Metalloestrogenic effects of cadmium are absent in long-term estrogen-deprived MCF-7 cells: Evidence for the involvement of constitutively activated estrogen receptor α and very low expression of G protein-coupled estrogen receptor 1.

Cadmium (Cd) has estrogen-like activities in breast cancer; it acts as a metalloestrogen in humans. Prospective cohort studies of Cd and breast cancer risk suggest a significant relationship between increased Cd intake and cancer incidence, with more pronounced effects for estrogen receptor α (ERα)-positive breast cancers. However, a recent systematic review with the highest level of evidence demonstrated no such relationship in post-menopausal women.

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.

Acute alloxan toxicity causes granulomatous tubulointerstitial nephritis with severe mineralization.

Alloxan had been recognized as having a direct nephrotoxic effect different from its diabetogenic action. We encountered previously unreported granulomatous tubulointerstitial nephritis with severe luminal and interstitial mineralization in one diabetic rat after one week of alloxan administration. Histopathologically, many dilated and occluded proximal and distal tubules were segmentally observed in the cortex and outer medulla.

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.

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.

Antimicrobial agent, tetracycline, enhanced upper alimentary tract Candida albicans infection and its related mucosal proliferation in alloxan-induced diabetic rats.

Alloxan-induced diabetic rats showed proliferative changes in the forestomach, accompanied by chronic inflammation, and one lesion progress to squamous cell carcinoma (SCC) without distant metastasis. The authors demonstrated that these lesions might be caused by Candida albicans infection. Antimicrobial therapy, particularly tetracycline treatment, has been blamed for a reduction in the number of competing bacterial organisms, which is frequently mentioned as a cause of candidiasis.

Diabetes enhances dental caries and apical periodontitis in caries-susceptible WBN/KobSlc rats.

Many epidemiologic studies have suggested that diabetes may be an important risk factor for periodontal disease. To determine whether diabetes induces or enhances periodontal disease or dental caries, dental tissue from diabetic male and nondiabetic female WBN/KobSlc rats and male and female age-matched nondiabetic F344 rats was analyzed morphologically and morphometrically for these 2 types of lesions. Soft X-ray examination revealed that the incidence and severity of both molar caries and alveolar bone resorption were much higher in male WBN/KobSlc rats with chronic diabetes than in nondiabetic female rats of the same strain.

Anti-osteoporosis effect of 5-bromo-2-(4-chlorobenzoyl)-(Z)-3-(2-cyano-3-hydroxybut-2-enonyl)aminobenzo[b]furan: a novel selective estrogen receptor modulator.

The benzo[b]furan derivative MU314 inhibits in vitro bone resorption as potently as β-estradiol (E(2)). Here, we examined the point of action on the anti-osteoporotic effects of MU314. MU314 (10 nM) suppressed lacunae formation by osteoclastic cells and ICI-182,780, a pure E(2) antagonist, inhibited this effect.

Enhanced tumorigenesis of forestomach tumors induced by N-Methyl-N'-nitro-N-nitrosoguanidine in rats with hypoinsulinemic diabetes.

Hyperinsulinemia and hyperglycemia in prediabetic and diabetic patients are thought to increase the risk of developing neoplasms because insulin is a growth factor with pre-eminent metabolic but also mitogenic effects. To determine the effect of hypoinsulinemic diabetic conditions on carcinogenesis, we examined N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced forestomach carcinogenesis in hypoinsulinemic diabetic WBN/Kob rats aged about 45 weeks (DM) compared with non-diabetic younger WBN/Kob rats (C1), non-diabetic Wistar rats age-matched to DM (C2), and non-diabetic Wistar rats age-matched to C1 (C3). All rats were treated with MNNG by gavage and were killed at 40 weeks after dosing.

Assessment of carotid plaque echolucency in addition to plaque size increases the predictive value of carotid ultrasound for coronary events in patients with coronary artery disease and mild carotid atherosclerosis.

Objectives: This study examined whether combined ultrasound assessment of plaque size and echolucency in the carotid artery had an additive effect for predicting coronary events in patients with coronary artery disease (CAD). Ultrasound assessment of either plaque size or echolucency of carotid artery provides prognostic information on coronary events. Combined assessment of plaque size and echolucency of carotid artery has the advantage of obtaining both structural and compositional information in the same artery in a single session.

Treatment of acute myocardial infarction with sirolimus-eluting stents results in chronic endothelial dysfunction in the infarct-related coronary artery.

Background: Sirolimus-eluting stent (SES) implantation aggravated endothelial vasomotor dysfunction in infarct-related coronary arteries.

Methods And Results: This study examined the effect of SES implantation on the duration of reperfusion-induced endothelial vasomotor dysfunction in infarct-related coronary arteries and on postinfarct left ventricular dysfunction in acute myocardial infarction (AMI). Patients with a first AMI due to occlusion of the left anterior descending coronary artery and successful reperfusion using SES (n=15) or bare metal stents (BMS; n=18) were examined.

Malignant Lymphoma with Severe Infiltrative Growth into Skeletal Muscles in WBN/Kob Rats.

Although spontaneously occurring neoplasms have been reported repeatedly in F344, SD and Wistar rats, which are commonly used strains for routine toxicologic and carcinogenicity studies, there are only a few reports of malignant lymphoma or lymphatic leukemia except for large granular lymphocytic leukemia (LGL) in F344 rats. Malignant lymphoma (lymphosarcoma) is thought to be uncommon in F344 rats. The authors encountered malignant lymphomas of the non-LGL leukemia type with characteristic pathologic features in WBN/Kob rats.

Effects of the antifungal agent itraconazole on proliferative changes of the forestomach mucosa in alloxan-induced diabetic rats.

Alloxan-induced diabetic rats frequently exhibit proliferative lesions of squamous hyperplasia accompanied by chronic inflammation and Candida albicans infection in the forestomach, and some lesions progress to squamous cell carcinoma (SCC). Candida infection causes not only hyperplastic changes with inflammation but might also lead to SCC in human oral mucosa. Thus, the present study was conducted to examine the effects of the antifungal agent itraconazole (ITCZ) on proliferative and inflammatory changes of the forestomach in alloxan-induced diabetic WBN/Kob rats.

Morphological study on dental caries induced in WBN/KobSlc rats (Rattus norvegicus) fed a standard laboratory diet.

In our previous studies, WBN/KobSlc was characterized as a rat strain in which only males began to develop pancreatitis, and then presented with diabetic symptoms. In the course of studying their pancreatic inflammation, we detected molar caries in prediabetic males feeding on a standard diet (CRF-1) widely used for experimental animals. The purpose of this study is to confirm whether the WBN/KobSlc strain is caries-susceptible to the diet reported to be non-cariogenic, and to examine the effect of a prediabetic condition on their dental caries.

Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease.

Objectives: We assessed the hypothesis that changes in endothelial vasomotor function in response to optimized therapy for atherosclerotic coronary artery disease predict future cardiovascular events.

Background: Although endothelial vasomotor dysfunction is a predictor of cardiovascular events, it remains unclear whether reversibility of endothelial dysfunction in response to risk factor reduction provides prognostic information.

Methods: This study included 251 patients with newly diagnosed coronary artery disease and an impaired flow-mediated dilation (FMD) of the brachial artery (FMD <5.

Prevention of proliferative changes of forestomach mucosa by blood glucose control with insulin in alloxan-induced diabetic rats.

Diabetes mellitus is one of the risk factors for carcinogenesis. Recently we reported that alloxan induces squamous cell carcinoma (SCC) with coincidental inflammation, bacteria/fungal infections, and a severe diabetic condition. The present study was conducted to examine the effects of blood glucose control with insulin on the proliferative changes of the forestomach in alloxan-induced diabetic rats.

Paradoxical effects of a selective cyclooxygenase-2 inhibitor, etodolac, on proliferative changes of forestomach in alloxan-induced diabetic rats.

A single intravenous injection of alloxan, a non-genotoxic diabetogenic chemical, induces proliferative changes in forestomach mucosa of rats, and some lesions progress to squamous cell carcinoma accompanied with inflammatory change. The present study was conducted to examine the effects of a selective cyclooxygenase-2 (COX-2) inhibitor, etodolac, on the proliferative changes of forestomach mucosa in alloxan-induced diabetic rats. Alloxan-induced diabetic rats were fed a diet containing 0.

Measurement of the platelet retention rate in a column of collagen-coated beads is useful for the assessment of efficacy of antiplatelet therapy.

Introduction: A simple, validated method to measure platelet function is unavailable for bedside use. Measurement of platelet retention rate using a column of collagen-coated beads and whole blood is a new, simple assay that reflects platelet aggregation. This study was aimed to examine the utility of this assay to assess efficacy of antiplatelet drug therapy.

Rapid improvement of carotid plaque echogenicity within 1 month of pioglitazone treatment in patients with acute coronary syndrome.

Objective: This study examined whether pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, may stabilize vulnerable plaque with use of ultrasound evaluation of carotid artery plaque echolucency in patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM).

Methods And Results: Treatment with pioglitazone (15 or 30mg/day, n=31) or placebo (n=30) was randomly assigned and initiated within 5 days after the onset of ACS in 61 patients with type 2 DM and echolucent carotid plaques. Vulnerable carotid plaques were assessed by measuring plaque echolucency using carotid ultrasound with integrated backscatter (IBS) before, at 2 weeks, and 1 month and 6 months after initiation of treatment.