Therapeutic efficacy of zeta-cypermethrin pour-on for the treatment of biting and sucking lice in cattle under field conditions

Objective To assess the efficacy of zeta-cypermethrin pour-on to control cattle lice. Design Five field trials in south-eastern Australia. Procedure Zeta-cypermethrin pour-on, deltamethrin pour-on and pour-on vehicle were applied to groups of 10 cattle. Lice were counted before treatment and 14, 28, 42 and 56 days after treatment. Results Zeta-cypermethrin pour-on given at 2.5 mg/kg was equivalent to, or marginally more effective than a deltamethrin pour-on at 0.75 mg/kg. It eliminated B bovis and H eurysternus and gave good control of L vituli and S capillatus. Zeta-cypermethrin at 1 mg/kg gave good control of B bovis and H eurysternus but was not satisfactory against L vituli and S capillatus. Conclusion Zeta-cypermethrin pour-on, given at 2.5 mg/kg, is an effective treatment for cattle lice control. Zeta-cypermethrin, and other synthetic pyrethroid pour-ons, are the treatment of choice to control B bovis.

Cyanocobalt(III) complexes of penta- and tetradentate-coordinated macrocyclic hexaamines

The pendent-arm macrocyclic hexaamine trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine (L) may coordinate in tetra-, penta- or hexadentate modes, depending on the metal ion and the synthetic procedure. We report here the crystal structures of two pseudo-octahedral cobalt(III) complexes of L, namely sodium trans-cyano(trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine)cobalt(III) triperchlorate, Na[Co(CN)(C13H30N6)](ClO4)(3) or Na{trans-[CoL(CN)]}(ClO4)(3), (I), where L is coordinated as a pentadentate ligand, and trans-dicyano(trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine) cobalt (III) trans-dicyano (trans-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diaminium)cobalt(III) tetraperchlorate tetrahydrate, [Co(CN)(2)(Cl4H32N6)][Co(CN)(2)(Cl4H30N6)](ClO4)(4)•-4H(2)O or trans-[CoL(CN)(2)]trans-[Co(H2L)(CN)(2)] (ClO4)(4)•-4H(2)O, (II), where the ligand binds in a tetradentate mode, with the remaining coordination sites being filled by C-bound cyano ligands. In (I), the secondary amine Co-N bond lengths lie within the range 1.944 (3)-1.969 (3) &ANGS;, while the trans influence of the cyano ligand lengthens the Co-N bond length of the coordinated primary amine [Co-N = 1.986 (3) &ANGS;]. The Co-CN bond length is 1.899 (3) &ANGS;. The complex cations in (11) are each located on centres of symmetry. The Co-N bond lengths in both cations are somewhat longer than in (I) and span a narrow range [1.972 (3)-1.982 (3) &ANGS;]. The two independent Co-CN bond lengths are similar [1.918 (4) and 1.926 (4) &ANGS;] but significantly longer than in the structure of (1), again a consequence of the trans influence of each cyano ligand.

Quantification of sulfur and sulfur-containing compounds in wastewaters by means of a combination of liquid chromatographic methods

Low-micromolar concentrations of sulfite, thiosulfate and sulfide, present in synthetic wastewater or anaerobic digester effluent, were quantified by means of derivatization with monobromobimane, followed by HPLC separation with fluorescence detection. The concentration of elemental sulfur was determined, after its extraction with chloroform from the derivatized sample, by HPLC with UV detection. Recoveries of sulfide (both matrices), and of thiosulfate and sulfite (synthetic wastewater) were between 98 and 103%. The in-run RSDs on separate derivatizations were 13 and 19% for sulfite (two tests), between 1.5 and 6.6% for thiosulfate (two tests) and between 4.1 and 7.7% for sulfide (three tests). Response factors for derivatives of sulfide and thiosulfate, but not sulfite, were steady over a 13-month period during which 730 samples were analysed. Dithionate and tetrathionate did not seem to be detectable with this method. The distinctness of the elemental sulfur and the derivatizing-agent peaks was improved considerably by detecting elution at 297 instead of 263 nm. (C) 2002 Elsevier Science B.V. All rights reserved.

Cleavage of hemoglobin by hookworm cathespin D aspartic proteases and its potential contribution to host specificity

Hookworms routinely reach the gut of nonpermissive hosts but fail to successfully feed, develop, and reproduce. To investigate the effects of host-parasite coevolution on the ability of hookworms to feed in nonpermissive hosts, we cloned and expressed aspartic proteases from canine and human hookworms. We show here that a cathepsin D-like protease from the canine hookworm Ancylosotoma caninum (Ac-APR-1) and the orthologous protease from the human hookworm Necator americanus (Na-APR-1) are expressed in the gut and probably exert their proteolytic activity extracellularly. Both proteases were detected immunologically and enzymatically in somatic extracts of adult worms. The two proteases were expressed in baculovirus, and both cleaved human and dog hemoglobin (Hb) in vitro. Each protease digested Hb from its permissive host between twofold (whole molecule) and sixfold (synthetic peptides) more efficiently than Hb from the nonpermissive host, despite the two proteases' having identical residues lining their active site clefts. Furthermore, both proteases cleaved Hb at numerous distinct sites and showed different substrate preferences. The findings suggest that the paradigm of matching the molecular structure of the food source within a host to the molecular structure of the catabolic proteases of the parasite is an important contributing factor for host-parasite compatibility and host species range.

Synthesis, characterization and DFT studies of the cobalt(III) complex of a tetrapodal pentadentate N4S donor ligand

The synthesis of the pentadentate ligand 2,6-bis(3,3-dimethyl-2,4-dioxocyclohexanyl)-4-thiaheptane (N(4)Samp) is described. The synthetic pathway involves the coupling of two 1,3-(dimethylenedioxy)-2-methyl-2-(methylene-p-toluenesulfonyl)propane moieties with sodium sulfide and subsequent synthetic elaboration to prepare the final N4S donor system. The cobalt(III) complex [Co(N(4)Samp)Cl](2+) has been prepared and subsequently crystallized as the tetrachlorozincate salt. The X-ray structure analysis confirms the pentadentate nature of the ligand and shows the thioether donor occupying one apex with four equivalent amine donors effectively occupying the equatorial plane of the molecule. The sixth coordination site is occupied by a chloro ligand. The electronic absorption and C-13 NMR spectra have been studied. DFT calculations have been employed to explore structural and mechanistic comparisons between [Co(N(4)Samp)Cl](2+) and an analogous pentaamine complex.

Earthquake statistics in a Block Slider Model and a fully dynamic Fault Model

We examine the event statistics obtained from two differing simplified models for earthquake faults. The first model is a reproduction of the Block-Slider model of Carlson et al. (1991), a model often employed in seismicity studies. The second model is an elastodynamic fault model based upon the Lattice Solid Model (LSM) of Mora and Place (1994). We performed simulations in which the fault length was varied in each model and generated synthetic catalogs of event sizes and times. From these catalogs, we constructed interval event size distributions and inter-event time distributions. The larger, localised events in the Block-Slider model displayed the same scaling behaviour as events in the LSM however the distribution of inter-event times was markedly different. The analysis of both event size and inter-event time statistics is an effective method for comparative studies of differing simplified models for earthquake faults.

A subset-oriented algorithm for minimizing the number of steps required for synthesis of cyclic-peptide libraries

Libraries of cyclic peptides are being synthesized using combinatorial chemistry for high throughput screening in the drug discovery process. This paper describes the min_syn_steps.cpp program (available at http://www.imb.uq.edu.au/groups/smythe/tran), which after inputting a list of cyclic peptides to be synthesized, removes cyclic redundant sequences and calculates synthetic strategies which minimize the synthetic steps as well as the reagent requirements. The synthetic steps and reagent requirements could be minimized by finding common subsets within the sequences for block synthesis. Since a brute-force approach to search for optimum synthetic strategies is impractically large, a subset-orientated approach is utilized here to limit the size of the search. (C) 2002 Elsevier Science Ltd. All rights reserved.

Medical marijuana initiatives - Are they justified? How successful are they likely to be?

The principal constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC), is moderately effective in treating nausea and vomiting, appetite loss, and acute and chronic pain. Oral THC (dronabinol) and the synthetic cannabinoid, nabilone, have been registered for medical use in the US and UK, but they have not been widely used because patients find it difficult to titrate doses of these drugs. Advocates for the medical use of cannabis argue that patients should be allowed to smoke cannabis to relieve these above-mentioned symptoms. Some US state governments have legislated to allow the medical prescription of cannabis, but the US federal government has tried to prevent patients from obtaining cannabis and threatened physicians who prescribe it with criminal prosecution or loss of their licence to practise. In the UK and Australia, committees of inquiry have recommended medical prescription (UK) and exemption from criminal prosecution (New South Wales, Australia), but governments have not accepted these recommendations. The Canadian government allows an exemption from criminal prosecution to patients with specified medical conditions. It has recently legislated to provide cannabis on medical prescription to registered patients, but this scheme so far has not been implemented. Some advocates argue that legalising cannabis is the only way to ensure that patients can use it for medical purposes. However, this would be contrary to international drug control treaties and is electorally unpopular. The best prospects for the medical use of cannabinoids lie in finding ways to deliver THC that do not involve smoking and in developing synthetic cannabinoids that produce therapeutic effects with a minimum of psychoactive effects. While awaiting these developments, patients with specified medical conditions could be given exemptions from criminal prosecution to grow cannabis for their own use, at their own risk.

Cyclization of pyrrhocoricin retains structural elements crucial for the antimircobial activity of the native peptide

Pyrrhacoricin is a naturally occurring antimicrobial peptide from the European fire bug Pyrrhocoris apterus. It has submicromolar activity against a range of Gram-negative bacterial strains and has created recent interest as a lead for the development of novel antibiotic compounds. In this study, we have used NMR spectroscopy to determine the solution structures of pyrrhocoricin and a synthetic macrocyclic derivative that has improved in vivo pharmaceutical properties. Native pyrrhocoricin is largely disordered in solution, but there is evidence of a subpopulation with ordered turn regions over residues 2-5, 4-7, and 16-19. The macrocyclic derivative incorporates a nine amino acid linker joining the N- and C-termini, which does not adversely affect the antimicrobial potency but leads to a broader spectrum of activity. The NMR data suggest that the turn conformations in the cyclic derivative are similar to those in the native form, thus implicating them in the biological function. (C) 2004 Wiley Periodicals, Inc.

Embracing ligands. A synthetic strategy towards new nitrogen-thioether multidentate ligands and characterization of the cobalt(III) complexes

The synthesis of the hexadentate ligand 2,2,9,9-tetra(methyleneamine)-4,7-dithiadecane (EtN(4)S(2)amp) is reported. The ligand is of a type in which bifurcations of the chain occur at atoms other than donor atoms. The cobalt(III) complex [Co(EtN(4)S(2)amp)](3+) (1) was isolated and characterized. The synthetic methodology also results in a number of by-products, notably 2,9,9-tris(methyleneamine)-9-methylenehydroxy-4,7-dithiadecane (Et(HO)N(3)S(2)amp) and an eleven-membered pendant arm macrocyclic ligand 6,10-dimethyl-6,10-bis(methyleneamine)-1,4-dithia-8-azaacycloundec-7- ene (dmatue). The complexes [Co(Et(HO)N(3)S(2)amp)](3+) (2), in which the alcohol is coordinated to the metal ion, and [Co(dmatue)Cl](2+) (4) were isolated and characterized. Et(HO)N(3)S(2)amp also undergoes complexation with cobalt(III) to produce two isomers endo-[Co(Et(HO) N(3)S(2)amp)Cl](2+) (endo-3) and exo-[Co(Et(HO) N(3)S(2)amp)Cl](2+) (exo-3), both with an uncoordinated alcohol group. endo- 3 has the alcohol positioned cis, and exo-3 trans, to the sixth metal coordination site. Reaction of 1 with isobutyraldehyde, paraformaldehyde and base in dimethylformamide results in the encapsulated complex [Co(1,5,5,9,13,13-hexamethyl-18,21-dithia-3,7,11,15-tetraazabicyclo[7.7.6]docosa- 3,14-diene)](ClO4)(3) . 2H(2)O ([Co(Me(6)docosadieneN(4)S(2))](3+) ( 5). All complexes have been characterized by single crystal X-ray study. The low-temperature (11 K) absorption spectrum of 1 has been measured in Nafion films with spin-allowed (1)A(1g) --> T-1(1g) and (1)A(1g) --> T-1(2g) and spin forbidden (1)A(1g) --> T-3(1g) and (1)A(1g) --> T-3(2g) bands observed. The octahedral ligand-field parameters were determined (10Dq = 22570 cm(-1), B = 551 cm(-1); C = 3500 cm(-1)). For 5 10Dq and B were determined (20580 cm(-1); 516 cm(-1), respectively) and compared with those for similar expanded cavity complexes [Co(Me(8)tricosatrieneN(6))](3+) and [Co(Me(5)tricosatrieneN(6))](3+).

The chemistry of novolac resins .3. C-13 and N-15 nmr studies of curing with hexamethylenetetramine

The reactions between novolac resins and hexamethylenetetramine (HMTA) which occur on curing have been studied by C-13 and N-15 high-resolution n.m.r. in both solution and the solid state. Strong evidence for the existence of many curing intermediates is obtained. New curing intermediates are reported along with experimental data to support previously postulated intermediates. The initial curing reactions between novolac and HMTA produce various substituted benzoxazines and benzylamines. Thermal decomposition/oxidation and further reactions of these initial intermediates generate methylene linkages between phenolic rings for chain extension and cross-linking. Among the three kinds of methylene linkages, the para-para methylene linkages are formed at relatively lower temperatures. Various imine, amide and imide side-products also concurrently appear during the process. The initial amount of HMTA plays a critical role in the curing reactivity and chemical structures of the cured resins. The lower the amount of HMTA, the lower the temperature at which curing occurs, and the lower the amount of the nitrogen-containing side-products in the finally cured resins. The ortho-linked intermediates are relatively stable, and can remain in the cured resins up to higher temperatures. The study provides an extensive description of the curing reactions of novolac resins. (C) 1997 Elsevier Science Ltd.

Carbohydrate-based templates for synthetic vaccines and drug delivery

Methyl tetra-O-allyl, and tetra-O-[2-(tetrahydro-2H-pyranyl)oxy.-3-oxapentyl glucosides, and tetra-O-(cyanoethyl)galactosyl azide were converted into derivatives containing linkers with terminal carboxylic acid functionalities at the anomeric position and bearing four arms with phthaloyl- or BOC-protected terminal amino groups. These molecules were suitable for use in solid-phase peptide synthesis and for the preparation of dendrimers, containing multiple copies of peptides. (C) 2001 Elsevier Science Ltd. All rights reserved.