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PubMed2001

Chromosomal mapping of the host resistance locus to rodent malaria (Plasmodium yoelii) infection in mice.

The disease outcome in malaria caused by the protozoan parasite Plasmodium is influenced by host genetic factors. To identify host genes conferring resistance to infection with the malaria parasite, we undertook chromosomal mapping using a whole-genome scanning approach in cross-bred mice. NC/Jic mice all died with high parasitemia within 8 days of infection with 1 x 10(5) parasitized erythrocytes. In contrast, 129/SvJ mice all completely excluded malaria parasites from the circulation and remained alive 21 days after infection. We performed linkage analysis in backcross [(NC/Jic x 129/SvJ)xNC/Jic] mice. The Pymr ( Plasmodium yoelii malaria resistance) locus was mapped to the telomeric portion of mouse Chromosome (Chr) 9. This locus controls host survival and parasitemia after infection. The Char1 locus ( P. chabaudi resistance locus 1), controlling host survival and peak parasitemia in P. chabaudi infection, was previously mapped to the same region. This host resistance locus mapping to Chr 9 may represent a ubiquitous locus controlling susceptibility to rodent malaria. Elucidation of the function of this gene will provide valuable insights into the mechanism of host defense against malaria parasite infection.

Animals↗

PubMed2005

Association of housing disrepair indicators with cockroach and rodent infestations in a cohort of pregnant Latina women and their children.

Health burdens associated with poor housing and indoor pest infestations are likely to affect young children in particular, who spend most of their time indoors at home. We completed environmental assessments in 644 homes of pregnant Latina women and their children living in the Salinas Valley, California. High residential densities were common, with 39% of homes housing > 1.5 persons per room. Housing disrepair was also common: 58% of homes had peeling paint, 43% had mold, 25% had water damage, and 11% had rotting wood. Evidence of cockroaches and rodents was present in 60% and 32% of homes, respectively. Compared with representative national survey data from the U.S. Department of Housing and Urban Development, homes in our sample were more likely to have rodents, peeling paint, leaks under sinks, and much higher residential densities. The odds of rodent infestations in homes increased in the presence of peeling paint [odds ratio (OR) 2.1; 95% confidence interval (CI), 1.5-3.1], water damage (OR 1.9; 95% CI, 1.2-2.7), and mold (OR 1.5; 95% CI, 1.0-2.1). The odds of cockroach infestation increased in the presence of peeling paint (OR 3.8; 95% CI, 2.7-5.6), water damage (OR 1.9; 95% CI, 1.2-2.9), or high residential density (OR 2.1; 95% CI, 1.2-3.8). Homes that were less clean than average were more prone to both types of infestations. Pesticides were stored or used in 51% of households, partly to control roach and rodent infestations. These data indicate that adverse housing conditions are common in this community and increase the likelihood of pest infestations and home pesticide use. Interventions to improve housing and promote children's health and safety in this population are needed.

Adult↗

PubMed1985

Decreased fibrinolytic activity in the rat uterus after laparotomy.

The influence of different intrauterine devices (IUDs) on the uterine fibrinolysis has been extensively studied in rodents with two uterine horns. In this experimental model an IUD is inserted into one horn by a surgical procedure including laparotomy and uterotomy. The effect of these two surgical steps on the fibrinolysis in the endometrium determined according to Todd's histochemical fibrin slide technique was studied in the present series comprising 26 rats. The fibrinolytic activity (FA) in the rat uterus was independent of the biopsy site in the uterine horns. However, significant depression of endometrial fibrinolysis was demonstrated 2 weeks after laparotomy, whereas no effect of a tiny incision in the uterine wall was recorded. In conclusion, a sham operation of the control horn in rodent studies on the fibrinolytic effect of IUDs according to this experimental model is not necessary.

Animals↗

PubMed2002

Animal- and herd-level risk factors for leptospiral seropositivity among sows in the Mekong delta, Vietnam.

In 1998, a total of 424 sows had sera collected in the Mekong delta in Vietnam. Of these, 283 sows were from 151 small-scale family farms in 19 villages, and 141 from seven large-scale state farms. The sera were subjected to the microscopic agglutination test (MAT) for antibodies to 13 Leptospira serovars. The overall leptospiral seroprevalence for titres > or =1:100 and > or =1:400, was 73 and 29%, respectively, and was higher (P=0.001) at small- than at large-scale farms. The highest seroprevalence was recorded for Leptospira interrogans serovar (sv) bratislava (52%). At small-scale farms, higher prevalences were found to serovars L. interrogans sv icterohaemorrhagiae (P=0.04) and L. interrogans sv pomona (P=0.02). Epidemiological information (at the individual-animal and herd-levels) was collected with a questionnaire. The data were analysed using logistic multiple regression. At the animal-level, sows seropositive for L. interrogans sv australis and sv autumnalis had less direct contact with sows in neighbouring pens (odds ratio (OR)=0.3 and 0.4, respectively) and sows seronegative for L. interrogans sv bratislava were of lower age (OR=0.1 for seropositivity). Also, sows seropositive for L. interrogans sv icterohaemorrhagiae had higher odds (OR=5.8) if they had not been born on the farm (had been introduced to it as gilts). Herds seropositive for sv javanica showed association with farms not taking measures to control the local rodent population (OR=7.8). Serovar pomona was also linked to the use of artificial insemination (AI), as opposed to natural-breeding services (OR=11.2). These results indicate that housing and management could affect the seroprevalence of Leptospira infection in pigs.

Age Factors↗

PubMed2002

Prenatal cocaine exposure disrupts non-spatial, short-term memory in adolescent and adult male rats.

The rise in the recreational use of cocaine in the last two decades has resulted in a growing health concern about fetal drug exposure. In exposed children, investigators have noted altered cognitive performance in complex or distracting, but not more controlled, situations. In rodent models, deficits in short-term memory have been noted in some, but not all, paradigms, although these studies also differ in routes of administration and dosing models. Here, we report short-term memory deficits in rats prenatally exposed to cocaine using an intravenous administration model to closer mimic cocaine doses and pharmacokinetics seen with human use. A spontaneous two object recognition task was used to avoid (1) clearly aversive or rewarding components, (2) reference memory component and (3) the use of external motivators, such as swimming stress or food deprivation/rewards. In this task, adolescent and adult male rats exposed to cocaine in utero demonstrated deficits in short-term memory compared with saline controls. No difference in the time spent exploring the objects or the number of failures was noted between the prenatal cocaine and saline rats. This study suggests that prenatal exposure to cocaine can result in a long-lasting deficit in non-spatial, short-term memory in a spontaneously performed task.

Aging↗

PubMed1993

Should carbogen and nicotinamide be given throughout the full course of fractionated radiotherapy regimens?

PURPOSE: Tumor radiosensitization with carbogen and nicotinamide (CON) was compared when both agents were given throughout fractionated radiotherapy with the sensitization observed when administered with only half of the fractions. The effect of overall treatment time on the local control of tumors irradiated in air or with CON was also investigated. METHODS AND MATERIALS: Local tumor control of a rodent adenocarcinoma, CaNT, was studied using eight different 20-fraction x-ray regimens. An overall time of either 10 or 20 days was used and CON was given with all, the first half or last half of the treatment. RESULTS: Relative to air, all six sensitizer combinations gave a large and significant increase in sensitization (p << 0.00001). Enhancement ratios were 1.9 and 2.1 when CON was given with all 20 fractions in either 10 or 20 days, respectively. For both overall times, enhancement ratios were reduced by 15-25% when CON was given with only half of the fractions. In air, reducing the treatment time from 20 to 10 days gave a small but significant decrease in the isoeffective doses. When CON was administered with either all or part of a schedule, varying the treatment time had little or no effect on local tumor control. No toxic side-effects were encountered when the sensitizers were administered 10 or 20 times, either once or twice per day. CONCLUSION: CON is an effective and non-toxic tumor radiosensitizer. In CaNT tumors, a significantly greater effect is seen when CON is given with every fraction of the schedule. The sensitizers reduced or abolished the sparing effect of overall time.

Adenocarcinoma↗

PubMed1978

Evidence in rat and mouse liver for temporal control of two forms of cytochrome P-450 inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

In the liver of perinatal rats or mice, the ratio of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon hydroxylase to total cytochrome P-450 content decreases, whereas the ratio of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced acetanilide 4-hydroxylase to total cytochrome P-450 content increases, between 18 or 19 days and 22 days following conception. The ontogenesis of inducible aryl hydrocarbon hydroxylase corresponds well with increases in a 56000-Mr electrophoretic band; we suggest this band represents the cytochrome P1-450 subunit. The later temporal expression of inducible acetanilide 4-hydroxylase closely parallels 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced increases in size of a 54000-Mr electrophoretic band and a 2--3-nm hypsochromic shift in the Soret peak of the total microsomal reduced cytochrome P-450 . CO complex. We suggest this band represents the cytochrome P-448 subunit. Previous work from this laboratory has shown that this developmental difference is separated by several weeks in rabbit liver, as compared with several day's separation shown in this report with rat or mouse liver. The data here therefore provide evidence in the rodent for temporal control of the expression of different structural gene products regulated by the Ah locus.

Aging↗

PubMed1993

Hypersensitivity to common indoor aeroallergens in asthmatic patients.

To study whether inhalant allergy to specific allergens is associated with inner city asthma, adult emergency room asthmatic patients (n = 41), and controls (n = 34) were examined for immediate hypersensitivity to six common indoor allergens using both skin tests and serologic tests. A highly significant association was observed between cat epidermis-specific IgE and asthma (P < .01) and this constituted the strongest association for a single allergen. The pooled variable of IgE to cat and/or dog epidermis had an even stronger disease association (P < .001). The presence of IgE to other allergens and the presence of two or more positive IgE tests did not enhance this association. After inclusion of three other significant covariates (elevated serum total IgE, longer duration of residence in the New York City area, and family history of atopic disease) in a logistic prediction model for asthma, skin test-detected IgE to cat and/or dog remained significantly associated with asthma (odds ratio 8.4, P = .019). A higher proportion of asthmatic patients had both IgE to cat and/or dog allergen and ongoing historical exposure to pets and/or rodents compared with controls (P < .005). Skin testing in general distinguished asthmatic patients better than serologic tests. These results suggest that inner city asthma in adults during a nonpeak pollen period is associated with hypersensitivity to specific indoor allergens. The potential to use environmental control to ameliorate disease in such patients may have significant health care implications.

Adult↗

PubMed1997

Oestrogen and progesterone control basic fibroblast growth factor mRNA in the rat uterus.

Cell proliferation and differentiation in the rodent uterus are probably controlled by the interaction of female sex steroids with polypeptide growth factors. Uterine basic fibroblast growth factor (bFGF) mRNA was measured by RNase protection during the time (days 2-4) of endometrial cell proliferation in the pregnant rat. bFGF transcripts were detected at each of the 3 days of pregnancy examined. To investigate the influence of oestrogen and progesterone on bFGF mRNA accumulation, ovariectomized rats were treated with oestradiol for 48 h followed by a single injection of oestradiol, progesterone, the two steroids co-injected or oil vehicle alone. Uterine RNA was collected 6 h after the last hormone injection. Steroid treatments increased steady-state uterine bFGF mRNA compared with vehicle control animals as measured by RNase protection. Northern blot analysis of c-fos and c-jun mRNAs from these same treatment groups revealed increased protooncogene expression in the uterus of hormone treated rats compared with the control animals. Temporal analysis of bFGF mRNA in ovariectomized rats at 1, 3 and 6 h after acute oestrogen and oestrogen-progesterone co-administration showed a dual pattern of transcript accumulation. Both hormone treatments increased bFGF mRNA within 1 h compared with vehicle injected rats. Co-administration of the two hormones, however, repressed bFGF mRNA accumulation relative to oestrogen at 3 and 6 h. Together, these studies provide evidence that bFGF control of uterine cell proliferation in pregnant rats can occur from newly synthesized bFGF. Moreover, the results suggest that progesterone is a potent stimulator of bFGF expression in the uterus.

Animals↗

PubMed1998

Evaluation of two oral baiting systems for wild rodents.

Tetracycline hydrochloride (TC)-treated peanut butter or rodent chow baits were distributed during March 1990, on separate 0.53 ha sites in Oglethorpe County, Georgia (USA). Rodents were trapped on a control site prior to bait distribution and on two baited sites 6 days post-distribution. Cleaned skulls from euthanized mammals were grossly examined for TC fluorescence using an ultraviolet (UV) light. Mandibles were sectioned and examined for TC fluorescence using an ultraviolet light microscope. All 21 cotton rats (Sigmodon hispidus), four eastern harvest mice (Rithrodontomys humulis), and two golden mice (Ochrotomys nuttalli) captured on the control site were negative for TC fluorescence. On the peanut butter bait site, mandible sections from 29 of 32 (91%) cotton rats, three of three (100%) eastern harvest mice, two of three (66%) golden mice, zero of five (0%) white-footed mice (Peromyscus leucopus), one of three (33%) short-tailed shrews (Blarina brevicauda), and zero of two (0%) least shrews (Cryptotis parva) were positive for TC. Results from the rodent chow bait site indicated that 18 of 25 (72%) cotton rats, zero of three (0%) eastern harvest mice, two of seven (29%) golden mice, zero of four (0%) white-footed mice, and zero of four (0%) least shrews were positive for TC fluorescence in mandible sections. These results suggest that a large portion of a free-ranging small rodent population can be administered biological markers or vaccines using baits.

Animal Feed↗

PubMed1993

Estrogen-induced calbindin-D 9k gene expression in the rat uterus during the estrous cycle: late antagonistic effect of progesterone.

Progesterone modulates estrogen-stimulated responses in the uterus. Calbindin-D 9k (CaBP9k), a 17 beta-estradiol-responsive gene expressed in the uterus, was used as a marker to examine the interactions between endogenous progesterone and estradiol in the rat. The variations in uterine CaBP9k messenger RNAs (mRNAs) during the rat estrous cycle indicated that CaBP9k gene expression was greatest during the estrogen-dominated phases (proestrus and estrus) and became totally repressed during diestrus, when progesterone predominates. Estradiol was found to be the major controlling factor of CaBP9k gene expression in vivo, progesterone antagonizing estrogen-induced CaBP9k gene expression. The inhibitory role of progesterone was further examined in two experiments. Mature cyclic rats were injected with the progesterone antagonist RU486 before the progesterone surge of proestrus, and the estrous cycle was mimicked in ovariectomized rats by sequential injections of estrogen and progestin. Progesterone did not appear to be involved in the rapid decrease in CaBP9k mRNA during estrus but was implicated in the down-regulation of the estrogen-stimulated CaBP9k gene expression at the end of estrus and during diestrus. This delayed effect of progesterone was confirmed in the ovariectomized rat model. CaBP9k mRNA accumulation in estrogen-primed ovariectomized rats was suppressed by estrogen followed 1 h later by the progesterone agonist R5020. This effect occurred more than 24 h after progestin treatment. The inhibition of the estrogen-induced CaBP9k gene expression in the rat uterus by progesterone is certainly mediated by the progesterone receptor, because progesterone had no effect without estrogen priming or when the antagonist RU486 was used. The delayed progesterone effect probably does not involve depletion of nuclear estrogen receptors, the major rapid mechanism proposed for estrogen inhibition by progesterone in the rodent uterus, or control of estrogen receptor synthesis, as shown by Northern blot analysis of estrogen receptor mRNA.

Animals↗

PubMed2005

Absorbencies of six different rodent beddings: commercially advertised absorbencies are potentially misleading.

Moisture absorbency is one of the most important characteristics of rodent beddings for controlling bacterial growth and ammonia production. However, bedding manufacturers rarely provide information on the absorbencies of available materials, and even when they do, absorption values are usually expressed per unit mass of bedding. Since beddings are usually placed into cages to reach a required depth rather than a particular mass, their volumetric absorbencies are far more relevant. This study therefore compared the saline absorbencies of sawdust, aspen woodchips, two virgin loose pulp beddings (Alpha-Dri and Omega-Dri), reclaimed wood pulp (Tek-Fresh), and corncob, calculated both by volume and by mass. Absorbency per unit volume correlated positively with bedding density, while absorbency per unit mass correlated negatively. Therefore, the relative absorbencies of the beddings were almost completely reversed depending on how absorbency was calculated. By volume, corncob was the most absorbent bedding, absorbing about twice as much saline as Tek-Fresh, the least absorbent bedding. Conversely, when calculated by mass, Tek-Fresh appeared to absorb almost three times as much saline as the corncob. Thus, in practical terms the most absorbent bedding here was corncob, followed by the loose pulp beddings; and this is generally supported by their relatively low ammonia production as seen in previous studies. Many factors other than absorbency determine whether a material is suitable as a rodent bedding, and they are briefly mentioned here. However, manufacturers should provide details of bedding absorbencies in terms of volume, in order to help predict the relative absorbencies of the beddings in practical situations.

Advertising↗

PubMedDate not supplied

The effects of diet, ad libitum overfeeding, and moderate dietary restriction on the rodent bioassay: the uncontrolled variable in safety assessment.

Ad libitum (AL) overfeeding is the most significant, uncontrolled variable affecting the outcome of the current rodent bioassay. There is a highly significant correlation between AL food consumption, the resultant obesity and body weight, and low 2-yr survival in rodents. AL feeding of diets with lowered protein, metabolizable energy (ME), and increased fiber does not improve survival. Only dietary restriction (DR) of all diets tested significantly improves survival and delays the onset of spontaneous degenerative disease (i.e., nephropathy and cardiomyopathy) and diet-related tumors. Moderate DR results in an incidence of spontaneous tumors similar to AL-fed rats, but the tumors are found incidentally and do not cause early mortality. There is a decreased age-adjusted incidence of pituitary and mammary gland tumors in moderate DR-fed rats, but tumor growth time is similar between AL and DR rats with only a delay in tumor onset time seen in DR-fed groups. Moderate DR does not significantly alter drug-metabolizing enzyme activities nor the toxicologic response to 5 pharmaceuticals tested at maximum tolerated doses (MTDs). However, moderate DR-fed rats did require much higher doses of 4 additional pharmaceutical compounds before classical MTDs were produced. Toxicokinetic studies of 2 of these compounds demonstrated equal or higher steady-state systemic exposures to parent drug and metabolites in moderate DR-fed rats. Markers of oxidative stress (lipid peroxidation, protein oxidation) are decreased and cytoprotective anti-oxidant markers are preserved in moderate DR-fed rats. But moderate DR does not delay reproductive senescence in female rats. Only marked DR delays reproductive senescence compared to AL and moderate DR-fed female rats. These and other data indicate that moderate DR is the most appropriate method of dietary control for the rodent bioassay when used to assess pharmaceuticals for human safety and compounds for risk assessment.

Animal Feed↗

PubMed1995

Strongyloides stercoralis: protective immunity to third-stage larvae inBALB/cByJ mice.

A murine model system was developed to study the induction and mechanism of protective immunity to L3 of Strongyloides stercoralis. L3 were implanted in BALB/cByJ mice in diffusion chambers constructed with 0.1- or 2.0-microns-pore-size membranes. Parasites survived equally well regardless or membrane type for 7 days, after which larval survival decreased in diffusion chambers constructed with 2.0-microns-pore-size membranes, which allowed host cells to enter. Survival of S. stercoralis L3 in diffusion chambers implanted in mice was assayed after immunization with live, heat-killed, and homogenized L3. Optimal immunization was achieved with 10,000 live L3, whereby immunized mice eliminated 97% of the larvae either contained within diffusion chambers or free within the tissues of the mouse by 24 hr postinfection. Sera from immunized mice had elevated levels of IgG1, IgM, and IgA parasitic-specific antibody; IgM was the only antibody isotype that recognized surface antigens of L3. Larvae were not killed in immunized mice if contact between host cells and the parasites was prevented. In the peripheral blood and diffusion chamber fluid of immunized mice, eosinophil levels were significantly higher when compared to the levels found in control mice. The rodent model developed in the present study has thus demonstrated that virtually complete immunity can be induced to the L3 of S. stercoralis and that larval killing was found to be associated with the presence of both specific antibody and eosinophils.

Animals↗

PubMed1995

Oncogenic potential of inhaled hydrazine in the nose of rats and hamsters after 1 or 10 1-hr exposures.

Hydrazine (N2H4) is used as a fuel for missiles and standby power systems of operational military aircraft. Maintenance of missiles and aircraft may result in accidental human exposure to high concentrations for brief periods of time. The purposes of this study were to assess the oncogenic potential of N2H4 in rats and male hamsters exposed to a high concentration of N2H4 for repeated short exposures and to investigate the relationships of acute and subchronic effects of N2H4 to nasal tumorigenesis. In phase 1 (acute and subchronic) and Phase 2 (lifetime experiments, groups of male and female Fischer 344 rats and male Syrian golden hamsters were exposed by inhalation to 0, 75 (Phase 2 only), or 750 ppm N2H4 for 1 (acute) or 10 (subchronic) 1-hr weekly exposures. Rodents were euthanized 24 hr after exposures 1 and 10 and 24 to 30 months poststudy initiation. Significant reductions in body weight were observed in N2H4-treated rodents compared to controls during the exposure interval. No hydrazine-induced mortality was detected. Histopathologic examination after the acute and subchronic exposures revealed degeneration and necrosis of transitional, respiratory, and olfactory epithelia in the anterior nose and, in rats exposed subchronically, squamous metaplasia of the transitional epithelium. Minimal to mild rhinitis resulted from N2H4 exposures. Apoptosis was observed in olfactory and squamous metaplastic transitional epithelium. Lesions occurred at sites reportedly having high air-flow and generally appeared to be more severe in the anterior portion of the nose. By 24 months, the squamous metaplastic transitional epithelium reverted back to normal-appearing transitional epithelium. By 24+ months, low incidences (sexes combined) of hyperplasia (5/194, 2.6%) and neoplasia (11/194, 5.7%) were detected, principally in the transitional epithelium of the 750 ppm N2H4-treated rats. A similar incidence of hyperplasia (2/94, 2%) and neoplasia (5/94, 5.3%) was detected in the high-exposure group of hamsters. The location and type of N2H4-induced proliferative lesions were similar to those reported in a chronic N2H4-exposure study (5.0 ppm x 6 hr/day x 5 days/week for 1 year) conducted in our laboratory, but the chronic study had much higher incidences (rats, sexes combined: hyperplasia 15.5% vs 2.6% and polypoid adenoma 44.6% vs 5.2%). The product (CD) of concentration + time was the same (750 ppm hours) for the high-dose groups for both studies, but the duration of exposure was 150 x longer and the concentration was 150 x lower in the chronic study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenomatous Polyps↗

PubMed1984

Heart and liver lipid fatty acid and behavior changes in mice after a diet change.

270-Day old, male Ham/ICR mice were subjected to a diet change from high protein and carbohydrate and low fat to a diet higher in fat and lower in carbohydrate and protein. Age matched mice were maintained on laboratory rodent chow as controls. The diet change was not defined so the observed differences could not necessarily be ascribed to altered protein, carbohydrate, or fat intake. Comparison of the controls with the experimental mice revealed the " junk food" mice differed in lipid fatty acid profiles of the heart and liver and in percentage of lipid palmitic and oleic acids in these organs and also in plasma. Appearance was altered in the experimental mice which had dull, greasy coats. In addition, the experimental animals were less active, slept singly, and were slower in negotiating a three-choice maze than their comparably housed counterparts, indicating altered activity/curiosity behavior.

Animals↗

PubMedDate not supplied

Plague in Lushoto district, Tanzania, 1980-1988.

Rodents were live-trapped in selected plague-inflicted villages from June 1980 to March 1988. Flea infestation rates were determined and the animals were serologically tested for plague. Clinically suspected and clinically healthy people in the affected areas were similarly tested for plague antibodies. Of 1596 rodent sera tested, 91 (5.7%) were positive for plague. These were mostly from Rattus rattus, Mastomys natalensis, Otomys spp. and Pelomys fallax. A total of 1772 fleas, of which Dinopsyllus lypusus, Xenopsylla brasiliensis and Ctenophthalmus calceatus comprised the largest proportion, was collected from the captured rodents. Total flea indices ranged from 0.67 to 1.12 fleas per rodent. A total of 2809 human cases and a mortality rate of 10.2% were recorded in 1980-1988. It was concluded that most rodent species in the area were suitable reservoirs of plague and that D. lypusus, X. brasiliensis and C. calceatus were probably responsible for transmitting the pathogen. Lack of effective quarantine measures during outbreaks was partly responsible for the spread of the disease to many villages, while inadequate rodent and flea control and poor sanitary measures could be responsible for continued outbreaks of plague in the area.

Animals↗

PubMed1988

The toxicity and mechanism of action of bromethalin: a new single-feeding rodenticide.

Bromethalin is a new rodenticide for the control of commensal rodents. Doses in excess of the LD50 (2 mg/kg in rats) will cause death within 8-12 hr and it is preceded by one to three episodes of clonic convulsions with death usually due to respiratory arrest. Multiple low doses or sublethal intoxication yields hind leg weakness and loss of tactile sensation in rodents. Histopathology of the brain and spinal cord of these animals revealed a spongy degeneration of the white matter which was shown upon ultramicroscopic examination to be intramyelenic edema. No inflammation or cellular destruction of neuronal tissue was noted. LD50 values ranged from 1.8 mg/kg in the cat to approximately 13 mg/kg in rabbits. The only apparent nonsusceptible species was the guinea pig which could tolerate doses in excess of 1000 mg/kg without effect. Identification of the desmethyl metabolite was demonstrated in the blood and liver of treated animals by comparison of chromatographic retention times to that of a reference standard, but direct mass spectral identification was unsuccessful in part due to the low dose which could be administered. Therefore, the metabolism of bromethalin was studied by indirect means. Animals were pretreated with three inducers of microsomal drug metabolism: phenobarbital, 3-methylcholanthrene (3MC), and Aroclor 1254 (Aroclor) and one inhibitor, SKF-525A. Pretreated mice or rats were given an LD50 dose of bromethalin or the desmethyl analog and the percentage of surviving animals was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Aniline Compounds↗