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PubMed1983

Specific suppression of humoral and delayed hypersensitivity responses by cyclophosphamide in an experimental model of autoimmunity.

The aim of this report is to investigate the effect of cyclophosphamide (CY) in an experimental model of autoimmunity to rat male accessory glands. The results indicated that 100 mg/kg of this drug suppressed humoral immune response that persisted for at least 45 days when administered 3 days after the first immunization of rats with modified rat male accessory glands (MRAG) in complete Freund's adjuvant (CFA). Administration of the drug 3 days before ID injection of antigen caused a shorter suppression of antibody formation. Delayed type hypersensitivity (DTH) studied 13 days after the first immunization was suppressed only in the animals that were administered CY after the antigen. The specificity of the immunosuppression was studied in rats treated with CY after the first immunization with MRAG using aggregated human gamma-globulin (AHGG) as an unrelated antigen. The studies demonstrated significant suppression of DTH (p less than 0.005) and humoral immunity only against MRAG. On the contrary, the response to AHGG was not significantly modified.

Animals↗

PubMedDate not supplied

[An experimental model of data base organization in glaucoma with computer processing (a preliminary note)].

The authors report on an experimental model of data base set up for glaucoma with possibilities of statistical-mathematical processing. The application is designed for miniprocessors of the INDEPENDENT or CORAL type in FORTRAN 77. The paper presents the level structure of the display, and the ways of using the information under the form of assisted diagnosis and prognosis, according to which the attention is then directed to the rhythm and detailed content of the future examination.

Computer Systems↗

PubMed1993

Arterial intimal flaps: a comparison of primary repair, aspirin, and endovascular excision in an experimental model.

The optimal management for traumatic arterial intimal injuries is unresolved. Three therapeutic options were compared in an experimental model employing a standard intimal flap created in 51 canine superficial femoral arteries. Group 1 (14 arteries) underwent resection with end-to-end repair. Group 2 (19 arteries) received acetylsalicylic acid (ASA) and observation only. Group 3 (21 arteries) underwent endovascular excision of the flap with angioscopic guidance. Control intimal flaps (18 arteries) were created and observed without further intervention. Patency in group 1 (primary repair) and group 2 (ASA) was 100%; the patency in both was significantly (p < 0.05) greater than in the controls, which was 67%. Patency in group 3 (endovascular excision) was 79%. Residual luminal defects were observed in only 8% of the arteries repaired primarily, but in 76% of the aspirin-treated arteries. Residual luminal defects following endovascular excision were present in 53% of the arteries remaining patent. Although resection and primary repair (group 1) provided better results than observation alone (control), addition of ASA (group 2) also sustained patency. However, a high incidence of residual intimal defects occurred, the natural history of which is unknown. While endovascular excision (group 3) may become a feasible alternative, current technology provided inferior patency with frequent residual intimal defects. These results suggest that observation alone supplemented with antiplatelet medication (ASA) may be adequate treatment, but longer follow-up is necessary for confirmation.

Angioscopy↗

PubMed1975

Experimental models for the modification of human drug self-administration: Methodological developments in the study of ethanol self-administration by alcoholics.

Experimental studies of human ethanol self-administration are reviewed, and a description is provided of the procedural evolution that has oc-urred in the experimental study of the determinants of human ethanol self-administration. Human experimental models of alcoholism have been established within residential laboratories which permit chronic availability of ethanol to volunteer alcoholic subjects. Experimentation within such environments has progressed from observational and descriptive studies of experimental intoxication to studies that manipulate experimental variables so as to modify (reduce) ethanol self-administration by alcoholic subjects. To observe systematic effects of manipulated variables it has been necessary to develop sensitive baselines of ethanol self-administration. When ethanol intake has been relatively unrestricted, wide spontaneous fluctuations have made difficult the evaulation of manipulated variables. When a variety of restrictions on ethanol availability have been imposed, sensitive self-administration baselines have been established which have permitted the direct experimental assessment of some of the determinants of ethanol self-administration. Six methodological principles are suggested for enhancing the information yield of future research on the determinants of ethanol self-administration. The same general methodology is suggested for research with other varieties of drug self-administration.

Administration, Oral↗

PubMedDate not supplied

Experimental models for antiphospholipid studies.

Three types of Experimental Animal Models have been used to investigate APA. 1) Passive transfer of APA to nocive mice. Branch et al injected pregnant Balb/c mice with purified IgG APA from patients with recurrent fetal loss. 2) Active immunization with APA. Backimer et al immunized Balb/c mice with a human monoclonal APA carrying the pathogenic idiotypes. 3) Immunization with beta 2 glycoprotein I (beta 2 GPI) (APA cofactor). Using affinity chromatography, we separated two distinct populations of antibodies. One was specific for beta 2GPI without binding to PL. Another population had a dual specificity for PL and beta 2GPI.

Abortion, Habitual↗

PubMed1998

An experimental model of acute encephalopathy after total body irradiation in the rat: effect of liposome-entrapped Cu/Zn superoxide dismutase.

PURPOSE: To develop an experimental model of acute encephalopathy following total body irradiation in rats and to define the therapeutic effect of liposome-entrapped Cu/Zn superoxide dismutase. METHODS AND MATERIALS: A total of 120 4-month-old rats received 4.5 Gy total body irradiation (TBI) while 120 rats received sham irradiation. A behavioral study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed 5 hours before irradiation and repeated the following days. Subcutaneous treatment was started 1 hour after irradiation and repeated daily for 2 weeks. In both the irradiated and sham group, three subgroups were defined according to the treatment received: liposome-entrapped Cu/Zn superoxide dismutase (0.5 mg/kg), liposomes only, normal saline. RESULTS: This work comprised two consecutive studies. In study A (90 rats) the one-way avoidance test was administered daily from day 0 to day 4 with a recall session at day 14. In study B (validation phase in 150 rats) the behavioral test was performed only from day 0 to day 6. Before irradiation, all rats showed a similar behavioral response. Study A (6 groups of 15 rats): Following TBI, irradiated rats treated with liposomes only or saline demonstrated a significant delay in learning the one-way avoidance test in comparison with sham-irradiated rats (0.05 < p <0.001 depending upon the day of evaluation and the subgroup type). In contrast, irradiated rats treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from sham-irradiated rats. Study B (6 groups of 25 rats): The results were the same as those in study A, demonstrating a significant delay in the learning of the test in the liposome and saline-treated irradiated rats in comparison with sham-irradiated rats (0.02 < p < 0.001). The irradiated rats, treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from the sham-irradiated controls. CONCLUSION: This study indicates that a relatively low dose of total body irradiation induces a substantial acute learning dysfunction in the rat. This effect is prevented by the administration of liposome-entrapped Cu/Zn superoxide dismutase.

Animals↗

PubMed2005

Experimental model of inappropriate sinus tachycardia: initiation and ablation.

OBJECTIVE: The purpose of the present study was to develop an experimental model of inappropriate sinus tachycardia (IST) by injecting a catecholamine into a fat pad containing autonomic ganglia (AG) innervating the sinus node (SN). METHODS: Initial protocols in 3 groups of pentobarbital anesthetized dogs consisted of (1) slowing the heart rate (HR) by electrical stimulation of AG in the fat pad; (2) the effect of intravenous injection of epinephrine (0.1-0.3 mg) on the HR and systolic blood pressure (BP); (3) the response of SN rate to intravenously injected isoproterenol (1 microgm/kg). These studies established a reference for the response to epinephrine injection (mean dose 0.2 +/- 0.9 mg, n = 14) into the fat pad at the base of the right superior pulmonary vein (RSPV). ECG leads, right atrial and His bundle electrograms, BP and core body temperature were continuously monitored. RESULTS: Epinephrine, injected into the fat pad, caused a significant increase in heart rate (HR, average: 211 +/- 11/min, p < 0.05 compared to control) but little change in systolic BP, 149 +/- 10 mmHg, p = NS (Group I, N = 8). The tachycardia lasted >30 minutes. Ice mapping and P wave morphology showed the tachycardia origin in the SN in 6/8 and in the crista terminalis (CT) in 2. Injection of 0.4 cc of formaldehyde into the FP restored HR (159 +/- 16) toward baseline (154 +/- 18). In Group II (N = 6), the same regimen induced a significant increase in both HR and systolic BP (194 +/- 17/min and 230 +/- 24 mmHg, respectively) compared to control values (143 +/- 23/min, 162 +/- 24 mmHg) which lasted for > 30 minutes. Ice mapping and P wave morphology showed that the pacemaker was in the SN (1), overlying the CT (2), or atrioventricular junction (2). Formaldehyde (0.4 cc) injected into the FP restored both HR and systolic BP toward baseline values (148 +/- 29/min and 152 +/- 24 mmHg, p = NS) and prevented, slowing of the HR by electrical stimulation of the AG; moreover, the same dose of epinephrine injected intravenously increased HR and SBP but only for 2-5 minutes; Isoproterenol (1 microg/kg) injected intravenously induced essentially the same increase in sinus rate after AG ablation as in the control state (194 +/- 15/min vs 193 +/- 23/min, p = NS). CONCLUSION: Experimental IST is mainly localized in the SN or CT. Ablation of the AG terminates IST without impairing the SN response to an adrenergic challenge.

Animals↗

PubMed1998

Tissue-specific galactosyltransferase abnormalities in an experimental model of rheumatoid arthritis.

OBJECTIVE: To investigate whether the observed pathophysiological similarities that develop in both the collagen induced experimental model of arthritis (CIA) and rheumatoid arthritis (RA) are associated with similar glycosylation changes, and to evaluate possible differences in the relative activity of the glycosylation enzyme beta, 1-4 galactosyltransferase (GTase) within various tissues, and thus provide a new insight into the potential pathogenic mechanisms controlling glycosylation changes. METHODS: Lymphocytic membrane-bound GTase activity was examined in 30 mice with CIA, 30 age matched controls and 10 adjuvant treated non-arthritic DBA/1 mice. Tissue-specific changes were assessed by comparison of GTase activity in peripheral (P.GTase) and paired splenic lymphocytes. In addition, we also investigated the effect that these changes may exert on the overall extracellular level of this enzyme, by assaying serum GTase (S.GTase) activity in these and a further group of 27 arthritic and 20 control mice. To analyse this synthetic abnormality in greater depth and to investigate the relevance of these glycosylation changes to the pathogenesis of arthritis, we also examined the humoral regulatory component associated with this system by assaying for both anti-collagen as well as anti-GTase antibodies. RESULTS: The induction of arthritis in DBA/1 mice results in a marked reduction in P.GTase activity, compared with age-matched unimmunised mice and the adjuvant controls. In contrast to the P.GTase, splenic GTase activity was found to be similar in all the groups examined. Correspondingly, serum GTase activity was also found to be significantly lower in the collagen induced arthritic mice. This overall reduction in beta, 1-4 GTase activity reflects the clinical severity of arthritis and is associated with increased levels of naturally occurring anti-GTase antibodies. CONCLUSIONS: The GTase defect seen in the peripheral B and T cells in rheumatoid arthritis is also evident in the arthritic DBA/1 mouse model of RA. This may indicate a common pathological process in both rheumatoid disease and CIA, in which changes in glycosylation are dependent on the aberrant modulation of GTase in circulating, but not splenic lymphocytes. The relative expression and activity of glycosyltransferases within various tissues may not only contribute to immunoglobulin G (IgG) glycosylation changes, but perhaps also the aberrant expression of cell surface carbohydrates and thus cell trafficking.

Animals↗

PubMed1989

Human serum transglutaminase and coeliac disease: correlation between serum and mucosal activity in an experimental model of rat small bowel enteropathy.

Transglutaminase (TG) activity is increased in the mucosa of patients with coeliac disease. Among 18 patients with untreated coeliac disease we have found a significant decrease (p less than 0.001) in serum levels of TG activity (0.72 (0.23) mU/ml). There was no significant differences between 16 treated coeliacs (1.24 (0.28) mU/ml) and 30 normal controls (1.63 (0.42) mU/ml). To evaluate the connection between serum and mucosal TG activity we used the experimental model of methotrexate induced acute hypoplastic enteropathy in the rat. Transglutaminase activity was unchanged in serum and mucosa 24 and 48 hours after MTX administration, but increased in mucosa (2.606 (0.95) v basal 0.207 (0.026) mU/mg protein, p less than 0.001) and significantly decreased in serum at 72 hours (2.08 (0.38) v basal 5.56 (1.50) mU/ml, p less than 0.001) during intestinal cell proliferation. Activity of the enzyme in the mucosa and serum returned to baseline levels within 120 hours. This experimental animal model helps to explain the data of TG activity in human intestinal mucosa and serum reported in this study. Results are mean (SD).

Animals↗

PubMed1989

Synopsis of the anticoagulant and antithrombotic profile of the low molecular weight heparinoid Org 10172 in experimental models.

Org 10172 shows dose-dependent antithrombotic activity in various experimental thrombosis models. It produces less hemorrhage at an equivalent antithrombotic effect than commercial heparin in various experimental bleeding models. It shows a better benefit (antithrombotic) to risk (bleeding) ratio than SP54 and commercial heparin. The benefit to risk ratio of Org 10172 is better than some LMW heparins and equivalent to other LMW heparins, depending on the method of preparation. The antithrombotic effect of Org 10172 in animal models has a much longer duration than that of commercial heparin and also LMW heparins. Org 10172 predominantly inactivates generated thrombin via the formation of HC II-thrombin complexes, whereas commercial heparin and LMW heparins inactivate generated thrombin via AT III-thrombin complexes.

Animals↗

PubMed2002

Laser doppler flow imaging of open lower leg fractures in an animal experimental model.

PURPOSE: Open lower leg fractures are frequently associated with severe soft tissue damage, followed by osteomyelitis. Using an animal experimental model, we investigated the effect of timing of coverage of a tibial fracture with a local muscle flap. METHODS: 80 rabbits had a tibial fracture induced in a standardised fashion, which was stabilised by screw osteosynthesis. After 3 (group A; n=40) and 7 days (group B; n=40), respectively, the tissue defect was covered by a local gastrocnemius flap. In increasing intervals from 1 to 2, 4, 8, and 16 weeks, the rabbits from each group were killed and the bone fracture was analysed histomorphologically. Cortical microcirculation was measured by 2-channel laser doppler flowmetry. RESULTS: Muscle flaps after 3 days improved perfusion significantly as compared with 7 days (24 Flux [standard error, 5 Flux] versus 10 Flux [3 Flux]; baseline, 1.4 Flux). Group A animals also displayed a lower rate of necrosis (0 versus 38). The incidence of osteomyelitis was higher in group B than in group A (24% versus 0%). CONCLUSION: Laser doppler flowmetry was proven to be a reliable, minimally invasive means for identifying avital tissue, leading to reduction in the loss of vital bone tissue in experimental settings.

Animals↗

PubMed2005

Experimental model of fistula-in-ano.

PURPOSE: This study was designed to create and evaluate an experimental porcine model of fistula-in-ano. METHODS: Initial cadaveric dissection enabled refinement of the technique for fistula formation and histoanatomical study of the porcine anal canal. Subsequently, three surgically created fistulas were treated by seton drainage in each of eight male pigs (weight, 38-41 kg). After 26 days, magnetic resonance imaging at 1.5 Tesla was performed and setons removed under general anesthesia, enabling clinical and microbiologic track assessment. Two pigs were killed for histologic fistula track assessment. RESULTS: Histoanatomical assessment noted a rudimentary internal anal sphincter, together with structures resembling anal glands. Artificial fistulas persisted during seton drainage and were more often associated with fecal than skin-derived organisms compared with both perineal and anal canal swabs (P = 0.002). All six fistulas assessed histologically had a lumen, and abundant surrounding granulation tissue similar to that seen in human fistula-in-ano. Epithelialization was not evident in any track. Fistulas were visualized as high signal tracks using magnetic resonance imaging. CONCLUSIONS: Porcine anal anatomy resembles that of humans, and an experimental model proved suitable when assessed by magnetic resonance imaging, microbiology, and histologically, which demonstrated abundant granulation tissue. This model could be further used to investigate fistula treatments.

Animals↗

PubMed1983

[Experimental model for hemodynamic and metabolic studies of extracorporeal circulation. Apropos of 14 cases].

The authors present an homogeneous and stable experimental model, the basic characteristics of which are: 14 extracorporeal bypass with: total bypass; normothermia; total haemodilution; beating heart; continuous flow in dogs anesthetised with chloralose. Three methods were employed: continuous recording of the venous lactate concentration; invasive electromagnetic measurement of the arterial blood flow; measurement of the tissular capillary blood flow with radioactive labelled microspheres. The statistic treatment of the informations gathered confirms that those experimentations took place in normothermia and constant: pH, venous and arterial pressure, cardiac pacing and arterial carotid blood flow. We noticed no modification of the body electrolytic repartition; blood gas variations do not modify haemodynamic conditions. Increase of the lactate concentration, as noticed in the literature, is in relation with a catecholamine hypersecretion and not with an anaerobic tissular function. Tissular capillary blood flow is constant if reported to cardiac index. This model will allow us to compare those results with new series where only one of the basic elements will be modified.

Animals↗

PubMed1994

[Experimental models of polycystic kidney disease].

An overview of actually accepted hypothesis of etiology and pathogenesis as well as overview of experimentally induced models of autosomal dominant polycystic kidney disease (ADPKD) is presented. Though chemically induced renal cysts in rats and other small laboratory animals fed by antioxidants (diphenylamine and s.o.) represent the commonest experimental model, strains of animals with inherited cystic kidney disease were inbred too. Experimental works on tissue cultures derived from patients with ADPKD, which are aimed especially on study of epithelial changes (epithelial hyperplasia and s.o.), deserved special attention. On conclusion, advantages of the different models and next steps necessary to accomplish for understanding etiology and pathogenesis of ADPKD are indicated.

Animals↗

PubMed1980

New experimental model of meningeal leukemia.

Meningeal leukemia is a common, often fatal complication of leukemia. Efforts to devise better prophylactic or therapeutic regimens have been limited by large gaps in knowledge regarding the pathogenesis of the process. This report describes a new experimental model of meningeal leukemia that should facilitate its study and fill some of the gaps. T-cell lymphomas, originally induced in C3H mice by Gross murine leukemia virus, were established as transplantable tumor lines in syngeneic mice. Three of ten tumor lines produced meningeal leukemia when injected i.v. into normal recipient animals. The others produced predominantly visceral lymphomas.

Animals↗

PubMed1983

Dimethyl sulfoxide does not suppress an experimental model of arthritis in rabbits.

We studied the ability of dimethyl sulfoxide (DMSO) to influence the course of an experimental model of inflammatory arthritis. A Dumonde-Glynn model of arthritis was induced in both tibio-femoral joints of 10 rabbits, using ovalbumin as the immunogen. At one month post induction of the arthritis, the right tibio-femoral joint of 6 animals was treated for 3 months with topical 80% DMSO--1 g/kg body weight applied to the shaved skin for 5 out of 7 days each week. In another 4 animals, the right tibio-femoral joint was injected with 0.5 ml of 80% DMSO at one month post induction of the arthritis. Joint radiographs were taken at monthly intervals. The rabbits were sequentially sacrificed and the joint tissues evaluated by a blinded observer. Neither the topical DMSO nor the intraarticular DMSO treated joints showed any favorable responses to therapy; in fact the topically treated joints exhibited somewhat more inflammatory and destructive changes than the untreated joints. However the repeated injection of DMSO into normal joints did not, of itself, produce any deleterious effects. This study indicates a need to assess more thoroughly a possible deleterious effect of DMSO on the course of untreated inflammatory arthritis.

Administration, Topical↗

PubMed2005

Evaluation of two experimental models of hepatic encephalopathy in rats.

The serious neuropsychological repercussions of hepatic encephalopathy have led to the creation of several experimental models in order to better understand the pathogenesis of the disease. In the present investigation, two possible causes of hepatic encephalopathy, cholestasis and portal hypertension, were chosen to study the behavioral impairments caused by the disease using an object recognition task. This working memory test is based on a paradigm of spontaneous delayed non-matching to sample and was performed 60 days after surgery. Male Wistar rats (225-250 g) were divided into three groups: two experimental groups, microsurgical cholestasis (N = 20) and extrahepatic portal hypertension (N = 20), and a control group (N = 20). A mild alteration of the recognition memory occurred in rats with cholestasis compared to control rats and portal hypertensive rats. The latter group showed the poorest performance on the basis of the behavioral indexes tested. In particular, only the control group spent significantly more time exploring novel objects compared to familiar ones (P < 0.001). In addition, the portal hypertension group spent the shortest time exploring both the novel and familiar objects (P < 0.001). These results suggest that the existence of portosystemic collateral circulation per se may be responsible for subclinical encephalopathy.

Animals↗

PubMed1997

B cell-deficient muMT mice as an experimental model for Mycoplasma infections in X-linked agammaglobulinemia.

B cell-deficient muMT mice were investigated as an experimental model for human X-linked agammaglobulinemia (XLA). Mice were intranasally infected with Mycoplasma pulmonis and in 16 out of 17 muMT mice, dissemination of the bacteria from the airways was observed. More than 50% of these mice developed arthritis and/or changes in periarticular tissues. Mycoplasmal infection in muMT mice thus resembles the disease seen in XLA patients implying the usefulness of the model.

Agammaglobulinemia↗