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Need for dietary control by caloric restriction in rodent toxicology and carcinogenicity studies.

The conditions under which laboratory animals are maintained can powerfully influence the results of toxicological studies utilized for risk assessment. Nutrition is of importance in toxicological bioassays and research, because diet composition and the conditions under which it is fed can affect the metabolism and activity of xenobiotic test substances and alter the results and reproducibility of long-term studies. It is known that ad libitum (AL) overfed sedentary laboratory rodents suffer from an early onset of degenerative disease and diet-related tumors that lead to poor survival in chronic bioassays. AL-fed animals are not well-controlled subjects for any experimental studies. Examination of study-to-study variability in food consumption, body weight, and survival in carcinogenicity studies for the same strain or stock of rodents shows tremendous laboratory-to-laboratory variability. However, a significant correlation between average food (calorie) consumption, adult body weight, and survival has been clearly established. The use of moderate dietary restriction (DR) results in a better controlled rodent model with a lower incidence or delayed onset of spontaneous diseases and tumors. Operationally simple, moderate DR significantly improves survival, controls adult body weight and obesity, reduces age-related renal, endocrine, and cardiac diseases, increases exposure time, and increases the statistical sensitivity of these expensive, chronic bioassays to detect a true treatment effect. A moderate DR regimen of 70-75% of the maximum unrestricted AL food intake is recommended as a nutritionally intelligent, well-established method in conducting well-controlled toxicology and carcinogenicity studies.

Animals↗
PubMed1993

Hantavirus infection--southwestern United States: interim recommendations for risk reduction. Centers for Disease Control and Prevention.

This report provides interim recommendations for prevention and control of hantavirus infections associated with rodents in the southwestern United States. It is based on principles of rodent and infection control and contains specific recommendations for reducing rodent shelter and food sources in and around the home, recommendations for eliminating rodents inside the home and preventing them from entering the home, precautions for preventing hantavirus infection while rodent-contaminated areas are being cleaned up, prevention measures for persons who have occupational exposure to wild rodents, and precautions for campers and hikers.

Animals↗
PubMed1997

Dietary cholesterol enhances torpor in a rodent hibernator.

Dietary cholesterol can affect both body lipid composition and steroid hormone concentration. We investigated whether a diet rich in cholesterol influences torpor patterns of hibernating chipmunks (Tamias amoenus) and, if so, whether these changes are better explained by diet-induced changes in body lipid composition or the concentration of testosterone, which at high levels inhibits torpor. Two groups of chipmunks were maintained either on a cholesterol diet (rodent chow containing 10% cholesterol) or a control diet (rodent chow) during pre-hibernation fattening and throughout the hibernation season. Torpid chipmunks on the cholesterol diet had significantly lower minimum body temperatures (-0.2 +/- 0.2 vs -0.6 +/- 0.2 degree C), lower metabolic rates (0.029 +/- 0.002 ml O2 g-1 h-1 vs 0.035 +/- 0.001 ml O2 g-1 h-1), and longer torpor bouts at -1 degree C (6.8 +/- 0.5 vs 4.1 +/- 1.0 days) than chipmunks on the control diet. Dietary cholesterol resulted in a significant increase in blood plasma cholesterol (sevenfold), liver cholesterol content (6.9-fold) and liver triglyceride content (3.5-fold) in comparison to controls. In contrast, dietary cholesterol had no detectable effect on the concentration of plasma testosterone, which was very low in both groups. Since torpor was deeper and longer in animals on the cholesterol diet our study suggests that torpor patterns of chipmunks were either directly affected by the dietary cholesterol or via changes in body lipid composition.

Animals↗
PubMed1989

A procedure for data analysis of the rodent micronucleus test involving a historical control.

No standard procedure of data analysis for rodent micronucleus tests involving historical controls has been established. In the present paper, under the presumption that the distribution of the historical control is stable and reliable, a procedure with three statistical steps is proposed to analyze the frequency of micronucleated polychromatic erythrocytes (MNPCEs). In the first step, the frequencies of MNPCEs in negative and positive control groups of a current experiment of the micronucleus test are compared with the distribution of historical negative and positive controls to examine the technical validity of the current experiment. In the second step, the frequency of MNPCEs in each treatment group is compared with the distribution of the historical negative control. In the third step, the dose-response relation is tested with the Cochran-Armitage trend test. A Monte Carlo stimulation study shows that the power of this procedure is acceptable and also this procedure is robust. An application of this procedure on real data reveals that it is effective in detecting clastogenic chemicals when the probability of a type I error is nearly .01.

Animals↗
PubMed1987

A head-only exposure system for controlled exposures of small rodents.

We have designed a low-cost, compact, head-only exposure system which is easy to use and allows exposure of up to 8 or 16 small rodents depending on the chamber used with the system. Animals are exposed without anesthesia or extreme restraint. Deflection tubes at the chamber inlet and outlet serve to provide turbulent flow within the chamber. Performance of the exposure system was evaluated by analyzing data which was collected during investigations of the kinetics of respirable nickel chloride (NiCl2) and cobalt chloride (CoCl2) aerosols in Sprague-Dawley rats. Acute 2 h exposure to NiCl2 at concentrations ranging from 129 to 1208 micrograms Ni/m3 (MMAD 0.7-0.9 micron, sigma g 1.2-1.5) had a mean run-to-run coefficient of variation (cv) in chamber concentration of 11.6%, and a mean within-run cv of 8.5%. A 26-day repeated exposure of 3 groups of rats to 18.4 micrograms Ni/m3 gave a mean run-to-run cv of 20.9%, mean within-run cv of 10.2%, and within-day cv of 14.5%. Acute exposure studies with CoCl2 at concentrations ranging from 298 to 1371 micrograms Co/m3 (MMAD 0.9, sigma g 1.4) produced a mean run-to-run cv of 8.4% and a mean within-run cv of 7.8%. The repeated exposure of 2 groups of rats for 5 days to CoCl2 at a concentration of 583 micrograms Co/m3 had a mean run-to-run cv of 10.1%, a within-run cv of 7.4% and a within-day cv of 6.8%. The distribution of aerosol within the chamber is shown to have been uniform, and chamber performance was linear over the range tested. This system provides an inexpensive and uniform means of conducting inhalation exposure studies with selected airborne contaminants that might represent a potential health hazard.

Aerosols↗
PubMed2005

Dopamine and noradrenaline control distinct functions in rodent microglial cells.

Microglial cells are the immune-competent elements of the brain. They not only express receptors for chemokines and cytokines but also for neurotransmitters such as GABA [Charles et al., Mol. Cell Neurosci. 24 (2003) 214], glutamate [Noda et al., J. Neurosci. 20 (2000) 251], and adrenaline [Mori et al., Neuropharmacology 43 (2002) 1026]. Here we report the functional expression of dopamine receptors in mouse and rat microglia, in culture and brain slices. Using the patch clamp technique as the functional assay we identified D1- and D2-like dopamine receptors using subtype-specific ligands. They triggered the inhibition of the constitutive potassium inward rectifier and activated potassium outward currents in a subpopulation of microglia. Chronic dopamine receptor stimulation enhanced migratory activity and attenuated the lipopolysaccharide (LPS)-induced nitric oxide (NO) release similar as by stimulation of adrenergic receptors. While, however, noradrenaline attenuated the LPS-induced release of TNF-alpha and IL-6, dopamine was ineffective in modulating this response. We conclude that microglia express dopamine receptors which are distinct in function from adrenergic receptors.

Adrenergic Agonists↗
PubMed1998

Turkey industry strategies for control of respiratory and enteric diseases.

Current strategies to control respiratory and enteric diseases of turkeys involve sanitation and biosecurity practices to prevent the introduction of infectious agents. In addition, proper husbandry and management practice reduce stress and help maintain a competent immune system. Industry-wide monitoring programs are used in conjunction with isolation, depopulation, and orderly marketing to eliminate pathogens that cause serious economic loss. Vaccines are available and utilized against some pathogens. Effective drug treatment is available and used for some diseases but is most commonly used to control secondary disease losses when treatment is not available for the primary disease.

Animal Husbandry↗
PubMed1991

[The use of pesticides indoors with special reference to pyrethrins. Description of problems and attempts at solution from the viewpoint of ecological health protection].

One of the primary concerns of ecological health protection is to take of preventive health measures via the assessment of indoor toxic levels and the implementation of regulations governing the use of such toxics. Underlying this concern is the premise that the use of toxics should be minimised to the greatest possible extent. The use of pesticides indoors, which is often carried out without adequate expert knowledge and in excessive quantities, is a problem that affects all aspects of life but has thus far been addressed only insufficiently. Two recent incidents in Berlin involving the use of pesticides urgently point to the need of increasing our understanding of this complex subject. The incidents in Berlin involved the incorrect utilization of pesticides--mainly pyrethroids--in schools, leading to illness among pupils and school staff. After a short description of the problem of the use of pesticides indoors, potential means of solving this problem are discussed. In addition, individual recommendations regarding the use of specific pesticides are discussed with the aim of minimising the health risks associated with their application.

Animals↗
PubMed1990

Immunoreactive erythropoietin in rodent submaxillary gland. Autonomic control of exocrine secretion and factors influencing its concentration.

The SMG of mice and rats contain a heterologous group of biologically active factors. Some are well known, can be obtained at high purity and are well-characterized. There is strong evidence for the presence of others although they have not been purified. Finally, some of them are questionable and/or have not yet been characterized. EPO would be one of the factors whose presence in the SMG is strongly suspected, although its biological activity has not been demonstrated yet. Its presence in the gland, therefore, is only supported by radioimmunoassay data and immunocytochemical methods. Immunoreactive EPO is undetectable in the mouse SMG until the 30th day of postnatal life, increasing thereafter at a uniform rate and reaching adult levels by 50-60 days of age. The parallelism between its concentration in extracts of the gland, the size and relative proportion of GCT cells, could be accepted as indirect evidence for its localization in these cells. The rise in iEPO concentration in SMGs after androgen treatment, its fall following orchiectomy, and its reduction after duct ligation in proportion to the degree of degranulation of GCT cells lend support to the above hypothesis. Salivary secretions induced by either NE or ISO contain high levels of iEPO. A significant depletion of gland content is also observed. These two sets of data indicate that SMG exocrine iEPO secretion occurs and that this secretion is mediated by adrenergic receptors. The question whether the SMG also functions as an endocrine organ in relation to EPO can not be answered at present.

Age Factors↗