Comparative evaluation of methods to determine intra-individual reference ranges in nutrition support team (NST)-related tests.

BACKGROUND: The intra-individual reference range is generally narrower than the commonly used reference range. Consequently, close monitoring of changes in the laboratory test results of individuals based on the inter-individual reference range remains challenging. METHODS: We examined the determination of individual reference ranges using four indicators of nutritional conditions: transferrin (TRF), albumin (ALB), retinol-binding protein (RBP), and transthyretin (TTR). The subjects comprised 20 healthy individuals and blood samples were collected and tested five times at 2-week intervals. We used the measurement results for the four indicators and examined individual reference ranges using four methods, including calculation methods based on the reference change value and Bayesian inference. RESULTS: The resulting intra-individual reference ranges were narrower than the currently used inter-individual reference range for all measurements using four methods. Furthermore, the intra-individual coefficient of variation [CV (intra)] was smaller than the inter-individual coefficient of variation [CV (inter)] for TRF, RBP, and TTR for all 20 subjects. The means CV (intra) for the four indicators were also lower than the corresponding CV (inter). CONCLUSIONS: The intra-individual reference range can be used to validate the standard deviation and coefficient of variation for currently used indicators. Moreover, Bayesian methods are speculated to be the most versatile.

Exercise ameliorates high-fat diet-induced impairment of differentiation of adipose-derived stem cells into neuron-like cells in rats.

Adipose-derived stem cells (ADSCs) can differentiate into neurons under particular conditions. It remains largely unknown whether this differentiation potential is affected by physical conditions such as obesity, which modulates the functions of adipose tissue. In this study, we determined the impact of either a 9-week high-fat diet (60% fat; HFD) or 9-week exercise training on the differentiation potential of ADSCs into neuron-like cells in male Wistar rats. Rats were randomly assigned to a normal diet-fed (ND-SED) group, HFD-fed (HFD-SED) group, or exercise-trained HFD-fed group (HFD-EX). After a 9-week intervention, ADSCs from all groups differentiated into neuron-like cells. Expression of neuronal marker proteins (nestin, ßIII-tubulin, and microtubule-associated protein 2 [MAP2]) and the average length of cell neurites were lower in cells from HFD-SED rats than in other groups. Instead, protein expression of COX IV and Cyt-c, the Bax/Bcl-2 and LC3-II/I ratio, and the malondialdehyde level in culture medium were higher in cells from HFD-SED rats. No significant difference between ND-SED and HFD-EX rats was observed, except for the average length of cell neurites in MAP2. Thus, HFD impaired the differentiation potential of ADSCs into neuron-like cells, which was accompanied by increases in apoptotic activity and oxidative stress. Importantly, exercise training ameliorated the HFD-induced impairment of neurogenesis in ADSCs. The adipose tissue microenvironment could influence the differentiation potential of ADSCs, a source of autologous stem cell therapy.

A standardized extract of Asparagus officinalis stem prevents reduction in heat shock protein 70 expression in ultraviolet-B-irradiated normal human dermal fibroblasts: an in vitro study.

BACKGROUND: Heat shock protein 70 (HSP70) exhibits protective effects against ultraviolet (UV)-induced premature skin aging. A standardized extract of Asparagus officinalis stem (EAS) is produced as a novel and unique functional food that induces HSP70 cellular expression. To elucidate the anti-photoaging potencies of EAS, we examined its effects on HSP70 expression levels in UV-B-irradiated normal human dermal fibroblasts (NHDFs). METHODS: NHDFs were treated with 1 mg/mL of EAS or dextrin (vehicle control) prior to UV-B irradiation (20 mJ/cm2). After culturing NHDFs for different time periods, HSP70 mRNA and protein levels were analyzed using real-time polymerase chain reaction and western blotting, respectively. RESULTS: UV-B-irradiated NHDFs showed reduced HSP70 mRNA levels after 1-6 h of culture, which were recovered after 24 h of culture. Treatment with EAS alone for 24 h increased HSP70 mRNA levels in the NHDFs, but the increase was not reflected in its protein levels. On the other hand, pretreatment with EAS abolished the UV-B irradiation-induced reduction in HSP70 expression at both mRNA and protein levels. These results suggest that EAS is capable to preserve HSP70 quantity in UV-B-irradiated NHDFs. CONCLUSIONS: EAS exhibits anti-photoaging potencies by preventing the reduction in HSP70 expression in UV-irradiated dermal fibroblasts.

Regular Voluntary Exercise Potentiates Interleukin-1ß and Interleukin-18 Secretion by Increasing Caspase-1 Expression in Murine Macrophages.

Moderate-intensity regular exercise improves proinflammatory responses of lipopolysaccharide- (LPS-) stimulated macrophages. However, intracellular events that mediate the beneficial effects of exercise were unclear. This study aimed to clarify the mechanism by which regular voluntary exercise (VE) improves proinflammatory cytokine production by macrophages challenged with LPS. Peritoneal macrophages from VE mice secreted considerably higher amounts of interleukin- (IL-) 1ß and IL-18 than did cells from sedentary control (SC) mice in the presence and absence of LPS, although tumor necrosis factor-α and IL-10 secretion were comparable between both groups. The mRNA levels of these cytokines increased significantly in response to LPS; similar levels were noted in macrophages from both SC and VE mice. Moreover, LPS evoked similar levels of degradation of inhibitor of κB (IκB) α and phosphorylation of IκB kinase ß, c-Jun N-terminal kinase, and p38 in macrophages from SC and VE mice. These results indicate that the increased IL-1ß and IL-18 secretion in VE mice are regulated posttranscriptionally. On the other hand, macrophages from VE mice showed higher amounts of caspase-1 protein than did cells from SC mice. These results suggest that regular VE potentiates IL-1ß and IL-18 secretion in LPS-challenged macrophages by increasing caspase-1 levels.

Effect of Circadian Rhythm on Clinical and Pathophysiological Conditions and Inflammation.

Circadian rhythms have long been known to regulate numerous physiological processes that vary across the diurnal cycle. The circadian clock system also controls various parameters of the immune system and its biological defense functions, allowing an organism to anticipate daily changes in activity and feeding and the associated risk of infection. Inflammation is an immune response triggered in living organisms in response to external stimuli. The risk of sepsis, an excessive inflammatory response, has been shown to have a diurnal variation. On the other hand, inflammatory responses are emerging to be induced by endogenous factors. Recent studies have suggested that chronic inflammation causes chronic diseases including rheumatoid arthritis, allergies, and aging-related diseases and that proteins encoded by clock genes affect the development of such chronic inflammatory diseases or increase the severity of their symptoms. Therefore, detailed understanding of circadian rhythm effects on inflammatory responses is expected to lead to new strategies for prevention or treatment of inflammatory diseases.

A circadian clock gene, Rev-erbα, modulates the inflammatory function of macrophages through the negative regulation of Ccl2 expression.

Disruption of the circadian rhythm is a contributory factor to clinical and pathophysiological conditions, including cancer, the metabolic syndrome, and inflammation. Chronic and systemic inflammation are a potential trigger of type 2 diabetes and cardiovascular disease and are caused by the infiltration of large numbers of inflammatory macrophages into tissue. Although recent studies identified the circadian clock gene Rev-erbα, a member of the orphan nuclear receptors, as a key mediator between clockwork and inflammation, the molecular mechanism remains unknown. In this study, we demonstrate that Rev-erbα modulates the inflammatory function of macrophages through the direct regulation of Ccl2 expression. Clinical conditions associated with chronic and systemic inflammation, such as aging or obesity, dampened Rev-erbα gene expression in peritoneal macrophages from C57BL/6J mice. Rev-erbα agonists or overexpression of Rev-erbα in the murine macrophage cell line RAW264 suppressed the induction of Ccl2 following an LPS endotoxin challenge. We discovered that Rev-erbα represses Ccl2 expression directly through a Rev-erbα-binding motif in the Ccl2 promoter region. Rev-erbα also suppressed CCL2-activated signals, ERK and p38, which was recovered by the addition of exogenous CCL2. Further, Rev-erbα impaired cell adhesion and migration, which are inflammatory responses activated through the ERK- and p38-signaling pathways, respectively. Peritoneal macrophages from mice lacking Rev-erbα display increases in Ccl2 expression. These data suggest that Rev-erbα regulates the inflammatory infiltration of macrophages through the suppression of Ccl2 expression. Therefore, Rev-erbα may be a key link between aging- or obesity-associated impairment of clockwork and inflammation.

Ghrelin augments the expressions and secretions of proinflammatory adipokines, VEGF120 and MCP-1, in differentiated 3T3-L1 adipocytes.

Ghrelin is a physiological-active peptide with growth hormone-releasing activity, orexigenic activity, etc. In addition, the recent study has also suggested that ghrelin possesses the pathophysiological abilities related with type 2 diabetes. However, the ghrelin-direct-effects implicated in type 2 diabetes on peripheral tissues have been still unclear, whereas its actions on the central nervous system (CNS) appear to induce the development of diabetes. Thus, to assess its peripheral effects correlated with diabetes, we investigated the regulatory mechanisms about adipokines, which play a central role in inducing peripheral insulin resistance, secreted from mature 3T3-L1 adipocytes stimulated with ghrelin in vitro . The stimulation with 50 nmol/L ghrelin for 24 h resulted in the significant 1.9-fold increase on vascular endothelial growth factor-120 (VEGF(120)) releases (p < 0.01) and the 1.7-fold on monocyte chemoattractant protein-1 (MCP-1) (p < 0.01) from 3T3-L1 adipocytes, respectively, while ghrelin failed to enhance tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-10 and adiponectin secretions. In addition, Akt phosphorylation on Ser473 and c-Jun NH2 -terminal protein kinase (JNK) phosphorylation on Thr183/Tyr185 were markedly enhanced 1.4-fold (p < 0.01) and 1.6-fold (p < 0.01) in the ghrelin-stimulated adipocytes, respectively. Furthermore, the treatment with LY294002 (50 µmol/L) and Wortmannin (10nmol/L), inhibitors of phosphatidylinositol 3-kinase (PI3K), significantly decreased the amplified VEGF(120) secretion by 29% (p < 0.01) and 28% (p < 0.01) relative to the cells stimulated by ghrelin alone, respectively, whereas these inhibitors had no effects on increased MCP-1 release. On the other hand, JNK inhibitor SP600125 (10 µmol/L) clearly reduced the increased MCP-1, but not VEGF(120), release by 35% relative to the only ghrelin-stimulated cells (p < 0.01). In conclusion, ghrelin can enhance the secretions of proinflammatory adipokines, VEGF(120) and MCP-1, but fails to affect IL-10 and adiponectin which are considered to be anti-inflammatory adipokines. Moreover, this augmented VEGF(120) release is invited through the activation of PI3K pathways and the MCP-1 is through JNK pathways. Consequently, our results strongly suggest that ghrelin can induce the development of diabetes via its direct-action in peripheral tissues as well as via in CNS.

Habitual exercise training acts as a physiological stimulator for constant activation of lipolytic enzymes in rat primary white adipocytes.

It is widely accepted that lipolysis in adipocytes are regulated through the enzymatic activation of both hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) via their phosphorylation events. Accumulated evidence shows that habitual exercise training (HE) enhances the lipolytic response in primary white adipocytes with changes in the subcellular localization of lipolytic molecules. However, no study has focused on the effect that HE exerts on the phosphorylation of both HSL and ATGL in primary white adipocytes. It has been shown that the translocation of HSL from the cytosol to lipid droplet surfaces requires its phosphorylation at Ser-563. In primary white adipocytes obtained from HE rats, the level of HSL and ATGL proteins was higher than that in primary white adipocytes obtained from sedentary control (SC) rats. In HE rats, the level of phosphorylated ATGL and HSL was also significantly elevated compared with that in SC rats. These differences were confirmed by Phos-tag SDS-PAGE, a technique used to measure the amount of total phosphorylated proteins. Our results suggest that HE can consistently increase the activity of both lipases, thereby enhancing the lipolysis in white fat cells. Thus, HE helps in the prevention and treatment of obesity-related diseases by enhancing the lipolytic capacity.

Melatonin promotes adipogenesis and mitochondrial biogenesis in 3T3-L1 preadipocytes.

Melatonin is synthesized in the pineal gland, but elicits a wide range of physiological responses in peripheral target tissues. Recent advances suggest that melatonin controls adiposity, resulting in changes in body weight. The aim of this study was to investigate the effect of melatonin on adipogenesis and mitochondrial biogenesis in 3T3-L1 mouse embryo fibroblasts. Melatonin significantly increased the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), a master regulator of adipogenesis, and promoted differentiation into adipocytes. Melatonin-treated cells also formed smaller lipid droplets and abundantly expressed several molecules associated with lipolysis, including adipose triglyceride lipase, perilipin, and comparative gene identification-58. Moreover, the hormone promoted biogenesis of mitochondria, as indicated by fluorescent staining, elevated the citrate synthase activity, and upregulated the expression of PPAR-γ coactivator 1 α, nuclear respiratory factor-1, and transcription factor A. The expression of uncoupling protein 1 was also observable both at mRNA and at protein level in melatonin-treated cells. Finally, adiponectin secretion and the expression of adiponectin receptors were enhanced. These results suggest that melatonin promotes adipogenesis, lipolysis, mitochondrial biogenesis, and adiponectin secretion. Thus, melatonin has potential as an anti-obesity agent that may reverse obesity-related disorders.

Association of blood pressure and body mass index with intraocular pressure in middle-aged and older Japanese residents: a cross-sectional and longitudinal study.

To clarify whether high blood pressure (BP) and high body mass index (BMI) are associated with elevated intraocular pressure (IOP), a cross-sectional and longitudinal study was conducted. This epidemiological study analyzed health examination data obtained between 2001 and 2005 from 896 Japanese individuals (aged 32-79 years) who had not undergone any ocular surgery or medical treatment for hypertension, ocular hypertension, or glaucoma. Multiple-regression analysis of our cross-sectional data showed that systolic and diastolic BP (SBP and DBP) and BMI had significant and near-significant positive associations with IOP in men (p＜0.05) and women (p＜0.1). Our longitudinal study from analyses of covariance found that the adjusted mean level of changes in IOP tended to increase with increased levels of SBP, DBP, and BMI in men (p＜0.1). In women also, changes in SBP and BMI tended to be positively related with that of IOP (p＜0.1). The results of this study suggested that BP and BMI were positively associated with IOP in middle-aged and older Japanese. Therefore, management of BP and improvement of obesity might be especially important to Japanese patients with open-angle glaucoma or ocular hypertension as they have a higher incidence of normal-tension glaucoma than Europeans and Americans.

Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERBα.

It is now evident that many nuclear hormone receptors can modulate target gene expression. REV-ERBα, one of the nuclear hormone receptors with the capacity to alter clock function, is critically involved in lipid metabolism, adipogenesis, and the inflammatory response. Recent studies suggest that REV-ERBα plays a key role in the mediation between clockwork and inflammation. The purpose of the current study was to investigate the role of REV-ERBα in the regulation of interleukin-6 (il6) gene expression in murine macrophages. REV-ERBα agonists, or overexpression of rev-erb α in the murine macrophage cell line RAW264 cells, suppressed the induction of il6 mRNA following a lipopolysaccharide (LPS) endotoxin challenge. Also, rev-erb α overexpression decreased LPS-stimulated nuclear factor κB (NFκB) activation in RAW264 cells. We showed that REV-ERBα represses il6 expression not only indirectly through an NFκB binding motif but also directly through a REV-ERBα binding motif in the murine il6 promoter region. Furthermore, peritoneal macrophages from mice lacking rev-erb α increased il6 mRNA expression. These data suggest that REV-ERBα regulates the inflammatory response of macrophages through the suppression of il6 expression. REV-ERBα may therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory diseases.

Association of smoking with intraocular pressure in middle-aged and older Japanese residents.

OBJECTIVES: To clarify whether smoking was associated with elevated intraocular pressure (IOP) and to evaluate the interrelationship among IOP, blood viscosity, and smoking. METHODS: This cross-sectional study analyzed health examination data obtained between 2001 and 2004 from 1113 individuals (829 men and 284 women), ranging in age from 28 to 79 years, who had not undergone any ocular surgery or medical treatment for hypertension, ocular hypertension, and glaucoma. RESULTS: Multiple-regression analysis showed that systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and number of cigarettes smoked per day had a significantly positive association with IOP in men (P < 0.05). In women also, SBP, DBP, and BMI were positively related to IOP (P < 0.05). On the contrary, age had a significant negative association with IOP in both sexes (P < 0.01). Analysis of covariance and multiple logistic regression analyses showed that the adjusted mean IOP and the multivariate odds ratios for IOP increased with increasing cigarette consumption in men (P for trend = 0.01 and 0.06, respectively). Analysis of covariance found that smoking was significantly associated with both high IOP and high hematocrit in men (P for trend <0.05); however, the adjusted mean IOP values were higher in smokers than in nonsmokers, regardless of the hematocrit level. CONCLUSIONS: The results of this study suggested that the IOP level may be substantially affected by smoking habit in middle-aged and older Japanese men.

INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors.

Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5-RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

Oligomerised lychee fruit-derived polyphenol attenuates cognitive impairment in senescence-accelerated mice and endoplasmic reticulum stress in neuronal cells.

Recently, the ability of polyphenols to reduce the risk of dementia and Alzheimer's disease (AD) has attracted a great deal of interest. In the present study, we investigated the attenuating effects of oligomerised lychee fruit-derived polyphenol (OLFP, also called Oligonol) on early cognitive impairment. Male senescence-accelerated mouse prone 8 (SAMP8) mice (4 months old) were given OLFP (100 mg/kg per d) for 2 months, and then conditioned fear memory testing was conducted. Contextual fear memory, which is considered hippocampus-dependent memory, was significantly impaired in SAMP8 mice compared with non-senescence-accelerated mice. OLFP attenuated cognitive impairment in SAMP8 mice. Moreover, the results of real-time PCR analysis that followed DNA array analysis in the hippocampus revealed that, compared with SAMP8 mice, the mRNA expression of Wolfram syndrome 1 (Wfs1) was significantly higher in SAMP8 mice administered with OLFP. Wfs1 reportedly helps to protect against endoplasmic reticulum (ER) stress, which is thought to be one of the causes for AD. The expression of Wfs1 was significantly up-regulated in NG108-15 neuronal cells by the treatment with OLFP, and the up-regulation was inhibited by the treatment of the cells with a c-Jun N-terminal kinase-specific inhibitor rather than with an extracellular signal-regulated kinase inhibitor. Moreover, OLFP significantly attenuated the tunicamycin-induced expression of the ER stress marker BiP (immunoglobulin heavy chain-binding protein) in the cells. These results suggest that OLFP has an attenuating effect on early cognitive impairment in SAMP8 mice, and diminishes ER stress in neuronal cells.

Self-rated anosognosia score may be a sensitive and predictive indicator for progressive brain atrophy in amyotrophic lateral sclerosis: an X-ray computed tomographic study.

We investigated whether a self-rated anosognosia score can be an indicator for progression of brain atrophy in patients with amyotrophic lateral sclerosis (ALS). Scores for 16 patients were compared with the ventricular areas of the bilateral anterior and inferior horns measured on x-ray computed tomography. Longitudinal enlargement was expressed as a monthly increase in size: (ventricular size at the initial scan - ventricular size at the follow-up scan)/scan interval (months). The anosognosia scores ranged from -4 to 3 and 3-18 in patients with and without frontotemporal lobar degeneration (FTLD), respectively (p = 0.0011). Anosognosia scores were significantly correlated with sizes of anterior (r = 0.704, p = 0.0016) and inferior (r = 0.898, p < 0.0001) horns. In non-demented patients for whom follow-up CT scans were available (n = 7), the scores were significantly correlated with the longitudinal increase in inferior horn size (r = 0.754, p = 0.0496), but not with that of anterior horn size (r = -0.166, p = 0.7111). In conclusion, anosognosia in ALS is associated with greater anterior and inferior horn sizes, reflecting frontotemporal lobar atrophy. Moreover, mild anosognosia in ALS patients without FTLD may predict impending inferior horn enlargement, reflecting medial temporal atrophy.

Induction of mitochondrial uncoupling enhances VEGF120 but reduces MCP-1 release in mature 3T3-L1 adipocytes: possible regulatory mechanism through endogenous ER stress and AMPK-related pathways.

Although white adipocytes contain a larger number of mitochondria per cytoplasmic volume, adipocyte mitochondrial uncoupling to reduce the efficiency of ATP production on cellular function including secretory regulation of bioactive molecules such as VEGF and MCP-1 remains to be elucidated. Here we induce mitochondrial uncoupling under hypoxia-independent conditions in mature 3T3-L1 adipocytes using a metabolic uncoupler, dinitrophenol (DNP). MCP-1 release was significantly decreased by 26% (p<0.01) in 24h DNP (30 µmol/L)-treated adipocytes compared to control cells. In contrast, secreted VEGF(120) lacking a heparin-binding domain was markedly increased 2.0-fold (p<0.01). CHOP content in these cells also were augmented (p<0.01), but no significant increase of endogenous oxidative stress was observed. Treatment with thapsigargin, which can induce exogenous endoplasmic reticulum (ER) stress, clearly attenuated MCP-1 release (p<0.01), but exhibited no effects on VEGF(120) secretion. On the other hand, exogenous H(2)O(2) amplified both MCP-1 and VEGF(120) secretion (p<0.05). In addition, under chronic activation of AMPK by AICAR, MCP-1 release was significantly diminished (p<0.05) but VEGF(120) secretion was increased (p<0.01). JNK phosphorylation in mature adipocytes was decreased by treatment with either DNP or AICAR (p<0.01). Enhanced VEGF(120) secretion with either DNP or AICAR was markedly suppressed by PI3K inhibitor LY294002 (p<0.01). Thus, induced mitochondrial uncoupling in adipocytes can reduce MCP-1 release through induction of endogenous ER stress and by reduced JNK activities via chronic activation of AMPK. Under this condition, VEGF(120) secretion was increased through PI3K-dependent pathways, which were chronically activated by AMPK, and not through ER stress. Because the decrease of MCP-1 secretion under mitochondrial uncoupling might attenuate chronic low-grade inflammation by suppressing macrophages recruitment to adipose tissue, clarification of the mechanism might reveal novel therapeutic targets for ameliorating obesity-associated insulin resistance in metabolic syndrome and type 2 diabetes.

Deep white matter hyperintensities, decreased serum low-density lipoprotein, and dilative large arteriopathy.

Deep white matter hyperintensities (DWMHs) seen on magnetic resonance imaging (MRI) are thought to reflect small-vessel diseases (SVDs) and may have a background that differs from that of stenotic large-vessel diseases. We assessed risk factors for DWMHs and investigated the association between DWMHs and dilative changes in the basilar artery (BA) on MRI in nonstroke patients. We reviewed clinical information and MRI findings for 149 outpatients aged 46-90 years, excluding those with a previous symptomatic cerebrovascular event. DWMHs were graded 0-3, and the maximal BA diameter and area were measured from the flow void on axial T2-weighted MRI to assess dilatation. We divided the patients into groups with and without DWMH grade 2 or 3, and compared clinical information and BA parameters in these groups. The two groups demonstrated significant differences in age, serum low-density lipoprotein (LDL) level, estimated glomerular filtration rate (eGFR), and BA parameters. An adjusted logistic regression analysis including BA diameter found that age (odds ratio [OR], 1.974 per 10 years; 95% confidence interval [CI], 1.030-1.112; P = .0006), LDL (OR, 0.811 per 10 mg/dL; 95% CI, 0.964-0.965; P = .0085), eGFR (OR, 0.835 per 10 mL/min/1.73 m(2); 95% CI, 0.967-0.998; P = .0229), and BA diameter (OR, 2.515 per 1 mm; 95% CI, 1.191-4.098; P = .0119) were independently associated with the presence of DWMHs. An analysis including the BA area yielded similar results. DWMHs are manifestations of SVDs and show a strong association with lower serum LDL level, lower eGFR, and BA dilatation.

Erythropoietin, 2,3 DPG, oxygen transport capacity, and altitude training in adolescent Alpine skiers.

BACKGROUND: Rapid growth during adolescence caused by metabolic changes and their metabolic response to anaerobic and aerobic exercise differs considerably from that in adults and this is especially true in the responses to stresses, such as altitude exposure. However, there is little information on the suitability of exercise training at altitude for young athletes. METHODS: Six male Korean adolescent alpine skiers (13-17 yr), with a skiing career of 3-5 yr, participated in the study. All subjects were exposed to an altitude of 2700 m (8858 ft) for 5 wk and altitude exposure consisted of 6 d/wk of training (4-5 h/d), with living quarters at 2100 m (-6890 ft) (Tignes, France). The 5 wk of ski training at altitude were maintained at the same level (the same number of slalom and giant slalom skiing trials) as at sea level. RESULTS: There was a significant increase in oxygen transport capacity, despite decreased erythropoietin (EPO) production (-31%) after altitude training. Red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and 2,3 DPG concentrations increased significantly during altitude exposure and after return to sea level. DISCUSSION: Results indicate that applying altitude training in adolescent skiers may improve their endurance performance. However, EPO production during altitude training needs to be evaluated in larger future studies.

Influence of mitochondrial DNA 5178 C/A polymorphism on serum cholesterol changes: a short-term follow-up in middle-aged Japanese men.

OBJECTIVE: The mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is reportedly associated with longevity in the Japanese population, and the Mt5178A genotype may exert anti-atherogenic effects. The aim of this study was to determine whether there were longitudinal differences in serum lipid levels between carriers of the Mt5178C genotype and those of the Mt5178A genotype and to assess the impact of these genotypes on serum cholesterol levels. METHODS: The serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were measured and the Mt5178 C/A genotypes determined in 110 Japanese men aged 41-66 (mean 52.3) years who had received medical checkups twice in the period 1999-2005. The longitudinal changes of TC, HDLC, and LDLC were calculated according to genotype. RESULTS: The serum levels of TC at baseline and follow-up were significantly different, whereas those of HDLC and LDLC were not. The changes in HDLC differed significantly between the two Mt5178 C/A genotype groups, with the changes in HDLC level being significantly greater in the Mt5178A genotype group than in the Mt5178C group (p = 0.015). CONCLUSIONS: The Mt5178 C/A genotype may modify longitudinal changes in serum TC and HDLC levels in middle-aged Japanese men.

Preventive and improvement effects of exercise training and supplement intake in white adipose tissues on obesity and lifestyle-related diseases.

Recent increases in the number of obese individuals and individuals suffering from lifestyle-related diseases, such as type 2 diabetes, that accompany obesity have become a serious social problem. White adipose tissue (WAT) is more than a mere organ for storage of energy; it is also a highly active metabolic and endocrine organ that secretes physiologically active substances collectively known as adipokines, including tumor necrosis factor-α and adiponectin. Dysregulated expression of adipokines in WAT that is hypertrophied by obesity has been closely associated with the phenomenon of insulin resistance. Therefore, WAT is currently considered to be one of the tissues that promote lifestyle-related diseases. Reduction of excess WAT that results from obesity is seen as an important strategy in preventing and improving lifestyle-related diseases. This review shows that exercise training as well as intake of supplements, such as polyphenols, is one strategy for this, because this regimen can result in reduction of WAT mass, which affects the expression and secretory response of adipokines.