Biomedical subjects

S Ohkawa

Publications and source records attributed to S Ohkawa.

At least 19 recordsLinked to original sources

PubMed2005

Evaluating the effects of spatial frequency on migraines by using pattern-reversal visual evoked potentials.

OBJECTIVE: To clarify the effects of contrast and spatial frequency in patients with migraine by means of pattern-reversal visual evoked potentials (PVEPs). METHODS: PVEPs were obtained from 14 patients who had migraine without aura (MO), 11 patients who had migraine with aura (MA), and 25 age-matched, healthy controls (CO). PVEPs were binocularly recorded with a reversal rate of 1Hz (2 reversal/s) at 3 spatial frequencies (0.5, 1.0 and 4.0 cpd) at high (98%), medium (83%) and low (29%) contrast. N75, P100 and N135 latency and the amplitudes of P50-N75, N75-P100 and P100-N135 were analyzed. RESULTS: Increased amplitude of PVEPs in patients with migraines were revealed at 3 different spatial frequencies in all components. The MO and the MA showed increased amplitudes mostly in high contrasts (98%). These findings were detected more at a high spatial frequency (4.0 cpd) than at a low spatial frequency (0.5 cpd). Increased amplitude with prolonged latency of N135 were found both in MO and MA at 4.0 cpd. CONCLUSIONS: We conclude that pattern stimuli of high contrasts may be particularly effective in uncovering abnormal cortical reactivity which may be modified in the primary and secondary visual cortex in the interictal state of migraine. SIGNIFICANCE: These findings indicate that there is abnormal visual cortex processing in patients with migraine.

Adult↗

PubMed2004

Positive impact of social intervention on disturbed neurobehavioral function in an elderly community-dwelling population: longitudinal investigation for longevity and aging in Hokkaido County (LILAC).

Several kinds of health consultation and rehabilitation for functional disorders aimed at stroke prevention and maintenance of cognitive function in an elderly population in Hokkaido county, Japan. Changes in cardiovascular and neurobehavioral endpoints between 2000 and 2002 were assessed in 72 of 115 subjects over 75 years of age. Direct social intervention, including lifestyle modification can have a positive impact, notably on subjects with cardiovascular disorders.

Aged↗

PubMed2003

Chronomics for chronoastrobiology with immediate spin-offs for life quality and longevity.

Effects of geomagnetic disturbance on heart rate variability (HRV), the 1/f fractal scaling in particular, are being assessed in adults living at high latitude, where magnetic storms are more frequent and more intense than at lower latitudes. The latter may constitute a signal or a proxy, and possibly a mechanism underlying both undesirable and desirable effects, depending upon circumstances yet to be elucidated. Any circadecadal stage-dependence of morbidity and/or mortality from certain conditions such as myocardial infarctions remains to be studied in both adult and pediatric populations. Further work could thus examine whether any associations of geomagnetic disturbances may account, at least in part, through effects upon the circulation, for long-term infra-annual changes, possibly anchored in the population's gene pool, observed in a number of anthropologic measurements at birth as well as in other population statistics. In order to assess the development of several chronome components of the electrocardiogram (ECG), around-the-clock ambulatory ECG were recorded from 19 infants (25 days-3 months of age), 22 children (3-9 years of age), 18 boys and girls (10-14 years of age), pubertal boys (15-20 years of age), and 10 young men (21-29 years of age). Time- and frequency-domain measures of HRV were obtained by spectral analysis, using the maximal entropy method (MEM). The frequency of detection of the circadian, circasemidian and circaoctohoran components, with periods of about 24, 12 and 8 h, respectively, was compared among the five groups for several HRV endpoints, notably 1/f fractal scaling, total spectral power within a 5-min span, and its distribution into several frequency regions. A circadian component is already detectable in a sizeable proportion of infants and children for most of the HRV indices considered. The incidence of detection of the circadian component increases with age for the spectral power in different frequency regions, notably around 10.5 s ("LF") and around 3.6 s ("HF"); it peaks around puberty for 1/f in our data; and it did not detectably change with age for the total spectral power. Similar changes with age are not observed for the circasemidian or circaoctohoran components. The latter characterizes primarily 1/f and less so the about 3.6 s power ("HF"). Several aspects of the HRV chronome may thus develop differently as a function of age. In 2000, we began a community-based study named "Longitudinal Investigation of Longevity and Aging in Hokkaido County (LILAC study)". The ambulatory blood pressure (BP) of middle-aged subjects, aged 40-74 years, was monitored 7-day/24-h, and the cardiovascular and neurobehavioral functions of elderly people above 75 years were evaluated. Our goal was the prevention of stroke and myocardial infarction and the decline in cognitive function of the elderly in a community. Of 115 elderly people recruited in a longitudinal community-based study in 2000, 72 completed yearly follow-ups in 2002. A cardiovascular score based on BP, pulse wave velocity, and 1-h ECG-based HRV endpoints served to distinguish between normal, mildly disordered, or disordered participants. A comparison of cognitive function in 2002 vs. 2000, assessed with the MMSE, HDSR, the Up & Go and Functional Reach tests, gauged any effect of social intervention. Cognitive function was maintained or improved, especially for people suffering from hypertension, tachycardia, or a decreased HRV, suggesting that cardiovascular function is a major factor affecting cognitive function.

Cardiovascular Diseases↗

PubMed2002

Graded response of heart rate variability, associated with an alteration of geomagnetic activity in a subarctic area.

It is becoming recognized that geomagnetic activity may influence biological processes, including the incidence of various human diseases. There is evidence that heart rate variability (HRV) may serve not only as an index of autonomic coordination of the circulation, but also as a powerful predictor of risk in apparently healthy subjects. This study focuses on the effects of geomagnetic disturbance on HRV, by comparing different indices of HRV of young, healthy men living in a subarctic area on days of low (Ap; 0-7), middle (Ap; 7-20), and high (Ap; 20-45) geomagnetic activity. The effect of geomagnetic disturbance on HRV is examined on the basis of 7-day records by Holter ECG, obtained longitudinally on 5 clinically healthy men, 21-31 years of age, in Alta, Norway (70 degree N). Frequency- and time-domain measures of HRV were analyzed for each subject on separate 24-hour spans. A graded alteration of HRV endpoints was found in association with increased geomagnetic activity. As time-domain measures of HRV, SDNNIDX and the 90% length of the Lorenz plot decreased statistically significantly on days with increased geomagnetic disturbance (p = 0.0144 and p = 0.0102, respectively). A graded decrease in frequency-domain HRV measures was also validated statistically for the total spectral power (decrease of 18.1% and 31.6% on days when 7 < Ap < 20 and 20 < Ap < 45 versus days when Ap < 7; p = 0.0013). The decrease in spectral power was mainly found at frequencies below 0.04 Hz, in the "ultra-low-frequency" (0.0001-0.003 Hz; 18.1% and 27.5% decrease, respectively; p = 0.0102) and "very-low-frequency" (0.003-0.04 Hz; 12.9% and 28.6% decrease, respectively; p = 0.0209) regions of the spectrum. The decrease in spectral power was much less pronounced around 10.5 sec ("low frequency"; N.S.) and around 3.6 sec ("high frequency"; N.S.). Evidence is provided here that HRV decreases on magnetically disturbed days, and that it does so in a dose-dependent fashion, HRV being depressed more on days when 20 < Ap < 45 than on days when 7 < Ap < 20, by comparison with days when Ap < 7. This graded response of HRV to geomagnetic activity should encourage us to search for human magnetoreceptors and for a better understanding of putative mechanisms of magnetoreception.

Adult↗

PubMed2002

Effects of rabeprazole, lansoprazole and omeprazole on intragastric pH in CYP2C19 extensive metabolizers.

AIM: To investigate the inhibitory effects on gastric acid secretion of three proton pump inhibitors, omeprazole, lansoprazole and rabeprazole, using a three-way crossover design in healthy Helicobacter pylori-negative,S-mephenytoin 4'-hydroxylase (CYP2C19) homo- and hetero-extensive metabolizers. METHODS: Eight healthy Japanese male volunteers were enrolled. After the administration of rabeprazole (10 mg/day), lansoprazole (30 mg/day) or omeprazole (20 mg/day), intragastric pH monitoring was commenced from 24 h before the first proton pump inhibitor dose, and continued for days 1-3 after proton pump inhibitor administration. The pH electrode was used for 48 h and changed just before pH monitoring on day 2. RESULTS: For the administration of 10 mg/day rabeprazole, the mean ratios of the 24-h pH > or = 3 holding time were 5.7 +/- 1.1%,13.6 +/- 2.2%, 35.3 +/- 2.7% and 62.8 +/- 3.1% for the pre-treatment day and days 1, 2 and 3, respectively. The same ratios for lansoprazole (30 mg/day) were 5.7 +/- 0.7%, 7.4 +/- 1.5%, 13.6 +/- 3.4% and 26.6 +/- 4.9%; the same ratios for 20 mg/day omeprazole were 5.9 +/- 0.9%, 6.1 +/- 1.2%, 11.4 +/- 2.8% and 16.4 +/- 4.6%. The mean ratio of the 24-h pH > or = 3 holding time of days 1-3 increased significantly compared to the pre-treatment day (P < 0.01) with the administration of rabeprazole and lansoprazole. The magnitude of inhibition of gastric acid secretion after rabeprazole administration was stronger than that after lansoprazole. A significant elevation of the mean ratio of the 24-h pH > or = 3 holding time was demonstrated on days 2 and 3 with omeprazole (P < 0.01). CONCLUSIONS: In H. pylori-negative CYP2C19 extensive metabolizers, rabeprazole (10 mg/day) shows a faster onset of rising intragastric pH and a stronger inhibition of gastric acid secretion than do lansoprazole (30 mg/day) or omeprazole (20 mg/day).

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2002

Effects of N-alpha-methyl-histamine on human H(2) receptors expressed in CHO cells.

BACKGROUND: Production of N-alpha-methyl-histamine (NAMH), a histamine H(3) receptor (H3R) agonist, is reportedly promoted in Helicobacter pylori infected human gastric mucosa. NAMH was suggested to act directly on histamine H(2) receptors (H2Rs) in animals to stimulate acid secretion and to be a H2R agonist. As H2Rs and H3Rs play different roles in gastric acid secretion, it is very important to verify that NAMH is a H2R agonist. AIMS: To determine whether NAMH is a H2R agonist, as well as a H3R agonist. METHODS: We used a Chinese hamster ovary (CHO) cell line expressing human H2Rs (CHO-H2R) and control CHO cells. Expression of human H2Rs was confirmed by tiotidine binding. cAMP production in CHO-H2R and control cells in response to histamine or NAMH was measured. cAMP production in response to 10(-7) M NAMH was also measured in the presence or absence of the H2R antagonist famotidine and the H3R antagonist thioperamide. RESULTS: NAMH dose dependently stimulated cAMP productions in CHO-H2R cells. This production was inhibited by famotidine but not by thioperamide. Control CHO cells were unresponsive to either histamine or NAMH. In addition, the effect of NAMH, in terms of cAMP production in CHO-H2R cells, was more potent than that of histamine-that is, with a lower EC(50) concentration and higher maximal cAMP production. Both NAMH and histamine, but not R-alpha-methyl-histamine, effectively inhibited [(3)H] tiotidine binding to CHO-H2R cells. CONCLUSIONS: NAMH, which is produced in the gastric mucosa by H pylori, is a potent H2R agonist as well as a H3R agonist.

Animals↗

PubMed2001

Impact of circadian amplitude and chronotherapy: relevance to prevention and treatment of stroke.

The long-acting calcium antagonist nifedipine reduces the incidence of stroke in Eastern Asia, as shown by the Shanghai Trial Of Nifedipine in the Elderly (STONE) and the Systolic Hypertension in China (Syst-China) trials. Recent trials in Japan have shown that benidipine may be more efficient than the former drug in preventing strokes in the elderly. Benidipine, commonly prescribed in Japan for a definite depressor effect, reportedly without causing remarkable fluctuations in blood pressure (BP), is investigated herein from a chronobiological viewpoint. Eighteen subjects (nine women and nine men, 39 to 87 years of age) with essential hypertension (office and ambulatory systolic, S/diastolic, D BP values above 160/95 mm Hg and 130/80 mm Hg, respectively) were enrolled in this investigation. Ambulatory BP was monitored at 30-min intervals for at least 24 h (ABPM-630, Colin Medical) before and after 4 weeks of crossover treatment with nifedipine tablets (twice daily, 20 mg/d) and benidipine (once daily, 4 mg/d, in the morning). The results indicate that: 1) benidipine and nifedipine reduce 24-h daytime (10:00-20:00) and nighttime (00:00-06:00) averages of SBP and DBP (P < 0.001); 2) the circadian double amplitude of BP is decreased after treatment with benidipine (from 28.6 to 21.1 mm Hg SBP and from 19.7 to 15.2 mm Hg DBP; P< 0.05), while the day-night difference in SBP is increased after treatment with nifedipine (18.6 vs 27.9 mm Hg, P< 0.01); and 3) the increase in the day-night difference of heart rate (HR) is significant after treatment with benidipine (13.6 vs 18.8 beats per minute, bpm; P< 0.05), but not with nifedipine. We have previously evaluated the usefulness of the circadian amplitude of BP as a prognostic tool of cardiovascular outcome, and found that an excessive circadian SBP or DBP amplitude was associated with an increased risk of vascular disease. The fact that benidipine reduces the circadian BP amplitude may be one reason for the superiority of this treatment over nifedipine in preventing an adverse outcome. A reduced heart rate variability (HRV) also predicts adverse cardiovascular outcomes in patients with overt cardiovascular disease and in hypertensive subjects. The fact that benidipine increases the day-night difference in HR may be another reason for the positive effects of this treatment.

Adult↗

PubMed2001

Potent and long-lasting action of lafutidine on the human histamine H(2) receptor.

BACKGROUND/AIM: Based on animal models, lafutidine, a novel histamine H(2) receptor (H(2)R) antagonist, is reported to show potent and long-lasting antagonisms of histamine H(2)R-mediated effects. However, no reports have been published concerning its direct interaction with the human H(2)R. This study aims at characterizing its interaction with human H(2)R. METHODS: Chinese hamster ovary cell lines stably expressing human H(2)Rs were obtained. The dose-dependent effects of lafutidine and famotidine on [(3)H]tiotidine binding and histamine-stimulated cAMP production were analyzed. The effects of preincubation with 2.78 x 10(-7) M of lafutidine or famotidine for 30 min on histamine-dependent cAMP production and [(3)H]tiotidine binding were also examined after 0, 1, 2, 4, and 12 h. This concentration is below the C(max) of lafutidine (10 mg p.o.) and above the C(max) of famotidine (20 mg p.o.). RESULTS: Lafutidine inhibited [(3)H]tiotidine binding and histamine-stimulated cAMP production as or more potently than famotidine. At higher concentrations lafutidine was more potent than famotidine. In addition, preincubation with 2.78 x 10(-7) M lafutidine, but not with 10(-5) M famotidine, had marked inhibitory effects which persisted as long as after extensive washing. CONCLUSION: Lafutidine shows a potent and long-lasting antagonism on the human H(2)R.

Acetamides↗

PubMed2001

Clinicopathological characteristics of left ventricular myocardium with transient asynergy: report of three cases.

The aim of the present retrospective study was to clarify the histopathologic substrates of left ventricular myocardium with transient asynergy due to acute ischemic insult in man. Three patients who had had prolonged chest pain, new abnormal Q waves and new ST segment elevation were studied. There was no significant elevation of serum creatine phosphokinase activity in two of the three patients. Echocardiograms on admission or the next day showed severe hypokinetic or akinetic motion and thinning of the anteroseptal and apical portions of the left ventricle and regional dilatation of the same portions. Disappearance of the abnormal Q waves, ST segment elevation resolution, and early T wave inversion were observed later. Complete improvement of the echocardiographic abnormalities was confirmed after a few weeks in all patients. Manifest ischemic lesions of subendocardial scars of the anteroseptal region of the left ventricle were detected in only one of the three cases by gross examination. However, on microscopic examination, islands of necrotic myocytes were interspersed with islands of viable cells throughout the jeopardized region in one case, although the scattered necrotic foci were restricted to the subendocardium and the trabeculae. Normal myocardium and subendocardial scars were observed in the other two cases. In conclusion, left ventricular myocardium with transient asynergy. detected clinically during acute ischemic attack, consists of normal myocardium or small ischemic lesions primarily in the subendocardium.

Aged↗

PubMed2001

Rare complication of saccular aneurysm and histological dissection: an autopsy study of 5865 elderly cases.

The purpose of this study was to examine complicated lesions of saccular aneurysm and dissection. We investigated the ascending aortae in 5865 consecutive elderly autopsy cases, and 5 cases (0.085%) of aortic saccular aneurysms associated with dissection at the edges were selected. Their edges characteristically protruded like a shelf, which histologically consisted of an inner part of the dissected media. All patients were female and their mean age was 76.8 (67-89) years. The aneurysmal walls at the center showed severe fragmentation and disappearance of the elastic lamellae of the remaining outer media. Thus, partial sections of these lesions were not sufficient but cross-sections of the whole diseased regions including the edges were essential for diagnosis. One patient had 3 saccular aneurysms and an adjacent shallow depression, which we called "healed microscopic dissection". Histologically, it showed disappearance of the inner media and was replaced by fibrosis in continuation from the intima. This lesion showed no findings of intramural hemorrhage or thrombus, and thus it will differ from organized thrombi in the dissected false lumen. Another patient presented had an aneurysmal rupture which resulted in cardiac tamponade. This case implies the need for surgical treatment of this entity.

Aged↗

PubMed2001

[Clinical features of elderly patients with hepatocellular carcinoma].

To clarify the clinical features and to select optimal treatment of hepatocellular carcinoma (HCC) in the elderly, 163 patients were divided into the following three groups and retrospectively evaluated: Group O (> or = 70 years of age, 47 cases), Group IM (< 70 and > or = 60 years, 70 cases) and Group Y (< 60 years, 46 cases). There were fewer HBsAg-positive cases and those in clinical stage III in Group O than in Group Y (p < 0.05). Although the percentage of women and small HCCs in Group O were somewhat higher than those in other groups, there were no significant differences among the three groups with regard to sex, size of nodule and time after blood transfusion. Most of the alcohol-abuser were in Group Y (p < 0.05). Some active treatment was possible in 76.6% of the elderly individuals, in 87.1% of the patients of Group IM, and in 78.3% of the Group Y, while few underwent hepatic resections (Group O, 4.3% vs. Group IM, 8.5% vs. Group Y, 8.6%) or PMCT (4.3% vs. 11.4% vs. 8.6%). The allocation of other therapeutic modalities in the three groups were also statistically identical. The prevalence of concomitant diseases was significantly higher in the elderly patients (53%) than in their younger counterparts (Group IM; 30%, Group Y; 28.2%) (p < 0.05). Although the reasons for the paucity of treatment in Group IM and Y (9 and 10 cases) were liver-associated factors (i.e., advanced clinical stage or tumor size), attempts to apply therapeutic measures were abandoned in 11 cases in Group O because of their advanced age (2 cases) or heart failure (1 case). The 5-year survival rate was higher in Group O (55%) than those in Group IM (32%) and Y (26%) (p < 0.01). These results suggest that because of the higher incidence of concomitant diseases, less invasive therapeutic modalities, such as PEI/PMCT, should be recommended for elderly patients with HCC.

Aged↗

PubMed2001

[An autopsied case of marked cardiac hypertrophy due to multifactorial heart disease in an 85 year-old man who had been socially active].

An autopsied 85-year-old man had suffered from a mild form of diabetes mellitus since the age of 67 and had experienced the first episode of heart failure with arapid ventricular rate of atrial fibrillation at the age of 72. He had remained socially active until he died suddenly of ventricular fibrillation, although he had complications of aortic regurgitation at the age of 76 and later mitral regurgitation at the age of 80. Chest roentgenograms showed gradual increase in the cardiothoratic ratio which reached 68.1% at the final stage. Autopsy revealedmarked left ventricular hypertrophy with a heart weight of 580 g, degeneration ofaortic valves, thickening of mitralvalve cusps and moderate coronary atherosclerosis without ischemic myocardial lesions. There were no specific lesions suggestive of primary cardiomyopathies on microscopic observations and the lesions of both aortic and mitral valves were not significant enough to explain the clinical findings of aortic and mitral regurgitation. Because the pathological examination failed to identify a single disease which was responsible for the marked cardiachypertrophy, we eventually reached the conclusion that the cardiac hypertrophy developed based on a multifactorial heart disease.

Activities of Daily Living↗

PubMed2001

[Testicular involvement in IgD multiple myeloma].

A 65-year-old man was admitted to our hospital in September 1997 because of back pain and renal dysfunction. He was diagnosed as having multiple myeloma due to the presence of IgD lambda monoclonal gammopathy and diffuse infiltration of plasma cells in the bone marrow. The patient achieved a partial response to DMVM-IFN-alpha combination therapy. His condition worsened in December 1998, but was ameliorated by VAD therapy. The patient's left testis became enlarged in December 1999, and an orchiectomy was performed. The normal testicular cells had been entirely displaced by myeloma cells comprising typical plasma cells and large lymphoid cells. Pleural, mediastinal, spinal, and right testicular involvement with myeloma subsequently developed. Despite attempts to treat the patient with more than one type of combination therapy, his condition worsened progressively, and he died in June 2000. Reports of IgD myeloma with testicular involvement are rare. The histopathology of our patient's resected testis, i.e. the two myeloma cell-plasmacytoid and lymphoid cell components showing differential immunostaining, was unique.

Aged↗

PubMed2000

In vivo development of decreased susceptibility to vancomycin in clinical isolates of methicillin-resistant Staphylococcus aureus.

To investigate the possibility of in vivo development of decreased vancomycin susceptibility, the vancomycin susceptibilities of 12 methicillin-resistant Staphylococcus aureus (MRSA) isolates serially recovered from six patients with vancomycin therapy were tested by standard MIC determination method and population analysis. While all of the MRSA isolates were susceptible to vancomycin (MICs, 1-2 microg/ml) by standard method, population analysis showed the upward shifts indicating decreased vancomycin susceptibility among serial isolates from two patients. These bacteria with decreased vancomycin susceptibility could be selected by using vancomycin selection of pre-therapy isolates under laboratory conditions. Furthermore, the reversion phenomenon of decreased vancomycin susceptibility was confirmed after 20 serial passages of the post-therapy isolates on drug-free agar. These data suggest that in vivo isolates may develop decreased vancomycin susceptibility that is not of such magnitude to cross a breakpoint threshold. This resistance may be unstable, and appears to result from a selective or inducible process that occurs in MRSA clinical strains during vancomycin therapy.

Aged↗

PubMed2000

Standardized thigh muscle area measured by computed axial tomography as an alternate muscle mass index for nutritional assessment of hemodialysis patients.

BACKGROUND: Quantification of muscle mass, which represents the largest protein pool in the body, is important for nutritional assessment but is difficult to achieve with conventional methods in hemodialysis patients. OBJECTIVE: We measured the cross-sectional area of the thigh occupied by muscle by using computed tomography and compared this with other muscle mass indicators. DESIGN: Thigh muscle area (TMA) was examined and correlated with creatinine production and various nutritional indexes in 163 patients undergoing hemodialysis. Where appropriate, TMA was expressed relative to bone area in the thigh (TBA) to avoid the influence of body size. RESULTS: TMA was highly correlated with creatinine production as measured in the spent dialysate (r = 0.85, P < 0.001), indicating that TMA substantially reflects total-body muscle mass. TMA standardized for TBA was negatively correlated with age and positively correlated with other nutritional indicators including body weight, body mass index, serum albumin, serum transthyretin, and protein catabolic rate. Multiple regression analysis revealed that of these variables, age, serum albumin, and protein catabolic rate independently predicted TMA standardized for TBA. By using correlations with various nutritional indicators, we concluded that patients with a value <10.0 for TMA standardized for TBA were likely to be malnourished whereas those with a value >13.0 were likely to be well nourished. CONCLUSIONS: These results indicate that TMA standardized for TBA, measured by computed tomography, is a reliable indicator of muscle mass that could be used for nutritional assessment of hemodialysis patients.

Aged↗

PubMed2000

Close association between high serum ALT and more rapid recurrence of hepatocellular carcinoma in hepatectomized patients with HCV-associated liver cirrhosis and hepatocellular carcinoma.

We investigated whether or not a high serum alanine aminotransferase (ALT) level is associated with a more rapid recurrence of hepatocellular carcinoma (HCC) in hepatectomized patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC) (HCV-LC) and HCC. Thirty-three hepatectomized patients with HCV-LC and HCC of a single nodule who had no histologic evidence of portal or hepatic vein invasion and who had been followed up for more than 3 years were included in the study. They were subdivided into two groups according to their serum ALT levels, ALT being a well-known marker of inflammatory necrosis in the liver. Seventeen patients whose serum ALT levels showed several peaks or plateaus above 80 international units (IU) were designated as the high ALT group, and 16 patients whose serum ALT levels showed a sustained low level below 80 IU until the first recurrence were designated as the low ALT group, and the interval between hepatectomy and the first recurrence was observed. In the high ALT group, HCC recurred within 3 years in 70.6% of the patients. In contrast, it recurred in only 18.8% of the low ALT group within the same period (p < 0.05). There was a significant difference (p = 0.0201) between the two groups in the cumulative nonrecurrence rate. The mean interval in recurrent patients between hepatectomy and the first recurrence in the high ALT group (23.6 +/- 2.8 months; mean +/- SE) was significantly (p < 0.02) shorter than that in the low ALT group (49.3 +/- 9.7 months). The expected interval between hepatectomy and recurrence was as short as 2.8 +/- 0.5 years (mean +/- SE) in the high ALT group, compared with 5.8 +/- 0.7 years in the low ALT group (p < 0.05). These results showed that the recurrence of HCC was accelerated in the high ALT group, suggesting that suppression of the rise in ALT level after hepatectomy by treatment with anti-inflammatory drugs may prolong the interval until recurrence by about 2 years in hepatectomized patients with HCC and HCV-LC.

Aged↗

PubMed2000

ESR study on the antioxidant activity of TAK-218 in biological model membranes.

TAK-218 has a 2,3-dihydrobenzofuran-5-amine (coumaran) structure which resembles alpha-tocopherol, and is a promising candidate as an agent for central nervous system (CNS) trauma and ischemia. The radical scavenging activity of TAK-218 was studied using electron spin resonance (ESR) spectroscopy. TAK-218 exhibited a more potent scavenging activity towards the hydroxyl radical than did the well-known hydroxyl radical scavengers, mannitol and dimethylsulfoxide. Towards the superoxide radical, TAK-218 showed equal potency to glutathione. TAK-218 reacted rapidly with stable radicals, such as galvinoxyl and 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH), and gave the quinone as a two-electron oxidized product in analogy with alpha-tocopherol. To exhibit an excellent antioxidative activity in living systems, the compounds should not only have the intrinsic radical scavenging activity but also good distribution in the biological lipid-bilayer membrane. To examine the antioxidant activity of TAK-218, the inhibition of lipid peroxidation by alpha-tocopherol and TAK-218 in liposomal membranes was studied using an ESR spin-label technique. Both alpha-tocopherol and TAK-218 completely inhibited lipid peroxidation by radicals generated in an aqueous layer using a water-soluble radical initiator, 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH). At a high incubation temperature (45 degrees C), alpha-tocopherol scavenged radicals more effectively than TAK-218 on the surface of the membrane, while TAK-218 scavenged radicals more effectively in the interior of the membrane. The difference between TAK-218 and alpha-tocopherol for radical scavenging in the membrane system derives from the different distribution pattern of these compounds. TAK-218 can penetrate the membrane freely and can scavenge the radical in the membrane interior. Furthermore, TAK-218 was shown to inhibit lipid peroxidation initiated by a lipid soluble radical initiator, 2,2'-azobis-(2,4-dimethylvaleronitrile) (AMVN), in a membrane more effectively than alpha-tocopherol.

Antioxidants↗

PubMed2000

Effects of exercise conditioning on vital age in hyperlipidemic women.

We attempted to determine the effectiveness of exercise prescription for women with hyperlipidemia (HL), because some HL women showed no significant improvement in serum lipid and lipoprotein profiles despite the continuation of exercise conditioning. We therefore tested the hypothesis that exercise can be clinically beneficial even when there are no alterations in total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and/or triglycerides (TG). Twenty-three women with HL (aged 54.3 +/- 7.6 yr) participated in our outpatient-supervised exercise conditioning program for 90 minutes each session, twice a week for 1 year, and also did home-based exercise three days a week. Vital age (VA) is a useful index for assessing functional status, especially the risk of coronary heart disease (CHD) and is computed from 11 independent variables measured not only when a person is at rest but also during exercise. Although TC and LDLC did not change significantly after the exercise conditioning, TG decreased significantly (P < 0.05). Furthermore, when we computed the corrected VA (VAc) assuming no changes in TC, LDLC, and TG, VAc was found to decrease significantly from 64.0 +/- 9.9 yr to 58.4 +/- 9.0 yr (P < 0.05). In conclusion, these results indicate the effectiveness of exercise conditioning on risk of CHD in HL women, irrespective of alterations in the concentrations of serum lipid and lipoprotein.

Adult↗