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[Urgent problems of experimental modelling of thermal skin burns].

The review presents a critical analysis of principal benefits and shortcomings of standard experimental models of surface and deep thermal burns of the skin. Comparison of the results of experimental studies must rest on reproduction of identical traumas in series of experiments. It is important to choose animals species, burn model, exposition time and thermal agent depending on the study aim. An algorithm of simple and available methods of reproduction of superficial and deep thermal burns of the skin on a rodent model is described.

Animals↗

A therapeutic role for melatonin antagonism in experimental models of Parkinson's disease.

To determine the effects of endogenous and exogenous melatonin on experimental models of Parkinson's disease (PD), Sprague-Dawley rats were exposed to intracerebroventricular implants of slow release melatonin, pinealectomy (PX), or constant light (LL) and then injected with central 6-hydroxydopamine (6-OHDA) or i.p. 1-methyl-4-phenyl,1-1,2,3,6-tetrahydropyridine (MPTP). The resulting impairment of motor function and related behavioural impairment were exacerbated by melatonin implantation, while PX and exposure to LL significantly reduced the severity of experimental PD. These results are consistent with previous work highlighting the importance of aberrant amine production in neurological disease and demonstrate that treatments that reduce endogenous melatonin bioavailability can ameliorate experimental PD. Furthermore, these findings illustrate that melatonin is not the universal remedy that it is currently claimed to be, and may pose considerable problems in neurological diseases characterised by dopamine degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Validation of an experimental model of fetal limb growth and development: practical applications for the study of fetal defects associated with therapeutic agents in pregnant women.

Numerous musculoskeletal disorders which occur during pregnancy require an effective, nonpharmacological treatment that is known to have no adverse effects on fetal development. The present report describes morphological and histological changes occurring in fetal mouse limbs maintained in a serum-free organ culture system. Limbs maintained in this organ culture system show a progressive rise in limb dimensions including surface area, perimeter, and limb length. Histological analysis of serial cross sections of the limbs revealed a statistically significant increase in histological scores of limb development, thickness of epidermal layer, and amount of collagen deposited in the bone and dermis of limbs by Day 4 of culture. Therefore, this in vitro model combined with contemporary computer image analysis represents an excellent experimental model which can be used readily to examine the effects of therapeutic modalities on the growth and development of many different organ systems.

Abnormalities, Drug-Induced↗

Anti-inflammatory activity of topical nimesulide gel in various experimental models.

OBJECTIVE AND DESIGN: The anti-inflammatory activity of topically applied nimesulide gel was compared in different experimental models with that of diclofenac and piroxicam gels. MATERIAL: Wistar albino rats of either sex were used. TREATMENT: In acute models, 50 mg of nimesulide or diclofenac were applied to right hind paws 1 h (carrageenan) or immediately before (formalin) irritant injection (sub-plantar). In adjuvant arthritis, 50 mg of nimesulide, diclofenac or piroxicam were applied daily to injected paws for 14 days. METHODS: Paw volume was measured by plethysmograph. Statistical significance was tested with Student's t-test. RESULTS: In the carrageenan paw odema, topical nimesulide gel exhibited similar anti-inflammatory activity to diclofenac gel, and was more effective than diclofenac gel in formalin-paw odema. In both acute (18 h) and chronic (14 d) phases of adjuvant arthritis, nimesulide gel was more effective than diclofenac or piroxicam gels. CONCLUSION: Topical nimesulide gel possesses higher anti-inflammatory activity than that of diclofenac or piroxicam gels.

Administration, Topical↗

Effect of cholecalciferol supplementation on blood glucose in an experimental model of type 2 diabetes mellitus in spontaneously hypertensive rats and Wistar rats.

BACKGROUND: Vitamin D might have an influence on glucose concentrations, due to the presence of VDR receptors on the pancreas. We established an experimental model of type 2 diabetes in spontaneously hypertensive rats (SHR) and Wistar rats in order to investigate the glycemic response. METHODS: SHR males (n=6) and Wistar rats (n=6) weighing approximately 89+/-5.5 g and 123.5+/-6.5 g, respectively, after 7 days of basal period, had the chow pattern substituted (350 kcal/100 g) for a hypercaloric/hyperlipidic (HC/HL) diet (490 kcal/100g) and then injected with 40 mg/kg (SHR) and 20 mg/kg (Wistar) streptozotocin I.P. After the creation of diabetes, the rats suffered daily gavage of cholecalciferol (12.5 microg/kg(-) (1)) for 14 days. The blood glucose was assessed twice a week with a glucometer. The data were analyzed by ANOVA. RESULTS: SHR and Wistar rats fed on a HC/HL diet gained 60 g and 32 g in once week, vs. the basal period, where they only gained 23 g and 13 g, respectively. The cholecalciferol supplementation did not change the glucose concentration in all of the SHR animals. About 40% of the group responded by treatment with reduction of about 60% in glucose concentrations. We did find a 40% of the blood glucose levels in all Wistar rats. CONCLUSIONS: Cholecalciferol is able to reduce blood glucose in this experimental diabetes model.

Animals↗

Computational and experimental models of the human torso for non-penetrating ballistic impact.

Both computational finite element and experimental models of the human torso have been developed for ballistic impact testing. The human torso finite element model (HTFEM), including the thoracic skeletal structure and organs, was created in the finite element code LS-DYNA. The skeletal structure was assumed to be linear-elastic while all internal organs were modeled as viscoelastic. A physical human surrogate torso model (HSTM) was developed using biosimulant materials and the same anthropometry as the HTFEM. The HSTM response to impact was recorded with piezoresistive pressure sensors molded into the heart, liver and stomach and an accelerometer attached to the sternum. For experimentation, the HSTM was outfitted with National Institute of Justice (NIJ) Level I, IIa, II and IIIa soft armor vests. Twenty-six ballistic tests targeting the HSTM heart and liver were conducted with 22 caliber ammunition at a velocity of 329 m/s and 9 mm ammunition at velocities of 332, 358 and 430 m/s. The HSTM pressure response repeatability was found to vary by less than 10% for similar impact conditions. A comparison of the HSTM and HTFEM response showed similar pressure profiles and less than 35% peak pressure difference for organs near the ballistic impact point. Furthermore, the peak sternum accelerations of the HSTM and HTFEM varied by less than 10% for impacts over the sternum. These models provide comparative tools for determining the thoracic response to ballistic impact and could be used to evaluate soft body armor design and efficacy, determine thoracic injury mechanisms and assist with injury prevention.

Biomechanical Phenomena↗

[Characterization of an experimental model of monosodium- glutamate-induced convulsions in the amphibian Bufo spp].

In previous reports, Feria-Velasco et al. characterized an experimental model of convulsions in rats induced by monosodium glutamate (MSG) with evaluation of the motor behavior and neurochemical parameters. In the present work, MSG injected in toads (Bufo spp) reproduced the model of convulsions with some peculiarities. The electrocorticographic recordings in toads after MSG injection were similar to those obtained in rats after administration of convulsant agents. Most of the toads injected with MSG (81.8%) showed convulsions preceded by an episode of stereotyped movements and signs of hyperexcitability. Latency for convulsions and frequency of convulsive episodes were similar to what has been reported in rats injected with MSG. However, the duration of convulsive period was larger than that seen in rats, and no deaths were recorded in toads. The peculiar feature of amphibia regarding their cerebral structures and their blood-brain barrier (BBB) make the amphibian model, an interesting and valuable one in studying experimentally induced convulsions, as well as the role of BBB in these phenomena.

Animals↗

[Diagnosis of brain death using trancranial Doppler ultrasonography in an experimental model of organ donation for transplantation].

OBJECTIVE: To create an experimental organ donor model and validate it by ultrasound evaluation of intracranial blood flow velocity. MATERIAL AND METHOD: Ten white New Zealand rabbits were assigned to either a control group or an experimental group. Brain death was induced in the experimental group by way of severe cranial hypertension. A diagnosis of brain death was based on physical examination and velocity of intracranial blood flow determined by transcranial doppler ultrasonography. Physical and ultrasound examinations were performed on all animals at baseline and at the time of the experiment. RESULTS: Physical examination and intracranial blood flow velocity were normal in the control group animals at baseline and during the study. The findings were also normal for the experimental group animals at baseline. After provocation of intracranial hypertension, we observed signs of brain death (absence of response to pain stimulus in one cranial par absence of brainstem reflexes, and apnea) in the experimental animals, and the velocity of flow in arteries at the base of the skull acquired the waveform known as sharp systolic peaks, which are characteristic of cerebral circulation failure. CONCLUSIONS: The results of physical examination and ultrasonography in this study provide adequate validation of this experimental model of brain death and demonstrate that transcranial doppler ultrasonography is useful for diagnosing brain death in the rabbit.

Animals↗

Healing process of sutureless choledochojejunostomy in an experimental model.

The healing characteristics and morphological features of sutureless choledochojejunostomy were investigated in a rat experimental model. The common bile duct of 34 conditioned Wistar rats was exposed, divided transversely and a choledochojejunostomy constructed with only a vinyl chloride tube positioned between the common duct and jejunum. The animals were killed 4, 12 and 52 weeks after surgery. Cholangiographic evaluation of the anastomosis in all three groups showed wide openings with dilatation of the extrahepatic bile duct. Microscopic examination of the anastomosis showed hyperplastic changes of the bile duct epithelium. The epithelial defect was completely covered with proliferative epithelium 12 weeks after operation. At long-term follow-up of 52 weeks there were no biliary strictures after the sutureless technique. This surgical approach may be useful for patients in whom sutured anastomosis of the bile duct might lead to stricture, such as those with a normal thin-walled bile duct.

Alanine Transaminase↗

Repopulation of laser-perforated chondroepiphyseal matrix with xenogeneic chondrocytes. An experimental model.

Growth of chondrocytes into a xenogeneic chondroepiphyseal matrix was investigated in an in vitro experimental model by combining viable calf chondrocytes with chick epiphyseal matrix devoid of viable chondrocytes. The chondrocytes were harvested from the wrist joints of newborn calves and cultured for 2 days. The epiphyses were harvested from the distal femurs and the proximal tibias of fetal chicks after development was arrested at 17 days by freezing. The epiphyseal specimens were prepared in four ways. These included femoral and tibial epiphyses without holes and femoral and tibial epiphyses with holes made by a laser. These epiphyseal specimens were co-cultured with calf chondrocytes for various periods. After digestion of the epiphyseal matrix, viable chondrocytes were counted in suspension. Chondrocyte division in the matrix was assessed by [3H]thymidine incorporation. The growth of calf chondrocytes into the xenogeneic chick matrix was evaluated by fluorescence microscopy on fresh thick epiphyseal sections. The percentage of viable chondrocytes in the xenogeneic epiphyseal matrix increased with culture time to a maximum at day 21. The addition of laser-drilled holes was found to extend a plateau of chondrocyte viability until day 29. A decrease in cell viability was detected at later observation points. This study demonstrates that xenogeneic matrix may serve as a morphogenetic scaffold for chondrocytic growth.

Animals↗

Experimental model of heterotopic uterus transplantation in the laboratory rat.

The present study describes a standardized experimental model of whole-uterus-and-ovaries heterotopic allotransplantation in the laboratory rat. Fifteen transplantation procedures were done. The anatomy of the pelvic region was studied with an additional 20 dissections, noting the topographical and vascular anatomy of the uterus, fallopian tubes, and ovarian vessels. Recipients were randomized into three groups. The average operative time was 150 min. The postoperative survival rate was 100%. Postoperative vascular anastomosis patency was 100%, and 26% at 72 hr. Recipients were euthanized at 24 hr (group I), 48 hr (group II), and 72 hr (group III); grafts were harvested and examined macroscopically, and fixed in formaline for histopathological and immunocytochemical analysis. Failure in 74% of the grafts at 72 hr was due to early thrombosis, starting from the capillary bed and progressing towards the main feeding pedicles. More studies must be undertaken to further understand the rejection mechanisms in transplanted reproductive organs. The efficiency, feasibility, and safety for such an operation in humans remain to be proven. We consider the present model a suitable tool to study all the above-mentioned goals.

Animals↗

Histologic study on the metastatic process in the experimental model of lymph node metastasis.

The process of lymph node metastasis was studied in an experimental model that was successfully established in our laboratory. The model O-1N carcinoma was transplanted to the buccal pouch of 60 hamsters, and seven or eight hamsters were killed every week from 1 to 8 weeks for histologic examination. At 3 weeks, neoplastic invasion of vascular spaces was demonstrated, and early stage lymph node metastases were seen in five of seven animals. At 5 weeks, lymph node metastases were more advanced, and lung metastasis occurred in one animal. At 8 weeks, lymph node metastases were seen in all eight animals and lung metastases were seen in two of them. Tumor cells initially seen as clusters in afferent lymphatic vessels and in the peripheral sinuses gradually spread to the medulla, replaced the entire lymph node, and extended into adjacent extranodal tissue. The process of metastasis closely resembled that seen in human oral carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

An experimental model of bulbar urethral stricture in rabbits using endoscopic radiofrequency coagulation.

OBJECTIVES: To develop an experimental model of endoscopic urethral stricture mimicking the human clinical situation. METHODS: Twenty-four New Zealand male rabbits were included. Eighteen animals (study group) underwent videourethroscopy with a pediatric resectoscope, and a 3 to 5-mm-long circumferential electrocoagulation of the bulbar urethra was performed, without postoperative urinary diversion. Six animals underwent the same procedure without application of electrocautery (control group). Each animal was assessed for urethral stricture on day 15 and day 30 by videourethroscopy and voiding cystogram. Among the study group, 8 animals were killed on day 15 and 10 on day 30 for histologic evaluation. All the control animals were killed on day 30 for histologic examination. RESULTS: Nine animals (50%) in the study group developed a significant bulbar stricture (reducing the lumen by more than 50%) at day 15. Histologic examination confirmed the presence of hyalin fibrosis mutilating the urethral wall. No spontaneous improvement of the stricture was observed on day 30. None of the controls developed urethral stricture, and histologic examination showed a normal urethra in each case. CONCLUSIONS: Endoscopic electrocoagulation of the urethral wall provides a reproducible model of stricture in the rabbit.

Animals↗

Disseminated aspergillosis due to Aspergillus flavus in an experimental model: efficacy of azole therapy.

The aim of this investigation was to create a reproducible experimental model of disseminated Aspergillus flavus aspergillosis, and to compare the relative therapeutic efficacies of itraconazole and fluconazole in this model. Temporarily immunosuppressed male Wistar rats received intravenous challenge by A. flavus conidia. Treatment was initiated 24 h later with oral itraconazole (1 mg kg-1 BW day-1), oral fluconazole (1 mg kg-1 BW day-1) or excipient only (infected-untreated rats); this was continued for 10 days. At this time, although 100% mortality had occurred among all infected-untreated rats, no mortality was noted among the control-uninfected, infected-itraconazole-treated or infected-fluconazole-treated rats. After killing, essential organs were processed for microbiological and histopathological studies. Aspergillus flavus was recovered in high colony counts from the organs of infected-untreated rats (lungs > liver > brain > kidneys), but in significantly lower colony counts, or not at all, from the organs of itraconazole-treated and fluconazole-treated rats. Histopathological alterations were pronounced in tissues of infected-untreated rats, but less so in treated rats. These data suggest that administration of itraconazole or fluconazole sufficiently early may prevent, or retard, progression of lesions in disseminated aspergillosis.

Administration, Oral↗

The extracorporeal perfusion of swine uterus as an experimental model: the effect of oxytocic drugs.

The objective of this study was to establish an experimental model for extracorporeal perfusion of swine uterus. In order to validate this model, we examined some biochemical parameters and determined the effect of oxytocic drugs (Oxytoxin, Prostaglandin E (2)) on extracorporeal perfused swine uteri. Thirty swine uteri were perfused with Krebs-Ringer bicarbonate-glucose buffer for a period up to eleven hours with the aim to preserve a viable organ, which should be responsive to hormones. The intrauterine pressure was recorded after administration of various concentrations of oxytocin and prostaglandin E (2). Perfusate pH, perfusate lactate, partial oxygen and carbon dioxide tensions, oxygen saturation, and hydrogencarbonate levels in the perfusate, all indicators of tissue ischemia or cell necrosis, showed good preservation of the organ for up to seven hours. We examined the relation of intrauterine pressure to oxytocin and prostaglandin E (2). Both were able to induce contractions of the uterus, whereas prostaglandin E (2) produced rhythmical contractions of smaller amplitude and a higher frequency. We could demonstrate that our perfusion system was able to preserve the swine uterus in a functional condition appropriate for the study of physiological questions.

Animals↗

Experimental model for local application of growth factors in skin re-epithelialisation.

We did an experimental study to assess the effects of different growth factors on re-epithelialisation of skin wounds by creating a partial-thickness defect in rats with a handle dermatome. Three different growth factors that are particularly involved in the re-epithelialisation phase of wound repair (epidermal growth factor (EGF), keratinocyte growth factor (KGF), and basic fibroblast growth factor (FGF-b) n = 10 in each group) were applied locally in a hydrocolloid dressing containing solutions of the different factors (EGF 10 micrograms/ml, KGF 3.3 ng/ml, bFGF 1 microgram/ml). The dressings were changed daily. The thickness of the epithelium, the percentage of re-epithelialisation, and the maturity of the epithelium were quantified and measured morphometrically. The results showed that: the experimental model allowed us to apply the growth factors, while continuously maintaining the dose within the maximum activity of the growth factor; when EGF, KGF, and bFGF were given according to the protocol there was significant thickening of the new epidermis (p < 0.01) and acceleration of the re-epithelialisation (p < 0.05) rate compared with controls, and significantly more mature epithelium grew (p < 0.05) all of which were evident on both the third and the fifth days; and EGF and KGF cause a more epidermal thickening than bFGF.

Animals↗

In vivo lung lavage as an experimental model of the respiratory distress syndrome.

Using adult guinea-pigs, we have developed an experimental model in which alveolar surfactant phospholipids are removed by repeated lung lavage in vivo, and in which the short-term survival of the animals is ensured by artificial ventilation. Blood gases, parameters of lung mechanics, and histologic and electron microscopic findings indicate that the lavage procedure induces a condition similar to the adult respiratory distress syndrome. We propose that our technique might be used for evaluation of pharmacological agents and various forms of artificial ventilation which have been suggested for treatment of this disease.

Animals↗

Ultrastructural localization of prolactin in estrogen-induced prolactinoma of the rat pituitary. Experimental models for the human prolactinomas and the effects of bromocriptine.

In order to establish the experimental model for human prolactinomas and its bromocriptine treatment, estrogen-induced prolactinoma was produced in the female Wistar rats, in which daily bromocriptine treatment was given for a week, 3 days or 1 day (24 hours). The prolactinoma was produced by giving 5 mg estrogen depot every four weeks. The rats were killed at 4, 12, 20, and 24 weeks after the initial injection of the estrogen. By immunoelectron microscopy, in the estrogen induced prolactinoma, PRL was localized in well developed lamellar or whorling rough endoplasmic reticulum (RER) and Golgi saccules. In the rats treated with bromocriptine for a week, the serum PRL levels were lowered and the atrophied cytoplasm was filled with secretory granules containing PRL. These data were comparable to those of the human prolactinomas and the present experiment will serve as an animal model for studying the morphofunctional changes of human prolactinomas induced by bromocriptine treatment. The experiment with bromocriptine treatment for 24 hours supported the proposed mechanism that bromocriptine evokes inhibition of exocytosis followed by continuous granule formation in Golgi complexes and subsequently lowers synthesis of PRL.

Animals↗