Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Rodent models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMedDate not supplied

Can we influence fibrosis in Crohn's disease?

Despite recent advances in the therapy of active Crohn's disease (CD) fibrostenosis remains a challenging complication of the disease. Transmural inflammation of CD is associated with phenotypic switch of the mesenchymal cells resulting in proliferation and collagen deposition. Both resident myofibroblasts and smooth muscle are candidate progenitor cells of the fibrogenic cells in CD stenoses. The principal growth factors involved in intestinal fibrosis have not been identified although TGF-beta 1 and 2, PDGF and IL-1 may be involved. Research aimed at elucidating the basic mechanisms underlying fibrosis in the gut has been hindered by the lack of an adequate animal model. Recently, however, new rodent models of chronic inflammation with distinct fibrosis have been described. Cell culture research has provided more information about possible pathways that may limit uncontrolled mesenchymal proliferation in the inflamed intestinal wall. The modulator role of neurotransmitters such as VIP, nitric oxide and prostaglandines is an important target for therapeutic intervention. Interfering with the phenotypic switch of mesenchymal cells may offer new therapeutic perspectives in the prevention of fibrostenosis. Further in vitro and animal studies as well as restenosis prevention studies are needed to develop pharmacological tools in the prevention of Crohn's disease fibrostenosis.

Animals↗
PubMed2006

Topical versus systemic vancomycin for deep sternal wound infection caused by methicillin-resistant Staphylococcus aureus in a rodent experimental model.

In 37 Wistar albino rats, we investigated the effects of topical vancomycin on deep sternal wound infection caused by methicillin-resistant Staphylococcus aureus. Partial median sternotomy was performed under sterile conditions. Group I (n=6) was the sham, and group II (n=7) was the control. Group III (n=8) received topical vancomycin, group IV (n=8) received systemic vancomycin, and group V (n=8) received topical and systemic vancomycin (combined). Rats in groups II through V were inoculated with 0.5 mL x 10(8) CFU/mL methicillin-resistant S. aureus in the mediastinum and sternum. No medication was given to groups I and II. Twenty-four hours after surgery, 40 mg/kg/day vancomycin was given topically in group III; systemically in group IV; and topically and systemically in group V After 7 days, smear samples from the mediastinum and tissue cultures from the sternum were obtained. We found 5.00 +/- 0 CFU/mL microorganisms in the mediastinum in group II, 1.90 +/- 1.70 in group III, 3.33 +/- 0.48 in group IV and 1.70 +/- 1.08 in group V. The quantity of microorganisms per gram of tissue in the sternum was 736 +/- 0.23 in group II, 6.01 +/- 0.33 in group III, 5.81 +/- 0.81 in group IV and 3.99 +/- 2.47 in group V The quantity of microorganisms was less in the 3 treatment groups than in the control group (P < 0.05). We conclude that topical plus systemic vancomycin treatment might be more effective in patients with deep sternal wound infections caused by methicillin-resistant S. aureus.

Administration, Topical↗
PubMed1989

Evaluation of CIEP and ELISA in a rodent malaria model.

Circulating antigens could be detected by both ELISA and CIEP in the sera of mice infected with Plasmodium berghei. However, ELISA was positive for circulating antigen even though the Giemsa stained smears did not show significant parasites. Hence, ELISA can have a diagnostic value for detection of antigens as a marker of active infection.

Animals↗
PubMed1986

Valva ileocaecalis: preservation during ileocolonic surgery employing a rodent experimental model.

Experimental and clinical data suggest that the valva ileocaecalis under neurogenic and hormonal influences, modulates antegrade and retrograde flow of succus entericus. A priori reasoning suggests that this function may influence nutrient absorption by and intraluminal endogenous microbial flora within the ileum. The hypothesis to be tested was, can anatomical and functional integrity of the valva ileocaecalis be preserved during the performance of a right hemicolectomy with reestablishment of intestinal continuity via a cecocolostomy? The methodology involved utilization of Lewis male rats weighing approximately 500 gm. General anesthesia was induced for all procedures. The animals were randomly assigned to three groups (10 animals/group): (A) sham operation; (B) pericecal dissection (preservation of the arteria et vena ileocolica); and (C) periileal dissection (ligation of the aforementioned vessels). Celiotomy was performed employing standard clean techniques, and was accompanied by a right hemicolectomy and an end-to-end or end-to-side cecocolostomy. Function of the heterotopic valva ileocaecalis was assessed 6-12 weeks post-operatively employing radiographic criteria (fluoroscopic analysis after intraluminal instillation of barium sulfate). Light microscopic analysis was performed subsequent to the radiographic studies. Periileal dissection associated with ligation of the arteria et vena ileocolica uniformly resulted in anastomotic disruption. Pericecal dissection associated with preservation of those vessels resulted in uniform anastomotic integrity, although two animals succumbed secondary to pneumonitis within 5 post-operative days. Radiographic analysis of the heterotopic valva ileocaecalis revealed intermittent antegrade and no retrograde flow of contrast material, which suggested functional integrity. Qualitative light microscopic analysis revealed architectural integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pro and anticonvulsant effects of xylazine on convulsion models in rodents.

Pretreatment of mice with 30 mg xylazine/kg ip protected against convulsions induced by amphetamine, but it intensified pentylenetetrazole- and strychnine-induced seizures. Xylazine pretreatment also protected rats against electroshock-induced convulsions. These findings support a noradrenergic mechanism being involved in the proconvulsant and/or anticonvulsant effects of xylazine.

Amphetamine↗
PubMed1997

Antimalaric effect of an alcoholic extract of Artemisia ludoviciana mexicana in a rodent malaria model.

Chloroquine resistance of Plasmodium falciparum first and of P. vivax more recently, stimulated the search for new antimalarics. Chinese investigators have introduced new compounds obtained from extracts of Artemisia annua which possess an antimalaric active principle different from those of the drugs in use. In Mexico eight species of Artemisia have been described and among them just A. ludoviciana has been empirically used in the treatment of intermittent fever. To know whether mexican Artemisia had antimalaric activity several in vivo experiments were performed. Different type of extracts from two Artemisia species were prepared and assayed in five different doses on mice infected by Plasmodium yoelii yoelii, in a four-day test scheme. Here, only the results of the assays on ethanolic extract of A. ludoviciana are presented. The results of the in vivo experiments showed that the parasite reproduction was inhibited up to 98.6% at the fifth day, as compared with the controls; the ED50 was of 29.2 mg/kg and the SM50 of 28.7. We looked after the presence of artemisinin in the ethanolic extract, without success.

Animals↗
PubMed1998

SV40 rodent tumour models as paradigms of human disease: transgenic mouse models.

Transgenic mice have been used to study the process of Simian Virus 40 (SV40)-induced oncogenesis in a broad range of tissues including mammary gland, salivary gland, pancreas, prostate, liver, lung, kidney, intestine, brain, choroid plexus, lens of the eye, bone, smooth muscle and cartilage. The focus of these studies rests primarily on the action of the major transforming viral oncoprotein, the large T antigen (TAg). In most transgenic studies, the DNA coding sequence of the SV40 TAg is placed under the control of a tissue specific promoter which is responsible for directing TAg expression to the selected organ. This review focuses on the process of viral oncogenesis in the mammary and salivary glands. The role of TAg in the induction of apoptosis in the mammary gland, and the time-dependency of TAg induced hyperplastic changes in the salivary gland, are emphasized.

Animals↗
PubMed1995

Lamotrigine has no antiparkinsonian activity in rat models of Parkinson's disease.

In rodent models of Parkinson's disease such as reserpinized or 6-hydroxydopamine substantia nigra lesioned rats, blockade of glutamate receptors of the NMDA (N-methyl-D-aspartate) or the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptor subtypes and concomitant treatment with L-DOPA (L-3,4-dihydroxyphenylalanine) or direct dopamine agonists restores locomotor activity and induces rotations. An alternative approach to interfere with glutamatergic transmission would involve the inhibition of glutamate release resulting in functional glutamate antagonism. The novel antiepileptic drug lamotrigine blocks the veratridine-evoked release of the excitatory transmitters L-glutamate and L-aspartate. Due to its presumed antiglutamatergic action it has been suggested that lamotrigine may be useful in the treatment of Parkinson's disease. In a preliminary open-label study in patients with Parkinson's disease some favourable effects were reported. The present study was undertaken to systematically investigate the effects of lamotrigine in rat models of Parkinson's disease. However, lamotrigine failed to exert antiparkinsonian activity in reserpinized rats when administered alone or in combination with the dopamine receptor agonist apomorphine. In rats bearing 6-hydroxydopamine lesions of the substantia nigra lamotrigine did not induce rotations when given alone and did not modify rotations induced by apomorphine or the preferential dopamine D2 receptor agonist lisuride. On the basis of these negative results it is predicted that lamotrigine will not have significant favourable effects on akinesia and rigidity in Parkinson's disease patients.

Animals↗
PubMed2005

Development and validation of a novel IL-10 deficient cell transfer model for colitis.

A number of rodent models for inflammatory bowel disease (IBD) have been developed, but most cannot be used to develop and validate new therapies for IBD. From the models developed, the IL-10 deficient mouse model is the one that results in a disease similar to human IBD; however, in this model, colitis occurs with variable incidence taking 3-4 months to develop. These are serious problems with the model when evaluating a new therapy because of the large-scale experiments required and the difficulty in performing an accurate pharmacological analysis. In this study, the IL-10 deficient mouse model was modified by transferring whole spleen and mesenteric lymph node cells from IL-10 deficient mice to CB-17 SCID mice. In this IL-10 deficient cell transfer model, chronic intestinal inflammation developed in all recipients within 2-3 weeks, which was far earlier than in donor IL-10 deficient mice. The pathological phenotypes were similar to those of IL-10 deficient mice and CD45RBhi T cell-transfer models. In addition, we assessed several agents for inflammatory bowel disease to validate the general utility of this cell transfer model. It is worth noting that TNFR-Ig or prednisolone, which is effective for treatment of patients with severe-fulminant Crohn's disease, markedly attenuated pathological clinical indices in this colitis model, whereas the immunosuppressive agents, azathioprine, tacrolimus, and cyclosporine A produced no significant effect. These results suggest that the IL-10 deficient cell transfer model is a good experimental model to use for developing new and effective therapies for active IBD.

Adrenal Cortex Hormones↗
PubMed2003

Temporal assessment of caspase activation in experimental models of focal and global ischemia.

Rodent models of focal and global ischemia were used to examine caspase activation. Several readouts were employed on identical tissue to provide correlative measurement of caspase induction, activation and enzymatic activity. In a rat focal ischemia model, caspase-3 enzymatic activity, as recorded by DEVD-AMC cleavage, peaked in penumbral cortex at 6-12 h following ischemia, correlating with increases in caspase 3-cleaved substrates of PARP and alpha-spectrin and subsequent disappearance of caspase-3 zymogen. Although induction of caspases 8 and 2 proteins was detectable as early as 6 h following ischemia, examination of the same tissues for caspase 8 or 2 enzymatic activities did not show significant modulation up to 12 h after ischemic insult. Caspase 9 induction was evident only after 24 h postischemia and did not correlate with elevated LDHD-AMC cleavage. Following global ischemia in gerbils, levels of caspase-3 enzyme activity peaked at 12 h in hippocampal tissue extracts. Cleaved caspase-3 signal was prominent in NeuN-positive layers in the CA1 region 6-12 h following ischemia. Interestingly, strong caspase-3 immunoreactivity was also detected in the subgranular zone of the dentate gyrus, a known region of ischemia-induced neurogenesis. Caspase-3 activation may be responsible for the loss of these cells, thereby hindering the endogenous recovery process.

Animals↗
PubMed2002

Plasmodium: assessment of the antimalarial potential of trifluralin and related compounds using a rat model of malaria, Rattus norvegicus.

A rodent model of malaria, Plasmodium berghei was used to assess the antimalarial potential of dinitroaniline herbicides. Trifluralin, pendimethalin, oryzalin, and benfluralin were all active against P. berghei in vitro at, or close to, submicromolar concentrations, with a rank order of potency similar to that against other protozoa. The dinitroanilines did not elicit a cytotoxic effect against a mammalian cell line at concentrations 100-fold higher than those for activity against P. berghei. Neither trifluralin nor oryzalin exhibited any antimalarial activity in vivo after oral administration at the maximum dose tolerated by the host. In a pharmacokinetic study, it was found that the lack of in vivo antimalarial activity was due to poor absorption. Other DNs which have better absorption characteristics than either trifluralin or oryzalin may offer more scope for antimalarial activity in vivo.

Animals↗
PubMed1999

Lessons for human inflammatory bowel disease from experimental models.

Experiments carried out in new rodent models of chronic intestinal inflammation provide important clues about the pathogenesis of human inflammatory bowel disease (IBD). Genetic factors and enteric microflora are driving forces regulating mucosal immune responses, some of which are pathogenic and lead to colitis. CD4(+) T cells are the major pathogenic cells in colitis, and the type of injury depends on the nature of the cytokine imbalance. The cytokine network controlled by CD4(+) T cells dictates the outcome of the mucosal immune responses. Certain cytokines, such as transforming growth factor-beta and interleukin-10, have a suppressive role, and immunoregulatory T cells capable of secreting these cytokines may be induced at intestinal mucosal sites. Lessons learned from these experimental models are leading to new strategies for the treatment of IBD.

Journal Article↗
PubMed2000

Are animal models of vasculitis suitable tools?

Several rodent models have been proposed for various forms of systemic vasculitis. The MRL-lpr mouse has been studied extensively as a model for systemic lupus erythematosus. Backcross experiments in combination with genetic linkage studies have firmly established that the phenotype of autoimmune disease is dependent on the combination of various background genes. It has also become apparent that environmental factors, particularly infections, modulate the disease phenotype. Specific interventions, such as the treatment of Brown Norway rats with agents resulting in polyclonal B cell stimulation or immunization with human myeloperoxidase and subsequent localized perfusion with neutrophil lysosomal extract and H2O2, have provided substantial insights into the cellular and molecular mechanisms leading to the development of vasculitis and glomerulonephritis. Even though the existing models may not exactly mirror any specific human disease, they offer reproducible, highly controlled conditions to answer specific questions about pathogenesis and novel therapeutic approaches.

Animals↗
PubMed2005

Reconstitution of a human immune system in immunodeficient mice: models of human alloreaction in vivo.

Rodents have been widely used for studies in transplantation immunology because of their short reproduction period and the relative ease of generating inbred mutant or transgenic strains. However, although many biological mechanisms are similar between rodents and humans, several features clearly distinguish the immune system in these species. Consequently, it is rarely possible to extrapolate observations from rodent models directly into clinical practice. In vitro studies with human cells are useful for elucidation of basic mechanisms, but in order to study complex biological phenomena, in vivo studies are indispensable. In later years, a number of interesting models have been described where immunodeficient mice have been reconstituted with human cells, so-called humanized mice, in order to study human immune responses in vivo. This has opened a new field of experimental immunology that has been applied to areas such as cancer, autoimmunity, allergy, infections, and transplantation biology. In this review, we shall concentrate on the use of severe combined immunodeficient mice reconstituted with human immune or stem cells for studies of human alloreaction in vivo.

Animals↗
PubMedDate not supplied

Oxymetholone: II. Evaluation in the Tg-AC transgenic mouse model for detection of carcinogens.

Several rodent models are under examination as possible alternatives to the classical 2-yr carcinogenicity bioassay. The Tg.AC transgenic mouse has been proposed as a shorter term model offering the possibility of detecting nongenotoxic and genotoxic carcinogenic agents. Retrospective studies of chemicals with established carcinogenic potential have revealed a close correlation between classical bioassay results and the production of skin tumors in the Tg.AC mouse model. Oxymetholone is a synthetic testosterone derivative that is a suspected carcinogen but has shown no evidence of genotoxic activity in a comprehensive battery of genetic toxicity assays. It currently is being tested by the National Toxicology Program (NTP) in a 2-yr rat carcinogenicity bioassay. Because of its nongenotoxicity and the ongoing chronic bioassay, oxymetholone was considered an ideal candidate for a prospective evaluation of the predictive validity of the Tg.AC dermal carcinogenicity model. Consequently, a 6-mo dermal study with oxymetholone in the Tg.AC mouse model was initiated and completed prior to disclosure of the NTP rat bioassay results. In this study, male and female hemizygous Tg.AC mice, 7-8 wk old, were housed individually in suspended plastic cages. An area of dorsal skin was shaved to accommodate dermal applications of 200-microl doses of vehicle control (acetone), drug (1.2, 6.0, or 12 mg oxymetholone in dimethylsulfoxide:acetone, 20:80), or positive control (1.25 microg 12-o-tetradecanoyl-phorbol-13-acetate [TPA]) solutions. Mice received oxymetholone or acetone daily or TPA twice weekly for 20 wk followed by a 6-wk recovery period. The acetone control groups exhibited low spontaneous incidences of papillomas, whereas dermal application of oxymetholone produced dose-related increases in the numbers of papilloma-bearing mice and the numbers of papillomas per animal. Females showed a somewhat greater response to the androgen than did the males. TPA caused an unequivocal increase in papillomas, with males exhibiting a greater response than females. The results of this study indicate that this nongerotoxic androgenic compound possesses proliferative properties. The results predict that chronic systemic administration of oxymetholone will most likely be associated with increased incidences of neoplasms.

Anabolic Agents↗