Showing papers in "Tohoku Journal of Experimental Medicine in 2008"
TL;DR: The ability of FABPs to regulate functions of the brain, one of the most fat-enriched tissues in the body, is demonstrated.
Abstract: Long chain fatty acids are important nutrients for brain development and function. However, the molecular basis of their actions in the brain is still to be clarified. Fatty acid-binding proteins (FABPs) belong to the multigene family of the intracellular lipid-binding protein. FABPs bind to long chain fatty acids, being involved in the promotion of cellular uptake and transport of fatty acids, the targeting of fatty acids to specific metabolic pathways, and the regulation of gene expression. FABPs are widely expressed in mammalian tissues, with distinct expression patterns for the individual protein. Although FABPs have been implicated to serve as regulators in systemic cellular metabolic pathways, recent studies have demonstrated the ability of FABPs to regulate functions of the brain, one of the most fat-enriched tissues in the body. This review summarizes the localization of FABPs in the brain, and recent progress in elucidating the function of FABPs in the brain.
104 citations
TL;DR: Salivary and serum cortisol concentrations and state and trait anxiety levels in RAS were significantly higher than those in the control group, suggesting that stress may be involved in the pathogenesis of RAS.
Abstract: Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal disorders. The aim of the study was to determine any association between anxiety levels and concentrations of salivary and serum cortisol in patients with RAS. It has been suggested that stress with its presumed effects on the immune system, constitutes one of the major causative agents of RAS. The concentrations of salivary and serum cortisol were measured in 38 patients with recurrent aphthous stomatitis, and 38 healthy controls. Salivary and serum cortisol levels were measured using a Luminenscent Immunoassay (LIA) method. Anxiety levels were evaluated using Spielberger's State-Trait Anxiety Inventory which measures both trait anxiety as a general aspect of personality (STAI-T) and state anxiety as a response to a specific situation (STAI-S). The salivary cortisol levels were 1.44 (+/- 0.58) microg dl(-1) in RAS patients and 0.91 (+/- 0.56) microg dl(-1) in controls (p = 0.001), while the serum cortisol levels were 3.13 (+/- 1.59) microg dl(-1) in RAS patients and 1.89 (+/- 1.11) microg dl(-1) in controls (p = 0.001). The state anxiety levels (STAI-S) were 48.85 (+/- 9.7) in RAS group and 39.45 (+/- 7.5) in control group (p = 0.001). The trait anxiety levels (STAI-T) were 49.78 (+/- 13.02) in RAS group and 38.49 (+/- 10.31) in control group (p = 0.001). Salivary and serum cortisol concentrations and state and trait anxiety levels in RAS were significantly higher than those in the control group. Our results suggest that stress may be involved in the pathogenesis of RAS.
101 citations
TL;DR: Results suggest that the low-energy extracorporeal cardiac shock wave therapy also is effective and safe for the treatment of peripheral artery disease.
Abstract: We have recently demonstrated that the low-energy extracorporeal cardiac shock wave (SW) therapy improves myocardial perfusion and cardiac function in a porcine model of chronic myocardial ischemia and also ameliorates myocardial ischemia in patients with severe coronary artery disease. The present study was designed to examine whether our SW therapy also is effective to ameliorate hindlimb ischemia in rabbits. Hindlimb ischemia was made by surgical excision of the entire unilateral rabbit femoral artery. One week after the operation, we performed the SW (n = 9) or sham-therapy (n = 9) to the ischemic region 3 times a week for 3 weeks. Three weeks after the SW therapy, the development of collateral arteries, the flow ratio of the ischemic/non-ischemic common iliac arteries, the blood pressure ratio of the ischemic/non-ischemic hindlimb, and the capillary density in the ischemic muscles were all significantly increased in the SW group compared with the control group, indicating that the SW therapy induced therapeutic angiogenesis. Importantly, no adverse effect, such as muscle damage, hemorrhage, or thrombosis, was noted with the therapy. Finally, we examined the role of endothelial nitric oxide synthesis (eNOS) and vascular endothelial growth factor (VEGF) in the mechanisms of SW-induced angiogenesis on day 28. The expression levels of eNOS and VEGF proteins in ischemic hindlimb muscles tended to be increased in the SW group compared with the control group. These results suggest that our low-energy SW therapy also is effective and safe for the treatment of peripheral artery disease.
65 citations
TL;DR: Flow velocities in basal cerebral arteries range widely and are significantly age-related, which was significant when subjects older than 40 years and < or = 40 years old were compared.
Abstract: Transcranial Doppler sonography (TCD) is a non-invasive diagnostic tool enabling evaluation of blood flow characteristics of basal intracerebral vessels via thin calvarian regions. Several factors may affect the normal values of cerebral hemodynamic parameters, and standard reference values for each laboratory are needed for precise interpretation of the results. The aims of this study were to determine normal values of flow velocities of basal cerebral arteries of our TCD laboratory, and to study the influence of age and gender on normal values. We studied 63 healthy volunteers (30 male and 33 females; age range, 5 - 69 years old) with TCD with a 2-MHz transcranial probe. The subjects were divided into 7 age groups: 5-10 years, 11-20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years and > 60 years. Mean velocity (V mean), peak systolic velocity (PSV), and end-diastolic velocities (EDV) were determined in middle, anterior and posterior cerebral arteries. No significant gender difference was found. However, there was a decrease in blood flow velocities in all vessels with advancing age, which was significant when subjects older than 40 years and < or = 40 years old were compared. V mean, PSV and EDV values were highest in the age group of 5 - 10 years old and lowest in volunteers older than the age of 60 (p < 0.05). As a conclusion, flow velocities in basal cerebral arteries range widely and are significantly age-related. Age matching of TCD data is a requirement for clinically relevant conclusions.
61 citations
TL;DR: Brain/ behavior correlational analyses suggest that the prefrontal cortex and posterior dorsomedial regions including the precuneus may be involved in self-awareness.
Abstract: In addition to their memory impairment, individuals with Alzheimer's disease (AD) often suffer from deficits in self-awareness. Awareness of memory deficits or metamemory is a multifaceted function, comprising on-line self-monitoring, generalized self-beliefs of memory efficacy, and generalized knowledge about memory functions. Awareness of memory problems in early-stage AD is a matter of clinical importance from a humanistic point of view, because higher levels of awareness may be associated with better future outcomes. Current methods of measuring awareness tend to fall into two categories, i.e., to introduce a questionnaire assessing patient/caregiver discrepancies; or to ask a patient to prospectively predict or retrospectively postdict their own memory performances. Characteristics of each measure as well as relationship between the two measures were discussed. For the performance prediction/postdiction paradigm, we used recognition memory of auditory verbal learning tests and awareness of memory deficits were examined in 24 individuals with early-stage AD. In addition to their significantly impaired recognition memory, individuals with AD displayed underawareness of memory deficits even at this early stage. They retrospectively overestimated memory performance after actual performance, but appeared to benefit from feedback and displayed intact on-line awareness of memory dysfunction, leading to normal prediction of the second session. However, individuals with AD again failed to retrospectively incorporate incidents of memory failure into generalized self-belief systems. Brain/behavior correlational analyses suggest that the prefrontal cortex and posterior dorsomedial regions including the precuneus may be involved in self-awareness.
57 citations
TL;DR: In determining MFT norms, total score and items testing dexterity were influenced by age, gender, and hand dominance, and rates of decline in numbers of pegs achieved were similar between hands.
Abstract: Stroke is the leading cause of long-term disability Accurate assessment of motor function is important for documenting disability and the effectiveness of rehabilitative treatment The Manual Function Test (MFT) was developed to evaluate unilateral manual performance in hemiparetic patients after stroke This test consists of eight items, including the pegboard task, an item assessing dexterity The total MFT score can range from 0 (severely impaired) to 32 (full function) We sought to determine normative data and explore influences of age, gender, and hand dominance Three-hundred thirty-three healthy adult subjects between 20 and 90 years old were studied Total MFT scores showed negative relationship to age Compared with subjects in their 20s, those 50 or more years old had lower total MFT scores for dominant hands, as did those 40 or more years old for nondominant hands For subjects in their 30s and 50s, total MFT scores for women were greater than for men concerning nondominant hands No such gender difference in total MFT scores was noted for dominant hands In the pegboard test, the number of pegs achieved for dominant hands was related to age when age was 50 or over, and when age 40 or over for nondominant hands However, rates of decline in numbers of pegs achieved were similar between hands In determining MFT norms, total score and items testing dexterity were influenced by age, gender, and hand dominance
57 citations
TL;DR: Using a more precise estimation method by selecting the optimum body posture, electrode arrangement, and frequency, an accurate assessment of VFA is obtained using the bioelectrical impedance method.
Abstract: Excessive visceral fat area (VFA) is a major risk factor in such conditions as cardiovascular disease. In assessing VFA, computed tomography (CT) is adopted as the gold standard; however, this method is cost intensive and involves radiation exposure. In contrast, the bioelectrical impedance (BI) method for estimating body composition is simple and noninvasive and thus its potential application in VFA assessment is being studied. To overcome the difference in obtained impedance due to measurement conditions, we developed a more precise estimation method by selecting the optimum body posture, electrode arrangement, and frequency. The subjects were 73 healthy volunteers, 37 men and 36 women, who underwent CT scans to assess VFA and who were measured for anthropometry parameters, subcutaneous fat layer thickness, abdominal tissue area, and impedance. Impedance was measured by the tetrapolar impedance method using multi-frequency BI. Multiple regression analysis was conducted to estimate VFA. The results revealed a strong correlation between VFA observed by CT and VFA estimated by impedance (r = 0.920). The regression equation accurately classified VFA > or = 100 cm(2) in 13 out of 14 men and 1 of 1 woman. Moreover, it classified VFA > or = 100 cm(2) or < 100 cm(2) in 3 out of 4 men and 1 of 1 woman misclassified by waist circumference (W) which was adopted as a simple index to evaluate VFA. Therefore, using this simple and convenient method for estimating VFA, we obtained an accurate assessment of VFA using the BI method.
56 citations
TL;DR: The above data suggest that ADSVFs could be differentiated into chondrocyte-like cells in the gel-embedding sheet method and could be useful in regenerative medicine to treat cartilage defects or cartilage degenerative disease.
Abstract: The incidence of arthritic diseases is rapidly increasing in most advanced countries. Articular cartilage, which is the most important tissue in the joint, consists of chondrocytes and abundant extracellular matrix, including aggrecan, and shows poor self-repair. We studied the potential of stem cells in mouse subcutaneous adipose tissue as a source of cells to regenerate cartilage tissue. Analysis of adipose-derived stromal vascular fraction culture cells (ADSVFs) using mesenchymal stem cell markers showed that CD90-positive cells accounted for 93.8%, CD105-positive cells for 68.5%, and p75 neurotrophin receptor (p75NTR, CD271)-positive cells for 36.1%. These results indicate that cells positive for mesenchymal stem cell markers are present in ADSVFs. The CD105-positive or -negative cells were isolated from ADSVFs by magnetic cell separation (MACS), and the efficiency of differentiation into chondrocytes was compared with using three methods of pellet method, gel-coating method, and gel-embedding sheet method. Using the CD105-positive cells and the gel-embedding sheet method, aggrecan mRNA was detected about three times higher than pellet and gel-coating methods. The above data suggest that ADSVFs could be differentiated into chondrocyte-like cells in the gel-embedding sheet method and could be useful in regenerative medicine to treat cartilage defects or cartilage degenerative disease. The use of cells sorted by mesenchymal stem cell markers from adipose tissue would gain position in the repair of cartilage tissue.
55 citations
TL;DR: adjusted average duration of fever indicated that oseltamivir was effective for both types, but more effective on influenza A, and the benefit increased for younger children, but the effectiveness is differed by type and age.
Abstract: Oseltamivir has been used for treatment of influenza A and B infections, but recent reports documented that it was less active against the latter. We compared the effectiveness of oseltamivir in children between laboratory confirmed influenza A and B over 4 influenza seasons from 2001 to 2005 in a pediatric clinic in Japan. Among 1,848 patients screened, 299 influenza A and 209 influenza B patients were administered oseltamivir (treated groups), and 28 influenza A and 66 influenza B patients were assigned as non-treated groups. The duration of fever, defined as period when patients had the maximum temperature higher than 37.5°C in three-time measurements in a day after the clinic visit, was evaluated among the four groups. In uni-variate analysis, the duration of fever was shorter for treated group than non-treated for influenza A (1.8 ± 0.9 days vs 2.6 ± 1.3 days, p < 0.01), but it was not significant for influenza B (2.4 ± 1.3 days vs 2.8 ± 1.2 days, p = 0.9). The fever duration was longer in treated influenza B than A patients (p < 0.01). Multi-variate analysis indicated younger age (< 6 years old) and higher body temperature at the clinic visit prolonged the duration of fever. Adjusted average duration of fever indicated that oseltamivir was effective for both types, but more effective on influenza A, and the benefit increased for younger children. Our data provide evidence that oseltamivir is beneficial for influenza infections, but the effectiveness is differed by type and age.
54 citations
TL;DR: Jaw surgery markedly improved the disease-specific HRQOL and psychological status in the patients with facial deformities and it is suggested that assessments of the HRQol and psychologicalstatus before treatment might predict the HRZOL and Psychological status after the treatment to a certain extent.
Abstract: Patients with malocclusion, especially those in need of surgical correction, have lower health related quality of life (HRQOL) and higher anxiety. We investigated the changes of HRQOL and psychological status following jaw surgery in the patients with facial deformities. Thirty-one adult orthodontic patients admitted to Tohoku University Hospital and diagnosed as malocclusion requiring jaw surgery were recruited for the study. The severity of malocclusion was assessed by Severity Score (SS) which is based on their cephalometric radiographs. They were divided into three groups according to the severity of malocclusion, i.e. Low-SS, Moderate-SS and High-SS. The subjects also completed a generic HRQOL (entire body health) instrument, and three disease-specific oral HRQOL instruments. HRQOL and psychological status of the patients were assessed before (T1) and at debonding of multibracketed appliances after surgery (T2). SS in each group significantly decreased to normal occlusion level (SS = 0-1). Oral function significantly improved from 11.8 ± 5.4 to 5.9 ± 4.3 in the Low-SS (p < 0.01), from 13.7 ± 6.5 to 8.8 ± 5.1 in the Moderate-SS (p < 0.05), and from 14.7 ± 6.7 to 7.8 ± 5.7 in the High-SS (p < 0.01). The patients after the surgical correction had improved disease-specific HRQOL and state anxiety irrespective of the severity before surgery, although the generic HRQOL, trait anxiety and depression were equal to that before the surgery. Furthermore, both postoperative anxiety and HRQOL were estimated by the preoperative anxiety and HRQOL. These results indicated that jaw surgery markedly improved the disease-specific HRQOL and psychological status in the present patients. We therefore suggest that assessments of the HRQOL and psychological status before treatment might predict the HRQOL and psychological status after the treatment to a certain extent.
54 citations
TL;DR: The consumption of repeatedly heated oil may predispose to atherosclerosis in estrogen-deficient states, and the protective effect of the soy oil may be lost once it was being repeatedly heated.
Abstract: Repeated heating of soy oil may promote lipid peroxidation. Oxidized unsaturated fatty acids may contribute to the pathogenesis of atherosclerosis, especially in estrogen-deficient states. This study was performed to explore the deleterious effects of repeatedly heated soy oil on the development of atherosclerosis using ovariectomized rats, which represent an estrogen-deficient state. Twenty-four female Sprague-Dawley rats were ovariectomized and were divided equally into four groups. The control group was fed with 2% cholesterol diet without any oil. The three treatment groups each received 2% cholesterol diet fortified with fresh, once-heated or five-times-heated (repeatedly heated) soy oil, respectively. Serum thiobarbituric acid reactive substances (TBARS), lipid profile and homocysteine levels were measured prior to ovariectomy and at the end of four months. Ovariectomized rats treated with repeatedly heated soy oil showed significant increases in lipid peroxidation and low-density lipoprotein (LDL) levels. Treatment with once-heated or repeatedly heated soy oil caused a significant increase in total cholesterol, while fresh soy oil caused significant reduction in homocysteine level as compared to other groups. Repeatedly heated soy oil caused significant increases in TBARS and LDL as compared to fresh oil. The higher level of homocysteine in the ovariectomized rats fed with repeatedly heated oil, as compared to those fed with fresh oil, also suggests the repeatedly heated oil contributes to the development of atherosclerosis. Importantly, the protective effect of the soy oil may be lost once it was being repeatedly heated. In conclusion, the consumption of repeatedly heated oil may predispose to atherosclerosis in estrogen-deficient states.
TL;DR: The results indicate that smoking is a major risk factor of cervical cancer and hormonal factors, which are related to early onset of menarche and low parity, are common risk factors for endometrial and ovarian cancers.
Abstract: During recent decades, the incidence of gynecologic cancers, i.e., cancers of the cervix, endometrium and ovary, has increased in Japan. However, risk factors of gynecologic cancers have not been fully clarified in Japan. To investigate common and site-specific risk factors among gynecologic cancers, we conducted a hospital-based case-control study. The cases, i.e., 151 cervical, 103 endometrial and 141 ovarian cancer cases and the controls (n = 2016) were selected from female patients aged 30 and over, who were admitted to a single hospital in Miyagi Prefecture from 1997 to 2003. Information on reproductive factors, exogenous hormone use, and lifestyles including smoking was collected using a self-administered questionnaire. Smoking was significantly associated with an increased risk of cervical cancer. A dose-response relationship with the number of cigarettes per day was also observed (p for trend = 0.004). Older age at menarche was associated with a decreased risk of endometrial and ovarian cancers. For these cancers, the decreased risk was detected with increasing parity number (endometrium, p for trend = 0.0001; ovary, p = 0.0002). There was no significant association between exogenous hormone use and gynecologic cancer risk. The results indicate that smoking is a major risk factor of cervical cancer. In addition, hormonal factors, which are related to early onset of menarche and low parity, are common risk factors for endometrial and ovarian cancers. The increase in female smokers and the decrease in fertility rate may contribute to the increase in gynecologic cancer incidence in Japan.
TL;DR: Sepsis is associated with the increased percentages of Treg cells and elevated plasma level of soluble CD25, and the elevation of these parameters might be a useful marker of infections in SIRS.
Abstract: The function of immune system is to protect hosts from invading microorganisms by destroying infected cells while minimizing damage to tissues. Among immune cells, CD4(+)CD25(+) regulatory T cells (Treg cells) control immune responses by limiting infectious processes. However, it remains unclear whether Treg cells are induced in systemic inflammatory response syndrome (SIRS) or infectious SIRS (i.e. sepsis). SIRS and sepsis are associated with stressful inflammatory conditions. We therefore measured CD25(+) T cells and circulating CD4(+) T cells, along with plasma levels of CD25, interleukin (IL)-6, and IL-10, in 20 septic patients (64 +/- 11 years), 16 SIRS patients (59 +/- 16 years), and control subjects: 13 elderly (60 +/- 16 years) and 14 young volunteers (28 +/- 3 years). Septic patients (23.3 +/- 11.8%, p < 0.01) showed significantly higher percentages of CD25(+) cells among CD4(+) T cells (i.e. Treg cells) than did either young (10.6 +/- 3.7%) or elderly volunteers (11.1 +/- 3.8%). The percentages of Treg cells in septic patients were higher than those in SIRS patients (12.4 +/- 6.9%, p < 0.01). Moreover, plasma levels of soluble CD25 were significantly higher in septic patients, compared to the levels in SIRS patients or volunteers (p < 0.01). No significant difference in plasma levels of IL-6 or IL-10 was found between septic patients and SIRS patients. Thus, sepsis is associated with the increased percentages of Treg cells and elevated plasma level of soluble CD25. The elevation of these parameters might be a useful marker of infections in SIRS.
TL;DR: It is understood that owing to molecular mechanisms that fuel homosynaptic competition among CFs and PFs is properly structured and mono-innervation by CFs is established.
Abstract: Cerebellar Purkinje cells (PCs) play a principal role in motor coordination and motor learning. To fulfill these functions, PCs receive and integrate two types of excitatory inputs, climbing fiber (CF) and parallel fiber (PF). CFs are projection axons from the inferior olive, and convey error signals to PCs. On the other hand, PFs are T-shaped axons of cerebellar granule cells, and convey sensory and motor information carried through the pontocerebellar and spinocerebellar mossy fiber pathways. The most remarkable feature of PC circuits is the highly territorial innervation by these two excitatory afferents. A single climbing CF powerfully and exclusively innervates proximal PC dendrites, whereas hundreds of thousands of PFs innervate distal PC dendrites. Recent studies using gene-manipulated mice have been elucidating that the PC circuitry is formed and maintained by molecular mechanisms that fuel homosynaptic competition among CFs and heterosynaptic competition between CFs and PFs. GluRdelta2 (a PC-specific glutamate receptor) and precerebellin or Cbln1 (a granule cell-derived secretory protein) cooperatively work for selective strengthening of PF-PC synapses, and prevent excessive distal extension of CFs that eventually causes multiple innervation at distal dendrites. In contrast, P/Q-type Ca2+ channels, which mediate Ca2+ influx upon CF activity, selectively strengthen the innervation by a single main CF, and expel PFs and other CFs from proximal dendrites that it innervates. Therefore, we now understand that owing to these mechanisms, territorial innervation by CFs and PFs is properly structured and mono-innervation by CFs is established. Several key issues for future study are also discussed.
TL;DR: The results suggest that oral functions significantly improve after conducting a six-month exercise program for oral function, and this improvement appears to be influenced by the number of remaining teeth.
Abstract: In Japan, one of the duties of the long-term care insurance system is the prevention of oral function degradation. Although various exercise programs for oral function have been developed and practiced in Japan, to date, no study has reported their effects. In the present study, we examined the effects of an exercise program on oral functions in healthy elderly people. Healthy elderly people participated in the study and were randomly divided into intervention and control groups (39 subjects/group). The exercise program consisted of four exercises: exercise for expression muscles, tongue, salivary glands, and swallowing. Before and after a six-month intervention period, we evaluated changes in oral functions, namely bite force, swallowing ability, and salivary flow rate. Fifty-four subjects completed the study protocol: 26 and 28 subjects from intervention and control groups, respectively. A significant improvement in all oral functions, including bite force, swallowing ability, as well as unstimulated and stimulated salivary flow rate, was observed in the intervention group after six months, whereas no improvement was observed in the control group. Further, among the intervention group, a significant improvement in oral functions was observed in 17 subjects with 20 or more remaining teeth, whereas no improvement was observed in the other nine with less than 20 teeth. Our results suggest that oral functions significantly improve after conducting a six-month exercise program for oral function. Further, this improvement appears to be influenced by the number of remaining teeth.
TL;DR: The alteration in Doppler waveform pattern of portal vein with fatty liver population suggests reduced vascular compliance in the liver.
Abstract: Paralleling the rise in the incidence of obesity and diabetes worldwide, nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as one of the major causes of chronic liver disease. Doppler sonography is used as a diagnostic method in the non-invasive assessment of the hemodynamics of hepatic vascular flow in liver diseases. We investigated the effects of fatty infiltration in the liver on the Doppler flow hemodynamics of the portal vein. Doppler sonography of the liver and portal vein was performed in 60 subjects with NAFLD and 20 healthy volunteers (control). The patients were grouped into mild (grade 1), moderate (grade 2), and severe (grade 3) according to sonographic appearance of hepatosteatosis (n = 20 for each group). The vein pulsatility index (VPI), mean flow velocity (MFV), peak maximum velocity (V(max)), and peak minimum velocity (V(min)) of the portal vein were significantly lower in patients with NAFLD than those of the controls (p < 0.001). The VPI was 0.20 in the patients and 0.31 in the control. The MFV was 12.3 cm/sec in the patients and 16.5 cm/sec in the control group. The portal vein flow was found to be decreased as the grade of fatty infiltration increased for VPI (r = -0.946, p < 0.001), MFV (r = -0.951, p < 0.001). The alteration in Doppler waveform pattern of portal vein with fatty liver population suggests reduced vascular compliance in the liver.
TL;DR: In Japan, the national screening for the hepatitis C virus (HCV) has been started for both the general population and the high-risk groups and the screening strategy appears to be more cost-effective than a no- screening strategy.
Abstract: In Japan, the national screening for the hepatitis C virus (HCV) has been started for both the general population and the high-risk groups. Our cost-effectiveness analysis was based on the result of the screening program including 99,001 people among the general population and 42,538 people among the high risk group from 2003 to 2006. The screening was performed using the three steps of the semi-quantitative HCV antibody test, the HCV core antigen test and the HCV-PCR test. A Markov model for HCV infected patients was constructed to estimate the future clinical benefits and the lifetime cost and the cost-effectiveness analysis was performed considering the recent treatment with peginterferon plus ribavirin. In the cost-effectiveness analysis, the cohort, in which the screening was implemented (= screening strategy), was compared with the similar cohort without the screening (= no-screening strategy) in both the general population and the high-risk group, stratified by age. The infection rates of the general population and the high-risk group were 0.36% and 0.81%, respectively. The incremental cost-effectiveness ratio (ICER), a measure of cost-effectiveness, of the general population and the high-risk group was calculated to be from 848 to 4,825 and − 749 to 2,297 $/life expectancy gained, respectively. The treatment effectiveness, transition probabilities and the infection rate varied in the one-way sensitivity analyses, but the superiority of the screening strategy regarding the cost-effectiveness was unchanged. In conclusion, the screening strategy in both the general population and the high-risk group therefore appears to be more cost-effective than a no-screening strategy.
TL;DR: The prevalence ofcomplex SAS in Japanese SAS patients is 5.0%, which is lower than previously reported prevalence of complex SAS in the USA and Australia.
Abstract: Sleep apnea syndrome (SAS) is basically divided into two types: obstructive and central SAS. Recently, the concept of complex SAS has been advocated. Complex SAS is defined as SAS that initially manifests as primarily obstructive SAS, but is characterized by the frequent central apneas after the removal of upper airway obstruction. To determine the prevalence and clinical significance of complex SAS among Japanese patients with SAS, 1,312 patients with SAS were enrolled in this study. Diagnosis of central SAS was made based on diagnostic polysomnography, and differentiation of obstructive SAS from complex SAS was made from polysomnographic findings for treatment with continuous positive airway pressure, which resolved upper airway obstruction. As a result, obstructive SAS was found in 1,232 of 1,312 patients with SAS (93.9%) and central SAS was found in 14 patients (1.1%). The overall prevalence of complex SAS was 5.0% (n = 66). The prevalence of complex SAS among 1,218 male and 94 female patients with SAS were 5.3% and 1.1%, respectively. Patients with complex SAS had significantly higher apnea/hypopnea indices than patients with either obstructive or central SAS, but were similar in both mean age and average body mass index to obstructive SAS patients. There were no significant between-group differences in numbers of patients with clinical complications including hypertension, cardiac diseases, or cerebrovascular diseases. In conclusion, the prevalence of complex SAS in Japanese SAS patients is 5.0%, which is lower than previously reported prevalence of complex SAS in the USA and Australia.
TL;DR: Promotion of a regular sleep habit is necessary to prevent DSPS among this population and Appropriate school schedule may decrease the mismatch between the individual's sleep-wake cycle and the school schedule.
Abstract: Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder with a typical onset in the second decade of life. DSPS is characterized by the sleep-onset insomnia and the difficulty in waking at the desired time in the morning. Although DSPS is associated with inability to attend school, the prevalence has been controversial. To elucidate a change in the prevalence of DSPS among young population, epidemiological survey was conducted on Japanese students. A total of 4,971 students of junior high school, senior high school, and university were enrolled in this cross sectional study in Tottori Prefecture. They answered anonymous screening questionnaire regarding school schedule, sleep hygiene and symptomatic items of sleep disorders. The prevalence of probable DSPS was estimated at 0.48% among the total subject students without gender difference. In university, the prevalence of the last year students showed the highest value (1.66%), while that of the first year students showed the lowest value (0.09%) among all school years from junior high school to university. The prevalence increased with advancing university school years. Thus, a considerable number of Japanese students are affected with DSPS. Senior students of university are more vulnerable to the disorder than younger students. Appropriate school schedule may decrease the mismatch between the individual's sleep-wake cycle and the school schedule. Promotion of a regular sleep habit is necessary to prevent DSPS among this population.
TL;DR: The main goal of this article is to update etiology, epidemiology, diagnosis, treatment and outcome of the various causes of mesenteric ischemia in order to elucidate its labyrinthine clinical riddle, by reviewing the current English medical literature.
Abstract: The main goal of this article is to update etiology, epidemiology, diagnosis, treatment and outcome of the various causes of mesenteric ischemia in order to elucidate its labyrinthine clinical riddle, by reviewing the current English medical literature. Mesenteric ischemia is a quite uncommon disorder, observed in the emergency department. It is a life-threatening vascular emergency that requires early diagnosis and intervention to restore mesenteric blood flow and to prevent bowel necrosis and patient death. Consequently, it is a vital diagnosis to make because of its high mortality rate and its thorny complications. The underlying causes vary, and the prognosis depends on the specific findings during clinical examination. Vague and nonspecific clinical findings and limitations of diagnostic studies make the diagnosis a significant challenge. The prognosis of acute mesenteric ischemia of any type is grave. The complications following this medical jigsaw puzzle are also severe. Patients in whom the diagnosis is missed until infarction occurs have a mortality rate of 90%. Even with good treatment, up to 50-80% of patients die. Survivors of extensive bowel resection face lifelong disability. Despite the progress in understanding the pathogenesis of mesenteric ischemia and the development of treatment modalities, the entity remains a diagnostic challenge for clinicians. Delay in diagnosis contributes to a high mortality rate. Early diagnosis and adequate treatment can improve the clinical outcome. Even if diagnostic modalities have improved since the first successful attempts to confront effectively this clinical entity, mesenteric ischemia still remains a lethal diagnostic enigma for the medical community.
TL;DR: Results suggest that emodin can stabilize the VAP in the aortic root of ApoE-knockout mice, which is probably due to its anti-inflammatory effect.
Abstract: Increasing evidence indicated that plaque stabilization is attributed to the composition of the atherosclerotic plaque, and inflammation plays an important role in the formation and progress of vulnerable atherosclerotic plaque (VAP), which is prone to rupture. Emodin, an important component of traditional Chinese herb rhubarb, has obvious anti-inflammatory effect, although its effect on atherosclerotic plaque stabilization is unknown. Apolipoprotein E (ApoE) is an important component of plasma lipoprotein with anti-atherosclerosis function, and the plaque in the aorta of ApoE-deficient mice has been demonstrated with characteristics of VAP. Therefore, this study was designed to determine whether emodin can stabilize the VAP in the ApoE-deficient mice and explain the possible mechanism. After fat-fed for 13 weeks, mice were randomized into three groups (11 animals/group) and intragastrically administrated with emodin, simvastatin or distilled water for 13 weeks, respectively. The plaque stability was evaluated by the morphology and composition of atherosclerotic plaques. Additionally, the expression of peroxisomal proliferator-activated receptor-gamma (PPAR-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase 9 (MMP-9) in plaques was determined by the immunohistochemistry method. We showed that emodin could decrease the lipid core area and the ratio of lipid to collagen content in plaques. In addition, emodin significantly inhibited the expression of GM-CSF and MMP-9, whereas it induced the expression of PPAR-gamma in plaques. In conclusion, these results suggest that emodin can stabilize the VAP in the aortic root of ApoE-knockout mice, which is probably due to its anti-inflammatory effect.
TL;DR: The long-term outcome of localized gastric MALT lymphoma after H. pylori eradication therapy was favorable, and a watch and wait strategy may be a reasonable approach for hRD since the majority might be in the process of turning into delayed CR.
Abstract: Mucosa-associated lymphoid tissue (MALT) lymphomas are localized primarily in the gastrointestinal tract and are characterized by an indolent nature and favorable outcome with specific therapy. Gastric MALT lymphomas are closely linked to Helicobacter pylori (H. pylori) infection, for which eradication therapy is recognized as an effective primary treatment for the disease. However, there is little information about long-term outcomes after the therapy. In the present study, we elucidated the long-term outcomes of 74 patients (70 H. pylori-positive and 4 negative cases) followed up by endoscopy at least 12 months after exclusive eradication therapy alone. The median follow-up period was 46 months. When the remission status was estimated at the time point of 12 months post-eradication, the numbers of patients with complete remission (CR), histologically residual disease with macroscopic normalization (hRD), partial remission with more than 50% tumor reduction (PR) or no response (NR) were 56, 12, 2 and 4, respectively. During follow-ups of over 12 months post-eradication, 11 of the 12 hRD cases were belatedly induced to CR but one CR case histologically relapsed into hRD. One of the 2 PR cases eventually turned into hRD 20 months later. Therefore, 66 CR, 3 hRD, 1 PR, and 4 NR cases (including 3 H. pylori-negative) were identified at the last follow-up of the present study. All 74 patients were followed up without any second-line therapies, but none exhibited disease progression. Thus, the long-term outcome of localized gastric MALT lymphoma after H. pylori eradication therapy was favorable. A watch and wait strategy may be a reasonable approach for hRD since the majority might be in the process of turning into delayed CR.
TL;DR: It is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.
Abstract: Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid containing two acyl chains, to convert phosphatidic acid. DG is produced through phosphoinositide turnover within the membrane and is well known to act as a second messenger that modulates the activity of protein kinase C in the cellular signal transduction. Recent studies have revealed that DG also activates several proteins, including Ras guanine-nucleotide releasing protein and ion channels such as transient receptor potential proteins. Therefore, DGK is thought to participate in a number of signaling cascades by modulating levels of DG. Previous studies have disclosed that DGK is composed of a family of the isozymes, which differ in the structure, enzymological property, gene expression and localization, subcellular localization, and binding molecules. The present review focuses on the stories of phosphoinositide turnover and DG, including historical views, structural features, metabolism, and relevant cellular phenomena, together with the characteristics of DGK isozymes and the pathophysiological findings on animal studies using knockout mice and models for human diseases. Now it is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.
TL;DR: The results indicate that mtSNPs T3394C, G4491A, T16189C and T16519C show susceptible tendency to T2DM and mt SNPs C5178A and A10398G seem to be genetic factors for against T2 DM.
Abstract: Mitochondrial single nucleotide polymorphisms (mtSNPs) have been reported to associate with type-2 diabetes mellitus (T2DM), but mtSNPs appear to be considerably different among different populations and regions. To determine mtSNPs in Chinese Han patients with T2DM, the entire sequences of the mitochondrial genomes from 72 T2DM Chinese (59 ± 4 years) and 50 age-matched healthy subjects (controls) in Chongqing region of Western China were directly sequenced and mtSNPs were analyzed. We found that M8, M9, D, G, R and A haplogroups exist in Chinese Han population and the frequency of haplogroup M9 was significantly higher in patients with T2DM than in the controls (p = 0.0006, OR 0.06 [95% CI 0.008-0.476]). MtSNPs T3394C in NADH dehydrogenase subunit 1 (ND1), G4491A in ND2, T16189C and T16519C were found with significantly higher frequency in patients with T2DM than in the controls (T16189C, p = 0.0045; T16519C, p < 0.0001; T3394C, p = 0.0015; G4491A, p = 0.0015). In contrast, the frequency of C5178A in ND2 and A10398G in ND3 was higher in the controls than in patients with T2DM (C5178A, p = 0.014; A10398G, p = 0.0011). Our results indicate that mtSNPs T3394C, G4491A, T16189C and T16519C show susceptible tendency to T2DM and mtSNPs C5178A and A10398G seem to be genetic factors for against T2DM. These mtSNPs determined in our study is useful and could be used for early diagnosis and prevention of T2DM in Chinese Han population.
TL;DR: Hyaluronan showed chondroprotective effects on the articular cartilage in a rat immobilized-knee model and was administered intra-articularly on the day of surgery and once a week.
Abstract: Joint immobilization is a useful and common treatment modality in orthopedics. However, it also causes unfavorable outcome such as articular cartilage degeneration. Intra-articular injection of hyaluronan has been accepted as a treatment of osteoarthritis, but its effects on immobilized joint remain to be clarified. Hyaluronan is a polysaccharide, distributed ubiquitously in various tissues. In this study, we examined the effect of hyaluronan on the articular cartilage in immobilized joints. The unilateral knee joints of adult male rats were immobilized at 150° in flexion with an internal plate and screws for 1, 2, 4, 6, 8, 12, or 16 weeks (n = 84). Hyaluronan or saline (50 μl/each injection) was administered intra-articularly on the day of surgery and once a week. The articular cartilage from the medial midcondylar region of the knee was obtained, and divided into non-contact, contact and transitional areas (between the non-contact and the contact areas). In each area, a degree of degeneration was evaluated by histomorphometric grading, and measurements of thickness and number of chondrocytes. Histological grading scores in the hyaluronan group were smaller at 12 and 16 weeks compared with those in the saline group. The thickness of the articular cartilage increased in the transitional area in both groups. The number of chondrocytes in the contact and transitional areas gradually decreased, but their number in the hyaluronan group was greater at 12 and 16 weeks compared with that in the saline group. Hyaluronan showed chondroprotective effects on the articular cartilage in a rat immobilized-knee model.
TL;DR: Results suggest that liver-specific silencing of the SCOT gene expression may be mediated in part by its 5'-flanking sequence, and suggest that these GC boxes may be important for SCot gene expression.
Abstract: The human succinyl-CoA: 3-ketoacid CoA transferase (SCOT) gene encodes the ketolytic enzyme that functions in the mitochondrial matrix. The activation of acetoacetate to acetoacetyl-CoA by SCOT is essential for the use of ketone bodies as an energy source. The ketolytic capacity of tissues is proportional to their level of SCOT activity. Normal hepatocytes, the site of ketone body synthesis, have no detectable SCOT protein. The absence of SCOT in hepatocytes is an important element in energy metabolism, suppressing ketolysis in the liver. To study the tissue-specific silencing of SCOT expression, we analyzed the promoter function of SCOT gene in three different human cell lines. Immunoblot analysis showed that SCOT protein was detectable in HeLa cervical cancer cells and Chang liver cells. However, SCOT protein was not detected in HepG2 hepatoma cells and liver tissues, indicating that HepG2 hepatoma cells maintain the characteristics of liver cells in the ketone body metabolism. Luciferase reporter assays in HeLa and Chang liver cells showed that the 361-bp proximal region of the SCOT gene was responsible for the basal promoter activity and contained two GC boxes, each of which was bound in vitro by Sp1, a ubiquitously expressed transcription factor. These results suggest that these GC boxes may be important for SCOT gene expression. Moreover, the region between -2168 and -361 appeared to inhibit the SCOT promoter activity in HepG2 cells. Thus, liver-specific silencing of the SCOT gene expression may be mediated in part by its 5'-flanking sequence.
TL;DR: PM has a beneficial effect on lipid metabolism in postmenopausal women, which may result from the activation of gene transcription through selective binding of phytoestrogens to ERalpha and ERbeta.
Abstract: Impaired lipid metabolism is an important health problem in postmenopausal women with insufficient estrogens, because dyslipidemia is a risk factor for development of atherosclerosis and the incidence of cardiovascular disease markedly increases after menopause. Pueraria mirifica (PM), a Thai herb, has been noticed as a source of phytoestrogens, estrogen-mimicking plant compounds. However, the clinical effects of PM on lipid metabolism and the underlying molecular mechanisms remain undetermined. Therefore, we examined the effects of PM on serum lipid parameters in a randomized, double-blind, placebo-controlled clinical trial. Nineteen postmenopausal women were randomly assigned to receive oral administration of PM powder or placebo. After 2 months of treatment, the PM group showed a significant increase in serum concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-1 (34% and 40%, respectively), and a significant decrease in low-density lipoprotein (LDL) cholesterol and apo B (17% and 9%, respectively), compared with baseline measurements. Moreover, significant decreases were observed in the ratios of LDL cholesterol to HDL cholesterol (37%) and apo B to apo A-1 (35%). Next, we determined the effects of PM phytoestrogens on the activation of estrogen receptor (ER)-mediated transactivation by transient expression assays of a reporter gene in cultured cells. Among PM phytoestrogens, miroestrol and coumestrol enhanced both ERalpha- and ERbeta-mediated transactivation, whereas other phytoestrogens, including daidzein and genistein, preferentially enhanced ERbeta-mediated transactivation. In conclusion, PM has a beneficial effect on lipid metabolism in postmenopausal women, which may result from the activation of gene transcription through selective binding of phytoestrogens to ERalpha and ERbeta.
TL;DR: Combined treatment with gefitinib and whole-brain irradiation in a lung cancer patient suffered from meningeal metastasis and in-frame deletion of codons 746 to 750 of the EGF gene revealed constitutive activation of the tyrosine kinase domain and high-affinity binding of gefithinib proved to be effective.
Abstract: Carcinomatous meningitis is a severe complication of lung cancer. Although treatment with gefitinib, a tyrosine kinase inhibitor of epidermal growth factor (EGF) receptor, has been reported to be highly effective against lung cancers harboring a mutated EGF gene, its effect against carcinomatous meningitis is unknown. Here, we report successful treatment of carcinomatous meningitis with gefitinib in a lung cancer patient suffered from meningeal metastasis. A 62-year-old, non-smoking, Japanese male was admitted for headache, failing vision, and temporary loss of consciousness and was subsequently diagnosed with stage IV lung adenocarcinoma and carcinomatous meningitis. A tumor sample revealed the in-frame deletion of codons 746 to 750 (E746 to A750) in exon 19 of the EGF gene, which leads to constitutive activation of the tyrosine kinase domain and high-affinity binding of gefitinib. The patient's performance status was poor owing to progression of the meningitis and elevated cerebrospinal fluid (CSF) pressure. Combined treatment with gefitinib (250 mg/day) and whole-brain irradiation (36 Gray total) proved to be effective. It is noteworthy that the level of gefitinib in the CSF was less than 1% of the serum level (serum: 117 nM before drug re-administration and 132 nM 2 hrs later; CSF: 0.9 nM both before and 2 hrs after drug re-administration). Gefitinib treatment should be considered for patients with carcinomatous meningitis and lung adenocarcinoma harboring a mutated EGF gene.
TL;DR: In vivo electron paramagnetic resonance studies demonstrated that signal decay times of nitroxyl radicals were significantly longer in livers of HO-1 CKO mice than that of control mice, indicating that radical scavenging activity was significantly compromised in the mutant liver.
Abstract: Heme oxygenase-1 (HO-1) is the rate-limiting enzyme of heme catabolism and has been assumed to be important in cellular response against oxidative stress through modification of the pro-oxidant heme into less toxic catabolites that behave as antioxidants. However, the precise mechanisms involved and the physiological significance of such activity remain to be clarified. To elucidate roles HO-1 plays in vivo, hepatocyte-specific conditional knockout (CKO) mice of HO-1 gene were generated by site-specific recombination using albumin-promoter-driven Cre-loxP system. In livers of HO-1 CKO mice HO-1 protein level decreased to approximately 30% of control mouse livers. The HO-1 CKO mice are viable, exhibit normal growth curves over six months, and show no histological and serological abnormalities. We found that several cytoprotective genes, such as NAD(P)H dehydrogenase quinone 1 and glutathione S-transferase P1, showed markedly elevated expression, suggesting the increase of oxidative stress in HO-1 CKO mice even under quiescent conditions. In vivo electron paramagnetic resonance studies demonstrated that signal decay times of nitroxyl radicals were significantly longer in livers of HO-1 CKO mice than that of control mice, indicating that radical scavenging activity was significantly compromised in the mutant liver. HO-1 CKO mice were susceptible to carbon tetrachloride hepatotoxicity. These results provide the first in vivo evidence that HO-1 acts to protect cells against the oxidative stress in both basal conditions and upon chemical insult.
TL;DR: The increased expression of COX-2 may be responsible for rapid proliferation of pancreatic cancer, and specific inhibition of COx-2 suppresses proliferation of Panc-1 cells in vitro and in nude mice, may be an effectual agent for Pancic cancer chemoprevention.
Abstract: Cyclooxygenase-2 (COX-2), a prostaglandin synthetase, is involved in development of certain tumors We therefore analyzed COX-2 expression in pancreatic cancer tissues (53 samples) and Panc-1 human pancreatic cancer cells by immunohistochemistry, RT-PCR and western-blotting analyses Also, immunohistochemistry of proliferating cell nuclear antigen (PCNA) was performed We found expression of COX-2 was dramatically upregulated in 36 of 53 cases (679%) and the expression of COX-2 was associated with the diameter (> 3 cm) of the tumors (p < 005), but not with the age, gender, tumor location, differentiation, lymph-node metastases and TNM stage The positivity rate of PCNA expression in the pancreatic cancer cells of the COX-2 positive group (3288 ± 1326%) was significantly higher than that in the COX-2 negative group (2456 ± 1151%) (p < 005) Then we investigated the effect of selective inhibitors of COX-2 (NS398 and celecoxib) on proliferation of Panc-1 cells by 3-(4,5 dimethyl-2-thiazolyl)-25-diphenyl-2H-tetrazolium bromide (MTT) assay Either NS398 or celecoxib suppressed proliferation of Panc-1 cells dose-dependently in vitro Furthermore, Panc-1 cells were implanted into nude mice, and celecoxib was administrated orally with feed The volume of the tumor xenografted into nude mice was decreased by 516% in the celecoxib group (p < 001) In conclusion, the increased expression of COX-2 may be responsible for rapid proliferation of pancreatic cancer, and specific inhibition of COX-2 suppresses proliferation of Panc-1 cells in vitro and in nude mice The selective inhibitor of COX-2 may be an effectual agent for pancreatic cancer chemoprevention