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At least 217 records · Page 12Linked to original sources
PubMed2003

The cytoprotective role of a low-molecular-weight heparin fragment studied in an experimental model of glomerulotoxicity.

Abnormal glomerular glycosaminoglycan metabolism is involved in the onset of the morphological and functional aberrations of glomerulopathies. In the present study, a heparin derivative, low-molecular-weight heparin, was tested for its ability to afford renoprotection in an established model of experimental glomerulopathy. Two groups of male albino rats of the Wistar strain (140 +/- 10 g) received a single intravenous injection of adriamycin (7.5 mg/kg) to induce glomerulopathy, and one of them received low-molecular-weight heparin (Certoparin Sodium, Troparin; 300 microg/day/rat s.c.) treatment, commencing on day 8, for a week. Urinary protein/creatinine ratio, serum albumin, urea, uric acid and creatinine clearance were evaluated. Renal cell injury was assessed in terms of renal tissue lactate dehydrogenase, aminotransferases (aspartate and alanine transaminases) and alkaline phosphatase activities, as well as renal antioxidant status (superoxide dismutase, catalase and glutathione peroxidase, reduced glutathione, vitamins E and C). The kidney tissue was subjected to histopathologic examination. Low-molecular-weight heparin significantly reduced proteinuria and improved creatinine clearance and serum albumin levels in the rats with glomerulopathy. The significant rise in serum uric acid in the rats with glomerulopathy was reversed by low-molecular-weight heparin. Altered tissue enzyme activities in response to injury, oxidative stress challenged renal antioxidant system and abnormal renal histology were observed in the untreated nephrotic rats, while low-molecular-weight heparin treatment protected the nephrotic rats against these changes. Thus, in this study, low-molecular-weight heparin was evaluated for its role in combating glomerular injury, on the basis of some salient biochemical parameters, oxidative injury indices and histologic picture. The ability of low-molecular-weight heparin to restore glomerular anatamo-functional features in this nephrotoxic condition illuminates its multi-faceted renoprotective role.

Animals↗
PubMed1995

Should Pseudomonas aeruginosa isolates resistant to one of the fluorinated quinolones be tested for the others? Studies with an experimental model of pneumonia.

A clinical isolate of Pseudomonas aeruginosa resistant to pefloxacin (Pef) but susceptible to ciprofloxacin (Cip) was studied to compare the in vitro and in vivo activities of Pef, ofloxacin (Ofl), and Cip. The time-kill curve method showed no bactericidal activity for Pef and Ofl, but a reduction of 4 log10 CFU/ml was achieved with Cip at 1 h. A model of experimental P. aeruginosa pneumonia was used to evaluate in vivo the relevance of the difference in susceptibility observed in vitro. At 36 h, a 100% cumulative survival rate was observed in Cip-treated rats, which was far higher than the survival rate obtained with Pef (53%) or Ofl (46%) (P < 0.001). At 4 h, no bacteremia was observed in Cip-treated rats, whereas 93% of the Pef-treated rats and 80% of the Ofl-treated rats were bacteremic (P < 0.001). The best pulmonary bacterial clearance was observed with Cip. Interestingly, Pef and Ofl, to which the strain was resistant in vitro, showed a fairly good in vivo activity despite sub-MIC concentrations. Cip was more effective than Pef and Ofl in terms of pulmonary and systemic bactericidal activity and provided the best survival rate in animals. We conclude that differences between the different quinolones in terms of the organism's sensitivity assessed in vitro may be relevant and that it might be useful to reconsider the use of a quinolone to which P. aeruginosa shows resistance if the organism shows sensitivity to no other agent.

Animals↗
PubMed2001

[Experimental models: interactions Synercid and beta-lactam antibiotics].

UNLABELLED: SYNERCID ALONE IN A RAT MODEL OF EXPERIMENTAL ENDOCARDITIS: Trials conducted using 2 injections daily showed that animals infected with meti-R resistant Staphylococcus aureus strains sensitive to erythromycin were cured in 3 days. The same is not true for infections caused by C-MLSB-R staphylococci. The daily dose cannot be increased due to the venous toxicity of Synercid, leading to the idea of testing Synercid in combination with other antibiotics. IN VITRO STUDIES: Several antibiotics have been tested in combination with Synercid. Several beta-lactams have been shown to exhibit an additive or synergetic effect on a collection of meti-R and meti-S S. aureus strains. IN VIVO STUDIES: In animals infected with C-MLSB-R meti-R S. aureus, the combination Synercid + cefepime increases the activity of cefipime and prevents selection of beta-lactam highly resistant strains. The results obtained with the Synercid + cefpirome combination are even more eloquent. Finally, Synercid, alone or in combination with these 2 cephalosporins, does not select resistant strains.

Animals↗
PubMed1991

[Relation between hepatic lipid metabolism and the formation of lipid plaques in the rabbit aorta in an experimental model of atherosclerosis].

The objective of the work was to follow up on a model of experimental atherosclerosis induced in rabbits by a 1% cholesterol diet the mutual relationship of the deposition of total cholesterol as well as esterified and free fatty acids in the liver and the formation of lipid plaques in the rabbit aorta. The authors investigated also the influence exerted on this process by the s.c. administration of calcium antagonists--Verapamil 0.25 mg.kg-1.day-1 (Lek Ljubl., Jugoslavia), Dilthiazem 2 mg.kg-1.day-1 (Lachema CSFR) and Isradipine 2.5 mg.kg-1.day-1 (Isradipine--N Sandoz, Ltd, Switzerland). The interference of calcium antagonists with the lipid metabolism in the liver as well as the transport mechanism of lipids in the blood stream is differentiated. Verapamil administered in therapeutic doses promotes HDL-cholesterol formation and thus hastens the cholesterol transport from the blood stream into the liver where the latter cumulates. This may be one of the mechanisms of the antiatherogenic action of verapamil. On the other hand, isradipine and in particular dilthiazem administered in treble doses, as compared with therapeutic doses, slightly potentiated the formation of lipid plaques in the rabbit aorta and reduced the HDL-cholesterol level and thus also the cholesterol shift to the liver.

Animals↗
PubMed1996

[An experimental model of hepatointestinal transplant in the pig with clinical applications].

A model of experimental hepatointestinal transplant in pigs, with clinical applications is presented. Ten animals received a graft composed by the liver and the full length of the small bowel. Two pigs died during the transplant and in eight the surgical procedure was well tolerated with a good revascularization of the grafts. The coagulation parameters were normal after the transplant and only minor biochemical disturbances were found. The main difficulties of the surgical technique are related with the poor tolerance of the pig to the portal and caval clamping, and the close relationships of the duodenum, pancreas and distal colon, produced by the 360 degrees anti-clockwise bowel rotation around the mesenteric vessels. Clamping the supraceliac aorta during the implant of the graft keeps the animal hemodynamically stable and makes unnecessary the use of the more complicated veno venous shunt.

Animals↗
PubMed2005

A new experimental model of acquired cholesteatoma.

OBJECTIVE: Cholesteatoma is a recurrent disease that is difficult control by otologists. This study aims to develop an experimental model of cholesteatoma that is easy to reproduce, using latex to induce the inflammatory reaction and propylene glycol as the foreign body in the middle ear. STUDY DESIGN: We used a new experimental model in which an intentional perforation was performed on the tympanic membrane of rats, followed by the introduction of a latex biomembrane. METHODS: A control group was submitted only to perforation of the tympanic membrane. Propylene glycol with latex was used in experimental group 1 and latex alone in experimental group 2. The rats were killed during the eighth week and their tympanic bullae were stained with hematoxylin and eosin. RESULTS: Eighty percent of the animals in group 1 and 90% in group 2 developed a cholesteatoma. No formation of cholesteatomas or inflammatory tissue occurred in the control group. CONCLUSION: The presence of inflammatory cells may provoke the production of cytokines (IL-1, IL-2, IL-6, IL-8) and growth factors, which, together with the latex biomembrane, which is known to contain a protein that favors vascular growth, may cause chemotactic migration of the squamous epithelium from the external auditory meatus to the middle year of the rat, causing a cholesteatoma. The induction of an experimental cholesteatoma in rats with latex and latex plus 50% propylene glycol was effective, representing an excellent experimental model. The theory of epithelial migration in the genesis of cholesteatomas was confirmed by our observations in rats. The latex induced an acute and chronic inflammatory reaction when in contact with the mucosa of the middle ear.

Animals↗
PubMed1998

Experimental models of Parkinson's disease: from the static to the dynamic.

The experimental models of Parkinson's disease (PD) available today can be divided into two categories according to the mode of action of the compound used: transient pharmacological impairment of dopaminergic transmission along the nigrostriatal pathway or selective destruction by a neurotoxic agent of the dopaminergic neurons of the substantia nigra pars compacta. The present article looks at the relative merits of each model, the clinical symptoms and neuronal impairment it induces, and the contribution it could make to the development of a truly dynamic model. It is becoming more and more clear that there is an urgent need for a chronic model integrating all the clinical features of PD including resting tremor, and reproducing the gradual but continuous nigral degeneration observed in the human pathology. Discrepancies have been reported several times between results obtained in classic animal models and those described in PD, and it would seem probable that such contradictions can be ascribed to the fact that animal models do not, as yet, reproduce the continuous evolution of the human disease. Dynamic experimental models which come closer to the progressive neurodegeneration and gradual intensification of motor disability so characteristic of human PD will enable us to investigate crucial aspects of the disease, such as compensatory mechanisms and dyskinesia.

Animals↗
PubMed1983

Peripheral neuropathy in the Twitcher mutant. A new experimental model of endoneurial edema.

The Twitcher mouse (Twi/Twi) is a recently identified mutant experimental model for human globoid leukodystrophy. Affected mice develop neurologic abnormalities with demyelination of white matter and peripheral nerve due to an inherited enzyme deficiency. The neuropathy has unusual pathologic features:severe interstitial edema and infiltration by eosinophils. To investigate its pathogenesis and to identify the mechanism of demyelination, we studied vascular permeability and measured endoneurial fluid pressure. Significantly increased endoneurial fluid pressure was detected in clinically affected animals (average, 6.4 cm H2O) versus controls (1.7 cm H2O), and these data are the first measurements of EFP to be reported in mice. Increased vascular permeability to horseradish peroxidase was visualized by electron microscopy with leakage of horseradish peroxidase between endothelial cells and flooding of the endoneurial interstitium. Numerous eosinophils were present in the interstitium, as well as some polymorphonuclear cells, occasional erythrocytes, and degranulating mast cells. Abnormalities of nerve fibers included swelling of Schwann cells with intracytoplasmic inclusions, demyelination, and remyelination. As well as being a model for globoid leukodystrophy, the Twitcher is the first spontaneously occurring experimental model for endoneurial edema and increased endoneurial fluid pressure.

Animals↗
PubMed1998

An experimental model of chronic renal allograft rejection in the rat using triple drug immunosuppression.

BACKGROUND: Chronic rejection is a major problem in renal transplantation. Various experimental models have been developed to study vasculopathy of chronic rejection. However, animal models resembling the clinical situation of renal transplantation with combination therapy of basic immunosuppression are not available. The aim of this study was to find an experimental model of a donor-recipient rat strain combination that, under triple drug immunosuppressive treatment (methylprednisolone, cyclosporine, and azathioprine), would develop chronic rejection within a few weeks. METHODS: Renal transplantations were performed in strain combinations of DA-->AO, PVG-->BN, and DA-->BN. In each group, 5-8 animals received triple drug treatment of methylprednisolone (2 mg/kg), azathioprine (2 mg/kg), and cyclosporine (5 mg/kg) daily, 5-10 animals were left without treatment, and 6 syngenic transplantations were performed. The grafts were monitored with ultrasound-guided fine needle aspiration biopsies to quantify the inflammation in the graft. Graft histology was performed in parallel and quantified by using the chronic allograft damage index (CADI). RESULTS: In nonimmunosuppressed animals, irreversible acute rejection with a high peak of inflammation appeared in every strain combination within 5-8 days. In triple drug-treated rats, the DA-->AO combination demonstrated a prolonged acute rejection but no characteristic chronic changes, and the PVG-->BN combination showed practically no inflammation and did not develop any signs of chronic rejection within 60 days (CADI: 2.7+/-2.1), but the DA-->BN combination showed an early, mild inflammatory response 5-7 days after transplantation and developed chronic rejection within 40-60 days after transplantation (CADI: 7.9+/-3.1). Syngenic animals showed no inflammation or histological alterations (CADI: 1.7+/-2.0). CONCLUSIONS: In conclusion, in the DA-->BN combination with triple drug treatment, early mild inflammation was followed by the development of chronic rejection and can be used as an experimental model that resembles the clinical situation in renal transplantation.

Animals↗
PubMedDate not supplied

An experimental model to study axonal regeneration of the rat spinal cord*.

An experimental model for study rat spinal cord regeneration is presented in this paper. Central axons regeneration has been shown after autologous peripheral nerve transplantation between two stumps of the transected spinal cord if cavitation and glial-connective scarring is reduced by microneurosurgical techniques. To this purpose, segments of nerve sciatic fascicles were inserted in a gap space of previously subpially complete or incomplete transected spinal cord and favourable oriented to both spinal cord stumps by biologic sealant. The technical details regarding spinal cord transection, nerve transplantation and spinal cord-nerve end-to-end anastomosis are described. Subpial nerve fascicles graft in previously subpial incomplete transected rat spinal cord allows to connect in suitable way white and gray matter of spinal cord stumps according to one's well established experimental plane and decreases postoperative mortality and the rat assessment during the stage of spinal shock, simultaneously allowing an easier and larger use of this experimental model.

Animals↗
PubMed2003

Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis.

OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals) or a sham operation (10 animals). Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining). RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.

Acute-Phase Reaction↗
PubMed1986

An in situ experimental model in rabbits for the study of rectal absorption.

An in situ experimental model of rectal absorption was studied in rabbits compared with in vivo determination of drug concentration in the plasma of postcaval vein using indomethacin as drug. Pharmacokinetic parameters were similar between in vivo and in situ. When results from both studies were compared, 60% of the drug administered to the rectum was absorbed from the superior hemorrhoidal vein and the remaining 40% was absorbed from the inferior hemorrhoidal vein. When an aspirin suppository was used in this model, the amount of unaltered aspirin absorbed in the rectal mucosa or space was greater than the absorbed salicylic acid which was metabolized or degradated from aspirin. In the case of insulin, these differences were not seen in the insulin concentration of venous plasma between insulin physiological saline and surfactant suspension. However, using the in situ model, the surfactant effect on rectal absorption of insulin was observed. From the above results, it was concluded that this in situ experimental model of rectal absorption has advantages in that it can be used directly to measure the rectal absorption rate and to determine ratios of easily metabolized and poorly absorbed drugs. Therefore, this model appears to be useful in evaluation of rectal absorption.

Animals↗
PubMed1982

[An experimental model of osteosarcomas in rats ].

Satisfactory experimental models for preclinical prediction in cancerology must answer the following criteria: reproducibility of the method used for inducing tumors; clinical, pathological and kinetic similarity with the corresponding human tumors. We have developed a model of osteosarcoma locally induced by insoluble radioactive cerium chloride (144Ce CI3) in Sprague Dawley rats. This method yields over 80% of bone tumors at the injection site, of which approximately half are histologically similar to human tumors. These tumors double their volume fairly slowly (in approximately 20 days); lung metastases occur both early and frequently (80% of animals). A transplantable tumor was developed from an induced osteosarcoma and adapted to the Curie strain. Transplantation in the bone, next to the bone, or under the skin is followed by widespread metastatic dissemination. The kinetics and histological features of the primary tumor are maintained. Tumor 85 strontium uptake is similar to that seen in human osteosarcomas. These new models of osteosarcomas are being used for evaluating new cancer chemotherapeutic agents and interferon, etc.

Animals↗
PubMed1998

Bisphosphonates and tetracycline: experimental models for their evaluation in calcium-related disorders.

PURPOSE: This work was aimed at synthesizing novel bisphosphonates (BPs) and examining them in comparison to clinically used BPs such as pamidronate and alendronate, and to tetracycline, in order to evaluate their potential as anticalcification and antiresorption agents. The correlation between the various models was examined in order to establish facile experimental models for pre-screening of potential compounds. METHODS: Nitrogen-containing heterocyclic, novel BPs such as 2-(3-methylimidazolio) ethylidene-1,1-bisphosphonic acid betaine (VS-5b), 2-(2-dimethylamino-4-pyrazinio)ethylidene-1,1-bisphosphonic acid betaine (VS-6b), and 2-(2-alpha-pyridylethylthio) ethylidene-1,1-bisphosphonic acid (ISA-225), were synthesized and evaluated in comparison to clinically used BPs, in various experimental models of resorption and calcification. RESULTS: The physicochemical properties of the novel compounds are slightly different than the BPs in clinical use: the pKa values are lower, the affinity for hydroxyapatite is lower and the solubilities of the calcium salts are higher. The anticalcification potencies of the novel compounds were high and ranked as follows: alendronate = pamidronate > VS-6b = VS-5b = ISA-225 > tetracycline. The in vivo antiresorption activity of VS-5b and VS-6b in comparison to that of the clinically employed, pamidronate, was shown to be similar and higher, respectively. CONCLUSIONS: The anticalcification activity of the novel compounds as well as that of tetracycline was lower than that of alendronate. The antiresorption activity of VS-6b was similar to that of pamidronate. A good correlation between the different models was found, enabling the facile screening of novel compounds. The activities of tetracycline and EDTA highlight the distinct behavior of BPs as "crystal poison." In addition, tetracycline was found to be a potent anticalcification agent in the ectopic calcification model.

Alendronate↗
PubMed2001

The role of inflammatory mediators in the failing heart: immunomodulation of cytokines in experimental models of heart failure.

Congestive heart failure may be produced by a variety of disorders, including dilated cardiomyopathy, hypertension, and ischemic heart disease. We have developed experimental models of these diseases, and found gene expressions of proinflammatory cytokines increased in the hearts of these animals. Various drugs for heart failure modulate the production of cytokines in experimental models of heart failure. Pimobendan, an inhibitor of phosphodiesterase III prolonged survival, attenuated inflammatory lesions, and decreased the production of cytokines and nitric oxide. Recent studies have shown that these inhibitory effects are due to inhibition of activation of NF-kappaB. In contrast, digitalis increased the production of cytokines and exacerbated myocarditis. Interleukin-10 prolonged survival, attenuated myocardial injury, and appears promising as a treatment of heart failure due to viral myocarditis. Endothelin-1 plays an important pathophysiological role in heart failure, and treatment with an endothelin antagonist had a cardioprotective effect in experimental models of heart failure.

Adjuvants, Immunologic↗
PubMed1991

Methods and limitations of an experimental model of long QT syndrome.

An experimental model of the long QT syndrome has been developed in conscious dogs. This report discusses the methods used in its preparation and the strengths and weaknesses of the model. This new model is suitable for screening the bradycardia-dependent proarrhythmic effects of drugs and for studying the electrophysiology of "torsades de pointes." Permanent bradycardia (RR: 1558 +/- 83 ms) was obtained in 37 dogs by chemically-induced complete atrioventricular block. A 10% further increase of ventricular repolarization (QT: 306 +/- 7.0 ms to 331 +/- 5.5 ms) was obtained in 28 of these dogs by diuretic-induced hypokalemia. Diuretics, despite saline replacement, induced some degree of functional renal failure and extracellular volume losses. The QT interval increased although ventricular cycle length decreased slightly. These biological and electrophysiological parameters were reproducible except for a slow increase in plasma creatinine. Cardiac failure and sudden death rarely occurred. The most severe, but reversible, renal failure occurred in some dogs given the highest diuretic doses. Hypokalemia resulted in ventricular arrhythmias in only 6 dogs, 2 of them exhibiting runs of ventricular tachycardia and even "torsade de pointes" as their potassium levels fell below 2 mmol/L. The results of studies with several drugs using the model, with or without hypokalemia, or with bradycardia worsened by propranolol are analysed.

Animals↗
PubMed1981

Factors influencing the establishment and spread of R-plasmids in an experimental model of urinary tract infection.

An experimental model simulating infection of the urinary tract was used to investigate factors influencing the transfer of plasmid-mediated drug resistance in the human bladder in the absence of antibiotic therapy. When a small number of cells carrying plasmid-mediated drug resistance was added to an established population of sensitive cells, it was found that varying the physical conditions of the bladder model had no significant effect on the spread of the plasmid and, under all conditions used, exponential spread of the plasmid through the originally sensitive population occurred. When the initial donor cells were killed shortly after addition to the model, exponential transfer of resistance amongst the established sensitive population still occurred. Thus, even in the absence of antibiotic therapy, only a small number of initial transfer events was required for a fully resistant population to be developed. This was true of both actively multiplying and early stationary phase cultures. An initially greater proportion of resistant cells, or the use of an antimicrobial agent to which some of the cells are resistant, would ensure that this process occurred more rapidly.

Bacteriological Techniques↗