Bilberry extract supplementation for preventing eye fatigue in video display terminal workers.

OBJECTIVES: To examine the effect of a dietary supplement containing bilberry extract (BE) on eye fatigue induced by acute video display terminal (VDT) loads. DESIGN AND SETTING: A prospective, randomized, double-blind, placebo-controlled study was performed from August 2012 to February 2013 in the Medical Corporation Jico-kai Yagi Hospital, and the Shinyokohama Shinoharaguchi Orthopedic Surgery and Dermatology Clinic, in Japan. PARTICIPANTS: Two hundred eighty-one office workers aged 20-40 years that used VDTs were screened by critical flicker fusion (CFF) and near point accommodation (NPA). INTERVENTION: The participants were randomized to either a BE (480 mg/day) or placebo (vehicle) group, and took allocated capsule, daily, for 8 weeks. MEASUREMENTS: The CFF, NPA, contrast visual acuity, functional visual acuity, keratoconjunctival epithelial damage, and fluorescein tear film break-up time were examined, and 18 subjective symptoms of eye fatigue were evaluated by questionnaire. Adverse events were reported via medical interviews. Data were collected both before and after VDT load at baseline, and 4, and 8 weeks after daily supplementation with either BE or placebo. RESULTS: Of 281 participants screened, 88 having relatively lower levels of CFF and NPA were enrolled in the study. Of these, 37 control and 43 BE group subjects completed the study. The VDT load-induced reduction in CFF was alleviated after 8 weeks of BE supplementation (95% confidence interval, 0.10-1.60; p=0.023), in contrast to placebo supplementation, while NPA variation was not. Of the subjective symptoms of eye fatigue, VDT load-induced ocular fatigue sensation, ocular pain, eye heaviness, uncomfortable sensation, and foreign body sensation were mitigated more in the BE group than in the control group, at week 8 (p<0.05). There were no severe adverse events in either group. CONCLUSIONS: BE supplementation improved some of the objective and subjective parameters of eye fatigue induced by VDT loads.

The effect of proteasome inhibitor MG132 on experimental inflammatory bowel disease.

Immunoproteasome up-regulation enhances the processing of nuclear factor-kappaB (NF-kappaB) and degradation of IkappaBalpha, which correlates with increased amounts of NF-kappaB in the various cells. Aberrant activation of NF-kappaB is involved in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to elucidate the effect of proteasome inhibitor MG132 on experimental IBD. We investigated the effects of MG132 on intestinal inflammation and epithelial regeneration in both interleukin-10-deficient (IL-10(-/-)) mice and mice with dextran sulphate sodium (DSS)-induced colitis. Body weight, histological findings and tumour necrosis factor (TNF)-alpha mRNA expression, epithelial cell proliferation and NF-kappaB p65 activity in colonic tissues were examined. The effects of MG132 on cell proliferation, migration and multiple drug resistance 1 (MDR1) gene expression were determined in vitro. MG132 ameliorated intestinal inflammation of IL-10(-/-) mice by decreasing TNF-alpha mRNA expression in the colonic tissues, which was associated with suppression of NF-kappaB activation, and reduced significantly the number of Ki-67-positive intestinal epithelial cells. On the other hand, MG132 did not reduce intestinal inflammation in mice with DSS-induced colitis, and delayed significantly the recovery of body weight and epithelial regeneration. MG132 also suppressed significantly epithelial cell proliferation, cell migration and MDR1 gene expression in vitro. Proteasome inhibition reduces T cell-mediated intestinal inflammation, but may interrupt both epithelial regeneration and barrier function of colonic mucosa. Optimal use of proteasome inhibitor should be kept in mind when we consider its clinical application for patients with IBD.

Effects of delta-opioid receptor stimulation and inhibition on hippocampal survival in a rat model of forebrain ischaemia.

BACKGROUND: It has been reported that delta-opioid (DOP) receptor agonists may be neuroprotective in the central nervous system. However, the DOP agonist [d-Ala(2), d-Leu(5)]enkephalin (DADLE) does not produce neuroprotection in severe forebrain ischaemia. The aim of this study was to examine the effects of DADLE on hippocampal neurone survival against less severe forebrain ischaemia. METHODS: Intraperitoneal injection of DADLE (0 or 16 mg kg(-1)) in male Sprague-Dawley rats was performed 30 min before ischaemia. Severe (10 min), moderate (8 min), or mild (6 min) forebrain ischaemia was produced by bilateral carotid occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anaesthesia. Naltrindole (10 mg kg(-1)) (DOP antagonist) was administered 30 min before DADLE in order to confirm DOP receptor activation in the neuroprotective efficacy of DADLE. Naltrindole alone was also administered 30 min before ischaemia to examine endogenous DOP agonism as a self-protecting mechanism against ischaemia. All animals were evaluated neurologically and histologically after a 1 week recovery period. RESULTS: DADLE improved neurone survival in hippocampal CA3 and dentate gyrus (DG) sectors. CA1 neurones were not protected against moderate and mild ischaemia. Naltrindole abolished DADLE neuroprotection in the CA3 and DG after both moderate and mild ischaemia. Interestingly, regardless of co-administration of DADLE, naltrindole significantly worsened neuronal injury in the CA1 region after mild ischaemia. CONCLUSIONS: These results suggest that DADLE provides limited neuroprotection to relatively ischaemia-resistant regions but not to selectively vulnerable regions. This was probably mediated by DOP stimulation. Pre-ischaemic treatment with a DOP antagonist, regardless of co-administration of DADLE, worsened neuronal damage at the selectively vulnerable regions only after mild forebrain ischaemia. These data suggest that DOP activation with endogenous DOP ligand may be involved in self-protecting ischaemia-sensitive regions of the brain.

Mineralization of basement membrane mediates dentogingival adhesion in mammalian and nonmammalian vertebrates.

In order to elucidate the mechanism of adhesion between the gingiva and the tooth, detailed comparative ultrastructural studies of the dentogingival border were done in the monkey and shark. The tissues were prepared with or without demineralization for the ultrastructural observations. At the border, the internal basement membrane, which is firmly bound to the junctional epithelium through hemidesmosomes, was specialized differently in these species. In the monkey, the lamina densa was closely associated at its enamel side with an additional layer which had characteristics of the lamina densa and was referred to as the supplementary lamina densa. In the shark, the lamina densa showed a unique, hemidesmosome-related specialization in the form of the intermittent occurrence of bulges along its surface facing the epithelium. In nondemineralized tissues a part of the basement membrane, that is, the supplementary lamina densa (monkey) and the main lamina densa but not bulges (shark), was preferentially mineralized. The mineral deposit was continuous with that in the enamel and enameloid/dentine, thus constituting an advancing edge of mineralization. The network arrangement of the mineral crystals in the monkey basement membrane resembled the pattern of the cord network of the basement membrane, suggesting the presence of a delicate mutual basement membrane-mineral interaction. Thus, the organic phase and the mineral phase are allowed to make contact at this mineralized area of the basement membrane and firmly bind to one another. Therefore, strong gingiva-tooth adhesion is established by partial mineralization of the internal basement membrane, in a way similar to that found in the previously reported association of maturation stage ameloblasts with the enamel.

The sulphydryl reagent, N-ethylmaleimide, disrupts sleep and blocks A1 adenosine receptor-mediated inhibition of intracellular calcium signaling in the in vitro ventromedial preoptic nucleus.

To explore the neuronal signaling mechanisms underlying sleep regulation in the rat, the present study examined continuous intra-third ventricle infusion of N-ethylmaleimide (NEM), a sulphydryl reagent that inhibits G(i/o) protein-coupled receptor-mediated signaling pathways. The diurnal infusion of NEM (0.01-10 micromol/10 h) dose-dependently inhibited both non-rapid eye movement sleep and rapid eye movement sleep. A maximal dose of NEM (10 micromol/10 h) dramatically inhibited day-time sleep (-57% for non-rapid eye movement sleep and -89% for rapid eye movement sleep) with a compensatory increase of sleep during the subsequent night-time (+33% for non-rapid eye movement sleep and +259% for rapid eye movement sleep). The day-time brain temperature was also increased by NEM, demonstrating effects of NEM on both sleep and body temperature levels. Immunostaining of the rat hypothalamus with a monoclonal antibody against the A1 adenosine receptor (A1R) was used to explore the distribution of a sleep-related G(i/o) protein-coupled receptor. Robust A1R-like immunoreactivity was found in the ventromedial preoptic nucleus and the supraoptic nucleus. Fura-2-based Ca(2+) imaging analysis of acute hypothalamic slices further demonstrated that the A1R agonist N(6)-cyclopentyladenosine (CPA; 200 nM) inhibited spontaneous Ca(2+) oscillations and high potassium (80 mM)-induced Ca(2+) flux in the ventromedial preoptic nucleus, while NEM (100-300 microM) and an A1R antagonist 8-cyclopentyl-dipropylxanthine (300 nM) blocked the CPA actions and increased the high potassium-induced Ca(2+) flux. From these results we suggest that NEM-sensitive G protein-coupled receptor(s) may play an important role in the regulation of sleep and body temperature in the rat and one possible mechanism is an A1R-mediated regulation of intracellular Ca(2+) concentrations in the ventromedial preoptic nucleus.

Direct determination of silicon in powdered aluminium oxide by use of slurry sampling with in situ fusion graphite-furnace atomic-absorption spectrometry.

A direct method for determination of silicon in powdered high-purity aluminium oxide samples, by slurry sampling with in situ fusion graphite-furnace atomic-absorption spectrometry (GF-AAS), has been established. A slurry sample was prepared by 10-min ultrasonication of a powdered sample in an aqueous solution containing both sodium carbonate and boric acid as a mixed flux. An appropriate portion of the slurry was introduced into a pyrolytic graphite furnace equipped with a platform. Silicon compounds to be determined and aluminium oxide were fused by the in situ fusion process with the flux in the furnace under optimized heating conditions, and the silicon absorbance was then measured directly. The calibration curve was prepared by use of a silicon standard solution containing the same concentration of the flux as the slurry sample. The accuracy of the proposed method was confirmed by analysis of certified reference materials. The proposed method gave statistically accurate values at the 95% confidence level. The detection limit was 3.3 microg g(-1) in solid samples, when 300 mg/20 mL slurry was prepared and a 10 microL portion of the slurry was measured. The precision of the determination (RSD for more than four separate determinations) was 14% and 2%, respectively, for levels of 10 and 100 microg g(-1) silicon in aluminium oxide.

Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation, and beta-oxidation of fatty acid in OLETF rats.

We investigated the efficacy of a 4-wk supplementation of conjugated linoleic acid (CLA) as free fatty acid (FFA) or triacylglycerol (TG) on serum leptin concentration, body-fat accumulation, and mitochondrial beta-oxidation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. A significant reduction of serum leptin concentration (42%) and a decrease in the wet weights of perirenal, epididymal, and omental/visceral-adipose tissue in TG-CLA and FFA-CLA groups were found in comparison with the OLETF control group. Both forms of CLA supplementation produced a 5.2% decrease in body weight compared with the control even though food intake was similar in the OLETF groups. Moreover, both forms of CLA enhanced carnitine-palmitoyltransferase activity in brown adipose tissue, perirenal adipose tissue, red gastrocnemius muscle, and liver in comparison with the OLETF control group. Serum concentrations of non-esterified fatty acid and TG also were reduced in rats fed diets supplemented with TG-CLA and FFA-CLA.

Interaction of phytoestrogens with estrogen receptors alpha and beta.

The human estrogen receptor (hER) exists as two subtypes, hER alpha and hER beta, that differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activities of soy isoflavones after digestion with enteric bacteria in competition binding assays with hER alpha or hER beta protein, and in a gene expression assay using a yeast system. The estrogenic activities of these isoflavones were also investigated by the growth of MCF-7 breast cancer cells. Isoflavone glycoside binds weakly to both receptors and estrogen receptor-dependent transcriptional expression is poor. The aglycones bind more strongly to hER beta than to hER alpha. The binding affinities of genistein, dihydrogenistein and equol are comparable to the binding affinity of 17 beta-estradiol. Equol induces transcription most strongly with hER alpha and hER beta. The concentration required for maximal gene expression is much higher than expected from the binding affinities of the compounds, and the maximal activity induced by these compounds is about half the activity of 17 beta-estradiol. Although genistin binds more weakly to the receptors and induces transcription less than does genistein, it stimulates the growth of MCF-7 cells more strongly than does genistein.

Molecular cloning of ring finger protein 21 (RNF21)/interferon-responsive finger protein (ifp1), which possesses two RING-B box-coiled coil domains in tandem.

We have cloned the full length of a novel cDNA, named ring finger protein 21 (RNF21), composed of the RING finger-B box-coiled coil (RBCC) domain and the B30.2 domain, which are characteristic of the RBCC-B30.2 family. As a structural feature, the RNF21 cDNA possessed at least three kinds of isoforms, due to alternative splicing, consisting of the long form with the RBCC-RBCC-B30.2 domain, the medium form with the RBCC-B30.2 domain, and the short form with only the RBCC domain. Moreover, respective transcripts corresponding to the three isoforms were detected in various human organs by reverse transcription-PCR and Northern blot analyses. Interestingly, the medium form of the RNF21 mRNA expressed most predominantly was dramatically up-regulated within 8-16 h by interferon stimulation of HeLa cells. These findings suggest that RNF21 is a downstream gene that may mediate interferon's biological action.

Lack of integrative control of heat production and heat loss after capsaicin administration.

Body temperature is usually regulated by opposing controls of heat production and heat loss. However, systemic administration of capsaicin activates heat loss and heat production simultaneously. Because capsaicin receptors are located mainly on primary sensory neurons and body temperature is regulated by the central nervous system, we investigated the brain mechanisms involved in these capsaicin-induced thermal responses. For this purpose, we examined the effects of spinalization and decerebration on these responses in artificially ventilated, urethane-anesthetized rats. Cervical spinal transection largely attenuated both responses, showing the critical involvement of the brain. Colonic temperature (Tc) did not change after the capsaicin administration to the spinalized rats. Decerebration between the hypothalamus and midbrain prevented the capsaicin-induced heat loss and enhanced the capsaicin-induced heat production. Consequently, Tc increased without a hypothermic period. The results show that capsaicin activates brainstem-controlled heat production and forebrain-controlled heat loss separately.

Sucrose-diet feeding induces gene expression of heat shock protein in rat brain under stress.

Stress-induced hyperphagia is enhanced in the presence of sweets, particularly sucrose, which may act to attenuate stress. Recently, it was also reported that heat shock protein (HSP) may be involved in the defense against stress. To explore whether sucrose alters gene expression of HSP under stress, we determined the HSP mRNA levels in the hypothalamus, cerebellum, and cerebral cortex after restraint stress in sucrose-diet-fed rats. Competitive RT-PCR revealed that gene expressions of HSP27 in the cerebral cortex and cerebellum and of HSP70 in the cerebral cortex, hypothalamus, and cerebellum were induced by restraint stress under a sucrose-diet-fed condition. However, restraint stress by itself or sucrose diet alone did not induce expression of HSP27 or HSP70 mRNA in any of the three anatomical parts. It is suggested that sucrose facilitates the gene expression of HSP27 and HSP70 in brain after restraint stress, which may attenuate stress.

Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet.

OBJECTIVE: To investigate the inhibitory effects of CT-II, extract of Nomame Herba, on lipase activity in vitro and on obesity in rats fed a high-fat diet in vivo. DESIGN: The assay for the inhibitory effect of CT-II on lipase activity was performed by measuring released free fatty acids after the incubation of the medium with CT-II, porcine pancreatic lipase and triolein (experiment 1). In vivo experiments, lean rats or obese rats (570-718 g) were fed a high-fat diet containing 60% fat with or without CT-II for 8 weeks (experiment 2), for 14 days (experiment 3) or for 12 weeks (experiment 4), respectively. MEASUREMENT: The time course of body weight, food intake, organ weight (parametrial fat, liver, heart and kidney) and plasma parameters (triglyceride, total cholesterol, glucose, AST, ALT and insulin), fecal output of total fat and total cholesterol were measured. Hepatic histological examinations were also performed. RESULTS: CT-II inhibited the porcine lipase activity dose-dependently in vitro (experiment 1). Body and liver weight were reduced and hepatic histological examination showed an amelioration of fatty liver in CT II treated animals (experiment 2). CT-II significantly inhibited body weight gain and plasma triglyceride elevation in a dose-dependent manner, without affecting food intake in lean rats fed the high-fat diet. Elevated plasma AST and ALT were also decreased (experiment 3). When obese rats fed the high-fat diet were treated with CT-II for up to 6 months, body weight was initially reduced and thereafter weight gain was significantly suppressed. Total body fat was also significantly reduced and significant reduction of plasma AST and ALT was observed (experiment 4). CONCLUSIONS: These results demonstrated that the lipase inhibitor CT-II is effective in preventing and ameliorating obesity, fatty liver and hypertriglyceridemia in rats fed a high-fat diet.

A short daytime nap modulates levels of emotions objectively evaluated by the emotion spectrum analysis method.

A novel objective technique, the emotion spectrum analysis method, was first applied to investigate emotional fluctuations before, during and after a daytime nap in eight healthy young adults (four males and four females). The subjects were allowed to freely nap between 13.00 and 14.00 h, in which stages 1 and 2 non-rapid eye movement sleep occurred on average for 5.9 and 20.8 min, respectively. Emotional components such as anger, joy, relaxation and sadness were numerically estimated on the basis of spatio-temporal behavior of 21-channel electroencephalogram and analyzed statistically. In comparison with the prenap waking level, the magnitudes of the anger, joy and relaxation components remained stably unchanged during the nap but elevated significantly during the postnap waking period. The sadness component exhibited little significant change throughout the observation period. From the results, we suggest that a short daytime nap modulates the emotions to improve the postnap mental states.

Ibotenic acid-induced lesions of the medial septum increase hippocampal membrane associated protein kinase c activity and reduce acetylcholine synthesis: prevention by a phosphatidylcholine/vitamin B12 diet.

Ibotenic acid infusion into the medial septum (MS) results in biochemical alterations in the hippocampus. The biochemical events involved in this neuronal lesion are poorly understood. We investigated the effect of a purified diet supplemented with egg phosphatidylcholine (PC) and vitamin B(12) on ibotenic acid-medicated biochemical changes in the rat hippocampus and crude synaptosomal membranes. Male Wistar rats with this MS lesion were fed a purified diet (control diet) or a purified diet supplemented with 5.7 g PC and 125 microg vitamin B(12) per 100 g (experimental diet) for 18 days. Sham-operated rats were fed the control diet. Compared with the sham-operated rats, MS-lesioned rats fed the control diet showed increased activity of membrane-bound protein kinase C (PKC), decreased activity of choline acetyltransferase, and decreased concentrations of acetylcholine in the hippocampus. The ratio of cholesterol to phospholipid in the crude synaptic membrane was lower in the lesioned rats than in the sham-operated rats, but this was not accompanied by any alteration in membrane lipid fluidity. MS-lesioned rats fed the experimental diet showed lowered PKC activity and elevated acetylcholine concentrations than did rats fed the control diet, but there were no significant effects on choline acetyltransferase activity and the lipid ratio. The ibotenic acid-mediated elevation of PKC activity was observed as early as 2 days postinjury in the control diet-fed rats but not in the experimental diet-fed rats. We propose that ibotenic acid mediates pathophysiologic actions through the activation of PKC and that PC combined with vitamin B(12) ameliorates the second messenger-mediated injury.

Effects of tea catechins on the ERE-regulated estrogenic activity.

Tea catechins exert many biological effects, including anticancer and antibacterial activities. Also, it is reported that some plant flavonoids exhibit estrogenic activity. In this study, we investigated estrogenic or antiestrogenic activities of catechins in HeLa cells transiently transfected with an estrogen response element (ERE)-regulated luciferase reporter and an estrogen receptor (ER) alpha or ERbeta expression vector. Catechins alone did not induce luciferase (luc) activity in either of the ERs. Addition of 17beta-estradiol (E2) plus epicatechin gallate (ECG) or epigallocatechin gallate (EGCG) at 5 x 10(-6) M resulted in significant decreases in the ERalpha-mediated luc activity compared with that of E2 alone. On the contrary, lower concentrations significantly increased the E2-induced luc activity. Similar effects were observed with tamoxifen. The ERbeta-mediated estrogenic activities were stimulated by catechins. In conclusion, some catechins, particularly EGCG, were antiestrogenic for ERalpha at higher doses, and co-estrogenic for ERalpha at lower doses and for ERbeta. The lower doses were found in human plasma after tea-drinking. In addition, some catechins may be antiendocrine disruptors because they suppressed bisphenol A-induced luc activities.

Bactericidal activity of manganese and iodide ions against Staphylococcus aureus: a possible treatment for acute atopic dermatitis.

We reported previously that balneotherapy using Kusatsu hot-spring water is useful for controlling the skin symptoms of acute flares/exacerbations of refractory cases of atopic dermatitis. As Staphylococcus aureus on the skin surface decreased in number or disappeared after balneotherapy, the hot-spring water was suspected to act against the microorganism. The hot-spring water showed strong bactericidal activity against S. aureus in vitro. In order to clarify the mechanism further, the bactericidal activity of the hot-spring water was examined by adding back cations and anions in same concentrations as those in the original hot-spring water, one at a time to cation- and anion-exchanged hot-spring water. The findings clearly demonstrated that the bactericidal activity was expressed by manganese and iodide ions in acidic conditions (pH 2.0-3.0). Thus, the probable mechanism for the improvement of skin manifestations through Kusatsu balneotherapy is the bactericidal activity of the hot-spring water against S. aureus. When added to water acidified with sulphuric acid (pH 2.0-3.0) a synergistic effect of the 2 ions was observed, so that an anti-staphylococcal effect was obtained even at low concentrations (1 mg/kg). Acidic solutions containing manganese and iodide ions may thus be clinically useful for treating skin conditions caused by S. aureus.

Colony-stimulating factors in rapid eye movement sleep and non-rapid eye movement sleep regulation.

Although several cytokines are known to be somnogenic, no study has been conducted to examine whether colony-stimulating factors (CSF) affect sleep. Therefore, we studied the effects of granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) on sleep in rats and their possible mechanism of action. At the dose of 10 pmol, GM-CSF or M-CSF significantly increased both non-rapid eye movement and rapid eye movement (REM) sleep or REM sleep only when infused intracerebroventricularly during the dark period. When injected locally in the hypothalamus, GM-CSF and M-CSF increased nitric oxide (NO) production. Thus, NOergic neural signals in the hypothalamus may take part in the somnogenic action of CSF.

Molecular cloning of rat efp: expression and regulation in primary osteoblasts.

We have previously identified an estrogen-responsive gene, efp (estrogen-responsive finger protein), by genomic binding-site cloning method. Here, we isolated a rat homologue of efp cDNA that encodes an open reading frame of 644 amino acids sharing high homology with human efp (69% identity at the protein level) and mouse efp (80% identity at the protein level). The efp protein has a RING finger, a variant type of zinc finger motif, B1 box and B2 box, each having a pair of zinc fingers, and coiled-coil domain, belonging to the RING finger-B box-Coiled Coil (RBCC) family. Several members of RBCC family including efp have characteristic C-terminal domain, forming a subfamily. Next, we detected efp mRNA in primary osteoblasts, one of estrogen target cells, derived from the calvariae of rat fetus. An anti-efp antibody revealed the efp protein is expressed and regulated by estrogen in the primary osteoblasts. Interestingly, the efp protein in primary osteoblasts is down-regulated by 1alpha,25-dihydroxyvitamin D(3) treatment that promotes the differentiation of the cells, whereas it is up-regulated by TGF-beta1 treatment that inhibits the differentiation of the cells. These findings suggest the possible involvement of the efp in the differentiation of osteoblastic cells.

Effect of coenzyme Q10 in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): evaluation by noninvasive tissue oximetry.

We evaluated the effect of coenzyme Q10 supplementation to two patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by using noninvasive tissue oximetry with near-infrared spectra of hemoglobin from the quadriceps muscle during bicycle ergometer exercise. Patients showed distinct oxygen consumption patterns reflecting the defect in oxidative phosphorylation and the impairment in oxygen utilization during exercise. Based on the oxygen consumption pattern, we considered one patient as having severe mitochondrial disorder and another patient as having mild one. After coenzyme Q10 supplementation, the oxygen consumption pattern of the patient with the severe form shifted to the mild one, while that of the patient with mild form remained unchanged. The shift of the pattern to the mild form correlated well with reduction of the sum of the serum lactate and pyruvate content during exercise. Noninvasive tissue oximetry may be useful to evaluate the effect of coenzyme Q10 supplementation to patients with mitochondrial encephalomyopathy including MELAS.