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PubMed2003

Gene delivery to the lung by means of syngeneic fibroblasts: an experimental model.

An experimental model, in which exogenous gene expression in the lung is achieved, has been established. A fibroblast cell line was transfected with the lacZ gene and was administered to syngeneic mice by either intravenous or intratracheal injection. Enzyme-linked immunosorbent assay and histochemical detection of beta-galactosidase revealed efficient gene delivery to the lung by either route. Kinetic studies demonstrated that the expression peaked immediately after the injection, and this high level was maintained for 7 days by intratracheal and for 14 days by intravenous administration. This system may have potential relevance for certain experimental models requiring specific gene delivery to the lung.

Animals↗
PubMedDate not supplied

Hypotonic intrapleural cisplatin chemotherapy as treatment for pleural carcinomatosis in an experimental model.

An experimental model of intrapleural (i.pl.) chemotherapy using hypotonic solutions of sodium chloride was developed as a treatment for malignancies in the pleural cavity. In the current study, isotonic (308 mOsm/L), hypotonic (154 mOsm/L) and super-hypotonic (62 mOsm/L) solutions that contained equal amounts of cisplatin (CDDP) were prepared for an evaluation of their therapeutic efficacy and the pharmacokinetics of the drug. After the i.pl. injection of solutions of CDDP into mice with i.pl. tumors, we found that the amount of platinum taken up by tumor cells was significantly higher as the osmolarity of the solution was reduced. Hypotonic conditions continued for 1 hour after i.pl. injection of hypotonic solution. The maximum concentration (Cmax) and the area under the curve of concentration versus time (AUC) for platinum in the plasma was significantly higher in rats given CDDP in a hypotonic solution than in rats given the drug in an isotonic solution. The duration of survival of ddy mice with i.pl. tumors that were given i.pl. CDDP in solutions of lower osmolarity was significantly longer than that of mice given CDDP in an isotonic solution. These results indicate that use of a hypotonic solution might enhance the therapeutic efficacy of CDDP in an experimental model of pleural carcinomatosis. This procedure also seems promising as a prophylactic and therapeutic modality for treatment of patients with i.pl. malignancies.

Animals↗
PubMed2000

Evidence for common autoimmune disease genes controlling onset, severity, and chronicity based on experimental models for multiple sclerosis and rheumatoid arthritis.

The pathogenicity of multiple sclerosis is still poorly understood, but identification of susceptibility genes using the animal model experimental allergic encephalomyelitis (EAE) could provide leads. Certain genes may be shared between different autoimmune diseases, and identification of such genes is of obvious importance. To locate gene regions involved in the control of EAE and to compare the findings with the susceptibility loci recently identified in a model for rheumatoid arthritis (pristane-induced arthritis), we made crosses between the encephalomyelitis- and arthritis-susceptible rat strain DA and the resistant E3 strain. Genetic analysis of animals produced in a F2 intercross identified 11 loci associated with specific EAE-associated traits. Interestingly, five of these loci were situated at the same position as major loci controlling pristane-induced arthritis and showed similarities in inheritance pattern and subphenotype associations. Our results show that different phases of EAE are controlled by different sets of genes and that common genes are likely to be involved in different autoimmune diseases.

Animals↗
PubMed2001

Sleep deprivation as a model experimental antidepressant treatment: findings from functional brain imaging.

This paper reviews the functional brain imaging studies in depressed patients treated with sleep deprivation. Sleep deprivation is an excellent experimental model of antidepressant treatments which offer new opportunities to understand the basic neural mechanisms. Its antidepressant effects are efficacious and rapid; sleep deprivation is easy to administer, inexpensive, and relatively safe; it can be studied in patients, normal controls, and animals; and it may lead to new treatments and new paradigms for antidepressant therapies. Seven published papers, coming from five different research centers, using either positron emission tomography (PET) with 18fluorodeoxyglucose (FDG) or single photon emission computerized tomography (SPECT) with Technetium-99-bexamethyl propyleneamine oxime (HMPAO) have relatively consistent findings. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders, and usually the normal controls, in the orbital medial prefrontal cortex, and especially in the ventral portions of the anterior cingulate cortex. Secondly, after sleep deprivation, these hyperactive areas normalize in the responders. The magnitude of the clinical improvement was significantly correlated with decreased local glucose metabolic rate or cerebral blood flow in three studies. The results are consistent with some but not all functional brain imaging studies of antidepressant medications in depressed patients. Finally, a SPECT study using a radioactively labeled D2 receptor antagonist suggests that the antidepressant benefits of sleep deprivation are correlated with endogenous release of dopamine.

Brain↗
PubMed2002

Comparison of PTFE, pericardium bovine and fascia lata for repair of incisional hernia in rat model, experimental study.

Incisional hernia is a frequent complication of abdominal surgery developing in 11-20 % of patients undergoing an abdominal operation. Regarding morbidity and loss of manpower, incisional hernias continue to be a fundamental problem for surgeons. In this experimental study, three commonly used mesh materials (Goretex PTFE; Tutoplast Fascia lata; Tutopatch Pericardium bovine) were compared according to effectiveness, strength, adhesion formation, histological changes, and early complications. Three groups, each consisting of 14 rats, have been formed as group A: polytetrafluoroethylene (PTFE), group B: pericardium bovine and group C: fascia lata. Evaluations were achieved at the end of the first and second postoperative week, respectively. Adhesion formation, wound maturation, bursting pressure, and tensile strength were evaluated. No statistically significant difference regarding adhesion formation was observed between groups although adhesion formation was less significant in PTFE and pericardium bovine groups than in the fascia lata group. Bursting pressure and tensile strength values were significantly higher in PTFE group than in the fascia lata group ( P<0.05). No statistically significant difference was observed between groups regarding wound maturation. In this experimental model, PTFE and pericardium bovine were found to be superior to fascia lata in abdominal wall repair.

Animals↗
PubMedDate not supplied

[Model experimental study of protein-calorie malnutrition in mice].

With a view to form an experimental model of protein-malnutrition, mice are fed with two different commercial diets, the "nutrixan" and the "provende" which are included in different concentrations to a rice starch. Only the "provende" gives an workable model with three different growths which differ from the normal by a decrease which is proportional to the protein-deficiency. The incidence of the age and weight of the animals and the period of life of the beginning of the malnutrition are studied.

Animals↗
PubMed1993

[Sleepiness. Experimental models].

Some experimental models of sleepiness are reviewed. The model of the narcoleptic dog is the best one to study the mechanisms of cataplexy. Idiopathic sleepiness can be experimentally studied by acting upon either circadian or homeostatic regulation of sleep. The paradoxical sleep rebound which occurs after its previous suppression has been explained by different theories which are summarized. Finally, the decrease of waking which follows either lesion or pharmacological alterations is useful to develop new molecules which can increase waking, in a safe manner.

Animals↗
PubMed1985

Radiation-induced hydronephrosis in the rat: a new experimental model.

An experimental model for investigating the effects of localized X-irradiation of a single ureter or the bladder trigone in rats is described. Obstruction of the urinary tract in the irradiated region gives rise to hydroureter and hydronephrosis and the development of these, as detected urographically, gives a clear-cut end point. After irradiation of the ureter with a single dose of 37.4 Gy many rats died of gut lesions but after 23.4 Gy only one such death occurred while 14 of 16 rats developed hydronephrosis. Irradiation of the bladder trigone was not associated with intercurrent deaths, even after 40 Gy, and after 25 Gy 9 of 11 rats developed hydronephrosis.

Animals↗
PubMed1996

Complications of combined intraoperative radiation (IORT) and external radiation (ERT) of the upper abdomen: an experimental model.

An experimental model in the rabbit is presented which is suitable for analysis of clinically relevant, early side-effects of combined upper abdominal IORT and ERT. Fractionated ERT alone given through an upper abdominal a.-p. field including the entire stomach caused gastric ulcerations within < or = 58 days. Latent times decreased with increasing dose and the ED50 for occurrence of ulcers was 39 +/- 3.3 Gy. Single doses of IORT of 20-40 Gy alone administered through a 2-cm diameter field localized on the coeliac axis and carefully excluding any intestinal mucosa caused neither gastric ulcerations nor other clinical symptoms. When ERT with 40 Gy was preceded by IORT with 20-40 Gy or by sham IORT, 13 out of 15 animals developed ulcers after latent times which in a life-table analysis were shown to be significantly shorter than after ERT alone. However, a statistically significant IORT dose-dependence of latent time or incidence of ulcers could not be demonstrated in the present experiment. The most significant histological changes were observed in the areas of gastric ulcers. Already during ERT, the mucosal epithelium was depleted and regenerative activity was evident in spite of ongoing fractionated irradiation. However, profound irregularities in glandular structure and distribution, as well as number of proliferating epithelial cells were still present in healed ulcers at 80 days. In summary, IORT to the coeliac artery did precipitate the development of gastric ulcers induced by subsequent ERT. On the one hand, the data indicate that the surgical procedure of IORT did contribute to this effect. On the other hand, IORT to the coeliac artery could cause transient, functional alterations in blood supply to the depending organs, i.e. the stomach, and could thus precipitate the development of radiation-induced ulcers.

Animals↗
PubMed1985

Chagas' heart disease: experimental models.

An experimental model embodies an evaluation procedure that helps the investigator to choose between possible alternatives. In this paper, consideration is given to a variety of aspects related to the host-parasite relationship in Trypanosoma cruzi infection and disease. Although several animal species have been used, there is still a lack of consistent experimental studies. A few examples of investigations mainly in dogs, monkeys, and rabbits are briefly described, showing the diversity of methodological approaches and, therefore, the difficulty experienced in comparing results and interpretations. Emphasis was given to the need for a suitable model presenting all possible stage of the infection as seen in man, as well as the functional and organic disorders commonly seen in this disease. The alterations of the autonomic nervous system involving the heart and other organs in Chagas' disease was stressed.

Acute Disease↗
PubMed2004

Differences in survival, brain damage, and cerebrospinal fluid cytokine kinetics due to meningitis caused by 3 different Streptococcus pneumoniae serotypes: evaluation in humans and in 2 experimental models.

BACKGROUND: Experimental meningitis with Streptococcus pneumoniae serotypes 1, 3, and 9 has resulted in pronounced differences in disease severity, but clinical meningitis studies addressing serotype-related differences in case-fatality rates are lacking. METHODS: Study subjects were Danish patients with pneumococcal meningitis due to serotype 1 (n=38), 3 (n=69), or 9V (n=59) during 1990-2002 for whom clinical information was available. The 3 serotypes were tested for brain damage and cerebrospinal fluid (CSF) inflammatory kinetics in 2 experimental models of meningitis. RESULTS: Patients with serotype 1 had a significantly lower case-fatality rate (3%), compared with patients with serotypes 3 (23%) and 9V (32%) (P=.0047, log-rank test). Age and serotype were independent prognostic factors for fatal outcome. In experimental meningitis, the median number of areas per brain slide with brain damage was significantly lower in rats infected with serotype 1 than in rats infected with serotypes 3 and 9V. Three distinct patterns of brain damage were observed: serotype 1, cortical hemorrhage; serotype 3, cortical necrosis and abscess formation; and serotype 9V, subcortical (callosal) abscess formation. Serotype 1 caused the poorest bacterial growth and lowest CSF levels of white blood cells, tumor necrosis factor- alpha, and interleukin-8 (P<.05). CONCLUSION: Case-fatality rates of patients with pneumococcal meningitis, the degree and pattern of brain damage, and CSF cytochemical alterations in experimental pneumococcal meningitis differ according to serotype.

Adult↗
PubMed1997

Polyclonal T cell elimination by prolonged immunostimulation in an experimental model.

An experimental model of immunological deficiency obtained by treating mice for 6 months with serum of human blood drawn from different healthy individuals has been studied. The results show that an alteration of a circulating lymphocyte population with alterations of the ratio CD4+/CD8+ appeared in mice stimulated for a long period with immunogens. Mice treated for 2-4 months showed an increase in B lymphocytes and a decrease in the total number of T lymphocytes, with a decrease in CD4+ lymphocytes and an increase in CD8+ lymphocytes. After 4 months, the CD8+ lymphocyte population started to decrease, with a ratio of CD4+/CD8+ reaching almost 1. In animals treated for 2-3 months, the mean survival time (MST) following experimental infection with Salmonella typhimurium presented a decrease to 5 days, and after 5-6 months of treatment presented a decrease to 3-2.5 days. The bacteraemia was modified in comparison with controls. Prolonged exposure to antigens also induced lymphocyte apoptosis: cells of animals treated for 4-6 months presented increased levels of apoptosis with a percentage that reached 30-35%. A semiquantitative evaluation of the level of heat shock protein (hsp) in splenic lymphocytes showed an increase in the presence of hsp60 and hsp70 in the first 3 months of treatment, which then remained constant for up to 6 months.

Animals↗
PubMed1988

The pathogenesis of spinal epidural abscess: microangiographic studies in an experimental model.

An experimental model of spinal epidural abscess was developed in rabbits by injecting Staphylococcus aureus into the posterior thoracolumbar epidural space. This model has been shown to reproduce the neurological, bacteriological, and radiological aspects of the human disease. In this study, the effect of the infectious epidural mass on the vasculature of the spinal cord in paraplegic rabbits was studied using microangiographic techniques. The normal vascular anatomy of the rabbit spinal cord was defined in control experiments. Vascular proliferation was demonstrated in the epidural space surrounding the abscesses. Anterior and paired posterior spinal arteries remained patent in paraplegic rabbits with mild or moderate spinal cord compression and in some cases of severe compression. In animals with severe compression, the anterior epidural venous plexus remained patent, but the dorsal spinal vein was occluded. Occlusion of perforating arteries occurred only with extreme spinal cord compression. These data indicate that the initial neurological deficit associated with experimental spinal epidural abscess is not due to vascular thrombosis.

Abscess↗
PubMed1999

Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model.

Both experimental and clinical data show evidence of a correlation between elevated blood levels of carcinoembryonic antigen (CEA) and the development of liver metastases from colorectal carcinomas. However, a cause-effect relationship between these two observations has not been demonstrated. For this reason, we developed a new experimental model to evaluate the possible role of circulating CEA in the facilitation of liver metastases. A CEA-negative subclone from the human colon carcinoma cell line CO115 was transfected either with CEA-cDNA truncated at its 3' end by the deletion of 78 base pairs leading to the synthesis of a secreted form of CEA or with a full-length CEA-cDNA leading to the synthesis of the entire CEA molecule linked to the cell surface by a GPI anchor. Transfectants were selected either for their high CEA secretion (clone CO115-2C2 secreting up to 13 microg CEA per 10(6) cells within 72 h) or for their high CEA membrane expression (clone CO115-5F12 expressing up to 1 x 10(6) CEA molecules per cell). When grafted subcutaneously, CO115-2C2 cells gave rise to circulating CEA levels that were directly related to the tumour volume (from 100 to 1000 ng ml(-1) for tumours ranging from 100 to 1000 mm3), whereas no circulating CEA was detectable in CO115 and CO115-5F12 tumour-bearing mice. Three series of nude mice bearing a subcutaneous xenograft from either clone CO115-2C2 or the CO115-5F12 transfectant, or an untransfected CO115 xenograft, were further challenged for induction of experimental liver metastases by intrasplenic injection of three different CEA-expressing human colorectal carcinoma cell lines (LoVo, LS174T or CO112). The number and size of the liver metastases were shown to be independent of the circulating CEA levels induced by the subcutaneous CEA secreting clone (CO115-2C2), but they were directly related to the metastatic properties of the intrasplenically injected tumour cells.

Animals↗
PubMed1980

Parenteral nutrition and repeated hemodialysis of bilaterally nephrectomized conscious dogs. I. Experimental model.

The experimental model of the anephric, daily hemodialyzed conscious dog with exclusive nutrition was realized by means of a closed batch hemodialysis system (Rhodial 75) and a highly permeable polyacrylonitrile membrane (RP 6 dialyzer). Technical details, parenteral feeding, hemodialysis, and amino acid solutions preparations were described to realize a stable condition of the animals for further metabolic analyses during the early anephric period.

Amino Acids↗
PubMed1991

The assessment of IUD mechanical resistance: an experimental model.

An experimental model to assess IUD resistance to mechanical fatigue is presented by which the performance of several IUD models has been tested both new and after variable intrauterine use, up to 33 months. According to the results of this study, IUD resistance decreases exponentially with time, and IUD shape apparently affects resistance. Therefore, prolonged intrauterine use apparently increases rupture liability. Moreover, it is suggested that some IUD features can minimize chances of intrauterine rupture and/or fragmentation.

Intrauterine Devices↗
PubMed1991

Trabecular bone remodeling: an experimental model.

An experimental model, capable of inducing controlled stress fields to the distal femoral metaphyses of large dogs, is presented. This model utilized an implantable hydraulic device incorporating five loading cylinders and platens in direct contact with an exposed plane of trabecular bone. A microprocessor controls the loading characteristics, and finite element models were created to calculate the induced stress and strain fields. The trabecular remodeling response is measured using serial in vivo computed tomography, in vitro microcomputed tomography, and histologic analysis. The results of the experiment indicate that significant remodeling can be induced by the activated implant. An increase in trabecular orientation toward the loaded platens was observed, and a statistically significant decrease in connectivity was documented. The greatest effect was associated with a change in the loading rate. A fast rise time (70 ms) loading waveform induced significant bone ingrowth at the implant interface when compared to a slow rise time waveform (700 ms), and demonstrated high correlations with the calculated stress fields as remodeling approached an equilibrium state.

Animals↗
PubMed1987

Partial ureteric obstruction: a new variable canine experimental model.

An experimental model of ureteric obstruction should be accurate and persistent, and allow variation of the degree of obstruction. A model was tested in 28 dogs consisting of insertion of an obstructing stent into the left ureter, and the degree of obstruction was varied by altering the internal diameter of the stents. The effects of such an obstruction on the following features were studied: renal intrapelvic pressure, intravenous urography, creatinine clearance, vascular casts, and both gross and histological examination. The procedure was well tolerated and caused a persistent, unchanging degree of partial ureteric obstruction. Pathological changes of obstructive uropathy were produced. This model can be used for further pathophysiological studies.

Animals↗