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1.
Dysphagia ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157395

RESUMO

Even though higher serum insulin-like growth factor-1 (IGF-1) levels have a positive effect on preventing reduction in muscle strength, a U-shaped association between IGF-1 and mortality has been reported. Since a recent experimental study revealed that IGF-1 is associated with atherosclerotic lesion formation, the inflammatory status of atherosclerosis could act as a confounding factor on the association between IGF-1 levels and reduced muscle strength. This study aimed to clarify the atherosclerosis-specific association between IGF-1 levels and reduced muscle strength. We conducted a cross-sectional study of 410 elderly men aged 60-89 years. Since a reduction in maximum voluntary tongue pressure against the palate (MTP) is reportedly associated with sarcopenia, we evaluated muscle strength by using MTP and defined reduced MTP as the lowest tertiles of the study population. Among study population, 295 showed no atherosclerosis (carotid intima-media thickness < 1.1 mm). Even though a significant inverse association between IGF-1 and reduced MTP was observed for subjects without atherosclerosis, no such association was detected for subjects with atherosclerosis. The known cardiovascular risk-factor adjusted odds ratio (OR) of a one-standard deviation (SD) increment (28.1 ng/mL) of IGF-1 for reduced MTP was 0.69 (0.51, 0.95) for subjects without atherosclerosis and 1.93 (1.05, 3.52) for subjects with atherosclerosis. IGF-1 was found to be inversely associated with a reduced MTP among elderly men without atherosclerosis but not among those with atherosclerosis. Atherosclerosis can thus act as a powerful confounding factor on the association between IGF-1 levels and a reduced MTP.

2.
Sci Rep ; 10(1): 4656, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170211

RESUMO

Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60-69 years who participated in a general health check-up at least twice from 2014-2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. This study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects.

3.
Environ Health Prev Med ; 25(1): 7, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085700

RESUMO

BACKGROUND: Anti-thyroid peroxidase antibody (TPO-Ab) has been shown to cause autoimmune thyroiditis by inducing a deleterious influence on thyroid hormone synthesis. Further, thyroglobulin, which has an important role in thyroid hormone synthesis, is reported to be high in the fluid from thyroid cysts. Therefore, TPO-Ab could be associated with the presence of thyroid cyst, partly by affecting the activity of thyroid hormone synthesis. METHODS: To investigate the association between TPO-Ab and thyroid cysts, we conducted a cross-sectional study of 1432 Japanese with normal thyroid function [i.e., normal range of free triiodothyronine (free T3) and free thyroxine (free T4)] between the ages of 40 and 74 years, who participated in an annual health check-up. RESULTS: In men, the statistical power did not reach a statistical significance value. Additionally, subjects with TPO-Ab showed lower odds ratios (ORs) of thyroid cysts than those without TPO-Ab. In women, subjects with TPO-Ab showed significantly lower ORs of thyroid cysts than those without TPO-Ab. The fully adjusted ORs were 0.68 (0.40, 1.18) for men and 0.40 (0.27, 0.60) for women. When evaluating the association between logarithmic values of TPO-Ab titer and thyroid cysts in both men and women, a notable inverse correlation was observed. The fully adjusted ORs were 0.68 (0.50, 0.92) for men and 0.68 (0.57, 0.81) for women. CONCLUSION: TPO-Ab titer revealed to be inversely associated with thyroid cysts among Japanese with normal thyroid function. The presence of a thyroid cyst could indicate a lower risk of having TPO-Ab among the general population with normal thyroid function.

4.
Fam Pract ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32086514

RESUMO

BACKGROUND: Multimorbidity is the presence of two or more chronic diseases and is associated with increased adverse outcomes, including hospitalization, mortality and frequency of use of medical institutions. OBJECTIVE: This study aimed to describe multimorbidity patterns, determine whether multimorbidity was associated with high medical expenditure, and determine whether mental diseases had an interaction effect on this association. METHODS: We conducted a claims data-based observational study. Data were obtained for 7526 individuals aged 0-75 years from a medical claims data set for Goto, Japan, over a 12-month period (2016-17). Annual medical expenditure was divided into quintiles; the fifth quintile represented high medical expenditure. Multimorbidity status was defined as the occurrence of two or more health conditions from 17 specified conditions. Odds ratios (OR) and 95% confidence intervals (CI) for high medical expenditure were calculated by number of comorbidities. RESULTS: In total, 5423 (72.1%) participants had multimorbidity. Multimorbidity was significantly associated with high medical expenditure, even after adjustment for age, sex and income category (OR: 10.36, 95% CI: 7.57-14.19; P < 0.001). Mental diseases had a significant interaction effect on the association between multimorbidity and high medical expenditure (P = 0.001). CONCLUSIONS: Multimorbidity is associated with high medical expenditure in Japan. Mental diseases may contribute to increased medical costs.

5.
J Atheroscler Thromb ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31932552

RESUMO

AIM: N-terminal pro-B-type natriuretic peptide (NT-proBNP), frequently used as a biochemical marker for detecting and monitoring heart failure, is also a risk marker for development of coronary heart disease and total stroke. However, studies that explore subtypes of ischemic stroke with regard to NT-proBNP are scarce. Here, we examined NT-proBNP and its impact upon subtypes of ischemic stroke (lacunar stroke, large-artery occlusive stroke and embolic stroke) among Japanese. METHODS: We measured NT-proBNP and categorized 4,393 participants of the Circulatory Risk in Communities Study into four groups (<55, 55-124, 125-399, and ≥ 400 pg/ml). We used a multivariable Cox proportional hazards model to examine association with risks of stroke and subtypes. RESULTS: During 4.7 years of follow-up, we identified 50 strokes, including 35 ischemic (15 lacunar, 6 largeartery occlusive, 10 embolic strokes) and 14 hemorrhagic strokes. NT-proBNP was associated with stroke risk: the multivariable hazard ratio of total strokes was 7.29 (2.82-18.9) for the highest and 2.78 (1.25-6.16) for the second highest NT-proBNP groups compared with the lowest group. The respective hazard ratios for the highest NT-proBNP group were 9.37 (3.14-28.0) for ischemic stroke and 6.81 (1.11-41.7) for lacunar stroke. Further adjustment for atrial fibrillation did not attenuate these associations. The associations were similarly observed for large-artery occlusive and embolic strokes. CONCLUSION: We found that even moderate serum levels of NT-proBNP were associated with the risk of total and ischemic strokes among Japanese whose NT-proBNP levels were relatively low compared with Westerners.

6.
Pharmacol Res Perspect ; 8(1): e00560, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31990455

RESUMO

M1 muscarinic acetylcholine receptor (M1 R) activation can be a new therapeutic approach for the treatment of cognitive deficits associated with cholinergic hypofunction. However, M1 R activation causes gastrointestinal (GI) side effects in animals. We previously found that an M1 R positive allosteric modulator (PAM) with lower cooperativity (α-value) has a limited impact on ileum contraction and can produce a wider margin between cognitive improvement and GI side effects. In fact, TAK-071, a novel M1 R PAM with low cooperativity (α-value of 199), improved scopolamine-induced cognitive deficits with a wider margin against GI side effects than a high cooperative M1 R PAM, T-662 (α-value of 1786), in rats. Here, we describe the pharmacological characteristics of a novel low cooperative M1 R PAM T-495 (α-value of 170), using the clinically tested higher cooperative M1 R PAM MK-7622 (α-value of 511) as a control. In rats, T-495 caused diarrhea at a 100-fold higher dose than that required for the improvement of scopolamine-induced memory deficits. Contrastingly, MK-7622 showed memory improvement and induction of diarrhea at an equal dose. Combination of T-495, but not of MK-7622, and donepezil at each sub-effective dose improved scopolamine-induced memory deficits. Additionally, in mice with reduced acetylcholine levels in the forebrain via overexpression of A53T α-synuclein (ie, a mouse model of dementia with Lewy bodies and Parkinson's disease with dementia), T-495, like donepezil, reversed the memory deficits in the contextual fear conditioning test and Y-maze task. Thus, low cooperative M1 R PAMs are promising agents for the treatment of memory deficits associated with cholinergic dysfunction.

7.
Psychosom Med ; 82(2): 215-223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31860529

RESUMO

OBJECTIVE: It has been suggested that urbanization, which has been expanding rapidly for the past several decades, increases the risk of cardiovascular disease (CVD) associated with psychological factors such as anger, but the evidence is limited. We examined the hypothesis that urbanicity modifies the association of anger expression with the risk of CVD. METHODS: A prospective study was conducted in 5936 residents of urban and rural communities aged 40 to 79 years who had completed an annual health checkup including a questionnaire on anger expression between 1995 and 1998. Associations of anger expression with the risk of CVDs were examined using Cox proportional hazards models, after adjusting for classical cardiovascular risk factors. RESULTS: During a median follow-up of 16.6 years, we identified 312 incident CVDs. The means (SDs) of anger expression were 24.7 (5.8) among urban residents and 24.6 (5.7) among rural participants (p = .87). Among urban residents, anger expression was positively associated with the risk of total CVD: the multivariable hazard ratio (95% confidence interval) was 1.27 (1.05-1.54). In contrast, no association was found among rural residents: the corresponding ratio (interval) was 0.96 (0.85-1.09), with a significant interaction between urban and rural residency with anger expression for incident CVD (p = .047). Similar associations were observed with the risk of CVD subtypes, including ischemic stroke and ischemic CVD. CONCLUSIONS: We found a positive association between anger expression and the risk of CVD among urban residents but not rural residents, suggesting that urbanicity enhances the anger-CVD association.

8.
Environ Health Prev Med ; 24(1): 69, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785607

RESUMO

BACKGROUND: Even though there is bidirectional association between hypertension and atherosclerosis, atherosclerosis itself is involved in the process of endothelial repair. To clarify the association of endothelial repair with hypertension, a cross-sectional study was conducted. METHODS: We conducted a cross-sectional study of 562 elderly Japanese men aged 60-69. As gamma-glutamyl transpeptidase (γ-GTP) could act as a marker of oxidative stress that injures endothelial cell and higher levels of CD34-positive cell indicate a higher activity of endothelial repair, we therefore performed a CD34-positive level specific analysis of γ-GTP on atherosclerosis and hypertension. RESULTS: In the present study population, hypertension was independently and positively associated with atherosclerosis (multivariable odds ratio (OR) = 2.09 (1.30, 3.35)). Among participants with high CD34-positive cells, γ-GTP showed significant and positive association with atherosclerosis (OR of the log-transformed value of γ-GTP (OR) = 2.26 (1.32, 3.86)) but not with hypertension (OR = 0.77 (0.51, 1.17)). Among participants with low CD34-positive cells, even γ-GTP showed no significant association with atherosclerosis (OR = 0.92 (0.51, 1.68)), but was significantly and positively associated with hypertension (OR = 1.99 (1.27, 3.12)). CONCLUSIONS: γ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension.


Assuntos
Aterosclerose/enzimologia , Hipertensão/enzimologia , gama-Glutamiltransferase/sangue , Idoso , Antígenos CD34/análise , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/patologia , Biomarcadores/sangue , Estudos Transversais , Células Endoteliais/química , Células Endoteliais/patologia , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/patologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances
9.
Environ Health Prev Med ; 24(1): 81, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31883515

RESUMO

BACKGROUND: Human T cell leukemia virus type-1 (HTLV-1) stimulates inflammation activity. Our previous study revealed a positive association between asymptomatic HTLV-1 infection and advanced periodontitis among elderly Japanese individuals with low levels of hematopoietic activity (reflected by reticulocyte levels). Since low hematopoietic activity has been correlated with low-grade inflammation and low-grade inflammation is associated with atherosclerosis, the status of atherosclerosis could, in turn, determine the nature of this association. METHODS: To this end, a cross-sectional study of 907 elderly Japanese individuals (aged 60-99 years), who had participated in dental health check-up during the period 2016-2018, was conducted. Advanced periodontitis was defined as periodontal pocket ≥ 6.0 mm. RESULTS: Among the study population, 295 (32.5%) were found to have atherosclerosis defined as a carotid intima-media thickness (CIMT) of ≥ 1.1 mm. HTLV-1 infection was positively associated with advanced periodontitis in participants with atherosclerosis, but no significant associations were observed among the participants without atherosclerosis. The known risk factors' (including reticulocyte and CIMT) adjusted odds ratio (OR) and 95% confidence interval (CI) of advanced periodontitis were OR 2.01 and 95% CI 1.06-3.81 for participants with atherosclerosis and OR 0.61 and 95% CI 0.34-1.12 for participants without atherosclerosis. CONCLUSION: This study found a significant association between HTLV-1 infection and advanced periodontitis among elderly Japanese with atherosclerosis. However, this association is absent in individuals without atherosclerosis, suggesting that atherosclerosis might act as a determinant in the association between HTLV-1 infection and advanced periodontitis among elderly Japanese.


Assuntos
Aterosclerose/epidemiologia , Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Periodontite/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/etiologia , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Infecções por HTLV-I/virologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Periodontite/etiologia , Fatores de Risco
10.
Pharmacol Biochem Behav ; 187: 172794, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31654653

RESUMO

Orexin-producing neurons in the lateral hypothalamus are a critical regulator of sleep/wake states, and their loss is associated with narcolepsy type 1 (NT1). Orexin peptides act on two G protein-coupled receptors: orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). OX2R knockout (KO) mice, but not OX1R KO mice, showed clear narcolepsy-like phenotypes, including fragmented sleep-wake cycles. Moreover, OX2R-selective antagonists have been shown to induce sleepiness in mice, and activation of OX2R has been reported to increase wakefulness. In this study, we characterized in vitro and in vivo profiles of a novel, highly selective OX2R agonist, TAK-925 [methyl (2R,3S)-3-[(methylsulfonyl)amino]-2-{[(cis-4-phenylcyclohexyl)oxy]methyl}piperidine-1-carboxylate]. TAK-925 activated human recombinant OX2R with 50% effective concentration value of 5.5 nM, and showed >5,000-fold selectivity over OX1R in calcium mobilization assays. TAK-925 induced OX2R-downstream signals similar to those displayed by orexin peptides in Chinese hamster ovary cells stably expressing human OX2R. In an electrophysiological study, TAK-925 activated physiological OX2R on histaminergic neurons in the mouse tuberomammillary nucleus (TMN). Subcutaneous (SC) administration of TAK-925 also modulated neuronal activity in various brain regions, including TMN, as measured by an immunohistochemical analysis using an anti-c-fos antibody. TAK-925 (SC) increased wakefulness in wild-type mice, but not in OX2R KO mice, during their sleep phase, demonstrating that a highly selective OX2R agonist can increase wakefulness in mice via OX2R activation. TAK-925 may have therapeutic potential to reduce hypersomnia in multiple disorders including NT1.

11.
Environ Health Prev Med ; 24(1): 42, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182010

RESUMO

BACKGROUND: We reported that human T cell leukemia virus 1 (HTLV-1) infection is positively associated with atherosclerosis. Recent evidence has revealed a close association of periodontitis with atherosclerosis, endothelial dysfunction, and disruption of the microcirculation. However, the association between HTLV-1 and advanced periodontitis has not been investigated to date. Since hematopoietic activity is closely linked to endothelial maintenance activity and is known to decline with age, we hypothesized that the state of hematopoietic activity influenced the association between HTLV-1 and advanced periodontitis in elderly participants. METHODS: A cross-sectional study was performed including 822 elderly participants aged 60-99 years who participated in a dental health check-up. Advanced periodontitis was defined as a periodontal pocket ≥ 6.0 mm. Participants were classified as having low or high hematopoietic activity according to the median values of reticulocytes. RESULTS: HTLV-1 infection was positively related to advanced periodontitis among participants with lower hematopoietic activity (lower reticulocyte count), but not among participants with higher hematopoietic activity (higher reticulocyte count). The adjusted odds ratio (95% confidence interval) considering potential confounding factors was 1.92 (1.05-3.49) for participants with a lower reticulocyte count and 0.69 (0.35-1.36) for participants with a higher reticulocyte count. CONCLUSIONS: Among elderly participants, the association between HTLV-1 infection and advanced periodontitis is influenced by hematopoietic activity. Since hematopoietic activity is associated with endothelial maintenance, these findings provide an efficient tool for clarifying the underlying mechanism of the progression of periodontitis among elderly participants.


Assuntos
Infecções por HTLV-I/fisiopatologia , Hematopoese/fisiologia , Periodontite/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Periodontite/virologia , Prevalência , Fatores de Risco
12.
Clin Interv Aging ; 14: 849-857, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190771

RESUMO

Purpose: Age-related reduction in bone marrow activity has been shown to cause anemia, and hypertension and endothelial dysfunction (atherosclerosis) are age-related diseases. However, recent studies have revealed a close association between bone marrow activity and endothelial maintenance. This study aimed to determine the association between elevated reticulocyte levels in conjunction with vigorous bone marrow activity and hypertension and atherosclerosis among the elderly. Study population and Methods: To determine the associations between reticulocyte levels and hypertension and atherosclerosis, we conducted a cross-sectional study of 2,098 elderly Japanese individuals, aged between 60 and 89 years, who had participated in an annual health check-up in 2014. Results: Of the total study population, 1,348 individuals were diagnosed with hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or having used antihypertensive medication), and 393 were diagnosed with atherosclerosis (carotid intima-media thickness ≥1.1 mm). Reticulocyte levels were found to be significantly positively associated with hypertension and inversely associated with atherosclerosis. Cardiovascular risk factor-adjusted odds ratios and 95% confidence intervals for hypertension and atherosclerosis, when raised incrementally by 1 standard deviation to determine reticulocyte levels (5.5×104 cells/µL for men and 5.0×104 cells/µL for women), were 1.12 (1.01, 1.25) and 0.83 (0.72, 0.94), respectively. Conclusion: Along with established cardiovascular risk factors, reticulocyte levels in elderly Japanese individuals were found to be positively associated with hypertension and inversely associated with atherosclerosis. This finding may help clarify the background mechanisms concerning the association between bone marrow activity and vascular remodeling.


Assuntos
Aterosclerose/epidemiologia , Hipertensão/epidemiologia , Reticulócitos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/fisiopatologia , Pressão Sanguínea , Estudos Transversais , Feminino , Humanos , Hipertensão/fisiopatologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances
13.
Environ Health Prev Med ; 24(1): 26, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043174

RESUMO

BACKGROUND: Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. METHODS: We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. RESULTS: High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. CONCLUSION: SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.


Assuntos
Plaquetas/metabolismo , Estatura/genética , Endotélio Vascular/fisiologia , Predisposição Genética para Doença , Hipertensão/sangue , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Contagem de Plaquetas
15.
Atherosclerosis ; 283: 85-91, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30818167

RESUMO

BACKGROUND AND AIMS: Endothelial injury is well-known as a process that can lead to chronic kidney disease (CKD) and atherosclerosis. Hematopoietic activity is known to be associated inversely with CKD and positively with atherosclerosis. Since bone-derived progenitor cells (CD34-positive cells) contribute to endothelial repair (including the progression of atherosclerosis), understanding the association between CKD and carotid intima-media thickness (CIMT), in relation to circulating CD34-positive cell count, may be an efficient means of clarifying the mechanisms underlying endothelial activity. METHODS: We conducted a cross-sectional study of 570 elderly Japanese men aged 60-69 years, who underwent a general health check-up. Participants were stratified as per a median circulating CD34-positive cell count (1.01 cells/µL). RESULTS: Independent of the known cardiovascular risk factors, CIMT was found to be positively associated with CKD in the participants with high circulating CD34-positive cell counts but not in participants with low counts. Odds ratios were 1.40 (1.04, 1.89) for participants with high and 1.01 (0.72, 1.43) for participants with low circulating CD34-positive cell counts after adjustment for known cardiovascular risk factors at 95% confidence intervals for CKD with one standard deviation increment of CIMT. CONCLUSIONS: A positive association between CIMT and CKD was observed among participants with high circulating CD34-positive cell counts but not among participants with low counts. Endothelial repair activity might determine the association between CKD and CIMT.

16.
Geriatr Gerontol Int ; 19(6): 557-562, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30920121

RESUMO

AIM: The cardio-ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34-positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34-positive cells. METHODS: We carried out a cross-sectional study of 249 Japanese men, aged 60-69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34-positive cells might indicate the influence of consumptive reduction of circulating CD34-positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34-positive cell levels, using the median value in this population (0.95 cells/µL) as the cut-off. RESULTS: For participants with low circulating CD34-positive cell levels, logarithmic values of circulating CD34-positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [ß] = -0.22, P = 0.014), but not for participants with high levels (ß = -0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima-media thickness were detected for participants with low circulating CD34-positive cell levels (ß = -0.02, P = 0.865), significant positive associations were identified for participants with high levels (ß = 0.22, P = 0.028). CONCLUSIONS: As circulating CD34-positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34-positive cell counts. Our results also show that a positive association between CAVI and carotid intima-media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis. Geriatr Gerontol Int 2019; 19: 557-562.


Assuntos
Tornozelo/irrigação sanguínea , Antígenos CD34/sangue , Endotélio Vascular/metabolismo , Idoso , Envelhecimento/sangue , Biomarcadores/sangue , Estudos Transversais , Endotélio Vascular/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Rigidez Vascular
17.
Aging (Albany NY) ; 11(2): 663-672, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30695751

RESUMO

Recent studies have revealed an inverse association between height and cardiovascular disease and that endothelial progenitor cells (CD34-positive cells) contribute to vascular maintenance, which is associated with cardiovascular disease. However, evidence of the association between height and CD34-positive positive cells among elderly participants is limited. To assess this association, we conducted a cross-sectional study of 231 elderly Japanese men aged 65-69. Since enhanced production of circulating CD34-positive cells in response to endothelial injury might act have a strong confounding effect on the association between height and circulating CD34-positive cells, the median value for the levels of these cells (0.93 cells/µL) was used to stratify the participants. Multivariable linear regression analysis demonstrated that height was significantly positively associated with circulating CD34-positive cells for those participants with low levels of circulating CD34-positive cells (n=114) but not for those with higher levels (n=117), with a multi-adjusted standardized parameter estimate (ß) of 0.27 (p=0.008) for low and 0.11 (0.275) for higher circulating CD34-positive cell levels. The positive association is limited to participants with relatively low circulating CD34-positive cell levels, whose productivity of these cells is not activated. Our findings indicate that height is an indicator of vascular maintenance capability in elderly Japanese men.

18.
Pain Pract ; 19(5): 476-483, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30659740

RESUMO

OBJECTIVES: There have been no community-based studies investigating the association between sleep duration and postherpetic neuralgia (PHN) development. The aim of the current study was to examine the association of sleep with herpes zoster (HZ) incidence and PHN. METHODS: In total, 12,329 residents (ages 50 to 103 years) of Shozu County, Japan, participated in our study from December 2009 to November 2010 and were followed up for 3 years. At baseline, the participants completed self-administered health questionnaires, including those on usual sleep duration. Three dermatologists diagnosed HZ on the basis of clinical symptoms and virus identification testing by polymerase chain reaction and serological tests, and evaluated pain using a modified Zoster Brief Pain Inventory survey form via telephone. We used a Cox proportional hazard regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HZ and PHN. We also performed mediation analysis to examine whether hyperesthesia and acute pain intensity mediated the association between sleep shortage and chronic pain intensity. RESULTS: During follow-up, 400 cases of HZ were identified. Of these, 55 participants developed PHN. Sleep duration was not associated with HZ incidence. Sleep shortage increased the risk for PHN (HR 2.02 [95% CI: 1.06 to 3.85]). Hyperesthesia and acute pain intensity mediated the association between sleep shortage and chronic pain intensity (indirect/total effect ratio = 50% mediation). CONCLUSIONS: Sleep shortage was associated with increased risk for PHN, and hyperesthesia and acute pain intensity appeared to mediate this association. Sleep shortage may be a novel risk factor for PHN.


Assuntos
Neuralgia Pós-Herpética/epidemiologia , Sono , Dor Aguda/epidemiologia , Dor Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Herpes Zoster/complicações , Humanos , Hiperestesia/epidemiologia , Hiperestesia/etiologia , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/etiologia , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
19.
Bioorg Med Chem Lett ; 29(4): 654-658, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30598349

RESUMO

The kisspeptin (Kp, Kp-54, metastin)/KISS1R system plays crucial roles in regulating the secretion of gonadotropin-releasing hormone. Continuous administration of nonapeptide Kp analogs caused plasma testosterone depletion, whereas bolus administration caused strong plasma testosterone elevation in male rats. To develop a new class of small peptide drugs, we focused on stepwise N-terminal truncation of Kp analogs and discovered potent pentapeptide analogs. Benzoyl-Phe-azaGly-Leu-Arg(Me)-Trp-NH2 (16) exhibited high agonist activity for KISS1R and excellent metabolic stability in rat serum. A single injection of a 4-pyridyl analog (19) at the N-terminus of 16 into male Sprague Dawley rats caused a robust increase in plasma luteinizing hormone levels, but unlike continuous administration of nonapeptide Kp analogs, continuous administration of 19 maintained moderate testosterone levels in rats. These results indicated that small peptide drugs can be successfully developed for treating sex hormone deficiency.

20.
J Atheroscler Thromb ; 26(2): 145-153, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29899172

RESUMO

AIMS: The frequency of breakfast intake has been reported to be inversely associated with the risk of cardiovascular events; however, it is uncertain what the impact of the energy and nutrient intakes from breakfast are. We assessed the association between these intakes from breakfast and the risk of stroke prospectively. METHODS: In a baseline survey of four Japanese communities between 1981 and 1990, we enrolled 3 248 residents (1 662 men and 1 586 women) aged 40-59 years who were free from stroke and heart disease and who responded to the 24-hour dietary recall survey. We assessed the dietary intake at breakfast, lunch, dinner, and other times separately. RESULTS: During the median 25-year follow-up, 230 individuals (147 men and 83 women) developed stroke. After adjustment for age, community, other dietary intakes, and lifestyle and physiological factors, the multivariable-adjusted hazard ratios (95% confidence intervals) of intracerebral hemorrhage for the highest versus lowest quartiles of energy intake from breakfast were 0.38 (0.15-0.99) in men and 1.36 (0.36-5.10) in women. For the major nutrients, a higher saturated or monounsaturated fat intake at breakfast was associated with a reduced risk of intracerebral hemorrhage in men, and remained statistically significant after further adjustment for intake of other major nutrients from breakfast. CONCLUSIONS: A higher intake of energy from breakfast, primarily saturated or monounsaturated fat, was associated with a reduced risk of intracerebral hemorrhage in Japanese men.


Assuntos
Desjejum , Dieta/efeitos adversos , Ingestão de Energia , Nutrientes/efeitos adversos , Acidente Vascular Cerebral/etiologia , Adulto , Pesquisa Participativa Baseada na Comunidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Vigilância da População , Prognóstico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia
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