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PubMed1989

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↗
PubMed1991

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↗
PubMed1977

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↗
PubMed1987

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1989

[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↗
PubMed1990

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

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

Adipose Tissue↗
PubMed1982

Conditioned aversion to a taste perceived while grooming.

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

Animals↗
PubMedDate not supplied

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

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

Acute Kidney Injury↗
PubMed1983

The stability of ergocalciferol in rodenticidal baits.

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

Drug Stability↗
PubMed1984

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

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

4-Hydroxycoumarins↗
PubMedDate not supplied

Fertility of female mice fed coumestrol and diethylstilbestrol.

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

Animals↗
PubMed1974

Lassa virus isolation from Mastomys natalensis rodents during an epidemic in Sierra Leone.

Lassa fever is a severe febrile illness of man, first recognized in West Africa in 1969. During an epidemic in Sierra Leone, Lassa virus was isolated for the first time from wild rodents of Mastomys natalensis. A high prevalence of infected Mastomys was found in houses occupied by patients with Lassa fever. The data presented provide the first demonstration of an extra-human cycle of Lassa virus transmission and suggest that rodent control may be an effective method of limiting the disease.

Animals↗
PubMed1971

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Disease Outbreaks↗