Effect of endurance training supplemented with green tea extract on substrate metabolism during exercise in humans.

Endurance training and ingestion of green tea extract (GTE), composed mainly of tea catechins (TC), are well known to enhance fat metabolism. However, their synergistic effects remain to be fully elucidated. We tested the hypothesis that endurance training supplemented with GTE would further accelerate whole-body fat utilization during exercise, compared with training alone, in humans. Twelve healthy male subjects [peak oxygen consumption (VO2peak), 50.7 ± 1.3 (SEM) mL/kg/min] were divided into two groups: GTE and placebo (PLA) groups. Subjects in both groups performed a cycle ergometer exercise at 60% of VO2peak for 60 min/day, 3 days/week, and daily ingested 572.8 or 0 mg TC in GTE and PLA groups for 10 weeks, respectively. Before and after training, respiratory gas exchange was measured during 90-min exercise at pre-training ∼55% of VO2peak. After training, the average respiratory exchange ratio during exercise remained unchanged in the PLA group (post-training: 0.834 ± 0.008 vs pre-training: 0.841 ± 0.004), whereas it was lower in the GTE group (post-training: 0.816 ± 0.006 vs pre-training: 0.844 ± 0.005, P<0.05). These results suggest that habitual GTE ingestion, in combination with moderate-intense exercise, was beneficial to increase the proportion of whole-body fat utilization during exercise.

Effects of functional training of dysphagia to prevent pneumonia for patients on tube feeding.

OBJECTIVE: The purpose of this study was to evaluate the effects of functional training on outbreak frequency of pneumonia for the elderly dysphagia patients who were being tube fed. METHODS: Subjects were divided into two groups; one group (n = 10) received oral care (i.e. non-training group) and the other group (n = 11) received functional training of dysphagia in addition to oral care (i.e. training group). The dental health team treated subjects once a week for 3 years (1999-2001). The frequency of pneumonia outbreaks and changes in activities of daily living scale (ADL) were evaluated for each year. RESULT: It was recognised that the frequency of pneumonia in the training group decreased year by year (p < 0.05). Cognitive items in ADL improved in two subjects of the training group. No statistical differences were recognised in the non-training group. CONCLUSION: It was suggested that once-a-week functional training of dysphagia with professional oral care might be effective in preventing pneumonia for elderly people who were being tube fed.

Effects of Saiko-ka-ryukotsu-borei-to in patients with hyperlipidemia.

We measured and compared levels of platelet-derived microparticles (PMPs), monocyte-derived microparticles (MMPs), CD62P on activated platelets, soluble E-selectin (sE-selectin), and anti-oxidized low density lipoprotein (LDL) antibody in hyperlipidemia patients and control subjects. Binding of anti-GPIIb/IIIa and anti-GPIb monoclonal antibodies to platelets was not significantly different between hyperlipidemia patients and controls. However, expression of CD62P on platelets and levels of PMPs were higher for hyperlipidemia patients than in controls, although the difference between groups in CD62P expression was not significant (PMPs: 534 +/- 63 vs. 388 +/- 47, p < 0.05; CD62P: 9.1% +/- 1.45 vs. 7.3% +/- 1.15, N.S.). Although there were no differences in expression of CD36 and CD40 by monocytes between the two groups, levels of MMPs were higher in hyperlipidemia patients than in controls (MMPs: 147 +/- 21 vs. 59 +/- 8, respectively, p < 0.01). Levels of anti-oxidized LDL antibody and sE-selectin were also higher in hyperlipidemia patients. We studied the effects of Saiko-ka-ryukotsu-borei-to on levels of these factors in patients with elevated triglyceride levels. After Saiko-ka-ryukotsu-borei-to treatment, levels of CD62P, PMPs, sE-selectin, and anti-oxidized LDL antibody were reduced significantly. Levels of triglycerides, total cholesterol and MMPs also decreased, but the changes were not significant. These findings suggest that Saiko-ka-ryukotsu-borei-to prevents the development of vascular complications in hyperlipidemia patients.

Effects of citrate on renal stone formation and osteopontin expression in a rat urolithiasis model.

Previous studies have described the inhibitory effects of citrate on calcium oxalate crystallization in place of crystal growth, but the effects of citrate on matrix proteins of stones has not been studied in vivo. To examine the effect of citrate on the matrix, we investigated the effect of citrate on osteopontin (OPN) expression, which we had previously identified as an important stone matrix protein. Control rats were treated with saline while rats of the stone group were treated with ethylene glycol (EG) and vitamin D3, and the citrate groups (low-dose and high-dose groups) were treated with a citrate reagent compound of sodium citrate and potassium citrate, in addition to EG and vitamin D3. The rate of renal stone formation was lower in the citrate groups than in the stone group. This was associated with a low expression of OPN mRNA in citrate-treated rats relative to that in the stone group. Citrate was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that citrate prevents renal stone formation by acting against not only the crystal aggregation and growth of calcium oxalate but also OPN expression.

Effects of allopurinol on renal stone formation and osteopontin expression in a rat urolithiasis model.

BACKGROUND: The inhibitory effect of allopurinol on calcium oxalate urolithiasis has been reported, but its effect on stone matrix proteins has not been studied in vivo. To clarify the effect of allopurinol on the matrix, we investigated its effect on the expression of osteopontin (OPN), which we previously identified as an important stone matrix protein. METHODS: Control rats were not treated. Rats of the stone group were given ethylene glycol (EG) and vitamin D(3), while the allopurinol groups (low-dose group and high-dose group) were treated with allopurinol in addition to receiving EG and vitamin D(3). RESULTS: The rate of renal stone formation was lower in the allopurinol groups than in the stone group. This was associated with a low expression of OPN mRNA in allopurinol-treated rats relative to that in the stone group. CONCLUSION: Allopurinol was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that allopurinol prevents renal stone formation by acting against not only the control of oxalate but also OPN expression.

Predominant information transfer from layer III pyramidal neurons to corticospinal neurons.

Connections of layer III pyramidal neurons to corticospinal neurons of layer V and corticothalamic neurons of layer VI in the rat primary motor cortex were examined in brain slices by combining intracellular staining with Golgi-like retrograde labeling of corticofugal neurons. Forty layer III pyramidal neurons stained intracellularly were of the regular-spiking type, showed immunoreactivity for glutaminase, and emitted axon collaterals arborizing locally in layers II/III and/or V. Nine of them were reconstructed for morphologic analysis; 15.2% or 3.8% of varicosities of axon collaterals of the reconstructed neurons were apposed to dendrites of corticospinal or corticothalamic neurons, respectively. By confocal laser scanning and electron microscopy, some of these appositions were revealed to make synapses. These findings suggest that corticospinal neurons receive information from the superficial cortical layers four times more frequently than corticothalamic neurons. The connections were further examined by intracellular recording of excitatory postsynaptic potential (EPSP) that were evoked in layer V and layer VI pyramidal neurons by stimulation of layer II/III. EPSPs evoked in layer V pyramidal neurons showed short and constant onset latencies, suggesting their monosynaptic nature. In contrast, most EPSPs evoked in layer VI pyramidal neurons had long onset latencies, showed double-shock facilitation of onset latency, and were largely suppressed by an N-methyl-D-aspartic acid receptor blocker, suggesting that they were polysynaptic. The results suggest that information from the superficial cortical layers is transferred directly and efficiently to corticospinal neurons in layer V and thereby exerts an important influence on cortical motor output. Corticothalamic neurons are, in contrast, considered relatively independent of, or indirectly related to, information processing of the superficial cortical layers.

Prevention of N-methylnitrosourea-induced colon carcinogenesis in rats by oxygenated carotenoid capsanthin and capsanthin-rich paprika juice.

Epidemiological and animal studies have provided evidence that dietary carotenoids may reduce the risk of certain types of cancer. An inhibitory activity of oxygenated carotenoid capsanthin, a potent antioxidant, and paprika juice rich in capsanthin (3.54 mg/100 ml) against colon carcinogenesis was investigated in F344 rats. In Experiment I (short-term assay), six rats each were given a gavage of 5 mg, 0.2 mg, or 0.008 mg capsanthin six times a week for Weeks 2-6 after receiving three intrarectal doses of 4 mg N-methylnitrosourea in Week 1. The number of colonic aberrant crypt foci, preneoplastic lesions, at Week 6 was significantly fewer (by 42%) in the 0.2 mg capsanthin group, but not in other groups, than the control group. In Experiment II (long-term assay), five groups of 30 or 25 rats each received an intrarectal dose of 2 mg N-methylnitrosourea three times a week for Weeks 1-3, and had either of 10 p.p.m. or 2 p.p.m. capsanthin solutions, 1:2.5 and 1:16.7 diluted solution of paprika juice (containing 10 p.p.m. or 2 p.p.m. capsanthin), and tap water (control fluid) as drinking fluid throughout the experiment. The experimental groups were fed 0.2 mg or 0.04 mg capsanthin/day/rat. The colon cancer incidence at Week 30 was significantly lower in the highly diluted paprika juice group (40%), but not in the moderately diluted paprika juice group (60%) and the capsanthin solution groups (68% and 68%) than the control group (83%). The results suggested that paprika juice may affect colon carcinogenesis. However, capsanthin alone failed to inhibit colon tumorigenesis, in spite of suppression of aberrant crypt foci formation in the short-term assay. Further studies are needed to explain this discrepancy.

Blood pressure biofeedback treatment of white-coat hypertension.

OBJECTIVE: The objective of the study was to compare blood pressure (BP) biofeedback treatment (BF) effects between white-coat hypertension and essential hypertension. METHODS: Fifteen white-coat hypertensive out-patients and 23 essential hypertensive out-patients were randomly assigned to groups A or B. Subjects in group A underwent BF once a week for a total of four sessions. Those in group B visited the clinic only to measure BP and later underwent the same BF. RESULTS: In group A, BPs of white-coat hypertensives and essential hypertensives were significantly reduced by 22/11 and 14/8 mmHg, respectively. In group B, they were unchanged during the same period but later suppressed by BF. Under BF, pulse and respiratory rates were significantly higher, and elevation of diastolic BP due to mental stress testing was better suppressed in white-coat hypertensives than in essential hypertensives. CONCLUSION: This treatment was effective in both types of hypertension, and pressor response to stress seems to be important in the differentiated BF effect.

Cbfa1 is a positive regulatory factor in chondrocyte maturation.

Cbfa1 is a transcription factor that belongs to the runt domain gene family. Cbfa1-deficient mice showed a complete lack of bone formation due to the maturational arrest of osteoblasts, demonstrating that Cbfa1 is an essential factor for osteoblast differentiation. Further, chondrocyte maturation was severely disturbed in Cbfa1-deficient mice. In this study, we examined the possibility that Cbfa1 is also involved in the regulation of chondrocyte differentiation. mRNAs for both Cbfa1 isotypes, type I Cbfa1 (Pebp2alphaA/Cbfa1) and type II Cbfa1 (Osf2/Cbfa1 or til-1), which are different in N-terminal domain, were expressed in terminal hypertrophic chondrocytes as well as osteoblasts. In addition, mRNA for type I Cbfa1 was expressed in other hypertrophic chondrocytes and prehypertrophic chondropcytes. In a chondrogenic cell line, ATDC5, the expression of type I Cbfa1 was elevated prior to differentiation to the hypertrophic phenotype, which is characterized by type X collagen expression. Treatment with antisense oligonucleotides for type I Cbfa1 severely reduced type X collagen expression in ATDC5 cells. Retrovirally forced expression of either type I or type II Cbfa1 in chick immature chondrocytes induced type X collagen and MMP13 expression, alkaline phosphatase activity, and extensive cartilage-matrix mineralization. These results indicate that Cbfa1 is an important regulatory factor in chondrocyte maturation.

Blood pressure biofeedback treatment, organ damage and sympathetic activity in mild hypertension.

BACKGROUND: Although biofeedback treatment is reported to be useful for patients with mild hypertension as an adjunct to medication, it is not certain whether the presence of organ damage affects its efficacy. The aim of this study is to clarify the clinical effects of biofeedback on mild hypertension in the absence and presence of organ damage. METHODS: Eleven mildly hypertensive outpatients without damage to the heart, brain, retina or kidney (4 men and 7 women), aged 40-65 years, and 11 mildly hypertensive outpatients with target organ damage and matching variables for age, sex and medication were included in this study. They underwent biofeedback treatment once a week for a total of four sessions. RESULTS: As a result of these sessions, mean blood pressures (MBP) in the organ-damage-negative (-) group and in the organ-damage-positive (+) group were significantly reduced by 12 +/- 11 and 12 +/- 8, respectively. The decrease was still significant 3 months after the treatment in the organ-damage (-) group, whereas no significant change was found 1 or 3 months after the treatment in the organ-damage (+) group. Throughout these sessions, the ratio of low frequency to high frequency of heart rate variance as well as systolic and MBP gradually decreased in each group (p < 0.01); this ratio of heart rate variance was smaller, and the alpha-wave amplitude on the electroencephalogram was larger in the organ-damage (-) group (p < 0.05). CONCLUSION: These results suggested that biofeedback intervention may be effective in mild hypertension, especially when the patient is organ damage (-). Sympathetic activity seems to play an important role in the differentiated response.

The effect of takusha, a kampo medicine, on renal stone formation and osteopontin expression in a rat urolithiasis model.

Kampo medicine is a traditional Japanese therapeutic system which originated in China and was used to treat various diseases for hundreds of years. Kampo medicine had been also used for the cure and the prevention of urinary calculi for many years, but the effect and the mechanism of this use of kampo medicine are unclear. We examined the inhibitory effect of the kampo medicine takusha on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) and vitamin D3 in rats. We also investigated the effect of takusha on osteopontin (OPN) expression, which we previously identified as an important stone matrix protein. The control group rats were non-treated; the stone group rats were administered EG and vitamin D3, and the takusha group was administered takusha in addition to EG and vitamin D3. The rate of renal stone formation was lower in the takusha group than in the stone group; thus, the OPN expression in the takusha group was smaller than in the stone group. Takusha was effective in preventing oxalate calculi formation and OPN expression in rats. These findings suggest that takusha prevents stone formation including not only calcium oxalate aggregation but also proliferation.

Prevention of N-methylnitrosourea-induced colon carcinogenesis in F344 rats by lycopene and tomato juice rich in lycopene.

Epidemiological studies have suggested a protective effect of lycopene and lycopene-rich tomatoes against various cancers. Here, the inhibition of colon carcinogenesis by lycopene and tomato juice was investigated. Seven-week-old female F344/NSlc rats received an intrarectal dose of 2 mg (experiment I) or 4 mg (experiment II) of N-methylnitrosourea 3 times a week for 3 weeks, and had free access to one of 4 drinking fluids: plain water (control group), 17 ppm lycopene water solution (Ly group), and diluted tomato juice containing 17 ppm (Tj group) or 3.4 ppm (tj group) lycopene, throughout the experiments. The colon cancer incidence at week 35 was significantly lower in the Tj group, but not in the Ly group, than in the control group: 21% and 33% vs. 54%, in experiment I (24 rats in each group). It was significantly lower in the Tj group than in the tj and control groups, 40% vs. 72% and 84%, in experiment II (25 rats in each group). An appreciable amount of lycopene (0.02 microgram/g) was detected in the colon mucosa of rats in the Tj group, but not in the tj group. The results suggest that tomato juice rich in lycopene may have a protective effect against colon carcinogenesis.

HLA and HPA typing in idiopathic thrombocytopenic purpura patients treated with Kami-kihi-to.

We performed human leukocyte antigen (HLA) and human platelet antigen (HPA) in patients with Kami-kihi-to-responsive idiopathic thrombocytopenic purpura. The HLA-A2, A61 and Cw1 were significantly increased in responders compared with nonresponders, as were HLA DRB1 *0901, DRB1 *1502, and DPB1 *0501. In contrast, HLA DPB1 *0201 and DPB1 *0901 were significantly decreased in responders. The a/b genotype of HPA-2 and a/a genotype of HPA-3 were markedly increased in nonresponders, and anti-GPIb antibody was also increased. These results suggest that HLA, HPA, and anti-GP antibody studies may predict the response of idiopathic thrombocytopenic purpura to Kami-kihi-to.

Effect of Polygala tenuifolia root extract on the tumor necrosis factor-alpha secretion from mouse astrocytes.

We investigated whether an aqueous extract of Polygala tenuifolia root (PTAE) inhibits secretion of tumor necrosis factor-alpha (TNF-alpha) from primary cultures of mouse astrocytes. PTAE dose-dependently inhibited the TNF-alpha secretion by astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). Interleukin-1 (IL-1) has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore also investigated whether IL-1 mediated inhibition of TNF-alpha secretion from primary astrocytes by PTAE. Treatment of PTAE to astrocytes stimulated with both LPS and SP decreased IL-1 secretion to the level observed with LPS alone. Moreover, incubation of astrocytes with IL-1 antibody abolished the synergistic co-operative effect of LPS and SP. These results suggest that PTAE may inhibit TNF-alpha secretion by inhibiting IL-1 secretion and that PTAE has an anti-inflammatory activity on the central nervous system curing some pathological disease states.

Impaired expression of noncollagenous bone matrix protein mRNAs during fracture healing in ascorbic acid-deficient rats.

In scorbutic patients, fractures are slow to heal because of impaired collagen synthesis. To investigate the influence of impaired collagen synthesis on the differentiation and proliferation of osteogenic and chondrogenic cells, we examined the expression of genes encoding bone matrix proteins, including osteonectin (ON), osteopontin (OPN), osteocalcin (OC), and matrix Gla protein (MGP), as differentiation markers for osteogenic and chondrogenic cells during fracture healing in Osteogenic Disorder Shionogi (ODS) rats, which have a hereditary defect in the ability to synthesize ascorbic acid (Asc). In ODS rats without Asc supplementation, intramembranous ossification was completely inhibited. Although a few fibroblast-like cells expressing ON mRNA were observed, no OPN mRNA-expressing cells were detected. During endochondral ossification, a small amount of metachromatic staining cartilage appeared at the fracture site, but there was no provisional calcification zone in the cartilage. Chondrocytes expressed ON and MGP mRNAs, but not OPN mRNA. When Asc was given to these rats, callus formation was soon detected around the fracture site, while OPN mRNA was expressed by differentiated osteoblasts and hypertrophic chondrocytes. Our data indicate that impaired collagen synthesis due to Asc deficiency inhibited the increase of ON and MGP mRNA-expressing cells as well as the appearance of OPN mRNA-expressing cells. Since OPN is considered to play an important role in normal and pathological mineralization, lack of OPN mRNA expression accompanying impaired collagen synthesis may have a role in defective mineralization and delayed fracture healing in scurvy.

Assessment of patients by DSM-III-R and DSM-IV in a Japanese psychosomatic clinic.

BACKGROUND: The aim of this study was to investigate the clinical features of psychosomatic disorders in Japan. METHODS: A total of 1,432 outpatients (515 males and 917 females; 9-95 years of age, mean age 36) attending a psychosomatic clinic for the first time were assessed by the DSM-III-R or DSM-IV semistructured interview. RESULTS: Major ICD-10 diagnoses found were eating disorder, other anxiety disorders, autonomic nervous dysfunction, somatoform disorders, and irritable bowel syndrome. The most frequent diagnosis on the DSM-III-R and DSM-IV axis I was 'somatoform disorders not otherwise specified', followed by bulimia nervosa, 'depressive disorder not otherwise specified', anorexia nervosa, conversion disorder, major depression or depressive disorder, 'panic disorder with agoraphobia', and 'psychological factors affecting physical or medical condition'. On axis II, 11-17% of the patients met the criteria for personality disorder. On axis IV, 78-80% had mild or moderate psychosocial stress; major psychosocial and environmental problems classified by the DSM-IV were the problems with primary supports and occupation. CONCLUSIONS: The results seem to reinforce the belief that the diagnoses on the DSM-III-R and DSM-IV axis I are inadequate for describing psychosomatic phenomena. A new diagnostic system in combination with the multidimensional assessments by the DSM-III-R and DSM-IV is needed to form the common guidelines of diagnoses and therapies in psychosomatic medicine.

Morphologic and hematologic characteristics of storage pool deficiency in beige rats (Chédiak-Higashi syndrome of rats).

Characterization of beige rats as having a platelet storage pool deficiency (SPD) was undertaken. Platelets from beige rats, an animal model of Chédiak-Higashi syndrome (CHS), completely lacked the ability to aggregate when stimulated with high dosages of collagen (50 micrograms/ml), and lacked secondary aggregation induced by adenosine diphosphate (ADP). Concentrations of ADP, ATP, and serotonin in the platelets of beige rats were significantly lower than those of control rats. However, platelet count remained within normal values. Electron microscopy revealed that platelets had fewer dense granules, whereas other organelles had normal structure. This morphologic and functional evidence confirms that platelets of beige rats have the typical characteristics of SPD.

Clinical effects of blood pressure biofeedback treatment on hypertension by auto-shaping.

OBJECTIVE: Although biofeedback has been reported to be efficacious in the treatment of hypertension, the degree of response has varied. This study investigated the mechanisms of blood pressure reduction by biofeedback. METHOD: Thirty outpatients with essential hypertension (10 men and 20 women) aged 38 to 65 years were studied. Subjects were randomly assigned to group A or B. Subjects in group A underwent biofeedback treatment once a week for a total of four sessions. Those in group B self-monitored their blood pressure during the sessions as the control period and later underwent the same biofeedback treatment. RESULTS: Blood pressure measured by doctor was reduced by 17 +/- 18/8 +/- 7 (p < .01) and elevation of pressure induced by mental stress testing was suppressed by 8 +/- 9 (p < .05)/4 +/- 8 during the treatment period in group A (mm Hg). In group B, both blood pressure measured by doctor and elevation of pressure by mental stress testing remained unchanged during the control period and they were later suppressed by 20 +/- 15/9 +/- 7 (p < .01) and 11 +/- 10(p < .05)/5 +/- 9 by the biofeedback treatment. Self-monitored pressure in both groups tended to decrease by the biofeedback treatment. Systolic and diastolic pressures as well as pulse rate decreased, skin temperature increased, and alpha-wave amplitude on electroencephalography increased during the therapy (p < .05). CONCLUSION: This treatment was effective in suppressing the pressor response to stress. Patients whose blood pressure increases with stress may be suited for biofeedback intervention.

Effects of all-trans retinoic acid on choriocarcinoma cells in vitro.

OBJECTIVES: To determine the activities of all-trans retinoic acid (RA) on choriocarcinoma cells in vitro. METHODS: The antiproliferative effect of all-trans RA on 4 choriocarcinoma cell lines was measured by the MTT assay. The effect of all-trans RA combined with methotrexate or actinomycin-D was then examined. The effect of all-trans RA on hCG secretion was also studied. The gene expression of retinoic acid receptors (RARs) was examined by RT-PCR. RESULTS: All-trans RA inhibited cell proliferation dose- and time-dependently; a 6-day exposure to 1 microM all-trans RA suppressed the cell growth by 67.8%-82.0% compared to the controls. An enhanced effect was observed in the combined administration of all-trans RA and methotrexate or actinomycin-D. The secretion of hCG increased 4-fold to 9-fold by the addition of 1 microM all-trans RA. RARs genes were expressed in all cell lines. CONCLUSION: The anticancer activity presented here appears to warrant further evaluation of all-trans RA as adjuvant therapy for choriocarcinoma.

In vitro and in vivo antibacterial activities of TOC-50, a new parenteral cephalosporin, against Enterococcus faecalis.

In vitro and in vivo antibacterial activities of TOC-50, a new parenteral cephalosporin, were assessed against Enterococcus faecalis. In vitro, TOC-50 had excellent activity, stronger than that of penicillin G, sulbactam/ampicillin, tazobactam/piperacillin, the cephalosporins tested, imipenem, vancomycin, gentamicin, tobramycin, arbekacin, amikacin, minocycline and ofloxacin against clinically isolated strains. In addition, TOC-50 was more active than penicillin G, sulbactam/ampicillin and imipenem against vancomycin-resistant E. faecalis NCTC 12201. In terms of bactericidal effect against the same strain, TOC-50 was superior to sulbactam/ampicillin and imipenem. In murine systemic infection models, TOC-50 had a potent protective activity against E. faecalis 42. Its protective activity was stronger than that of imipenem or vancomycin.