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[Restenosis after coronary angioplasty. Contribution of experimental models].

Restenosis is the main complication of coronary angioplasty. Many experimental models have been developed over the last few years, reflecting very active research work in this field. The value of experimental models may be discussed under two headings: improvement in our understanding of the mechanisms of restenosis and the development of preventing strategies. The smooth muscle cell is the main cause of restenosis, experimental models having demonstrated a triple response which has been observed clinically: proliferation, migration to the intima and synthesis of the extracellular matrix. The mechanisms controlling this response are not fully understood, the most likely candidates being desendethelialisation, platelets and other circulating components of the blood, vasopressive hormones especially the renin-angiotensin system, growth factors and finally the degree of direct trauma to the smooth muscle cells. Experimental models also allow evaluation of therapeutic strategies elaborated to reduce the frequency of restenosis in clinical practice: three strategies are identifiable: systemic treatment, local treatment and genetic therapy. At the present time, none of these approaches has been clearly shown to be effective clinically though some positive results have been observed in the animal.

Angioplasty, Balloon, Coronary↗

Comparative development of Taenia solium in experimental models.

Various mammals were evaluated as experimental models of adult Taenia solium. Suppressed and nonsuppressed hosts were used as experimental models. Infections were performed per os with cysticerci obtained from pigs; immunosuppression was induced with methyl prednisolone acetate at intervals of 10-14 days after infection. Tapeworms developed in hamsters, gerbils, and chinchillas but failed to develop in rabbits, cats, pigs, and rhesus monkeys. In infectable animals, treatment with the steroid facilitated maintenance and development of the parasite, and more tapeworms were obtained. Mature and some pregravid proglottids were recovered from hamsters and gerbils, whereas a gravid T. solium was obtained from a chinchilla at 12 wk postinfection. Eggs recovered from the chinchilla transformed into cysticerci in a pig 12 wk after oral infection. The T. solium-chinchilla experimental system seems to be an alternative definitive host for this parasite and thus the basis for a great diversity of studies.

Animals↗

[Reinvestigation of streptozotocin induced diabetic cataract as a standard experimental model].

In order to find an appropriate model of experimentally induced streptozotocin diabetic cataract rat for evaluation of the anti-cataract agents. Experimental diabetic cataracts were induced in 3 rat strains (Sprague-Dawley SD, Brown Norway BN, Wistar WIS), age 5 and 7 weeks old, by intravenous injection of 70 mg/kg streptozotocin. The cataract progression was followed by morphological and biochemical assessment. Two types of initial cataractous change were observed in SD and WIS rats which mainly consisted of water-vacuole formation in the peripheral area and a diffuse cloudiness progressing around the anterior Y-suture area. The initial change of BN rats was a Y-suture dissociation and fine water-clefts with dot-like vacuoles. Those initial changes in SD and WIS rats differed from those in BN. No difference in aldose reductase activities among the three strains was found, but BN rats had significantly higher sorbitol dehydrogenase activity than SD or WIS rats. It seems that 7-week-old BN rats are more suitable for experimental diabetic cataract models than SD or WIS.

Age Factors↗

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↗

Cerebral concussion in the monkey: an experimental model.

A statistically significant experimental model has been developed for reproducing head injury by impact in the monkey. Results with 80 monkeys subjected to occipital impact under specified conditions ( duration of phenomena, 1 to 10 milliseconds) enable the construction of curves relating the production of experimental cerebral concussion in 10, 50, and 90 percent of the monkeys to the average impulse of the blow in pounds-seconds, as well as to the average linear acceleration of the head. These curves are proposed as a baseline from which blows to various parts of the head, as well as nonimpacting impulsive loads, can be studied under various conditions of protection and according to varioucs time regimes.

Acceleration↗

[Experimental model of Lyme disease in rats].

BACKGROUND: An experimental model in rats can contribute to the understanding of the pathogenesis and improvement of treatment of Lyme borreliosis. OBJECTIVE: To develop a Lyme arthritis experimental model in Sprague-Davies rats. MATERIAL AND METHODS: An intraperitoneal inoculation of Borrelia burgdorferi in three groups of Sprague-Davies rats was made. The first group was inoculated with dead B. burgdorferi. The second group was inoculated with low virulence B-31 B. burgdorferi. The third group was inoculated with high virulence B-297 B. burgdorferi. RESULTS: After six months of follow-up, none of the rats in the first two groups presented arthritis whereas in the third group 18 rats (72%) developed arthritis in one or more joints. Histologic showed synovial hypertrophy and inflammatory infiltration composed of polymorphonuclear leukocytes, plasma and mast cells in the infected joint. B. burgdorferi was isolated in the liver and spleen cultures taken 14 days after inoculation in 40% of the rats inoculated with B-297 strain. CONCLUSION: An easy and inexpensive experimental model of Lyme arthritis in rats has been developed.

Animals↗

Myocardial preservation during anoxic arrest. Experimental model ventricular fibrillation.

An experimental model with anaesthetized healthy mongrel dogs on extracorporeal circulation is described. Anaesthesia and cardiopulmonary bypass are the same as used in clinical practice. Various methods of myocardial preservation were investigated and their protective effect was judged by cardiac performance after termination of 60 min of anoxic arrest. In this study, the first part of an experimental series, electrically-induced fibrillation during 60 min of normothermic and local hypothermic anoxic arrest was investigated. In group I, the hearts were fibrillated immediately after cross-clamping. In group II, which served as controls, the hearts were allowed to fibrillate spontaneously after aortic cross-clamping. All the hearts in group I went into an ischaemic contracture, whereas those in group II showed a 50% recovery, but with a strongly reduced cardiac performance after termination of anoxic arrest and cardiopulmonary bypass. Measurements of myocardial surface pH demonstrated a rapidly developed acidosis during the period of anoxic arrest. The most impressive finding by light microscopy was pronounced myocardial oedema. External cooling by 4 degrees C glucose 5.5% continuously flushed into the pericardial sac in combination with electrically-induced fibrillation proved to be ineffective as a protective method. None of the eight dogs in this group survived. External cooling combined with intraventricular injection of 4 degrees C glucose 5.5% seemed to protect the hearts against ischaemic damage, insofar that all six hearts in this group were able to take over the circulation after declamping. The working capacity was, however, impaired and a relatively long period of mechanical support and stimulation with inotropic drugs was necessary.

Animals↗

Fertility in cryptorchidism: improved timing of fixation and treatment in an experimental model.

Modifications were made in an experimental model in the rat to make it more analogous to human cryptorchidism and more useful in evaluating treatment. The age of experimental bilateral cryptorchidism was changed from 3 days to 11 days. Neither group was able to father offspring. The age at orchiopexy also was modified from the range of 21 to 28 days to exactly 21 days. The ability to father offspring improved significantly (72 versus 30 per cent) and it was not significantly different from previously reported sham operated rats (84 per cent). The current experimental model demonstrates that early surgical treatment can restore fertility to mechanically cryptorchid animals. The model can be used to evaluate the effects of varying types and timing of treatment.

Age Factors↗

A novel experimental model for the study and evaluation of experimental vaccines to Actinobacillus pleuropneumoniae.

A novel experimental model to study immune protection to Actinobacillus pleuropneumoniae in the rat is described. One-week-old rats born from immunized mothers were challenged intraperitoneally with a suspension of A. pleuropneumoniae serotype 1 and mortality recorded up to 48 h postinfection. Immunization with inactivated whole cells (IWC) or a whole cell extract (WCE) from A. pleuropneumoniae serotype 1 resulted in protection against an homologous challenge, particularly in the case of WCE where protection was observed at the highest challenge dose of approximately 1000 50% lethal doses.

Actinobacillus Infections↗

[Laboratory animal anaesthesia: influence of anaesthetic protocols on experimental models].

The use of experimental animals requires anaesthesia to provide immobility and analgesia. Animals require anaesthesia not only for ethical reasons but also because pain and stress can alter the quality of research results. Recognition of pain, and its treatment is important throughout the procedure. Before anaesthesia, animals are acclimated and rehydrated. Except in small rodents and in ruminants, in order to avoid vomiting, a fast of 8 to 12 hours before anaesthesia is recommended. In order to protect animals against suffering and distress during transfer, restraint and management, a premedication is administered. Most human anaesthetic products can be used in animals. There are some specific veterinary anaesthetics. Moreover, the anaesthetic effects could be different from specie to an other. In most big animals, induction is realized by intravenous administration. In small rodents, venous puncture and contention could be difficult, and anaesthetic agents may be injected via intraperitoneal or intramuscular way. The principal inconvenient of these administration routes is the impossibility to adjust dose to animal response. In large animals, human anaesthesia material can be used. Some technical adaptations could be necessary in smaller animals. In rodents or in neonatology, specific devices are recommended. ECG, arterial pressure, tidal volume, expired CO(2) and oxygen saturation monitoring assess quality of, and tolerance to anaesthesia. If animals are awaked after anaesthesia, postoperative management is closed to human clinical problems. During animal experimentations, anaesthesia may interact with results. All anaesthetic drugs alter normal physiology in some way and may confound physiologic results. In the literature, most publications do not mention this possible interaction. Investigators need to understand how animals are affected by anaesthetic drugs in order to formulate anaesthetic protocols with minimal effects on data. Extrapolation between different animal species and human and animals about the effects of anaesthetic agents are very hazardous. Great differences exist between the effects observed in vitro and in whole animals. The effects of the anaesthetics could be totally different if they are used alone or in association. The same anaesthetic could have opposite effects from an organ to another. For results validation, the anaesthesia side effects (hypoventilation, hypotension, cooling em leader ) have to be minimized. All new experimental models should require discussing the possible interferences between anaesthesia and results and to compare results obtained with different anaesthetic protocols.

Anesthesia↗

Participation of interleukin-5, interleukin-8 and leukotriene B4 in eosinophil accumulation in two different experimental models.

There are several experimental models describing in vivo eosinophil (EO) migration, including ip injection of a large volume of saline (SAL) or Sephadex beads (SEP). The aim of this study was to investigate the mechanisms involved in the EO migration in these two models. Two consecutive injections of SAL given 48 hr apart, induced a selective recruitment of EO into peritoneal cavity of rats, which peaked 48 hr after the last injection. SEP, when injected ip, promoted EO accumulation in rats. The phenomenon was dose-related and peaked 48 hr after SEP injection. To investigate the mediators involved in this process we showed that BW A4C, MK 886 and dexamethasone (DXA) inhibited the EO migration induced by SAL and SEP. To investigate the source of the EO chemotactic factor we showed that mast cells, macrophages (MO), but not lymphocytes, incubated in vitro in presence of SAL released a factor which induced EO migration. With SEP, only mast cells release a factor that induced EO migration, which was inhibited by BW A4c, MK 886 and DXA. Furthermore, the chemotactic activity of SAL-stimulated mast cells was inhibited by antisera against IL-5 and IL-8 (interleukins). SAL-stimulated MO were only inhibited by anti-IL-8 antibodies as well SEP-stimulated mast cells. These results suggest that the EO migration induced by SAL may be dependent on resident mast cells and MO and mediated by LTB4, IL-5 and IL-8. SEP-induced EO migration was dependent on mast cells and may be mediated by LTB4 and IL-8. Furthermore, IL-5 and IL-8 induced EO migration, which was also dependent on resident cells and mediated by LTB4. In conclusion, EO migration induced by SAL is dependent on mast cells and MO, whereas that induced by SEP is dependent on mast cells alone. Stimulated mast cells release LTB4, IL-5 and IL-8 while MO release LTB4 and IL-8. The IL-5 and IL-8 release by the SAL or SEP-stimulated resident cells may act in an autocrine fashion, thus potentiating LTB4 release.

Analysis of Variance↗

The pathogenesis of pancreatic pseudocysts--a canine experimental model.

In summary, an experimental model that mimics the pseudocyst formation in man was produced in dogs. The following conditions were met: encapsulated cyst containing pancreatic juice; an actively secreting pancreas with hyperamylasemia and pancreatitis; a ductal communication; and more pronounced effects with partial pancreatic ductal obstruction.

Amylases↗

[Neurobiology of parkinsonism. II. Experimental models].

The study of experimental models of parkinsonism has contributed to the knowledge of basal ganglia functions, as well as to the establishment of several hypothesis for the explanation of the cause and expression of central neurodegenerative disorders. In this review we present and discuss several models such as 6-hydroxydopamine, MPTP and manganese, all of them widely used to characterize the behavioral, cellular and molecular mechanisms of parkinsonism.

Animals↗

In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part I. An experimental model for contrast media studies.

An experimental model using in vivo fluorescence microscopy for studies of renal cortical blood flow was tested in 40 mice. The model was suitable for testing a wide variety of hypotheses concerning alterations in renal cortical blood flow, including the possibility of inhomogeneous capillary blood flow distribution in response to i.v. infusions. The experimental model was tested for the effects of i.v. infusion of mannitol (0.3 mol/l). Effects of anesthesia and mechanical kidney fixation on renal cortical blood flow were studied. Neuroleptic analgesia was less hazardous to the animals than pentobarbital. Due to artifacts from respiratory and peristaltic motion, it was not possible to use neuroleptic analgesia without mechanical kidney fixation. A rating scale was designed for evaluating the capillary blood flow. The correlation between repeated ratings by the same observer was 0.806 and between 2 different observers 0.59.

Anesthesia↗

Chronic vascular rejection: histologic comparison between two murine experimental models.

BACKGROUND: We previously developed an experimental model to study chronic vascular rejection (CVR) in mice, the orthotopic aortic allograft. More recently we performed human arterial grafts into SCID/Beige mice reconstituted with human spleen cells. We report herein the differences in CVR lesions. MATERIAL AND METHODS: In the first model, recipient mice were C57BL/6 (H-2b), and donor mice were DBA/2 (H-2d). In the second model, terminal branches of the human superior mesenteric artery were transplanted into SCID/Beige mice in the infrarenal aorta. Human immune reconstitution was achieved by a single intraperitoneal injection of 30 x 10(6) human spleen cells. The presence of human lymphocytes and IgG was verified weekly. In both models, the vascular grafts were inserted in the infrarenal aortic position using the sleeve technique. The transplanted mice were sacrificed at 35 days after the operation. The grafts were analyzed by histology and morphometry. The mean intimal thickening was calculated based on transverse sections at 0.1-mm intervals. RESULTS: Typical CVR lesions developed with neointimal thickening, T-cell infiltration, and smooth muscle cell (SMC) proliferation in both models. In the mouse aortic model, disappearance of SMC in the media was noted in contrast to human arterial transplants, where the media remained intact. CONCLUSION: Other groups have noted that arteries conserve their media in clinical organ transplants. From this point of view, the lesions in the second experimental model (human arteries) better reflect the pathology of CVR in clinical transplantation than the murine aortic transplant model.

Animals↗

Partial ureteral obstruction: a new variable and reversible canine experimental model.

OBJECTIVES: To develop a new experimental model of partial ureteral obstruction that is simple, reliable, variable, and reversible. METHODS: A 6 F ureteral catheter was inserted into the left ureteral orifice and was cut 2 cm distal to the orifice. The most distal part of the ureter was ligated around the catheter. The catheter lumen was partially obstructed by insertion of stylets of three different diameters. The catheter and the stylet were fixed inside the bladder. The model was tested in 12 dogs, which were stratified into three groups according to the diameter of the obstructing stylet. All the dogs were subjected to intravenous urography (IVU) and technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) renal scan at 2 and 4 weeks following induction of partial ureteral obstruction. RESULTS: Three different grades of hydroureteronephrosis were obtained according to the diameter of the obstructing stylet. The IVU and 99mTc-MAG3 renal scan studies were repeated at 2 and 4 weeks following removal of the ureteral catheter and ureteroneocystostomy and showed marked improvement in the configuration and function of the corresponding renoureteral units. CONCLUSIONS: Our experimental model fulfills the requirements for a useful model of partial ureteral obstruction, namely, simplicity, reliability, variability, and reversibility.

Animals↗

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↗

Endoscopic sclerotherapy or selective embolisation of esophageal varices. An endoscopic and portographic study in an experimental model.

In an experimental animal model with portal hypertension and esophageal varices, endoscopic sclerotherapy of the varices with Aethoxysclerol was compared with selective embolisation of the coronary vein with absolute ethanol. After 4 courses of endoscopic sclerotherapy the varices were permanently obliterated, as documented by portography and endoscopy. Selective embolisation also caused obliteration of the coronary vein and varices, but early and repeated recanalisation occurred, and permanent obliteration was only obtained when embolisation was combined with endoscopic sclerotherapy. Portal vein thrombosis occurred when embolisation was repeated more than 3 times. Hepatic blood flow was significantly higher in animals treated by endoscopic sclerotherapy than in nontreated controls and animals treated by selective embolisation alone.

Animals↗