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At least 1,045 records · Page 58Linked to original sources

PubMed1997

Why the internal mammary artery is an ideal graft for myocardial revascularisation? (an experimental model with omentoplasty).

Ten dogs underwent coronary artery bypass grafting through a right thoracotomy. Free internal mammary artery grafts (IMA) was used for aortocoronary bypass to right coronary artery (RCA) without temporary cardiopulmonary bypass. In upper median laparotomy approach, mobilization and lengthening of the omentum was performed through the retrosternal part of the diaphragm. An epiploic muff was effectuated surrounding the IMA graft. After three months the animals were sacrificed and the grafts folded by omentum were used for microscopical study. The histological evaluation has shown that the omentum has formed a new adventitia around the graft. In the new-formed adventitia, newly formed vessels can be found and these are grouped around the adventitia-media border zone, very rarely penetrating into the external layer of the media. This graft-omentoplasty offer a good experimental model which facilitates to investigate in vivo the blood supply needed by free IMA grafts through the adventitia in experimental conditions. The biological mechanism of angiogenesis in graft wall can be investigate as well.

Animals↗

PubMed1995

[Contribution of the experimental model of bacterial endocarditis].

Bacterial endocarditis is a difficult to cure infection, due to poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response which could cooperate with antibiotic action. The contribution of animal models to a better understanding of the pathophysiology of the infection and to definition and improvement of therapeutic regimens of endocarditis in humans, remains of great importance due to the difficulties encountered in clinical trials. The advantage of the experimental model is that besides the fact that is closely simulates the characteristics of the infection in humans, it provides clear endpoints which allow statistical comparisons among different therapeutic regimens. The animal model has definitively established that bactericidal therapy is warranted and that in vitro susceptibility tests, especially those evaluating the killing rate, have a good predictive value on therapeutic outcome. Two main aspects are discussed for their relevance to human therapy and represent our recent contribution: (i) the kinetics of antibiotic diffusion into vegetations, with special reference to data obtained with autoradiography; and (ii) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis. This animal model has also helped to define the importance of antibiotic dosing strategies to achieve in vivo synergism and to outline the predictive value of some drug pharmacokinetic and dynamic properties on the in vivo response to therapy.

Animals↗

PubMed1994

An experimental model of the production of early after depolarizations by injury current from an ischemic region.

An ischemic myocardial region contains cells with a depolarized resting membrane potential. This depolarization leads to an intercellular current flow between the ischemic region and the surrounding normal myocardial cells which has been termed an "injury current". We have devised an experimental model system in which an isolated guinea pig ventricular cell is electrically coupled to a model depolarized cell in order to evaluate the effects of this injury current on the electrical properties of a normal ventricular cell exposed to drugs which increase calcium current or decrease potassium current. Using low doses of isoproterenol, forskolin, or Bay K 8644 (or 8-bromo-cyclic adenosine monophosphate in the pipette) we found that the action potential duration of the isolated cell was lengthened, but that early afterdepolarizations (EADs) were not produced unless the cell was also coupled to a depolarized cell model representing an adjacent ischemic region. A similar prolongation of the action potential was produced by low doses of quinidine, but EADs were not produced unless coupling to a depolarized cell model was added. EADs could not be produced in any cells in the absence of the drugs even though the coupling to the depolarized cell model was increased up to the level at which the action potential was indefinitely prolonged. At higher isoproterenol concentrations, EADs or spontaneous activity were produced without coupling to the depolarized cell model. Under these conditions, coupling of the cell to a cell model with normal resting membrane potential stopped the spontaneous activity and prevented the occurrence of EADs even with high levels of resistive coupling.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1994

In vivo bactericidal activities of ciprofloxacin and pefloxacin in an experimental model of Serratia marcescens endocarditis.

The critical concentrations of pefloxacin and ciprofloxacin in serum, corresponding to the lowest concentration in serum able to achieve a 2-log-unit reduction in the CFU in vegetations after a 24-h exposure at a steady-state concentration obtained by a continuous intravenous infusion, were determined in an experimental model of Serratia marcescens endocarditis in rabbits. In vitro data showed that the MICs of ciprofloxacin and pefloxacin were 0.06 and 0.25 mg/liter, respectively. The killing curves indicated a maximum killing rate at a concentration four times that of the MICs. In vivo, the critical concentrations of pefloxacin and ciprofloxacin in serum were 0.4 and 0.24 mg/liter, respectively, corresponding to a concentration of four times the MICs.

Animals↗

PubMed2006

Experimental models and high-throughput diagnostics for tissue regeneration.

During wound healing, cells recreate functional structures to regenerate the injured tissue. Understanding the healing process is essential for the development of new concepts and the design of novel biomimetic approaches for delivery of cells, genes and growth factors to accelerate tissue regeneration. To this end, realistic experimental models and high-throughput diagnostics are necessary to understand the molecular mechanisms of healing and reveal the genetic networks that determine tissue repair versus regeneration. Following a brief overview of the biology of wound healing, this review covers the in vitro and in vivo models that are employed at present to study the healing process. Discussion then covers the application of high-throughput genomic and proteomic technologies in epithelial development, living skin substitutes and wound healing. Finally, this review provides a perspective on novel technologies that should be developed to facilitate the understanding of wound healing complications and the design of therapeutics that target the underlying deficiencies.

Animals↗

PubMed1982

Establishment of an experimental model of human hepatoblastoma.

Establishment of xenografts or cell culture lines in which the alpha-fetoprotein (AFP) characteristic of clinical hepatoblastoma persists have been difficult. The serially transplantable strain (HB-3) of highly AFP-producing hepatoblastoma was successfully established in nude mice. And a highly AFP producing cell line (c-HB-3) is easily obtained by HB-3. This strain and line give us an ideal experimental model of hepatoblastoma in vivo and in vitro.

Animals↗

PubMed1987

Magnetic resonance imaging of osteoarthritis: correlation with gross pathology using an experimental model.

Conventional radiography has several limitations in the study of osteoarthritis (OA): changes occur late, they are restricted to bone, and they do not correlate well with the patient's symptoms. Magnetic resonance imaging (MRI) can visualize with great detail the soft tissue changes in and around joints. We have obtained MR images of knees using an experimental model of OA in order to study the early changes of OA, to correlate the images with the gross pathology, and to compare MR images with radiographs. The changes on MRI correlated with the gross pathological changes as assessed by Kendall's rank correlation test as follows: meniscal changes, tau = 0.58 (p less than 0.01); osteophytes, tau = 0.59 (p less than 0.05); capsular fibrosis, tau = 0.55 (p less than 0.05); and overall, tau = 0.68 (p less than 0.001). Abnormalities were evident on MRI as early as 4 weeks after the onset of the disease, which is 8 weeks before they appear on radiographs. Thus, MRI can show changes in OA earlier than radiography can, and the images correlate with the gross pathology.

Animals↗

PubMed1998

Mechanism of brain protection by nitroxide radicals in experimental model of closed-head injury.

Reactive oxygen-derived species were previously implicated in mediation of post-traumatic brain damage; however, the efficacy of traditional antioxidants in preventing/reversing the damage is sometimes limited. The present work focused on the mechanisms underlying the neuroprotective activity of cell permeable, nontoxic, antioxidants, namely stable nitroxide radicals in an experimental model of rat closed-head injury. Brain damage was induced by the weight-drop method and the clinical status was evaluated according to a neurological severity score at 1 h and 24 h, where the difference between these scores reflects the extent of recovery. The metal chelator deferoxamine as well as three nitroxide derivatives, differing in hydrophilicity and charge, and one hydroxylamine (a reduced nitroxide) facilitated the clinical recovery and decreased the brain edema. The nitroxides, but neither the hydroxylamine nor deferoxamine, protected the integrity of the blood-brain barrier. Superoxide dismutase also improved the clinical recovery but did not affect brain edema or the blood-brain barrier. The results suggest that by switching back and forth between themselves, the nitroxide and hydroxylamine act catalytically as self-replenishing antioxidants, and protect brain tissue by terminating radical-chain reactions, oxidizing deleterious metal ions, and by removal of intracellular superoxide.

Animals↗

PubMedDate not supplied

Developmental phases of inflammation-induced massive lymphoid hyperplasia and extensive changes in epithelium in an experimental model of allergy: implications for a direct link between inflammation and carcinogenesis.

Direct evidence that inflammation is linked to carcinogenesis has yet to be established. Very few data are available on the developmental phases of inflammation-induced immune dysfunction that may lead to tumorigenesis. In a series of studies conducted in the 1980s and 1990s, an experimental model of acute and chronic inflammation was established in guinea pig conjunctiva by topical application of fluoresceinyl ovalbumin (FLOA) for up to 30 months. In this updated report, some of the findings are reanalyzed and expanded to identify that at lease 3 developmental phases were involved during the entire course of inflammatory responses including (1) an acute response (phase A) involving IgE-mast cell sensitization and degranulation; (2) an intermediate phase (phase B), a desensitization phenomenon and loss of mast cell function and neovascularization; (3) a chronic response (phase C) and induction of massive lymphoid hyperplasia, follicular formation with germinal centers, increased swollen goblet cells, extensive epithelial thickening and thinning, and angiogenesis. The results suggest evidence of a direct association between inflammation and the development of tumor-like lesions in lymphoid tissues and extensive changes in adjacent epithelia. Confirmation that inflammation induces irreversible changes in lymphoid and epithelial tissues leading to lymphoid tumorigenesis and/or carcinogenesis requires further studies. Understanding the developmental phases of immune dysfunction may provide unique opportunities for diagnosis and treatment of inflammatory diseases, autoimmune disorders, and cancers including lymphomas associated with Sjogren syndrome, squamous cell carcinoma of the conjunctiva, and other lymphomas or epithelial cancers. It is suggested that inflammatory mediators are ideal targets (biomarkers) for diagnosis, chemoprevention, and therapy for several cancers.

Acute Disease↗

PubMed1996

An experimental model of intracranial hemorrhage during thrombolytic therapy with t-PA.

Multiple clinical trials have proven that thrombolytic therapy is an effective treatment for acute myocardial infarction. Spontaneous intracranial hemorrhage (ICH) occurs in a small percentage of patients as a result of the treatment. The etiology of the ICH is unknown and there is currently no established experimental model for this side effect. A model of ICH during thrombolytic therapy has been developed using spontaneously hypertensive rats (SHR). The SHR were made susceptible to ICH during thrombolytic therapy by bilateral ligation of the external jugular veins. This procedure produced asymptomatic hemorrhagic lesions in the brains of the animals in the hours preceding the administration of t-PA/heparin. The incidence of ICH following the administration of test substances was assessed by histological examination and by measuring the red blood cell count in a sample of cerebrospinal fluid taken from the atlanto-occipital space. t-PA administration produced a low frequency of ICH in this model. The incidence and severity of ICH were dramatically increased, and significant mortality at 24h was observed, by combining heparin were administered sequentially rather than simultaneously. Furthermore, ICHs were observed whether the t-PA dose was administered over 4 h, 1 h, or as a double bolus 30 min apart. The potentiation of ICH by heparin was dose dependent and proportional to the prolongation of the aPTT. Although the precise mechanism of ICH during thrombolytic therapy is unknown, many similarities exist between the observations made in this model and in the human clinical experience.

Animals↗

PubMed2004

Prevalence and clinical characteristics of an experimental model of 'ice-cream headache' in migraine and episodic tension-type headache patients.

This study was designed to compare the prevalence and clinical characteristics of 'cold-induced headache' between migraine and episodic tension-type headache patients. Seventy-six migraine and 38 episodic tension-type headache patients were included in the study. An experimental model of an 'ice-cream headache' was developed for the study. The pain occurrence period, its location and quality were recorded for each patient who felt pain in their head during the test procedure. Pain in the head occurred in 74% of migraine and 32% of 'tension-type headache' patients. Although the most frequent pain location was the temple in both groups of patients, this rate was greater than twofold in migraine patients when compared with episodic tension-type headache patients. While headache quality was throbbing in 71% of migraine patients, it was so in only 8% of the episodic tension-type headache patients. Considering all the results, it seems that 'cold-stimulus headache' is not only more frequent in migraine patients, but also its location and quality differ from 'tension-type headache'.

Adolescent↗

PubMed1996

An experimental model for the evaluation of lipid peroxidation in lens membranes.

Lipid peroxidation has been associated with a number of specific manifestations related both to lens aging and cataract development. The assessment of the effect of various naturally occurring prooxidants as well as the development of antioxidant strategies has often been limited by the lack of appropriate and simple experimental models. In this study we discuss the adaptation of a method based on the incorporation of a fluorescent probe (parinaric acid) into biological membranes to monitor early stages of lipid peroxidation. After establishing the appropriate conditions, the method can be successfully applied to study peroxidation in bovine lens membranes, allowing for the evaluation of the effect of several free radical generating systems, including the following metal-dependent initiators: ascorbate/ iron, hydrogen peroxide/copper and cumene hydroperoxide/ copper. The inhibitory effect of the chelating agent diethylene-triaminepenta-acetic acid and the competitive hydroxyl radical scavenger sorbitol, was consistently observed on parinaric acid degradation, on hydroxyl radical yield and on the amount of thiobarbituric acid reactive material produced. It could be shown that oxidative degradation of the probe gives direct information on lens membrane susceptibility to a specific peroxidation system. Parinaric acid can therefore be used as an efficient oxidation probe to evaluate oxidative damage inflicted to lens membranes by different systems, allowing also the evaluation of the antioxidant effect of various drugs including those with potential anticataractogenic effect.

Animals↗

PubMed1997

[Cell membrane alterations and protein synthesis in experimental models of cerebral ischemia: pharmacological implications in the treatment of ischemic disease].

Brain ischemia causes a large variety of cellular and tissular disturbances that can lead to cerebral infarction. A lack of glucose and oxygen supply that is constantly needed for normal brain function produces a lesion becoming more severe as the duration of the ischemic period increases. Experimental models allow to examine the effect of permanent versus transient ischemia with reperfusion. Cellular and tissular ischemic disturbances can, to a certain extent, be separated from those occurring at reperfusion. Ischemia causes severe and at times non-recoverable alterations, suggesting that minimizing the duration of ischemia by favoring recanalization would be clinically desirable. However, many alterations occurring at reperfusion time do also favor lesion progression. Certain surviving neurons at the penumbra region can become affected during reperfusion as the infarct progresses. Reperfusion injury seems to offer a comparatively larger window for therapeutical intervention aimed to protect cells from death. Several postischemic changes such as alteration of cell membranes, induction of heat shock protein (Hsp70) and protein synthesis inhibition are considered here, together with putative pharmacological treatments directed to reduce or arrest postischemic lesion progression.

Animals↗

PubMed2001

Antifungal activities of two new azasordarins, GW471552 and GW471558, in experimental models of oral and vulvovaginal candidiasis in immunosuppressed rats.

Sordarins constitute a new class of antifungal agents with a novel mechanism of action involving the selective inhibition of fungal protein synthesis. A further evolution of this class of antifungals has led to a new family of sordarin derivatives called azasordarins. The therapeutic efficacies of two new azasordarins, GW471552 and GW471558, were studied in experimental models of oral and vulvovaginal candidiasis in immunosuppressed rats. In all cases rats were immunosuppressed with dexamethasone in the drinking water. Oral candidiasis was established by inoculating 0.1 ml of a yeast suspension containing 5 x 10(8) cells of Candida albicans 4711E with a cotton swab on three alternate days. Vulvovaginal candidiasis was established in ovariectomized and estrus-induced rats by intravaginal inoculation of 10(7) CFU of C. albicans 4711E in 0.1 ml of saline. GW471552 and GW471558 were administered at 1, 5, and 10 mg/kg of body weight via the subcutaneous route. In oral candidiasis, azasordarins were administered each 8 h for 7 consecutive days, while in vaginal candidiasis the compounds were given each 4 h for 3 consecutive days. Antifungal activity of azasordarins was assessed by colony counts and by histological examination 1 day after treatment. In the oral infection model, GW471552 and GW471558 administered at 5 mg/kg significantly reduced (P < 0.05) the number of CFU of C. albicans compared with untreated controls. In addition, GW471552 and GW471558 given at 10 mg/kg eradicated C. albicans from the oral cavities of 100% of infected animals. Against vulvovaginal infection, both compounds showed significant therapeutic efficacy. GW471552 was able to eradicate the vaginal fungal burden at a dose of 10 mg/kg, and it significantly reduced the number of CFU of C. albicans in vaginas of rats treated with a dose of 5 mg/kg (P < 0.05). GW471558 showed greater efficacy, eradicating the fungal burden of 100% of infected rats at a dose of 5 mg/kg and significantly reducing (P < 0.05) the C. albicans vaginal counts even at a dose of 1 mg/kg. In both therapeutic efficacy studies, the histological findings confirmed the microbiological results. The experimental results presented show that the tested azasordarins are effective against oral and vulvovaginal candidiasis in immunosuppressed rats and could be promising antifungal agents for use in humans.

Animals↗

PubMed1991

The effects of intra-arterial vasoconstrictors on the distribution of a radiolabelled low molecular weight marker in an experimental model of liver tumour.

Regional chemotherapy for colorectal liver metastases has not demonstrated a convincing survival benefit over systemic chemotherapy. This may be due to poor delivery of chemotherapeutic drugs to hypovascular liver tumour. Since vasoactive agents may influence hepatic blood flow this study investigated the effects of systemic and regional vasoconstrictors on the delivery of a regionally delivered marker in an experimental model of liver tumour. Systemic administration of angiotensin II caused a significant retention of marker in normal liver, but not in tumour compared to controls. Regional delivery of angiotensin II and phenylephrine caused significantly greater retention of marker in tumour than liver with an overall 4-fold increased retention of marker one minute after its injection. Ninety minutes after injection there was still significant retention of marker compared to control animals. Regional delivery of hepatic artery vasoconstrictors increase delivery of marker and may increase delivery of chemotherapeutic drug to liver tumour.

Angiotensin II↗

PubMed2004

An experimental model of allergic asthma in cats sensitized to house dust mite or bermuda grass allergen.

BACKGROUND: Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. METHODS: House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. RESULTS: Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. CONCLUSIONS: Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

Animals↗

PubMed2006

Immuno-proteasome subunit LMP7 is up-regulated in the ischemic kidney in an experimental model of renovascular hypertension.

Immuno-proteasome is thought to be responsible for the processing of intracellular antigens and is induced when cells are treated with the inflammatory cytokines promoting cellular immunity. We tested the possibility that immuno-proteasome can be up-regulated in renal cells exposed to a long-lasting ischemia and inflammation in an experimental model of two-kidney, one-clip renovascular hypertension in the rat. Western blotting showed that immuno-proteasome subunit, LMP7, was up-regulated in the clipped ischemic kidney that was atrophic, but not in the contralateral unclipped kidney that underwent compensatory hypertrophy. Immunohistochemical analysis revealed that LMP7 was highly expressed in cortical epithelial and endothelial cells of the ischemic kidney. Surprisingly, the second immuno-subunit, LMP2, was almost undetectable, indicating that renal ischemia may induce exclusively the LMP7 subunit. We also found that renal ischemia neither reduced the SDS-stimulated proteasomal activity nor affected a high level of the PA28 activator. Thus, the results provide evidence that LMP7 immuno-subunit is induced in renal cells exposed to a long-lasting renal ischemia and inflammation, and that there is a direct link between LMP induction and renal atrophy. This opens an opportunity to study a role for LMP-containing proteasomes in the kidneys and other organs undergoing reduction in mass in diseases accompanied by a long-lasting ischemia and inflammatory responses.

Animals↗

PubMed1999

Changes in hippocampal and cortical B1 bradykinin receptor biological activity in two experimental models of epilepsy.

An increased response to the activation of receptors mediating excitatory effects may be involved in some forms of epilepsy. In this study, it has been tested whether B1 bradykinin receptors (which mediate excitatory effects in the peripheral nervous system and have little constitutional expression in the central nervous system) may be proposed in this role. Two experimental models of epilepsy (kindling and kainate) have been employed, and glutamate outflow experiments have been performed in hippocampal and cortical slices taken from control, kindled and kainate-treated rats. The endogenous B1 receptor agonist Lys-des-Arg9-bradykinin (10(-7) M) did not affect electrically-evoked glutamate overflow in control animals, but concentration-dependently increased it in kindled rats (maximal effect +40 to + 50%) and, to a lesser extent (+20%), in kainate-treated rats. These effects were fully prevented by the selective B1 receptor antagonist R-715 (10(-6) M), but not by the selective B2 receptor antagonist Hoe 140 (10(-6) M). The observed changes in B1 bradykinin receptor biological activity may play a role in epileptic hyperexcitability.

Animals↗