Family Dysfunction Differentially Affects Alcohol and Methamphetamine Dependence: A View from the Addiction Severity Index in Japan

We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas

Cellular function of osteocytes in normal and αklotho-deficient mice

During the last decade, osteocyte-derived factors i.e., sclerostin, dentin matrix protein-1, fibroblast growth factor 23 (FGF23) that reduces serum phosphate concentration by mediating FGF receptor 1c/αklotho in the kidney, have been highlighted for osteocytes’ fine-turned regulation on bone remodeling and phosphate homeostasis. Osteocytes are interconnected through gap junctions between their cytoplasmic processes, and thereby, build upon the functional syncytia, referred to as the osteocytic lacunar-canalicular system (OLCS). Osteocytes appear to communicate surrounding osteocytes and osteoblasts by means of two possible pathways of molecular transport throughout the OLCS : One is a passageway of their cytoplasmic processes, and the other is a pericellular space in the osteocytic canaliculi. The regularly-oriented OLCS in mature compact bone appears to efficiently serve for molecular transport, mechanosensing and targeted bone remodeling that would erase microdamages in bone. In a disrupted signaling state of FGF23/αklotho, serum concentration of phosphate would be markedly-elevated. Despite highly-elevated serum phosphate, αklotho -deficient mice revealed defective mineralization in bone matrix. OLCS in αklotho -deficient mice were irregularly-distributed and the connectivity of cytoplasmic processes of osteocytes was very poor, so that osteocytes did not seem to form functional syncytia. Therefore, osteocytes’function cooperated with other bone cells, rather than serum concentration of calcium/phosphate, and this seems to play a central role in maintaining bone mineralization. In this review, the biological function of the regularly-arranged OLCS in a normal state will be introduced, as well as dysfunctional osteocytes in αklotho-deficient state, using animal models

Predictive factors of efficacy of combination therapy with basal insulin and liraglutide in type 2 diabetes when switched from longstanding basal-bolus insulin: Association between the responses of β- and α-cells to GLP-1 stimulation and the glycaemic control at 6?months after switching therapy

Aims: To evaluate the glycaemic control of combination therapy with basal insulin and liraglutide, and to explore the factors predictive of efficacy in patients with type 2 diabetes when switched from longstanding basal-bolus insulin therapy. Methods: We studied 41 patients who switched from basal-bolus insulin therapy of more than 3 years to basal insulin/liraglutide combination therapy. Glycaemic control was evaluated at 6 months after switching therapy and used to subdivide the patients into good-responders (HbA1c <7.0% or 1.0% decrease) and poor-responders (the rest of participants). To evaluate the glucose-dependent insulin/glucagon responses without/with liraglutide, a 75-g oral glucose tolerance test (OGTT) was performed twice, before (1st-OGTT) and 2-days after (2nd-OGTT) liraglutide administration. Results: Twenty-eight patients (68.3%) were identified as good-responders. No differences were found in baseline characteristics including insulin/glucagon responses during 1st-OGTT between the groups. 2nd-OGTT revealed that paradoxical hyperglucagonemia were significantly improved in both groups, but significant increases in insulin secretory response were observed only in good-responders. Logistic regression analyses revealed that the improvement of the insulin-response during 2nd-OGTT compared to that during 1st-OGTT is associated with the good-responder. Conclusions: Enhancement of glucose-dependent insulin-response under liraglutide administration is a potential predictor of long-term glycaemic control after switching the therapies

Verification of the Addiction Severity Index Japanese Version (ASI-J) as a Treatment-Customization, Prediction, and Comparison Tool for Alcohol-Dependent Individuals

Objective: To demonstrate the usefulness of the Addiction Severity Index Japanese Version (ASI-J) in Japanese alcohol-dependent individuals. The ASI is a frequently used clinical and research instrument that measures severities in seven functional domains in people with substance abuse disorders. Methods: A total of 370 male inpatients with a history of alcohol dependence participated in the study. Forty-nine participants were excluded in the final analysis due to lack of reliability (i.e., patient misrepresentation or inability to understand). We used the ASI-J and a series of indexes that determined patient states during and post-treatment. Results: The correlations between ASI Composite Scores (CSs), which were calculated through a weighted formula and indicated the severity of each problem area, were significant but low in eight relations and not significant in 13 relations, indicating substantial independence of the problem areas. Significant differences were found in Family/Social CSs between abstinent and relapsed alcohol-dependent individuals. The questions of undesirable attitude were significantly related to the CSs of Employment, Drug use, Family/Social, and Psychiatric sections. Significant differences were observed in patient demographics, CS, and ASI Severity Rating (SR) and interviewer’s subjective scoring between alcohol-dependent individuals and drug abusers. CSs in Japanese alcohol-dependent individuals were generally similar to corresponding CSs in individuals from other countries, with the exception of The Netherlands. Conclusions: This study demonstrated that the ASI-J is useful for understanding individual profiles of problems for each patient and planning customized treatment. The ASI-J served as a predictive tool for relapse and compliance to treatment afterward and was shown to be useful as a comparison tool in clarifying similarities and differences between substance abuser groups

Impaired early-phase suppression of glucagon secretion after glucose load is associated with insulin requirement during pregnancy in gestational diabetes

Aims/Introduction: The role of glucagon abnormality has recently been reported in type 2 diabetes; however, its role in gestational diabetes mellitus (GDM) is still unknown. The glucose intolerance in GDM is heterogeneous, and not all patients require insulin treatment during pregnancy. Here, we investigated whether glucagon abnormality is associated with the requirement for insulin treatment during pregnancy. Materials and Methods: A total of 49 pregnant women diagnosed with GDM were enrolled. They underwent a 75-g oral glucose tolerance test during mid-gestation, and we measured their plasma glucagon levels (by a new sandwich enzyme-linked immunosorbent assay) at fasting (0 min), and at 30, 60 and 120 min after glucose load in addition to the levels of plasma glucose and serum insulin. All participants underwent another oral glucose tolerance test at postpartum. Results: Of the 49 patients, 15 required insulin treatment (Insulin group) and 34 were treated with diet therapy alone until delivery (Diet group). The early-phase glucagon secretion after glucose load, as determined by the changes in glucagon from the baseline to 30 min, was paradoxically augmented during mid-gestation in the Insulin group, but not in the Diet group. The impaired glucagon suppression during mid-gestation in the Insulin group was not associated with insulin secretory/sensitivity indexes studied, and was ameliorated postpartum, although the plasma glucose levels remained higher in the Insulin group versus the Diet group. Conclusions: Impaired early-phase suppression of glucagon could be associated with the requirement for insulin treatment during pregnancy in patients with GDM

Indian Monsoonal Variations During the Past 80 Kyr Recorded in NGHP-02 Hole 19B, Western Bay of Bengal: Implications From Chemical and Mineral Properties

金沢大学理工研究域地球社会基盤学系Detailed reconstruction of Indian summer monsoons is necessary to better understand the late Quaternary climate history of the Bay of Bengal and Indian peninsula. We established a chronostratigraphy for a sediment core from Hole 19B in the western Bay of Bengal, extending to approximately 80 kyr BP and examined major and trace element compositions and clay mineral components of the sediments. Higher δ 18 O values, lower TiO 2 contents, and weaker weathering in the sediment source area during marine isotope stages (MIS) 2 and 4 compared to MIS 1, 3, and 5 are explained by increased Indian summer monsoonal precipitation and river discharge around the western Bay of Bengal. Clay mineral and chemical components indicate a felsic sediment source, suggesting the Precambrian gneissic complex of the eastern Indian peninsula as the dominant sediment source at this site since 80 kyr. Trace element ratios (Cr/Th, Th/Sc, Th/Co, La/Cr, and Eu/Eu*) indicate increased sediment contributions from mafic rocks during MIS 2 and 4. We interpret these results as reflecting the changing influences of the eastern and western branches of the Indian summer monsoon and a greater decrease in rainfall in the eastern and northeastern parts of the Indian peninsula than in the western part during MIS 2 and 4. © 2018. American Geophysical Union. All Rights Reserved

Verification of the Addiction Severity Index Japanese Version (ASI-J) as a Treatment-Customization, Prediction, and Comparison Tool for Alcohol-Dependent Individuals

Objective: To demonstrate the usefulness of the Addiction Severity Index Japanese Version (ASI-J) in Japanese alcohol-dependent individuals. The ASI is a frequently used clinical and research instrument that measures severities in seven functional domains in people with substance abuse disorders. Methods: A total of 370 male inpatients with a history of alcohol dependence participated in the study. Forty-nine participants were excluded in the final analysis due to lack of reliability (i.e., patient misrepresentation or inability to understand). We used the ASI-J and a series of indexes that determined patient states during and post-treatment. Results: The correlations between ASI Composite Scores (CSs), which were calculated through a weighted formula and indicated the severity of each problem area, were significant but low in eight relations and not significant in 13 relations, indicating substantial independence of the problem areas. Significant differences were found in Family/Social CSs between abstinent and relapsed alcohol-dependent individuals. The questions of undesirable attitude were significantly related to the CSs of Employment, Drug use, Family/Social, and Psychiatric sections. Significant differences were observed in patient demographics, CS, and ASI Severity Rating (SR) and interviewer’s subjective scoring between alcohol-dependent individuals and drug abusers. CSs in Japanese alcohol-dependent individuals were generally similar to corresponding CSs in individuals from other countries, with the exception of The Netherlands. Conclusions: This study demonstrated that the ASI-J is useful for understanding individual profiles of problems for each patient and planning customized treatment. The ASI-J served as a predictive tool for relapse and compliance to treatment afterward and was shown to be useful as a comparison tool in clarifying similarities and differences between substance abuser groups

Potent Effects of Flavonoid Nobiletin on Amplitude, Period, and Phase of the Circadian Clock Rhythm in PER2::LUCIFERASE Mouse Embryonic Fibroblasts.

Flavonoids are natural polyphenols that are widely found in plants. The effects of flavonoids on obesity and numerous diseases such as cancer, diabetes, and Alzheimer's have been well studied. However, little is known about the relationships between flavonoids and the circadian clock. In this study, we show that continuous or transient application of flavonoids to the culture medium of embryonic fibroblasts from PER2::LUCIFERASE (PER2::LUC) mice induced various modifications in the circadian clock amplitude, period, and phase. Transient application of some of the tested flavonoids to cultured cells induced a phase delay of the PER2::LUC rhythm at the down slope phase. In addition, continuous application of the polymethoxy flavonoids nobiletin and tangeretin increased the amplitude and lengthened the period of the PER2::LUC rhythm. The nobiletin-induced phase delay was blocked by co-treatment with U0126, an ERK inhibitor. In summary, among the tested flavonoids, polymethoxy flavones increased the amplitude, lengthened the period, and delayed the phase of the PER2::LUC circadian rhythm. Therefore, foods that contain polymethoxy flavones may have beneficial effects on circadian rhythm disorders and jet lag

Association between Experience of Child Abuse and Severity of Drug Addiction Measured by the Addiction Severity Index among Japanese Drug-Dependent Patients

The aim of the present study was to clarify the association between child abuse experiences and drug addiction severity among Japanese drug-dependent patients using the Addiction Severity Index-Japanese version (ASI-J). One hundred and eleven inpatients and outpatients with drug dependence participated in the study. Some of the questions on the ASI-J asked about lifetime experiences of abuse. A higher percentage of female participants experienced child abuse compared with male participants. Male participants who experienced child abuse (MEA) had a significantly higher severity of drug use than men who did not experience it (MNEA). Female participants who experienced child abuse (FEA) had significantly more serious problems in family/social relationships than female participants who did not experience it (FNEA). Patients in the MEA group were arrested less frequently for drug charges, experienced more serious problems with their fathers, and experienced more severe anxiety in their lifetime compared with the MNEA group. The FEA group experienced more serious troubles with their sexual partners, close friends, and families and experienced more severe psychiatric problems in their lifetime compared with the FNEA group. These results suggest gender differences in the problems experienced by drug-dependent patients with child abuse experiences, and gender-specific interventions may be more effective in treating their drug dependence