Free radicals in alcoholic myopathy: Indices of damage and preventive studies

Chronic alcoholic myopathy affects up to two-thirds of all alcohol misusers and is characterized by selective atrophy of Type If (glycolytic, fast-twitch, anaerobic) fibers. In contrast, the Type I fibers (oxidative, slow-twitch, aerobic) are relatively protected. Alcohol increases the concentration of cholesterol hydroperoxides and malondialdehyde-protein adducts, though protein-carbonyl concentration levels do not appear to be overtly increased and may actually decrease in some studies. In alcoholics, plasma concentrations of a-tocopherol may be reduced in myopathic patients. However, a-tocopherol supplementation has failed to prevent either the loss of skeletal muscle protein or the reductions in protein synthesis in alcohol-dosed animals. The evidence for increased oxidative stress in alcohol-exposed skeletal muscle is thus inconsistent. Further work into the role of ROS in alcoholic myopathy is clearly warranted. (C) 2002 Elsevier Science Inc.

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.

Fatal monensin toxicity in a dog after chewing a bovine intra-ruminal slow-release device

A 20kg, 10-month-old male Kelpie developed a rapid onset of profound paresis progressing to flaccid paralysis and dyspnoea, followed by death about 36 hours after chewing on a partly discharged anti-bloat capsule from a dead cow. Intoxication by monensin in the capsule was considered the cause of death. No Lodes holocyclus were found on the dog. Evidence of muscle damage was seen in clinical biochemistry assays of plasma, but consent for necropsy was not obtained. The median lethal dose for Beagle dogs of the material contained in anti-bloat capsules is 0.5-1.0g. As this represents a serious toxicity risk if dogs chew these devises, the manufacturer includes a warning on potential dog toxicity in product literature.

Simulation of insect movement with respect to plant architecture and morphogenesis

Developments in computer and three dimensional (3D) digitiser technologies have made it possible to keep track of the broad range of data required to simulate an insect moving around or over the highly heterogeneous habitat of a plant's surface. Properties of plant parts vary within a complex canopy architecture, and insect damage can induce further changes that affect an animal's movements, development and likelihood of survival. Models of plant architectural development based on Lindenmayer systems (L-systems) serve as dynamic platforms for simulation of insect movement, providing ail explicit model of the developing 3D structure of a plant as well as allowing physiological processes associated with plant growth and responses to damage to be described and Simulated. Simple examples of the use of the L-system formalism to model insect movement, operating Lit different spatial scales-from insects foraging on an individual plant to insects flying around plants in a field-are presented. Such models can be used to explore questions about the consequences of changes in environmental architecture and configuration on host finding, exploitation and its population consequences. In effect this model is a 'virtual ecosystem' laboratory to address local as well as landscape-level questions pertinent to plant-insect interactions, taking plant architecture into account. (C) 2002 Elsevier Science B.V. All rights reserved.

Dynamin-dependent endocytosis is necessary for convergent-extension movements in Xenopus animal cap explants

Cadherin cell-cell adhesion molecules are important determinants of morphogenesis and tissue patterning. C-cadherin plays a key role in the cell-upon-cell movements seen during Xenopus gastrulation. In particular, regulated changes in C-cadherin adhesion critically influence convergence-extension movements, thereby determining organization of the body plan. It is also predicted that remodelling of cadherin adhesive contacts is important for such cell-on-cell movements to occur. The recent demonstration that Epithelial (E-) cadherin is capable of undergoing endocytic trafficking to and from the cell surface presents a potential mechanism for rapid remodelling of such adhesive contacts. To test the potential role for C-cadherin endocytosis during convergence-extension, we expressed in early Xenopus embryos a dominantly-inhibitory mutant of the GTPase, dynamin, a key regulator of clathrin-mediated endocytosis. We report that this dynamin mutant significantly blocked the elongation of animal cap explants in response to activin, accompanied by inhibition of C-cadherin endocytosis. We propose that dynamin-dependent endocytosis of C-cadherin plays an important role in remodelling adhesive contacts during convergence-extension movements in the early Xenopus embryo.

Arsenic inhibits the repair of DNA damage induced by benzo(a)pyrene

In order to study the effect of arsenic on DNA damage, Sprague-Dawley rats were dosed with sodium arsenite (10 mg/kg) with or without 800 mug of benzo(a)pyrene (BP) by intramammilary injection. The animals were sacrificed on day 1, 3, 5, 10 and 27 and the mammary gland tissues were collected for DNA adduct measurement using a P-32 post-labeling assay. Animals dosed with arsenic alone did not show any DNA adducts. DNA adduct levels in rats dosed with BP alone reached a maximum level by day 5, reducing to 13% of this level by day 27. Adduct levels in rats dosed with arsenic and BP also reached a maximum by day 5 but only 80% of the level observed in the BP group. However, 84% of this amount still remained by day 27. The First Nucleotide Change (FNC) technique was used for the screening of 115 samples of various tissues from mice that had been chronically exposed to sodium arsenate for over 2 years revealed that inorganic arsenic did not attack the two putative hotspots (codons 131 and 154) of the hOGG1 gene. These results support the hypothesis that arsenic exerts its biological activity through DNA repair inhibition. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Comparison between human and animal isolates of Shiga toxin-producing Escherichia coli O157 from Australia

There is very little human disease associated with enterohaemorrhagic Escherichia coli O157 in Australia even though these organisms are present in the animal population. A group of Australian isolates of E. coli O157:H7 and O157:H- from human and animal sources were tested for the presence of virulence markers and compared by XbaI DNA macrorestriction analysis using pulsed-field gel electrophoresis (PFGE). Each of 102 isolates tested contained the gene eae which encodes the E. coli attaching and effacing factor and all but one carried the enterohaemolysin gene, ehxA, found on the EHEC plasmid. The most common Shiga toxin gene carried was stx(2c), either alone (16%) or in combination with stx(1) (74%) or stx(2) (3%) PFGE grouped the isolates based on H serotype and some clusters were source specific. Australian E. coli O157:H7 and H- isolates from human, animal and meat sources carry all the virulence markers associated with EHEC disease in humans therefore other factors must be responsible for the low rates of human infection in Australia.

A review on the role of duckweed in nutrient reclamation and as a source of animal feed

The family of lemnacae colloquially known as duckweed contains the world's smallest species of flowering plants (macrophytes). Aquatic and free-floating, their most striking qualities are a capacity for explosive reproduction and an almost complete lack of fibrous material. They are widely used for reducing chemical loading in facultative sewage lagoons, but their greatest potential lies in their ability to produce large quantities of protein rich biomass, suitable for feeding to a wide range of animals, including fish, poultry and cattle. Despite these qualities there are numerous impediments to these plants being incorporated into western farming systems. Large genetically determined variations in growth in response to nutrients and climate, apparent anti-nutritional factors, concerns about sequestration of heavy metals and possible transference of pathogens raise questions about the safety and usefulness of these plants. A clear understanding of how to address and overcome these impediments needs to be developed before duckweed is widely accepted for nutrient reclamation and as a source of animal feed.

Therapeutic potential of selective superoxide dismutase mimetics

Selective superoxide dismutase (SOD) mimetics are potentially useful in pathological conditions in which there is an overproduction of the superoxide anion O-2.(-). These pathological conditions include inflammation, ischemia/reperfusion, shock, various cardiovascular disorders, amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. A major step forward in this field was the development of small-molecule selective SOD mimetics that penetrate cell membranes, These selective SOD mimetics catalytically remove O-2.(-) without interfering with nitric oxide (NO), peroxynitrite (ONOO-) or other radicals such as hydroxyl radical or hydrogen peroxide (H2O2). These selective SOD mimetics (SC-52608, SC-55858, M-40403 and M-40401) have been shown to have benefits in animal models of inflammation, ischemia/reperfusion, shock, thrombosis and diabetes. The next challenge with selective SOD mimetics is to develop therapeutic potential into therapeutic agents.

Stressful animal housing conditions and their potential effect on sympathetic neurotransmission in mice

Although the sympathetic nervous system (SNS) plays a major role in mediating the peripheral stress response, due consideration is not usually given to the effects of prolonged stress on the SNS. The present study examined changes in neurotransmission in the SNS after exposure of mice (BALB/c) to stressful housing conditions. Focal extracellular recording of excitatory junction currents (EJCs) was used as a relative measure of neurotransmitter release from different regions of large surface areas of the mouse vas deferens. Mice were either group housed (control), isolation housed (social deprivation), group housed in a room containing rats (rat odor stress), or isolation housed in a room containing rats (concurrent stress). Social deprivation and concurrent stressors induced an increase of 30 and 335% in EJC amplitude, respectively. The success rate of recording EJCs from sets of varicosities in the concurrent stressor group was greater compared with all other groups. The present study has shown that some common animal housing conditions act as stressors and induce significant changes in sympathetic neurotransmission.

Hemodynamic and ventilatory effects of manual respiratory physiotherapy techniques of chest clapping, vibration, and shaking in an animal model

Chest clapping, vibration, and shaking were studied in 10 physiotherapists who applied these techniques on an anesthetized animal model. Hemodynamic variables (such as heart rate, blood pressure, pulmonary artery pressure, and right atrial pressure) were measured during the application of these techniques to verify claims of adverse events. In addition, expired tidal volume and peak expiratory flow rate were measured to ascertain effects of these techniques. Physiotherapists in this study applied chest clapping at a rate of 6.2 +/- 0.9 Hz, vibration at 10.5 +/- 2.3 Hz, and shaking at 6.2 +/- 2.3 Hz. With the use of these rates, esophageal pressure swings of 8.8 +/- 5.0, 0.7 +/- 0.3, and 1.4 +/- 0.7 mmHg resulted from clapping, vibration, and shaking respectively. Variability in rates and forces generated by these techniques was 80% of variance in shaking force (P = 0.003). Application of these techniques by physiotherapists was found to have no significant effects on hemodynamic and most ventilatory variables in this study. From this study, we conclude that chest clapping, vibration, and shaking 1) can be consistently performed by physiotherapists; 2) are significantly related to physiotherapists' characteristics, particularly clinical experience; and 3) caused no significant hemodynamic effects.