高齢者における日中光曝露が夜間尿中メラトニン分泌への与える影響 : 平城京スタディ横断解析

CONTEXT:Melatonin is involved in a variety of diseases, including cancer, insomnia, depression, dementia, hypertension, and diabetes; its secretion is influenced by environmental light. Although daylight exposure increases nocturnal melatonin secretion in a controlled laboratory setting, whether it increases nocturnal melatonin secretion in an uncontrolled daily life setting remains unclear.OBJECTIVE:We aimed to determine the association between daylight exposure in an uncontrolled daily life setting and urinary 6-sulfatoxymelatonin excretion.DESIGN AND PARTICIPANTS:A cross-sectional study was conducted in 192 elderly individuals (mean age, 69.9 yr).MEASURES:We measured ambulatory daylight exposure using a wrist light meter in two 48-h sessions; furthermore, we measured overnight urinary 6-sulfatoxymelatonin excretion, an index of melatonin secretion, on the second night of each session.RESULTS:The median duration of daylight exposure of at least 1000 lux was 72 min (interquartile range, 37-124). Univariate linear regression analysis showed marginal to significant associations between log-transformed urinary 6-sulfatoxymelatonin excretion and age, current smoking status, benzodiazepine use, day length, log-transformed duration of daylight exposure of at least 1000 lux, and daytime physical activity. In a multivariate model, log-transformed duration of daylight exposure of at least 1000 lux was significantly associated with log-transformed urinary 6-sulfatoxymelatonin excretion (regression coefficient, 0.101; 95% confidence interval, 0.003-0.199; P = 0.043). Furthermore, an increase in the duration of daylight exposure of at least 1000 lux from 37 to 124 min (25th to 75th percentiles) was associated with a 13.0% increase in urinary 6-sulfatoxymelatonin excretion (6.8 to 7.7 μg).CONCLUSIONS:Daylight exposure in an uncontrolled daily life setting is positively associated with urinary 6-sulfatoxymelatonin excretion in the elderly.博士（医学）・乙第1308号・平成25年3月15日Copyright © 2012 by The Endocrine Societ

Identification of Cysteine Proteases and Screening of Cysteine Protease Inhibitors in Biological Samples by a Two-Dimensional Gel System of Zymography and Reverse Zymography

We have developed a two-dimensional (2D-) gel system of zymography and reverse zymography for the detection and characterization of proteases and protease inhibitors. Isoelectric focusing (IEF) agarose gels with pH gradients were employed for separation in the first-dimension and sodium dodecyl sulfate (SDS)-polyacrylamide gel copolymerized with gelatin used for the second dimension. Proteases and protease inhibitors separated by IEF gel were applied on the second gel without trichloroacetic acid (TCA) fixation. Protease activity in the 2D-gel was visualized as transparent spots where gelatin substrate was digested after commassie brilliant blue (CBB) staining. Some of the transparent spots from the skin mucus extract of rainbow trout were determined to be a cysteine protease through use of E-64 or CA-074. In the reverse zymography technique, the gel was incubated with papain solution at 37 ºC for 18 h. Cysteine protease inhibitors from broad bean seeds were detected as clear blue spots after CBB staining. The amino (N-) terminal sequences of four papain inhibitor spots thus detected were demonstrated to be identical to that of favin β chain, a broad bean lectin. Taken together, our system can be considered to be an efficient technique for discovering and characterizing new proteases and protease inhibitors in biological samples. This is the first report describing a 2D-gel system of zymography and reverse zymography

Integrating Cancer Patients’ Satisfaction with Rescue Medication in Pain Assessments

A patient’s pain intensity rating alone is insufficient grounds for determining the pain medication and dosage to administer daily. This study aimed to investigate whether a convenient assessment method could be developed that would reflect the effectiveness of an opioid analgesic on cancer patients’ pain management. We investigated pain intensity （worst, least, average, current） and the effectiveness of the opioid rescue medication in terms of patient satisfaction. This study used Spearman’s rank correlation coefficients to evaluate the relationships between patient satisfaction with rescue medication and both pain intensity and the medication’s perceived effectiveness. Data from 60 participants with a mean age of 60.5±11.4 years （range: 31-79 years） were analyzed. Thirty-eight （63.3%） participants were male, and 22 （36.7%） were female. The correlations found between rescue medication satisfaction and both the worst numerical rating scale （NRS） rating （r＝−0.15, P＝0.16） and the average NRS rating （r＝−0.13, P＝0.13） were not statistically significant. A significant positive correlation was observed between rescue medication satisfaction and the medication’s perceived effectiveness （r＝0.79, P＜0.0001）. Patient satisfaction with their rescue medication can be routinely assessed without imposing a significant burden on the patient. A new assessment method incorporating rescue medication satisfaction and pain intensity measures could allow routine pain assessments to reflect both pain intensity and the effectiveness of opioid analgesics. This new assessment method is potentially preferable to self-reported pain intensity and can identify patients for whom treatment is a priority. It also facilitates rapid dose adjustments and reduces the side effects of overdose due to unnecessary increases in opioid analgesics

Renal shear wave velocity by acoustic radiation force impulse did not reflect advanced renal impairment

[Aim] Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end‐stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. [Methods] Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non‐CKD group), and 39 end‐stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. [Results] Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non‐CKD group and in the ESRD group, and no difference was found between the non‐CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non‐CKD group and the ESRD group, even when ages were matched and depth was adjusted. [Conclusion] Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages

Abnormalities in brain structure and behavior in GSK-3alpha mutant mice

<p>Abstract</p> <p>Background</p> <p>Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis.</p> <p>Results</p> <p>Similar to the previously described behaviours of GSK-3β^+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3α KO mice exhibited a deficit in fear conditioning, however memory formation as assessed by a passive avoidance test was normal, suggesting that the animals are sensitized for active avoidance of a highly aversive stimulus in the fear-conditioning paradigm. Changes in cerebellar structure and function were observed in mutant mice along with a significant decrease of the number and size of Purkinje cells.</p> <p>Conclusion</p> <p>Taken together, these data support a role for the GSK-3α gene in CNS functioning and possible involvement in the development of psychiatric disorders.</p

Impact of serum retinol-binding protein 4 levels on regulation of remnant-like particles triglyceride in type 2 diabetes mellitus

Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles triglyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7 ± 4.1 kg/m2, waist circumference (WC) 88.4 ± 10.7 cm, and HbA1c (NGSP) 7.2 ± 1.9 %). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG (r = 0.2544 and P = 0.0056), TG (r = 0.1852 and P = 0.041), RLP-TG/TG (r = 0.23765 and P = 0.0241), and age (r = - 0.2082 and P = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG (P = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM. © 2013 Naoto Yamaaki et al

Clinical Study Impact of Serum Retinol-Binding Protein 4 Levels on Regulation of Remnant-Like Particles Triglyceride in Type 2 Diabetes Mellitus

Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles triglyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7±4.1 kg/m 2 , waist circumference (WC) 88.4±10.7 cm, and HbA1c (NGSP) 7.2±1.9%). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG ( = 0.2544 and = 0.0056), TG ( = 0.1852 and = 0.041), RLP-TG/TG ( = 0.23765 and = 0.0241), and age ( = −0.2082 and = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG ( = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM

水耕栽培野菜の抗酸化活性とミネラル含有量の測定

Many kinds of minerals and antioxidants are contained in foods. However, correlation between antioxidant activities and mineral contents have not been discussed in detail. In this study, therefore, we examined antioxidant activities of two typical hydroponic lettuces (i.e., furyl lettuce and green leaf lettuce) and their mineral contents. Antioxidant activities were measured by using Trolox (6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid) as a typical water-soluble model compound of vitamin E. Mineral contents were measured simultaneously for multiple elements using Inductively Coupled Plasma- Atomic Emission Spectrometry (ICP-AES).As a result, antioxidant activities of both lettuces at the leaf part and green leaf lettuce were higher than those at the stem part. In the same manner, mineral contents of those contents at the leaf part were also larger than the stem part. Thus, we found for the first time appreciable correlations between the mineral contents and the antioxidants activities in such hydroponic vegetables