Biomedical subjects

Eiji Ishimura

Publications and source records attributed to Eiji Ishimura.

At least 19 recordsLinked to original sources

PubMed2007

Annual change in bone mineral density in predialysis patients with chronic renal failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D.

Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The aim of this study was to examine how a decrease in renal function affects annual bone mineral density (BMD) changes in predialysis CRF patients and to examine the factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF patients (age, 61.3 +/- 10.8 years; serum creatinine 2.7 +/- 1.2 mg/dl) was measured by peripheral quantitative computed tomography (pQCT) twice with a 1-year interval. The total BMD of the radius significantly decreased over a year (P < 0.001), and both trabecular and cortical BMD showed a significant decrease. Significant positive correlations with BMD changes were found for estimated creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)(2)D (r = 0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger reductions in creatinine clearance and serum 1,25(OH)(2)D. Of several bone metabolic markers examined, baseline serum osteocalcin was significantly positively correlated with annual BMD changes (r = -0.276, P < 0.05). Multiple regression analysis showed that baseline serum 1,25(OH)(2)D (beta = 0.434) was a significant predictor of decreases in total and trabecular BMD (R (2) = 0.188, P < 0.01; and R (2) = 0.207, P < 0.01), independent of other confounding factors. These results indicate that BMD decreases as renal function deteriorates in predialysis CRF patients, and that osteocalcin is a clinically useful marker associated with the decrease in BMD. The serum 1,25(OH)(2)D level is the principal factor affecting BMD of the radius, suggesting that supplementation with an active form of vitamin D is of importance for predialysis CRF patients.

Aged↗

PubMed2007

Central pulse wave velocity is responsible for increased brachial-ankle pulse wave velocity in subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism affects 5-15% of the general population, and is associated with increased morbidity from cardiovascular disease. We recently reported a significant increase in brachial-ankle pulse wave velocity (baPWV), a parameter of arterial stiffening and an independent predictor for the presence of cardiovascular disease, in subclinical hypothyroidism. The current study was performed to assess which arterial segment is responsible for enhanced baPWV in subclinical hypothyroidism. PATIENTS AND METHODS: Central PWV (PWV in heart-femoral segments), peripheral PWV (PWV in femoral-ankle segments), and baPWV were measured in subclinical hypothyroid patients and normal subjects. RESULTS: Central PWV, baPWV, and peripheral PWV were significantly higher in subclinical hypothyroid patients than in normal subjects. BaPWV was significantly and positively correlated with central and peripheral PWV in both groups. However, a significant and positive correlation between central and peripheral PWV in normal subjects was not found in subclinical hypothyroid patients. Moreover, stepwise regression analysis showed that the association of central PWV with baPWV was stronger than that of peripheral PWV, whereas in normal subjects central PWV was not associated with baPWV. CONCLUSIONS: Our results demonstrate that central and peripheral PWV are significantly higher in subclinical hypothyroid patients, and that the increase in baPWV depends more strongly on central PWV than on peripheral PWV in these patients. This suggests that increased elastic arterial stiffening of the aorta, rather than of peripheral muscular arteries, might be more responsible for increased general arterial stiffening in subclinical hypothyroid patients.

Ankle↗

PubMed2006

Low circulating endogenous secretory receptor for AGEs predicts cardiovascular mortality in patients with end-stage renal disease.

OBJECTIVE: Receptor for advanced glycation end-products (RAGE) is involved in diabetic vascular complications. We have recently shown that plasma endogenously secretory RAGE (esRAGE), an alternatively spliced form of RAGE, is closely associated with metabolic syndrome and atherosclerosis. Here, we evaluated if plasma esRAGE is a predictor of cardiovascular mortality in a cohort of 206 (171 nondiabetic) patients with end-stage renal diseases (ESRD). METHODS AND RESULTS: The cohort was followed for a median of 111 months, and 74 deaths including 34 cardiovascular deaths were recorded. Plasma esRAGE was measured at baseline. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly higher in subjects in the lowest tertile of plasma esRAGE than those in the middle or the highest tertile both in all and nondiabetic subjects alone. In all subjects, as compared with the lowest tertile of plasma esRAGE, the hazards ratios for the highest and middle tertile were 0.40 (95% CI, 0.18 to 0.89) and 0.26 (0.10 to 0.66), respectively. The higher risk for lower esRAGE was still significant even after adjusted either with body mass index, hypertension, dyslipidemia and vascular complications, but was confounded by age and diabetes. CONCLUSIONS: Low circulating esRAGE is a predictor for cardiovascular mortality in ESRD patients.

Aged↗

PubMed2006

Laparoscopic adrenalectomy on a patient with primary aldosteronism during pregnancy.

A pregnant 26-year-old woman was referred for evaluation and management of progressive hypertension and hypokalemia at 14 weeks of gestation. Her plasma aldosterone level was markedly elevated and magnetic resonance imaging showed a right adrenal tumor. Primary aldosteronism due to an aldosterone producing-adenoma was diagnosed. Because of progressive severe hypertension, a laparoscopic adrenalectomy was performed at 17 weeks of gestation. The procedure was completed without complication, and plasma aldosterone and potassium levels rapidly improved post-operatively. However, her hypertension persisted and the growth retardation of the fetus was found. Regrettably, intrauterine fetal death was confirmed at 26 weeks of gestation. Histological examination of the placenta revealed that the placental artery had very thick walls which had apparently caused a critical failure in fetal blood flow. The optimal timing of laparoscopic surgery during pregnancy and perioperative management were subsequently discussed.

Adenoma↗

PubMed2006

Annual fat mass change is a significant predictor of mortality in female hemodialysis patients.

BACKGROUND: Although obesity confers an increased risk of mortality in the general population, it has been reported to be associated with improved survival in dialysis patients. However, the influence of fat mass change over time on mortality in dialysis patients has not been determined. METHODS: This relationship was examined in 190 female maintenance hemodialysis patients. Fat mass was measured twice with a 12-month interval, using dual energy X-ray absorptiometry (DEXA). The patients were followed up for 5 years, and predictors for all-cause death were examined using Kaplan-Meier analysis and Cox proportional hazards analyses. RESULTS: During the 5-year follow-up period, 65 patients died. Annual fat mass changes in the expired group tended to be greater than in the surviving group (-1.0 +/- 2.5 vs. -0.3 +/- 2.6 kg; P = 0.0776), although initial body fat mass was not significantly different. Kaplan-Meier analysis revealed that patients with decreased fat mass (N = 110) had a significantly lower survival rate, compared with those with increased fat mass (N = 80; P = 0.021). Multivariate Cox proportional hazards analyses demonstrated that annual fat mass change was a significant predictor of all-cause mortality after adjustments for confounding factors, such as age, serum albumin, serum creatinine, and the presence of diabetes. An increase in annual fat mass of 1 kg reduced mortality by 14.5%. CONCLUSIONS: These results demonstrate that the decrease in annual fat mass is a significant predictor for mortality in female hemodialysis patients. Fat mass change is also a useful parameter for measurement of nutritional status in hemodialysis patients.

Absorptiometry, Photon↗

PubMed2006

Direct in vitro evidence of the suppressive effect of cinacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels.

Clinical studies have been performed to determine the effect of cinacalcet HCl (cinacalcet), an allosteric modulator of the calcium-sensing receptor (CaR), on primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism of uremia (SHPT). However, no in vitro studies on human parathyroid cells have been reported to date. In this study, the inhibitory effect of cinacalcet on PTH secretion was analyzed in primary cultured parathyroid cells obtained from patients. The investigation involved three PHPT and three SHPT patients subjected to therapeutic parathyroidectomy. Notably, all SHPT patients were resistant to intravenous vitamin D analogue therapy. Removed parathyroid tumors were used for immunohistochemistry and parathyroid cell primary culture. Immunohistochemical analyses revealed diminished expression of CaR and vitamin D receptor (VDR) in all parathyroid tumors. PTH secretion from cultured parathyroid cells of PHPT and SHPT patients was suppressed by extracellular Ca2+ and cinacalcet in a dose-dependent manner. Rates of suppression of PTH secretion in PHPT and SHPT by cinacalcet (1000 nmol/l) were 61% +/- 21% and 61% +/- 19%, respectively. Cinacalcet demonstrates significant potency in the suppression of PTH secretion in primary cultured human parathyroid cells in vitro, despite reduced levels of the target protein, CaR. Data from this in vitro analysis support the clinical application of cinacalcet in PHPT and SHPT therapy.

Cinacalcet↗

PubMed2006

Body composition and cardiovascular risk in hemodialysis patients.

Death rate is unacceptably elevated in end-stage renal disease patients treated with hemodialysis. Excessive body fat, or obesity, is the well-known risk factor for cardiovascular disease and other health problems in the general population. However, hemodialysis patients with a higher body mass index (BMI) have a lower risk of death, as shown by many studies. There are several explanations for the paradox of BMI in dialysis patients. First, although body mass is composed of fat mass and fat-free mass (lean mass), it is unknown which is more important, fat mass or lean mass, in predicting outcome of hemodialysis patients. Second, it is also possible that functions of adipose tissue are altered in renal failure so that accumulation of body fat leads to less atherogenicity and beneficial properties become predominant. Third, an increased fat mass may be protective against death after harmful events. In this article, we explore these possibilities using either the data of our own cohort of hemodialysis patients or the existing registry data of Japan. We conclude that in hemodialysis patients, fat mass rather than lean mass plays a protective role against mortality, that the fat mass-adipocytokine relationship is altered, and that a low BMI is associated with increased risk of fatality after cardiovascular events rather than the risk of occurrence of such events.

Adiponectin↗

PubMed2006

Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism.

OBJECTIVE: While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT)-PCR and immunohistochemistry. RESULTS: FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23. CONCLUSIONS: Serum calcium may regulate circulating FGF-23 levels in PHPT.

Calcium↗

PubMed2006

Paraarticular trabecular bone loss at the ultradistal radius and increased arterial stiffening in postmenopausal patients with rheumatoid arthritis.

OBJECTIVE: We recently reported enhanced arterial thickening in patients with rheumatoid arthritis (RA) and the importance of increased bone resorption in this process. Our aim was to examine whether arterial stiffening, another aspect of atherosclerosis, is also increased in patients with RA, and to determine if it is an important risk factor. METHODS: The subjects were 47 patients with RA and 49 healthy controls, all postmenopausal women. Subjects having risk factors for atherosclerosis were excluded. Femoral-ankle (fa) pulse wave velocity (PWV) and brachial-ankle (ba) PWV were measured in all patients using a waveform analyzer. Bone mineral density (BMD) at the ultradistal radius was assessed by peripheral quantitative computed tomography. Inflammation markers (C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, platelet count) and bone resorption markers (urinary excretion of deoxypyridinoline and N-terminal telopeptide) were also measured. RESULTS: The median values of faPWV and baPWV in RA patients were 1124 cm/s [interquartile range (IQR) 1040-1175] and 1539 cm/s (IQR 1297-1738), respectively, which were significantly greater than the respective values of 982 cm/s (IQR 819-1054; p < 0.001) and 1322 cm/s (IQR 1112-1398; p = 0.004) in controls. In multiple regression analysis, the presence of RA emerged as an independent factor associated with the greater faPWV and baPWV when adjusted for age, blood pressure, and smoking. In RA patients alone, BMD in the trabecular bone component, but not for the total bone (cortical plus trabecular), at the ultradistal radius correlated significantly with both faPWV and baPWV. Multiple regression analysis showed that trabecular BMD at the distal radius was a significant factor independently associated with greater faPWV and baPWV when adjusted for age, blood pressure, and smoking. None of the measured inflammation markers or bone resorption markers correlated with either faPWV or baPWV in patients with RA. CONCLUSION: Patients with RA show increased arterial stiffening, in addition to the arterial thickening we have previously reported, supporting the notion of enhanced atherosclerosis in RA patients. Paraarticular bone loss in the trabecular bone component at the ultradistal radius is a factor significantly associated with increased arterial stiffening in RA patients.

Amino Acids↗

PubMed2005

Positive correlation of serum bio-intact PTH(1-84) but not intact PTH with parathyroid gland size in hemodialysis patients.

To evaluate the usefulness of newly-developed bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH(1-84) molecule, serum PTH level determined by Bio-PTH assay, in comparison with second-generation intact PTH (I-PTH) assay, was examined for its correlation with parathyroid gland size. Serum PTH was determined in 46 male HD patients, together with bone formation markers bone alkaline phosphatase, intact osteocalcin, N-terminal propeptide of type I collagen, and bone resorption markers deoxypyridinoline, pyridinoline, beta-crossLaps. Maximal diameter of parathyroid gland was determined with ultrasonography as the parathyroid gland size. Serum Ca and Pi correlated significantly with parathyroid gland size rationalizing our method to define parathyroid gland size. Serum Bio-PTH was correlated significantly in a positive manner with parathyroid gland size (R = 0.308, P = 0.0474), whereas serum I-PTH did not. Furthermore, parathyroid gland size did not exhibit a significant correlation with any of bone formation markers or bone resorption markers. The lack of correlation between bone markers and parathyroid gland size in HD patients may be explained by the occurrence of refractoriness of bone to PTH. In conclusion, serum Bio-PTH assay could provide a better assay than I-PTH assay to estimate parathyroid function in HD patients, due mainly to its exclusive correlation with parathyroid gland size.

Alkaline Phosphatase↗

PubMed2005

Associations between physical activity, peripheral atherosclerosis and bone status in healthy Japanese women.

The aim of this cross-sectional study was to investigate whether physical activity and bone status may affect arterial thickening and stiffening in healthy Japanese women. Healthy women (n = 149; mean age, 54 years) were recruited from those who participated in a local health check program at the Osaka City University Hospital. Physical activity was assessed by physical functioning score of SF-36, and bone status by bone mineral density (BMD) in lumbar spine and calcaneus osteo-sono index (OSI). Arterial wall thickening assessed by intima-media thickness (IMT) in common carotid artery (CA) and femoral artery (FA), and arterial wall stiffening by peak wave velocity (PWV) in heart-carotid (hc) and heart-femoral (hf) as central segment and in heart-brachial (hb) and femoral-ankle (fa) as peripheral segment, respectively. By Spearman Rank correlation, lumbar spine BMD was correlated negatively with CA IMT (rho = -0.225, p < 0.05) and FA IMT (rho = -0.215, p < 0.05), and calcaneus OSI with FA IMT (rho = -0.330, p < 0.0001) but not CA IMT (rho = -0051, p = 0.5335). Both lumbar spine BMD and calcaneus OSI correlated negatively with PWV in all segments (all p < 0.05). Physical functioning score correlated weakly but significantly in a negative manner with all PWV segments (all p < 0.05) but not IMT. Multiple regression analyses revealed a significant association of calcaneus OSI (beta = -0.240, p = 0.0039) but not lumbar spine BMD (beta = -0.067, p = 0.4541) with FA IMT, although neither lumbar spine BMD nor calcaneus OSI was associated with CA IMT. Furthermore, physical functioning score was independently associated with hb and fa PWV but not hc and hf PWV, suggesting the preferential association with peripheral segment including lower extremities. Neither lumbar spine BMD nor calcaneus OSI was associated with any segment of PWV. In conclusion, it was suggested that calcaneus OSI might be associated with arterial wall thickening preferentially in femoral artery, and that physical activity may be associated with arterial wall stiffening in peripheral segment including lower extremity but not in central segment in healthy Japanese women.

Atherosclerosis↗

PubMed2005

Serum levels of 1-84 and 7-84 parathyroid hormone in predialysis patients with chronic renal failure measured by the intact and bio-PTH assay.

BACKGROUND: The intact parathyroid hormone (PTH) assay detects both PTH(1-84) and the PTH(7-84)-like fragment, which is reported to be an antagonist of the biological action of PTH(1-84). It is debatable which of the two assays is clinically more useful, the intact or bio-PTH assay, the latter of which only detects PTH(1-84). It is also unknown whether serum levels of the PTH(7-84)-like fragment have clinical significance. METHODS: Serum PTH concentrations in 104 predialysis patients with chronic renal failure (CRF; serum creatinine 3.53 +/- 1.93; 62 males and 42 females; 61.0 +/- 11.5 years old) were measured using both the intact and bio-PTH assays, and the concentration of the PTH(7-84)-like fragment was calculated by subtracting bio-PTH from intact PTH. Three bone formation and three bone resorption markers were measured simultaneously. RESULTS: The PTH values measured using the two assays were strongly positively correlated (r = 0.959, p < 0.0001), and were also significantly positively correlated with the three bone formation and three bone resorption markers to a similar degree. The PTH(7-84)-like fragment was significantly positively correlated with both the intact and bio-PTH (r = 0.855, p < 0.0001 for intact PTH; r = 0.672, p < 0.0001 for bio-PTH), and was also significantly positively correlated with each of the six bone metabolism markers. There is no significant relationship between the bio-PTH/PTH(7-84)-like fragment ratio and clinical parameters including bone metabolic markers. CONCLUSION: From the strong relationship between the two assays, and the similar degree of the relationship between each PTH assay and each of the six bone metabolism markers, it is considered that the bio-PTH and intact PTH assays have similar clinical significance in predialysis CRF patients. Serum levels of the PTH(7-84)-like fragment seem to increase as serum PTH(1-84) increases. The results suggest that the serum PTH(7-84)-like fragment has little specific clinical effect on bone metabolism, even when assessed by the ratio of bio-PTH/PTH(7-84)-like fragment.

Blood Chemical Analysis↗

PubMed2005

Increased pulse wave velocity in subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism affects 5-15% of the general population and is associated with increased morbidity from cardiovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a parameter of arterial stiffening and a good independent predictor for the presence of coronary artery disease. This study was performed to assess whether subclinical hypothyroidism might cause enhanced baPWV. PATIENTS AND METHODS: baPWV was examined in subclinical hypothyroid patients (n = 50) and normal control subjects (n = 50). RESULTS: Diastolic blood pressure (DBP), a main risk factor for cardiovascular disease, and baPWV were both significantly higher in subclinical hypothyroid patients than normal subjects. baPWV was significantly positively correlated with age and systolic, diastolic, and pulse pressure and significantly negatively correlated with pulse rate in both subclinical hypothyroid patients and normal subjects. In contrast, there was no significant correlation of baPWV with free T3, free T4, TSH, total, high-density lipoprotein- and low-density lipoprotein-cholesterol, and the preejection time to ejection time ratio. A comparison of individual values of baPWV and DBP and regression slopes in two groups revealed that baPWV values increase to a larger extent than the increase in DBP in subclinical hypothyroid patients. In both groups, stepwise regression analysis showed a significant and independent association of DBP with baPWV. CONCLUSIONS: The present study demonstrated significant increases of baPWV and DBP in subclinical hypothyroid patients. Furthermore, the results suggest that increased DBP might be one of the main factors responsible for increased arterial stiffening in subclinical hypothyroid patients.

Aged↗

PubMed2005

Serum concentrations of cross-linked N-telopeptides of type I collagen: new marker for bone resorption in hemodialysis patients.

BACKGROUND: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). METHODS: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (beta-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient's bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. RESULTS: Serum NTX correlated significantly with beta-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as beta-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, beta-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. CONCLUSION: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.

Adult↗

PubMed2005

Plasma levels of adiponectin and soluble thrombomodulin in hypothyroid patients with normal thyroid function following levothyroxine replacement therapy.

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and adiponectin (ApN) is a newly-identified adipocytokine, which is expressed in human adipose cells and may have a protective effect against the development of coronary artery disease. The aim of the study was to evaluate the involvement of ApN secretion in hypothyroid patients with normal thyroid function following levothyroxine (L-T(4)) replacement therapy, and to associate plasma ApN levels with intima-media thickness (IMT) in the common carotid artery (CCA), an indicator of early atherosclerosis, and cardiovascular parameters including soluble thrombomodulin (sTM), a plasma endothelial injury marker. The CCA IMT and plasma levels of ApN and sTM were measured in 52 hypothyroid patients and in age-, sex- and body mass index (BMI)-matched normal control subjects. Thirty-six of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T(4) replacement therapy. Although the basal CCA IMT was significantly higher in hypothyroid patients [0.633 +/- 0.018 mm (mean +/- S.E.)] than in control subjects (0.552 +/- 0.022 mm, P < 0.005), both groups had similar baseline ApN and sTM levels [10.23 +/- 0.76 vs. 10.10 +/- 0.93 microg/ml: NS; and 2.58 +/- 0.14 vs. 2.68 +/- 0.20 ng/ml: NS, respectively]. Simple regression analysis revealed that plasma ApN was significantly correlated in a positive manner with age (r = 0.339, P = 0.015), HDL-cholesterol (r = 0.295, P = 0.048), and sTM (r = 0.490, P = 0.0005), but not with CCA IMT (r = 0.059, P = 0.742). In multivariate analysis, the plasma ApN level was significantly associated with that of sTM (r = 0.546, P = 0.0001) and with serum high-density lipoprotein (HDL)-cholesterol levels (r = 0.291, P = 0.029) in hypothyroid patients. During 1 year of L-T(4) replacement therapy, hypothyroid patients showed a significant decrease in CCA IMT, to 0.553 +/- 0.016 mm (P < 0.0001), a level comparable to normal controls, but no significant change in ApN (from 10.79 +/- 1.07 to 10.6 9+/- 1.14 microg/ml, NS) or sTM (from 2.59 +/- 0.15 to 2.74 +/- 0.18 ng/ml, NS). Hence, we provide evidence that ApN and sTM might not contribute to enhanced atherosclerosis, as reflected by increased CCA IMT in hypothyroid patients. However, this is the first report to demonstrate a positive and significant association of sTM with ApN. These data support the hypothesis that sTM is one of the determinant of ApN and thus suggest the presence of an sTM-associated regulatory mechanism for ApN secretion in hypothyroid patients.

Adiponectin↗

PubMed2005

Aortic calcification in haemodialysis patients with diabetes mellitus.

BACKGROUND: Certain metabolic disorders, such as hyperphosphatemia induce vascular calcification in haemodialysis patients; it is unclear, however, whether these disorders contribute to aortic calcification in diabetic haemodialysis patients. This study examined the risk factors of aortic calcification in a large number of haemodialysis patients, and compared risk factors between diabetic and non-diabetic patients. METHODS: The subjects were 667 patients on maintenance haemodialysis: 184 with type 2 diabetes and 483 without. Aortic calcification was measured semi-quantitatively using a plain computed tomography image of the abdominal aorta, and an aortic calcification index (ACI) was calculated. RESULTS: The ACI of the diabetic subjects was significantly higher than that of those without diabetes (57.3+/-22.1 vs 44.8+/-28.3%, P < 0.0001), although the dialysis vintage of the former was significantly shorter (P < 0.001). Multiple regression analyses showed that diabetes was a significant independent risk factor for increased ACI. Multiple regression analyses, performed separately in diabetics and non-diabetics, revealed that advanced age, higher systolic blood pressure, smoking and longer haemodialysis vintage were common independent risk factors significantly associated with increased ACI in both patient groups (R2 = 0.296, P < 0.0001 for non-diabetics; R2 = 0.193, P < 0.0001 for diabetics). Higher serum phosphate concentration was not significantly associated with increased ACI in diabetic patients (P = 0.429), although it was a significant independent factor in non-diabetic patients (beta = 0.150, P < 0.0005). CONCLUSION: Aortic calcification in diabetic haemodialysis patients is more advanced, compared with non-diabetic patients, even with short haemodialysis vintage. Since disorders of mineral metabolism are not significantly associated with aortic calcification in diabetic haemodialysis patients, aortic calcification in these patients could be affected by metabolic abnormalities associated with the diabetic state per se, independent of other confounding factors; and aortic calcification may be advanced even before haemodialysis induction.

Adult↗

PubMed2005

Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells.

CONTEXT: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process. OBJECTIVE: Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro. METHODS: The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies. RESULTS: The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+. CONCLUSIONS: These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells.

Calcium↗

PubMed2005

Serum BAP as the clinically useful marker for predicting BMD reduction in diabetic hemodialysis patients with low PTH.

With decrease of serum PTH in hemodialysis (HD) patients, other factors besides parathyroid hormone (PTH) become important in regulating bone metabolism. We investigated which serum bone metabolic marker is the best to predict the bone mineral density (BMD) reduction in HD patients with serum PTH<180 pg/ml. The bone formation markers, bone alkaline phosphatase (BAP), intact osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP), and the bone resorption markers, deoxypyridinoline (DPD), pyridinoline (PYD), and beta-crossLaps (beta-CTx) were measured in serum from 137 HD patients. BMD of all patients was measured twice, approximately 1.5 years before and 1.5 years after measurement of their markers of bone metabolism. In all 137 HD patients, serum BAP was the only marker significantly higher in those with BMD reduction than in those without. In 42 diabetes mellitus (DM) HD patients with serum PTH<180 pg/ml, hypothetically low bone turnover state, serum BAP was again the only marker to discriminate those with BMD reduction from those without. At serum PTH<60 pg/ml, serum BAP retained tendency toward higher value. These findings suggest that serum BAP might be the most sensitive to identify small changes of bone metabolism in low bone turnover state. Retrospective study confirmed the usefulness of serum BAP in clinical practice by significantly higher values in those with bone loss at PTH<180 pg/ml even in under routine sample handling. In conclusion, serum BAP is a clinically useful bone formation marker to predict the BMD reduction in DM HD patients with low level of PTH.

Absorptiometry, Photon↗