the eastern Arctic where the two sexes were harvested. The differences were attributed to losses from the females during fetal development and lactation as reported in previous studies. Major compounds increased with age in males at most sites, however the lack of a significant increase with age at some sites was in part due to high organochlorine concentrations in young year classes (2-5 years), particularly at eastern sites such as Iqaluit and Pangnirtung. Lower concentrations of SigmaHCH and SigmaDDT compounds in young males in 2001 relative to 1995 at Hendrickson Island could be due to declining levels in the environment, changes in the diet, or differences in organochlorine loads transferred from the female after birth. Age-corrected least square mean concentrations in males showed significantly higher levels of many compounds, such as p,p'-DDE and SigmaCHB, at south Baffin Island sites than those in the west. Two notable exceptions were HCBz and beta-HCH which were higher in the west. Methoxyclor was detected in males at Sanikiluaq (58 ng g-1) and in both sexes at Kimmirut, but at no other sites. Principal component analysis grouped the 16 sites into five major groupings based on the similarity of normalised organochlorine pesticide and PCB levels. Sites from the western Arctic were grouped by higher proportions of HCBz, beta-HCH and gamma-HCH and higher chlorinated PCBs. Endosulfan and alpha-HCH comprised a larger proportion of total organochlorine residues in the northern Hudson Bay sites, while methoxychlor, chlordane compounds and octachlorobiphenyls were enriched at Sanikiluaq in eastern Hudson Bay. The analysis showed that the relative amounts of several key compounds are similar in the beluga stocks over large spatial areas (i.e. eastern versus western sites), however, some stocks have distinct fingerprints which can be used to differentiate them from adjacent stocks. Ratios of major HCH isomers largely corresponded with air and surface water measurements conducted during the 1990s, but low alpha-/beta- and alpha-/gamma-HCH ratios in all three western Arctic collections indicate rapid losses of the alpha-isomer from the food web, proportionately higher beta- and gamma-isomers in the Beaufort Sea, or a combination of the two processes. Chlordane residue patterns generally correspond to those from previous studies, however, interpretation of spatial trends are difficult due to the aging of the probable sources in the south, possible atmospheric input from new sources and complex transport pathways.

Concentrations of mercury in tissues of beluga whales (Delphinapterus leucas) from several communities in the Canadian Arctic from 1981 to 2002.

Beluga whales have been hunted for food by Native People in the Canadian Arctic since prehistoric time. Here we report the results of analyses of total mercury in samples of liver, kidney, muscle and muktuk from collections over the period 1981-2002. We compare these results with human consumption guidelines and examine temporal and geographic variation. Liver has been analyzed more frequently than other organs and it has been used as the indicator organ. Mercury accumulates in the liver of the whales over time so that the whale ages are usually linked statistically to their levels of mercury in liver. Virtually all the samples of 566 animals analyzed contained mercury in liver at concentrations higher than the Canadian consumption guideline of 0.5 microg g-1 (wet weight) for fish. (There is no regulatory guideline for concentrations in marine mammals in Canada.) Samples from locations in the Mackenzie Delta in the western Canadian Arctic and from Pangnirtung in the eastern Canadian Arctic were obtained more often than from other location and these offered the best chances to determine whether levels have changed over time. Statistical outlier points were removed and the regressions of (ln) mercury in liver on age were used to calculate the level of mercury in whales of age 13.1 years in order to compare age-adjusted levels at different locations. These age-adjusted levels and also the slopes of regressions suggested that levels have increased in the Mackenzie Delta over the sampling period although not in a simple linear fashion. Other locations had fewer collections, generally spread over fewer years. Some of them indicated differences between sampling times but we could not establish whether these differences were simply temporal variation or whether they were segments of a consistent trend. For example, the levels in whales from Arviat were considerably higher in 1999 than in 1984 but we have only two samples. Similarly, samples from Iqaluit in 1994 exceeded considerably those in 1993 and the interval seems too short to reflect any regional temporal trend and more likely represent an extreme case of year-to-year variation. Previous analyses of data from geographically distinct groups had suggested that whales in the western Canadian Arctic had higher levels of mercury than those from the eastern Canadian Arctic. The present analysis suggests that such regional differences have diminished and are no longer statistically significant. No site has indicated significant decreases in more recent samples. The levels of total mercury in the most analyzed organs fell in the order of liver (highest levels), kidney, muscle and muktuk (lowest level). While muktuk had the lowest level of the organs most frequently analyzed, it is the preferred food item from these whales and it still exceeded the consumption guideline in most instances.

Diagnostic value of the serum folate assay.

The diagnostic value of the serum folate assay has been assessed in 90 patients, each of whom had a macrocytic anaemia and a low serum vitamin B(12) level. Twenty-nine (32%) patients were found to have anaemia due primarily to folate deficiency. The cause of the low serum vitamin B(12) levels is uncertain in the 22 (25%) patients with normal or borderline vitamin B(12) absorption. The effect of folic acid therapy was studied in four of these patients, and in each case the serum vitamin B(12) rose slowly to a normal level. The serum folate was low in only four (7.5%) of the 54 patients with pernicious anaemia, and the levels rose to normal on treatment with vitamin B(12) alone. A high serum folate occurred in eight (15%) pernicious anaemia patients. A normal serum folate indicated the diagnosis of pernicious anaemia or megaloblastic anaemia following partial gastrectomy. However, a normal serum folate and a very low vitamin B(12) level was found in two patients with idiopathic steatorrhoea. It is concluded that the serum folate assay is a valuable routine test in patients who have a macrocytic anaemia and low serum vitamin B(12). A low folate level makes the diagnosis of pernicious anaemia unlikely and is a strong indication for full investigation of small intestinal function.

Vitamin B12 absorption studies: effect of parenteral non-radioactive B12 on serum level of 57CO vitamin B12.

The intestinal absorption of (57)Co vitamin B(12) has been measured by counting the radioactivity in the serum, and the effect of the parenteral administration of 1 mg. non-radioactive vitamin B(12) two hours after the oral dose has been studied. When parenteral vitamin B(12) was not given, the mean radioactivity in the serum was lower in both patients with pernicious anaemia and in control subjects, and the results in the patients with pernicious anaemia were more definitive. There was no significant difference between the results obtained with an Ekco scaler and those with an I.D.L. scaler. This is the simplest and most convenient method of measuring vitamin B(12) absorption. It is suggested that the test be standardized by giving 0.5 mug. (57)Co vitamin B(12) with a maximal histamine stimulation of intrinsic factor secretion, but without a parenteral dose of non-radioactive vitamin B(12). The results are expressed most usefully as a percentage of the administered dose per litre of serum or plasma.

Red blood cell abnormalities in cardiac valvular disease.

Nineteen patients with morphological abnormalities of the red blood cells are described, and these formed approximately 3% of the total cases of cardiac valvular disease. In two patients the abnormal blood film developed after the insertion of an aortic and mitral valve prosthesis respectively, but in another two patients the abnormal blood film was corrected by aortic valve surgery. Anisopoikilocytosis may have been associated with microangiopathic haemolytic anaemia in one patient, but in the others the cardiac valvular disease was severe and other mechanical factors were not present. The mitral valve was involved in 16 patients and the aortic valve in eight. Elliptocytosis was the only abnormality in 11 blood films, schistocytes and burr cells were present in seven, and in three there were a few microspherocytes. Family studies in seven patients produced evidence of hereditary elliptocytosis in three. Anaemia was present in only two patients. One of these had infective endocarditis, and the other developed overt haemolytic anaemia following the replacement of a diseased mitral valve by a Starr-Edwards prosthesis. In this latter case there was a transiently positive direct antiglobulin test, and the anaemia and abnormal blood picture were corrected without further surgical treatment. Haemolytic anaemia did not develop in 23 patients after the insertion of an aortic valve prosthesis or homograft. Indirect evidence of haemolysis was obtained in some patients who were not anaemic. There was a reticulocytosis in one third and serum haptoglobins were decreased or absent in over half of the patients tested.

Measurement of intestinal absorption of 57-Co vitamin B-12 by serum counting.

The results of the measurement of vitamin B(12) absorption by counting the radioactivity of 5 ml. serum obtained eight to 10 hours after the ingestion of an oral dose of 0.5 mug. vitamin B(12) labelled with 0.5 muc. (57)Co are compared with those obtained with the urinary excretion (Schilling) test. Inadequate urine collection and impaired renal function were responsible for low results in the Schilling test in four of the 12 control subjects, and an incomplete urine collection in four patients with pernicious anaemia could have led to doubt about the validity of the low result. The measurement of serum radioactivity for 1,000 seconds gave conclusive results, the range in the patients with malabsorption of vitamin B(12) being between 0 and 24 counts per minute, and in the control subjects and other patients with megaloblastic anaemia between 28 and 64 counts per minute. The highest serum radioactivity level in a patient with pernicious anaemia was 19 counts per minute. Serum counting is simpler than the Schilling test and may be done alone when the patient's renal function is known to be poor, when urine collection is expected to be unreliable, or when the flushing dose of vitamin B(12) should be avoided. Otherwise there is an advantage in doing both tests together for confirmation.

Regioselective C-3-O-acylation and O-methylation of 4,6-O-benzylidene-beta-D-gluco- and galactopyranosides displaying a range of anomeric substituents.

The regioselective C-3-O-acylation and O-methylation of a range of 4,6-O-benzylidene-beta-D-gluco- and galactopyranosides has been studied. Regioselectivity is achieved by forming the copper chelate of the 2,3-diol using either sodium hydride and copper(II) chloride, or copper(II) acetylacetanoate, or copper(II) acetate, prior to introduction of the acylating or methylating agent.

Detection of IgG and IgE serum antibodies to Culicoides salivary gland antigens in horses with insect dermal hypersensitivity (sweet itch).

We postulated that all horses exposed to the bites of Culcoides (midges) would have an antibody response to the antigen secreted in Culcoides saliva, but that IgE antibody would be restricted to allergic individuals. Using immunohistology on sections of fixed Culicoides, we have demonstrated the presence of antibodies in horse serum which recognise Culicoides salivary glands. Antibodies were detected in the serum of horses with insect dermal hypersensitivity and in the serum of normal horses exposed to Culicoides bites. In contrast, no antibodies were detected in serum from native Icelandic ponies which had not been exposed to Culicoides. Anti-salivary gland IgG antibodies were detected in serum from both allergic and healthy horses exposed to Culicoides. IgE antibodies were only detected in horses with signs of insect dermal hypersensitivity, they were not found in serum of healthy controls nor in the serum of horses with a history of hypersensitivity but in remission at the time of sampling. Using western blotting we confirmed the presence of antibodies to Culicoides antigens and demonstrated that individual horses react to different numbers of antigens. This paper demonstrates the ability of serum from allergic horses to detect Culcoides antigens and will enable further studies to isolate and characterise the allergens.

Antiphospholipid antibodies and hemodialysis vascular access thrombosis.

Screening for the presence of APL for hemodialysis dependent individuals is yet another critical link where medical and nursing interventions will prolong vascular access survival and decrease morbidity. Because of the continuity they provide, hemodialysis nurses and advanced practice nurses are in excellent positions to identify individuals with persistent vascular thrombosis and make recommendations for further screening.

Framing the work: development of a renal nursing professional practice model.

In 1997, a nursing care model task group was formed to develop a framework to guide the development of the nursing care delivery system in a newly merged hospital corporation. A collective group of experienced and motivated nurses in the renal program met to develop an integrated renal nursing professional practice model. In addition it was recognized that a city-wide model involving the two acute care renal centres would be advantageous. The challenge was to clearly articulate the professional roles and relationships of nurses and nurse practitioner/clinical nurse specialists in a constantly changing environment. This process provided the opportunity to identify key trends influencing renal care and possibilities for changing practice. Networking across the corporations was enhanced, partnerships were formed, and a sense of value for the work that was being undertaken developed. The group's endeavours resulted in an integrated nursing professional practice model that emphasizes accountability and continuity and places value on therapeutic relationships. Another strength of the model is the acknowledgement of the collaborative nature of the multidisciplinary team. After two years of development, the model was implemented. A city-wide Renal Nursing Professional Practice Council has been established in order to provide leadership in evaluating the model. This will include assessing the success of implementation, impact on patient/family care, and collaborative rewards experienced by staff. Future planning will address the potential need for a multidisciplinary focus within the practice council.

How five advanced practice nurses in nephrology spend their time.

The purpose of this paper is to report the results of a descriptive study undertaken to examine the scope of practice of five Masters-prepared nephrology nurse practitioner/clinical nurse specialists (NP/CNS) in a mid-size university teaching hospital program. Four of the NP/CNSs practised in three acute care sites, and one in the regional dialysis program. Impetus for the study came from two sources. First, a sixth person practising in the role was retiring and was not to be replaced. Second, the current three-site model for acute care was being transformed into a two-site model, thus creating opportunities to reduce variability in practice among the NP/CNSs. The study examined the activities of the NP/CNS role through the completion of a time documentation tool (TDT) by five nurse practitioners on each of 10 consecutive days of practice. The TDT was adapted from Ackerman's Model of Advanced Practice (1996). The model outlines five domains of practice for advanced practice nurses (APN): direct comprehensive care, support of systems, research, education, and publication and professional leadership. The NP/CNSs spent an average of 9.21 hours at work daily with a range of 8.6 to 10.3 hours. The TDT captured an average of 8.6 hours of working time with a range of 7.3 to 9.9 hours. An average of 72% of time was spent in clinical practice (range 64-83%). An average of 16% (range 11-20%) of time was spent in support of systems. Research (average 4%, range 3-7%), education (average 6%, range 3-16%), and publication and professional leadership (average 2%, range 0-6%) figured less prominently. The major activities performed within the clinical practice domain and the support of systems domain showed less variability across sites than was anticipated. The results of the study have helped the NP/CNSs and their management colleagues analyze and adapt the role to changing clinical requirements and economic realities.

Temporal trends in "legacy" organochlorine contaminants in blubber of ringed seals (Phoca hispida) from Ulukhaktok, NT, Canada between 1972 and 2010.

In blubber of ringed seals (Phoca hispida) from Ulukhaktok, NT, residues of DDT, other organochlorine pesticides, and PCBs declined between 1972 and 2010. The rate of decline varied: concentrations of the DDT-group began to fall after 1981, whereas those of PCBs fell rapidly between 1972 and 1981, and then slowed. Concentrations of cis- and trans-chlordane and of HCB in both sexes, and of cis-nonachlor in males, declined slowly between 1978 and 2010; those of other organochlorine pesticides remained steady. Exponential half-lives of p,p'-DDT and p,p'-DDE in female seals are about 9 and 36 y (corresponding to initial declines of 7.8% and 1.9% per year, respectively) and those of PCB congeners from about 20 to 60 y (declines of 3.2% to <1.5% per year); the more refractory residues may be detectable for centuries to come. Exploratory PCA of PCB congener distribution identified temporal changes apparently not related to molecular structure.

Nanogel vaccines targeting dendritic cells: contributions of the surface decoration and vaccine cargo on cell targeting and activation.

Dendritic cells (DCs) play crucial roles in initiating and promoting immune defences, providing a pivotal target for vaccines. Although nanoparticle/nanogel-based delivery vehicles are showing potential for delivering vaccines to the immune system, there is little information on their characteristics of interaction with DCs. While particle uptake by DCs has been shown, the mechanism of cell targeting has not been studied. Moreover, it is still unclear how particle surface decoration influences the handling of such vaccines by DCs. Accordingly, chitosan nanogels carrying a model antigen, ovalbumin (ova), were analysed for interaction with and processing by DCs. Nanogel surfaces decorated with alginate (alg) or mannosylated alginate (alg-man), were used for targeting particular DC receptors. DC uptake of particles was observed, being dependent on endosomal-based processes. Inhibiting PI3-kinase or lipid raft activities impaired the uptake, which was only reduced, indicating the involvement of more than one endocytic pathway; notably, this was observed with both nanogel-delivered or free ova. Importantly, surface decoration of particles was less influential on particle uptake, contrasting with the ova cargo which played the major role. Such influence of the vaccine cargo has to date been largely ignored. When receptors interacting directly with ova were blocked, this altered the uptake of alg-nanogels and alg-man-nanogels carrying ova. The nanogels did have an influential role, in that modulation of DC functional activity owed more to the nanogel structure. Using an in vitro restimulation assay with ova-specific lymphocytes, nanogel-delivered and free ova were similarly effective at inducing specific antibody. Nanogel-delivered ova with mannose surface decoration was superior to free ova for inducing interferon-γ production by T-lymphocytes. Together, the data demonstrates that particle-based vaccine delivery should consider the influences of both the surface decoration and the vaccine cargo; each can influence different aspects of the interaction with DCs. Such combined influences are likely to impinge on the characteristics of the immune response induced.