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Biomedical subjects

Ryo Okazaki

Publications and source records attributed to Ryo Okazaki.

At least 19 recordsLinked to original sources
PubMed2006

High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces all features of human type 2 diabetic nephropathy: a new rat model of diabetic nephropathy.

BACKGROUND AND AIM: We have developed a new rat model that mimics the natural course of diabetic nephropathy seen in type 2 diabetes. METHODS: Nine days after intravenous injection of streptozotocin (STZ) (40 mg/kg) or vehicle to 8-week-old male Sprague-Dawley rats, the animals' right kidneys were surgically removed. Two weeks after surgery, the STZ-injected rats were fed on either a high-fat (ST+HF) or a normal (ST) diet, while the vehicle-injected rats were fed on the high-fat diet (HF). RESULTS: Baseline biochemical markers did not differ between the three groups. Only the ST+HF group showed a significant increase in plasma glucose levels after 15 weeks, and simultaneously plasma insulin levels started to decrease, followed by an increase in plasma total cholesterol and triglyceride levels at 25 weeks and slightly later by an increase in blood pressure. In the ST+HF group, significant microalbuminuria was detected at 15 weeks followed by overt proteinuria, both of which were absent in the other two groups. Also in ST+HF, the creatinine clearance rate increased until week 15, and then gradually decreased. Histologically, ST+HF rats showed mesangial expansion at week 25, and diffuse glomerular sclerosis at the end of the experiments. CONCLUSION: The chronological changes in biochemical, physiological and histological markers in ST+HF rats are reminiscent of human type 2 diabetes and nephropathy. Our new model of type 2 diabetic nephropathy should help us to understand the pathophysiology of the disease and serve to explore measures to prevent and treat diabetic nephropathy.

Animals↗
PubMed2005

Elevated C-reactive protein: a common marker for atherosclerotic cardiovascular risk and subclinical stages of pulmonary dysfunction and osteopenia in a healthy population.

Atherosclerotic cardiovascular disease, osteopenia, and pulmonary dysfunction are the serious health problems, and several experimental studies have suggested that inflammation has a role in them. The present study was conducted to evaluate the usefulness of the plasma CRP is as a common marker for detecting these diseases in the general population in their subclinical stages. In a cross-sectional study, we measured the pulse wave velocity (PWV), quantitative osteo-sono-assessment index (OSI), pulmonary functions, and the plasma level of C-reactive protein (CRP) in 7283 consecutive healthy subjects (age 50+/-11 years). The PWV was higher and the OSI and pulmonary function parameters were below normal in subjects with an elevated CRP level (> or =0.2 mg/dl) than in subjects with a CRP level within the normal range. We divided the subjects into quartiles for each of these parameters and found that the first quartiles represented patients with subclinical states of the aforementioned abnormal conditions. Logistic regression analysis demonstrated that the odds ratios of an elevated CRP level were individually significant in subjects with an elevated CRP level for each abnormality in women and for abnormal PWV and pulmonary dysfunction in men. In conclusion, in addition to being a marker of elevated atherosclerotic cardiovascular risk, elevated plasma CRP seems to be a marker of the early stages of osteopenia and pulmonary dysfunction in healthy subjects.

Adult↗
PubMed2005

High risk of osteopenia and bone derangement in postsurgical patients with craniopharyngiomas, pituitary adenomas and other parasellar lesions.

Hypopituitarism is a well-known cause of secondary osteoporosis. However, patients receiving surgery for pituitary tumors or parasellar lesions have not been well studied for their bone sequel in Japan. We measured bone mineral density (BMD) and urinary type I collagen N-telopeptide (uNTX) in 35 postoperative patients including 25 with pituitary tumor (PT), 6 with craniopharyngioma (CP), and 4 others who had not been on sex hormone replacement, raloxifene, or bisphosphonate therapy. Compared with patients with PT, patients with CP had lower BMD and higher uNTX. Five out of 6 patients with CP had BMD lower than 80% of young adult mean (YAM), whereas 11 out of 22 patients with PT had BMD less than 80% of YAM. Patients with CP had significantly lower serum levels of gonadotropins, and they also tended to have lower serum levels of sex steroids, although statistically not significantly. Two postoperative patients with CP on sex steroid replacement, who were not included in the current analysis, had normal BMD. Of all the subjects, the prominent difference between patients with normal BMD and normal value of uNTX and patients with low BMD and elevated uNTX value was that the latter received higher dose of hydrocortisone replacement. The present study confirms postsurgical patients with pituitary or parasellar lesions, especially those with CP, are at high risk for osteopenia. In designing replacement therapy for those patients, it is important to consider bone by minimizing the dose of glucocorticoid, including sex steroids, and using other drugs that protect bone.

Adolescent↗
PubMed2005

[Parathyroid hormone -- its mechanisms of action and issues on clinical application].

PTH, recently approved for severe osteoporosis in US and Europe, acts as an anabolic agent for bone when given intermittently. However, when continuously given, PTH acts as a catabolic agent for bone, as seen in primary hyperparathyroidism. The mechanisms by which PTH acts in opposite directions are largely unknown. In this review, some of the possible mechanisms will be discussed.

Bone and Bones↗
PubMed2005

[Parathyroid disorders and bone metabolism].

Parathyroid hormone acts directly on bone by stimulating both bone resorption and bone formation with the relative excess in the former when it acts continuously. Thus in primary hyperparathyroidism characterized by chronic PTH excess, bone mineral density (BMD) is decreased with relatively high levels of bone turnover markers. In contrast, PTH deficient hypoparathyroidism such as post-operative hypoparathyroidism, BMD is increased with relatively low bone tunover markers. In pseudohypoparathyroidism, which characterized by PTH resistance in kidney, bone response to PTH is sometimes preserved. In some cases, high bone turnover state is observed, which correlates with serum PTH levels.

Bone Density↗
PubMed2004

Secretion of high-molecular-weight adrenocorticotropic hormone from a pituitary adenoma in a patient without Cushing stigmata. Case report.

The authors report a case in which a patient harbored a corticotroph macroadenoma that secreted biologically inactive high-molecular-weight adrenocorticotropic hormone (ACTH) as well as authentic ACTH 1-39. The secretion of the high-molecular-weight ACTH was determined using gel chromatography. The authors believe that these two molecules competed with each other at the ACTH receptor and, thus, the bioactivity of ACTH 1-39 was masked and Cushing features were not manifested in the patient. This type of silent corticotroph adenoma may be categorized as a clinically nonfunctioning adenoma. Plasmas from patients with silent corticotroph adenomas, which are identified by positive immunohistochemical staining of ACTH, should be frozen, stored, and analyzed using gel chromatography to examine whether the tumors produce and secrete high-molecular-weight ACTH.

Adenoma↗
PubMed2003

Increased pulse wave velocity associated with reduced calcaneal quantitative osteo-sono index: possible relationship between atherosclerosis and osteopenia.

Although the associations between arterial calcification or advanced atherosclerosis and osteopenia have been well documented, it is not clear whether the one is the result of the other or they coprogress from the early stages through common mechanisms. Thus, we measured pulse wave velocity (PWV), which reflects earlier phase atherosclerosis, and osteo-sono assessment index (OSI), which correlates with bone mineral density, in 7865 Japanese subjects (4183 males and 3682 females, aged 50 +/- 12 yr) and analyzed their association. PWV was determined by the volume rendering method; OSI was measured by the calcaneal quantitative ultrasound method. We evaluated the influence of age, gender, menopausal state, and established atherosclerotic risk factors on this association. In a linear regression analysis, OSI negatively correlated with PWV in both genders, and this association was more prominent in females (r = -0.38, P < 0.01) than in males (r = -0.17, P < 0.01). In females, this relationship was stronger after the menopause. In a multivariate analysis, PWV was significantly associated with OSI independent of age and conventional atherosclerotic risk factors. In females, this association was independent from menopause. These results suggest that common or related mechanisms, which may be accelerated after menopause, control both atherosclerosis and osteoporosis from the early stages.

Adult↗
PubMed2003

Influences of increased oxidative stress on endothelial function, platelets function, and fibrinolysis in hypertension associated with glucose intolerance.

The effect of oxidative stress on endothelial function, platelet function, and fibrinolysis in hypertension with or without glucose intolerance was examined. The endothelium, platelets and fibrinolysis play important roles in the progression of atherosclerosis and interact with each other. We have previously demonstrated that glucose intolerance impairs endothelial function in hypertension, but its precise mechanisms have not been clarified. Hypertensive patients were divided by the results of 75-g oral glucose tolerance test into a normal glucose metabolism group (n = 65) and a glucose intolerance group (n = 47). The plasma level of thiobarbituric acid-reactive substances (TBARS) was assessed as a marker of oxidative stress. Endothelial function was assessed by flow-mediated dilatation (FMD), platelet function by the concentration of ADP dose inducing half-maximal aggregation (EC50), and fibrinolytic parameters by radioimmunoassay. These functions were assessed before and after acute administration of vitamin C. FMD was reduced while TBARS and fibrinolytic parameters were higher in patients with glucose intolerance than in those with a normal glucose metabolism. Vitamin C increased FMD and reduced fibrinolytic parameters significantly in the glucose intolerance group, but not in the group with normal glucose metabolism. On the other hand, the EC50 was similar in both groups. In conclusion, glucose intolerance aggravates oxidative stress, thereby contributing to the impairment of endothelial function in patients with hypertension. These abnormalities affect fibrinolysis but not platelet function.

Adult↗
PubMed2003

[Osteosarcoma in rats receiving long-term PTH injection].

Daily injection of human PTH (1-34) to osteoporotics has been shown to increase bone mineral density and reduce fracture risk within 18 months. Despite its impressive effects on human bone, safety became a big issue when it was revealed that up to 53% of rats received hPTH (1-34) for 2 years developed osteosarcoma. On the interpretation of the data, most experts agreed that this is unlikely to predict an increased risk of osteosarcoma in human osteoporotic patients. Some of the reasonings are as follows: (1) fundamental differences in bone metabolism between rat and human, (2) rats received PTH at a dose 12-25 folds of the human dosage, for 80-90% of their life span whereas in human PTH would be used for only 2-3% of the life span.

English Abstract↗
PubMed2002

Association between activating mutations of calcium-sensing receptor and Bartter's syndrome.

Bartter's syndrome is a heterogeneous disorder characterised by deficient renal reabsorption of sodium and chloride, and hypokalaemic metabolic alkalosis with hyper-reninaemia and hyperaldosteronaemia. Mutations in several ion transporters and channels have been associated with the pathogenesis of Bartter's syndrome. We describe two hypocalcaemic patients with deficient parathyroid hormone secretion who also showed characteristics of Bartter's syndrome. We found activating mutations of the gene for the calcium-sensing receptor (CASR) in both patients. Activation of this calcium-sensing receptor inhibits the activity of a renal outer-medullary potassium channel that is mutated in type 2 Bartter's syndrome. We therefore suggest that some activating mutations of CASR could provide new mechanisms for the development of Bartter's syndrome.

Adult↗
PubMed2002

Estrogen promotes early osteoblast differentiation and inhibits adipocyte differentiation in mouse bone marrow stromal cell lines that express estrogen receptor (ER) alpha or beta.

Although cells of the osteoblast lineage express functional ERs, direct effects of estrogen on bone formation remain obscure. In the present study, we have investigated estrogen effects on osteoblastic and adipocytic differentiation from a mouse bone marrow stromal cell line, ST-2, which had been manipulated to overexpress either human ER alpha (ST2ER alpha) or ER beta (ST2ER beta). Treatment with bone morphogenetic protein-2 increased alkaline phosphatase activity as well as the number of Oil Red O-positive adipocytes, indicating that bone morphogenetic protein-2 stimulated both osteoblastic and adipocytic differentiation from these bipotential cells. In both ST2ER alpha and ST2ER beta cells, cotreatment with E2 caused enhancement of alkaline phosphatase activity and suppression of lipid accumulation. These effects were completely reversed by an ER antagonist, ICI182780. Therefore, the estrogen regulation occurred in an ER-specific manner but without ER subtype specificity. Moreover, dose response curves of the opposing effects of estrogen on osteoblastogenesis and adipogenesis formed an apparent mirror image, consistent with a reciprocal regulation of differentiation into the two cell lineages. These results demonstrate that estrogen directly modulates differentiation of bipotential stromal cells into the osteoblast and adipocyte lineages, causing a lineage shift toward the osteoblast. Such effects would lead to direct stimulation of bone formation and thereby contribute to the protective effects of estrogen on bone.

Adipocytes↗