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Evaluation of inbred germ-free Fischer 344 albino rats as an experimental model for oral candidiasis.

Inbred germ-free Fischer 344 albino rats were evaluated as models for experimental candidiasis in order to investigate bacterial interaction with Candida albicans. Female rats were exposed to C. albicans in their drinking water and killed at intervals from 2 to 22 days after initial contact with the contaminant. C. albicans was cultured from their mouths from day 2 but from day 12 the number of colonies decreased. From day 2 to 9 all rats showed oral histological signs of candidal infestation, but after 9 days the number declined to 3 out of 9 at 22 days. The dorsal surface of the tongue was the best histological indicator of candidal infestation. All the rats had tongue lesions from day 4 to 9, and from day 6 there was also a concomitant localized loss of filiform papillae. The number of rats with all forms of tongue involvement also decreased after 9 days with only 3 out of 9 affected at 22 days. It is concluded that Fischer 344 inbred germ-free rats can be used on a limited scale as a model for candidiasis and bacterial interaction with C. albicans, the dorsal surface of the tongue would be the best site for studying candidal experimental lesions and it is probable that better results can be achieved with complete standardization of contamination and preparation procedures.

Animals↗

Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis.

There exists no ideal model for experimental ulcerative colitis in common laboratory animals. Therefore, we tried in the present study to establish a reproducible model for inducing colitis in rats by using acetic acid. A blind loop of the colon including the cecum, ascending colon and part of the transverse colon, was brought out through two colostomies. After mechanical washing with warm normal saline, acetic acid was instilled at different doses (4, 6 and 8%) for different exposure times (10, 15, 20, 25 and 30 s). The excluded colon was examined by light microscopy on the 1st, 2nd, 3rd, 4th, 7th and 14th days after operation and acetic acid instillation. We found that 4% acetic acid for 15 s produced a moderate, superficial colitis on the 1st day after operation, whereafter a uniform colitis evolved in all rats on the 4th day after operation. The developed colitis showed morphological similarities with human ulcerative colitis. Signs of healing and regeneration of the mucosa were seen on the 7th day, and the mucosa became almost normal at the 14th day after operation. 6 or 8% acetic acid solution or exposure times exceeding 15 s resulted in severe, deep colitis with a concomitant high mortality rate. In contrast, at exposure times less than 15 s, acetic acid induced only mild superficial colitis. We conclude that by using 4% acetic acid for 15 s in the excluded colon a uniform and reproducible colitis pathologically resembling human ulcerative colitis could be achieved. Furthermore, no mortality was encountered and the general health of the rats was similar to that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Experimental model of bladder instability in rabbits.

OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g) were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1)- urine culture; 2)- cystometric study; 3)- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

Journal Article↗

HBV and HDV replication in experimental models: effect of interferon.

The use of HBV and HDV experimental models has significantly contributed to understand the viral life cycle and to systematically test antiviral effects of various drugs on a pre-clinical level. Similar replication strategies of related hepadna viruses permit the use of chimpanzees (Pan troglodytes), woodchucks (Marmota monax), ground and tree squirrels (Spermophilus beecheyi) or Pekin ducks (Anas domesticus) as appropriate animal models. Cell culture systems for in vitro infection or transfection using both primary cultures of human and non-human hepatocytes and non-hepatocytes and cell lines have recently been identified. The advantages and restrictions of these experimental models with respect to evaluation of interferon effects on viral and hepatocellular gene expression are discussed.

Animals↗

[Role of the dopaminergic system in experimental models of epilepsy].

It has been shown that neuroleptics which interact selectively with either D-1 or D-2 dopamine receptors possess a marked difference in their propensity on seizures. The aim of this work was to investigate whether the D-1 antagonist SCH 23390 differs from haloperidol (D-2 antagonist) in models of experimental epilepsy induced by electrical stimulation of selected brain regions (hippocampus and amygdala), in rabbits. Haloperidol increased and SCH 23390 significantly decreased the susceptibility to seizures in both models investigated. The data suggest that the D-1 and D-2 receptor subtypes have different roles in the mechanisms underlying seizures.

Amygdala↗

[The hamster's larynx as an experimental model].

A macroscopic study and with light microscopy as well is performed in the larynx of 4 hamsters. Morphology of hamster's larynx is described. Transitional epithelium is found out on the epiglottis base and caudally to the vocal cords. Hamster's larynx may be a good model for experimental study of changes during carcinogenesis.

Animals↗

Rat experimental model of continuous regional arterial infusion of protease inhibitor and its effects on severe acute pancreatitis.

OBJECTIVES: The rat experimental model of continuous regional arterial infusion of protease inhibitor (CRAI) on acute pancreatitis has yet to be established. Therefore, the aims of this study were (1) to establish the rat experimental model of CRAI and (2) to evaluate the effects of nafamostat on rat severe acute pancreatitis via different routes of administration. METHODS: The rat internal jugular vein or the celiac artery was infused with nafamostat, and the concentration of nafamostat in the lung and pancreas was measured. After the induction of severe acute pancreatitis, rats received intravenous or regional intraarterial infusion of nafamostat and then concentrations of trypsinogen activated peptide (TAP) and serum interleukin (IL-6), and histologic sections of the pancreas were examined and the 96-hour survival rate was evaluated. RESULTS: CRAI rats had higher concentrations of nafamostat in the pancreas than those infused intravenously. However, CRAI rats had lower concentrations of nafamostat in the lung that those infused intravenously. CRAI significantly reduced the levels of TAP and pancreatic necrosis. Moreover, the levels of serum IL-6 and the mortality rate were significantly reduced after CRAI compared with the intravenous infusion of nafamostat. CONCLUSION: The effectiveness of the rat experimental model of CRAI on acute pancreatitis was clearly demonstrated. The concentration of nafamostat in the lung and pancreas and the effects of nafamostat differ according to the route of administration.

Animals↗

Inhibition by D-MePhe-Pro-Arg-H (GYKI-14766) of thrombus growth in experimental models of thrombosis.

The antithrombotic action of the highly effective synthetic thrombin inhibitor D-MePhe-Pro-Arg-H (GYKI-14766) was studied in various models of experimental thrombosis. The compound administered to rats and rabbits by i.v. bolus injections, continuous i.v. infusions, subcutaneously and orally, respectively, induced significant decrease in thrombus weight (i) in a quantitative venous thrombosis model with stasis based on vascular lesion in rats, (ii) in an extracorporeal arterio-venous shunt model in rabbits, and (iii) prevented the occlusion of the vessel in arterial thrombosis induced by mechanical damage in rats. By using the arterio-venous shunt model in rabbits the inhibitory effect on thrombus growth could be demonstrated as a function of dose and time in self-controlled experiments. Blood level of the inhibitor determined by a bioassay varied between 0.09-0.67 microgram/ml whole blood when doses of 15 and 20 mg/kg were administered orally. A correlation was found between thrombin time, platelet aggregation induced by thrombin ex vivo and the weight of thrombi formed.

Amino Acid Sequence↗

Intracranial hypertension and brain oedema in albino rabbits. Part I: Experimental models.

Three models of experimental cerebral oedema in rabbits are described, one producing vasogenic oedema with a cold lesion, the other producing a cytotoxic cerebral oedema with a metabolic inhibitor, 6-aminonicotinamide (6-ANA), and finally a model employing in the same animal both vasogenic and cytotoxic injuries. The following parameters were assessed: behaviour, EEG, intracranial pressure (ICP), cerebral elastance (Em), blood brain barrier integrity, brain water, electrolyte content, and volume change. Behaviour was normal in the cold lesion group, was abnormal following the administration of 6-ANA, and pronouncedly abnormal in animals with a combined lesion. Mean ICP (PaCO2 37 +/- 42 torr) in the control group was 2.7 +/- 2 torr, in the cold lesion group 8.4 +/-6, in the 6-ANA group it was 8.7 +/- 4, and in the combined lesion group 15.8 +/- 8 torr. Em for the control group was 2.6 +/- 1.3 torr, in the cold lesion group it was 5.6 +/- 4 torr, in the 6-ANA group it was 8.8 +/- 5 torr, and in the combined lesion group it was 8.0 +/- 4 torr. The 6-ANA group manifested oedema that involved primarily the grey matter. In the control animals grey matter water content was 79.99 +/- 0.8%, and in the 6-ANA group it was 81.73 +/- 0.9% (P less than 0.001). A group had both grey and white matter content measurements under the area of a sham lesion, and this was 79.2 +/- 1.3% for the left hemisphere and 79.1 +/- 1.3% for the right. Following a cold lesion of the left hemisphere, the water content was 81.85 +/- 1% (P less than 0.005), and 80.25 +/- 1% (P less than 0.01) in the unlesioned right hemisphere. In those animals with combined cold lesion and 6-ANA administration, the water content of the left hemisphere increased to 82.8 +/- 1% (P less than 0.05 from vasogenic oedema alone), and in the right hemisphere to 81.1 +/- 1% (P less than 0.5 from vasogenic oedema alone).

Animals↗

Experimental models for human implantation.

An understanding of the cellular and molecular basis of blastocyst implantation in the human remains as yet a black box, however, a few experimental models using human and non-human primate species have addressed this issue. This review attempts to highlight, based on experimental evidence, the paradigm shifts in our understanding of the endocrine basis of embryo implantation, and the nature of dialogue between a growing, viable conceptus and maternal endometrial cells in the establishment of 'receptivity' for blastocyst implantation. It is being proposed that an existing inflammation paradigm of blastocyst implantation could be tested using an experimental model to compare tissue behaviour of conceptus associated endometrial cells with that occurring after induction of deciduoma in hormone-primed uterus. We anticipate that an in vitro model of blastocyst implantation using the experimental models of homotypic and heterotypic cultures of uterine epithelial and stromal fibroblast cells expressing structural and functional phenotypic responses as observed in situ may provide us with necessary clues about the temporal and spatial nature of cellular and molecular functions involving various endocrine and paracrine factors at implantation.

Animals↗

Dietary calcium and blood pressure in experimental models of hypertension. A review.

More than 80 studies have reported lowered blood pressure after dietary calcium enrichment in experimental models of hypertension. The evidence presented here suggests that dietary calcium may act concurrently through a number of physiological mechanisms to influence blood pressure. The importance of any given mechanism may vary depending on the experimental model under consideration. Supplemental dietary calcium is associated with reduced membrane permeability, increased Ca(2+)-ATPase and Na,K-ATPase, and reduced intracellular calcium. These results suggest that supplemental calcium may limit calcium influx into the cell and improve the ability of the VSMC to extrude calcium. This could be a direct effect of calcium on the VSMC or an indirect effect mediated hormonally. The calcium-regulating hormones have all been found to have vasoactive properties and therefore may influence blood pressure. Furthermore, CGRP and the proposed parathyroid hypertensive factor are both vasoactive substances that are responsive to dietary calcium. Therefore, diet-induced variations in calcium-regulating hormones may influence blood pressure. Modulation of the sympathetic nervous system is another important way that dietary calcium can influence blood pressure. There is evidence of altered norepinephrine levels in the hypothalamus as a consequence of manipulations of dietary calcium as well as changes in central sympathetic nervous system outflow. Dietary calcium has also been shown to specifically modify alpha 1-adrenergic receptor activity in the periphery. In some experimental models of hypertension, dietary calcium may alter blood pressure by changing the metabolism of other electrolytes. For example, the ability of calcium to prevent sodium chloride-induced elevations in blood pressure may be attributed to natriuresis. However, natriuresis does not account for all of the interactive effects of calcium and sodium chloride on blood pressure. Sodium chloride-induced hypertension may be due in part to calcium wasting and subsequent elevation of calcium-regulating hormones. Chloride is an important mediator of this effect because it appears that sodium does not cause calcium wasting when it is not combined with chloride. More attention to the central nervous system effects of dietary calcium is needed. Not only can calcium itself influence neural function, but many of the calcium-regulating hormones appear to affect the central nervous system. The influence of calcium and calcium-regulating hormones on central nervous system activity may have important implications for blood pressure regulation and also may extend to other aspects of physiology and behavior.

Animals↗

An experimental model of symptomatic vasospasm induced by oxyhemoglobin in rabbits.

BACKGROUND AND PURPOSE: There are many experimental models for studies of cerebral vasospasm. However, no ideal model has been established thus far to comparatively reproduce the ischemic state of the brain that may occur in patients after subarachnoid hemorrhage. METHODS: In the present study, we attempted to induce severe vasospasm in rabbits by using an oxyhemoglobin-rich blood product prepared from hemolyzed arterial blood and evaluate neurological symptoms, cerebral angiogram, cerebral blood flow, and histology. RESULTS: Clinically significant neurological symptoms were observed in about half of the rabbits. There was no significant correlation between angiographic results of the vasospastic state of the main artery and the severity of neurological symptoms observed. However, the cerebral blood flow was significantly lower than in the control group and significantly correlated with the severity of neurological symptoms. On histological examination, lesions were found in about half of the rabbits. Development of obvious infarction was found more frequently than in other reported models. CONCLUSIONS: These results suggest that this model is appropriate as an experimental model of vasospasm occurring after subarachnoid hemorrhage and is especially useful in that it induces vasospasm intense enough to cause obvious infarction.

Animals↗

Mechanical allodynia is more strongly manifested in older rats in an experimental model of peripheral neuropathy.

Partial peripheral nerve injury often leads to chronic neuropathic pain characterized by symptoms such as allodynia. In the present study, employing a rat model of experimental neuropathy produced by partial denervation of the tail, we examined whether peripheral nerve injury-induced mechanical and thermal allodynia were affected by the animal's age at the time of the injury. The motive of this study was the demonstration in other neuropathy models of the age effects on the manifestation of neuropathic pain symptoms following partial peripheral nerve injury. We compared two groups of young (n = 23, 7-8 weeks old, 150-200 g) and old rats (n = 14, 16-18 months old, 550-800 g). We found that the older rats exhibited more vigorously the behavioral signs of mechanical allodynia during the first week after the nerve injury. With respect to thermal (cold or warm) allodynia, however, we detected no significant difference between young and old rat groups. The results of the present study, as those of previous studies, support the idea that the age at the time of partial peripheral nerve injury affects the severity of certain neuropathic pain symptoms appearing after the injury. However, the present results argue against the suggestion from previous studies that younger subjects are more vulnerable to partial peripheral nerve injury-induced neuropathic pain symptoms.

Aging↗

Scintigraphic evaluation of lacrimal glands using a rabbit experimental model.

The aim of this study was to establish an experimental model to evaluate functional changes in lacrimal gland parenchyma using gamma scintigraphy. Although the lacrimal glands of the rabbit have frequently been used for ophthalmological research, scintigraphic evaluation of these glands has received far less attention and we could not find any reports concerning this topic in the literature. Ten rabbits were used for the study; in 4 of them, the orbital region was dissected to provide the topographic anatomy of the lacrimal glands. Four rabbits underwent a static scintigraphy after excision of a unilateral lacrimal gland. Changes in the pattern of tracer uptake indicated the exact position of the gland on the scintiscan. One rabbit served as a control, and another one was used to prove the surgical accessibility of the gland. Using a frontal projection of the head the (99m)TcO(-)(4) uptake of the rabbit lacrimal glands could be identified and evaluated in the upper lateral region of the scintiscan. In conclusion, the lacrimal glands of the rabbit provide an appropriate experimental model to study quantitative disturbances of lacrimal secretion using scintigraphy and enable the assignment of functional impairment to morphological changes of the lacrimal parenchyma.

Animals↗

An experimental model for advanced ovarian cancer.

Intraperitoneally transplanted tumors implanted and began developing with ascites in about 62% of the female rats within 4 to 6 weeks after transplantation. The tumor used in this study was an adenocarcinoma and which originated from a primary ovarian cancer in rats of the same strain (Wistar). The morphology and biological behavior of the tumor were very similar to the tumor in humans. Moreover, the preliminary results with cisplatin therapy indicate that intraperitoneal cancer corresponding to stage III or IV in the FIGO classification is a promising model for experimental therapeutic studies of common epithelial carcinoma at an advanced stage.

Animals↗

[Canrenone: an effective antihypertensive in an experimental model of hypertension in which the active transport of sodium is diminished].

Recent studies in essential hypertensive patients and rats with genetic hypertension strongly suggested that the development of primary hypertension results from a transient and chronic "cascade" of events; I) excess Na+ intake, II) secretion of natriuretic factors, III) abnormal cell Na+ homeostasis in the vascular wall, due to the presence of inherited and induced abnormalities in different Na+ transport system and IV) increase in cytosolic free Ca2+ content and sympathetic drive. In vitro studies have previously shown that canrenone, an antihypertensive antialdosterone drug, behaves like a partial agonist at the digitalis-receptor site of the Na+, K+-pump. In particular, it has been shown that canrenone counterbalances the increases in internal Na+ and cytosolic free Ca2+ contents induced by ouabain in cultured smooth muscle cells. We thus investigated the effect of canrenone administration in a model of experimental hypertension with increased endogenous "ouabain-like" factors (rats with reduced renal mass under excess Na+ intake: RRM-salt rats). Results presented here confirm that RRM-salt rats exhibit: volume expansion, strongly decreased plasma renin activity, increased endogenous "ouabain-like" factors and (IV) decreased Na+, K+-pump activity and increased Na+ content in erythrocytes. In addition, we found that canrenone is antihypertensive in this model and this is associated with a tendency to normalize volume expansion, plasma levels of endogenous "ouabain-like" factors, Na+, K+-pump activity and Na+ content in erythrocytes. In conclusion, our results suggest that administration of canrenone to RRM-salt rats may induce a lowering of blood pressure by antagonism with endogenous "ouabain-like" factors at the vascular wall.

Animals↗

Hypertension produced by sodium depletion and unilateral nephrectomy: a new experimental model.

Unilateral nephrectomy of sodium-restricted male Sprague-Dawley rats produced a sustained elevation in systolic blood pressure (SBP) that was reversed by sodium repletion. A chronic intraperitoneal infuson of SQ14,225 prevented the development of hypertension in sodium-deplete unilaterally nephrectomized rats. Sodium depletion of two-kidney rats increased SBP to a lesser extent, while unilateral nephrectomy of sodium replete animals had no effect. These results provide evidence for a new model of experimental hypertension in the rat and emphasize the importance of a renal component, as demonstrated by unilateral nephrectomy, in the maintenance of normal pressure-volume relationships.

Animals↗

[The contribution of experimental models to the physiopathology and treatment of infectious endocarditis].

The model of experimental endocarditis can be used for the investigation of the different steps in the physiopathologic process leading to the formation of the infected cardiac vegetation. It has also greatly contributed to the knowledge of the characteristics of the infected vegetation. These data allow a better understanding of the therapeutic consequences (both preventive and curative) of the physiopathologic process.

Animals↗