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Biosecurity and minimal disease herds.

The minimal disease concept is a way of raising pigs so that some specific diseases are absent. Many bacteria and viruses can be transferred by pigs, air, or mechanical contact. To avoid contamination, the herd location should take into consideration disease transmission possibilities. Herd health status and source herd health status should be continuously monitored. To maintain herd health status, specific rules need to be followed for herd construction and establishment, compound perimeter, people movement, down time, animal transportation, feed use and delivery, vehicle movement, material, dead animal disposition, and rodent control. All new incoming animals should go through quarantine, and in some herds, safer methods such as AI, embryo transfer, MEW, or hysterectomy and fostering need to be used.

Animal Feed

Leptospira interrogans serovar icterohaemorrhagiae seropositivity and the reproductive performance of sows.

The reproductive performance of 28 sows seropositive to Leptospira interrogans serovar icterohaemorrhagiae was compared with that of 87 Leptospira sp. seronegative dams belonging to the same herd. Sows were sampled during 1988 to 1993. During this period the herd was not submitted to any kind of intervention (antibiotic therapy, immunoprophylaxis or rodent control). Relative risks (RR) of return to heat, mummified fetuses, stillbirth, and weak newborn piglets for infected sows were assessed and the differences in means of total piglets born per litter, piglets born alive, piglets effectively housed, weaned piglets, stillbirths, mummified fetuses, weak newborn piglets, weight at birth of the piglets effectively housed, weight at 21 days of life and weight at weaning were evaluated. Seropositive dams had a greater risk of having weak newborn piglets (RR = 1.67, 1.02 < or = CI 95% < or = 2.72) and also of having more weak newborn piglets per litter (P = 0.01). Other variables examined were not different (P > 0.05).

Aging

Seroprevalence of murine typhus and fièvre boutonneuse in certain human populations in Egypt.

A study was conducted between 1984 and 1987 to determine the prevalence of Rickettsia typhi and Rickettsia conorii infections among humans residing in the Nile Delta, Suez Canal area and Nile Valley of Egypt. Serum specimens were obtained from garbage and rodent control workers, other unclassified occupational workers, and from patients with fever of undetermined aetiology. All sera were assayed for IgA + IgM + IgG (IgAMG) antibody mixture and if positive, reassayed for specific IgM antibody to rickettsia by the indirect fluorescent antibody technique. R. typhi antibody was found in 19% (33/178) of the garbage collectors, whereas only 1% (2/178) had demonstrable antibody to R. conorii. Among those with other occupations, R. typhi antibody was detected in 0.7% (2/295) and none had R. conorii antibody. The antibody prevalence rate for R. typhi among patients with febrile illness ranged from 25 to 41%, and from 2 to 15% for R. conorii, at three different locations in Egypt. In addition, IgM antibody to R. typhi was demonstrated in some patients showing symptoms compatible with rickettsial disease and in some patients who seroconverted, indicating that R. typhi was the cause of illness among some of these patients. These findings support previous observations that R. typhi and R. conorii are the causes of human rickettsial disease in Egypt, and that humans are commonly infected with R. typhi.

Adult

Experiments on direct and secondary poisoning by fluoroacetamide (1081) in wildlife and domestic carnivores.

Fluoroacetamide (1081 or F.A.A) is used in Israel for field rodent control. Experiments on direct and secondary, short and long term poisoning caused by 1081 were carried out. Mongoose (Herpestes ichneumon), hyena (Hyaena hyaena), cats and dogs were susceptible. Barn owls (Tyto alba), buzzards (Buteo buteo) and black kites (Milvus m. migrans) were markedly resistant. Barn owls tolerated total direct poisoning ranging from 6.8 to 10.9, and a final dose ranging from 0.8 to 2.0 mg/kg. In secondary poisoning, total doses ranging from 1.7 to 7.1, and final doses ranging from 0.2 to 1.3 mg/kg were tolerated. Buzzards tolerated total direct poisoning ranging from 6 to 12.0, and final doses ranging from 0.7 to 1.3 mg/kg. In secondary poisoning, doses ranging from 0.8 to 10.3 and final doses ranging from 0.2 to 2.4 mg/kg were tolerated. One black kite tolerated a total direct dose of 6.1 and final dose of 0.7 mg/kg, another survived a total dose of 2.3 and final dose of 0.2 mg/kg in secondary poisoning. A small-scale secondary poisoning experiment on two Palestine vipers (Vipera palestinae), a Syrian black snake (Coluber jugularis) and two Montpellier snakes (Malpolon monspessulanus) indicated that these species were resistant to total doses ranging from 0.1 to 3.2 and final doses of 0.1 to 0.8 mg/kg.

Amides

Haemorrhagic fever with renal syndrome: memorandum from a WHO meeting.

Haemorrhagic fever with renal syndrome (HFRS) is a public health problem throughout most of the European and Asian land mass. Although predominantly associated with rural areas, it is now being recognized as an urban problem in some countries, and also presents a particular hazard to laboratory staff who use rodents for biomedical research. In wild rodents (rats, mice and voles) the infection is asymptomatic. Human infection with the HFRS agent(s) is sporadic, but under special circumstances epidemics occur; the infection may be completely silent, or associated with mild or severe disease. Severe cases are usually seen in the Far East. The epidemiological features of the disease vary from country to country and depend upon a variety of factors, the elucidation of which requires a multidisciplinary approach. The recently discovered Hantaan virus is the etiologic agent of HFRS in Asia. It is now possible to detect Hantaan virus antigen by immunofluorescence using either infected mouse lung or infected human cells as substrate. Prevention measures to date have concentrated on rodent control; the role played by the ectoparasites of rodents, if any, has still to be elucidated. Antigens have been detected in rodents captured in HFRS-endemic areas in China, Finland, Japan, Sweden, and the Soviet Union. None of these have been cultured as yet, but preliminary results with the Puumala agent detected in Finland indicate a relationship with the Hantaan virus. Sera collected from Scandinavian patients react to a high titre with both Puumala and Hantaan agents, whereas sera collected from patients in East Asia have much higher titres against the homologous antigen. Surveillance is very important and further research on the virus is needed, especially to identify the virus in the West and to determine strain differences.

Adolescent

Heterogeneic autoantibody against neurofilament protein in the sera of animals with experimental kuru and Creutzfeldt-Jakob disease and natural scrapie infection.

Heterogeneic autoantibodies against axonal neurofilament proteins of mature mouse neurons grown in vitro were detected by the indirect immunofluorescence technique in 12.7% (9 of 71) of the sera from nonhuman primates infected with kuru, in 14.5% (17 of 117) and 4% (1 of 25), respectively, of the sera from nonhuman primates and laboratory rodents infected with Creutzfeldt-Jakob disease, and in 35% (7 of 20) of the sera from sheep naturally infected with scrapie. Autoantibody titers ranged from 1:16 to 1:512 in Creutzfeldt-Jakob disease-infected animals, 1:32 to 1:512 in kuru-infected animals, and 1:64 to 1:1,024 in sheep with natural scrapie. The sera from 11 monkeys and 17 hamsters infected with scrapie and from 19 chimpanzees inoculated with brain tissues from humans with other neurological diseases did not contain autoantibodies. Of the 41 chimpanzees with Creutzfeldt-Jakob disease, 6 had autoantibodies against neurofilament proteins before experimental inoculation, whereas 6 others developed autoantibodies after inoculation, 4 developed autoantibodies during the asymptomatic phase, and 2 developed autoantibodies during the terminal clinical phase. Of the 48 chimpanzees with kuru, 2 had autoantibodies before inoculation, 6 developed autoantibodies after inoculation, 3 developed autoantibodies during the asymptomatic phase, and 3 developed autoantibodies during the terminal clinical phase. Among the normal nonhuman primate controls, 4.6% (9 of 195) had autoantibodies. In contrast, no autoantibodies were detected in 49 control rodents and 13 control sheep. The increased incidence of autoantibodies against neurofilament proteins in animals with kuru, Creutzfeldt-Jakob disease, and scrapie constitutes the first evidence of an immunological reaction in this group of atypical infections caused by unconventional viruses and suggests that neurofilaments may be involved in pathogenesis.

Animals

Aberrant crypts, putative precancerous lesions, in the study of the role of diet in the aetiology of colon cancer.

Progress in the field of diet and colon cancer would be greatly enhanced by the development of a methodology which allowed for the identification and quantification of the early precursor lesions of colon cancer. Recently we described a method (Bird, 1987) consisting of staining the fixed, unsectioned colon with methylene blue for viewing the mucosal surface with the aid of a light microscope. With this methodology we observed early focal lesions in the colons of rodents which had been treated with a colon carcinogen but no lesions in the colons of control rodents. We termed these lesions aberrant crypts (AC). Based on our preliminary observations we hypothesized that AC represent precursor lesions of colon cancer. The findings from our subsequent studies (summarized in this paper) support this contention. We therefore suggest that evaluation of the characteristics of AC will further our understanding of the carcinogenic process as it occurs in the rodent colon and will provide a basis for the investigation of the role of diet in the aetiology of the disease.

Animals

Maintenance of thyroid hormone production during exercise-induced weight loss.

Calorie restriction reduces thyroxine (T4) and 3,5,3'-triiodothyronine (T3) production, but the effects of exercise-induced weight loss on thyroid hormone metabolism in rodents are unclear. We studied the effects of chronic exercise on T4 and T3 metabolism comparing exercising (exercise) rats pair fed to sedentary (control) rodents and to weight-matched underfed sedentary animals (underfed; caloric intake 75% of ad libitum-fed controls). The exercise group utilized voluntary running wheels (28 days), and thyroid hormone metabolism was assessed using a three-compartment kinetics model. The exercise and underfed groups were equivalent in weight, but protein mass was greater in the exercise vs. underfed groups (30.4 +/- 0.5 vs. 27.9 +/- 0.5 g; P less than 0.05). During exercise, the T4 plasma clearance rate (PCR) was decreased (-39.2%; P less than 0.01) and the T4 concentration in serum was increased (48.6%; P less than 0.01), resulting in an unchanged T4 plasma appearance rate (PAR) vs. the control group. The decrease in T4 PCR in the exercise group was associated with a lower transport rate of T4 out of the slow pool (P less than 0.01). In the underfed group there was a reduction in both T4 serum concentration and PAR (-36%; P less than 0.01) compared with the control group, which was associated with a decrease in the volume of distribution (-25%; P less than 0.01). T3 PAR decreased 38.7% (P less than 0.01) during underfeeding but only 16.9% (P = not significant) during exercise vs. the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Is 2-dimethylaminoethanol (deanol) indeed a precursor of brain acetylcholine? A gas chromatographic evaluation.

Acute administration of deanol-p-acetamidobenzoate (Deaner; deanol) has been reported to elevate brain choline (CH) and acetylcholine (ACh) levels. We have developed a specific and sensitive gas chromatographic assay to measure deanol levels in tissue and have applied this assay to our studies of the effect of acute deanol administration on deanol, ACh and Ch levels in rodent brains. Details of the method are described in this text. This procedure is quantitative and yields reproducible results over a wide range of deanol concentrations (0.30-200 nmol). Seven endogenous and pharmacological parameters have been studied using this procedure. In control rodent brain, liver, heart, lung and plasma, we detected no free endogenous deanol (less than 1 nmol/g). After deanol administration, we were able to detect deanol in tissue and have attempted to determine a relationship between these levels and values of ACh in the same tissue. Regardless of deanol pretreatment time (1-30 minutes) or doses (33.3-3000 mg/kg i.p.) used, we detected no increase in mouse whole brain ACh levels. Likewise, there was no detectable elevation in ACh levels in rat whole brain, cortex, striatum or hippocampus after a 15-minute pretreatment with 550 mg/kg of deanol (i.p.). The only elevation in ACh levels which we detected occurred selectively in the striatum of mice pretreated with a massive dose (900 mg/kg i.p.) of deanol for 30 minutes. This selective increase in striatal ACh levels oculd not, however, be related to levels of deanol in the striatum because there was no greater accumulation of deanol in the striatum than in other brain areas tested or in whole brain. These data do not confirm the results of other investigators who reported elevations in whole brain or striatal ACh levels after acute administration of lower doses of deanol. The data emphasize the need for further investigation into the mode of action of deanol and question its suggested role as an immediate precursor of ACh synthesis in the central nervous system.

Acetylcholine

Effect of intrastriatal and intranigral administration of synthetic neuromelanin on the dopaminergic neurotoxicity of MPTP in rodents.

Previous studies showed that the neurotoxin MPTP and its toxic metabolites bind with high affinity to neuromelanin (NM). Therefore, the presence of NM in human and primate but not in rodent substantia nigra, theoretically may be responsible for the species-selective dopaminergic (DA) toxicity of MPTP. We measured DA levels in rodent striatum 7 days after an acute single challenge with MPTP (40 mg/kg, s.c.) given alone or 24 h following unilateral intrastriatal injections of synthetic DA-NM in mice and intrastriatal or intranigral pigment administration in rats. Ipsilateral striatal DA levels were unaffected in control rodents treated with unilateral intrastriatal or intranigral DA-NM. In mice, systemic MPTP produced marked striatal DA depletions which were mildly increased in the striata given prior DA-NM injections. In rats, a species resistant to MPTP, administration of toxin did not affect striatal DA levels. However, after pretreatment with unilateral intrastriatal DA-NM, MPTP induced mild DA falls in ipsilateral striata. By contrast, intranigral administration of DA-NM followed by MPTP, did not alter ipsilateral striatal DA in rats. The findings suggest that intrastriatal DA-NM in mice and rats may augment or initiate, respectively. MPTP-induced damage to sensitive DA-nerve-terminals perhaps by its action as a depot for binding and protracted release and action of the toxin. Lack of effect of intranigral DA-NM which is retained extraneuronally suggests that role of NM in the toxicity of MPTP may depend on its location within DA cell bodies in the nigra.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

In vivo carcinogenesis assay of DL-methadone.HCl in rodents.

The extensive clinical use of methadone encouraged the performance of a carcinogenesis bioassay to support risk assessment in man. An oral LD50 of 178 mg/kg was obtained in B6C3F1 mice. Physiologic changes induced by mean oral doses of 15, 30, and 60 mg/kg for 90 days included dose-related central nervous system (CNS) stimulation, fighting, tolerance development, sex-related alteration of food consumption, and no drug-related pathology. In the chronic study dosages were 15 and 60 mg/kg for mice, 16 and 28 mg/kg for male rats, and 46 and 88 mg/kg for female rats. Survival incidences for treated and control rodents were 72-86% for mice and 80-90% for rats. Deaths related to morphologic changes of aging occurred in all groups. CNS stimulation and fighting were more common to male rodents. Growth rates were unchanged for mice but a dose-related inhibition occurred for rats. Higher doses stimulated food intake in both species. Neither the type nor incidence of neoplasia was drug related but a few nonneoplastic lesions may have been. Preliminary plasma methadone levels at necropsy were dose related in the rat.

Animals

Neuroprotective effect of NMDA receptor glycine recognition site antagonism persists when brain temperature is controlled.

Several lines of inquiry have indicated that glycine plays an important role in both glutamatergic neurotransmission and pathophysiology of cerebral ischemia. However, subacute outcome trials demonstrating the efficacy of glycine antagonists as neuroprotectants have not been performed with rigorous control of brain temperature. In this study, we investigated the effect of N-methyl-D-aspartate (NMDA) receptor glycine recognition site antagonism in a temperature-controlled rodent model of transient focal ischemia. Male Wistar rats underwent 75 min of intraluminal middle cerebral artery occlusion (MCAO). During MCAO and the first 24 h of reperfusion, rats (n = 10) were administered e55-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021) i.v. as a bolus infusion of 5 mg/kg followed by 3.5 mg/kg/h (Low-Dose) or 10 mg/kg followed by 7 mg/kg/ h (High-Dose) for 24 h. Cortical temperature was controlled at 38.0 +/- 0.1 degrees C during MCAO and the first 6 h of reperfusion. A 7-day recovery interval was allowed. Mean total infarct volume was reduced by approximately 40% in both high- and low-dose groups (p < 0.01). The preponderance of infarct reduction occurred in the cortex (p < 0.01). Neurologic function correlated with the size of cerebral infarct (p = 0.001). Neurologic grade was similarly improved by treatment with either dose (p = 0.01). These results demonstrate that neuroprotection achieved by antagonism of the glycine recognition site persists when brain temperature is controlled, indicating a potent mechanism of action other than attenuating a hyperthermic response to ischemia.

Animals

Melatonin: the dark force.

Although the pineal gland was described 2,300 years ago, its functions remained obscure and productive research was limited until 1958, when Lerner and associates defined melatonin. In 1965 Wurtman and Axelrod advanced the "melatonin hypothesis," according to which the pineal gland acts as a transducer responding to changes in circumambient light by changing its rates of melatonin output. Sites and mechanisms of melatonin action are still poorly understood. Two consistent effects are the induction of sleep and an antigonadotropic influence on reproductive structure and behavior. The former is demonstrable and clinically useful in human subjects; the latter has been shown in birds, rodents, and sheep. Alteration of skin color by the contraction of melanophores was effected by pineal extracts before the discovery of melatonin. This phenomenon, seen in reptiles, amphibians, and fish, has received little recent attention. Areas of greater interest and potential importance include the antimitotic effects of melatonin on some types of tumor cells in culture and the apparent in vivo protection of immunocompetent lymphocytes during chronic stress, which reduces the functional capacity of lymphocytes in control rodents. Clinical application of the antimitotic and immunosupportive properties of melatonin seems likely in the near future. Unfortunately, this innocent molecule has been touted in two recent books and many advertisements as an aphrodisiac, rejuvenator, protector against disease, and general wonder-worker. Because interest in melatonin is high, all physicians can expect questions and may have use for the information provided in this review.

Animals

Swine dysentery control in the German Democratic Republic and the suitability of injections of tiamulin for the programme.

In 1977 swine dysentery was made a notifiable disease in the German Democratic Republic, with the intention of eradicating it by the systematic treatment of clinically affected herds using intensive medication and hygiene control programmes. On individual farms the scheme appeared to be successful, but the national incidence of the disease did not decline, owing to the continuous presence of latently infected herds and the movement of carrier pigs to uninfected farms. In 1981 the scheme was re-appraised and a new scheme was introduced in one region where all the breeding herds were screened for the presence of Treponema hyodysenteriae; all positive herds were treated with either metronidazole or tylosin, and the movement of pigs into the region was controlled. This programme effectively eradicated the disease from the region and is being introduced to the rest of the country. Owing to concern about the safety of metronidazole and the development of resistance to tylosin, alternative antimicrobials were examined and tiamulin was selected to assess its suitability for inclusion in the programme. A 560 sow breeding herd and progeny were treated for five days with tiamulin at 10 mg/kg bodyweight. This was coupled with extensive cleaning, disinfection and rodent control programmes. The results of the trial showed that the clinical disease stopped in two days and that no further clinical signs were seen in the subsequent two-and-a-half years. Bacterial monitoring of faeces samples and colonic scrapings from dead pigs failed to identify viable T hyodysenteriae. There was a significant increase of 0.6 piglets weaned per litter and improvements in weaning weights and growth rates. It was concluded that tiamulin was suitable for inclusion in the swine dysentery eradication programme in the GDR.

Animals

Disinfecting poultry production premises.

Hygiene and sanitation play a major role in any effective disease control programme for poultry production premises. One of the important requirements to facilitate hygiene and sanitation is adoption of the 'all-in/all-out' method (i.e. all the birds within a single establishment should be of the same age group), together with the restriction of each enterprise to a single type or species of bird. Poultry premises and buildings should comply with requirements for isolation from the environment and strict observance of principles of hygiene and disease prevention (e.g. restrictions on movement of staff, equipment and vehicles). A poultry site must be prepared methodically for the entry of each new batch (removal of birds, litter and manure; vector and rodent control; dry and wet cleaning; disinfection; fumigation). Attention should be paid to the terminal sanitation of houses and equipment after depopulation (physical and chemical cleaning, pressure washing, disinfection, fumigation). Particular care should be exercised in the performance of sanitary procedures after a disease outbreak. Immediate disposal of dead and diseased birds is an important and effective tool in preventing the dissemination of any disease. Disposal methods include the use of burial pits, tanks, burial in trenches, burning, rendering and composting. Regular visual inspection, together with routine testing by microbiological monitoring methods, is very effective in checking the efficacy of cleaning and disinfection.

Animal Husbandry

[Antibodies against Hantaan virus and Leptospira in subjects at risk in Rome].

A survey on the prevalence of Hantaan and leptospiral antibodies on mammalogists and rodent control personnel was performed. None of the 66 trappers studied (using IFI ) had detectable Hantaan antibody, while only 2 out of 20 mammalogists presented antibody at low titer (1:32). For leptospiral antibody the microagglutination test (MAT) using live leptospires as antigen was performed. 14 out of 66 trappers, or 21.2 per cent, had antibodies, at titer of 1:50 or more, to various leptospiral serovars: L.icterohaemorrhagiae in 12 cases, L.hardjo in 1 case, L.bratislava in 1 case. On the contrary, none of the mammalogists showed positivity for any of 16 serovars used. The environmental risk factors could justify the high prevalence of leptospiral antibodies in the field workers (trappers), while continuous laboratory contacts with rodents explain the presence of Hantaan virus antibodies in mammalogists .

Agglutination Tests