Decreased tear volume in patients with metabolic syndrome: the Osaka study.
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ABSTRACT:
SUBMITTER: Kawashima M
PROVIDER: S-EPMC3932960 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cathepsin S (CTSS) activity is elevated in Sjögren's Syndrome (SS) patient tears. Here we tested whether protease inhibition and cystatin C (Cys C) levels are reduced in SS tears, which could lead to enhanced CTSS-driven degradation of tear proteins. CTSS activity against Cys C, LF and sIgA was tested in SS or healthy control tears. Tears from 156 female subjects (33, SS; 33, rheumatoid arthritis; 31, other autoimmune diseases; 35, non-autoimmune dry eye (DE); 24, healthy controls) were analyzed for CTSS activity and Cys C, LF, and sIgA levels. Cys C and LF showed enhanced degradation in SS tears supplemented with recombinant CTSS, but not supplemented healthy control tears. CTSS activity was significantly increased, while Cys C, LF and sIgA levels were significantly decreased, in SS tears compared to other groups. While tear CTSS activity remained the strongest discriminator of SS in autoimmune populations, combining LF and CTSS improved discrimination of SS beyond CTSS in DE patients. Reductions in Cys C and other endogenous proteases may enhance CTSS activity in SS tears. Tear CTSS activity is reconfirmed as a putative biomarker of SS in an independent patient cohort while combined LF and CTSS measurements may distinguish SS from DE patients.
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Project description:The tear matrix metalloproteinase-9 (MMP-9) immunoassay (Inflammadry) exhibits variable results in dry eye (DE) patients. We investigated if the tear volume in DE patients affects the results of MMP-9 immunoassay in clinical and in vitro settings. This cross-sectional study enrolled 188 eyes of 188 DE patients. The clinical symptoms and signs of DE were assessed using the Ocular Surface Disease Index and visual analog scale, strip meniscometry, tear break-up time, and tear meniscus height (TMH), area (TMA), and depth (TMD) using swept-source optical coherence tomography and corneal and conjunctival staining scores. For quantitative evaluation, the bands produced by the InflammaDry test were analyzed with ImageJ. DE subjects were grouped according to MMP-9 positivity and TMH. The InflammaDry-positive group showed greater TMH, TMA, and TMD than the MMP-9-negative group (p < 0.05). InflammaDry test band density in the high TMH group was significantly greater than that in the low and normal TMH groups (p < 0.05). InflammaDry test band density correlated positively with TMH, TMA, and TMD (all p < 0.05). InflammaDry test results were influenced by tear volume. Low tear volume in aqueous tear-deficient DE may induce false-negative results, and reflex tearing during the test may induce false-positive results.
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Project description:Eukaryotic initiation factor 2A (eIF2A) is a 65 kDa protein that functions in minor initiation pathways, which affect the translation of only a subset of messenger ribonucleic acid (mRNAs), such as internal ribosome entry site (IRES)-containing mRNAs and/or mRNAs harboring upstream near cognate/non-AUG start codons. These non-canonical initiation events are important for regulation of protein synthesis during cellular development and/or the integrated stress response. Selective eIF2A knockdown in cellular systems significantly inhibits translation of such mRNAs, which rely on alternative initiation mechanisms for their translation. However, there exists a gap in our understanding of how eIF2A functions in mammalian systems in vivo (on the organismal level) and ex vivo (in cells). Here, using an eIF2A-knockout (KO) mouse model, we present evidence implicating eIF2A in the biology of aging, metabolic syndrome and central tolerance. We discovered that eIF2A-KO mice have reduced life span and that eIF2A plays an important role in maintenance of lipid homeostasis, the control of glucose tolerance, insulin resistance and also reduces the abundance of B lymphocytes and dendritic cells in the thymic medulla of mice. We also show the eIF2A KO affects male and female mice differently, suggesting that eIF2A may affect sex-specific pathways. Interestingly, our experiments involving pharmacological induction of endoplasmic reticulum (ER) stress with tunicamycin did not reveal any substantial difference between the response to ER stress in eIF2A-KO and wild-type mice. The identification of eIF2A function in the development of metabolic syndrome bears promise for the further identification of specific eIF2A targets responsible for these changes.
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Project description:PurposeTear secretion is critical for maintenance of healthy ocular surface and vision. Most of normal subjects and dry eye patients feel worsening of ocular dryness in the afternoon, however, diurnal variation of tear meniscus volume has not been directly measured because there was no appropriate method. We used a simple, non-invasive technique, tear strip meniscometry (SM) by self-examination. Previous investigations indicated the values of SM correlated strongly with those of the Schirmer test, tests of tear break up time, and tear meniscus height measurement by anterior optical coherence tomography. The purpose of this study was to capture diurnal variation of aqueous availability at the tear meniscus by measuring wetted length using SM through self-examination.MethodsThirty-six medical personnel (mean age; 35.7 years) participated and SM self-examination was performed using a mirror seven times a day. The strip is applied for 5 seconds to the lateral side of the lower lid tear meniscus without touching the ocular surface.ResultsThe measured SM value was the highest upon awakening (4.44 ± 3.14 mm) and gradually decreased in the evening; 3.81 ± 3.12 at 9:00, 3.31 ± 2.72* at 12:00, 2.89 ± 1.88* at 15:00, 2.92 ± 1.87* at 18:00, 2.78 ± 1.85* at 21:00, and 2.89 ± 1.75* at bedtime with statistical significance compared to the value upon awakening (*P < 0.05, Dunnett's multiple comparison test). Proportion of number of subjects with low SM value (< 4 mm) to total number of subjects was 52.8% upon awakening and 83.3% at 21:00, and gradually increased toward evening.ConclusionOur results could identify diurnal variation of tear meniscus volume in the general population.
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Project description:PurposeTo assess the efficacy and safety of an intranasal tear neurostimulator (ITN) device in Sjögren syndrome (SS) patients.MethodsThis was a two-visit prospective, randomized, controlled, same-day crossover study in participants with SS. Inclusion criteria were assessed at a baseline screening visit and included an Ocular Surface Disease Index (OSDI) score ≥13, and a Schirmer with anesthesia ≤10 mm/5 min (in at least one eye), with a cotton swab stimulation induced increase of ≥4 mm in the same eye. Participants returned for the application visit, where they received intranasal and extranasal applications of the ITN in random sequence, separated by at least 60 min. Schirmer scores were measured in both eyes after each application and compared to baseline values. Generalized linear models were performed to compare the change in Schirmer scores from baseline, and generalized estimating equations were used to account for correlations from repeated measurements in the same eye and measurements from two eyes of the same patient.ResultsFifty-five participants were screened and 35 were enrolled (all female), ranging in age from 31 to 72 years (mean, 57 years). The baseline OSDI score ranged from 14 to 91 (mean, 50.5), and the baseline Schirmer score had a mean (SD) of 6.4 (3.5) ranging from 0 to 20 (mm/5min). Improvement in Schirmer scores was significantly greater for intranasal device application (13.5 mm/5min, 95% CI: 10.4, 16.5) compared to extranasal device application (0.8mm/5min, 95% CI: -0.9, 2.4) (p<0.0001). The effects of the intranasal device application were significant regardless of the participant's baseline Schirmer score and systemic SS medication usage (p<0.05).ConclusionIntranasal application of the ITN device significantly increased tear production in a subset of SS patients compared to baseline and was more effective than extranasal application. While production of the ITN device was recently discontinued, our findings suggest that other therapies that neurostimulate the lacrimal function unit may be effective in a subset of SS patients.
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Project description:Physical activity is a cornerstone in the treatment of obesity and metabolic syndrome (MetS). Given the leading physical activity barrier of time commitment and safety concerns about vigorous exercise in high-risk groups, this study aimed to investigate the effects of two extremely time-efficient training protocols (<?30 min time effort per week), either performed as high- (HIIT) or moderate-intensity interval training (MIIT) over 12 weeks, in obese MetS patients. In total, 117 patients (49.8?±?13.6 years, BMI: 38.2?±?6.2 kg/m2) were randomized to HIIT (n?=?40), MIIT (n?=?37) or an inactive control group (n?=?40). All groups received nutritional counseling to support weight loss. Maximal oxygen uptake (VO2max), MetS severity (MetS z-score), body composition and quality of life (QoL) were assessed pre-and post-intervention. All groups significantly reduced body weight (~?3%) but only the exercise groups improved VO2max, MetS z-score and QoL. VO2max (HIIT:?+?3.1 mL/kg/min, p?<?0.001; MIIT:?+?1.2 mL/kg/min, p?<?0.05) and MetS z-score (HIIT: -?1.8 units, p?<?0.001; MIIT: -?1.2 units, p?<?0.01) improved in an exercise intensity-dependent manner. In conclusion, extremely low-volume interval training, even when done at moderate intensity, is sufficiently effective to improve cardiometabolic health in obese MetS patients. These findings underpin the crucial role of exercise in the treatment of obesity and MetS.
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Project description:BackgroundMetabolic syndrome (MS) is a well-known risk factor of cardiovascular diseases that is focused on central obesity. Recent studies have reported the association between pericardial adipose tissue (PAT) volume and MS. However, no studies have demonstrated the cutoff PAT volume that represents the best association with MS.MethodsThe data of 374 subjects were analyzed cross-sectionally to compare PAT, measured on coronary multidetector computed tomography, and various metabolic parameters according to MS. After PAT volumes were divided into tertiles, various metabolic parameters were compared among tertiles; furthermore, the odds ratio for developing MS was calculated. Finally, we demonstrated the cutoff PAT volume that represented the best association with MS by using the receiver-operating characteristic curve.ResultsWe found that 27.5% of the subjects had MS, and the mean PAT volume was 123.9 cm3 . PAT showed a significant positive correlation with body mass index, waist circumference, and levels of glucose, triglyceride, high-sensitivity C-reactive protein, uric acid, and homocysteine, but a negative correlation with high-density lipoprotein cholesterol. Furthermore, after dividing into tertiles, PAT volume was also significantly associated with various metabolic parameters. The odds ratio for having MS was 4.19 (95% confidence interval, 2.27-7.74) in the top tertile of PAT volumes after adjusting for age, sex, and smoking. The cutoff PAT volume that represented the best association with MS was 142.2 cm3 .ConclusionPAT was significantly associated with MS and various metabolic parameters. The cutoff PAT volume of 142.2 cm3 showed the best association with MS.
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Project description:Obesity is a risk factor for cognitive decline and gray matter volume loss in aging. Studies have shown that different metabolic factors, e.g., dysregulated glucose metabolism and systemic inflammation, might mediate this association. Yet, even though these risk factors tend to co-occur, they have mostly been investigated separately, making it difficult to establish their joint contribution to gray matter volume structure in aging. Here, we therefore aimed to determine a metabolic profile of obesity that takes into account different anthropometric and metabolic measures to explain differences in gray matter volume in aging. We included 748 elderly, cognitively healthy participants (age range: 60 - 79 years, BMI range: 17 - 42 kg/m2) of the LIFE-Adult Study. All participants had complete information on body mass index, waist-to-hip ratio, glycated hemoglobin, total blood cholesterol, high-density lipoprotein, interleukin-6, C-reactive protein, adiponectin and leptin. Voxelwise gray matter volume was extracted from T1-weighted images acquired on a 3T Siemens MRI scanner. We used partial least squares correlation to extract latent variables with maximal covariance between anthropometric, metabolic and gray matter volume and applied permutation/bootstrapping and cross-validation to test significance and reliability of the result. We further explored the association of the latent variables with cognitive performance. Permutation tests and cross-validation indicated that the first pair of latent variables was significant and reliable. The metabolic profile was driven by negative contributions from body mass index, waist-to-hip ratio, glycated hemoglobin, C-reactive protein and leptin and a positive contribution from adiponectin. It positively covaried with gray matter volume in temporal, frontal and occipital lobe as well as subcortical regions and cerebellum. This result shows that a metabolic profile characterized by high body fat, visceral adiposity and systemic inflammation is associated with reduced gray matter volume and potentially reduced executive function in older adults. We observed the highest contributions for body weight and fat mass, which indicates that factors underlying sustained energy imbalance, like sedentary lifestyle or intake of energy-dense food, might be important determinants of gray matter structure in aging.
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Project description:Metabolic Syndrome in Men (METSIM) Study
| PRJNA246253 | ENA