Dysplasia In Rats Research Articles

Chronic hypoxia induces nonreversible right ventricle dysfunction and dysplasia in rats.

The purpose of this study was to evaluate the reversibility of right ventricular (RV) remodelling after pulmonary artery hypertension (PAHT) secondary to 3 wk of hypobaric hypoxia. A group of 10 adult male Wistar rats were studied and were the following: control normoxic (C), after 3 wk of chronic hypoxia (CH), and after 3 wk of exposure to hypoxia followed by 3 wk of normoxia recovery (N-RE). Mean pulmonary artery pressure was 11 +/- 2 mmHg in the C group, 35 +/- 2 mmHg in the CH group, and 14 +/- 3 mmHg in the N-RE group. RV function was assessed by echocardiography. In the CH group, the pulmonary flow measured in Doppler mode depicted a midsystolic notch and a decrease of the pulmonary acceleration time compared with control [17 +/- 1 vs. 34 +/- 1 ms (n = 10), respectively; P < 0.05]. RV thickening measured in M-mode was apparent in the CH group compared with the control group [2.84 +/- 0.40 vs. 1.73 +/- 0.26 mm (n = 10), P < 0.05]. In the N-RE group, the RV wall was significantly thinner compared with the CH group [1.56 +/- 0.08 vs. 1.73 +/- 0.26 mm (n = 10), P < 0.05]. The calculated RV diameter shortness fraction was not different between the CH group and C group (34 +/- 4.2% vs. 36 +/- 2.8%) but decreased in the N-RE group [20 +/- 2.4% (n = 10), P < 0.01]. The E-to-A wave ratio on the tricuspid Doppler inflow was significantly lower in the CH group and N-RE group compared with the C group [0.70 +/- 0.8 and 0.72 +/- 0.1 vs. 0.88 +/- 0.2 (n = 10), respectively; P < 0.05]. In the isolated perfused heart using the Langendorff method, RV compliance was increased in the CH group and decreased in the N-RE group. In the N-RE group, fibrous bands with metaplasia were observed on histological sections of the RV free wall. We conclude that PAHT induces nonreversible RV dysfunction with dysplasia.

Clinical Application of Experimental Cortical Dysplasia in Rats

This report details clinical and experimental studies of focal cortical dysplasia. The first part deals with 14 surgical cases of children with intractable epilepsy. At surgery, intraoperative electrocorticography was performed to localize the epileptic foci under neuroleptanalgesia. Thirteen patients showed epileptiform discharges on this preresection electrocorticography. All foci in noneloquent areas were resected. Patients who had undergone total lesionectomy with complete focus resection showed the most favorable postoperative results. However, the positive correlation between the intraoperative electrocorticographic findings and the pathologic classification of cortical dysplasia was not found in the present study. Nine patients have been seizure free with reduced medication and two patients have achieved worthwhile improvement. We conclude that intraoperative electrocorticography can improve the surgical outcome for intractable epilepsy by localizing epileptic foci for resection. The second part describes a kainic acid—induced experimental model of focal cortical dysplasia, which demonstrated not only the epileptic properties of the dysplasia but also the perilesional epileptogenicity. The findings supported the surgical results for the patients with focal cortical dysplasia. ( J Child Neurol 2005;20:351—356).

Gene expression profiling of testosterone and estradiol-17 beta-induced prostatic dysplasia in Noble rats and response to the antiestrogen ICI 182,780.

We previously demonstrated that 1) treatment of Noble rats for 16 wk with testosterone (T) and estradiol-17 beta (E2) led to 100% incidence of dorsolateral prostate (DLP) dysplasia and hyperprolactinemia and 2) blockade of PRL release with bromocriptine cotreatment significantly lowered the incidence of DLP dysplasia. In the current study, we sought to determine whether E2 exerts direct effects, independent of PRL, in this model system. The pure antiestrogen ICI 182,780 (ICI), reported to have no effect on PRL release in female rats, was administered biweekly to T + E2-treated rats at 3 mg/kg body weight. ICI cotreatment completely prevented DLP dysplasia development but it also blocked hyperprolactinemia in the dual hormone-treated rats. Gene profiling with an 1185 gene rat cDNA array identified approximately 100 genes displaying > or = 3-fold changes in rat lateral prostates (LPs) following T + E2 treatment. Significantly more genes were up-regulated (77) than down-regulated (14), reflecting cellular/molecular changes associated with enhanced cell proliferation, DNA damage, heightened protein and RNA synthesis, increased energy metabolism, and activation of several proto-oncogenes and intracellular signaling pathways. Post hoc analyses, using quantitative real-time RT-PCR, corroborated differential expression of eight genes, exhibiting three different patterns of altered expression. Genes encoding the early growth response protein 1 and metalloendopeptidase meprin beta-subunit were similarly altered in T + E2- and T + E2 + ICI-treated animals when compared with untreated controls. In contrast, transcripts of fos-related antigen-2, growth arrest and DNA damage-inducible protein-45, and signal transducer and activator of transcription-3 were significantly increased in the LPs of T + E2-treated animals, but the increases were reversed by cotreatment with ICI. Differential expression of fos-related antigen-2 and growth arrest and DNA damage-inducible protein-45 were further confirmed at the protein level by immunohistochemistry. Lastly, levels of A-RAF, VIP-1 receptor, and calpastatin mRNA were distinctly lessen in rat LPs under T + E2 influence, but rebound with ICI cotreatment. In conclusion, our findings further implicated pituitary PRL in the induction of dysplasia in rat LP. Gene profiling provided clues that molecular events related to enhancement of cell proliferation, DNA damage, and activation of proto-oncogenes and transforming factors may be causally linked to the genesis of LP dysplasia in this rat model.

Clinical and histopathological features of dextran sulfate sodium induced acute and chronic colitis associated with dysplasia in rats.

We examined the clinical and histopathological features of the dextran sulfate sodium (DSS) induced acute and chronic colitis in rats as a model for studying basic biology of the inflamed colonic mucosa. Acute colitis was induced in male Wistar rats by 4 days (AI) or 7 days (AII) of oral 5% (wt/vol) DSS (mol. wt. 54,000) in their drinking water. Chronic colitis was induced in 8 experimental groups: CI=7 days DSS followed by 10 days water (=one cycle); CII=two cycles; CIII to CVIII (three to eight cycles) received only 4 days 5% DSS followed by 10 days drinking water. The entire colons were examined histologically; dysplasia was graded as: indefinite/probably negative for dysplasia, indefinite/probably positive for dysplasia, low-grade dysplasia, or high-grade dysplasia. The earliest clinical findings in the acute colitis group over 4 days occurred on day 2 (hemoccult positive stools, loose stools or diarrhea and weight loss). The maximal disease activity was noted on day 7 accompanied by a 53% mortality rate. The histological inflammation scores were significantly higher on day 7 than on day 4. All rats had extensive ulcerations predominantly in the rectum and cecum. The number of rats having ulcerations was markedly lower in the chronic colitis groups. The majority (75%) of the crypt lesions suspicious for dysplasia were classified as mucosa indefinite/probably negative for dysplasia. We classified 18 crypt lesions as low-grade dysplasia and one lesion as high-grade dysplasia (after eight cycles). No invasive carcinoma was observed. Most low-grade dysplasias (83%) occurred after five cycles of DSS/water, located mostly in the rectum (44%) and colon transversum (33%). Our findings suggest that the DSS colitis model in rats may be an interesting model for studying the sequence chronic inflammation-dysplasia in human ulcerative colitis. Further long-term studies with the present DSS colitis model in rats might also prove it as a reliable model to study the sequence high-grade dysplasia and colitis associated-cancer.

Effect of all‐trans retinoic acid on apoptosis and expression of regulatory genes (Bcl‐2, Fas, ICE) in experimentally induced gastric epithelial cell dysplasia in rats

OBJECTIVE: To study the mechanism and effect of all‐trans retinoic acid on apoptosis and the expression of Bcl‐2, Fas and ICE in experimentally induced dysplastic gastric epithelial cells. METHODS: Apoptosis and expression of Bcl‐2, Fas and ICE in gastric epithelial cells was studied using the terminal dUTP nucleotide end‐labeling (TUNEL) technique. The immunohistochemistry of Wistar rats enrolled in three groups was studied: group 1, blank controls; group 2, dysplasia induced by N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG) and then treated with all‐trans retinoic acid; and group 3, dysplasia induced by MNNG and treated with a placebo. RESULTS: In the three groups, the rates of dysplasia were 0, 26.7 and 73.3%; the apoptosis indices were 8.3 ± 3.1, 7.8 ± 2.6 and 2.2 ± 0.4; the expression of Bcl‐2 was 13.3, 33.3 and 66.7%; and overexpression of Bcl‐2 was 6.7, 6.7 and 33.3%, respectively. There were significant differences between group 2 and group 3 (P &lt; 0.05), but no significant differences were found between group 2 and group 1 (P &gt; 0.05). The expression rates of Fas were 46.7, 40 and 6.7%; the overexpression rates were 13.3, 26.7 and 13.3%, respectively; the expression rates of ICE were 20, 60 and 13.3%; the overexpression rates were 0, 13.3 and 6.7% in the three groups, respectively. The expression rates of Fas and ICE in group 2 were significantly different from that of group 3 (P &lt; 0.05), but there were no significant differences in overexpression rates between group 2 and group 3. No significant differences were found either in expression or overexpression of Fas and ICE between group 2 and group 1. CONCLUSIONS: These results suggest that all‐trans retinoic acid inhibits Bcl‐2 expression, promotes Fas expression, enhances ICE expression and gastric mucosal epithelial cell apoptosis, and thus may reverse or inhibit the progression to cancer.

Hippocampal dysplasia in rats exposed to cocaine in utero

Prenatal cocaine exposure can result in neurobehavioral disturbances and structural modifications of the central nervous system. In the present study, cocaine was injected into pregnant rats and the brains of their offspring were examined at the light microscopic level. As adults, cocaine-exposed offspring exhibited subtle, but consistent, hippocampal abnormalities. In particular, the stratum pyramidale (particularly the CA1 region) was interrupted by frequent gaps in lamination, and ectopic pyramidal cells were found in stratum oriens and radiatum.

Dental dysplasia in rats and mice.

Malformations of the maxillary incisors, diagnosed as dental dysplasia, were observed as a spontaneous background lesion in 3% (females) to 9% (males) of CD-1 mice and 14.5% (females) to 10.5% (males) of CD (Sprague-Dawley) rats in a chronic inhalation study. Lesions were reported grossly as overgrown, maloccluded, or malformed incisors. Microscopic findings included tooth pulp and periodontal abscesses, fractured and necrotic teeth, periodontal cysts, malformations of the incisor roots, and expansile masses, including odontomas, of the incisor roots. Development of lesions followed a pattern of tooth pulp necrosis and/or traumatic disruption of the epithelial root sheath at the base of the tooth. Feeding a powdered ration, which reduced the normal wearing of the incisors, and repeated clipping of overgrown incisors were believed to contribute to the incidence of disease.

Induction of colorectal cancer in rats by 20-methylcholanthrene

Colorectal carcinoma was induced in Sprague-Dawley rats by 20-methylcholanthrene. Macroscopical studies revealed that the tumors, either sessile type or semi-pedunculated polyp, were generally observed after 32 weeks of the carcinogen treatment. In the distal colon 46.9% tumors appeared, whereas 20.4% and 32.6% tumors were found in the rectum and proximal colon, respectively. Sequential histiopathological studies indicated that hyperplaria of goblet cells was common in early stages, which was reduced thereafter. Carcinogenesis progressed with the appearance of the different grades of dysplasia in colorectal mucosa with first incidence of the severe dysplasia in rats at the 20th week and in situ carcinoma at the close of 28th week. Most of the carcinomas were multifocal in origin and were well differentiated adenocarcinoma with primary invasion at the submucosa. In immunohistological studies, this carcinoma was also reactive with monoclonal antibody 660, prepared against a colorectal carcinoma associated mucin antigen.

Nuclear DNA content in dimethylhydrazine-induced colonic carcinoma and mucosal dysplasia in rats.

Mucosal dysplasia and carcinoma infiltrating the submucosal layer were induced in rats with dimethylhydrazine. The nuclear DNA content of the cells was measured, and the correlation between the DNA distribution pattern and histopathologic findings was evaluated. In mild and moderate dysplasias, histograms of the nuclear DNA content showed a narrow range of distribution with a sharp peak in the diploid area. In severe dysplasia, however, there was wide distribution and no peak value; this was reminiscent of carcinoma. Based on the findings of this report, the authors suggest that severe dysplasia be regarded as intramucosal carcinoma.

Chlorhexidine-induced lingual keratosis and dysplasia in rats

Chlorhexidine-induced lingual keratosis and dysplasia in rats

Chlorhexidine‐Induced Lingual Keratosis and Dysplasia in Rats

CHLORHEXIDINE IS an antibacterial agent that has been used extensively in recent years outside of the United States as a mouthwash for the prevention of periodontal disease. The observations of diminished plaque for­ mation and decreased severity of gingival inflammation have been confirmed in studies on monkeys.' Chlor­ hexidine also has been reported to increase the gingival healing rate following periodontal surgery, when incor­ porated into the periodontal dressing. Inflammatory and ulcerative lesions have been described in some pa­ tients using therapeutic doses of the drug as a mouth­ wash. However, the safety of the drug in humans has been emphasized in a number of reports, in which var­ ious medical parameters were found to be normal after 2 years of continuous daily use of the agent. Keratinization of palatal mucosa was found to be normal, the metabolism of oral epithelium, as determined by the activity of oxidative enzymes, was normal, and there was no evidence of inflammation or premalignant changes. The drug has been reported to be relatively nontoxic in experimental animals. Rats were able to tolerate 0.2% aqueous solutions as the only source of drinking water for periods of 6 months, with no obvious interference in growth and reproduction. Tissue culture studies, on the other hand, have demonstrated a high degree of toxic­ ity. 4 Exposure of human gingival fibroblasts, human newborn fibroblasts and HeLa cells to Chlorhexidine at concentrations as low as 0.004% resulted in impaired cellular function or cell death. Exposure of cells to 0.2% Chlorhexidine for 30 seconds produced suppression of protein synthesis as evidenced by release of radioactive chromium. Chlorhexidine was also found to be toxic to polymorphonuclear leukocytes, using the trypan blue dye technique. In view of the wide use of Chlorhexidine, the fact that some oral changes have been reported in humans and the absence of oral mucosal studies in experimental animals, the present study was undertaken to investigate the effect of Chlorhexidine ingestion on rat oral mucosa. The tongue was selected as the oral mucosal site of interest for several reasons. The tongue would be most likely to come in contact with the compound if delivered via the drinking water. In addition, the histol­ ogy of normal tongue in laboratory rats has been well described, and the organ presents two different surfaces for study. The dorsal surface is well keratinized and composed of highly specialized papillary structures, while the ventral surface is smooth and relatively nonkeratinized.