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PubMedDate not supplied

[The methodological aspects of experimental modelling and of assessing the hereditary sequelae of the irradiation of one and both parents].

The paper summarises some methodological approaches which may be used in experimental modelling and study of hereditary radiation effects in mammals. These approaches are aimed to the elucidation of the possible specific character (aggravation) of radiation damage in the offspring determined by the participation of two exposed parents in conception. The main attention is drawn to the dependence of hereditary radiation effects yield on the stages of the cell cycle of the parent germ cells at the moment of exposure and to criteria of evaluation of radiation damage in the offspring during the ontogenetic development.

Animals↗
PubMed1999

[The activation patterns during atrial fibrillation in an experimental model].

INTRODUCTION AND OBJECTIVES: In atrial fibrillation, along with the mechanisms of complete reentry and random activation focal activation patterns have been described which have been attributed both to propagation from the endocardium and to the existence of zones with automatic activity. The objectives of present study are to analyze and quantify the atrial activation patterns in an experimental model of atrial fibrillation. MATERIAL AND METHODS: In 11 Langendorff-perfused rabbit hearts atrial fibrillation was induced by atrial burst pacing after right atrial dilatation with an intra-atrial balloon. A multiple electrode consisting of 121 electrodes and positioned in the right atrial free wall was used to construct the activation maps corresponding to 10 segments of 100 ms in 11 different episodes of sustained atrial fibrillation (one per experiment). RESULTS: Of the 110 segments analyzed, 44 (40%) corresponded to random activation patterns. Fifteen segments (14%) corresponded to complete reentry, and in these cases the number of consecutive rotations ranged from 1 to 2.25 (mean 1.4 +/- 0.4). In 49 segments (44%) a single activation front was seen to pass through the recording area without block; alternatively, two simultaneous fronts were recorded that did not re-excite the zone activated by the other. In two segments (2%) there was a focal activation pattern without evidence of propagation from the epicardium surrounding the activated zone. CONCLUSIONS: a) in the experimental atrial fibrillation model used, random activation patterns are more frequent than complete reentry patterns; b) complete reentry can occur in areas smaller than 1 cm2, and c) focal activation during atrial fibrillation is rare.

Analysis of Variance↗
PubMedDate not supplied

Current gene-mapping strategies in experimental models of multiple sclerosis.

Both family-based linkage analyses and population-based association studies have failed to identify disease-regulatory non-human leucocyte antigen genes of importance in multiple sclerosis (MS). Instead, investigators have employed experimental models, which offer major advantages in genetic studies. We summarize the current main methodologies used and the status of both the human and experimental approaches. Why is it important to find genes regulating MS? There is an immense number of cellular and molecular interactions defined in the immunological field and it is very difficult to unravel those that are critical to an inflammatory disease, such as MS, by classical hypothesis-driven research. Unbiased genetics defines evolutionary conserved gene polymorphisms and pathways regulated by these genes, which are central in the pathogenesis. These, in turn, are of interest as therapeutic targets and pharmacogenetic markers.

Animals↗
PubMedDate not supplied

An experimental model combining microdialysis with electrophysiology, histology, and neurochemistry for studying excitotoxicity in spinal cord injury. Effect of NMDA and kainate.

We used an experimental model that we previously developed to characterize the damage caused by the agonists of glutamate receptors, N-methyl-D-aspartate (NMDA) and kainate, in the spinal cord in vivo, thereby testing further the utility of this model. Microdialysis was used to administer the toxins and to sample the release of other substances in response to these agents. The blockage of electrical conduction was monitored by recording the amplitudes of evoked potentials during administration of the damaging substances, and damage was assessed by postmortem histological examination. The released amino acids in microdialysates were measured by HPLC. Administration of 5 mM NMDA + 5 mM kainate into the gray matter blocked most postsynaptic responses and caused the release of amino acids. Administration of 10 mM NMDA and 10 mM kainate significantly destroyed cell bodies near the fiber. The advantage of this model is that histological, neurochemical, and electrophysiological parameters were obtained in the same experiment.

Amino Acids↗
PubMed1992

Experimental model of autoimmune hemolytic anemia induced in mice with levodopa by intraperitoneal injection or oral feeding.

In this paper we describe a murine experimental model of autoimmune hemolytic anemia induced with multiple injections or oral feeding of levodopa. Strain A mice were intraperitoneally injected or fed with levodopa, at a dose equivalent to the one used in human therapy, and subsequently they developed cycles of IgM, IgG and IgA anti-mouse red blood cells (MRBC) autoantibody responses. Levodopa injection induced serum IgM and IgG anti-MRBC responses and levodopa feeding enhanced the serum anti-MRBC IgA response. The appearance of autoantibodies in the serum was followed by binding of the autoantibodies to mice erythrocytes and three phases of anemia. Red cell bound IgM and IgG autoantibodies were predominant in levodopa-injected mice whereas red cell bound IgA autoantibodies were predominant in levodopa-fed mice. The specificity of the serum IgA autoantibody was not restricted since it interacted with erythrocytes of various species.

Administration, Oral↗
PubMed2000

Translocation of indigenous microflora in an experimental model of sepsis.

Translocation of viable bacteria from gut to bloodstream and other sterile body sites during shock has been demonstrated in several experimental and clinical studies. The factors causing translocation and its incidence at different stages of shock are not known. The aim of the study was to evaluate the importance of several factors causing translocation of indigenous microflora in an experimental model of septic shock based on intraperitoneal Escherichia coli sepsis in rats. Counts of inoculated E. coli and translocated bacteria in different locations, gut morphology and haematological values were evaluated at different stages of sepsis. Sepsis developed in all animals and E. coli achieved the highest counts in blood 6 h after inoculation. Translocation was commonest at 6 and 12 h after inoculation. Frequently translocating bacteria were lactobacilli, bifidobacteria, bacteroides and peptostreptococci. In early sepsis, translocation was associated with high E. coli counts in blood, yet in late sepsis the opposite correlation was present. Low infiltration by neutrophils in the ileum and decreased mitotic activity in the colon were associated with a high translocation rate. In early sepsis, translocation was associated with low lymphocyte counts, but in late sepsis, with low neutrophil counts. Translocation of bacteria (including anaerobes) that colonise the gut in high counts takes place during sepsis. Putative influencing factors such as activity of the primary disease (bacterial counts in blood), gut morphology or haematological values seem to have different impacts on translocation, depending on the stage of the disease.

Animals↗
PubMed1981

Control of carbon dioxide in modified Mapleson A and D (Hafnia) anaesthetic systems. An experimental model.

The effects of varying ventilations (VE) and fresh gas flows (FGF) on end-expiratory CO2 (FECO2) levels were investigated in an experimental model lung, employing the Hafnia modification of the Mapleson A and D anaesthetic systems during CO2-absorption and CO2-wash-out (rebreathing). Identical results were found in both systems: FECO2 was constant and independent of FGF with CO2-absorption and constant VE, whereas rebreathing resulted in increasing FECO2 levels as FGF was decreased. As control of FECO2 in the rebreathing systems by regulating FGF could only take place within FECO2 levels higher than that determined by VE at complete CO2-absorption, e.g. for the Hafnia A and D rebreathing systems, control of FGF necessitates relative hyperventilation. FECO2 with constant FGF decreased with increasing VE during CO2-absorption, as well as during rebreathing, although this decrease was less in the rebreathing systems. Thus a decrease in FECO2 with rising VE can be avoided and hypocapnia prevented. The results agree with those obtained in clinical studies.

Anesthesiology↗
PubMed2003

In situ analysis of coronary terminal arteriole diameter responses: technical report of a new experimental model.

INTRODUCTION: To date, investigation of coronary arteriole vasomotor activity has been limited to arterioles >30- 40 microm. Here, we introduce a new experimental model to allow for in situ microscopy of terminal coronary arterioles. METHODS: Rat hearts were perfused in a closed loop system (priming volume 20 ml) which was placed on a computer-controlled microscope stage. FITC-dextran and tetrodotoxin (TTX, 50 microM) were added. Tilting of the microscope by 90 degrees allowed for visual access to the ventricular surface. Arterioles were identified by the flow direction of fluorescent beads (1 microm). Images were recorded on video tape, and arteriole diameters were measured offline. Stability of the preparation and maintenance of coronary flow reserve were analyzed. Responses of coronary flow and arteriole diameters to the vasodilators papaverine and Na-nitroprusside were recorded. RESULTS: In TTX-arrested control hearts coronary flow and terminal arteriole diameters were stable for 2 h. Administration of papaverine and Na-nitroprusside increased coronary flow from 6.4 +/- 0.7 to 13.3 +/- 1.3 ml/min, decreasing coronary resistance by 52 +/- 3%. Terminal coronary arteriole diameters increased from 12.0 +/- 0.9 to 13.6 +/- 1.0 microm, decreasing hindrance of this vessel segment by 45 +/- 11%. CONCLUSION: Preservation of coronary terminal arteriolar tone and adequate responsiveness to vasodilators in the TTX-arrested isolated heart were demonstrated. Thus, this model may serve to complement our understanding of coronary microvascular control mechanisms by extending observations to the terminal arteriolar bed.

Animals↗
PubMedDate not supplied

Sensitivity of cortical transit and furosemide response in the diagnosis of renal obstruction. An experimental model.

Several radionuclide parameters are routinely used for the diagnosis of renal obstruction. In order to evaluate the sensitivity of those parameters, an experimental model of partial ureteral obstruction in rats was used. Neither the cortical transit time, nor the response to furosemide could serve to discriminate between obstructive and nonobstructive kidneys. These parameters were, however, more or less related to the degree of impairment of the single kidney glomerular filtration rate and should probably be considered as functional parameters reflecting the grade of the obstructive phenomenon.

Animals↗
PubMed1990

Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses.

Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (IA); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, IV, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), IA. Synovial fluid specimens were obtained at posttreatment hour (PTH) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at PTH 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at PTH 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens. At PTH 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and WBC count was higher (range, 88,000 to 227,200 cells/microliters) and predominantly neutrophilic (95 to 99%) at PTH 0 than before inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

A study of the action of anticonvulsant drugs on an experimental model of epilepsy.

Repeated electrical low intensity stimulation of various regions of the brain has been shown to induce epileptic seizure activity. This experimental model of epilepsy has been used in our laboratory in rats. Male rats, anaesthetized with nembutal (20 mg/kg, i.p.) and ketalar (60 mg/kg, i.p.) were implanted stereotaxically with electrodes in the dorsal hippocampus and neocortex and received 2 hours stimulation sessions via the hippocampal electrodes (1 sec, 60 Hz, 200-800 microA) one stimulus per minute, during which electrographical and behavioral seizures were induced. The effect of anticonvulsant drugs was tested on this model: phenobarbital (40 mg/kg) reduced the quantity of epileptic electrographic activity and abolished the behavioral aspects of the seizures; diphenylhydantoin (20 mg/kg) reduced the quantity of epileptic electrographic activity, but had no effect on the behavioral component of the seizures; diazepam (6 mg/kg) only blocked the behavioral component of the seizures leaving the animal stuporous and immobile, but the electrographical component was unaffected; carbamazepine (10 mg/kg) had no effect on the electrographical epileptic seizures and reduced the behavioral aspects, but to a lesser extent than diazepam.

Animals↗
PubMed1995

Role of light chain variable region in myeloma with light chain deposition disease: evidence from an experimental model.

Light chain deposition disease (LCDD) results from a propensity of some human monoclonal L chains to form tissue deposits. We designed an experimental model for in vivo expression of human kappa L chain sequences in mice and compared a somatically mutated LCDD chain with a closely related control kappa chain, both encoded by the unique V kappa IV gene. Mice secreting the LCDD chain but not those producing the control chain showed deposits with a distribution similar to that observed in patients. These data show that discrete changes in V region sequences can play a major role in tissue deposition of human L chains.

Amino Acid Sequence↗
PubMed2003

Implementation of a redox microarray: an experimental model for future nanoscale biomolecular computing using integrated circuits.

The possibility of constructing high-density parallel computing architectures using molecular electronics technology is explored. By employing molecular computing devices, new circuitsystem integration could be realised. To clarify the proposed concept, an experimental model of a redox microarray is presented. A first experimental system for a redox microarray consists of a two-dimensional array of platinum microelectrodes to catalyse reversible reactions of redox-active molecules. Experimental results of active wave propagation in the redox microarray are presented to demonstrate the potential of molecular computing devices for creating artificially programmable reaction-diffusion dynamics for specific target applications.

Journal Article↗
PubMed1990

Pancreatic transplantation in the rat. An experimental model.

Following the induction of experimental diabetes in two groups of rats using an isograft model, a comparative study was made of two types of pancreas transplants in which several procedures were employed. The vascular anastomosis in one group were to the renal artery and vein, and in the other, to the iliac vessels. The pancreatic ducts in one subgroup were ligated, in another, they were diverted to the urinary system; in a third sub-group, they were diverted to the intestine. The results obtained for the sub-group with the transplant anastomosed to the renal vessels were the best. It is suggested that this was due to two factors: the simplicity of the technique and the short operating times. In this present work the two best methods of dealing with the exocrine secretion were diversion to the ureter and ligation of the common bile duct. The worst results were in the group with duodeno-cystostomy.

Animals↗
PubMed1990

[Experimental model of hepatitis A in rhesus monkeys (Macaca mulatta) infected with human hepatitis A virus].

The focus of this paper is characterization of Hepatitis A experimental model obtained for the first time in rhesus monkeys (M. mulatta) infected with fecal isolate from a patient with Hepatitis A (HAV-H1). Monkeys were susceptible to oral and intravenous routes of HAV inoculation. The disease could be reproduced regularly in 4 passages as a result of which HAV strain continuously pathogenic for M. mulatta has been established. All 17 infected monkeys developed Hepatitis A with characteristic (except jaundice) patterns: shedding of virus with the stool, elevations of serum alanine aminotransferase level, appearance of IgM anti-HAV, morphological changes developed in the liver. Our data have demonstrated that the course of experimental Hepatitis A infection in M. mulatta is similar (in many respects) to that observed in man.

Administration, Oral↗
PubMed1975

Effects of acute and chronic paleocerebellar stimulation on experimental models of epilepsy in the cat: studies with enflurane, pentylenetetrazol, penicillin, and chloralose.

Effects of acute and chronic paleocerebellar stimulation were evaluated in four experimental models of epilepsy in 24 adult cats chronically implanted with bilaterally symmetric parasagittal electrocorticographic electrodes and anterior lobe cerebellar stimulation electrodes. Pentylenetetrazol was given intraveneously in 50-mg increments or 4% enflurane was inspired until grand mal seizures occurred spontaneously or were triggered by photic or auditory stimuli. Alpha-chloralose, 50 mg/kg, was injected intraperitoneally to produce a model of stimulus-sensitive myoclonus and sodium penicillin G, 350,000 units/kg, was injected intramuscularly to produce a model of petit mal epilepsy. One- to 250-Hz electrical stimulation of paleocerebellar cortical surfaces was performed with constant-voltage or constant-current stimulators at threshold and suprathreshold intensities with average intensities of 8 V and 2.5 mA, respectively. Acute or chronic, threshold or suprathreshold paleocerebellar stimulation did not predictably alter the electrographic or clinical manifestations in any of these four models.

Acoustic Stimulation↗
PubMed2005

The N- and L-type calcium channel blocker cilnidipine suppresses renal injury in dahl rats fed a high-sucrose diet, an experimental model of metabolic syndrome.

BACKGROUND/AIMS: The L/N-type calcium channel blocker (CCB) cilnidipine has been demonstrated to suppress progressive renal disease in a variety of experimental models, but the characteristic effects of N-type calcium channel blocking action on renal injury have not been examined in detail. Therefore, we investigated the beneficial effects of cilnidipine on renal injury in Dahl salt-sensitive (Dahl S) rats fed a high-sucrose diet (HSD), which mimics metabolic syndrome, and compared them with the effects of an L-type CCB, amlodipine. METHODS: Male Dahl S rats were divided into groups with similar blood pressure at 8 weeks of age and fed an HSD. They received vehicle, cilnidipine or amlodipine for 27 weeks. At 35 weeks of age, urine and blood samples were collected for physiological analysis, and the kidneys were removed for histopathological evaluation. RESULTS: Cilnidipine reduced albuminuria, glomerular hypertrophy, glomerular expression of ICAM-1, ED-1-positive cell infiltration and interstitial fibrosis compared with vehicle-treated rats. In contrast, amlodipine had no effect on these parameters. Urinary norepinephrine excretion, renal expression of renin mRNA and renal tissue levels of angiotensin II were increased only in the amlodipine-treated group. CONCLUSION: Cilnidipine provided superior protection against renal damage compared with amlodipine in Dahl S rats given an HSD. The different effects between these two drugs may be partly explained by their different actions on the renal sympathetic nerve activity and the renin-angiotensin system through the N-type calcium channel blocking action.

Amlodipine↗
PubMed2006

Evaluation of Merci Retriever by experimental modeling.

The Merci Retriever is the first device for mechanical embolus removal in patients with cerebral ischemia. Use of the device was evaluated using experimental models. Three stroke model systems were created: silicone embolism model with flow system, pig embolism model, and silicone-pig tortuous artery model. The series of extraction procedures (capture, retrieval, and aspiration) was examined in the models under flow control. Coagulated blood clot was adopted as embolic material, to simulate embolic stroke of the carotid or middle cerebral arteries. Retrieval of the clot was successful in only one of six trials in the silicone model of the carotid artery, as the clot easily worked free from the helical tip. Aspiration was successful in three of the six trials. Retrieval was successful in two of four trials in the middle cerebral artery and aspiration was successful in two. Retrieval was successful in all five trials in the pig embolism model, and three of five trials in the silicone-pig tortuous artery model. The Merci Retriever does not always retain the embolism, and the helix tends to distort in acute or rough lumen. Aspiration is not always successful.

Animals↗