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[Functional evaluation of an experimental model of cutaneous microcirculation and pO2 after surgical excision: traditional method vs laser CO2].

Within an experimental study project about the interaction between Laser and biological tissues, the authors utilized a Laser Doppler Flowmeter device and a Polarographic method to study the cutaneous microcirculation and the tissue pO2. Under standardized conditions, the experimental model considered the microcirculation measurement and the ptiO2 before and after the exsection of a cutaneous lozenge on the animals back realized with traditional surgical methods (scalpel and electrotome) or with a last generation CO2 Laser in continuous and in pulsed mode. The Laser Doppler Flowmeter showed that the largest perturbation of the microcirculatory flux occurred after the exsection realized with the scalpel and the electrotome. The CO2 Laser utilized in continuous mode showed an influence slightly lower on the microcirculation while in pulsed mode the perturbation was absent. The ptiO2 measurement showed similar results emphasizing that the CO2 surgical Laser technique is less invasive than the traditional. To sum up, these functional methods allowed a careful microcirculation an ptiO2 evaluation and provided useful information about vasal and metabolic alterations, showing that the CO2 surgical Laser utilized in pulsed mode appears to be the less harmful surgical technique for the tissues surrounding the exsection site.

Laser-Doppler Flowmetry↗

Transcatheter arterial embolization for malignant osseous and soft-tissue sarcomas. I. A rabbit experimental model.

PURPOSE: To evaluate the effect of transcatheter arterial embolization (TAE) on metastatic bone tumors in an experimental study. METHODS: Fifteen Japanese white rabbits were transplanted with VX2 sarcoma cells into the iliac crest. In 10 rabbits, the arterial supply to the iliac bone tumors, internal iliac artery and iliolumbar artery were then embolized with particles of gelatin sponge. The therapeutic effect was evaluated by comparison with the natural course of control tumors in the other five rabbits. RESULTS: After TAE, extensive necrosis, fibrosis, and vacuolization within the tumors were confirmed histologically. In the control rabbits, 19% +/- 7% of the entire tumor was found to be spontaneous tumor necrosis; in contrast, the tumors of the TAE group showed necrosis as 62% +/- 22% of the entire tumor. In one TAE group rabbit, no active tumor cell could be detected in the residual tumor. CONCLUSION: TAE was found to be an effective treatment for bone tumors in an experimental model.

Animals↗

Osteoporosis increases the severity of cartilage damage in an experimental model of osteoarthritis in rabbits.

OBJECTIVE: To evaluate the effect of osteoporosis (OP) in cartilage damage developed in an experimental model of osteoarthritis (OA) in mature female rabbits in order to investigate the relationship between OP and OA. METHODS: OA was experimentally induced by anterior cruciate section and partial medial meniscectomy in the left knee of 12 rabbits. OP was experimentally induced prior to OA in six rabbits by bilateral ovariectomy (OVX) and systemic corticosteroid administration during 4 weeks. Knees were evaluated with high resolution magnetic resonance imaging (MRI) before knee surgery to rule out any detrimental effect of corticosteroids on cartilage. Gross and microscopic cartilage changes were assessed 16 weeks after surgery in bilateral knees. Left knees were considered osteoarthritic or osteoarthritic plus osteoporotic. Right knees were used as osteoporotic and healthy controls, respectively. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry (DXA) at the lumbar spine, global knee and subchondral knee bone, and its variations correlated with cartilage abnormalities. RESULTS: MRI before knee surgery disclosed no cartilage or bone abnormalities in any of the studied groups. OP increased the severity of cartilage abnormalities in experimental knee OA significantly (P<0.05). Cartilage damage was inversely correlated with BMD variations measured at the lumbar spine (r=-0.74; P=0.015). BMD changes in global and subchondral knee bone also showed a trend to correlate inversely with cartilage damage. CONCLUSIONS: Prior induction of OP increases the severity of cartilage damage in experimental OA. Increase in cartilage damage correlates with bone loss. These findings suggest a direct relationship between OP and OA.

Absorptiometry, Photon↗

An experimental model for the study of transient lower oesophageal sphincter relaxation and motor function of the proximal stomach in humans.

A simple and reliable experimental model would be useful in human research on new drugs which target transient lower oesophageal sphincter (LOS) relaxation. The aim was to investigate the effect of repeated distensions on the rate of transient LOS relaxation, LOS pressure and motor function of the proximal stomach. Twelve healthy subjects were studied with a multilumen manometric assembly incorporating a sleeve sensor for the LOS and a bag positioned in the proximal stomach and connected to a barostat. Intrabag volume was set at 75% of the threshold for gastric discomfort and maintained for two 30-min distension periods separated by a 45-min washout with the bag deflated. The studies lasted 145 +/- 2 min. The rate of transient LOS relaxations was similar during the two distensions, 3.5;2-4 vs 3;2.5-4 (median;interquartile range) and so was LOS pressure. Baseline intrabag pressure, as a measure of gastric tone, and the number of pressure waves, as a measure of phasic contractions, were also similar, 11.3;9.3-12.3 mmHg vs 10.8;9.3-12.5 mmHg and 16;13-28 mmHg vs 19;15-29 mmHg, respectively. Our model allows to perform 1-day studies which can assess two experimental conditions on transient LOS relaxations and motor function of the proximal stomach within an acceptable time span.

Adult↗

[Experimental models in research].

The purpose of this study is to collect the main classifications of experimental research models and their possible applications in experimental research. Literature search was done using the most important data bank available on the internet (PUBMED, MEDLINE, SCIELO, LILACS, COCHRANE). A compilation of the experimental studies developed at the Plastic Surgery Post Graduate Program of the Federal University of São Paulo/Paulista School of Medicine was also done. Animals models were classified regarding sanitary and genotypical status. The understanding of the main classifications of the research experimental models is essential to improve and confirm procedures and techniques already described as well as the development of new ones.

Animals↗

Isolated perfused rat liver: an experimental model for studies on ammonium and amino acid metabolism.

Isolated perfused rat liver is a well-established experimental model for studies on hepatic amino acid and ammonia metabolism. Some aspects and modifications of the liver-perfusion technique are discussed. Perfusion studies with the intact liver have the fundamental advantage that the structural and functional organization of the liver is preserved; however, the experimental system is more complex in view of subcellular and intercellular compartmentation and the recently demonstrated metabolic interactions of different cell populations at the acinar level. These problems of complexity by compartmentation can be largely solved by introducing further techniques such as organ spectrophotometry, the retrograde/antegrade perfusion technique, use of micro-oxygen-electrodes, use of selective inhibitors, radiolabeled compounds, different fractionation techniques of the liver tissue. By means of these approaches, intracellular events can be followed up not only indirectly by analyzing the composition of the perfusate before and after a liver passage, but also directly in the different subcellular and subacinar compartments of a structurally and metabolically intact liver.

Amino Acids↗

The efficacy of 9-cis retinoic acid in experimental models of cancer.

9-cis retinoic acid (9-cis RA) is a retinoid receptor pan-agonist that binds with high affinity to both retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Using a variety of in vivo and in vitro cancer models, we present experimental data that 9-cis RA has activity as a potential chemotherapeutic agent. Treatment of the human promyelocytic leukemia cell line HL-60 with 9-cis RA decreases cell proliferation, increases cell differentiation, and increases apoptosis. Induction of apoptosis correlates with an increase in tissue transglutaminase (type II) activity. In vivo, 9-cis RA induces complete tumor regression of an early passage human lip squamous cell carcinoma xenograft. Finally, 9-cis RA inhibits the anchorage-independent growth of the human breast cancer cell lines MCF-7 and LY2 (an antiestrogen-resistant MCF-7 variant). Transient co-transfection assays indicate that 9-cis RA inhibits estrogen receptor transcription of an ERE-tk-LUC reporter through RAR or RXR receptors. These data suggest that retinoid receptors can antagonize estrogen-dependent transcription and provides one possible mechanism for the inhibition of cell growth by 9-cis RA in breast cancer cell lines. In summary, these findings present evidence that 9-cis RA has a wide range of activities in human cancer models.

Animals↗

Experimental model of dissecting aneurysms.

BACKGROUND AND PURPOSE: The pathogenesis and optimal treatment for arterial dissection are still unclear. We devised an experimental model of arterial dissection and observed the morphologic changes with angiography. METHODS: Sixty-four experimental dissections were created in the common carotid arteries of 34 mongrel dogs. After a small incision was made in the arterial adventitia, it was dissected from the media. Elliptical defects (2, 4, 6, and 8 mm in groups I-A, I-B, I-C, and I-D, respectively; n = 47) or longitudinal incisions (4, 6, and 8 mm in groups II-A, II-B, and II-C, respectively; n = 17) were made in the intima distal to the adventitial incision to serve as an entry zone for dissection. RESULTS: Immediately after the lesions were created, the influx of blood into the dissected cavity produced massive subadventitial hematomas, resulting in stenotic changes in all of the arteries, including seven with occlusion. Follow-up (1-week) angiograms demonstrated complete healing, with normal arterial calibers in 11 (79%) of 14 I-A lesions and aneurysm formation in nine (69%) of 13 I-B lesions. All 10 I-D lesions had complete arterial occlusion. Persistent stenosis was observed in all 10 I-C lesions; six of these developed aneurysms. Pathologic examination of the freshly dissected cavities revealed a clot-filled cleft between the media and adventitia. Mature aneurysms, evaluated 3 mo later, had endothelialization within the aneurysmal dome. CONCLUSION: Morphologic changes after arterial dissection are closely related to the size of the intimal entry zone, which may determine whether a dissecting aneurysm forms.

Aortic Dissection↗

Antiviral effect of zidovudine in the experimental model of adult T cell leukemia in rabbits.

The antiviral effect of zidovudine was examined in an experimental model of adult T cell leukemia in rabbits. AZT retarded the growth of HTLV-I-transformed rabbit cell line (F647a) and inhibited the transformation of normal peripheral blood lymphocytes in co-culture with the cell line. Inhibition of the transformation was achieved at a much lower concentration of AZT than the suppression of cell growth. Seven newborn F1 hybrids were inoculated intraperitoneally with 1 x 10(7) F647a cells and then were given AZT intraperitoneally, either at a high dose (300 mg/kg/day) or a low dose (30 mg/kg/day) for three weeks. Four newborn animals similarly given F647a cells were left untreated as a control. Examinations carried out three weeks after cell inoculation revealed the following: the HTLV-I provirus was not or hardly detected by the polymerase chain reaction in the peripheral blood lymphocytes of animals given a high dose of AZT, whereas the provirus was detected in all untreated control animals as well as in two animals given a low dose of AZT. In addition, lymphocytic infiltration was not observed in the major organs of the former animals, but was observed in those of the latter animals. These indicate the effectiveness of AZT administration for the prevention of HTLV-I infection and ATL-like disease in rabbits.

Animals↗

In vivo interaction of lead with aminolevulinic acid dehydratase and induction of a thermolabile factor: an experimental model.

Aminolevulinic acid dehydratase (ALA-D) activity of male albino Wistar rats was used as an experimental model for a study on the interaction of lead with biological systems. Lead at 1 mg/kg was administered i.p. and the rats were killed immediately, and at 30 min, 1, 2, 3, and 4 h after treatment. It was shown that lead (Pb) interacted directly with the enzyme molecule immediately after treatment, first on the active site of zinc (Zn) and then on the thiolic groups. Induction of the so-called thermolabile factor (TF) seemed to occur later, i.e., it may only be shown from the 2nd-3rd h after treatment. The long-term persistence of lead-induced TF in the acute phase of intoxication may be the key to the interpretation of some chronic toxic effects.

5-Aminolevulinate Synthetase↗

Lipid monolayers on Hg as a valid experimental model for lipid membranes under electrical fields.

Monolayers spread on Hg drops are shown as a suitable experimental set up to study the influence of external electric fields on the structure of lipid membranes. The electrical response exhibits a sharp transition at 24 degrees C, the transition temperature of DMPC. In addition, voltammetric response of monolayers of mixtures of DMPC/DMPE adsorbed on mercury, shows a similar trend to that found for dipole potential of monolayers of the same composition spread on an air-solution interface. It is concluded that a lipid monolayer adsorbed in a mercury-solution interface, has comparable properties as those found in other experimental models of lipid membranes in similar conditions. In addition, they constitute an ideal set up to study the effect of electrical fields on the dynamic conformation of lipids as a function of packing change produced by the condensation in the gel state or by the interaction of polar head groups.

Chemical Phenomena↗

Experimental model of oral antityphoid vaccination with live streptomycin-dependent Salmonella typhimurium in C57BL/6 mice.

The present experimental model offered the opportunity to study particular aspects concerning the avirulence stability of live streptomycin-dependent (Sm D) Salmonella vaccines, under conditions resembling human enteric fever. The results seem to indicate that, in practice, the risk of reversion to a virulent form during oral antityphoid vaccination with Sm D strains remains slight even after the interruption of concomitant streptomycin administration.

Animals↗

The superficial mandibular gland of the rabbit: a new experimental model for scintigraphic evaluation of salivary glands.

The aim of this study was to provide an appropriate experimental model to study functional changes in salivary glands using scintigraphy. Although the rabbit was frequently used for laboratory experiments, there are only a few studies that describe the exact position of its different salivary glands on the sialoscintigram. Twenty rabbits were used for the study; ten of them were anatomically dissected to provide the required topographic anatomy on the different salivary and lacrimal glands. The remaining ten animals underwent a static scintigraphy after extirpation of a particular salivary gland. Changes in the pattern of tracer uptake indicated the exact position of every gland allowing its evaluation. The results show that the 99mTcO4- uptake can only be selectively evaluated in two salivary glands, the superficial mandibular gland and the parotid gland. The superficial mandibular gland was proved to be a particularly useful model to evaluate functional changes of salivary gland parenchyma due to its well defined and high enhanced structure which allows a precise detection and measurement of the tracer uptake. Additionally, the good surgical accessibility of this gland and the existence of a well defined capsule facilitate associated histological studies of its parenchyma.

Animals↗

A controlled experimental model of revision implants: Part II. Implementation with loaded titanium implants and bone graft.

We used an experimental model producing an aggressive tissue response associated with implant loosening in humans: a 6 mm polymethylmethacrylate (PMMA) cylinder was pistoning 500 microm concentrically in a 7.5 mm hole, with polyethylene (PE) particles, for 8 weeks. At 8 weeks, the PMMA implant was revised with a titanium alloy (Ti) implant, and an identical primary Ti implant was inserted contralaterally for 4 weeks. With this protocol, we evaluated primary and revision plasma-sprayed Ti implants which were loaded under stable conditions with or without allograft, or under unstable conditions without allograft (bilateral primary and revision implants, n 8 per group, 48 implants in 24 dogs). Revision implants had lower interfacial shear strength, less bone in contact with and adjacent to the implant, and resulted in higher levels of IL-6beta and TNFalpha and lower levels of TGFbeta. In both the revision and primary settings, allograft increased shear strength, stiffness and energy, bone-implant contact, and bone area adjacent to the implant. Unstable implants could not generate a mechanically sound interface, and further exacerbated the difference between primary and revision. We conclude that factors important for improving the fixation of revision implants were bone graft and a stable interface.

Animals↗

New experimental model of ureteropelvic junction obstruction allowing easy access for percutaneous surgery.

To assess the usefulness of an experimental model of ureteropelvic junction (UPJ) obstruction designed to facilitate subsequent percutaneous surgery, a right UPJ obstruction was created in 10 pigs by an open retroperitoneal surgical approach. With the pig in the left lateral decubitus position, a 0.038-inch Terumo guidewire was inserted via a 1-cm longitudinal upper-third ureterotomy and advanced up and down so as to bridge the UPJ from the flank to the urogenital opening. A UPJ obstruction was then induced by securing two 2-0 chromic gut ties, separated by an interval of 1 cm, over the Terumo guidewire and a 6F ureteral catheter, which was removed immediately after this procedure. After closure of the ureterotomy, the kidney was anchored horizontally to the muscle wall, and the Terumo guidewire was coiled subcutaneously in the flank and fixed to the urogenital opening. Each pig developed marked hydronephrosis, diagnosed by ultrasonography, after a mean interval of 8.3 days. Retrograde ureteropyelography confirmed this pronounced dilation of the right collecting system above a tight UPJ stricture (mean length 1.17 cm). Subsequent percutaneous access to the UPJ over the Terumo guidewire in the lateral decubitus position was facilitated by the almost-horizontal plane of dilation (mean operating time 14 minutes). Pathologic examination of the UPJ revealed mild periureteral fibrosis, but the muscle layer and urothelium remained normal. We have developed a reliable and reproducible model of secondary UPJ obstruction especially designed for percutaneous surgery. This model should provide a better understanding of current endoscopic techniques such as endopyelotomy and could help to promote new treatment concepts such as percutaneous endoscopic pyeloplasty.

Anastomosis, Surgical↗

Prostaglandin E1 suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage-dependent glomerulonephritis.

Prostaglandin E1 (PGE1) suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage dependent glomerulonephritis. Macrophages are mediators of glomerular injury in models of proliferative glomerulonephritis. We have recently shown that macrophages in glomerulonephritis have low prostaglandin E2 (PGE) generation, and other evidence implicates eicosanoids as regulators of macrophage activation. Here we have studied in rats the effect of 15(s)-15-methyl PGE1 (M-PGE1) on accelerated nephrotoxic nephritis, a model of acute macrophage-dependent glomerular injury. M-PGE1 ameliorated proteinuria (day 4; 61 +/- 13 mg/24 h, n = 9; vehicle treated, 164 +/- 17 mg/24 h, n = 11; P less than 0.002) and glomerular hypercellularity; quantification of infiltrating macrophages by isolating glomerular cells showed reduction in the numbers of macrophages (44 +/- 9/glomerulus; vehicle treated, 119 +/- 15/glomerulus; P less than 0.02) with inhibition of Ia antigen expression on infiltrating macrophages (8 +/- 5%; vehicle treated 25 +/- 4% P less than 0.05). Glomerular binding of nephrotoxic globulin and levels of autologous antibodies were not affected by M-PGE1. Thus the mechanism of suppression involves inhibition of macrophage accumulation and activation. M-PGE1 administered to normal rats did not affect numbers of resident leucocytes (12.6 +/- 1.5/glomerulus; vehicle treated, 13.2 +/- 1.3/glomerulus) or alter Ia antigen expression (4.1 +/- 0.2 Ia + cells/glomerulus; vehicle treated, 3.9 +/- 0.6/glomerulus). This study suggests a therapeutic role for PGE1 in this type of glomerulonephritis, and has implications for the pathophysiology of macrophage-mediated inflammation.

Alprostadil↗

An experimental model for extracorporeal renal surgery: ex situ removal of artificially induced renal staghorn calculi in ambiothermia.

An experimental model for the evaluation of surgical techniques and preservation in extracorporeal surgery is described: staghorn calculi were induced in 15 dogs by the injection of methylmethacrylate into the renal pelvis. Removal of the calculi was carried out 3-4 weeks later on a workbench, using microsurgical techniques and ex situ radiographies. 15 min of warm ischaemic and 6 h of ambiothermic preservation were well tolerated as could be demonstrated by determination of the serum creatinine following autotransplantation and immediate contralateral nephrectomy.

Animals↗

Contrasting activities of thyrotropin receptor antibodies in experimental models of Graves' disease induced by injection of transfected fibroblasts or deoxyribonucleic acid vaccination.

The development of experimental models of autoimmune hyperthyroid Graves' disease has proved a difficult challenge, but recently two novel methods have led to their successful development in mice. We describe our studies on replicating the adjuvant modified, human TSH receptor (TSHR) and major histocompatibility complex class II transfected fibroblast injection system, and the plasmid DNA vaccination method as models resembling the human disorder. The fibroblast injection model in female AKR/N (H-2k) mice led to 70% of the animals developing thyroid-stimulating antibodies and their thyroid glands showed large goiters with histological features of thyroid cell activation characteristic of Graves' glands. Consistent with the clinical homolog, there was no inflammatory cell infiltrate of the thyroid gland. Detailed studies on the anti-TSHR antibodies such as thyroid-stimulating blocking antibody, antibodies to the native TSHR by flow cytometry, and TSH-binding inhibiting Ig showed that they were heterogeneous and did not correlate with disease activity, thus resembling those present in patients with Graves' disease. In contrast, the plasmid DNA vaccination model in female BALB/c (H-2d) mice led to the generation of low levels of anti-TSHR antibodies by flow cytometry, which were undetectable for thyroid-stimulating antibodies, TSH-stimulating blocking antibodies, and TSH-binding inhibiting Ig activity. Moreover, this model too was not accompanied by lymphocytic cell infiltration. The data demonstrate the high incidence of hyperthyroid disease induced in the adjuvant modified, transfected fibroblast model in AKR/N mice to allow pathological mechanisms of disease to be studied.

Animals↗