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Results for “Models, Experimental”

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At least 19 recordsLinked to original sources

PubMed1991

Deep venous thrombosis in the baboon: an experimental model.

Experimental models of deep venous thrombosis, heretofore, have not been available for laboratory studies. This investigation establishes a novel model of venous thrombosis by inhibiting the protein C system combined with venous stasis and subtle venous injury. Ten adolescent baboons were studied in pairs, with one animal receiving saline solution (B2, B4, B6, B8, B10) and one being exposed to thrombogenic reagents (B1, B3, B5, B7, B9). These reagents represented a combination of a monoclonal antibody (HPC4) to protein C, 1 to 4 mg/kg administered over 5 minutes, and tumor necrosis factor administered over 3 minutes at a dose of 150 micrograms/kg through a catheter placed into the left superficial femoral vein with distal ligation. To encourage stasis, a pediatric size blood pressure cuff was inflated to 40 mm Hg on the right thigh for 50 minutes of every hour during the first experimental day (day 1) in B5 to B10. The animals were observed for a 6-hour period on day 1 and then for an 11- to 15-day period until sacrifice. Hemodynamic and hematologic parameters were recorded along with duplex imaging of the iliac veins and inferior vena cava on a daily basis. Venography was performed on day 1, day 4, and the day of sacrifice. At sacrifice the entire iliac and vena caval system was carefully dissected, opened, and photographed. Experimental animals given the HPC4 and tumor necrosis factor developed left iliac vein thrombosis extending into the inferior vena cava. Duplex imaging, venography, and autopsy revealed that control animals receiving saline solution never developed comparable thrombus. Experimental subjects exhibited thrombus on duplex imaging by day 4 (B1), day 3 (B3), day 2 (B5), 120 minutes (B7), and 360 minutes (B9) after receiving HPC4 and tumor necrosis factor. Venograms performed on day 1 exhibited thrombus in B5, B7, and B9. The extent of thrombus, the timing of its occurrence, and its effect on the animals' left leg followed a dose-dependent relationship for the animals in which the occlusive blood pressure cuff was used. Significantly greater declines in blood pressure, white blood cell count, and platelet count were found in affected animals given HPC4 and tumor necrosis factor reagents as compared to control subjects. All affected animals demonstrated the appearance of fibrin split products and a markedly prolonged prothrombin time. This investigation, for the first time, establishes a reproducible model of deep venous thrombosis involving inhibition of protein C that will facilitate further laboratory studies on venous thrombosis.

Animals↗

PubMed1975

Arterial and muscle oxygen tension in experimental models of asthma. Experimental models of asthma.

The immediate-type airway response in anesthetized dogs and rhesus monkeys to two antigens (ascaris and keyhole limpet hemocyanin) and pharmacologic agents (histamine, methacholine and prostaglandin F2alpha) were studied. The pulmonary function abnormalities demonstrated by changes in breathing frequency, peak expiratory flow rate, pulmonary resistance, expiratory-inspiratory time ratio, tidal volume, and dynamic compliance were compared with simultaneous determinations of arterial pO2, muscle pO2 or both, using indwelling electrodes. The results demonstrate that the O2 determinations provide an additional parameter of study of these experimental models of asthma, and that it may be one of the more sensitive indicators of an induced airway response of the immediate-type. The hypoxia parallels the degree of severity of the respiratory response and demonstrates a further similarity of this model to human asthma.

Animals↗

PubMed1978

Autoimmunity in multiple slcerosis: do we have an experimental model?

Experimental autoimmunity of the CNS has been well characterized--the antigen has been identified, effector cell specificity has been defined, and the relationship between cellular sensitization and antibody production has been partially clarified. In the guinea pig, experimental allergic encephalomyelitis (EAE) is induced by one injection of myelin basic protein in complete Freund's adjuvant (BP/CFA). If BP/CFA is preceded by repeated injections of basic protein in incomplete Freund's adjuvant (BP/IFA), EAE is not induced; the guinea pigs survive and ultimately produce antibody. Induction and prevention of EAE as well as antibody induction by this schedule are dependent on the presence of the intact encephalitogenic (T-cell) site in the polypeptide used for sensitization and preimmunization. In contrast, B cell sites (those peptide sequences which bind antibody) are independent of the T-cell site. At least 5 specific antigenic regions (B-cell sites) have been demonstrated in the BP molecule. High mycobacteria levels bypass the specificity requirement of helper T-cells but cannot bypass the specificity requirement of effector T-cells. In spite of the sophisticated immunologic techniques available, our knowledge of humoral and cellular sensitivity in multiple sclerosis (MS) patients is very limited. The experimental demonstration of an analogy between EAE and MS is weak: a) Demonstration of BP-sensitized cells or BP-specific antibodies in peripheral blood of MS patients has not been successful. b) Anti-myelin serum factors reported to be associated with both disease states (experimental autoimmunity and MS) are clearly not identical. Nevertheless, successful treatment of EAE in animals by BP/IFA injections has encouraged consideration of clinical trials to test the therapeutic value of BP injections in MS patients. If successful, the question will be answered: if unsuccessful, the dilemma still remains.

Adjuvants, Immunologic↗

PubMedDate not supplied

[Model experimental study of protein-calorie malnutrition in mice].

With a view to form an experimental model of protein-malnutrition, mice are fed with two different commercial diets, the "nutrixan" and the "provende" which are included in different concentrations to a rice starch. Only the "provende" gives an workable model with three different growths which differ from the normal by a decrease which is proportional to the protein-deficiency. The incidence of the age and weight of the animals and the period of life of the beginning of the malnutrition are studied.

Animals↗

PubMed1991

The assessment of IUD mechanical resistance: an experimental model.

An experimental model to assess IUD resistance to mechanical fatigue is presented by which the performance of several IUD models has been tested both new and after variable intrauterine use, up to 33 months. According to the results of this study, IUD resistance decreases exponentially with time, and IUD shape apparently affects resistance. Therefore, prolonged intrauterine use apparently increases rupture liability. Moreover, it is suggested that some IUD features can minimize chances of intrauterine rupture and/or fragmentation.

Intrauterine Devices↗

PubMed1991

Trabecular bone remodeling: an experimental model.

An experimental model, capable of inducing controlled stress fields to the distal femoral metaphyses of large dogs, is presented. This model utilized an implantable hydraulic device incorporating five loading cylinders and platens in direct contact with an exposed plane of trabecular bone. A microprocessor controls the loading characteristics, and finite element models were created to calculate the induced stress and strain fields. The trabecular remodeling response is measured using serial in vivo computed tomography, in vitro microcomputed tomography, and histologic analysis. The results of the experiment indicate that significant remodeling can be induced by the activated implant. An increase in trabecular orientation toward the loaded platens was observed, and a statistically significant decrease in connectivity was documented. The greatest effect was associated with a change in the loading rate. A fast rise time (70 ms) loading waveform induced significant bone ingrowth at the implant interface when compared to a slow rise time waveform (700 ms), and demonstrated high correlations with the calculated stress fields as remodeling approached an equilibrium state.

Animals↗

PubMedDate not supplied

Meningeal carcinomatosis: development of an experimental model.

An experimental model of meningeal carcinomatosis has been produced by intracisternal inoculation of Walker 256 carcinoma cell suspension into Wistar rats. The tumor grows rapidly and is fatal in about 15 days if 10(6) cells are injected. The histopathological pattern observed is similar to that seen in diffuse leptomeningeal involvement of systemic cancer in human beings. The model will be useful for investigating the pathophysiology of the neurological disability produced by meningeal carcinomatosis and the efficacy of chemotherapeutic agents.

Animals↗

PubMed1975

The lymphoid bone marrow. An experimental model.

An experimental model is proposed whereby rat bone marrow is converted to a lymphoid-like tissue. A single i.p. injection of hydroxyurea (250 mg/kg body weight) destroys replicating marrow cells in DNA synthesis. Bone marrow erythroblasts constitute the vast majority of cells in cycle under the steady-state of hematopoiesis. Six hours following a single injection of hydroxyurea, selective damage of erythroblasts is noted. The depleted erythroid compartment appears to be replenished by cells of a lymphoid configuration. At 24 hr after injection the erythroid compartment is restored to normal activity. It is suggested that 6 hr after administration of hydroxyurea, lymphoid cells of rat bone marrow may be a source of stem cells for the depleted erythroid compartment.

Animals↗

PubMed1990

1990 Volvo Award in clinical sciences. The consistency and accuracy of roentgenograms for measuring sagittal translation in the lumbar vertebral motion segment. An experimental model.

An experimental model of the L4-L5 lumbar motion segment was developed that allowed precise manipulation of sagittal translation, rotation of L5 relative to L4, tilt of L4 on L5, and control of roentgenogram quality (image clarity) by placing a water bath between the tube and the vertebral body. A series of experiments were designed to systematically assess the consistency and accuracy of sagittal translation measurements from roentgenograms of varying quality, using different measurement protocols and various rater combinations on models with varying degrees of concomitant motions (rotations and tilts). Study 1 assessed the effects of roentgenogram quality, raters, and seven measurement methods on the consistency and accuracy of evaluating translations in the sagittal plane. Results indicated very high reliabilities across roentgenogram quality, raters, and measurement. As expected, high-quality roentgenograms were more accurately evaluated than lower-quality roentgenograms. However, closer inspection of the consequences of errors in measured translations indicated surprisingly high false-positive and false-negative rates, with significant differences observed between measurement methods. Study 2 assessed the effects of concomitant motions and measurement methods on the consistency and accuracy of evaluations. Within-rater consistency and accuracy indices were remarkably high and similar across measurement methods and degrees of concomitant motions. However, important differences in the false-positive and false-negative rates were again observed. Method 2, described by Morgan and King, demonstrated the overall best performance and the least interference due to concomitant motions. Study 3 assessed the effects of raters and measurement methods on the consistency of measuring translation in clinical roentgenograms, where concomitant motion factors may be present, but not explicitly considered. Results indicated substantially lower within- and between-rater consistency estimates relative to consistencies obtained from the model, although these magnitudes were similar to those reported by others evaluating clinical roentgenograms. The implications of lower consistency estimates relative to increased false-positive and false-negative rates must be more closely examined. These studies present evidence suggesting that high consistency and accuracy indices do not ensure acceptable false-positive and false-negative rates and, thus, provide empirical evidence supporting the view that using roentgenograms as a basis for diagnosing instability often can lead to errors in classification. This is less so when observed translations are relatively large (+/- 5+ mm) on roentgenograms that are relatively clear, with little obliquity, and when concomitant motions are minimal.(ABSTRACT TRUNCATED AT 400 WORDS)

Awards and Prizes↗

PubMed1978

Immune-complex mediated colitis in rabbits. An experimental model.

An experimental colitis in rabbits is described, following the intravenous injection of preformed immune complexes of human serum albumin (HSA) and anti-HSA into non-sensitised rabbits. Tissue damage was localised to the colon by the Auer technique of inducing local non-specific inflammation, by the rectal instillation of dilute formalin. Formalin alone gave transient changes that reverted to normal within 24 hours. In rabbits given intravenous immune complexes formed in antigen-excess, a severe colitis was initiated, with histological features including mucosal ulceration, mixed inflammatory cell infiltration in the lamina propria, and crypt abscess formation. It is possible that immune-complex damage may be one of the pathogenic mechanisms involved in human ulcerative colitis.

Animals↗

PubMedDate not supplied

Experimental models in interventional neuroradiology.

Various experimental models have been developed to test interventional neuroradiologic techniques. Most have been used to test various devices and embolic materials, and a small number of models have been designed for teaching or training purposes. Experimental models in endovascular techniques have seldom been used to stimulate disease processes in order to facilitate their understanding.

Animals↗

PubMed1977

Electrical bone-growth stimulation in an experimental model of delayed union.

An experimental model has been devised for the consistent production of delayed bone healing of the tibia in adult dogs. A double-blind trial, with bias eliminated, was used to evaluate the use of a commercially available direct-current bone-growth stimulator with this model. The stimulator produced a statistically significant acceleration of bone healing at four weeks in the experimental model. Osteogenesis was normal, and no dysplastic, inflammatory, or neoplastic changes were found. This research has shown that electrical stimulation of bone is safe and augments bone formation. The bone-growth stimulator unit remains on trial, but in future it may alter the management of many difficult orthopaedic problems.

Animals↗

PubMed1990

Experimental models of hepatic fibrosis: a review.

No experimental model reproduces exactly human liver fibrosis by etiology. Nonetheless, each of the models reviewed in this article has served to enhance our understanding of pathogenetic mechanisms of liver fibrosis. There have been important common findings derived from several different models. The best example is the role of Ito cells in liver fibrogenesis. Involvement of Ito cells was consistently seen in the experimental models regardless of whether the fibrogenic stimulus was nutritional, hepatotoxic, or immunologic. Cellular and molecular mechanisms of Ito cell activation have begun to be explored in different models. Another example is the role of TGF beta in liver fibrogenesis. In both murine schistosomiasis model and Tsukamoto-French rat model, TGF beta was shown to be closely associated with fibrogenesis. With both in vitro and in vivo experimental approaches using cellular and molecular techniques, the experimental model of liver fibrosis will continue to provide data on the pathogenetic mechanisms of liver fibrogenesis. Future genetic and molecular approaches may allow development animal models with liver fibrosis that is inducible and genetically similarity to that of man.

Animals↗

PubMedDate not supplied

Experimental models of hypersensitivity pneumonitis.

Experimental models of hypersensitivity pneumonitis are important tools for the study of the pathogenesis of this disease. In this paper we review the characteristics of the main animal models developed until now. The HP models in rats seem to be particularly appropriate for studying pigeon fancier's disease and the HP induced by chemicals, as well as for studying mediators of acute lesions induced by immunocomplexes. However, the HP models developed in rats are of less value in the evaluation of other aspects of the pathogenesis of this clinical entity in humans. The murine models of HP offer several advantages: the ease and simplicity of intranasal administration, the ability to produce acute and subacute pulmonary lesions similar to those found in humans, the possibility of reproducing lesions similar to those of nonaffected exposed subjects and the possibility of pharmacologically modulating the process. Their disadvantages lie in the different pulmonary lymphocyte response and the difficulty in reproducing a model of chronic fibrosis. The HP models in rabbits are extraordinarily useful for evaluating the immunological mechanisms through which subjects repeatedly exposed to the antigen do not develop clinical manifestations. However, the rabbit has several immunological differences when compared to humans, and the effect of some immunomodulators in this animal is different. The models of HP in guinea-pigs have as advantages the ease in handling the animals, the possibility of pharmacological manipulation, and the ability to induce an acute phase that is very similar to that observed in humans. The drawback, however, is the low lymphocyte response and the striking eosinophilic reaction that contrast with the bronchoalveolar data found in HP in humans. In conclusion, there is no ideal model to reproduce all the findings observed in humans, suggesting that the experimental animal and the method of developing HP should be selected on the basis of concrete research aims.

Alveolitis, Extrinsic Allergic↗

PubMed1975

An experimental model of Pseudomonas aeruginosa renal infection in rats.

The model of experimental pyocyanic renal infection in rats based on direct inoculation of bacteria to the renal parenchyma is described. The authors describe in detail the procedure and evaluation of the results with respect to microbiology, histology and reproducibility. The method produced a focal supurrative inflammation with a significant bacteriologica finding in renal tissue for 8 weeks at the least. The inflammation has a tendency to form focal cicatrices not accompanied by diffuse shrinkage of the kidney. The method is well reproducible and its technique is relatively simple thus permitting to induce infection in a large series of animals within a short period of time. In the second part of the paper, the use of this method in testing the therapeutical efficacy of gentamicin, carbenicillin and their combination is reported. The results showed gentamicin to be more effective than carbenicillin and the combination of the two to have the highest therapeutical effect. Moreover, their combination made it possible to reduce the dosage of the antibiotics and thereby reduce their potential undesirable effect. Further, the results showed the described model of experimental renal infection to be well suited for testing the efficacy of chemotherapeutics and resolving some problems of the treatment of infectious diseases.

Bacteriuria↗

PubMed1975

The simulated drinking gang: an experimental model for the study of a systems approach to alcoholism. I. Description of the model.

This two-part paper deals with an experimental model for studying interactional behavior from a systems point of view. The experimental model incorporates a research strategy utilizing both a token economy and the simulation of a naturally occurring clinical phenomenon, the alcoholic drinking gang. The model is primarily geared to do two things: a) study the changes in clinical behavior that occur when experimental conditions are manipulated to facilitate the formation of the behavioral "system" as opposed to experimental conditions which interfere with system formation; and b) build into the model tasks which produce measurable performance data as a method of monitoring behavior deemed essential for the successful development of an operational system. The experimental model involved admitting up to six alcoholic individuals to a research ward specifically designed for studies utilizing experimentally induced intoxication. Each study was divided into a 7-day predrinking period, a 10- to 14-day drinking period, during which time alcohol was available to research subjects, and a 5- to 7-day withdrawal period. A token economy was established which allowed for the following essential features to be present: a) a group of chronic alcoholic individuals who desire to go through a drinking experience together; b) the pooling of resources in order to purchase alcohol; c) rules established by the group for the sharing of whatever alcohol becomes available to the group; and d) the opportunity to earn money for the purchase of additional alcohol after the initial supply runs out, in order to keep the group drinking experience going. All "money", or tokens, could be earned only via successful performance at the Cooperative Task Device (CTD), a cooperative, two-person game, and tokens could be utilized to purchase three types of commodities from an automated dispensing machine, alcohol, cigarettes, and television time. Automated data recording provided detailed data about CTD performance and commodity-purchasing records. The discussion centers around difficulties inherent in a simulated model of natural behavior. It is pointed out that laboratory simulation vs. natural setting, as the preferred site for carrying on behavioral research, remains an active controversy, and the arguments on both sides are presented. Difficulties inherent in doing "systems" research are also discussed. A series of alternative hypotheses to explain behavior within the simulated drinking gang are listed, and the data that would be necessary in order to substantiate these alternative hypotheses are also listed. It is maintained that the simulated drinking gang is an advantageous experimental model in that it closely approximates the basic criteria of the naturally occurring phenomenon, while at the same time allowing subjects a range of behaviors, each of which substantiates a different hypothesis about the central organizing feature in alcoholic groups.

Alcohol Drinking↗

PubMed1991

Campomelic syndrome: experimental models and pathomechanism.

Experimental teratogenic models of the campomelic syndrome in duck and chick embryos and in frog tadpoles are presented. The association of selective growth impairment of the peripheral and facial nerve trunks including the spinal cord and nerve roots is suggested as an underlying cause for adaptive shortening of the corresponding skeletal parts. Buckling may occur because the growing bones tend to accommodate to these underdeveloped neurological structures even at the cost of a deformity. It is suggested that investigation of the effects of "skeletal" teratogens upon the nervous system may be more logical than concentrating upon bone growth which may be the secondary effect.

Abnormalities, Drug-Induced↗

PubMed1992

Experimental models for spinal cord injury research: physical and physiological considerations.

This paper describes historical and current experimental models used to develop our current understanding of the biomechanics and pathophysiology of traumatic spinal cord injury; the advantages and limitations of current experimental models; considerations for selecting an appropriate injury model based on experimental objectives; and key physiological factors in the spinal cord injury response that may interact with the injury response and alter the outcome. All of the above must be considered in the development and selection of an appropriate experimental injury model that meets specific needs. Various experimental models have been developed to study spinal cord injury and the pathophysiological and physical mechanisms responsible for tissue damage and loss of function. Such modeling may involve inherently different biomechanical variables with alternative outcomes and purposes. There is not, therefore, a single "ideal" experimental injury model just as there is no "stereotypical" clinical spinal cord injury. Instead, the goals and objectives of the research dictate specific requirements on the model. In all cases, however, both physical and physiological aspects of the model should be considered, and measured if possible, to ensure interlaboratory comparability and possible clinical relevance. Also, experimental techniques, especially anesthesia, and surgical procedures, should be carefully reviewed for interactions with the injury response or potential therapeutic interventions to ensure validity of interpretation. It is hoped that data correlating physical spinal cord injury parameters with functional outcome will ultimately be combined with data on vertebral injury and spinal failure mechanics to further our understanding of clinical injury. Such approaches should lead to interventions that reduce the incidence and severity of traumatic human spinal cord injury.

Animals↗