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PubMed2025

Bioluminescence Imaging to Study Recombinant Orthopoxvirus Infection in Animal Models.

Bioluminescent images of viral replication in live animals (in vivo) reveal disease dynamics and effects of medical countermeasures over time. After selecting an appropriate orthopoxvirus animal model for the study, a recombinant virus with the firefly luciferase gene inserted in the genome is used to infect the animals. On the day of bioluminescent imaging, the substrate, D-luciferin, is prepared; animals are sedated and injected with the substrate and IVIS imager is utilized; various bioluminescent images are acquired; then animals recover and are able to continue in the study. Ex vivo imaging can also be completed after animals are euthanized at experimental endpoint. This approach allows real-time imaging of viral kinetics within an animal, and analysis of images can provide an additional quantitative measure throughout the study. Bioluminescent imaging not only provides scientific benefits but also benefits to animal welfare. For these reasons, bioluminescent imaging should be considered for any in vivo orthopoxvirus study.

Animals↗
PubMed1977

The olive babbon (Papio anubis) as an animal model for research in affective disorders of man.

Efforts were made to develop an animal model for studies of the role of biogenic amines in a group of human "mood" diseases including mania and depression. Subadult, male olive baboons (Papio anubis), both normal and psychologically disturbed individuals, were anesthetized and administered 18O-enriched air for 60-130 minutes. Afterwards blood, urine, and cerebrospinal fluid were collected every hour, for 10 hours. The samples were subsequently fragmentographically analyzed for labelled metabolites of serotonin, dopamine, and norepinephrine. The results showed that significant incorporation of 18O was found in all metabolities studied, with a peak after about 4 hours. The effect of chlorpromazine injection on 18o-incorporation was also measured. It was found that chlorpromazine caused a faster rise in labelling and indicated the stimulation of dopamine turnover in the brain. The usefulness of the animal model and the in vivo labelling technique for biogenic amine determination in the brain was demonstrated by the fact that the technique was subsequently used in human patients with neurologic disease.

Affective Symptoms↗
PubMed1978

Animal models of schizophrenia: the case for LSD-25.

Some of the difficulties of trying to establish an animal model of schizophrenia are first considered. Then, after a review of the evidence on the experimental psychopathology of schizophrenia, particularly that concerned with attention and arousal, it is concluded that the core feature which needs to be modeled in animals is some aspect of "input dysfunction." It is argued that, of the pharmacological strategies, LSD-25 comes nearest to meeting that requirement, for two reasons. First, the phenomenology of an LSD "model psychosis" closely parallels that of the natural disease. Secondly, the experimental effects of the drug, both in animals and man, are very similar to or can be closely aligned theoretically with those of schizophrenia. An example is quoted from work in the author's laboratory where LSD was found to produce psychophysiological effects virtually identical to those observed occurring naturally in acute psychotic patients and in normal subjects high in "psychotic" personality traits. It is suggested that the rejection of LSD as a drug model was premature, especially as the currently popular preference for amphetamine has not been vindicated, either by the latter's ability to mimic an important central feature of the psychotic state or by work on dopamine as a specific common mediator of amphetamine psychosis and of schizophrenia.

Animals↗
PubMed1978

Idiopathic paraproteinaemia. I. Studies in an animal model--the ageing C57BL/KaLwRij mouse.

A search for a suitable animal model for studies on idiopathic paraproteinaemia showed that an age-dependent increase in the appearance of homogeneous immunoglobulins in serum was common to all of the seven mouse strains investigated to date. The highest frequency was found in C57Bl/KaLwRij mice. Further investigations in this strain demonstrated that, except for some quantitative differences, most of the features of human and C57BL Mouse idiopathic paraproteinaemia were essentially the same. No clear-cut correlation was found between the idiopathic paraproteinaemia and, in the old C57B1 mice, a rather frequently occurring reticulum cell sarcoma B and amyloidosis. The mouse idiopathic paraproteinaemia can be regarded as an analogue of the human idiopathic paraproteinaemia and therefore as a suitable model for further experimental studies.

Aging↗
PubMed1976

Advantages and limitations of animal models in the evaluation of antiviral substances.

Since many antiviral substances with potential for use in humans are in various phases of evaluation, criteria must be developed for selection of those compoinds with the greatest probability of efficacy and least toxicity. We lack background experience in evaluation of antivirals to permit extrapolation from in vitro tests to use in humans; it is of critical importance, therefore, to develop animal models for evaluation of antiviral substances before trials in humans and to establish guidelines for the relative predictive reliability of in vitro screening and evaluation in animal models. The complexity of drug-host and virus-host interaction and other factors may limit the predictive value of some or all experimental systems. Although the use of animal models is an important phase in the evaluation of antiviral chemotherapeutic agents, the models must be carefully studied and the interaction of drug and virus in the experimental animal specifically defined if optimal guidelines for the predictive value of model systems are to be developed. These guidelines must then be modified as experience is gained with antiviral substances that reach human trials.

Amantadine↗
PubMed1977

A new animal model for the prediction of antidepressant activity.

Animal models presently in use for the screening of potential antidepressant drugs yield numerous false positives and false negatives. In search of a more specific model, we have studied the effects of psychotropic compounds on the behavioural changes induced in rats by the removal of the olfactory bulbs. We have observed that subchronic treatment with antidepressants in general reverses the behavioural alterations displayed by bulbectomized rats in tests of conditioned behaviour. The present paper describes a brief test, the so-called anxiosoif test, which may be used to assess the effects of drugs on the behaviour of bulbectomized rats. Removal of the olfactory bulbs leads to increased water intake in the anxiosoif test and to an attenuation of avoidance when the drinking spout is electrified. This latter effect can be reversed by subchronic treatment with the antidepressant drugs amitriptyline and mianserine (Org GB 94). It is suggested that the behavior of bulbectomized rats may be used as a specific tool in the prediction of antidepressant activity of novel compounds.

Animals↗
PubMedDate not supplied

Animal models for human sexuality.

The value of animal models in biomedical research is firmly established, and many basic principles of human psychology have been explicated as the result of comparative studies. There is pressing need for non-human models in the behavioural sciences as represented by psychiatry, psychology and ethology; and such models should be constructed, provided their validity can be assured. Valid models cannot be based exclusively on similarity in the formal properties of behaviour. Commonality of descriptive terms as applied to different species does not guarantee identity of the concepts to which the terms apply. Model builders must evaluate interspecific similarities and differences in the causes, mediating mechanisms and functional outcomes of behaviour. The validity of interspecific generalization can never exceed the reliability of intraspecific analysis; and the latter is an indispensable antecedent of the former. Existing and potential models for homosexuality and other psychosexual characteristics of human beings are evaluated within the perspective provided by the foregoing generalizations.

Animals↗
PubMed1977

Animal models of hypersensitivity pneumonitis: a review.

The etiology of hypersensitivity pneumonitis has been ascribed to each major type of immune injury. Data obtained from animal models support the spontaneous human situation in which a contunuum of events results in disease. The major attempts at gaining insight into this disease spectrum through animal models are reviewed.

Alveolitis, Extrinsic Allergic↗
PubMed1975

The cockerel as an animal model for atherosclerosis research.

The chicken is a good animal model for the study of atherosclerosis research because it is: 1. Omnivorous. 2. Small and suitable for prolonged laboratory investigation. 3. Able to develop spontaneous atherosclerosis. 4. Capable of producing atherosclerosis after cholesterol feeding with elevated hypercholesterolemia. A diet of 1/4% cholesterol plus 5% cottonseed oil added to starter-grower-mash resulted in aortic atherosclerosis with a slight but significant increase in plasma cholesterol. 5. Plasma levels of cholesterol and triglyceride are similar to those in humans. 6. Lipid composition of high and low density lipoproteins as well as chylomicrons resembles those of humans. 7. Has been noted that there is no essential difference between vascular lesions seen in chickens as a result of cholesterol diet and that of atherosclerosis observed in man.

Animals↗
PubMed1979

An animal model of fulminant hepatic failure in the rat.

A reproducible animal model of fulminant hepatic failure was developed by intraperitoneal administration of D-galactosamine hydrochloride to Sprague-Dawley rats. Biochemical and morphological hepatic injury and brain edema resembled human fulminant hepatic failure. This model would facilitate further studies of the pathogenesis of brain dysfunction and evaluation of treatment in fulminant hepatic failure.

Amino Acids↗
PubMed1979

Animal models in cancer research which could be useful in studies of the effect of alcohol on cellular immunity.

Alcohol appears to exert a depressive effect on host immunity. Animal models useful in studying immune responsiveness in cancer research are discussed, which could be of value in studying the effect of alcoholism. Allogeneic tumor grafts are poorly rejected in immunosuppressed mice. Of the four major cellular elements of the immune system, the macrophage appears to have a critical role in immune surveillance. Several conditions occur which abrogate or restrict the tumoricidal activity of macrophages. Stress induced by physical restraint results in depressed macrophage activation. The tumoricidal activation induced in macrophages by interferon was markedly depressed in the presence of the corticosteroids, hydrocortisone, prednisone, and dexamethasone. In addition, prostaglandins (PGE1 and PGE2) also were found to decrease interferon activation of macrophages. Since immune deficiency is a trait of alcoholism and cancer, animal models with defined, measurable, immunological parameters would be useful in studying the effect of alcohol on cellular immunity.

Adrenal Cortex Hormones↗
PubMed1979

The opossum as an animal model for studying radiation esophagitis.

Six opossums were evaluated as a possible animal model of radiation esophagitis. In a single exposure to the esophagus, four animals received 60Co radiation of various doses; two served as controls. Pre- and postirradiation evaluations using fiberoptic endoscopy, mucosal biopsy, barium esophagography, and manometry were performed. Esophagitis developed at one week in irradiated animals. Opossums receiving 17.5, 20, and 22.5 Gy (1,750; 2,000; and 2,250 rad) became anorexic one week postirradiation, and abnormal motility subsequently developed. The controls and the animal receiving 15 Gy (1,500 rad) remained normal. Histological changes in the irradiated opossum esophagus resembled those found in humans.

Animals↗
PubMed1978

Animal models: importance in research on hemorrhage and thrombosis.

Despite some sentiments against animal research, animal models continue to be important in studying hemorrhage and thrombosis. Examples of genetic models are dogs and pigs with von Willebrand's disease. The homozygous von Willebrand pig appears to be resistant to arteriosclerosis, presumably due to impairment of the platelet aggregating function. Among acquired models, pigs are gaining in favor, perhaps because their clotting and platelet characteristics resemble those in humans. Species vary markedly in their normal plasma levels of platelet aggregating factor/von Willebrand factor (PAF/vWF). One promising approach to the study of thrombosis is using platelet anti-aggregating drugs to inhibit PAF/vWF dependent platelet thrombus formation; a drug-induced von Willebrand state seems feasible.

Animals↗
PubMed1978

Palmerston North mice, a new animal model of systemic lupus erythematosus.

This report describes a previously unrecognized animal model of SLE, the PN mouse. Although outbred PN mice were studied originally as models of polyarteritis nodosa, their inbred descendants have autoimmune disease which closely resembles SLE. In the current study, positive indirect immunofluorescence tests for ANA appeared when the mice were 5 months old, and 80% of mice were ANA-positive at 10 months of age. Anti-DNA were detected in sera from newborn mice and from 53% of mice under 2 months of age. Seventy-six percent of PN mice developed anti-DNA at the age of 10 months. Glomerular deposits of IgG, IgM, IgA, and complement appeared at 2 to 4 weeks of age, and examination of renal tissue by electron microscopy showed basement membrane thickening and dense intramembranous deposits. Neoplasms arose in 14% of PN mice. Female mice died earlier than male mice, and the most common causes of death were glomerulonephritis and arteritis. It was concluded that the serologic and histologic characteristics of disease in PN mice resembled SLE.

Animals↗
PubMed1976

The use of organ cultures and animal models in the study of Mycoplasma pneumoniae infections.

Organ cultures of ciliated tracheal epithelium derived from various animal species have been used to study several different mycoplasma infections. Human and hamster tracheal cultures have been used in particular to study Mycoplasma pneumoniae which, of all the human mycoplasmas, is the only one which damages the cultures. One reason for this is the capacity of the virulent organisms to attach to the cells; strains which are prevented from attaching or have lost this capacity do not damage the cultures. The organ culture system is therefore valuable in looking at the organisms-cell relationship but it is necessary to use animal models to study immunological processes. Hamsters, and more recently guinea pigs, have been used in this respect. The hamster model has been used to study the pathogenesis of M. pneumoniae pneumonia and also recovery from and resistance to infection. Humoral immune mechanisms seem more important than cell-mediated mechanisms in resistance, and the probable importance of local immunity is discussed. It is pointed out that it should be possible to establish the mechanisms underlying the development of M. pneumoniae sequelae where conditions, similar to those seen in man, occur in animals. Finally, the way in which the hamster model has been used to study the effect of tetracycline and erythromycin on the course of disease is discussed. As in man, therapy often improves the pneumonia but does not eradicate the organisms. This is probably due, at least in part, to the fact that the antibiotics are only mycoplasmastatic. Drugs with mycoplasmacidal properties are needed and the animal model would obviously prove helpful in evaluating these.

Animals↗
PubMed1978

An animal model for the study of regional lung function.

An animal model for the study of regional lung function is described. In sheep, the bronchus to the right apical lobe (RAL) of the lung arises directly from the trachea. A tracheal divider, inserted under local anesthesia via a permanent tracheostomy, was used to separate the ventilation of the RAL from that of the rest of the lung. Lobar blood flow was estimated from the RAL contribution to the pulmonary clearance of an intravenous bolus of 85Kr. Gas exchange was measured by conventional methods. Expressed as a percentage of the value obtained for the whole lung, lobar expired volume was 14.7 +/- 4.3%, capillary perfusion was 12.3 +/- 4.2%, oxygen uptake was 14.7 +/- 4.9%, and carbon dioxide production was 13.4 +/- 5.5% (mean +/- SD of 25 studies in 11 animals breathing air). The model permits the study of experimental conditions confined to a single lobe of the lung and offers the advantages of an intact chest wall, spontaneous ventilation and an unanesthetized animal.

Animals↗