Veterinary drug delivery: Potential for skin penetration enhancement

A range of topical products are used in veterinary medicine. The efficacy of many of these products has been enhanced by the addition of penetration enhancers. Evolution has led to not only a highly specialized skin in animals and humans, but also one whose anatomical structure and skin permeability differ between the various species. The skin provides an excellent barrier against the ingress of environmental contaminants, toxins, and microorganisms while performing a homeostatic role to permit terrestrial life. Over the past few years, major advances have been made in the field of transdermal drug delivery. An increasing number of drugs are being added to the list of therapeutic agents that can be delivered via the skin to the systemic circulation where clinically effective concentrations are reached. The therapeutic benefits of topically applied veterinary products is achieved in spite of the inherent protective functions of the stratum corneum (SQ, one of which is to exclude foreign substances from entering the body. Much of the recent success in this field is attributable to the rapidly expanding knowledge of the SC barrier structure and function. The bilayer domains of the intercellular lipid matrices within the SC form an excellent penetration barrier, which must be breached if poorly penetrating drugs are to be administered at an appropriate rate. One generalized approach to overcoming the barrier properties of the skin for drugs and biomolecules is the incorporation of suitable vehicles or other chemical compounds into a transdermal delivery system. Indeed, the incorporation of such compounds has become more prevalent and is a growing trend in transdermal drug delivery. Substances that help promote drug diffusion through the SC and epidermis are referred to as penetration enhancers, accelerants, adjuvants, or sorption promoters. It is interesting to note that many pour-on and spot-on formulations used in veterinary medicine contain inert ingredients (e.g., alcohols, amides, ethers, glycols, and hydrocarbon oils) that will act as penetration enhancers. These substances have the potential to reduce the capacity for drug binding and interact with some components of the skin, thereby improving drug transport. However, their inclusion in veterinary products with a high-absorbed dose may result in adverse dermatological reactions (e.g., toxicological irritations) and concerns about tissue residues. These a-re important considerations when formulating a veterinary transdermal product when such compounds ate added, either intentionally or otherwise, for their penetration enhancement ability. (C) 2001 Elsevier Science B.V. All rights reserved.

Colourful objects through animal eyes

To understand how bees, birds, and fish may use colour vision for food selection and mate choice, we reconstructed views of biologically important objects taking into account the receptor spectral sensitivities. Reflectance spectra a of flowers, bird plumage, and fish skin were used to calculate receptor quantum catches. The quantum catches were then coded by red, green, and blue of a computer monitor; and powers, birds, and fish were visualized in animal colours. Calculations were performed for different illumination conditions. To simulate colour constancy, we used a von Kries algorithm, i.e., the receptor quantum catches were scaled so that the colour of illumination remained invariant. We show that on land this algorithm compensates reasonably well for changes of object appearance caused by natural changes of illumination, while in water failures of von Kries colour constancy are prominent. (C) 2000 John Wiley & Sons, Inc.

A survey of Australian consumers' attitudes towards UHT milk

A telephone survey was conducted in Melbourne and Brisbane to obtain a profile of milk consumption in Australia and determine consumers' attitudes regarding UHT milk. It was anticipated that this survey would reveal the reasons for the low level of UHT milk consumption in Australia. Pasteurised milk was the main milk type used by more than 80% of respondents. For UHT milk this figure was much lower (approximately 10%), even though two thirds of respondents had tried UHT milk. Factors that were found to influence UHT milk consumption included existing milk consumption habits, consumer perception, flavour and price. The majority of non-users of UHT milk stated habit of using other milk type as their main reason for not using UHT milk. Other reasons included poor nutritional value, poor flavour and not real/pure milk, indicating a negative consumer perception of the product. The flavour of UHT milk was identified as a problem, with nearly half of UHT milk users considering it to be worse than the flavour of pasteurised milk. However, a small proportion of UHT milk users preferred the flavour of UHT milk, with the majority of them stating that it was creamier, richer and/or stronger than the flavour of pasteurised milk. Prior to post-farmgate deregulation, price was shown to discourage consumers from using UHT milk. At the time of the survey, post-farmgate prices in Victoria were deregulated resulting in UHT milk being priced below that of pasteurised milk in some instances. This was believed to contribute to a significantly higher market share of the product in Melbourne than in Brisbane.

Evaluation of liquid Bacillus thuringiensis var. israelensis products for control of Australian Aedes arbovirus vectors

Laboratory bioassay studies were conducted in southeast Queensland, Australia,: on the efficacy of Teknar (R), VectoBac (R) 12AS, and Cybate (R) (active ingredient: 1,200 international toxic units Bacillus thuringiensis var, israelensis [Bti]) against 3rd instars of the arbovirus vectors Aedes aegypti. Ae. notoscriptus, Ae. vigilax, and Ae. camptorhynchus. Probit analyses were then used to determine LD,, (median lethal dose), LD95, and lethal dose ratios (LDR). Aedes aegypti and Ae. notoscriptus, both container-habitat species, tolerated the highest Bti concentrations compared with saltmarsh Ae. vigilax and Ae. camptorhynchus. For example, the LDR for Ae. vigilax versus Ae. notoscriptus exposed to Cybate was 0.14 (95% confidence limit [CL] 0.03-0.61). Similarly, the Cybate LDR for Ae. camptorhynchus versus Ae. notoscriptus was 0.22 (95% CL 0.07-0.70). Teknar produced similar results with an LDR of 0.21 (95% CL 0.04-1.10) for Aedes vigilax versus Aedes notoscriptus. Differences in product efficacy were found when tested against the 2 container-breeding species. Cybate was less effective than Teknar with LDRs of 1.55 (95% CL 0.65-3.67) and 1.87 (95% CL 0.68-5.15) for Aedes aegypti and Ae. notoscriptus, respectively. The significant differences in susceptibility between mosquito species and varying efficacy between products highlight the importance of evaluating concentration-response data prior to contracting with distributors of mosquito control products. This information is crucial to resistance management strategies.

Immune responses to ISCOM (R) formulations in animal and primate models

ISCOMs(R) are typically 40 nm cage-like structures comprising antigen, saponin, cholesterol and phospholipid. ISCOMs(R) have been shown to induce antibody responses and activate T helper cells and cyrolytic T lymphocytes in a number of animal species, including non-human primates. Recent clinical studies have demonstrated that ISCOMs(R) are also able to induce antibody and cellular immune responses in humans. This review describes the current understanding of the ability of ISCOMs(R) to induce immune responses and the mechanisms underlying this property. Recent progress in the characterisation and manufacture of ISCOMs(R) will also be discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.

N-15 natural abundance of fossil peat reflects the influence of animal-derived nitrogen on vegetation

delta(15)N signatures of fossil peat were used to interpret past ecosystem processes on tectonically active subantarctic Macquarie Island. By comparing past vegetation reconstructed from the fossil record with present-day vegetation analogues, our evidence strongly suggests that changes in the delta(15)N signatures of fossil peat at this location reflect mainly past changes in the proportion of plant nitrogen derived from animal sources. Associated with uplift above sea level over the past 8,500 years, fossil records in two peat deposits on the island chronicle a change from coastal vegetation with fur and elephant seal disturbance to the existing inland herbfield. Coupled with this change are synchronous changes in the delta(15)N signatures of peat layers. At two sites N-15-enriched peat delta(15)N signatures of up to +17parts per thousand were associated with a high abundance of pollen of the nitrophile Callitriche antarctica (Callitrichaceae). At one site fossil seal hair was also associated with enriched peat delta(15)N. Less N-15 enriched delta(15)N signatures (e.g. -1.9parts per thousand to +3.9parts per thousand) were measured in peat layers which lacked animal associated C. antarctica and Acaena spp. Interpretation of a third peat profile indicates continual occupation of a ridge site by burrowing petrels for most of the Holocene. We suggest that N-15 signatures of fossil peat remained relatively stable with time once deposited, providing a significant new tool for interpreting the palaeoecology.

Latin interchanges and direct products

In this paper we focus on the identification of latin interchanges in latin squares which are the direct product of latin squares of smaller orders. The results we obtain on latin interchanges will be used to identify critical sets in direct products. This work is an extension of research carried out by Stinson and van Rees in 1982.

From molecular complexes to zwitterions and final products. Reactions between C3O2 and amines

The formation of molecular complexes (prereactive intermediates) between C3O2 and amines (ammonia, dimethylamine, trimethylamine, and 4-(dimethylamino)pyridine) as well as the subsequent transformation of the complexes into C3O2-amine zwitterions in cryogenic matrixes (ca. 40 K) has been observed. In the case of dimethylamine, the formation of tetramethylmalonamide has also been documented. Calculations using density functional theory (B3LYP/6-31G(2d, p)) are used to assign all above species and are in excellent agreement with the IR spectra.

Geographic variation of natural products of tropical nudibranch Asteronotus cespitosus

Extracts of the dorid nudibranch Asteronotus cespitosus from two geographically separate regions of Australia and from the Philippines were compared using thin-layer, high-performance liquid and gas chromatography and H-1 NMR analysis. Halogenated metabolites were detected in all mollusk specimens. The major component detected in digestive tissue of specimens from the Great Barrier Reef in northeastern Australia was 4,6-dibromo2-(2',4'-dibromophenoxy)phenol (1), with minor amounts of 3,5-dibromo-2(3',5'-dibromo-20-methoxyphenoxy)phenol (2). In a specimen collected from northwestern Australia, only 3,5-dibromo-2-(3',5'-dibromo-2'-methoxyphenoxy)phenol was found. The specimen from the Philippines contained 2,3,4,5-tetrabromo-6-(2'-bromophenoxy) phenol (3) together with a novel chlorinated pyrrolidone (4). In addition, the sesquiterpenes dehydroherbadysidolide (5) and spirodysin (6) were detected in the digestive organs and mantle tissue of the nudibranchs from the Great Barrier Reef and from the Philippines, whereas these chemicals were not found in the specimen from northwestern Australia. All of the chemicals (1-3,5, and 6) have previously been isolated from the sponge Dysidea herbacea, as have chlorinated metabolites related to 4. This is the first time the characteristic halogenated metabolites that typify Dysidea herbacea have been reported from a carnivorous mollusk, which implies a dietary origin as opposed to de novo synthesis.

A review of animal models for the study of arsenic carcinogenesis

As inorganic arsenic is a proven human carcinogen, significant effort has been made in recent decades in an attempt to understand arsenic carcinogenesis using animal models, including rodents (rats and mice) and larger mammals such as beagles and monkeys. Transgenic animals were also used to test the carcinogenic effect of arsenicals, but until recently all models had failed to mimic satisfactorily the actual mechanism of arsenic carcinogenicity. However, within the past decade successful animal models have been developed using the most common strains of mice or rats. Thus dimethylarsinic acid (DMA), an organic arsenic compound which is the major metabolite of inorganic arsenicals in mammals, has been proven to be tumorigenic in such animals. Reports of successful cancer induction in animals by inorganic arsenic (arsenite and arsenate) have been rare, and most carcinogenetic studies have used organic arsenicals such as DMA combined with other tumor initiators. Although such experiments used high concentrations. of arsenicals for the promotion of tumors, animal models using doses of arsenicals species closed to the exposure level of humans in endemic areas are obviously the most significant. Almost all researchers have used drinking water or food as the pathway for the development of animal model test systems in order to mimic chronic arsenic poisoning in humans; such pathways seem more likely to achieve desirable results. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.