The effect of large doses of thiamine on the horse

Extract

In conjunction with a trial to determine the effect of nematode infestation upon the liveweight gain and wool production of young sheep (Brunsdon, unpublished), information was sought on the seasonal succession and availability on pasture of infective larvae of the principal trichostrongyle genera parasitic in sheep. Data were collected in the form of nematode populations found at postmortem examination of Romney lambs, previously maintained worm-free, which were exposed to risk of parasitism in the field. A series of these lambs ran with the flock in the above-mentioned trial and served as indicators of the abundance of infective larvae on the pasture.     

Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.     

Boreal forest futures: Modelling the controls on tree species range limits and transient responses to climate change

Range limits and broad-scale geographic variations in the productivity of boreal and northern deciduous tree species in Europe are simulated with a bioclimatic model (STASH). STASH is based on a small number of distinct mechanisms by which climate is thought to affect the survival, regeneration and growth of trees. Survival is limited by summer warmth requirements and winter cold tolerance; regeneration, additionally by winter chilling requirements; and growth rate by net assimilation, which in turn is related to photosynthetically active radiation, growing-season length, temperature (relative to species-specific optima) and soil moisture supply (relative to evaporative demand). These mechanisms are quantified either as thresholds (for survival and regeneration) or multipliers (for growth), based on bioclimatic variables computed from monthly climate normals interpolated three-dimensionally to a 10-minute grid. Growing-season and growing degree day calculations take into account the effects of chilling. The drought calculations also take into account the effects of soil-moisture storage by means of a physically based evapotranspiration calculation coupled to a one-layer soil hydrology model. STASH is used to examine changes in potential range limits under a 2xCO₂ climate-change scenario. Associated transient responses at selected sites in the boreal and boreo-nemoral zones of Sweden are also simulated, using the forest gap model FORSKA2. The species-specific survival and regeneration constraints and growth responses of STASH modify the growth, establishment and mortality of trees in FORSKA2. The results obtained in this way differ sharply from the results of conventional forest gap models, where growth rates are assumed to decline to zero at minimum and maximum growing degree day limits. For example, towards the southern limit ofPicea abies (Norway spruce), STASH correctly shows no decline in productivity, but rather an abrupt cut-off corresponding to a chilling requirement during regeneration that is not met further south or west. In transient warming scenarios, this mechanism has the effect that natural regeneration can be blocked due to the warm winters even as yield is increasing due to the longer and warmer summers. STASH predicts drastic changes in species distributions in response to the large climate changes (especially winter warming) expected for northern Europe. Some of the common boreal species (e.g.,Picea abies; Pinus sylvestris; Alnus incana) are unlikely to survive in much of their present range, withdrawing to the far north. Other species already widespread may be able to occupy some of the few sites that are today unavailable to them (e.g.,Betula spp.;Corylus avellana). Other temperate deciduous species such asFagus sylvatica could have dramatic range expansions, potentially occupying large tracts of the present boreal zone. FORSKA2 transient simulations illustrate some of the possible routes towards different types of forest in a changed climate. Some sites in the north show little change in species composition, but sites towards the southern boundary of the boreal zone could develop a new suite of dominants. The degree of sensitivity of a particular site depends both on the climate change prediction and on the transient dynamics of the forest community. Many types of transient behaviour are shown to be possible. Coupled with uncertainties about the future role of dispersal and changes in disturbance rate, the complexity and variety of these transient responses imply a highly uncertain future for the north European boreal forests.     

Physicochemical and Functional Properties of Protein Recovered from Fish Waste

ABSTRACT

This work aimed to evaluate the physicochemical and functional properties of proteins recovered from whitemouth croaker (Micropogonias furnieri) and Argentine anchovy (Engraulis anchoita) residues obtained by the process of acid solubilization using HCl at pH = 2 and alkaline solubilization using NaOH at pH = 12 and isoelectric precipitation (pH = 5.5). The proximate composition and functional properties were determined. The solubilization and water holding capacity (WHC) of the recovered protein were studied in the pH range of 3, 5, 7, 9, and 11. The high protein content and lowest lipid reduction presented by the protein recovered from the whitemouth croaker residue and obtained by the acid solubilizing process was 97.1 and 98.4%, respectively. The maximum solubilized protein was at pH 3 and 11, and the minimum solubilized protein was at pH 5 for both species. The greater ability to retain oil was observed for the alkaline solubilization process (8.3 and 7.3). The lower WHC was at pH 5. The acid and alkali residue concentrates of the whitemouth croaker presented higher WHC at pH 3 and 11. These proteins can be used in preparing edible films and have been used to produce bioactive compounds for supplements or functional ingredients.     

Successful drug development despite adverse preclinical findings part 2: examples

To illustrate the process of addressing adverse preclinical findings (APFs) as outlined in the first part of this review, a number of cases with unexpected APF in toxicity studies with drug candidates is discussed in this second part. The emphasis is on risk characterization, especially regarding the mode of action (MoA), and risk evaluation regarding relevance for man. While severe APFs such as retinal toxicity may turn out to be of little human relevance, minor findings particularly in early toxicity studies, such as vasculitis, may later pose a real problem. Rodents are imperfect models for endocrine APFs, non-rodents for human cardiac effects. Liver and kidney toxicities are frequent, but they can often be monitored in man and do not necessarily result in early termination of drug candidates. Novel findings such as the unusual lesions in the gastrointestinal tract and the bones presented in this review can be difficult to explain. It will be shown that well known issues such as phospholipidosis and carcinogenicity by agonists of peroxisome proliferator-activated receptors (PPAR) need to be evaluated on a case-by-case basis. The latter is of particular interest because the new PPAR α and dual α/γ agonists resulted in a change of the safety paradigm established with the older PPAR α agonists. General toxicologists and pathologists need some understanding of the principles of genotoxicity and reproductive toxicity testing. Both types of preclinical toxicities are major APF and clinical monitoring is difficult, generally leading to permanent use restrictions.     

Physicochemical,Microbiological, and Sensory Properties of Pâté Elaborated from Whitemouth Croaker (Micropogonias furnieri) Muscle

The aim of this research was to formulate a unique product, croaker pâté, and to determine its physicochemical, microbiological, and sensorial characterization. Three formulations of pâté were elaborated. The pâtés fit in the stipulated regulations for the microbiological test. Regarding the texture, the pâtés presented a significant difference (p < 0.05) among each other. In the sensorial tests, the favorite pâté of the panel was formulation 3; in the acceptance test, it had higher levels of acceptance for color, flavor, and global acceptance in comparison with commercial pâté.     

Evaluation of a flat-plate PIT tag interrogation system at Bonneville Dam

In the spring of 1996 and 1997, a prototype 400 kHz flat-plate (pass-by) passive integrated transponder tag interrogation (PIT tag) system was installed at the terminus of the downstream migrant (DSM) channel of the Bonneville Dam First Powerhouse, located on the Columbia River. The system was designed to interrogate previously PIT tagged juvenile salmonids migrating down the Columbia River without interfering with the traditional subsampling of fish passing through the facility. In addition, the design enables fish of virtually any size, and debris, to pass over the system's antennas without the port restrictions imposed by traditional pass-through PIT tag interrogation systems. We describe the fish facility in addition to the flat-plate system and its operation. The system tag reading efficiency was evaluated during 1996 and 1997 using a direct method based on the release of known numbers of tagged test fish and an indirect statistical procedure based on tagged run-at-large fish. The results showed that PIT tag reading efficiency during both years using the direct method averaged 97%, while that using the statistical procedure averaged 99% for the dual multiplexed antenna array. During the 1996 and 1997 field seasons 4371 and 14 733 fish, respectively, were recorded. Daily system functionality was monitored using stick tests (i.e., the passing of PIT tagged sticks across the antenna array).