Misreporting of dietary energy, protein, potassium and sodium in relation to body mass index in young Japanese women.

OBJECTIVE: Although under-reporting of dietary intake is more common in persons with a high body mass index (BMI), it is not well known whether or not misreporting is selective for different foods (and hence energy and nutrients), particularly in non-Western populations. We examined misreporting of dietary intake against biomarkers and its relation with BMI in young Japanese women. DESIGN: Cross-sectional study. SUBJECTS: A total of 353 female Japanese dietetic students aged 18-22 years (mean BMI: 21.4 kg/m(2), mean fat intake: 29.8% of energy). METHODS: Misreporting of dietary energy, protein, potassium and sodium (assessed by a self-administered diet history questionnaire) was examined against respective biomarkers (estimated energy expenditure and 24-h urinary excretion). Reporting accuracy was calculated as the ratio of reported intake to that estimated from corresponding biomarkers (complete accuracy: 1.00). RESULTS: Mean reporting accuracy of absolute intake (amount per day) varied considerably (0.86-1.14). Reporting accuracy of absolute intake decreased with increasing BMI (P for trend <0.001). However, no association was observed between reporting accuracy of energy-adjusted values and BMI (P for trend >0.15), indicating that BMI-dependent misreporting was canceled by energy adjustment. This was owing to positive correlation between the reporting accuracy of energy intake and that of absolute intake of the three nutrients (Pearson correlation coefficient: 0.49-0.67, P<0.0001). CONCLUSIONS: Although differential misreporting of absolute intake was associated with BMI, differential misreporting of energy-adjusted value was not. These findings support the use of energy-adjusted values in the investigation of diet-disease relationships among lean populations with a low-fat intake.

Metabolic fate of (-)-[4-(3)H]epigallocatechin gallate in rats after oral administration.

After oral administration of [4-(3)H]EGCg to rats, the radioactivity in blood, major tissues, urine, and feces was measured over time. The radioactivity in blood and most tissues remained low for 4 h postdose, began to increase after 8 h, peaked at 24 h, and then decreased. Major urinary excretion of radioactivity occurred in the 8-24 h period, and the cumulative radioactivity excreted by 72 h was 32.1% of the dose. The radioactivity in the feces was 35.2% of the dose within 72 h postdose. In the case of rats pretreated with antibiotics (antibiotic-pretreated rats), the radioactivity levels of the blood and urine were definitely lower than those in rats not pretreated with antibiotics (normal rats). The radioactivity recovered in the antibiotic-pretreated rat urine was estimated to be only (1)/(100) of that in the normal rat urine. These results clearly demonstrated that the radioactivity detected in the blood and urine of normal rats mostly originated from degradation products of EGCg produced by intestinal bacteria. Furthermore, a main metabolite in the normal rats was purified and identified as 5-(5'-hydroxyphenyl)-gamma-valerolactone 3'-O-beta-glucuronide (M-2). In feces of the normal rats, EGC (40.8% of the fecal radioactivity) and 5-(3',5'-dihydroxyphenyl)-gamma-valerolactone (M-1, 16.8%) were detected. These results suggested that M-1 was absorbed in the body after degradation of EGCg by intestinal bacteria, yielding M-1 with EGC as an intermediate. Furthermore, M-2 was thought to be formed from M-1 in the intestinal mucosa and/or liver, then to enter the systemic circulation, and finally to be excreted in the urine. Taking into account all of the above findings, a possible metabolic route of EGCg orally administered to rats is proposed.

Low tissue plasminogen activator relative to plasminogen activator inhibitor-1 as a marker of cardiac complication in children with Kawasaki disease.

To determine whether the fibrinolytic system is related to the occurrence of cardiac complication in Kawasaki disease, we measured tissue plasminogen activator, plasminogen activator inhibitor-1, and related factors in the plasma of children with Kawasaki disease. Patients (mean age, 1.8 years) were classified into patients with cardiac complication (n = 9) and no complication (n = 14) groups echocardiographically. They underwent single, high-dose, intravenous-gamma-globulin infusion therapy. Blood was drawn just before and the day after the single high-dose intravenous gamma-globulin infusion therapy (acute phase), and at early and late convalescent phases. Leukocytosis was normalized immediately after the single, high-dose, intravenous gamma-globulin infusion therapy. C-reactive protein and fibrinogen were increased in the acute phase and normalized by convalescent phases. D-dimer fraction of fibrin degradation products changed in a similar manner. Tissue plasminogen activator and plasminogen activator inhibitor-1 were increased in acute phase. The tissue plasminogen activator/plasminogen activator inhibitor-1 ratio was lower in the complication group than in the no complication group throughout the observation period (0.095 versus 0.208 after single, high-dose, intravenous gamma-globulin infusion therapy, p = 0.006; 0.094 versus 0.183 at late convalescent phase, p = 0.024). A low tissue plasminogen activator/plasminogen activator inhibitor-1 ratio can predict the propensity for cardiac complication, and can help the physician to decide whether additional therapies are necessary in acute phase Kawasaki disease.

Synthesis of (-)-[4-3H]epigallocatechin gallate and its metabolic fate in rats after intravenous administration.

Because a great deal of attention has been focused on the metabolism of (-)-epigallocatechin gallate (EGCg), quantitative analysis of this compound is required. For this purpose we developed a method of chemical synthesis of [4-(3)H]EGCg. Synthesized [4-(3)H]EGCg showed 99.5% radiochemical purity and a specific activity of 13 Ci/mmol. To clarify the excretion route of EGCg, the radioactivity levels of bile and urine were quantified after intravenous administration of [4-(3)H]EGCg to bile-duct-cannulated rats. Results showed that the radioactivity of the bile sample excreted within 48 h accounted for 77.0% of the dose, whereas only 2.0% of the dose was recovered in the urine. The excretion ratio of bile to urine was calculated to be about 97:3. These results clearly showed that bile was the major excretion route of EGCg. Time-course analysis of the radioactivity in blood was also performed to estimate the pharmacokinetic parameters following intravenous administration of [4-(3)H]EGCg. In addition, EGCg metabolites excreted in the bile within 4 h after the intravenous dose of [4-(3)H]EGCg were analyzed by HPLC. The results showed that 4',4"-di-O-methyl-EGCg was present in the conjugated form and made up about 14.7% of the administered radioactivity.

[Effective combination therapy of plasma exchange and subsequent cyclophosphamide pulses for catastrophic antiphospholipid antibody syndrome: a case report].

A 7-year-old girl with catastrophic antiphospholipid antibody syndrome was described. She firstly admitted to the local hospital with the complaints of persistent fever and abdominal pain, and was diagnosed as systemic lupus erythematosus with the laboratory findings as follows; positive for antinuclear antibody, anti-DNA antibody, and platelet-associated IgG, thrombocytopenia, and hypocomplementemia. 10 days after the initiation of oral prednisolone, she suddenly manifested tonic convulsion and unconsciousness accompanied by high fever. Because of the unresponsiveness to the methylprednisolone pulse therapy for supposed CNS lupus, she was transferred to our hospital. Her unconsciousness persisted, and pulsation on dorsalis pedis was not palpable on admission. Laboratory investigation revealed the falsely positive VDRL, a prolonged aPTT, positive for lupus-anticoagulant and antiphospholipid antibody. The magnetic resonance image demonstrated multiple spotty hyperintensity (T2) in the brain consistent with multiple hemorrhagic infarcts. Arteriogram demonstrated the infarct of dorsalis pedis, and coronary aneurysms. These findings were compatible with the criteria of catastrophic antiphospholipid antibody syndrome, she was diagnosed as catastrophic antiphospholipid antibody syndrome. The plasma exchange and subsequent cyclophosphamide-pulse therapy, which was given once a month for first 6 months, and later, at 3 months intervals, was effectively administered. This combination and oral anti-thrombotic therapy revealed effective for this kind of fatal disorder.

Disposition and pharmacokinetics of phenethyl isothiocyanate and 6-phenylhexyl isothiocyanate in F344 rats.

Naturally occurring phenethyl isothiocyanate (PEITC) and its synthetic homolog 6-phenylhexyl isothiocyanate (PHITC) are both effective inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumor development in A/J mice and F344 rats. To help explain why PHITC is considerably more efficacious than PEITC in chemopreventive potency, comparative disposition and pharmacokinetics data for male F344 rats were obtained after a single gavage dose of 50 micromol/kg (3.71 microCi/micromol) [14C]PEITC or 50 micromol/kg (6.59 microCi/micromol) [14C]PHITC in corn oil. After [14C]PEITC dosing, whole blood 14C peaked at 2.9 h, with an elimination half-life (T1/2e) of 21.7 h; blood 14C from [14C]PHITC-treated rats peaked at 8.9 h, with an T1/2e of 20.5 h. In lungs, the target organ, the T1/2e for [14C]PHITC and its labeled metabolites were more than twice that for [14C]PEITC and its labeled metabolites. The effective dose (area under the concentration-time curve) for 14C from PHITC was greater than 2.5 times the area under the concentration-time curve of 14C from PEITC in liver, lungs, and several other tissues. During 48 h, approximately 16.5% of the administered dose of [14C]PHITC was expired as [14C]CO2, more than 100 times the [14C]CO2 expired by rats treated with [14C]PEITC. In rats given [14C]PEITC, 88.7 +/- 2.2% and 9.9 +/- 1.9% of the dose appeared in the urine and feces, respectively, during 48 h; however, rats given [14C]PHITC excreted 7.2 +/- 0.8% of the dose of 14C in urine and 47.4 +/- 14.0% in the feces. Higher effective doses of PHITC in the lungs and other organs may be the basis, in part, for its greater potency as a chemopreventive agent.

Inhibitory effects of tea catechins, black tea extract and oolong tea extract on hepatocarcinogenesis in rat.

Inhibitory effects of individual tea catechins ((--)-epicatechin, (--)-epigallocatechin, (--)-epicatechin gallate, (--)-epigallocatechin gallate), black tea extract and oolong tea extract on hepatocarcinogenesis were investigated. Male F344 rats received a single dose of diethylnitrosamine (200 mg/kg, i.p.), and thereafter phenobarbital (0.05%) was administered in the drinking water for a period of 6 weeks. Tea catechins, black tea extract or oolong tea extract were given during the entire experimental period, during only the initiation period or during only the promotion period. All four tea catechins, black tea extract and oolong tea extract (0.05 or 0.1%) significantly decreased the number and area of preneoplastic glutathione S-transferase placental form-positive foci in the liver. These results suggest that tea catechins, black tea extract and oolong tea extract have a chemopreventive action against hepatocarcinogenesis.

Levels of pulmonary surfactant protein A in fetal lung and amniotic fluid from protein-malnourished pregnant rats.

Surfactant protein A (SP-A) is a major apo-protein of pulmonary surfactant, which lines the alveolar walls, lowering the surface tension to prevent lung collapse. Pregnant rats were divided into two groups which received a diet with either 5% or 20% protein from gestational day 9. By a sensitive immunoassay, SP-A levels in the fetal lungs and the amniotic fluid showed a dramatic increase with advancing gestation after the initial appearance on gestational day 18 in both diet groups. Significantly lower levels of SP-A in pregnant rats fed 5% protein diet than those in pregnant rats fed 20% protein diet were observed in the fetal lungs on gestational day 21 and in the amniotic fluid on gestational days 20 and 21. The profiles of increased SP-A levels in the amniotic fluid reflected those in the fetal lungs during gestation. Immunohistochemical examination with anti-rat SP-A antibody at 21 days of gestation showed that the immunoreactive staining of bronchiolar epithelial Clara cells and alveolar type II cells were weaker in the fetal lung sections from pregnant rats fed 5% protein diet than in those from pregnant rats fed 20% protein diet. It is concluded that protein malnutrition in pregnant rats affects the biosynthesis of SP-A in the fetal lungs, which may have important consequences for prematurity and decreased respiratory functions in the neonatal lungs at birth.

Immunohistochemical localization of surfactant protein A in N-bis (2-hydroxypropyl) nitrosamine-induced lung tumors in rats.

Surfactant protein A (SP-A) is most abundant protein associated with pulmonary surfactant which is synthesized by alveolar type II cells in the alveoli. In this study, we localized SP-A in experimentally induced pulmonary hyperplasias and tumors in rats, by immunohistochemistry. When rats were given a single intraperitoneal injection of N-bis (2-hydroxypropyl) nitrosamine (BHPN) followed by exposed to mixture gases of O3 and NO2, hyperplastic alveolar type II cells stained with the antibody against SP-A were located in the alveolar walls near the alveolar ducts. Adenomas and adenocarcinomas were stained with the anti-SP-A antibody in the lung parenchyma. These immunohistochemical findings suggested that the lung tumors induced in rats treated with BHPN and additionally exposed to mixture gases of O3 and NO2 are derived from mainly alveolar type II cells.

Absorption of tea catechins into rat portal vein.

Following the oral administration of tea catechins, (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate and (-)-epigallocatechin gallate, respectively, to rats, the presence of these catechins in the portal blood was examined. It was confirmed by HPLC and mass spectrometry analysis that each of the administered catechins was present in the blood. These results clearly indicate that four predominant catechins in fresh tea leaves are absorbed, at least in part, into the rat portal vein.

Sendai virus infection changes the subcellular localization of tryptase Clara in rat bronchiolar epithelial cells.

Tryptase Clara activates the infectivity of Sendai and influenza viruses proteolytically. In this study, we investigated changes in the subcellular localization of tryptase Clara in rat bronchioles with progression of Sendai virus infection. Tryptase Clara and Sendai virus F2 antigen were localized by light and electron immunohistochemical studies. In the uninfected rat lung, tryptase Clara was specifically localized in the secretory granules of respiratory bronchiolar epithelial nonciliated cells, but not in bronchiolar ciliated, or alveolar cells. In the initial stage of Sendai virus infection with slight pathological changes, however, anti-tryptase Clara was highly reactive in luminal peripheral membranes of both nonciliated and ciliated epithelial cells of the bronchioles together with some Sendai virus envelope glycoprotein, F2 antigen. In the progressed stage, tryptase Clara was hard to detect, with heavy accumulation of F2 antigen in the epithelial cells. These immunohistochemical results support our previous findings that in the bronchial lavage fluid tryptase Clara is significantly increased both in amount and activity after viral infection. These results suggest that Sendai virus stimulates the secretion of tryptase Clara from nonciliated bronchiolar epithelial cells to the airway lumen. Accumulation of tryptase Clara on the luminal surface of the bronchiolar epithelial cells and/or in the airway lumen may produce favourable conditions for proteolytic viral activation and multiplication.

A non-glycosylated form of pulmonary surfactant protein A appears in rat amniotic fluid.

Surfactant protein A (SP-A) is a family of glycoproteins that have a triplet with 26, 32 and 36 kDa under reducing conditions in rat lung. We wanted to evaluate the SP-A forms in amniotic fluid of pregnant rats compared to those found in rat lungs. By Western blot analysis, glycosylated SP-A, was not found in the amniotic fluid in contrast to the pulmonary surfactant triplet SP-A, which comprises a 26 kDa protein and its glycosylated 32 and 36 kDa forms. The SP-A concentration in amniotic fluid was barely detectable at 18 days of gestation (20 +/- 12 ng.ml-1), and then increased and reached 700 +/- 333 ng.ml-1 at the final gestational day 21, as determined by an enzyme-linked immunoabsorbent assay. Immunohistochemically, SP-A was found in some epithelial cells of larger respiratory bronchi, but not, or to a lesser degree, in smaller respiratory bronchi at gestational day 18. At 21 days of gestation, SP-A was detected in bronchial and bronchiolar nonciliated epithelial Clara cells, alveolar epithelial type II cells and some alveolar macrophages. The ratio of the 26, 32 and 36 kDa SP-A forms in bronchoalveolar, bronchobronchiolar and tracheal lavage fluids prepared from adult rats was 6:29:65, 84:5:11 and 100:0:0, respectively. These findings show the presence of a non-glycosylated SP-A in rat amniotic fluid. This may reflect the increased ratio of non-glycosylated SP-A to bronchoalveolar, bronchobronchiolar and tracheal lavage fluids, respectively.

Serum lipoprotein(a) in healthy Japanese children 5 years of age.

Serum lipoprotein(a) [Lp(a)] concentrations were investigated in 155 Japanese children aged 5 years. The frequency distribution of Lp(a) concentrations was highly skewed and ranged from 1 to 109 mg/dL. The mean and median values of Lp(a) were 16.5 mg/dL (s.d. 17.3 mg/dL) and 12 mg/dL. The incidence of Lp(a) concentrations > or = 30 mg/dL was significantly high in children with total cholesterol > or = 200 mg/dL, not including the case of familial hypercholesterolaemia. Log Lp(a) values showed an inverse correlation with bodyweight and body mass index. No significant differences in Lp(a) levels could be seen between the groups according to the presence or absence of coronary heart disease and cerebral vascular accident in family histories. The results suggest that Lp(a) in Japanese children aged 5 years was essentially the same as that in adults. Further study may be needed to disclose the factors that influence Lp(a) concentration in childhood.

Heterogeneity of immunohistochemical staining with pulmonary surfactant protein A among fractionated alveolar macrophages which involves metabolism of pulmonary surfactant.

Alveolar macrophages (AM) which are separated into four fractionated subpopulations (I, II, III and IV), represented differential immunohistochemical staining with antibody against pulmonary surfactant protein A (SP-A). In light microscopy, the least dense AM (fraction I) were intensely stained with antibody to SP-A in numerous granules of the cytoplasm, whereas the most dense cells (fraction IV) showed immuno-reactivity with the antibody in several granules distributed in the spreading and elongating cytosol. By Western blot analysis, antibody to SP-A recognized a triplet of nature molecules of SP-A in AM lysate. However, the antigen of the AM lysate almost disappeared when the cells were cultured for more than two days, which indicate that AM do not synthesize SP-A and have digested intracellular SP-A during the cultivation. Immunoelectron microscopically, AM of fraction IV sometimes had very large vacuoles including lamellar body-like structures, probably pulmonary surfactant immediately after taken up from the alveolar lumen by them, which were heavily deposited with gold particles indicating antigenic site of SP-A. Whereas cells of fraction I contained numerous cytoplasmic vacuoles that were frequently labelled with the immuno-gold particles and were not associated with lamellar body-like structures, which may indicate that the materials in the vacuoles are digesting. The results of this experiments suggest that pulmonary surfactant, layered on the alveolar epithelium, is in part taken up by higher dense AM and is digested during a process of their maturation in the direction of lower dense cells, which undergo an important role of metabolism of pulmonary surfactant by AM subpopulations.

Effects of pulmonary surfactant and surfactant protein A on phagocytosis of fractionated alveolar macrophages: relationship to starvation.

Pulmonary surfactant isolated from bronchoalveolar lavage fluid of rat lung contained a high content of surfactant protein A (SP-A) in starved for 2 days compared to fed controls, but this phenomena returned to baseline following more than 4 days starvation. As determined by immunoperoxidase staining of lung sections using SP-A antibody, SP-A could be consistently observed in nonciliated bronchiolar (Clara) cells, alveolar type II cells and some alveolar macrophages (AM). Fc receptor-mediated phagocytosis of AM was enhanced by SP-A, which was dependent on the dosis and reached a maximum at 10 micrograms of SP-A/ml. Antibody to SP-A completely inhibited the enhanced response of phagocytosis. When exposed AM subpopulations, separated into four fractions (I, II, III and IV) by discontinuous Percoll gradient, to SP-A or pulmonary surfactant prepared from rats fed and starved for 2 days enhanced their phagocytic activity in high dense cells (III and IV), particularly to SP-A and pulmonary surfactant from rats starved for 2 days. Whereas little change in lower dense fractions (I and II) were seen in all exposures except for SP-A that enhanced the cells of fraction II. These results supported the concept that pulmonary surfactant and its apoprotein, SP-A, are a factor to regulate lung defense system including activation of AM that undergo different processes following starvation.

Refractory hypertension in childhood--efficacy of captopril therapy.

Because of the advance of techniques and age-matched apparatus for blood pressure measurement, and because of the availability of age-related normal values in childhood, the knowledge of the number of children having elevated blood pressures has recently improved. In a group of healthy children, the first important task is to determine how many incidences of "essential hypertension" there are among them, which may appear in childhood and persist into adulthood. This should urge us to undertake periodical examinations of healthy children. On the other hand, the treatment of "secondary hypertension" has similarly been improved. Since 1979 in particular, captopril, an orally active angiotensin I-converting enzyme inhibitor, has successfully been administered to treat children with malignant hypertension and who respond poorly to conventional antihypertensive therapies. We report 3 cases that received captopril for refractory hypertension: a 2-year-old boy with renal and renovascular anomalies, a 7-year-old boy with moyamoya disease after surgical operation, and a 17-year-old youth with Cushingoid syndrome due to chronic administration of steroids against mixed connective tissue disease. After the introduction of captopril, good pressure control was obtained in all 3 cases, although reasonable effects of measurement values of the renin-angiotensin-aldosterone system (decrease in angiotensin I & II, increase in I/II ratio, etc.) were found only in the first case.