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Volume 219 (2009)
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- Issue 2 Pages 79-
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Volume 219, Issue 1
September
Displaying 1-10 of 10 articles from this issue
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Invited Review for the 90th Anniversary
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Kenta Ito, Yoshihiro Fukumoto, Hiroaki Shimokawa2009 Volume 219 Issue 1 Pages 1-9
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSIschemic heart disease is the leading cause of death and the number of refractory severe patients is increasing. Therefore, it is crucial to develop new therapeutic strategies for severe ischemic heart disease. We found that a low-energy shock wave (SW) (about 10% of energy density that used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Based on this in vitro study, we have started in vivo studies and have demonstrated that extracorporeal cardiac shock wave therapy with a low-energy SW upregulates the expression of VEGF, induces neovascularization, and improves myocardial ischemia in a porcine model of chronic myocardial ischemia without any adverse effects in vivo. On the basis of the promising results in animal studies, we have subsequently developed a new, non-invasive angiogenic therapy with low-energy SW for ischemic heart disease. Our extracorporeal cardiac SW therapy improved symptoms and myocardial perfusion evaluated with stress-scintigraphy in patients with severe coronary artery disease without indication of percutaneous coronary intervention or coronary bypass surgery. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective to ameliorate LV remodeling after acute myocardial infarction in pigs and to enhance angiogenesis in hindlimb ischemia in rabbits. Based on these animal studies, we are also conducting clinical studies in patients with acute myocardial infarction and those with peripheral artery disease. Thus, our extracorporeal cardiac SW therapy is an effective, safe, and non-invasive angiogenic strategy in cardiovascular medicine and its indication is now rapidly expanding.View full abstractDownload PDF (1566K)
Regular Contributions
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Yoko Komada, Yasushi Nishida, Kazuyoshi Namba, Takashi Abe, Satoru Tsu ...2009 Volume 219 Issue 1 Pages 11-16
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSPrevious studies have suggested that patients with obstructive sleep apnea syndrome (OSAS) are at an increased risk of motor vehicle accidents (MVAs). This study is the first systematic investigation of MVA risk among Japanese drivers with obstructive sleep apnea syndrome (OSAS). We investigated the rate of MVAs in the preceding 5 years and dozing off at the wheel in Japanese male OSAS drivers (n = 616, mean [S.D.] age: 46.3 [10.1] years old) and age-matched male controls (n = 600), and the characteristics of OSAS patients who experienced multiple MVAs as well as the effectiveness of continuous positive airway pressure (CPAP) treatment in reducing MVA risk. The odds ratio of MVA in the OSAS group compared to a general population was 2.36. Multivariate logistic regression analysis revealed that MVA was significantly associated with either subjective sleepiness beyond normal limits (Epworth sleepiness scale: ESS ≥ 11) or serious respiratory disorders (apnea hypopnea index: AHI ≥ 40). AHI scores were significantly higher in the group with multiple MVAs than in those with a single MVA, despite the ESS score in the former group being significantly lower. CPAP treatment was effective for reduction of MVA. The MVA rate among OSAS patients in the research area was significantly higher than that among the controls. Subjective excessive daytime sleepiness and severity of OSAS are independently associated with the occurrence of MVA. In conclusion, early diagnosis and treatment of OSAS drivers especially with serious respiratory disorder should be made to prevent multiple MVAs.View full abstractDownload PDF (393K) -
Ying Lu, Shuang Yang2009 Volume 219 Issue 1 Pages 17-23
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSAngiotensin II (Ang II) plays a pathophysiological role in the genesis of cardiac hypertrophy as a hypertrophic stimulus. But little is known about the terminal steps, in which Ang II reprograms cardiac gene expression. Histone deacetyltransferases (HDACs) are considered as the integrators of divergent stress-response pathways during heart remodeling. However, the exact role of HDACs in the hypertrophic process is not clear yet. Therefore, we studied the expression of HDAC2, one of Class I HDACs, and the effect of valproic acid (VPA), a nonspecific HDAC inhibitor, in the Ang II-induced cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were prepared from 1-day-old Wistar rats and treated with Ang II. The mRNA levels of HDAC2 and β-myosin heavy chain (β-MHC), a hypertrophic marker gene, were determined by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of HDAC2 and c-fos, an immediate early response gene, was evaluated by immunohistochemistry, and the surface areas of cardiomyocytes were measured using Motic Images software. The expression levels of HDAC2 mRNA and protein were increased in a time-dependent manner during the hypertrophic process, accompanied with the increment of β-MHC and c-fos proteins. Ang II also increased the surface area of cardiomyocytes by more than twofold. VPA significantly reversed these changes. These results suggest that Ang II may induce cardiomyocyte hypertrophy through HDACs in combination with c-fos and that VPA has the protective effect on cardiomyocyte hypertrophy. Thus, HDAC inhibition is a feasible therapeutic strategy that holds promise in the treatment of cardiac hypertrophy.View full abstractDownload PDF (808K) -
Masahiro Ieko, Sumiyoshi Naito, Mika Yoshida, Kaoru Kanazawa, Kazuhiro ...2009 Volume 219 Issue 1 Pages 25-31
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSSoluble fibrin monomer appears in the bloodstream during the extremely early stage of blood coagulation and generally forms a complex with fibrinogen, termed soluble fibrin monomer complex (FMC). Determination of FMC can provide information regarding the state of thrombotic diseases; thus it is important to investigate whether FMC serves as an early indicator of myocardial infarction (MI). We investigated hemostatic and fibrinolytic parameters including FMC to determine their capabilities for indicating thrombotic conditions in the coronary artery. Blood samples from 47 patients with acute MI were obtained within 48 hours (acute phase) and during 120 - 600 hours (recovery phase), respectively, after MI onset. Plasma FMC was significantly elevated in the acute phase, compared with that during the recovery phase and in healthy controls (p = 0.001), suggesting that its elevation indicates thrombotic events in the coronary artery of MI patients. D-dimer, a marker of thrombus formation accompanied with fibrinolysis, was increased in both phases in the patients. In addition, FMC and D-dimer were significantly increased within 24 hours after onset as compared to 24 - 48 hours (p = 0.003 and p = 0.011). Furthermore, cardiac troponin T, a marker of myocardial damage, was significantly higher after 24 hours than within the first 24 hours (p = 0.001). Receiver operating characteristic (ROC) analysis of FMC for early MI diagnosis indicates that FMC, rather than D-dimer, is a better marker within 24 hours of onset. Measuring plasma FMC may be useful for early diagnosis of MI recurrence and deciding primary treatment.View full abstractDownload PDF (458K) -
Nihat Kalay, Okay Caglayan, Hasan Akkaya, Ibrahim Ozdogru, Ali Dogan, ...2009 Volume 219 Issue 1 Pages 33-37
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSAortic dissection (AD) is a disease characterized by tear of the aortic intimal layer and separation of the arterial wall. Some risk factor such as hypertension and Marfan syndrome is well known in AD. However, the role of genetic factors in AD is largely unknown. Insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with cardiovascular diseases; patients with D allele have higher serum and tissue ACE levels. We investigated the relationship between the I/D polymorphism of the ACE gene and non-syndromic acute AD. Sixteen patients diagnosed with AD were included in the study (mean age: 60.1 ± 6.2 years). The diagnosis was established by clinical evaluation and imaging techniques. The control group consisted of 22 age-matched patients without AD (60.9 ± 7.3 years), who suffered from chest pain. Incidence of hypertension was similar in dissection and control groups (62% vs. 59%). The I/D polymorphism was investigated in both groups by PCR analysis. Dissection types according to the DeBakey classification were identified as type 1 (proximal + distal) in 7 patients (43%), type 2 (proximal) in 5 patients (31%), and type 3 (distal) in 4 patients (25%). The D/D and D/I polymorphisms are present in 13 and 3 AD patients, respectively. None of patients with AD have the II polymorphism. The frequencies of the D allele (DD + ID) are significantly higher in dissection group than control (100% vs. 68%, P < 0001). These results indicate that the D allele of ACE gene is a risk factor for AD.View full abstractDownload PDF (347K) -
Isao Tsuji, Kazumi Ami, Ayako Miyazaki, Naoko Hujinami, Hiroshi Hoshia ...2009 Volume 219 Issue 1 Pages 39-42
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSPatients with unexplained infertility following standard infertility screening tests usually undergo timing therapy that coordinates the time of ovulation and coitus, controlled ovarian hyperstimulation, or intrauterine insemination. If the treatment is unsuccessful, diagnostic laparoscopy is performed. However, with recent improvements in the assisted reproductive technology (ART), there has been a growing tendency that bypasses diagnostic laparoscopy and proceeds directly to ART. Therefore, the value of diagnostic laparoscopy in current fertility practice is under debate. In the present study, we evaluated the usefulness of diagnostic laparoscopy for patients with unexplained infertility and normal hysterosalpingography (HSG) findings. Between January 1997 and December 2006, 57 infertile patients with normal HSG findings underwent diagnostic laparoscopy at Kinki University Hospital. In 46 (80.7%) of these patients, diagnostic laparoscopy revealed pathologic abnormalities. Specifically, endometriosis and peritubal and/or perifimbrial adhesions were found in 36 (63.2%) and 5 (8.8%) of the patients, respectively. In 8 patients (14.0%), the management plan was switched to ART because of severe tubal diseases. Among the 57 patients, 29 pregnancies (50.9%) were achieved, including 6 ART-mediated pregnancies. We conclude that diagnostic laparoscopy is beneficial for patients with unexplained infertility and normal HSG findings. Indeed, by diagnostic laparoscopy, we are able to detect the cause(s) of infertility in the pelvic cavity and to design a suitable management plan, which could lead to postoperative pregnancy. Therefore, because of the potential diagnostic and therapeutic benefits, patients with unexplained infertility and normal HSG findings should undergo diagnostic laparoscopy prior to ART.View full abstractDownload PDF (345K) -
Chengcheng Zhou, Yu Zhou, Jing Li, Yuan Zhang, Lu Jiang, Xin Zeng, Xia ...2009 Volume 219 Issue 1 Pages 43-51
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSPolymorphisms in the X-ray repair cross-complementing group 1 (XRCC1) gene have been reported as a potential risk factor for the development of oral cancer; however, the overall results are still controversial. In the present study, we therefore performed a meta-analysis of eight case-control studies that examined the association of oral cancer with XRCC1 gene polymorphisms in different populations, including codon 194 (Arg-Trp), 280 (Arg-His) and 399 (Arg-Gln), based on the data identified in Medline of up to June 2008. Literature-based searching was conducted to gather data and both fixed-effects and random-effects model were used to pool the odds ratio (OR). Publication bias and between-study heterogeneity were also evaluated. The eligible studies included 1,326 cases and 3,130 controls. The OR of various comparisons showed that the oral cancer risk was not associated with the selected three XRCC1 polymorphisms (P > 0.05). However, after stratification, significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer risk among Asians, showing an OR of 1.347 (95% confidence interval (CI): 1.000, 1.814) for allele comparison, 1.378 (95% CI: 1.070, 1.775) for TT homozygotes versus CC homozygotes, and 1.420 (95% CI: 1.041, 1.936) for comparison under the dominant model. Publication bias was not shown around the studies; however, ORs among these three polymorphisms all yielded significant between-study heterogeneity (P < 0.05) and a part of the heterogeneity was from ethnic differences. We suggest that the Arg194Trp polymorphism in the XRCC1 gene may be a biomarker of oral cancer susceptibility among Asian population.View full abstractDownload PDF (657K) -
Masayuki Izumi, Takashi Seki, Koh Iwasaki, Kazuichi Sakamoto2009 Volume 219 Issue 1 Pages 53-62
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSAbnormal lipid metabolism in adipose tissue is closely related to the occurrence and progression of a wide variety of metabolic syndromes. We have analyzed the pharmacological effects of Chinese herbal medicines on cell differentiation and lipid metabolism in adipocytes. Yi-Gan-San (YGS) is a Chinese herbal medicine that is effective in treating the behavioral and psychological symptoms of dementia; however, its physiological mechanism remains unclear. We analyzed the effects of YGS on lipid accumulation in mouse 3T3-L1 adipocytes. Adipocyte differentiation was induced in mouse 3T3-L1 preadipocytes by treatment with the mixture of dexamethasone, 3-iso-butyl-1-methylxanthine, and insulin, and cells were cultured for 8 days with Chinese herbal medicines, including YGS. YGS effectively reduced the lipid accumulation in the differentiated 3T3-L1 cells in a dose-dependent manner, but had no effect on cell viability. YGS also reduced the activity of glycerol-3-phosphate dehydrogenase, an enzyme involved in lipid synthesis. In contrast, YGS gave no noticeable effect on glucose uptake and fatty acid uptake in the differentiated 3T3-L1 cells. Moreover, we established the stably transfected 3T3-L1 cell lines, each of which expresses the luciferase reporter gene under the control of sterol regulatory element-binding protein-1c (SREBP-1c) or FoxO1. SREBP-1c is a transcription factor involved in fatty acid synthesis, and FoxO1 is a forkhead-type transcription factor involved in adipocyte differentiation. Using these cell lines, we showed that YGS reduced the transcriptional activity of SREBP-1c, whereas YGS increased the activity of FoxO1. Thus, YGS may suppress lipid synthesis and fat accumulation in adipocytes through modulating the activities of SREBP-1c and FoxO1.View full abstractDownload PDF (1739K) -
Takahiko Nohara, Misao Ueda, Akira Ohta, Toshitugu Sugimoto2009 Volume 219 Issue 1 Pages 63-69
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSThe assessment of growth, including the developmental change in bone mass, is crucial for child health care. We herein report normative values of bone mineral density (BMD) for calcaneus obtained from a large cross-section sample in Japanese school children. To investigate yearly physical growth from pre-school age to adulthood, we measured height, weight, body mass index (BMI), and BMD in 3,835 school children aged 3 to 18 (1,886 boys and 1,949 girls). Participating institutions included kindergarten, junior high schools, high schools, and a college of technology. The growth pattern (or velocity) of BMD (the ratio of trabecular bone area of the calcaneum) shows 3 phases according to the age rage: 3-10, 11-15, and 16-18 years for boys, and 3-7, 8-15, and 16-18 years for girls, both peaking at age 16 years. Likewise, that of weight shows 3 phases: 3-4, 5-15 and 16-18 years for boys, and 3-4, 5-14 and 15-18 years for girls, while the growth pattern of height shows 2 phases: 3-15 and 16-18 years for boys, and 3-13 and 14-18 years for girls, both sexes peaking at approximately 16 years. Therefore, the physical growth pattern of the school children shows progressive growth until 16 years, at which time growth is generally completed. In children under 16 years old, BMD of the calcaneus is higher in girls than in boys. Boys and girls show a similar growth pattern in body height and weight before peak development; however, the physical growth of boys eventually exceeds that of girls.View full abstractDownload PDF (985K) -
Xin-Fang Leong, Mohd Nadzri Mohd Najib, Srijit Das, Mohd Rais Mustafa, ...2009 Volume 219 Issue 1 Pages 71-78
Published: 2009
Released on J-STAGE: August 28, 2009
JOURNAL FREE ACCESSOxidization of dietary cooking oil increases the risk of cardiovascular diseases such as hypertension by increasing the formation oxidative oxygen radicals. The aim of study was to investigate the effects of repeatedly heated palm oil on blood pressure, plasma nitrites, and vascular reactivity. Nitrites were measured, as an indirect marker for nitric oxide production. Male Sprague-Dawley rats were divided into four groups: control group fed with basal diet and other three groups fortified with 15% weight/weight fresh palm oil (FPO), palm oil heated five times (5HPO) or palm oil heated ten times (10HPO) for 24 weeks. The oil was heated to 180°C for 10 min. Blood pressure was measured at baseline and at intervals of four weeks for 24 weeks using non-invasive tail-cuff method. Following 24 weeks, the rats were sacrificed and thoracic aortas were dissected for measurement of vascular reactivity. Blood pressure was elevated significantly (p < 0.05) in 5HPO and 10HPO groups, with the 10HPO group showing higher values. Aortic rings from animals fed with heated oil showed diminished relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. Acetylcholine and sodium nitroprusside cause endothelium-dependent and endothelium-independent relaxation, respectively. Relaxation responses remained unaltered in the FPO group, with the attenuated contractile response to phenylephrine, compared to control group. FPO increased plasma nitrites by 28%, whereas 5HPO and 10HPO reduced them by 25% and 33%, respectively. Intake of repeatedly heated palm oil causes an increase in blood pressure, which may be accounted for by the attenuated endothelium-dependent vasorelaxant response.View full abstractDownload PDF (325K)
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