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Synovial fluid analyses detect and differentiate proteoglycan metabolism in canine experimental models of osteoarthritis and disuse atrophy.

Canine experimental models of osteoarthritis (OA) and disuse atrophy were used to study cartilage metabolism. The synovial fluids from the OA joints showed elevated levels of keratan sulfate (KS) epitope and link protein, indicating increased catabolism. Analysis of fluids from joints with disuse atrophy showed high levels of KS epitope, but no increase in link protein. Quantitation of a novel chondroitin sulfate (3B3) epitope showed it to be present only in the synovial fluids and articular cartilage of the OA joints. The results indicate that these may be important indicators, or markers, of degenerative joint disease.

Animals↗

Impact directly over the cardiac silhouette is necessary to produce ventricular fibrillation in an experimental model of commotio cordis.

OBJECTIVES: In an experimental model of sudden death from chest wall impact (commotio cordis), we sought to define the chest wall areas important in the initiation of ventricular fibrillation (VF). BACKGROUND: Sudden death can result from an innocent chest blow by a baseball or other projectile. Observations in humans suggest that these lethal blows occur over the precordium. However, the precise location of impact relative to the risk of sudden death is unknown. METHODS: Fifteen swine received 178 chest impacts with a regulation baseball delivered at 30 mph at three sites over the cardiac silhouette (i.e., directly over the center, base or apex of the left ventricle [LV]) and four noncardiac sites on the left and right chest wall. Chest blows were gated to the vulnerable portion of the cardiac cycle for the induction of VF. RESULTS: Only chest impacts directly over the heart triggered VF (12 of 78: 15% vs. 0 of 100 for noncardiac sites: p < 0.0001). Blows over the center of the heart (7 of 23; 30%) were more likely to initiate VF than impacts at other precordial sites (5 of 55; 9%, p = 0.02). Peak LV pressures generated instantaneously by the chest impact were directly related to the risk of VF (p < 0.0006). CONCLUSIONS: For nonpenetrating, low-energy chest blows to cause sudden death, impact must occur directly over the heart. Initiation of VF may be mediated by an abrupt and substantial increase in intracardiac pressure. Prevention of sudden death from chest blows during sports requires that protective equipment be designed to cover all portions of the chest wall that overlie the heart, even during body movements and positional changes that may occur with athletic activities.

Animals↗

Experimental model to study sedimentary kidney stones.

An experimental model to reproduce, to some extent, the conditions prevailing during the formation of the so-called sedimentary urinary stones, was developed. The results obtained demonstrated that in the absence of organic matter no calcium phosphate crystals were deposited in cavities with scarce liquid renovation. Nevertheless, in such case a regular hydroxyapatite layer was developed on the walls around the cavity. The presence of crystallization inhibitors cannot stop indefinitely the crystal development. Therefore, phytate manifested important inhibitory effects in concentrations normally found in urine (0.77-1.54 x 10(-6) mol/l), whereas citrate only manifested important inhibitory effects when found at high urinary concentrations (2.64 x 10(-3) mol/l). When mucin (a glycoprotein) was present in the urine, a clear deposit of calcified organic material was formed. The organic matter appeared mixed with the spherulites of hydroxyapatite, this demonstrating the capacity of the glycoprotein agglomerates to act as heterogeneous nucleants of calcium salts and their important role in the formation of sedimentary stones. The structural features of the obtained in vitro deposits were compared with the fine structure of human sedimentary phosphate calculi. Scanning electron microscopy images demonstrated a good correspondence between in vitro experiments and in vivo observations.

Calcium Phosphates↗

Transfer of the rat tail: an experimental model for free osteocutaneous transfer.

A new experimental model for free transfer of the rat tail has been developed. The vascular and nerve anatomy of the tail was studied in ten Wistar rats. The caudal artery (average diameter: 0.8 mm) provides the principal arterial supply to the tail. The main venous drainage is from bilateral dorsolateral subcutaneous veins (average diameter: 1.2 mm). The inferior caudal trunk establishes the cutaneous nerve branches to the skin of the tail. Free transfer of the tail to the carotid artery and external jugular vein, with the attachment of the tail to the dorsum, allows for clinical monitoring of the transfer, without risk of autophagia. This transfer is easy to perform, simple to monitor, and provides consistent yet challenging microsurgery for the beginning microvascular surgeon. In addition to its utility as a training model, it may also have an application as an easy research model for composite tissue transfer.

Anastomosis, Surgical↗

Regulation of regional perfusion distribution in the lungs. Experimental model and effect of alveolar pressure.

An experimental model for studying changes in regional perfusion distribution in the lungs of a dog was described. The right upper lobe was separated in vivo from the rest of the lungs by a balloon catheter and gas exchange of the lobe was artificially done asynchronously with the rest of the lungs by using a gas of interest at a prescheduled aveolar pressure. 99mTc-albumin microsphere was the agent of choice for multiple sequential studies in one dog. Alveolar gas composition reached a plateau after the 4th inflation of the right upper lobe. Effect of alveolar pressure on regional perfusion distribution was studied by using nitrogen and air as exchange gases. Perfusion distribution in the right upper lobe was the least at the maximal alveolar pressure of 14 to 19 cm H2O, while it was the greatest at the tidal maximal alveolar pressure of 1 to-1cm H2O with either gas. Alveolar hyperinflation in a localized lung region due to the increase in regional alveolar pressure reduced regional perfusion distribution.

Air↗

The squirrel monkey as an experimental model for Plasmodium falciparum erythrocyte rosette formation.

Experimental cerebral malaria was recently found to occur in the squirrel monkey Saimiri sciureus when infected with the human malaria parasite Plasmodium falciparum. This report is concerned with the existence of spontaneous rosette formation ex vivo (infected blood samples) and in vitro (cultured parasites) between red blood cells (RBC) infected with squirrel monkey-adapted P. falciparum isolates and normal squirrel monkey RBC. Transfer of P. falciparum with high rosette formation tendencies (90-100 R+) from one donor monkey to several recipients gave rise to parasites that varied extensively in their ex vivo rosette formation capacity (4-96% R+). However, all individual parasites readily form rosettes after 24 hr of in vitro culture (60-95% R+). Host factors may be involved in the modulation of rosette formation, although it is found to occur both in splenectomized and spleen-intact animals. Cross-rosette formation is seen between parasitized human RBC and normal squirrel monkey RBC and vice versa, and rosettes formed by RBC of the two hosts are similarly affected by pH, temperature, EDTA, trypsin, as well as squirrel monkey and African human hyperimmune IgG. These characteristics of rosette formation are preserved after long-term in vitro culture in human RBC. Rosettes formed by some isolates are highly sensitive to heparin while others are not, suggesting at least two distinct mechanisms of rosette formation. This idea is also supported by the observation that specific squirrel monkey antisera to heparin-sensitive strains does not dissociate rosettes formed by a heparin-resistant strain. The results suggest that rosettes and anti-rosette formation antibodies formed by squirrel monkeys and humans exhibited similar characteristics, and that the squirrel monkey is therefore a good experimental model to study erythrocyte rosette formation and cerebral malaria.

Animals↗

[Protective effect of Astragalus membranaceus (Fisch.) Bge. and Hedysarum polybotrys Hand.-Mazz. on experimental model of cerebral ischemia in rats].

The experimental model of middle cerebral artery embolism in rats was made by inserting nylon thread. It was discovered that Astragalus membranaceus decoction(both 4.26 g.kg-1 and 7.1 g.kg-1) could reduce the capillary hyperpermeability and alleviate the dyskinesia caused by cerebral ischemia in rats. Purified Hedysarum polybotrys decoction (waste substances removed with alcohol after decocting with water) (12.5 g.kg-1) could reduce the water content in brain caused by occlusion of bilateral carotids in rats. Purified Hedysarum polybotrys decoction showed a tendency to reduce the water content in brain, but without statistical significance.

Animals↗

Percutaneous creation of acute type-B aortic dissection: an experimental model for endoluminal therapy.

PURPOSE: To evaluate the feasibility of a percutaneously created type-B aortic dissection as an experimental model for percutaneous therapy. This model was used to evaluate the hemodynamic effects of single-balloon fenestration of the intimal flap. MATERIALS AND METHODS: Acute type-B dissections were created in descending aortae of 15 swine via a femoral (n = 6) or carotid (n = 9) approach. The initial subintimal tear was made with use of a Colapinto needle. The dissections were extended to a predefined position in the aorta. The proximal and distal tears were balloon dilated. The mural flap was balloon fenestrated in six animals, just above the celiac artery. Aortograms were obtained to establish the presence and extent of the dissection. Manometry was performed in both lumina to evaluate the hemodynamics of the dissected aorta and the effects of balloon fenestration in this model. Pathologic specimens were also examined. RESULTS: Creation of dissection was successful in 11 of 15 animals, with six developing true lumen narrowing (group A). The other five animals (group B) had flow in both lumina without evidence of true lumen narrowing. After the creation of a single-balloon fenestration in the group A swine, the arteriograms revealed no evidence of blood admixture between the true and false lumina, and there was no change in the intravascular pressures. Examination of the explanted aortae showed a more extensive circumferential dissection in group A animals as compared with group B. CONCLUSION: The percutaneously created acute type-B aortic dissection is a feasible model for experimentation. The hemodynamics of the aorta did not change after single-balloon fenestration in this model.

Aortic Dissection↗

An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits.

The present study describes the characterization of an experimental model of closed head injury (CHI) in the mouse. This model is a modification of a setup described and used previously in the rat. The weight-drop device was modified and adapted to the size and weight of the mouse and the typical parameters that define the severity of the injury and its outcome were evaluated. The posttraumatic accumulation of water, i.e., cerebral edema, the disruption of the blood-brain barrier (BBB), histopathology, motor and cognitive functions were studied up to 30 days following CHI. Increases in cerebral water content and of BBB permeability were observed in the injured hemisphere at 4 h (p < 0.05) and 24 h (p < 0.01) postinjury, respectively. By 7 days, edema disappeared, while the BBB remained open for up to 30 days. The motor function was evaluated by a set of criteria termed neurological severity score (NSS). NSS was severely impaired immediately after CHI and later showed a spontaneous progressive recovery, although some residual deficits, mainly of beam-walk and balance, were still present at 30 days. Mice trained in the Morris water maze before the injury demonstrated highly significant deficits in memory retention up to at least 11 days postinjury (p < 0.01). Histopathological analysis revealed significant neuronal cell death in CA1, CA2, and CA3 regions of the left hippocampus following CHI. However, in the right hippocampus, overt neuronal cell death was observed only in area CA3 at 7 days after CHI. These results suggest that the modified model of CHI in mice can reproduce the posttraumatic sequelae observed in rats and show that some of the data obtained in this model are essentially similar to those observed in human head injury. The experimental model of CHI in mice may be a useful tool for studies in animals that carry specific genetic alterations, aimed at manipulating neurochemical pathways involved in the pathophysiology of brain damage.

Animals↗

[Experimental models for hepatic metastases from colorectal tumors].

Over recent years, the interest in the development of experimental models of colorectal liver metastases has increased due to the need for new adjuvant therapies to improve the treatment of both colorectal cancer and liver metastases. The induction of colon cancer by carcinogens in the rat with spontaneous liver metastases fairly closely mimicks the natural history of colon cancer but a low yield of both colonic cancer (less than 50%) and liver metastases (approx. 25%) is obtained after 6 months of latency. Direct intraportal injection of cells derived from a colon carcinoma cell line is the experimental model most often used. Although it bypasses the natural history of cancer this simple model produces up to 100% of liver metastases 6 weeks after injection of cells. These two models have been used for several studies of liver metastases concerning their morphology, their modulating factors and their vascularisation. They have been used to test new adjuvant therapies for colorectal cancer.

Animals↗

An experimental model of diabetes and cancer in rats.

The aim of this study was to develop an experimental model for the study of cancer associated with diabetes. For diabetes induction, Sprague-Dawley rats were given streptozotocin (STZ, 90 mg/kg body weight (BW), by intraperitoneal injection on the second day of life. For mammary tumour induction, rats were injected with 50 mg/kg BW of N-nitroso-N-methylurea (NMU) at 50, 80 and 110 days old. The neoplastic process and the effect of tamoxifen treatment was examined in non-diabetic and diabetic rats. The latency period, NMU-induced tumour incidence and the number of tumours per rat in diabetic rats versus controls were 117 +/- 7 days versus 79 +/- 9 days (P < 0.001); 93% versus 95% (NS); and 5.2 +/- 1.6 versus 2.7 +/- 0.5 (P < 0.02). A more benign histological pattern for tumours in diabetic animals was observed. Mammary tumours in diabetic rats grew more slowly than in controls. Tamoxifen (1 mg/kg/day) treated diabetic rats showed tumour regression in 67% of NMU-induced mammary tumours versus 53% in controls (NS). Our results show that tumour progression seems to be affected by diabetes in this experimental model. We suggest this is the result of changes to insulin-like growth factors and their receptors, which occur in diabetics, and our future research will examine this hypothesis.

Animals↗

[Measurement of coronary flow reserve by pressure/temperature sensor guide wire-based thermodilution in experimental models].

OBJECTIVES: Recently, a combined 0.014 pressure/temperature sensor-mounted guide wire has been developed to simultaneously measure fractional flow reserve and coronary flow reserve (CFR) by thermodilution (CFR-thermo). The accuracy of CFR-thermo was compared with CFR obtained by flow rate (CFR-flow) in experimental models. METHODS: Using an experimental model made from a straight-rigid tube (4 mm diameter) filled with 36 degrees C water, CFR-thermo and CFR-flow were measured under different conditions of sensor position and injected water temperature (0-40 degrees C). A side branch (2 mm diameter) was then placed at 4, 6, 8 and 10 cm from the injected site just proximal to the stenosis. The degree of stenosis ranged from 0 to 75% (0%, 25%, 50%, 75%). CFR-thermo and CFR-flow were calculated from the inverse ratio of the mean transit time and the flow ratio during high flow to low flow rates. RESULTS: Under the conditions without the side branch, there were good correlations between CFR-thermo and CFR-flow if the temperature of the injected water was under 28 degrees C and the sensor was not placed within 4 cm from the injection site. With the side branch, CFR-thermo was smaller than CFR-flow although there were good correlations between CFR-thermo and CFR-flow. The value of CFR-thermo increased with more distal positions of the side branch to the injected site. CONCLUSIONS: Temperature of the injected water, and the position of the sensor, the side branch and the stenotic lesion may influence measurements of CFR-thermo. These effects should be considered when CFR is measured by the thermodilution method.

Blood Flow Velocity↗

A finite element model of skin deformation. II. An experimental model of skin deformation.

Skin flap design has traditionally been based on geometric models which ignore the elastic properties of skin and its subcutaneous attachments. This study reviews the theoretical and experimental mechanics of skin and soft tissues (I) and proposes a mathematical model of skin deformation based on the finite element method (III). Finite element technique facilitates the modeling of complex structures by analyzing them as an aggregate of smaller elements. This paper gives the results of an animal model developed to study the deformation and mechanical properties of skin, including its viscoelastic properties (hysteresis, creep, and stress relaxation). A new skin extensometer, constructed with digital stepper motors and controlled with a microcomputer, is described to measure these properties for both skin and its subcutaneous attachments. Deformation grids quantitated from photographs with a digitalizing tablet are presented, and computer software is introduced to standardize and analyze them (II). The mathematical model is used to simulate wound closures such as the ellipse and rectangular advancement flap. In addition, a series of mathematical experiments performed to simulate deformation of a strip of skin are described; the relationships between the various elastic constants are investigated; and a comparison of these simulations with actual deformation is presented. Limitations of the model and areas for future investigation are discussed (III).

Animals↗

Role of the bowel flora for development of immunity to hsp 65 and arthritis in three experimental models.

An infectious aetiology in rheumatoid arthritis (RA) has for long been suggested, although no conclusive evidence for this is at present available. Lately a large interest has been devoted to the involvement of heat shock proteins (hsps) in autoimmune disorders due to their conserved structure and immunogenic properties. Immunity to hsps has been observed both in human autoimmune conditions and in experimental models of autoimmune disease. We have studied the role of the bacterial flora and hsp immunity in the arthritic response in three experimental models of arthritis; type II collagen arthritis (CIA), adjuvant arthritis (AA) and oil induced arthritis (OIA); by using germ free and conventional DA rats. A high incidence of severe arthritis developed in all the models evaluated irrespectively of whether the animals were in the conventional or germ free state. This confirms earlier results which show a minor effect of the bacterial flora in CIA and AA in high responder strains. These results also show that a severe OIA can develop in germ free animals. Despite the severe arthritic response induced, no serum antibody levels to hsp 65 could be detected in the germ free animals, which was in contrast to the conventional animals where a positive anti-hsp 65 serum response was seen in 35-80% of the animals with CIA, AA or OIA. These results show that development of a humoral response to hsp 65 in these models of arthritis is dependent on the presence of a bacterial flora. Further, the lack of humoral immunity in germ free animals despite a severe arthritic response indicates that humoral immunity to hsp 65 is not involved in development of disease in these three models of experimental arthritis.

Animals↗

[3 experimental models applied to the study of urothelial tumors of the bladder].

Three important models can be used in experimental carcinogenesis: Clonogenic assays which can be used to study tumor cells in vitro. This method is particularly useful in order to investigate biochemical markers and chromosomal spreads. Chemically-induced bladder tumors in various animals are used to analyse the mechanisms of induction and development of these cancers. The athymic mice have provided, over the last twenty years, an immunological system suitable for the heterotransplantation of human tumor tissues. These three experimental models, which are complementary, are reviewed and discussed.

Animals↗

[The experimental model of establishment and maintenance of social hierarchy in laboratory mice].

The goal of the investigation is to establish a new experimental model of social hierarchy in laboratory mice. The important feature of the model is a group of two males only placed into the special experimental cage. The cage consists of two nestling chambers and central chamber. Observations were made 3 times per day (20 min each) throughout 5 days. Aggression, defence and sniffing behaviours of both partners were recorded during each observation period using video camera. Social rank was detected by asymmetry in aggressive behaviour. It was shown that social hierarchy was established during the first four tests limited by the first 24 h after pairing. After this period aggression and defence behaviours were greatly decreased. After the first 5 tests a stabilization in aggression (number of wins, active attacks and not direct aggression) and defence (number of vertical defensive postures and escapes) as well as sniffing behaviours took place. But a strong asymmetry in mentioned here behaviours in males of different ranks (dominants and subordinates) was kept up. Thus we offer a new experimental model of minimal society, which entirely reproduces a pattern of establishment and maintenance of social hierarchy. Our model demonstrates significant differences in agonistic, defence and sniffing behaviours between males of different social rank.

Aggression↗

Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics.

To develop a reliable experimental model of vascular headache, we studied the dose-response relationship between headache and i.v. nitroglycerin (NTG) in 10 healthy subjects. NTG was infused intravenously over periods of 10 min separated by wash-out periods. Doses of 0.25, 0.50, 1.00 and 2.00 micrograms/kg/min were applied successively with one placebo infusion and wash-out period inserted randomly and double blindly. The subjects scored their headache intensity on a scale 0-10. After 1-8 weeks a retest was performed. Nine subjects developed headache already at 0.25 microgram/kg/min, whereas one had no headache at any dose. Headache severity did not increase with doses above 0.5 microgram/kg/min. This ceiling effect was reproducible. The headache was moderate, usually throbbing, bifrontal and not associated with other migrainous features. It reached maximum within 2.5-5.5 min (medians) at various doses and declined rapidly after NTG discontinuation. Wash-out periods of 10-20 min were sufficient. The reproducibility of headache intensity and character was satisfactory in the retest experiment. There were no unpleasant side effects and no visible flushing. Thus blindness was maintained. I.v. NTG is suitable as an experimental headache model. A constant infusion of 0.5 microgram/kg/min will be suitable for studies of arterial diameter, pulsations, blood flow, etc. Comparative studies of sensitivity should use the present infusion schedule but with the two highest doses substituted by 0.06 and 0.125 microgram/kg/min.

Adult↗

Nematocide activity of 6,7-diarylpteridines in three experimental models.

The in vitro nematocide activity of seventeen 6,7-diarylpteridines has been tested using three different experimental models, Caenorhabditis elegans, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. The method of evaluation of inhibition in the secretion of acetylcholinesterase by H. polygyrus seems to be the most indicated to avoid false positives. The in vivo activities, against Trichinella spiralis, of the most in vitro active pteridines have been assayed. All pteridine derivatives bearing 6,7-di-p-bromophenyl substituents have shown in vitro nematocide activities in the three experimental models used. Amongst all the pteridines tested in vivo, only 2,4-pteridinedithione derivatives exhibited moderate activity.

Animals↗