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Evaluation of endothelium-protective effects of drugs in experimental models of endothelial damage.

Endothelium-protective properties of pharmacological agents may be assessed by using different experimental models of endothelial dysfunction or injury. The model of endothelial dysfunction induced by vessel perfusion with polymorphonuclear leukocytes (PMN) was used for evaluation of pentoxifylline (PTX) effects on vasoconstrictor responses to noradrenaline (NA) in the rabbit renal artery. Addition of PMN into the perfusion solution significantly increased the responses to NA at all doses. PTX administration (10(-5) mol x l(-1)) significantly diminished the constrictor responses to NA in vessels perfused with PMN+PTX when compared to the responses in PMN-perfused vessels (at dose 0.1 microg: 32.25 vs. 14.25, at dose 1 microg: 51 vs. 27.75 (p<0.01), at dose 10 microg 74.25 vs. 39.75 (p<0.05), all values expressed as median of perfusion pressure in mm Hg). The model of endothelial damage induced by repeated NA administration in 5 doses (10-50 microg of NA) was used for evaluation of the endothelium-protective effect of sulodexide (SLX). It was found that SLX (120 U/l) significantly decreased the number of desquamated endothelial cells (EC) compared to the control group (controls: 131.4+/-20.1 EC, +SLX: 83.3+/-13.8 EC, p<0.01). These results confirmed the favorable endothelium-protective effects of pentoxifylline and sulodexide in the two experimental models.

Animals↗

Autoimmune tubulointerstitial nephritis: insight from experimental models.

Many forms of tubulointerstitial nephritis (TIN) may have an autoimmune origin. To understand the pathogenesis of autoimmune TIN it is important to examine suitable animal models where the initiation and development of tubulointerstitial diseases can be assessed with precision. Experimental models of autoimmune anti-tubular basement membrane (anti-TBM) disease for example have allowed to define the nephritogenic role of antibodies which target tubulointerstitial moieties. Several tubulointerstitial antigens which are recognized by specific anti-TBM antibodies have been characterized at a molecular level in these models. The CBA/CaH-kdkd mouse strain represents another model of TIN where complex T-cell networks are uniquely altered, resulting in cell-mediated interstitial nephritis. Characteristic tubular alterations (up-regulation of adhesion molecules and CD44, cytokine and chemokine secretion) are prominent in several models of experimental TIN, promoting T-cell and monocyte infiltration. The complex interplay between tubular epithelial cells and immune cells is probably a prerequisite for a coordinated immune response in many forms of TIN, resulting in autoimmune renal tubulointerstitial injury and ultimately in renal failure.

Animals↗

Studies in calf venous pump function utilizing a two-valve experimental model.

OBJECTIVES: to explore the hydrodynamic mechanisms involved in the regulation of ambulatory venous pressure. DESIGN: an experimental model of calf venous pump was constructed with collapsible tubes and valves. MATERIAL: the model consisted of a conduit and a pump with an intervening competent valve. Another valve that could allow reflux into the pump was mounted above the pump. METHODS: conduit pressure and recovery times were monitored under conditions of different degrees of ejection fraction and reflux into the pump. Model variables included using poorly compliant tubes for the pump, the conduit and for both the pump and conduit. RESULTS: the latex tube exhibited a non-linear volume-pressure relationship and a bi-modal regimen of compliance. This bestowed pressure-buffering properties. Ambulatory venous hypertension resulted when reflux beyond buffering capacity occurred. Substituting less compliant PTFE for latex at the pump had a relatively minor effect on post-ejection pressure and recovery times. Using PTFE at the conduit had a profound but divergent effect on both of these parameters. Conduit capacitance reduction had a similar effect. CONCLUSION: conduit elastance plays a significant role in the regulation of ambulatory venous pressure in this experimental model. The hydrodynamic principles illustrated by the model may enhance our understanding of the human calf venous pump.

Blood Pressure Determination↗

Experimental model for low level laser therapy on ischemic random skin flap in rats.

PURPOSE: To develop an experimental model to be used in the study of low level Laser therapy on viability of random skin flap in rats. METHODS: The sample was 24 Wistar-EPM rats. The random skin flap measured 10 x 4 cm and a plastic sheet was interposed between the flap and donor site. Group 1 (control) underwent sham irradiation with diode laser (830 nm). Group 2 was submitted to laser irradiation with diode laser (830 nm). The animals were submitted to Laser therapy with 36 J/cm(2) energy density (72 seconds) immediately after the surgery and on the four subsequent days. The probe was usually held in contact with the skin flap surface on a point at 2.5 cm cranial from the flap base. On the seventh postoperative day, the percentage of necrotic area was measured and calculated. RESULTS: Group 1 reached an average necrotic area of 48.86%, Group 2 - 23.14%. After the statistic analysis, compared with the control group, Group 2 showed a statistically significant increase in survival area (p<0.001). CONCLUSION: The experimental model proved to be reliable to be used in the study of effects of low level laser therapy in random skin flap in rats.

Analysis of Variance↗

An experimental model for anaplastic astrocytomas and glioblastoma using adult F344 rats and N-methyl-N-nitrosourea.

An experimental model for induction of gliomas corresponding to human anaplastic astrocytomas and glioblastomas is reported. Eleven week old F344 and ACI rats were given 100 or 200 p.p.m. N-methyl-N-nitrosourea (MNU) solution as their drinking water for 42 weeks. Gliomas were induced at very high incidences (82.5-92.5%) in each group. Induced gliomas showed apparent evidence of morphologic malignancy by an analysis based on diagnostic criteria of human astrocytomas. All of the gliomas from the killed animals were classified histologically into subtypes according to the classification scheme used in the diagnosis of human gliomas. The majority of macrotumors more than 1 mm in diameter in both strains were diagnosed as anaplastic astrocytomas and glioblastomas. Immunohistochemically, tumor cells in these tumors were almost negative for glial fibrillary acidic protein, while ultrastructurally neoplastic astrocytes contained glial filaments. A strain difference was observed in the ratio of histological subtypes of macrotumors. In F344 rats, astrocytic tumors diagnosed as anaplastic astrocytomas and glioblastomas of an astrocytic type formed the majority, whereas glioblastomas of mixed oligo-astrocytic type predominated in ACI rats. The results indicate that MNU-administration to adult F344 rats may provide a suitable experimental model for gliomas which occur in adult humans.

Animals↗

Alpha-tocopherol derivatives in an experimental model of filtering surgery.

PURPOSE: To evaluate the efficiency and reliability of alpha-tocopherol in an experimental model of glaucoma filtering surgery. METHODS: Thirty pigmented rabbits were randomly divided into three study groups. Twenty-four hours before surgery, the animals were injected subconjunctivally with 0.5 ml of solution that depended on the group of treatment: group I (n = 10), 0.75% ethanol in balanced saline solution (BSS); group II (n = 10), 100 mg alpha-tocopherol acetate (ATA) in 0.75% ethanol in BSS; group III (n = 10), 100 mg alpha-tocopherol acid succinate (ATS) in 0.75% ethanol in BSS. The animals were followed during 30 days (intraocular pressure, IOP; filtering surgery; inflammatory reaction). RESULTS: IOPs were significantly lower in the treatment groups (ATA and ATS) than in the control group from days 7 and 10, respectively, till the end of the study. On day 7, the mean IOP in the ATA group was 15.8 versus 22.1 mm Hg in the control group. On day 10, the mean IOP in the ATS group was 15 versus 22.78 mm Hg in the control group. Filtering blebs showed statistically significant differences between the control and treated groups from day 5 to day 16. CONCLUSIONS: alpha-Tocopherol (ATA and ATS) showed better IOP control and bleb survival in this experimental model of filtering surgery.

Animals↗

Experimental model for transanal endorectal pull-through surgery. Technique of De la Torre and Ortega.

BACKGROUND: We describe an experimental model for transanal endorectal pull-through surgery using the method of de la Torre and Ortega that can be used for training purposes in experimental laboratories. METHODS: Ten rabbits were submitted to the transanal endorectal pull-through technique of de la Torre and Ortega. Animals were randomly selected in the Botucatu School of Medicine experimental laboratory. Animals weighted between 2800 and 4400 g. Colons were not prepared, and antibiotic therapy was not used; dipyrone was administered postoperatively for analgesic purposes. We standardized resected segment size, recorded surgical time, and observed survival and possible complications for 1 month. RESULTS: All animals survived the initial follow-up period without infection. Bowel movements returned quickly, and all animals were evacuating regularly within the first 24 hours. Mean surgical time was 48.6 minutes. CONCLUSIONS: The experimental model proposed in this study is very useful for training and improving surgical techniques using the method of de la Torre and Ortega. The rabbit is an excellent animal for this surgery because of its size and postoperative resistance.

Anal Canal↗

[Daunomycin rats. Second Report. Is it possible to use daunomycin rats as an experimental model of chronic renal failure?].

We have previously reported that daunomycin rats can be used as an experimental model of chronic renal failure. We have since studied whether the result were reproducible by repeating the experiment. In this experiment we used larger numbers of rats and many more parameters of investigation compared with the previous experiment. The period of observation was extended to 42 weeks. Twenty-one female Wistar rats were given an injection of 12 mg/Kg of daunomycin into the jugular vein by the one-shot method. Ten control rats were injected with physiological saline. Eighteen daunomycin rats developed chronic renal failure within the observation period. Renal failure was confirmed by the levels of BUN and creatinine, the uremic peak 2a and the pathological findings. One rat died from a tumor and another rat died from thrombosis of the descending aorta. In only one rat was not at the level defined as chronic renal failure, although it was impaired even in this case. There was a correlation between the lifespan of the daunomycin rats and the amount of urine protein at 4 weeks. Rats with heavy proteinuria at 4 weeks died of uremia at an early age. There was a variety of evidence of daunomycin damage when rats were autopsied, not only in the renal glomeruli but also in the pancreas, liver and spleen. Some parts of the pancreas and liver showed vacuolated cells. We supposed that these various changes of many internal organs of daunomycin rats were secondary changes for chronic renal failure. We reconfirmed that daunomycin rats can be used as an experimental model of chronic renal failure.

Animals↗

[Modification of an experimental model of chronic pancreatic and biliary fistula in the minipig (author's transl)].

An improvement in Corring's experimental model in the minipig is described. The model requires: -- a complete diversion of the biliopancreatic secretion and the possibility of its reintroduction into the duodenum; -- a particular anaesthesiological, technical and management problems taken up during the course of the research. Data are also given about basal pancreatic and biliary secretions in this particular experimental model.

Anesthesia↗

[Experimental model of combined pathology of tuberculosis-opisthorchiasis].

An experimental model of tuberculosis-opisthorchiasis pathology was developed. The results of two experimental series with the use of this model showed that in cases with mixed pathology the specific process is aggravated irrespective of whether the infectious process develops in opisthorchiasis or the latter occurs in attendance to tuberculosis. Delayed hypersensitivity in such cases is suppressed markedly in the absence of its initial activation.

Animals↗

Magnetic resonance imaging in experimental models of brain disorders.

This review gives an overview of the application of magnetic resonance imaging (MRI) in experimental models of brain disorders. MRI is a noninvasive and versatile imaging modality that allows longitudinal and three-dimensional assessment of tissue morphology, metabolism, physiology, and function. MRI can be sensitized to proton density, T1, T2, susceptibility contrast, magnetization transfer, diffusion, perfusion, and flow. The combination of different MRI approaches (e.g., diffusion-weighted MRI, perfusion MRI, functional MRI, cell-specific MRI, and molecular MRI) allows in vivo multiparametric assessment of the pathophysiology, recovery mechanisms, and treatment strategies in experimental models of stroke, brain tumors, multiple sclerosis, neurodegenerative diseases, traumatic brain injury, epilepsy, and other brain disorders. This report reviews established MRI methods as well as promising developments in MRI research that have advanced and continue to improve our understanding of neurologic diseases and that are believed to contribute to the development of recovery improving strategies.

Animals↗

An experimental model for chronic lymphedema.

Although a multitude of operations exist for the treatment of lymphedema, none is highly successful. An experimental model that reliably and easily produces chronic lymphedema in an extremity would be useful to study treatments in a controlled and comparative manner and would enhance our understanding of the physiology and treatment of lymphedema. Many models that simulate clinical lymphedema have been described, but they suffer from cumbersome protocols, high laboratory costs, and an inconsistent yield of permanent lymphedema. We describe an experimental model for chronic lymphedema in the lower extremity of the rat that creates a lymphatic block in the groin induced by radiation treatment and one operation--surgical division of the superficial and deep lymphatics. All animals develop stable chronic lymphedema of the lower extremity within days of operation, with swelling that persists for at least 9 months. A mortality rate of 8 percent was associated with this technique. Methods for quantification of limb swelling are described, as is analysis of the lymphatic block by lymphoscintigraphic imaging of lymph channels and nodes. This model has the advantages of simplicity of technique, cost-effective use of rodent subjects, reproducibility of lymphedema, and quantification of results.

Animals↗

Experimental models of chronic focal epilepsy: a critical review of four models.

A number of experimental (i.e., animal) models have been developed to induce chronic focal epilepsy. Three of the most commonly employed are the alumina cream, kainic acid, and the electrical kindling techniques. A fourth approach involving the application of minute quantities of tetanus toxin to discrete brain sites, although relatively under-utilized, may be favorably compared to the aforementioned models.

Aluminum Oxide↗

Hydroxylapatite beads as an experimental model to study the adhesion of lactic acid bacteria from the oral cavity to hard tissues.

The oral environment contains many different types of microorganisms, including both Gram-negative and Gram-positive cocci, bacilli, and spirochetes. From the ecological point of view, the oral cavity is a perfect niche for certain bacteria such as lactobacilli because they interact, forming different types of communities. Lactobacilli have been associated with the generation of caries in some reports, secondary to the cariogenic Streptococcus. In previous papers, the isolation and identification of 145 strains from healthy subjects and from subjects with active caries were performed. Strains were characterized by their surface properties and also by the production of inhibitory substances. From all the strains, one isolated from the teeth of healthy patients and another from a patient with caries, sharing some surface properties, were selected for further study of their adhesion properties in an experimental model by using hydroxylapatite beads. Adhesion is the first step in the association of microorganisms with surfaces or mucous membranes. The first approach is a nonspecific interaction of both surfaces; later some other types of interactions can occur, involving more specific mediators of adhesions. Many different assays are available to study the adhesion phenomenon; some of them use predictive characteristics, and others use experimental models resembling the in vivo situation. Two model systems predominate. The most widely used has been saliva-coated hydroxylapatite or hydroxylapatite coated with buffers, proteins, and other substances. In an attempt to increase knowledge of the mechanisms of adhesion of oral lactobacilli with hard surfaces, this chapter describes an experimental model for studing the adhesion between lactobacilli and hard tissues represented by hydroxylapatite, the component most abundant in the teeth. The following steps were performed: 1. Obtaining the microorganisms. 2. Preparation of the hydroxylapatite beads. 3. Adhesion assay.

Dental Caries↗

Experimental modelling of human spinal cord injury: a model that crosses the species barrier and mimics the spectrum of human cytopathology.

STUDY DESIGN: Literature review and presentation of an experimental model of human spinal cord injury, (SCI). OBJECTIVES: Experimental designs seek to mimic and model the physical processes by which human SCI occurs and replicate the variety of chronic pathologies that characterize its long term effects. The variations in biological processes that are present between species have contributed to recent difficulties in generalizing experimental findings to the human condition. In this review, one finds: (1) a discourse on the pathological nature of the chronic human lesion, (2) a consideration of how the physical properties of soft tissue injury result in acute and chronic changes in the spinal substance, (3) a description of a device (ESCID) that is able to replicate and dynamically monitor physical indices of SCI as they take place in experimental models, and (4) a summary of how use of this device in different species has allowed the biomechanical descriptors of such injuries to be easily compared even in murine models. SETTING: Ohio State University, Ohio, USA. RESULTS: Careful attention to the details of injury device design has finally allowed a direct comparison of contusion-type injury models in the rat and mouse. Biomechanical outcomes with predictive capabilities have evolved that allow the investigator to create the range of pathologies seen in the human lesion even in these small vertebrates. The predictive cytopathology and our ability to manipulate the mouse genome will allow the testing of specific hypotheses related to cause and effect in experimental spinal cord injuries. Since the biomechanics, pathology, and chronic outcomes appear to be similar to those seen in the human, these animal models should facilitate rapid progress in the design of human therapeutics. CONCLUSIONS: Biomechanics of certain elements of experimental spinal injury are surprisingly accurate descriptors of acute and chronic pathologies in the spinal cord. This tenet applies across species and has often allowed more accurate design of clinical trials in the past few decades. As molecular approaches to this problem evolve, the use of species with known genomes appear warranted. Models that take advantage of these approaches are likely to produce innovations that quicken the pace of human trial strategies.

Animals↗

Flucytosine+fluconazole association in the treatment of a murine experimental model of cryptococcosis.

The efficacy of flucytosine (5-FC) and fluconazole (FLU) association in the treatment of a murine experimental model of cryptococcosis, was evaluated. Seven groups of 10 Balb C mice each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans. Six groups were allocated to receive 5-FC (300 mg/kg) and FLU (16 mg/kg), either combined and individually, by daily gavage beginning 5 days after the infection, for 2 and 4 weeks. One group received distilled water and was used as control. The evaluation of treatments was based on: survival time; macroscopic examination of brain, lungs, liver and spleen at autopsy; presence of capsulated yeasts in microscopic examination of wet preparations of these organs and cultures of brain homogenate. 5-FC and FLU, individually or combined, significantly prolonged the survival time of the treated animals with respect to the control group (p < 0.01). Animals treated for 4 weeks survived significantly longer than those treated for 2 weeks (p < 0.01). No significant differences between the animals treated with 5-FC and FLU combined or separately were observed in the survival time and morphological parameters. The association of 5-FC and FLU does not seem to be more effective than 5-FC or FLU alone, in the treatment of this experimental model of cryptococcosis.

Animals↗

A radionuclide model for studying changes in the regional blood volumes during early endotoxic shock: an experimental model.

Septic shock constitutes a great threat to patients undergoing major abdominal surgery and also to trauma patients. The current state of knowledge on pathophysiological mechanisms in septic shock is not fully known. The aim of this study was to develop an experimental model that resembled the clinical situation and allowed the exploration of central and peripheral vascular mechanisms in endotoxic shock. Seven anesthetized sheep (weighing 30-45 kg) were provoked to lethal endotoxic shock by intravenous injection of 3 mg/kg bodyweight Escherichia coli endotoxin. The arterial pressure was monitored. Serial radionuclide images of the chest and abdomen were recorded after injecting technetium-99m-labeled RBC's. The volumetric (blood) alterations of liver, spleen, kidney, heart, and lungs, as well as peripheral muscle were measured. Prior to injection of endotoxin base-line data were obtained. Two to 4 minutes after injection, spleen volume decreased by -36% (mean) followed by a slow restoration; the left ventricular volume and kidneys increased by a maximum of 10-15%, while the liver volume increased by 38% of initial volume.

Animals↗

Central nervous system involvement in pregnant rabbits with experimental model of antiphospholipid syndrome.

A postmortem neuropathological investigations were carried out on 23 female rabbits divided into 3 groups; pregnant animals with experimental antiphospholipid syndrome (APS), nonpregnant rabbits with antiphospholipid syndrome and nonpregnant animals without antiphospholipid syndrome. The aim of study was to analyze the CNS changes related to experimental model of APS in rabbits and to answer, whether pregnancy influences the intensity of CNS changes related to APS. The findings suggest that the experimental model of APS used in our study appeared to be effective in the development of the CNS involvement in rabbits. The extent thickening of CNS vessel wall is the most common feature of vasculopathy related to APS. In rabbits, pregnancy seems to be a factor facilitating the CNS damage related to APS.

Animals↗