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1.
Sci Rep ; 14(1): 12173, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806551

RESUMO

Carotenoids play a role in preventing and impeding the progression of atherosclerotic cardiovascular diseases (ASCVDs) through their anti-oxidative effects. This study evaluated associations between ASCVD risk and skin carotenoid (SC) levels, reflecting dietary carotenoid intake. Participants' ASCVD risk was assessed using the Hisayama ASCVD risk prediction model, and SC levels were measured through a reflection spectroscope (Veggie Meter). The associations between high ASCVD risk and SC levels were analyzed using logistic regression analysis and a restricted cubic spline (RCS) model. A total of 1130 men and women (mean age: 56 years) from participants who underwent a health examination in Seirei Center for Health Promotion and Prevention Medicine in 2019 and 2022 were analyzed. Of these, 4.6% had moderate or high ASCVD risk. Mean SC values were 236, 315, 376, 447, and 606 in quintile Q1 to Q5, respectively. The adjusted odds ratios (95% confidence intervals) of SC quintile for moderate- or high-risk ASCVD was 0.24 (0.12-0.51) in Q5 (495 ≤), 0.42 (0.23-0.77) in Q4, 0.50 (0.29-0.88) in Q3, and 0.68 (0.41-1.12) in Q2 compared to Q1 (< 281). High SC values continuously showed non-linear inverse association with moderate- or high-risk for ASCVD in Japanese adults. Non-invasive SC measurements may be a good indicator for recommending carotenoids to prevent cardiovascular disease.


Assuntos
Aterosclerose , Carotenoides , Pele , Humanos , Feminino , Masculino , Carotenoides/metabolismo , Carotenoides/análise , Pessoa de Meia-Idade , Estudos Transversais , Japão/epidemiologia , Pele/metabolismo , Pele/química , Aterosclerose/epidemiologia , Idoso , Adulto , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Análise Espectral/métodos , População do Leste Asiático
2.
Nat Commun ; 14(1): 8158, 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071217

RESUMO

Insulin secretion from pancreatic ß cells is regulated by multiple stimuli, including nutrients, hormones, neuronal inputs, and local signalling. Amino acids modulate insulin secretion via amino acid transporters expressed on ß cells. The granin protein VGF has dual roles in ß cells: regulating secretory granule formation and functioning as a multiple peptide precursor. A VGF-derived peptide, neuroendocrine regulatory peptide-4 (NERP-4), increases Ca2+ influx in the pancreata of transgenic mice expressing apoaequorin, a Ca2+-induced bioluminescent protein complex. NERP-4 enhances glucose-stimulated insulin secretion from isolated human and mouse islets and ß-cell-derived MIN6-K8 cells. NERP-4 administration reverses the impairment of ß-cell maintenance and function in db/db mice by enhancing mitochondrial function and reducing metabolic stress. NERP-4 acts on sodium-coupled neutral amino acid transporter 2 (SNAT2), thereby increasing glutamine, alanine, and proline uptake into ß cells and stimulating insulin secretion. SNAT2 deletion and inhibition abolish the protective effects of NERP-4 on ß-cell maintenance. These findings demonstrate a novel autocrine mechanism of ß-cell maintenance and function that is mediated by the peptide-amino acid transporter axis.


Assuntos
Sistema A de Transporte de Aminoácidos , Células Secretoras de Insulina , Proteínas do Tecido Nervoso , Animais , Humanos , Camundongos , Glucose/metabolismo , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Sistemas Neurossecretores/metabolismo , Peptídeos/metabolismo , Sistema A de Transporte de Aminoácidos/metabolismo
3.
Intern Med ; 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38104990

RESUMO

Objective The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and hospitals in Japan have been forced to respond to the situation. This study evaluated the broad-spectrum antimicrobial use before and during the COVID-19 pandemic in an acute tertiary-care hospital. Methods This single-center, retrospective study was conducted between January 2019 and June 2021. Patients We reviewed patients treated with three broad-spectrum antipseudomonal agents: carbapenems, tazobactam/piperacillin, and cefepime. Monthly aggregated hospital antimicrobial consumption was measured as days of therapy (DOTs) per 1,000 patient-days, and the monthly incidences of Clostridioides difficile infection (CDI), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenemase-producing Enterobacteriaceae (CPE) were recorded. Results The median monthly carbapenem-DOTs during the pre-pandemic and pandemic era were 8.4 and 8.2 per 1,000 patient-days, respectively. A time-series analysis showed non-significant changes in the level between periods (coefficients: 2.08; 95% confidence interval [CI]: -2.9 to 7.0; p=0.44). No change in the trend of monthly carbapenem-DOTs was observed after intervention. No post-intervention changes in the incidence of MRPA or CPE were observed; however, the trend in the incidence of CDI per 1,000 patient-days significantly differed between the two periods (coefficient: -0.04; 95% CI: -0.07, 0.00; p=0.01), and a downward trend was observed in the monthly CDI incidence during the COVID-19 period. Conclusion The consumption of broad intravenous antimicrobial agents has not changed significantly during the pandemic. We need to maintain the quality of medical care, including antimicrobial stewardship, even in specialized resource-limited facilities during a pandemic.

4.
Medicine (Baltimore) ; 102(1): e32628, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607851

RESUMO

Limited data are available regarding part-time infectious disease consultations (IDCs) and their importance in tertiary care teaching hospitals in Japan. This is a retrospective review of IDCs from June 2016 to March 2021 and describes IDC services provided by part-time infectious disease specialists once a week for 4 hours, and their impact on the quality of medical care, including antimicrobial stewardship. Data, such as the requesting department, requesting reasons, and final diagnoses, were analyzed. In April 2018, part-time infectious disease specialists launched consultation services and attended an antimicrobial stewardship team conference. Meropenem, tazobactam/piperacillin, and cefepime monthly days of therapy (DOT) were calculated to assess the effect of each intervention; a pre-post analysis was conducted using the Kruskal-Wallis test. Additional quality improvement (QI) projects related to infectious diseases were implemented. There were 237 IDCs during the study period. Consultations were mostly requested by the General Internal Medicine, Emergency Medicine, and Cardiology departments. The most common diagnoses were bone/joint, respiratory, and genitourinary infections. Infectious disease services, even on a part-time basis, achieve good outcomes in patient management, antimicrobial stewardship, and QI projects. DOT/1000 patient-days were reduced for meropenem and cefepime, while it increased for tazobactam/piperacillin. The DOT/1000 patient-days for the 3-antipseudomonal agents significantly decreased during this period. After implementing the QI tetanus vaccination project in the Emergency Room, the number of tetanus toxoid vaccinations per month increased.


Assuntos
Antibacterianos , Doenças Transmissíveis , Humanos , Antibacterianos/uso terapêutico , Cefepima , Meropeném , Centros de Atenção Terciária , Estudos Retrospectivos , População do Leste Asiático , Encaminhamento e Consulta , Doenças Transmissíveis/diagnóstico , Combinação Piperacilina e Tazobactam
5.
Sci Rep ; 12(1): 15135, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071095

RESUMO

Antibiotic stewardship programs reduce antibiotic use without negative clinical outcomes. However, epidemiological data describing the relationship between implementing antimicrobial stewardship and candidemia incidence are scarce. This study aimed to evaluate the effect of antibiotic stewardship on the incidence of hospital acquired candidemia. We conducted a retrospective study from April 2017 to September 2020. We reviewed patients that were treated with three broad-spectrum antipseudomonal agents: carbapenem, tazobactam/piperacillin, and cefepime. Monthly aggregated hospital antimicrobial consumption was measured as days of therapy (DOTs) per 1000 patient-days, and the monthly incidence of hospital acquired candidemia was recorded. The median monthly carbapenem-DOTs during pre-intervention and intervention were 28.4 and 10.0, respectively. Time-series analysis showed significant level changes after intervention: - 10.0 DOTs (p = 0.02). There was a downward trend in the monthly carbapenem-DOTs after intervention. The median hospital-acquired candidemia incidence was 0.17 and 0.08 per 1000 patient-days during pre-intervention and intervention periods, respectively. Time-series analysis showed a significant level change after intervention (- 0.16 per 1000 patient-days; p = 0.048). The trend in the incidence of hospital-acquired candidemia did not significantly change between pre-intervention and intervention. Decreased broad-spectrum antibiotic use (particularly carbapenem) by our antimicrobial stewardship term may reduce hospital-acquired candidemia incidences.


Assuntos
Gestão de Antimicrobianos , Candidemia , Antibacterianos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Carbapenêmicos/uso terapêutico , Hospitais , Humanos , Estudos Retrospectivos
6.
Antioxidants (Basel) ; 11(8)2022 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-36009289

RESUMO

The antioxidant and anti-inflammatory effects of carotenoid have been determined to aid in the prevention of a wide range of oxidative disorders, arteriosclerosis, obesity, and various types of cancers. In order to keep high carotenoid levels in the body, much of the vegetable and fruit (V/F) intake is mandatory. However, the actual intake of V/F is not enough in many countries. The aim of this study was to assess whether brief dietary education using the Veggie Meter (VM) that could measure skin carotenoid (SC) levels could induce the increase in carotenoid levels via V/F intake. Two hundred and sixty-one elementary and junior high school students (ages 7−14 years old) received brief educational session and SC evaluation by VM, and the changes in SC levels were examined after 6 months. The baseline VM scores ranged from 131 to 825, and the average significantly increased from 400.0 ± 124.7 (standard deviation) to 447.4 ± 140.4 at Month 6 (p < 0.0001). The percentage of increase at month 6 was negatively correlated with the baseline values (r = −0.36, p < 0.0001). This finding implies that subjects who became aware of their inferiority tended to make a significant effort to change their behavior. The multivariate logistic regression analysis demonstrated that subjects taking much of green and yellow vegetables, drinking vegetable/tomato juice, and eating any fruit had higher VM scores than the average value. In conclusion, the educational approach using VM was supposed to be an effective method of raising awareness of the V/F shortage and increasing V/F intake that could indue the increase in SC levels.

7.
J Infect Chemother ; 28(10): 1424-1426, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35724914

RESUMO

Staphylococcus pettenkoferi is a coagulase-negative staphylococci (CoNS) species first isolated in 2002. Human infections caused by S. pettenkoferi are rare. We herein report three cases of S. pettenkoferi bacteremia in a tertiary care hospital in Japan. Staphylococcus pettenkoferi can be a causative pathogen of catheter related blood stream infection including complicated infection, and unknown source of bacteremia. All of the patients presented with fever and shaking chills, and good clinical outcome. Further research is needed to determine the role of this organism as a pathogen and frequency.


Assuntos
Bacteriemia , Infecções Estafilocócicas , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Coagulase , Humanos , Japão , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus , Centros de Atenção Terciária
8.
Eur J Pharmacol ; 892: 173754, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33248114

RESUMO

Fibrotic scarring is an important prognostic factor of acute respiratory distress syndrome (ARDS). There are currently no antifibrotic drugs or other therapeutic agents for ARDS. Lysyl oxidase-like 2 (LOXL2), an amine oxidase, contributes to fibrotic scarring by facilitating collagen cross-linking. Recent clinical trials revealed that a monoclonal inhibitory antibody against LOXL2 failed to show benefit over placebo in patients with fibrotic disorders involving the lungs. These clinical results raise the possibility that targeting the extracellular enzymic activity of LOXL2 is not in itself sufficient to prevent fibrotic scarring. We investigated the role of LOXL2 in the pathogenesis of ARDS in vivo, in vitro, and in samples from patients with ARDS. After lung injury, LOXL2 was unevenly expressed in the nuclei of lung fibroblasts and myofibroblasts in the fibrotic phase. Nuclear LOXL2 expression was upregulated in lung fibroblasts after transforming growth factor-beta1 (TGF-ß1)-treatment. LOXL2 silencing abrogated the TGF-ß1-induced expression of a myofibrogenic-progenitor marker, the appearance of proto-myofibroblasts, and the evolution of differentiated myofibroblasts in lung fibroblasts. Nuclear upregulation of Snail was evident in myofibroblasts during the fibrotic phase after lung injury. We detected high levels of LOXL2 protein in the lungs of ARDS patients, specifically during the proliferative and fibrotic phases. Our results highlight nuclear LOXL2 in fibroblasts as a primary causative driver of cell-fate decision toward myofibroblasts and of the progression of fibrotic scarring. A nuclear-LOXL2-targeted agent could be a promising therapeutic strategy against fibrotic disorders including ARDS.


Assuntos
Aminoácido Oxirredutases/metabolismo , Fibroblastos/enzimologia , Pulmão/enzimologia , Fibrose Pulmonar/enzimologia , Síndrome do Desconforto Respiratório/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoácido Oxirredutases/genética , Animais , Bleomicina , Diferenciação Celular , Linhagem Celular , Núcleo Celular/enzimologia , Núcleo Celular/patologia , Proliferação de Células , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Fibroblastos/patologia , Humanos , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miofibroblastos/enzimologia , Miofibroblastos/patologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/patologia , Estudos Retrospectivos , Fatores de Transcrição da Família Snail/metabolismo
9.
Nutrients ; 11(12)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31835384

RESUMO

"Autistic traits" include a wide range of severity levels. They are often subclinical, and widely distributed in the general population. It is possible that food selectivity due to hyper- or hypo-reactivity to smell or texture, an autistic feature, may result in inadequate nutrient intakes even among non-clinical adults with autistic traits. However, dietary intake of adults with autistic traits has not been elucidated. This study aimed to investigate an association between dietary intake and autistic traits. We cross-sectionally analyzed data of 1440 men and 613 women extracted from the Eating Habit and Well-Being study. Autistic traits were assessed using the Japanese version of the Subthreshold Autism Trait Questionnaire (SATQ), and dietary intake was assessed using a validated food frequency questionnaire. Iron and vitamin B12 intakes were marginally and inversely associated with the SATQ score in men. The SATQ score in women was positively associated with carbohydrate intake, but had an inverse association with protein, mineral, vitamin, and dietary fiber intakes. Low intakes of seaweed, fish and shellfish, and vegetables were observed in participants with severe autistic traits. Associations of autistic traits with food selectivity and low nutrient intakes should be further investigated to promote a new dietary strategy in the general population.


Assuntos
Transtorno Autístico , Dieta , Comportamento Alimentar , Estado Nutricional , Adulto , Povo Asiático , Coleta de Dados , Ingestão de Energia , Feminino , Humanos , Japão , Masculino , Minerais , Alimentos Marinhos , Alga Marinha , Inquéritos e Questionários , Verduras , Vitaminas/administração & dosagem
10.
Nutrients ; 11(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991676

RESUMO

Epidemiological studies have suggested that there is an association between diet and mental health. The aim of this study was to investigate the association between the intake of six minerals and mental disorders in a cross-sectional study. We used data from the Eating Habit and Well-being study in Japanese workers. Kessler's six-item psychological distress scale was used to detect mental disorders, with a cut-off score of 12/13, and a validated food frequency questionnaire was used to estimate dietary mineral intake. A total of 2089 participants with no history of depression were included. The prevalence of mental disorders was 6.9%. The lowest quartiles of zinc, copper, and manganese intakes were associated with mental disorders, whereas the lowest quartiles of calcium, magnesium, and iron intake were not associated with mental disorders. Combination analysis of high (≥median) or low (

Assuntos
Ansiedade/etiologia , Cobre/deficiência , Depressão/etiologia , Dieta , Comportamento Alimentar , Manganês/deficiência , Zinco/deficiência , Adulto , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/etiologia , Estudos Transversais , Deficiências Nutricionais/complicações , Depressão/epidemiologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Inquéritos sobre Dietas , Ingestão de Energia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Razão de Chances , Prevalência
11.
J Nutr Sci ; 7: e29, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30459946

RESUMO

Data on the combination of foods consumed simultaneously at specific eating occasions are scarce, primarily due to a lack of assessment tools. We applied a recently developed meal coding system to multiple-day dietary intake data for assessing its ability to estimate food and nutrient intakes and characterise meal-based dietary patterns in the Japanese context. A total of 242 Japanese adults completed sixteen non-consecutive-day weighed dietary records, including 14 734 eating occasions (3788 breakfasts, 3823 lunches, 3856 dinners and 3267 snacks). Common food group combinations were identified by meal type to identify a range of generic meals. Dietary intake was calculated on the basis of not only the standard food composition database but also the substituted generic meal database. In total, eighty generic meals (twenty-three breakfasts, twenty-one lunches, twenty-four dinners and twelve snacks) were identified. The Spearman correlation coefficients between food group intakes calculated based on the standard food composition database and the substituted generic meal database ranged from 0·26 to 0·85 (median 0·69). The corresponding correlations for nutrient intakes ranged from 0·17 to 0·82 (median 0·61). A total of eleven meal patterns were established using principal components analysis, and these accounted for 39·1 % of total meal variance. Considerable variation in patterns was seen in meal type inclusion and choice of staple foods (bread, rice and noodles) and drinks, and also in meal constituents. In conclusion, this study demonstrated the usefulness of a meal coding system for assessing habitual diet, providing a scientific basis towards the development of simple meal-based dietary assessment tools.

12.
J Occup Health ; 60(6): 467-474, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30175718

RESUMO

OBJECTIVES: Shift workers are at an increased risk of diet-related chronic conditions. We aimed to investigate dietary intake and dinner timing among shift workers. METHODS: A questionnaire survey was administered to the employees of 43 companies in Japan between December 2013 and February 2014. The dietary intake of workers was assessed through a validated food frequency questionnaire (FFQ). Nutrient intake was evaluated by adjusting the total energy intake using a nutrient residual model. Analysis of covariance was used to obtain the means of total energy and nutrient intake by the work schedule (shift or daytime), and the means of total energy and nutrient intake by dinner timing (regular or irregular). RESULTS: Valid responses were obtained from 2,062 daytime and 302 shift workers. A valid response rate to the FFQ was slightly but significantly lower among shift workers than among daytime workers (87.1% and 91.8 %). When compared to daytime workers, shift workers were more likely to eat dinner at irregular times (46.7% vs. 3.6%). Shift work was associated with a higher mean body mass index (23.4 kg/m2 vs. 22.3 kg/m2), a higher proportion of being overweight (27.7% and 18.8%), higher total energy intake, and lower intakes of dietary fiber, vitamin B2, folic acid, vitamin C, potassium, calcium, magnesium and iron. Moreover, irregular dinner timing was associated with lower intakes of protein, folic acid, and zinc in daytime workers, and lower intakes of carbohydrate and copper in shift workers. CONCLUSIONS: These findings indicate a need to improve the diet of shift workers.


Assuntos
Dieta/estatística & dados numéricos , Comportamento Alimentar/psicologia , Jornada de Trabalho em Turnos/psicologia , Jornada de Trabalho em Turnos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Análise de Variância , Índice de Massa Corporal , Ingestão de Energia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Inquéritos e Questionários , Adulto Jovem
13.
Eur J Pharmacol ; 819: 35-42, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29154935

RESUMO

Paclitaxel is an effective chemotherapeutic agent, but has some treatment-limiting adverse effects that markedly decrease patients' quality of life. Peripheral neuropathy is one of these, and no treatment for it has been established yet. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is secreted from the stomach and has widespread effects on multiple systems. We investigated the pharmacological potential of ghrelin in preventing paclitaxel-induced peripheral neuropathy using wild-type mice, ghrelin-null mice, and growth hormone secretagogue receptor-null mice. In wild-type mice, ghrelin administration alleviated mechanical and thermal hypersensitivity, and partially prevented neuronal loss of small unmyelinated intraepidermal nerve fibers but not large myelinated nerve fibers. Moreover, ghrelin administration decreased plasma oxidative and nitrosative stress and increased the expression of uncoupling protein 2 (UCP2) and superoxide dismutase 2 (SOD2) in the dorsal root ganglia, which are mitochondrial antioxidant proteins, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial number. Both ghrelin-null mice and growth hormone secretagogue receptor-null mice developed more severe nerve injuries than wild-type mice. Our results suggest that ghrelin administration exerts a protective effect against paclitaxel-induced neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions, and that endogenous ghrelin has a neuroprotective effect that is mediated by ghrelin/growth hormone secretagogue receptor signaling. Ghrelin could be a promising therapeutic agent for the management of this intractable disease.


Assuntos
Antioxidantes/metabolismo , Grelina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Grelina/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Nervos Periféricos/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Receptores de Grelina/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Proteína Desacopladora 2/genética
14.
J Endocr Soc ; 1(10): 1259-1271, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29264451

RESUMO

CONTEXT: Kisspeptin receptor (KISS1R) is expressed in hypothalamic gonadotropin-releasing hormone neurons and responsible for pubertal onset and reproductive functions. KISS1R mutations remain a rare cause of congenital hypogonadotropic hypogonadism (CHH). OBJECTIVE: The aim of this study was to identify the genetic cause of CHH in a patient and to functionally characterize a KISS1R mutation. DESIGN: The patient was a 47-year-old Japanese man whose parents were first cousins. He lacked secondary sexual characteristics owing to normosmic CHH. Exon segments for the KISS1R gene in this patient were screened for mutations. Functional analyses were performed using HEK293 cells expressing KISS1R mutants. Molecular dynamics simulations were performed to compare the ligand-KISS1R mutant complex with those of wild-type KISS1R variants. RESULTS: A homozygous mutation (c.440C>T, p.P147L) in KISS1R was identified. The P147L mutation did not affect either receptor expression level or subcellular localization in the recombinant expression system. Intracellular calcium measurements and cellular dielectric spectroscopy demonstrated that the P147L mutation impaired receptor function to an extent more severe than that of a previously reported L148S mutation. A receptor-ligand binding assay showed the P147L mutation causes a substantial loss of ligand-binding affinity. Molecular dynamics simulations revealed the P147L mutation decreases the contact surface area of the ligand-receptor complex in an expanded ligand-binding pocket. CONCLUSION: We identified a loss-of-function mutation in KISS1R associated with CHH. Our results demonstrated that the P147L mutation causes a severe phenotype and functional impairment resulting from the loss of ligand-binding affinity due to an expanded ligand-binding pocket.

15.
Biochem Biophys Res Commun ; 493(1): 677-683, 2017 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-28864416

RESUMO

Neuromedin U (NMU), a highly conserved peptide in mammals, is implicated in energy homeostasis and glycemic control, and may also be involved in the regulation of adipoinsular axis function. However, the role of NMU in regulating insulin secretion has not been clearly established. In this study, we investigated the role of NMU in the regulation of insulin secretion both in vitro and in vivo. We found that NMU and NMU receptor (NMUR) 1 were expressed in mouse islets and ß cell-derived MIN6-K8 cells. In mice, NMU suppressed glucose-stimulated insulin secretion (GSIS) both in vitro and in vivo. Additionally, an NMUR1 agonist inhibited GSIS in both MIN6-K8 cells and mice islets. Moreover, NMU attenuated intracellular Ca2+ influx in MIN6-K8 cells, potentially causing a decrease in insulin secretion. siNmu-transfected MIN6-K8 cells showed elevated GSIS. Treatment with anti-NMU IgG increased GSIS in isolated mouse pancreatic islets. These results suggested that NMU can act directly on ß cells through NMUR1 in an autocrine or paracrine fashion to suppress insulin secretion. Collectively, our results highlight the crucial role of NMU in suppressing pancreatic insulin secretion, and may improve our understanding of glucose homeostasis.


Assuntos
Sinalização do Cálcio/fisiologia , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Neuropeptídeos/metabolismo , Receptores de Neurotransmissores/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Secreção de Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
Endocr J ; 64(Suppl.): S41-S46, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652543

RESUMO

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), is produced in the human stomach. Although ghrelin has therapeutic potential for cancer cachexia, ghrelin treatment may have a concern about accelerating cancer progression. Here, using the human lung adenocarcinoma cell line HLC-1, we investigated the effects of ghrelin on molecular mechanisms linked to cancer progression, including cell viability, proliferation, resistance to apoptosis, and mitochondrial activity. Both types of mouse alveolar epithelial cells (types I and II) expressed the GHSR, as did the human normal airway cell lines BEAS-2B and HLC-1. Treatment with ghrelin (10-2, 10-1, 1, 10 µM) did not affect cell viability or proliferation. Pretreatment of HLC-1 cells with ghrelin (10 µM) did not affect resistance to paclitaxel-induced apoptosis. The parameters of mitochondrial respiration, including basal respiration, proton leak, ATP production, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration, of the HLC-1 cells pretreated with or without ghrelin were unchanged. Taken together, ghrelin does not influence cancer progression in lung adenocarcinoma cells.


Assuntos
Adenocarcinoma/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Grelina/uso terapêutico , Neoplasias Pulmonares/patologia , Adenocarcinoma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Progressão da Doença , Grelina/administração & dosagem , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos
17.
Intern Med ; 56(9): 1067-1070, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28458314

RESUMO

Intramyocardial dissecting hematoma is a rare but potentially fatal complication of myocardial infarction. The decision to adopt a surgical or conservative strategy may depend on the clinical and hemodynamic stability of patients. Regardless, the precise and temporal assessment of the structure of hematoma is imperative. We herein report the first case of a patient with early spontaneous remission of intramyocardial dissecting hematoma successfully managed by a conservative approach with multimodality imaging.


Assuntos
Hematoma/diagnóstico por imagem , Hematoma/etiologia , Infarto do Miocárdio/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Remissão Espontânea , Resultado do Tratamento
18.
Int J Mol Sci ; 18(3)2017 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-28245616

RESUMO

Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence-clearance-regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections.


Assuntos
Envelhecimento , Senescência Celular , Pneumopatias/complicações , Pneumopatias/etiologia , Pneumonia/complicações , Pneumonia/etiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Resistência à Doença , Suscetibilidade a Doenças , Humanos , Pneumopatias/diagnóstico , Fenótipo , Pneumonia/diagnóstico , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/microbiologia , Risco
19.
J Appl Glycosci (1999) ; 64(4): 83-90, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-34354500

RESUMO

Salmon cartilage proteoglycan fractions have recently gained favor as ingredients of functional food and cosmetics. An optimal hot water method to extract proteoglycan from salmon cartilage has recently been developed. The extracted cartilage includes hyaluronan and collagen in addition to proteoglycan as counterparts that interact with each other. In this study, biochemical analyses and atomic force microscopical analysis revealed global molecular images of proteoglycan in the hot water extract. More than seventy percent of proteoglycans in this extract maintained their whole native structures. Hyaluronan purified from the hot water extract showed a distribution with high molecular weight similar to hyaluronan considered to be native hyaluronan in cartilage. The current data is evidence of the quality of this hot water cartilage extract.

20.
Heart Vessels ; 31(12): 1923-1929, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26936452

RESUMO

Lipoprotein(a) [Lp(a)], which is genetically determined, has been reported as an independent risk factor for atherosclerotic vascular disease. However, the prognostic value of Lp(a) for secondary vascular events in patients after coronary artery disease has not been fully elucidated. This 3-year observational study included a total of 176 patients with ST-elevated myocardial infarction (STEMI), whose Lp(a) levels were measured within 24 h after primary percutaneous coronary intervention. We divided enrolled patients into two groups according to Lp(a) level and investigated the association between Lp(a) and the incidence of major adverse cardiac and cerebrovascular events (MACCE). A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of MACCE than those with lower Lp(a) levels (log-rank P = 0.034). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the occurrence of MACCE after adjusting for other classical risk factors of atherosclerotic vascular diseases (hazard ratio 1.030, 95 % confidence interval: 1.011-1.048, P = 0.002). In receiver-operating curve analysis, the cutoff value to maximize the predictive power of Lp(a) was 19.0 mg/dl (area under the curve = 0.674, sensitivity 69.2 %, specificity 62.0 %). Evaluation of Lp(a) in addition to the established coronary risk factors improved their predictive value for the occurrence of MACCE. In conclusion, Lp(a) levels at admission independently predict secondary vascular events in patients with STEMI. Lp(a) might provide useful information for the development of secondary prevention strategies in patients with myocardial infarction.


Assuntos
Lipoproteína(a)/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Idoso , Área Sob a Curva , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Admissão do Paciente , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores de Tempo , Resultado do Tratamento
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