Takako Saito

Hypoadiponectinemia in patients with cerebral infarction: comparison with other atherosclerotic disorders.

The present study was undertaken to determine serum adiponectin level in patients with cerebral infarction and to further analyze any difference in serum adiponectin levels among atherosclerotic disorders. One hundred fifty-two subjects with atherosclerotic disorders were enrolled, 110 males and 42 females, with the age of 67.0 ± 9.9 years (mean ± SD). They were divided into 62 patients with cerebral infarction, 48 patients with ischemic heart disease, and 42 patients with arteriosclerosis obliterans. Thirty-two subjects matched by age, gender, and body mass index served as controls. Serum adiponectin levels were 7.2 ± 0.6 &mgr;g/mL (mean ± SE) in the patients with cerebral infarction, 7.2 ± 0.8 &mgr;g/mL in those with ischemic heart disease, and 6.9 ± 0.9 &mgr;g/mL in those with arteriosclerosis obliterans. They were significantly less than the level of 12.6 ± 1.9 &mgr;g/mL in the control group (P < 0.01). However, there was no difference in serum adiponectin level among three groups of atherosclerotic disorders. In the patients with acute cerebral infarction, serum adiponectin level was temporarily reduced from 7.3 ± 0.9 to 6.2 ± 0.8 &mgr;g/mL 14 days after the hospitalization (P < 0.01), followed by recovery to the basal value. The present findings indicate that serum adiponectin levels are equivalently reduced in patients with atherosclerotic disorders, and that serum adiponectin is changeable under acute phase of cerebral infarction.

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients With Type 2 Diabetes

Background Osteoporosis and chronic kidney disease are common conditions in older adults, and often occur concurrently. Bone disease is caused by increased bone turnover accompanying secondary hyperparathyroidism, and by factors such as bone metabolic disorder accompanying kidney disease and postmenopausal or age-related osteoporosis, even in hemodialysis patients. Raloxifene is commonly used for the treatment of postmenopausal osteoporosis in the general population, and may be a treatment option for osteoporosis in hemodialysis patients. However, the effects of raloxifene in hemodialysis patients with type 2 diabetes have not been examined in detail. Objectives This study was performed to investigate the effects of raloxifene on bone turnover markers and bone density in postmenopausal women with type 2 diabetes mellitus who were undergoing hemodialysis in Japan. Patients and Methods The subjects were 60 female patients on maintenance hemodialysis (non-diabetic, n=30; diabetic, n=30). Raloxifene hydrochloride (60 mg) was administered to 14 diabetic patients and 14 non-diabetic patients for one year, and these patients were compared with control groups (no raloxifene) of 16 diabetic patients and 16 non-diabetic patients. Serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx), bone alkaline phosphatase, and intact parathyroid hormone (iPTH) were measured, and bone density was determined by quantitative heel ultrasound at the speed of sound (SOS) in the calcaneus during this period. Results There were no significant differences in the levels of bone turnover markers except for iPTH after treatment of diabetic and non-diabetic patients with raloxifene for one year. SOS increased after treatment with raloxifene, but was significantly decreased in the control groups. Treatment with raloxifene resulted in a significant decrease in NTx and a significant increase in SOS in both diabetic and non-diabetic patients. There were no significant differences between the diabetic and non-diabetic patients who received raloxifene. Conclusions Treatment with raloxifene can suppress reduction in bone density in postmenopausal women with type 2 diabetes who are undergoing hemodialysis.

Hypotonicity reduces the activity of murine aquaporin-2 promoter induced by dibutyryl cAMP

The present study was undertaken to determine whether hypotonicity regulates the aquaporin‐2 (AQP‐2) gene in vitro. The 5′‐flanking region of the AQP‐2 gene contains the tonicity‐response enhancer (TonE) promoter located between −570 and −560 bp, and another distinct hypertonicity‐responsive region between −6.1 and −4.3 kb of the AQP‐2 gene. The 5′‐flanking region of murine AQP‐2 gene up to −9.5 kb was cloned into a luciferase (Luc) reporter plasmid. The constructs, which have TonE and/or the hypertonicity‐responsive region, together with the murine AQP‐2 gene, were co‐transfected into murine IMCD3 cells. When the cells were co‐transfected with the construct containing more than 1.1 kb of the 5′‐flanking region of murine AQP‐2 gene (–9.5AQP2, −6.1AQP2 and −1.1AQP2) and the AQP‐2 gene, 24 h exposure to 5 μmol l−1 dibutyryl cAMP (DBcAMP) significantly increased the Luc activity by 2.3‐fold in the isotonic medium (300 mosmol kg−1). In the hypotonic medium (225 mosmol kg−1), basal activity was not altered, and the response of Luc activity to 24 h exposure to 5 μmol l−1DBcAMP was abolished. Similar findings were obtained in isosmotic, urea‐supplemented medium (estimated tonicity, 225 mosmol kg−1). The response of Luc activity to 5 μmol l−1 DBcAMP in the hypotonic medium was not affected in cells either transfected with 0.36 kb of the 5′‐flanking region of AQP‐2 or co‐transfected with −1.1AQP2 and a dominant‐negative TonE binding protein (pDNTonEBP). Pre‐incubation of cells with 1 μmol l−1 SP600125, an inhibitor of c‐Jun N‐terminal kinase (JNK), restored the response of Luc activity to 5 μmol l−1 DBcAMP under hypotonic conditions. These findings may indicate that hypotonicity reduces the cAMP‐induced AQP‐2 promoter activity mediated via TonE by activating JNK kinase.

Serum adiponectin and markers of endothelial injury in hemodialysis patients with arteriosclerosis obliterans

BackgroundArteriosclerosis obliterans (ASO) in hemodialysis patients is the dominant cause of morbidity evolving from arteriosclerosis. Adiponectin is an adipose-derived cytokine which, because of its modulation of endothelial adhesion molecules, has potential anti-inflammatory and anti-atherogenic properties. However, the implications of adiponectin and endothelial function in ASO of hemodialysis patients has not been fully elucidated.MethodsIn this study we measured serum levels of adiponectin, adhesion molecules (VCAM-1 and ICAM-1), and an endothelial cell injury marker (CD146) in patients with ASO. We sought to determine clinical and laboratory correlates of ASO in ESRD patients. A total of 80 hemodialysis patients and 82 patients with normal serum creatinine levels were enrolled. Serum levels of adiponectin, ICAM-1, VCAM-1, and CD146 were measured by ELISA.ResultsSerum adiponectin levels in 41 hemodialysis patients with ASO were significantly lower than in 39 patients without ASO. Serum CD146 levels in hemodialysis patients with ASO were significantly higher than in patients without ASO. There were no significant differences between levels of ICAM-1 and VCAM-1 in these two groups. Similar results were obtained for patients with normal renal function. Serum adiponectin was related to hemodialysis duration and BMI in hemodialysis patients. In patients with normal renal function, adiponectin was related to HDL-cholesterol, triglyceride, and ICAM-1.ConclusionA decrease in serum adiponectin levels and an increase in serum CD146 may be closely associated with the development of ASO, regardless of renal function. However, there are different mechanisms determining serum adiponectin levels in patients with normal kidney function and in hemodialysis patients.

Metabolic and hemodynamic advantages of an acetate-free citrate dialysate in a uremic case of congenital methylmalonic acidemia.

ethylmalonic acidemia (MMA) is an or-ganic acidemia in the class of diseasescaused by enzymatic defects in the catabolism ofbranched-chain amino acids (valine, isoleucine,methionine, and threonine), odd-chain fatty ac-ids,andcholesterol.MMAisanautosomalreces-sive disorder caused by a deficiency in methyl-malonyl–coenzyme A (CoA) mutase (encoded bythe

Vasopressin-dependent upregulation of aquaporin-2 gene expression in aged rats with glucocorticoid deficiency

Aim:  The study was undertaken to determine whether ageing affects kidney expression of the aquaporin‐2 (AQP2) water channel in glucocorticoid‐deficient rats.

Combination Therapy of Angiotensin Converting Enzyme Inhibitor and Angiotensin AT1 Receptor Antagonist in Diabetic Nephropathy

Background The present study was undertaken to determine whether combination therapy of angiotensin converting enzyme inhibitor (ACEI) and angiotensin AT1 receptor antagonist (ARA) is a useful tool for reducing albuminuria in diabetic nephropathy. Methods Thirty-four subjects with diabetic nephropathy were enrolled in the present study. All the subjects had hypertension and urinary albumin index (UAI) Results Blood pressure was significantly decreased in Group 1 subjects. Blood pressure was also reduced in Groups 2 and 3, but its reduction was not significant. Imidapril significantly reduced UAI in Group 1, from 213.1 ± 46.6 to 111.6 ± 35.6 ( p p p Conclusion These results indicate that the addition of ARA to consecutive therapy with ACEI augments a protective effect against the progression of diabetic nephropathy.

Hypothermia and hypokalemia in a patient with diabetic ketoacidosis

We present the case of a 36-year-old man with type-1 diabetes who was hospitalized with diabetic ketoacidosis (DKA). On admission, he had hypothermia, hypokalemia and combined metabolic and respiratory alkalosis, in addition to hyperglycemia. Hypothermia, hypokalemia and metabolic alkalosis, with a concurrent respiratory alkalosis, are not commonly seen in DKA. After admission, intravenous infusion of 0.45% saline was administered, which resulted in the development of pure metabolic acidosis. After starting insulin infusion, hypokalemia and hypophosphatemia became evident and finally resulted in massive rhabdomyolysis. Hyperkalemia accompanying oliguric acute kidney injury (AKI) warranted initiation of hemodialysis (HD) on Day-five. On the 45th hospital day, his urine output started to increase and a total of 22 HD sessions were required. We believe that in this case severe dehydration, hypothermia and hypokalemia might have contributed to the initial symptoms of DKA as well as the prolongation of AKI.