Eosinophilic inflammation that begins in the juvenile stage causes hydronephrosis and urothelial cancer in mutant mice.

Obstructive hydronephrosis is caused by various factors such as chronic inflammation and tumors. Eosinophils and chitinase-like proteins (CLPs) are involved in the pathogenesis of hydronephrosis in mice; however, the specific mechanisms remain unknown. In this study, we morphologically analyzed a novel mouse model of obstructive hydronephrosis from onset to progression to clarify the effects of eosinophils and CLP on the development of hydronephrosis and tumorigenesis.

Malignant stromal cell tumor of the spleen in a WBN/Kob rat.

Primary splenic stromal tumors have rarely been reported in rodents. We report the case of a 90-week-old male WBN/Kob rat with a nodular demarcated mass in the spleen, which was kept as a non-treated animal in a long-term animal study. Histopathology revealed round to short spindle-shaped tumor cells arranged in a solid growth pattern.

High-fat diet-induced nonalcoholic steatohepatitis is accelerated by low carnitine and impaired glucose tolerance in novel murine models.

Carnitine deficiency and impaired glucose tolerance (IGT) exacerbate liver steatosis. Given the current lack of ideal murine nonalcoholic steatohepatitis (NASH) models, we investigated new NASH models using jvs/+ mice with low carnitine and wild-type mice with low-dose alloxan-induced IGT. The jvs/+ and wild-type mice were divided into jvs/+ mice fed a high-fat diet (HFD) from 3 weeks of age (HF hetero group), wild-type mice with low-dose alloxan treatment fed HFD (AL + HF wild group), wild-type mice fed HFD (HF wild group), and two types of mice fed a normal diet-jvs/+ and wild-type (intact group).

Spontaneous cholangiofibrosis adjacent to a dilated common bile duct with intestinal metaplasia in a Royal College of Surgeons rat.

A 130-week-old male Royal College of Surgeons rat kept as a non-treated animal in a long-term animal study presented with a mass in the hepatic portal region that adhered to a dilated common bile duct and the duodenum. Histopathologically, the solitary mass showed expansive growth with no apparent compression and continued to dilate the common bile duct, which had a hyperplastic epithelium with intestinal metaplasia. The mass mainly consisted of small to large dilated and/or tortuous ducts with abundant dense connective tissue and many inflammatory cells.

Superimposition of hypertension on diabetic peripheral neuropathy affects small unmyelinated sensory nerves in the skin and myelinated tibial and sural nerves in rats with alloxan-induced type 1 diabetes.

Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus, and hypertension is considered to be a risk factor for DPN in patients with type 1 diabetes (T1DM). However, the morphological effects of hypertension on DPN are unclear. In this study, we investigated the effect of hypertension on DPN by investigating the changes in unmyelinated and myelinated nerve fibers in hypertensive rats with alloxan (AL)-induced T1DM.

Hyperglycemia Suppresses Age-Related Increases in Corneal Peripheral Sensory Nerves in Wistar Bon Kobori (WBN/Kob) Rats.

Purpose: Nerve fiber density in the cornea is an alternative marker for diabetic peripheral neuropathy combined with intraepidermal nerve fiber density (IENFD). Recent studies investigated corneal nerves using rodent models of diabetes. Male Wistar Bon Kobori (WBN/Kob) rats spontaneously develop long-lasting diabetes and human-like diabetic peripheral neuropathy with vascular lesions.

Extended Duration of Hyperglycemia Result in Human-Like Corneal Nerve Lesions in Mice With Alloxan- and Streptozotocin-Induced Type 1 Diabetes.

Purpose: Previous experimental studies assessing corneal nerves as a measure of the severity of diabetic peripheral neuropathy have yielded discordant results; this may have been due to the effect of the short duration of the induced diabetes. We investigated whether increases in the duration of hyperglycemia result in the development of corneal lesions in a mouse model of alloxan (AL)- or streptozotocin (STZ)-induced type 1 diabetes. We further determined whether corneal nerve fiber density, intraepidermal nerve fiber density (IENFD), and sural nerve morphology can be used as morphologic markers of diabetic peripheral neuropathy in rodent models.

Effect of combined dyslipidemia and hyperglycemia on diabetic peripheral neuropathy in alloxan-induced diabetic WBN/Kob rats.

Clinical and experimental research have suggested that dyslipidemia aggravates diabetic peripheral neuropathy (DPN). However, whether dyslipidemia is a risk factor for DPN remains unclear. To investigate the effect of dyslipidemia on DPN, morphological features of peripheral nerves were analyzed in diabetic rats treated with a high-fat diet (HFD).

Macrophage-Associated Gelatinase Degrades Basement Membrane at the Optic Fissure Margins During Normal Ocular Development in Mice.

Purpose: Basement membrane degradation and macrophage aggregation at the optic fissure margins are crucial to optic fissure closure during normal murine eye development. Basement membrane degradation is also an essential step in cancer development, and matrix metalloproteinases (MMPs) play an important role. In this study, we investigated MMP alteration at the degrading basement membrane of optic fissure margins in mice and attempted to clarify the relationship between MMP activity and macrophages.

Long-term Hyperglycemia Naturally Induces Dental Caries but Not Periodontal Disease in Type 1 and Type 2 Diabetic Rodents.

Periodontal disease (PD) in patients with diabetes is described as the sixth complication of diabetes. We have previously shown that diabetes increases dental caries, and carious inflammation might have a strong effect on the adjacent periodontal tissue in diabetic rodent models. However, the possibility that hyperglycemia may induce PD in diabetic animals could not be completely eliminated.

Induction of Severe Chronic Hyperplastic Candidiasis in Rat by Opportunistic Infection of C. albicans through Combination of Diabetes and Intermittent Prednisolone Administration.

Chronic hyperplastic candidiasis progresses from squamous cell hyperplasia to squamous cell carcinoma (SCC); however, the oncogenic mechanism remains unclear. In the present study, we attempted to induce opportunistic Candida albicans infection and establish chronic hyperplastic candidiasis in rats by combining diabetic condition and prednisolone administration, followed by analysis of the inflammatory cells involved in the disease progression. Female Wistar Bunn/Kobori (WBN/Kob) rats were divided into 3 groups: alloxan-induced diabetic rats (A group) along with diabetic (AP group) and nondiabetic (P group) rats intermittently treated with prednisolone.

Malignant mast cell tumor of the thymus in an Royal College of Surgeons (RCS) rat.

A 152-week-old male Royal College of Surgeons (RCS) rat kept as a non-treated animal in a long-term animal study presented with a soft mass in the anterior mediastinum, which adhered to the pleura of the lung. Histopathologically, the mass mainly consisted of round to short spindle-shaped tumor cells that had infiltrated through the hyperplastic thymic tissue. The tumor cells were arranged in loose to dense sheets.

Hyperglycemia simultaneously induces initial caries development and enhances spontaneous occlusal surface wear in molar teeth related to parotid gland disorder in alloxan-induced diabetic rats.

Diabetes and salivary gland dysfunction are major factors that induce dental caries in experimental animals, but there are no reports analyzing the association of dental caries and salivary glands in an animal model of diabetes mellitus (DM). To clarify the initial development of dental caries and preceding salivary gland disorder, we performed a histopathological analysis on teeth and salivary glands in diabetic Wistar rats 7 weeks after alloxan treatment (DM group) in comparison with nondiabetic rats (Non-DM group) and functional analysis on saliva secretion during the experimental period. Pilocarpine-induced salivary fluid secretion in diabetic rats gradually decreased with continuous hyperglycemia from immediately after alloxan treatment to the time of autopsy.

Acute alloxan renal toxicity in the rat initially causes degeneration of thick ascending limbs of Henle.

Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear.

Lack of Correlation between Aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 Protein Expression and Promoter Methylation in Squamous Cell Carcinoma Accompanying Candida albicans-Induced Inflammation.

Hyperplastic candidiasis is characterized by thickening of the mucosal epithelia with Candida albicans infection with occasional progression to squamous cell carcinoma (SCC). C. albicans is a critical factor in tumor development; however, the oncogenic mechanism is unclear.

Effect of deoxycorticosterone acetate-salt-induced hypertension on diabetic peripheral neuropathy in alloxan-induced diabetic WBN/Kob rats.

The relationship between hypertension and diabetic peripheral neuropathy (DPN) has recently been reported in clinical research, but it remains unclear whether hypertension is a risk factor for DPN. To investigate the effects of hypertension on DPN, we analyzed morphological features of peripheral nerves in diabetic rats with hypertension. Male WBN/Kob rats were divided into 2 groups: alloxan-induced diabetic rats with deoxycorticosterone acetate-salt (DOCA-salt) treatment (ADN group) and nondiabetic rats with DOCA-salt treatment (DN group).

Probiotic (yogurt) containing Lactobacillus gasseri OLL2716 is effective for preventing Candida albicans-induced mucosal inflammation and proliferation in the forestomach of diabetic rats.

Oral and esophageal candidiasis sometimes leads to mucosal hyperplasia, and progresses to carcinoma. We have produced an animal model for hyperplastic mucosal candidiasis in the forestomach that has a proliferative lesion of the squamous epithelium with chronic inflammation and C. albicans infection, some of which advanced to squamous cell carcinoma.

Assessment of Alloxan-Induced Diabetic Rats as a Periodontal Disease Model Using a Selective Cyclooxygenase (COX)-2 Inhibitor.

Several recent studies have reported that alloxan-treated rats with long-term hyperglycemia can develop naturally occurring periodontal disease (PD). Our previous studies detected dental caries in the same model. Therefore, these two lesions of different etiologies are expected to occur concurrently.

A novel diabetic murine model of Candida albicans-induced mucosal inflammation and proliferation.

Chronic hyperplastic candidiasis (CHC) lesions will progress to dysplasia with some of these developing squamous cell carcinoma (SCC). It is well known that diabetic patients are predisposed to candidiasis. Previously, we found that alloxan-induced diabetic rats spontaneously have mucosal hyperplasia with C.

The effect of food hardness on the development of dental caries in alloxan-induced diabetic rats.

We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents.

Insulin-ameliorated peripheral motor neuropathy in spontaneously diabetic WBN/Kob rats.

Rodent models of diabetes develop a slowing of nerve conduction velocity and mild axonal atrophy, but generally lack overt degenerative neuropathy. Spontaneously diabetic Wistar Bonn Kobori (WBN/Kob) rats develop severe diabetic peripheral motor neuropathy with a slowing of nerve conduction velocity. We examined the effect of glycemic control, using insulin implant, on neuropathic changes in these rats.

Altered gene expression profiles associated with enhanced skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate in streptozotocin-diabetic mice.

To examine the mechanisms of diabetes-enhanced inflammation, ear inflammation was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in streptozotocin (STZ)-injected diabetic and control mice. The inflammatory response was determined from ear thickness and histology. The mRNA expression of several inflammation-related genes 8, 24 and 32 h after TPA treatment was determined by quantitative real-time RT-PCR.

Glycemic control with insulin prevents progression of dental caries and caries-related periodontitis in diabetic WBN/KobSlc rats.

We have previously reported that dental caries progress in spontaneously and chemically induced diabetic rodent models. The aim of this study was to clarify the relationship between hyperglycemia and dental caries by evaluating the preventive effect of glycemic control with insulin on the progression of the lesions in diabetic rats. Male WBN/KobSlc rats aged 15 weeks were divided into groups of spontaneously diabetic rats (intact group), spontaneously diabetic rats with insulin treatment (INS group), alloxan-induced prolonged diabetic rats (AL group), and alloxan-induced prolonged diabetic rats with insulin treatment (AL + INS group).

Alloxan-induced hyperglycemia causes rapid-onset and progressive dental caries and periodontitis in F344 rats.

We have previously shown that diabetes increases dental caries, and periodontitis might be a secondary change resulting from dental caries in spontaneous diabetic rodent models. However, the lesions in these models were slow to manifest, and the intensity and frequency were mild and varied among individuals. The goal of this study was to confirm the reproducibility of caries development in chemically induced diabetic rats and investigate whether alloxan, which induces immediate and severe hyperglycemia in experimental animals, increases the lesions.

Iridal coloboma induces dyscoria during miosis in FLS mice.

Objective: Fatty liver Shionogi (FLS) mice exhibit characteristic retinochoroidal coloboma because of a failure in fusion of the embryonic optic fissure. However, the same pathogenesis should result in iridal coloboma that has not been reported in this strain. The purpose of this study was to describe the physiologic and morphometric changes in iridal tissue involved in ocular coloboma in FLS mice.