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Akihisa Iguchi

Publications and source records attributed to Akihisa Iguchi.

At least 19 recordsLinked to original sources

Dopamine D2 receptor plays a role in memory function: implications of dopamine-acetylcholine interaction in the ventral hippocampus.

RATIONALE: The role of the hippocampal dopaminergic system in mnemonic function has not been clarified yet. OBJECTIVE: We previously reported that the dopamine D2 receptor (D2R) is involved in the regulation of acethylcholin (ACh) release in the hippocampus. In this study, we further investigated ACh-dopamine (DA) interaction in the hippocampus and its involvement in mnemonic function. METHODS: For experiment 1, rats fed with Cholin (Ch)-deficient chow were used. We examined the effects of D2R antagonist, raclopride, on cognitive performance using a passive avoidance task. We further carried out in vivo microdialysis to assess the effect of infusion of D2R agonist, quinpirole, into the ventral hippocampus on its capacity to release ACh. For experiment 2, rats fed with normal chow were used. The performance of a radial arm maze task was assessed to examine the effects of hippocampal injection of D2R agonist, quinpirole, on memory impairment induced by scopolamine, a muscarinic ACh antagonist. RESULTS: In experiment 1, rats fed with Ch-deficient chow showed impaired performances indicated by prolonged latency on retention trials of a passive avoidance task following the hippocampal injection of D2R antagonist, and showed reduced capacity to release ACh following the injection of D2R agonist compared with rats fed with normal chow. In experiment 2, memory impairment induced by the intraperitoneal injection of scopolamine was ameliorated by the injection of D2R agonist into the ventral hippocampus. CONCLUSION: These results indicate the possible involvement of hippocampal ACh-DA interaction in mnemonic processing.

Acetylcholine↗

End-of-life care at group homes for patients with dementia in Japan. Findings from an analysis of policy-related differences.

In Japan, the number of group homes for patients with dementia (GHs) has been increasing in recent years. A growing number of elderly people now prefer to spend their final years in group homes or other long-term care facilities, a choice that their families support. The aim of this nationwide study is to clarify the current end-of-life care policies and practices of GHs. The subjects were 3701 managing directors of GHs. Data were collected through mailed, anonymous, self-reported questionnaires in 2003. The content of the questionnaires included: (1) general characteristics of the GH, (2) end-of-life care policies and experiences, (3) available end-of-life care services at the GH, (4) staff education concerning end-of-life care, and (5) types of information provided to users and families. The response rate was 45.6%. Many GHs had implemented progressive policies for end-of-life care. GHs with progressive policies for end-of-life care were found to have different backgrounds than those with regressive policies. Only a few GHs provided end-of-life care education for their staff. GHs with progressive policies for end-of-life care tended to have the following characteristics: availability of medical intervention within and outside of the GH, self-contained physical plant and staff education about end-of-life care. Further research is needed to determine the most effective end-of-life care systems for GHs.

Aged↗

l-Citrulline and l-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits.

The objective of this study was to evaluate the influence of ingested l-arginine, l-citrulline, and antioxidants (vitamins C and E) on the progression of atherosclerosis in rabbits fed a high-cholesterol diet. The fatty diet caused a marked impairment of endothelium-dependent vasorelaxation in isolated thoracic aorta and blood flow in rabbit ear artery in vivo, the development of atheromatous lesions and increased superoxide anion production in thoracic aorta, and increased oxidation-sensitive gene expression [Elk-1 and phosphorylated cAMP response element-binding protein]. Rabbits were treated orally for 12 weeks with l-arginine, l-citrulline, and/or antioxidants. l-arginine plus l-citrulline, either alone or in combination with antioxidants, caused a marked improvement in endothelium-dependent vasorelaxation and blood flow, dramatic regression in atheromatous lesions, and decrease in superoxide production and oxidation-sensitive gene expression. These therapeutic effects were associated with concomitant increases in aortic endothelial NO synthase expression and plasma NO(2)(-)+NO(3)(-) and cGMP levels. These observations indicate that ingestion of certain NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis. This approach may have clinical utility in the treatment of atherosclerosis in humans.

Animals↗

Mechanisms of the inhibitory effect of epigallocatechin-3-gallate on cultured human vascular smooth muscle cell invasion.

OBJECTIVE: Although we recently showed that the administration of catechins reduced the neointimal formation in a rat balloon-injury model, the precise molecular mechanisms are largely unknown. In the present study, we tried to determine these mechanisms using an in vitro SMC invasion system. METHODS AND RESULTS: Boyden chamber assay was used to examine the effect of catechins on the invasive behavior of SMCs. The invasive activity of SMCs through collagen gel was restrained by EGCG in a concentration-dependent manner. The data from gelatin and collagen zymography and Western blot revealed that EGCG blocks the activation of pro-matrix metalloproteinase (MMP)-2 during an invasion assay and in the conditioned medium of cultured SMCs as well as the activities of MMP-2 and membrane type 1-MMP (MT1-MMP) even at 0.1 to 0.3 micromol/L of EGCG. EGCG was found to restrain MT1-MMPcat-dependent pro-MMP-2 activation. EGCG upregulated the expression of tissue inhibitor of MMP-2 (TIMP-2) protein. Reverse zymography showed that the increased TIMP-2 to expression was validated by an increased activity. The data from decreased TIMP-2 activity using its siRNA suggested that upregulation of TIMP-2 expression may be one of the major mechanisms for inhibition of SMC invasion by EGCG. CONCLUSIONS: These results indicate that EGCG targets multiple MMP-mediated SMC cellular events and provides a new major mechanism for the SMC invasion through upregulation of TIMP-2 expression to modulate MMP activity.

Antioxidants↗

Effect of smoking habit on age-related changes in serum lipids: a cross-sectional and longitudinal analysis in a large Japanese cohort.

To observe the effect of smoking habit on age-related serum lipid levels, we examined a large cohort of Japanese cross-sectionally and longitudinally. The participants included 103,648 Japanese men and women 17-94 years of age, who had received annual health examinations from 1989 to 2003. In cross-sectional analysis, total and LDL cholesterol levels of smokers were lower than those of nonsmokers up to an elderly age in men and up to middle age in women. Smoking was associated with decreased HDL cholesterol levels up to the 65-74 years age group in men and 55-64 years in women. The triglyceride levels were higher in smokers in both genders than those of nonsmokers below 55-64 years. In the longitudinal analysis, although smoking was associated with lower total and LDL cholesterol up to 60 years of age in women, beyond the sixties an inverted association was observed. The associations of smoking with lower LDL cholesterol levels in men and lower HDL cholesterol in both genders were fairly consistent at any given age. The increase of triglyceride levels in female smokers remained rather constant between 25 and 75 years, whereas the increase in triglyceride levels in male smokers was greater with older ages up to middle age. These results suggest that the effect of smoking on the serum lipid levels is dependent on age and gender.

Adolescent↗

Influence of behavioral and psychological symptoms of dementia (BPSD) and environment of care on caregivers' burden.

With increasing population of older adults in need of care, caregiver's burden is becoming a major concern. We investigated the relative contributions of BPSD of care recipients, caregiver's background and the care environment to caregiver's burden assessed by using Zarit burden interview (ZBI). Among BPSD, inability of finding the way home, inability of managing money and fecal incontinence were the most difficult symptoms to cope with. A path analysis, by which we constructed a network model to clarify the contributions of the factors examined to the caregiver's burden, indicated that the severity of dementia, the feeling of "would rather die than be in the same condition" and the physical pain of the caregivers showed great direct influences on the score of the ZBI. In conclusion, we clarified kinetic and dynamic interactions of factors affecting caregiver's burden by using a path analysis. The model indicates that the caregiver's burden can be affected not merely by the illness of the care recipients but by the caregiver's background and the care environment.

Activities of Daily Living↗

Lack of correlation between total lymphocyte count and nutritional status in the elderly.

BACKGROUND & AIMS: Malnutrition is a widespread but largely unrecognized problem in aged people. Although absolute total lymphocyte count (TLC) has been proposed as a useful indicator of nutritional status, there is little evidence that low TLC levels reflect malnutrition in the elderly. To examine whether TLC is a suitable marker of malnutrition in the elderly. METHODS: A total of 161 elderly subjects (44 males and 117 females, mean age+/-SD: 77.9+/-7.4; range: 65-95 years) were enrolled from geriatric clinical settings. The participants were categorized according to severely low, low, or normal TLC. Anthropometry measurements, serum albumin, total cholesterol levels, and total score on the mini-nutritional assessment (MNA) were determined. RESULTS: There were no significant differences among the three TLC groups with regard to anthropometry measurements, serum albumin, total cholesterol levels, or MNA score. There was a significant negative correlation of TLC with age, but not with other nutritional markers. The clinical nutritional screening tool, MNA score, was well correlated with all of the nutritional parameters used in the present study except for TLC. CONCLUSION: TLC is not a suitable marker of malnutrition in the elderly.

Aged↗

Evaluation of Mini-Nutritional Assessment for Japanese frail elderly.

OBJECTIVE: We evaluated the Mini-Nutritional Assessment (MNA) test and the short-form MNA as screening tools for malnutrition in the Japanese elderly population. METHODS: A cross-sectional study of 226 elderly Japanese patients (78.6 +/- 0.5 y of age, mean +/- standard deviation; 67 men and 159 women) in various settings was carried out. Nutritional assessment included MNA, anthropometric measurements, and biochemical markers. RESULTS: According to the original cutoff point of the full MNA, 19.9% of those assessed were malnourished, 58.0% were at risk of malnutrition, and 22.1% were well nourished. Significant correlations were found between full MNA scores and age (r = -0.14), body mass index (r = 0.59), serum albumin (r = 0.60), total cholesterol (r = 0.36), midarm circumference (r = 0.50), and triceps skinfold (r = 0.37). The sensitivity and specificity of the full MNA score (< 17) for hypoalbuminemia were 0.810 and 0.860, respectively. With a cutoff point lower than 18, sensitivity and specificity hypoalbuminemia were 0.857 and 0.815, respectively. Using a short-form MNA score 12 and higher as normal, its sensitivity and specificity for predicting undernutrition were 0.859 and 0.840, respectively. CONCLUSIONS: The full and short forms of the MNA were useful tools to identify elderly Japanese patients with malnutrition or risk of malnutrition. However, the full MNA cutoff point for malnutrition should be modulated for this population.

Aged↗

Predictive model for assessing cognitive impairment by quantitative electroencephalography.

OBJECTIVE: To assess the utility of quantitative electroencephalographic analysis as an indicator of cognitive impairment, we examined the correlation between Mini-Mental State Examination (MMSE) scores and quantitative electroencephalographic (QEEG) power values in elderly patients and constructed a regression model to predict MMSE scores. BACKGROUND: Because of the growing number of elderly individuals with cognitive deficits, there is an increasing need for simple and objective methods with which to evaluate cognitive function. Although QEEG is reportedly a useful method for this purpose, few researchers have constructed a QEEG-based model for predicting the degree of cognitive impairment in clinical settings. METHOD: We evaluated brain function using QEEG in 44 elderly patients with memory complaints and compared the results with their MMSE scores. RESULTS: In the correlation analysis, no significant correlation was found between MMSE scores and QEEG power values. However, a regression model created using relative QEEG and gender for predicting MMSE scores had an adjusted R2 of 0.471. CONCLUSIONS: This finding suggests that QEEG analysis may be a useful indicator of cognitive decline in patients with memory complaints.

Aged↗

Effects of home massage rehabilitation therapy for the bed-ridden elderly: a pilot trial with a three-month follow-up.

OBJECTIVES: To assess the effects of home massage rehabilitation therapy on the bed-ridden elderly. DESIGN: Alternatively allocated trial. SETTING: Subjects' homes, three home nursing stations, 13 visit care stations and one day service centre in Aichi prefecture, Japan. SUBJECTS: Bed-ridden patients who were 65 years and above, no dementia, stable general condition, and receiving no rehabilitation therapy. INTERVENTION: Thirty-minute sessions of home massage rehabilitation therapy by a massage practitioner 2 or 3 days a week for three consecutive months or usual care. MAIN MEASUREMENTS: Barthel Index (BI), Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score. RESULTS: Fifty-three subjects were recruited, 26 in the home massage rehabilitation group (HMG) and 27 in the routine care group without massage (RCG). The protocol was completed for 40 subjects, 22 in the HMG and 18 in the RCG. There were no significant differences between the baseline characteristics of both groups; age, presence of spouse, diseases associated with disabilities and use of day care rehabilitation (p = 0.76, 0.36, 0.94 and 0.71, respectively). The total BI score of the HMG (15.27+/-4.51) at baseline was nonsignificantly lower (p= 0.03) than those of the RCG (11.44+/-5.90). Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score of both groups at baseline were matched (p = 0.12, 0.32 and 0.89, respectively). There were no statistical differences between the intergroup changes over time in BI, Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score (p = 0.35, 0.08, 0.70 and 0.55, respectively). CONCLUSION: Home massage rehabilitation therapy did not show a positive effect on the bed-ridden elderly, either mentally or physically. We would require large-size trials to determine whether it is effective.

Activities of Daily Living↗

[Terminal care of the elderly].

In 2001, the Japan Geriatrics Society released its position statement regarding the terminal care of the elderly. In the statement, it is stated as a technical issue that any medical practice implemented in terminal care should warrant its profit to the patient (position 6). Standardization of all medical practices and methods of care for dying patients is desired, and should be based upon scientific evidence regarding the profitability of the practice for the patient. The standardization of care should aim to exclude physicians' arbitrariness and to endorse patients' autonomy. However, healthcare systems and related scientific evidences that warrant patients' autonomy have not been sufficiently established in Japan. Under the circumstances, we have been engaging in research into the terminal care for older adults from 1997 to date by formulating a research team working under the scheme of comprehensive research project for longevity sciences funded by the ministry of health, labor and welfare. This article reviews findings achieved mainly from the research carried out by the members of the research team.

Aged↗

[Awareness of dementia in older adults attending dementia-prevention programs in community healthcare centers].

Recently, the dementia-prevention program hosted by the Ministry of Health, Welfare and Labor has been widely implemented. We administered a questionnaire to 347 elderly adults (mean age: 71, mean MMSE score: 27.2) who attended programs in community healthcare centers. The questionnaire consisted of questions concerning: (1) belongings (2) knowledge about dementia (3) opinions about revealing the diagnosis of dementia to patients (4) anxiety for own onset of dementia. Regarding the knowledge about dementia, 17% of the participants knew about drug therapy, and 13% of them knew about legal guardianship. The results indicated a limited knowledge about facilities where demented people can be placed (home: 39%, hospital: 43%, nursing home: 62%, group-home: 25%). As for revealing the diagnosis, 68% of the participants hoped they would be informed of the diagnosis if they become demented, while 66% of them felt anxiety about having dementia in the future. In terms of difference by age (> or = 70 v.s. < or = 69), while the older group had low knowledge about the facilities and felt more anxiety about their own onset of dementia (chi2 test p < 0.05, Mann-Whitney U test p < 0.05), there were no intergroup difference regarding their expectations of being told about the diagnosis of dementia. Overall, the results of the questionnaire suggest that appropriate education of dementia to older adults may contribute to early diagnosis of the community level, thereby may maximize the effect of therapeutic interventions.

Aged↗

[National survey on the current status of programs to teach end-of-life care to undergraduates of medical and nursing schools in Japan].

AIM: We conducted a national survey to examine the current status of programs to teach end-of-life care to undergraduates of Japanese medical and nursing schools in 2004. METHODS: Our survey focused on the following areas: (1) the present status of curricula to teach end-of-life care, (2) topics covered in the curricula, (3) details of the timing of existing end-of-life care teaching programs and of departments responsible for it, (4) teaching methods, (5) education assessment tool, (6) reading list of textbooks. RESULTS: 50.6% of the medical schools and 40.9% of the nursing schools participated. Most of the schools offered end-of-life care education programs, and 45% of the medical schools and 68.9% of the nursing schools offered education concerning end-of-life care for elderly. The most frequent teaching timing was the fourth year of medical school and the third year of nursing school. Broader end-of-life topics were covered in the curriculum in the nursing schools than the medical schools. One fourth of the nursing schools offered a separate course in end-of-life care. The mean number of teaching hours was 7.6 in the medical schools and 35.5 in the nursing schools. More nursing schools offered educational programs in which students can gain experience with end-of-life care than medical schools. A few institutions used practiced examinations to evaluate students' learning. A reading list of end-of-life care textbooks was provided in 10% of the medical schools and 35.6% of the nursing schools. CONCLUSION: Our survey suggested that systematizing end-of-life care education and improvement in text content are on the way.

Adult↗

The entorhinal cortex regulates blood glucose level in response to microinjection of neostigmine into the hippocampus.

OBJECTIVE: Microinjectin of neostigmine, an inhibitor of acetylcholine esterase, into the rat hippocampus elicited stress-like responses reflected by the release of adrenocorticotropic hormone (ACTH) and blood glucose elevations. The entorhinal cortex is regarded as an interface between the hippocampus and neocortex. The current study was designed to examine the role of the entorhinal cortex in regulation of blood glucose elevation induced by hippocampal neostigmine injection. MATERIAL AND METHODS: We produced the entorhinal cortex lesions in 9 week-old male Wistar rats by the bilateral injections of the cell-selective neurotoxin, ibotenic acid (15microg/microl). Two weeks after the injections, neostigmine methylsulfate (sigma, 5x10(-8) mol) was microinjected into the rat hippocampus in a volume of 1microl for 1min using a CMA/100 microinjection pump. Plasma ACTH levels were measured by radioimmunoassay. Plasma glucose concentrations were determined by the immobilized enzyme membrane/H2O2 method with a compact glucose analyzer Antsense II (Bayer Medical Co.Ltd,Tokyo, Japan). RESULTS: Compared with sham-operated control rats, the entorhinal lesions produced by ibotenic acid significantly attenuated the elevations of blood glucose evoked by the microinjection of neostigmine into the hippocampus. However, no significant difference of plasma ACTH in response to the injection was observed between the entorhinal-lesioned rats and controls. CONCLUSION: The results of the present study indicate that the entorhinal cortex plays a role in the central nervous systems regulation of blood glucose and may be involved in a stress response presumably via an alternative pathway.

Animals↗

The effect of high glucose on NO and O2- through endothelial GTPCH1 and NADPH oxidase.

Although endothelial dysfunction deteriorates diabetic angiopathy, the mechanisms are obscure. We revealed that high glucose augmented eNOS through stimulation of eNOS mRNA in cultured BAECs. NO was decreased and O2- was increased simultaneously. NOS inhibitor, inhibited O2- release, so did NADPH oxidase inhibitor. The effects were synergistic. Both intracellular BH4 level and GTPCH1 activity were decreased by high glucose, in line with decrease of GTPCH1 mRNA. HMG-CoA reductase inhibitor, atorvastatin increased GTPCH1 mRNA and activity, and BH4 level. Conclusively, high glucose leads to eNOS dysfunction by inhibiting BH4 synthesis and atorvastatin stimulate BH4 synthesis directly, and it may work as atherogenic process.

Animals↗

Combined effect of testosterone and apocynin on nitric oxide and superoxide production in PMA-differentiated THP-1 cells.

Human inducible nitric oxide synthase (iNOS) is most readily observed in macrophages from patients with inflammatory diseases like atherosclerosis. The aim of the present study was to find out the combined effect of male sex hormone; testosterone and apocynin (NADPH oxidase inhibitor) on cytokine-induced iNOS production. THP-1 cells were differentiated into macrophages by phorbol myristate acetate (PMA). Expression of iNOS was induced by the addition of cytokine mixture? Testosterone was added at different concentrations (10(-6)-10(-12) M) with apocynin (1 mM). Testosterone (10(-8), 10(-10) M) inhibited NOx production in cytokine-added THP-1 cells which was further confirmed by quantikine assay of iNOS protein and RT-PCR analysis. Testosterone treatment decreased 40% of superoxide anion production. Testosterone showed inhibition of NADPH oxidase, especially expression of p67phox and p47phox (cytosol subunits). Addition of testosterone with apocynin further decreased the expression of p67phox and p47phox subunits of NADPH oxidase. The findings of the present study suggest that, testosterone; the male androgen plays an important role in the prevention of atherogenesis. Even though apocynin does not have any role on NO production, addition of apocynin together with testosterone is effective in suppressing iNOS activity.

Acetophenones↗