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At least 919 records · Page 51Linked to original sources

PubMed2005

Combination of nucleoside analogues in the treatment of chronic hepatitis B virus infection: lesson from experimental models.

Owing to the persistence of hepatitis B virus (HBV) and the selection of drug-resistant mutants, a new concept of antiviral therapy for chronic hepatitis B relies on the combination of nucleoside analogues. In experimental models of HBV infection, several key points concerning these combinations were addressed. (i) Is it possible to achieve a synergic antiviral effect with polymerase inhibitors? (ii) Is it possible to impact on intracellular viral covalently closed circular DNA? (iii) What is the impact of the cross-resistance patterns of the different nucleoside analogues? (iv) What is the effect of viral load suppression on the restoration of specific antiviral cellular responses? The clinical impact of these key issues is discussed in the perspective of new clinical trials.

Animals↗

PubMed2005

Complications of intestinal milking: experimental model.

BACKGROUND: Intestinal milking is a frequently used method in abdominal surgery for various purposes; although it is frequently used for eliminating distension, moving faeces, bezoar or other foreign objects proximal or distal, there are no experimental or prospective studies in the surgical literature with respect to complications of the method. The purpose of the present study was to investigate complications of the milking process in an experimental model. METHODS: Forty-four outbred, 8-month old Wistar albino male rats with weights ranging between 195 and 225 g were used. Four rats were used for preliminary study. The other 40 rats were divided into two equal groups. In the study group (n = 20), a plastic sphere, 3 mm in diameter was sent to the stomach via oro-gastric tubes. This sphere was then moved into the cecum by milking. In the control group rats (n = 20) the small intestines were manipulated at 1-cm intervals but milking was not performed. RESULTS: In the study group six rats (30%) developed grade 1, 11 rats (55%) developed grade 2, and three rats (15%) developed grade 3 peritoneal adhesion. In the control group, 18 rats (90%) had no adhesions and only two rats (10%) developed grade 1 adhesion (chi(2) = 34, P < 0.0001). In the study group, four rats (20%) had small bowel obstruction, whereas no rats in the control group developed small bowel obstruction (Fisher's P > 0.05). Peritoneal smear culture was positive in 11 rats (55%) in the study group, whereas it was positive in two rats (10%) in the control group (Fisher's P < 0.01). CONCLUSIONS: Intestinal milking is a process that can cause severe peritoneal adhesions and peritoneal contamination, which may lead to small bowel obstruction. Avoiding milking to the extent possible in eliminating distension intraluminal material that may cause obstruction, and preferring alternative methods is important for reducing postoperative morbidity.

Animals↗

PubMed2002

[Acinetobacter, a nosocomial pathogen. Contribution of experimental models].

EPIDEMIOLOGY: The increasing importance of Acinetobacter as a nosocomial pathogen responsible for outbreaks in intensive care units has been pointed out for twenty years. Today Acinetobacter infections are essentially pneumonia in patients under mechanical ventilation. EXPERIMENTAL MODELS: Most clinical isolates are resistant to b-lactam antibiotics as well as to other drugs. Animal models represent an essential step between in vivo testing an<d clinical studies, necessary to understand physiopathology, pharmacology and efficacy of therapy. The virulence of clinical isolates of Acinetobacter spp has been studied in a mouse model of systemic infection. Pharmacological studies and efficacy of antibiotics have been studied in a mouse model of Acinetobacter pneumonia. HUMAN THERAPEUTICS: The majority of strains are multi-resistant to antibiotics and the infections they cause are difficult to treat. Isolated or combined Sulbactam has often been used with success.

Acinetobacter↗

PubMed1991

Evaluation of bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of decasilate in experimental models.

The bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of 8-(2-phenylethyl)-1-oxa-diazaspiro[4,5]decan-2-one 2-tiophenecarboxylate (decasilate, CAS 76652-72-7) have been evaluated using different experimental models. 1. Decasilate showed a remarkable spasmolytic activity against histamine-induced contractions in the isolated guinea-pig tracheal preparation with an IC50 of 2.7 x 10(-6) mol/l. In addition, the oral administration of decasilate (5-30 mg.kg-1) significantly reduced the histamine aerosol-induced bronchospasm in guinea-pigs. 2. Decasilate had a preventive effect against antigen-induced contractions of ileum segments from sensitized guinea-pigs (EC50 8.0 x 10(-6) mol/l) and relaxed them when added after the antigen challenge (IC50 9.5 x 10(-7) mol/l). 3. Both carrageenin- and dextran-induced rat hind paw oedemas were significantly reduced by the oral administration of decasilate with ED50 values of 169.5 and 34.5 mg.kg-1, respectively. However, it was ineffective against the cotton pellet-induced granuloma in the rat. 4. Furthermore, decasilate had a significant mucolytic activity in rabbits and reduced the number of tussive seizures induced by an aerosol of citric acid in guinea-pigs. The pharmacological profile of decasilate suggests that it might be useful in the management of chronic bronchitis.

Animals↗

PubMed1988

[A critical analysis of experimental models of alcoholic cardiomyopathy].

Numerous experimental data on alcoholic cardiomyopathy were reviewed and classified basing on the mode of alcohol taking: 1) voluntary alcoholization; 2) semivoluntary alcoholization; 3) forced introduction of alcohol. The advantages and shortcomings of the methods in similating alcoholic cardiomyopathy were assessed. Efforts were made to identify the underlying pathogenetic factors of the disease. The most perfect simulation was achieved in liquid alcohol diet (semivoluntary model) combined with inhibition of the defence enzymes of the myocardium, for instance, inhibition of catalase activity. Alcoholic cardiomyopathy is shown to develop more rapidly in high doses of ethanol and long-lasting alcoholization.

Administration, Inhalation↗

PubMed1987

Radiation retinopathy as an experimental model for ischemic proliferative retinopathy and rubeosis iridis.

We produced radiation retinopathy in capuchin monkeys and studied them with fluorescein angiography and light and electron microscopy. The animals were followed up from ten days to 3 1/2 years after radiation in order to determine whether this could provide an experimental model for other chronic ischemic-proliferative retinopathies, such as diabetes. The first change detected after radiation was the focal loss of capillary endothelial cells and pericytes. As the areas of acellular capillaries became confluent, cotton-wool spots became visible ophthalmoscopically. These increased in number and then faded away, leaving large areas of retinal capillary perfusion. Histologic studies showed occlusion first of the deeper, smaller retinal vessels and then gradually of the larger vessels. Intraretinal neovascularization as well as apparent recanalization then developed, but no new vessels extended through the internal limiting lamina into the vitreous. Rubeosis iridis with neovascular glaucoma developed 2 1/2 to 3 1/2 years postirradiation, and vitreous aspirate demonstrated a high level of angiogenic factor.

Animals↗

PubMed1985

The human erythrocyte ghost: a new experimental model for studying adenosine transport.

Previous work on adenosine transport has always had problems with the interference of adenosine metabolism, due to its high metabolic rate and because the enzymes involved are consistently present in most tissues. A new experimental model for studying adenosine transport in human erythrocyte ghosts is presented in this work: Human erythrocyte ghosts were sealed in the presence of erythro-3(2-hydroxynonyl)adenine and P1-P5-di(adenosine)5'-pentaphosphate, inhibitors of adenosine deaminase and adenosine kinase, respectively. These ghosts proved to lack adenosine metabolism when incubated in [U-14C]adenosine at 10 microM concentration at lack 37 degrees C for 60 min. Ghosts were 99.4% sealed in the correct orientation and had constant intracellular water volume. With these characteristics, the erythrocyte ghost preparation has many advantages for studying adenosine transport without adenosine metabolism interference. Adenosine transport was studied following the technique of W. R. Lieb and W. D. Stein [(1974) Biochim. Biophys. Acta 373, 165-177, 178-196.] Experiments to study Zero-trans influx and efflux, equilibrium exchange, and infinite-trans influx and efflux are presented. Adenosine transport did not behave linearly in any of these experimental procedures. Adenosine basic kinetic constants, calculated according to the procedure of Lieb and Stein, were R1----2 = 4.1 X 10(-4), R2----1 = 3.97 X 10(-4), Ree = 1.94 X 10(-4), Roo = 6.08 X 10(-4), K1----2 = 125.67 microM, and K2----1 = 84.36 microM. Lieb and Stein rejection criteria were used to distinguish a simple pore from a simple carrier. The data accumulated indicate that adenosine transport is carried out by a system that satisfies the criteria used for the simple carrier model. Asymmetric behavior was observed indicating lower affinity of the carrier for adenosine influx, although Vmax values for influx and efflux were similar.

Adenosine↗

PubMed1999

Nidovirus infections: experimental model systems of human neurologic diseases.

The presence of terminally differentiated slow- and non-dividing cells in the central nervous system (CNS) provides a safe harbor for viral persistence and latency and constitutes a unique immunologic environment for viral infections. Studies of experimental model systems of viral infections of the CNS provide insight into mechanisms of viral persistence and immune-mediated pathology. Nidoviruses are comprised of 2 families of viruses, coronaviruses and arteriviruses, and are common pathogens of humans and a variety of animal species. Both families of viruses contain neurotropic strains that produce experimental neurologic diseases in rodents. These include acute meningitis and encephalitis; acute poliomyelitis; and chronic inflammatory, immune-mediated, demyelination. Coronavirus-induced demyelinating disease mimics many of the pathologic features of Multiple Sclerosis (MS).

Animals↗

PubMed1996

The T61 human breast cancer xenograft: an experimental model of estrogen therapy of breast cancer.

Endocrine therapy is one of the principal treatment modalities of breast cancer, both in an adjuvant setting and in advanced disease. The T61 breast cancer xenograft described here provides an experimental model of the effects of estrogen treatment at a molecular level. T61 is an estrogen receptor positive tumor which was originally derived from a T1N0M0 invasive ductal cancer and has been carried as a serially transplanted xenograft in nude mice. T61 is a hormone sensitive tumor whose growth is suppressed by both estrogen and tamoxifen, in contrast to other estrogen receptor positive tumors such as MCF-7 which are stimulated by estrogen. Molecular studies have demonstrated that T61 expresses easily detectable levels of mRNA for a number of peptide growth factors, including transforming growth factor alpha (TGF-alpha) and insulin-like growth factors I and II (IGF-I and IGF-II), but not transforming growth factor beta-I (TGF-beta1). Of these, IGF-II is the only peptide whose expression is altered by endocrine therapy. Treatment of T61-bearing nude mice with physiologic doses of estrogen is accompanied by loss of IGF-II mRNA expression within 24 hours, and rapid regression of tumor. T61 tumor growth is also inhibited in animals treated with a monoclonal antibody which blocks binding of ligand to the IGF-I receptor, which mediates the mitogenic signal of bound IGF-II through autophosphorylation of its intracellular tyrosine kinase domain. These results demonstrate the utility of the T61 model in the study of the molecular mechanism of estrogen therapy in breast cancer, and suggest that in this system, modulation of a specific growth factor (IGF-II) by endocrine therapy can have profound effects on tumor growth.

Animals↗

PubMed1996

Importance of photo activation of rose bengal for platelet activation in experimental models of photochemically induced thrombosis.

Generation of oxygen free radicals in the lumen of a vessel leads to NO inactivation, modification of lipid components of platelets and endothelial cell membranes, and platelet activation. On this basis, many experimental models of thrombosis have been developed, where the formation of a platelet rich thrombus follows the illumination of a vessel with an appropriately filtered light after intravenous administration of Rose Bengal or another sensitizing dye. However the detailed mechanism of thrombus formation remains poorly known. This work appreciates the contribution of platelet activation directly induced by oxygen free radicals in formation of the platelet rich thrombus, from a study of human platelet aggregation in presence of photo-activated Rose Bengal. The results demonstrate that direct activation of platelets by free radicals generated by Rose Bengal is of low or no importance in formation of the thrombus. Therefore, the main trigger of platelet aggregation and thrombosis in these models is primary endothelial cells injury.

Fluorescent Dyes↗

PubMed2002

[In vivo activity of amoxicillin in a non-toxigenic Corynebacterium diphtheriae rabbit endocarditis experimental model].

The mortality of non-toxigenic Corynebacterium diphtheriae endocarditis is high (27%). One explanation could be tolerance to amoxicillin. The aim of this work was to evaluate in vivo the tolerance phenomenon, in a rabbit endocarditis experimental model. Two strains of non-toxigenic Corynebacterium diphtheriae were compared: a tolerant one and a non-tolerant one. EACH ANIMAL WAS RANDOMLY ASSIGNED TO ONE OF THE FOLLOWING GROUPS: no treatment, continuous infusion of amoxicillin simulating 200 mg/kg/24 h in humans, or fractionated infusion of amoxicillin simulating 66 mg/kg/8 h in humans. Surviving bacteria were counted in vegetations after one or three days of treatment. The 24 h fractionated amoxicillin infusion was more efficacious on the non-tolerant strain than on the tolerant strain. On the tolerant strain, 24 h amoxicillin was more efficacious as a continuous infusion than as a fractionated one.

Amoxicillin↗

PubMedDate not supplied

Behavior of plasma hemoglobin in an experimental model of occlusive mesenteric ischemia.

The difficulties in establishing the diagnosis of mesenteric ischemia are responsible for the high mortality rate that is associated with this clinical condition. We studied the behavior of plasma hemoglobin in an experimental model of occlusive mesenteric ischemia in mice. Our results showed a clear relationship between the duration of ischemia and plasma hemoglobin levels. With regard to the time frames studied (3 hours, 6 hours, 12 hours, and 24 hours), comparison with control groups produced calculated P values of less than 0.01 for all time frames with the exception of the 3-hour group. This test may have the potential to aid in the diagnosis of mesenteric ischemia as well as the follow-up of its course after various therapeutic approaches.

Animals↗

PubMed2000

Increased expression of epidermal growth factor-receptor in an experimental model of colitis in rats.

BACKGROUND: Epidermal growth factor and related proteins share some structural homology and bind to one common receptor. We have shown previously that exogenously applied EGF protects colonic mucosa against injury in an experimental model of colitis in rats and that the endogenously expressed ligands for the EGF-receptor are predominantly transforming growth factor alpha precursors. The aim of our present study was to evaluate the EGF-receptor expression in response to mucosal injury in the same model of colitis. METHODS: The trinitrobenzene sulphonic acid (TNBS)/ethanol-induced model of colitis in rats was used and EGF-receptor expression was evaluated using ribonuclease protection assay and Western blot analysis. The extent of mucosal injury and inflammation was characterized by using a microscopic and macroscopic damage score and by estimation of the myeloperoxidase activity in colonic specimens. RESULTS: Irritation of the colonic mucosa leads to severe colonic inflammation with tissue oedema, erosions and mucosal ulcers and to a significant increase in myeloperoxidase activity expressed by neutrophil granulocytes and macrophages. A significant increase in EGF-receptor mRNA expression was obtained at 8-24 h followed by an increased expression of the EGF-receptor protein at 1-5 days after the induction of colitis. On Western blot analysis only one immunoreactive band with a molecular weight of approximately 170 kDa was detected. CONCLUSIONS: Mucosal inflammation leads to a significant increase in the EGF-receptor expression in the early phases of colitis. These findings support our hypothesis that EGF and related proteins and their common receptor play a pivotal role in mucosal defence and repair.

Actins↗

PubMed2004

Noxious chemical stimulation of rat facial mucosa increases intracranial blood flow through a trigemino-parasympathetic reflex--an experimental model for vascular dysfunctions in cluster headache.

Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.

Animals↗

PubMed1995

Experimental models for leishmaniasis and for testing anti-leishmanial vaccines.

In public health terms, leishmaniases are diseases of humans and dogs, whereas, in epidemiological terms, Leishmania spp. are considered to represent infections of a wide variety of animals, which represent the natural reservoirs of the various parasite species involved. Humans and dogs (which may be considered secondary or 'accidental' hosts in the leishmanial life-cycle) often exhibit severe clinical signs and symptoms when infected, whereas reservoir hosts generally show a few, minor or no signs. This situation makes the definition of a suitable laboratory model a difficult one, since the various experimental hosts may behave either like a reservoir or an accidental host. This review discusses the concept of animal models for leishmaniases and provides a critical evaluation of the most common experimental models and their respective advantages and disadvantages. In this state-of-the-art review, particular emphasis is given to the value of using mouse, hamster, cotton-rat, dog and primate models, especially in the context of testing potential anti-leishmanial vaccines.

Animals↗

PubMed2001

Sulbactam efficacy in experimental models caused by susceptible and intermediate Acinetobacter baumannii strains.

Sulbactam and imipenem were compared in an experimental pneumonia model in immunocompetent mice, using a susceptible strain of Acinetobacter baumannii, and in an experimental endocarditis model in rabbits, using an intermediately susceptible strain. In the former, sulbactam was as efficacious as imipenem in terms of survival, sterility of lungs and in the bacterial clearance from lungs and blood, provided that the t > MIC for sulbactam (1.84 h) was similar to that for imipenem (2.01 h). In the endocarditis model, imipenem (t > MIC, 2.12 h) was more efficacious than sulbactam (t > MIC, 1.17 h) in bacterial clearance from vegetations. These results show the efficacy of sulbactam in infections caused by susceptible strains of A. baumannii, with an MIC up to 4 mg/L, provided that doses reach a t > MIC similar to that of imipenem. The activity of sulbactam was time dependent.

Acinetobacter↗

PubMed1997

Effects of avitriptan, a new 5-HT 1B/1D receptor agonist, in experimental models predictive of antimigraine activity and coronary side-effect potential.

Several acutely acting antimigraine drugs, including ergotamine and sumatriptan, have the ability to constrict porcine arteriovenous anastomoses as well as the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects of avitriptan (BMS-180048; 3-[3-[4-(5-methoxy-4-pyrimidinyl)-l-piperazinyl[propyl]-N-methyl-l H-indole-5-methane-sulfonamide monofumarate), a new 5-HT 1B/1D receptor agonist. In anaesthetized pigs, avitriptan (10, 30, 100 and 300 micrograms.kg-1) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow was increased. The mean +/- SEM i.v. dose of avitriptan eliciting a 50% decrease (ED50) in the porcine carotid arteriovenous anastomotic blood flow was calculated to be 76 +/- 23 micrograms.kg-1 (132 +/- 40 nmol.kg-1) and the highest dose (300 micrograms.kg-1) produced a 72 +/- 4% reduction. In recent comparative experiments (DeVries et al. 1996), the mean +/- SEM ED50 (i.v.) of sumatriptan in decreasing carotid arteriovenous anastomotic blood flow was 63 +/- 17 micrograms.kg-1 (158 +/- 43 nmol.kg-1), with a reduction of 76 +/- 4% by 300 micrograms.kg-1, i.v. Both avitriptan (pD2; 7.39 +/- 0.09; Emax: 13.0 +/- 4.5% of the contraction to 100 mM K+) and sumatriptan (pD2: 6.33 +/- 0.09; Emax: 15.5 +/- 2.3% of the contraction to 100 mM K+) contracted the human isolated coronary artery. The above results suggest that avitriptan should be able to abort migraine headaches in patients, but may exhibit sumatriptan-like effects on coronary arteries. Initial clinical studies have demonstrated the therapeutic action of the drug in acute migraine.

Animals↗

PubMedDate not supplied

Characterization of allograft rejection in an experimental model of small intestinal transplantation.

Graft rejection continues to be a major barrier to the success of clinical small intestinal transplantation. The objective of this study was to characterize histopathologic and immune parameters of allograft rejection in an experimental model of small intestinal transplantation. Heterotopic intestinal transplants were performed in allogeneic and isogeneic rat strain combinations. An additional group of allogeneic recipients was treated with tacrolimus (1 mg/kg/day) for 7 days beginning on posttransplant day 1. Recipients of allografts and isografts were killed on days 1 to 7 following transplantation, and tacrolimus-treated allograft recipients were killed on days 4 and 7. Grafts and native intestines were examined for histopathology and cytokine gene expression. Very early rejection was observed on posttransplant day 3 and severe rejection was apparent by day 7. The key histopathologic features of acute graft rejection including apoptosis, crypt epithelial cell injury, and an inflammatory infiltrate were uniformly identifiable on day 4 and progressed in severity through day 7. Interleukin (IL)-2, IL-4, IL-5, IL-6, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha mRNA were readily detectable in allografts on days 1 to 7. However, only IFN-gamma mRNA showed a significant early and sustained increase in allografts as compared to isografts and native intestine. Treatment of allograft recipients with tacrolimus abrogated the major histopathologic features of rejection and markedly inhibited IFN-gamma gene expression. These results indicate that graft rejection in small intestinal transplantation is characterized by a local and specific immune response marked by IFN-gamma production that results in crypt epithelial cell injury and apoptosis. Tacrolimus abrogates the histopathologic features of rejection in association with a marked inhibition of IFN-gamma gene expression.

Acute Disease↗