Bioavailability and activity of 0.1% amcinonide preparations: comparison with proprietary topical corticosteroid formulations of differing potencies

The activity of a 0.1% amcinonide cream was compared with those of selected proprietary topical corticosteroid formulations of potencies differing according to the United Kingdom (U.K.) MIMS classification (very potent, potent and moderately potent) using a standard six hour vasoconstrictor assay with multiple reading times. Statistical analysis indicated that 0.1% amcinonide cream feU within the category of a very potent preparation. Three 0.1% amcinonide formulations (cream, combination cream and combination ointment, the last two containing anti-infective agents) were equipotent in the skin-blanching test

Doing agribusiness in China

There is a widespread belief that partner arrangements between New Zealand and Chinese businesses have a high risk of failure as a result of different ways of doing business. This article presents perspectives on these cross-cultural problems, developed from interviews with nine informants from the food and agribusiness sector, including four New Zealand entrepreneurs who currently work and live in China. Also interviewed were five Chinese who are either entrepreneurs themselves, or middle to senior management working closely with New Zealanders. The information presented here is the first stage of a research project investigating cross-cultural business relationships between New Zealanders and Chinese in New Zealand agribusinesses operating in China

Possible dosage regimens for topical steroids assessed by vasoconstrictor assays using multiple applications

The bioavailabilities and activities of three amcinonide preparations and Betnovate cream were assessed using three multiple-dosage regimen vasoconstrictor assays in 10 volunteers. Applications were made once daily, twice daily and every alternate day with an initial three times daily loading dose applied on the first day only. Blanching responses first increased and then decreased due to tachyphylaxis. It is proposed that clinically the most advantageous dosage regimen is a once daily application with no loading dose

Le test de McKenzie-Stoughton: méthode de mesure de l’effect réservoir

A la suite de I'observation que firent Mac Kenzie et Stoughton en 1962, montrant que I'application locale de cortico'ldes anti-inflammatoires peut produire un blanchiment de la peau, des tests ont ete mis au point pour apprecier la constitution d'une telle paleur chez des sujets volontaires. Les techniques qui ont ete publiees sont variables quant a la methode d'application (avec ou sans occlusion), la duree d'application du cortico'lde (.c'est-a-dire duree breve de 6 a 8 heures ou prolongee de 16 a 20 heures) et quant a la methode d'appreciation de la reponse, enregistree par exemple comme etant presente ou absente, ou bien cotee, soit avec une simple lecture,. soit avec des lectures repetees, pendant un certain temps. Les auteurs ont mis au point des essais standart de vasoconstriction avec et sans occlusion, pour apprecier les preparations quant a leur efficacite clinique pour determiner la biodisponibilite des cortico'ldes a partir des supports pour applications locales. A condition que I'investigateur et Ie volontaire se conforment strictement au protocole du test les methodes suivantes ont une precision surprenante d'appreciation (Barry et Woodford, 1978)

Dairy farming with reduced inductions

The New Zealand (NZ) dairy industry is reliant on seasonal pasture production and a concentrated calving interval to best match pasture supply and animal demand. To achieve this goal, some farmers induce lactation in late calving cows. This has animal welfare implications, which could result in non-tariff trade barriers to NZ dairy products (Blackett, Compton and Glassey, C. 2006, Stevens, J., Burton, L, Rendel, J. 2000). Additionally there are concerns with drug residues in the milk from herds where a large percentage of cows are induced. New standards were introduced in the 2010-11 season by the NZ Veterinarians Association (NZVA), Dairy NZ, Dairy Companies Association of NZ (DCANZ) and Federated Farmers. In the 2011-12 season the level of inductions within an individual herd will not exceed 8% reducing to 4% in 2012-13. There will be requirements for information about the stage of pregnancy; the age of the cow (under eight years old) and body condition score (4.5 to 6.5). Although this reduction may seem onerous, the NZVA has stated that only 3% of the national herd was induced in the season just finished, with 98% of farms being under 15% (Benny 2011). A survey of Canterbury dairy farmers in 2008 found that 36% operate a nil induction policy (Pangborn, 2008). With reduced levels of inductions farmers will be forced to adopt an eight week mating system if they are to maintain the traditional calving patterns. If the number of late calving cows cannot be reduced to fewer than 4%, then a larger number of cows will be culled. If a pregnant cow is worth $2,000 and a non-pregnant cow$500 there could be significant capital losses. The purpose of this paper is to review the basics of getting cows in calf and strategies for reduced inductions, discuss the results of the nil induction policy of the Lincoln University Dairy Farm (LUDF), and look at the plan of one Canterbury farm to meet the new guidelines

Activity of OP0595-β-lactam combination against Gram-negative bacteria with extended-spectrum, AmpC and carbapenem-hydrolysing β-lactama

Background: OP0595 is a diazabicyclooctane that (i) acts as a PBP2-ctive antibacterial, (ii) inhibits Class A and C β-lactamases and (iii), like mecillinam, gives β-lactamase-independent potentiation of β-lactams targeting other PBPs. We tested its behaviour against β-lactam-resistant Enterobacteriaceae and non-fermenters. Methods: Organisms were UK clinical isolates; MICs were determined by CLSI agar dilution for OP0595 alone or combined at 1–4 mg/L with aztreonam, biapenem, cefepime or piperacillin. Results: MICs of OP0595 for Escherichia coli, Enterobacter, Citrobacter and Klebsiella spp. were mostly 1–4 mg/L but values >4 mg/L were seen for minorities of isolates irrespective of other resistances, and for 50%–60% of those with ertapenem resistance involving porin loss plus ESBL or AmpC activity. OP0595 MICs for Serratia, Proteeae and non-fermenters mostly were >4 mg/L. When its MIC was ≤4 mg/L, OP0595's antibacterial activity dominated combination activity. For ‘OP0595-resistant’ (MIC >4 mg/L) isolates with Class A or C β-lactamases OP0595 achieved strong potentiation of substrate β-lactams, contingent on β-lactamase inhibition. β-Lactamase-independent potentiation was evident with aztreonam, cefepime and piperacillin—less so for biapenem—for many OP0595-resistant Enterobacteriaceae with Class B carbapenemases, which are not inhibited by OP0595. OP0595 acted solely as a β-lactamase inhibitor for non-fermenters. Conclusions: OP0595 inhibited Enterobacteriaceae, not non-fermenters; its combinations had broad activity versus Enterobacteriaceae, largely contingent on OP0595's antibacterial activity but also on inhibition of Class A and C β-lactamases and on the β-lactam-enhancer effect, which allowed activity against many OP0595-resistant metallo-β-lactamase-producing Enterobacteriaceae. For non-fermenters OP0595 acted only as a β-lactamase inhibitor

Activity of RX-04 Pyrrolocytosine Protein Synthesis Inhibitors against Multidrug-Resistant Gram-Negative Bacteria

Pyrrolocytosines RX-04A-D are designed to bind to the bacterial 50S ribosomal subunit differently from currently-used antibiotics. The four analogs had broad anti-Gram-negative activity: RX-04A inhibited 94.7% of clinical Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa at 0.5-4 μg/ml, with no MICs >8 μg/ml. MICs for multi-resistant carbapenemase producers were up to two-fold higher than for control strains, with values ≥8 μg/ml for one Serratia isolate with porin and efflux lesions. mcr-1 did not affect MICs

In vitro activity of cefepime/zidebactam (WCK 5222) against Gram-negative bacteria

Background: Diazabicyclooctanes (DBOs) inhibit class A, class C and some class D β-lactamases. A few also bind PBP2, conferring direct antibacterial activity and a β-lactamase-independent ‘enhancer' effect, potentiating β-lactams targeting PBP3. We tested a novel DBO, zidebactam, combined with cefepime. Methods: CLSI agar dilution MICs were determined with cefepime/zidebactam in a chequerboard format. Bactericidal activity was also measured. Results: Zidebactam MICs were ≤2 mg/L (mostly 0.12–0.5 mg/L) for most Escherichia coli, Klebsiella, Citrobacter and Enterobacter spp., but were >32 mg/L for Proteeae, most Serratia and a few E. coli, Klebsiella and Enterobacter/Citrobacter. The antibacterial activity of zidebactam dominated chequerboard studies for Enterobacteriaceae, but potentiation of cefepime was apparent for zidebactam-resistant isolates with class A and C enzymes, illustrating β-lactamase inhibition. Overall, cefepime/zidebactam inhibited almost all Enterobacteriaceae with AmpC, ESBL, K1, KPC and OXA-48-like β-lactamases at 1 + 1 mg/L and also 29 of 35 isolates with metallo-carbapenemases, including several resistant to zidebactam alone. Zidebactam MICs for 36 of 50 Pseudomonas aeruginosa were 4–16 mg/L, and the majority of AmpC, metallo-β-lactamase-producing and cystic fibrosis isolates were susceptible to cefepime/zidebactam at 8 + 8 mg/L. Zidebactam MICs for Acinetobacter baumannii and Stenotrophomonas maltophilia were >32 mg/L; potentiation of cefepime was frequent for S. maltophilia, but minimal for A. baumannii. Kill curve results largely supported MICs. Conclusion: Zidebactam represents a second triple-action DBO following RG6080, with lower MICs for Enterobacteriaceae and P. aeruginosa. Clinical evaluation of cefepime/zidebactam must critically evaluate the reliance that can be placed on this direct antibacterial activity and on the enhancer effect as well as β-lactamase inhibition

Elevated immune gene expression is associated with poor reproductive success of urban blue tits

Urban and forest habitats differ in many aspects that can lead to modifications of the immune system of wild animals. Altered parasite communities, pollution, and artificial light at night in cities have been associated with exacerbated inflammatory responses, with possibly negative fitness consequences, but few data are available from free-living animals. Here, we investigate how urbanization affects major immune pathways and experimentally test potentially contributing factors in blue tits (Cyanistes caeruleus) from an urban and forest site. We first compared breeding adults by quantifying the mRNA transcript levels of proteins associated with anti-bacterial, anti-malarial (TLR4, LY86) and anti-helminthic (Type 2 transcription factor GATA3) immune responses. Adult urban and forest blue tits differed in gene expression, with significantly increased TLR4 and GATA3, but not LY86, in the city. We then experimentally tested whether these differences were environmentally induced by cross-fostering eggs between the sites and measuring mRNA transcripts in nestlings. The populations differed in reduced reproductive success, with a lower fledging success and lower fledgling weight recorded at the urban site. This mirrors the findings of our twin study reporting that the urban site was severely resource limited when compared to the forest. Because of low urban survival, robust gene expression data were only obtained from nestlings reared in the forest. Transcript levels in these nestlings showed no (TLR4, LY86), or weak (GATA3), differences according to their origin from forest or city nests, suggesting little genetic or maternal contribution to nestling immune transcript levels. Lastly, to investigate differences in parasite pressure between urban and forest sites, we measured the prevalence of malaria in adult and nestling blood. Prevalence was invariably high across environments and not associated with the transcript levels of the studied immune genes. Our results support the hypothesis that inflammatory pathways are activated in an urban environment and suggest that these differences are most likely induced by environmental factors