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Oestrogens and prostate cancer.

Androgens are essential for stimulating normal development, growth and secretory activities of the prostate whereas oestrogens are generally regarded as inhibitors of growth. Evidence for the local synthesis of oestrogens includes the detection of aromatase mRNA and protein in the stroma of human non-malignant tissues and in malignant tissue, where it is detected in epithelial tumour cells. As well, aromatase activity was measured by biochemical assay and protein was detected in prostatic non-malignant and tumour cell lines. Taken together with the identification of direct oestrogenic actions on the prostate, these results suggest that alterations in local oestrogen synthesis may have significant consequences in malignancy of these organs. Genetically modified mouse models were studied in order to evaluate the action of oestrogens alone or in combination with androgens on the prostate gland. Hypogonadal (hpg) mice are deficient in gonadotrophins and androgens but showed direct proliferative responses to oestradiol. The responses were characterised by discrete lobe-specific changes including smooth-muscle regression, fibroblast proliferation, inflammation, and basal epithelial cell proliferation and metaplasia. The aromatase knockout (ArKO) mouse, deficient in oestrogens due to a non-functional aromatase enzyme, developed prostatic hyperplasia during the lifelong exposure to elevated androgens, however, no malignant changes were detected in the prostate at any time. In contrast, combined androgen and oestrogen treatment has been shown to induce prostatic dysplasia and adenocarcinoma. These results demonstrate that malignant changes to the prostate gland are dependent upon both androgenic and oestrogenic responses and that neither hormone alone is sufficient to evoke aberrant patterns of growth, resulting in malignancy.

Androgens↗

Models of risk assessments for biologicals or related products in the European Union.

In the context of veterinary biologicals, environmental risk assessment means the evaluation of the risk to human health and the environment (which includes plants and animals) connected with the release of such products. The following categories or types of veterinary biologicals can be distinguished: non-genetically modified organisms (non-GMOs) (inactivated/live) GMOs (inactivated/live) carrier products related products (e.g. non-specific "inducers'). Suitable models used in risk assessment for these products should aim to identify all possible adverse effects. A good working model should lead, at least, to a qualitative judgement on the environmental risk of the biological product (e.g. negligible, low, medium, severe, unacceptable). Quantifiable outcomes are rare; therefore, the producer of a biological product and the European control authorities should accept only models which are based on testable points and which are relevant to the type of product and its instructions for use. In view of animal welfare aspects, models working without animals should be preferred. In recent years, some of these methods have been integrated into safety tests described in European Union Directives and in monographs of the European Pharmacopoeia. By reviewing vaccine/registration problems (e.g. Aujeszky's disease live vaccine for pigs, and vaccinia-vectored rabies vaccine), several models used in risk assessment are demonstrated and discussed.

Animals↗

Microdetermination of double-stranded DNA by linear sweep voltammetry with phenosafranine.

A novel voltammetric method for the determination of microamounts of fish sperm double-stranded (ds) DNA based on its interaction with phenosafranine (PSF) is proposed in this paper. In a pH 3.5 Britton-Robinson (B-R) buffer solution, PSF had a well-defined second-order derivative linear-sweep voltammetric reductive peak at -0.32 V (vs. SCE) on a mercury electrode. After the addition of dsDNA into the PSF solution, the reductive peak current decreased significantly without a shift of the peak potential, and no new peak appeared. The experiment results showed that a new supramolecular complex was formed after the interaction of dsDNA with PSF, which resulted in a decrease of the diffusion coefficient, and then a decrease of the reductive peak current. The interaction conditions and the electrochemical detection conditions were carefully investigated. Under the optimal conditions, the decrease of the peak current was proportional to the dsDNA concentration in the range 1.0 - 40.0 microg/mL with the linear regression equation DeltaI(p)''(nA) = 32.59C(microg/mL) - 4.03 (n = 13, gamma = 0.998) and a detection limit of 0.25 microg/mL (3 sigma). The interaction mechanism was considered based on the aggregation of the dsDNA-PSF supramolecular complex; the stoichiometry of this supramolecular complex was calculated based on voltammetric data with a binding number of 3 and a binding constant of 2.76 x 10(12). This method was successfully applied to the determination of synthetic samples and the polymerase chain reaction (PCR) product of the nopaline synthase gene (NOS) DNA from genetically modified organisms (GMOs) with satisfactory results.

Animals↗

Life forms protectable as subjects of U.S. patents -- microbes to animals (perhaps).

Scientists, businessmen, universities and industries with fundamental or peripheral interests in technology as applied to life processes will be keenly interested in recent U.S. Patent Office decisions. These decisions indicate that new higher life forms, animal or plant, are proper subjects of patents if they are not naturally occurring (and are not human in the case of animals). In contrast to plants and other organisms, genetically modified animals have had no mode of protection as intellectual property except possibly as a trade secret or utility patent. The Ex parte Allen decision, reached by the Patent Office Board of Appeals and Interferences, directly addressed the issue of animal patentability in view of the broad reading of 35 U.S.C. section 101 by the U.S. Supreme Court in the Chakrabarty decision. The subject invention concerned polyploid oysters. Claims directed toward polyploid oysters produced by a particular process were rejected under 35 U.S.C. section 103 and section 101. The Board, reversing the 35 U.S.C. section 101 - based rejection in view of the Chakrabarty decision, indicated that the claimed polyploid oysters were non-naturally occurring manufactures or compositions of matter within the confines of patentable subject matter under 35 U.S.C. section 101. A similar decision affecting the patentable status of plants or segments thereof had previously been reached by the Patent and Trademark Office in the case of Ex parte Hibberd, 227 U.S.P.Q. 443 (Bd. Pat. App. 1985). The Hibberd utility patent application concerned "genetically engineered" maize which had high levels of the tryptophan.

Animals↗

[From bioethics to the new technology ethics].

Just as what we can all "technoscience" is emerging in our everyday life, a reflection should be conducted concerning the implications of the scientific and technical progress within our society from now on globalised. We will tackle successively: 1. The ambiguities and paradoxes related to the development of new technologies: in the field of bioethics: artificial reproduction, mammal cloning, genetically modified organisms. towards the ethics of new technologies: ethics of information and communication technologies and ethics of space policy; 2. Nature, foundation and characteristics of the ethical approach; the precaution principle must be completed with two other principles: the principle of experience and the principle of vigilance; 3. The modalities of a democratic management of the ethical approach: it is a matter of defining the role of the three main actors, i.e.: experts, politicians and citizens representing public opinion. It is necessary to promote the ethical approach within a democratic context, that is to ensure a dialogue between experts, policy decision-makers and public opinion on all of the applications of science and technology. It is from such a permanent and renewed dialogue that will emerge the image we give from ourselves in the present world.

Bioethics↗

Use of molecular techniques in bioremediation.

In a practical sense, biotechnology is concerned with the production of commercial products generated by biological processes. More formally, biotechnology may be defined as "the application of scientific and engineering principles to the processing of material by biological agents to provide goods and services" (Cantor, 2000). From a historical perspective, biotechnology dates back to the time when yeast was first used for beer or wine fermentation, and bacteria were used to make yogurt. In 1972, the birth of recombinant DNA technology moved biotechnology to new heights and led to the establishment of a new industry. Progress in biotechnology has been truly remarkable. Within four years of the discovery of recombinant DNA technology, genetically modified organisms (GMOs) were making human insulin, interferon, and human growth hormone. Now, recombinant DNA technology and its products--GMOs are widely used in environmental biotechnology (Glick and Pasternak, 1988; Cowan, 2000). Bioremediation is one of the most rapidly growing areas of environmental biotechnology. Use of bioremediation for environmental clean up is popular due to low costs and its public acceptability. Indeed, bioremediation stands to benefit greatly and advance even more rapidly with the adoption of molecular techniques developed originally for other areas of biotechnology. The 1990s was the decade of molecular microbial ecology (time of using molecular techniques in environmental biotechnology). Adoption of these molecular techniques made scientists realize that microbial populations in the natural environments are much more diverse than previously thought using traditional culture methods. Using molecular ecological methods, such as direct DNA isolation from environmental samples, denaturing gradient gel electrophoresis (DGGE), PCR methods, nucleic acid hybridization etc., we can now study microbial consortia relevant to pollutant degradation in the environment. These techniques promise to provide a better understanding and better control of environmental biotechnology processes, thus enabling more cost effective and efficient bioremediation of our toxic waste and contaminated environments.

Bacteria↗

Contaminants in feed for food-producing animals.

Outbreaks of Bovine Spongiform Encephalopathy (BSE) and food borne microbial infections, dioxin contaminated animal products, the presence of veterinary drug residues, microbial resistance to antibiotics, mycotoxins, agricultural and industrial chemicals, etc. are serious concerns for the food industry in many countries. Since the direct links between feed safety and safety of foods of animal origin are obvious, feed production and manufacture should be considered as an integral part of the food production chain. Industry is responsible for the quality and safety of food and feed that is produced. This paper is a brief review of some microorganisms as source of infections for farm animals that could result in human illnesses. These include Salmonella enterica, Bacillus anthracis, Toxoplasma gondii, Trichinella spiralis, prions, Listeria monocytogenes, EHEC, Campylobacter, Clostridium botulinum, Hog Cholera virus, Foot and Mouth Disease virus, etc. as well as other contaminants associated with animal feed such as mycotoxins, veterinary drugs, dioxins and PCB and Genetically Modified Organisms.

Animal Feed↗

[Applied ecology: retrospect and prospect].

Applied ecology is evolved into a principal part of modern ecology that rapidly develops. The major stimulus for the development of applied ecology roots in seeking the solutions for the problems of human populations, resources and environments. Through four decades, the science of applied ecology has been becoming a huge group of disciplines. The future for the applied ecology should concern more with human-influenced and managed ecosystems, and acknowledge humans as the components of ecosystems. Nowadays and in future, the top-priorities in applied ecology should include following fields: sustainable ecosystems and biosphere, ecosystem services and ecological design, ecological assessment of genetically modified organisms, ecology of biological invasions, epidemical ecology, ecological forecasting, ecological process and its control. The authors believe that the comprehensive and active research hotspots coupled some new traits would occur around these fields in foreseeable future.

Conservation of Natural Resources↗

DNA vaccines for aquacultured fish.

Deoxyribonucleic acid (DNA) vaccination is based on the administration of the gene encoding the vaccine antigen, rather than the antigen itself. Subsequent expression of the antigen by cells in the vaccinated hosts triggers the host immune system. Among the many experimental DNA vaccines tested in various animal species as well as in humans, the vaccines against rhabdovirus diseases in fish have given some of the most promising results. A single intramuscular (IM) injection of microgram amounts of DNA induces rapid and long-lasting protection in farmed salmonids against economically important viruses such as infectious haematopoietic necrosis virus (IHNV) and viral haemorrhagic septicaemia virus (VHSV). DNA vaccines against other types of fish pathogens, however, have so far had limited success. The most efficient delivery route at present is IM injection, and suitable delivery strategies for mass vaccination of small fish have yet to be developed. In terms of safety, no adverse effects in the vaccinated fish have been observed to date. As DNA vaccination is a relatively new technology, various theoretical and long-term safety issues related to the environment and the consumer remain to be fully addressed, although inherently the risks should not be any greater than with the commercial fish vaccines that are currently used. Present classification systems lack clarity in distinguishing DNA-vaccinated animals from genetically modified organisms (GMOs), which could raise issues in terms of licensing and public acceptance of the technology. The potential benefits of DNA vaccines for farmed fish include improved animal welfare, reduced environmental impacts of aquaculture activities, increased food quality and quantity, and more sustainable production. Testing under commercial production conditions has recently been initiated in Canada and Denmark.

Animal Welfare↗

Study of gene transfer in vitro and in the digestive tract of gnotobiotic mice from Lactococcus lactis strains to various strains belonging to human intestinal flora.

The use of genetically modified organisms (GMO) in dairy products requires evaluation of the DNA transfer capacity from such organisms among the human intestinal microflora. Thus, both in vitro and in vivo [in the digestive tract (DT) of mice] transfer from Lactococcus lactis donor strains of the conjugative plasmid pIL205 (CmR) and the non-conjugative plasmid pIL253 (EmR) to: (1) recipient strains isolated from human faecal flora Bacteroides sp., Bifidobacterium sp., Peptostreptococcus sp. (strictly anaerobic bacterial strains) and Enterococcus faecalis, (2) a whole human faecal flora, was studied. In both cases, no gene transfer was observed to strictly anaerobic bacterial strains. DNA transfer was only observed to the E. faecalis strain: in vivo CmR E. faecalis transconjugants were isolated from sequentially multi-associated mice and when the recipient strains associated with the mice, they were a defined mixture of Bacteroides sp., Bifidobacterium sp., Peptostreptococcus sp. and E. faecalis strains. When mice were associated with the whole human faecal flora, the plasmid pIL205 was transferred into some facultative anaerobic streptococci. It was also shown that DNA transfer occurred even when the lactococcal donor strain was transient in the DT of the gnotobiotic host animals.

Animals↗

Neuroectodermal grafting: a new tool for the study of neurodegenerative diseases.

Transgenic and knockout mice have contributed much to our current understanding of the role played by single genes during development and in pathological processes of the CNS, such as neuro-degeneration. However, embryonic lethality resulting from the disruption of important genes has often hindered the interpretation of such experiments. Grafting of immature cells from genetically modified organisms into healthy recipients promises to efficiently bypass this problem. We have used neural transplantation techniques which allow us to keep CNS tissue of knockout and transgenic mice viable for a prolonged period of time in the brain or in the kidney capsule of healthy recipients. We have characterized biological parameters such as growth, proliferation and differentiation and also the formation of an intact blood-brain barrier (BBB) after grafting of wild-type telencephalic anlage in this system. We have also employed this technique to study the longterm properties of neuroepithelial tissue derived from knockout mice. The results of our studies are discussed in the context of neurodegenerative diseases.

Adenosine Triphosphatases↗

Potential use of genetically modified pigs as organ donors for transplantation into humans.

1. Transplantation is currently viewed as a successful treatment for end-stage organ failure. Its more widespread use is severely limited by a shortage of human organ donors. This has stimulated the scientific and medical communities to look at the potential use of animals to solve this problem. For a number of reasons, the pig appears to be the preferred species. 2. The initial immunological problem encountered in pig-to-primate transplantation is a process of hyperacute rejection, which is mediated by the binding of antibodies to the graft endothelium followed by the activation of the complement cascade. We have sought to overcome these initial immunological challenges by focusing our attention not only on the recipient of the graft but also on the donor. Therefore, we have generated transgenic animals with specific genetic modifications designed to inhibit the activation of the complement cascade. Upon transplantation to baboons of organs derived from these transgenic pigs, we have been able to demonstrate that hyperacute rejection can be prevented. We will discuss the generation of these and other transgenic animals and their potential role in clinical xenotransplantation.

Animals↗

Environmental safety issues for genetically modified animals.

Organisms modified by the techniques of modern biotechnology may differ significantly from normal organisms or organisms modified by other methods. Before transgenic organisms are introduced into the environment, the potential environmental effects should be assessed. In general, modification of ecologically important traits in undomesticated species presents the greatest environmental risk. Transgenic livestock probably pose low risk to the environment. Transgenic fish and live virus-based vaccines pose greater risks and present challenging questions for environmental risk assessment.

Animals↗

[Modern biotechnology: a new box for Pandora?].

In a bird's-eye view attention has been paid to a number of items of biotechnology. Amongst others to the beginning of the recombinant DNA technology or genetic modification. Mentioned are the bull Herman, the American tomato 'Flavr Savr' and the sheep Dolly. And further something about the supporters and the opponents of genetic modification and the safety of it. The why of transgenic plants and animals. The legislation and the Netherlands as possible transgene-production country.

Animals↗