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Biomedical subjects

T Niwa

Publications and source records attributed to T Niwa.

At least 127 records · Page 7Linked to original sources
PubMed1995

Serum pyridinolines as specific markers of bone resorption in hemodialyzed patients.

Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline were quantified in uremic patients undergoing maintenance hemodialysis and in healthy subjects. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline in the hemodialyzed patients were significantly higher than those in healthy subjects. Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline decreased significantly after hemodialysis with reduction rates of about 40%. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline correlated significantly with intact parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase. Lysyl pyridinoline showed better correlations with these parameters than hydroxylysyl pyridinoline. Parathyroidectomy markedly decreased serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline. These results indicate that serum pyridinolines, especially lysyl pyridinoline, may be used as specific biochemical markers of bone resorption in hemodialyzed patients.

Acid Phosphatase↗
PubMed1995

Improved static compression behaviors and tablettabilities of spherically agglomerated crystals produced by the spherical crystallization technique with a two-solvent system.

PURPOSE: Poorly compressible crystals of acebutolol hydrochloride were agglomerated by the spherical crystallization technique with a two-solvent system to improve the compressibility for direct tabletting. The mechanism of improvements in static compression behaviors and tablettabilities of the spherically agglomerated crystals were investigated. METHODS: The improvement of static compression behaviors of the agglomerated crystals was determined by measuring the stress relaxations and elastic recoveries of compressed powder of original and agglomerated crystals. The improved tablettability of agglomerated crystals was evaluated by the pressure transmission ratio upon compression, the ejection pressure for releasing the tablet from the die and the tablet strength, i.e., tensile strength required for breaking. RESULTS: The higher relaxation pressure and the lower elastic recovery of the agglomerated crystals than of the original crystals were found. The pressure transmission ratio data showed that the friction pressures of the two crystals were similar during the compression period. The ejection pressure of the agglomerated crystals was lower than that of the original crystals. The tensile strength of the tablet of agglomerated crystals was greater than that of the original crystals. CONCLUSIONS: The compressibility and tablettability of the spherically agglomerated crystals prepared by the spherical crystallization technique were much improved due to their increased plastic property and reduced adhesive property compared to the original crystals.

Acebutolol↗
PubMed1995

Immunohistochemical detection of advanced glycation end products in dialysis-related amyloidosis.

beta 2-Microglobulin (beta 2m) isolated from the amyloid deposits in patients with dialysis-related amyloidosis (DRA) has been demonstrated to be modified with advanced glycation end products (AGE). We produced a monoclonal anti-AGE antibody which localized AGE to amyloid deposits in patients with DRA by immunohistochemistry. The connective tissues in the carpal tunnel were obtained from surgical specimens in six patients with DRA. AGE were localized to the beta 2m-positive amyloid deposits in these patients using the monoclonal anti-AGE antibody. AGE were also detected in infiltrating cells surrounding the amyloid deposits. The AGE-positive cells were identified as macrophages, since they showed positive staining with anti-CD68 antibody. In conclusion, AGE were demonstrated by immunohistochemical technique to be present in both beta 2m-positive amyloid deposits and surrounding macrophages in patients with DRA.

Adult↗
PubMed1995

[Interferon-associated retinopathy].

BACKGROUND: Recently interferons have been utilized for hepatitis C or some other tumorous conditions. However, a new interferon-associated retinopathy has been reported. There are to our knowledge, no publications in German-speaking countries. PATIENTS: Four patients developed after interferon therapy cotton-wool spots combined with splinter hemorrhage. RESULTS: The retinopathy occurred 5-30 days after the beginning of the therapy. In one case the retinopathy aggravated following dose elevation, whereas in two other cases the cotton-wool spots and hemorrhages disappeared irrespective of continued interferon therapy. CONCLUSIONS: Interferons cannot be primarily responsible for the development of retinopathy.

Aged↗
PubMed1995

Hepatocyte growth factor stimulates liver regeneration and elevates blood protein level in normal and partially hepatectomized rats.

The effects of recombinant human hepatocyte growth factor (HGF) on liver growth and function of normal and partially hepatectomized rats have been examined. HGF was continuously administered into the jugular vein because it was rapidly eliminated from the plasma (t1/2 alpha; approximately 4.5 min) and degraded. In normal rats, the labeling index of hepatocytes was increased about 6 times by the administration of HGF. HGF also decreased the prothrombin time and increased the hepaplastin and serum albumin content. In 70%-hepatectomized rats, HGF stimulated liver regeneration and increased the level of blood proteins such as hepaplastin in a dose-dependent manner. The stimulation of serum protein level seemed to result from not only the increase of hepatic cell number but also the direct effect of HGF on the protein production in hepatocytes, because HGF rapidly enhanced the protein synthesis prior to the increase of cell number and increased the mRNA content of albumin in the liver in vivo. In addition, a combination of heparin with HGF further accelerated the effects of HGF described above, possibly due to the decrease of HGF clearance. These findings suggest that HGF accelerates both the hepatic regeneration and function in vivo, and that rhHGF is clinically expected to be a potent therapeutic agent in hepatectomy and liver injury.

Albumins↗
PubMed1995

Interleukin 8 and biocompatibility of dialysis membranes.

To determine whether interleukin 8 (IL-8) can be used as an index of biocompatibility of dialysis membranes, the effects of hemodialysis (HD) on plasma IL-8 levels and the expression of IL-8 mRNA in peripheral blood mononuclear cell (PBMC) were compared among regenerated cellulose (RC), polyacrylonitrile (PAN) and polymethylmethacrylate (PMMA) dialyzers. HD using RC dialysers significantly increased plasma IL-8 levels and induced abundant expression of IL-8 mRNA in PBMC. HD using PMMA dialyzers also increased plasma IL-8 levels and induced slight expression of IL-8 mRNA. In contrast, HD using PAN dialyzers neither increased plasma IL-8 levels nor induced the expression of IL-8 mRNA. In vitro studies demonstrated that IL-8 was considerably adsorbed by PAN membranes and not at all by RC and PMMA. These studies indicate that plasma IL-8 level and expression of PBMC IL-8 mRNA can be used as indices of biocompatibility of dialysis membranes.

Acrylic Resins↗
PubMed1995

Efficient removal of albumin-bound furancarboxylic acid by protein-leaking hemodialysis.

Furancarboxylic acid (3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, CMPF), an inhibitor of erythropoiesis, cannot be removed by conventional hemodialysis due to its strong albumin binding, resulting in its accumulation in uremic serum. We used protein-leaking hemodialysis with BK-F dialyzers in 8 uremic patients for 4 months to determine its effect on the serum levels of CMPF. Pre-hemodialysis serum levels of CMPF significantly decreased to about 50% after 4 months by protein-leaking hemodialysis, while those of BUN and serum creatinine did not change significantly. Pre-hemodialysis hematocrit and hemoglobin levels significantly increased by protein-leaking hemodialysis. These results indicate that protein-leaking hemodialysis reduces serum levels of albumin-bound CMPF and improves anemia.

Adult↗
PubMed1995

Elevated serum levels of 3-deoxyglucosone, a potent protein-cross-linking intermediate of the Maillard reaction, in uremic patients.

3-Deoxyglucosone (3-DG) has been identified as an intermediate of the Maillard reaction in vitro. We measured serum 3-DG levels using gas chromatography/mass spectrometry and found a marked elevation in serum 3-DG levels in uremic patients compared with healthy subjects. The uremic patients with diabetes showed significantly higher serum concentrations of 3-DG than those without diabetes. 3-DG was demonstrated to be a potent protein-cross-linking agent in the reaction with lysozyme, leading to browning, fluorescence formation and polymerization of the protein by formation of advanced glycation end products (AGE). The increase in serum 3-DG levels in the uremic patients suggests that 3-DG may be responsible for the development of uremic complications by promoting the formation of AGE.

Adult↗
PubMed1995

[Aerosolization of lactide/glycolide copolymer (PLGA) nanospheres for pulmonary delivery of peptide-drugs].

Lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate (NA) used as a model peptide-drug have been developed by the emulsion-phase separation method in an oil phase as reported previously. In the present study, the aerosolization of nanospheres in dry and wet dispersion methods was investigated in vitro to evaluate their applications to pulmonary delivery of peptide-drug. The size distribution of aerosolized nanosphere dispersions and pulmonary deposition behaviors of inhaled particles were investigated using a lazer diffraction light-scattering particle sizer and an artificial model lung (Cascade Impactor: CI), respectively. It was found that the freeze-drying of nanospheres with a hydrophilic surface active agent effectively improved the inhalation behavior. Further, the mixing of nanospheres with lactose led to the reduction of their adhesion to an inhalation device (Spinhaler). It was supposed that the mists of nanosphere-suspension generated from a jet nebulizer might be inhaled into the lower bronchus and alveolus, because their respirable fraction (RF) value, i.e., the deposition percentage on stage 2 to 6 of CI, defined as a pulmonary inhalation index, reached a maximum of over 50%.

Administration, Inhalation↗
PubMed1995

Species and sex differences of testosterone and nifedipine oxidation in liver microsomes of rat, dog and monkey.

1. Species and sex differences in testosterone hydroxylation and nifedipine oxidation in liver microsomes from rat, dog and monkey have been investigated. 2. The formation of 2 alpha-, 2 beta-, 6 beta-, and 16 alpha-hydroxytestosterone and androstenedione in the male rat was higher than that in the female rat. Microsomes prepared from the male rat oxidized nifedipine about eight times faster than did those from the female rat. In contrast, marked sex-related differences were not seen in the dog and monkey. 3. Nifedipine oxidase activity in rat, dog and monkey correlated significantly with the activities for both testosterone 2 beta-hydroxylation and 6 beta-hydroxylation, suggesting the involvement of P4503A isozymes in these reactions. The ratios of formation of the 2 beta- to 6 beta-hydroxytestosterone in male rat and monkey were 0.17 and 0.18 respectively, whereas that in dog was 0.46. The corresponding activity ratios catalysed by P450DPB-1, a P4503A isoform purified from dog liver microsomes, was 0.36. 4. The formation of 16 beta-hydroxytestosterone was higher than that of the 16 alpha-hydrolated metabolite in liver microsomes from monkey, whereas 16 alpha-hydroxytestosterone was the predominant metabolite in the rat and dog, indicating species differences in stereoselectivity at the 16-position.

Animals↗
PubMed1995

Species- and gender-related differences in amine, alcohol and phenol sulphoconjugations.

1. Species-, gender- and strain-related differences in amine sulphoconjugations were studied in 105,000 g supernatants of liver samples isolated from mouse, rat, guinea pig, rabbit, dog, monkey and man and were compared with those of alcoholic and phenolic compounds. Substrates examined were desipramine (an alkylamine), piperazine and piperidine derivatives (alicyclic amines), aniline (an arylamine), tiaramide and dehydroepiandrosterone (alcoholic compounds) and 2-naphthol (a phenolic compound). 2. Sulphoconjugating activities of alicyclic and aryl-amines and tiaramide varied depending on the animal species, sex and strain used. In all animal species examined, the activity for desipramine was low or negligible but for 2-naphthol was consistently detected and high. Amine sulphoconjugations were higher in rabbit than in other animal species. Dog hepatic 105,000g supernatants exhibited low or neglible activities for amines and tiaramide. Females showed higher sulphoconjugating activities for all substrates in mouse and for amines and tiaramide in rat; males exhibited higher activities for 2-naphthol in rat and monkey and for amines in rabbit; there were no clear sex-related differences in other sulphoconjugations. 3. Among BALB/c, C57BL/6, DBA/2, and AKR mouse strains, the AKR strain showed higher activities towards amines and tiaramide than others. 4. In human liver 105,000g supernatants, sulphoconjugating activities for alicyclic amines, dehydroepiandrosterone, and 2-naphthol were detected. Among them, higher activities were observed in piperazine and phenol sulphoconjugations. There were no sex-related differences in the activities of all substrates examined. Good correlations were observed in activities between alicyclic amine and dehydroepiandrosterone sulphoconjugations. 5. These results indicate that activities of amine and alcohol sulphoconjugations vary considerably depending on the substrate, species, sex and strain but phenol sulphoconjugation is consistently detected in all species examined.

Adolescent↗
PubMed1995

[An autopsy case of gliomatosis cerebri with marked swelling of the spinal cord].

We report a 26-year-old male with diffuse infiltration of neoplastic glial cell to the bilateral hemisphere, basal ganglia, cerebellum, brain stem and markedly swollen spinal cord. Initial complaints were general malaise and disturbance of eye movements. The patient died after 30 months. The characteristics of this case included diffuse severe swelling of the brain stem and spinal cord (from the cervical to thoracic levels) shown on MRI without marked change of the hemispheres, cerebellum or basal ganglia. This is a rare case report of spinal swelling that was visually and radiologically apparent, although at present 11 cases of gliomatosis cerebri with histologically proven invasion to the spinal cord. From these facts, it is thought that this case is important from the aspect of the differential diagnosis of the spinal cord lesions.

Adult↗
PubMed1995

[A case of near total tracheal obstruction from recurrent esophageal carcinoma].

We have treated a 58-year-old man with almost complete tracheal occlusion arising as a result of recurrence of esophageal cancer. Although laser photoresection using partial cardiopulmonary bypass was desirable, neither laser nor cardiopulmonary bypass was available in our hospital. It was then decided to resect the tumor by forceps. In order to prevent bleeding from tumor during such emergency procedure, intratumoral injection of ethanol was preceded and tracheal lumen could be opened successfully. He was managed by insertion of a Dumon silicone stent seven days after the emergency. The result was satisfactory for maintaining the patency of the airway where the stent was placed. Unfortunately the patient died 113 days after the insertion of Dumon silicone stent from massive hemoptysis, which might resulted from the rupture of vessel feeding the tumor or the perforation of aorta involved by the tumor.

Carcinoma, Squamous Cell↗
PubMed1995

Potential bile acid metabolites. 23. Syntheses of 3-glucosides of nonamidated and glycine- and taurine-amidated bile acids.

The 3-glucosides of nonamidated lithocholic, chenodeoxycholic, ursodeoxycholic, deoxycholic, and cholic acids, and their double conjugate forms with glycine and taurine were synthesized. The key reactions used were 1) beta-D- glucosidation at C-3 by the Koenigs-Knorr condensation reaction of 3 alpha-hydroxylated bile acid methyl (or p-nitrophenyl) esters with 1 alpha-bromo-1-deoxy-2, 3, 4, 6-tetra-O-acetyl-D-glucopyranose in the presence of cadmium carbonate in refluxing benzene; 2) indirect and direct amidations at C-24 by the activated p-nitrophenyl ester and by the diethylphosphorylcyanide methods, respectively, using glycinate ester and taurine as coupling agents; and 3) simultaneous alkaline hydrolysis of the hydroxyl-protecting and ester groups in both the sugar and aglycone moieties.

Amides↗
PubMed1994

Endogenous synthesis of N-methylnorsalsolinol in rat brain during in vivo microdialysis with epinine.

The in vivo metabolic pathway for the synthesis of N-methylnorsalsolinol, an analogue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was studied in the rat brain. N-Methyldopamine (epinine) was perfused at the striatum of the rat brain by in vivo microdialysis. N-Methylnorsalsolinol (NMNSAL) was identified in the brain dialysate after epinine perfusion using gas chromatography-selected-ion monitoring mass spectrometry (GC-SIM-MS). We demonstrated that NMNSAL could be synthesized from epinine with an aldehyde by the Piclet-Spengler condensation reaction in the rat brain.

Aldehydes↗
PubMed1994

In vitro drug release behavior of D,L-lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate prepared by a novel spontaneous emulsification solvent diffusion method.

Nanospheres with D,L-lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion method. Nafarelin acetate (NA), a luteinizing hormone-releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone-dichloromethane-water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200-300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of the rapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water-soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug-release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found tht the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the porous matrix structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Novel toxins and Parkinson's disease: N-methylation and oxidation as metabolic bioactivation of neurotoxin.

In human brains, a series of monoamine-derived 1,2,3,4-tetrahydroisoquinolines and the 6,7-dihydroxy derivatives has been identified. A tetrahydroisoquinoline was found to cause parkinsonism in monkey, but its toxicity was not so potent as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Two metabolic steps were found to increase cytotoxicity of isoquinolines. N-Methylation by a non-specific N-methyltransferase was proved by in vivo and in vitro experiments. The N-methylated compound was oxidized into N-methylisoquinolinium ion by monoamine oxidase from human brain mitochondria. The oxidation was proved by microdialysis in the rat brain. The isoquinolinium ion was more cytotoxic than the two metabolic precursors. N-Methylation of dopamine-derived 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines was detected by in vivo microdialysis in the rat striatum, and their presence in the human brain was confirmed by GC-MS. The metabolic bioactivation may be a general pathway to produce neurotoxins as the pathogenic agents of Parkinson's disease.

Adenosine Triphosphate↗