An orthotopic penetrating keratoplasty model was developed in the rat. An oversized (0.5 mm) graft was used and 8 interrupted sutures were applied. These sutures were not removed. Eleven grafts out of 13 were rejected by the 3rd week in the disparate group (Brown Norway rat to Lewis rat transplantation group), which was characterized by edema, opacity, and neovascularization. All grafts remained clear in the syngeneic group (Lewis rat to Lewis rat transplantation group). Immunohistochemical examination was performed. This model seems to be a reliable and reproducible one to evaluate rejection reaction in corneal transplantation.
Animals ; Female ; Graft Rejection ; Keratoplasty, Penetrating/immunology/*methods/pathology ; Lymphocyte Subsets/immunology/pathology ; Macrophages/immunology/pathology ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Transplantation, Homologous ; Transplantation, Isogeneic

This study was conducted in order to determine the functionality of mineral-rich salt with lower NaCl and higher mineral contents on blood pressure and lipid metabolism in Dahl salt-sensitive rats. A 1% salt solution was administered to five-week-old male Dahl rats- one normal and three salt groups (Purified salt, sun-dried salt, and bamboo salt) for 15 weeks. On the basis of the salt production process, the sun-dried group was classified into two subgroups: SS1 (2-year) and SS2 (>5-year) depending on the storage period of the mineral-rich salt. The relationships between salt intake and changes in blood pressure, serum lipids, and serum mineral concentrations were then examined. The results showed that intake of SS2, which is stored for five years, and BS (bamboo salt) resulted in continuous delay of the increase in blood pressure and inhibited angiotensin-converting enzyme (ACE) activity. In addition, a significant decrease in the triglyceride level in serum lipids of approximately 30% was observed in the SS2 group compared to the PS (purified salt) group. However, all salt intake groups showed an increase in total cholesterol levels compared to the normal group. The results demonstrate that intake of mineral-rich salt is beneficial for the human body and results in reduced blood pressure and triglyceride levels in serum lipids, however, conduct of more research will be needed in order to explore other functions.
Blood Pressure* ; Cholesterol ; Human Body ; Humans ; Lipid Metabolism ; Male ; Rats, Inbred Dahl* ; Triglycerides

No abstract available.
Adipocytes ; Estradiol ; Rats, Inbred OLETF

It has become increasingly clear that cytokines play an important role in modulating neuroendocrine regulation, especially in the secretion of corticotropin (ACTH) in the pituitary. Oncostatin M (OSM), a cytokine of IL-6 family has been reported to increase ACTH secretion and pro-opiomelanocortin (POMC) transcription in murine corticotroph pituitary tumor cells (AtT20 cells). The present study was undertaken to determine the effects of OSM on hormonal release in primary culture of rat pituitary cells. Growth hormone or prolactin release was not affected by OSM. OSM (1 nM) stimulated ACTH release (35.1% increase versus control, p>0.001) in dispersed pituitary cells of rat to a lesser extent than in AtT20 cells. Corticotropin releasing hormone (CRH) (10 nM) also induced a 2.3-fold increase of ACTH secretion (p>0.001), but co-treatment of OSM and CRH did not exhibit any synergistic effect on ACTH secretion. We conclude OSM has a stimulatory effect on ACTH secretion in normal rat pituitary cell cultures, and OSM acts mainly on corticotroph, supporting the potential role of OSM to modulate immune-endocrine regulation in the pituitary.
Animal ; Cells, Cultured ; Corticotropin/secretion* ; Cytokines/pharmacology ; Cytokines/metabolism* ; Inflammation Mediators/pharmacology ; Inflammation Mediators/metabolism* ; Male ; Peptides/pharmacology ; Peptides/metabolism* ; Pituitary Gland/metabolism* ; Pituitary Gland/drug effects ; Pituitary Gland/cytology ; Prolactin/secretion* ; Rats ; Rats, Inbred WF ; Somatotropin/secretion*

BACKGROUND AND OBJECTIVES: The necessity of a well established allergic rhinitis model is needed for the research of pathophysiology and therapeutic trial of allergic rhinitis. We investigated the potential of the inbred Brown-Norway (BN) rats, the high IgE-responder for allergic stimulation, as a model for allergic rhinitis using different durations of local sensitization with ovalbumin. MATERIALS AND METHOD: BN rats were divided into 3 groups according to the duration of local sensitization (LS), 1, 4, and 8 weeks, respectively. They were sensitized generally with ovalbumin in aluminum hydroxide and pertussis toxin followed by 1, 4, and 8 weeks of LS with ovalbumin nebulization. The frequency of sneezing, ovalbumin specific serum IgE, and the degree of eosinophil infiltration into the nasal mucosa in experimental groups were compared with the control group. RESULTS: After allergen challenge, the frequency of sneezing and ovalbumin specific IgE levels were significantly increased compared with the control group, and irrespective of the duration of LS. Eosinophil infiltration was significantly increased in the groups with 4 and 8 weeks of LS, but more severe in the group with 4 weeks of LS. CONCLUSION: BN rats were the suitable strain for the allergic rhinitis model and 4 to 8 weeks of LS was appropriate for allergic rhinitis model.
Aluminum Hydroxide ; Animals ; Eosinophils ; Immunoglobulin E ; Models, Animal ; Nasal Mucosa ; Ovalbumin ; Pertussis Toxin ; Rats* ; Rats, Inbred BN ; Rhinitis* ; Sneezing

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is widely observed in diabetes mellitus, resulting in diabetic vascular complications. Kruppel-like factor 2 (KLF2) is implicated as being a key molecule that maintains endothelial function. We evaluated the expression of KLF2 in endothelial cells cultured in high glucose and investigated its functional implication in a diabetic animal model. SUBJECTS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in physiologically high glucose (35 mM) condition. The Otsuka Long Evans Tokushima Fatty (OLETF) strain of rat was used as an excellent model of obese type II diabetes, and their lean littermates are Long Evans Tokushima Otsuka (LETO) rats. RESULTS: In HUVECs cultured in physiologically high glucose condition, FOXO1 was activated whereas KLF2 and endothelial nitric oxide synthase (eNOS) expression was near completely abolished, which was completely reversed by FOXO1 small interfering ribonucleic acid. In the vessels harvested from the OLETF rats, the animal model of type II diabetes, KLF2 and eNOS expression were found depleted. When vascular remodeling was induced in the left common carotid artery by reduction of blood flow with partial ligation of the distal branches, greater neointimal hypertrophy was observed in OLETF rats compared with the control LETO rats. CONCLUSION: KLF2 suppression in endothelial cells by high glucose is a possible mechanism of diabetic endothelial dysfunction. The strategy of replenishing KLF2 may be effective for preventing diabetic vascular dysfunction.
Animals ; Carotid Artery, Common ; Diabetes Mellitus ; Diabetic Angiopathies ; Endothelial Cells ; Glucose ; Human Umbilical Vein Endothelial Cells ; Hypertrophy ; Ligation ; Models, Animal ; Nitric Oxide Synthase Type III ; Rats ; Rats, Inbred OLETF ; RNA ; Sprains and Strains

OBJECTIVES: Type 2 diabetes mellitus (T2DM) increases fracture risk despite normal to high levels of bone mineral density. Bone quality is known to affect bone fragility in T2DM. The aim of this study was to clarify the trabecular bone microstructure and cortical bone geometry of the femur in T2DM model rats. METHODS: Five-week-old Otsuka Long-Evans Tokushima Fatty (OLETF; n = 5) and Long-Evans Tokushima Otsuka (LETO; n = 5) rats were used. At the age of 18 months, femurs were scanned with micro-computed tomography, and trabecular bone microstructure and cortical bone geometry were analyzed. RESULTS: Trabecular bone microstructure and cortical bone geometry deteriorated in the femur in OLETF rats. Compared with in LETO rats, in OLETF rats, bone volume fraction, trabecular number and connectivity density decreased, and trabecular space significantly increased. Moreover, in OLETF rats, cortical bone volume and section area decreased, and medullary volume significantly increased. CONCLUSIONS: Long-term T2DM leaded to deterioration in trabecular and cortical bone structure. Therefore, OLETF rats may serve as a useful animal model for investigating the relationship between T2DM and bone quality.
Animals ; Bone Density ; Diabetes Mellitus, Type 2 ; Femur ; Models, Animal ; Rats ; Rats, Inbred OLETF

The p53 gene has a significant role in controlling genomic stability of cancer. The purpose of this study was to evaluate the tumor response of allograft colorectal tumor treated with Ad5CMV-p53 in a syngeneic rat model. Two weeks after the inoculation of WB-2054-M5 tumor cells in the flank of rats, rats were randomly assigned by tumor size to one of three groups (n=18 in each): phosphate buffered saline (PBS), Ad5CMV, and Ad5CMV-p53. Recombinant adenovirus or PBS was administered through intratumoral injection at three divided doses every other day for 4 weeks. Apoptosis of the tumors was evaluated using TUNEL assay. After 2 and 4 weeks of treatment, the volume (cm3) of tumors in PBS, Ad5CMV, and Ad5CMV-p53 was as follows: 2 week: 1.66 +/-0.43, 1.40 +/-0.47, 0.75 +/-0.26 (p<0.001), 4 week: 4.41 +/-0.88, 3.93 +/-1.86, 2.33 +/-0.51 (p<0.001). Tumor growth showed no statistically significant difference between the PBS and Ad5CMV groups (6-week vol. p=0.32). The TUNEL assay results revealed more apparent apoptotic cells in Ad5CMV-p53-treated tumors than in other groups. Growth of allograft colorectal cancer in the syngeneic rat model was significantly suppressed by intratumoral Ad5CMV-p53 gene therapy. These results demonstrate that gene replacement therapy with p53 may provide a novel modality of treatment in conjunction with other present treatments for metastatic colorectal cancer.
Adenocarcinoma/genetics/pathology/therapy ; Adenoviridae/*genetics ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival/genetics ; Colorectal Neoplasms/*genetics/pathology/*therapy ; Disease Models, Animal ; Female ; Gene Therapy/*methods ; Gene Transfer Techniques ; Men ; Protein p53/*genetics/*therapeutic use ; Rats ; Rats, Inbred WF ; Recombinant Proteins/therapeutic use ; Research Support, Non-U.S. Gov't ; Transplantation, Isogeneic ; Treatment Outcome

The pathogenesis of diabetic retinopathy has not been fully explained. The earliest histological lesion is the loss of intramural pericytes and thickening of the basement membrane. Increased activity of the polyol pathway is a probable mechanism for these two abnormalities. Investigations have suffered from the lack of an exact animal model simulating the human condition. Examination of the retina in the spontaneously diabetic SHR/N:Mcc-cp rat demonstrated degeneration and loss of intramural pericytes, a progressive increase in basement membrane thickness, and microinfarctions with an area of non-perfusion. Therefore, this model may be used to clarify the biochemical mechanisms linking the metabolic abnormalities of diabetes and retinopathy.
Animal ; Diabetic Retinopathy/pathology* ; Disease Models, Animal ; Female ; Hybridization ; Male ; Rats ; Rats, Inbred SHR/genetics ; Rats, Inbred Strains/genetics ; Retina/pathology* ; Retinal Degeneration/pathology

The pathogenesis of diabetic retinopathy has not been fully explained. The earliest histological lesion is the loss of intramural pericytes and thickening of the basement membrane. Increased activity of the polyol pathway is a probable mechanism for these two abnormalities. Investigations have suffered from the lack of an exact animal model simulating the human condition. Examination of the retina in the spontaneously diabetic SHR/N:Mcc-cp rat demonstrated degeneration and loss of intramural pericytes, a progressive increase in basement membrane thickness, and microinfarctions with an area of non-perfusion. Therefore, this model may be used to clarify the biochemical mechanisms linking the metabolic abnormalities of diabetes and retinopathy.
Animal ; Diabetic Retinopathy/pathology* ; Disease Models, Animal ; Female ; Hybridization ; Male ; Rats ; Rats, Inbred SHR/genetics ; Rats, Inbred Strains/genetics ; Retina/pathology* ; Retinal Degeneration/pathology