RESUMO
AIM: The efficacy of titratable fixed-ratio combination therapy by a combination preparation of insulin degludec and liraglutide (IDegLira) in Japanese patients with type 2 diabetes, focusing particularly on the change in Fibrosis-4 index (FIB-4), a noninvasive method for the evaluation of liver fibrosis, was investigated. METHODS: As the full analysis set, 113 patients were treated with IDegLira. The patients were categorized into two groups according to the absence (GLP-1RA-naïve group, n = 72) or presence (GLP-1RA-treated group, n = 41) of glucagon-like peptide-1 receptor agonist (GLP-1RA) use before starting IDegLira. The clinical parameters were retrospectively determined over 6 months. RESULTS: The glycated hemoglobin value was significantly reduced in both groups. The bodyweight significantly decreased from 67.4 ± 11.0 kg at baseline to 66.4 ± 11.6 kg at 6 months in the GLP-1RA-naïve group, although it slightly increased in the GLP-1RA-treated group. FIB-4 significantly decreased from 1.60 ± 0.84 at baseline to 1.49 ± 0.74 at 6 months in the GLP-1RA-naïve group. Although FIB-4 significantly increased in the GLP-1RA-treated group, it remained within the low-risk level for liver fibrosis. CONCLUSION: Fixed-ratio combination therapy using IDegLira for the treatment of type 2 diabetes is useful for glycemic control and weight management. In particular, IDegLira may be more effective for lowering FIB-4 than adding unused oral antidiabetic agents or increasing the dose of insulin in GLP-1RA-naïve patients.
Assuntos
Relações Mãe-Filho , Apego ao Objeto , Período Pós-Parto , Psicometria/normas , Adulto , Análise Fatorial , Feminino , Humanos , Lactente , Recém-Nascido , GravidezRESUMO
Introduction The dose of roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, required to treat anemia, the hemoglobin level and the rate of hemoglobin target achievement were retrospectively investigated in non-dialyzed chronic kidney disease (CKD) patients with and without type 2 diabetes. Methods As the full analysis set, 25 subjects (10 with diabetes and 15 without diabetes) were observed over six months among 44 non-dialyzed CKD patients who received roxadustat. The target hemoglobin level was set at 110-130 g/L. Results The comorbidities of diabetes and body weight at baseline were significantly associated with each dose of roxadustat at six months and the change in each dose of roxadustat from the initiation of roxadustat treatment. There was no significant difference in the amount of increase in the hemoglobin level (14±11 g/L vs. 15±8 g/L) and the rate of hemoglobin target achievement (70% vs. 67%) between patients with and without diabetes. Each dose of roxadustat gradually decreased in patients without diabetes, whereas it increased in those with diabetes. Each dose of roxadustat was significantly higher in patients with diabetes than in those without diabetes at 3 (60±21 mg vs. 42±14 mg) and 6 (61±22 mg vs. 41±14 mg) months after the initiation of roxadustat treatment. Conclusion Roxadustat is useful for the treatment of anemia in both CKD patients with and without diabetes. However, the dose required to achieve the target hemoglobin level may be higher in patients with diabetes than in those without diabetes.
RESUMO
AIMS: The efficacy of dulaglutide was assessed according to the pretreatments administered before the initiation of dulaglutide in patients with type 2 diabetes. METHODS: In total, 89 patients treated using dulaglutide (0.75 mg, once a weekly) were investigated. The subjects were divided into the three groups based on the form in which therapy was started: additional therapy (n = 35), switched from dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 32) and switched from daily glucagon-like peptide-1 receptor agonists (GLP-1 RAs, n = 30). The changes in medication adherence were determined in the daily GLP-1 RAs group using questionnaire surveys. RESULTS: The HbA1c values significantly decreased after the initiation of dulaglutide in all groups (additional therapy group, - 1.4 ± 1.6%; DPP-4 inhibitors group, - 1.2 ± 1.3%; and daily GLP-1 RAs group, - 0.5 ± 0.7%). Forty-six percent of the subjects in the daily GLP-1 RAs group reported that the incidence of forgetting injections of GLP-1 RA was decreased. The reduction of HbA1c was significantly greater in the subjects who reported a decrease in the incidence of forgetting injections (0.9 ± 0.9%) in comparison to those in which there was no change (0.1 ± 0.4%). CONCLUSIONS: Dulaglutide is considered effective in patients with type 2 diabetes and inadequate glycemic control, regardless of whether their pretreatment includes daily GLP-1 RA treatment.
RESUMO
PURPOSE: The Hospital Anxiety and Depression Scale (HADS) is a self-report questionnaire widely used to assess anxiety and depression. To the best of our knowledge, only four studies have examined the factor structure of the HADS for assessing pregnant women, with conflicting results. This study aimed to assess the factor structure and measurement invariance of the HADS for use with pregnant Japanese women. PARTICIPANTS AND METHODS: A total of 936 pregnant Japanese women completed the HADS questionnaire at three time points: the first and third trimester of pregnancy, and postpartum. We examined the factor structure of the HADS in Group 1 (n = 466) using exploratory factor analysis (EFA). We then compared the models identified in Group 1 with those from previous studies using confirmatory factor analysis (CFA) in Group 2 (n = 470). We performed multiple-group CFA for Group 2 to test the measurement invariance of the best-fit model across the three time points. RESULTS: The EFA for the Group 1 data at the three time points revealed a two-factor model. In the CFA, the two-factor model from Group 1 showed the best fit with the data at the three time points. In the multiple-group CFA for Group 2, we confirmed the configural and metric invariance of the two-factor model across the three time points. CONCLUSION: Our findings provide evidence for a two-factor structure and weak measurement invariance of the HADS in pregnant Japanese women during the peripartum period.
RESUMO
PURPOSE: Postpartum depression is a well-known risk factor, and postpartum anxiety and parity are potential risk factors, for mother-infant bonding disorder. However, few studies have focused on the relationships among these factors and mother-infant bonding. This cross-sectional study explored the associations between depression, anxiety and parity, and mother-infant bonding. MATERIALS AND METHODS: Japanese mothers, both primiparas and multiparas, completed the Mother-to-Infant Bonding Scale (MIBS) and the Hospital Anxiety and Depression Scale (HADS) one month after childbirth. We performed a stepwise multiple regression analysis with the forward selection method to assess the effects of HADS anxiety and depression scores and parity as independent variables on mother-infant bonding as the dependent variable. RESULTS: A total of 2379 Japanese mothers (1116 primiparas and 1263 multiparas) took part in the study. MIBS score (2.89 ± 2.68 vs 1.60 ± 2.11; p < 0.0001) was significantly higher in primiparas than in multiparas. HADS anxiety (6.55 ± 4.06 vs 4.63 ± 3.41; p < 0.0001) and depression (6.56 ± 3.43 vs 5.98 ± 3.20; p < 0.0001) scores were also significantly higher in primiparas than in multiparas. A stepwise multiple regression analysis with the forward selection method revealed that HADS depression and anxiety scores and parity were significantly associated with MIBS score (p = 0.003, 0.015 and 0.023). CONCLUSION: Depression, anxiety and primiparity were negatively associated with mother-infant bonding one month after childbirth.
RESUMO
AIMS: The changes in patients' satisfaction with the treatment, medication adherence and unused drugs before and after switching from daily DPP-4 inhibitors to once-weekly trelagliptin administration were prospectively investigated in patients with type 2 diabetes. METHODS: After excluding 46 patients who declined to switch from daily DPP-4 inhibitors, 79 subjects were included in the present study. The clinical parameters and results of questionnaire surveys regarding satisfaction with treatment as well as impressions of the amount of medicine/number of doses, medication adherence, and unused drug were examined at the baseline and 3â¯months after switching from daily DPP-4 inhibitors to trelagliptin in 75 patients with type 2 diabetes. RESULTS: Although the value of HbA1c did not change (7.0%⯱â¯0.5% to 7.0%⯱â¯0.6%), the scores representing satisfaction with the treatment (25.2⯱â¯6.4 to 26.4⯱â¯6.0), impression of the amount of medicine (-0.3⯱â¯1.0 to 0.3⯱â¯1.0) and number of doses (0.3⯱â¯1.0 to 0.8⯱â¯0.6), and medication adherence (0.8⯱â¯0.4 to 0.9⯱â¯0.3) as assessed by the questionnaire surveys were significantly improved after switching from DPP-4 inhibitors. The self-reported amount of unused drugs was significantly reduced after switching. CONCLUSIONS: Switching from daily DPP-4 inhibitors to once-weekly trelagliptin improved the satisfaction with the treatment, impression of the prescribed medicine and medication adherence in the type 2 diabetic patients who expresses a desire to reduce their prescription medicines. In such patients, improvements in the glycemic control and long-term prognosis might be expected through the reduction of unused drugs.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Uracila/análogos & derivados , Idoso , Diabetes Mellitus Tipo 2/patologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Estudos Prospectivos , Uracila/farmacologia , Uracila/uso terapêuticoRESUMO
Objective: We compared the clinical course of type 2 diabetic patients whose basal insulin preparations were replaced from insulin glargine (IGlar) 100 units/mL (U100) to IGlar biosimilar or IGlar 300 units/mL (U300). Methods: After propensity score matching, 34 patients whose basal insulin preparation was switched from IGlar U100 to IGlar biosimilar and 102 switched to IGlar U300 were observed for 6 months. Results: The HbA1c level and body weight did not change significantly after the replacement in the IGlar biosimilar or IGlar U300 groups. In the IGlar biosimilar group, the frequency of subjects who experienced hypoglycemia after the replacement (12%) was not different from before (12%). However, the frequency was significantly lower after the replacement (2%) than before (13%) in the IGlar U300 group. The change in the HbA1c level after the replacement showed a significant association with the HbA1c level at the baseline but not with the kind of IGlar. Hypoglycemia was frequently observed in subjects who had experienced hypoglycemia before the replacement. Conclusions: IGlar biosimilar and IGlar U300 induced similar HbA1c and body weight changes among type 2 diabetic patients. IGlar biosimilar is a suitable option for patients with a low risk for hypoglycemia.
RESUMO
Investigations of the validity of labeling regarding genetically modified (GM) products were conducted using polymerase chain reaction (PCR) methods for foreign-made processed foods made from corn and potato purchased in the Tokyo area and in the USA. Several kinds of GM crops were detected in 12 of 32 samples of processed corn samples. More than two GM events for which safety reviews have been completed in Japan were simultaneously detected in 10 samples. GM events MON810 and Bt11 were most frequently detected in the samples by qualitative PCR methods. MON810 was detected in 11 of the 12 samples, and Bt11 was detected in 6 of the 12 samples. In addition, Roundup Ready soy was detected in one of the 12 samples. On the other hand, CBH351, for which the safety assessment was withdrawn in Japan, was not detected in any of the 12 samples. A trial quantitative analysis was performed on six of the GM maize qualitatively positive samples. The estimated amounts of GM maize in these samples ranged from 0.2 to 2.8%, except for one sample, which contained 24.1%. For this sample, the total amount found by event-specific quantitative analysis was 23.8%. Additionally, Roundup Ready soy was detected in one sample of 21 potato-processed foods, although GM potatoes were not detected in any sample.
Assuntos
Alimentos Geneticamente Modificados , Solanum tuberosum/genética , Zea mays/genética , DNA de Plantas/análise , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase/métodos , Glycine max/genética , Tóquio , Estados UnidosRESUMO
Clostridium stercorarium Xyn10B is a modular enzyme comprising two family-22 carbohydrate-binding modules (CBMs), a family-10 catalytic module of glycoside hydrolases, a family-9 CBM, and two S-layer homologous modules consecutively from the N-terminus. To investigate the role of the family-22 CBMs, truncated proteins were constructed: a recombinant catalytic module polypeptide (rCD), a CBM polypeptide composed of two family-22 CBMs (rCBM) and a polypeptide composed of the family-22 CBMs and the catalytic module (rCBM-CD). We found that rCBM-CD was highly active toward beta-1,3-1,4-glucan; however, rCD was negligibly active toward the same substrate. The V(max)/K(m) value of rCBM-CD for beta-1,3-1,4-glucan was 7.8 times larger than that for oat-spelt xylan, indicating that rCBM-CD should be specified as a beta-1,3-1,4-glucanase rather than a xylanase despite the fact that family-10 catalytic modules are well-known xylanase modules. These results indicate that the family-22 CBMs in rCBM-CD are essential for hydrolysis of beta-1,3-1,4-glucan.
Assuntos
Clostridium/enzimologia , Xilosidases/metabolismo , beta-Glucanas , Estabilidade Enzimática , Glucanos/metabolismo , Hidrólise , Substâncias Macromoleculares , Polissacarídeos/metabolismo , Ligação Proteica , Subunidades Proteicas , Especificidade por Substrato , TemperaturaRESUMO
A simple method using Florisil cartridges was developed for the determination of dimethylformamide (DMF) in sucrose esters of fatty acids present in sugar esters (SuE) and sucrose acetate isobutyrate (SAIB) used as food additives. SuE was dissolved in acetone and loaded on a Florisil cartridge. SAIB was dissolved in hexane, loaded on a Florisil cartridge and washed with 10% acetone in hexane. The columns were eluted with acetone and DMF in the eluates was determined by GC with an FID detector. Recoveries of DMF at the level of 0.5-100 micrograms/g were 93.3-102.6%. The determination limit was 0.5 microgram/g.
Assuntos
Dimetilformamida/análise , Ácidos Graxos/análise , Aditivos Alimentares/análise , Cromatografia Gasosa , Ésteres/análise , Silicatos de MagnésioRESUMO
Genetially modified organisms (GMOs) were explored in food samples obtained from November 2000 to March 2003 in the Tokyo area by using PCR and real-time PCR techniques. The existence of Roundup Ready Soybean (RRS) was surveyed in processed foods derived from soybeans, such as tofu, boiled soybean, kinako, nama-age, abura-age, natto, miso, soymilk and yuba. RRS was detected in 3 of 37 tofu, 2 of 3 nama-age, 2 of 3 yuba and 3 of 3 abura-age samples. The CBH351 in 70 processed corn foods, NewLeaf Plus and NewLeaf Y in 50 processed potato foods, and 55-1 papaya in 16 papayas were surveyed. These GMOs were not detected among the samples. Qualitative and quantitative analyses of RRS and genetically modified (GM) corn were performed in soybean, corn and semi-processed corn products such as corn meal, corn flour and corn grits. RRS was detected in 42 of 178 soybean samples, and the amount of RRS in RRS-positive samples was determined. The content was in the range of 0.1-1.4% in identity-preserved soybeans (non-GMO), and 49.8-78.8% in non-segregated soybeans. On the other hand, GM corns were detected in 8 of 26 samples. The amount of GM corn in GM corn-positive samples was in the range of 0.1-2.0%.
Assuntos
Análise de Alimentos/métodos , Alimentos Geneticamente Modificados , Glycine max/genética , Plantas Geneticamente Modificadas , Alimentos de Soja/análise , Carica/genética , Reação em Cadeia da Polimerase/métodos , Solanum tuberosum/genética , Zea mays/genéticaRESUMO
To examine the possibility of module interaction in the thermal unfolding of different modular architectures, four truncated proteins were constructed from Clostridium stercorarium Xyn10B: a family 10 catalytic module (CM10), a polypeptide compound of one family 22 carbohydrate-binding module (CBM22-2) and the catalytic module (CBM22-CM10), two family 22 CBMs and the catalytic module (2CBM22-CM10), and only two family 22 CBMs (2CBM22). Thermal unfolding of four proteins were observed by differential scanning calorimetry. CM10 was unfolded reversibly and denatured as one component. The unfolding of protein CBM22-CM10 comprising CBM22-2 connected with CM10 was irreversible, and can be assumed to be one-component denaturation. Protein 2CBM22, with two CBM22s in tandem, unfolded as two independent modules. However, 2CBM22-CM10, with two CBM22s, unfolded as two and not the expected three separate components. These findings constitute the first reported case in which differences in thermal unfolding units and mechanisms were derived from differences in the modular architectures of proteins.
Assuntos
Clostridium/enzimologia , Endo-1,4-beta-Xilanases/metabolismo , Desnaturação Proteica , Varredura Diferencial de Calorimetria , Metabolismo dos Carboidratos , Catálise , Endo-1,4-beta-Xilanases/química , Endo-1,4-beta-Xilanases/genética , Concentração de Íons de Hidrogênio , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Temperatura , TermodinâmicaRESUMO
A family 22 carbohydrate-binding module (CBM22) from Clostridium stercorarium Xylanase10B raised the optimum temperature of the xylanase, but in the remaining activity of heating test, apparently the catalytic module alone showed higher remaining activity. Differential scanning calorimetry showed that CBM22 conferred resistance to thermal unfolding of the enzyme and prevented the enzyme from refolding after thermal unfolding.
Assuntos
Metabolismo dos Carboidratos , Endo-1,4-beta-Xilanases/metabolismo , Sequência de Bases , Varredura Diferencial de Calorimetria , Catálise , Primers do DNA , Estabilidade EnzimáticaRESUMO
Clostridium josui xylanase Xyn10A is a modular enzyme comprising two family-22 carbohydrate-binding modules (CBMs), a family-10 catalytic module (CM), a family-9 CBM, and two S-layer homologous modules, consecutively from the N-terminus. To study the functions of the family-22 CBMs, truncated derivatives of Xyn10A were constructed: a recombinant CM polypeptide (rCM), a family-22 CBM polypeptide (rCBM), and a polypeptide composed of the family-22 CBMs and CM (rCBM-CM). Recombinant proteins were characterized by enzyme and binding assays. rCBM-CM showed the highest activity toward xylan and weak activity toward some polysaccharides such as barley beta-glucan and carboxymethyl-cellulose. Although rCBM showed an affinity for insoluble and soluble xylan as well as barley beta-glucan and Avicel in qualitative binding assays, removal of the CBMs negligibly affected the catalytic activity and thermostability of the CM.
Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Clostridium/genética , Clostridium/metabolismo , Catálise , Celulose/metabolismo , Escherichia coli/metabolismo , Hordeum/química , Plasmídeos/genética , Polissacarídeos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Termodinâmica , beta-Glucanas/metabolismoRESUMO
Clostridium stercorarium Xyn10B having hydrolytic activities on xylan and beta-1,3-1,4-glucan is a modular enzyme composed of two family-22 carbohydrate-binding modules (CBMs), a family-10 catalytic module of the glycoside hydrolases, a family-9 CBM, and two S-layer homologous modules, consecutively from the N-terminus. We investigated the function of family-9 and family-22 CBMs in a modular enzyme by comparing the enzymatic properties of a truncated enzyme composed of two family-22 CBMs and the catalytic module (rCBM22-CM), an enzyme composed of the catalytic module and family-9 CBM (rCM-CBM9), an enzyme composed of two family-22 CBMs, the catalytic module, and family-9 CBM (rCBM22-CM-CBM9), and the catalytic module polypeptide (rCM). Although the addition of family-9 CBM to rCM and rCBM22-CM did not significantly change catalytic activity toward xylan and beta-1,3-1,4-glucan, the addition of family-22 CBM to rCM and rCM-CBM9 drastically enhanced catalytic activity toward xylan and especially beta-1,3-1,4-glucan. Furthermore, the addition of family-22 CBM to rCM and rCM-CBM9 shifted the optimum temperature from 65 degrees C to 75 degrees C, but that of family-9 CBM to rCM and rCBM22-CM did not affect the optimum temperature. These facts suggest that the enzyme properties of Xyn10B were mainly dependent on the presence of the family-22 CBMs but not family-9 CBM.
Assuntos
Metabolismo dos Carboidratos , Clostridium/enzimologia , Endo-1,4-beta-Xilanases/metabolismo , Glicosídeo Hidrolases/metabolismo , Sequência de Bases , Primers do DNA , Eletroforese em Gel de Poliacrilamida , Endo-1,4-beta-Xilanases/química , Glicosídeo Hidrolases/química , Plasmídeos , Especificidade por SubstratoRESUMO
Clostridium thermocellum CelJ is a modular enzyme containing a family 30 carbohydrate-binding module (CBM) and a family 9 catalytic module at its N-terminal moiety. To investigate the functions of the CBM and the catalytic module, truncated derivatives of CelJ were constructed and characterized. Isothermal titration calorimetric studies showed that the association constants (K(a)) of the CBM polypeptide (CBM30) for the binding of cellopentaose and cellohexaose were 1.2 x 10(4) and 6.4 x 10(4) M(-1), respectively, and that the binding of CBM30 to these ligands is enthalpically driven. Qualitative analyses showed that CBM30 had strong affinity for cellulose and beta-1,3-1,4-mixed glucan such as barley beta-glucan and lichenan. Analyses of the hydrolytic action of the enzyme comprising the CBM and the catalytic module showed that the enzyme is a processive endoglucanse with strong activity towards carboxymethylcellulose, barley beta-glucan and lichenan. By contrast, the catalytic module polypeptide devoid of the CBM showed negligible activity toward these substrates. These observations suggest that the CBM is extremely important not only because it mediates the binding of the enzyme to the substrates but also because it participates in the catalytic function of the enzyme or contributes to maintaining the correct tertiary structure of the family 9 catalytic module for expressing enzyme activity.