Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Models, Experimental”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMedDate not supplied

[Experimental models for Alzheimer's disease research].

INTRODUCTION AND DEVELOPMENT: Current animal models for Alzheimer's research include transgenic mice that express a mutant form of human beta-amyloid precursor protein (APP). However, the mutant mice with the human APP transgene also have their own endogenous APP gene, which may interfere with APP processing to generate beta-amyloid peptide. CONCLUSION: By genetic and immunochemical analyses, our laboratory has discovered that there are animals in the nature, the chick embryo and the dog in particular, which may be better experimental models than the transgenic mice, because they contain the same machinery as humans to process APP and they are easier to access, manipulate or explore their neurology. These species may be natural experimental models to study the cell biology of Alzheimer's APP and potential assay systems for drugs used to regulate beta-amyloid production as well as for the assay of new therapeutic strategies against so devasting disease.

Alzheimer Disease↗
PubMed2004

Time course of apoptotic tumor response after a single dose of chemotherapy: comparison with 99mTc-annexin V uptake and histologic findings in an experimental model.

UNLABELLED: In tumors the process of apoptosis occurs over an interval of time after chemotherapy. To determine the best timing for detecting apoptosis in vivo with (99m)Tc-annexin V after chemotherapy, we examined the changes in (99m)Tc-annexin V accumulation over time in comparison with those of caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) expression level after cyclophosphamide treatment in an experimental model. METHODS: Hydrazinonicotinamide (HYNIC)-annexin V was labeled with (99m)Tc ((99m)Tc-annexin V). Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. Eleven days after the inoculation, the rats were randomly divided into the group receiving a single dose of cyclophosphamide (150 mg/kg intraperitoneally) and the control group. (99m)Tc-Annexin V (18.5 MBq [0.5 mCi] per rat) was injected intravenously in the rats 4, 12, and 20 h after the treatment and also to the control rats (n = 5 in each group). Radioactivity in tissues was determined 6 h after (99m)Tc-annexin V injection. Immunostaining of caspase-3 and TUNEL were performed to detect apoptosis, and the rates of positively stained cells were calculated. RESULTS: (99m)Tc-Annexin V accumulation in tumors significantly increased at 20 h (0.077 +/- 0.007 [%ID/g] x kg, where %ID/g = percentage injected dose per gram) but not at 4 or 12 h (0.048 +/- 0.008 and 0.052 +/- 0.014 [%ID/g] x kg, respectively) after cyclophosphamide treatment. (99m)Tc-Annexin V accumulation in tumors and the rate of apoptotic cells determined by caspase-3 immunostaining and TUNEL were significantly higher in treated rats 20 h after cyclophosphamide treatment as compared with control rats. CONCLUSION: The effective detection of apoptotic tumor response with (99m)Tc-annexin V required 20 h after cyclophosphamide treatment in an experimental model. The present results provide an important basis for determining the best timing of annexin V imaging after the start of chemotherapy in a clinical setting.

Animals↗
PubMed1992

Chemically-induced chronic nerve compression in rabbits--a new experimental model for the carpal tunnel syndrome.

In order to create an experimental model for the carpal tunnel syndrome without the use of the commonly applied foreign bodies (silicone or rubber tubes, tourniquets etc.), the present study tried to induce a chemically provoked compression of the median nerve in rabbits. In 9 female rabbits 1 ml of Aethoxskerol 3% (Hydrox-polyethoxy dodecan) was instilled into the carpal tunnel around the median nerve after visualisation of the nerve. The other foreleg served as the control and was treated with the same amount of saline solution. Electroneurophysiologic parameters were registered preoperatively, 1 month and 6 months post surgery and histomorphologic investigations by light and electron microscopy were performed after 6 months. 6 months after treatment with Aethoxysklerol, a statistically significant lengthening of the distal latency period as well as a significant reduction of the compound potential amplitude could be observed. In accordance with these findings, morphological investigation revealed the presence of extensive granulation tissue around the median nerve together with signs of demyelination. Our results indicate that we were able to produce the development of extensive granulation tissue in the carpal tunnel of rabbits with subsequent compression of the median nerve which was confirmed by histomorphologic investigation as well as by measurement of nerve conductive velocity.

Animals↗
PubMed1981

Experimental model of disseminated intravascular coagulation induced by sustained infusion of endotoxin.

Experimental disseminated intravascular coagulation (DIC) was induced by sustained infusion of endotoxin into the femoral vein in rats. The severity of DIC was determined with reference to various parameters, such as fibrinogen and fibrin degradation products (FDP), prothrombin time (PT), partial thromboplastin time (PTT), platelet count, and number of renal glomeruli having fibrin thrombi. Experimental DIC could be induced by a 4-h sustained infusion of endotoxin in a dose of 100 mg/kg. The DIC induced in rats showed a close resemblance to human DIC as judged from such changes as an elevation in FDP, prolongation of PT and PTT, depression in fibrinogen and platelet count, and increase in glomeruli having fibrin thrombi. This experimental model has an advantage in that severity of DIC can be determined by measuring various parameters. It will be of use in the studies aimed at the establishment of a therapy for DIC as well as in the studies on DIC in rats.

Animals↗
PubMed1984

A reproducible experimental model of focal cerebral ischemia in the cat.

In the past experimental methods used for producing focal cerebral ischemia have had considerable difficulty with regard to reproducibility of the size of the infarcted region. In this study we have developed an experimental model which enables us to consistently produce focal regions of cerebral ischemia (resulting in infarction) which vary little in size in a number of animals. Thirty-seven cats (3-4 kg b. wt.) anesthetized with chloralose and urethane were used. Physiologic monitoring and adjustments maintained arterial blood values as follows: pCO2 27-35 Torr, pO2 100-150 Torr, pH +/- 7.4, glucose 200 mg%, hematocrit greater than 25. The left middle cerebral artery was exposed via a transorbital approach and occluded for 1-2 h with and without left and/or both carotid artery occlusion. Sixteen hours following the ischemic episode, the animals were sacrificed and sections of fresh brain tissue were processed for vital staining using 1% tetrazolium solution. With this method normal brain areas appear dark red, ischemic regions (without infarction) appear gray and irreversibly infarcted areas appear pinkish-white. The volumetric dimensions of the lesioned area were measured using a planimeter. The same tissue was also evaluated histologically by means of standard histopathologic techniques on paraffin-embedded material. Infarcted areas as delineated macroscopically by the tetrazolium correlated well with the light microscopic findings. Ten animals subjected to a 2-h occlusion of the left middle cerebral artery (LMCA) and both carotid arteries resulted in a reproducible infarct which was 3.2 +/- 0.7 ml in volume. This represents 13.3 +/- 2.9% of the total volume of both cerebral hemispheres (above the level of the inferior colliculus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Experimental models of hypothermic circulatory arrest.

This article reviews information obtained from experimental models of hypothermic circulatory arrest, which models have been developed in our and other laboratories over the past several years. The described experiments clearly demonstrate an ability to produce and completely reverse hypothermic circulatory arrest in newborn and developing animals, allowing for a comprehensive evaluation of those physiological variables and therapeutic interventions that would potentially reduce or accentuate ischemic brain damage. Further experiments will allow for a determination of whether or not specific modalities of therapy will reverse secondary systemic complications, thereby allowing for more complete recoverability and ultimately reduced brain damage.

Animals↗
PubMed2002

Experimental model of escape phenomenon in hamsters and the effectiveness of YM-53601 in the model.

1. The aim of this study was to establish an experimental model of the escape phenomenon, in which plasma cholesterol, initially reduced by a 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor such as pravastatin, increases again on long-term administration. We also evaluated the efficacy of YM-53601 ((E)-2-[2-fluoro-2- (quinuclidin-3-ylidene) ethoxy]-9H-carbazole monohydrochloride), a squalene synthase inhibitor, in this model. 2. Pravastatin inhibited cholesterol biosynthesis in hamster primary hepatocytes (IC(50), 14 nM). After pre-treatment with pravastatin, in contrast, almost no effect on cholesterol biosynthesis was seen. 3. In hamsters fed a high fat diet, 3 mg kg(-1) pravastatin for 9 days decreased plasma non-HDL cholesterol (total cholesterol - high density lipoprotein cholesterol) (P<0.01), but this effect was lost between 17 and 27 days of treatment, accompanied by an increase in HMG-CoA reductase activity. No such increase in plasma non-HDL cholesterol was seen with YM-53601 at 30 mg kg(-1) after 9 (P<0.001), 17 (P<0.01) or 27 (P<0.001) days of treatment. Replacement of pravastatin with YM-53601 caused a decrease in plasma non-HDL cholesterol by 53% (P<0.001) and in HMG-CoA reductase activity. 4. This animal model thus satisfactorily replicates the escape phenomenon observed in humans and may therefore be useful in evaluation of lipid-lowering agents, specifically comparison of HMG-CoA reductase inhibitors. Further, YM-53601 may be useful in the treatment of hypercholesterolemia without induction of the escape phenomenon.

Animals↗
PubMed1988

Evaluation of single-drug and combination antifungal therapy in an experimental model of candidiasis in rabbits with prolonged neutropenia.

We developed an experimental model of candidiasis in rabbits with prolonged neutropenia. Rabbits were made neutropenic with cytosine arabinoside (Ara-C) administered through an indwelling silastic catheter that had been surgically implanted in the external jugular vein. Neutropenia was sustained with intravenous Ara-C, and bacterial complications were prevented with parenteral ceftazidime plus ampicillin. Candidiasis was established by intravenously administering Candida albicans or Candida tropicalis (1-2 x 10(5) colony-forming units) and resulted in hepatic and splenic lesions that mimicked those associated with hepatosplenic candidiasis in humans. The kidney proved to be the site most refractory to eradication of Candida spp. and offered a target organ for assessing antifungal therapy. We evaluated amphotericin B, 5-flucytosine, ketoconazole, and rifampin, alone and in combination. Although each agent reduced the colony counts of Candida in the liver, spleen, and lung, the combination of amphotericin B and 5-flucytosine was the only regimen effective in eradicating renal candidiasis.

Agranulocytosis↗
PubMed1988

Early diagnosis of adult respiratory distress syndrome: an experimental model of complement-mediated pulmonary injury.

This article presents an experimental model of pulmonary injury resembling subclinical human adult respiratory distress syndrome (ARDS) mediated by leukocytes. The activation of complement was prolonged by an intraperitoneal injection of a suspension of zymosan in paraffin. The first step in the development of the disease was an accumulation of polymorphonuclear leukocytes in the lungs. No significant changes were observed on chest radiographs or computed tomograms and the pathophysiologic changes were only minimal in spite of the characteristic structural changes. The criteria currently used for the diagnosis of ARDS are not sensitive enough to detect the subclinical phase of the disease.

Animals↗
PubMed1999

Behavioral and morphologic studies of the chronically compressed cauda equina. Experimental model of lumbar spinal stenosis in the rat.

STUDY DESIGN: An experimental model in rats of chronically compressed cauda equina was produced, and behavioral and morphologic changes were examined. OBJECTIVES: To provide a useful model for analyzing the pathophysiologic changes of the cauda equina by chronic compression and to examine behavioral and morphologic changes in this model. SUMMARY OF BACKGROUND DATA: Several animal models have been reported in which various materials were used to compress the cauda equina. However, the pathophysiology of the cauda equina by chronic compression is not yet well understood. Studies in which rats were used are scarce. METHODS: A silicone sheet was applied to the spinal canal at L4 in the rat. Walking durations on treadmill tests and paw-withdrawal latencies to thermal stimuli were measured before and after the operation for 24 weeks. Histologic changes also were examined. RESULTS: Walking durations decreased after chronic compression. However, paw-withdrawal latencies were not significantly changed. Histologically, the number of large-diameter myelinated axons decreased after compression, whereas the number of small-diameter myelinated axons increased. Electron microscopic observation indicated that the continuous degeneration and regeneration of axons occurred throughout the chronic compression experiment. CONCLUSIONS: The current model and behavioral assessments may be useful in analyzing the pathophysiology of chronically compressed cauda equina.

Animals↗
PubMed2005

An experimental model of Stanford type B aortic dissection.

PURPOSE: To create an experimental model of aortic dissection with a long-lasting patent false lumen as a proper animal model for development of less-invasive treatment for aortic dissection. MATERIALS AND METHODS: Fifteen adult beagle dogs (weight, 10-12 kg) were used. The descending aorta was exposed by a left thoracotomy at the sixth intercostal space. The entry for the aortic dissection was created surgically just distal to the origin of the left innominate artery and the reentry was 5 cm distal to the entry point. Normal saline solution was injected into the aortic wall (ie, media) between these two points to create the dissection. The dogs were followed up at 1 day, 3 months, 1 year, and 2 years. RESULTS: All 12 surviving dogs had completely patent true and false lumina without any thrombi. Microscopic examination showed that the dissection was created in the tunica media layer, making it identical to aortic dissection in humans. Color Doppler imaging confirmed the patency of the true and false lumina and the relatively narrowed true lumen. CONCLUSION: In this canine model of aortic dissection, the false lumen has excellent long-term patency and the dissection plane is histologically similar to that in human aortic dissection. This model may contribute to the development of new treatments for Stanford type B aortic dissection.

Aortic Dissection↗
PubMed1995

Topical application of a corticosteroid destabilizes the host-parasite relationship in an experimental model of the oral carrier state of Candida albicans.

Using an experimental model in the mouse we have shown that both local and central lines of defense, involving CD4+ T cells, participate in a dynamic interaction to maintain a long-term carrier state of Candida albicans in the oral cavity. We have tested the impact of a predisposing factor to oral candidiasis in the form of a topical application of a corticosteroid (Topsyn gel) to the oral mucosa for 75 mice twice a day for a 20-day period. Very rapidly after the treatment was initiated, i.e. on day 4, the residual population of Candida increased up to 40-fold and by day 21, the population was 400-fold that of the carrier state. The resident population of intraepithelial CD4+ T cells in the oral mucosa virtually disappeared during the treatment. A topical corticosteroid application also resulted in a massive depletion of T cells in the lymph nodes and in the transient abrogation of the DTH reaction to Candida antigens. On cessation of treatment, normal levels of both Candida and intraepithelial CD4+ T cells were also quickly restored. These results suggest that resistance to superficial invasion by Candida is linked to the presence of an oral mucosal line of defense and that topical application of corticosteroids may dramatically shift the host-parasite relationship in favor of Candida.

Administration, Topical↗
PubMed1982

Quantification of the inflammatory reaction and collagen accumulation in an experimental model of open wounds in the rat. A methodological study.

An experimental model for studying the early healing of open wounds in the rat is described. With this model, exudate is easily collected, a standardized granulation tissue is achieved at different post-wounding time intervals and local treatment of the wounds is possible. The model involves the use of stainless steel rings with covers, fastened to the edges of two circular full-thickness open wounds, one on each side of the animal's back in the thoracic region. Blood flow and water content of the granulation tissue were determined acutely 3, 5, 7 and 10 days after wounding. The collagen accumulation in the granulation tissue was assessed by the amount of hydroxyproline, at the same time intervals. The amount of exudate which accumulated in the chamber was measured daily. Blood flow in the granulation tissue, as measured by radioactive microspheres, reached a maximum of 947 ml X min-1 X (100 g dry weight)-1 7 days after wounding. The water content, as assessed by freeze-drying, also reached its peak on the 7th day (5.5 ml X (g dry weight)-1). Changes in water content were found to be due to changes in interstitial fluid volume, as studied by 59Fe-labelled erythrocytes and 51Cr-EDTA. The amount of hydroxyproline in the granulation tissue increased from 22 micrograms X (mg dry weight)-1 on day 3 to 37 micrograms X (mg dry weight)-1 on day 10. Exudation increased to 28 microliters X h-1 X cm2-1 on day 4 and then declined. The results suggest that the inflammatory reaction, expressed as alterations in blood flow and water content, reaches a maximum on day 7 after wounding. The data also demonstrate a continuous increase in the collagen content of the granulation tissue during the 10-day period of observation. In addition, exudation was found to reach a peak on the 4th to 5th day, and then declined.

Animals↗
PubMedDate not supplied

[Experimental models of angiogenesis (in vitro and in vivo)].

The multiplicity of experimental models of angiogenesis in vitro and in vivo complicates the choice of a straightforward strategy to accurately identify the anti-angiogenic potential of a natural or synthetic compound with antitumoral activity. In the absence of such consensus, it is clear that the demonstration of an activity lies in the use of several models, both in vitro and in vivo. A rapid overview of the most currently used models, especially in vitro, is presented, with an emphasis on their limitations. Several examples of research strategies for identifying antitumoral anti-angiogenic compounds are used in illustration.

Allantois↗
PubMed2001

An experimental model to study intrusive forces in rats.

We have developed an experimental model for the study of the response of the periodontal ligament and bone to intrusive orthodontics forces in rats. Thirty-five Wistar rats, body weight 250 gr., were grouped as follows: control (GI), 48 hs (GII), 96 hs (GIII), 7 days (GIV). A steel band was cemented to the first upper right molar with a welded spring running to the occlusal surface of the second molar to exert a vertical force of 15 gr. The left side of treated animals was also used as control. The animals were sacrificed at the corresponding treatment times. Radiographs of the left and right halves of the jawbones were taken with an ultrafine grain industrial film. Seven measurements of the width of the periodontal ligament were taken. The data reveal narrowing of the periodontal ligament at the peri-apex and the furcation area for the animals in Group II. Conversely, Group III and IV animals exhibited widening of the periodontal ligament, particularly in the animals submitted to the force for 7 days. Statistical analysis of the data by Student's paired t test showed that the difference for the latter group was statistically significant (p < 0.05). The data for the horizontal measurements do not afford conclusive results. The present results confirm the value of the model to study the response to vertical intrusive forces.

Alveolar Process↗
PubMed1987

An experimental model for studying reversible intestinal ischemia.

We have developed a simple experimental model for studying reversible intestinal ischemia. The model is based on tenting the mesenteric vessels (artery and vein) to a tied loop of the small bowel in rat and, after a certain time, lowering them down again. Total and partial ischemia (created by tenting 2 and 1 cm, respectively) were demonstrated by laser Doppler flowmetry, as was the revascularization obtained after bringing the vessels down again. Alterations in mucosal permeability after ischemia were determined by depositing fluorescent dextran 3000 in the tied loop and measuring its concentration in the portal blood, and mucosal damage due to ischemia was assessed by measuring the activity of N-acetyl-beta-glucosaminidase, a lysosomal enzyme, in the gut lumen. There was a significant increase in the intestinal permeability to dextran 3000 after total ischemia for 10 min or more, and the permeability was directly related to the duration of the ischemia. After the intestine had been subjected to total ischemia for 30 min or more, the activity of N-acetyl-beta-glucosaminidase in the luminal contents was significantly increased. The permeability after partial ischemia for 30 min was less than that after total ischemia for 30 min. After total ischemia for 10 min followed by revascularization for 30 or 60 min, the permeability did not differ from that in animals not subjected to ischemia. It is concluded that this simple model may be used to study reversible small intestinal ischemia and factors that influence mucosal permeability.

Acetylglucosaminidase↗
PubMed1984

[Experimental model of venous hemorrhagic infarction by cerebral sinus occlusion].

A new experimental model of the hemorrhagic infarction was devised to study the pathophysiology of the hemorrhagic infarction of the venous origin. To make a model of the hemorrhagic infarction by sinus occlusion, mixture of alpha-cyanoacrylate monomer and pantopaque was injected through a catheter introduced into the superior sagittal sinus in 15 dogs, using embolization technique. These dogs were divided into three groups according to the volume of the mixture injected into the sinus. In control groups (3 dogs), no mixture was injected. For partial sinus occlusion (5 dogs), 0.5-1.0 ml of mixture was injected into the sinus and 1.0-1.5 ml of mixture, for complete sinus occlusion (7 dogs). Changes of intracranial pressure (ICP), superior sagittal sinus pressure (SSSP), tissue pressure (TP) rCBF and histological changes were evaluated before and after sinus occlusion. The following results were obtained. (1) In control groups, ICP, SSSP and TP were 9 +/- 2.2 mmHg, 4 +/- 2.5 mmHg and 4-5 mmHg respectively, but in partial and complete sinus occlusion, SSSP and TP were higher than ICP. ICP, SSSP & TP were 32 +/- 5.4 mmHg, 35 +/- 6.5 mmHg and 37-42 mg, in partial sinus occlusion and 62 +/- 5.9 mmHg, 65 +/- 6.0 mmHg, 65-72 mmHg in complete sinus occlusion. (2) R-CBF in partial sinus occlusion showed no change even after sinus occlusion, but in complete sinus occlusion, decreased to 20% of that of the control group due to marked venous congestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Ice treatment of injured ligaments: an experimental model.

Using the radiocarpal ligament of the domestic pig as an experimental model the effects of ice therapy were studied. The results indicate that application of ice causes: (1) Increased subcutaneous swelling to injured or uninjured soft tissue; (2) A diminution of histological evidence of inflammation in injured ligamentous tissue.

Animals↗