Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Models, Experimental”

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 703 records · Page 39Linked to original sources
PubMed1989

Comparative study of four antifungal drugs in an experimental model of murine cryptococcosis.

A comparative study among amphotericin B, 5-fluorocytosine, itraconazole and fluconazole in the treatment of experimental cryptococcosis in mice, was carried out. Seventy male Balb C mice were inoculated intraperitoneally with 10(7) cells of Cryptococcus neoformans var. neoformans. They were divided in 7 groups of 10 animals each one: 1) treated with fluconazole by gavage at a daily dose of 16 mg/kg; 2) treated with itraconazole by gavage at a daily dose of 16 mg/kg; 3) treated with 5-fluorocytosine by gavage at a daily dose of 300 mg/kg; 4) treated with amphotericin B intraperitoneally at a dose of 6 mg/kg every other day; 5) control animals receiving polietilenglicol 200 by gavage; 6) control animals receiving distilled water by gavage and 7) control animals receiving sterile distilled water by intraperitoneal route. All the treatments started 5 days after the challenge inoculation and they were given for 2 weeks. The following parameters were taken into account: survival time, macroscopic aspect of the organ after the complete autopsy, microscopic investigation of yeasts in brain, lungs, spleen and liver, histopathology studies of these organs, the colony forming units per gram and massive seeding of brain and lungs. The survival index of the different groups was the most efficient method to measure the antifungal compounds activity. Amphotericin B increased significantly the animals survival and modified the histopathologic response in the studied organs. The colony forming units and the massive seeding in brain and lung showed that this antifungal agent is unable of producing the biological cure of this experimental model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Systemic penicillin as an experimental model of epilepsy.

Systemic use of high-dose penicillin was studied in rats and cats to establish an experimental model of epilepsy. In rats, intraperitoneal injection of 2.5 to 5.0 million units/kg (MU/kg) penicillin was effective to induce spikes in 45.7 +/- 31.0 min (means +/- SD) and seizure in 71.5 +/- 38.4 min. In cats, intravenous administration of penicillin at 0.5 to 1.0 MU/kg induced spikes in 10.4 +/- 7.8 min and seizure in 32.2 +/- 19.8 min. Intraperitoneal use of penicillin at 1.0 to 2.0 MU/kg caused spikes in 24.0 +/- 18.4 min and seizure in 71.2 +/- 38.3 min. Pretreatment with intravenous isoniazid at 16.3 +/- 10.3 mg/kg significantly delayed the appearance of intravenous penicillin-induced spikes to 63.1 +/- 49.8 min or prevented the appearance of spikes and abolished the occurrence of seizures. Acupuncture at various points increased the penicillin-induced spikes and seizures.

Acupuncture Therapy↗
PubMed1995

Characterisation of an experimental model of stroke produced by intracerebral microinjection of endothelin-1 adjacent to the rat middle cerebral artery.

A novel experimental model of stroke has been developed using the powerful vasoconstrictor peptide, endothelin-1, to occlude the middle cerebral artery (MCA) of anaesthetised rats. Intracerebral microinjections of endothelin-1 were administered under stereotaxic guidance adjacent to the MCA, and after 3 days rats were perfusion fixed for histopathological determination of ischaemic brain damage. The pattern of brain damage noted using this model was similar to that reported following permanent surgical occlusion of the MCA. Brain damage was apparent in the dorsal and lateral neocortex (98 +/- 12 mm3) and striatum (32 +/- 3 mm3) ipsilateral to the insult. Rats anaesthetised with halothane and barbiturate exhibited a similar volume of brain damage. However, infarct volume increased when the duration of halothane anaesthesia was extended from 5 to 180 min post-occlusion. Neuroprotection studies demonstrated that dizocilpine (5 mg/kg, i.p.), administered 30 min prior to MCA occlusion, reduced the volume of cortical brain damage by 51% (P < 0.05) but did not alter the volume of striatal brain damage. The present results demonstrate that microinjections of endothelin-1 adjacent to the rat MCA result in a reproducible pattern of focal cerebral infarction which is sensitive to the duration of anaesthesia and can be reduced by dizocilpine.

Anesthesia↗
PubMed1990

The ovariectomized, lactating rat as an experimental model for osteopenia: calcium metabolism and bone changes.

The ovariectomized, lactating rat (Sprague-Dawley) is proposed as an experimental model for the rapid development of osteopenia which may be used to test the effectiveness of bone-retentive drugs potentially useful in treating osteoporotic women. Rats were ovariectomized (OVX) on day 2 postpartum and were kept on a low-calcium diet (0.1%). Measurements of serum total calcium, ionic calcium, albumin and parathyroid hormone were conducted between days 4 and 21 of lactation. Serum total and ionic calcium and albumin were significantly lower and serum parathyroid hormone was significantly higher in all lactating rats at 16 days postpartum compared to nonlactating controls. Mean bone mass of the femurs of OVX lactating rats measured at day 21 was approximately 50% of that of non-lactating intact controls. The enhanced duodenal calcium absorption (in everted gut sacs) associated with lactation was not affected by OVX and neither was the average litter weight gain between 2 and 14 days of lactation. In conclusion, lactation coupled with a low-calcium diet resulted in marked osteopenia, depressed serum calcium (both total and ionic) and significantly elevated serum parathyroid hormone concentration. The rapid and extensive bone loss of this model makes it appropriate for the study of therapeutic agents designed to retain bone mass.

Animals↗
PubMed2005

[Experimental model of recurrent acute otitis media: morphological study of the cochlear damage using scanning electron microscopy].

We designed an experimental model of acute otitis media to study its effects in the hair cells of the organ of Corti. Thirty Sprague-Dawley rats were used, and divided into three groups. The rats from the first group were exposed to one episode of acute otitis media, the second group to two episodes and the third group were induced with three episodes of acute otitis media. After that, all cochleas were processed by specific surface specimen method. Finally, each organ of Corti was examined using scanning electron microscopy. Damage to hearing cells was compared between the three groups involved in the study. Significant great loss of sensory cells was found when the episodes of acute otitis media were repeated, in both turns of the cochlea: basal (alpha = 0.002) and distal (alpha = 0.001). The results reported in this study indicate the importance of specialized treatment in children affected with recurrent acute otitis media to prevent cochlear damage.

Acute Disease↗
PubMedDate not supplied

Activity of ruboxyl, a nitroxyl derivative of daunorubicin, on experimental models of colorectal cancer metastases.

We evaluated the activity of ruboxyl (Rbx), a nitroxyl analogue of daunorubicin (Dauno), in experimental models of hepatic metastases from colorectal carcinoma (CRC) and compared it with its parent compound and with 5-fluorouracil (5FU). In mice treated by intraperitoneal injections Rbx and 5FU proved more effective than Dauno: the Index of Inhibition of Metastases in comparison with controls was 43% for Dauno, 70% for 5FU and 84% for Rbx. In BDIX rats implanted with the syngeneic cell line DHD K12/TRb, both Rbx and 5FU, administered as a continuous intravenous infusion for 7 days, reduced the development of liver metastases from a median of 23.8 +/- 2.16 for controls to 3.2 +/- 1.3 for 5FU and 1.0 +/- 1.4 for Rbx (p < 0.0001 versus controls for both treatments): the comparison of Rbx and 5FU showed a trend in favour of this new anthracycline. Median survival was prolonged from 40.6 +/- 3.4 days in controls to 56.0 +/- 5.8 days with Rbx and 58.0 +/- 4.69 days with 5FU. Considering that in a phase I study Rbx showed only minor and manageable toxic side effect, its activity in the clinical treatment of CRC metastases may deserve further attention.

Adenocarcinoma↗
PubMed1996

Cyclosporin A delays the presentation of intimal hyperplasia in an experimental model of arterial autograft.

A study was made of the effect of cyclosporin A on intimal hyperplasia in an experimental model of arterial autograft. Fifty female Sprague-Dawley rats weighing 250-300 g were employed. Using a microsurgical technique, an arterial autograft measuring approximately 5 mm in length was implanted in right common iliac artery. Two groups were established: group I (control), consisting of 25 animals subjected only to arterial autograft, and group II (preoperative cyclosporin A), also consisting of 25 animals, which received a daily subcutaneous dose of 5 mg/kg cyclosporin A (Sandimmun, Sandoz) for 4 days before the surgical procedure. The animals were sacrificed on postoperative days 7, 14, 21, 30 or 50. Specimens were studied by optical microscopy, transmission and scanning electron microscopy, autoradiography, and morphometry. Endothelialization of the graft zone was slow in the cyclosporin-treated group. Hyperplasia was delayed notably, but at 30 days the hyperplastic process had improved and at 50 days it was similar to that of the control group. In the cyclosporin-treated group, thymidine was not taken up by the medial layer; the absence of medial thymidine uptake correlated with ultrastructural evidence of medial degeneration with lipid vacuolization of the smooth muscle cells and the presence of macrophages. These results suggest that cyclosporin A does not inhibit intimal hyperplasia but instead delays its occurrence, probably because of the drug's toxicity for smooth muscle cells.

Animals↗
PubMed2005

Involvement of nitric oxide in neurodegeneration: a study on the experimental models of Parkinson's disease.

The present study was undertaken to explore involvement of nitric oxide (NO) in the experimental models of Parkinson's disease. Neurodegeneration was induced by unilateral injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) in the right striatum. Lesions were functionally evaluated by amphetamine-induced asymmetrical behaviour and by decrease in the tyrosine hydroxylase (TH) immunostaining. An induction in the expression of iNOS and augmentation in nitrite content was observed in both the models. The extent of increase in iNOS expression was, however, different but the elevation in the nitrite content was comparable in both the models. The increase in iNOS expression inversely correlated with the tyrosine hydroxylase (TH) immunolabeling. Animals pretreated with a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), exhibited complete protection against amphetamine induced rotations in both the models. Thus, augmented NO availability subsequent to iNOS induction seems to play an important role in the initial phase of neurodegeneration.

Animals↗
PubMed2001

Intraoperative immunophotodetection for radical resection of cancers: evaluation in an experimental model.

The aim of our study was to assess the technique of immunophotodetection (IPD) in intraoperative situations in an experimental model and to determine its capacity to detect very small tumor masses. IPD is a recent technology involving fluorescent dye-labeled monoclonal antibodies (MAbs) directed against tumor-associated antigens. Up to now, no intraoperative device for IPD has been developed, and limits of detection of the technique are unknown. MAb-dye conjugates were prepared using the anti-carcinoembryonic antigen MAb 35A7 labeled with indocyanine and (125)I. Time-dependent (6, 12, 24, 48, and 96 h post i.v. injection) and dose-dependent (10, 40, and 100 microg of conjugate) biodistribution studies were performed in nude mice bearing an LS174T peritoneal carcinomatosis demonstrating high tumor uptake (up to 21% of the injected dose/g of tumor 48 h postinjection). Intraoperative IPD was studied, using a newly developed device, in 16 mice 48 h after i.v. injection of 40 microg of the (125)I-MAb 35A7-indocyanine conjugate. The fluorescent status of 333 biopsies was compared with their histological analysis. Sensitivity was 90.7%, specificity was 97.2%, the positive predictive value was 94.7%, and the negative predictive value was 94.9%. Detection of very small nodules (<1 mg in weight or <1 mm in diameter) was possible. However, we observed a decrease in sensitivity as a function of tumor mass: 100% for nodules >10 mg versus 78% for nodules < or =1 mg. These experiments demonstrate that intraoperative IPD is easy to use and associated with high sensitivity and specificity, even for low tumor masses. On the basis of these encouraging results, intraoperative IPD should be assessed in a clinical study.

Animals↗
PubMed1989

[Experimental model of ischemic injury of the spinal cord after temporary occlusion of the thoracic artery in the dog].

An experimental model for the ischemic damage of the spinal marrow is described by occlusion of the descending thoracic aorta at a level with the 5th or 6th thoracic vertebrae during 30 min. 17 dogs were operated in general anesthesia. The thoracic aorta was clamped by a Pean's clamp in the 1st group (11 animals). One dog was not paralysed, another dog died after thrombosis of the aorta in the locality of clamping. The occlusion was carried out by means of a tourniquet in a 2nd group (6 animals) and pH, blood gas values, and blood pressure in the axillary artery or the common carotid artery were measured. An increase of the blood pressure above the initial value was prevented by slow infusion of nitroprusside. The oxygen pressure in the spinal marrow tissue was measured continuously simultaneously. All these animals survived the operation and a complete damage of the spinal marrow occurred.

Animals↗
PubMed1997

Experimental model of obstructive jaundice in mongrel dog: study of subsequent pathological changes in liver.

BACKGROUND: Attempts at creating an experimental model of obstructive jaundice in large animals have been unsuccessful because of frequent fistulization of the ligated bile duct. OBJECTIVES: To produce a model of obstructive jaundice in mongrel dogs and to study subsequent serial pathological changes in the liver. METHODS: Four techniques were evaluated in four dogs to produce obstructive jaundice. After creation of a successful model, subsequent clinical and biochemical outcome and serial pathological changes in the liver were studied in another 14 dogs. RESULTS: Complete extrahepatic biliary dissection produced a model of persistent obstructive jaundice. Serial histological changes included inflammation and edema in the first 14 days followed by lymphocytic infiltration at 28 days. Fibrosis started by day 7 and resulted in architectural distortion by day 21. CONCLUSION: An acute, complete and irreversible model of obstructive jaundice can be produced by extrahepatic biliary tree excision and ligation. Serial pathological changes showed acute inflammation, followed by fibrosis and architectural distortion.

Animals↗
PubMed2003

Microarray analysis of nonhuman primates: validation of experimental models in neurological disorders.

Nonhuman primates (NHPs) have provided robust experimental animal models for many human-related diseases due to their similar physiologies. Nonetheless, profound differences remain in the acquisition, progression, and outcome of important diseases such as AIDS and Alzheimer's, for which the underlying basis remains obscure. We explored the utility of human high-density oligonucleotide arrays to survey the transcription profile of NHP genomes. Total RNA from prefrontal cortices of human (Homo sapiens), common chimpanzee (Pan troglodytes), cynomolgous macaque (Macaca fascicularis), and common marmoset (Callithrix jacchus) was labeled and hybridized to Affymetrix U95A GeneChip probe arrays. Corresponding data obtained previously from common chimpanzee and orangutan (Pongo pygmaeus) were added for comparison. Qualitative (present or not detected) and quantitative (expression level) analysis indicated that many genes known to be involved in human neurological disorders were present and regulated in NHPs. A gene involved in dopamine metabolism (catechol-O-methyltransferase) was absent in macaque and marmoset. Glutamate receptor 2 was up-regulated, and transcription-associated genes were down-regulated in NHPs compared with humans. We demonstrate that transcript profiling of NHPs could provide comparative genomic data to validate and better focus experimental animal models of human neurological disorders.

Adult↗
PubMedDate not supplied

Experimental models used to measure direct and indirect ethanol teratogenicity.

The teratogenic effects of ethanol have been widely studied in a variety of experimental models. In humans, ethanol teratogenicity results from both direct and indirect effects. This paper reviews the differences between direct and indirect effects of ethanol on the developing fetus. Experimental paradigms are discussed that attempt to differentiate between direct and indirect effects. For the purpose of this review, direct effects of ethanol are caused by ethanol interacting with the fetal cell. Indirect effects of ethanol teratogenicity are defined as any perturbation of the developing fetus resulting from ethanol exposure but not caused by ethanol's interacting with the fetal cell. Indirect effects of ethanol teratogenicity include: ethanol-induced maternal undernutrition; ethanol-induced placental dysfunction and acetaldehyde teratogenicity.

Abnormalities, Drug-Induced↗
PubMed1998

Perfluorocarbon broncho-alveolar lavage and liquid ventilation versus saline broncho-alveolar lavage in adult guinea pig experimental model of meconium inhalation.

OBJECTIVE: This study compares perfluorocarbon broncho-alveolar lavage (PFC-BAL) with isotonic saline broncho-alveolar lavage (saline-BAL) in an experimental model of meconium aspiration in adult guinea pigs. DESIGN: Prospective controlled experimental study. PATIENTS AND METHODS: Ten male guinea pigs were given 1 ml of human meconium, diluted to 10% in isotonic saline, via tracheostomy and then artificially ventilated. After stabilization, five animals (control group) underwent BAL with 10 ml/ kg isotonic saline solution. After bronchial suctioning, a further BAL with 2 ml/kg saline was performed. The other five animals (study group) underwent BAL with 100 ml/kg of PFC (RIMAR 101). Bronchosuction was effected at 5 min and then a BAL with PFC 2 ml/kg was performed. Both groups received conventional mechanical ventilation during the lavage procedures. Within 20 min all the saline-BAL treated animals died, whereas the PFC-BAL treated animals survived and were then treated with total liquid ventilation (TLV) by gravity. MEASUREMENTS AND RESULTS: After meconium inhalation in both groups, a large alveolar-arterial oxygen difference, hypercarbia, severe acidosis and tachycardia were noticed. In PFC treated animals, an improvement in blood gases was noted and acid-base balance remained stable compared to saline-BAL treated animals. No haemodynamic change was observed during or after PFC-BAL, while during saline-BAL there was evidence of bradycardia, hypotension and respiratory failure, which led to the death of the animals. The histological lung sections in the PFC-BAL group showed evidence of normal alveolar expansion with a minimal presence of meconium debris in the small bronchioles. In saline-BAL treated animals, the lung structure appeared severely compromised with the presence of meconium in bronchioles and alveoli, intra-alveolar oedema and haemorrhagic areas. CONCLUSIONS: This study confirms the detrimental effects of meconium aspiration and the impairment of lung function following saline-BAL. By contrast, PFC-BAL and TLV by gravity seemed to prevent absorption of meconium, facilitate its removal, improve gas exchange and reduce lung barotrauma.

Acute Disease↗
PubMed2005

Dilemma of virulence of Streptococcus suis: Canadian isolate 89-1591 characterized as a virulent strain using a standardized experimental model in pigs.

Virulence of Streptococccus suis capsular type 2 strain 89-1591 has been controversial in literature. A standardized experimental model with specific-pathogen free piglets was used for a new evaluation of this strain. Twenty-nine piglets were allotted in 4 separated groups. Group 1 consisted of negative control animals which received broth medium. Groups 2, 3, and 4 were intravenously challenged with 2 mL of S. suis, strains 1330, 89-1591, and 166', respectively. The strain 1330 is a recognized avirulent Canadian strain. The strain 166' is a reference French virulent isolate. Pigs inoculated with strain 1330 did not present clinical signs of a S. suis infection. Contamination in organs and bacterial blood circulation were rare and lesions were almost non-existent. Infection of pigs with S. suis strain 89-1591 (group 3) and 166' (group 4) caused severe clinical problems, animals infected with S. suis 166' were the most affected. Pigs presented with clinical signs such as high body temperature, lameness, nervous symptoms, and even mortality. Lesions associated with S. suis were numerous for both strains, but more evident in animals of group 4. It can be concluded that S. suis strain 89-1591 is virulent, although its virulence seems to be lower than that of the French strain. Results of an experimental infection with strain 89-1591 may depend on different factors such as the route of inoculation and the immunological status of the animals used. Using conventional animals, with an unknown status regarding previous S. suis infections, equivocal results may be obtained, and this may explain differences reported by some authors with the same strain.

Analysis of Variance↗
PubMed2002

Experimental models of fetal obstructive nephropathy.

Urinary tract obstruction in the developing human fetus is an important cause of postnatal kidney failure and is the most common cause of end-stage renal disease and chronic renal failure in boys less than 4 years of age. Although the pathogenesis of renal dysplasia resulting from urinary tract obstruction is not well defined, it is clear that the earlier the obstruction occurs during in utero nephrogenesis the more severe the histopathological changes. Efforts to intervene in the human fetus have been hampered by an inaccuracy of diagnosis and by a lack of validation of in utero features predictive of poor outcome. A number of experimental models of obstructive renal dysplasia have been developed, which result in the consistent histopathological features of tubular cell apoptosis, mesenchymal expansion with mesenchymal myocyte transformation, and decreased glomerular endowment and glomerular injury. Defining the optimal timing of release of obstruction and restoring normal developmental gene and protein patterns should guide future intervention in these processes. Experimental animal models that closely simulate human development and disease will, thus, be essential for exploring these questions, and for assessing novel fetal therapies for future human application.

Animals↗
PubMedDate not supplied

Pentamidine-induced dysglycaemia: experimental models in the rat.

In order to analyse further the pathophysiology of pentamidine effects on blood glucose regulation, the following experimental models were established in rats: impairment of the renal function, bile duct ligation, inhibition of the P450 cytochrome enzyme system. In otherwise intact rats, 7.5 mg/day pentamidine was well tolerated whereas doses of 15 mg/day induced severe, relapsing and eventually lethal hypoglycaemia within a few days. Induction of a renal insufficiency of graded severity by treatment with gentamycin, subtotal nephrectomy and total bilateral nephrectomy resulted in repetitive, severe (sometimes lethal) hypoglycaemia, alternating with hyperglycaemia, glucosuria and ketonuria in pentamidine-treated rats (7.5 mg/d). No long-standing insulin-dependent diabetes was observed. In the dysglycemic animals, plasma insulin levels were inappropriate to the concomitant glycaemia; no stimulation was obtained by i.v. glucose. Glucagon levels were higher than normal, suppressible by i.v. glucose, responsive to IV arginine and to hypoglycaemia. Dysglycemic events were more frequent and marked in the rats with the most severe renal functional derangement. They were more frequent in the rats treated with pentamidine mesylate than in those treated with the isethionate salt. Control uremic rats (free of pentamidine) remained euglycaemic. The islets of Langerhans displayed severe vascular congestion and degranulation and necrosis of the B cells, while the non B cells (and particularly the A cells) were intact. Exocrine pancreatitis was occasionally observed in the most severely uremic rats. In contrast with uremic rats, neither surgical ligation of choledocus, nor treatment by P450 cytochrome inhibitors (particularly ketoconazole) precipitated dysglycaemia in the pentamidine-treated rats. These experimental data: 1) strengthen the concept of inappropriate insulin release from pentamidine-lesioned islet B cells due to pentamidine accumulation; 2) indicate a predominant role for renal insufficiency in determining the accumulation of this drug; 3) emphasize the clinical importance of renal insufficiency as a risk factor for pentamidine-induced dysglycaemia. Association with ketoconazole does not appear to be a risk factor.

Animals↗
PubMed1998

Establishment of an experimental model of colon cancer which replicates the regional extension pattern of human colorectal adenocarcinoma.

OBJECTIVE: The aim of this study was to develop an experimental model of colon adenocarcinoma based on the orthotopic implantation of tumor cells in syngenic rats, which reproduces the regional extension pattern of human colorectal adenocarcinoma. EXPERIMENTAL DESIGN: Cell cultures: cell line DHD/K12-PROb. ANIMALS: BD-IX rats. Tumour implantation: intra-caecal injection containing 1 x 10(6) cells in 0.25 ml of PBS. DESIGN: randomized observation study of three groups until five rats were shown to have cancer implantations in each group: GROUP I: sacrificed one week after the injection (n = 6), GROUP II: sacrificed two weeks after the injection (n = 9), GROUP III: sacrificed four weeks after the injection (n = 10). MEASUREMENTS: macroscopic and histological examination, with particular emphasis on caecal lesions. Tumours were classified according to the TNM system (UICC, 1987). RESULTS: GROUP I: tumors were found in 83% of cases (5/6), 4 of which were classified as T1N0M0 and 1 as T2N0M0. GROUP II: tumour in 55.5% of cases (5/9). One was classified as T1N0M0, 3 as T2N0M0 and 1 as T3N0MPER. GROUP III: tumors were found in 50% of cases (5/10). Two were classified as T4N0M0, 2 as T4N1MPER, and 1 as T3N1MPER. The degree of wall infiltration of the tumor showed statistical differences between groups I and III and groups II and III (p < 0.05). CONCLUSIONS: Our model offers a step by step reproduction of events described for human colorectal adenocarcinoma. It was therefore easy to predict how long it would take to achieve a degree of local extension, which is essential in the design of cancer experiments. Moreover, this model has the advantage that it uses immunocompetent rats, which facilitates the methodology.

Adenocarcinoma↗