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PubMed1999

A novel in vitro experimental model for ovarian endometriosis: the three-dimensional culture of human ovarian surface epithelial cells in collagen gels.

OBJECTIVE: To develop an in vitro experimental model of ovarian endometriosis using human cells and to investigate the pathogenesis of endometriosis. DESIGN: Controlled in vitro coculture study. SETTING: A department of obstetrics and gynecology at a university hospital. PATIENT(S): Ovaries and endometrium were obtained from patients who underwent a hysterectomy because of gynecologic disease. INTERVENTION(S): Human ovarian surface epithelial (OSE) cells were cultured alone and OSE cells and endometrial stromal (ES) cells were cultured together in a three-dimensional collagen gel culture system with or without the addition of E2. MAIN OUTCOME MEASURE(S): The aggregated collagen gels containing the cultured cells were examined morphologically. RESULT(S): The OSE cells in single culture with E2 formed circular arrangements. These cells were immunohistochemically positive for cytokeratin but negative for epithelial membrane antigen. In the cocultures of OSE and ES cells with E2, the OSE cells formed a lumen structure surrounded by ES cells. Immunoreactivity for cytokeratin and epithelial membrane antigen was detected in the glandular cells and cilia were identified on the cell surface by electron microscopy. Without the addition of E2, no structures were detected. CONCLUSION(S): A new in vitro experimental model was established with the aid of human OSE cells. Endometriotic lesions can arise through a process of metaplasia from OSE cells in the presence of E2 and ES cells.

Adult↗

PubMed1994

Antiarrhythmic effects of nebivolol in experimental models in vivo.

Antiarrhythmic effects of nebivolol, a cardioselective beta 1-adrenoceptor blocker facilitating vascular release of nitric oxide (NO), were investigated in different experimental models. In the reperfusion-induced arrhythmias after 5 min of left coronary artery ligation in rats, nebivolol 1.25 mg/kg intravenously (i.v.) reduced the incidence of ventricular tachycardia (VT) from 85% in the solvent group to 33% (p < 0.05) and decreased that of ventricular fibrillation (VF) to 20% vs. 67% in the solvent group, (p < 0.05). In ischemia-induced arrhythmias resulting from 20-min coronary artery ligation in rats, nebivolol 1.25 mg/kg i.v. reduced the incidence of VT to 50% as compared with 87% in the solvent group and decreased the incidence of VF to 17% as compared with 67% in the solvent group (p < 0.05). In electrically stimulated hearts in open-chest guinea pigs, nebivolol produced a dose-dependent (0.16-2.5 mg/kg i.v.) increase in VF threshold (VFT). In guinea pigs with ouabain-induced cardiotoxicity, nebivolol 1.25 mg/kg i.v. (n = 7) doubled the doses of ouabain required to provoke toxic ECG changes as compared with those in the solvent-pretreated group. In rats with aconitine-induced cardiac toxicity, nebivolol 1.25 mg/kg i.v. significantly reduced the incidence of ventricular arrhythmias. Our results demonstrate that nebivolol suppresses arrhythmias in various experimental models in vivo.

Animals↗

PubMed1996

Experimental models of congenital hydrocephalus and comparable clinical problems in the fetal and neonatal periods.

Morphological and developmental changes of the ventricular system are analyzed in three major experimental models of congenital hydrocephalus in the rat: 6-aminonicotinamide (6-AN)-induced and LEW/Jms and HTX mutant hydrocephalus. The clinically comparable forms of hydrocephalus and problems occurring during each period of intrauterine hydrocephalus are then discussed. Comparative morphological study revealed that 6-AN-induced hydrocephalus was comparable to the Dandy-Walker syndrome and that the critical period regarding this syndrome in fetal life was at the time of "legal termination". The LEW/Jms and HTX mutant models were identical with regard to the form of progressive hydrocephalus in the postnatal period, but the condition underlying the hydrocephalus during the fetal period differed. The LEW/Jms model was comparable to primary congenital aqueductal stenosis (aqueductal agenesis), and the hydrocephalic state appeared in the period of "intrauterine preservation" before pulmonary maturation was completed. On the other hand, the HTX fetuses demonstrated secondary change of the aqueduct in the perinatal period, although the model was considered to be of congenital communicating hydrocephalus. Cerebrospinal fluid (CSF) dynamics studied in the fetuses with 6-AN-induced hydrocephalus disclosed considerable pathophysiology comparable to "hydromyelic hydrocephalus." The historical trends of animal experimental models of congenital hydrocephalus are reviewed and comparable clinical problems suggested by those models discussed further.

6-Aminonicotinamide↗

PubMed1994

[Studies of experimental model of reflux esophagitis in rats by ligature on both lower portion of duodenum and most of forestomach].

It has been well established that reflux of gastroduodenal contents causes reflux esophagitis. Experimental model of reflux esophagitis in rats was devised by 24hrs ligature on both lower portion of duodenum and most of forestomach. Erosion of esophageal mucosa and thickening of esophageal wall developed in macroscopic findings. Histologically, many neutrophils were found from lamina propria to muscular layer, mainly in lamina propria. Edema and thickening of submucosal layer developed in cases with 24hrs ligature. These severe inflammatory changes in submucosal layer suggested that it caused thickening of esophageal wall. Bile reflux was found in gastric contents of this model. No mucosal lesions were found in cases with ligature on lower portion of duodenum. Findings in this experimental model of reflux esophagitis suggested significant roles of gastric juice and bile acids in the pathogenesis of reflux esophagitis. This model was thought to be useful for studies of pathophysiology of reflux esophagitis caused by reflux of gastroduodenal contents.

Animals↗

PubMedDate not supplied

The choice of experimental models in cancer research: the key to ultimate success or failure?

The technologies available for assessing the size and physiological status of malignant tumours are becoming more and more sophisticated. Some of these detect phenotypic biochemical alterations resulting from the genetic changes associated with malignant transformation. Many, however, monitor the abnormal relationship between the tumour mass and the host, detecting pathophysiological changes which result from the host/tumour interaction. The most important of these involve the microregional heterogeneities of nutrients resulting from diffusion patterns around abnormal, newly-formed vascular networks, or inflammatory or immune responses of the host to the tumour. In order to validate new technologies for introduction to clinical medicine they are usually extensively tested in experimental models for cancer. The relevance of these models (whether in vitro cell cultures or experimental tumours) must be considered carefully at the outset, with the factors that influence the parameter being measured, e.g., oxygen or energy status, being given special attention. The genetic similarity of tumour and host, the site of tumour growth, the size of the tumour, the burden it imposes and the immunocompetence of the host are all important features of the experimental model. Inappropriate models may give totally misleading information which cannot be extrapolated to human cancers.

Animals↗

PubMed2002

The 21-day postnatal rat ventricular cardiac muscle cell in culture as an experimental model to study adult cardiomyocyte gene expression.

The purpose of this study was to develop and characterize a cardiomyocyte culture system for use as an experimental model to study the mechanism(s) by which cardiac muscle cells permanently exit the cell cycle during early neonatal life. Ventricular cardiomyocytes, isolated by retrograde perfusion of hearts from 21-day-old and adult rats, were compared through 10 days of culture. Expression patterns of genes encoding developmentally programmed proteins were determined to be similar between cardiomyocytes cultured from 21-day-old and adult rats, using the reverse transcription polymerase chain reaction. A lacZ-expressing reporter gene was used to test the efficiency of gene delivery in cultured cardiomyocytes. Transfections using cationic liposomes yielded 24+/-7, 25+/-7 and 10+/-1% cardiomyocytes positive for beta-galactosidase activity in cultured 1-day, 21-day and adult cardiomyocytes, respectively. Direct needle microinjection resulted in 48+/-7, 35+/-6 and 37+/-5% cardiomyocytes positive for enzymatic activity in 1-day, 21-day and adult cardiomyocytes, respectively. Cell cycle-specific cDNA arrays were used to analyze the expression pattern of cell cycle-related genes in 12-O-tetradecanoyl-phorbol-13-acetate (TPA)- and non-TPA-treated cultured 21-day cardiomyocytes. Based on the similarity of cultured 21-day to adult ventricular cardiomyocytes and their high transfection efficiencies, we propose the use of cultured cardiomyocytes from 21-day-old rat ventricles as an experimental model system for the study of adult cardiomyocyte gene expression and cell cycle machinery.

Animals↗

PubMed2002

Protective effect of melatonin in a chronic experimental model of Parkinson's disease.

Parkinson's disease is a chronic condition characterized by cell death of dopaminergic neurons mainly in the substantia nigra. Among the several experimental models used in mice for the study of Parkinson's disease 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced parkinsonism is perhaps the most commonly used. This neurotoxin has classically been applied acutely or sub-acutely to animals. In this paper we use a chronic experimental model for the study of Parkinson's disease where a low dose (15 mg/kg bw) of MPTP was administered during 35 days to mice to induce nigral cell death in a non-acute way thus emulating the chronic condition of the disease in humans. Free radical damage has been implicated in the origin of this degeneration. We found that the antioxidant melatonin (500 microg/kg bw) prevents cell death as well as the damage induced by chronic administration of MPTP measured as number of nigral cells, tyrosine hydroxylase levels, and several ultra-structural features. Melatonin, which easily passes the blood-brain barrier and lacks of any relevant side-effect, is proposed as a potential therapy agent to prevent the disease and/or its progression.

Animals↗

PubMed1995

Hepatocyte-like cells in the pancreatic islets: study of the human foetal pancreas and experimental models.

OBJECTIVE: To determine the existence of hepatocyte-like cells in the human foetal pancreas. STUDY DESIGN: Foetal pancreas was examined in parallel with two experimental models involving pancreatic tissue regeneration. Foetal pancreases (n = 20; 10 to 18 weeks) were obtained from spontaneous abortions and were histologically examined using haematoxylin-eosin and PAS staining. Tissues from food-deprived and copper-deficient female Wistar rats were studied following D-penicillamine administration, and tissue from female hamsters was evaluated following administration of a pancreatic carcinogen. Histological examination in animal studies included haematoxylin-eosin staining, and diaminobenzidine histochemistry. RESULTS: The presence of a characteristic cell-type whose morphology was distinct from islets cells and exocrine pancreas cells was observed in human foetal pancreatic islets. These cells were morphologically similar to hepatocyte-like cells and were compatible to those observed in the experimental models. Topographical relationships suggest that these originate from stem cells which are related to the pancreas duct cells. CONCLUSION: We conclude that hepatocyte-like cells or precursors exist in the human foetal pancreas.

3,3'-Diaminobenzidine↗

PubMed2004

Neuronal cytoskeletal alterations in an experimental model of depression.

It has been proposed that depression is associated with hippocampal morphological changes. The apical dendrite atrophy of hippocampal CA3 pyramidal neurons has been described in experimental models of depression. The aim of the present study was to determine which cytoskeletal components are involved in the morphological changes previously described in the hippocampus of depressed animals. The expression of different neuronal cytoskeletal markers was analyzed by immunohistochemistry in rats exposed to a learned helplessness paradigm, an experimental model of depression. Rats were trained with 60 inescapable foot shocks (0.6 mA/15 s) and escape latencies and failures were tested 4 days after training. Animals in which learned helplessness behavior persisted for 21 days were included in the depressed group. No foot shocks were delivered to control rats. Microtubule-associated protein 2 (MAP-2) and light (NFL; 68 kDa), medium (NFM; 160 kDa) and heavy (NFH; 200 kDa) neurofilament subunit immunostainings were analyzed employing morphometric parameters. In the depressed group, NFL immunostaining decreased 55% (P<0.05) and 60% (P<0.001) in CA3 and dentate gyrus, respectively. In the same areas, MAP-2, NFM and NFH immunostainings did not differ between depressed and control animals. Since NFL is present in the core of mature neurofilament, it is proposed that hippocampal depression-associated plastic alterations may be due to changes in the dynamics of the neurofilament assembly.

Animals↗

PubMedDate not supplied

Experimental models of temporary normothermic liver ischemia.

Hepatic ischemia/reperfusion injury has so far been investigated in various experimental models. A clinical transfer of experimental results is, however, problematic because of anatomical and physiological differences and also the inevitable simplification of experimental work. The choice of model must therefore be adapted to the clinical question to be answered. The simplest procedure for inducing normothermic ischemia is to clamp the hepatoduodenal ligament. Models that do not avert portal congestion are regarded as unsuitable. Our current understanding of the pathogenesis of ischemia/reperfusion injury depends mainly on studies whose authors have investigated either global liver ischemia with a portocaval shunt, spleen transposition and in the isolated perfused system, or partial ischemia. This review is a critical examination of various approaches to the study of normothermic hepatic ischemia in experimental animals.

Age Factors↗

PubMed1994

Formulation of a generalized experimental model for a manually driven flywheel motor and its optimization.

A manually driven brick-making machine has recently been developed without the benefit of any design data. The machine consists of three main units: a pedal-driven flywheel motor; the transmission between the flywheel shaft and the input shaft of the process machine; and the process unit, consisting of auger, cone and die. The machine was essentially developed on the basis of general mechanical design experience and intuition. In spite of this, it proved to be functional and economically viable. However, it was felt essential to develop it scientifically. This paper reports on the full development of the pedal-driven flywheel motor. As this is a human-machine system it is highly unlikely that a logic-based model can be established. Therefore an experimental method is adopted to evolve a generalized experimental model, which is further optimized to satisfy several objective functions.

Journal Article↗

PubMed1987

Carbon disulfide axonopathy. Another experimental model characterized by acceleration of neurofilament transport and distinct changes of axonal size.

The role of axonal transport in the development of structural changes of axons can be examined using experimental models. Two different compounds, 2,5-hexanedione (2,5-HD) and carbon disulfide (CS2), cause axonopathies characterized by the formation of neurofilaments (NF) containing enlargements in preterminal regions of central and peripheral axons. These axonopathies are excellent experimental models of the giant axonal neuropathies, a group of acquired and inherited human diseases of the central and peripheral nervous system. We previously reported that following administration of 2,5-HD, transport of NF is accelerated while number of NF and cross-sectional area are decreased in regions of the axon proximal to the enlargements. We proposed that acceleration of NF transport leads to a 'longitudinal' redistribution of NF which are decreased proximally and increased distally where they form the NF containing axonal enlargements. We have now carried out morphometric, transport and immunocytochemical studies in primary visual axons of rats exposed to CS2. NF-containing axonal enlargements were observed in optic tract and superior colliculus and they increased in number in a proximodistal direction. There was no detectable axonal degeneration and the cross-sectional area of axons proximal to the enlargements was decreased. Transport of NF was markedly accelerated. Immunostaining showed that all 3 NF subunits and phosphorylated epitopes of the 200-kDa NF subunit were present in the NF-containing axonal enlargements. All these findings were similar to those previously observed in the 2,5-HD axonopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

[Normal values for hematological and hemostatic parameters in the rabbit. Determination of new parameters for experimental models of thrombosis and hemostasis].

PURPOSES: Assessment of normal haematological values in the rabbit using a semi-automatic analyser. Evaluation of new haemostatic parameters necessary for experimental models in thrombosis and haemostasis. MATERIAL AND METHODS: 20 New Zealand male rabbits of 2-2.5 kg were anaesthetized and blood was collected from the jugular vein. The following haematological determinations were carried out using a semi-automatic analyser: red blood cells count, haemoglobin, haematocrit, indexes, white blood cells count, platelet count and mean platelet volume. The parameters used to assess the physiological haemostasis in rabbit were: bleeding time, fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time; and others not yet determined in the rabbit: antithrombin III, thrombin-antithrombin complexes and F1+2 fragments to measure the basal thrombin-formation activity, and fibrin D-dimer and fibrinogen degradation products for fibrinolysis activity. RESULTS: The haematological results obtained were similar than with other techniques, but with no stress influence. Normal values for haemostatic parameters studied are shown, including the parameters for the determination of physiological thrombin-formation and fibrinolysis activity. F1+2 fragments and fibrinogen degradation products could not be evaluated. CONCLUSIONS: The haematological results obtained were completely normal. All the haemostatic parameters studied were found useful to determine the physiological activity of coagulation and fibrinolysis in the rabbit, and specially for experimental models of hypercoagulability and hyperfibrinolisys states.

Animals↗

PubMedDate not supplied

Physiologic intracranial calcification with hyperintensity on MR imaging: case report and experimental model.

CT and MR imaging showed basal ganglia calcification that appeared as high signal intensity on T1-weighted images of a patient with pseudohypoparathyroidism. MR imaging of an experimental model of calcium phosphate suspensions showed a signal similar to that seen in the patient. Additionally, T1 and T2 relaxation times of the solutions were measured and showed decreases in both parameters with increasing calcium phosphate concentrations. Intracranial calcification can appear as high signal intensity on T1-weighted images. An experimental model shows that the calcium salt decreases the T1 of surrounding water. Therefore, calcium, and possibly other elements, may induce paramagnetic susceptibility effects.

Adolescent↗

PubMed1994

Sequential study of an experimental model of graft vs. host disease (GvHD) in non-immunosuppressed F1 (CBA/J x C57BL/6) mice.

In order to determine the optimal day for the evaluation of an experimental model of GvHD in F1 mice and the histopathologic evolution of the lesions in different organs, we studied 10-day-old F1 (CBA/J x C57BL/6) mice inoculated with splenic lymphoid cells of the male parental CBA/J strain (n = 42) that were sacrificed between 1 and 14 days postinoculation. The evolution of the relative spleen index (RSI) and the histopathologic lesions in different organs were also determined. F1 mice inoculated with Medium 199 were used as controls. Significant RSI increases (p < 0.0001) were found in the experimental group between 2 and 14 days postinoculation, with a peak at the eighth day, associated with the most severe histopathologic lesions in the organs studied. We suggest the eighth day as the optimal time for evaluation of this experimental model.

Animals↗

PubMed1964

COMPARISON OF IMMUNE MECHANISMS IN VARIOUS EXPERIMENTAL MODELS OF CHOLERA.

Two of the main features of human cholera-induction of diarrhoea and confinement of the infection to the lumen of the intestinal tract-may be reproduced in three experimental models: (a) the streptomycin-treated, starved guinea-pig; (b) the intestinal loop in the adult rabbit; and (c) the suckling rabbit. In this paper the author compares the two last-mentioned models with his earlier work in guinea-pigs.Intestinal antibody (coproantibody) was highly protective, while circulating antibody had little or no effect, in all three models. The protective coproantibody was specific for the heat-stable vibrio antigens. It did not affect the growth of vibrios in the intestine, and its function may possibly be regarded as antitoxic rather than antibacterial. Oral vaccination protected adult rabbits against challenge by the loop technique. Heat-killed vaccine was as effective in this respect as live vaccine.The author feels that the present uncertainty concerning the protective value of cholera vaccination may be due to the fact that conventional vaccine is designed to induce high serum titres only. He considers that since oral vaccine has been shown to induce and maintain the production of coproantibody in human volunteers, a field trial should be carried out to determine whether coproantibody is as protective in man as it has proved to be in the experimental models.

Adult↗

PubMed1996

A new rodent experimental model of esophageal atresia and tracheoesophageal fistula: preliminary report.

In spite of the interest paid by pediatric surgeons to esophageal atresia (EA) with tracheoesophageal fistula (TEF), no animal experimental model has been available for investigation. This preliminary report describes a reproducible fetal model of these malformations. Time-mated pregnant rats were given 1.5, 1.75, or 2 mg/kg of Adriamycin intraperitoneally on days 6 to 9 of gestation, and the litters were recovered on day 21 (near full-term). The amount of amniotic fluid was measured, and the fetuses were dissected and studied histologically. The findings were compared with those of suitable control fetuses. Adriamycin-exposed fetuses weighed less than controls. EA with TEF (Gross' type C) was found in 28%, 45%, and 41% of animals in the three dose groups (respectively). The malformation was anatomically identical to that of the human neonate, and the amount of amniotic fluid in affected fetuses increased significantly. In one instance, an H-type fistula was observed. In addition to esophageal interruption, many other malformations fitting within the human VATER association were found: duodenal atresia (41%, 50%, and 47%, respectively), anorectal (28%, 50%, and 41%), renal (81%, 100%, and 100%), and limb malformations (0%, 2.3%, and 13.8%). This new, easily reproducible and relatively inexpensive experimental model of one of the most interesting pediatric surgical malformations permits new research into both its embryogenesis and the biology of the malformed fetus.

Abnormalities, Drug-Induced↗

PubMed1996

Thromboxane receptor blockade improves oxygenation in an experimental model of acute lung injury.

BACKGROUND: Adult respiratory distress syndrome remains a major cause of morbidity and mortality. We investigated the role of thromboxane receptor antagonism in an experimental model of acute lung injury that mimics adult respiratory distress syndrome. METHODS: Three groups of rabbit heart-lung preparations were studied for 30 minutes in an ex vivo blood perfusion/ventilation system. Saline control (SC) lungs received saline solution during the first 20 minutes of study. Injury control (IC) lungs received an oleic acid-ethanol solution during the first 20 minutes. Thromboxane receptor blockade (TRB) lungs received the same injury as IC lungs, but a thromboxane receptor antagonist (SQ30741) was added to the blood perfusate just prior to study. Blood gases were obtained at 10-minute intervals, and tidal volume, pulmonary artery pressure, and lung weight were continuously recorded. Oxygenation was assessed by measuring the percent change in oxygen tension over the 30-minute study period. Tissue samples were collected from all lungs for histologic evaluation. RESULTS: Significant differences were found between SC and IC lungs as well as TRB and IC lungs when comparing pulmonary artery pressure (SC = 33.1 +/- 2.2 mm Hg, TRB = 35.4 +/- 2.1 mm Hg, IC = 60.4 +/- 11.1 mm Hg; p < 0.02) and percent change in oxygenation (SC = -20.6% +/- 10.3%, TRB = -24.2% +/- 9.5%, IC = -57.1% +/- 6.2%; p < 0.03). None of the other variables demonstrated significant differences. CONCLUSIONS: Thromboxane receptor blockade prevents the pulmonary hypertension and the decline in oxygenation seen in an experimental model of acute lung injury that mimics adult respiratory distress syndrome.

Animals↗