Carotid artery calcification and atherosclerosis at the initiation of hemodialysis in patients with end-stage renal disease.

AIMS: Vascular calcification and atherosclerosis frequently develop in end-stage renal disease (ESRD). Although several reports have investigated both carotid artery calcification (CAAC) and carotid atherosclerosis in ESRD patients, the relationship between the two vascular conditions has remained unclear. The aim of this study was to assess the prevalence of CAAC and carotid artery plaque (CAP) in patients with ESRD and to investigate potential factors contributing to the development of CAAC and CAP. MATERIAL AND METHOD: This cross-sectional study assessed CAAC and CAP using multidetector computed tomography and high-resolution B-mode ultrasonography, respectively, in 135 patients with ESRD at the start of hemodialysis. The prevalence of CAAC and CAP was examined. The risk factors associated with CAAC and CAP were also evaluated using a logistic regression model. RESULTS: CAAC and CAP were found in 71% and 65%, of the patients, respectively. A logistic regression analysis adjusted for age and gender showed that CAAC was significantly associated with age, hypertension, dyslipidemia, serum albumin, calcium-phosphorus product, proteinuria and CAP. In contrast, in the same analysis, CAP was significantly correlated with age, male gender, diabetes, intact parathyroid hormone, proteinuria and CAAC. In the multivariate analysis, CAAC was independently associated with age, hypertension, and calcium-phosphorus product. Male gender was identified as an independent determinant for CAP. Furthermore, CAP remained as an independent risk factor of CAAC (odds ratio (OR): 13.89; 95% confidence interval (CI): 4.08-47.29), and CAAC also showed a high OR for having CAP (OR: 11.74; 95% CI: 4.12-33.51). CONCLUSION: Both CAAC and CAP were associated with traditional and/or non-traditional risk factors. The risk factors of CAAC were different from those of CAP. CAAC or CAP was identified to be an independent risk factor for each other with a high OR, thus suggesting a strong relationship between carotid calcification and atherosclerosis.

Interleukin-6 may mediate malnutrition in chronic hemodialysis patients.

Studies were performed to investigate the relationship between serum interleukin-6 (IL-6) and the nutritional status in chronic hemodialysis patients. Serum IL-6 in 45 patients (21 men and 24 women), each with chronic renal failure and having undergone hemodialysis for more than 3 years, was measured before and after a dialysis session. The nutritional status of each patient was evaluated by measuring body mass index (BMI), body weight loss for 3 years, midarm muscle area (MAMA), serum albumin, prealbumin, and insulin-like growth factor-1. Serum IL-6 was significantly higher in the patients undergoing hemodialysis (11.7 +/- 2.8 pg/mL) than in healthy volunteers (< 0.6 pg/mL). There was no further increase in serum IL-6 after a dialysis session when the extracellular water volume was corrected by the ultrafiltrate volume. Predialytic serum IL-6 was significantly correlated with serum albumin (r = -0.4, P = 0.006), cholinesterase (r = -0.51, P = 0.001), body weight change for 3 years (r = -0.48, P = 0.001) and MAMA r = -0.39, P = 0.05). With the patients divided into two groups, a high serum IL-6 (>10 pg/mL) group and low serum IL-6 (<10 pg/mL) group, the body weight loss for 3 years (-4.60% +/- 1.39% v 0.76 +/- 0.75%, P < 0.01) was significantly higher, and the serum albumin level (3.66 +/- 0.10 g/dL v 3.96 +/- 0.05 g/dL, P < 0.05) was significantly lower in those patients with high serum IL-6 than in those with low serum IL-6. The results of a multiple regression analysis indicated that the serum IL-6 level was dependent on the duration of hemodialysis, age, and the dialysis membrane properties. These results suggest that the nutritional status in chronic hemodialysis patients was affected, at least in part, by the circulating IL-6 level. Multiple factors, such as long-term hemodialysis, aging, and the use of a regenerated cellulose membrane dialyzer, were associated with this increased level of IL-6.

Xenobiotic responsive element in the 5'-upstream region of the human P-450c gene.

The nucleotide sequence of the 5'-upstream region up to about -4.1 kb of the human P-450c gene was determined. Two kinds of repetitive sequences were located; one was the Alu sequence which was inserted at three positions (-3127 to -3038, -3017 to -2770, and -2167 to -1851), and the other was the SINE-R element located just upstream of the most distal Alu sequences. The region other than the two repeated sequences showed an overall similarity of 70% to that of the rat P-450c gene. Survey of XRE or its homologues, responsible for the inducible expression of the rat P-450c gene, revealed eight XRE core sequences in this region of the human P-450c gene. Three of them were carried in the Alu sequences. A fusion gene which was constructed by ligating the upstream region of the human P-450c gene to the chloramphenicol acetyltransferase (CAT) gene expressed the CAT activity in response to the inducer, methylcholanthrene, when transfected into Hepa-1 cells. Stepwise decrease in CAT activity in three regions was observed as the 5'-upstream sequence containing XRE motifs was removed. However, the XRE core sequence in the Alu sequences seemed inactive, because elimination of the three elements in the Alu sequences did not affect the expressed CAT activity. In accordance with this observation, competition experiments using gel mobility shift assay showed that XRE core sequences in the Alu sequences could not compete with the XRE sequence for the inducer-bound receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Overweight as another nutritional risk factor for the long-term survival of non-diabetic hemodialysis patients.

OBJECTIVE: Studies were performed to investigate the association of the body mass index (BMI) with long-term survival of non-diabetic hemodialysis patients who were monitored for up to 12 years. METHODS: In 116 patients having undergone hemodialysis in 1984, a Kaplan-Meier survival analysis was performed, and a proportional hazard model was applied to calculate the relative risk of mortality in body mass index quintiles. RESULTS: Those patients with BMI of less than 16.9 kg/m2 and more than 23.0 kg/m2 showed lowered survival relative to the patients with BMI of 17.0-18.9 kg/m2. A proportional hazard model revealed that the patients with BMI of less than 16.9 kg/m2 had the highest risk of mortality independent of age, gender, smoking, duration of hemodialysis, serum albumin, blood pressure and urea reduction rate. Those patients with BMI of over 19.0 kg/m2 also had a high risk of mortality which was progressively elevated with increasing BMI. This higher risk of mortality in those patients with high BMI was associated with such atherosclerotic risk factors as low HDL-cholesterol and high total-/HDL-cholesterol ratio. The number of hospitalizations showed a similar trend to mortality in the body mass index quintiles. The survivors lost their body weight slightly but significantly for 12 years, although there were no significant changes in serum albumin and creatinine. Serum albumin, prealbumin and IGF-1 were within normal range in 1996, suggesting that the survivors did not exhibit severe malnutrition. CONCLUSIONS: These results suggest that long-term survival could be attained by patients with relatively low BMI who have no serious nutritional problems. Nutritional intervention might be required in the overweight patients, in addition to extremely lean patients.

The conversion of native adenylylated glutamine synthetase into phosphotyrosine enzyme by micrococcal nuclease.

Micrococcal nuclease treatment of the native adenylylated glutamine synthetase from M. smegmatis yielded adenosine and phosphotyrosyl enzyme. The rate of the deadenosylation reaction was monitored by the appearance of the adenosine in HPLC analysis. The o-phosphotyrosyl enzyme had catalytic activity comparable to that of the adenylylated enzyme suggesting that the adenosine part in AMP was not essential to the regulation of the enzyme activity. Further, upon treatment of the phosphotyrosyl enzyme with alkaline phosphatase, the glutamine synthetase activity was increased. This means that the regulation site of glutamine synthetase by covalent modification simply requires the phosphorylation of the tyrosine residue.

Energy-transfer rate in crystals of double-complex salts composed of [Ru(N-N)3](2+) (N-N = 2,2'-bipyridine or 1,10-phenanthroline) and [Cr(CN)6](3-): effect of relative orientation between donor and acceptor.

A block single-crystal was obtained using a diffusion method with a concentrated acetone-water (vol. 1/1) solution of [Ru(phen)(3)]Cl(2).6H(2)O (phen = 1,10-phenanthroline) and a concentrated aqueous solution of K(3)[Cr(CN)(6)], without evaporating solvents. The crystal was identified as a double-complex salt including two acetone and fourteen solvent water molecules, [Ru(phen)(3)](2)[Cr(CN)(6)]Cl.2(CH(3))(2)CO.14H(2)O (1). Measurement of the X-ray diffraction pattern of the double-complex salt was performed using an X-ray diffractometer with an Imaging-Plate (IP) Weissenberg camera. 1 crystallizes in the triclinic space group P1, with a = 13.930(5) A, b = 14.783(5) A, c = 11.137(6) A, alpha = 89.87(4) degrees, beta = 107.47(3) degrees, gamma = 96.68(3) degrees, and Z = 2. The crystal structure is very different from that of [Ru(bpy)(3)](2)[Cr(CN)(6)]Cl.8H(2)O (2) (bpy = 2,2'-bipyridine), which could be obtained using the same procedure and crystallizes in the monoclinic space group C2, with a = 22.414(2) A, b = 13.7686(15) A, c = 22.207(2) A, beta = 90.713(8) degrees, and Z = 4. The distance between the central-metal ions of ruthenium(II) and chromium(III) complexes in [Ru(phen)(3)](2)[Cr(CN)(6)]Cl.2(CH(3))(2)CO.14H(2)O (7.170 A) is shorter than that in [Ru(bpy)(3)](2)[Cr(CN)(6)]Cl.8H(2)O (9.173 A) by about 2 A, while the rate of energy transfer from the (3)MLCT state of [Ru(N-N)(3)](2+) to the (2)E(g) state of [Cr(CN)(6)](3-) in the former salt (9.5 x 10(5) s(-1)) is far slower than that in the latter one (6.0 x 10(6) s(-1)) at 77 K. These results indicate that the energy-transfer rate strongly depends, not upon the distance between central metal ions, rather, upon the mutual relative orientation between the donor and the acceptor complexes in double-complex salts.