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1.
Arch Gerontol Geriatr ; 124: 105453, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38704920

BACKGROUND: Physical frailty and cognitive decline are common issues in geriatrics within an aging society, yet the association between them remains controversial. This study aims to evaluate the association between physical frailty and cognitive decline among community-dwelling older Japanese women. METHODS: A prospective cohort study was conducted in an urban area of Tokyo, Japan, involving community-dwelling older adults 65 years or older. Physical frailty was evaluated using the Japanese version of the Cardiovascular Health Study criteria, consisting of five components: shrinking, weakness, exhaustion, slowness, and low activity. Participants were classified as robust, pre-frail, or frail based on the presence of one or more criteria. Cognitive decline was defined as at least a three-point decrease in the Mini-Mental State Examination score from baseline. The association between physical frailty and cognitive decline was examined using binomial logistic regression, adjusting for potential confounders. The analysis yielded multivariable odds ratios (ORs) and 95 % confidence intervals (CIs), with robust participants using as the reference group. RESULTS: A total of 2,122 individuals participated in the baseline survey, with 805 included in the analysis (mean age: 72.9 ± 5.1 years). At baseline, 363 participants were classified as pre-frail, while 32 were classified as frail. During the two-year follow-up period, 68 participants experienced cognitive decline. The multivariable OR (95 % CI) for frailty, using robust as the reference, was 3.50 (1.13, 10.80). Furthermore, a linear relationship was observed between physical frailty and cognitive decline. CONCLUSION: Among older Japanese women, there exists a dose-response relationship between physical frailty status and cognitive decline.

2.
Nutrition ; 124: 112453, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38669830

OBJECTIVE: This study aimed to develop a simpler approach for diagnosing sarcopenia by using only bioelectrical impedance vector analysis parameters. METHODS: The study design was a cross-sectional study. The research was conducted based on the Itabashi Longitudinal Study on Aging, a community-based cohort study, with data collected from the 2022 and 2023 surveys in Itabashi Ward, Tokyo, Japan. The development cohort consisted of 1146 participants from the 2022 survey, and the validation cohort included 656 participants from the 2023 survey. Both cohorts were comprised of community-dwelling older adults with similar inclusion criteria. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. The logistic model utilized height divided by impedance at 50 kHz and phase angle to establish a new regression equation to identify sarcopenia. Regression equations were generated for the development cohort and validated for the validation cohort. Discriminatory ability was assessed using the area under the receiver operating characteristic curve (AUC) for men and women. RESULTS: The prevalence of sarcopenia was 20.7% and 14.8% in the development and validation cohort, respectively. The AUC (95% confidence interval) of the logistic model in discriminating sarcopenia was 0.92 (0.88, 0.95) for men and 0.82 (0.78, 0.86) for women in the development cohort and 0.85 (0.78, 0.91) for men and 0.90 (0.86, 0.95) for women in the validation cohort. CONCLUSION: The study demonstrated that a simple formula using bioelectrical parameters at 50 kHz proved useful in identifying sarcopenia in the older adult population.

3.
Nutrients ; 16(8)2024 Apr 16.
Article En | MEDLINE | ID: mdl-38674872

Smartphone applications aimed at enhancing physical, cognitive, and social activities through mobile health (mHealth) technology are of increasing interest. Their feasibility and acceptability, alongside impacts on frailty phenotype scores and step counts among older adults with frailty, remain to be fully validated. This study presents a 13-week preliminary intervention trial assessing an mHealth app's feasibility in a cohort of 34 eligible older adults, including 5 frail and 29 pre-frail participants. The intervention entailed a 6-week course on app usage, followed by 7 weeks of observation, with four participants withdrawing early. Feasibility was determined by login and active use rates, with a target login rate of 60% or higher. Post-intervention, 100% session attendance and a median login rate of 88.4% were observed. Acceptability was high, with 73% affirming the app's health benefits. Notably, frailty scores and step counts improved post-intervention, underscoring the app's potential for supporting older adults with frailty.


Feasibility Studies , Frail Elderly , Frailty , Independent Living , Mobile Applications , Telemedicine , Humans , Pilot Projects , Aged , Male , Female , Aged, 80 and over , Telemedicine/methods , Smartphone , Patient Acceptance of Health Care/statistics & numerical data , Geriatric Assessment/methods
4.
Eur Geriatr Med ; 15(2): 571-577, 2024 Apr.
Article En | MEDLINE | ID: mdl-38214867

PURPOSE: This pilot study compared serum metabolites in participants with and without sarcopenia. METHODS: Metabolomic techniques were applied to identify serum metabolites and novel biomarkers specific to patients with sarcopenia. In accordance with AWGS2019 criteria, sarcopenia was defined as low muscle mass plus either low muscle strength/low physical function, and severe sarcopenia was defined as low muscle mass, low muscle strength, and low physical function all together. RESULTS: The sarcopenia group had higher hypoxanthine, galactose, and mannose levels but lower triethanolamine and homogentisic acid levels than the non-sarcopenia group. The severe sarcopenia group had lower levels of alpha-tocopherol than the mild and moderate sarcopenia groups. CONCLUSION: This study is the first to identify hypoxanthine as a potential biomarker for sarcopenia in humans and provides new insights into the pathophysiology of sarcopenia. Furthermore, the identified metabolites may be useful for the early detection of sarcopenia.


Sarcopenia , Humans , Sarcopenia/diagnosis , Pilot Projects , Muscle Strength/physiology , Biomarkers , Hypoxanthine
5.
Geriatr Gerontol Int ; 24 Suppl 1: 123-129, 2024 Mar.
Article En | MEDLINE | ID: mdl-38116709

AIM: Muscle mass and strength correlate with cognitive function; however, it remains unclear whether dynapenia (i.e., muscle weakness with preserved muscle mass) is relevant. This study aimed to explore whether dynapenia is associated with global cognitive function in community-dwelling older Japanese adults. METHODS: This cross-sectional study used data from the Integrated Research Initiative for Living Well with Dementia Cohort Study, which pooled data from five community-based geriatric cohorts. Dynapenia was defined as muscle weakness without muscle mass loss according to the Asian Working Group for Sarcopenia criteria. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). An ordered logistic regression analysis was conducted with dynapenia as the exposure and with cognitive decline stages, defined as an MMSE score of 27-30 for normal cognition, 24-26 for possible cognitive decline, and <24 for cognitive decline, as the outcome, stratified by sex and adjusted for age, muscle mass, education, alcohol consumption, smoking habits, living alone, and non-communicable diseases. RESULTS: We analyzed data for 3338 participants (2162 female) with preserved muscle mass. Of these, 449 (13.5%) had dynapenia, and 79 (2.4%) exhibited cognitive decline. Multivariate odds ratios (95% confidence interval) for cognitive decline among those with dynapenia, compared with those without dynapenia, were 1.51 (1.02-2.24) for males and 2.08 (1.51-2.86) for females. CONCLUSIONS: Muscle weakness is associated with cognitive decline, even in individuals with preserved muscle mass. Further studies are needed to better understand the association between muscle weakness and cognitive decline over time in order to develop dementia prevention strategies for those with dynapenia. Geriatr Gerontol Int 2024; 24: 123-129.


Cognitive Dysfunction , Dementia , Sarcopenia , Male , Humans , Female , Aged , Independent Living , Cohort Studies , Cross-Sectional Studies , Japan/epidemiology , Sarcopenia/complications , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Muscle Weakness/epidemiology , Cognitive Dysfunction/epidemiology , Dementia/epidemiology
6.
Front Public Health ; 11: 1148404, 2023.
Article En | MEDLINE | ID: mdl-37081953

Introduction: This study examined whether the association between sarcopenia severity and cognitive function differed according to sex and age in community-dwelling older adults in Japan. Methods: This is a cross-sectional study of older adults (age ≥ 65 years) consisting of five regional cohorts integrated as the Integrated Research Initiative for Living Well with Dementia (IRIDE) Cohort Study. Sarcopenia severity was determined based on the Asian Working Group for Sarcopenia 2019, which assessed grip strength, walking speed, and skeletal muscle mass index. Poor cognitive function was defined as a Mini-Mental State Examination score of ≤ 23. Odds ratios (ORs) and 95% confidence intervals (CIs) for poor cognitive function were calculated by sex and age group (65-74 and ≥75 years) using binomial logistic regression models, which were adjusted for age, educational attainment, history of non-communicable diseases, smoking and drinking habits, living alone, frequency of going outdoors, exercise habits, and depressive symptom. Results: Of the 8,180 participants, 6,426 (1,157 men aged 65-74 and 1,063 men aged 75 or older; 2,281 women aged 65-74 and 1,925 women aged 75 or older) were analyzed. The prevalence ratio of sarcopenia and severe sarcopenia were 309 (13.9%) and 92 (4.1%) among men and 559 (13.3%) and 166 (3.7%) among women, respectively. A total of 127 (5.8%) men and 161 (3.9%) women had a poor cognitive function. Setting non-sarcopenia as a reference, the adjusted ORs (95% CI) of poor cognitive function were 2.20 (1.54, 3.15) for sarcopenia and 3.56 (2.20, 5.71) for severe sarcopenia. A similar trend was observed in analyses stratified by sex and age, with linear associations (P for trend <0.05) in both categories. Furthermore, there was a significant interaction (P < 0.05) between sex and sarcopenia severity, indicating a stronger linear association of sarcopenia severity with poor cognitive function in women compared with men. Discussion and conclusion: Sarcopenia severity was linearly associated with poor cognitive function in adults aged ≥ 65 years, with a stronger association in women compared with men.


Independent Living , Sarcopenia , Male , Humans , Female , Aged , Cohort Studies , Japan/epidemiology , Cross-Sectional Studies , Sarcopenia/epidemiology , Cognition
7.
Int J Public Health ; 68: 1604647, 2023.
Article En | MEDLINE | ID: mdl-36911572

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has affected people's physical activity, sedentary behavior, and sleep. This study aimed to clarify the association between combining these factors, integrated as adherence to 24-h movement guidelines, and depressive status during the COVID-19 pandemic. Methods: At the end of October 2020, we sent self-administered questionnaires to 1,711 adults aged ≥18. We assessed physical activity, sedentary behavior, sleep duration, adherence to 24-h movement guidelines, depressive status, and confounding factors. Results: Of the 640 valid responses, 90 (14.1%) reported a depressive status. Multivariable odds ratios (95% confidence interval) of depressive status were 0.22 (0.07, 0.71) for all three recommendations of the 24-h movement guidelines and those who met none of the recommendations as reference. The number of guidelines met was associated with depressive status in a dose-response fashion. Conclusion: Meeting the 24-h movement guidelines was associated with a lower prevalence of depressive status during the COVID-19 pandemic. Adults should adhere to these guidelines to maintain their mental health during future quarantine life.


COVID-19 , Depression , Exercise , Adult , Humans , Cross-Sectional Studies , East Asian People , Exercise/psychology , Pandemics , Sleep/physiology , Depression/epidemiology
8.
Article En | MEDLINE | ID: mdl-36767135

PURPOSE: This study investigated the effect of online home-based resistance exercise training on fitness, depression, stress, and well-being. A total of 67 individuals participated. Of them, 28 participants (13 men and 15 women, average age: 45.1 ± 12.2 years) performed the same exercise training online (n = 17), using Zoom, or in person (n = 11) in 2020 (Study 1). In addition, 39 participants (15 men and 24 women; average age: 47.6 ± 10.8 years) performed eight weeks of online home-based resistance exercise training in 2021 (Study 2). The participants performed low-load resistance exercises twice a week for eight weeks (16 sessions). Muscle strength, thigh muscle cross-sectional area, fitness parameters, blood pressure, mental health (Center for Epidemiologic Studies-Depression Scale-CES-D; and Kessler Psychological Distress scale-K6), and well-being (Well-Being Index-WHO-5) were measured pre-and post-resistance training. In Study 1, eight weeks of online home-based resistance training improved CES-D (p = 0.003), and a similar tendency was observed in resistance training (RT) with the in-person group (p = 0.06). There was a significant improvement in CES-D symptoms after the online home-based resistance training in Study 2 (p = 0.009). However, there were no significant changes in the WHO-5 and K6. Our results suggest that online low-load resistance training improves fitness parameters and curbs depressive status.


Resistance Training , Male , Middle Aged , Humans , Female , Adult , Resistance Training/methods , Pilot Projects , Depression/therapy , Physical Fitness , Exercise/physiology , Muscle Strength/physiology
9.
J Epidemiol ; 32(12): 543-550, 2022 12 05.
Article En | MEDLINE | ID: mdl-33840650

BACKGROUND: Knee extensor muscle strength and cardiorespiratory fitness (CRF) are major components of physical fitness. Because the interactive association of knee extensor muscle strength and CRF with bone health remains unclear, we aimed to investigate such association in Japanese adults. METHODS: Altogether, 8,829 Japanese adults (3,731 men and 5,098 women) aged ≥45 years completed the maximum voluntary knee extension test, submaximal exercise test, medical examination, and a questionnaire on lifestyle habits. Using an osteo-sono assessment index, low bone stiffness tendency was defined as 80% under the young-adults mean. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after confounder adjustment. RESULTS: Overall, 542 men (14.5%) and 978 women (19.2%) had low bone stiffness tendency. We observed an inverse association between muscle strength and low bone stiffness tendency after adjustment for CRF in both sexes (P for linear trend <0.001). Compared with the lowest CRF, the multivariable ORs for low bone stiffness tendency in the highest CRF were 0.47 (95% CI, 0.36-0.62) for men and 1.05 (95% CI, 0.82-1.35) for post-menopausal women (P < 0.001 and P = 0.704, respectively). No interactive association between muscle strength and CRF for low bone stiffness tendency existed in both sexes and irrespective of menopausal status. CONCLUSION: Knee extensor muscle strength and CRF were associated additively, not synergistically, with bone health. Maintaining high levels of both physical fitness components may improve musculoskeletal health in the cohort. The relationship between physical fitness and bone status should be longitudinally investigated in the future.


Cardiorespiratory Fitness , Adult , Female , Humans , Male , Cardiorespiratory Fitness/physiology , Cross-Sectional Studies , Japan/epidemiology , Muscle Strength/physiology , Physical Fitness/physiology
10.
Connect Tissue Res ; 62(6): 689-697, 2021 11.
Article En | MEDLINE | ID: mdl-33334200

Purpose: In our previous study, we demonstrated that hyaluronan induces odontoblastic differentiation of dental pulp stem cells via interactions with CD44. However, it remains unclear whether CD44 expression by dental pulp stem cells is required for odontoblastic differentiation.Methods: We searched for a compound other than hyaluronan that induces odontoblastic differentiation of dental pulp stem cells and used western blotting to determine whether CD44 is involved in the induction of odontoblastic differentiation by the compound. We further validated the cell signaling details of the compound-induced expression of dentin sialophosphoprotein (DSPP), which is known as a marker of odontoblastic differentiation.Results: We investigated shikonin, which is one of the derivatives of naphthoquinone, the skeleton of vitamin K. Shikonin-induced expression of DSPP was inhibited by PI3K, AKT, and mTOR inhibitors. Additionally, shikonin-induced expression of DSPP was inhibited in dental pulp stem cells transfected with siRNA against CD44.Conclusions: Shikonin can stimulate dental pulp stem cells to undergo odontoblastic differentiation through a mechanism involving the AKT-mTOR signaling pathway and CD44. Although expression of CD44 is important for inducing odontoblastic differentiation of dental pulp stem cells, the relationship between the AKT-mTOR signaling pathway and CD44 expression, in the context of shikonin stimulation, has not yet been elucidated. This study suggests that shikonin may be useful for inducing odontoblastic differentiation of dental pulp stem cells, and that it may have clinical applications, including protection of the dental pulp.


Naphthoquinones , Odontoblasts , Cell Differentiation , Cells, Cultured , Dental Pulp/metabolism , Extracellular Matrix Proteins/metabolism , Hyaluronic Acid/metabolism , Naphthoquinones/metabolism , Naphthoquinones/pharmacology , Phosphoproteins/genetics , Phosphoproteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Stem Cells , TOR Serine-Threonine Kinases/metabolism
11.
Article En | MEDLINE | ID: mdl-31766623

Low cardiorespiratory fitness (CRF) and obesity are independent risk factors for dyslipidemia. We investigated the synergistic effects of CRF and obesity on the incidence of dyslipidemia among Japanese women. Of 7627 participants, 927 normolipidemic Japanese women completed a submaximal exercise test, medical examination, and a questionnaire on smoking and alcohol drinking. The incidence of dyslipidemia was defined as having at least one of the following: high-density lipoprotein cholesterol < 40 mg/dL, low-density lipoprotein cholesterol ≥ 140 mg/dL, fasting triglyceride ≥ 150 mg/dL, or physician-diagnosed dyslipidemia. Multivariable hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using a Cox proportional hazard regression model. During the follow-up period of ≤16 years (median 1 year), 196 (21.1%) women developed dyslipidemia. Compared with those in the body mass index (BMI)-specific (< or ≥25.0 kg/m2) lowest CRF tertile, the multivariable HRs for dyslipidemia in the highest CRF tertile were 1.36 (95% CI, 0.75-2.48) for women with BMI ≥ 25 kg/m2 and 0.70 (95% CI, 0.45-1.09) for those with BMI < 25 kg/m2 (p < 0.01 for interaction). These results suggest that CRF and BMI are interdependent and, together, they affect the incidence of dyslipidemia among Japanese women. CRF is inversely related to a lower incidence of dyslipidemia with low BMI.


Body Mass Index , Cardiorespiratory Fitness , Dyslipidemias/epidemiology , Adult , Aged , Cholesterol, HDL , Cholesterol, LDL , Cohort Studies , Exercise Test , Fasting , Female , Humans , Incidence , Japan/epidemiology , Middle Aged , Obesity , Physical Fitness , Proportional Hazards Models , Risk Factors , Smoking , Triglycerides
12.
Clin Exp Dent Res ; 4(5): 174-181, 2018 Oct.
Article En | MEDLINE | ID: mdl-30386639

The aim of this research was to investigate the value of autofluorescence imaging of oral cancer across different stages of tumor growth, to assist in detecting tumors. A xenograft mouse model was created with human oral squamous cell carcinoma cell line HSC-3 being subcutaneously inoculated into nude mice. Tumor imaging was performed with an autofluorescence imaging method (Illumiscan®) using the luminance ratio, which was defined as the luminance of the tumor site over the luminance of normal skin tissue normalized to a value of 1.0. This luminance ratio was continuously observed postinoculation. Tumor and normal skin tissues were harvested, and differences in the concentrations of flavin adenine dinucleotide and nicotinamide adenine dinucleotide were examined. The luminance ratio of the tumor sites was 0.85 ± 0.05, and there was no significant change in the ratio over time, even if the tumor proliferated and expanded. Furthermore, flavin adenine dinucleotide and nicotinamide adenine dinucleotide were significantly lower in tumor tissue than in normal skin tissue. A luminance ratio under 0.90 indicates a high possibility of tumor, irrespective of the tumor growth stage. However, this cutoff value was determined using a xenograft mouse model and therefore requires further validation before being used in clinical diagnosis.

13.
Clin Physiol Funct Imaging ; 38(3): 360-365, 2018 May.
Article En | MEDLINE | ID: mdl-28448687

To test the applicability of postexercise blood flow restriction (PEBFR) in practical training programmes, we investigated whether PEBFR enhances muscle hypertrophy induced by multiple-set high-load resistance exercise (RE). Seven men completed an eight-week RE programme for knee extensor muscles. Employing a within-subject design, one leg was subjected to RE + PEBFR, whereas contralateral leg to RE only. On each exercise session, participants performed three sets of unilateral knee extension exercise at approximately 70% of their one-repetition maximum for RE leg first, and then performed three sets for RE + PEBFR leg. Immediately after completion of the third set, the proximal portion of the RE + PEBFR leg was compressed with an air-pressure cuff for 5 min at a pressure ranging from 100 to 150 mmHg. If participants could perform 10 repetitions for three sets in two consecutive exercise sessions, the work load was increased by 5% at the next exercise session. Muscle thickness and strength of knee extensor muscles were measured before and after the eight-week training period and after the subsequent eight-week detraining period. There was a main effect of time but no condition × time interaction or main effect of condition for muscle thickness and strength. Both muscle thickness and strength increased after the training period independent of the condition. This result suggests that PEBFR would not be an effective training method at least in an early phase of adaptation to high-load resistance exercise.


Muscle Contraction , Quadriceps Muscle/blood supply , Resistance Training/methods , Tourniquets , Adaptation, Physiological , Adult , Exercise Tolerance , Humans , Hypertrophy , Lower Extremity , Male , Muscle Strength , Quadriceps Muscle/diagnostic imaging , Quadriceps Muscle/physiology , Regional Blood Flow , Time Factors , Young Adult
14.
Langmuir ; 33(36): 8906-8913, 2017 09 12.
Article En | MEDLINE | ID: mdl-28759233

The temperature and concentration dependencies of the crystallization of two small-molecular semiconductors were clarified by constructing quasi-phase diagrams at air/oil interfaces and in bulk oil phases. A quinoidal quaterthiophene derivative with four alkyl chains (QQT(CN)4) in 1,1,2,2-tetrachroloethane (TCE) and a thienoacene derivative with two alkyl chains (C8-BTBT) in o-dichlorobenzene were used. The apparent crystal nucleation temperature (Tn) and dissolution temperature (Td) of the molecules were determined based on optical microscopy examination in closed glass capillaries and open dishes during slow cooling and heating processes, respectively. Tn and Td were considered estimates of the critical temperatures for nuclear formation and crystal growth, respectively. The Tn values of QQT(CN)4 and C8-BTBT at the air/oil interfaces were higher than those in the bulk oil phases, whereas the Td values at the air/oil interfaces were almost the same as those in the bulk oil phases. These Gibbs adsorption phenomena were attributed to the solvophobic effect of the alkyl chain moieties. The temperature range between Tn and Td corresponds to suitable supercooling conditions for ideal crystal growth based on the suppression of nucleation. The Tn values at the water/oil and oil/glass interfaces did not shift compared with those of the bulk phases, indicating that adsorption did not occur at the hydrophilic interfaces. Promotion and inhibition of nuclear formation for crystal growth of the semiconductors were achieved at the air/oil and hydrophilic interfaces, respectively.

15.
J Pharm Sci ; 106(3): 792-802, 2017 03.
Article En | MEDLINE | ID: mdl-27989368

Single-walled carbon nanotubes (SWCNTs) attract great interest in biomedical fields including application for drug delivery system. In this study, we developed a novel gene delivery system employing SWCNTs associated with polycationic and amphiphilic H-(-Lys-Trp-Lys-Gly-)7-OH [(KWKG)7] peptides having pegylation. SWCNTs wrapped with (KWKG)7 formed a complex with plasmid DNA (pDNA) in aqueous solution based on polyionic interaction but later underwent aggregation. On the other hand, a complex of pDNA and SWCNT-(KWKG)7 modified with polyethylene glycol (PEG) chains of 12 units [SWCNT-(KWKG)7-(PEG)12] afforded good dispersion stability for 24 h even in a cell culture medium. The in vitro cellular uptake of SWCNT-(KWKG)7-(PEG)12/pDNA complex prepared with fluorescence-labeled pDNA was evaluated with fluorescent microscopic observation and flow cytometry. The uptake by A549 human lung adenocarcinoma epithelial cells increased along with the extent of pegylation, suggesting the importance of dispersion stability in addition to the cationic charge which facilitates ionic cellular interaction. The expression of pDNA encoding the monomeric Kusabira-Orange 2 fluorescent protein in the form of the SWCNT-(KWKG)7-(PEG)12/pDNA complex demonstrated remarkable enhancement of transfection depending also on the extent of pegylation and the N/P ratio. The potential of the SWCNT composite wrapped with polycationic and amphiphilic (KWKG)7 with pegylation as a carrier for gene delivery was demonstrated.


Gene Transfer Techniques , Nanotubes, Carbon/chemistry , Peptide Fragments/chemistry , Peptide Fragments/genetics , Polyethylene Glycols/chemistry , A549 Cells , Electrophoresis, Gel, Two-Dimensional/methods , Humans , Peptide Fragments/administration & dosage , Polyethylene Glycols/administration & dosage
16.
Biol Pharm Bull ; 39(10): 1687-1693, 2016.
Article En | MEDLINE | ID: mdl-27725447

A novel sustained release formulation of mitomycin C (MMC) was developed by employing single-walled carbon nanotubes (SWCNTs) wrapped by designed peptide with polyethylene glycol (PEG) modification (pegylation) as a nano-scale molecular platform. The amino groups of polycationic and amphiphilic H-(-Cys-Trp-Lys-Gly-)(-Lys-Trp-Lys-Gly-)6-OH [CWKG(KWKG)6] peptide associated with SWCNTs were modified using PEG with 12 units (PEG12) to improve the dispersion stability of the composite. Then thiol groups of peptide were conjugated with MMC using N-ε-maleimidocaproic acid (EMCA) as a linker via transformation of aziridine group of MMC. The obtained SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC composites particularly that with 13.6% PEG modification extent of amino groups, showed good dispersion stability both in water and in a cell culture medium for 24 h. The release of MMC from SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC was confirmed to follow first-order kinetics being accelerated by the pH increase in good agreement with the results observed for MMC-dextran conjugate with the same conjugation structure. The SWCNTs-CWKG(KWKG)6-(PEG)12 composite exhibited a considerably low cytotoxicity against cultured human lung adenocarcinoma epithelial cell line (A549). In contrast, SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC demonstrated delayed but relatively corresponding antitumor activity with free MMC at the same concentration. The results suggested the potential role of SWCNTs-CWKG(KWKG)6-(PEG)12 as a carrier for a controlled release drug delivery system (DDS).


Antibiotics, Antineoplastic/administration & dosage , Mitomycin/administration & dosage , Nanotubes, Carbon , Peptides/administration & dosage , Polyethylene Glycols/administration & dosage , A549 Cells , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Cell Survival/drug effects , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Humans , Mitomycin/chemistry , Mitomycin/pharmacology , Nanotubes, Carbon/chemistry , Peptides/chemistry , Peptides/pharmacology , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology
17.
J Pharm Sci ; 105(9): 2815-2824, 2016 09.
Article En | MEDLINE | ID: mdl-27179670

Single-walled carbon nanotubes (SWCNTs) attract great interest in biomedical applications including drug and gene delivery. In this study, we developed a novel delivery system using SWCNTs associated with designed polycationic and amphiphilic peptides. Wrapping of SWCNTs with H-(-Lys-Trp-Lys-Gly-)7-OH [(KWKG)7] resulted in stable dispersion in water, but the composite aggregated in the buffered solution. This dispersion instability was also evident in a cell culture medium with fetal bovine serum. To improve the aqueous dispersibility, the SWCNTs-(KWKG)7 composite was further modified with polyethylene glycol (PEG) at the lysine residues via amide bond formation and the highest modification extent of 13.3% of the amino groups which corresponded to 2 PEG chains in each peptide molecule was achieved with fluorescein isothiocyanate-labeled carboxyl-PEG12. The uptake of the SWCNTs composite by A549 human lung adenocarcinoma epithelial cells was evaluated by visual observation and fluorescence activated cell sorting analysis for SWCNTs wrapped with a mixture of (KWKG)7 with PEGylation and H-(-Cys-Trp-Lys-Gly-)-OH-(KWKG)6 [CWKG(KWKG)6] labeled with fluorescent boron-dipyrromethene tetramethylrhodamine and 7-fold higher uptake comparing with SWCNTs-peptide composite without PEGylation was obtained suggesting the importance of dispersibility in addition to a cationic charge. The superior potential of SWCNTs composites assisted by polycationic and amphiphilic peptides with PEGylation was thus demonstrated.


Drug Delivery Systems , Gene Transfer Techniques , Nanotubes, Carbon/chemistry , Peptides/chemistry , Peptides/toxicity , A549 Cells , Amides/chemistry , Cell Survival/drug effects , Cells, Cultured , Dipeptides , Excipients , Humans , Lysine/chemistry , Nanotubes, Carbon/toxicity , Oligopeptides , Polyethylene Glycols/chemistry
18.
J Endod ; 41(12): 2079-82, 2015 Dec.
Article En | MEDLINE | ID: mdl-26602450

Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis.


Jaw Neoplasms/diagnostic imaging , Neoplasms, Muscle Tissue/diagnostic imaging , Periapical Periodontitis/diagnosis , Adult , Cone-Beam Computed Tomography , Diagnosis, Differential , Humans , Jaw Neoplasms/pathology , Jaw Neoplasms/surgery , Magnetic Resonance Imaging , Male , Neoplasms, Muscle Tissue/pathology , Neoplasms, Muscle Tissue/surgery , Radiography, Panoramic
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