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Rodent lymphocytes express functionally active glutamate receptors.

RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group III) glutamate receptors are expressed in rodent lymphocytes. Flow cytometry showed that activation of iGluR NR1 by N-methyl-D-aspartate (NMDA) increased intracellular free calcium and reactive oxygen species (ROS) levels and activated caspase-3. The latter effect was attenuated by the NMDA antagonist, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), by the antioxidant N-acetylcysteine and by cyclosporin A. Treatment with L-2-amino-4-phosphonobutyric acid (L-AP4), an mGluR Group III agonist, increased lymphocyte ROS levels but to a lower extent than did NMDA. Activation of lymphocytes with both NMDA and L-AP4 caused a synergistic increase in ROS levels and induced necrotic cellular death without elevating the caspase-3 activation observed in the presence of NMDA alone. These results show that lymphocyte iGluR NR1 and mGluR Group III receptors may be involved in controlling rodent lymphocyte functions and longevity as they regulate events in cell proliferation, maturation, and death.

Aminobutyrates↗

The effects of overfeeding and moderate dietary restriction on Sprague-Dawley rat survival, pathology, carcinogenicity, and the toxicity of pharmaceutical agents.

Ad libitum (AL) overfeeding is the most significant uncontrolled variable effecting the rodent bioassay. There is a highly significant correlation between food consumption, the resultant body weight, and two-year survival in laboratory rats. We have studied the effects of AL overfeeding, moderate dietary restriction (DR) and several modified diets on Sprague-Dawley (SD) rat longevity, spontaneous disease, carcinogenesis and the toxicity of pharmaceuticals. AL feeding of diets varying in protein, fiber and metabolizable energy content did not significantly alter two-year rat survival. Moderate DR (within the range of reported AL food intake) of all diets tested significantly improved survival and delayed the onset of spontaneous degenerative disease and diet-related tumors compared to AL-fed rats. Moderate DR resulted in a similar incidence of spontaneous tumors by 2 years, however, the tumors were more likely to be incidental and not result in early mortality. There was a decreased, age-adjusted incidence of pituitary and mammary gland tumors, but tumor volume and growth time was similar between AL and DR groups indicating similar tumor progression with a delay in tumor onset. Moderate DR did not change Phase I and Phase II drug metabolizing enzyme levels and did not significantly alter the toxicological response to 5 pharmaceuticals tested at maximum tolerated doses (MTDs). Additional studies with 4 pharmaceutical candidates did demonstrate that moderate DR allowed higher doses of compounds to be given before classical MTDs were observed. However, toxicokinetic studies of two of these compounds demonstrated steady state systemic exposures that were either equal of higher in the moderate DR fed rats. These and other data indicate that the moderate DR fed SD rat is a more appropriately controlled rodent model for toxicity and carcinogenicity studies to assess human safety of candidate pharmaceuticals.

Animals↗

Lassa fever.

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Adolescent↗

Influence of polyunsaturated and saturated dietary lipids on adipose tissue, brain and mitochondrial membrane fatty acid composition of a mammalian hibernator.

Dietary lipid composition profoundly influences the hibernation pattern of the chipmunk Eutamias amoenus. The object of the present study was to investigate whether these physiological changes following feeding of saturated and unsaturated lipids were associated by compositional changes of fatty acids of tissues and membranes. Animals were fed with rodent chow (control diet), rodent chow with 10% sunflower seed oil (unsaturated diet) and rodent chow with 10% sheep fat (saturated diet). Diet-induced changes in the fatty acid composition of depot fat and brain total lipids and of mitochondrial phospholipids were determined. The fatty acid unsaturation index was lower in animals on saturated diet than in animals on unsaturated diet (depot fat 86.1 vs. 145.9; heart mitochondria 207.6 vs. 247.1; liver mitochondria 148.4 vs. 173.5). Pronounced differences between dietary groups were also observed in n-3 or n-6 fatty acids or their ratios of depot fat, brain and liver mitochondria. Generally, the diet-induced differences in tissue and membrane fatty acid composition in E. amoenus were more pronounced than those observed previously in non-hibernating species. Selective feeding and incorporation of high amounts of unsaturated fatty acids into tissues and cell membranes may be an important preparation for hibernation of E. amoenus which lowers its body temperature during torpor to about 0 degrees C.

Adipose Tissue↗

Conditioned aversion to a taste perceived while grooming.

Four experiments were conducted to determine how the characteristics of conditioned taste aversion (CTA), as described from studies conducted in the drinking and feeding contexts, applied in the grooming context. In Experiment 1, sodium saccharin was mixed with a "neutral-tasting" jelly and applied to the fur of male Sprague-Dawley rats. Rats injected with LiCl after the applications strongly avoided saccharin solutions in subsequent 1-hr, 2-choice (Saccharin solution vs water) drinking tests, whereas rats injected with NaCl or given plain jelly on the fur showed only an initial neophobic response to the saccharin solution. Thus, the taste of saccharin was perceived while grooming and the CTA formed in the grooming context generalized to drinking. In experiments 2-4, we obtained evidence that: (a) rats discriminated between one intensity of saccharin applied to the fur and another used in the test solution; and (b) rats differentiated between qualities of the two tastants applied to the fur in that saccharin overshadowed NaCl; and (c) taste qualities were more important than toxic properties when two stimuli (Saccharin, LiCl) were used (saccharin overshadowed NaCl in subsequent drinking tests). We speculate that taste, while grooming might play a role in social communication in some vertebrates. Further, CTA and grooming might have uses in rodent control (e.g., in agricultural situations) not previously considered such as in delivering a non-attractive, low-salience toxin so that the taste of the crop overshadows that of the bait, and induces crop aversion.

Animals↗

Snake venoms in science and clinical medicine. 1. Russell's viper: biology, venom and treatment of bites.

Russell's viper, Vipera russelli (Shaw), is distributed erratically in 10 south Asian countries and is a leading cause of fatal snake bite in Pakistan, India, Bangladesh, Sri Lanka, Burma and Thailand. In Burma it has been the 5th most important cause of death. Its venom is of great interest to laboratory scientists and clinicians. The precoagulant activity of the venom was used by Macfarlane and others to elucidate the human clotting cascade. Up to 70% of the protein content is phospholipase A2, present in the form of at least 7 isoenzymes. Possible clinical effects of the enzyme include haemolysis, rhabdomyolysis, pre-synaptic neurotoxicity, vasodilatation and shock, release of endogenous autacoids and interaction with monoamine receptors. Russell's viper bite is an occupational hazard of rice farmers throughout its geographical range. Defibrination, spontaneous haemorrhage, shock and renal failure develop with frightening rapidity. In several countries, Russell's viper bite is the commonest cause of acute renal failure. There is a fascinating geographical variation in the clinical manifestations, doubtless reflecting differences in venom composition. Conjunctival oedema is unique to Burma, acute pituitary infarction to Burma and south India, and rhabdomyolysis and neurotoxicity to Sri Lanka and south India. Treatment with potent specific antivenom rapidly controls bleeding and clotting disorders, but may not reverse nephrotoxicity and shock. Causes of death include shock, pituitary and intracranial haemorrhage, massive gastrointestinal haemorrhage and acute tubular necrosis or bilateral renal cortical necrosis. The paddy farmer and the Russell's viper coexist in fragile symbiosis. The snake controls rodent pests but inevitably interacts with man, often with mutually disastrous results.

Acute Kidney Injury↗

Scientific issues associated with the validation of in vitro and in vivo methods for assessing endocrine disrupting chemicals.

The assays required to assess the potential of chemicals to act as endocrine disrupting (ED) agents are either in place or are under current development. However, the validation and utilisation of these assays is currently being hampered by uncertainties regarding their purpose and required sensitivity, and uncertainties as to the intrinsic variability of the parameters being measured. This article discusses these several sources of uncertainty and the intrinsic variability of many of the key assay parameters. It is concluded that current uncertainties regarding the use of ED assays, and the extrapolation of rodent effects to humans, are due to the absence of an extensive agreed rodent control database for the developmental parameters under study, coupled to the established intrinsic variability of these parameters between strains/species of test animals and test protocols. Only when these factors are generally accepted, well studied and controlled for, will it be possible to employ ED assays with confidence and to relate assay data to effects likely to be seen in humans.

Animals↗

The stability of ergocalciferol in rodenticidal baits.

Concentrations of the rodenticide ergocalciferol (vitamin D2) in samples of rodent baits laid in foodstores and in the laboratory were monitored over several months. Bait samples were solvent extracted and ergocalciferol concentration determined by high pressure liquid chromatography (HPLC). Ergocalciferol levels were constant for more than 21 days in dry samples and did not fall by more than 30% in 100 days. When water (10% w/w) was added to the baits in the laboratory the ergocalciferol concentration fell by approximately 30% in 30 days. In these wet laboratory samples there was a rapid visible growth of fungus and in normal rodent control use baits should have been replaced when such deterioration became evident.

Drug Stability↗

Laboratory trials of three anticoagulant rodenticides for use against the Indian field mouse, Mus booduga Gray.

The efficacy of three anticoagulant rodenticides for use against the Indian field mouse, Mus booduga, was evaluated in the laboratory. The poisons, namely warfarin, bromadiolone and brodifacoum, were all found to be toxic enough at the concentrations normally used against other commensal and field rodents. With brodifacoum (0.001 25%), bromadiolone (0.005%) and warfarin (0.025%), 83% of the animals died respectively after 1, 1 and 6 days' feeding. It is suggested that brodifacoum and bromadiolone might be more economical than warfarin for use in practical rodent control.

4-Hydroxycoumarins↗

Patterns of infection by Salmonella and Yersinia spp. in commensal house mouse (Mus musculus domesticus) populations.

AIMS: This study sought to examine the risk posed by house mice transmitting pathogens to livestock on typical mixed-agriculture farms in the UK. METHODS AND RESULTS: In a 10-month longitudinal study at one farm, 222 faecal samples were taken from mice and 57 swabs from the farm environment; 3.2% and 15.8%, respectively, were positive for Yersinia. Seventy-five intestinal samples were taken from house mice from three other farms and 9.3% were positive for Yersinia. The commonest species was Y. enterocolitica (of a wide range of serotypes); all isolates were non-pathogenic, except one of Y. pseudotuberculosis. Salmonella was not isolated from any sample. CONCLUSION: This study provides additional evidence that house mice are generally not significant vectors of either pathogenic Yersinia strains or Salmonella species. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first longitudinal study of Yersinia in any small mammal population, and shows infection to be a dynamic series of generally non-pathogenic, transient infections.

Animals↗

Transmission of encephalomyocarditis virus in pigs estimated from field data in Belgium by means of R0.

Transmission of encephalomyocarditis-virus (EMCV) has been estimated in experiments, but never using field data. In this field study, a farm in Belgium was selected where the presence of EMCV was confirmed by necropsy and virus isolation. Serology was used to estimate the transmission parameter R0. In one compartment with 630 pigs, 6 pens were fully sampled, in the remaining 38 pens, 2 randomly selected pigs were bled. The 151 pigs were bled twice and their serum was tested in a virus neutralisation test. Seroprevalence at the first and second sampling was 41 and 43% respectively, with a cut off value of 1:40. R0 was estimated for 2 scenarios, in- and excluding mortality based on the final sizes from the serological results of the second sampling. The R0 for the fully sampled pens was estimated between 0.6 and 1.7, the combined estimated R0 of these 6 pens was 1.36 (95%-CI 0.93-2.23). The median of the estimated R0 of the partially sampled pens was 1.3 and 1.4. Sampling two pigs per pen provided insight into the spread of the virus in the compartment, while the fully sampled pens provided an accurate estimation of R0. The low R0 strongly suggests that EMCV is not very effectively transmitted between pigs. The number of seropositive pigs in a pen and the spread in the compartment suggests that other routes of infection are more important, in this case most likely rodents. Preventing viral spread should therefore be focussed on rodent control instead of reduction of contact between pigs.

Animals↗

Human leptospirosis in Bulgaria, 1989-2001: epidemiological, clinical, and serological features.

A total of 455 confirmed and reported to the Bulgarian Ministry of Health leptospirosis cases between 1989 and 2001 were analysed. Overall incidence of the disease was 0.42/100.000 population (range 0.20-0.64/100.000). The overall fatality rate was 6.6%. Infection was acquired through occupational (30.3%), recreational (45.1%), and accidental (4.6%) exposure or was home contracted (5.1%). A tendency towards the main mode of transmission moving from occupational to recreational exposure was noted. Fishing and livestock farming together accounted for more than half of all leptospirosis cases. Leptospirosis was contracted more frequently through indirect contact with animal excreta and less commonly through direct contact with animal urine or tissue. Serovars belonging to 10 different serogroups caused infection during the 13-year study period. Two serogroups, Icterohaemorrhagiae and Pomona, accounted for more than 87% of all leptospirosis cases. The third main cause was serogroup Australis. The significant change in the infecting serovars has to be related to widely performed vaccinations of cattle and pigs but still inefficient measures for rodent control. The most frequently reported symptoms were fever, myalgia, jaundice, and hepatomegaly. Anicteric cases (40.3%) had milder flu-like course. Acute renal failure was reported in 52 (33.8%) of the patients, all of them with icteric leptospirosis. Knowledge of epidemiological, clinical, and serological features of leptospirosis in Bulgaria during the 13-year study period is an appropriate base to outline measures for successful prevention and early diagnosis of the disease.

Adult↗

Fertility of female mice fed coumestrol and diethylstilbestrol.

Coumestrol, a compound produced by various legumes which exerts estrogen-like activity in animals, and diethylstilbestrol (DES) were studied as chemical agents for controlling reproduction in mice. Female mice were fed control diets or diets containing 100 ppm coumestrol for eight days. Female mice were exposed to males and reproductive tracts examined 14 days later. Litter size was not affected by 100 ppm dietary coumestrol but feed consumption was reduced 17%. Similar trials were conducted with mice fed 1 ppm DES. Vaginal plugs were present in 50% of the females fed 1 ppm DES, but no fetal pups were present. Feed intake was reduced 37% by the DES. Levels of 0, .1, .25, .50, .75 and 1.0 ppm DES were compared in two strains of mice, Swiss and ICR. Reproduction in both strains was totally inhibited by all DES treatments. The use of DES to control rodent populations warrants further investigation.

Animals↗

Antibody responses to two encephalomyocarditis virus vaccines in rhesus macaques (Macaca mulatta).

Two groups of rhesus macaques (Macaca mulatta) housed in rodent-controlled outdoor corrals were inoculated with two different encephalomyocarditis virus (EMCV) vaccines. One group (n = 45) received a vaccine made from an inactivated field isolate of virus cultured during an outbreak at a zoo in Florida. This vaccine produced fourfold increases in the titers of 28 animals (62%); the increases persisted for at least 18 months (last test) after a single injection of the vaccine. The other group (n = 51) received a vaccine made from an inactivated porcine field strain of the virus. This vaccine did not produce titers in any of the vaccinees.

Animals↗

Chlamydiosis in workers at a duck farm and processing plant.

An outbreak of chlamydiosis was investigated in workers at a duck farm and processing plant during winter 1989. Chlamydia psittaci was isolated from ducks, but there was little evidence of clinical chlamydiosis in the ducks. Serological tests showed that 76% of workers had been exposed to infection, 12% recently, 16% had not been exposed and 8% had inconclusive test results. There was a strong association (P < 0.05) between years of employment and exposure to infection. Infection appeared to be contracted during the first year of employment. Measures were implemented to reduce shed contamination and control rodents and wild birds. At the same time, ducks were medicated, the processing plant was modified, work practices were altered and workers were advised about chlamydiosis to reduce the risk of human infection.

Adult↗

Dietary calcium and dairy modulation of adiposity and obesity risk.

Dietary calcium plays a key role in the regulation of energy metabolism and obesity risk. This appears to be mediated primarily by dietary calcium modulation of circulating calcitriol, which in turn regulates adipocyte intracellular calcium ([Ca2+]i). Increased [Ca2+]i stimulates lipogenic gene expression and activity and inhibits lipolysis, resulting in increased adipocyte lipid accumulation. Since calcitriol stimulates adipocyte Ca2+ influx, low calcium diets promote adiposity, while dietary calcium-suppression of calcitriol reduces adiposity. These concepts are confirmed in controlled rodent studies as well as by epidemiological and clinical trial data, all of which confirm protection from obesity with high calcium intakes. Moreover, dairy sources of calcium exert markedly greater effects which are most likely attributable to additional bioactive compounds in dairy which act synergistically with calcium to attenuate adiposity.

Animals↗