Reaction of (R,S)-dihydrolipoic acid and homologs with iron.
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Disulfides↗
Biomedical subjects
T Kawabata
Publications and source records attributed to T Kawabata.
Pathology considerations for, and subsequent risk assessment of, chemicals identified as immunosuppressive in routine toxicology.
Several proposals have been made with the aim of assisting in the early identification of chemicals with immunotoxic potential. The Organisation for Economic Cooperation and Development is now likely to incorporate enhanced immunopathology into the test guideline for the 28-day rat study, which may be regarded as a Tier I investigation. However, no guidelines have yet been proposed either for how the new data generated will be evaluated, or for how a subsequent risk assessment will be made. In this paper, considerations for the immunopathological assessment of the thymus, spleen, lymph nodes and bone marrow are described, together with comments on haematological and organ weight changes that may be associated with immunotoxicity. Their interpretation will depend on the doses at which changes are manifest, the quantity and quality of the effects observed and the presence and severity of other forms of toxicity. Lastly, risk assessment and the approach to Tier II testing in immunotoxicity is discussed. It is concluded that much of this work must be on a case-by-case basis, but should not in principle differ from the approach adopted for any other type of toxicity identified ina 28-day study.
Animals↗
Relationship between atrial natriuretic peptide and plasma volume during graded exercise with water immersion.
To assess the relationship between atrial natriuretic peptide (ANP) and the reduction in plasma volume (PV) during exercise, we measured changes in PV and ANP in seven male volunteers during treadmill exercise in air (AE) and with water immersion (WE) together with time control studies of rest in air and in water. Blood samples were collected from a catheter in the antecubital vein at exercise intensities of 32, 49, 65, and 78% of peak oxygen consumption (VO2). Plasma ANP in AE increased significantly from the resting value [15 +/- 1 (SE) pg/ml] only at 78% of peak VO2 (29 +/- 5 pg/ml), whereas ANP in WE increased significantly at exercise levels of > 49% of peak VO2 and reached 68 +/- 9 pg/ml at 78% of peak VO2. Although PV in AE and WE decreased significantly with VO2 of > 49% of peak VO2 (P < 0.01), the decrease from the resting value in WE was significantly greater than that in AE of > 65% of peak VO2 (P < 0.01) and the decreases at 78% of peak VO2 were -9.7 +/- 0.8 and -6.1 +/- 1.7%, respectively. The difference in the decrease in PV between AE and WE at corresponding VO2 correlated strongly with that in the increase in ANP (r = -0.97; P < 0.01). These results are consistent with the hypothesis that ANP may be involved in the fluid shift from the intra- to extravascular space during exercise.
Adult↗
Antiproteinuric effect of a thromboxane receptor antagonist, S-1452, on rat diabetic nephropathy and murine lupus nephritis.
To shed light on the role of thromboxane A2 (TXA2) in renal injury, we evaluated the effects of S-1452, a TXA2 receptor antagonist, on rats with streptozotocin (STZ)-induced diabetic nephropathy and murine lupus nephritis. In STZ diabetes rats (n = 6), urinary protein excretion significantly increased from 8 weeks and was about 5 times as much as that in normal rats at 10 weeks after induction of diabetes. In S-1452-treated rats (n = 6), increase in urinary protein was rarely observed and was significantly inhibited at 8 and 10 weeks after induction of diabetes. In (NZB x NZW)F1 mice, no proteinuria was detected in vehicle controls (n = 20) and S-1452-treated mice (n = 20) from 0 to 8 weeks after initiation of S-1452 treatment. Proteinuria was observed in 3, 7 and 8 mice in the control group, and 0, 2 and 5 mice in the S-1452 group at 12, 16 and 20 weeks after initiation of S-1452 treatment, respectively. Proteinuria developed more slowly in S-1452-treated mice than in vehicle controls. In conclusion, TXA2 receptor antagonist, S-1452, suppresses the progression of renal injury.
Acetylglucosaminidase↗
Synthesis and evaluation of novel nonpeptide angiotensin II receptor antagonists: imidazo[4,5-c]pyridine derivatives with an aromatic substituent.
Starting from recently reported nonpeptidic angiotensin II (AII) receptor antagonists, we have designed and prepared a new series of 6-arylimidazo[4,5-c]pyridine derivatives. Variation of phenyl groups at the 4-, 6- or 7-position of imidazo[4,5-c]pyridine showed that substitution at the 6-position resulted in receptor-binding activity almost as potent as that of DuP 753. This led to synthesis and evaluation of an extensive series of 6-aryl-imidazo[4,5-c]pyridine derivatives. Some of them were 4-fold more potent in vitro than DuP 753, but only showed weak antihypertensive activity in vivo when given orally to rats.
Angiotensin Receptor Antagonists↗
Synthesis and evaluation of novel pyrazolo[1,5-alpha]pyrimidine derivatives as nonpeptide angiotensin II receptor antagonists.
A novel series of 6-alkyl-7-oxo-4,7-dihydropyrazolo[1,5-alpha]pyrimidine-3-carboxyli c acid derivatives was prepared as angiotensin II (AII) receptor antagonists. When evaluated in an in vitro binding assay using COS cells transfected with a cDNA encoding a human AT1 angiotensin II receptor, the compounds in this series showed Ki values in the range of 0.4-4.0 nM. In anesthetized spontaneously hypertensive rats (SHRs), administration of the 6-propyl derivative 4d (1 mg/kg, i.v.) reduced the mean blood pressure (MBP) by a maximum of more than 30 mmHg from the normal value.
Angiotensin II↗
Effects of an HMG-CoA reductase inhibitor, pravastatin, and bile sequestering resin, cholestyramine, on plasma plant sterol levels in hypercholesterolemic subjects.
To study exogenous sterol metabolism during the suppression or stimulation of cholesterol biosynthesis induced by treatments for hyperlipidemia, we determined plasma plant sterol concentrations before and after administration of an HMG-CoA reductase inhibitor, pravastatin, and compared these with changes in these plasma sterol levels by the bile-sequestrating resin, cholestyramine. The effects of the drugs were also studied in a sitosterolemic patient who has had increased plasma levels of plant sterols. Plasma cholesterol levels determined by the HPLC method were decreased significantly after administration of pravastatin. Plasma plant sterol (sitosterol and campesterol) as well as cholestanol concentrations were also significantly reduced. Cholestyramine administration decreased plasma levels of cholesterol, but did not change those of plant sterols in the hypercholesterolemic subjects. Pravastatin had little effect in a sitosterolemic patient on plasma levels of sterols, where cholestyramine decreased the plasma levels of both cholesterol and cholestanol. These results indicate that treatment with the HMG-CoA reductase inhibitor decreases plasma plant sterol concentrations, and suggest that the increased plasma plant sterol levels in sitosterolemia might not be due to the decreased cholesterol biosynthesis in vivo.
Acyl Coenzyme A↗
English plantain and psyllium: lack of cross-allergenicity by crossed immunoelectrophoresis.
BACKGROUND: English plantain (Plantago lanceolata) weed pollen and psyllium (Plantago ovata) husk dust are inhalant allergens. Because of the phylogenetic relationship between these plant species, cross-allergenicity has been a concern. OBJECTIVE: The purpose of this study was to investigate the possible cross-allergenicity of plantain and psyllium. METHODS: Homologous and heterologous crossed immunoelectrophoresis (CIE) were performed using a commercial English plantain pollen extract and an extract of psyllium seed embryo. Crossed radioimmunoelectrophoresis (CRIE) was performed using sera from subjects who were RAST positive only to plantain (group A), RAST positive only to psyllium (group B), RAST positive to both plantain and psyllium (group C), or RAST negative to both (group D). RESULTS: All of the group A plantain subjects showed IgE binding to at least one of the six plantain allergens in homologous plantain CRIEs while only one of the sera from the group B subjects reacted very weakly to these plantain allergens. In homologous psyllium CRIE, all group B subjects showed pronounced IgE binding to 2 to 7 of the seven psyllium allergens. Several of the plantain subjects demonstrated only very weak binding to psyllium allergens. Heterologous CRIEs demonstrated little relevant IgE binding. CONCLUSIONS: These results indicate that there is little cross-allergenicity between psyllium husk and English plantain pollen.
Allergens↗
Bone mineral density changes in distracted callus stimulated by pulsed direct electrical current.
To evaluate the effect of application of pulsed direct current electrical stimulation to callus tissue, a 1-cm bone-lengthening model using an external lengthener was applied to rabbit tibia. Twenty-microampere pulsed direct current was applied 12 hours daily from the day of osteotomy until 40 days after the completion of lengthening. The area, bone mineral content, and bone mineral density of the distracted callus and of the proximal and distal segments of the tibia were evaluated using dual-energy xray absorptiometry. The absolute and relative values of bone mineral density of the electrically stimulated callus were significantly increased as compared with those in the control group. Pulsed direct current electrical stimulation may be indicated in bone lengthening to stimulate the poorly mineralized callus, and may shorten the overall time course of leg lengthening.
Absorptiometry, Photon↗
[The construction of a model for predicting adolescent smoking behavior from a 7-year follow-up survey].
Predictive factors for adolescent smoking behavior were examined prospectively in a cohort of 199 adolescents who participated in a survey in March 1983 and were followed up about 7 years later. In 1983, as junior high school students (grades 1-3), subjects completed a questionnaire which consisted of variables on smoking behaviors of subjects' family and friends, attitudes toward smoking, knowledge about the effects of smoking on health, and self-prediction of future smoking behavior. In 1990, a similar survey including variables on subjects' smoking behavior was again carried out. At that time, all were 20 years or older. It was found that the number of friends in 1983 who smoke was strongly associated with smoking behavior in 1983, and for both sexes smoking behavior in 1983 and self-prediction of future smoking behavior in 1983 were the factors which were associated with smoking behavior in 1990. Furthermore, a model for predicting smoking behavior was deduced from the foregoing results and the findings of prior studies. The covariance structure analysis supported the validity of the model and revealed that smoking behavior in 1983, number of friends who smoke, and self-prediction of future smoking behavior were important in predicting smoking behavior 7 years later.
Adolescent↗
[The effect of intraoperative gastric juice retention on the incidence of postoperative nausea and vomiting].
The effect of intraoperative gastric juice retention on the incidence of nausea and vomiting during the first 24 h after anesthesia was studied prospectively in 166 patients (ASA PS I-II) for elective surgery, excluding the patients requiring gastric tube (NG tube) postoperatively. The incidences of postoperative nausea and vomiting in the recovery room and during the first 24 h after operation were 5.7 and 10.0% in NG group, in which NG tube was inserted after intubation and taken off after gastric suction at the end of operation; 15.8 and 7.9% in RA group, in which ranitidine 1 mg.kg-1 was premedicated; and 12.1 and 6.9% in NN group, in which NG tube or ranitidine was not used, respectively. There were no statistical differences in the incidence between these three groups and between NG + RA group and NN group. Other factors such as age, duration of anesthesia and operative procedure also did not influence the incidence. The results suggest that the retention of gastric juice during operation has little effect on the incidence of postoperative nausea and vomiting.
Adolescent↗
An improved simple colorimetric method for quantitation of non-transferrin-bound iron in serum.
A simple method for direct quantitation of non-transferrin-bound iron (NTBI) in serum is introduced. NTBI was separated from serum by adding excess nitrilotriacetic acid disodium salt (NTA) to serum to form an Fe-NTA complex and then ultrafiltrated using a micro-filter. The NTBI in the ultrafiltrate was quantitated using a bathophenanthroline-based method. The optimal detection condition and several potential confounding factors were investigated. The actual measurements to samples in vivo and in vitro showed that this method is very practical.
Animals↗
[Postoperative care of neobladder using a detubularized intestinal segment].
Neobladder using a detubularized intestinal segment was constructed in 74 cystectomized patients between October 1986 and July 1994. There were 65 males (87.8%) and 9 females (12.2%) with an average age of 63 years (range 36 to 77 years). The mean follow-up period was 35 months (range 7 to 85). Problems of postoperative care assessed were continence, renal function, metabolic consequences, neoplasms and other complications. Moreover, the impact of these problems on the quality of life was evaluated by a self-administered questionnaire. Continence in the daytime was achieved in 70/74 (94.6%) patients. Nocturnal incontinence was noted in 15/74 (20.3%) patients. Serum BUN and creatinine levels were maintained within normal limits. Metabolic acidosis (base excess < -5.0 occurred in 7/74 (9.5%) patients, 4 patients of whom needed alkalizing agents. Colon adenomas in neobladder were found and resected in 3 patients. The other postoperative complications were stone formation in neobladder in 4 (5.4%), urethral stricture in 7 (9.5%) and ureteral stenosis in 3 (4.1%) patients respectively, which were satisfactorily corrected by endourological procedures. As to quality of life assessment, the majority was satisfied, whereas 11% of the patients reported emotional distress and limitations in the usual physical activities by nocturnal incontinence. Our finding suggest that nocturnal incontinence is the most important problem and we need longer follow-up to evaluate the problems of metabolic consequences and neoplasms of the urinary tract.
Adult↗
Alpha-lipoate can protect against glycation of serum albumin, but not low density lipoprotein.
Protein glycation may play a role in the pathogenesis of diabetic complications. alpha-Lipoate (1,2-dithiolane-3-pentanoate) has been reported to prevent glycation and structural modification of bovine serum albumin (BSA). To elucidate the protective mechanism, we tested the effects of enantiomerism, thiol moiety and hydrophobicity of alpha-lipoate on glycation of BSA and low density lipoprotein (LDL). When BSA (1 mM) was incubated with 500 mM glucose in the presence of alpha-lipoate homologues or dihydrolipoate (6,8-dimercaptooctanoate, DHLA) at 37 degrees C for 72 h, both alpha-lipoate (racemic, R- and S-forms) and DHLA inhibited BSA glycation similarly, but tetranorlipoate (1,2-dithiolane-3-carboxylate) did not. However, under similar conditions, alpha-lipoate did not inhibit LDL glycation. Scatchard plot analysis demonstrated that 6 mol of alpha-lipoate bind to 1 mol of BSA with a formation constant of 8.7 x 10(4) M-1. Therefore, we concluded that alpha-lipoate protects BSA glycation by hydrophobic binding near the glycation sites of BSA.
Glycation End Products, Advanced↗
The short-chain homologue of dihydrolipoic acid, tetranordihydrolipoate, protects against iron-induced lipid peroxidation in the aqueous phase.
Because iron is involved in catalysis of many biological oxidations, it is important to investigate new and novel antioxidants in terms of their effect on iron-catalyzed oxidations. We investigated the effect of dihydrolipoic acid (6,8-dimercaptooctanoic acid (DHLA)), its homologues (4,6-dimercaptohexanoic acid (bisnorDHLA) and 2,4-dimercaptobutanoic acid (tetranorDHLA)) and methyl 6,8-dimercaptooctanoate (methylDHLA) on Fe(II)-citrate-catalyzed lipid peroxide-dependent lipid peroxidation in lipid-dispersed and liposome systems. In the lipid-dispersed system, tetranorDHLA inhibited conjugated diene formation induced by Fe(II)-citrate. In the presence of tetranorDHLA, oxygen was consumed more rapidly in the reaction mixture than in the presence of the other compounds, but the oxidation rate of Fe(II)-citrate in the reaction mixture was slower than in the presence of the other compounds. This suggests that tetranorDHLA inhibited lipid peroxidation by the oxidation of tetranorDHLA itself at the site where the lipid was oxidized.
In Vitro Techniques↗
Schmorl's nodes on magnetic resonance imaging. Their incidence and clinical relevance.
Schmorl's nodes were observed in 76 (19%) of 400 patients with lumbar symptoms, and in 10 (9.4%) of 106 control patients. In the lumbar group, the highest incidence was 57%, in the second decade of life, and the lowest was 5%, in the sixth decade of life. Using MRI, among both groups, a total number of 218 Schmorl's nodes were observed at 170 disc levels; however, plain x-ray revealed only 73 (33%) of them. There were associated posterior disc herniations at 39 disc levels in 30 cases (39%), most of which were at the L4/5 level. The ratio of the cases showing only Schmorl's nodes to those with associated disc herniations at the same level increased markedly with age. Three of the four teenaged patients with multiple Schmorl's nodes at four or more disc levels had a history of hard sports. Schmorl's nodes, therefore, appear to be a type of vertical disc herniation, and to be an important pathognomonic condition, especially for young people.
Adolescent↗
Right atrial pressure and forearm blood flow during prolonged exercise in a hot environment.
Right atrial pressure (RAP) at rest is known to be reduced by an increase in skin blood flow (SkBF) in a hot environment. However, there is no clear evidence that this is so during exercise. To clarify the effect of the increase in SkBF on RAP during exercise, we measured forearm blood flow (FBF) (as an index of SkBF) and RAP continuously using a Swan-Ganz catheter in five male volunteers exercising on a cycle ergometer at 60% of peak aerobic power for 50 min in a hot environment (30 degrees C, relative humidity 20%). Cardiac output increased from 5.5 +/- 0.2 l/min at rest to 17.9 +/- 1.2 l/min (mean +/- SE, P < 0.01) in the first 10 min of exercise and then remained steady until the end of exercise. FBF did not change significantly during the first 5 min, but then increased from 2.7 +/- 0.5 ml/100 ml per min at rest to 10.8 +/- 1.7 ml/100 ml per min (P < 0.001) by 25 min as pulmonary arterial blood temperature (Tb) rose from 37.0 +/- 0.1 degrees C to 38.1 +/- 0.1 degrees C (P < 0.001). FBF then reached a plateau, despite a continuing increase in Tb. RAP increased significantly from 4.3 +/- 0.8 to 7.6 +/- 1.2 mm Hg (P < 0.001) during the first 5 min of exercise and then gradually declined to 6.1 +/- 1.0 mm Hg by 25 min (P < 0.001 vs. 5 min) and further to 5.7 +/- 1.0 mm Hg by 50 min, a value not significantly higher than at rest.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Salt consumption and body fluid balance during cold exposure in rats.
We investigated the effect of exposure to cold on salt consumption and the role of salt consumption on the maintenance of body fluid balance in male Wistar rats. The rats were provided with both tap water and NaCl solution ad lib during 16-h exposure to cold (10 degrees C) and normal (25 degrees C) air temperature conditions. The concentration of the NaCl solution was 0.9% for one group (0.9% NaCl group; n = 7) and 1.8% for the other (1.8% NaCl group; n = 6). At 10 degrees C, weight loss was greater than that at 25 degrees C, and fluid and Na balance were negative in the 0.9% NaCl group. However, the calculated Na concentration of the fluid consumed in the 0.9% NaCl group was about 135 mEq/l Na (0.8% NaCl) at both 10 degrees C and 25 degrees C. In the 1.8% NaCl group, the values indicating fluid and Na balance under both temperature conditions were similar, while the calculated concentration of Na in fluid consumed at 10 degrees C (187 mEq/l Na: 1.1% NaCl) was higher than that at 25 degrees C (153 mEq/l Na: 0.9% NaCl). These results suggest that the consumption of hypertonic NaCl solution indicating increased salt appetite during exposure to cold counteracts the loss of body fluid and Na via urine.
Acclimatization↗