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Laboratory and field trials of permethrin-treated cotton used as nesting material to control fleas (Insecta: Siphonaptera) on cricetid rodents.

Upholstery cotton treated with four different concentrations (0.25-2.0%) (2,500-20,000 ppm) of an aqueous permethrin solution, used as nesting material by white mice, was laboratory-tested against the potential plague vectors Oropsylla montana (Baker), Thrassis bacchi (Rothschild), and Orchopeas howardi (Baker) and found highly effective (P less than 0.001) for 1 yr. Similarly treated cotton gauze was tested under ambient and 75% RH and was found to be highly effective (P less than 0.001) in both environments for 1 yr. A separate test determined that the LD50 of permethrin-treated cotton was less than 10 ppm. Cotton tested with 0.5% permethrin and distributed under field conditions to cricetid rodents for use as nesting material was found to be highly effective (P less than 0.001 as a pulicide for greater than 4 mo when tested during winter in Larimer County, Colo. Permethrin-treated cotton was less successful in controlling fleas on cricetid rodents during the summer months in a New Mexico hyperendemic plague area.

Animals↗

The effects of diet, overfeeding and moderate dietary restriction on Sprague-Dawley rat survival, disease and toxicology.

Overfeeding by ad libitum (AL) food consumption is the most significant, uncontrolled variable affecting the outcome of the current rodent bioassay. The correlation of food consumption, the resultant adult body weight and the 2-y survival in Sprague-Dawley rats is highly significant. Feeding natural ingredient diets that varied in protein, fiber and metabolizable energy content did not improve low 2-y survival if Sprague-Dawley rats were allowed AL food consumption. Moderate dietary restriction (DR) of all diets tested significantly improved survival and delayed the onset of spontaneous degenerative disease (i.e., nephropathy and cardiomyopathy) and diet-related tumors. By 2 y, moderate DR resulted in an incidence of spontaneous tumors similar to that seen with AL consumption; however, the tumors were more likely to be incidental and did not result in early mortality. There was a decreased age-adjusted incidence in pituitary and mammary gland tumors, but tumor volume and growth time were similar in the AL and DR groups, indicating a similar tumor progression with a delay in tumor onset. Moderate DR did not significantly alter drug-metabolizing enzyme activities or the toxicologic response to five pharmaceuticals tested at maximum tolerated doses (MTD). However, moderate DR did require higher doses of compounds to be given before classical MTD were produced with four pharmaceutical drug candidates. Toxicokinetic studies of two of these compounds demonstrated steady-state systemic exposures that were equal or higher in moderate DR-fed rats. These and other data indicate that moderate DR is the most appropriate method of dietary control for rodent bioassays used to assess human safety of candidate pharmaceuticals.

Animals↗

Field trials of calciferol combined with warfarin against wild house-mice (Mus musclus L.).

A combination of calciferol (vitamin D(2)) and warfarin, each at 0.025% in medium oatmeal bait, failed to control six of seven house-mouse (Mus musculus L.) populations infesting urban and farm buildings. In three further treatments with both calciferol and warfarin at 0.05% in dehusked canary seed bait plus 5% corn oil, mortality, estimated from the consumption of pre- and post-treatment census bait, ranged between 94.2 and 97.4%. Finally, among sixteen treatments done with calciferol at 0.1% and warfarin at 0.025% in various cereal baits, the best results (97.0-100%) were obtained in six treatments where the bait-base was whole canary seed; this was so whether the poison bait was applied directly or after a 3-day pre-baiting period. It is concluded that calciferol at 0.1% plus warfarin at 0.025% is an effective combination against house-mice, especially when used with whole canary seed. The role played by warfarin in the poison mixture needs to be investigated further.

Animals↗

Toxicology and histopathology of some rodenticides and palatable food items combinations on the common mice Mus musculus var. albus in Egypt.

In this study the palatability tests of certain food items as attractants in the poisoned-baits for the albino mouse Mus musculus var. albus showed that the food items of treacle, maize oil, dry or wet sugar and milk powder act as more attractive pleasant materials that encourage the mice to consume more of those baits containing such items. The most palatable combination of tested food items to the mouse Mus musculus was that consisting of crushed maize + treacle + maize oil + milk powder. The least amount of food consumed by the mice was that of rice and or rice + treacle + oil + milk powder. The use of wheat grain alone was much better than crushed maize alone or and combined with wet or dry sugar. The tested anticoagulant rodenticides were greatly effective against the albino mouse Mus musculus var. albus, since they could cause a final mortality of hundred percent in a mean time ranging merely between 7 & 9 days. Chlorophacinone was more potent and effective than coumachlor; at its lowered concentrations of 25 and 44.5 ppm was more acceptable than coumachlor. The consumed amounts of zinc phosphide baits were comparatively utmost lower than those of anticoagulants poisoned baits. Feeding the pregnant females on prepared baits consisting of crushed maize, treacle, milk powder, maize oil and lower concentration of each of coumachlor, chlorophacinone and zink phosphide, to a more or less extent, reduced females weight according to the tested lower concentration, versus the weight of pregnant females in control treatment which was increased by 14.4%. In comparison to both the tested anticoagulant rodenticides, the measured reduction of females weight caused by zinc phosphide (6 ppm) was, to a more extent, higher as the mean weight gradually decreased from 27.4 up to 16.3 g. Chlorophacinone at its minimized concentrations was least effective in reducing the number and mean weight of developing fetuses. However, coumachlor at its tested concentration of 2 ppm caused abortion after the first and the second weeks of pregnancy reached to 100%. Zinc phosphide at both tested concentrations of 0.6 and 6 ppm was ineffective on the abortion and resorption of fetuses; the fed females on baits containing 0.6 and/or 6.0 ppm zinc phosphide ate their youngsters at the 2nd and 4th day after birth, respectively. The histopathological changes of liver, kidney, lung and intestine due to feeding of the Mouse Mus musculus var. albus on the poisoned baits of tested different rodenticides were recorded and photographed.

Abortion, Induced↗

Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats.

The inducible isoform of heme oxygenase (HO), HO-1, has been shown to play an important role in attenuating tissue injury. Because HO-1 catalyzes the rate-limiting step in bilirubin synthesis, we examined the hypothesis that bilirubin is a key mediator of HO-1 cytoprotection, employing a rat model of endotoxemia. Bilirubin treatment resulted in improved survival and attenuated liver injury in response to lipopolysaccharide infusion. Serum levels of NO and tumor necrosis factor alpha, key mediators of endotoxemia, and hepatic inducible nitric oxide synthase (iNOS) expression were significantly lower in bilirubin-treated rodents versus control animals. Both intraperitoneal and local administration of bilirubin also was found to ameliorate hindpaw inflammation induced by the injection of lambda-carrageenan. Consistent with in vivo results, bilirubin significantly inhibited iNOS expression and suppressed NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. In contrast, bilirubin treatment induced a threefold increase in LPS-mediated prostaglandin synthesis in the absence of significant changes in cyclooxygenase expression or activity, suggesting that bilirubin enhances substrate availability for eicosanoid synthesis. Bilirubin had no effect on LPS-mediated activation of nuclear factor kappaB or p38 mitogen-activated protein kinase, consistent with a nuclear factor kappaB-independent mechanism of action. Taken together, these data support a cytoprotective role for bilirubin that is mediated, at least in part, through the inhibition of iNOS expression and, potentially, through stimulation of local prostaglandin E2 production. In conclusion, our findings suggest a role for bilirubin in mollifying tissue injury in response to inflammatory stimuli and support the possibility that the phenomenon of "jaundice of sepsis" represents an adaptive physiological response to endotoxemia. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

Animals↗

Reproductive success of bromadiolone-resistant rats in absence of anticoagulant pressure.

Resistance to anticoagulant rodenticides in brown rats (Rattus norvegicus Berk.) is associated with pleiotropic effects, notably with an increased dietary vitamin K requirement. Owing to this disadvantage, resistance is believed to be selected against if anticoagulant selection is absent. In small experimental populations of wild brown rats, an investigation was carried out to establish whether tolerance to anticoagulant exposure changed over a period of 2 years. In the same populations, DNA microsatellite markers were used to infer parentage, and this made it possible to estimate reproductive success of sensitive and resistant rats and estimate effective population size, Ne. Even though there was evidence for a selection against resistant rats with high vitamin K requirement, anticoagulant tolerance was not seen to be significantly influenced in the absence of bromadiolone selection. As the population size under investigation was small, random genetic drift may have played a role in this. In the presence of bromadiolone selection, however, the tolerance was significantly increased, suggesting that continuous selection will increase the proportion of highly resistant rats in the population. It was found that, for both males and females, surprisingly few individuals contributed to the next generation with numerous offspring, and most breeders contributed with none or a single offspring. The expected higher reproductive success and consequent increase in proportional numbers of sensitive rats in the absence of anticoagulant selection could not be observed. Among the resistant rats, moderately resistant females were found to be better breeders than highly resistant breeders, but for resistant males the reverse was true. This could be explained by the fact that the increased vitamin K requirement results in sex differential selection; in highly resistant males the selection presumably takes place at the immature stage, whereas in females the vitamin K requirement becomes crucial at the reproductive stage, as vitamin K is not only essential for the blood clotting process but also for bone formation.

4-Hydroxycoumarins↗

An index technique to monitor broadcast calibration and bait pick up, plus rodent and avian sign under arid conditions.

As part of product-performance and wildlife-hazards studies of 2% zinc phosphide (Zn3P2) steam-rolled-oat baits (11.2 kg ha-1) to reduce vole populations (Microtus spp) in alfalfa (Medicago sativa), we used randomly located, brushed-dirt plots (eight approximately 930-cm2 plots per 0.2-ha enclosure) to monitor bait-broadcast and -removal patterns, as well as to index vole and avian sign. Research was conducted in 18 x 0.2-ha enclosures containing 2.5-year-old stands of alfalfa; a 2-day pre-bait (placebo baits broadcast in all enclosures) period followed by a 14-day test-bait period (placebo and 2% Zn3P2 baits in nine enclosures each) characterized the bait exposures. Baits were broadcast manually by two certified pesticide applicators (CPAs) using Spyker Model-75 spreaders. Baits that fell onto plots were counted < 30 min later to assess the uniformity of bait distribution. The main statistical design was a 2 (placebo or Zn3P2 baits) x 3 (vole-only, vole-pheasant, vole-quail exposures) x 14 (days) factorial, with days considered repeated measurements. In the six vole-only enclosures, baits were removed from the brushed-dirt plots and replaced with four 0% or 2% Zn3P2 baits (one per 232.6-cm2 quadrant; 32 per enclosure); these 'placed' baits were then monitored daily for removal, while the surfaces of all plots were monitored daily for the presence:absence of animal/bird sign. Key results were: (a) 3.51 (+/- 2.66) and 3.39 (+/- 3.52) mean (+/- SD) baits were found on plots after pre-bait and test-bait broadcasts, respectively--less than the predicted 4.52 particles per 930-cm2 plot; (b) baits 'placed' on plots in placebo-baited enclosures were removed earlier than those in Zn3P2-baited enclosures--data in agreement with observed vole mortality; and (c) species x bait interactions occurred for both the vole- and pheasant-sign counts, but not quail-sign counts--data also indirectly confirming Zn3P2-induced mortality effects on voles and pheasants. This technique has utility for a variety of wildlife biology and chemical registration studies; although limited to arid conditions, the technique affords useful indices of broadcast calibration, bait pick-up, as well as target and non-target species mortality.

Animals↗

Expression of fos and jun proto-oncogenes in benign versus malignant human uterine tissue.

OBJECTIVE: The objective of this study was to evaluate expression of fos and jun proto-oncogenes in benign human uterine tissue compared with malignant uterine tissue. METHODS: Forty-two endometrial tissue specimens were obtained at the time of hysterectomy. Tissue samples from different phases of the menstrual cycle and from postmenopausal patients were stained using immunohistochemical methods to detect Fos and Jun proteins, estrogen and progesterone receptor status, and Ki67 (detects a nuclear antigen associated with proliferating cells). Tissue was examined microscopically for nuclear staining in endometrial epithelium and stroma. The endometrium was based on the patient's last menstrual period, pathologic dating, and proliferative versus nonproliferative status as determined by Ki67. Benign and malignant specimens were subjected to Northern blot analysis to evaluate levels of expression of c-fos, c-jun, and jun-B mRNA. The pattern of c-fos mRNA expression in malignant samples was further evaluated using in situ hybridization. RESULTS: In proliferative, secretory, postmenopausal, and progesterone-influenced, uterine specimens immunohistochemically stained and examined, the endometrial and stromal nuclei stained for both Fos and Jun in varying intensities. However, no pattern was found in the variation of intensity according to the phase of the endometrium. Similarly, in malignant and benign endometrial tissue examined by Northern blot and in situ hybridization analyses, expression of proto-oncogene mRNAs was readily detectable, but no statistical correlation between type of tissue examined, grade of adenocarcinoma, and stage of endometrial cancer was found in this study. CONCLUSIONS: In rodent models, control of uterine cell proliferation is related to change in expression of fos and jun proto-oncogenes. Our results indicate that hormonal control is likely to be different in human endometrium and probably involves genes other than the proto-oncogenes under study. Expression of Fos and Jun do not correlate with endometrial cancer stage and grade.

Adenocarcinoma↗

Experimental transmission of murine malaria by the oral route.

A total of 116 young male CD1 mice were orally inoculated with mouse blood; half of the animals received 0.2 ml of uninfected blood and the others were given 0.2 ml of Plasmodium berghei yoelii-infected blood in six experiments performed at different times. Almost 30% of the experimental mice acquired malaria as demonstrated by the observation of parasites in their blood. In no case were parasites found in the blood of control mice. Rodent malaria parasites may be transmitted to CD1 mice by the ingestion of mouse blood parasitized by P. b. yoelii. As far as we know, this study represents the first demonstration of oral transmission of murine malaria. Oral transmission studies in this mouse-Plasmodium model may produce very important information on the biology of the malaria parasites.

Administration, Oral↗

Plague and Glasnost. First information about human cases in the USSR in 1989 and 1990.

In October 1989 the first case of plague death in the USSR was reported to WHO. This occurrence in man did not surprise plague experts. The country has extensive enzootic areas and the persistence of natural foci, which can be silent for many years, has been well studied. It is known that the plague bacillus can survive and multiply in the soil of rodent burrows and restart local or more extensive transmissions in carrier animals. Isolated cases in man can remain accidental or they may signal a larger epizootic outbreak. The official policy of the comprehensive antiplague services was to eradicate the natural foci by antirodent activities which proved impossible. The present report from the Central Asian part of the USSR in the wake of Glasnost augurs well for the surveillance of plague worldwide as for a period of over fifty years the occurrence of cases in man in this country had been denied.

Animals↗

Profiling, mimicking and masking the flavor of a selected rodenticide.

In Experiment 1, rats drank strychnine solution followed by an injection of LiCl. Generalization of learned strychnine avoidance to 4 non-toxic flavors was then assessed. Additional conditioning and generalization trials followed until 24 flavors had been presented. In Experiment 2, rats were conditioned to avoid individual flavors, or flavor mixtures concocted on the basis of avoidance generalization observed in Experiment 1. Tests followed for generalization of learned avoidance from the simple flavors to the mixtures, from the mixtures to the simple flavors, and from either to strychnine. In Experiment 3, two concentrations of NaCl were mixed with strychnine or one of the flavors (SOA) used in the previous experiments. These stimuli, as well as SOA alone, strychnine alone, and each of the NaCl concentrations, were presented to rats during conditioning. Generalization followed, as in the previous experiments. In Experiment 1, strychnine avoidance generalized to 'bitter' flavors (ps less than 0.01). In Experiment 2, avoidance of flavor mixtures generalized more strongly to strychnine than did learned avoidance of simple flavors (ps less than 0.01). In Experiment 3, NaCl masked or otherwise suppressed the 'bitter' flavor of strychnine or SOA insofar as no groups conditioned with a 'bitter'-salt mixture generalized avoidance to 'bitter' alone (ps less than 0.01). Rats are therefore capable of recognizing the flavor components of strychnine. Moreover, when these components are mixed in proportion to the degree of generalized avoidance, a mimic (either in terms of flavor characteristics or perceived intensity) of strychnine is obtained. Avoidance learning appears useful in the development of rodenticide baits and pre-bait formulations.

Animals↗

Brain-derived neurotrophic factor (BDNF) and food intake regulation: a minireview.

Neurotrophins, and in particular BDNF, play important roles in proliferation, differentiation and survival of neurons during development, as well as in the synaptic activity and plasticity in many groups of mature neurons. Several lines of evidence suggest that BDNF and its high affinity receptor TrkB contribute to food intake and body weight control. In rodents, pharmacological treatments with BDNF induce reduction in food intake, whereas genetic models with an altered BDNF/TrkB signalling display hyperphagia and obesity. Genetic studies in humans have shown that mutations in the BDNF or TrkB genes may account for certain types of obesity or other forms of eating disorders. Since circulating levels of BDNF correlate with eating disorders in humans and peripheral BDNF treatments reduce hyperphagia and hyperglycaemia in obese diabetic rodents, an endocrine role of BDNF appears plausible and requires further investigation. A central anorectic action of BDNF has also been documented, with a primary focus on the hypothalamus and a more recent highlight on the brainstem integrator of energy homeostasis, the dorsal vagal complex. In this review, we will briefly present neurotrophins and their receptors and focus on experimental evidence which point out BDNF as a signalling component of food intake regulation, with a particular emphasis on the localization of the central anorectic action of BDNF.

Animals↗

Comparative uptakes and biodistributions of internalizing vs. noninternalizing copper-64 radioimmunoconjugates in cell and animal models of colon cancer.

Copper-64-labeled monoclonal antibodies (mAbs) have previously demonstrated unexpectedly effective tumor control in rodent models of cancer at relatively low tumor-absorbed radiation doses. This property has been associated with delivery platforms resulting in cellular internalization. The purpose of the present studies was to evaluate the in vitro internalization and in vivo distribution of a two-antibody model of 64Cu radioimmunotherapy (RIT) in the same cell and animal models of cancer. Biodistributions of an internalizing antibody, cBR96, and a noninternalizing antibody, cT84.66, labeled with 64Cu, were obtained in nude mice bearing LS174T colon carcinoma xenografts from 15 min to 48 h. The 64Cu-DOTA-cBR96 conjugate demonstrated rapid tumor uptake, reaching 20.2% ID/g at 3 h and peaking at 35.4% ID/g by 24 h. Tumor accumulation of 64Cu-DOTA-cT84.66 was more gradual, 8.19% ID/g at 3 h and 43.8% ID/g by 24 h, but maximum uptake was not statistically different from 64Cu-DOTA-cBR96. Mouse xenograft dosimetry was estimated to be 1128 rad/mCi (304.9 mGy/MBq) for 64Cu-DOTA-cBR96 and 1409 rad/mCi (380.5 mGy/MBq) for 64Cu-DOTA-cT84.66. In LS174T cells, internalized radioactivity increased by a factor of 3.8 over 4 h for 64Cu-DOTA-cBR96, but remained unchanged 64Cu-DOTA-cT84.66. When normalized to uptake at 1 h, cellular efflux of 64Cu was essentially identical for both mAbs. The biodistributions and tumor dosimetry of these internalizing and noninternalizing radiolabeled mAbs were sufficiently similar for direct comparison of the therapeutic efficacies of low doses of 64Cu RIT agents in the same animal model of cancer.

Animals↗

Oral inoculation with Type III secretion mutants of Yersinia pseudotuberculosis provides protection from oral, intraperitoneal, or intranasal challenge with virulent Yersinia.

The enteric pathogen Yersinia pseudotuberculosis (Yptb) causes gastroenteritis, mesenteric lymphadenitis, and systemic infections in humans, livestock, and wild animals. Yptb Type III secretion system (pTTSS) mutants efficiently colonize lymphoid tissues, but not the gastrointestinal tract, spleen, or liver. Here, we show that a single oral inoculation of pTTSS mutants prevents morbidity in almost 100% of mice challenged intragastrically with virulent Yptb. In addition, a single oral inoculation of a pTTSS mutant protected 50% of mice challenged intraperitoneally or intranasally with virulent Yptb. In addition, the intranasally challenged mice that succumbed to infection lived significantly longer than non-immunized mice. Thus, pTTSS mutants can function as live attenuated vaccine when delivered orally. Potential uses for these attenuated strains include use as a livestock vaccine, a rodent plague control reagent in endemic areas around the world, and a vector for delivery of other antigens to the mesenteric lymph nodes.

Administration, Oral↗