Plasma Profiles of Glucose, Insulin and Lipids in the Male WBN/Kob-Lepr(fa) Rat, a New Model of Type 2 Diabetes with Obesity

Plasma profiles of glucose, insulin and lipids were examined in the male WBN/Kob-Lepr(fa) (fa/fa) rat, a new model of type 2 diabetes (T2D), in comparison with age-matched original male WBN/Kob (lean) rats. The fa/fa rats developed hypertriglycemia, obesity and hyperglycemia from 5, 7, and 9 weeks of age, respectively. Plasma insulin levels in fa/fa rats were significantly higher than those in lean rats at 5 weeks of age, but after 11 weeks of age gradually declined to the levels in lean rats. HOMA-IR, a measure of insulin resistance status, showed that fa/fa rats had insulin resistance. The fa/fa rat has the potential to become an important animal model of T2D with obesity.     

Physiological changes induced by salt intake in female Spontaneously Diabetic Torii‐Leprfa (SDT fatty) rat,a novel obese type 2 diabetic model

Salt plays an important role in the control of blood pressure in obesity and diabetes mellitus. In this study, we investigated physiological changes such as blood pressure and renal function in salt‐loaded female Spontaneously Diabetic Torii‐Lepr^fa (SDT fatty) rats. SDT fatty rats were given 1% NaCl in drinking water for 14 weeks, from 4 to 18 weeks of age. Significant salt‐sensitive hypertension was observed in the salt‐loaded SDT fatty rats. Moreover, the salt‐loaded rats showed a decrease of creatinine clearance and deterioration on pathological renal findings, including glomerulosclerosis and tubular and interstitial lesions. Female SDT fatty rat is a useful model for investigating the mechanisms of high salt sensitivity in obesity and diabetes mellitus.     

Blood pressure characteristics of female spontaneously diabetic Torii-Lepr(fa) rats

Blood pressure in female SDT-fa/fa rats was periodically investigated at ages 8, 16, and 24 weeks. Furthermore, an insulin therapy was performed for 5 weeks in the female rats at age 11 weeks, and the change of blood pressure was examined. In addition to obesity, hyperglycemia, hyperinsulinemia, and hyperlipidemia, hyperleptinemia and increased urinary angiotensinogen level were observed during the experimental period. Blood pressure was elevated at ages 8 and 16 weeks, but that at 24 weeks was comparable to that in Sprague-Dawley (SD) rats. Heart rate was decreased from age 8 to 24 weeks. Insulin therapy induced good glycemic control and improvement of hyperlipidemia, but the blood pressure was not reduced. Blood pressure in female SDT-fa/fa rats was elevated temporarily. The blood pressure was not decreased by insulin treatment. SDT-fa/fa rat is a useful model to investigate the relation between diabetes mellitus and hypertension.     

Bone morphological analyses in Spontaneously Diabetic Torii (SDT) fatty rats

The Spontaneously Diabetic Torii (SDT) fatty rat, a model for obese type 2 diabetes, shows bone quantitative abnormalities, namely low bone mineral density (BMD). The objective of this study was to evaluate bone morphological changes, in particular identifying the bone qualitative abnormalities, in the SDT fatty rat. Male SDT fatty rats showed increases in total trabecular area and trabecular number and decreases in trabecular thickness in cancellous bones of the proximal tibia, indicating trabecular miniaturization. The SDT fatty rat is useful for investigation of pathophysiological changes in bone quality in diabetic osteoporosis.     

Effects of ovariectomy on bone metabolism and bone mineral density in spontaneously diabetic Torii-Lepr(fa) rats

The Spontaneously Diabetic Torii-Lepr(fa) (SDT- fa/fa) rat is a new model of obese type 2 diabetes. The female SDT-fa/fa rat shows obesity, hyperglycemia and hyperlipidemia from a young age. However, it is not known whether diabetes and estrogen deficiency can lead to bone abnormalities in the female SDT-fa/fa rat. The objective of the present study was to investigate the effects of ovariectomy (OVX) on bone metabolism and bone mineral density (BMD) in the female SDT-fa/fa rat. Female Sprague-Dawley rats were used as control animals. The BMDs of the whole tibia and fifth lumbar (L5) vertebral body were analyzed at 30 weeks after OVX. Serum osteocalcin, a bone formation marker, and urine deoxypyridinoline (DPD), a bone resorption marker, were sequentially analyzed before and at 5, 15 and 30 weeks after OVX. Serum osteocalcin and urine DPD levels were lower in SDT-fa/fa rats than in control rats before OVX. Both serum osteocalcin and urine DPD levels were elevated in control rats 5-30 weeks after OVX, but only the urine DPD levels were elevated in SDT-fa/fa rats 5-30 weeks after OVX. SDT-fa/fa rats showed a decrease in the BMDs of the whole tibia and L5 vertebral body compared with control rats. OVX decreased the BMDs of the whole tibia and L5 vertebral body in control rats, but not in SDT-fa/fa rats. These data suggest that estrogen deficiency is not a risk factor for bone loss in type 2 diabetes mellitus.     

Effect of oral administration of 3,3',4,4',5-pentachlorobiphyenl on the intestinal microbiota of Sprague–Dawley rats

The effect of the endocrine-disrupting chemical 3,3',4,4',5-pentachlorobiphyenl (PCB 126) on intestinal microbiota after oral administration, and the improvement of intestinal microbiota and feces quantity by the subsequent administration of Lactobacillus acidophilus or Lactobacillus reuteri was investigated. All the rats were given 100 μg/kg bodyweight of PCB 126. The changes in bacterial counts were confirmed using a culture method. The administration of PCB 126 tended to decrease the bacterial counts of lactobacilli (10^9.6−10^10.2 to 10^8.8−10^9.2) and bifidobacteria (10^5.3−10^6.1 to 10^3.6−10^4.2), and to increase those of Enterobacteriaceae (10^8.2−10^9.1 to 10^9.4−10^10.3) and staphylococci (10^6.6−10^7.4 to 10^7.2−10^8.4) compared to no PCB 126 administration. After administration of PCB 126, L. acidophilus or L. reuteri orally administered to rats caused Enterobacteriaceae and staphylococci counts to decrease, suggesting that the intestinal microbiota was improved by the lactobacilli. The administration of L. acidophilus and L. reuteri improved the balance of intestinal microbiota, and defecation volume returned to its normal level. L. acidophilus and L. reuteri have a remedial effect on intestinal microbiota affected by PCB 126 and can function to lessen accumulated PCB 126 volume.     

Effect of repeated stress in early childhood on the onset of diabetes mellitus in male Spontaneously Diabetic Torii rats

Spontaneously Diabetic Torii (SDT) rats were discovered from SD rats and represent a confirmed spontaneous type 2 diabetes mellitus model. We investigated the effect of repeated stress in early childhood on SDT rats fed a high-fat diet, on locomotor activity and on the onset of diabetes mellitus. Regarding stress, a water immersion-restraint stress (WIRS) burden was applied 10 times every other day from 4 weeks of age. The results of the study showed, that the locomotor activity of the young SDT rats was clearly lower than that of the SD rats, and their locomotor activity was inferred to be congenitally low. In addition, the stress-burdened SDT rats showed delayed onset of diabetes mellitus and impaired glucose tolerance compared with the rats not receiving stress burden. The locomotor activity of SDT rats is less than that of SD rats, and they SDT rats are thought to have poor at spontaneous energy expenditure. On the other hand, the feeding efficiency of the WIRS-burdened SDT rats was reduced, and in comparison with the SDT rats with no WIRS burden, energy expenditure was increased; this is suggested to influence the onset of diabetes mellitus.     

Clinical, immunological and histopathological findings in a subpopulation of dogs with pododermatitis

Abstract   Clinical, immunological and histopathological findings in 20 adult dogs of varying breeds with chronic (≥ 6 months) inflammation confined to the pedal skin were compared over a 2-year period with those of a group of age-matched controls ( n  = 20). All affected dogs were pruritic but systemically well. Lesions were present on all four feet in 18/20 cases. Affected feet were characteristically erythematous, swollen, painful and alopecic. Sinus tracts were evident in 4/20 dogs. Despite a methodical series of diagnostic tests, no underlying cause was identified. None of the dogs responded to antimicrobial therapy administered for 8 weeks, none had evidence of ectoparasitism and none satisfied the criteria for atopic dermatitis. There was no response to a dietary trial using a novel protein source. The condition was characterized histopathologically by epidermal hyperplasia, hyperkeratosis, spongiosis, dermal oedema and perivascular aggregates of lymphocytes and plasma cells. Clinical signs did not correlate with histopathological findings. Affected dogs had significantly elevated serum IgG and IgM concentrations. The results of lymphocyte proliferation assays and phenotypic studies to determine the relative percentage of CD3⁺, CD4⁺, CD8⁺ and CD21⁺ lymphocyte subsets, and the ratio of CD4⁺/CD8⁺ cells were not significantly different between groups. No age, sex or seasonal predilections were noted. All dogs subsequently responded to immunosuppressive doses of prednisolone or cyclosporin. The term immunomodulatory-responsive lymphocytic–plasmacytic pododermatitis is proposed to denote what may be a previously unrecognized condition in some dogs with pododermatitis of undetermined aetiology.     

Age-related changes in leukocytes and T cell subsets in peripheral blood of Japanese Black cattle

It is well known that the immune system changes with age during development and maturation in Holstein cattle. But age-related changes in leukocytes and T cell subsets in peripheral blood of Japanese Black cattle still remain unclear. The aim of the present study was to investigate comparative changes of leukocytes (granulocytes, monocytes, B cells and T cells) and T cell subsets (CD4⁺, CD8⁺, γδ, CD8⁺γδ and WC1⁺γδ T cells) in Japanese Black cattle aged 0.5, 1, 2, 6, 18 and 36–41 (adult) months on flow cytometry using specific monoclonal antibodies for the cell surface markers. T cell proportion was approximately 40% in 2-month-old cattle and decreased to 20.6% in adults. In contrast, B cell proportion significantly increased from 7.4% to 28.2% with age. In T cell subsets the percentage of CD4⁺ T cells significantly increased from 40.5% to 60%, but that of WC1⁺γδ T cell subset significantly decreased with age. The percentages of CD8⁺ and CD8⁺γδ T cells did not change. The present study details the proportional changes in leukocyte and T cell subsets with age in the peripheral blood of Japanese Black cattle and these findings are similar to those described for Holstein cattle.     

Maternal high‐fat diet promotes onset of diabetes in rat offspring

The onset and progression of type II diabetes is closely related to environmental factors, in particular dietary habit. Moreover, the environmental exposures very early in life can influence the risk for development of type II diabetes later in life. In this study, we investigated pathophysiological changes in the pups of maternal Spontaneously Diabetic Torii (SDT) rats that were fed a high‐fat diet (HFD) throughout gestation and lactation. Maternal SDT rats were continued on HFD for 5 weeks, from day 8 of gestation to day 21 after birth, and biological analyses of the pups were performed from 2 to 22 weeks of age. Results of serum lipid levels in pups from dams fed HFD were higher than pups from dams fed a standard diet, and the onset of diabetes was significantly accelerated in pups from dams fed HFD. In pathological analyses, pups from dams fed HFD showed increases in liver weight and vacuolation of hepatic cells at 2 weeks of age. In conclusion, the metabolic disorder of lipids and glucose in SDT rats is closely related to the nutritional condition of dams during the periods of gestation and lactation.     

Frequency of pulmonary mineralization and hypoxemia in 21 dogs with pituitary-dependent hyperadrenocorticism

The purpose of this study was to determine the frequency of hypoxemia and pulmonary mineralization using ^99mTc-methylene diphosphonate (^99mTc-MDP) in dogs with pituitary-dependent hyperadrenocorticism (PDH). Twenty-one dogs with PDH were pro-spectively evaluated using thoracic radiography, arterial blood gas analysis, and bone phase and pulmonary perfusion scintigraphy (using ^99mTc-macro-aggregated albumin [^99mTc-MAA]). The radiographs and bone and perfusion studies were evaluated subjectively. An averaged quantitative count density ratio was calculated between the thorax and cranial thoraco-lumbar vertebrae from lateral thoracic ^99mTc-MDP images. Thoracic: vertebral ratios were calculated using ^99mTc-MDP studies from 21 control dogs. The thoracic: vertebral ratios were compared between the 2 groups (PDH and control). The mean age (±SD) of the 21 PDH dogs was 10.2 (±3) years, whereas the mean age of the control group was 9.8 (±3) years. Seven of the 21 dogs with PDH were hypoxemic (denned as an arterial partial pressure of oxygen [PaO₂] <80 mm Hg) with an average PaO₂ (±SD) of 62 (±15) mm Hg. Of the 7 hypoxemic dogs, 2 were found to have pulmonary mineralization based on bone scintigraphic images. Pulmonary perfusion abnormalities were not identified using ^99mTc-MAA in any of the 21 PDH dogs. Six PDH dogs had an abnormal interstitial pulmonary pattern and 5 of these dogs were hypoxemic. The average quantitative thoracic: vertebral ratio was not significantly different between the PDH and control dogs (0.5 ± 0.4 versus 0.4 ± 0.1, P = .16). Causes of hypoxemia other than pulmonary thromboembolism should be considered in dogs with PDH. Pulmonary mineralization may contribute to hypoxemia in dogs with PDH.     

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. In this study, we evaluated the use of diabetic rats as a PD model by employing a selective COX-2 inhibitor reported to be effective against PD. Six-week-old female F344 rats were divided into 3 groups: intact rats (control), alloxan-induced diabetic rats fed a standard diet (AL) and alloxan-induced diabetic rats fed a diet containing 0.01% etodolac (AL+Et). The animals were euthanized at 26 weeks of age, and their oral tissues were examined histopathologically. Gingivitis, marginal periodontitis and alveolar bone resorption were markedly enhanced along with dental caries in the AL group compared with the control group. However, the COX-2 inhibitor had no effect on periodontal inflammation in the AL+Et group. In addition, in the AL group, periodontitis was notably nonexistent around the normal molars, and gingivitis was scarcely worse than that in the control group. In the diabetic rats, the progression of periodontal inflammation was closely correlated with the severity of adjacent dental caries, and marginal periodontitis was frequently continuous with apical periodontitis. In conclusion, an alloxan-induced diabetic rat is not a model of PD but of dental caries. It is probable that in this model, hyperglycemia may enable crown caries to progress to apical periodontitis, while the associated inflammation may rostrally expand to surrounding periodontal tissue.     

Reduction of adult hippocampal neurogenesis is amplified by aluminum exposure in a model of type 2 diabetes

In this study, we investigated the effects of chronic aluminum (Al) exposure for 10 weeks on cell proliferation and neuroblast differentiation in the hippocampus of type 2 diabetic rats. Six-week-old Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were selected and randomly divided into Al- and non-Al-groups. Al was administered via drinking water for 10 weeks, after which the animals were sacrificed at 16 weeks of age. ZDF rats in both Al- and non-Al-groups showed increases in body weight and blood glucose levels compared to ZLC rats. Al exposure did not significantly affect body weight, blood glucose levels or pancreatic β-cells and morphology of the pancreas in either ZLC or ZDF rats. However, exposure to Al reduced cell proliferation and neuroblast differentiation in both ZLC and ZDF rats. Exposure to Al resulted in poor development of the dendritic processes of neuroblasts in both ZLC and ZDF rats. Furthermore, onset and continuation of diabetes reduced cell proliferation and neuroblast differentiation, and Al exposure amplified reduction of these parameters. These results suggest that Al exposure via drinking water aggravates the impairment in hippocampal neurogenesis that is typically observed in type 2 diabetic animals.     

18FDG-PET IMAGING IN CANINE LYMPHOMA AND CUTANEOUS MAST CELL TUMOR

Positron Emission Tomography (PET) using the glucose analog 2-deoxy-2-[¹⁸F]fluoro- d -glucose (¹⁸FDG) is a common imaging modality for diagnosis and management of many human malignancies. We evaluated ¹⁸FDG-PET in dogs with either multicentric lymphoma (LSA) or cutaneous mast cell tumor (MCT). A prototype large field-of-view PET scanner was used to collect whole-body images in nine dogs with LSA or MCT. Both tumors were characterized by avidity for ¹⁸FDG. In dogs with LSA, ¹⁸FDG-PET correctly identified involvement of superficial and internal lymph nodes, liver, and spleen. Repeated PET scans after induction chemotherapy demonstrated resolution of abnormal ¹⁸FDG uptake within these sites. In dogs with MCT, ¹⁸FDG-PET correctly identified MCT metastasis to regional lymph nodes in all dogs in which this was suspected or confirmed with cytology or biopsy before the PET scan. In two dogs, additional sites of mast cell disease were identified with ¹⁸FDG-PET that were undetected on physical examination and/or regional lymph node cytology. ¹⁸FDG-PET holds promise as a whole-body staging method for canine LSA and MCT.     

Hepatic activity of 3-hydroxy-3-methylglutaryl-CoA reductase in rats with alimentary zinc deficiency

Recent studies demonstrated that zinc deficiency lowers hepatic cholesterol concentrations in rats fed on diets that were rich in polyunsaturated fatty acids (PUFA); in contrast, in rats fed on diets that were rich in saturated fatty acids, zinc deficiency did not influence hepatic cholesterol concentrations (Eder and Kirchgessner 1993, 1994a,b, 1995). To date the mechanism underlying those effects is unclear. Based on ¹⁴C-incorporation into tissue lipids, a study by Patel et al. (1975) suggested that zinc deficiency impairs the hepatic synthesis of cholesterol. However, their investigation did not include studies on enzymes involved in cholesterol synthesis. The present study therefore was focused on the effects of zinc deficiency on the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) which is the key enzyme in the regulation of cholesterol biosynthesis. Therefore, rats were fed zinc-deficient diets containing either linseed oil or olive oil as sources of fat, and the activity of HMG-CoA reductase was assayed in hepatic microsomes.     

Treadmill exercise prevents diabetes-induced increases in lipid peroxidation and decreases in Cu,Zn-superoxide dismutase levels in the hippocampus of Zucker diabetic fatty rats

In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.     

IN VITRO EVALUATION OF CANINE GRANULOCYTES LABELED WITH 99mTC-HEXAMETHYLPROPYLENEAMINE OXIME:

Technetium-99m hexamethylpropyleneamine oxine (^99mTc-HMPAO) and Indium-111 oxine (¹¹¹In-oxine) labeled canine gramulocytes were evaluated in vitro over a six hour period. Labeling efficiency for ^99mTC-HMPAO and ¹¹¹In-oxine labeled granulocytes was 39.6%± 8.0% and 60.6%± 17.6% (mean ± SD) respectively. The mean in vitro elution of the radiolabel ranged from 8.7-14.0% for the ^99mTc-HMPAO grannulocytes and from 6.1-9.0% for the ¹¹¹In-oxine granulocytes. Mean cell viability, for the ^99mTc-HMPAO, ¹¹¹In-oxine and non-radiolabeled control granulocytes ranged from 97.8-99.4%, 96.4-98.5% and 98.2-99.0%, respectively. The phagocytic ability of the ^99mTc-HMPAO, ¹¹¹In-oxine and control granulocytes ranged from 47.5-54.1%, 38.9-56.2% and 46.6-57.8% respectively over the six hour study period. Although labeling efficiency using ¹¹¹In-oxine was significantly (P=0.05) better than ^99mTc-HMPAO, there was no significant difference in label retention of the two radiolabels. There was no significant difference in viability or phagocytic function during the six hour study period. Considering the potential cost advantage and the superior imaging qualities of Technetium-99m relative to Indium-111, ^99mTc-HMPAO appears to be a good alternative to ¹¹¹In-oxine as a granulocyte label.     

不同剂量链脲佐菌素及不同性别大鼠糖性白内障模型的比较研究

本试验旨在研究不同剂量链脲佐菌素(streptozocin,STZ)及不同性别在建立大鼠糖性白内障模型方面的差异。将65、70和75 mg/kg 3个浓度STZ通过一次性腹腔注射建立雌、雄性大鼠糖性白内障模型,36 h后尾静脉采血测血糖,3周后进行裂隙灯检查,每天测量动物饮食量及排粪尿量变化,每周测定体重。试验结果显示,70 mg/kg STZ比65 mg/kg STZ糖性白内障发生时间缩短约1周,且比75 mg/kg STZ死亡率低。同浓度STZ腹腔注射后雌性大鼠糖尿病发生时间为72 h,雄性大鼠为36 h,白内障发生时间雌性比雄性大鼠慢约1周。试验结果表明,腹腔注射70 mg/kg STZ在糖性白内障模型建立所需时间及模型稳定性等方面具有优势,雄性大鼠较雌性更易于建立糖性白内障模型。     

TECHNETIUM-99M AND IODINE-131 THYROID SCINTIGRAPHY IN NORMAL AND RADIOTHYROIDECTOMIZED COCKATIELS (NYMPHICUS HOLLANDICUS)

Thyroid scintigraphy using sodium ^99mTechnetium pertechnetate (⁹⁹TcO₄-) was performed in normal and radiothyroidectomized cockatiels ( Nymphicus hollandicus ). ¹³¹I scintigraphy was performed in the course of ablating the thyroid glands. The thyroid glands in normal birds were clearly visualized, but were not individually resolvable. Thyroid glands were not visualized in thyroid-ablated birds. With ^99mTcO₄ scans, thyroid (or other region of interest)/body count density ratios were used for comparisons of normal and thyroid-ablated birds. Normal ^99mTcO₄- thyroid/body ratios (mean +/− SD) for the dorsal and lateral views were 1.83 +/− 0.31 and 1.70 +/− 0.34 respectively. Pertechnetate thyroid/body count density ratios decreased (to 0.93 -/−0.14 and 0.88 +/− 0.12 for dorsal and lateral views respectively) after thyroid ablation, while crop/body ratios increased. ^99mTcO₄- thyroid scintigraphy, therefore, was capable of detecting hypofunctional thyroid abnormalities in ¹³¹I radiothyroidectomized cockatiels.     

TREATMENT OF DIFFERENTIATED THYROID CARCINOMA IN 7 DOGS UTILIZING 131I

Seven dogs with thyroid gland carcinoma were treated with ¹³¹I and hormone suppressive therapy either alone (3 dogs) or in combination with surgery (3 dogs) or ¹³⁷Cs teletherapy and chemotherapy (1 dog). Empirically chosen doses of 75 to 137 mCi of ¹³¹I were given orally (2 dogs) and intravenously (5 dogs). Adverse effects were limited to acute, transient bone marrow hypoplasia and pancytopenia. Nominal objective reduction in tumor volume or size and number of pulmonary metastases was observed in 4 dogs treated with ¹³¹I and thyroxine. Of these 4 dogs, 2 had stable disease for periods of 4 and 12 months while a third dog had stable disease for 27 months following two ¹³¹I treatments at 3 month intervals. The fourth dog had progressive disease. Two dogs with mediastinal metastases showed reduction in localization of ^99mTc pertechnetate and radioiodine following 2 and 3 treatments using ¹³¹I. It appears that relatively high doses of ¹³¹I can be used safely for the treatment of canine thyroid tumors and that further investigation can be justified to define its efficacy.