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PubMed1997

The application of image analysis in the measurement of the myocardial infarct area in an experimental model.

BACKGROUND: Thrombolytic therapy improves left ventricular ejection fraction and survival. Using the image analysis method, the study was undertaken to evaluate the effects of intraaortic balloon pump used in conjunction with reperfusion in reducing infarct size by measuring the infarct area. Also, the usefulness of image analysis as an objective method for the measurement of myocardial infarct area is evaluated. METHODS: 22 dogs were subjected to proximal left anterior descending coronary artery occlusion. The dogs were classified into 3 groups. In group I (n = 7), occlusion lasted for 6 hours. In group II (n = 6), 2 hours of occlusion were followed by reperfusion. In group III, (n = 9) after 2 hours of occlusion, the dogs were assisted with the intraaortic balloon pump throughout the 4 hours of reperfusion. The measurement of the infarcted area components (fragmentation, edema, hemorrhage and polymorphonuclear infiltrations) was followed by a semiautomatic method including in connection a microscope photographic camera, a scanner and a computer with the appropriate software. The results were analyzed statistically using the t-test. RESULT: In group I, the mean value of fragmentation was 28.2%, in group II, 10.1% (p < 0.01 versus group I) and in group III, 3.9% (p < 0.01 versus I and p < 0.05 versus group II). CONCLUSION: Reperfusion and intraaortic balloon pump increased the salvage of the ischemic myocardium over that achieved by reperfusion alone in a canine occlusion - reperfusion model. Image analysis could be considered as an accurate and objective method for the measurement of the myocardial infarct area in the experimental model of our study and it could be used in any other experimental study in which the accurate measurement of myocardial infarct area is needed.

Animals↗
PubMed1985

An experimental model to study blood and inflammatory neutrophils.

We sought to develop an experimental animal model in order to study the effects of hypothermia on host defences under conditions which were similar to those used for humans. We required a large animal which could tolerate arterial and venous catheters and serial blood sampling without significantly altering its blood volume and blood pressure. The animal should be intubated and ventilated to control blood gases and fluid and electrolyte balance. Finally the model should have anatomic, metabolic and physiologic similarities to humans. We describe an experimental pig model which appears to fulfill these criteria and provide important information relevant to man.

Animals↗
PubMed1996

First experience with laparoscopic spine fusion in an experimental model in the pig.

BACKGROUND: We elucidated whether anterior lumbar spine fusion with interbody implants (BAK) can be performed in an experimental model in the pig using a transperitoneal laporoscopic approach. METHODS: In seven animals, a pneumoperitoneum with an intraabdominal pressure of 12 mmHg was induced, and five trocars were placed in the middle, as well as in the left and right lateral aspect of the abdomen. With the use of specially designed instruments, the bifurcations of the aorta and vena cava were prepared. The sacral artery, overlying the anterior aspect of the L5/S1 disc space, was retracted, allowing the exposure of the disc space. A working trocar was then fixed to the spine bodies above (L6) and below (S1) the disc, and instrumentation was completed by destruction of the disc, insertion of distraction plug, and implantation of the BAK cage. X-ray control allowed exact positioning of the cage. RESULTS: There were no major complications during the operative procedure, in particular no bleeding from major blood vessels and no injury to intraperitoneal organs. Cages were implanted in all animals in correct position, as indicated by postoperative X-ray control. CONCLUSIONS: We conclude from our experiments that in the pig model implants for anterior interbody lumbar spine fusion can be inserted successfully using the laparoscopic approach. We propose that the pig model represents an ideal tool for training before applying this operative procedure in men.

Animals↗
PubMed1977

New experimental model for the primary evaluation of topical contra-inflammatory agents.

Assays of steroidal and non-steroidal drugs in an experimental model of dermatitis induced in the ear of the rabbit by the application of a solution of croton oil revealed clearly differentiable inhibitory effects on the rise in skin temperature, the oedema and the increase in tissue mass due to the inflammatory process. The results obtained in this test system fairly accurately reflect the relative therapeutic potencies of known dermatocorticoids and, in conjunction with those found by other methods, afford a more exact characterization of the activity profiles of non-steroidal contra-inflammatory agents.

Administration, Topical↗
PubMed2002

An experimental model of human body louse infection with Rickettsia prowazekii.

Rickettsia prowazekii is transmitted to humans by the body louse. A new experimental model of body louse infection with R. prowazekii is reported here. Eight hundred human lice were infected by feeding on a rabbit that was made bacteremic by injecting 2x106 plaque-forming units of R. prowazekii. The bacterium invaded the stomach cells and was released in feces, in which it was detected 5 days after infection. At day 6 after infection, as a result of the cell burst and the spread of erythrocytes in the hemolymph, the louse became bright red and died within 4 h. The life span of infected lice was shortened by 20-23 days, compared with that of uninfected control lice. Infected lice did not transmit R. prowazekii to their progeny. Through cell culture, rickettsiae were cultivated from fecal samples up to 10 days after their emission. The administration of doxycycline to the rabbit during louse feeding did not cure lice from R. prowazekii infection.

Animals↗
PubMed2005

Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota.

There are now many experimental models of inflammatory bowel disease (IBD), most of which are due to induced mutations in mice that result in an impaired homeostasis with the intestinal microbiota. These models can be clustered into several broad categories that, in turn, define the crucial cellular and molecular mechanisms of host microbial interactions in the intestine. The first of these components is innate immunity defined broadly to include both myeloid and epithelial cell mechanisms. A second component is the effector response of the adaptive immune system, which, in most instances, comprises the CD4+ T cell and its relevant cytokines. The third component is regulation, which can involve multiple cell types, but again particularly involves CD4+ T cells. Severe impairment of a single component can result in disease, but many models demonstrate milder defects in more than one component. The same is true for both spontaneous models of IBD, C3H/HeJBir and SAMPI/Yit mice. The thesis is advanced that 'multiple hits' or defects in these interacting components is required for IBD to occur in both mouse and human.

Animals↗
PubMed1983

Correlation between Ito cells and fibrogenesis in an experimental model of hepatic fibrosis. A sequential stereological study.

The relationship between Ito cells and hepatic fibrogenesis has been investigated in an experimental model: intraperitoneal injection of heterologous serum in rats leads to the appearance of fibrous septa within 5 weeks. Groups of rats were sacrificed at various intervals (from 2.5 to 20 weeks), saline-injected rats being used as controls. Liver fragments were prepared for light and electron microscopy and determination of hydroxyproline. Ito cells were identified by defined morphological criteria on 1 micron sections. The volume density (VD) of Ito cells and fibrous septa, and the Ito cell index were determined. Ito cells represent a very relevant component of early septa. In later stages, the VD of cells with morphological features of Ito cells falls to very low values. This might be related to modulation of Ito cells to fibroblasts. The increase of tissue hydroxyproline is delayed with respect to the peak VD of septal Ito cells, actually corresponding to the fall in the VD of septal Ito cells. The striking increase in the VD of total Ito cells cannot be related to a theoretically possible increase in the volume of single Ito cells, as VD always parallels the Ito cell index. These data suggest a hyperplastic reaction, possibly associated with a cellular migration from the lobules to early septa.

Animals↗
PubMed1999

Effectiveness and toxicity of gentamicin in an experimental model of pyelonephritis: effect of the time of administration.

Temporal variations in the renal toxicity of aminoglycosides have been reported for experimental animals as well as for humans. In fact, maximal renal toxicity of aminoglycosides was observed when the drug was given during the rest period, while a lower toxicity was observed when the drug was injected during the activity period. The aim of the present study was to evaluate temporal variations in the effectiveness and renal toxicity of gentamicin in an experimental model of pyelonephritis in rats. The experiments were carried out with female Sprague-Dawley rats (185 to 250 g). They had free access to food and water throughout the study and were maintained on a 14-h light-10-h dark cycle. Animals were divided into four groups corresponding to the respective time of induction of pyelonephritis and treatment: 0700, 1300, 1900, and 0100 h. Pyelonephritis was induced by a direct inoculation of Escherichia coli (10(7) to 10(8) CFU) in the left kidney. Animals were treated for 3 and 7 days with a single daily dose of gentamicin (20 and 40 mg/kg of body weight, respectively) or saline (NaCl, 0.9%) at either 0700, 1300, 1900, or 0100 h. Animals treated at 0100 h for 3 days with gentamicin (20 mg/kg) showed a significantly lower number of bacteria in their kidneys than did all other groups (P < 0.01). After 7 days of treatment, the efficacy, evaluated by the log CFU per gram of tissue and by the percentage of sterilized kidneys, was also higher when gentamicin was administered at 0100 h. The beta-galactosidase and the N-acetyl-beta-D-glucosaminidase activities were significantly higher in urine of rats given gentamicin at 1300 h than in urine of rats treated at another time of day (P < 0.05). Gentamicin injected at 1300 h induced a significantly greater increase of [3H]thymidine incorporation into DNA of renal cortex (P < 0.01), a significantly greater inhibition of sphingomyelinase activity (P < 0.05), and significantly more histopathological lesions than the same dose injected at another time of the day. Creatinine and blood urea nitrogen levels in serum were significantly higher (P < 0.05) and the creatinine clearance was significantly lower (P < 0.05) when gentamicin was injected at 1300 h than when it was injected at another time of day. Our data suggest temporal variations in both the toxicity and the effectiveness of gentamicin, the drug being more effective and less toxic when injected during the activity period of the animals.

Animals↗
PubMed1982

An overall review on prenylamine mechanisms of action in experimental models of myocardial damage.

In this review we present the effects of a well-known antianginal drug, prenylamine (PNL), in experimental models of acute myocardial damage induced by a beta-agonistic drug, isoproterenol (ISP), in several trials conducted in our laboratory in both rats (n = 204) and monkeys (n = 26). PNL significantly inhibited ISP-induced lesions, protecting the majority of animals studied. Studies dealing with the site of action of the drug, such as 45Ca, 3H-PNL and 3H-ISP trials, showed a clear membrane effect slowing down Ca transport. Correlation between ECG (inhibition of ST depression after ISP) and pathological findings in monkeys was also obtained in one of our experiments. These series of assays were useful in obtaining a more complete idea of activity and site of action of the drug. It seems that, in acute models, PNL acts as a calcium antagonistic drug rather than an adrenergic moderator.

Angina Pectoris↗
PubMedDate not supplied

An experimental model of hypoxia on isolated rat heart in recirculating system: study of fatty acid metabolism with an iodinated fatty acid.

An experimental model of hypoxia was developed on isolated rat heart to study the effects of hypoxia on cardiac performance and metabolism. Fatty acid (FA) metabolism was explored by external detection with a labelled FA, iodohexadecenoic acid (IHA). Hearts, after 30 min preperfusion in an open system, were transferred in a recirculating system for 40 min and perfused with oleate, glucose, lactate, pyruvate and IHA, either in normoxia (pO2 = 660 mmHg) or in hypoxia (pO2 = 220 mmHg). After 40 min hypoxic recirculation, oxygen uptake and dynamic parameters, except the heart rate, decreased respectively by 56% and 44%, and remained constant throughout the perfusion. Glucose utilization increased 2 fold, endogenous glycogen fell by 50% and lactate + pyruvate production increased 3 fold, showing a stimulation of glycolysis. Oleate uptake decreased by 28%, while triglycerides content remained higher. The ATP/ADP ratio decreased by 24%. Conversely to oleate, IHA uptake was not significantly modified, but its intracellular fate showed a higher radioactivity in all lipid fractions: polar lipids, diglycerides, free FAs and triglycerides. beta oxidation of IHA, evidenced by iodide production, decreased by 39%. The external detection of cardiac radioactivity allowed us to obtain time-activity curves that were analyzed with a 4-compartment mathematical model. The data evidenced an esterification ratio significantly higher in hypoxia. The metabolism of IHA as estimated by the intracellular analysis or, in a non-invasive way, by external detection, was similar to the metabolism of oleate. Thus, lipid metabolism, in hypoxia, can be explored by external detection with IHA.

Animals↗
PubMed2000

[Experimental model of subretinal neovascularization].

PURPOSE: To study the effect of transpupillary photocoagulation with a diode laser in the development of an experimental model of choroidal neovascularization (CNV) in the pigmented rat. METHODS: Diode laser was applied in Long-Evans rats using a setting of 75 microm spot size, 0.05 seconds durations and 200 mW intensity. Follow up was performed by fundus photography and fluorescein angiography that was performed weekly. The animals were sacrificed 7, 14, 21, 30, 45, 52, 60 and 75 days after photocoagulations, the eyes were enucleated and studied by light microscopy. RESULTS: Variation in burn intensity and diameter was common. During the experiment 42 of 93 burns (45%) showed fluorescein staining and late leakage. Neovascularization was confirmed with histopatology in all lesions that showed fluorescein leakage. CONCLUSIONS: Transpupillary diode laser may induce CNV in the pigmented rat. This model may be useful in the in vivo study of choroidal angiogenesis and its therapeutic modulation.

Animals↗
PubMed1992

Beneficial effects of a retinoic acid analog, CBS-211 A, on an experimental model of keratoconjunctivitis sicca.

We report the effects of CBS-211 A, a synthetic retinoic acid analog, on a previously described experimental model of keratoconjunctivitis sicca (KCS) in the rabbit. A 9-week topical treatment with 0.02% CBS-211 A in aqueous vehicle significantly increased the conjunctival goblet cell density (P less than 0.01, impression cytology counting), stopped the evolution of the corneo-conjunctival surface alteration (P less than 0.05, rose bengal test), and restored a basically normal mucosecretory product quality in goblet cells (lectin histochemistry) compared to vehicle treatment. The results assess the efficacy of this compound in reversing KCS pathology in a relevant model different from general vitamin A deficiency models, and strongly support the rationale for using such a well-tolerated retinoid in dry eye treatment.

Administration, Topical↗
PubMedDate not supplied

[Gastric emptying and metabolic acidosis. I. Study of an experimental model in rats, using an ammonium chloride solution administered through the orogastric route].

The goal of the study was get an experimental model of metabolic acidosis which was appropriated in future gastric emptying studies. For this proposal were utilized 141 female Wistar rats in three stages: in the first (n = 27) was defined the installation, manutention and spontaneous recuperation of the metabolic acidosis produced by the orogastric infusion of a two ml by 100 g of an 0.5 M ammonium chloride solution; in the second (n = 60), it was studied the gastric emptying of the same solution utilized in the first stage and in the last stage (n = 54) it was determined the gastric emptying of the water, for excluding the possibility that the acidificant solution had caused any lesion in the gastric mucosa. As control group were utilized animals fed as a sodium chloride solution in the same concentration and volume that the acidificant solution. The results showed that 6 hours after the infusion, the gastric emptying of two above mentioned meals was complete and there was still a moderate metabolic acidosis in the group with infusion of ammonium chloride solution. Further more, the metabolic acidosis persisted in moderate values until 8 hours after the infusion. Based on these data the interval between 6 and 8 hours after the infusion of the these solutions was considered the best to the further studies about metabolic acidosis and gastric emptying. Finally, the gastric emptying of water, studied in rats with acidosis and controls demonstrated no differences between them. This was interpreted as a clue that the ammonium chloride solution did not modificate the integrity of the gastric mucosa.

Acidosis↗
PubMedDate not supplied

Monitoring of somatosensory evoked potentials in cerebral ischemia: an experimental model.

We have studied Mongolian gerbils using somatosensory evoked potentials (SEP) recordings before, during and after an ischemic event. In six experimental animals, cerebral ischemia was reproduced by clamping both carotid arteries for ten minutes. Two recordings were made during this period at 4' and 8'. An additional four recordings were made after removal of the clamp at 4', 8', 12' and 20'. Four animals were utilized as a control group, and were subjected to the identical experimental protocol, with the exclusion of carotid artery clamping. During ischemia we observed an evident alteration of the SEP recordings in the experimental animals, and a more or less rapid recovery during the post-ischemic period. This experimental model may be useful for the monitoring and the evaluation of the evolution of cerebro-vascular damage during the post-ischemic period.

Animals↗
PubMed1998

Material and functional properties of articular cartilage and patellofemoral contact mechanics in an experimental model of osteoarthritis.

The purposes of this study were to determine the in situ functional and material properties of articular cartilage in an experimental model of joint injury, and to quantify the corresponding in situ joint contact mechanics. Experiments were performed in the anterior cruciate ligament (ACL) transected knee of the cat and the corresponding, intact contralateral knee, 16 weeks following intervention. Cartilage thickness, stiffness, effective Young's modulus, and permeability were measured and derived from six locations of the knee. The total contact area and peak pressures in the patellofemoral joint were obtained in situ using Fuji Pressensor film, and comparisons between experimental and contralateral joint were made for corresponding loading conditions. Total joint contact area and peak pressure were increased and decreased significantly (alpha=0.01), respectively, in the experimental compared to the contralateral joint. Articular cartilage thickness and stiffness were increased and decreased significantly (alpha=0.01), respectively, in the experimental compared to the contralateral joint in the four femoral and patellar test locations. Articular cartilage material properties (effective Young's modulus and permeability) were the same in the ACL-transected and intact joints. These results demonstrate for the first time the effect of changes in articular cartilage properties on the load transmission across a joint. They further demonstrate a substantial change in the joint contact mechanics within 16 weeks of ACL transection. The results were corroborated by theoretical analysis of the contact mechanics in the intact and ACL-transected knee using biphasic contact analysis and direct input of cartilage properties and joint surface geometry from the experimental animals. We conclude that the joint contact mechanics in the ACL-transected cat change within 16 weeks of experimental intervention.

Animals↗
PubMed1996

Hepatic Morphological alterations induced by zidovudine (ZDV) in an experimental model.

Zidovudine (AZT) inhibits HIV replication. Many studies have demonstrated its toxic myopathic effect in both HIV-positive patients treated with the drug and experimental animal models. So far hepatic lesions induced by AZT have not been reported. In our study, an experimental rat model was used in which the rats were administered AZT (1 mg/ml) in drinking water; histological and ultrastructural alterations were observed in the liver of treated animals and compared with the findings in control animals. The histological alterations detected were turbid swelling, vacuolar degeneration and microvacuolar fatty degeneration of panlobular distribution; these lesions were progressively greater as the duration of treatment increased. The ultrastructural alterations detected involved the mitochondria (similar to those described in cardiac muscle), smooth and rough endoplasmic reticulum (SER and RER), and the accumulation of fat and glycogen in the hepatocytes of treated animals. The histopathological and ultrastructural findings in our experimental model suggest hepatotoxicity induced by AZT or its catabolites in treated, as compared to control animals.

Animals↗
PubMed1989

A new experimental model for in vivo studies on differentiation and proliferation of leukemic cells using a mouse myeloid leukemia aneuploid line.

We developed an experimental model to investigate in vivo differentiation and proliferation of leukemia cells using mouse myeloid leukemia aneuploid cells (LL-2) and syngeneic SL mice. The LL-2 cells were near-tetraploid cells isolated from mouse myeloid leukemia cell line M1 (clone D501). In suspension culture, the LL-2 cells were myeloblastic and grew well like parent D501 cells, but were distinct from the parental cells due to the large size of their nucleus, double chromosome number and DNA content. The LL-2 cells as well as D501 cells could be induced to differentiate in vitro into mature macrophage-like cells by a protein inducer of differentiation. After transplantation of 4 X 10(6) LL-2 cells into the intraperitoneal cavity of syngeneic SL mice, most of them died of leukemia within 10 weeks. On microscopic examination of the peritoneal cells of the mice, the transplanted LL-2 cells were clearly distinguishable from normal host cells by the size of their nucleus. We determined the increase in the LL-2 cells in the peritoneal cavity by morphological examination of the large-sized LL-2 cells. Survival times of the mice inoculated with the LL-2 cells were prolonged by administrations of an inducer of differentiation, poly(I).poly(C). We found morphological changes in the peritoneal blastic LL-2 cells to mature macrophage-like cells after the serial administrations of poly(I).poly(C) to the recipient mice. Thus the aneuploid LL-2 cells that grow in syngeneic mice may be useful to study in vivo differentiation and proliferation of leukemia cells, and to develop a therapeutic strategy of leukemia using various treatments including differentiation inducers.

Aneuploidy↗
PubMed2002

Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion.

Infiltration of the central nervous system by neoplastic cells in patients with glioblastoma multiforme (GBM) leads to neurological dysfunction and eventually to death. The elucidation of the mechanisms underlying the aggressive nature of GBM aims at improving radio-, chemo- and gene therapy. This review is focused on the use of rat C6 glioma as an experimental model system for GBM and provides an overview of the experimental data published in the literature using this cell line in elucidating the mechanism of tumor growth, angiogenesis and invasion, and in the design and evaluation of anticancer therapies. Understanding the stages of malignant brain tumor progression requires a series of experimental approaches with a varying degree of complexity. Implantation of malignant cells into animal brain tissue closely resembles in vivo tumor growth and has the advantage over simplified models that inflammatory and vascular mechanisms are activated. However, the complexity of these models makes it difficult to identify the individual processes involved in sustained tumor growth, angiogenesis and invasion. In cell culture models, the effect of growth factors, extracellular matrix components, proteases and adhesion molecules can be investigated. The secretion of tumor-derived factors into the medium can also be analyzed when simplified models are used. This review is a compilation of experimental data focused on the characterization of tumor-related processes and on the evaluation of new therapies for the treatment of malignant glial neoplasms using rat C6 glioma as a model system.

Animals↗