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M Hoshino

Publications and source records attributed to M Hoshino.

At least 73 records · Page 4Linked to original sources
PubMed1998

alpha-->beta transition of beta-lactoglobulin as evidenced by heteronuclear NMR.

Whereas bovine beta-lactoglobulin is a predominantly beta-sheet protein, it has a marked alpha-helical preference and can be considered to be a useful model of the alpha-->beta transition, a key issue for understanding the folding and biological function of a number of proteins. In order to understand the mechanism of the alpha-->beta transition, the backbone structures of the recombinant bovine beta-lactoglobulin A in the native state and in the highly helical state induced by 2,2,2-trifluoroethanol were characterized by 1H, 13C and 15N multidimensional NMR spectroscopy. Overall, the secondary structures in the native state were similar to those of the crystal structure. On the other hand, beta-lactoglobulin in the 2,2,2-trifluoroethanol state was composed of many alpha-helical segments. The presence of the persistent alpha-helices in the helical state and the core beta-sheet in the native state suggested that during folding native-like core beta-sheet and several non-native helices are formed first and the remaining beta-sheet is subsequently "induced" through interaction with the pre-existing beta-sheet.

Animals↗
PubMed1998

A novel protein containing Cdc10/SWI6 motifs regulates expression of mRNA encoding catecholamine biosynthesizing enzymes.

Catecholaminergic (dopaminergic, noradrenergic, and adrenergic) transmitter phenotypes require the cooperative actions of four biosynthetic enzymes: tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase. Mechanisms that control expression of these enzymes in a transmitter phenotype-specific manner, however, are poorly understood. Here, we provide evidence that overexpression of a novel cdc10/SWI6 motif-containing protein, V-1, elicits the coordinate up-regulation of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine beta-hydroxylase mRNAs in the neuronal cell line PC12D, and as a result, catecholamine levels are increased. Furthermore, V-1 is strongly expressed in the cytoplasm of rat chromaffin cells of adrenal medulla. Thus, V-1 may act as a cytoplasmic protein/protein adapter and be involved in control of the catecholaminergic phenotype expression via an intracellular pathway signaling to the nucleus.

Adrenal Medulla↗
PubMed1998

Preoperative Diagnosis of Breast Diseases by Dynamic MR Mammography:Cut-off Point Establishment for Signal Intensity Ratio.

We have demonstrated that the dynamic study for breast lesions by magnetic resonance imaging(MRI)can differentiate benign from malignant lesions objectively.The cases were 57 histopathologically appraised breast lesions, including 20 cases of breast cancer, 28 cases of mastopathy, 8 cases of fibroadenoma and 1 caseof intraductal papillomatosis. We plotted time-signal intensity ratio curves and then determined 95% confidence intervals, plotting the signal intensity ratio for both breast cancer and mastopathy every 30 seconds during dynamic magnetic resonance mammography(MRM)after gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)administration, and further established cut-off points to differentiate between them. We then tried of estimate objectively the benign-malignant differentiation to breast lesions by confirming their signal intensity ratio to be more or less than the cut-off points. We advocate this procedure, and call it the " dynamic ratio method. " As a result, we found highly significant differences between breast cancer and mastopathy at 30 and 60 seconds after Gd-DTPA administration(P < 0.0001). We also confirmed that the cut-off point for the dynamic ratio method was equivalent to 1.4 and 1.8 times the precontrast signal intensity value at30 and 60 seconds after administration of Gd-DTPA respectively. By performing this dynamic ratio method preoperatively we can assess objectively not only the malignancy of breast lesions, but also neighboring infiltration, extending intraductal component, and lymph node metastasis. Furthermore, the dynamic ratio method provides detailed information for selecting the appropriate region for breast conserving surgery preoperatively, and can be expected to reduce unnecessary biopsies of benign cases. The dynamic ratio method had a sensitivity of 95.0%, a specificity of 81.1% and a positive predictive value of 73.1%. Also, for detectinginvasive ductal carcinoma, the sensitivity of the dynamic ratio method was 100.0%.

Journal Article↗
PubMed1998

Leukotriene D4 activates mitogen-activated protein kinase through a protein kinase Calpha-Raf-1-dependent pathway in human monocytic leukemia THP-1 cells.

Leukotriene D4 (LTD4) is a major lipid mediator involved in inflammatory and allergic disorders including bronchial asthma. Despite its potent biological activity, little is known about the receptor and intracellular signaling pathways. Here we analyzed the signal transduction mechanisms through LTD4 receptors using human monocytic leukemia THP-1 cells. When these cells were stimulated with LTD4, intracellular calcium concentration was increased and mitogen-activated protein kinase (MAP kinase) was activated severalfold. This activation was inhibited by staurosporine or GF109203X treatment or abolished by protein kinase C depletion. Cytosolic protein kinase Calpha was translocated to the membrane, and Raf-1 was activated by LTD4 treatment in a similar time course. LTD4-induced Raf-1 activation was diminished by protein kinase C depletion in the cells. A chemotactic response of THP-1 cells toward LTD4 was observed which was inhibited by pertussis toxin (PTX) pretreatment. Thus, LTD4 has at least two distinct signaling pathways in THP-1 cells, a PTX-insensitive mitogen-activated protein kinase activation through protein kinase Calpha and Raf-1 and a PTX-sensitive chemotactic response. This cellular signaling can explain in part the versatile activities of LTD4 in macrophages under inflammatory and allergic conditions.

Biological Transport↗
PubMed1998

Three-dimensional direction and interrelationship of prisms in cuspal and cervical enamel of dog tooth.

The three-dimensional architecture of enamel prisms was examined in cuspal enamel and compared with that in cervical enamel by light and electron microscopy as well as computer-assisted reconstruction using the developing enamel of several dog teeth. Dog tooth enamel consists of two groups of alternately arranged enamel prisms oriented in opposite sideward directions basically forming thick horizontal rings, partly branching off from the stem. Along a 8-10 enamel prism-wide group, the enamel prisms emerge in parallel tilting uniformly to the same sideward direction. In cervices, groups of enamel prisms are arranged nearly in parallel displaying a regular arrangement of prisms. Approaching the cusp of tooth, the groups of enamel prisms fuse to a concentric cusp-centered arrangement and the prisms exhibit no periodic arrangement as shown in the cervical enamel. It is suggested that the three-dimensional structure of enamel becomes complicated close to the cusp, contributing to the chewing stress of tooth.

Ameloblasts↗
PubMed1998

Fusion variations of pancreatic ducts in patients with anomalous arrangement of pancreaticobiliary ductal system.

Fusion variations of the pancreatic ducts were studied to elucidate the significance of such variations. We classified structural fusion anomalies of the main and accessory pancreatic ducts on endoscopic retrograde cholangio-pancreatography (ERCP) in 37 patients with anomalous arrangement of the pancreaticobiliary ductal system (AAPB). The fusion variations of the pancreatic ducts were classified into five types: common, ansa pancreatica, branch fusion, looped, and separated. These fusion variations, except for common type, were found in 68% of the 37 patients with AAPB on ERCP. Fusion variations of the pancreatic ducts were very frequent (93%) in the 30 patients with congenital cystic dilatation of the common bile duct (CCD). The branch confluence fashion, in which the terminal bile duct communicated with a pancreatic duct branch, was found only in patients with cystic dilatation cyst of the CCD, and it appeared that cystic dilatation cyst of CCD might differ from spindle or cylindrical cyst originating from embryonic formation of an anomalous confluence. It was also suggested that in patients with fusion variations of the pancreatic ducts, the flow of pancreatic juice might be disordered, leading to the development of acute pancreatitis or pancreatic dysfunction. Consequently, it appears to be necessary to carefully examine patients with AAPB for the presence or absence of any fusion variations of the pancreatic ducts and to observe such patients with long-term monitoring by ERCP, and computed temography, and with pancreatic function tests.

Adult↗
PubMed1998

Bronchial subepithelial fibrosis and expression of matrix metalloproteinase-9 in asthmatic airway inflammation.

BACKGROUND: Bronchial asthma is characterized by airway structural changes, including mucosal inflammation and subepithelial collagen deposition. An imbalance between the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is thought to play a critical role in the synthesis or degradation of the extracellular matrix of the airway architecture. However, the relationship between subepithelial basement membrane thickness and these enzymes in asthma has not been determined. OBJECTIVE: We compared the thickness of collagen and tenascin deposition and the expression of MMP-9 and TIMP-1 in bronchial biopsy specimens from subjects with asthma and control subjects. METHODS: Bronchial biopsy specimens were obtained from 25 subjects with asthma and 10 healthy control subjects to estimate the extent of collagen and tenascin deposition in subepithelial reticular basement membrane by immunohistochemical staining. Using a computer-assisted image analysis system, we quantitated expression of both epithelial and submucosal MMP-9 and TIMP-1. The numbers of inflammatory cells were also determined. RESULTS: Subjects with asthma exhibited greater thickness of collagen III (P <.01), collagen V (P <.01), and tenascin (P <.01) deposition in reticular basement membrane than did control subjects. The proportions of epithelium and submucosa immunoreactive to MMP-9 and TIMP-1 were significantly higher in the subjects with asthma than in the control subjects (each P <.001). Submucosal expression of MMP-9 was significantly higher than that of TIMP-1 in subjects with asthma (P <.01). Significant correlations were found between the number of myofibroblasts and thicknesses of collagen III (rs = 0. 70, P <.001), collagen V (rs = 0.67, P <.001), and tenascin (rs = 0. 58, P <.01) in subjects with asthma. On the other hand, the number of eosinophils was correlated with degree of mucosal expression of MMP-9 (rs = 0.43, P <.05) and TIMP-1 (rs = 0.69, P <.001). In subjects with asthma, a significant inverse correlation was found between subepithelial fibrosis and FEV1 (type III collagen, rs = -0. 89, P <.001; type V collagen, rs = -0.90, P <.001; tenascin, rs = -0. 88, P <.001), and airway responsiveness (type III collagen, rs = -0. 59, P <.01; type V collagen, rs = -0.47, P <.05; tenascin, rs = -0. 48, P <.05). CONCLUSION: These findings suggest that collagen III, collagen V, and tenascin deposition in basement membrane in subjects with bronchial asthma are associated with increased expression of MMP-9, which may be produced by eosinophils, and that airway remodeling in subjects with asthma may be related to air-flow obstruction and airway hyperresponsiveness.

Adolescent↗
PubMed1998

Effects of effusion in the middle ear and perforation of the tympanic membrane on otoacoustic emissions in guinea pigs.

The influence of fluid in the middle ear and of perforation and closure of the tympanic membrane (TM) on otoacoustic emissions (OAEs) was evaluated in guinea pigs. Click-evoked otoacoustic emissions (CEOAEs) and distortion product otoacoustic emissions (DPOAEs) were measured after the auditory bulla was opened. Neither OAE level changed significantly when fluid filled only half the space in the bulla, but both OAE levels disappeared when fluid completely filled the bulla. These changes were reversible. Thus, the presence of fluid in the bulla influenced CEOAE and DPOAE levels only when its volume filled more than half the space of the bulla. Changes in both CEOAE and DPOAE levels were affected by the size of the perforation of the tympanic membrane. For the smallest perforation, the reduction in both CEOAE and DPOAE levels was restricted to the lower frequencies. However, as the size of the perforation increased, a decrease in high-frequency function occurred. Thus, the results indicate that the magnitude of both OAEs was proportional to the size of the perforation. Both OAE levels improved after the perforation was closed. Because CEOAEs were more sensitive than DPOAEs to perforation and closure of the TM, DPOAEs may be better suited for OAE measurement in ears with perforated TMs.

Acoustic Stimulation↗
PubMed1998

A comparative study of the effects of ketotifen, disodium cromoglycate, and beclomethasone dipropionate on bronchial mucosa and asthma symptoms in patients with atopic asthma.

Asthma is a chronic inflammatory disorder of the airways that is characterized by infiltration of many inflammatory cells into the bronchial mucosa. We compared the effects of ketotifen, disodium cromoglycate (DSCG), and beclomethasone dipropionate (BDP) on inflammatory cells in the bronchial mucosa and on the asthma symptoms of patients with atopic asthma. In this 12-week parallel study, 32 patients were randomly allocated to either the ketotifen group (2 mg day-1, n = 13), DSCG group (8 mg day-1, n = 9) or BDP (400 micrograms day-1, n = 10). Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Before and after treatment, pulmonary function and bronchial responsiveness to methacholine were evaluated, and fibreoptic bronchoscopy and biopsy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. We performed immunohistochemistry using specific monoclonal antibodies for activated eosinophils (EG2), mast cells (AA1), and T cells (CD3, CD4, and CD8). Our clinical findings showed significant improvement in symptom score and bronchial responsiveness (P < 0.01) each) in all groups. Both the DSCG and the BDP groups had significantly better symptom scores than the ketotifen group (P < 0.05, both groups). PEF significantly increased in the DSCG group in comparison to the ketotifen (P < 0.01) and BDP (P < 0.05) groups, FEV1% increased significantly in the DSCG (P < 0.01) and BDP (P < 0.05) groups in comparison to the ketotifen group. Compared with their baseline values, treatment significantly decreased EG2+ activated eosinophils, and CD3+ and CD4+ T cells, in each group (P < 0.01). Both the DSCG (P < 0.05) and the BDP groups (P < 0.01) exhibited significant decreases in AA1+ mast cell count, but this was not observed in the ketotifen group. Comparing before- and after-treatment values, only the DSCG group exhibited a significant decrease in the number of CD8+ T cells (P < 0.01). Ketotifen, DSCG, and BDP all showed anti-inflammatory activity as determined by examination of the bronchial mucosa of asthmatic patients; and both the DSCG and BDP groups had better clinical responses than the ketotifen group.

Adolescent↗
PubMed1998

Chain-like conformation of heat-denatured ribonuclease A and cytochrome c as evidenced by solution X-ray scattering.

BACKGROUND: Although the characterization of heat-denatured proteins is essential for understanding the thermodynamic mechanism of protein folding, their structural features are still unclear and controversial. In order to address this problem, we studied the size and shape of the heat-denatured states of bovine ribonuclease A (RNase A) and horse ferricytochrome c (cytochrome c) by solution X-ray scattering. RESULTS: RNase A has four disulfide bonds, whereas cytochrome c, with a covalently bound heme group, has no disulfide bond. Guinier plots show that the heat-denatured RNase A is relatively compact, but the heat-denatured cytochrome c is expanded. On the other hand, the Kratky plots of the two proteins are similar, indicating that the heat-denatured proteins assume a chain-like disordered conformation. The X-ray scattering of RNase A and cytochrome c at various temperatures confirmed that their thermal transitions from a globular native state to a chain-like extended conformation can be approximated well by a two-state transition. CONCLUSIONS: These results indicate that the heat-denatured RNase A and cytochrome c are substantially unfolded according to the criteria of solution X-ray scattering, although the heat-denatured RNase A remains compact because of the presence of the disulfide bonds. The results also confirm that the thermal denaturation occurs cooperatively with the breakdown of secondary and tertiary structure.

Animals↗
PubMed1998

Inhaled corticosteroid reduced lamina reticularis of the basement membrane by modulation of insulin-like growth factor (IGF)-I expression in bronchial asthma.

BACKGROUND: Pathological studies of bronchial biopsy specimens have confirmed the apparent thickening of lamina reticularis of the epithelial basement membrane. Corticosteroids have proven to be most effective in modifying airway inflammation. However, there is not much data on the effects of corticosteroid-treatment on the basement membrane. OBJECTIVE: To investigate the effects of inhaled beclomethasone dipropionate (BDP) on the thickness of basement membrane and cellular infiltration into the bronchial mucosa, and the expression of growth factors in patients with asthma. METHODS: We studied bronchial biopsies from 24 asthmatic patients before and after treatment with inhaled BDP, 400 microg twice a day or placebo, for 6 months in a double-blind manner. Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. The thickness of the basement membrane was determined by electron microscopy. Inflammatory cells and the expression of growth factors were examined by immunohistochemistry in endobronchial biopsy specimens. RESULTS: After 6 months of treatment, we observed a significant improvement of asthma symptoms (P<0.01), PEF (P<0.01), diurnal variation of PEF (P<0.05), and airway responsiveness (P< 0.05) in the BDP group compared with the placebo group. This was accompanied by a significant decrease in the thickness of the lamina reticularis (P < 0.001), and in the number of activated eosinophils (P<0.01), T-lymphocytes (P<0.01), and fibroblasts (P < 0.05) in BDP-treated patients. There was also a reduction in the expression of insulin-like growth factor (IGF)-I (P < 0.01). Significant correlation was found between the IGF-I expression and collagen thickening (rs = 0.34, P<0.01), and the number of fibroblasts (rs = 0.45, P < 0.01). CONCLUSION: These results suggest that corticosteroid treatment in asthma can reduce the lamina reticular thickness by modulation of IGF-I expression with consequent inhibition of the airway infiltration by inflammatory cells, and therefore may help to prevent remodelling of the airways.

Administration, Inhalation↗
PubMed1998

Ozone exposure generates free radicals in the blood samples in vitro. Detection by the ESR spin-trapping technique.

Generation of free radicals in the reaction of ozone with blood samples and related salt solutions was investigated in vitro by using ESR spin-trapping technique with DMPO. In the reactions of low levels of ozone, a carbon-centered radical was spin-trapped with DMPO, giving rise to the 6-line ESR signal in both whole blood and blood plasma. In the blood plasma, DMPO-spin adduct of hydroxyl radical (DMPO-OH) was detected together with the spin adduct of carbon-centered radical. The present spin-trapping study demonstrates that, when exposed to ozone, 0.9% NaCl solution in the presence of DMPO gives rise to the formation of DMPO-OH. The addition effects of ethanol, which is a .OH scavenger, into the NaCl solution reveal that DMPO-OH is produced by the reaction of DMPO with both .OH and unidentified oxidants originated from the reaction of Cl- and ozone. Based on these observations, we consider that .OH is generated similarly in the blood plasma exposed to ozone. The ESR study of DMPO-spin adducts in the ozone-exposed aqueous solution of NaOCl indicates that Cl- reacts with ozone to give ClO-. Presumably, further oxidation of ClO- by ozone leads to the formations of .OH and the unidentified oxidants.

Blood↗
PubMed1998

Expression of growth factors and remodelling of the airway wall in bronchial asthma.

BACKGROUND: Bronchial asthma is characterised by airway structural changes, including mucosal inflammatory infiltration and subepithelial collagen deposition, that may represent the morphological basis for the chronicity of the disease. The relationship between airway wall thickness and growth factors in asthma has not been elucidated. METHODS: Bronchial biopsy specimens were obtained from 21 asthmatic patients and eight healthy subjects and the basement membrane thickness was measured by light microscopy and electron microscopy. At the same time the numbers of eosinophils and fibroblasts were assessed and the expression of transforming growth factor beta 1 (TGF-beta 1), platelet derived growth factor (PDGF), and insulin like growth factor (IGF) I in the bronchial mucosa was examined by immunostaining. The relationship between the degree of thickening of the subepithelial layer and both the clinical data and pulmonary function were also investigated. RESULTS: The basement membrane of the asthmatic patients was thicker than that of the healthy controls (median 8.09 versus 4.02 microns). Electron microscopic examination of the basement membrane revealed thickening of the subepithelial lamina reticularis; this thickening significantly correlated with the number of fibroblasts in the submucosa in the asthmatic subjects (rs = 0.88) but not in the controls (rs = 0.70). There was a significantly higher number of eosinophils in the airways of the asthmatic subjects than in the healthy subjects (EG1 + cells: 52.0 versus 2.0/mm2, EG2 + cells: 56.0 versus 1.5/mm2). The expression of each growth factor in the bronchial mucosa was similar in asthmatic and healthy subjects (TGF-beta 1: 18.0% versus 16.0%, PDGF: 37.0% versus 32.5%, IGF-I: 15.0% versus 8.0%). A weak but statistically significant correlation was found between the number of fibroblasts and the expression of TGF-beta 1 in asthmatic subjects (rs = 0.50). There was a significant correlation between the thickness of the subepithelial layer in asthmatic subjects and the attack score (rs = 0.58) and a significant inverse correlation between the subepithelial collagen thickness in asthmatic subjects and airway hypersensitivity (rs = -0.65). CONCLUSIONS: These findings indicate that the thickening of the subepithelial layer in bronchial asthma is due to an increase in fibroblasts, and that the thickness of the subepithelial collagen appears to be linked to an increase in bronchial responsiveness and exacerbation of clinical manifestations.

Adolescent↗
PubMed1998

Effect of the leukotriene receptor antagonist pranlukast on cellular infiltration in the bronchial mucosa of patients with asthma.

BACKGROUND: It has been reported that pranlukast reduces the antigen induced immediate and late phase asthmatic responses, airway hyperreactivity to acetylcholine, and pulmonary eosinophil accumulation in guinea pigs. A study was undertaken to test the hypothesis that pranlukast may reduce the number of inflammatory cells in the bronchial mucosa of patients with asthma. METHODS: A double blind, placebo controlled study was performed in 17 mild to moderate asthmatic subjects to examine changes in inflammatory cell infiltration in response to pranlukast (225 mg orally twice per day for four weeks). Comparisons of the mean daily beta 2 agonist use, symptom score, FEV1 percentage predicted, and airway methacholine responsiveness were made before and after treatment. Using fibreoptic bronchoscopy, bronchial biopsy specimens were obtained before and after treatment with either pranlukast (n = 10) or placebo (n = 7). Immunohistology was performed using monoclonal antibodies for CD3, CD4, CD8, CD68, NP57, AA1, EG1, EG2, gamma GTP and CD19. RESULTS: When the pranlukast and placebo treated groups were compared there were decreases in beta 2 agonist use, symptom score, and airway methacholine responsiveness after pranlukast but no increase in FEV1 was seen. The clinical response in patients treated with pranlukast was accompanied by a reduction in CD3 (median difference -37, 95% confidence interval (CI) -69 to -1; p < 0.05), CD4 (median difference -28, 95% CI -49 to -8; p < 0.01), AA1 (median difference -15, 95% CI -26 to 0; p < 0.05) and EG2 positive cells (95% CI -35 to 0; p < 0.05), but not in EG1 positive eosinophils, gamma GTP positive cells, and CD19 positive plasma cells. CONCLUSIONS: These results support the view that pranlukast may act by inhibition of bronchial inflammation in patients with asthma.

Adrenergic beta-Agonists↗
PubMed1998

Diurnal variation of peak expiratory flow in children with cough variant asthma.

Cough variant asthma (CVA) is thought to be a variant form of asthma in which cough is the sole clinical manifestation of airways hyperresponsiveness, a characteristic feature of asthma. Another characteristic feature of asthma includes an increased diurnal variation of peak expiratory flow (PEF) compared to normal subjects. To examine whether diurnal variation of PEF might also increase in children with CVA, we have examined the degree of diurnal variation of PEF in these children (n = 7) by measuring peak flow serially for a week, and compared it with those in mild to moderate asthma (n = 17) and in control children without cough (n = 8). In control children without cough, the average value of the mean diurnal variation of PEF was 10.4 +/- 0.8%. In both groups of children with asthma and with CVA, there was a significant increase in the value (20.5 +/- 1.3% and 23.6 +/- 3.6%, respectively) compared to that in control children (p < 0.01 in both groups), although there was no significant difference between these 2 groups. These results show that mild, but significant airway obstruction is occurring in children with CVA, although clinical wheezing is not recognized. Serial measurements of diurnal variation of PEF may be helpful for the diagnosis of CVA in children.

Asthma↗
PubMed1998

[Niceritrol decreases serum phosphate levels in chronic hemodialysis patients].

Since phosphorus retention in hemodialysis (HD) patients is known to be an important factor in the development of secondary hyperparathyroidism and renal osteodystrophy, phosphate binders have been needed for the control of serum phosphate levels (P). However, the calcium-containing phosphate binders that have been used widely can cause a rise in serum calcium levels and cause secondary hypoparathyroidism. We have recently experienced decreases in P after the administration of niceritrol (NT), a prodrug of nicotinic acid, for the treatment of low HDL-cholesteremia (HDL-C) in HD patients. The aim of the present study was to assess the mechanism of the P-lowering effect of NT in comparison with nicomol (NC), another prodrug of nicotinic acid. NT (750 mg/day) or NC (600 mg/day) was given orally to 10 or 14HD patients respectively. Blood samples were collected before the first dialysis of each week for the determination of serum urea nitrogen (UN), Cr, Ca, P, total cholesterol (TC), triglyceride (TG) and HDL-C. Serum nicotinic acid concentration (NAC) by gas chromatograph mass-spectrometry method was determined before, 4 weeks and 8 weeks after the administration of these drugs. After NT administration, P was decreased from 6.2 +/- 0.4 mg/dl to 5.1 +/- 0.4 mg/dl (1st week, p < 0.001, Mean +/- SE) and 4.5 +/- 0.3 mg/dl (2nd weeks, p < 0.001) with no change in UN, Cr or Ca levels; these significant decreases in P lasted for 8 weeks. NAC increased significantly after NT administration from 25.5 +/- 1.3 ng/ml to 549.8 +/- 102.2 ng/ml (4 weeks, p < 0.01) and 431.7 +/- 51.4 ng/ml (8 weeks, p < 0.01). HDL-C also increased (33.6 +/- 4.0 mg/dl vs 42.7 +/- 4.6 mg/dl, p < 0.05), but TC and TG did not change. In contrast, no significant changes were observed in P, NAC and HDL-C after NC administration. These discrepancies could be ascribed to the differences in serum NAC levels. These data suggest that NT could be useful for the control of P in HD patients. However further studies are needed to confirm the mechanism of the P-lowering effect of NT.

Anticholesteremic Agents↗